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We report a fatal case of Crimean-Congo hemorrhagic fever in Portugal. An 83-year-old man, initially suspected of having Mediterranean spotted fever, was later confirmed to have Crimean-Congo hemorrhagic fever by the detection of viral genome in the patient's serum and the presence of specific IgM antibodies.

The introduction of invasive species has become an increasing environmental problem in freshwater ecosystems due to the high economic and ecological impacts it has generated. This systematic review covers publications from 2010 to 2020, focusing on non-native invasive freshwater bivalves, a particularly relevant and widespread introduced taxonomic group in fresh waters. We collected information on the most studied species, the main objectives of the studies, their geographical location, study duration, and type of research. Furthermore, we focused on assessing the levels of ecological evidence presented, the type of interactions of non-native bivalves with other organisms and the classification of their impacts. A total of 397 publications were retrieved. The studies addressed a total of 17 species of non-native freshwater bivalves; however, most publications focused on the species Corbicula fluminea and Dreissena polymorpha, which are recognised for their widespread distribution and extensive negative impacts. Many other non-native invasive bivalve species have been poorly studied. A high geographical bias was also present, with a considerable lack of studies in developing countries. The most frequent studies had shorter temporal periods, smaller spatial extents, and more observational data, were field-based, and usually evaluated possible ecological impacts at the individual and population levels. There were 94 publications documenting discernible impacts according to the Environmental Impact Classification for Alien Taxa (EICAT). However, 41 of these publications did not provide sufficient data to determine an impact. The most common effects of invasive bivalves on ecosystems were structural alterations, and chemical and physical changes, which are anticipated due to their role as ecosystem engineers. Despite a considerable number of studies in the field and advances in our understanding of some species over the past decade, long-term data and large-scale studies are still needed to understand better the impacts, particularly at the community and ecosystem levels and in less-studied geographic regions. The widespread distribution of several non-native freshwater bivalves, their ongoing introductions, and high ecological and economic impacts demand continued research. Systematic reviews such as this are essential for identifying knowledge gaps and guiding future research to enable a more complete understanding of the ecological implications of invasive bivalves, and the development of effective management strategies., (© 2024 Cambridge Philosophical Society.)

Background: The success of haemodialysis (HD) critically depends on the effective use of arteriovenous fistulas (AVFs). The precise needling technique is vital to minimise complications and ensure functional vascular access., Objective: This study assesses the effectiveness of a nursing consultation protocol, which integrates physical examination (PE) with Doppler Ultrasound (DUS), in preparing patients for the first AVF needling., Design/participants: A cross-sectional analysis at a Portuguese National Health Service Hospital engaged thirty new HD patients, four HD needling experienced nurses and one HD vascular access nurse. This study examines the accuracy of PE in assessing the matured AVF by the four nurses compared to a trained vascular access nurse encompassing systematic PE and DUS., Measurements: The primary data incorporated AVF characteristics derived from PE (inspection, palpation, and auscultation) and DUS findings (vein depth, diameter, and blood flow). A secondary focus was evaluating the change in nurses' perceived needling complexity following the nursing consultation., Results: The nursing consultation significantly enhanced the identification of crucial AVF features, such as accessory veins (p = 0.002), and improved the accuracy of AVF morphology assessments. This led to identifying longer needling tracks (p = 0.031) and a higher number of safe needling points (p = 0.016). Nurses reported a notable reduction in perceived complexity and potential adverse events following this method (p = 0.027)., Conclusions: Integrating structured PE with DUS in a nursing consultation framework significantly improves the preparation for AVF needling. This approach enhances the efficiency and safety of AVF needling and boosts nurse confidence and patient care in HD settings., (© 2024 European Dialysis & Transplant Nurses Association/European Renal Care Association.)

Background: Artificial intelligence chatbot tools responses might discern patterns and correlations that may elude human observation, leading to more accurate and timely interventions. However, their reliability to answer healthcare-related questions is still debated. This study aimed to assess the performance of the three versions of GPT-based chatbots about prosthetic joint infections (PJI)., Methods: Thirty questions concerning the diagnosis and treatment of hip and knee PJIs, stratified by a priori established difficulty, were generated by a team of experts, and administered to ChatGPT 3.5, BingChat, and ChatGPT 4.0. Responses were rated by three orthopedic surgeons and two infectious diseases physicians using a five-point Likert-like scale with numerical values to quantify the quality of responses. Inter-rater reliability was assessed by interclass correlation statistics., Results: Responses averaged "good-to-very good" for all chatbots examined, both in diagnosis and treatment, with no significant differences according to the difficulty of the questions. However, BingChat ratings were significantly lower in the treatment setting (p = 0.025), particularly in terms of accuracy (p = 0.02) and completeness (p = 0.004). Agreement in ratings among examiners appeared to be very poor., Conclusions: On average, the quality of responses is rated positively by experts, but with ratings that frequently may vary widely. This currently suggests that AI chatbot tools are still unreliable in the management of PJI., Competing Interests: Declarations. Conflicts of interest: The authors declare no conflicts of interest., (© 2024. The Author(s).)

The food enzyme glucan-1,4-α-glucosidase (4-α-d-glucan glucohydrolase; EC 3.2.1.3) is produced with the non-genetically modified Aspergillus niger strain DP-Azh100 by Genencor International B.V. It was considered free from viable cells of the production organism. The food enzyme is intended to be used in four food manufacturing processes. Since residual amounts of total organic solids (TOS) are removed in two processes, dietary exposure was calculated only for the two remaining processes. It was estimated to be up to 1.390 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level at the highest dose tested of 1000 mg TOS/kg bw per day, which when compared with the estimated dietary exposure, resulted in a margin of exposure of at least 719. A search for the homology of the amino acid sequence of the food enzyme to known allergens was made and one match to a respiratory allergen was found. Known sources of food allergens were used in the food enzyme manufacturing process. The Panel considered that the risk of allergic reactions upon dietary exposure to this food enzyme cannot be excluded, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Post-translational cycles of α-tubulin detyrosination and tyrosination generate microtubule diversity, the cellular functions of which remain largely unknown. Here we show that α-tubulin detyrosination regulates kinetochore-microtubule attachments to ensure normal chromosome oscillations and timely anaphase onset during mitosis. Remarkably, detyrosinated α-tubulin levels near kinetochore microtubule plus-ends depend on the direction of chromosome motion during metaphase. Proteomic analyses unveil that the KNL-1/MIS12/NDC80 (KMN) network that forms the core microtubule-binding site at kinetochores and the microtubule-rescue protein CLASP2 are enriched on tyrosinated and detyrosinated microtubules during mitosis, respectively. α-tubulin detyrosination enhances CLASP2 binding and NDC80 complex diffusion along the microtubule lattice in vitro. Rescue experiments overexpressing NDC80, including variants with slower microtubule diffusion, suggest a functional interplay with α-tubulin detyrosination for the establishment of a labile kinetochore-microtubule interface. These results offer a mechanistic explanation for how different detyrosinated α-tubulin levels near kinetochore microtubule plus-ends fine-tune load-bearing attachments to both growing and shrinking microtubules., (© 2024. The Author(s).)

Introduction: Motivation plays a crucial role in the academic success and professional development of medical students. Understanding the intricacies of motivation within the context of medical education is essential for designing effective interventions and support systems. The aim of this study was to explore the adaptation of the Academic Motivation Scale within the framework of the self-determination theory and of the self-efficacy theory to assess motivation among medical students., Methods: The study adapted the Academic Motivation Scale to the Portuguese context, drawing upon insights from the self-determination theory. Two existing Portuguese scales, MATAMS and Ribeiro et al scale, served as foundational frameworks for the adaptation process. The study included qualitative interviews, which informed the creation of the Minho Medical Academic Motivation Scale - Minho-MEDAMS. This scale was applied to 281 medical students. To assess the scale's validity, we used the exploratory and confirmatory factor analyses, and the Cronbach's alpha to measure internal consistency., Results: The exploratory factor analysis showed strong results with a KMO of 0.862, leading to five factors and the removal of two items. The initial confirmatory factor analysis indicated poor fit, prompting the removal of items with low R-squared values. The final Minho-MEDAMS includes 18 items: six for intrinsic motivation, nine for extrinsic motivation and three for amotivation. This refined scale demonstrates high internal consistency (α = 0.831), making it a reliable tool for assessing medical students' motivation., Conclusion: The successful adaptation of the Academic Motivation Scale within the self-determination theory framework presents a valuable instrument for assessing motivation in medical students. The Minho-MEDAMS offers a comprehensive understanding of motivational dynamics, facilitating targeted interventions and support mechanisms to enhance student engagement and success. Its validity and reliability render it a practical tool for educators, administrators, and researchers in the field of medical education. Ultimately, the Minho-MEDAMS contributes to the advancement of strategies aimed at cultivating motivated and proficient healthcare professionals.

