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Swainsonine is a natural [alpha]-mannosidase inhibitor found in numerous poisonous plants, such as Astragalus lentiginosus. Its mechanism of action is through the inhibition of Golgi [alpha]-mannosidase II activity in the N-glycan biosynthesis pathway. As a result, swainsonine inhibits the production of complex [beta]1,6-branched N-linked glycans, which are related to the malignant phenotype of tumor cells. In this study, we investigated whether treatment with swainsonine affects the sensitivity of Ehrlich ascites carcinoma (EAC) cells to cisplatin. To this end, male C57BL/6 mice were treated with swainsonine (SW - 0.5mg/kg, i.p., twice-daily for ten days) and/or cisplatin (Cis - 0.25mg/kg, i.p., every other day for a total of five applications) two days after transplantation with EAC cells. The results showed a greater reduction in the ascites volume in mice from the CisSW group (63.5%) than in mice from the Cis group (45.7%), an elevated induction of apoptosis by CisSW treatment when compared to Cis alone, as demonstrated by higher percentage of cells in the subG1 phase in that group (p<0.0001 Kruskal-Wallis, p<0.0001 control vs. CisSW, p<0.001 Co vs. Cis post-test Dunn), and an increase in the median survival from 12.5 days observed in the control group to 27 days in the CisSW group, which corresponds to a 116% survival increase (p=0.0022 Co vs. CisSW Log-rank test). In addition, the mice from the Cis group had a median survival of only 15 days, an increase of just 20% compared to controls. Our results indicate that swainsonine increases the sensitivity of EAC cells to cisplatin. [ABSTRACT FROM AUTHOR]

Objectives: Lithium disilicate (LS) ceramic emerges as a compelling option for customized implant abutments. However, ensuring its safety and reliability requires clarification on key aspects, notably its impact on inflammation and potential for cell adhesion. This study delves into these considerations, examining the influence of LS ceramic on cytokine release and the transcriptional profile of human gingival fibroblasts (hGFs) in direct contact with various LS surfaces., Methods: hGFs were cultured on LS disks featuring three distinct surfaces (unpolished, polished, and polished glaze), while titanium disks served as reference material and cells cultured directly on plates as controls. The surface of the disks was analyzed using a scanning electron microscope. The cell metabolism was analyzed by MTT test, cytokine release by MAGPIX and the expression of genes related to cell adhesion was evaluated by qPCR., Results: The disks exhibited similar topography with smooth surfaces, except for the unpolished LS disks, which had an irregular surface. Contact with LS surfaces did not substantially reduce cell metabolism. Moreover, it generally decreased cytokine release compared to controls, particularly pro-inflammatory mediators like IL-1β, IL-6, and TNF-α. Significantly increased expression of genes related to cell adhesion to LS was observed, comparable to titanium, the gold standard material for implant abutments., Significance: This study unveils that LS ceramic not only fails to trigger pro-inflammatory cytokine release, but also significantly enhances gene expression associated with cell adhesion. These mechanisms are closely linked to gene pathways such as PTK2, SRC, MAPK1, and transcription factors ELK-1 and MYC. In summary, the findings underscore LS ceramic's potential as a biocompatible material for implant abutments, shedding light on its favorable inflammatory response and enhanced cell adhesion properties., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Fatty acid profile, physicochemical composition, and carcass traits of 32 young Nellore bulls were assessed following the supplementation of Acacia mearnsii extract at levels of 0, 10, 30, and 50 g/kg of total dry matter (DM) in a completely randomized experiment with four treatments and eight replicates. Adding 50 g/kg DM of condensed tannins (CT) from Acacia mearnsii in the bulls' diet reduced DM intake, average daily gain, and meat lipid oxidation (P ≤ 0.05). The pH, centesimal composition, collagen, and meat color indexes of the longissimus muscle were not altered by the addition of Acacia mearnsii (P > 0.05). Cooling loss increased (P = 0.049) linearly. Including Acacia mearnsii in diet reduced the Warner-Bratzler shear force (WBSF, P = 0.018) of longissimus muscle of the bulls. The concentration of C16:0, C17:0, C24:0, t9,10,11,16-18:1, c9t11-18:2, C18:2n-6, C20:4n-6, 20:5n-3, 22:5n-3, and 22:6n-3 in the muscle increased due to the addition of Acacia in the diet (P ≤ 0.05), with the highest muscle concentrations caused by the addition of 10 to 30 g Acacia. c9-18:1 and t16-18:1 reduced linearly. ƩSFA, ƩBI, Ʃcis- and ƩMUFA, Ʃn-3, Ʃn-6, and ƩPUFA (P ≤ 0.05) quadratically increased at higher concentrations of addition of Acacia, above 30 g/kg DM. It is recommended to include Acacia mearnsii extract up to 30 g/kg total DM in diets for young bulls as it improves CLA, PUFA and TI and reduces lipid oxidation. Acacia mearnsii extract as source of CT at 50 g/kg DM negatively impacted the young bulls performance., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have influenced the study reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Visceral Leishmaniasis, caused by Leishmania infantum, is a tropical neglected disease and the most dangerous form of Leishmaniasis. It occurs zoonotically, with domestic transmission posing risks to humans as dogs have high susceptibility and are natural reservoirs of the parasite. Given their epidemiological role, improvements are needed in diagnosing Canine Visceral Leishmaniasis (CVL). Thus, we mapped linear epitopes from the rLiNTPDase2 antigen through peptide microarray and identified six positive epitopes. Validation through peptide ELISA revealed three promising peptides with accuracies of 78.6%, 85.92%, and 79.59%. Their combination yielded 97.58% accuracy. Negative epitopes were also found, which interacted with CVL-negative and Chagas Disease positive samples. Their removal from the rLiNTPDase2 sequence resulted in the rNT2.neg, which obtained enhanced specificity over rLiNTPDase2. The rNT2.neg validation achieved 87.50% sensitivity, 90.55% specificity, and 93.5% accuracy within 127 CVL-positive and 96 CVL-negative samples. Therefore, three peptides and rNT2.neg show significant promise for CVL diagnosis., 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 Inc. All rights reserved.)

