Search

Main Conclusion: The redox homeostasis and photosynthetic pigments changes vary with Tetranychus ludeni infestation, with longer-cycle genotypes showing greater tolerance and efficiency in antioxidant defense. Infestations of Tetranychus ludeni Zacher (Tetranychidae) have been frequently observed in soybean plants. In this context, understanding the oscillation of redox homeostasis is crucial for detecting and assessing the stress levels caused in the plants by these organisms. The impacts of these infestations on redox metabolism and photosynthetic pigments are currently unknown. Therefore, we examined the hypothesis that T. ludeni infestations in soybean plants can influence redox homeostasis and photosynthetic pigments in a spatiotemporal manner, varying between different infestation times, modules and genotypes. For this purpose, soybean plants of the genotypes Monsoy, maturity group 5.7, and Brasmax, maturity group 6.3, grown in a controlled environment, were exposed to infestation and evaluated at two periods: 14 and 24 days. A variation in the distribution of T. ludeni within the infested plants over time increased the activity of ascorbate peroxidase and catalase, especially in Monsoy, reducing the content of hydrogen peroxide and superoxide, which prevented lipid peroxidation in the apical region in both genotypes. In the basal region, low chlorophyll indices corroborated by the yellow coloration of trifoliate leaves, high levels of membrane stability loss, and accumulation of hydrogen peroxide and superoxide characterized senescent trifoliate leaves in Brasmax, 24 days post infestation. Thus, the infestation of T. ludeni has a complex and significant impact on the redox metabolism of soybean plants, especially in shorter-cycle genotypes such as Brasmax. Furthermore, the oscillation of homeostasis can be considered as a good biochemical marker for selecting more suitable genotypes that are less sensitive and prone to infestations., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The objective of the present study was to evaluate a blend of functional oils (FO) composed of copaiba and garlic essential oils, pepper oleoresin and cashew nut liquid to mitigate the effects of heat stress on productivity, egg quality, organ morphology of the gastrointestinal tract, serum biochemical profile, nutrient metabolism and body temperature of Japanese quail. A completely randomized design was used in a 3 × 2 factorial scheme (without additive; 300 and 500 mg FO/kg of feed x birds raised in a thermal comfort (TC) and heat stress (HS) environment), with 6 replicates of 8 birds per plot. The birds under HS had lower feed intake (P = 0.0000), egg mass (P = 0.0000), laying rate (P = 0.0000) and higher percentage of infertile non-commercial eggs (P = 0.0004), lower head temperature amplitude (P = 0.0000) and higher average of body temperature (P = 0.0312). HS worsened the external and internal quality of the eggs. Birds kept in HS showed higher values of cholesterol (P = 0.0000) and glutamic-pyruvic transaminase (P = 0.0272). The use of 300 and 500 g FO/ton of feed improved the feed conversion (P = 0.0000) and egg mass (P = 0.0000) of the quail bred under HS, respectively, by 8.4 and 7.2% and increased the relative weight of liver (P = 0.0064) and pancreas (P = 0.0492). The use of such additives also provided a higher % of yolk (P = 0.0018) and reduced the percentage of albumen (P = 0.0029) of the eggs produced in TC, in addition to reducing the amplitude of head temperature (P = 0.0484) of birds bred under HS. The breeding of Japanese quail under HS results in negative impacts on the production, physiological and qualitative aspects of the eggs. The use of 300 g/ton of FO in the diet of Japanese quail leads to improvements in feed conversion, increased liver capacity in nutritional metabolism and results in eggs with a higher proportion of yolks, being, therefore, an alternative for feeding quail in a hot climate., Competing Interests: DISCLOSURES The authors Hemylla Sousa Santos Barros, Rodrigo Fortunato de Oliveira, Cibele Silva Minafra, Ana Paula Cardoso Gomide, Francisco Ribeiro de Araujo Neto, Jennifer Cristina Ribeiro Gonçalves, Flávio Henrique de Souza Queiroz, Gabriel Martins Nobre, Bárbara Di Renzo Dos Santos Vilarinho, Manoel Correia Lima, Saullo Diogo de Assis and Fabiana Ramos dos Santos formally declared that there is no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

