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Jessica Perez, Javier Cifuentes, Monica Cuellar, Alejandra Suarez-Arnedo, Juan C Cruz, Carolina Muñoz-Camargo GINIB Research Group, Department of Biomedical Engineering, Universidad de los Andes, Bogotá, ColombiaCorrespondence: Carolina Muñoz-Camargo; Juan C Cruz Tel +57-1 3394949 Ext. 1789, 1853Email c.munoz2016@uniandes.edu.co; jc.cruz@uniandes.edu.coIntroduction: Controlled delivery of therapeutic molecules in a localized manner has become an area of interest due to its potential to reduce drug exposure to healthy tissues and consequently to minimize undesirable side effects. We have recently introduced novel cell-penetrating vehicles by immobilizing the antimicrobial peptide Buforin II (BUF-II) on magnetite nanoparticles (MPNPs). Despite the potent translocating abilities of such nanobioconjugates, they failed to preserve the antimicrobial activity of native BUF-II. In this work, we explored immobilization on MNPs with the aid of polymer surface spacers, which has been considered as an attractive alternative for the highly efficient conjugation of various biomolecules.Methods: Here, we immobilized BUF-II on polyetheramine-modified magnetite nanoparticles to preserve its structural integrity. As a result, for the obtained nanobioconjugates the lost antimicrobial activity against gram-positive and gram-negative bacteria was only 50% with respect to the native BUF-II. The nanobioconjugates were also characterized via FTIR, DLS, TEM, and TGA. Delivery on THP-1, HaCaT, HFF, and Escherichia coli cells was conducted to confirm capability for cell membrane translocation.Results: Colocalization with Lysotracker showed an endosomal escape efficiency of about 73∓12% in THP-1 cells. Avoidance of endocytic pathways of internalization was qualitatively confirmed by a delivery assay at low temperature. Nuclear penetration of the nanobioconjugates was corroborated via confocal microscopy and showed high biocompatibility as demonstrated by hemolysis levels below 5% and acute cytotoxicity of around 15%.Conclusion: The obtained nanobioconjugates were capable of translocating the cell membrane and nuclei of different normal and cancerous cell lines without significantly decreasing viability. This makes the vehicle addressable for a number of applications ranging from antimicrobial topical treatments to the delivery of nucleotides and therapeutic molecules with difficulties to bypass cell membranes.Keywords: Buforin-II conjugates, drug delivery, translocation, cell-penetrating peptides, nanomaterials

Monica Cuellar,1 Javier Cifuentes,1 Jessica Perez,1 Alejandra Suarez-Arnedo,1 Julian A Serna,1 Helena Groot,2 Carolina Muñoz-Camargo,1 Juan C Cruz1 1Department of Biomedical Engineering, Universidad de los Andes, Bogotá, Colombia; 2Human Genetics Laboratory, Department of Biological Sciences, Universidad de los Andes, Bogotá, Colombia Introduction: One of the major challenges of modern pharmacology is the development of systems for the delivery of therapeutic molecules in a controlled and localized manner. One strategy is to use nanostructured supports, which are well suited to carry a large number of molecules on a per mass basis. A major challenge for these supports is, however, their limited ability to bypass the cell membrane. Recent studies propose that to overcome this issue, potent translocating cell-penetrating peptides (CPPs) can be conjugated to their surfaces. Methods: Here, we conjugated the antimicrobial CPP buforin II (BUF2) to the surface of magnetite nanoparticles to enhance their cell penetration. Conjugates were characterized via Fourier transform infrared spectroscopy, dynamic light scattering, and thermogravimetric analysis, and their biocompatibility was corroborated. The conjugates were delivered in both bacterial and mammalian cells demonstrating the intracellular inclusion in THP-1 cells for the first time. Results: Despite the promising outcome, our studies showed that the obtained conjugates failed to maintain the native antimicrobial activity of BUF2. We hypothesize that to overcome this issue, a flexible linker can be inserted prior to conjugation. Conclusion: Our study highlights the potential of BUF2-magnetite conjugates as cell-penetrating vehicles for the targeted delivery of pharmacological agents. This provides support for the idea of a promising combined drug delivery and antimicrobial peptide therapy. Keywords: BUF2-magnetite, antimicrobial activity, cell-penetrating peptides, nanomaterials, drug delivery

Human biomonitoring of toxic and essential trace elements is critically important for public health protection. Amazonian riverine communities exhibit distinctive dietary patterns, heavily reliant on locally sourced fish, fruits, and vegetables. These habits may result in unique exposure profiles compared to urban populations. However, comprehensive assessments of their exposure to toxic and essential metals are lacking, representing a critical gap in understanding the health risks faced by these communities. This study aimed to establish baseline levels of 21 metals and metalloids in human blood and explore the influence of sociodemographic factors, dietary habits, and lifestyle choices as potential sources of exposure to these elements. A cross-sectional biomonitoring investigation was conducted with 1,024 individuals from 13 communities in the Tapajós and Amazon Basins (Pará, Brazil). Most of the elements in study was determined for the first time in the region. Blood samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). The levels of all elements were summarized by quantiles and compared with cutoff values from other Brazilian populations. Multiple linear regression was used to assess possible associations between element concentrations and sociodemographic characteristics, dietary habits, and lifestyle choices. High detection rates (64%-100%) were observed, indicating the widespread presence of these elements. Elevated blood concentrations were found for mercury (median 21.1 μg.L -1 , interquartile range: 12-34 μg.L -1 ), selenium (median 166 μg.L -1 , interquartile range: 137-208 μg.L -1 ), and lead (median 34 μg.L -1 , interquartile range: 20.8-64 μg.L -1 ). Regression analysis revealed a positive association between mercury levels and fish consumption, while manioc flour intake showed no relationship to lead levels. In conclusion, our findings emphasize the need for continued monitoring and public policy development for these vulnerable populations. Further studies should assess long-term trends and investigate the health implications of prolonged exposure to diverse chemicals in Amazonian riverside communities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Skin wound treatments require efficient and targeted delivery of therapeutic agents to promote fast tissue regeneration and prevent infections. Hydrogels are one of the most popular products in the wound care market, although their use as medicated wound dressings remains a massive challenge when hydrophobic drugs are needed due to the hydrophilic nature of these soft materials. In this study, we developed innovative, dynamic hydrogels based on polyvinyl alcohol (PVA), pyrogallol as a hydrogen bond crosslinker, and casein micelles as hydrophobic reservoirs of silver sulfadiazine (SSD) for enzyme-activated smart delivery at wound sites. The hydrogel formulation was optimized for mechanical strength, viscoelastic behavior, water absorption capacity, and drug-loading efficiency. In vitro drug delivery studies revealed a sustainable release profile of SSD for over 24 h from the micelles within the hydrogel network. Furthermore, biocompatibility evaluation using mouse fibroblast L929 cells demonstrated that the hydrogel did not inhibit cell viability, while in vivo experiments on Caenorhabditis elegans (C. elegans) proved its safety in complex organisms. This versatile hydrogel also has anti-inflammatory and antibacterial effects stemming from the therapeutic polyphenol, which could benefit the healing process. The combination of PVA, pyrogallol, and casein-based nanocarriers could offer an approach to wound healing, providing a new platform for hosting hydrophobic therapeutic substances. Overall, this hydrogel system shows great promise in wound care and could broaden the applications of this family of soft materials for treating various skin injuries., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Validations of previously detected quantitative trait loci (QTLs) to assess their reliability are crucial before implementing breeding programs. The objective of this study was to determine the reliability and practical usefulness of previously reported QTLs for resistance to stem tunneling by the Mediterranean stem borer (MSB) and yield. These authors used approximately 600 recombinant inbred lines (RILs) from a multiparent advanced generation intercross (MAGIC) population to map QTL using a genome-wide association study (GWAS) approach., Methods: We identified RILs situated at the extremes of resistance and yield distributions within the whole MAGIC, and those QTLs were evaluated per se and crossed to a tester (A638) using lattice designs. In each set, a significant single-nucleotide polymorphism (SNP) was considered validated if (1) the same SNP was associated with the trait with a p -value < 0.02, or (2) within a ±2-Mbp interval, an SNP associated with the trait exhibited a p -value < 0.02 and demonstrated linkage disequilibrium ( r 2 > 0.2) with the SNPs previously reported., Results and Discussion: The novel QTL validation approach was implemented using improved experimental designs that led to higher heritability estimates for both traits compared to those estimated with the whole MAGIC population. The procedure used allowed us to jointly validate several QTL and to ascertain their possible contribution to hybrid improvement. Specifically, nearly three-quarters of the QTLs for tunnel length were confirmed. Notably, QTLs located in the genomic region 6.05-6.07 were consistently validated across different sets and have been previously linked to resistance against stalk tunneling in various mapping populations. For grain yield, approximately 10 out of 16 QTLs were validated. The validation rate for yield was lower than for tunnel length, likely due to the influence of dominance and/or epistatic effects. Overall, 9 out of 21 QTLs for tunnel length and 6 out of 17 QTLs for grain yield identified in our previous research were validated across both validation sets, indicating a moderate genetic correlation between per se and testcross performance of inbred lines. These findings offer insights into the reliability of QTL and genomic predictions, both derived from assessments conducted on the entire MAGIC population. Genomic predictions for tunnel length based on inbred line evaluations could be useful to develop more resistant hybrids; meanwhile, genomic prediction for yield could only be valid in a homozygous background., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 López-Malvar, Reséndiz-Ramirez, Butrón, Jiménez-Galindo, Revilla and Malvar.)