Trypanosomatids have achieved significant evolutionary success in parasitizing various groups, yet reptiles remain relatively unexplored. The utilization of advanced molecular tools has revealed an increased richness of trypanosomatids in vertebrate hosts. The aim of this study was to identify the trypanosomatid species infecting Bothrops moojeni and Crotalus durissus kept in captivity from 2000 to 2022. Blood samples were obtained from 106 snakes: 73C. durissus and 33 B. moojeni. Whole blood was collected for hemoculture, blood smears and centrifugated to obtain the blood clot that had its DNA extracted and submitted to Nested PCR (18S rDNA gene) to detect Trypanosomatidae. Positive samples were quantified and submitted to both conventional (Sanger) and next generation sequencing (NGS). Cloning of the amplified PCR product was performed for only one individual of C. durissus. To exclude the possibility of local vector transmission, attempts to capture sandflies were conducted using six CDC-LT type light traps. Molecular diagnosis revealed that 34% of the snakes presented trypanosomatid DNA, 47.94% in C. durissus and 3.9% in B. moojeni. The cloning process generated four colonies identified as a new MOTU named Trypanosomatidae sp. CROT. The presence of DNA of five trypanosomatids (Trypanosoma cruzi TcII/VI, Trypanosoma sp. DID, Trypanosoma cascavelli, Trypanosomatidae sp. CROT, Leishmania infantum and Leishmania sp.) and one free-living kinetoplastid (Neobodo sp.) was revealed through NGS and confirmed by phylogenetic analysis. The haplotypic network divided the T. cascavelli sequences into two groups, 1) marsupials and snakes and 2) exclusive to marsupials. Therefore, the diversity of Kinetoplastea is still underestimated. Snakes have the ability to maintain infection with T. cruzi and L. infantum for up to 20 years and the DNA finding of Neobodo sp. in the blood of a C. durissus suggests that this genus can infect vertebrates., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Western equine encephalitis virus (WEEV) is a mosquitoborne virus that reemerged in December 2023 in Argentina and Uruguay, causing a major outbreak. We investigated the outbreak using epidemiologic, entomological, and genomic analyses, focusing on WEEV circulation near the Argentina‒Uruguay border in Rio Grande do Sul state, Brazil. During November 2023‒April 2024, the outbreak in Argentina and Uruguay resulted in 217 human cases, 12 of which were fatal, and 2,548 equine cases. We determined cases on the basis of laboratory and clinical epidemiologic criteria. We characterized 3 fatal equine cases caused by a novel WEEV lineage identified through a nearly complete coding sequence analysis, which we propose as lineage C. Our findings highlight the importance of continued surveillance and equine vaccination to control future WEEV outbreaks in South America.

