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Objective Determine the pharmacokinetics (PK) and exposure–response of hydroxychloroquine (HCQ) and desethylhydroxychloroquine (DHCQ) in paediatric SLE (pSLE).Methods We conducted an exploratory phase 2, direct-to-family trial. Children enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry with a diagnosis of pSLE were eligible if they were receiving HCQ as standard of care for ≥3 months. Biological samples were collected at up to four visits over a 6-month period. At each visit, plasma was obtained to measure the concentrations of HCQ and DHCQ, as well as cytokines. HCQ and DHCQ plasma PK data were analysed using a population PK modelling approach.Results Twenty-five subjects provided a total of 88 plasma concentrations for PK analysis. There was a poor linear fit between HCQ concentrations and total body weight (R2=0.03). There was a decline in both interferon (IFN)-alpha and IFN-gamma with higher concentrations of HCQ and DHCQ. Volume of distribution for HCQ in plasma was higher in children compared with published values in adults (73 000 L vs 44 000 L), but clearance values in children were similar to adults.Conclusions We report the first population PK model for HCQ and DHCQ in children using data from a novel direct-to-family clinical trial. We observed high interindividual variability in HCQ PK and found that weight-based dosing for HCQ is poorly correlated with drug concentrations, suggesting the need to use therapeutic drug monitoring to individualise dosing. Furthermore, our results suggest that the current weight-based dosing paradigm for HCQ may result in suboptimal drug exposures, particularly for children with obesity. Accordingly, additional studies of HCQ are needed in pSLE to determine the optimal drug concentration and dosing to reduce disease activity and improve outcomes.Trial registration number NCT04358302.

Introduction Direct-to-family clinical trials efficiently provide data while reducing the participation burden for children and their families. Although these trials can offer significant advantages over traditional clinical trials, the process of designing and implementing direct-to-family studies is poorly defined, especially in children with rheumatic disease. This paper provides lessons learnt from the design and implementation of a self-controlled, direct-to-family pilot trial aimed to evaluate the effects of a medication management device on adherence to hydroxychloroquine in paediatric SLE.Methods Several design features accommodate a direct-to-family approach. Participants meeting eligibility criteria from across the USA were identified a priori through a disease registry, and all outcome data are collected remotely. The primary outcome (medication adherence) is evaluated using electronic medication event-monitoring, plasma drug levels, patient questionnaires and pill counts. Secondary and exploratory endpoints include (1) lupus disease activity measured by a remote SLE Disease Activity Index examination and the Systemic Lupus Activity Questionnaire; and (2) hydroxychloroquine pharmacokinetics and pharmacodynamics. Recruitment of the initial target of 20 participants was achieved within 10 days. Due to initial recruitment success, enrolment was increased to 26 participants. Additional participants who were interested were placed on a waiting list in case of dropouts during the study.Discussion and dissemination Direct-to-family trials offer several advantages but present unique challenges. Lessons learnt from the protocol development, design, and implementation of this trial will inform future direct-to-family trials for children and adults with rheumatic diseases. Additionally, the data collected remotely in this trial will provide critical information regarding the accuracy of teleresearch in lupus, the impact of adherence to hydroxychloroquine on disease activity and a pharmacokinetic analysis to inform paediatric-specific dosing of hydroxychloroquine.Trial registration number ClinicalTrials.gov Registry (NCT04358302).

BACKGROUND:Recurrent bleeding is one of the major causes of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). Antifibrinolytic therapy is known to reduce recurrent bleeding, however, its beneficial effect on outcome remains unclear. The effect of treatment with tranexamic acid (TXA) until aneurysm treatment on clinical outcome is evaluated. METHODS:Patients with an aSAH from two high-volume tertiary referral treatment centers in the Netherlands, Academic Medical Center (AMC) and Radboud University Medical Center (RUMC), between January 2012 and December 2015 were included. Patients were classified into one of two groups; standard treatment or TXA treatment. Demographic and clinical characteristics, in-hospital complications and clinical outcome were compared between the two groups. Multivariate logistic regression was used to adjust for the influence of treatment center and baseline differences. RESULTS:Standard treatment was given in 509 patients, and 119 patients received additional TXA therapy before aneurysm occlusion. Patients treated with TXA did not experience less recurrent bleeding adjusted or unadjusted for treatment center (adjusted odds ratio [aOR] 0.80, 95% confidence interval [95% CI]: 0.37-1.73). In-hospital mortality, was significantly lower in the TXA group than the standard care group (adjusted OR [aOR] 0.42, 95% CI: 0.20-0.85). Poor outcome (mRS 4-6) assessed after six months was not different between treatment groups (aOR 1.05, 95% CI: 0.64-1.74). CONCLUSIONS:Pooled data from two high-volume treatment centers did not show improved clinical outcome after additional TXA treatment in aSAH patients. However, TXA treatment was associated with a decrease in mortality.

