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Prey often rely on multiple defences against predators, such as flight speed, attack deflection from vital body parts, or unpleasant taste, but our understanding on how often and why they are co-exhibited remains limited. Eudaminae skipper butterflies use fast flight and mechanical defences (hindwing tails), but whether they use other defences like unpalatability (consumption deterrence) and how these defences interact have not been assessed. We tested the palatability of 12 abundant Eudaminae species in Peru, using training and feeding experiments with domestic chicks. Further, we approximated the difficulty of capture based on flight speed and quantified it by wing loading. We performed phylogenetic regressions to find any association between multiple defences, body size, and habitat preference. We found a broad range of palatability in Eudaminae, within and among species. Contrary to current understanding, palatability was negatively correlated with wing loading, suggesting that faster butterflies tend to have lower palatability. The relative length of hindwing tails did not explain the level of butterfly palatability, showing that attack deflection and consumption deterrence are not mutually exclusive. Habitat preference (open or forested environments) did not explain the level of palatability either, although butterflies with high wing loading tended to occupy semi-closed or closed habitats. Finally, the level of unpalatability in Eudaminae is size dependent. Larger butterflies are less palatable, perhaps because of higher detectability/preference by predators. Altogether, our findings shed light on the contexts favouring the prevalence of single versus multiple defensive strategies in prey., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Evolutionary Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The esbarrada and volta sobre patas manoeuvres are critical in Criollo horse equestrian activities, yet their kinematics remain largely unexplored. This observational study aimed to kinematically describe the manoeuvres in Criollo breed horses and explore the relationship between static goniometry and dynamics. A 2D kinematic analysis was conducted on 31 Criollo horses performing the manoeuvres using high-speed cameras. Joint angles were measured using static goniometry and analysed in relation to dynamic performance. The esbarrada covered a distance of 4.28 ± 0.99 m in 1.15 ± 0.11 s at a velocity of 3.77 ± 0.55 m/s. Joint angles showed a mean fetlock extension of 75.4° ± 5.3° and hock flexion of 43.2° ± 4.1°. In the volta sobre patas , significant differences were found in turn duration (first: 0.96 ± 0.07 s, second: 1.12 ± 0.09 s, p = 0.03) and thoracic limb suspension (first: 0.23 ± 0.02 s, second: 0.28 ± 0.03 s, p = 0.02). Static goniometry indicated that limb conformation did not significantly correlate with protraction angles during the esbarrada ( p = 0.27). The volta sobre patas demonstrated prolonged duration and increased thoracic limb suspension in the second turn. Also, the findings suggest that static conformation does not predict dynamic limb movement during the esbarrada .

Introduction: The scientific community highlighted the relevance of 3D physical models since the beginning of the XXI century, complementary to three-dimensional(3D) digital volume by computer tomography, to support court discussions on medico-legal issues. The recreation of 3D evidence can be an important tool for investigators and experts, providing a better understanding of the causes and circumstances of the events involved in a crime., Objective: The present study aims to assess the reproducibility of 3D printed and 3D tomographic volumes generated from mandibles following simulated forensic injuries, highlighting the recreation of crime tools., Material and Methods: Concerning the study design presented, data collection was performed in three phases. Nine simulated injuries of forensic interest were selected (phase1) and all the mandibles were scanned tomographically, individually, by Cone Beam Computed Tomography CBCT (phase 2). Then, in phase 3, the DICOM images were used for 3D printing with the Ender 3® printer by the Fused Deposition Modeling (FDM) technique. The data analysis followed two procedures: the comparison between the artificial mandible and 3D tomographic volume (AT) and the comparison between the artificial mandible and 3D printed volume, or the copy (AC). Data were analyzed using T-Student and ICC tests and presented in Bland-Altman plots., Conclusion: The analogic technique applied in 3D printed volume, when compared with computerized technique, using 3D digital images and measurement, showed to be accurate and reproducible. Further studies are needed in search of standardization for three-dimensional measurements in digitized and printed volumes., (Copyright © 2024. Published by Elsevier Ltd.)

Therapeutics for suicide management is limited, taking weeks to work. This open-label clinical trial with 18 treatment-resistant depressive patients tested subcutaneous esketamine (8 weekly sessions) for suicidality. We noted a rapid and enduring effect of subcutaneous esketamine, lasting from one week to six months post-treatment, assessed by the Beck Inventory for Suicidality (BSI). There was an immediate drop in suicidality, 24 h following the initial dose, which persisted for seven days throughout the eight-week dosing period. Additionally, this study is the first to examine a six-month follow-up after multiple administrations of subcutaneous esketamine, finding consistently lower levels of suicidality throughout this duration. Conversely, suicidality also was measured along the 8-weeks of treatment by a psychiatrist using the Montgomery-Asberg Depression Rating Scale (MADRS), which showed significant reduction only after two treatment sessions expanding until the last session. Moreover, notably, 61% of patients achieved remission on suicidality (MADRS). These results suggest that weekly subcutaneous esketamine injections offer a cost-effective approach that induces a rapid and sustained response to anti-suicide treatment. This sets the stage for further, more controlled studies to corroborate our initial observations regarding the effects of SC esketamine on suicidality. Registered trial at: https://ensaiosclinicos.gov.br/rg/RBR-1072m6nv., Competing Interests: Declaration of competing interest The author(s) have no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Colorectal cancer (CRC) is the third most common cancer worldwide. In the United States alone, CRC was responsible for approximately 52,550 deaths in 2023, with an estimated 153,020 new cases. CRC presents with synchronous peritoneal spread in 5-10% of patients, and up to 20-50% of patients with recurrent disease will develop metachronous colorectal cancer peritoneal metastatic (CRC-PM) disease. Eradication of the tumor, tumor margins and microscopic residual disease is paramount, as microscopic residual disease is associated with local recurrences, with 5-year survival rates of less than 35%. The success of resection and reduction of residual disease depends on the accuracy with which cancer cells and normal tissue can be intra-operatively distinguished. Fluorescence Molecular Imaging (IFMI) and tumor-targeted contrast agents represent a promising approach for intraoperative detection and surgical intervention. Proper target selection, the development of scalable imaging agents and enhanced real-time tumor and tumor microenvironment imaging are critical to enabling enhanced surgical resection. LGR5 (leucine-rich repeat-containing G-protein-coupled receptor 5), a colonic crypt stem cell marker and the receptor for the R-spondins (RSPO) in the Wnt signaling pathway, is also expressed on colorectal cancer stem cells (CSC) and on CRC tumors and metastases, suggesting it could be a useful target for imaging of CRC. However, there are numerous diverging reports on the role of LGR5 in CRC therapy and outcomes. Herein, we report on the synthesis and validation of a 37 amino acid RSPO1-mimetic peptide, termed RC18, that was specifically designed to access the R-spondin binding site of LGR5 to potentially be used for interoperative imaging of CRC-PM. The receptor-binding capabilities of the RC18 indicate that direct interactions with LGR5 neither significantly increased LGR5 signaling nor blocked RSPO1 binding and signal transduction, suggesting that the RSPO1-mimetic is functionally inert, making it an attractive contrast agent for intraoperative CRC-PM imaging.