Purpose: The optimal duration of antibiotic therapy for fracture-related infection (FRI) has not been well defined. Our aim was to assess the recurrence rate of infection in patients who underwent six, 12, or 24 weeks of antibiotic therapy following surgical treatment for FRI one year after antibiotic discontinuation. Additionally, complications were monitored., Methods: Patients with FRI underwent surgical treatment, and antibiotic therapy was initiated. The patients were divided into groups at the 6th and 12th weeks of antibiotic therapy. The primary endpoint was the recurrence of deep or superficial infection at 90 days and one year after the end of antimicrobial therapy., Results: There was no difference in the recurrence of infection 90 days or one year after stopping antibiotic therapy among patients treated for six, 12, or 24 weeks (p = 0.98 and p = 0.19, respectively). The overall recurrence rate of infection 90 days after stopping antibiotic therapy was 4.9% (8/163), and one year after discontinuation of antibiotic therapy was 9.8% (16/163). There was a statistically significant difference in the incidence of adverse effects among the three groups (chi-square; p = 0.01). Adverse effects were more common in the group treated for 24 weeks than in the groups treated for 6 weeks (z score, p = 0.017) or 12 weeks (z score, p = 0.005)., Conclusion: Antibiotic therapy longer than 6 weeks did not reduce the recurrence of FRI after one year of follow-up. Additionally, antibiotic treatment for 24 weeks increases adverse events such as skin reactions and acute renal failure., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Supplementing swine diets with phytase increases phosphorus release by approximately 50% from cereal phytates. The increase in phosphorus availability allows for a reduction in dietary phosphorus supplementation from mineral sources and decreases the environmental impact of pork production through a decrease in phosphorus excretion. Superdosing phytase has been reported to boost swine productivity, improve the digestibility of other nutrients, and mitigate the antinutritional effects of phytates. However, there are significant cost differences among phytase products. Bacterial phytases are considered more modern, often with a higher cost of inclusion. A study was conducted with 288 piglets that were 21 d of age and weighed 6.43 ± 0.956 kg. Pigs were divided into four groups. Each group of pigs was fed a different experimental diet varying in phytase source and level: fungal phytase ( Aspergillus niger ) at 500 FTU/kg of diet, fungal phytase at 2,000 FTU/kg, bacterial phytase ( Escherichia coli ) at 500 FTU/kg, and bacterial phytase at 2,000 FTU/kg. No differences were found for phytase sources or doses on productivity at 14 and 21 d postweaning. However, piglets supplemented with 2,000 FTUs/kg of phytase in the diet during the first 21 d of nursery exhibited a 5.8% better feed conversion ( P  = 0.02). An interaction between phytase source and dose was observed for average live weight and daily weight gain over the 42-d nursery period ( P  < 0.05). Supplementing the diet with 2,000 FTU/kg of fungal phytase improved daily weight gain and live weight throughout the experimental period compared to piglets supplemented with 500 FTU/kg of the same phytase source. Additionally, it resulted in better final weights compared to piglets supplemented with 500 FTU/kg of bacterial phytase. Phytase inclusion at 2,000 FTU/kg improved feed conversion by 2.07% over the 42-d nursery period. The most economically favorable feed conversion ratios were observed when supplementing the diet with fungal phytase at 2,000 FTUs/kg., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science.)

The Pantanal region, the largest floodplain in the world, has a huge biodiversity and is an important livestock center. Bovine brucellosis has been reported in the region over the last three decades, posing implications for cattle industry as well as for the maintenance of biodiversity. We aimed to investigate the presence of B. abortus S19 vaccine strain DNA in unvaccinated domestic and wild ungulates from the Brazilian Pantanal. Fifty-two heifers, 63 ovine, 24 domestic pigs, 28 feral pigs, and three Pampas deer were sampled. Brucella spp. was detected through bcsp31 PCR of blood samples in 45.3% (77/170) of the sampled animals, of which 36.4% (28/77) showed positivity in ery PCR corresponding to B. abortus S19 strain. Feral pigs presented the highest occurrence of positive samples in bcsp31 PCR (75%), followed by ovine (47.6%), domestic pigs (41.7%), and unvaccinated heifers (30.8%). We did not observe positivity in Pampas deer. Our results strongly suggest that vaccination against bovine brucellosis may promote spill-over of B. abortus S19 strain in the Pantanal region. Moreover, our data indicate that wild strains of Brucella circulates in the Pantanal Biome., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Cardiovascular pathology is the main cause of death in chronic kidney disease (CKD) patients. CKD is associated with the accumulation of uremic toxins in the bloodstream, and indoxyl sulfate (IS) is one of the most abundant uremic toxins found in the blood of CKD patients. We conducted an in vitro study to assess the mechanisms underlying the IS-induced endothelial dysfunction that could lead to cardiovascular diseases. We also studied their extracellular vesicles (EVs) owing to their capacity to act as messengers that transmit signals through their cargo., Main Methods: EVs were characterized by nanoparticle tracking analysis, transmission electron microscopy, flow cytometry, and tetraspanin expression. Cell lysates and isolated EVs were analyzed using liquid chromatography coupled with mass spectrometry, followed by Gene Set Enrichment Analysis to identify the altered pathways., Key Findings: Proteomic analysis of endothelial cells revealed that IS causes an increase in proteins related to adipogenesis, inflammation, and xenobiotic metabolism and a decrease in proliferation. Extracellular matrix elements, as well as proteins associated with myogenesis, response to UV irradiation, and inflammation, were found to be downregulated in IS-treated EVs. Fatty acid metabolism was also found to be increased along with adipogenesis and inflammation observed in cells., Significance: The treatment of endothelial cells with IS increased the expression of proteins related to adipogenesis, inflammation, and xenobiotic metabolism and was less associated with proliferation. Furthermore, EVs from cells treated with IS may mediate endothelial dysfunction, since they present fewer extracellular matrix elements, myogenesis, inflammatory factors, and proteins downregulated in response to UV radiation., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest related to the content of this article., (Copyright © 2024. Published by Elsevier Inc.)