The ‘uveitis masquerade syndrome’ is a large group of neoplastic and non-neoplastic conditions that mimic and are initially misdiagnosed as uveitis. These eye diseases account for approximately 5% of all presentations at tertiary referral uveitis clinics. Vitreoretinal lymphoma is one of the most common of the neoplastic conditions that present as uveitis. With a 5-year survival rate under 50%, it is vitally important to recognize this diagnosis promptly. Other malignancies that may masquerade as uveitis include systemic lymphomas, primary uveal lymphoma, leukemias, multiple myeloma, uveal melanoma, metastatic cancers, and in children, retinoblastoma, medulloepithelioma, and post-transplantation lymphoproliferative disorder. Paraneoplastic syndromes are also possible uveitis mimics. Non-neoplastic conditions that may present as uveitis include the ocular ischemic syndrome and other vascular eye diseases, central serous chorioretinopathy, inherited retinal diseases, rhegmatogenous retinal detachment, pigment dispersion syndrome, intraocular foreign bodies, and in children, juvenile xanthogranuloma and Coats disease. In this article, we review the uveitis masquerade syndrome. Our major focus is vitreoretinal lymphoma, but we also summarize the other neoplasms and non-neoplastic diseases that may masquerade as uveitis.

Stress is widely known to have debilitating effects on physical health and mental wellbeing, particularly on one’s coping styles, personality traits, and outlook on life. Cumulative and chronic stress, which can serve as a triggering or aggravating factor for many pathological disorders if left unaddressed, has been linked to many life-threatening diseases. While many studies have looked at how optimism and pessimism are used as a form of coping mechanism, few have examined how different bio-psycho-social reactions to stress shape the level of optimism and pessimism. Using a sample of adult individuals aged 18 and older in the United States (n = 3361), this study addressed the following research questions: (1) What types of stress are predictive of optimism and pessimism? (2) Which responses to stress and coping mechanisms are most predictive of optimism and pessimism? (3) Do optimism and pessimism share the same stress-related risk and protective factors? Overall, this study found that while optimism and pessimism share conceptual similarities, they are not necessarily influenced by the same stress mechanisms. Stress, whether personal or financial, was associated with a negative outlook on life. This study showed that having good sleep quality and a lower number of psychological stress symptoms was linked to increasing optimism and reducing pessimism, while overeating or eating unhealthily was connected to both optimism and pessimism. Additionally, this study found that exercise/walking and emotional support mediated the effects of the responses to stress on the respondents’ level of optimism and pessimism.

Abstract Foraging is known to be one of the most important activities in the behavioral budget of chickens. However, how these animals adapt different foraging strategies to diverse environmental variations is currently poorly understood. To gain further insight into this matter, in the present study, hens were submitted to the sloped-tubes task. In this task, the experimenter can manipulate the information that enables the hens to find a food reward (visible or not), placed in one of two hollow tubes. First, 12 hens were tested under free-choice conditions (no penalty for exhaustive searching in both tubes). Under these conditions, the hens adopted a non-random, side-biased strategy when the food location was not directly visible. Then, we divided the hens in two cohorts of equal size to study deeper the hens’ foraging strategy when faced (1) with a different container, or (2) with a restrictive environmental constraint under forced-choice conditions (no food reward if the unbaited tube is visited first). This latter constraint increased the risk of the hen not receiving food. A change in the containers didn’t modify the search behavior of the hens. However, in forced-choice conditions when the location of the food was not directly visible, four out of six hens learned to choose by exclusion. We conclude that hens can selectively adapt their foraging strategy to the point of adopting an exclusion performance, depending on available information and environmental constraints (high or low risk).

Abstract Projected to impact 310 million children by the next decade, childhood obesity is linked to serious health issues like metabolic disturbance and cardiovascular diseases. This study introduces a novel approach for the integrated assessment of inflammatory, glycemic and lipid disorders in obese children in resources-limited settings and also identifies key factors contributing to these changes. Conducting a cross-sectional analysis of 231 children aged 5–12 years from public schools in Brazil's semi-arid region, the research involved collecting medical history, anthropometric measurements, and blood samples to analyze glycemic and lipid profiles, along with C-reactive protein levels. We used an adapted the Molecular Degree of Perturbation model to analyze deviations in metabolic markers from a healthy control group. Statistical analyses included Mann–Whitney and Fisher exact tests, backward logistic regression, and hierarchical cluster analysis. The study identified a direct and independent association between elevated Metabolic Disturbance Degree and both overweight and obesity in children, with significant differences in CRP, Triglycerides, and HDL levels noted between obese and healthy-weight groups. The findings highlight the critical need for early detection and comprehensive understanding of obesity-related changes to mitigate the severe health risks associated with childhood obesity.