Aim: This preliminary study investigated the differences in event-related potential and reaction time under two groups (athletes vs. non-athletes)., Material and Methods: The P300 was analyzed for Fz, Cz, and Pz electrodes in thirty-one healthy volunteers divided into two groups (volleyball athletes and non-athletes). In addition, the participants performed a saccadic eye movement task to measure reaction time., Results: The EEG analysis showed that the athletes, in comparison to the no-athletes, have differences in the P300 in the frontal area (p = 0.021). In relation to reaction time, the results show lower reaction time for athletes (p = 0.001)., Conclusions: The volleyball athletes may present a greater allocation of attention during the execution of the inhibition task, since they have a lower reaction time for responses when compared to non-athletes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Costa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Antimicrobial films were prepared with chitosan containing the methanolic extract of M. tenuiflora leaves (FECT20%, FECT30%, and FECT40%), and their antimicrobial activities were evaluated by agar diffusion. The films were characterized by IR spectroscopy, scanning electron microscopy (SEM) and TG/DTG curves. TG/DTG curves showed thermal stability of chitosan-extract films up to 166 ºC. Micrographs of chitosan-extract films revealed an increase in porosity with the addition of extract. The FECT40% film showed inhibition zone diameters (IZ) against Micrococcus luteus, Staphylococcus aureus, Bacillus subtilis, and B. cereus, ranging from 1.0 ± 0.02 to 0.72 ± 0.09 cm. Only FECT30% and FECT40% inhibited the P. aeruginosa with IZs of 0.68 ± 0.02 and 0.77 ± 0.06 cm, respectively. In turn, the extract showed inhibition against B. subtilis and B. cereus, with IZs values of 0.92 ± 0.2 cm and 0.72 ± 0.05 cm, respectively. Additionally, the crude extract presented antioxidant potential with inhibition percentages of 32.74% ± 0.90 for ABTS and 27.04% ± 1.36 for DPPH. The antimicrobial and antioxidant activities of the crude extract, as well as the antimicrobial property of chitosan-extract films, suggests the potential of these biopolymers for the development of wound healing bandages and new food packaging alternatives., (© 2024 Wiley‐VCH GmbH.)

We experimentally demonstrate resonance of first-order vector vortex beams (VVB) with a triangular optical cavity. We also show that, due to their symmetry properties, the VVBs commonly known as radial and azimuthal beams do not resonate at the same cavity length, which could be explored to use the triangular resonator as a mode sorter. In addition, an intracavity Pancharatnam phase shifter (PPS) is implemented in order to compensate for any birefringent phase that the cavity mirrors may introduce., (© 2024. The Author(s).)

Gender dysphoria is socially more visible and discussed today, but still underdiagnosed. It refers to distress and/or impaired function caused by inconsistency between the sex assigned at birth and gender identification. Clinical manifestations are variable. Lack of training and investment in gender issues make the diagnosis and management in primary care complex, particularly in conservative and isolated communities, with poor access to information and specialized health services. We describe the diagnosis of gender dysphoria and use of a patient centered multidisciplinary and family approach in a 12-year-old rural born adolescent, assigned female at birth. Our aim is to raise awareness of early symptoms and signs of gender dysphoria and problems faced by transgender people and their families during childhood, leading to gender dysphoria, and we hope our successful approach might improve healthcare provision for these patients, particularly in rural areas.

Camera traps became the main observational method of a myriad of species over large areas. Data sets from camera traps can be used to describe the patterns and monitor the occupancy, abundance, and richness of wildlife, essential information for conservation in times of rapid climate and land-cover changes. Habitat loss and poaching are responsible for historical population losses of mammals in the Atlantic Forest biodiversity hotspot, especially for medium to large-sized species. Here we present a data set from camera trap surveys of medium to large-sized native mammals (>1 kg) across the Atlantic Forest. We compiled data from 5380 ground-level camera trap deployments in 3046 locations, from 2004 to 2020, resulting in 43,068 records of 58 species. These data add to existing data sets of mammals in the Atlantic Forest by including dates of camera operation needed for analyses dealing with imperfect detection. We also included, when available, information on important predictors of detection, namely the camera brand and model, use of bait, and obstruction of camera viewshed that can be measured from example pictures at each camera location. Besides its application in studies on the patterns and mechanisms behind occupancy, relative abundance, richness, and detection, the data set presented here can be used to study species' daily activity patterns, activity levels, and spatiotemporal interactions between species. Moreover, data can be used combined with other data sources in the multiple and expanding uses of integrated population modeling. An R script is available to view summaries of the data set. We expect that this data set will be used to advance the knowledge of mammal assemblages and to inform evidence-based solutions for the conservation of the Atlantic Forest. The data are not copyright restricted; please cite this paper when using the data., (© 2024 The Ecological Society of America.)

This article describes a digital workflow for ceramic veneer preparation using computer-aided design and computer-aided manufacturing technology. A digital waxing was planned on the exocad software program to reestablish esthetic and functional parameters. Then, the digital guides for veneer preparation were designed by using the Meshmixer design software program to control the tooth structure removed during preparation to the minimal thickness necessary for the definitive restorations. The digital guides were printed in an additively manufactured clear resin and used in the preparation appointment, allowing a more conservative and controlled preparation., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is essential for the classification of pancreatic cystic lesions (PCLs). Recently, intracystic glucose has been suggested as an alternative to carcinoembryonic antigen (CEA) level as a predictor of mucinous cystic lesions (M-PCLs). This study aims to evaluate the diagnostic performance of intra-cystic glucose in distinguishing between M-PCLs and non M-PCLs (NM-PCLs) and to analyze the possibility of on-site glucose measurement with a standard glucometer., Methods: Patients with PCLs submitted to EUS-FNA with simultaneous intracystic glucose measurement between 2017 and 2022 were included. The diagnostic performance of glucose versus CEA for the differentiation between M-PCLs and NM-PCLs was compared to a final diagnosis based on the analysis of surgical specimen, intracystic biopsy or, if this data was unavailable, multidisciplinary evaluation. A cut-off of <50 mg/dL was used for the diagnosis of MCLs. Additionally, the agreement between on-site glucose determination with a standard glucometer and laboratory glucose measurement was assessed., Results: Mucinous lesions accounted for 56% of all PCLs. The median values of glucose and CEA for M-PCLs were 18 mg/dL and 286 ng/mL, respectively. Intracystic glucose had a sensitivity and specificity of 93.2% and 76.5%, respectively, for the diagnosis of MCLs (versus 55.6% and 87.5%, respectively, for CEA). The area under the curve was 0.870 for on-site glucose (versus 0.806 for CEA). An excellent correlation was observed between on-site and laboratory glucose measurement (ρ=0.919)., Conclusions: The measurement of intracystic glucose showed superior performance compared with CEA in distinguishing between M-PCLs and NM-PCLs, with excellent correlation between on-site and conventional lab glucose measurement. Thus, on-site intracystic glucose appears to be an excellent biomarker for the characterization of PCLs due to its low cost, high availability, and the need for a minimal cyst fluid volume for its determination.

Competing Interests: Competing interests: None declared.