Objectives: We report the safety, tolerability and efficacy of tofacitinib in patients with juvenile idiopathic arthritis (JIA) in an ongoing long-term extension (LTE) study., Methods: Patients (2-<18 years) with JIA who completed phase 1/3 index studies or discontinued for reasons excluding treatment-related serious adverse events (AEs) entered the LTE study and received tofacitinib 5 mg two times per day or equivalent weight-based doses. Safety outcomes included AEs, serious AEs and AEs of special interest. Efficacy outcomes included improvement since tofacitinib initiation per the JIA-American College of Rheumatology (ACR)70/90 criteria, JIA flare rate and disease activity measured by Juvenile Arthritis Disease Activity Score (JADAS)27, with inactive disease corresponding to JADAS ≤1.0., Results: Of 225 patients with JIA (median (range) duration of treatment, 41.6 (1-103) months), 201 (89.3%) had AEs; 34 (15.1%) had serious AEs. 10 patients developed serious infections; three had herpes zoster. Two patients newly developed uveitis. Among patients with polyarticular course JIA, JIA-ACR70/90 response rates were 60.0% (78 of 130) and 33.6% (47 of 140), respectively, at month 1, and generally improved over time. JIA flare events generally occurred in <5% of patients through to month 48. Observed mean (SE) JADAS27 was 22.0 (0.6) at baseline, 6.2 (0.7) at month 1 and 2.8 (0.5) at month 48, with inactive disease in 28.8% (36 of 125) of patients at month 1 and 46.8% (29 of 82) at month 48., Conclusions: In this interim analysis of LTE study data in patients with JIA, safety findings were consistent with the known profile of tofacitinib, and efficacy was maintained up to month 48., Trial Registration Number: NCT01500551., Competing Interests: Competing interests: HIB has received research grants from Bristol Myers Squibb, Novartis and Pfizer; is an employee of Cincinnati Children’s Hospital Medical Center; has received consulting fees or other remuneration from AbbVie, AstraZeneca/MedImmune, Bayer, Biocon, Boehringer Ingelheim, Bristol Myers Squibb, Cerecor, Eli Lilly, EMD Serono, Janssen, Novartis, Pfizer, Roche, R-Pharm and Sobi; and is a member of speaker bureaus for Novartis and Pfizer. JDA has received honorarium from Novartis. JFB has received research grants from AbbVie, Bristol Myers Squibb, Janssen, Pfizer and Roche. ALB is a member of speaker bureaus for AbbVie, Novartis and Roche. RC has received consulting fees or other remuneration from AbbVie, Bristol Myers Squibb, Eli Lilly, GSK, Novartis, Pfizer, Roche and Sanofi. GS has received consulting fees or other remuneration from Novartis and Sobi and research support from IpiNovyx. CN has received research grants from AbbVie, AstraZeneca, Bristol Myers Squibb, Eli Lilly, GSK, Pfizer and UCB. MV-DM is an employee of Clínica de Investigacion en Reumatologia y Obesidad, SC. HP, CC, CWh, KeK and SL are employees and stockholders of Pfizer. AW was an employee and stockholder of Pfizer at the time of this analysis. AM has received consulting fees or other remuneration from Aurinia, Bristol Myers Squibb, Eli Lilly, EMD Serono, Janssen and Pfizer. DL’s institution, the Cincinnati Children’s Hospital Medical Center, has received research grants from Bristol Myers Squibb, Janssen, Novartis, Pfizer, Roche and UBC; and has received consulting fees or other remuneration from AstraZeneca, Boehringer Ingelheim, GSK, Roche, Novartis, Pfizer, Takeda and UBC. DL is also a data safety and monitoring board member or chairperson for the National Institutes of Health and the Canadian Arthritis Society. NR has received honoraria for consultancies or speaker bureaus from Ablynx, AstraZeneca/MedImmune, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, EMD Serono, F Hoffmann-La Roche, GS, Janssen, MSD, Novartis, Pfizer, R-Pharm, Sanofi, Servier, Sinergie and Sobi. The IRCCS Istituto Giannina Gaslini, where NR works as a full-time public employee, has received contributions from Bristol Myers Squibb, Eli Lilly, F Hoffmann-La Roche, GS, Janssen, Novartis, Pfizer and Sobi; this funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties. EA-A, GC, WDLP, LJ, ÖK, KaK, RR-C, JCRR, LW-W, JEW and CWo have declared no conflicts., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Predicting the interfacial properties of peptides is important for replacing oil-derived surfactants in cosmetics, oil, and agricultural applications. This work validated experimentally the estimations of surface tension at the critical micelle concentration (ST CMC ) of six peptides performed through a random forest (RF) model in a previous contribution. In silico interfacial tensions of the peptides were obtained in the system decane-water, and dilational experiments were applied to elucidate the foaming potential. The RF model accurately classified the peptides into high and low potential to reduce the ST CMC . The simulations at the decane-water interface correctly identified peptides with high, intermediate, and low interfacial properties, and the dilational rheology allowed the estimation of the possible potential of three peptides to produce foams. This study sets the basis for identifying surface-active peptides, but future work is necessary to improve the estimations and the correlation between dilational properties and foam stabilization.