IntroductionBreast cancer is a significant public health problem around the world, ranking first in deaths due to cancer in females. The therapy to fight breast cancer involves different methods, including conventional chemotherapy. However, the acquired resistance that tumors develop during the treatment is still a central cause of cancer-associated deaths. One mechanism that induces drug resistance is cell communication via extracellular vesicles (EVs), which can carry efflux transporters and miRNA that increase sensitive cells’ survivability to chemotherapy.MethodsOur study investigates the transcription changes modulated by EVs from tamoxifen- and doxorubicin-resistant breast cancer cells in sensitive cells and how these changes may induce acquired drug resistance, inhibit apoptosis, and increase survivability in the sensitive cells. Additionally, we exposed human macrophages to resistant EVs to understand the influence of EVs on immune responses.ResultsOur results suggest that the acquired drug resistance is associated with the ability of resistant EVs to upregulate several transporter classes, which are directly related to the increase of cell viability and survival of sensitive cells exposed to EVs before a low-dose drug treatment. In addition, we show evidence that resistant EVs may downregulate immune system factors to evade detection and block cell death by apoptosis in sensitive breast cancer cells. Our data also reveals that human macrophages in contact with resistant EVs trigger a pro-inflammatory cytokine secretion profile, an effect that may be helpful for future immunotherapy studies.DiscussionThese findings are the first transcriptome-wide analysis of cells exposed to resistant EVs, supporting that resistant EVs are associated with the acquired drug resistance process during chemotherapy by modulating different aspects of sensitive cancer cells that coffer the chemoresistance.

Abstract The Brownian motion of a point particle induced by quantum vacuum fluctuations of a massless real scalar field in Einstein’s universe is studied. By assuming the small displacement condition, the dispersion in the momentum and position of a point particle coupled to the massless scalar field are obtained. As a consequence of the homogeneity and isotropy properties of the Einstein’s Universe, we find that all components of these physical observables are identical. We also examine divergent behaviors associated with the physical momentum and position dispersions, which we attribute to the IR $$^{1}\times $$ 1 × S $$^{3}$$ 3 compact topology of Einstein’s universe. Finally, based on the small displacement condition assumed, we analyze the limit of validity of our investigation.

BackgroundEmotions can be regulated through several regulatory strategies that are involved in the development of psychopathological symptoms. Despite the well-established association between psychopathology and emotion dysregulation, little is known about the relationship between individual symptoms of depression and anxiety and emotion regulation strategies (ERS), as well as between ERS themselves.MethodWe conducted a cross-sectional study and examined the interactions between six ERS (reappraisal, engagement, rumination, suppression, arousal control, and distraction) and assessed their distinctive association with the activation of specific symptoms of depression and anxiety in a community sample of 376 adults (80.4% female; Mage = 32.70; SDage = 11.80). The Regulation Emotion Systems Survey (RESS) was used to measure ERS. The Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) were used to assess psychological symptoms. An exploratory graph analysis was performed to examine the structural properties of the network of interactions between these behaviors. Additionally, to test the association of ERS with the activation of the depression symptoms network, an expected symptoms activity (ESA) was conducted.ResultsSix communities were found that correspond to the six ERS. Rumination and suppression have a significant association with symptom activation (particularly low self-esteem), whereas reappraisal reduces symptomatic activation. The effect of arousal control, engagement, and distraction appears to depend on the remaining ERS rather than having much influence on their own.ConclusionThis study provides insight into how ERS interact with each other and with individual symptoms of depression and anxiety. Understanding the effects of these interactions on symptom activation and comorbidity can improve our understanding of psychopathology.

Abstract Recently, the tiger-cat species complex was split into Leopardus tigrinus and Leopardus guttulus, along with other proposed schemes. We performed a detailed analysis integrating ecological modeling, biogeography, and phenotype of the four originally recognized subspecies—tigrinus, oncilla, pardinoides, guttulus—and presented a new multidimensional niche depiction of the species. Species distribution models used > 1400 records from museums and photographs, all checked for species accuracy. Morphological data were obtained from institutional/personal archives. Spotting patterns were established by integrating museum and photographic/camera-trap records. Principal component analysis showed three clearly distinct groups, with the Central American specimens (oncilla) clustering entirely within those of the Andes, namely the pardinoides group of the cloud forests of the southern Central-American and Andean mountain chains (clouded tiger-cat); the tigrinus group of the savannas of the Guiana Shield and central/northeastern Brazil (savanna tiger-cat); and the guttulus group in the lowland forests of the Atlantic Forest domain (Atlantic Forest tiger-cat). This scheme is supported by recent genetic analyses. All species displayed different spotting patterns, with some significant differences in body measurements/proportions. The new distribution presented alarming reductions from the historic range of − 50.4% to − 68.2%. This multidimensional approach revealed a new species of the elusive and threatened tiger-cat complex.