There is an urgent need to develop new, safer, and more effective drugs against Chagas disease (CD) as well as related kinetoplastid diseases. Targeting and inhibiting the Trypanosoma cruzi proteasome has emerged as a promising therapeutic approach in this context. To expand the chemical space for this class of inhibitors, we performed virtual screening campaigns with emphasis on shape-based similarity and ADMET prioritization. We describe the ideation and application of robustly validated shape queries for these campaigns, which furnished 44 compounds for biological evaluation. Five hit compounds demonstrated in vitro antitrypanosomal activity by potential inhibition of T. cruzi proteasome and notable chemical diversities, particularly, LCQFTC11. Structural insights were achieved by homology modeling, sequence/structure alignment, proteasome-species comparison, docking, molecular dynamics, and MMGBSA binding affinity estimations. These methods confirmed key interactions as well as the stability of LCQFTC11 at the β4/β5 subunits' binding site of the T. cruzi proteasome, consistent with known inhibitors. Our results warrant future assay confirmation of our hit as a T. cruzi proteasome inhibitor. Importantly, we also shed light into dynamic details for a proteasome inhibition mechanism that shall be further investigated. We expect to contribute to the development of viable CD drug candidates through such a relevant approach., 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 B.V. All rights reserved.)

Although the ankle is often involved in low energy trauma, high-energy trauma may occur, being this considered more serious and more common of affecting young and active men. The purpose of the present study was to evaluate and compare the functionality, pain and quality of life of active and inactive adult individuals whose ankle fracture was surgically treated. Seventy-six patients split into two groups (active, n = 58 X inactive, n = 18), of the men (active, n = 38; inactive, n = 9) and women (active, n = 20; inactive, n = 9) gender participated in this prospective study. The IPAQ, MMSE, SF-36, VAS, sociodemographic and clinical questionnaires were applied in person right after surgery. The SF-36 and VAS questionnaires were reapplied 3 months in average after the surgery. Active and inactive patients of both genders show significant differences (p ≤ 0.05) in the functional capacity and physical aspect domains; and the bodily pain domain revealed significant difference in active and inactive men (p ≤ 0.05) between the periods post-surgical and 3 months after surgery (on average). Moderate and significant correlations were found (p ≤ 0.05) between functional capacity, physical aspect and bodily pain domains of the SF-36 and the VAS pain scores for active and inactive patients of both genders in the final follow-up period. Other significant correlations (p < 0.05) for inactive men (physical aspect and bodily pain) and inactive women (functional capacity and bodily pain) are observed (after 3 months of surgery). Three months after surgery (on average), active and inactive men had functional limitations and pain symptoms. These factors seem to have negatively influenced the patient's social involvement, worsening their quality of life. Most active and inactive patients had a positive self-perception of their general health status, emotional aspects and mental health domains. Regarding active women, we observed lower energy and vitality after the same postoperative period., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The objective of this meta-analysis is to compare the effects on muscle strength and hypertrophy of low and high-intensity aerobic training with BFR (LI-BFR and HI-BFR) versus low and high-intensity aerobic training without BFR (LI and HI). The search was performed in five databases, by two independent researchers, and the terms and keywords used to optimize the searches were related to blood flow restriction and aerobic training. All studies were evaluated for methodological quality using the PEDro scale and for quality of evidence using the GRADE system. Meta-analyses were conducted using RevMan software. After data extraction, 11 studies met all eligibility criteria and were included in the systematic review. The results of the overall analysis between LI-BFR vs. LI showed a significant difference in muscle strength of knee extensors; for hypertrophy, LI was superior to LI-BFR with clinical relevance. Comparing HI-BFR vs. HI there was no superiority for muscle strength. In conclusion, for strength gains very low-quality evidence was found to support no superiority between LI-BFR and HI-BFR compared to LI and HI, respectively. For muscle hypertrophy, superiority of LI was found compared to LI-BFR, with a very low level of evidence., Competing Interests: The authors declare that they have no conflict of interest.., (Thieme. All rights reserved.)

