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Epoxyeicosatrienoic acids (EET) and related epoxy fatty acids (EpFA) are endogenous anti-inflammatory compounds, which are converted by the soluble epoxide hydrolase (sEH) to dihydroxylethersatrienoic acids (DHETs) with lessened biological effects. Inhibition of sEH is used as a strategy to increase EET levels leading to lower inflammation. Rheumatoid arthritis is a chronic autoimmune disease that leads to destruction of joint tissues. This pathogenesis involves a complex interplay between the immune system, and environmental factors. Here, we investigate the effects of inhibiting sEH with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) on a collagen-induced arthritis model. The treatment with TPPU ameliorates hyperalgesia, edema, and decreases the expression of important pro-inflammatory cytokines of Th1 and Th17 profiles, while increasing Treg cells. Considering the challenges to control RA, this study provides robust data supporting that inhibition of the sEH is a promising target to treat arthritis.

Several randomized controlled trials (RCTs) comparing en bloc resection of bladder tumor (ERBT) to conventional transurethral resection of bladder tumor (cTURBT) have reported controversial results. In particular, the 1-yr recurrence rate ranged from 5% to 40% for ERBT and from 11% to 31% for cTURBT. We provide an updated analysis of an RCT comparing the 1-yr recurrence rate for ERBT versus cTURBT for a cohort of 219 patients comprising 123 (56.2%) in the ERBT group and 96 (43.8%) in the cTURBT group. At 1 yr, 11 patients in the ERBT group and 12 in the cTURBT group experienced recurrence. The heterogeneity in recurrence observed in other RCTs could be explained by the scarce and heterogeneous adoption of tools and techniques that have been proved to lower the recurrence rate, supporting the need for implementation of a TURBT checklist. This prompted us to create a checklist of items for RCTs to standardize how TURBT is performed in trials, facilitate comparison between studies, assess the applicability of results in real-life practice, and provide a push towards high-quality resections to improve oncological outcomes. The checklist could have utility as a user-friendly guide for reporting TURBT procedures to improve our understanding of trials involving this procedure. Patient summary: We compared the recurrence rate at 1 year for bladder cancer treated with two different approaches to remove bladder tumors in our center. The rates were comparable for the two groups. Other studies have found widely differing recurrence rates, so we propose use of a checklist to standardize these procedures and provide more consistent outcomes for patients.

Con la revolución de septiembre de 1868 se instaura un régimen político en el que las libertades civiles se ven más respetadas, en particular la libertad de prensa, por lo cual se desarrollan desde el comienzo y de forma significativa varias tipologías de actividades editoriales, desde las satíricas hasta las políticas, vinculadas a las distintas corrientes que hacen valer sus propuestas con respecto a las instituciones que deberán remplazar a las viejas. También el carlismo se muestra más bien activo en el ámbito periodístico, cuando –por primera vez en su historia– toma el camino de la lucha pacífica, si bien sin abandonar la opción de una vía armada. Tras un apartado de contextualización y de análisis general de las características de la prensa carlista en el primer periodo del Sexenio, se pasa a un caso de estudio específico, tomando en consideración dos periódicos, uno continuación del otro: El Legitimista Español y La Legitimidad, no tan estudiados como los más conocidos La Esperanza, La Regeneración o El Pensamiento Español. La elección de estos dos periódicos permite profundizar en las cuestiones políticas a las que los carlistas han de enfrentarse en la primera parte del Sexenio, ya que su director es uno de los diputados tradicionalistas más activos en las Cortes: Cruz Ochoa, quien será, tras 1872, un convencido combatiente de la guerra civil.

Abstract A compact broadband Edge-Line Coupler (ELC) based on Parity Time-reversal Duality (PTD) symmetry has been conceived, designed, constructed and measured. The coupler connects four PTD bifilar edge lines (BELs), recently introduced by the authors. The PTD-BELs are constituted by a parallel plate waveguide whose walls are formed by a junction between Perfect Electric Conductor (PEC) and Perfect Magnetic Conductor (PMC) boundary conditions. Reversing the axis orthogonal to the plates interchanges the position of PEC and PMC. Such a waveguide supports unimodal transverse electromagnetic (TEM) propagation, extremely confined along the top and bottom junction edges; its propagation is protected against backscattering from any discontinuity that preserves the PTD symmetry. The ELC presented here is constituted by a 4-port junction in which each port is intrinsically matched due to the PTD symmetry, strongly coupled with a second port, strongly decoupled with a third port, and weakly coupled with a fourth port. The ELC is designed by using a mushroom metasurface for the PMC portion of the device; the connection is based on a switch circuit which imposes open and short conditions on the two opposite sides of the structure. Switching simultaneously the open and short circuits reroutes the signal in a different port, while maintaining the same level of coupling with the other ports. A static prototype has been built and its measurements have confirmed the matching performance and the good directionality of the coupler in a broadband frequency range between 24 and 30 GHz.