Background: This study began with a search in three databases, totaling six libraries (ChemBridge-DIVERSet, ChemBridge-DIVERSet-EXP, Zinc_Drug Database, Zinc_Natural_Stock, Zinc_FDA_BindingDB, Maybridge) with approximately 2.5 million compounds with the aim of selecting potential inhibitors with antiproliferative activity on the chimeric tyrosine kinase encoded by the BCR-ABL gene. Methods: Through hierarchical biochemoinformatics, ADME/Tox analyses, biological activity prediction, molecular docking simulations, synthetic accessibility and theoretical synthetic routes of promising compounds and their lipophilicity and water solubility were realized. Results: Predictions of toxicological and pharmacokinetic properties (ADME/Tox) using the top100/base (600 structures), in comparison with the commercial drug imatinib, showed that only nine exhibited the desired properties. In the prediction of biological activity, the results of the nine selected structures ranged from 13.7% < Pa < 65.8%, showing them to be potential protein kinase inhibitors. In the molecular docking simulations, the promising molecules LMQC01 and LMQC04 showed significant values in molecular targeting (PDB 1IEP—resolution 2.10 Å). LMQC04 presented better binding affinity (∆G = −12.2 kcal mol−1 with a variation of ±3.6 kcal mol−1) in relation to LMQC01. The LMQC01 and LMQC04 molecules were advanced for molecular dynamics (MD) simulation followed by Molecular Mechanics with generalized Born and Surface Area solvation (MM-GBSA); the comparable, low and stable RMSD and ΔE values for the protein and ligand in each complex suggest that the selected compounds form a stable complex with the Abl kinase domain. This stability is a positive indicator that LMQC01 and LMQC04 can potentially inhibit enzyme function. Synthetic accessibility (SA) analysis performed on the AMBIT and SwissADME webservers showed that LMQC01 and LMQC04 can be considered easy to synthesize. Our in silico results show that these molecules could be potent protein kinase inhibitors with potential antiproliferative activity on tyrosine kinase encoded by the BCR-ABL gene. Conclusions: In conclusion, the results suggest that these ligands, particularly LMQC04, may bind strongly to the studied target and may have appropriate ADME/Tox properties in experimental studies. Considering future in vitro or in vivo assays, we elaborated the theoretical synthetic routes of the promising compounds identified in the present study. Based on our in silico findings, the selected ligands show promise for future studies in developing chronic myeloid leukemia treatments.

This study aimed to isolate, purify and characterize secondary metabolites present in Amburana acreana leaves, native to the state of Rondônia, using classical chromatographic methods and 1D, 2D nuclear magnetic resonance spectroscopy. From the hydroethanolic leaves extract of A. acreana, p-hydroxybenzoic acid, vanillic acid, coumarin, campesterol 3-β-D-glucoside and amburoside B, all known compounds, were identified. To the best of our knowledge, this is the first report of isolation and chemical characterization of secondary metabolites in A. acreana. In addition, in vitro assays indicated that amburoside B does not have inhibitory potential on the growth of gram-negative bacteria. The presence of these compounds suggests that, thus far, amburosides (A and B) could be chemotaxonomic markers of the genus Amburana.

The irreproducibility in scientific research has become a critical issue. Despite the essential role of rigorous methodology in constructing a scientific article, more than half of publications, on average, are considered non-reproducible. The implications of this irreproducibility extend to reliability problems, hindering progress in technological production and resulting in substantial financial losses. In the context of laboratory animal research, this work emphasizes the importance of choosing an appropriate experimental model within the 3R’s principle (Refine, Reduce, Replace). This study specifically addresses a deficiency in data specification in scientific articles, revealing inadequacies in the description of crucial details, such as environmental conditions, diet, and experimental procedures. For this purpose, 124 articles from journals with relevant impact factors were analyzed, conducting a survey of data considered important for the reproducibility of studies. Important flaws in the presentation of data were identified in most of the articles evaluated. The results of this study highlight the need to improve the description of essential information, standardizing studies, and ensuring the reproducibility of experiments in areas such as metabolism, immunity, hormones, stress, among others, to enhance the reliability and reproduction of experimental results, aligning with international guidelines such as ARRIVE and PREPARE.