Background : The presence of the rs35705950 variant in the MUC5B gene promoter is a critical genetic risk factor in idiopathic pulmonary fibrosis (IPF). It has been associated with usual interstitial pneumonia (UIP) in several interstitial lung diseases (ILDs). In antisynthetase syndrome (ASSD), most high-resolution computed tomography (HRCT) patterns are inflammatory, but up to 13% have UIP, leading to a worse prognosis. Methods : This single-center study included 60 patients with ASSD-ILD. We investigated whether carrying the MUC5B rs35705950 promoter variant was associated with UIP. To estimate the strength of the association between the genotype of the MUC5B rs35705950 promoter variant and the fibrotic pattern we used the odds ratio (cOR), and to assess the effect of confounding variables (age, evolution time, and sex), we performed a logistic regression to obtained the adjusted odds ratio (aOR). Results : The GT genotype of the MUC5B rs35705950 promoter variant is associated with up to a 4-fold increased risk of UIP (cOR 5.0, 95% CI 1.13-22.10), and the effect was even maintained after adjusting for potentially confounding variables such as sex, age, and time to progression (aOR 5.2, 95% CI 1.04-25.89). Conclusions : our study supports the role of MUC5B rs35705950 in ASSD-ILD with UIP. It reinforces that this polymorphism in our population could have a similar genetic basis to that already described in other ILDs that present predominantly fibrotic patterns.

The treatment setting influences acute myeloid leukemia (AML) outcomes. Most cancer patients receive care in the community, yet few studies have evaluated the effectiveness of clinical programs outside of academic or National Cancer Institute (NCI)-designated cancer centers. This was a multi-level, case-controlled study of real-world outcomes for initial AML treatment in a community-based network for 1,391 patients with AML between 2011 and 2018. We benchmarked survival within our network against the Surveillance, Epidemiology, and End Results (SEER) database. Coarsened exact matching was performed against 17,186 chemotherapy-treated patients in the SEER database. Cox proportional and accelerated failure time multivariable modeling were performed to identify patient, disease, therapy and center characteristics associated with the risk of AML mortality. Within the network, 799 patients were treated at six specialized blood cancer centers and 592 at 63 other hospitals. Patients receiving high-intensity induction at specialized centers had improved median survivals of 31 months versus 18 months [P<0.001] at non-specialized centers. Median survivals were 13 for non-specialized centers versus 10 months for SEER [P<0.001], and 18 for the entire network versus 10 months for SEER [P<0.001]. Multivariable modeling showed significant impacts from age ( HR = 1.025), high-intensity induction therapy ( HR = .695), diagnosis year ( HR = .937), neighborhood income ( HR = .997; P<0.01), higher acuity ( HR = 1.002) and Charlson comorbidity score ( HR = 1.117). AML treatment may be effectively delivered in the community hospital setting, with specialized centers producing better outcomes for higher intensity treatments., Competing Interests: The authors of this publication declare no competing financial or other conflicts of interest.

Leptospirosis and toxoplasmosis are re-emerging zoonosis caused by infection with pathogenic spirochaetes of Leptospira and the protozoa Toxoplasma gondii, respectively. Wild boars (Sus scrofa), an exotic invasive species in Brazil, could play a role in the diseases' epidemiological cycles, but this issue is still unexplored. This study aimed to evaluate the Leptospira spp. and T. gondii seropositivity in wild boars in Rio Grande do Sul state, south Brazil. Of evaluated animals, 16% (13/80) and 85% (52/61) had antibodies to T. gondii and Leptospira spp., respectively. Sex, weight, age, hunt location and season of hunt were evaluated by their association with seropositivity for both pathogens, but none of them had statistical significance. This study revealed that wild boars should be considered as a potential source of Leptospira spp. and T. gondii dissemination for humans and animal species in shared environments in Rio Grande do Sul state., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Obesity is a complex disease for which pharmacotherapy is often used. Anti-obesity drugs (AODs) are characterized by inducing a variable inter-subject body weight reduction (BWR), the attainment of a plateau after their maximal effect is achieved, and weight regain after drug discontinuation, which complicate individualized treatment of obesity., Objective: This exploratory analysis aimed to compare the first-month body weight reduction in kg (1mo-BWRkg) and tolerance development (moT) of four known interventions with low (placebo), intermediate (phentermine or mazindol monotherapy), and high (5 active ingredients fixed-dose combination) efficacy, as predictors of their 6-month body weight reduction efficacy in percent (6mo-BWR%). In addition, a detailed analysis of the 6-to-12-month BWR follow-up in subjects under orlistat or diet and exercise regimens was performed., Materials and Methods: The analysis included 662 adult subjects with obesity. After the construction of average efficacy and weight rebound curves, subjects were grouped into various 1mo-BWRkg, moT, and 6mo-BWR% intervals, or 6-month body weight rebound parameters for further evaluation., Results: The 6mo-BWR% efficacy level of interventions was confirmed, although a general high intersubject variation was observed. 1mo-BWRkg + moT was found as an acceptable predictor of 6mo-BWR%. Between 50 and 80% of the 6-to-12-month follow-up completers maintained at least 5% BWR%., Conclusion: Short-term AODs are useful adjuvants for the 1-year rational treatment of obesity. 1mo-BWRkg + moT is an acceptable parameter to predict the 6mo-BWR% efficacy of these interventions.

This study aimed to explore the relationship between the inter-limb differences in unilateral countermovement (CMJ) height and the inter-limb differences in bilateral CMJ force production, and to elucidate whether the self-reported preferred leg contributes more to force production than the non-preferred leg. Twenty-three senior basketball players performed in a single session eight unilateral CMJs (four with each leg) and four bilateral CMJs. Impulse, peak force, mean force were recorded during the bilateral CMJ, and jump height during the unilateral CMJ. Small correlations were observed between the inter-limb differences in unilateral CMJ height and the inter-limb asymmetries in bilateral CMJ impulse, peak force, and mean force ( p ≥ 0.171; r ≤-0.142). The self-reported preferred leg revealed a higher performance in 7 out of 23 participants (Kappa = -0.20) for the unilateral CMJ height, 7 out of 23 participants (Kappa = -0.11) for the bilateral CMJ impulse, 6 out of 23 participants (Kappa = -0.36) for the bilateral CMJ peak force, and 8 out of 23 participants (Kappa = -0.34) for the bilateral CMJ mean force. These results highlight that the asymmetries detected during bilateral CMJs cannot be extrapolated to unilateral CMJs, and that the preferred leg generally contributes less to force production than the non-preferred leg during both bilateral and unilateral CMJs.