Griffinia gardneriana Ravenna, Griffinia liboniana Morren and Griffinia nocturna Ravenna (Amarillydaceae) are bulbous plants found in tropical regions of Brazil. Our work aimed to determine the alkaloid profiles of Griffinia spp. and evaluate their anxiolytic potential through in vivo and in silico assays. The plants grown in greenhouses were dried and their ground bulbs were subjected to liquid-liquid partitions, resulting in alkaloid fractions that were analyzed by gas chromatography coupled to mass spectrometry (GC-MS). Anxiolytic activity was evaluated in zebrafish (Danio rerio) through intraperitoneal injection at doses of 40, 100 and 200 mg/kg in light-dark box test. GC-MS analyses revealed 23 alkaloids belonging to different skeleton types: lycorine, homolychorine, galanthamine, crinine, haemanthamine, montanine and narcisclasine. The chemical profiles were relatively similar, presenting 8 alkaloids common to the three species. The major component for G. gardneriana and G. liboniana was lycorine, while G. nocturna consisted mainly of anhydrolycorine. All three alkaloid fractions demonstrated anxiolytic effect. Furthermore, pre-treatment with diazepam and pizotifen drugs was able to reverse the anxiolytic action, indicating involving the GABAergic and serotonergic receptors. Molecular docking showed that the compounds vittatine, lycorine and 11,12-dehydro-2-methoxyassoanine had high affinity with both receptors, suggesting them to be responsible for the anxiolytic effect., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Background: cardiovascular diseases (CVDs), which encompass heart and blood vessel issues, stand as the leading cause of global mortality for many people., Methods: the present study intends to perform discrimination between seven well-known CVDs (bundle branch block, cardiomyopathy, myocarditis, myocardial hypertrophy, myocardial infarction, valvular heart disease, and dysrhythmia) and one healthy control group, respectively, by feeding a set of machine learning (ML) models with 10 non-linear features extracted every 1 s from electrocardiography (ECG) lead signals of a well-known ECG database (PTB diagnostic ECG database) using multi-band analysis performed by discrete wavelet transform (DWT). The ML models were trained and tested using a leave-one-out cross-validation approach, assessing the individual and combined capabilities of features, per each lead or combined, to distinguish between pairs of study groups and for conducting a comprehensive all vs. all analysis., Results: the Accuracy discrimination results ranged between 73% and 100%, the Recall between 68% and 100%, and the AUC between 0.42 and 1., Conclusions: the results suggest that our method is a good tool for distinguishing CVDs, offering significant advantages over other studies that used the same dataset, including a multi-class comparison group (all vs. all), a wider range of binary comparisons, and the use of classical non-linear analysis under ECG multi-band analysis performed by DWT.

Background: Hepatitis B virus (HBV) vaccination is recommended for non-immunised patients with rheumatic diseases starting biological disease-modifying antirheumatic drugs (bDMARDs). There is some evidence that HBV vaccination is effective in patients under conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), but it is currently unclear whether this also applies to bDMARDs., Objectives: To assess the efficacy and safety of HBV vaccination in patients with inflammatory arthritides treated with bDMARDs., Methods: A prospective cohort with inflammatory arthritides treated with bDMARDs, negative for anti-HBs and anti-HBc and never vaccinated for HBV was recruited. Engerix B was administered at 0, 1 and 6 months and anti-HBs was reassessed ≥1 month after last dose. Response was defined as anti-HBs≥10 IU/L and compared against vaccinated healthy controls. Disease flare, serious adverse events and immune-related disorders not previously present were recorded., Results: 62 patients, most treated with TNF inhibitors (TNFi), and 38 controls were recruited. Most patients were taking csDMARDs (67.7%) and were in remission/low disease activity (59.4%). Only 20/62 patients (32.3%) had a positive response to vaccination, in comparison to 36/38 age-matched controls (94.7%, p<0.001). Response was seen in 19/51 patients treated with TNFi (37.3%) and in 1/11 (9.1%) patients treated with non-TNFi (p=0.07), including 1/6 treated with tocilizumab (16.7%). Among TNFi, response rates ranged from 4/22 (18.2%) for infliximab to 8/14 (57.1%) for etanercept. No relevant safety issues were identified., Conclusions: HBV vaccination response in patients with rheumatic diseases treated with bDMARDs was poorer than expected. Our data reinforce the recommendation for vaccination prior to starting bDMARDs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We propose a solvable class of 1D quasiperiodic tight-binding models encompassing extended, localized, and critical phases, separated by nontrivial mobility edges. Limiting cases include the Aubry-André model and the models of Sriram Ganeshan, J. H. Pixley, and S. Das Sarma [Phys. Rev. Lett. 114, 146601 (2015)PRLTAO0031-900710.1103/PhysRevLett.114.146601] and J. Biddle and S. Das Sarma [Phys. Rev. Lett. 104, 070601 (2010)PRLTAO0031-900710.1103/PhysRevLett.104.070601]. The analytical treatment follows from recognizing these models as a novel type of fixed points of the renormalization group procedure recently proposed in Phys. Rev. B 108, L100201 (2023)10.1103/PhysRevB.108.L100201 for characterizing phases of quasiperiodic structures. Beyond known limits, the proposed class of models extends previously encountered localized-delocalized duality transformations to points within multifractal critical phases. Besides an experimental confirmation of multifractal duality, realizing the proposed class of models in optical lattices allows stabilizing multifractal critical phases and nontrivial mobility edges in an undriven system without the need for the unbounded potentials required by previous proposals.

Introduction: Neuroscience studies brain dynamics through the analysis of electrical signals. Cortical activity estimated by electroencephalography brings accurate information about perceptions of human behavior. The examination of resting states in relation to subsequent behaviors indicates that intrinsic cortical activity (ICA) has implications for decision-making processes, especially when inserted in the context of military activities and associated with stress. The objective of this study was to compare the absolute alpha power (AAP) in the ICA in the pre-task moment of novice specialized military (NG) with experienced (ExpG), associating with the level of stress., Materials and Methods: This was a cross-sectional, observational study with 19 military personnel (32.1 years old), divided into NG (10) and ExpG (9). The ICA was the outcome variable, with the level of stress and the time of specialization in military tasks as the exposure variables. ICA analysis were carried out based on the cortical areas to compare the ICA of the NG with that of the ExpG. The association of stress level with ICA was estimated by linear regression via linear models., Results: There was a significant difference in almost all cortical areas, and the averages were always higher in Exp. The high stress level was associated with greater AAP both for the NG and for the ExpG, and at the medium level, the AAP was obtained, varying according to each cortical area., Conclusion: The AAP in ExpG was significantly higher than that in NG, indicating a lower level of cortical activity and greater efficiency in sensory, motor, and visual tasks., (© The Association of Military Surgeons of the United States 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Biofilms are complex microecosystems with valuable ecological roles that can shelter a variety of microorganisms. Spirochetes from the genus Leptospira have been observed to form biofilms in vitro, in rural environments, and in the kidneys of reservoir rats. The genus Leptospira is composed of pathogenic and non-pathogenic species, and the description of new species is ongoing due to the advent of whole genome sequencing. Leptospires have increasingly been isolated from water and soil samples. To investigate the presence of Leptospira in environmental biofilms, we collected three distinct samples of biofilms formed in an urban setting with poor sanitation: Pau da Lima, in Salvador, Bahia, Brazil. All biofilm samples were negative for the presence of pathogenic leptospires via conventional PCR, but cultures containing saprophytic Leptospira were identified. Whole genomes were generated and analyzed for twenty isolates obtained from these biofilms. For species identification, we used digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) analysis. The obtained isolates were classified into seven presumptive species from the saprophytic S1 clade. ANI and dDDH analysis suggest that three of those seven species were new. Classical phenotypic tests confirmed the novel isolated bacteria as saprophytic Leptospira. The isolates presented typical morphology and ultrastructure according to scanning electron microscopy and formed biofilms under in vitro conditions. Our data indicate that a diversity of saprophytic Leptospira species survive in the Brazilian poorly sanitized urban environment, in a biofilm lifestyle. We believe our results contribute to a better understanding of Leptospira biology and ecology, considering biofilms as natural environmental reservoirs for leptospires., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: None of the authors acted as reviewer or editor of this article. None of the authors disclosed personal conflicts of interest or financial relationships relevant to this publication.