Tick-borne pathogens are a worldwide threat to public health that can only be mitigated by knowledge on tick-host associations coupled with surveillance of their infection by pathogenic microorganisms. This information is not equally available throughout tick vector distribution range and is deficient in some geographical areas. In this study we did a molecular survey of tick-borne pathogens associated with different tick species in Morocco. We analyzed four different species of Hyalomma (Hyalomma aegyptium, Hyalomma anatolicum, Hyalomma dromedarii and Hyalomma impeltatum) and Rhipicephalus sanguineus sensu lato ticks from four vertebrate hosts and from the vegetation. The most common tick species collected was H. aegyptium feeding on Testudo graeca tortoises, followed by H. anatolicum from the vegetation. Hyalomma aegyptium feeding on T. graeca was found infected with Borrelia turcica, representing the first detection for Western North Africa, and Rickettsia sibirica mongolitimonae, also detected for the first time in Morocco. Rickettsia aeschlimannii was also detected in H. aegyptium feeding on T. graeca. Additionally, R. aeschlimannii was detected in H. anatolicum from the vegetation, and Rickettsia massiliae in R. sanguineus s.l. from an Algerian hedgehog Atelix algirus. Because H. aegyptium are common parasites of T. graeca tortoises, and these animals are subjected to pet trade, it is important to evaluate the associated human health risks through regular surveillance and perform awareness campaigns for prevention of the general public., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The toxicity of tacrolimus metabolites and their potential pharmacodynamic (PD) interactions with tacrolimus might respectively explain the surprising combination of higher toxicity and lower efficacy of tacrolimus despite normal blood concentrations, described in extensive metabolizers. To evaluate such interactions, we produced tacrolimus metabolites in vitro and characterized them by high resolution mass spectrometry (HRMS, for all) and nuclear magnetic resonance (NMR, for the most abundant, M-I). We quantified tacrolimus metabolites and checked their structure in patient whole blood and peripheral blood mononuclear cells (PBMC). We explored the interactions of M-I with tacrolimus in silico, in vitro and ex vivo. In vitro metabolization produced isoforms of tacrolimus and of its metabolites M-I and M-III, whose HRMS fragmentation suggested an open-ring structure. M-I and M-III open-ring isomers were also observed in patient blood. By contrast, NMR could not detect these open-ring forms. Transplant patients expressing CYP3A5 exhibited higher M-I/TAC ratios in blood and PBMC than non-expressers. Molecular Dynamics simulations showed that: all possible tacrolimus metabolites and isomers bind FKPB12; and the hypothetical open-ring structures induce looser binding between FKBP12 and calcineurins, leading to lower CN inhibition. In vitro, tacrolimus bound FKPB12 with more affinity than purified M-I, and the pool of tacrolimus metabolites and purified M-I had only weak inhibitory activity on IL2 secretion and not at all on NFAT nuclear translocation. M-I showed no competitive effect with tacrolimus on either test. Finally, M-I or the metabolite pool did not significantly interact with tacrolimus MLR suppression, thus eliminating a pharmacodynamic interaction., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Melanie Campana reports administrative support and equipment, drugs, or supplies were provided by MedinCell SA. Rudy Mevizou reports administrative support and equipment, drugs, or supplies were provided by MedinCell SA. Pierre Marquet reports a relationship with MedinCell SA that includes: consulting or advisory, equity or stocks, and funding grants. Melanie Campana reports a relationship with MedinCell SA that includes: employment and equity or stocks. Alfonso Lopez-Noriega reports a relationship with MedinCell SA that includes: employment and equity or stocks. Pierre Marquet reports a relationship with Sandoz France that includes: consulting or advisory and funding grants. Pierre Marquet reports a relationship with Chiesi SA France that includes: consulting or advisory and funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: Lung cancer is the most common cause of cancer death in Portugal. The Dutch-Belgian lung cancer screening (LCS) study (NELSON), the biggest European LCS study, showed a lung cancer mortality reduction in a high-risk population when being screened. In this study, the cost-effectiveness of LCS, based on the NELSON study protocol and outcomes, was evaluated compared with no screening in Portugal. Methods: The present study modified an established decision tree by incorporating a state-transition Markov model to evaluate the health-related advantages and economic implications of low-dose computed tomography (LDCT) LCS from the healthcare standpoint in Portugal. The analysis compared screening versus no screening for a high-risk population aged 50-75 with a smoking history. Various metrics, including clinical outcomes, costs, quality-adjusted life years (QALYs), life-years (LYs) and the incremental cost-effectiveness ratio (ICER), were calculated to measure the impact of LDCT LCS. Furthermore, scenario and sensitivity analyses were executed to assess the robustness of the obtained results. Results: Annual LCS with volume-based LDCT resulted in €558 million additional costs and 86,678 additional QALYs resulting in an ICER of €6440 per QALY for one screening group and a lifetime horizon. In total, 13,217 premature lung cancer deaths could be averted, leading to 1.41 additional QALYs gained per individual diagnosed with lung cancer. Results are robust based on the sensitivity analyses. Conclusion: This study showed that annual LDCT LCS for a high-risk population could be cost-effective in Portugal based on a willingness to pay a threshold of one-time the GDP (€19,290 per QALY gained).

E-scooters have become increasingly popular for short-distance travel in urban areas, but this rise in usage also brings about an increased risk of accidents. Studies have shown that approximately 40% of electric scooter accident victims admitted to hospitals suffer head injuries. Therefore, it is crucial to implement safety measures and improve safety systems and equipment to mitigate these risks. One approach to gaining insights into the injuries users face is through simulations using the multi-body method. This method allows for the reconstruction of accidents by modeling and analyzing the dynamic behavior of interconnected bodies. This study aims to assess the impacts on the user's head and the injuries they may sustain in electric scooter accidents using numerical methods. Initially, a reference scenario was established based on a YouTube video, with the assumption that the user was an average-height man. Simulations were conducted for various percentiles, including both males and females. Different velocities were simulated to determine the threshold velocity at which survival becomes practically impossible. Two scenarios were considered: one where the car braked for 0.333 s and another where the distance between the start the braking task and the collision was kept constant. The location of the first head impact on the vehicle was also examined. Injury assessment was conducted using two criteria: Head Injury Criterion (HIC) and Brain Injury Criterion (BrIC). The study found that smaller individuals are more vulnerable to severe injuries, and higher car velocities correlate with more severe user injuries. Furthermore, the location of the first impact varies between genders, with women more likely to experience impacts in the lower part of the windshield, while men tend to experience impacts in the central zone. This study highlights the importance of considering user characteristics and accident dynamics in assessing injury risks associated with e-scooters., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Formal nursing leaders play an important role in promoting and sustaining evidence-based practice (EBP) in the clinical context, particularly by creating a conducive environment for change and increasing clinicians' awareness of the positive results of EBP. However, nursing leaders encounter both barriers and facilitators in their work; therefore, it is important to understand their perceptions on this topic., Objective: The objective of this study was to understand the perceptions of formal nursing leaders about barriers and facilitators for EBP., Methods: A descriptive exploratory study with a qualitative approach was conducted. A convenience sample was obtained, consisting of formal nursing leaders from three Portuguese health care institutions. Data were collected through semi-structured interviews. Content analysis was conducted using MAXQDA Analytic Pro 2022 software., Results: Seventeen formal nursing leaders were interviewed. Five categories of EBP barriers were identified: (1) scarce resources and inefficient resource management; (2) non-conducive organizational culture; (3) distance between academia and the clinical context; (4) demotivation; and (5) resistance to change. Seven categories of EBP facilitators were identified: (1) availability of resources and efficient resource management; (2) conducive organizational culture; (3) partnerships between academia and the clinical context; (4) motivation and commitment; (5) leadership; (6) organization that regulates professional practice; and (7) multidisciplinary meetings., Conclusions: This study identified barriers and facilitators for EBP through the perceptions of formal nursing leaders. Collaborative multidisciplinary efforts by leaders, direct care professionals, academics, and researchers should be conducted to overcome barriers and strengthen facilitators for EBP., Spanish Abstract: http://links.lww.com/IJEBH/A242., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 JBI. Unauthorized reproduction of this article is prohibited.)