Ibrutinib (IB) is a tyrosine kinase inhibitor (TKI) that has immunomodulatory action and can be used as second-line therapy for steroid-refractory or steroid-resistant chronic Graft versus Host Disease (cGVHD). Mesenchymal stromal cells (MSCs) are distributed throughout the body and their infusion has also been explored as a second-line therapeutic alternative for the treatment of cGVHD. Considering the currently unknown effects of IB on endogenous MSCs, as well as the possible combined use of IB and MSCs for cGVHD, we investigated whether adipose tissue-derived MSCs present IB-targets, as well as the consequences of treating MSCs with this drug, regarding cell viability, proliferation, phenotype, and anti-inflammatory potential. Interestingly, we show for the first time that MSCs express several IB target genes. Also of note, the treatment of such cells with this TKI elevated the levels of CD90 and CD105 surface proteins, as well as VCAM-1. Furthermore, IB-treated MSCs presented increased mRNA expression of the anti-inflammatory genes PD-L1, TSG-6, and IL-10. However, continued exposure to IB, even at low doses, compromised the viability of MSCs. These data indicate that the use of IB can stimulate an anti-inflammatory profile in MSCs, but also that a continued exposure to IB can compromise MSC viability over time., (© 2024. The Author(s).)

This study aimed to analyze students' and graduates' perceptions regarding the use of Problem-Based Learning (PBL) in nurse education. This is a qualitative study that employs the comprehensive and interpretative approach proposed by Dialectical Hermeneutics. Four focus groups were conducted with the participation of 17 students and 16 graduates from a higher education institution that implements PBL in nurse education. The analysis of results allowed for the identification of five thematic categories: difficulty in adapting to the method; attainment of autonomy in one's own learning; encouragement of clinical reasoning development; enhancement of communication and interpersonal relationships; and integration between theory and practice. It is evident that the use of PBL promotes alignment with the propositions of curriculum guidelines for nurse education by fostering the development of skills and competencies such as autonomy, communication, interpersonal relationships, and clinical reasoning through comprehensive and contextualized practices. However, students encounter challenges with the changes observed when introduced to PBL, which are overcome during the implementation process.