Pain is one of the most debilitating symptoms in rheumatic diseases. Pain often persists after total knee replacement in osteoarthritis, or when inflammation is minimal/absent in rheumatoid arthritis. This suggests that pain transitions to a chronic state independent of the original damage/inflammation. Mitochondrial dysfunction in the nervous system promotes chronic pain and is linked to NLRP3 inflammasome activation. Therefore, we investigated the role of mitochondrial dysfunction and NLRP3 inflammasome activation in the transition from acute to persistent inflammation-induced nociplastic pain and in persistent monoiodoacetate-induced osteoarthritis pain. Intraplantar injection of carrageenan in mice induced transient inflammatory pain that resolved within 7 days. A subsequent intraplantar PGE 2 injection induced persistent mechanical hypersensitivity, while in naive mice it resolved within one day. Thus, this initial transient inflammation induced maladaptive nociceptor neuroplasticity, so-called hyperalgesic priming. At Day 7, when mice were primed, expression of NLRP3 inflammasome pathway components was increased, and dorsal root ganglia (DRG) neurons displayed signs of activated NLRP3 inflammasome. Inhibition of NLRP3 inflammasome with MCC950 prevented the transition from acute to chronic pain in this hyperalgesic priming model. In mice with persistent monoiodoacetate-induced osteoarthritis pain, DRG neurons displayed signs of mitochondrial oxidative stress and NLRP3 inflammasome activation. Blocking NLRP3 inflammasome activity attenuated established osteoarthritis pain. In males, NLPR3 inhibition had longer-lasting effects than in females. Overall, these data suggest that NLRP3 inflammasome activation in sensory neurons, potentially caused by neuronal oxidative stress, promotes development of persistent inflammatory and osteoarthritis pain. Therefore, targeting NLRP3 inflammasome pathway may be a promising approach to treat chronic pain., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology.)

Introduction: New evidence and extrapolated data from other coronaviruses suggest that symptoms and consequences of COVID-19 may persist beyond the cure. The aims of this study were to evaluate persistent symptoms after SARS-CoV-2 infection and its impact on physical condition, activities of daily living, and quality-of-life; establish whether symptom persistence is associated with higher disability; and document the evolution of the multiple domains after a home exercise program., Methods: Prospective study with patients referred to a Physical and Rehabilitation Medicine clinic, after SARS-CoV-2 infection. Patient evaluations, including a symptom questionnaire, the 1-Min Sit-to-stand test (1-MSTS), the EQ-5D questionnaire and the London Chest Activity Daily Living (LCA-DL) questionnaire, were performed before and after a home exercise program., Results: Seventy-four patients were included. The majority (n = 71) had been hospitalized (mean stay 19.66 ± 13.35 days), 51% required intensive care. At first evaluation, 54 days after symptom onset, a mean of 18.6 repetitions in the 1-MSTS were performed. The percentage of LCA-DL was above 28% in 23% of the patients. Impairments on EQ-5D were present in 44% for mobility and 44% for anxiety/depression. Mean EQ-5D VAS was 66.5 out of 100. Fifty-one (70%) had at least one persistent symptom (Symptomatic Group), while 22 (30%) were asymptomatic (Asymptomatic Group). The Symptomatic Group had statistically significantly worse mean results on 1-MSTS (16.8 vs 22.9; p < 0.001), % LCA-DL score, EQ-D5 (7.8 vs 5.7; p < 0.001) and EQ-D5-VAS. No patient characteristic, clinical background, comorbidity, or hospitalization characteristics was significantly different between groups. Every patient was given a home exercise program; 47 patients joined an additional rehabilitation program or were clinically discharged and were therefore excluded from the second evaluation. Twenty-seven patients participated in a second evaluation. In the matched analysis, mean 1-MSTS improved by 3.4 repetitions. Mean LCA-DL, mean EQ-5D score (7.1 to 6.6) and EQ-VAS score changed favourably and significantly., Conclusion: Two months after infection by SARS-CoV-2, persistent symptoms were frequent in patients referred to a Physical Medicine and Rehabilitation clinic. Additionally, the SARS-CoV-2 infection, as well as the persistence of symptoms, had a negative impact in the physical condition and functionality in ADL and quality-of-life. With a home exercise program in place, a statistically significant improvement was observed. Referral of patients with persistent symptoms to Physical and Rehabilitation Medicine may be warranted.

Background: The saccadic eye movement is responsible for providing focus to a visual object of interest to the retina. In sports like volleyball, identifying relevant targets quickly is essential to a masterful performance. The training improves cortical regions underlying saccadic action, enabling more automated processing in athletes., Objective: We investigated changes in the latency during the saccadic eye movement and the absolute theta power on the frontal and prefrontal cortices during the execution of the saccadic eye movement task in volleyball athletes and non-athletes. We hypothesized that the saccade latency and theta power would be lower due to training and perceptual-cognitive enhancement in volleyball players., Methods: We recruited 30 healthy volunteers: 15 volleyball athletes (11 men and 4 women; mean age: 15.08 ± 1.06 years) and 15 non-athletes (5 men and 10 women; mean age: 18.00 ± 1.46 years). All tasks were performed simultaneously with electroencephalography signal recording., Results: The latency of the saccadic eye movement presented a significant difference between the groups; a shorter time was observed among the athletes, associated with the players' superiority in terms of attention level. During the experiment, the athletes observed a decrease in absolute theta power compared to non-athletes on the electrodes of each frontal and prefrontal area., Conclusion: In the present study, we observed the behavior of reaction time and absolute theta power in athletes and non-athletes during a saccadic movement task. Our findings corroborate the premise of cognitive improvement, mainly due to the reduction of saccadic latency and lower beta power, validating the neural efficiency hypothesis., Competing Interests: The authors have no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Aims: Acute kidney injury (AKI) is highly prevalent during hospitalization of patients with type 2 diabetes (T2D). We aimed to assess the impact of AKI and its severity and duration on the risk of hypoglycaemia in hospitalized patients with T2D., Methods: Retrospective cohort analysis of patients with T2D, admitted at a University Hospital in 2018-2019. AKI was defined as an increase in serum creatinine by ≥ 0.3 mg/dl (48 h) or ≥ 1.5 times baseline (7 days), and hypoglycaemia as blood glucose concentration < 70 mg/dl. Patients with chronic kidney disease stage ≥ 4 were excluded. We registered 239 hospitalizations with AKI and randomly selected 239 without AKI (control). Multiple logistic regression was used to adjust for confounding factors and ROC curve analysis to determine a cutoff for AKI duration., Results: The risk of hypoglycaemia was higher in the AKI group (crude OR 3.6, 95%CI 1.8-9.6), even after adjusting for covariates (OR 4.2, 95%CI 1.8-9.6). Each day of AKI duration was associated with a 14% increase in the risk of hypoglycaemia (95%CI 1.1-1.2), and a cutoff of 5.5 days of AKI duration was obtained for increased risk of hypoglycaemia and mortality. AKI severity was also associated with mortality, but showed no significant association with hypoglycaemia. Patients with hypoglycaemia had 4.4 times greater risk of mortality (95%CI 2.4-8.2)., Conclusions: AKI increased the risk of hypoglycaemia during hospitalization of patients with T2D, and its duration was the main risk factor. These results highlight the need for specific protocols to avoid hypoglycaemia and its burden in patients with AKI., (© 2023. The Author(s).)

