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This paper describes patterns of infestation with Tunga penetrans (L., 1758) within the poor community of Araruama municipality, State of Rio de Janeiro, Brazil, assessed by the number of persons and domestic animals parasitized. The overall prevalence of infestation was 49.2% (211 parasitized hosts) of the 429 examined. Humans (p < 0.01) and dogs (p < 0.01) were the most important hosts with 62.6% and 35.6% respectively. Dogs were considered as the potential infestation source to humans. Considering sex and age groups, both measures showed a significant difference (p < 0.01): female (62.2% infested of 143 examined) and male (43.9% infested of 98 examined). All age classes were found infested with significant difference (G = 42.5; p < 0.01) and most of the infestation occurred in children in the 0-9-year old category (27.3%). In contrast and based on mean of chigoe burden per person, the parasitic intensity was significantly higher on male than on female in all age categories, except for the 50+ (H = 27.1; p < 0.01) and decreasing with the increase of age (chi2 = 69.7, A = -124.6, p < 0.01). Growing urbanization, improved housing and sewage systems, use of appropriate footwear, examination of the feet principally in young children, antitetanus prophylaxis and reduction of stray dogs population are the major prophylactic methods recommended.

Em 1977 foi diagnosticado o primeiro caso autóctone de leishmaniose visceral (LV) humano no Município do Rio de Janeiro. A partir de 1980, foram diagnosticados 54 casos autóctones em diversas localidades, sendo que desde 1993 ocorreram 17 casos humanos autóctones notificados. Oito deles ocorreram no bairro de Barra de Guaratiba e o restante distribuído pelos bairros: Camorim, Colônia, Grota Funda, Grumari, Ilha de Guaratiba e Carapiá. Entre setembro de 1996 a dezembro de 1999, foram realizadas capturas de flebotomíneos em 18 localidades nas encostas do maciço da Pedra Branca, no município, e coletados 18.303 espécimes com predomínio de L. intermedia (87,33%), L. migonei (6,59%), L. longipalpis (3,10%) e L. firmatoi (1,90%). A espécie L. longipalpis predominou em Barra de Guaratiba (46,80%), permanecendo ausente nas outras seis localidades onde também ocorreram casos de LV, o que sugere a participação de outras espécies tais como L. migonei e L. firmatoi, pertencentes ao mesmo grupo parafilético da espécie vetora, na cadeia de transmissão da LV na região.

Abstract Background The diaphragm is the major respiratory muscle affected by Duchenne muscular dystrophy (DMD) and is responsible for causing 80% of deaths. The use of mechanical forces that act on the body or intermittent pressure on the airways improves the quality of life of patients but does not prevent the progression of respiratory failure. Thus, diseases that require tissue repair, such as DMD, represent a group of pathologies that have great potential for cell therapy. The application of stem cells directly into the diaphragm instead of systemic application can reduce cell migration to other affected areas and increase the chances of muscle reorganisation. The mdx mouse is a suitable animal model for this research because its diaphragmatic phenotype is similar to human DMD. Therefore, the aim of this study was to assess the potential cell implantation in the diaphragm muscle after the xenotransplantation of stem cells. Methods A total of 9 mice, including 3 control BALB/Cmice, 3 5-month-old mdx mice without stem cell injections and 3 mdx mice injected with stem cells, were used. The animals injected with stem cells underwent laparoscopy so that stem cells from GFP-labelled rabbit olfactory epithelium could be locally injected into the diaphragm muscle. After 8 days, all animals were euthanised, and the diaphragm muscle was dissected and subjected to histological and immunohistochemical analyses. Results Both the fresh diaphragm tissue and immunohistochemical analyses showed immunopositive GFP labelling of some of the cells and immunonegativity of myoblast bundles. In the histological analysis, we observed a reduction in the inflammatory infiltrate as well as the presence of a few peripheral nuclei and myoblast bundles. Conclusion We were able to implant stem cells into the diaphragm via local injection, which promoted moderate muscle reorganisation. The presence of myoblast bundles cannot be attributed to stem cell incorporation because there was no immunopositive labelling in this structure. It is believed that the formation of the bundles may have been stimulated by cellular signalling mechanisms that have not yet been elucidated.

Abstract Background Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants ubiquitously distributed. They are generated by incomplete combustion of organic materials such as wood or fossil fuels. Due to their carcinogenic, mutagenic effects and to their wide distribution in the environment, these pollutants pose many concerns to researchers and regulators. In our laboratories we investigated the effect of benzo(a)pyrene (BaP) exposure in the marine diatom Thalassiosira pseudonana, which has become an important model organism in aquatic toxicology studies. Results In order to investigate the mechanism of action of PAHs, we exposed the diatoms for 24 h to 36.45 μg/L of BaP which inhibits the growth by about 30%, and analysed the relative protein expression profile by a quantitative proteomics approach based on iTRAQ labels. The proteomics profile analysis showed that around 10% of the identified proteins were regulated and one fourth of them confirmed the gene expression changes seen by DNA microarray. Particularly interesting was the down regulation of the Silicon transporter 1 (SIT1), an enzyme that is responsible for the uptake of silicon from the media into the diatom cells. Regulation of SIT1 upon BaP treatment was also confirmed at the gene expression level. Conclusions The potential use of the regulated proteins found in this study as early indicators of environmental exposure to PAHs is discussed. In particular, SIT1 is considered a promising biomarker and SIT1 expression changes were confirmed also when the diatoms were exposed to field samples, e.g. marine surface sediments contaminated by PAHs.