Herein we report a study on the sequential substitution of different nucleophiles on cyanuric chloride to obtain potential candidates for metal sensors (5a-c). The set of nucleophiles on the 1,3,5-triazine ring includes a phenolic BODIPY, an aminoalkyl pyridine and aminoalkyl phosphoramidates, each one designed to play a specific role in the final fluoroionophore. Three new triazine triads were synthesized in similar yields: 5a (45%), 5b (43%) and 5c (52%) after a methodical sequential combination of the nucleophiles via thermodependent nucleophilic aromatic substitution of the three chlorine atoms of cyanuric chloride. To ratify the synthetic results we simulated the reaction mechanisms for the different nucleophiles, aiming to address the distinctive orthogonality and temperature control inherent in this process, identifying and providing a sound rationale for any preferential sequence of nucleophiles inserted into the triazine core. According to our experimental and computational analysis (thermo- and kinetic preferences), we have identified the following preferential order for the sequential substitution: p -hydroxybenzaldehyde > 2-(pyridin-2-yl)ethanamine > aminoalkyl phosphoramidate, indicating that all steps follow a single-step process (concerted) in two stages, where nucleophilic addition precedes leaving group dissociation. The Meisenheimer σ-complex was identified as a transition state structure, with insufficient stability to exist as an intermediate. We observed a consistent and progressive increase in barrier height: 2-8 kcal mol -1 for the first step, 9-15 kcal mol -1 for the second step, and >15 kcal mol -1 for the third substitution. These findings align with the experimental observation of thermodependency in the sequential substitution.

Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a severe rare liver disease that affects between 1/50,000 and 1/100,000 children. In physiological conditions, bile is produced by the liver and stored in the gallbladder, and then it flows to the small intestine to play its role in fat digestion. To prevent tissue damage, bile acids (BAs) are kept in phospholipid micelles. Mutations in phosphatidyl choline transporter ABCB4 (MDR3) lead to intrahepatic accumulation of free BAs that result in liver damage. PFIC3 onset usually occurs at early ages, progresses rapidly, and the prognosis is poor. Currently, besides the palliative use of ursodeoxycholate, the only available treatment for this disease is liver transplantation, which is really challenging for short-aged patients. To gain insight into the pathogenesis of PFIC3 we have performed an integrated proteomics and phosphoproteomics study in human liver samples to then validate the emerging functional hypotheses in a PFIC3 murine model. We identified 6246 protein groups, 324 proteins among them showing differential expression between control and PFIC3. The phosphoproteomic analysis allowed the identification of 5090 phosphopeptides, from which 215 corresponding to 157 protein groups, were differentially phosphorylated in PFIC3, including MDR3. Regulation of essential cellular processes and structures, such as inflammation, metabolic reprogramming, cytoskeleton and extracellular matrix remodeling, and cell proliferation, were identified as the main drivers of the disease. Our results provide a strong molecular background that significantly contributes to a better understanding of PFIC3 and provides new concepts that might prove useful in the clinical management of patients., (© 2024 The Authors. BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

Despite technological advances in the proteomics field, sample preparation still represents the main bottleneck in mass spectrometry (MS) analysis. Bead-based protein aggregation techniques have recently emerged as an efficient, reproducible, and high-throughput alternative for protein extraction and digestion. Here, a refined paramagnetic bead-based digestion protocol is described for Opentrons® OT-2 platform (OT-2) as a versatile, reproducible, and affordable alternative for the automatic sample preparation for MS analysis. For this purpose, an artificial neural network (ANN) was applied to maximize the number of peptides without missed cleavages identified in HeLa extract by combining factors such as the quantity (μg) of trypsin/Lys-C and beads (MagReSyn® Amine), % (w/v) SDS, % (v/v) acetonitrile, and time of digestion (h). ANN model predicted the optimal conditions for the digestion of 50 μg of HeLa extract, pointing to the use of 2.5% (w/v) SDS and 300 μg of beads for sample preparation and long-term digestion (16h) with 0.15 μg Lys-C and 2.5 μg trypsin (≈1:17 ratio). Based on the results of the ANN model, the manual protocol was automated in OT-2. The performance of the automatic protocol was evaluated with different sample types, including human plasma, Arabidopsis thaliana leaves, Escherichia coli cells, and mouse tissue cortex, showing great reproducibility and low sample-to-sample variability in all cases. In addition, we tested the performance of this method in the preparation of a challenging biological fluid such as rat bile, a proximal fluid that is rich in bile salts, bilirubin, cholesterol, and fatty acids, among other MS interferents. Compared to other protocols described in the literature for the extraction and digestion of bile proteins, the method described here allowed identify 385 unique proteins, thus contributing to improving the coverage of the bile proteome., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Fernando J. Corrales reports financial support was provided by Spain Ministry of Science and Innovation. Fernando J. Corrales reports financial support was provided by Community of Madrid. Fernando J. Corrales reports financial support was provided by Spanish Scientific Research Council. Matias A. Avila reports financial support was provided by Carlos III Health Institute. If there are other authors, they 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Small mammals have a short lifetime and are strictly associated with their environment. This work aimed to use histopathology to assess the health of Holochilus chacarius in a rice agroecosystem in the Pantanal of Mato Grosso do Sul. During necropsy, fragments of the lung, kidney, skin, liver, and reproductive system of 33 animals were collected and submitted to histological processing. Tissue damages were evaluated as mild, moderate, and severe and arranged in a matrix for further statistical analysis. Furthermore, we used generalized linear models to verify the influence of tissue changes on the body condition, obtained by a regression between body mass and length. In the lungs, we found an intense inflammatory infiltrate associated with anthracosis that had a negative influence on the body's condition. Also, we observed degenerative and inflammatory changes in the liver, kidneys, skin, and reproductive system that ranged from mild to moderate. The histopathological lesions observed in this study may be associated with environmental alterations of anthropic origin such as the exposure to soot from wildfires and heavy metals, evidenced by lesions in the lung, kidney, and liver. The present study provided a histopathological matrix as a new approach that allows to classify and quantify the tissue alterations. Tissue changes when associated with body condition demonstrated to be an effective tool to assess the health of small free-living mammals, showing that these animals can be used as bioindicators of environmental condition., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The phytochemical investigation of the leaves and trunk bark of a specimen of Ocotea aciphylla collected in the southern portion of the Amazon forest led to the isolation of an oxabicyclo[3.2.2]nonane-type neolignan and 15 bicyclo[3.2.1]octanoid neolignans, 14 of which are unreported compounds ( 2 - 15 ), including one with an unusual oxidation pattern of the side chain at C-1' and two rare 7.1',8.3'-connected bicyclo[3.2.1]octanoid derivatives. Their structures and relative configurations were determined by extensive spectrometric analysis based on 1D- and 2D-NMR spectroscopy and HRESIMS data, while their absolute configurations were unambiguously assigned using electronic and vibrational circular dichroism data assisted by density functional theory calculations. Additionally, known sesquiterpenes, phenylpropanoids, and phytosterols were also isolated.