Soft robotic technologies for therapeutic biomedical applications require conformal and atraumatic tissue coupling that is amenable to dynamic loading for effective drug delivery or tissue stimulation. This intimate and sustained contact offers vast therapeutic opportunities for localized drug release. Herein, a new class of hybrid hydrogel actuator (HHA) that facilitates enhanced drug delivery is introduced. The multi-material soft actuator can elicit a tunable mechanoresponsive release of charged drug from its alginate/acrylamide hydrogel layer with temporal control. Dosing control parameters include actuation magnitude, frequency, and duration. The actuator can safely adhere to tissue via a flexible, drug-permeable adhesive bond that can withstand dynamic device actuation. Conformal adhesion of the hybrid hydrogel actuator to tissue leads to improved mechanoresponsive spatial delivery of the drug. Future integration of this hybrid hydrogel actuator with other soft robotic assistive technologies can enable a synergistic, multi-pronged treatment approach for the treatment of disease., (© 2023 Wiley‐VCH GmbH.)

Background: Cannabidiol (CBD) is increasingly studied for its therapeutic potential in neurodegenerative diseases. Previous research on acute CBD administration has demonstrated cardiovascular benefits in hypertensive rats, including reduced mean blood pressure and oxidative stress., Aim: To investigate the long-term cardiovascular effects of chronic CBD treatment in renovascular hypertension induced by the 2-kidney-1-clip (2K1C) model., Methods: Male Wistar rats (180-200 g, 8 weeks old) underwent 2K1C or SHAM surgery. Six weeks later, rats received chronic CBD treatment (20 mg/kg, twice daily for 14 days). A combination of ex vivo, in vitro, and in vivo methods was used to assess CBD's cardiovascular effects in 2K1C hypertensive rats., Results: Chronic CBD treatment significantly reduced blood pressure and the depressor response to hexamethonium (a ganglionic blocker). It also normalized variability in low-frequency (LF) power and LF/high-frequency (HF) ratio. CBD enhanced vasodilation and reduced vasoconstriction in the mesenteric artery of 2K1C rats, accompanied by decreased expression of aortic reactive oxygen species (ROS)., Conclusion: Our findings suggest that chronic CBD treatment exerts antihypertensive effects by improving baroreflex sensitivity and vascular function while decreasing arterial ROS levels and sympathetic nerve activity. These results underscore CBD's potential therapeutic role in managing cardiovascular complications associated with renovascular hypertension., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The aim of this study was to evaluate the effect of freezing rates using direct (LF: Liquid nitrogen) and indirect (RF: Cryogenic refrigerator and UF: ultra-freezer) methods at temperatures of (-20, -80, and - 196 °C) on the enzymatic susceptibility with α-amylase for microparticles. In vitro digestibility parameters and technological properties were also analyzed. Lower rates resulted in larger ice crystals, damaging the starch structure. Hydrolysis was more pronounced at slower rates RF: 0.07 °C/min and UF: 0.14 °C/min, yielding maximum values of RDS: 37.63% and SDS: 59.32% for RF. Type A crystallinity remained unchanged, with only a noted increase in crystallinity of up to 6.50% for FR. Starch pastes were classified as pseudoplastic, with RF exhibiting superior textural parameters and apparent viscosity. (RF: 7.18 J g -1 and UF: 7.34 J g -1 ) also showed lower values of gelatinization enthalpy. Freezing techniques were viable in facilitating the diffusion of α-amylase and reducing RS by up to 81%., Competing Interests: Declaration of competing interest The authors have declared no conflicts of interest for this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background/Objectives : The antinociceptive and anti-inflammatory effects of a patent-pending ointment containing plant extracts from Eucalyptus globulus , Curcuma longa , Hamamelis virginiana , Echinacea purpurea , and Zingiber officinale were evaluated. Methods : Plant extracts were chemically characterized by gas chromatography-mass spectroscopy. The antinociceptive activity of the ointment was assessed using the hot plate, tail flick, and formalin tests, whereas the anti-inflammatory activity was measured using the acute and chronic TPA-induced ear edema tests. Mechanisms of action were evaluated using inhibitors from signaling pathways related to pain response and by using histological analysis and assessing the expression and activity of pro-inflammatory mediators. Results : The ointment showed antinociceptive and anti-inflammatory effects like those observed with diclofenac gel (1.16% v / v ) and ketoprofen gel (2.5% v / v ). The antinociceptive actions of the ointment are mediated by the possible participation of the opiodergic system and the nitric oxide pathway. The anti-inflammatory response was characterized by a decrease in myeloperoxidase (MPO) activity and by a reduction in ear swelling and monocyte infiltration in the acute inflammation model. In the chronic model, the mechanism of action relied on a decrease in pro-inflammatory mediators such as COX-2, IL-1β, TNF-α, and MPO. An in-silico study with myristic acid, one of the compounds identified in the ointment's plant mixture, corroborated the in vivo results. Conclusions : The ointment showed antinociceptive activities mediated by the decrease in COX-2 and NO levels, and anti-inflammatory activity due to the reduction in IL-1β and TNFα levels, a reduction in MPO activity, and a decrease in NF-κB and COX-2 expression.

The emergence of bacterial resistance to antibiotics poses a global health threat, necessitating innovative solutions. The contemporary challenge lies in bacterial resistance, impacting morbidity, mortality, and global economies. Antimicrobial peptides (AMPs) offer a promising avenue for addressing antibiotic resistance. The Antimicrobial Peptide Database catalogs 3569 peptides from various organisms, representing a rich resource for drug development. Histones, traditionally recognized for their role in nucleosome structures, have gained attention for their extracellular functions, including antimicrobial and immunomodulatory properties. This review aims to thoroughly investigate antimicrobial peptides derived from histones in various organisms, elucidating their mechanisms. In addition, it gives us clues about how extracellular histones might be used in drug delivery systems to fight bacterial infections. This comprehensive analysis emphasizes the importance of histone-derived peptides in developing innovative therapeutic strategies for evolving bacterial challenges., (© 2024. The Author(s).)

Anhydrous ammonia has seen a rapid increase in demand due to recent developments in clean energy technologies. As it is a potential carrier of hydrogen, the transportation industry is currently facing significant logistic challenges as well as safety risks. Based on the causes and effects, this study categorizes incident patterns based on the historical incidents from 1971 to 2021 in the United States during transportation. Analysis of temporal patterns revealed that government regulations and improvement of safety infrastructures have made the biggest impact on lowering incident rates. Spatial analysis methods are also applied to understand the relationships between these incidents and spatial factors, such as land area, number of ammonia production facilities, total average production capacity, and total length of freight railway and highway in each US state. The spatial and temporal patterns and interpretations provide safety references to manage the growing hazardous transport in clean energy., (© 2024 The Author(s). Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.)