Cortical organoids derived from human induced pluripotent stem cells (hiPSCs) represent a powerful in vitro experimental system to investigate human brain development and disease, often inaccessible to direct experimentation. However, despite steady progress in organoid technology, several limitations remain, including high cost and variability, use of hiPSCs derived from tissues harvested invasively, unexplored three-dimensional (3D) structural features and neuronal connectivity. Here, using a cost-effective and reproducible protocol as well as conventional two-dimensional (2D) immunostaining, we show that cortical organoids generated from hiPSCs obtained by reprogramming stem cells from human exfoliated deciduous teeth (SHED) recapitulate key aspects of human corticogenesis, such as polarized organization of neural progenitor zones with the presence of outer radial glial stem cells, and differentiation of superficial- and deep-layer cortical neurons and glial cells. We also show that 3D bioprinting and magnetic resonance imaging of intact cortical organoids are alternative and complementary approaches to unravel critical features of the 3D architecture of organoids. Finally, extracellular electrical recordings in whole organoids showed functional neuronal networks. Together, our findings suggest that SHED-derived cortical organoids constitute an attractive model of human neurodevelopment, and support the notion that a combination of 2D and 3D techniques to analyze organoid structure and function may help improve this promising technology., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Infertility is a major health issue, affecting 15% of reproductive-age couples with male factors contributing to 50% of cases. Asthenozoospermia (AS), or low sperm motility, is a common cause of male infertility with complex aetiology, involving genetic and metabolic alterations, inflammation and oxidative stress. However, the molecular mechanisms behind low motility are unclear. In this study, we used a metabolomics approach to identify metabolic biomarkers and pathways involved in sperm motility., Methods: We compared the metabolome and lipidome of spermatozoa of men with normozoospermia (n = 44) and AS (n = 22) using untargeted LC-MS and the metabolome of seminal fluid using 1 H-NMR. Additionally, we evaluated the seminal fluid redox status to assess the oxidative stress in the ejaculate., Results: We identified 112 metabolites and 209 lipids in spermatozoa and 27 metabolites in the seminal fluid of normozoospermic and asthenozoospermic men. PCA analysis of the spermatozoa's metabolomics and lipidomics data showed a clear separation between groups. Spermatozoa of asthenozoospermic men presented lower levels of several amino acids, and increased levels of energetic substrates and lysophospholipids. However, the metabolome and redox status of the seminal fluid was not altered inAS., Conclusions: Our results indicate impaired metabolic pathways associated with redox homeostasis and amino acid, energy and lipid metabolism in AS. Taken together, these findings suggest that the metabolome and lipidome of human spermatozoa are key factors influencing their motility and that oxidative stress exposure during spermatogenesis or sperm maturation may be in the aetiology of decreased motility in AS., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Highly pathogenic Burkholderia pseudomallei is the causative agent of melioidosis, a neglected tropical disease endemic in Southeast Asian tropical region. This bacterium encompasses diverse virulence factors which further undergo dynamic gene-expression flux as it transits through distinct environmental niches within the host which may lead to manifestation of differential clinical symptoms. B. pseudomallei, is classified as a Tier 1 select agent in the United States and regarded as a risk group 3 organism in India with the potential to be used as bioweapon. Considering these facts, it is vital to uncover both physiological and genetic heterogeneity of B. pseudomallei, particularly to identify any novel virulence factors that may contribute to pathogenicity. B. pseudomallei strain CM000113 was isolated from a clinical case in India, characterized it for its physiological, biochemical, and prominently genetic traits through WGS. It has a type 2 morphotype with faster doubling time and high biofilm producing capacity as compared to Pseudomonas aeruginosa. The genome size is 7.3 Mbp and it is phylogenetically close to B. pseudomallei strain Mahidol 1106a and Burkholderia mallei Turkey 2. We observed genetic heterogeneity, as key virulence factors that were identified shows sequence dissimilarity with reference strains. Additionally, presence of genomic islands, harbouring two virulence factors, GmhA and GmhB2, associated with pathogenesis indicates possibility of horizontal gene transfer. These results emphasize the need for an extensive study focusing the genome of B. pseudomallei and its associated heterogeneity, to identify molecular biomarkers aiding to develop point-of-care diagnostic kits for early diagnosis of melioidosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Food waste is a significant concern when it comes to food safety. It is a well-known fact that fruit and vegetable wastage is high worldwide; however, quantitative data, especially on such waste in the retail sector, are limited. Wasted vegetables are sources of essential dietary compounds, benefiting from their revalorization. Studies related to the evaluation of the quantity and quality of these vegetables discarded in the retail sector can allow for the proposal of relevant alternatives for their use and the guarantee of food safety. This study aimed to assess wasted vegetables (beetroot, carrot, chayote, and cucumber) in the city of Pirassununga (Brazil) and characterize the purees obtained from these vegetable wastes. The purees were characterized in terms of microbiological aspects, color, proximal and mineral composition, phenolic concentration, and antioxidant activity. It was observed that 90% of the discarded vegetables were free from microbiological contamination and could be considered suitable for consumption according to the adopted classifications. Additionally, the purees had high nutritional levels, such as phenolics and fiber. Thus, considering the high levels of vegetable waste generated in the retail sector, and high value nutritional, vegetable waste could be viable in the development of new products, making it an important retail strategy for the circular economy.

Newly prepared tetracyclic imidazo[4,5-b]pyridine derivatives were synthesized to study their antiproliferative activity against human cancer cells. Additionally, the structure-activity was studied to confirm the impact of the N atom position in pyridine nuclei as well as the chosen amino side chains on antiproliferative activity. Targeted amino substituted regioisomers were prepared by using uncatalyzed amination from corresponding chloro substituted precursors. The most active compounds 6 a, 8 and 10 showed improved activity in comparison to standard drug etoposide with IC 50 values in a nanomolar range of concentration (0.2-0.9 μM). NMR-based metabolomics is a powerful instrument to elucidate activity mechanism of new chemotherapeutics. Multivariate and univariate statistical analysis of metabolic profiles of non-small cell lung cancer cells before and after exposure to 6 a revealed significant changes in metabolism of essential amino acids, glycerophospholipids and oxidative defense. Insight into the changes of metabolic pathways that are heavily involved in cell proliferation and survival provide valuable guidelines for more detailed analysis of activity metabolism and possible targets of this class of bioactive compounds., (© 2024 Wiley-VCH GmbH.)

Competing Interests: Conflict of interest: None declared.