Introduction : Prediction models for periprosthetic joint infections (PJIs) are gaining interest due to their potential to improve clinical decision-making. However, their external validity across various settings remains uncertain. This study aimed to externally validate promising preoperative PJI prediction models in a recent multinational European cohort. Methods : Three preoperative PJI prediction models - by Tan et al. (2018), Del Toro et al. (2019), and Bülow et al. (2022) - that have previously demonstrated high levels of accuracy were selected for validation. A retrospective observational analysis of patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) at centers in the Netherlands, Portugal, and Spain between January 2020 and December 2021 was conducted. Patient characteristics were compared between our cohort and those used to develop the models. Performance was assessed through discrimination and calibration. Results : The study included 2684 patients, 60 of whom developed a PJI (2.2 %). Our cohort differed from the models' original cohorts with respect to demographic variables, procedural variables, and comorbidity prevalence. The overall accuracies of the models, measured with the c  statistic, were 0.72, 0.69, and 0.72 for the Tan, Del Toro, and Bülow models, respectively. Calibration was reasonable, but the PJI risk estimates were most accurate for predicted infection risks below 3 %-4 %. The Tan model overestimated PJI risk above 4 %, whereas the Del Toro model underestimated PJI risk above 3 %. Conclusions : The Tan, Del Toro, and Bülow PJI prediction models were externally validated in this multinational cohort, demonstrating potential for clinical application in identifying high-risk patients and enhancing preoperative counseling and prevention strategies., Competing Interests: At least one of the (co-)authors is a member of the editorial board of Journal of Bone and Joint Infection. The peer-review process was guided by an independent editor, and the authors also have no other competing interests to declare., (Copyright: © 2024 Seung-Jae Yoon et al.)

Systemic sclerosis (SSc) is a complex connective tissue disease involving microvasculopathy, immune dysregulation, and extensive organ fibrosis. It affects various systems including the skin, lungs, heart, and gastrointestinal tract. Management is challenging due to the disease's heterogeneity and often requires more than just pharmacological treatment. Severe cases may necessitate amputation due to complications like tissue necrosis. This case report discusses the treatment of a 60-year-old man with cutaneous diffuse SSc who required multiple upper limb amputations due to progressive gangrene. Despite initial pharmacological and vascular interventions, the patient's condition led to metacarpophalangeal and transradial amputations. A multidisciplinary approach was crucial in determining the level of amputation and managing post-surgical rehabilitation. Following the transradial amputation, the patient participated in a comprehensive rehabilitation program to optimize functional recovery and prepare for prosthesis fitting. The case highlights the need for a multidisciplinary strategy in managing severe SSc complications and underscores the importance of tailored rehabilitation in improving functional outcomes and quality of life for amputees., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sousa et al.)

Biological invasions cause biodiversity erosion on a global scale. Invasive species spreading beyond their natural range compete with native fauna for food and space, push native species to suboptimal habitats, impairing their behaviour and thus limiting their occurrence. Freshwater ecosystems are especially vulnerable to biological invasions and their ecological and economic impacts. The invasive Asian clams (Corbicula spp.), due to their opportunistic life style, can occur at densities of thousands ind. m -2 . They act as ecosystem engineers transforming bottom substrata through accumulation of shells. Our goal was to determine the effect of substratum modification by living Corbicula and their shells on substratum choice and behaviour of Unio tumidus and Anodonta anatina, two European freshwater mussel species of the highly imperilled Unionidae family. We assessed their substratum selection in pairwise choice tests (pure sand vs. sand modified by living Corbicula or their shells, sand modified by shells vs. living Corbicula). Next, we tested locomotion and burrowing of unionids on pure substratum and substrata modified by Corbicula. Unionids avoided sand modified by living Corbicula and their empty shells, not distinguishing between these two types of substratum modification. In the presence of Corbicula, their burrowing was shallower or it took them longer to obtain the same depth as in the pure sand. Additionally, on sand modified by Corbicula shells, we observed a locomotion increase (U. tumidus) or slowing down (A. anatina). Our research showed a novel mechanism of negative impact of Corbicula on unionids, consisting in pushing them away from their optimal habitats. This may contribute to their habitat loss and future declines in invaded ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: Ultrasound derived carotid intima-media thickness (cIMT) is valuable for cardiovascular risk stratification. We assessed the relative importance of traditional atherosclerosis risk factors and plasma proteins in predicting cIMT measured nearly a decade later., Method: We examined 6,136 UK Biobank participants with 1,461 proteins profiled using the proximity extension assay applied to their baseline blood draw who subsequently underwent a cIMT measurement. We implemented linear regression, stepwise Akaike Information Criterion-based, and the least absolute shrinkage and selection operator (LASSO) models to identify potential proteomic as well as non-proteomic predictors. We evaluated our model performance using the proportion variance explained ( R 2 )., Result: The mean time from baseline assessment to cIMT measurement was 9.2 years. Age, blood pressure, and anthropometric related variables were the strongest predictors of cIMT with fat-free mass index of the truncal region being the strongest predictor among adiposity measurements. A LASSO model incorporating variables including age, assessment center, genetic risk factors, smoking, blood pressure, trunk fat-free mass index, apolipoprotein B, and Townsend deprivation index combined with 97 proteins achieved the highest R 2 (0.308, 95% C.I. 0.274, 0.341). In contrast, models built with proteins alone or non-proteomic variables alone explained a notably lower R 2 (0.261, 0.228-0.294 and 0.260, 0.226-0.293, respectively). Chromogranin b (CHGB), Cystatin-M/E (CST6), leptin (LEP), and prolargin (PRELP) were the proteins consistently selected across all models., Conclusion: Plasma proteins add to the clinical and genetic risk factors in predicting a cIMT measurement. Our findings implicate blood pressure and extracellular matrix-related proteins in cIMT pathophysiology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Chen, Kho, Guarischi-Sousa, Zhou, Panyard, Azizi, Gupte, Watson, Abbasi and Assimes.)

Mare milk has a unique protein composition that makes it a preferred option for adult and infant nutrition. Several functional properties have been attributed to this milk, but with little current evidence. In fact, knowledge on mare milk composition is still limited. In particular, studies addressing the performance of mare milk proteins during human gastrointestinal digestion are scarce, which limits the understanding of mare milk nutritional quality and functionality. For this reason, the present study describes the digestibility of mare milk proteins and the release of peptides as affected by management and lactation stage, factors which are known to affect milk composition. Mare milk samples from 3 different farms collected during 6 mo of lactation (n = 54) were subjected to a static in vitro gastrointestinal model to measure peptide release and protein digestibility. In the present study, a detailed description of protein and individual amino acid behavior during the digestion process was given. For the first time, digestion of the 2 equine β-lactoglobulin isoforms (I and II) was described individually. In addition, it was found that lactation stage and management system can significantly affect protein digestibility and peptide release during gastrointestinal digestion of mare milk. Presumably, differences in the composition of mare milk influence the protein structure and enzyme accessibility, which might have an impact on digestion behavior. Although no specific bioactive peptides were identified, several precursors of previously described bioactive peptides were found. These findings could support the idea of mare milk as a food with added value., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Electronic waste (e-waste) is a global problem, and many countries have established laws and regulations to promote its proper disposal and recycling. E-waste contains a significant content of printed circuit boards (PCBs), composed of metals and other valuable metals that may become scarce in Earth's crust - Copper (Cu), nickel (Ni), gold (Au), silver (Ag), palladium (Pd), and others. The main objective of this review is to explore the potential for producing nanoparticles (NPs) from the metals extracted through PCB recycling, with applications in the cosmetics, cement manufacturing, and carbon dioxide (CO 2 ) capture industries. For this purpose, the recycling methods for PCBs e-waste, using physical processes (gravity, magnetic, electrostatic separation, and flotation), metallurgical processes (pyrometallurgy and hydrometallurgy), and purification techniques to obtain an enriched metal solution for the subsequent nanoparticle synthesis was performed. The production of NPs is a novel approach to obtain value-added products for industry. Therefore, recent research from pre-treatment of PCBs to NPs production is summarized, aligning with the circular economy principles and sustainable development goals. Towards this end, wasted PCBs can be transformed into valuable materials with innovative and potential applications in cosmetics, cement manufacturing, and carbon dioxide capture, contributing to a more sustainable future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