Changes in temperature and the deposition of potential pollutants in the soil, such as heavy metals, may damage plant communities, altering their physiological processes. High temperature may also cause a series of morpho-anatomical, physiological and biochemical changes in plants. However, tolerant plant species tend to restrict these harmful effects. The present study investigates the impact of atmospheric warming on the accumulation capacity of heavy metals (Zn, Ni, Cu) in the roots and leaves of a pioneer species (Croton floribundus) and a non-pioneer species (Esenbeckia leiocarpa) native to the Atlantic Forest of southeastern Brazil. The experimental design involved exposing the plants to two soil treatments: without excess metals (-M) and with excess metals (+M), along with varying thermoperiods of 26 °C day/19 °C night and 32 °C day/20 °C night in growth chambers. Over a 28-day period, we assessed weekly metal content, translocation, growth parameters, a non-enzymatic antioxidant (glutathione) and indicators of cell damage or oxidative stress (chlorophylls a and b, total chlorophyll (a+b), carotenoids, malondialdehyde and conjugated diene hydroperoxide contents). Both species exhibited increased metal accumulation under excess metals, employing distinct translocation strategies. C. floribundus showed high translocation rates of Ni to leaves and E. leiocarpa immobilized Ni in the roots. Atmospheric warming reduced Cu and Ni translocation from roots to leaves in both species. C. floribundus displayed lower physiological damage compared to E. leiocarpa, demonstrating robust growth. We concluded that the pioneer species possessed greater tolerance to oxidative stress induced by temperature and metal-related environmental factors than the non-pioneer species, confirming our hypothesis. In addition, our finding provides valuable insights for conservation and management of ecosystems affected by climatic and pollutant changes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Evaluate the association between serum urea at admission and during hospital stay with return of spontaneous circulation (ROSC) and in-hospital mortality in patients with in-hospital cardiac arrest (IHCA)., Methods: This retrospective study included patients over 18 years with IHCA attended from May 2018 to December 2022. The exclusion criteria were the absence of exams to calculate delta urea and the express order of "do-not-resuscitate". Data were collected from the electronic medical records. Serum admission urea and urea 24 hours before IHCA were also collected and used to calculate delta urea., Results: A total of 504 patients were evaluated; 125 patients were excluded due to the absence of variables to calculate delta urea and 5 due to "do-not-resuscitate" order. Thus, we included 374 patients in the analysis. The mean age was 65.0 ± 14.5 years, 48.9% were male, 45.5% had ROSC, and in-hospital mortality was 91.7%. In logistic regression models, ROSC was associated with lower urea levels 24 hours before IHCA (OR: 0.996; CI95%: 0.992-1.000; p: 0.032). In addition, increased levels of urea 24 hours before IHCA (OR: 1.020; CI95%: 1.008-1.033; p: 0.002) and of delta urea (OR: 1.001; CI95%: 1.001-1.019; p: 0.023) were associated with in-hospital mortality. ROC curve analysis showed that the area under the ROC curve for mortality prediction was higher for urea 24 hours before IHCA (Cutoff > 120.1 mg/dL) than for delta urea (Cutoff > 34.83 mg/dL)., Conclusions: In conclusion, increased serum urea levels during hospital stay were associated with worse prognosis in IHCA., 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 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Curcumin serves as a photosensitizer (PS) in the context of microbial inactivation when subjected to light exposure, to produce reactive oxygen species, which exhibit efficacy in eradicating microorganisms. This remarkable property underscores the growing potential of antimicrobial photodynamic therapy (aPDT) in the ongoing fight against bacterial infections. Considering this, we investigate the efficacy of various in vitro curcumin formulations within a PDT protocol designed to target Staphylococcus aureus. Specifically, we conduct a comparative analysis involving synthetic curcumin (Cur-Syn) and curcumin derivatives modified with chlorine (Cl), selenium (Se), and iodine (I) (Cur-Cl, Cur-Se, Cur-I). To assess the impact of aPDT, we subject S. aureus to incubation with curcumin, followed by irradiation at 450 nm with energy doses of 3.75, 7.5, and 15 J/cm 2 . Our investigation encompasses an evaluation of PS uptake and photobleaching across the various curcumin variants. Notably, all three modifications (Cur-Cl, Cur-Se, Cur-I) induce a significant reduction in bacterial viability, approximately achieving a 3-log reduction. Interestingly, the uptake kinetics of Cur-Syn and Cur-Se exhibit similarities, reaching saturation after 20 min. Our findings suggest that modifications to curcumin have a discernible impact on the photodynamic properties of the PS molecule., (© 2024 American Society for Photobiology.)

This study aimed to analyze the perceptions of obstetricians and gynecology-obstetrics residents at a federal school maternity hospital regarding legal abortion in cases of sexual violence pregnancy, understand their motivations, strengths, and feelings, and identify their experience with this topic. The first stage consisted of answering a self-administered questionnaire. The selection criteria were: obstetricians linked to the obstetric center, director of the medical division, and residents of the institution's obstetrics-gynecology program. In total, 36 questionnaires were answered and returned. The second stage corresponded to an interview using a saturation sampling criterion. Six physicians were interviewed. The interviews were evaluated using a thematic content analysis. The questionnaires showed that all participants had already provided care to women in situations of sexual violence and that most of them had already participated in a legal abortion procedure in these cases. The interviews highlighted the dilemmas faced by professionals in providing care to these women and the lack of professional training to handle these cases. The speeches of women were sometimes seen as an object of suspicion regarding the veracity of sexual violence, and sometimes as an object that caused professionals to feel emotionally affected while listening to them, allowing professionals to approach the victims and offer more humanized care. The results pointed to the importance of addressing this topic in the areas of health and providing training beyond the technical-scientific focus in order to support the development of new care strategies.