Rice (Oryza sativa L.) and many other wetland plants form an apoplastic barrier in the outer parts of the roots to restrict radial O2 loss to the rhizosphere during soil flooding. This barrier facilitates longitudinal internal O2 diffusion via gas-filled tissues from shoot to root apices, enabling root growth in anoxic soils. We tested the hypothesis that Leaf Gas Film 1 (LGF1), which influences leaf hydrophobicity in rice, plays a crucial role in tight outer apoplastic barriers formation in rice roots. We examined the roots of a rice mutant (dripping wet leaf 7, drp7) lacking functional LGF1, its wild type, and an LGF1 overexpression line for their capacity to develop outer apoplastic barriers that restrict radial O2 loss. We quantified the chemical composition of the outer part of the root and measured radial O2 diffusion from intact roots. The drp7 mutant exhibited a weak barrier to radial O2 loss compared to the wild type. However, introducing functional LGF1 into the mutant fully restored tight barrier function. The formation of a tight barrier to radial O2 loss was associated with increased glycerol ester levels in exodermal cells, rather than differences in total root suberization or lignification. These results demonstrate that, in addition to its role in leaf hydrophobicity regulation, LGF1 plays an important role in controlling the function of the outer apoplastic barriers in roots. Our study suggests that increased deposition of glycerol esters in the suberized root exodermis establishes a tight barrier to radial O2 loss in rice roots., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Both plasticity and robustness are pervasive features of developmental programs. The dauer in Caenorhabditis elegans is an arrested, hypometabolic alternative to the third larval stage of the nematode. Dauers undergo dramatic tissue remodeling and extensive physiological, metabolic, behavioral, and gene expression changes compared to conspecifics that continue development and can be induced by several adverse environments or genetic mutations that act as independent and parallel inputs into the larval developmental program. Therefore, dauer induction is an example of phenotypic plasticity. However, whether gene expression in dauer larvae induced to arrest development by different genetic or environmental triggers is invariant or varies depending on their route into dauer has not been examined. By using RNA-sequencing to characterize gene expression in different types of dauer larvae and computing the variance and concordance within Gene Ontologies (GO) and gene expression networks, we find that the expression patterns within most pathways are strongly correlated between dauer larvae, suggestive of transcriptional robustness. However, gene expression within specific defense pathways, pathways regulating some morphological traits, and several metabolic pathways differ between the dauer larvae. We speculate that the transcriptional robustness of core dauer pathways allows for the buffering of variation in the expression of genes involved in adaptation, allowing the dauers induced by different stimuli to survive in and exploit different niches.

Superparamagnetic iron oxide micro- and nanoparticles have significant applications in biomedical and chemical engineering. This study presents the development and evaluation of a novel low-cost microfluidic device for the purification and hyperconcentration of these magnetic particles. The device, fabricated using laser ablation of polymethyl methacrylate (PMMA), leverages precise control over fluid dynamics to efficiently separate magnetic particles from non-magnetic ones. We assessed the device's performance through Multiphysics simulations and empirical tests, focusing on the separation of magnetite nanoparticles from blue carbon dots and magnetite microparticles from polystyrene microparticles at various total flow rates (TFRs). For nanoparticle separation, the device achieved a recall of up to 93.3 ± 4% and a precision of 95.9 ± 1.2% at an optimal TFR of 2 mL/h, significantly outperforming previous models, which only achieved a 50% recall. Microparticle separation demonstrated an accuracy of 98.1 ± 1% at a TFR of 2 mL/h in both simulations and experimental conditions. The Lagrangian model effectively captured the dynamics of magnetite microparticle separation from polystyrene microparticles, with close agreement between simulated and experimental results. Our findings underscore the device's robust capability in distinguishing between magnetic and non-magnetic particles at both micro- and nanoscales. This study highlights the potential of low-cost, non-cleanroom manufacturing techniques to produce high-performance microfluidic devices, thereby expanding their accessibility and applicability in various industrial and research settings. The integration of a continuous magnet, as opposed to segmented magnets in previous designs, was identified as a key factor in enhancing magnetic separation efficiency.

Introduction: There are no reports in LATAM related to longitudinal humoral and cellular response to adenovirus based COVID-19 vaccines in people with Multiple Sclerosis (pwMS) under different disease modifying therapies (DMTs) and neutralization of the Omicron and Wuhan variants of SARS-COV-2., Methods: IgG anti- SARS-COV-2 spike titer were measured in a cohort of 101 pwMS under fingolimod, dimethyl fumarate, cladribine and antiCD20, as well as 28 healthy controls (HC) were measured 6 weeks after vaccination with 2 nd dose (Sputnik V or AZD1222) and 3 nd dose (homologous or heterologous schedule). Neutralizing capacity was against Omicron (BA.1) and Wuhan (D614G) variants and pseudotyped particles and Cellular response were analyzed., Results: Multivariate regression analysis showed anti-cd20 (β= -,349, 95% CI: -3655.6 - -369.01, p=0.017) and fingolimod (β=-,399, 95% CI: -3363.8 - -250.9, p=0.023) treatments as an independent factor associated with low antibody response (r 2 adjusted=0.157). After the 2nd dose we found a correlation between total and neutralizing titers against D614G (rho=0.6; p<0.001; slope 0.8, 95%CI:0.4-1.3), with no differences between DMTs. Neutralization capacity was lower for BA.1 (slope 0.3, 95%CI:0.1-0.4). After the 3rd dose, neutralization of BA.1 improved (slope: 0.9 95%CI:0.6-1.2), without differences between DMTs. A fraction of pwMS generated anti-Spike CD4+ and CD8+ T cell response. In contrast, pwMS under antiCD20 generated CD8+TNF+IL2+ response without differences with HC, even in the absence of humoral response. The 3rd dose significantly increased the neutralization against the Omicron, as observed in the immunocompetent population., Discussion: Findings regarding humoral and cellular response are consistent with previous reports., Competing Interests: The authors declare that this study received funding from Novartis and donations from Merck Argentina and Synthon Bagó. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. Author Berenice Anabel Silva, as principal investigator, received a 2-year research grant from the Research Council of the Ministry of Health of the Government of the City of Buenos Aires, Argentina., (Copyright © 2024 Silva, Miglietta, Casabona, Wenker, Eizaguirre, Alonso, Casas, Lázaro, Man, Portuondo, Lopez Bisso, Zavala, Casales, Imhoff, Steinberg, López, Carnero Contentti, Deri, Sinay, Hryb, Chiganer, Leguizamon, Tkachuk, Bauer, Ferrandina, Giachello, Henestroza, Garcea, Pascuale, Heitrich, Podhajcer, Vinzón, D’Alotto-Moreno, Benatar, Rabinovich, Pitossi and Ferrari.)