A young male adult presented with a two-week-long history of myoarthralgia, vomiting, febrile sensation, holocranial headache with photophobia, neck stiffness, anorexia, and weight loss. He worked as a butcher in a local slaughterhouse, and two of his coworkers had recently been diagnosed with brucellosis. On his fourth visit to the Emergency Department (ED), fever was observed for the first time. He was admitted for subacute meningitis. A lumbar puncture revealed high protein concentration, low glucose concentration, and pleocytosis without predominance. He was started on empirical treatment for acute meningitis and neurobrucellosis with ceftriaxone, doxycycline, and rifampin. There was a complete symptom remission over one week. The etiological investigation yielded a positive cerebrospinal fluid (CSF) and serum Rose Bengal Tests (RBTs), as well as a positive anti- Brucella IgG titer, leading to a final diagnosis of neurobrucellosis. After nine months of antimicrobial therapy and two years of follow-up, the patient remained asymptomatic., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Duarte et al.)

The ectoparasite Amyloodinium ocellatum is a dinoflagellate that causes severe morbidity and mortality in both brackish and marine warmwater aquaculture fishes worldwide. A. ocellatum has a triphasic life cycle based on a free-living flagellate (the dinospore), a parasitic stage (the trophont) and a resting and reproductive cyst (the tomont). Current chemical treatments have shown some efficacy in eliminating dinospores but fail to inactivate the tomonts. Here we evaluated the efficacy of alternative treatments in vitro through sporulation tests and the quantification of dinospore production and motility. Hydrogen peroxide and peracetic acid efficiently decreased dinospore production at low concentrations, but total inactivation of tomonts was only achieved with higher dosages. Tomont inactivation was also observed with disinfectants such as sodium hypochlorite and Virkon S. This work provides insights into effective and environmentally friendly alternatives for the elimination of resistant forms of the marine parasite A. ocellatum.

Background: While risk stratification for atherosclerotic cardiovascular disease (ASCVD) is essential for primary prevention, current clinical risk algorithms demonstrate variability and leave room for further improvement. The plasma proteome holds promise as a future diagnostic and prognostic tool that can accurately reflect complex human traits and disease processes. We assessed the ability of plasma proteins to predict ASCVD., Method: Clinical, genetic, and high-throughput plasma proteomic data were analyzed for association with ASCVD in a cohort of 41,650 UK Biobank participants. Selected features for analysis included clinical variables such as a UK-based cardiovascular clinical risk score (QRISK3) and lipid levels, 36 polygenic risk scores (PRSs), and Olink protein expression data of 2,920 proteins. We used least absolute shrinkage and selection operator (LASSO) regression to select features and compared area under the curve (AUC) statistics between data types. Randomized LASSO regression with a stability selection algorithm identified a smaller set of more robustly associated proteins. The benefit of plasma proteins over standard clinical variables, the QRISK3 score, and PRSs was evaluated through the derivation of Δ AUC values. We also assessed the incremental gain in model performance using proteomic datasets with varying numbers of proteins. To identify potential causal proteins for ASCVD, we conducted a two-sample Mendelian randomization (MR) analysis., Result: The mean age of our cohort was 56.0 years, 60.3% were female, and 9.8% developed incident ASCVD over a median follow-up of 6.9 years. A protein-only LASSO model selected 294 proteins and returned an AUC of 0.723 (95% CI 0.708-0.737). A clinical variable and PRS-only LASSO model selected 4 clinical variables and 20 PRSs and achieved an AUC of 0.726 (95% CI 0.712-0.741). The addition of the full proteomic dataset to clinical variables and PRSs resulted in a Δ AUC of 0.010 (95% CI 0.003-0.018). Fifteen proteins selected by a stability selection algorithm offered improvement in ASCVD prediction over the QRISK3 risk score [Δ AUC: 0.013 (95% CI 0.005-0.021)]. Filtered and clustered versions of the full proteomic dataset (consisting of 600-1,500 proteins) performed comparably to the full dataset for ASCVD prediction. Using MR, we identified 11 proteins as potentially causal for ASCVD., Conclusion: A plasma proteomic signature performs well for incident ASCVD prediction but only modestly improves prediction over clinical and genetic factors. Further studies are warranted to better elucidate the clinical utility of this signature in predicting the risk of ASCVD over the standard practice of using the QRISK3 score., Competing Interests: Conflict of Interest None of the authors have conflicts of interest to report

Aims/hypothesis: The plasma proteome holds promise as a diagnostic and prognostic tool that can accurately reflect complex human traits and disease processes. We assessed the ability of plasma proteins to predict type 2 diabetes mellitus (T2DM) and related traits., Methods: Clinical, genetic, and high-throughput proteomic data from three subcohorts of UK Biobank participants were analyzed for association with dual-energy x-ray absorptiometry (DXA) derived truncal fat (in the adiposity subcohort), estimated maximum oxygen consumption (VO 2 max) (in the fitness subcohort), and incident T2DM (in the T2DM subcohort). We used least absolute shrinkage and selection operator (LASSO) regression to assess the relative ability of non-proteomic and proteomic variables to associate with each trait by comparing variance explained (R 2 ) and area under the curve (AUC) statistics between data types. Stability selection with randomized LASSO regression identified the most robustly associated proteins for each trait. The benefit of proteomic signatures (PSs) over QDiabetes, a T2DM clinical risk score, was evaluated through the derivation of delta (Δ) AUC values. We also assessed the incremental gain in model performance metrics using proteomic datasets with varying numbers of proteins. A series of two-sample Mendelian randomization (MR) analyses were conducted to identify potentially causal proteins for adiposity, fitness, and T2DM., Results: Across all three subcohorts, the mean age was 56.7 years and 54.9% were female. In the T2DM subcohort, 5.8% developed incident T2DM over a median follow-up of 7.6 years. LASSO-derived PSs increased the R 2 of truncal fat and VO 2 max over clinical and genetic factors by 0.074 and 0.057, respectively. We observed a similar improvement in T2DM prediction over the QDiabetes score [Δ AUC: 0.016 (95% CI 0.008, 0.024)] when using a robust PS derived strictly from the T2DM outcome versus a model further augmented with non-overlapping proteins associated with adiposity and fitness. A small number of proteins (29 for truncal adiposity, 18 for VO 2 max, and 26 for T2DM) identified by stability selection algorithms offered most of the improvement in prediction of each outcome. Filtered and clustered versions of the full proteomic dataset supplied by the UK Biobank (ranging between 600-1,500 proteins) performed comparably to the full dataset for T2DM prediction. Using MR, we identified 4 proteins as potentially causal for adiposity, 1 as potentially causal for fitness, and 4 as potentially causal for T2DM., Conclusions/interpretation: Plasma PSs modestly improve the prediction of incident T2DM over that possible with clinical and genetic factors. Further studies are warranted to better elucidate the clinical utility of these signatures in predicting the risk of T2DM over the standard practice of using the QDiabetes score. Candidate causally associated proteins identified through MR deserve further study as potential novel therapeutic targets for T2DM., Competing Interests: Conflict of Interest None of the authors have conflicts of interest to report.