Raphanus sativus L. is a potential source of raw material for biodiesel fuel due to the high oil content in its grains. In Brazil, this species is cultivated in the low rainfall off-season, which limits the productivity of the crop. The present study investigated the effects of water restriction on the physiological and biochemical responses, production components, and oil quality of R. sativus at different development stages. The treatments consisted of 100% water replacement (control), 66%, and 33% of field capacity during the phenological stages of vegetative growth, flowering, and grain filling. We evaluated characteristics of water relations, gas exchange, chlorophyll a fluorescence, chloroplast pigment, proline, and sugar content. The production components and chemical properties of the oil were also determined at the end of the harvest cycle. Drought tolerance of R. sativus was found to be mediated primarily during the vegetative growth stage by changes in photosynthetic metabolism, stability of photochemical efficiency, increased proline concentrations, and maintenance of tissue hydration. Grain filling was most sensitive to water limitation and showed a reduction in yield and oil content. However, the chemical composition of the oil was not altered by the water deficit. Our data suggest that R. sativus is a drought-tolerant species.

Ibrutinib, a tyrosine kinase inhibitor with a broad spectrum of action, has been successfully explored to treat hematological and solid cancers. Herein, we investigated the anti-cancer effect of Ibrutinib on melanoma cell lines. Cytotoxicity was evaluated using the MTT assay. Apoptosis, mitochondrial membrane potential, reactive oxygen species (ROS) production, cell proliferation, and cell cycle stages were determined by flow cytometry. LDH release and Caspase 3/7 activity were determined by colorimetric and luminescent assays, respectively. Cell migration was evaluated by wound scratch assay. Gene expression was determined by real-time PCR. Gene Ontology (GO) enrichment analysis of melanoma clinical samples was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). MTT assays showed that Ibrutinib is toxic for MeWo, SK-MEL-28, and WM164 cells. The annexin V/PI staining, Caspase 3/7 activity, and LDH release in MeWo cells revealed that apoptosis is the primary mechanism of death caused by Ibrutinib. Corroborating such observation, we identified that Ibrutinib treatment impairs the mitochondrial membrane potential of such cells and significantly increases the transcriptional levels of the pro-apoptotic factors ATM , HRK , BAX , BAK , CASP3 , and CASP8 . Furthermore, Ibrutinib showed antimetastatic potential by inhibiting the migration of MeWo cells. Finally, we performed a functional enrichment analysis and identified that the differential expression of Ibrutinib-target molecules is associated with enrichment of apoptosis and necrosis pathways in melanoma samples. Taken together, our results clearly suggest that Ibrutinib can be successfully explored as an effective therapeutic approach for melanomas.

The murine model of experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA was used to investigate the relationship among pro-inflammatory cytokines, alterations in renal function biomarkers, and the induction of the TRAIL apoptosis pathway during malaria-associated acute kidney injury (AKI). Renal function was evaluated through the measurement of plasma creatinine and blood urea nitrogen (BUN). The mRNA expression of several cytokines and NaPi-IIa was quantified. Kidney sections were examined and cytokine levels were assessed using cytometric bead array (CBA) assays. The presence of glomerular IgG deposits and apoptosis-related proteins were investigated using in situ immunofluorescence assays and quantitative real-time PCR, respectively. NaPi-IIa downregulation in the kidneys provided novel insights into the pathogenesis of hypophosphatemia during CM. Histopathological analysis revealed characteristic features of severe malaria-associated nephritis, including glomerular collapse and tubular alterations. Pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, were upregulated. The TRAIL apoptosis pathway was significantly activated, implicating its role in renal apoptosis. The observed alterations in renal biomarkers and the downregulation of NaPi-IIa shed light on potential mechanisms contributing to renal dysfunction in ECM. The intricate balance between pro- and anti-inflammatory cytokines, along with the activation of the TRAIL apoptosis pathway, highlights the complexity of malaria-associated AKI and provides new therapeutic targets.