This study aims at identifying molecular biomarkers differentiating responders and non-responders to treatment with Tumor Necrosis Factor inhibitors (TNFi) among patients with axial spondyloarthritis (axSpA). Whole blood mRNA and plasma proteins were measured in a cohort of biologic-naïve axSpA patients ( n = 35), pre and post (14 weeks) TNFi treatment with adalimumab. Differential expression analysis was used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi. A treatment-associated signature suggests a reduction in inflammatory activity. We found transcripts and proteins robustly differentially expressed between baseline and week 14 in responders. C-reactive protein (CRP) and Haptoglobin (HP) proteins showed strong and early decrease in the plasma of axSpA patients, while a cluster of apolipoproteins (APOD, APOA2, APOA1) showed increased expression at week 14. Responders to TNFi treatment present higher levels of markers of innate immunity at baseline, and lower levels of adaptive immunity markers, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender, and AFF3 , the top differentially expressed gene at baseline, enabled an accurate prediction of response to adalimumab in our cohort (AUC = 0.97). In conclusion, innate and adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in axSpA patients. A model including clinical and gene expression variables should also be considered.

The increasing demand for highly pure biopharmaceuticals has put significant pressure on the biotechnological industry to innovate in production and purification processes. Nucleic acid purification, crucial for gene therapy and vaccine production, presents challenges due to the unique physical and chemical properties of these molecules. Meeting regulatory standards necessitates large quantities of biotherapeutic agents of high purity. While conventional chromatography offers versatility and efficiency, it suffers from drawbacks like low flow rates and binding capacity, as well as high mass transfer resistance. Recent advancements in continuous beds, including monoliths and cryogel-based systems, have emerged as promising solutions to overcome these limitations. This review explores and evaluates the latest progress in chromatography utilizing monolithic and cryogenic supports for nucleic acid purification.

Bats have a long evolutionary history with trypanosomatids, but the role of these flying mammals on parasite transmission cycles in urban areas, especially for Trypanosoma and Leishmania species, remains poorly known. The objective of this study was to evaluate the species richness of trypanosomatids parasitizing a bat community in Campo Grande (CG), a state capital within the Cerrado of the Brazilian Midwest. We evaluated 237 bats of 13 species by means of hemoculture and molecular detection in spleen samples. The bat community of CG appears to participate in the transmission cycles of various species of trypanosomatids. We report an overall trypanosomatid detection rate of 34.2% (n = 81), involving 11 out of 13 sampled bat species. We identified six species of trypanosomatids from 61 bats by analyzing SSU rRNA and/or kDNA: Trypanosoma cruzi DTU TcI, T. c. marinkellei, T. dionisii, Leishmania infantum, L. amazonensis, and T. janseni, with this latter being detected by hemoculture for the first time in a bat species. We also detected a Molecular Operational Taxonomic Unit, Trypanosoma sp. DID, in the phyllostomids Glossophaga soricina and Platyrrhinus lineatus. The highest trypanosomatid richness was observed for Sturnira lilium, which hosted three species: L. infantum, T. dionisii and T. janseni. Given that visceral leishmaniasis is endemic in CG, special focus should be placed on L. infantum. Moreover, L. amazonensis and T. cruzi warrant attention, since these are zoonotic parasites responsible for human cases of tegumentary leishmaniasis and Chagas disease, respectively. In this respect, we discuss how bat communities may influence the Leishmania spp. transmission in endemic areas., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Purpose The primary objective of this study was to compare placenta growth factor (PlGF) levels in the serum and vitreous of diabetic retinopathy (DR) patients to non-diabetic controls. Additionally, the study aimed to establish associations between serum and vitreous PlGF concentrations and to examine the correlation between vitreous PlGF in DR patients and morphological parameters. Methods This study included serum and vitreous samples from 38 patients, including 21 patients with DR and 17 non-diabetic controls. The control group included non-diabetic patients with rhegmatogenous retinal detachment with retinal tears secondary to posterior vitreous detachment or trauma. PlGF levels were quantified in vitreous and serum samples using an enzyme-linked immunosorbent assay (ELISA). Optical coherence tomography (OCT) scans from DR patients were evaluated to measure the central retinal thickness (CRT) and macular volume (MV). Results DR patients had significantly higher mean vitreous PlGF levels compared to non-DR patients (70.0±39.2 vs. 46.47±9.7 pg/mL, p-value=0.004). However, no significant increase in mean serum PlGF levels was observed in DR patients (p-value=0.232). Within the DR group, proliferative DR (PDR) patients presented significantly higher vitreous PlGF levels than non-PDR (NPDR) patients (76.5±41.0 vs. 42.5±5.0 pg/mL, p-value=0.009). There was no association between serum and vitreous PlGF levels. The correlation between vitreous PlGF levels and morphological parameters was r sp =0.175, p-value=0.488 for CRT, and r sp =0.288, p-value=0.262 for MV. Conclusion This study emphasizes the important role of PlGF in neovascularization, specifically highlighting its overexpression exclusively in vitreous from PDR patients. The observed increase in PlGF levels may be indicative of disease severity. The lack of correlation between vitreous and serum PlGF levels suggests a potential dissociation between intravitreal and systemic PlGF synthesis. Consequently, targeting PlGF in therapeutic approaches may offer an additional strategy for ocular pathologies with a neovascular component., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Mesquita et al.)