Stroke is a neurological deficit of cerebrovascular origin that promotes physical impairments of adult individuals. The present study is aimed to demonstrate whether hemorrhagic stroke affects the maximum molar bite force. The prospective study carried in Centro Universitario Claretiano de Batatais, Brazil, determined the distribution of the sample into two groups: hemorrhagic stroke group (n=18, median age, 62.5 years) and disease-free group (n=18, median age, 62.0 years), with 10 men and 8 women in each group. Subjects were paired one-to-one (age and body mass index). The dynamometer was used to measure the maximum molar bite force (right and left). All analyses were performed with a significance level of 5% (Student’s t-test). Differences were found on the right (p=0.048) and left (p=0.042) molar bite force, with lower bite force (both sides) in hemorrhagic stroke group. The study suggests that hemorrhagic stroke negatively affects the maximum molar bite force and necessitates changes in food intake to nutritious and softer consistency foods.

ABSTRACT Desmodus rotundus, vampire bats, transmit dangerous infections, and brucellosis is a hazardous zoonotic disease, two adversities that coexist in the subtropical and tropical areas of the American continent. Here, we report a 47.89% Brucella infection prevalence in a colony of vampire bats inhabiting the tropical rainforest of Costa Rica. The bacterium induced placentitis and fetal death in bats. Wide-range phenotypic and genotypic characterization placed the Brucella organisms as a new pathogenic species named Brucella nosferati sp. nov., isolated from bat tissues, including the salivary glands, suggesting feeding behavior might favor transmission to their prey. Overall analyses placed B. nosferati as the etiological agent of a reported canine brucellosis case, demonstrating its potential for infecting other hosts. To assess the putative prey hosts, we analyzed the intestinal contents of 14 infected and 23 non-infected bats by proteomics. A total of 54,508 peptides sorted into 7,203 unique peptides corresponding to 1,521 proteins were identified. Twenty-three wildlife and domestic taxa, including humans, were foraged by B. nosferati-infected D. rotundus, suggesting contact of this bacterium with a broad range of hosts. Our approach is appropriate for detecting, in a single study, the prey preferences of vampire bats in a diverse area, demonstrating its suitability for control strategies where vampire bats thrive. IMPORTANCE The discovery that a high proportion of vampire bats in a tropical area is infected with pathogenic Brucella nosferati and that bats forage on humans and many wild and domestic animals is relevant from the perspective of emerging disease prevention. Indeed, bats harboring B. nosferati in their salivary glands may transmit this pathogenic bacterium to other hosts. This potential is not trivial since, besides the demonstrated pathogenicity, this bacterium possesses all the required virulent arsenal of dangerous Brucella organisms, including those that are zoonotic for humans. Our work has settled the basis for future surveillance actions in brucellosis control programs where these infected bats thrive. Moreover, our strategy to identify the foraging range of bats may be adapted for exploring the feeding habits of diverse animals, including arthropod vectors of infectious diseases, and therefore of interest to a broader audience besides experts on Brucella and bats.