Computational models that predict pharmacokinetic properties are critical to deprioritize drug candidates that emerge as hits in high-throughput screening campaigns. We collected, curated, and integrated a database of compounds tested in 12 major end points comprising over 10,000 unique molecules. We then employed these data to build and validate binary quantitative structure-activity relationship (QSAR) models. All trained models achieved a correct classification rate above 0.60 and a positive predictive value above 0.50. To illustrate their utility in drug discovery, we used these models to predict the pharmacokinetic properties for drugs in the NCATS Inxight Drugs database. In addition, we employed the developed models to predict the pharmacokinetic properties of all compounds in the DrugBank. All models described in this paper have been integrated and made publicly available via the PhaKinPro Web-portal that can be accessed at https://phakinpro.mml.unc.edu/.

Objectives  This study evaluated pain intensity in elderly subjects with hip fractures admitted to the emergency sector and undergoing preoperative pericapsular nerve group (PENG) block. Additionally, the degree of tolerable hip flexion was assessed. Methods  A prospective, randomized, and controlled clinical trial with parallel groups. The control group consisted of elderly subjects with hip fractures undergoing standardized intravenous systemic analgesia. The intervention group consisted of elderly patients with hip fractures undergoing PENG block and standardized systemic analgesia. The groups were evaluated at rest and during movement using the Pain Assessment in Advanced Dementia (PAINAD) scale. We determined pain intensity and reduction, in addition to the degree of tolerable flexion of the fractured hip. All patient assessments occurred before the medication or block administration and at 45 minutes, 12, 24, and 36 hours postmedication or block. Results  Preoperatively and 24 hours after PENG block, elderly subjects with hip fracture showed a significant reduction in pain at rest or movement compared to control patients ( p  < 0.05), with 60% of patients assessed at rest demonstrating desirable pain reduction (≥50%) and only 13.3% of the control group achieving the desired pain reduction. During movement, after undergoing PENG block, 40% of subjects demonstrated the desired pain reduction and no patient from the control group. The intervention group also showed a significant improvement in the tolerable hip flexion group ( p  < 0.05). Conclusion  Preoperative PENG block in elderly subjects with hip fractures admitted to the emergency sector provided a significant reduction in pain compared with the control group., 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/ ).)

Leishmaniasis is an endemic disease in more than 90 countries, constituting a relevant public health problem. Limited treatment options, increase in resistance, and therapeutic failure are important aspects for the discovery of new treatment options. Drug repurposing may accelerate the discovery of antiLeishmanial drugs. Recent tests indicating the in vitro potential of antimalarials Leishmania resulted in the design of this study. This study aimed at evaluating the susceptibility of Leishmania (L.) amazonensis to chloroquine (CQ) and quinine (QN), alone or in combination with amphotericin B (AFT) and pentamidine (PTN). In the in vitro tests, first, we evaluated the growth inhibition of 50 % of promastigotes (IC 50 ) and cytotoxicity for HepG2 and THP-1 cells (CC 50 ). The IC 50 values of AFT and PNT were below 1 µM, while the IC 50 values of CQ and QN ranged between 4 and 13 µM. Concerning cytotoxicity, CC 50 values ranged between 7 and 30 µM for AFT and PNT, and between 22 and 157 µM for the antimalarials. We also calculated the Selectivity Index (SI), where AFT and PTN obtained the highest values, while the antimalarias obtained values between 5 and 12. Both antimalarials were additive (ƩFIC 1.05-1.8) in combination with AFT and PTN. For anti-amastigote activity, the drugs obtained the following ICA 50 values: AFT (0.26 µM), PNT (2.09 µM), CQ (3.77 µM) and QN (24.5 µM). In the in vivo tests, we observed that the effective dose for the death of 50 % of parasites (ED 50 ) of AFT and CQ were 0.63 mg/kg and 27.29 mg/kg, respectively. When combining CQ with AFT, a decrease in parasitemia was observed, being statistically equal to the naive group. For cytokine quantification, it was observed that CQ, despite presenting anti-inflammatory activity was effective at increasing the production of IFN-γ. Overall, our data indicate that chloroquine will probably be a candidate for repurposing and use in drug combination therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Herein, we present an overview of continuous flow chemistry, including photoflow and electroflow technologies in the preparation of active pharmaceutical ingredients (APIs) and fine chemical intermediates. Examples highlighting the benefits and challenges associated with continuous flow processes, mainly involving continuous thermal, photo- and electrochemical transformations, are drawn from the relevant literature, especially our experience and collaborations in this area, with emphasis on the synthesis and prospective scale-up.