Introduction: Neuromyelitis optica spectrum disorders (NMOSD) and MOG-associated disease (MOGAD) are an increasingly recognized group of demyelinating disorders of the central nervous system. Previous studies suggest that prognosis is predicted by older age at onset, number of relapses, the severity of the first attack and autoantibody status., Objective: To study prognostic factors associated with disability progression and additional relapses in the 3-year follow-up of a national NMOSD/MOGAD cohort., Results: Out of 180 of the initial Portuguese cohort, data on 82 patients was available at the end of the follow-up period (2019-2022). Two patients died. Twenty (24.4%) patients had one or more attack in this period (25 attacks in total), mostly transverse myelitis (TM) (56.0%) or optic neuritis (32.0%). MOGAD was significantly associated with a monophasic disease course (p = 0.03), with milder attacks (p = 0.01), while AQP4 + NMOSD was associated with relapses (p = 0.03). The most common treatment modalities were azathioprine (38.8%) and rituximab (18.8%). AQP4 + NMOSD more frequently required chronic immunosuppressive treatment, particularly rituximab (p = 0.01). Eighteen (22.5%) had an EDSS ≥6 at the end of the follow-up. AQP4 + NMOSD (p < 0.01) and the occurrence of transverse myelitis (TM) during disease (p = 0.04) correlated with an EDSS≥6 at the end of the follow-up period. MOGAD was significantly associated with an EDSS<6 (p < 0.01), and MOG+ cases that reached an EDSS>6 were significantly older (64.0 ± 2.8 versus 31.0 ± 17.1, p = 0.017). A bivariate logistic regression model including the serostatus and TM attacks during disease history successfully predicted 72.2% of patients that progressed to an EDSS≥6., Conclusion: This study highlights that myelitis predict increased disability (EDSS≥6) in NMOSD/MOGAG and AQP4 positivity is associated with increased disability., Competing Interests: Declaration of competing interest Authors declare no conflict of interest regarding this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To assess the influence of two conventional and one adapted cheek and lip retractors and three emissivity setting values on intraoral infrared thermography (IT) temperature values., Methods: The sample was composed by 50 volunteers. Three cheek and lip retractors were tested: Group 1-flex retractor (FR); Group 2-FR adapted with Styrofoam; Group 3-U-type retractor (UR) for cheek and lip. All thermograms were acquired using FLIR T650 infrared camera. A set of three thermograms in frontal norm were acquired for each lip and cheek retractor at 0.91, 0.96, and 0.98ε, with an interval of 15 min between each set of images to avoid thermal interference. All images were assessed by two observers. The ROIs' mean temperature of the four upper incisors was recorded. Two-way ANOVA and Sidak post-test were used for data assessment with a significance level of 5%., Results: Group 3 showed higher mean temperature than Groups 1 and 2 at all emissivity settings for all assessed teeth (P < .05). 0.91ε showed higher temperature than 0.96ε and 0.98ε for all assessed variables (P < .01). Contralateral teeth assessed using Group 3 at 0.91ε showed statistical differences between each other (P < .05). No statistical difference was observed between contralateral teeth assessed using Groups 1 and 2 at 0.96ε and 0.98ε (P > .05)., Conclusions: The choice of cheek and lip retractor and emissivity setting can interfere on intraoral IT temperature values. U-type cheek and lip retractor and 0.91ε setting should not be used for IT image acquisition when assessing dental tissues., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology and the International Association of Dentomaxillofacial Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: We assessed and compared molecular tissue changes at the entheses in patients with psoriasis (PsO) and psoriatic arthritis (PsA) and in healthy controls (HCs) in vivo using multispectral optoacoustic tomography (MSOT) and described their relationship with clinical and ultrasound findings of enthesitis., Methods: A cross-sectional study (MSOT and Arthrosonography in PsA) in biologic disease-modifying antirheumatic drug-naïve patients with PsA and PsO and HCs was performed. Participants underwent clinical, ultrasonographic, and MSOT examination of six entheses (lateral humeral epicondyle, distal patellar tendon attachment, and Achilles tendon attachment). MSOT-measured hemoglobin (Hb), oxygen saturation (SO 2 ), collagen, and lipid levels were quantified, and mean differences between groups were calculated using linear mixed effects models. MSOT-measured analytes were compared between entheses with and without clinical and ultrasound anomalies., Results: Ninety participants were included (30 PsO, 30 PsA, and 30 HCs), 540 entheses were clinically assessed, and 540 ultrasound and 830 MSOT scans were obtained. Patients with PsA and PsO showed increased oxygenated Hb (PsA: P = 0.003; PsO: P = 0.054) and SO 2 (PsA: P < 0.001; PsO: P = 0.001) levels and decreased collagen signals (PsA: P < 0.001; PsO: P < 0.001) compared with HCs, with more pronounced changes in PsA. Significantly lower collagen levels (P = 0.01) and increased lipids (P = 0.03) were recorded in tender entheses compared with nontender ones. Erosions and enthesophytes on ultrasound were associated with significant differences in SO 2 (P = 0.014) and lipid signals (P = 0.020), respectively., Conclusion: Patients with PsA and PsO exhibit an analogous metabolic pattern at the entheses that is exacerbated in the presence of inflammation. These findings support the notion of a psoriatic disease spectrum characterized by common immunometabolic tissue changes., (© 2024 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

The management of prosthetic joint infections is a complex and multilayered process that is additionally complicated by the formation of bacterial biofilm. Foreign material provides the ideal grounds for the development of an intricate matrix that hinders treatment and creates a difficult environment for antibiotics to act. Surgical intervention is often warranted but requires appropriate adjunctive therapy. Despite available guidelines, several aspects of antibiotic therapy with antibiofilm activity lack clear definition. Given the escalating challenges posed by antimicrobial resistance, extended treatment durations, and tolerance issues, it is essential to ensure that antimicrobials with antibiofilm activity are both potent and diverse. Evidence of biofilm-active drugs is highlighted, and alternatives to classical regimens are further discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ferreira, Pos, Nogueira, Ferreira, Sousa and Abreu.)

The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) is the standard-of-care for estrogen receptor (ER)-positive, HER2-negative (ER+/HER2- advanced/metastatic breast cancer (mBC). However, the impact of CDK4/6i on circulating immune cells and circulating tumor cells (CTCs) in patients receiving CDK4/6i and ET (CDK4/6i+ET) remains poorly understood. This was a prospective cohort study including 44 patients with ER+/HER2- mBC treated with CDK4/6i+ET in either first or second line. Peripheral blood samples were collected before (baseline) and 3 months (t2) after therapy. Immune cell's subsets were quantified by flow cytometry, and microfluidic-captured CTCs were counted and classified according to the expression of cytokeratin and/or vimentin. Patients were categorized according to response as responders (progression-free survival [PFS] ≥ 6.0 months; 79.1%) and non-responders (PFS < 6.0 months; 20.9%). CDK4/6i+ET resulted in significant changes in the hematological parameters, including decreased hemoglobin levels and increased mean corpuscular volume, as well as reductions in neutrophil, eosinophil, and basophil counts. Specific immune cell subsets, such as early-stage myeloid-derived suppressor cells, central memory CD4+ T cells, and Vδ2+ T cells expressing NKG2D, decreased 3 months after CDK4/6i+ET. Additionally, correlations between the presence of CTCs and immune cell populations were observed, highlighting the interplay between immune dysfunction and tumor dissemination. This study provides insights into the immunomodulatory effects of CDK4/6i+ET, underscoring the importance of considering immune dynamics in the management of ER+/HER2- mBC.

Neoadjuvant pembrolizumab plus chemotherapy (P + CT) has emerged as a standard of care for stage II-III triple-negative breast cancer (TNBC). However, the best anthracycline-cyclophosphamide (AC) schedule remains to be determined. While the KEYNOTE-522 regimen employs AC every 3 weeks (q3w AC), previous studies have shown overall survival benefits of dose-dense regimens for early-stage breast cancer. The Neo-Real study (GBECAM-0123) is a real-world data effort evaluating patients with TNBC treated with neoadjuvant P + CT in ten cancer centers since July 2020. The objective of this analysis was to evaluate the effectiveness and safety of dose-dense AC (ddAC) versus q3w AC. Among 333 patients included until November 2023, 311 completed neoadjuvant therapy and 279 underwent surgery with pathology reports available; ddAC was used in 58.2% and q3w AC in 41.8% of the cases. Most patients (69.1%) had stage II TNBC. A pCR was observed in 65.4% with ddAC and 58.7% with q3w AC (P = 0.260), while RCB 0-1 occurred in 82.4% and 73.5%, respectively (P = 0.115). Patients with stage III disease had a numerically higher pCR with ddAC (59% vs 40%, P = 0.155), while pCR rates were similar regardless of AC regimen in stage II disease (66.6% vs 64.5%; P = 0.760). While no significant disparities in drug discontinuation was noted, ddAC showed a trend towards higher rates of grade ≥3 AE (40.5% vs. 30.7%, P = 0.092). The Neo-Real study could not rule out a difference between ddAC and q3w AC during neoadjuvant P + CT. The observation of a potentially higher pCR with ddAC in stage III disease warrants further investigation., (© 2024. The Author(s).)