Introduction: Parkinson's disease (PD) presents a significant challenge in medical science, as current treatments are limited to symptom management and often carry significant side effects. Our study introduces an innovative approach to evaluate the effects of gdnf overexpression mediated by CRISPRa in an in vitro model of Parkinson's disease. The expression of gdnf can have neuroprotective effects, being related to the modulation of neuroinflammation and pathways associated with cell survival, differentiation, and growth., Methods: We have developed a targeted delivery system using a magnetite nanostructured vehicle for the efficient transport of genetic material. This system has resulted in a substantial increase, up to 200-fold) in gdnf expression in an In vitro model of Parkinson's disease using a mixed primary culture of astrocytes, neurons, and microglia., Results and Discussion: The delivery system exhibits significant endosomal escape of more than 56%, crucial for the effective delivery and activation of the genetic material within cells. The increased gdnf expression correlates with a notable reduction in MAO-B complex activity, reaching basal values of 14.8 μU/μg of protein, and a reduction in reactive oxygen species. Additionally, there is up to a 34.6% increase in cell viability in an In vitro Parkinson's disease model treated with the neurotoxin MPTP. Our study shows that increasing gdnf expression can remediate some of the cellular symptoms associated with Parkinson's disease in an in vitro model of the disease using a novel nanostructured delivery system., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Guzmán-Sastoque, Sotelo, Esmeral, Albarracín, Sutachan, Reyes, Muñoz-Camargo, Cruz and Bloch.)

Subjective caregiver burden is highly prevalent in family caregivers. Despite several studies investigating the relationship between subjective caregiver burden and coping strategies, results remain inconsistent. The aim of our study was to systematically review current literature on the relationship between subjective caregiver burden and coping in family carers of dependent adults and older people. A secondary objective was to analyse possible sources of heterogeneity in the estimated effect. The study design was a systematic review with meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) guidelines. We searched several international databases (CINAHL, LILACS, PsycINFO and PubMed) up to February 2024. We performed several subgroup analyses to examine whether study design, methodological quality or care recipient dependency influenced results. Of the 1064 records identified in our search, a total of 80 studies met inclusion criteria. We found a significant association between greater use of dysfunctional coping and higher levels of subjective caregiver burden ( r ‾ $\overline{r}$  = 0.400; 95% CI = 0.315, 0.478); higher use of second-order active coping was significantly associated with lower caregiver burden ( r ‾ $\overline{r}$  = -0.213; 95% CI = -0.316, -0.105). Problem-focused coping showed no statistically significant association with levels of subjective burden; emotion-focused coping was associated with caregiver burden only after controlling for confounding variables ( r ‾ $\overline{r}$  = -0.258; 95% CI = -0.441, -0.055); several individual strategies of this dimension such as acceptance ( r ‾ $\overline{r}$  = -0.135; 95% CI = -0.238, -0.028), positive reappraisal ( r ‾ $\overline{r}$  = -0.178; 95% CI = -0.255, -0.099) and religious coping ( r ‾ $\overline{r}$  = -0.083; 95% CI = -0.162, -0.002), were associated with lower burden. We found that several dimensions of coping strategies are significantly associated with levels of subjective caregiver burden experienced by carers. These results can inform future research evaluating the effectiveness of interventions aimed at improving carers' mental health., (© 2024 The Authors. Stress and Health published by John Wiley & Sons Ltd.)

Alchemical free energy methods are useful in computer-aided drug design and computational protein design because they provide rigorous statistical mechanics-based estimates of free energy differences from molecular dynamics simulations. λ dynamics is a free energy method with the ability to characterize combinatorial chemical spaces spanning thousands of related systems within a single simulation, which gives it a distinct advantage over other alchemical free energy methods that are mostly limited to pairwise comparisons. Recently developed methods have improved the scalability of λ dynamics to perturbations at many sites; however, the size of chemical space that can be explored at each individual site has previously been limited to fewer than ten substituents. As the number of substituents increases, the volume of alchemical space corresponding to nonphysical alchemical intermediates grows exponentially relative to the size corresponding to the physical states of interest. Beyond nine substituents, λ dynamics simulations become lost in an alchemical morass of intermediate states. In this work, we introduce new biasing potentials that circumvent excessive sampling of intermediate states by favoring sampling of physical end points relative to alchemical intermediates. Additionally, we present a more scalable adaptive landscape flattening algorithm for these larger alchemical spaces. Finally, we show that this potential enables more efficient sampling in both protein and drug design test systems with up to 24 substituents per site, enabling, for the first time, simultaneous simulation of all 20 amino acids.

Microfluidic separators play a pivotal role in the biomedical and chemical industries by enabling precise fluid manipulations. Traditional fabrication of these devices typically requires costly cleanroom facilities, which limits their broader application. This study introduces a novel microfluidic device that leverages the passive Zweifach-Fung principle to overcome these financial barriers. Through Lagrangian computational simulations, we optimized an eleven-channel Zweifach-Fung configuration that achieved a perfect 100% recall rate for particles following a specified normal distribution. Experimental evaluations determined 2 mL/h as the optimal total flow rate (TFR), under which the device showcased exceptional performance enhancements in precision and recall for micrometer-sized particles, achieving an overall accuracy of 94% ± 3%. Fabricated using a cost-effective, non-cleanroom method, this approach represents a significant shift from conventional practices, dramatically reducing production costs while maintaining high operational efficacy. The cost of each chip is less than USD 0.90 cents and the manufacturing process takes only 15 min. The development of this device not only makes microfluidic technology more accessible but also sets a new standard for future advancements in the field.

Gymnema sylvestre (GS) and berberine (BBR) are natural products that have demonstrated therapeutic potential for the management of obesity and its comorbidities, as effective and safe alternatives to synthetic drugs. Although their anti-obesogenic and antidiabetic properties have been widely studied, comparative research on their impact on the gene expression of adipokines, such as resistin (Res), omentin (Ome), visfatin (Vis) and apelin (Ap), has not been reported., Methodology: We performed a comparative study in 50 adult Mexican patients with obesity treated with GS or BBR for 3 months. The baseline and final biochemical parameters, body composition, blood pressure, gene expression of Res, Ome, Vis, and Ap, and safety parameters were evaluated., Results: BBR significantly decreased ( p < 0.05) body weight, blood pressure and Vis and Ap gene expression and increased Ome, while GS decreased fasting glucose and Res gene expression ( p < 0.05). A comparative analysis of the final measurements revealed a lower gene expression of Ap and Vis ( p < 0.05) in patients treated with BBR than in those treated with GS. The most frequent adverse effects in both groups were gastrointestinal symptoms, which attenuated during the first month of treatment., Conclusion: In patients with obesity, BBR has a better effect on body composition, blood pressure, and the gene expression of adipokines related to metabolic risk, while GS has a better effect on fasting glucose and adipokines related to insulin resistance, with minimal side effects.