Extracellular DNA (eDNA) is a major component of bacterial biofilms. In this study, we performed a three-dimensional analysis of Leptospira biofilm using advanced imaging by confocal laser scanning microscopy (CLSM) and multi-parameter analysis by COMSTAT 2 software, with quantification of Leptospira and eDNA fluorescence. To investigate the role of eDNA in Leptospira biofilm, we treated Leptospira biflexa biofilms with DNase I enzyme (DNase), which digested eDNA, and compared DNase treated biofilms and controls. There was a significant reduction of the biomass of biofilms treated with DNase, by spectrophotometry and COMSTAT analysis. The multiparameter analysis evidenced for DNase-treated biofilms a significant decrease in the surface area and the average thickness; opposing to a significant augmentation of the surface/biovolume ratio and the roughness coefficient (Ra*), when compared to controls. We analyzed the parameters of DNase-treated biofilms by Pearson's correlation coefficient and found significant positive correlations between biomass and average thickness; biomass and surface area; surface area and average thickness. On the other hand, there were significant negative correlations between Ra* and biomass; Ra* and average thickness; Ra* and surface area. These findings suggest that eDNA digestion results in biofilm instability and alteration of the three-dimensional architecture, justifying the negative correlation between Ra* and the above-mentioned parameters. In conclusion, our study showed that eDNA digestion produced a massive structural loss, instability, and dramatic changes in the three-dimensional architecture of Leptospira biflexa biofilm. These findings contribute to a better understanding of the role of eDNA and highlight the importance of eDNA as a key component in Leptospira biofilms., Competing Interests: Conflict of interestThe authors declare that they have no conflicts of interest., (© Association of Microbiologists of India 2023.)

The Real Relationship is a relational construct that has influenced other constructs, like the working alliance, although empirically neglected. The development of the Real Relationship Inventory provides a reliable and valid way of measuring the Real Relationship in research and clinical applications. This study aimed to validate and explore the psychometric properties of the Real Relationship Inventory Client Form with a Portuguese adult sample in the context of psychotherapy. The sample includes 373 clients currently in psychotherapy or concluded recently. All clients completed the Real Relationship Inventory (RRI-C) and the Working Alliance Inventory. The confirmatory analysis revealed the same two factors in the RRI-C for the Portuguese adult population, Genuineness and Realism. The observation of the same factor structure suggests the cross-cultural value of the Real Relationship. The measure demonstrated good internal consistency and acceptable adjustment. A significant correlation was found between the RRI-C and the Working Alliance Inventory and significant correlations between the Bond and Genuineness and Realism subscales. The present study reflects on the RRI-C while also contributing to the importance of the Real Relationship in different cultures and clinical contexts.

Case Report: A 68-year-old male treated with secukinumab for psoriatic arthritis suspended treatment for three months due to COVID pandemic. Upon secukinumab reintroduction, anorexia and weight loss ensued and four months later he had an abrupt onset of low-grade fever, fatigue, flu-like symptoms, dyspnoea and widespread inflammatory arthralgias. Laboratory investigations showed de novo anaemia, leukopenia, lymphopenia, cytocholestasis, elevated acute phase reactants, C3 complement consumption, proteinuria (1630mg/24h), active urine sediment, positive antinuclear (1:1280) and anti-double-stranded DNA (212.3 IU/mL) antibodies. Chest imaging showed peripheral pulmonary embolism, lobar pneumonia, and a small bilateral pleural effusion. Drug-induced lupus erythematosus (DILE) was suspected, and the patient was hospitalised. Secukinumab was discontinued and treatment with enoxaparin, antibiotics, enalapril, hydroxychloroquine and prednisolone 0.5mg/kg qd was started. Clinical and laboratorial remission ensued after one month except for proteinuria (decreased to 653mg/24h). Proliferative lupus nephritis was assumed and mycophenolate mofetil was introduced, with sustained complete remission over a 33-month follow-up., Discussion: This is the second reported case of systemic secukinumab-associated DILE, and the first with renal involvement. Clinical and laboratory features of DILE are reviewed and compared with previously described cases.

The phenomenon of intermittency has remained a theoretical concept without any attempts to approach it geometrically with the use of a simple visualization. In this paper, a particular geometric model of point clustering approaching the Cantor shape in 2D, with a symmetry scale θ being an intermittency parameter, is proposed. To verify its ability to describe intermittency, to this model, we applied the entropic skin theory concept. This allowed us to obtain a conceptual validation. We observed that the intermittency phenomenon in our model was adequately described with the multiscale dynamics proposed by the entropic skin theory, coupling the fluctuation levels that extended between two extremes: the bulk and the crest. We calculated the reversibility efficiency γ with two different methods: statistical and geometrical analyses. Both efficiency values, γstat and γgeo, showed equality with a low relative error margin, which actually validated our suggested fractal model for intermittency. In addition, we applied the extended self-similarity (E.S.S.) to the model. This highlighted the intermittency phenomenon as a deviation from the homogeneity assumed by Kolmogorov in turbulence.

Objectives: Patient centred care is an increasingly important paradigm. Applying a treat-to-target strategy to the impact of the disease in patients' lives seems a very promising tool to serve this purpose. We aimed to evaluate if maximum acceptable impact scores (target-values) defined at the population level provide an appropriate representation for most individual patients. To determine if the individually established target values of impact are consistent enough to be used in a treat-to-target strategy., Methods: Consecutive patients with rheumatoid arthritis were asked to indicate, in two consecutive visits, the maximum severity of impact they considered acceptable to live with for the rest of their lives, in the seven domains of Rheumatoid Arthritis Impact of Disease score. The individual adequacy of population-based reference values was assessed by measures of dispersion. Stability of individual target-values were evaluated through intraclass correlation coefficient. Socio-demographic, clinical and psychological features were tested as co-factors of stability., Results: 299 patients were included. The dispersion of targets was wide (CV>0.68), thus limiting the use of any population-based single values as targets for the individual patients. Although the mean target values were very similar in both visits for all domains, reliability was poor in all cases (ICCs: 0.37-0.47). Only 25-30% of the patients selected the same target value in the 2 visits. No explanatory factors for (non-)stability were identified., Conclusions: Quantified impact targets defined at population level are not appropriate for individual patient care. Research on alternative tools to support patient-centred, target-oriented management strategies is warranted.