The study of host-parasite interactions is essential to understand the role of each host species in the parasitic transmission cycles in a given community. The use of ecological network highlights the patterns of interactions between hosts and parasites, allowing us to evaluate the underlying structural features and epidemiological roles of different species within this context. Through network analysis, we aimed to understand the epidemiological roles of mammalian hosts species (n = 67) and their parasites (n = 257) in the Pantanal biome. Our analysis revealed a modular pattern within the network, characterized by 14 distinct modules, as well as nestedness patterns within these modules. Some key nodes, such as the multi-host parasites Trypanosoma cruzi and T. evansi, connect different modules and species. These central nodes showed us that various hosts species, including those with high local abundances, contribute to parasite maintenance. Ectoparasites, such as ticks and fleas, exhibit connections that reflect their roles as vectors of certain parasites. Overall, our findings contribute to a comprehensive understanding of the structure of host-parasite interactions in the Pantanal ecosystem, highlighting the importance of network analysis as a tool to identifying the main transmission routes and maintenance of parasites pathways. Such insights are valuable for parasitic disease control and prevention strategies and shed light on the broader complexities of ecological communities., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mayaro virus (MAYV) is an emerging arbovirus member of the Togaviridae family and Alphavirus genus. MAYV infection causes an acute febrile illness accompanied by persistent polyarthralgia and myalgia. Understanding the mechanisms involved in arthritis caused by alphaviruses is necessary to develop specific therapies. In this work, we investigated the role of the CCL2/CCR2 axis in the pathogenesis of MAYV-induced disease. For this, wild-type (WT) C57BL/6J and CCR2 -/- mice were infected with MAYV subcutaneously and evaluated for disease development. MAYV infection induced an acute inflammatory disease in WT mice. The immune response profile was characterized by an increase in the production of inflammatory mediators, such as IL-6, TNF, and CCL2. Higher levels of CCL2 at the local and systemic levels were followed by the significant recruitment of CCR2 + macrophages and a cellular response orchestrated by these cells. CCR2 -/- mice showed an increase in CXCL-1 levels, followed by a replacement of the macrophage inflammatory infiltrate by neutrophils. Additionally, the absence of the CCR2 receptor protected mice from bone loss induced by MAYV. Accordingly, the silencing of CCL2 chemokine expression in vivo and the pharmacological blockade of CCR2 promoted a partial improvement in disease. Cell culture data support the mechanism underlying the bone pathology of MAYV, in which MAYV infection promotes a pro-osteoclastogenic microenvironment mediated by CCL2, IL-6, and TNF, which induces the migration and differentiation of osteoclast precursor cells. Overall, these data contribute to the understanding of the pathophysiology of MAYV infection and the identification future of specific therapeutic targets in MAYV-induced disease.IMPORTANCEThis work demonstrates the role of the CCL2/CCR2 axis in MAYV-induced disease. The infection of wild-type (WT) C57BL/6J and CCR2 -/- mice was associated with high levels of CCL2, an important chemoattractant involved in the recruitment of macrophages, the main precursor of osteoclasts. In the absence of the CCR2 receptor, there is a mitigation of macrophage migration to the target organs of infection and protection of these mice against bone loss induced by MAYV infection. Much evidence has shown that host immune response factors contribute significantly to the tissue damage associated with alphavirus infections. Thus, this work highlights molecular and cellular targets involved in the pathogenesis of arthritis triggered by MAYV and identifies novel therapeutic possibilities directed to the host inflammatory response unleashed by MAYV., Competing Interests: The authors declare no conflict of interest.