Background: An assessment program should be inclusive and ensure that the various components of medical knowledge, clinical skills, and professionalism are assessed. The level and the variation over time in the strength of the correlation between these components of assessment is still a matter of study. Based on the meaningful learning theory and the integrated learning theory, we hypothesize that these components increase their connections during the medical school course., Methods: This is a retrospective cohort study that analyzed data collected for a 10-year period in one medical school. We included students from the 3rd to 6th year of medical school from 2011 to 2021. Three assessment components were addressed: Knowledge, Clinical Skills, and Professionalism. For data analysis, Pearson correlation coefficients (R) and R 2 were calculated to study the correlation between variables and a z-test on Fisher's r-to-z was used to determine the differences between correlation coefficients., Results: 949 medical students were included in the study. The correlation between Clinical Skills and Professionalism showed a medium to strong association (Pearson's R ranging from 0.485 to 0.734), while the correlation between Knowledge and Professionalism was weaker but exhibited a steady evolution with Pearson's R fluctuating between 0.075 and 0.218. The Knowledge and Clinical Skills correlation became statistically significant from 2013 onwards and peaking at Pearson's R of 0.440 for the cohort spanning 2016-2019. We also revealed a strengthening of correlations between Professionalism and Clinical Skills from the beginning to the end of clinical training, but not with the knowledge component., Conclusions: This analysis contributes to our understanding of the dynamics of correlations of different assessment components within an institution and provides a framework for how they interact and influence each other., Trial Registration: This study was not a clinical trial, but a retrospective observational study, without health care interventions. Nevertheless, we provide herein the number of the study as submitted to the Ethics committee - CEICVS 146/2021., (© 2024. The Author(s).)

The food enzyme β -galactosidase ( β -d-galactoside galactohydrolase; EC 3.2.1.23) is produced with the genetically modified Bacillus licheniformis strain DSM 34099 by Kerry Group Services International, Ltd. (KGSI). The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and its DNA. The production strain met the requirements for the qualified presumption of safety (QPS) approach. The food enzyme is intended to be used in two food manufacturing processes. Dietary exposure was estimated to be up to 7.263 mg total organic solids/kg body weight per day in European populations. Given the QPS status of the production strain and the absence of concerns resulting from the food enzyme manufacturing process, toxicity tests, other than an assessment of allergenicity, were considered unnecessary by the Panel. A search for the identity of the amino acid sequence of the food enzyme to known allergens was made and one match with a food allergen from kiwi fruit was found. The Panel considered that a risk of allergic reactions upon dietary exposure to this food enzyme, particularly in individuals sensitised to kiwi fruit, cannot be excluded. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

The food enzyme triacylglycerol lipase (triacylglycerol acylhydrolase; EC 3.1.1.3) is produced with the non-genetically modified Rhizopus arrhizu s strain AE-TL(B) by Amano Enzyme Inc. A safety evaluation of this food enzyme was made previously, in which EFSA concluded that this food enzyme did not give rise to safety concerns when used in two food manufacturing processes. Subsequently, the applicant requested to extend its use to include four additional processes and to revise the use levels. In this assessment, EFSA updated the safety evaluation of this food enzyme when used in a total of six food manufacturing processes. As the food enzyme-total organic solids (TOS) are removed from one food manufacturing process, the dietary exposure to the food enzyme-TOS was estimated only for the remaining five processes. Dietary exposure was calculated to be up to 0.086 mg TOS/kg body weight (bw) per day in European populations. When combined with the no observed adverse effect level reported in the previous opinion (1960 mg TOS/kg bw per day, the highest dose tested), the Panel derived a margin of exposure of at least 22,791. Based on the data provided for the previous evaluation and the revised margin of exposure in the present evaluation, the Panel concluded that this food enzyme does not give rise to safety concerns under the revised intended conditions of use., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Despite the high prevalence of TP53 pathogenic variants (PV) carriers in the South and Southeast regions of Brazil, germline genetic testing for hereditary breast cancer (HBC) is not available in the Brazilian public health system, and the prevalence of Li-Fraumeni syndrome (LFS) is not well established in other regions of Brazil. We assessed the occurrence of TP53 p.R337H carriers among women treated for breast cancer (BC) between January 2021 and January 2022 at public hospitals of Brasilia, DF, Brazil. A total of 180 patients who met at least one of the NCCN criteria for HBC underwent germline testing; 44.4% performed out-of-pocket germline multigene panel testing, and 55.6% were tested for the p.R337H variant by allelic discrimination PCR. The median age at BC diagnosis was 43.5 years, 93% had invasive ductal carcinoma, 50% had estrogen receptor-positive/HER2 negative tumors, and 41% and 11% were diagnosed respectively at stage III and IV. Two patients (1.11%) harbored the p.R337H variant, and cascade family testing identified 20 additional carriers. The TP53 p.R337H detection rate was lower than that reported in other studies from south/southeast Brazil. Nonetheless, identifying TP53 PV carriers through genetic testing in the Brazilian public health system could guide cancer treatment and prevention.

Background: Breastfeeding has been associated with maternal and infant health benefits but has been inversely associated with body mass index (BMI) prepartum. Breastfeeding and BMI are both linked to socioeconomic factors., Methods: Data from parous female participants with available breastfeeding information from the Million Veteran Program cohort was included. BMI at enrollment and earliest BMI available were extracted, and polygenic scores (PGS) for BMI were calculated. We modeled breastfeeding for one month or more as a function of BMI at enrollment; earliest BMI where available pre-pregnancy; and PGS for BMI. We conducted Mendelian randomization for breastfeeding initiation using PGS as an instrumental variable., Results: A higher BMI predicted a lower likelihood of breastfeeding for one month or more in all analyses. A +5 kg/m 2 BMI pre-pregnancy was associated with a 24% reduced odds of breastfeeding, and a +5 kg/m 2 genetically predicted BMI was associated with a 17% reduced odds of breastfeeding., Conclusions: BMI predicts a lower likelihood of breastfeeding for one month or longer. Given the high success of breastfeeding initiation regardless of BMI in supportive environments as well as potential health benefits, patients with elevated BMI may benefit from additional postpartum breastfeeding support.

Background: This study delves into the States' accountability for health-related Sustainable Development Goal (SDG) indicators from 2016 to 2020. An analysis of Voluntary National Reviews (VNR) is employed as an instrument to scrutinize the alignment of States' indicators with the global indicator framework, shedding light on global health governance within the context of the 2030 Agenda and States' strategic prioritization. A curation of 60 health-related indicators from 195 VNRs, produced during the aforementioned period, is organized into thematic groups., Results: Our results highlight a concerning discrepancy in the reporting frequency of various health-related themes. The findings reveal a paradoxical coexistence characterized by the concurrent strengthening and diminution of the global health governance articulated in the Agenda's global health governance. This manifests in the increased utilization and consistency of health-related indicators over the study years, coupled with an emphasis on infectious diseases and child and maternal health indicators. Conversely, a discernible governance decline is evidenced by the inadequate representation of health-related indicators in VNRs, notably within the domains of universal health coverage and health system indicators. Furthermore, High-Income States exhibit diminished accountability., Conclusions: The VNRs unveil a paradox wherein burgeoning technical capacity coexists with governance deficits, a phenomenon attributable to both statistical capabilities and political preferences. The prevalent use of proxy indicators in VNRs oversimplifies the presentation of official indicators, thereby compromising the aspirational goal of pioneering statistical innovations for measuring intricate issues in the SDGs. In light of our conceptualization of the 2030 Agenda's global health as a regime complex governance, we advocate for comprehensive investigations into each health regime cluster. This approach aims to unravel disputes, discern patterns, and elucidate States' preferences concerning specific thematic areas. Functioning as an accountability mechanism for the Agenda's governance, VNRs underscore States' adaptability and short-term learning capabilities, offering valuable insights for identifying harmful goal prioritization. The discretionary nature of indicator selection by States in the VNRs, enabled by the Agenda's proposition of a contextual adaptation of the SDGs and a blind eye to the guideline's request to review all SDG indicators, highlights a critical flaw in the VNR as an accountability mechanism., (© 2024. The Author(s).)