Probing two-dimensional single-layer quantum magnets remains a significant challenge. In this Letter, we propose exploiting tunneling spectroscopy in the presence of magnetic impurities to obtain information about the magnon dispersion relations in analogy to quasiparticle interference in nonmagnetic materials. We show that this technique can be used to establish the dispersion relations even for frustrated magnets, where the presence of an impurity generally leads to a nontrivial spin texture. Finally, we consider the problem of establishing Chern magnon bands in 2D magnets showing how tunable impurities allow one to probe the nature of the surface states.

Obstructive Sleep Apnea (OSA) corresponds to episodes of complete or partial upper airway obstruction during sleep. The gold standard for diagnosing OSA is polysomnography; however, metabolomics is an innovative and highly sensitive method that seeks to identify and quantify small molecules in biological systems. Identify the metabolites most frequently associated with obstructive sleep apnea in adults. The search for articles was conducted between October 2020 and August 2021, in electronic databases, such as MEDLINE/PubMed, Scielo, Embase, and Cochrane, through the combination of descriptors: obstructive sleep apnea, metabolomic, adult. This systematic review included all cross-sectional studies published, including human patients aged 18 years or older, of both genders who underwent type I or II polysomnography and metabolomics study. The search strategy selected 3697 surveys, and 4 of them were selected to be a part of this systematic review. Based on the analyzed surveys, it was found that all of them were able to diagnose OSA, reaching a sensitivity of 75-97%, and specificity that ranged from 72 to 100%; besides differentiating patients with OSA (severe, moderate, and mild) from simple snorers with a mean sensitivity of 77.2% and specificity of 66.25%. These findings suggest that, in addition to being used as a screening and diagnostic strategy for OSA, metabolomics has the potential to be used for severity stratification and to monitor the disease's progression., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Japanese Society of Sleep Research 2023, corrected publication 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Since the beginning of 2020, Coronavirus Disease 19 (COVID-19) has attracted the attention of the World Health Organization (WHO). This paper looks into the infection mechanism, patient symptoms, and laboratory diagnosis, followed by an extensive assessment of different technologies and computerized models (based on Electrocardiographic signals (ECG), Voice, and X-ray techniques) proposed as a diagnostic tool for the accurate detection of COVID-19. The found papers showed high accuracy rate results, ranging between 85.70% and 100%, and F1-Scores from 89.52% to 100%. With this state-of-the-art, we concluded that the models proposed for the detection of COVID-19 already have significant results, but the area still has room for improvement, given the vast symptomatology and the better comprehension of individuals' evolution of the disease.

There is a high demand for stroke rehabilitation in the Brazilian public health system, but most studies that have addressed rehabilitation for unilateral spatial neglect (USN) after stroke have been performed in high-income countries. Therefore, the aim of this study was to analyze USN patient recruitment in a multicenter noninvasive brain stimulation clinical trial performed in Brazil and to provide study design recommendations for future studies. We evaluated the reasons for exclusion of patients from a multicenter, randomized, double-blinded clinical trial of rehabilitation of USN patients after stroke. Clinical and demographic variables were compared between the included and excluded patients. A descriptive statistical analysis was performed. Only 173 of the 1953 potential neglect patients (8.8%) passed the initial screening. After screening evaluation, 87/173 patients (50.3%) were excluded for clinical reasons. Cognitive impairment led to the exclusion of 21/87 patients (24.1%). Low socioeconomic status led to the exclusion of 37/173 patients (21.4%). Difficulty obtaining transportation to access treatment was the most common reason for their exclusion (16/37 patients, 43.3%). The analyzed Brazilian institutions have potential for conducting studies of USN. The recruitment of stroke survivors with USN was restricted by the study design and limited financial support. A history of cognitive impairment, intracranial stenting or craniectomy, and lack of transportation were the most common barriers to participating in a multicenter noninvasive brain stimulation trial among patients with USN after stroke.

Objectives: Indigenous Australians experience cumulative forms of oppression. Using intersectionality as the underlying analytical framework, and with oral health as an outcome, we demonstrate how oppressions are interlinked and cannot be treated in isolation. The study aimed to quantify the cumulative effect of two forms of oppression on Indigenous Australian oral health inequities., Methods: This observational study was conducted Feb 2018-Jan 2020. Recruitment occurred through Aboriginal Community Controlled Health Organisations in South Australia, Australia. Eligibility included identifying as Indigenous, residing in South Australia and aged 18+ years. Socio-demographic factors, health-related characteristics, experience of racism, negative life events and self-reported oral health outcomes were collected. The main outcomes were fair/poor self-rated oral health and oral health related quality of life, measured by OHIP-14. Effect-measure modification was used to verify differences on effect sizes per strata of negative life events and racism. The presence of modification was indicated by Relative Excess Risk due to Interactions (RERIs)., Results: Data were obtained for 1,011 participants, median age 37 years, 66% female and 63% residing in non-metropolitan locations. Over half (52%) had experienced racism in the past 12 months and 85% had experienced one or more negative life events. Around one-third (34%) rated their oral health as fair/poor and the mean OHIP-14 score was 17. A higher proportion of participants who had experienced both racism and negative life events (46%) were male (52%), aged 37+ years (47%), resided in metropolitan locations (57%), reported difficulty paying a $100 dental bill (47%), had fair/poor self-rated oral health (54%) and higher mean OHIP-14 scores (20). The RERIs observed were 0.31 for fair/poor self-rated oral health and 0.23 for mean OHIP-14. The positive RERIs indicated a super-additive effect between racism, negative life events (effect modifier) and self-reported oral health outcomes., Conclusion: The more oppressions participants experienced, in the form of racism and negative life events, the greater the burden of poor self-reported oral health. The study is one of the first to use intersectionality as a theory to explain oral health inequities as experienced by Indigenous Australians., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jamieson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this first analysis, samples from 23 BC survivors (group 1) and 291 healthy female controls (group 2) were characterised through the V3 and V4 regions that encode the "16S rRNA" gene of each bacteria. The samples were sequenced by next-generation sequencing (NGS), and the taxonomy was identified by resorting to Kraken2 and improved with Bracken, using a curated database called 'GutHealth&#95;DB'. The α and β-diversity analyses were used to determine the richness and evenness of the gut microbiota. A non-parametric Mann-Whitney U test was applied to assess differential abundance between both groups. The Firmicutes/Bacteroidetes (F/B) ratio was calculated using a Kruskal-Wallis chi-squared test. The α-diversity was significantly higher in group 1 ( p = 0.28 × 10 -12 for the Chao index and p = 1.64 × 10 -12 for the ACE index). The Shannon index, a marker of richness and evenness, was not statistically different between the two groups ( p = 0.72). The microbiota composition was different between the two groups: a null hypothesis was rejected for PERMANOVA ( p = 9.99 × 10 -5 ) and Anosim ( p = 0.04) and was not rejected for β-dispersion ( p = 0.158), using Unifrac weighted distance. The relative abundance of 14 phyla, 29 classes, 25 orders, 64 families, 116 genera, and 74 species differed significantly between both groups. The F/B ratio was significantly lower in group 1 than in group 2, p < 0.001. Our study allowed us to observe significant taxonomic disparities in the two groups by testing the differences between BC survivors and healthy controls. Additional studies are needed to clarify the involved mechanisms and explore the relationship between microbiota and BC survivorship.