Objectives: A timely diagnosis is imperative for curing cancer. However, in patients with rheumatic musculoskeletal diseases (RMDs) or paraneoplastic syndromes, misleading symptoms frequently delay cancer diagnosis. As metabolic remodelling characterises both cancer and RMD, we analysed if a metabolic signature can indicate paraneoplasia (PN) or reveal concomitant cancer in patients with RMD., Methods: Metabolic alterations in the sera of rheumatoid arthritis (RA) patients with (n=56) or without (n=52) a history of invasive cancer were quantified by nuclear magnetic resonance analysis. Metabolites indicative of cancer were determined by multivariable regression analyses. Two independent RA and spondyloarthritis (SpA) cohorts with or without a history of invasive cancer were used for blinded validation. Samples from patients with active cancer or cancer treatment, pulmonary and lymphoid type cancers, paraneoplastic syndromes, non-invasive (NI) precancerous lesions and non-melanoma skin cancer and systemic lupus erythematosus and samples prior to the development of malignancy were used to test the model performance., Results: Based on the concentrations of acetate, creatine, glycine, formate and the lipid ratio L1/L6, a diagnostic model yielded a high sensitivity and specificity for cancer diagnosis with AUC=0.995 in the model cohort, AUC=0.940 in the blinded RA validation cohort and AUC=0.928 in the mixed RA/SpA cohort. It was equally capable of identifying cancer in patients with PN. The model was insensitive to common demographic or clinical confounders or the presence of NI malignancy like non-melanoma skin cancer., Conclusions: This new set of metabolic markers reliably predicts the presence of cancer in arthritis or PN patients with high sensitivity and specificity and has the potential to facilitate a rapid and correct diagnosis of malignancy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Oral film (OF) research has intensified due to the effortless administration and advantages related to absorption in systemic circulation. Chitosan is one of the polymers widely used in the production of OFs; however, studies evaluating the maintenance of the active principles' activity are incipient. Propolis has been widely used as an active compound due to its different actions. Printing techniques to incorporate propolis in OFs prove to be efficient. The objective of the present study is to develop and characterize oral films based on chitosan and propolis using printing techniques and to evaluate the main activities of the extract incorporated into the polymeric matrix. The OFs were characterized in relation to the structure using scanning and atomic force electron microscopy; the mechanical properties, disintegration time, wettability, and stability of antioxidant activity were evaluated. The ethanolic extract of green propolis (GPEE) concentration influenced the properties of the OFs. The stability (phenolic compounds and antioxidant activity) was reduced in the first 20 days, and after this period, it remained constant.

Growth and carcass traits are essential selection criteria for beef cattle breeding programs. However, it is necessary to combine these measurements with body composition traits to meet the demand of the consumer market. This study aimed to estimate the genetic parameters for visual scores, growth (pre and post-weaning weights), and carcass (rib eye area (REA), back and rump fat thickness) traits in Nellore cattle using Bayesian inference. Data from 12,060 animals belonging to the HoRa Hofig Ramos herd were used. Morphological traits were evaluated by the MERCOS methodology. The heritability estimates obtained ranged from low to high magnitude, from 0.15 to 0.28 for visual scores, 0.13 to 0.44 for growth, and from 0.42 to 0.46 for carcass traits. Genetic correlations between visual scores and growth traits were generally of moderate to high magnitudes, however, visual scores showed low correlations with carcass traits, except between sacral bone and structure and REA. Selection for visual score traits can lead to favorable responses in body weight and vice versa, but the same is not true for carcass traits. Morphological categorical traits can be used as complementary tools that add value to selection.

Paper is one of the packaging materials that presents a biodegradable character, being used in several areas; however, its barrier properties (gases and fat) and mechanics are reduced, which limits its application. Coating papers with synthetic polymers improve these properties, reducing their biodegradability and recyclability. The objective of this work was to develop and characterize coated paperboard, using the tape casting technique, with different ratios of film form agar-agar/chitosan (AA:CHI, 100:0, 50:50, and 0:100) and different numbers of coating layers (operating times for application of 14.25 min and 28.5 min for one and two layers, respectively). A significant reduction in water absorption capacity was found by applying a 0:100 coating (approximately 15%). Considering all coating formulations, the water vapor permeability reduced by 10 to 60% compared to uncoated paperboard, except for two layers coated with 0:100. The tensile index (independent of AA:CHI) was higher in the machine direction (22.59 to 24.99 MPa) than in the cross-section (11.87-13.01 MPa). Paperboard coated only with chitosan showed superior properties compared to the other formulation coatings evaluated.

Lately, several machine learning (ML) techniques are emerging as alternative and efficient ways to predict how component properties influence the properties of the final mixture. In the area of civil engineering, recent research already uses ML techniques with conventional concrete dosages. The importance of discussing its use in the Brazilian context is inserted in an international context in which this methodology is already being applied, and it is necessary to verify the applicability of these techniques with national databases or what is created from national input data. In this research, one of these techniques, an artificial neural network (ANN), is used to determine the compressive strength of conventional Brazilian concrete at 7 and 28 days by using a database built through publications in congresses and academic works and comparing it with the reference database of Yeh. The data were organized into nine variables in which the data samples for training and test sets vary in five different cases. The eight possible input variables were: consumption of cement, blast furnace slag, pozzolana, water, additive, fine aggregate, coarse aggregate, and age. The response variable was the compressive strength of the concrete. Using international data as a training set and Brazilian data as a test set, or vice versa, did not show satisfactory results in isolation. The results showed a variation in the five scenarios; however, when using the Brazilian and the reference data sets together as test and training sets, higher R 2 values were obtained, showing that in the union of the two databases, a good predictive model is obtained.