Objective: The purpose of this study is to evaluate the phenotypic characteristics and typification of Creole goats in five localities of the Ayacucho region in south-central Peru., Materials and Methods: Data from 149 goats (25 males and 124 females) were collected, excluding animals under 2 years of age, pregnant, and sick. Seven qualitative characteristics and 11 zometric measurements were evaluated, and then 9 zometric indices were estimated., Results: In the region, goats with composite colors predominated (76.50%). Additionally, supernumerary (24.20%) and divergent teats (22.60%) were observed in females, while males exhibited a scrotal bifurcation (32.00%). The origin of the flock had a significant effect (p < 0.05) on body measurements, as well as on pelvic index, transverse pelvic index, longitudinal pelvic index, compactness index, and load cannon bone index, except for body index (BOI), proportionality index, dactyl thorax index (DTI), and relative cannon bone thickness index (< p > 0.05). In the Ayacucho region, there is a predominance of light animals (57.72%) with a significant DTI (< p < 0.05) among the populations, including goats with good balance and capable of walking long distances. Furthermore, there are compact animals (47.65%) with a significant BOI (< p < 0.05) among the flock populations, which animals are of the biotype of meat. Conversely, the strongest positive correlation (< r = 0.89) was discovered between chest girth and body weight., Conclusion: In the Ayacucho region, there are various creole goat biotypes range from light to very compact heavy goats, with a predominance of meat biotype animals, as well as a marked size dimorphism between localities of origin., Competing Interests: The authors declare that they have no conflict of interest., (© The authors.)

Electrical stimulation has emerged as a cornerstone technique in the rapidly evolving field of biomedical engineering, particularly within the realms of tissue engineering and regenerative medicine. It facilitates cell growth, proliferation, and differentiation, thereby advancing the development of accurate tissue models and enhancing drug-testing methodologies. Conductive hydrogels, which enable the conduction of microcurrents in 3D in vitro cultures, are central to this advancement. The integration of high-electroconductive nanomaterials, such as graphene oxide (GO), into hydrogels has revolutionized their mechanical and conductivity properties. Here, we introduce a novel electrostimulation assay utilizing a hybrid hydrogel composed of methacryloyl-modified small intestine submucosa (SIS) dECM (SISMA), chitosan methacrylate (ChiMA), and GO-polyethylene glycol (GO-PEG) in a 3D in vitro culture within a hypoxic environment of umbilical cord blood cells (UCBCs). Results not only demonstrate significant cell proliferation within 3D constructs exposed to microcurrents and early growth factors but also highlight the hybrid hydrogel's physiochemical prowess through comprehensive rheological, morphological, and conductivity analyses. Further experiments will focus on identifying the regulatory pathways of cells subjected to electrical stimulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jaramillo, Arévalo, González-Hernández, Cortés, Perdomo-Arciniegas, Cruz and Muñoz-Camargo.)

Phleboliths are reported as calcifications that occur in vascular malformations, associated with changes in blood flow dynamics, thrombus formation and subsequent calcifications. Radiological examination, such as cone beam computed tomography (CBCT) could help in demonstrating the presence of a calcifiied mass. A 45-year-old male was referred to our service with an asymptomatic nodular purplish lesion located on the ventrolateral tongue. Within the lesion, a stony mass was also evident on palpation. A digital dental radiograph demonstrated two circumscribed radiopaque structures. Phleboliths associated with vascular malformation was the main diagnostic hypothesis. The patient underwent a sclerotherapy protocol allowing surgical accessibility to the area. Phlebolyts were surgically removed using electrocoagulation. Histopathological examination revealed phleboliths in the context of a vascular malformation with intense fibrosis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Tissue-engineered vascular grafts (TEVGs) poised for regenerative applications are central to effective vascular repair, with their efficacy being significantly influenced by scaffold architecture and the strategic distribution of bioactive molecules either embedded within the scaffold or elicited from responsive tissues. Despite substantial advancements over recent decades, a thorough understanding of the critical cellular dynamics for clinical success remains to be fully elucidated. Graft failure, often ascribed to thrombogenesis, intimal hyperplasia, or calcification, is predominantly linked to improperly modulated inflammatory reactions. The orchestrated behavior of repopulating cells is crucial for both initial endothelialization and the subsequent differentiation of vascular wall stem cells into functional phenotypes. This necessitates the TEVG to provide an optimal milieu wherein immune cells can promote early angiogenesis and cell recruitment, all while averting persistent inflammation. In this study, we present an innovative TEVG designed to enhance cellular responses by integrating a physicochemical gradient through a multilayered structure utilizing synthetic (poly (ester urethane urea), PEUU) and natural polymers (Gelatin B), thereby modulating inflammatory reactions. The luminal surface is functionalized with a four-arm polyethylene glycol (P4A) to mitigate thrombogenesis, while the incorporation of adhesive peptides (RGD/SV) fosters the adhesion and maturation of functional endothelial cells. The resultant multilayered TEVG, with a diameter of 3.0 cm and a length of 11 cm, exhibits differential porosity along its layers and mechanical properties commensurate with those of native porcine carotid arteries. Analyses indicate high biocompatibility and low thrombogenicity while enabling luminal endothelialization and functional phenotypic behavior, thus limiting inflammation in in-vitro models. The vascular wall demonstrated low immunogenicity with an initial acute inflammatory phase, transitioning towards a pro-regenerative M2 macrophage-predominant phase. These findings underscore the potential of the designed TEVG in inducing favorable immunomodulatory and pro-regenerative environments, thus holding promise for future clinical applications in vascular tissue engineering., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Rodríguez-Soto, Riveros-Cortés, Orjuela-Garzón, Fernández-Calderón, Rodríguez, Vargas, Ostos, Camargo, Cruz, Kim, D’Amore, Wagner and Briceño.)