In early symptomatic COVID-19 treatment, high dose oral favipiravir did not accelerate viral clearance., Background: Favipiravir, an anti-influenza drug, has in vitro antiviral activity against SARS-CoV-2. Clinical trial evidence to date is inconclusive. Favipiravir has been recommended for the treatment of COVID-19 in some countries., Methods: In a multicentre open-label, randomised, controlled, adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomised to one of ten treatment arms including high dose oral favipiravir (3.6g on day 0 followed by 1.6g daily to complete 7 days treatment) or no study drug. The primary outcome was the rate of viral clearance (derived under a linear mixed-effects model from the daily log 10 viral densities in standardised duplicate oropharyngeal swab eluates taken daily over 8 days [18 swabs per patient]), assessed in a modified intention-to-treat population (mITT). The safety population included all patients who received at least one dose of the allocated intervention. This ongoing adaptive platform trial was registered at ClinicalTrials.gov (NCT05041907) on 13/09/2021., Results: In the final analysis, the mITT population contained data from 114 patients randomised to favipiravir and 126 patients randomised concurrently to no study drug. Under the linear mixed-effects model fitted to all oropharyngeal viral density estimates in the first 8 days from randomisation (4,318 swabs), there was no difference in the rate of viral clearance between patients given favipiravir and patients receiving no study drug; a -1% (95% credible interval: -14 to 14%) difference. High dose favipiravir was well-tolerated., Interpretation: Favipiravir does not accelerate viral clearance in early symptomatic COVID-19. The viral clearance rate estimated from quantitative measurements of oropharyngeal eluate viral densities assesses the antiviral efficacy of drugs in vivo with comparatively few studied patients., (© 2024. The Author(s).)

The ability of nature to produce structurally complex molecules makes the determination of the absolute configuration of natural products a challenging task. Although extensive NMR analysis generally allows for the reliable assignment of relative configurations, the assignments of absolute stereochemistry are commonly performed by empirical comparisons of optical rotation (OR) and/or electronic circular dichroism (ECD) data obtained for related molecules. Such an approach, however, may lead to misassignments and consequent error propagations. Herein, we present the case of the bicyclo(3.2.1)octane neolignan named (+)-nectamazin A. This compound was first reported in 2009 from Nectandra amazonum Nees. (Lauraceae) and had its absolute configuration determined as 7R,8S,3'S,4'R,5'S by means of experimental ECD spectroscopy. Our chemical studies on Ocotea aciphylla (Lauraceae) led to the isolation of (+)-nectamazin A. The extensive analysis of OR, ECD, and vibrational CD data aided by quantum chemical calculations, however, indicated (+)-nectamazin A to have the 7S,8R,3'R,4'S,5'R absolute configuration, in conflict with the configuration reported in the literature. The cause of the original incorrect assignment of (+)-nectamazin A derives from the direct comparison of experimental OR and ECD data obtained for structurally related molecules with different chromophoric systems. As an alternative, VCD spectroscopy is presented as a more reliable and sensitive technique to stereochemical investigations of bicyclo(3.2.1)octane neolignans., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: Aging of the HIV-infected population and prolonged use of ARTs, produced metabolic alterations, including increased fracture risk. FRAX is a validated, computer-based clinical fracture risk calculator which estimates 10-year risk of major fracture, and hip fracture. However may underestimate risk in HIV-infected individuals. Several experts recommend considering HIV a cause of secondary osteoporosis., Methodology: Were included 52 men living with HIV, classified as high, moderate and low risk using ABRASSO graphic tool., Results: High risk prevalence found for major fracture and hip fracture were both 2 (4.2 %) using FRAX; while 10 (20.8 %) and 14 (29.2 %) using modified FRAX, respectively. Considering bone densitometry, 5 (12.8 %) were high risk for hip fracture and was noticed an increase in high risk major fracture from 4.2 % with FRAX to 5.1 % with FRAX considering bone densitometry. As for the low risk, 19 (39.6 %) for major fracture and 23 (47.9 %) for hip fracture with FRAX. While low risk modified FRAX were 0 (0 %) for major fracture and 8 (16.7 %) for hip fracture. It was also evidenced an association of high risk for major fracture and hip fracture with modified FRAX using Fisher's exact test [p=0.0273 (bilateral)]., Conclusion: It was concluded is recommended using modified FRAX for people living with HIV for better control and therapeutic decision-making about osteometabolic alterations provocated for the virus and ARTs., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Currently, analysis of interim PET (iPET) according to the Deauville score (DS) is the most important predictive factor in Hodgkin lymphoma (HL); however, there is room for improvement in its prognostic power. This study aimed to evaluate the prognostic value of quantitative PET analysis (maximum standard uptake value [SUV max ], total metabolic tumor volume [TMTV] and total lesion glicolysis [TLG]) at baseline (PET0) and iPET in a retrospective cohort of newly diagnosed classical HL. For positive iPET (+ iPET), the reduction of quantitative parameters in relation to PET0 (ΔSUV max , ΔTMTV and ΔTLG) was calculated. Between 2011 and 2017, 234 patients treated with ABVD were analyzed. Median age was 30 years-old, 59% had advanced stage disease, 57% a bulky mass and 25% a + iPET (DS 4-5). At baseline, high TLG was associated with an increased cumulative incidence of failure (CIF) (p = 0.032) while neither SUV max , TMTV or TLG were associated with overall survival (OS) or progression-free