Objective: Rheumatoid arthritis (RA) CD8+ T cells maintain their effector proinflammatory phenotype by changing their metabolism toward aerobic glycolysis. However, their massive energy and biosynthesis needs may require additional substrates other than glucose. Since systemic alterations in lipid metabolism have been reported in RA patients, we explored the role of fatty acid (FA) metabolism in CD8+ T cells to identify potential targets to curb their proinflammatory potential., Methods: The expression of FA metabolism-related genes was analyzed for total CD8+ T cells and CD8+ T cell subsets in the data of RA patients and healthy controls retrieved from the GEO database. Functional assays were performed using peripheral blood CD8+ T cells isolated from RA (n = 31), psoriatic arthritis (n = 26), and spondyloarthritis (n = 21) patients receiving different therapies (disease-modifying antirheumatic drugs, biologics, and JAK inhibitors) and from healthy controls (n = 14). We quantified the expression of FA transporters, lipid uptake, intracellular FA content, cytokine production, activation, proliferation, and capacity to inhibit tumor cell growth, either with or without FA metabolism inhibitors., Results: The CD8+ T cell gene expression profile of FA metabolism-related genes was significantly different between untreated RA patients and healthy controls. RA patients who had a good clinical response after 6 months of methotrexate therapy had significantly increased expression of FA metabolism-related genes. Cell surface expression of the FA transporters FA binding protein 4 (FABP4) and G protein-coupled receptor 84 (GPR84) and FA uptake were higher in effector and memory CD8+ T cells from RA patients compared to those from healthy controls. In vitro blockade of FA metabolism significantly impaired CD8+ T cell effector functions., Conclusion: RA CD8+ T cells present an altered FA metabolism, which could provide potential therapeutic targets to control their proinflammatory profile, particularly therapies directed against the transport and oxidation of free FA., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Adenosine receptors mainly control synaptic function, and excessive activation of adenosine receptors may worsen the onset of many neurological disorders. Accordingly, the regular intake of moderate doses of caffeine antagonizes adenosine receptors and affords robust neuroprotection. Although caffeine intake alters brain functional connectivity and multi-omics analyses indicate that caffeine intake modifies synaptic and metabolic processes, it is unclear how caffeine intake affects behavior, synaptic plasticity and its modulation by adenosine. We now report that male mice drinking caffeinated water (0.3 g/L) for 2 weeks were behaviorally indistinguishable (locomotion, mood, memory) from control mice (drinking water) and displayed superimposable synaptic plasticity (long-term potentiation) in different brain areas (hippocampus, prefrontal cortex, amygdala). Moreover, there was a general preservation of the efficiency of adenosine A 1 and A 2A receptors to control synaptic transmission and plasticity, although there was a tendency for lower levels of endogenous adenosine ensuring A 1 receptor-mediated inhibition. In spite of similar behavioral and neurophysiological function, caffeine intake increased the energy charge and redox state of cortical synaptosomes. This increased metabolic competence likely involved a putative increase in the glycolytic rate in synapses and a prospective greater astrocyte-synapse lactate shuttling. It was concluded that caffeine intake does not trigger evident alterations of behavior or of synaptic plasticity but increases the metabolic competence of synapses, which might be related with the previously described better ability of animals consuming caffeine to cope with deleterious stimuli triggering brain dysfunction.

Synthetic polymer coatings impact the biodegradable behavior of cellulosic packaging material. The environmental consequences of food packaging disposal have increased consumer concern. The present study aimed to use natural polymer coatings incorporating palmitic acid and activated carbon applied to paperboard surfaces as a sustainable alternative to improve cellulosic packaging material's moisture and fat barrier properties, minimizing the environmental impact. The coating formulation was defined using a Factorial Experimental Design with independent variables: chitosan, palmitic acid, activated carbon concentrations, and the number of coating layers. The highest concentration of chitosan (2.0% w / w ) filled the pores of the cellulosic paperboard network, supporting the compounds incorporated into the filmogenic matrix and improving the fat resistance. The water vapor permeability of the coated paperboard material (range: 101 ± 43 to 221 ± 13 g·d -1 ·m -2 ) was influenced by the hydrophobicity effect of palmitic acid, the non-polar characteristic of activated carbon, and the number of applied layers. The coating formulation selected was a chitosan concentration of 2.0% ( w / w ), a palmitic acid concentration of 1.8% ( w / w ), an activated carbon concentration of 1.2% ( w / w ), and an application of three layers. The coating provides the potential for a paperboard surface application, improving the cellulosic packaging material's fat and moisture barrier properties and maintaining biodegradability and recyclability.

Copolymers composed of low-molecular-weight polyethylenimine (PEI) and amphiphilic Pluronics® are safe and efficient non-viral vectors for pDNA transfection. A variety of Pluronic® properties provides a base for tailoring transfection efficacy in combination with the unique biological activity of this polymer group. In this study, we describe the preparation of new copolymers based on hydrophilic Pluronic® F68 and PEI (F68PEI). F68PEI polyplexes obtained by doping with free F68 (1:2 and 1:5 w/w) allowed for fine-tuning of physicochemical properties and transfection activity, demonstrating improved in vitro transfection of the human bone osteosarcoma epithelial (U2OS) and oral squamous cell carcinoma (SCC-9) cells when compared to the parent formulation, F68PEI. Although all tested systems condensed pDNA at varying polymer/DNA charge ratios (N/P, 5/1−100/1), the addition of free F68 (1:5 w/w) resulted in the formation of smaller polyplexes (<200 nm). Analysis of polyplex properties by transmission electron microscopy and dynamic light scattering revealed varied polyplex morphology. Transfection potential was also found to be cell-dependent and significantly higher in SCC-9 cells compared to the control bPEI25k cells, as especially evident at higher N/P ratios (>25). The observed selectivity towards transfection of SSC-9 cells might represent a base for further optimization of a cell-specific transfection vehicle.

Starches are promising molecules in the production of edible films. However, the hydrophilic nature of these materials is among the main limitations of packaging based on natural polymers. An underexplored alternative is the incorporation of emulsions. This work aimed to produce films based on crosslinked cassava starch with emulsions based on watermelon seed oil (WSO) extracted with pressurized ethanol. The effect of incorporating watermelon seed oil emulsion (WSOE) on the microscopic, structural, mechanical, hydrophilic, and thermal properties of films was analyzed. The internal structure and roughness of the films were significantly affected by increasing WSOE concentration. The WSOE incorporation increased the elongation capacity of the films and reduced the strain at break. WSOE concentrations did not significantly affect the water solubility, permeability, and X-ray diffraction but decreased the wettability of the films. The analysis of the thermal properties showed that the films did not present phase separation in the studied temperature range. Overall, WSOE improved the properties of the films based on cross-linked cassava starch, but it is necessary to optimize the production conditions of the films. These materials may potentially be used as biodegradable food packaging, controlled-release films, and edible coatings in food protection.