Background and Aims: EUS-guided through-the-needle microforceps biopsy (EUS-TTNB) was introduced as a new diagnostic tool to establish pancreatic cyst histotype and help to better risk stratify the patients. The aim of this study was to describe the technical success, diagnostic yield, and adverse events of through-the-needle biopsy and discuss the technique variations, focusing on future procedure standardization., Methods: We performed a prospective single-center study including patients with presumed mucinous cysts harboring worrisome features or indeterminate cyst type on imaging, submitted to EUS-TTNB using Moray® microforceps between March 2018 and September 2021. Specimens were processed as a cell-block., Results: We included 40 patients. Technical success was 97.5%. The diagnostic yield was 72.5% for TTNB whereas for cyst fluid cytology/analysis it was 27.5%. Moreover, without TTNB 5 mucinous lesions would not have been diagnosed. TTNB had a sensitivity of 76% and a specificity of 91%, while FNA cytology had a sensitivity and specificity of 35% and 91%, respectively. Moreover for IPMN lesions, subtyping was possible in 63% of cases. TTNB resulted in change in clinical management in 20% of patients. We registered three adverse events: 2 self-limited intracystic bleeding and 1 patient with abdominal pain not associated with pancreatitis., Conclusion: TTNB proved superior to cyst fluid analysis and cytology for the definition of cyst histotype and mucinous cyst diagnosis with acceptable risk profile. Further studies should explore the best steps for procedure standardization., (© 2022 S. Karger AG, Basel.)

Systemic arterial hypertension (SAH) is a major risk factor for several secondary diseases, especially cardiovascular and renal conditions. SAH has a high prevalence worldwide, and its precise and early recognition is important to prevent the development of secondary outcomes. In this field, the study of biomarkers represents an important approach to diagnosing and predicting the disease and its associated conditions. The use of biomarkers in hypertension and hypertension-related disorders, such as ischemic stroke, intracerebral hemorrhage, transient ischemic attack, acute myocardial infarction, angina pectoris and chronic kidney disease, are discussed in this review. Establishing a potential pool of biomarkers may contribute to a non-invasive and improved approach for their diagnosis, prognosis, risk assessment, therapy management and pharmacological responses to a therapeutic intervention to improve patients' quality of life and prevent unfavorable outcomes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Colony morphology (size, color, edge, elevation, and texture), as observed on culture media, can be used to visually discriminate different microorganisms., Methods: This work introduces a hybrid method that combines standard pre-trained CNN keras models and classical machine-learning models for supporting colonies discrimination, developed in Petri-plates. In order to test and validate the system, images of three bacterial species ( Escherichia coli , Pseudomonas aeruginosa , and Staphylococcus aureus ) cultured in Petri plates were used., Results: The system demonstrated the following Accuracy discrimination rates between pairs of study groups: 92% for Pseudomonas aeruginosa vs. Staphylococcus aureus , 91% for Escherichia coli vs. Staphylococcus aureus and 84% Escherichia coli vs. Pseudomonas aeruginosa ., Conclusions: These results show that combining deep-learning models with classical machine-learning models can help to discriminate bacteria colonies with good accuracy ratios.

The Hippo pathway plays central roles in relaying mechanical signals during development and tumorigenesis, but how the proteostasis of the Hippo kinase MST2 is regulated remains unknown. Here, we found that chemical inhibition of proteasomal proteolysis resulted in increased levels of MST2 in human breast epithelial cells. MST2 binds SCF βTrCP E3 ubiquitin ligase and silencing βTrCP resulted in MST2 accumulation. Site-directed mutagenesis combined with computational molecular dynamics studies revealed that βTrCP binds MST2 via a non-canonical degradation motif. Additionally, stiffer extracellular matrix, as well as hyperactivation of integrins resulted in enhanced MST2 degradation mediated by integrin-linked kinase (ILK) and actomyosin stress fibers. Our study uncovers the underlying biochemical mechanisms controlling MST2 degradation and underscores how alterations in the microenvironment rigidity regulate the proteostasis of a central Hippo pathway component., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michele Pagano reports a relationship with Coho Therapeutics that includes: equity or stocks. Michele Pagano reports a relationship with CullGen that includes: board membership. Michele Pagano reports a relationship with Kymera Therapeutics that includes: board membership. Michele Pagano reports a relationship with SEED Therapeutics that includes: board membership. Michele Pagano reports a relationship with Santi Therapeutics that includes: consulting or advisory. M.P. is a consultant for and has financial interests in Coho Therapeutics, CullGen, Kymera Therapeutics, and SEED Therapeutics. M.P. is a cofounder of Coho Therapeutics, is on the SAB of CullGen and Kymera Therapeutics, and is a consultant for Santi Therapeutics. The other authors declare no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A 77-year-old female with previous medical history of non-cirrhotic chronic hepatitis B and hepatocellular carcinoma treated with sequential partial hepatectomy followed by transarterial chemoembolization complained of pruritus and jaundice. Magnetic resonance cholangiopancreatography revealed a peri-hilar ill-defined stenosing lesion suggestive of malignancy. Endoscopic retrograde cholangiopancreatography with cholangioscopy confirmed a circumferential peri-hilar stenosis with fragile mucosa and tortuous dilated vessels and biopsies of this area were consistent cholangiocarcinoma. After 3 months, she presented with new-onset dyspnea and bilioptysis and abdominal computed tomography revealed a bronchial-biliary fistula. ERCP was performed to place a self-expandable metal stent in the biliary tract, which resulted in rapid clinical improvement. The patient has been followed for 2 years and remains globally stable with two episodes of worsening of bilioptysis secondary to stent obstruction by lithiasis that were easily resolved with Fogarty balloon-assisted extraction, with rapid improvement. This case demonstrates the long-term efficacy of endoscopic biliary drainage with self-expandable metallic stent for bronchial-biliary fistula in the setting of cholangiocarcinoma. .

Objectives: Many axial spondylarthritis (axSpA) patients receive a conventional synthetic DMARD (csDMARD) in combination with a TNF inhibitor (TNFi). However, the value of this co-therapy remains unclear. The objectives were to describe the characteristics of axSpA patients initiating a first TNFi as monotherapy compared with co-therapy with csDMARD, to compare one-year TNFi retention and remission rates, and to explore the impact of peripheral arthritis., Methods: Data was collected from 13 European registries. One-year outcomes included TNFi retention and hazard ratios (HR) for discontinuation with 95% CIs. Logistic regression was performed with adjusted odds ratios (OR) of achieving remission (Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP < 1.3 and/or BASDAI < 2) and stratified by treatment. Inter-registry heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Peripheral arthritis was defined as ≥1 swollen joint at baseline (=TNFi start)., Results: Amongst 24 171 axSpA patients, 32% received csDMARD co-therapy (range across countries: 13.5% to 71.2%). The co-therapy group had more baseline peripheral arthritis and higher CRP than the monotherapy group. One-year TNFi-retention rates (95% CI): 79% (78, 79%) for TNFi monotherapy vs 82% (81, 83%) with co-therapy (P < 0.001). Remission was obtained in 20% on monotherapy and 22% on co-therapy (P < 0.001); adjusted OR of 1.16 (1.07, 1.25). Remission rates at 12 months were similar in patients with/without peripheral arthritis., Conclusion: This large European study of axial SpA patients showed similar one-year treatment outcomes for TNFi monotherapy and csDMARD co-therapy, although considerable heterogeneity across countries limited the identification of certain subgroups (e.g. peripheral arthritis) that may benefit from co-therapy., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The association between exposure to air pollutants and respiratory diseases is well known. This study aimed to identify the association between this exposure and hospitalizations for COVID-19 in São José dos Campos, SP, a medium-sized city, between April 2020 and April 2021. Hospitalization data, concerning code B34.2, was supplied by DATASUS, and data concerning pollutants and climate variables were supplied by CETESB. Cases were quantified by sex, age, length of hospital stay in days, and type of discharge, whether hospital discharge or death. The negative binomial regression model was chosen. Estimates were produced for the relative risk (RR) of significant exposure to pollutants (P≤0.05) with a 10 µg/m3 increase of pollutant, as well as for excess hospitalizations. There were 1873 hospitalizations, with a daily average of 4.7 (±3.8), ranging from zero to 21: 716 deaths (38.2%) were recorded, 1065 admissions were men, and women were less susceptible (OR=0.82). The average age of women was higher than that of men; in cases of death, men were older than women; discharged patients were younger. All the above variables were significant. The risk of ozone exposure was higher and more significant in Lag 2, and the risk of nitrogen dioxide exposure was high in Lag 3, which was the period of the highest increase in hospitalizations, at 11.3%. The findings of this study, the first conducted in Brazil, corroborate the results of studies conducted in other centers.