Abstract The epidemiology of psoriasis and cutaneous mycoses is scarce in Brazil. Thus, this cross-sectional study aimed to characterize the distribution of these diseases in Paraná. Data was obtained from the Outpatient Information System (SIA - Sistema de Informações Ambulatoriais), between 2016 and 2020. The procedures were filtered by the International Classification of Diseases (ICD). A total of 201,161 outpatient procedures were registered for psoriasis and psoriatic arthritis. The distribution concerning gender was similar (50.93% feminine; 49.07% masculine). The mean age was 51.55 years. The most frequent procedure was methotrexate dispensing (23.17%), followed by acitretin (14.29%) and adalimumab (12.55%). Adjusting to total population, the prevalence of procedures was 0.35%. Regarding cutaneous mycoses, 1,756 procedures were registered. 65% of them referred to females. White race/color was predominant (82.97%). The mean age was 37.6 years. The distribution concerning age varied according to the type of mycosis. Medical appointments (48.92%) and surgical pathology exam/biopsy (38.71%) were the most frequent procedures. The prevalence of procedures was 0.004%. This is the first epidemiological study using SIA about the population affected by psoriasis, psoriatic arthritis, and cutaneous mycoses in a Brazilian state. We believe that these findings allow relevant contribution to science and public policies in Brazil.

ObjectivesThis study tested the acceptability and efficacy of an Acceptance and Commitment Therapy and compassion-based intervention (LIFEwithIBD) in people with IBD through a two-arm RCT.MethodsParticipants were recruited at the Gastroenterology Department of the Coimbra University Hospital between June and September 2019. Of the 355 patients screened, those who accepted to participate were randomly assigned to one of two conditions: experimental group (LIFEwithIBD; n = 25) or control group (waitlist; n = 29). Participants completed self-report measures at baseline (T0), post-intervention (T1), and 3-month (T2) and 12-month (T3) follow-ups. Intervention acceptability was assessed. Efficacy was examined using intent-to-treat ANCOVA at post-intervention after adjusting for baseline values of depressive, anxiety, and stress symptoms (primary outcomes). Linear mixed models for all longitudinal outcomes were also analysed. Inflammatory and disease biomarkers were determined at T0 and T3.ResultsAcceptability results revealed a high level of satisfaction and perceived usefulness regarding the intervention. Both groups experienced a significant decrease in stress symptoms and IBD symptom perception at T1. No significant differences were observed at follow-up for the primary outcomes. The experimental group reported significantly lower Crohn’s disease Symptom severity at T2 than the control group. Post-hoc analyses designed to mitigate floor effects revealed substantial treatment effects for the experimental group regarding anxiety symptoms. No significant differences were observed in clinical biomarkers from T0 to T3.ConclusionThe LIFEwithIBD intervention shows promising, although preliminary, benefits for managing disease activity and reducing anxiety symptoms in IBD patients with high severity of psychological distress.Clinical trial registration: https://www.clinicaltrials.gov/ct2/show/NCT03840707, identifier NCT03840707.

The decline of insect pollinators is a growing concern for many reasons, one of which is the impact it may have on the production of protein. Insects play a crucial role in the pollination of many crops and wild plants, both of which may impact global protein production. Pollinator-dependent leguminous crops such as soybean have an important role in meeting the protein requirements of the global population, whilst a number of pollinator-dependent fodder plants such as clover and alfalfa are widely fed to livestock. Thus, without pollinators, the availability of many plant-based products, as well as the production of protein derived from livestock, could be greatly affected. This represents an important and largely overlooked aspect of pollinator reliance which further emphasises the importance of conserving pollinator biodiversity and managing pollination services more effectively in both arable and livestock farming systems. Doing so will ensure the sustainable ongoing production of both plant and animal-based protein and contribute towards achieving sustainable food and nutrition security for populations around the world.

We report a human coronavirus OC43 infection outbreak in hospitalized patients and healthcare workers in São Paulo, Brazil, occurring after SARS-CoV-2 cases disappeared. Infection was associated with healthcare workers in 5 (29.4%) patients. Routine surveillance including a respiratory virus panel can improve coronavirus detection in both healthcare professionals and patients.

A retrospective study was made of 83 diabetic patients admitted to the Department of Internal Medicine between January 1986 and December 1993, with acute intercurrence of the disease. The authors considered some clinical features (age, type and frequency of complication, form of presentation, causal aetiology, laboratory findings and therapeutic options). Statistical relationships between different populations were made using the unpaired Student's T. method. Results were compared with those in the literature, leading to some significant conclusions.