survival (PFS). In multivariate analysis, only iPET was associated with CIF (p < 0.001). Among ΔSUV max , ΔTMTV and ΔTLG, only a ΔSUV max  ≥ 68.8 was significant for PFS (HR: 0.31, CI95%: 0.11-0.86, p = 0.024). A subset of patients with improved PFS amongst + iPET was identified by the quantitative (ΔSUV max  ≥ 68.8%) analysis. In this real-world Brazilian cohort, with prevalent high-risk patients, quantitative analysis of PET0 did not demonstrate to be prognostic, while a dynamic approach incorporating the ΔSUV max to + iPET succeeded in refining a subset with better prognosis. These findings warrant validation in larger series and indicate that not all patients with + iPET might need treatment intensification., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bats have been reported as reservoir host of Leishmania spp. worldwide, mostly by molecular detection. However, it is still unclear whether bats act as reservoirs of Leishmania infantum to sandflies vectors. In this sense, the investigation of amastigotes forms in the target organs, and the characterization of their associated inflammation, may help to clarify the epidemiological importance of bats in endemic areas for leishmaniasis. The aim of this work was to investigate the host-parasite relationships under microscopic evaluation and predict the epidemiological role of two phyllostomid bats species naturally infected by L. infantum in an endemic area for human leishmaniasis. Fragments of skin, liver and spleen of L. infantum positive and negative bats ( Artibeus planirostris and Carollia perspicillata) by qPCR, were studied by histological and immunohistochemical techniques. Both groups, positive and negative, did not show differences in the histopathological study, presenting only discrete tissue changes. Liver and skin showed mild inflammatory reactions. Findings on spleen consisted of reactivity of the lymphoid follicles, expressive presence of apoptotic cells and macrophages containing abundant phagocytic cells debris. We did not find amastigote forms in tissues by histological and IHC techniques in positive qPCR bats. Our results allow us to hypothesize that phyllostomid bats seem to have an important role in reducing the risk of transmission, possibly acting as dead-end host., Competing Interests: None., (© 2023 The Authors.)

Objectives: The Global Leadership Initiative on Malnutrition (GLIM) criteria establish a diagnosis of malnutrition based on the presence of at least one phenotypic and one etiologic criterion. This study aimed to assess the concurrent and predictive validity of the GLIM criteria in hospitalized cancer patients., Methods: This is an observational retrospective study, including 885 cancer patients, ages >18 y, admitted to a medical oncology inpatient unit between 2019 and 2020. All patients at risk for malnutrition according to the Nutritional Risk Screening 2002 score were assessed by the subjective global assessment (SGA) and 14 different combinations of the GLIM criteria. The SGA was considered the gold standard for assessing the concurrent validity of the GLIM combinations. For a subsample of patients with data available on inflammatory markers (n = 198), the serum albumin and C-reactive protein were included in the combinations as etiologic criteria. The predictive validity of the different combinations was tested using the occurrence of surgical complications as the clinical outcome. The sensitivity and specificity values were calculated to assess the concurrent validity, univariate and multivariate logistic regression models were used to test predictive validity. Adequate concurrent and predictive validity were determined as sensitivity and specificity values >80% and odds ratio values ≥2.0, respectively., Results: The median age of the patients was 61.0 y (interquartile range = 51.0-70.0). Head and neck cancer was the prevailing diagnosis and 375 patients were at nutritional risk. According to the SGA, 173 (26.1%) patients were malnourished (SGA categories B or C) and the prevalence of malnutrition ranged from 3.9% to 30.0%, according to the GLIM combinations. None of the tested combinations reached adequate concurrent validity; however, the presence of malnutrition according to four combinations independently predicted surgical complications., Conclusions: The predictive validity of the GLIM was satisfactory in surgical cancer patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Treatments of Inflammatory Bowel Disease (IBD) are able to control symptoms in most cases, however, a fraction of patients do not improve or have a loss of response to treatments, making it important to explore new therapeutic strategies. Hyperbaric oxygen therapy (HBO) may represent one of them. The aim of this study was to evaluate the effects of HBO therapy in an experimental model of IBD., Methods: Sixty male BALBc mice were divided into six groups. Group 1 was colitis-induced with trinitrobenzene sulfonic acid (TNBS) + ethanol, group 2 received TNBS + ethanol plus HBO, group 3 received only ethanol, group 4 received ethanol plus HBO, group 5 received saline solution, and group 6 received saline solution plus HBO. HBO was performed for four days, subsequently, the mice were evaluated daily. At the end of the study, samples from the intestine were collected for histological analysis as well as for measurement of antioxidant enzymes and cytokine levels., Results: HBO significantly improved the clinical and histological status of the animals. Treatment with HBO increased the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) in all of the groups; moreover, the difference was only significant between the TNBS and TNBS + HBO groups and treatments promoted a reduction in the proinflammatory cytokines IFN-γ, IL-12, IL-17 and TNF-α and increased the anti-inflammatory cytokines IL-4 and IL-10, with no changes in IL-13., Conclusion: HBO effectively treats TNBS-induced colitis by increasing the activity of antioxidant enzymes and modulating cytokine profiles., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)