While titanium dental implants have already been clinically established, ongoing research is continuously being conducted to advance the fields of osseointegration and bacterial resistance, seeking further improvements in these areas. In this study, we introduce an innovative method for treating titanium surfaces within tightly sealed packaging. Specifically, titanium discs, enclosed in surgical-grade packaging, underwent treatment using cold atmospheric plasma (CAP). The surfaces were thoroughly characterized in terms of wettability, crystalline structure, and chemical composition. Hemocompatibility analyses were conducted using blood diluted in sodium citrate (1:9) exposed to titanium discs for 30 min inside a CO 2 incubator at 37 °C. Subsequently, various blood parameters were evaluated, including prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet adhesion. Microbiological analyses were also performed using Pseudomonas aeruginosa (ATCC 27853) for 4 h at 37 °C. The treatment with CAP Jet resulted in a reduction in contact angle without causing any changes in the crystalline structure. No statistically significant differences were observed in the blood parameters. The plasma-treated samples exhibited lower PT and APTT values compared to those of the control group. The surfaces treated with CAP Jet showed increased platelet activation, platelet density, and thrombus formation when compared with the untreated samples. Moreover, the treated surfaces demonstrated lower bacterial colony formation compared with other surfaces.

The evaluation of environmental and spatial influence in freshwater systems is crucial for the conservation of aquatic diversity. So, we evaluated communities of Odonata in streams inside and outside sustainable use areas in the Brazilian western Amazon. We predicted that these streams would differ regarding habitat integrity and species α and β diversity. We also predict that environmental and spatial variables will be important for both suborders, but with more substantial effects on Zygoptera species, considering their nature of forest-specialist. The study was conducted in 35 streams, 19 inside and 16 outside sustainable use areas. The streams outside presented high species richness, abundance, and number of exclusive forest-specialist species from Zygoptera and higher scores of habitat integrity. In contrast, one sustainable use area presented the lowest values of these metrics. Besides, we found that environmental and spatial variables were significantly associated to Zygoptera species composition, but not with Anisoptera, which can be explained by their cosmopolitan nature. Our results indicated that an interplay between environmental and spatial processes determines the structure of the metacommunities of Zygoptera. The less effective dispersal rates and narrow ecological tolerance of Zygoptera species make them more influenced by local conditions and dispersal limitation, and more sensible to habitat modifications. We highlight the importance of improving the local management of the sustainable use areas by environmental agencies, mainly on areas that are losing their capacity to maintain the aquatic fauna, and implementation of social policies toward traditional people., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The aim of this study was to analyze the healing action of low-intensity laser therapy associated with Himatanthus drasticus in wound healing in mice. The study was experimental, analytical, controlled, randomized, and prospective. Twenty Wistar rats were divided into four groups: control with injury, injury + laser, wound + Himatanthus drasticus, and wound + laser + Himatanthus drasticus. The animals underwent surgical skin wounds on their backs, and different treatments were applied based on the group. The healing process was evaluated histologically through the analysis of collagen fibers, neovascularization, and inflammatory reaction. The results showed that low-intensity laser