Gut microbiota modulation might constitute a mechanism mediating the effects of beer on health. In this randomized, double-blinded, two-arm parallel trial, 22 healthy men were recruited to drink 330 mL of nonalcoholic beer (0.0% v/v) or alcoholic beer (5.2% v/v) daily during a 4-week follow-up period. Blood and faecal samples were collected before and after the intervention period. Gut microbiota was analyzed by 16S rRNA gene sequencing. Drinking nonalcoholic or alcoholic beer daily for 4 weeks did not increase body weight and body fat mass and did not changed significantly serum cardiometabolic biomarkers. Nonalcoholic and alcoholic beer increased gut microbiota diversity which has been associated with positive health outcomes and tended to increase faecal alkaline phosphatase activity, a marker of intestinal barrier function. These results suggest the effects of beer on gut microbiota modulation are independent of alcohol and may be mediated by beer polyphenols.

Rheumatic diseases, such as osteoarthritis and rheumatoid arthritis, affect over 750 million people worldwide and contribute to approximately 40% of chronic pain cases. Inflammation and tissue damage contribute to pain in rheumatic diseases, but pain often persists even when inflammation/damage is resolved. Mechanisms that cause this persistent pain are still unclear. Mitochondria are essential for a myriad of cellular processes and regulate neuronal functions. Mitochondrial dysfunction has been implicated in multiple neurological disorders, but its role in sensory processing and pain in rheumatic diseases is relatively unexplored. This review provides a comprehensive understanding of how mitochondrial dysfunction connects inflammation and damage-associated pathways to neuronal sensitization and persistent pain. To provide an overall framework on how mitochondria control pain, we explored recent evidence in inflammatory and neuropathic pain conditions. Mitochondria have intrinsic quality control mechanisms to prevent functional deficits and cellular damage. We will discuss the link between neuronal activity, mitochondrial dysfunction and chronic pain. Lastly, pharmacological strategies aimed at reestablishing mitochondrial functions or boosting mitochondrial dynamics as therapeutic interventions for chronic pain are discussed. The evidence presented in this review shows that mitochondria dysfunction may play a role in rheumatic pain. The dysfunction is not restricted to neuronal cells in the peripheral and central nervous system, but also includes blood cells and cells at the joint level that may affect pain pathways indirectly. Pre-clinical and clinical data suggest that modulation of mitochondrial functions can be used to attenuate or eliminate pain, which could be beneficial for multiple rheumatic diseases., 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., (© 2022 Silva Santos Ribeiro, Willemen and Eijkelkamp.)

Purpose: Pandemic-induced lockdowns disrupted sport training and competition. We aimed to identify the impact on the mental health of high-level athletes and clarify whether the effects differ for team-based and individual athletes., Methods: This cross-sectional survey, stratified by sex and sport type, collected demographic data and mental health measurements from 274 Brazilian high-performance athletes (142 from team sports and 132 from individual sports) involved with the Brazilian Olympic Committee program for the Tokyo Olympics 2021. Depression, disturbed sleep, and anxiety were assessed by the 9-Item Patient Health Questionnaire, 7-Item Insomnia Severity Index, and 7-Item Generalized Anxiety Disorder scale respectively. Responses were analyzed dichotomously according to published threshold values, characterizing the relative frequency distribution of prevalence (PCRS) or non-prevalence of clinically relevant symptoms (NPCRS)., Results: Out of all participants, 47 [17.1%], Z(274) = 15.38, p = .001, 32 [11.7%], Z(274) = 17.94, p = .001, and 49 [17.9%], Z(274) = 15.04, p = .001 had PCRS of anxiety, insomnia, and depression, respectively. There were no significant differences in the PCRS among genders. Compared with individual sport athletes, team sport athletes were more likely to report PCRS of insomnia (12 [37.5%] vs 20 [62.5%], Z(274) = -2.00, p = .046), and depression (18 [36.7%] vs 31 [63.3%], Z(274) = -2.63, p = .009) but not for anxiety., Conclusion: Athletes reported high levels of mental health problems during the lockdown. Team sport athletes reported worse symptoms of insomnia and depression than individual sport athletes, possibly due to the impact of unaccustomed social isolation and lack of social team activity. Therefore, it becomes relevant to consider psychological support to team sport athletes who for some reason, such as a pandemic, enduring crisis even injury rehabilitation needs to be isolated., (© 2022. The Author(s).)

Background and Aim: gastric inflammatory fibroid polyps constitute only 0.1 % of all gastric polyps. They are usually amenable to resection by snare polypectomy. However, on rare occasions, these lesions may require resection by endoscopic submucosal dissection. This study aimed to evaluate the effectiveness and safety of endoscopic submucosal dissection in the management of gastric inflammatory fibroid polyps not amenable to resection with snare polypectomy., Methods: a retrospective observational study of all consecutive patients who underwent endoscopic submucosal dissection for gastric inflammatory fibroid polyps between January 2011 and December 2020 was performed., Results: there were nine cases of gastric inflammatory fibroid polyps resected by endoscopic submucosal dissection. Most patients were female (7/9) with a mean age of 62.2 years. All gastric inflammatory fibroid polyps were described as solitary antral subepithelial lesions with a mean diameter of 16.7 mm, which appeared well-circumscribed and homogeneous lesions located at muscularis mucosa and submucosa without deeper invasion on endoscopic ultrasound. All lesions were successfully resected by en bloc and complete resection with free margins obtained in 8/9 specimens. Adverse events were reported in 2/9 cases including one intra-procedural bleeding successfully controlled with hemostatic clips and one aspiration pneumonia that evolved favorably. Mean follow-up duration was 33.7 months and no delayed complications or cases of recurrence were reported., Conclusions: endoscopic submucosal dissection appears safe and effective for the resection of gastric inflammatory fibroid polyps that present as large subepithelial lesions, if performed by experienced endoscopists after adequate characterization by endoscopic ultrasound, with high rates of technical success and low recurrence rates.