In teleosts, two PepT1-type (Slc15a1) transporters, i.e., PepT1a and PepT1b, are expressed at the intestinal level. They translocate charged di/tripeptides with different efficiency, which depends on the position of the charged amino acid in the peptide and the external pH. The relation between the position of the charged amino acid and the capability of transporting the dipeptide was investigated in the zebrafish and Atlantic salmon PepT1-type transporters. Using selected charged (at physiological pH) dipeptides: i.e., the negatively charged Asp-Gly and Gly-Asp, and the positively charged Lys-Gly and Gly-Lys and Lys-Met and Met-Lys, transport currents and kinetic parameters were collected. The neutral dipeptide Gly-Gln was used as a reference substrate. Atlantic salmon PepT1a and PepT1b transport currents were similar in the presence of Asp-Gly and Gly-Asp, while zebrafish PepT1a elicited currents strongly dependent on the position of Asp in the dipeptide and zebrafish PepT1b elicited small transport currents. For Lys- and Met-containing dipeptides smaller currents compared to Gly-Gln were observed in PepT1a-type transporters. In general, for zebrafish PepT1a the currents elicited by all tested substrates slightly increased with membrane potential and pH. For Atlantic salmon PepT1a, the transport current increased with negative potential but only in the presence of Met-containing dipeptides and in a pH-dependent way. Conversely, large currents were shown for PepT1b for all tested substrates but Gly-Lys in Atlantic salmon. This shows that in Atlantic salmon PepT1b for Lys-containing substrates the position of the charged dipeptides carrying the Lys residue defines the current amplitudes, with larger currents observed for Lys in the N-terminal position. Our results add information on the ability of PepT1 to transport charged amino acids and show species-specificity in the kinetic behavior of PepT1-type proteins. They also suggest the importance of the proximity of the substrate binding site of residues such as LysPepT1a/GlnPepT1b for recognition and specificity of the charged dipeptide and point out the role of the comparative approach that exploits the natural protein variants to understand the structure and functions of membrane transporters.

ObjectiveDementias and mild cognitive impairment (MCI) are associated with variously combined changes in the neurotransmitter system and signaling, from neurotransmitter synthesis to synaptic binding. The study tested the hypothesis that different dementia subtypes and MCI may share similar reductions of brain availability in amino acid precursors (AAPs) of neurotransmitter synthesis and concomitant similar impairment in energy production and increase of oxidative stress, i.e., two important metabolic alterations that impact neurotransmission.Materials and methodsSixty-five demented patients (Alzheimer’s disease, AD, n = 44; frontotemporal disease, FTD, n = 13; vascular disease, VaD, n = 8), 10 subjects with MCI and 15 control subjects (CTRL) were recruited for this study. Cerebrospinal fluid (CSF) and plasma levels of AAPs, energy substrates (lactate, pyruvate), and an oxidative stress marker (malondialdehyde, MDA) were measured in all participants.ResultsDemented patients and subjects with MCI were similar for age, anthropometric parameters, biohumoral variables, insulin resistance (HOMA index model), and CSF neuropathology markers. Compared to age-matched CTRL, both demented patients and MCI subjects showed low CSF AAP tyrosine (precursor of dopamine and catecholamines), tryptophan (precursor of serotonin), methionine (precursor of acetylcholine) limited to AD and FTD, and phenylalanine (an essential amino acid largely used for protein synthesis) (p = 0.03 to

Resumo: Introdução: A pedagogia freiriana aponta a educação como uma prática social consoante a uma realidade em transformação e direcionada às demandas de seu público. Na educação médica, aplica-se tal concepção quando o ato pedagógico é um modelo de cuidado para os discentes. Nesse sentido, estratégias que promovem a expressão de sentimentos de forma livre, lúdica e criativa são práticas que promovem o cuidado e contribuem para uma formação humanista e reflexiva, como preconizado nas DCN para o curso de graduação em Medicina. O objetivo deste relato de experiência é compartilhar uma experiência bem-sucedida da utilização de memes em uma atividade de feedback do componente curricular de Saúde Coletiva de um curso de Medicina de uma universidade federal brasileira. Relato de experiência: No último encontro do semestre, os estudantes, reunidos em pequenas equipes, foram orientados a criar memes que refletissem suas principais percepções acerca do módulo, ou seja, que destacassem os momentos mais marcantes e os aprendizados compartilhados ao longo do semestre. Em seguida, a turma toda se reuniu por videochamada, e um representante de cada equipe fez o feedback apreciativo do semestre utilizando o meme criado, além de compartilhar o “momento a-há” elegido pelo grupo, ou seja, o mais marcante e transformador do módulo. Discussão: Percebe-se que a utilização de memes e outros recursos lúdicos na educação médica é importante e recomendada, pois, além de tornar o processo de aprendizagem mais ativo e efetivo, o que está de acordo com os princípios das DCN, é uma forma de cuidado em saúde com os discentes. Além disso, essa dinâmica permite uma maior interação entre os alunos e estimula o senso de pertencimento. Ademais, a realização de feedbacks na graduação de Medicina é fundamental para o processo de aprendizado e também para o aprimoramento de habilidades necessárias à prática profissional, e essa atividade se mostrou facilitada e efetiva quando feita por meio do uso de memes. Conclusão: A utilização de memes na sessão de feedback se mostrou benéfica, criativa e salutogênica, além de ser uma estratégia que preza o cuidado e a expressão de sentimentos dos alunos, e, por isso, deve ser encorajada.