Abstract The economic, social, cultural and political milieus that influence injection drug-related HIV risk behaviors along the US–Mexico border in the previous decade have been studied comparing cities on an East–West axis. In an effort to inform interventions targeting factors beyond the individual level, we used a cross-sectional study design comparing people who inject drugs during 2016–2018, living on a North–South axis, in two cities—Ciudad Juárez, Chihuahua, Mexico and El Paso, Texas, USA—situated at the midpoint of the 2000 US–Mexico borderland stretch. We conceptualize injection drug use and its antecedents and consequences as influenced by factors operating at various levels of influence. Results of analysis comparing samples recruited from each border city indicated significant differences in demographic, socioeconomic, micro- and macro-level factors that affect risk. Similarities emerged in individual-level risk behaviors and some dynamics of risk at the drug use site most frequented to use drugs. In addition, analyses testing associations across samples indicated that different contextual factors such as characteristics of the drug use sites influenced syringe sharing. In this article, we reflect on the potential tailored interventions needed to target the context of HIV transmission risk among people who use drugs and reside in binational environment.

Abstract Scleractinian corals are primary contributors to the structural complexity of coral reef ecosystems. The structure derived from their carbonate skeletons underpins the biodiversity and myriad of ecosystem services provided by coral reefs. This study used a trait-based approach to provide new insights into the relationships between habitat complexity and coral morphology. Three-Dimensional (3D) photogrammetry techniques were used to survey 208 study plots on the island of Guam, from which structural complexity metrics were derived and physical traits of corals were quantified. Three traits at the individual colony level (e.g., morphology, size, and genera) and two site-level environmental characteristics (e.g., wave exposure and substratum-habitat type) were examined. Standard taxonomy-based metrics were also included at the reef-plot level (e.g., coral abundance, richness, and diversity). Different traits disproportionately contributed to 3D metrics of habitat complexity. Larger colonies with a columnar morphology have the highest contribution to surface complexity, slope, and vector ruggedness measure, whereas branching and encrusting columnar colonies have the highest contribution to planform and profile curvature. These results highlight the importance of considering colony morphology and size in addition to conventional taxonomic metrics for the understanding and monitoring reef structural complexity. The approach presented here provides a framework for studies in other locations to predict the trajectory of reefs under changing environmental conditions.

Purpose The isometric mid-thigh pull (IMTP) test is a strength test usually requiring expensive equipment like a force platform. Low-cost alternatives could make IMTP testing more accessible. Previous research reported high systematic bias when comparing low-cost devices with more expensive criterion devices (force platforms). This study investigated the concurrent validity and intra-session reliability of a custom-built low-cost IMTP device using a load cell. Methods Overall, 17 recreationally resistance-trained men (25 ± 6 years, 83 ± 14 kg, 178 ± 7 cm, 5 ± 3 years of resistance training experience) first visited the laboratory to be familiarized with testing protocols and returned 2–3 days later for IMTP testing with the low-cost device and a laboratory-grade force platform. Results The overall bias was trivial (–0.8%, 95% CI: –5.7 to 4.3%). The typical error of the estimate was moderate (10.2%, 95% CI: 7.4–16.2%). A strong correlation of 0.91 (95% CI: 0.76–0.97) was found between peak force values from both devices; the low-cost IMTP device accounted for 81.3% of the variation in force platform. The low-cost IMTP also demonstrated acceptable scores for reliability and agreement (ICC = 0.96, 95% CI: 0.89–0.98; typical error = 5.0%, 95% CI: 3.7–7.7%), similar to the criterion (ICC = 0.97, 95% CI: 0.91–0.99; typical error = 4.5%, 95% CI: 3.3–7.1%). Conclusions The low-cost IMTP device using a load cell was valid and reliable for maximal force production in recreationally trained men and provided results comparable with those of a force platform.

Abstract In this paper we investigate the Quantum Brownian motion of a point particle induced by quantum vacuum fluctuations of a massless scalar field in (3 + 1)-dimensional Minkowski spacetime with distinct conditions (Dirichlet, Neumann, mixed and quasiperiodic). The modes of the field are confined and compactified to a finite length region, which consequently provides a natural measure scale for the system. Useful expressions for the Wightman function have been obtained, which allow us to calculate analytical expressions for the velocity dispersion in all condition cases considered. We also obtain expressions for the velocity dispersion in the short and late time regimes. Finally, we exhibit some graphs in order to show the behavior of the velocity dispersions, discussing important divergencies that are present in our results.