Circular economy, and concerns about environmental waste, is fostering the development of sustainable alternative products in a range of industries. In the dermo-cosmetic field, the market for sustainable anti-aging skincare products has increasingly grown over the last years. The innovation of this work was to develop chitosan films incorporating lemongrass essential oil (LEO) that could potentially be applied as a green cosmetic skin treatment due to their anti-oxidant and antimicrobial properties, using renewable and biodegradable materials. Different concentrations of LEO (i.e., 0.5, 1.0, and 1.5 % w/w) were formulated into chitosan filmogenic matrices, forming skincare bioactive films. Their antioxidant properties and water vapor permeability were strongly governed by the LEO concentration. Chitosan bioactive films containing 0.5 % LEO showed cellular viability over 70 %, while those with 1.5 % LEO had similar antioxidant capacity as NAC (N-acetyl-L-cysteine), used as the positive control to inactivate intracellular reactive oxygen species (ROS) in HaCat cells not treated with H 2 O 2 . The developed bioactive films showed activity against Escherichia coli and Staphylococcus aureus. Our LEO-loaded chitosan biofilms may be used as sheet masks with antioxidant and antimicrobial properties for skincare, with high flexibility and selected permeability, and without cytotoxic risks., 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 © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The renewal of the natural resources is one of the most concerning aspects of modern farming. In animal production, there are many barriers breeders and researchers have to overcome to develop new practices to improve reproductive potential and hasten sexual maturation of the commercially viable species, while maintaining meat quality and sustainability. With the utilization of molecular biology techniques, there have been relevant advances in the knowledge of spermatogenesis, especially in mammals, resulting in new possibilities to control male fertility and the selection of desirable characteristics. Most of these discoveries have not been implemented in animal production. In this review, recent studies are highlighted on the molecular pathways involved in spermatogenesis in the context of animal production. There is also exploration of the interaction between environmental factors and spermatogenesis and how this knowledge may revolutionize animal production techniques. Furthermore, new insights are described about the inheritance of desired characteristics in mammals and there is a review of nefarious actions of pollutants, nutrition, and metabolism on reproductive potential in subsequent generations. Even though there are these advances in knowledge base, results from recent studies indicate there are previously unrecognized environmental effects on spermatogenesis. The molecular mechanisms underlying this interaction are not well understood. Research in spermatogenesis, therefore, remains pivotal as a pillar of animal production sustainability., Competing Interests: Declarations of interest None to declare., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Stress, as a physiological response, is a major factor that affects several processes, including reproductive functions. The main hormonal players of stress are cortisol (humans) and corticosterone (rodents). Sertoli cells (SCs), as key contributors for the testicular homeostasis maintenance, are extensively challenged by different hormones, with glucocorticoid corticosterone being the signaling modulator that may impact these cells at different levels. We aimed to characterize how corticosterone modulates SCs energy balance, putting the mitochondrial performance and signaling output in perspective as the cells can disperse to the surroundings. TM4 mouse SCs were cultured in the absence and presence of corticosterone (in nM: 20, 200, and 2000). Cells were assessed for extracellular metabolic fluxes, mitochondrial performance (cell respirometry, mitochondrial potential, and mitochondrial complex expressions and activities), and the expression of androgen and corticosteroid receptors, as well as interleukine-6 (IL-6) and glutathione content. Corticosterone presented a biphasic impact on the extracellular fluxes of metabolites. Low sub-physiological corticosterone stimulated the glycolytic activity of SCs. Still, no alterations were perceived for lactate and alanine production. However, the lactate/alanine ratio was decreased in a dose-dependent mode, opposite to the mitochondrial complex II activity rise and concurrent with the decrease of IL-6 expression levels. Our results suggest that corticosterone finely tuned the energetic profile of mouse SCs, with sub-physiological concentrations promoting glycolytic expenditure, without translating into cell redox power and mitochondrial respiratory chain performance. Corticosterone deeply impacted the expression of the pro-inflammatory IL-6, which may alter cell-to-cell communication in the testis, in the last instance and impact of the spermatogenic performance., Competing Interests: The authors declare that they have no conflict of interest.