Objectives Knowledge about multiple sclerosis (MS) is crucial for those who provide care and support as caregivers. However, despite the key benefits of acquiring relevant information to properly assume the caregiving role, caregivers’ knowledge of MS is poorly investigated. The aim of this study was to develop and validate the Caregivers’ Knowledge of Multiple Sclerosis (CareKoMS), a self-assessed questionnaire, to test MS knowledge in caregivers of people with MS.Design Cross-sectional study.Setting Italy.Participants Two-hundred caregivers (female: 49%) were asked to self-administer the 32-item CareKoMS questionnaire; they had a median age of 60 years (IQR: 51–68 years) and a medium–high educational level (36.5% primary school and 63.5% high school/university). Item analysis using item difficulty index, item discrimination index, Kuder-Richardson-20 coefficient and item-total correlation were assessed. Once excluding less useful items, reliability, floor and ceiling effects and construct validity were calculated on the 21-item CareKoMS final version.Results Psychometric evaluation indicates that the 21-item CareKoMS was a good questionnaire with no ceiling or floor effects registered. Internal consistency was satisfactory and acceptable as indicated by the mean value of 0.74 of Kuder-Richardson-20. No ceiling or floor effects have been observed. Interestingly, educational level and disease duration correlated with MS knowledge.Conclusion CareKoMS is a valid self-assessed questionnaire on MS knowledge for caregivers that may be used in clinical practice and research. Assessing knowledge of MS among caregivers is essential to facilitate their caregiving role and thus decrease the burden of disease management.

BackgroundLipoxin A4 (LXA4) has anti-inflammatory and pro-resolutive roles in inflammation. We evaluated the effects and mechanisms of action of LXA4 in titanium dioxide (TiO2) arthritis, a model of prosthesis-induced joint inflammation and pain.MethodsMice were stimulated with TiO2 (3mg) in the knee joint followed by LXA4 (0.1, 1, or 10ng/animal) or vehicle (ethanol 3.2% in saline) administration. Pain-like behavior, inflammation, and dosages were performed to assess the effects of LXA4in vivo.ResultsLXA4 reduced mechanical and thermal hyperalgesia, histopathological damage, edema, and recruitment of leukocytes without liver, kidney, or stomach toxicity. LXA4 reduced leukocyte migration and modulated cytokine production. These effects were explained by reduced nuclear factor kappa B (NFκB) activation in recruited macrophages. LXA4 improved antioxidant parameters [reduced glutathione (GSH) and 2,2-azino-bis 3-ethylbenzothiazoline-6-sulfonate (ABTS) levels, nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA and Nrf2 protein expression], reducing reactive oxygen species (ROS) fluorescent detection induced by TiO2 in synovial fluid leukocytes. We observed an increase of lipoxin receptor (ALX/FPR2) in transient receptor potential cation channel subfamily V member 1 (TRPV1)+ DRG nociceptive neurons upon TiO2 inflammation. LXA4 reduced TiO2‐induced TRPV1 mRNA expression and protein detection, as well TRPV1 co-staining with p-NFκB, indicating reduction of neuronal activation. LXA4 down-modulated neuronal activation and response to capsaicin (a TRPV1 agonist) and AITC [a transient receptor potential ankyrin 1 (TRPA1) agonist] of DRG neurons.ConclusionLXA4 might target recruited leukocytes and primary afferent nociceptive neurons to exert analgesic and anti-inflammatory activities in a model resembling what is observed in patients with prosthesis inflammation.