Objectives: To assess the presence and anatomical distribution of activated fibroblasts in the joints and entheses of patients with psoriasis with arthralgia and to test how fibroblast activation visualised by 68 gallium-labelled fibroblast activation protein inhibitor-04 ( 68 Ga-FAPI-04)-positron emission tomography (PET)/CT correlates with clinical tenderness, musculoskeletal ultrasound findings and progression to psoriatic arthritis (PsA)., Methods: We conducted a prospective cohort study in patients with psoriasis and arthralgia who underwent clinical and ultrasound evaluation and whole-body PET/CT imaging with 68 Ga-FAPI-04. 68 Ga-FAPI-04 uptake at synovial and entheseal sites was assessed by maximal standardised uptake values (SUVmax) and PET/CT Joint Index (JI); logistic regression models were used to investigate its correlation with clinical and ultrasound findings. Survival analyses were performed on patients with at least 6 months of follow-up., Results: 36 patients with psoriasis were enrolled. 68 Ga-FAPI-04 uptake was found in 318 (7.9%) joints and 369 (7.3%) entheses in 29 (80.6%) participants, with a mean SUVmax (SD) of 3.2 (1.8) for joints and 2.9 (1.6) for entheses. Large joints and the lower limbs were predominantly affected. A significant positive relationship was found between 68 Ga-FAPI-04-PET/CT signal intensity and the 68 tender joint count (SUVmax: p<0.001; PET/CT-JI: p<0.001) and tender entheses count (SUVmax: p<0.001; PET/CT-JI: p=0.002). No correlations were found with ultrasound findings (SUVmax: p=0.969; PET/CT-JI: p=0.720). Patients with relevant synovio-entheseal 68 Ga-FAPI-04 uptake showed a statistically significant higher risk of developing PsA (p=0.02), independent of ultrasound findings., Conclusions: Patients with psoriasis presenting with arthralgia show localised signs of resident tissue activation in joints and entheses, which are associated with higher risk of developing PsA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The betta (Betta splendens) is a carnivorous ornamental species that requires live food. In this study, we evaluated the growth and survival of Betta splendens fingerlings fed ex-situ biofloc (BFT). A total of 375 fingerlings (8.3 ± 4.1 mg and 0.8 ± 0.14 cm) were distributed into 15-L plastic tanks (n=25), with five replicates for each of the following treatments: (i) exclusive live food (LF100), (ii) exclusive biofloc (BFT100), (iii) live food supplemented with biofloc (LF100-BFT100), and a reduction of 15% (iv) and 30% (v) in live food with biofloc supplementation (LF85-BFT100 and LF70-BFT100, respectively). The fish were fed newly hatched brine shrimp (Artemia spp. nauplii) and/or fresh biofloc, twice daily, over a 16-day experimental period. Dietary supplementation of Beta splendens with ex-situ BFT (LF100-BFT100, LF85-BFT100, and LF70-BFT100) resulted in a similar final weight (P>0.05) compared to exclusive brine shrimp (LF100). Regarding total length, the fish in the LF100-BFT100 group were superior to those in the LF100 group (P<0.05). The LF100 and LF100-BFT100 groups showed survival rates of 100% and 98.4%, respectively, which were not statistically different (P>0.05). For all analyzed variables, fish exclusively fed biofloc (BFT100) exhibited unfavorable performance. These results indicate that dietary ex-situ biofloc supplementation, without reducing the supply of live food, can be an interesting alternative in the rearing of Betta splendens since biofloc improves growth performance and maintains a good survival rate.

Freshwater mussels (Bivalvia, Unionida) play essential roles in the well-functioning of ecosystems, even providing essential services to humans. However, these bivalves face numerous threats (e.g. habitat loss and fragmentation, pollution, introduction of invasive species, and climate change) which have already led to the extinction of many populations. This underscores the need to fully characterize the biology of these species, particularly those, such as Potomida acarnanica , that are still poorly studied. This study presents the first mitogenome of P. acarnanica (Kobelt, 1879), an endemic species of Greece with a distribution limited to only two river basins. The mitochondrial genome of a P. acarnanica specimen, collected at Pamisos River (Peloponnese, Greece), was sequenced by Illumina high-throughput sequencing. This mitogenome (16,101 bp) is characterized by 13 protein-coding genes, 22 transfer RNA and 2 ribosomal RNA genes. The size of this mitogenome is within the range of another Potomida mitogenome already published for the species Potomida littoralis . In the phylogenetic inference, P. acarnanica was recovered as monophyletic with P. littoralis mitogenome in the Lamprotulini tribe, as expected. This genomic resource will assist in genetically characterizing the species, potentially benefiting future evolutionary studies and conservation efforts., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Endolysosomes perform a wide range of cellular functions, including nutrient sensing, macromolecule digestion and recycling, as well as plasma membrane repair. Because of their high activity in cancerous cells, endolysosomes are attractive targets for the development of novel cancer treatments. Light-activated compounds termed photosensitizers (PS) can catalyze the oxidation of specific biomolecules and intracellular organelles. To selectively damage endosomes and lysosomes, HT-29 colorectal cancer cells were incubated with nanomolar concentrations of meso-tetraphenylporphine disulfonate (TPPS 2a ), an amphiphilic PS taken up via endocytosis and activated by green light (522 nm, 2.1 J.cm -1 ). Several cellular responses were characterized by a combination of immunofluorescence and immunoblotting assays. We showed that TPPS 2a photosensitization blocked autophagic flux without extensive endolysosomal membrane rupture. Nevertheless, there was a severe functional failure of endolysosomes due to a decrease in CTSD (cathepsin D, 55%) and CTSB (cathepsin B, 52%) maturation. PSAP (prosaposin) processing (into saposins) was also considerably impaired, a fact that could be detrimental to glycosphingolipid homeostasis. Therefore, photosensitization of HT-29 cells previously incubated with a low concentration of TPPS 2a promotes endolysosomal dysfunction, an effect that can be used to improve cancer therapies., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The global decline of freshwater mussels and their crucial ecological services highlight the need to understand their phylogeny, phylogeography and patterns of genetic diversity to guide conservation efforts. Such knowledge is urgently needed for Unio crassus, a highly imperilled species originally widespread throughout Europe and southwest Asia. Recent studies have resurrected several species from synonymy based on mitochondrial data, revealing U. crassus to be a complex of cryptic species. To address long-standing taxonomic uncertainties hindering effective conservation, we integrate morphometric, phylogenetic, and phylogeographic analyses to examine species diversity within the U. crassus complex across its entire range. Phylogenetic analyses were performed using cytochrome c oxidase subunit I (815 specimens from 182 populations) and, for selected specimens, whole mitogenome sequences and Anchored Hybrid Enrichment (AHE) data on ∼ 600 nuclear loci. Mito-nuclear discordance was detected, consistent with mitochondrial DNA gene flow between some species during the Pliocene and Pleistocene. Fossil-calibrated phylogenies based on AHE data support a Mediterranean origin for the U. crassus complex in the Early Miocene. The results of our integrative approach support 12 species in the group: the previously recognised Unio bruguierianus, Unio carneus, Unio crassus, Unio damascensis, Unio ionicus, Unio sesirmensis, and Unio tumidiformis, and the reinstatement of five nominal taxa: Unio desectusstat. rev., Unio gontieriistat. rev., Unio mardinensisstat. rev., Unio nanusstat. rev., and Unio vicariusstat. rev. Morphometric analyses of shell contours reveal important morphospace overlaps among these species, highlighting cryptic, but geographically structured, diversity. The distribution, taxonomy, phylogeography, and conservation of each species are succinctly described., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In this pilot study, we aimed to evaluate the feasibility of whole genome sequencing (WGS) as a first-tier diagnostic test for infants hospitalized in neonatal intensive care units in the Brazilian healthcare system. The cohort presented here results from a joint collaboration between private and public hospitals in Brazil considering the initiative of a clinical laboratory to provide timely diagnosis for critically ill infants. We performed trio (proband and parents) WGS in 21 infants suspected of a genetic disease with an urgent need for diagnosis to guide medical care. Overall, the primary indication for genetic testing was dysmorphic syndromes (n = 14, 67%) followed by inborn errors of metabolism (n = 6, 29%) and skeletal dysplasias (n = 1, 5%). The diagnostic yield in our cohort was 57% (12/21) based on cases that received a definitive or likely definitive diagnostic result from WGS analysis. A total of 16 pathogenic/likely pathogenic variants and 10 variants of unknown significance were detected, and in most cases inherited from an unaffected parent. In addition, the reported variants were of different types, but mainly missense (58%) and associated with autosomal diseases (19/26); only three were associated with X-linked diseases, detected in hemizygosity in the proband an inherited from an unaffected mother. Notably, we identified 10 novel variants, absent from public genomic databases, in our cohort. Considering the entire diagnostic process, the average turnaround time from enrollment to medical report in our study was 53 days. Our findings demonstrate the remarkable utility of WGS as a diagnostic tool, elevating the potential of transformative impact since it outperforms conventional genetic tests. Here, we address the main challenges associated with implementing WGS in the medical care system in Brazil, as well as discuss the potential benefits and limitations of WGS as a diagnostic tool in the neonatal care setting., (© 2024 Wiley Periodicals LLC.)