Abstract Aedes aegypti control is achieved with chemical insecticides that can promote insecticide resistance. In the search for new forms of control, the use of botanical products is currently growing and many tests with oils have already been performed. The plant diversity of Araripe National Forest enables the study of several species against this vector. To evaluate the larvicidal effect of essential oils from plants of this forest, we used field rosemary, copaiba, bay leaf, cashew and pequi. The work was divided into three stages: all oils with the same dosage; the best oil at dosages of 0, 5, 10, 20, 50 and 75 µg/mL; and the best dosage at temperatures of 15, 20, 25, 30 and 35 °C. The oils of field rosemary, copaiba, bay leaf, cashew and pequi were good insecticides when used at dosages above 5 μg/mL. The bay leaf oil showed high larvicidal activity at all dosages tested, showing the highest efficiency at 75 μg/mL. Temperatures of 15 and 35 °C increased the susceptibility of the insect to the effect of the bay leaf oil. The essential oils of field rosemary, copaiba, bay leaf, cashew and pequi, from Araripe National Forest, applied at a dosage of 5μg/mL, showed insecticidal action, although with low efficiency

Atmospheric mercury (Hg) observations in the lower free troposphere (LFT) can give important insights into Hg redox chemistry and can help constrain Hg background concentrations on a regional level. Relatively continuous sampling of LFT air, inaccessible to most ground-based stations, can be achieved at high-altitude observatories. However, such high-altitude observatories are rare, especially in the Southern Hemisphere (SH), and atmospheric Hg in the SH LFT is unconstrained. To fill this gap, we continuously measured gaseous elemental mercury (GEM; hourly) and reactive mercury (RM; integrated over ∼ 6–14 d) for 9 months at Maïdo mountain observatory (2160 m a.s.l.) on remote Réunion Island (21.1∘ S, 55.5∘ E) in the tropical Indian Ocean. GEM exhibits a marked diurnal variation characterized by a midday peak (mean: 0.95 ng m−3; SD: 0.08 ng m−3) and a nighttime low (mean: 0.78 ng m−3; SD: 0.11 ng m−3). We find that this diurnal variation is likely driven by the interplay of important GEM photo-reemission from the islands' vegetated surfaces (i.e. vegetation + soil) during daylight hours (8–22 ng m−2 h−1), boundary layer influences during the day, and predominant LFT influences at night. We estimate GEM in the LFT based on nighttime observations in particularly dry air masses and find a notable seasonal variation, with LFT GEM being lowest from December to March (mean 0.66 ng m−3; SD: 0.07 ng m−3) and highest from September to November (mean: 0.79 ng m−3; SD: 0.09 ng m−3). Such a clear GEM seasonality contrasts with the weak seasonal variation reported for the SH marine boundary layer but is in line with modeling results, highlighting the added value of continuous Hg observations in the LFT. Maïdo RM is 10.6 pg m−3 (SD: 5.9 pg m−3) on average, but RM in the cloud-free LFT might be about twice as high, as weekly–biweekly sampled RM observations are likely diluted by low-RM contributions from the boundary layer and clouds.

The design, synthesis, and evaluation of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are big challenges today. In this work, two 5-acetamido-2-hydroxy benzoic acid derivatives were proposed, increasing the alkyl position (methyl) in an acetamide moiety, and synthesized, and their structural elucidation was performed using 1H NMR and 13C NMR. The changes in methyl in larger groups such as phenyl and benzyl aim to increase their selectivity over cyclooxygenase 2 (COX-2). These 5-acetamido-2-hydroxy benzoic acid derivatives were prepared using classic methods of acylation reactions with anhydride or acyl chloride. Pharmacokinetics and toxicological properties were predicted using computational tools, and their binding affinity (kcal/mol) with COX-2 receptors (Mus musculus and Homo sapiens) was analyzed using docking studies (PDB ID 4PH9, 5KIR, 1PXX and 5F1A). An in-silico study showed that 5-acetamido-2-hydroxy benzoic acid derivates have a better bioavailability and binding affinity with the COX-2 receptor, and in-vivo anti-nociceptive activity was investigated by means of a writhing test induced by acetic acid and a hot plate. PS3, at doses of 20 and 50 mg/kg, reduced painful activity by 74% and 75%, respectively, when compared to the control group (20 mg/kg). Regarding the anti-nociceptive activity, the benzyl showed reductions in painful activity when compared to acetaminophen and 5-acetamido-2-hydroxy benzoic acid. However, the proposed derivatives are potentially more active than 5-acetamido-2-hydroxy benzoic acid and they support the design of novel and safer derivative candidates. Consequently, more studies need to be conducted to evaluate the different pharmacological actions, the toxicity of possible metabolites that can be generated, and their potential use in inflammation and pain therapy.