Despite the significant advancements in drone sensory device reliability, data integrity from these devices remains critical in securing successful flight plans. A notable issue is the vulnerability of GNSS to jamming attacks or signal loss from satellites, potentially leading to incomplete drone flight plans. To address this, we introduce SiaN-VO, a Siamese neural network designed for visual odometry prediction in such challenging scenarios. Our preliminary studies have shown promising results, particularly for flights under static conditions (constant speed and altitude); while these findings are encouraging, they do not fully represent the complexities of real-world flight conditions. Therefore, in this paper, we have furthered our research to enhance SiaN-VO, improving data integration from multiple sensors and enabling more accurate displacement predictions in dynamic flight conditions, thereby marking a significant step forward in drone navigation technology.

We present a minimal Landau theory of plastic-to-crystal phase transitions in which the key components are a multipole-moment order parameter that describes the orientational ordering of the constituent molecules, coupling between such order parameter and elastic strains, and thermal expansion. We illustrate the theory with the simplest non-trivial model in which the orientational ordering is described by a quadrupole moment, and use such model to calculate barocaloric effects in plastic crystals that are driven by hydrostatic pressure. The model captures characteristic features of plastic-to-crystal phase transitions, namely large changes in volume and entropy at the transition, as well as the linear dependence of the transition temperature with pressure. We identify temperature regions in the barocaloric response associated with the individual plastic and crystal phases, and those involving the phase transition. Our model is in overall agreement with previous experiments in powdered samples of fullerite C _60 , and predicts peak isothermal entropy changes of ${\sim}90 \,\mathrm{J K^{-1} kg^{-1}}$ and peak adiabatic temperature changes of ${\sim}35 \,\mathrm{K}$ under $0.60\,$ GPa at $265\,$ K in fullerite single crystals.

Deoxynivalenol (DON) is a predisposing factor for necrotic enteritis. This study aimed to investigate the effects of a DON and Clostridium perfringens (CP) challenge on the intestinal morphology, morphometry, oxidative stress, and immune response of broilers. Additionally, we evaluated the potential of a Lactobacillus spp. mixture as an approach to mitigate the damage induced by the challenge. One-day-old broiler chickens (n = 252) were divided into seven treatment groups: Control, DON, CP, CP + DON, VL (DON + CP + viable Lactobacillus spp. mixture), HIL (DON + CP + heat-inactivated Lactobacillus spp. mixture), and LCS (DON + CP + Lactobacillus spp. mixture culture supernatant). Macroscopic evaluation of the intestines revealed that the CP + DON group exhibited the highest lesion score, while the VL and HIL groups showed the lowest scores. Microscopically, all Lactobacillus spp. treatments mitigated the morphological changes induced by the challenge. DON increased levels of reactive oxygen species (ROS) in the jejunum, and CP increased ROS levels in the jejunum and ileum. Notably, the Lactobacillus spp. treatments did not improve the antioxidant defense against CP-induced oxidative stress. In summary, a Lactobacillus spp. mixture, whether used as a probiotic, paraprobiotic, or postbiotic, exerted a partially protective effect in mitigating most of the intestinal damage induced by DON and CP challenges.

Factors associated with SARS-CoV-2 infection risk are still debated. This case–control study aims to investigate the possible relationship between SARS-CoV-2 infection, evaluated through antibody response, and the main sociodemographic, occupational, clinical-anamnestic, and biochemical factors in a population of Modena province (Northern Italy), mainly workers. Both workers who voluntarily joined the screening campaign proposed by companies and self-referred individuals who underwent serological testing were enrolled. Subjects with antibody positivity were recruited as cases (n = 166) and subjects tested negative (n = 239) as controls. A questionnaire on sociodemographic, occupational, and clinical data was administered through telephone interviews. Serum zinc/iron/copper/chromium/nickel, vitamins D/B12, folates, triglycerides, and LDL/HDL/total cholesterol were measured. Cases lived more often in urban areas (61.8% vs. 57%). Cases and controls did not differ significantly by working macrocategories, but the percentage of workers in the ceramic sector was higher among cases. Low adherence to preventive measures in the workplace was more frequent among seropositives. Folate concentration was significantly lower among cases. Therefore, adequate folate levels, living in rural areas, and good adherence to preventive strategies seem protective against infection. Workers in the ceramic sector seem to be at greater risk; specific factors involved are not defined, but preventive interventions are needed.