Introduction: Cerebral venous thrombosis (CVT) is a rare but potentially fatal disease in pediatric age with an important morbimortality. In adults several factors have been associated with worse outcomes, however there are still few studies in children. This study aims to identify risk factors associated with clinical manifestations and long-term sequelae in pediatric CVT., Methods: Retrospective analysis of pediatric inpatients admitted to a tertiary-care hospital due to CVT between 2008 and 2020., Results: Fifty-four children were included, 56% male, median age of 6.5 years (9 months-17.3 years). Permanent risk factors were identified in 13 patients (malignancy, 8; hematologic condition, 5) and transient risk factors in 47, including head and neck infections (57%) and head trauma (15%). Multiple venous sinuses involvement was present in 65% and the deep venous system was affected in four patients. Seventeen percent had intracranial hemorrhage and 9% cerebral infarction. Sixty-four percent of patients with multiple venous sinuses involvement presented with severe clinical manifestations: impaired consciousness, intracranial hypertension, acute symptomatic seizures or focal deficits. Regarding long-term prognosis, six patients had major sequelae: epilepsy ( n  = 3), sensory motor deficits ( n  = 2), and cognitive impairment ( n  = 3). Permanent risk factors were associated with severe clinical manifestations ( p  = 0.043). Cerebral infarction and intracranial hemorrhage were associated with major sequelae ( p  = 0.006 and p  = 0.03, respectively, adjusted for age and sex)., Conclusion: Permanent risk factors, involvement of multiple venous sinuses, intracranial hemorrhage, and cerebral infarction, were related to worse prognosis. Detection and early management of risk factors may limit CVT extension and reduce its morbimortality., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: Status epilepticus is an important cause of pediatric neurological emergency. Immediate treatment is essential to prevent definitive neurological damage. Several antiepileptic drugs are available for the management of status epilepticus., Methods: Retrospective study of patients admitted at the emergency department of a tertiary hospital for 5 years (2014-2019). We analyzed the compliance to the treatment guidelines for pediatric status epilepticus., Results: One hundred and seventeen admissions were identified, 23.9% of these were febrile status epilepticus. Among the other cases, the most frequent cause was genetic (22.2%). The majority were convulsive status epilepticus (93.1%), 58.7% of which were generalized tonic-clonic seizures. Benzodiazepines were the most used first and second line drug (98.2% and 94.8%). The most frequent third drug used was diazepam (56.4%) followed by phenytoin (18.2%). An infra-therapeutic antiepileptic drug dose was given in 48.7% of cases. 49.6% presented with a prolonged status epilepticus and 6.8% needed intensive care. Incorrect sequence of drugs and infra-therapeutic doses were associated with prolonged status (p<0.001 and p<0.05) and an increased number of antiepileptic drugs used (p<0.001 and p<0.05)., Conclusions: Benzodiazepines were the most frequently first and second line drugs used for status epilepticus management. Surprisingly, the most frequently third line drugs used were also benzodiazepines. These findings were partially explained by the misuse of infra-therapeutic doses of these drugs. Noncompliance with the implemented guidelines was associated with unfavorable outcomes., (Copyright © 2021 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Predation is a dominant structuring force in ecological communities. In aquatic environments, predation on bivalves has long been an important focal interaction for ecological study because bivalves have central roles as ecosystem engineers, basal components of food webs, and commercial commodities. Studies of bivalves are common, not only because of bivalves' central roles, but also due to the relative ease of studying predatory effects on this taxonomic group. To understand patterns in the interactions of bivalves and their predators we synthesised data from 52 years of peer-reviewed studies on bivalve predation. Using a systematic search, we compiled 1334 studies from 75 countries, comprising 61 bivalve families (N = 2259), dominated by Mytilidae (29% of bivalves), Veneridae (14%), Ostreidae (8%), Unionidae (7%), and Dreissenidae and Tellinidae (6% each). A total of 2036 predators were studied, with crustaceans the most studied predator group (34% of predators), followed by fishes (24%), molluscs (17%), echinoderms (10%) and birds (6%). The majority of studies (86%) were conducted in marine systems, in part driven by the high commercial value of marine bivalves. Studies in freshwater ecosystems were dominated by non-native bivalves and non-native predator species, which probably reflects the important role of biological invasions affecting freshwater biodiversity. In fact, while 81% of the studied marine bivalve species were native, only 50% of the freshwater species were native to the system. In terms of approach, most studies used predation trials, visual analysis of digested contents and exclusion experiments to assess the effects of predation. These studies reflect that many factors influence bivalve predation depending on the species studied, including (i) species traits (e.g. behaviour, morphology, defence mechanisms), (ii) other biotic interactions (e.g. presence of competitors, parasites or diseases), and (iii) environmental context (e.g. temperature, current velocity, beach exposure, habitat complexity). There is a lack of research on the effects of bivalve predation at the population and community and ecosystem levels (only 7% and 0.5% of studies respectively examined impacts at these levels). At the population level, the available studies demonstrate that predation can decrease bivalve density through consumption or the reduction of recruitment. At the community and ecosystem level, predation can trigger effects that cascade through trophic levels or effects that alter the ecological functions bivalves perform. Given the conservation and commercial importance of many bivalve species, studies of predation should be pursued in the context of global change, particularly climate change, acidification and biological invasions., (© 2024 Cambridge Philosophical Society.)

Introduction: The onset of the COVID-19 pandemic brought about global uncertainties and fears, escalating the dissemination of fake news. This study aims to analyze the impact of fake news on COVID-19 vaccine adherence among pregnant women, providing crucial insights for effective communication strategies during the pandemic., Methods: A cross-sectional, exploratory study was conducted with 113 pregnant women under care at a Women's Health Reference Center. Data analysis included relative frequency and odds ratio to assess the relationship between sociodemographic and behavioral variables regarding vaccination., Results: In the behavioral context of vaccination, internet access shows a significant association with decision-making, influencing vaccine refusal due to online information. Nuances in the odds ratios results highlight the complexity of vaccine hesitancy, emphasizing the importance of information quality. Pre-vaccination sentiments include stress (87.61%), fear (50.44%), and anxiety (40.7%), indicating the need for sensitive communication strategies., Discussion: Results revealed that pregnant women with higher education tend to adhere more to vaccination. Exposure to news about vaccine inefficacy had a subtle association with hesitancy, while finding secure sources was negatively associated with hesitancy. The behavioral complexity in the relationship between online information access and vaccination decision underscores the need for effective communication strategies., Conclusions: In the face of this challenging scenario, proactive strategies, such as developing specific campaigns for pregnant women, are essential. These should provide clear information, debunk myths, and address doubts. A user-centered approach, understanding their needs, is crucial. Furthermore, ensuring information quality and promoting secure sources are fundamental measures to strengthen trust in vaccination and enhance long-term public health.