Objectives: Rheumatic immune-related adverse events (irAE) such as (poly)arthritis in patients undergoing immune checkpoint inhibitor (ICI) treatment pose a major clinical challenge. ICI therapy improves CD8 + T cell (CD8) function, but CD8 contributes to chronic inflammation in autoimmune arthritis (AA). Thus, we investigated whether immune functional and metabolic changes in CD8 explain the development of musculoskeletal irAE in ICI-treated patients., Methods: Peripheral CD8 obtained from ICI-treated patients with and without arthritis irAEs and from AA patients with and without a history of malignancy were stimulated in media containing 13 C-labelled glucose with and without tofacitinib or infliximab. Changes in metabolism, immune-mediator release, expression of effector cell-surface molecules and inhibition of tumour cell growth were quantified., Results: CD8 from patients with irAE showed significantly lower frequency and expression of cell-surface molecule characteristic for activation, effector-functions, homing, exhaustion and apoptosis and reduced release of cytotoxic and proinflammatory immune mediators compared with CD8 from ICI patients who did not develop irAE. This was accompanied by a higher glycolytic rate and ATP production. Gene-expression analysis of pre-ICI-treated CD8 revealed several differentially expressed transcripts in patients who later developed arthritis irAEs. In vitro tofacitinib or infliximab treatment did not significantly change the immune-metabolic profile nor the capacity to release cytolytic mediators that inhibit the growth of the human lung cancer cell line H838., Conclusions: Our study shows that CD8 from ICI-treated patients who develop a musculoskeletal irAE has a distinct immune-effector and metabolic profile from those that remain irAE free. This specific irAE profile overlaps with the one observed in CD8 from AA patients and may prove useful for novel therapeutic strategies to manage ICI-induced irAEs., Competing Interests: Competing interests: KB: Consultancy and/or speaker fees and/or travel reimbursements: Abbvie, Bristol Myers Squibb (BMS), Gilead/Galapagos, Janssen, Merck Sharp & Dohme (MSD), Mundipharma, Novartis, Pfizer, Roche, Viatris, UCB. Scientific support: Medical Faculty of University of Heidelberg, Rheumaliga Baden-Württemberg e.V., AbbVie, Novartis. MMSC: Scientific support: Novartis, Pfizer. JCH: honoraria: BMS, MSD, Novartis, Roche, Pierre Fabre, Sanofi, Almirall; consultant or advisory role: MSD, Pierre Fabre, Sunpharma; Scientific support: BMS; Travel support: Pierre Fabre. PC: honoraria: Roche, Takeda, Gilead, AstraZeneca, Novartis; scientific support: Roche, Takeda, Amgen, Merck, AstraZeneca, Novartis; travel support: AstraZeneca, Merck, Janssen, Daiichi Sankyo, Takeda, Novartis, Elli Lilly; data safety monitoring and/or advisory board: Pfizer, Chugai, Boehringer Ingelheim, Roche. JG: honoraria: Galapagos; travel support: Elli Lilly. HML: Scientific funding: Abbvie, Novartis, Pfizer, Roche; consulting fees and honoraria: Abbvie, AstraZeneca, Actelion, Amgen, Bayer Vital, Boehringer Ingelheim, BMS, Celgene, GlaxoSmithKline (GSK), Galapagos, Janssen, Elli Lilly, Medac, MSD, Novartis, Pfizer, Roche, Sanofi, UCB; travel support: Abbvie, AstraZeneca, Boehriner Ingelheim, BMS, Celgene, GSK, Gilead, Janssen, Elli Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, UCB; data safety monitoring and/or advisory board: Abbvie, AstraZeneca, Amgen, Boehriner Ingelheim, BMS, Celgene, GSK, Gilead, Janssen, Elli Lilly, Medac, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The purpose of this study was to develop oral films (OFs) based on agar-agar with the incorporation of mushroom powder (MP) as a source of phenolic compounds. To this end, three different OFs were produced using different concentrations of MP, containing sorbitol and agar-agar. The OFs were characterized based on visual assessment, mass, thickness, moisture content, folding endurance, surface pH, contact angle, and phenolic compound content, scanning electron microscopy, X-ray diffraction, and FTIR, as well as an assessment of their antioxidant capacity. In general, all the OFs showed film-forming capacity after the incorporation of MP, although their mass, thickness, moisture content, and folding endurance differed significantly. The surface pH value remained close to neutrality (∼6.7), regardless of MP concentration. The incorporation of MP increased the crystallinity of the OFs in comparison to that of the agar-based film, but all the OFs showed similar FTIR spectra. The oral films containing 2 g of MP showed antioxidant capacity by ABTS ●+ and FRAP of 3.68±0.23 and 14.61±0.66 mMol ET/g OF, respectively, and total phenolic content of 3.55±0.27 µmol GAE/g OF. Thus, oral films offer an innovative source of delivery of active compounds, and their consumption does not cause oral mucosal irritation., Competing Interests: Declaration of interests 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 © 2021 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

The incidence of metabolic diseases such as type 2 diabetes mellitus (DM) and obesity has been increasing dramatically. Both diseases are closely linked and new approaches for type 2 DM treatment aim to enable weight loss. A combined therapy of dapagliflozin and exenatide has been used against type 2 DM, influencing allbody glucose dynamics. Spermatogenesis is highly dependent on the metabolic cooperation established between Sertoli cells (SCs) and developing germ cells. To study the effects of dapagliflozin and exenatide on SC metabolism, mouse SCs were treated in the presence of sub-pharmacologic, pharmacologic, and supra-pharmacologic concentrations of dapagliflozin (50, 500, 5000 nM, respectively) and/or exenatide (2.5, 25, 250 pM, respectively). Cytotoxicity of these compounds was evaluated and the glycolytic profile, glycogen content assay, and lipid accumulation of SCs were determined. Dapagliflozin treatment decreased fat cellular deposits, demonstrating its anti-obesity properties at the cellular level. Polytherapy of exenatide plus dapagliflozin increased lactate production by SCs, which has been reported to improve sperm production and quality. Thus, the results herein suggest that the use of these two pharmacological agents can protect male fertility, while improving their glucose homeostasis and inducing weight loss.

Food classification systems have been proposed to improve food quality criteria. Among these systems, "processing level" has been used as a criterion. NOVA classification, as the denotation "ultra-processed" food (UPF), has been widely used in different countries. However, even though some studies have pointed out some controversial aspects, no study has evaluated its comprehension by the population where it is used as reference. Therefore, this study explored the understanding of the term UPF for Brazilian consumers, where this denotation has been used in the last 8 years. A questionnaire was used, with questions referring to different aspects of self-assessment of knowledge about UPF. Altogether, 939 valid participants completed the questionnaire, and 81.9% of them declared to know the term UPF. For 78.2%, a better definition for UPF should be "foods that have gone through many processes in industry". Finally, it was concluded that the term UPF is still confusing for most Brazilians, indicating the risk of use and the urgent necessity to improve the classifications systems and consequently consumer understanding. Only when all parties interested in healthy food work together could this problem be solved.

Purpose: De novo lipogenesis (DNL) is critical for cell growth and maintenance, and acetyl-CoA precursors can be derived from different substrates. We developed a 13 C NMR analysis of lipid extracts from cultured microglia cells administered with [U- 13 C]glucose that informs overall lipogenic activity as well as the contribution of glucose to lipogenic acetyl-CoA., Methods: BV-2 microglial cell line cultured with glucose and glutamine was provided with [U- 13 C]glucose and unlabeled glutamine for 24 h and studied in either the presence or absence of lipopolysaccharide (LPS). Cells were then extracted for lipids and the crude lipid fraction was analyzed by 13 C NMR. 13 C-isotopomer signals in the fatty acid ω - 1 and ω - 2 signals representing consecutive or non-consecutive enrichment of the fatty acid chain by [1,2- 13 C 2 ]acetyl-CoA were quantified and applied to a probabilistic model of acetyl-CoA precursor and fatty acid enrichment., Results: Glucose contributed 72 ± 2% of lipogenic acetyl-CoA while DNL from all sources accounted for 16 ± 2% of lipid turnover. With LPS, there was a significant decrease in glucose contribution (59 ± 4%, p < 0.05) while DNL was unchanged (11 ± 3%)., Conclusions: A simple 13 C NMR analysis of the crude lipid fractions of BV-2 cells administered with [U- 13 C]glucose informs DNL activity and the contribution of glucose to the acetyl-CoA precursors. While DNL was preserved in the presence of LPS, there was redirection of lipogenic acetyl-CoA sources from glucose to other substrates. Thus, in the present article, we describe a novel and simple 13 C NMR analysis approach to disclose the overall lipogenic activity and substrate contribution to DNL, suitable for evaluating DNL rates in cell cultures., (© 2021 John Wiley & Sons, Ltd.)