The present study investigated the effects of different intensities of FIFA11+ on the physical performance of U-15 soccer players. Eighteen U-15 soccer players (13.3 ± 0.7 years) performed five randomized conditioning activities (CA), with each CA separated by 3–7 days. The five CA were: 1) FIFA11+ at level 1 (F1); 2) FIFA11+ at level 2 (F2); 3) FIFA11+ at level 3 (F3); 4) FIFA11+ at reduced version (FR); and 5) Standard warm-up of the players (Control). The subjective session rating of perceived exertion (session-RPE), countermovement jump (CMJ), 10-m sprint, and 505 agility test were measured 5 min after each CA. CMJ was higher in the FR (29.6 ± 5.5 cm) compared to the F1 (27.7 ± 4.6 cm) (p0.05). The sprint performance was higher in the Control (1.937±0.166 s) and FR (1.931±0.123 s) compared to the F1 (2.006±0.113 s) (p0.05). Agility performance did not differ between conditions (FR: 2.756±0.205 s; F1: 2.7286±0.229 s; F2: 2.832±0.228 s; F3: 2.804±0.209 s; CON: 2.756±0.205 s; p>0.05). Session-RPE was considered hard for all CA, with no significant differences among conditions (p>0.05). The internal training load was higher in the F1, F2, and F3 compared to the FR and CON (p

Leishmaniasis is a group of parasitic diseases with the potential to infect more than 1 billion people; however, its treatment is still old and inadequate. In order to contribute to changing this view, this work consisted of the development of complexes derived from MI metal ions with thioureas, aiming to obtain potential leishmanicidal agents. The thiourea ligands (HLR) were obtained by reactions of p-toluenesulfohydrazide with R-isothiocyanates and were used in complexation reactions with AgI and AuI, leading to the formation of complexes of composition [M(HLR)2]X (M = Ag or Au; X = NO3− or Cl−). All compounds were characterized by FTIR, 1H NMR, UV-vis, emission spectroscopy and elemental analysis. Some representatives were additionally studied by ESI-MS and single-crystal XRD. Their properties were further analyzed by DFT calculations. Their cytotoxicity on Vero cells and the extracellular leishmanicidal activity on Leishmania infantum and Leishmania braziliensis cells were evaluated. Additionally, the interaction of the complexes with the Old Yellow enzyme of the L. braziliensis (LbOYE) was examined. The biological tests showed that some compounds present remarkable leishmanicidal activity, even higher than that of the standard drug Glucantime, with different selectivity for the two species of Leishmania. Finally, the interaction studies with LbOYE revealed that this enzyme could be one of their biological targets.

Aim of study: To address diversification of citrus cultivars to increase the variety and profitability of orchards to adapt them to environmental changes. Area of study: State of São Paulo, a subtropical region of southeastern Brazil. Material and methods: The study evaluated the phenological intervals, thermal sum, vegetative and productive performance, and fruit quality of the sweet orange cultivars ‘Rubi’ (R), ‘Lue Gin Gong’ (LGG) and ‘Valencia Delta Seedless’ (VDS) grafted onto 'Rangpur' lime (RL) and 'Swingle' citrumelo (SC). The field experiment was conducted over consecutive growing seasons 2018-2021. Main results: The duration of the phenological intervals was little influenced by the rootstocks. The harvest time was approximately 245 days after anthesis (DAA) for R, 402 DAA for LGG, and 407 DAA for VDS, regardless of rootstock. Scion cultivars grafted onto RL showed larger canopy volumes and greater weight, length, and diameter of fruits than those of SC trees, and the combinations with SC were more productively efficient than RL due to lower canopy volume. The R scion cultivar presented superior yield performance and fruit colouration than LGG and VDS. The physicochemical quality of the fruits showed improved results with the combinations of LGG/RL, LGG/SC, VDS/RL, and VDS/SC. Research highlights: These results may be useful when planning the diversification of scion/rootstock combinations for new orchards, identifying dual-market orange cultivars for industrial processing and natural consumption, and determining the combinations that are better adapted to undesirable climatic conditions.

Background: Neurotransmitters deficits in Frontotemporal Dementia (FTD) are still poorly understood. Better knowledge of neurotransmitters impairment, especially in prodromal disease stages, might tailor symptomatic treatment approaches. Methods: In the present study, we applied JuSpace toolbox, which allowed for cross-modal correlation of Magnetic Resonance Imaging (MRI)-based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, GABAergic and glutamatergic neurotransmission.We included 392 mutation carriers (157 GRN, 164 C9orf72, 71 MAPT), together with 276 non-carrier cognitively healthy controls (HC). We tested if the spatial patterns of grey matter volume (GMV) alterations in mutation carriers (relative to HC) are correlated with specific neurotransmitter systems in prodromal (CDR® plus NACC FTLD = 0.5) and in symptomatic (CDR® plus NACC FTLD≥1) FTD. Results: In prodromal stages of C9orf72 disease, voxel-based brain changes were significantly associated with spatial distribution of dopamine and acetylcholine pathways; in prodromal MAPT disease with dopamine and serotonin pathways, while in prodromal GRN disease no significant findings were reported (p