Objective: To evaluate whether anti-PL7 and anti-PL12 autoantibodies are associated with a greater extent of the fibrotic component of ILD in ASSD patients., Methods: Patients with ILD-ASSD who were positive for one of the following autoantibodies: anti-Jo1, anti-PL7, anti-PL12, and anti-EJ were included. Clinical manifestations, CPK levels, pulmonary function tests, and HCRT assessments were prospectively collected according to the Goh index. The fibrotic, inflammatory, and overall extension of the Goh index and DL CO were assessed by multiple linear analyses and compared between ASSD antibody subgroups., Results: Sixty-six patients were included; 17 were positive for anti-Jo1 (26%), 17 for anti-PL7 (26%), 20 for anti-PL12 (30%), and 9 (14%) for anti-EJ. Patients with anti-PL7 and anti-PL12 had a more extensive fibrotic component than anti-Jo1. Anti-PL7 patients had a 7.9% increase in the fibrotic extension (cβ = 7.9; 95% CI 1.863, 13.918), and the strength of the association was not modified after controlling for sex, age, and time of disease evolution (aβ = 7.9; 95% CI 0.677, 15.076) and also was associated with an increase in ILD severity after adjusting for the same variables, denoted by a lower DL CO (aβ =  - 4.47; 95% CI - 8.919 to - 0.015)., Conclusions: Anti-PL7-positive ASSD patients had more extensive fibrosis and severe ILD than the anti-Jo1 subgroup. This information is clinically useful and has significant implications for managing these patients, suggesting the need for early consideration of concurrent immunosuppressive and antifibrotic therapy., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Bodybuilding, as a high-performance sport, requires regular strength and resistance exercises with the principal objective of increasing muscle hypertrophy. However, many bodybuilders resort to the use of anabolic-androgenic steroids (AASs) to improve their performance in a short period of time. This study employs a survey-type, cross-sectional, descriptive-analytical method to evaluate the profile of bodybuilding athletes in the State of Sergipe, Brazil, and verify the level of knowledge/awareness about the health risks and impacts resulting from the use of such substances. Finite- and convenience-type populations are assessed, including individuals of both sexes, aged older than 18 years, self-declared bodybuilding athletes residing in the State of Sergipe, Brazil, and participating in regional and/or state competitions. As a result, no significant relationships were determined between sex ( p = 0.492), age ( p = 0.460), family income ( p = 0.141), and medical follow-up sessions. For the variables level of education and medical follow-up vs. no follow-up sessions, a significant result was achieved ( p = 0.01), with 74.3% of individuals reporting having follow-up treatment and 25.7% responding that they had no follow-up treatment, a percentage representing the group that completed their higher education. The substances most used by the athletes were Sustanon 250 or Durateston, Nandrolone Decanoate (Deca or Deca-Durabolin), and Testosterone. The most-reported acute side effects were acne at 33.8% ( n = 20), irritability at 32.1% ( n = 19), alopecia (hair loss), and nervousness at 23.7% ( n = 14). The most-reported chronic side effects were arterial hypertension at 36.0% ( n = 9), liver disease at 28.0% ( n = 7), and cancer (non-specific) at 8.0% ( n = 2). We concluded that, regardless of the athletes' socioeconomic profiles, the use of AASs was high, with two or more substances being used in combination and for a prolonged period. Thus, it is necessary to promote awareness campaigns regarding the use of AASs and their effects on high-performance and recreational athletes.

When updating beliefs, humans tend to integrate more desirable information than undesirable information. In stable environments (low uncertainty and high predictability), this asymmetry favors motivation towards action and perceived self-efficacy. However, in changing environments (high uncertainty and low predictability), this process can lead to risk underestimation and increase unwanted costs. Here, we examine how people (n = 388) integrate threatening information during an abrupt environmental change (mandatory quarantine during the COVID-19 pandemic). Given that anxiety levels are associated with the magnitude of the updating belief asymmetry; we explore its relationship during this particular context. We report a significant reduction in asymmetrical belief updating during a large environmental change as individuals integrated desirable and undesirable information to the same extent. Moreover, this result was supported by computational modeling of the belief update task. However, we found that the reduction in asymmetrical belief updating was not homogeneous among people with different levels of Trait-anxiety. Individuals with higher levels of Trait-anxiety maintained a valence-dependent updating, as it occurs in stable environments. On the other hand, updating behavior was not associated with acute anxiety (State-Anxiety), health concerns (Health-Anxiety), or having positive expectations (Trait-Optimism). These results suggest that highly uncertain environments can generate adaptive changes in information integration. At the same time, it reveals the vulnerabilities of individuals with higher levels of anxiety to adapt the way they learn., (© 2024. The Author(s).)

With the expansion of organic agriculture, research is needed to indicate economically and ecologically viable fertilizer options, especially in semiarid regions, with low soil organic matter and nitrogen content. In the Brazilian semiarid region, vermicomposts are widely used by farmers and are scientifically investigated; however, there is no information for millicompost, a new type of organic compound that has shown very promising results in other regions. Thus, this study aimed to analyze the decomposition rate, nutrient release, and microstructure evaluation of vermicomposts from different sources and of millicompost produced from plant residues, with the application of mineral nitrogen-urea and organo-mineral fertilizer in the Brazilian semiarid region. The experimental design was a randomized block in a 4 × 3 factorial scheme, with four replicates; four organic composts (millicompost, commercial vermicompost, vermicompost from bovine manure, vermicompost from goat manure); and three types of fertilization (without fertilizer, with mineral-urea and organo-mineral fertilizer). The organic composts were decomposed using litterbags at the soil surface. The variable's decomposition rate and the nutrient release were evaluated at six-time intervals (0, 30, 60, 90, 120, and 150 days), and microstructure was evaluated at the beginning and the end of the experiment, with scanning electron microscopy (SEM). The highest decomposition was verified for commercial vermicompost rich in macro and micronutrients and with lower P contents. The lignin:N ratio and the initial P content were more important in the permanence of the organic compost in the field than the C:N ratio. Regardless of the organic composts, the use of urea as a mineral fertilizer stimulated decomposition more than the organo-mineral fertilizer. The initial composition of the nutrients was decisive in the dynamics of nutrient release, mass loss, and decomposition of C. There was no pattern in the release order of macronutrients. However, for the micronutrients, the release order was Cu > Fe > Mn, in all treatments. Microstructure analysis is a visual analysis where differences are detected through microphotographs and the biggest difference occurred with millicompost, which showed elongated fibers and fiber bundles, forming a relatively open structure characteristic of the presence of fulvic acid. However, the addition of organo-mineral fertilizer formed agglomerates in compacted micro-portions, helping the mineralization of C and N., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To understand the factors associated with the practice of chemsex among MSM in Brazil, especially during the Mpox health crisis, and to design effective prevention and intervention strategies specifically for this population., Design: A cross-sectional and analytical study using an electronic survey, conducted from September to December 2022, during the peak of the Mpox outbreak in Brazil., Sample: A total of 1452 MSM aged 18 and older., Measurements: Data were collected via the REDCap platform through a survey with 46 questions. These addressed demographic data, sexual affiliations, practices, experiences with Mpox, healthcare service usage, and stigma or fear related to Mpox., Results: The prevalence of chemsex was 19.42% (n = 282). Multivariate Poisson modeling indicated a high incidence of chemsex among those diagnosed with Mpox and those involved in high-risk behaviors. The practice of chemsex was six times higher among those diagnosed with Mpox (95% CI: 4.73-9.10). MSM who engage in bugchasing had a prevalence twice that of the main outcome (95% CI: 1.31-3.16)., Conclusion: There is a significant need for targeted interventions for MSM in Brazil, especially given the Mpox outbreak. This study highlights the strong relationships between chemsex, experiences with Mpox, and various sexual behaviors, underscoring the importance of effective public health initiatives., (© 2024 The Authors. Public Health Nursing published by Wiley Periodicals LLC.)

Competing Interests: Conflict of interest statement. None declared.