The paramount importance of a healthy diet in the prevention of type 2 diabetes is now well recognized. Blueberries (BBs) have been described as attractive functional fruits for this purpose. This study aimed to elucidate the cellular and molecular mechanisms pertaining to the protective impact of blueberry juice (BJ) on prediabetes. Using a hypercaloric diet-induced prediabetic rat model, we evaluated the effects of BJ on glucose, insulin, and lipid profiles; gut microbiota composition; intestinal barrier integrity; and metabolic endotoxemia, as well as on hepatic metabolic surrogates, including several related to mitochondria bioenergetics. BJ supplementation for 14 weeks counteracted diet-evoked metabolic deregulation, improving glucose tolerance, insulin sensitivity, and hypertriglyceridemia, along with systemic and hepatic antioxidant properties, without a significant impact on the gut microbiota composition and related mechanisms. In addition, BJ treatment effectively alleviated hepatic steatosis and mitochondrial dysfunction observed in the prediabetic animals, as suggested by the amelioration of bioenergetics parameters and key targets of inflammation, insulin signaling, ketogenesis, and fatty acids oxidation. In conclusion, the beneficial metabolic impact of BJ in prediabetes may be mainly explained by the rescue of hepatic mitochondrial bioenergetics. These findings pave the way to support the use of BJ in prediabetes to prevent diabetes and its complications.

Bile acids (BA) have shown promising effects in animal models of obesity. However, the said effects are thought to rely on a thermogenic effect, which is questionably present in humans. A previous work has shown that the BA chenodeoxycholic acid (CDCA) can revert obesity and accelerate metabolism in animal and cell culture models. Thus, the aim of this study was to understand if this obesity reduction is indeed thermogenically-dependent. A CRISPR/Cas9 model of TGR5 (BA receptor) knockdown in 3T3-L1 adipocytes was developed to diminish thermogenic effects. Various parameters were assessed, including mitochondrial bioenergetics by Seahorse flux analysis, oxidative stress and membrane potential by fluorometry, intermediary metabolism by NMR, protein content assessment by Western Blot, gene expression by qPCR, and confocal microscopy evaluation of mitophagy. CDCA was still capable, for the most part, of reversing the harmful effects of cellular obesity, elevating mitophagy and leading to the reduction of harmed mitochondria within the cells, boosting mitochondrial activity, and thus energy consumption. In summary, CDCA has a non-thermogenic, obesity reducing capacity that hinges on a healthy mitochondrial population, explaining at least some of these effects and opening avenues of human treatment for metabolic diseases.

The objective of this study was to determine whether the addition of grape residue flour (GRF) in the diet of suckling lambs would improve their health and consequently enhance their growth. We used 48 lambs, 30 days of age divided into four treatments with four repetitions each, with each repetition consisting of three animals. The groups were identified as follows: G-0%, used as a control (without GRF) and G-0.5%, G-1% and G-2% referring to treatment with grape residue flour in doses of 0.5%, 1%, and 2% of inclusion in the concentrate, respectively. Lambs in groups G-1% and G-2% had higher final body weights, weight gain and average daily gain (ADG) compared to the other groups. GRF dietary supplementation had good antioxidant potential, being able to stimulate glutathione S-transferase (GST) activity and consequently reduce levels of reactive oxygen species (ROS) in lambs that consumed the highest dose of GRF (G-2%). GRF supplementation improved humoral responses, with increased serum levels of heavy-chain and light-chain immunoglobulins; however, there was a reduction in serum ceruloplasmin levels in these lambs. We observed higher concentrations of glucose and triglycerides in lambs in the 2% group. There were lower lymphocyte counts in lambs that received GRF. Lambs supplemented with the highest doses of GRF (G-1% and G-2%) had lower total bacterial counts in the feces. We conclude that the use of GRF in the supplementation of suckling lambs improved animal health, as it stimulated the antioxidant and immune systems and consequently favored their growth., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The Tocantins-Araguaia Basin is one of the largest river systems in South America, located entirely within Brazilian territory. In the last decades, capital-concentrating activities such as agribusiness, mining, and hydropower promoted extensive changes in land cover, hydrology, and environmental conditions. These changes are jeopardizing the basin's biodiversity and ecosystem services. Threats are escalating as poor environmental policies continue to be formulated, such as environmentally unsustainable hydropower plants, large-scale agriculture for commodity production, and aquaculture with non-native fish. If the current model persists, it will deepen the environmental crisis in the basin, compromising broad conservation goals and social development in the long term. Better policies will require thought and planning to minimize growing threats and ensure the basin's sustainability for future generations., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Simultaneous bilateral rupture of the quadricipital tendon is an extremely rare lesion. We report a case of this injury after low-energy trauma in a patient with type-II diabetes mellitus. Both knees were surgically approached in the same surgical procedure. Early rehabilitation is essential for the adequate functional recovery of the knee. The aim of the present report was to describe an atypical case of this type of injury after minimal trauma, as well as to detail the surgical technique used to treat it., Competing Interests: Conflito de Interesses Os autores declaram não haver conflito de interesses., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

Background: Since the beginning of the COVID-19 pandemic, researchers and health authorities have sought to identify the different parameters that drive its local transmission cycles to make better decisions regarding prevention and control measures. Different modeling approaches have been proposed in an attempt to predict the behavior of these local cycles., Objective: This paper presents a framework to characterize the different variables that drive the local, or epidemic, cycles of the COVID-19 pandemic, in order to provide a set of relatively simple, yet efficient, statistical tools to be used by local health authorities to support decision making., Methods: Virtually closed cycles were compared to cycles in progress from different locations that present similar patterns in the figures that describe them. With the aim to compare populations of different sizes at different periods of time and locations, the cycles were normalized, allowing an analysis based on the core behavior of the numerical series. A model for the reproduction number was derived from the experimental data, and its performance was presented, including the effect of subnotification (ie, underreporting). A variation of the logistic model was used together with an innovative inventory model to calculate the actual number of infected persons, analyze the incubation period, and determine the actual onset of local epidemic cycles., Results: The similarities among cycles were demonstrated. A pattern between the cycles studied, which took on a triangular shape, was identified and used to make predictions about the duration of future cycles. Analyses on effective reproduction number (R t ) and subnotification effects for Germany, Italy, and Sweden were presented to show the performance of the framework introduced here. After comparing data from the three countries, it was possible to determine the probable dates of the actual onset of the epidemic cycles for each country, the typical duration of the incubation period for the disease, and the total number of infected persons during each cycle. In general terms, a probable average incubation time of 5 days was found, and the method used here was able to estimate the end of the cycles up to 34 days in advance, while demonstrating that the impact of the subnotification level (ie, error) on the effective reproduction number was <5%., Conclusions: It was demonstrated that, with relatively simple mathematical tools, it is possible to obtain a reliable understanding of the behavior of COVID-19 local epidemic cycles, by introducing an integrated framework for identifying cycle patterns and calculating the variables that drive it, namely: the R t , the subnotification effects on estimations, the most probable actual cycles start dates, the total number of infected, and the most likely incubation period for SARS-CoV-2., Competing Interests: Conflicts of Interest: None declared., (©Eduardo Atem De Carvalho, Rogerio Atem De Carvalho. Originally published in JMIRx Med (https://med.jmirx.org), 18.03.2021.)

Background: A dysregulated glucose metabolism in synovial fibroblasts (SF) has been associated with their aggressive phenotype in rheumatoid arthritis (RA). Even though T helper (Th) cells are key effector cells in the propagation and exacerbation of synovitis in RA, little is known about their influence on the metabolism of SF. Thus, this study investigates the effect of Th cells on the glucose metabolism and phenotype of SF and how this is influenced by the blockade of cytokines, janus kinases (JAKs) and glycolysis., Methods: SF from patients with RA or osteoarthritis (OA) were cultured in the presence of a stable glucose isotopomer ([U- 13 C]-glucose) and stimulated with the conditioned media of activated Th cells (ThCM). Glucose consumption and lactate production were measured by proton nuclear magnetic resonance ( 1 H NMR) spectroscopy. Cytokine secretion was quantified by ELISA. The expression of glycolytic enzymes was analysed by PCR, western blot and immunofluorescence. JAKs were blocked using either baricitinib or tofacitinib and glycolysis by using either 3-bromopyruvate or FX11., Results: Quiescent RASF produced significantly higher levels of lactate, interleukin (IL)-6 and matrix metalloproteinase (MMP) 3 than OASF. Stimulation by ThCM clearly changed the metabolic profile of both RASF and OASF by inducing a shift towards aerobic glycolysis with strongly increased lactate production together with a rise in IL-6 and MMP3 secretion. Interestingly, chronic stimulation of OASF by ThCM triggered an inflammatory phenotype with significantly increased glycolytic activity compared to unstimulated, singly stimulated or re-stimulated OASF. Finally, in contrast to cytokine-neutralizing biologics, inhibition of JAKs or glycolytic enzymes both significantly reduced lactate production and cytokine secretion by Th cell-stimulated SF., Conclusions: Soluble mediators released by Th cells drive SF towards a glycolytic and pro-inflammatory phenotype. Targeting of JAKs or glycolytic enzymes both potently modulate SF's glucose metabolism and decrease the release of IL-6 and MMP3. Thus, manipulation of glycolytic pathways could represent a new therapeutic strategy to decrease the pro-inflammatory phenotype of SF.

Background: The Old-World bollworm, Helicoverpa armigera (Hübner), was recently documented attacking cotton and soybean plants in Brazil; however, restricted basic knowledge on host plant interactions and landscape use in Brazil have limited the effectiveness of control measures. In this study, we evaluated the suitability of different crops commonly cultivated in Brazil as hosts for H. armigera and H. zea, and examined their contribution to the establishment and size of H. armigera and H. zea field populations. We also estimated the proportions of H. armigera and H. zea moths that used cotton, noncotton C 3 plants, and C 4 plants as hosts in four regions in Brazil through the length of the cropping season., Results: Viability of H. armigera larvae was highest on cotton (46.1%), followed by millet (39.5%), sorghum (31.2%), soybean (24.2%), and maize (21.1%). Noncotton C 3 hosts served as the major source of H. armigera moths in all regions evaluated, and C 4 hosts were a source of H. armigera mainly in regions where winter maize is typically cultivated. H. armigera moths that used cotton plants as natal hosts were observed during the reproductive stage of the crop mainly in the state of Bahia. Only C 4 host plants were a consistent source of H. zea moths, primarily when maize was in the reproductive stage. H. armigera individuals were the main species infesting cotton and soybean fields while H. zea individuals were the main species infesting maize ears., Conclusions: Regional differences in the host use and population dynamics of H. armigera among the regions evaluated may be attributed to variation in alternative host utilization (crops, noncrops, and weeds) and the possible occurrence of facultative diapause and or migration., (© 2020 Society of Chemical Industry.)

Mitochondria play a central role in metabolic reprograming that occurs in numerous disease conditions. A precise evaluation of the extent of mitochondrial involvement in the metabolic alterations is essential for a better definition of metabolically based therapeutic strategies. In this chapter, some simple protocols are presented, using carbon 13 tracers and nuclear magnetic resonance isotopomer analysis, for the evaluation of mitochondrial contributions to intermediary metabolism and the metabolic effects of the implementation of some mitochondrial regulatory mechanisms.