therapy and Himatanthus drasticus treatment improved the healing process in terms of collagen synthesis, decreased inflammatory cell migration, fibroblast proliferation, neovascularization, wound size reduction, and edema reduction. However, the combination of laser and Himatanthus drasticus did not show significant improvement compared to individual treatments. There were no statistical differences in polymorphonuclear cells between the treatment groups. Low-intensity laser therapy and Himatanthus drasticus have demonstrated positive properties in improving the healing process. Further research is needed to better understand their individual and combined effects. The study contributes to the exploration of alternative wound healing methods and encourages further investigation in this field., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Introduction: Acute kidney injury (AKI) is a frequent complication of severe COVID-19 and is associated with high case fatality rate (CFR). However, there is scarcity of data referring to the CFR of AKI patients that underwent kidney replacement therapy (KRT) in Brazil. The main objective of this study was to describe the CFR of critically ill COVID-19 patients treated with acute kidney replacement therapy (AKRT)., Methods: Retrospective descriptive cohort study. We included all patients treated with AKRT at an intensive care unit in a single tertiary hospital over a 15-month period. We excluded patients under the age of 18 years, patients with chronic kidney disease on maintenance dialysis, and cases in which AKI preceded COVID-19 infection., Results: A total of 100 out of 1479 (6.7%) hospitalized COVID-19 patients were enrolled in this study. The median age was 74.5 years (IQR 64 - 82) and 59% were male. Hypertension (76%) and diabetes mellitus (56%) were common. At the first KRT prescription, 85% of the patients were on invasive mechanical ventilation and 71% were using vasoactive drugs. Continuous veno-venous hemodiafiltration (CVVHDF) was the preferred KRT modality (82%). CFR was 93% and 81 out of 93 deaths (87%) occurred within the first 10 days of KRT onset., Conclusion: AKRT in hospitalized COVID-19 patients resulted in a CFR of 93%. Patients treated with AKRT were typically older, critically ill, and most died within 10 days of diagnosis. Better strategies to address this issue are urgently needed.

Background:  Patients with epilepsy (PWE) frequently have comorbid psychiatric disorders, the most common of which are depression and anxiety. Attention deficit disorder with hyperactivity (ADHD) is also more frequent among PWE, though that condition has been scarcely studied among the adult PWE population., Objective:  This study aimed to compare the presence of ADHD symptoms between adult PWE and the general population., Methods:  This was an observational case-control study. Ninety-five adult PWE from a tertiary center in southern Brazil were compared with 100 healthy controls. All subjects were submitted to three structured scales: 1) the World Health Organization Adult ADHD Self-Report Scale version 1.1 (ASRS); 2) the Hospital Anxiety and Depression Scale (HADS); and 3) the Adverse Events Profile (AEP). Dichotomic variables were analyzed through chi-square test and Fisher's exact test, as appropriate, and non-parametric variables were analyzed through the Mann-Whitney U test., Results:  Medians and interquartile ranges (IR) were: 1) ASRS: 26.00 (IR: 18 to 38) among PWE versus 17.00 (IR: 11 to 24) among controls, p  < 0.001; 2) HADS: 14.00 (IR: 8 to 21) among PWE versus 11.00 (IR: 8 to 16) among controls, p  = 0.007; 3) AEP: 3800 (IR: 31 to 49) among PWE versus 33.00 (IR: 23 to 43) among controls, p  = 0.001., Conclusion:  PWE showed a higher burden of symptoms of ADHD, depression, and anxiety when compared with controls, which replicates in the Brazilian population the findings of current literature that point toward a higher prevalence of such disorders among PWE., Competing Interests: There is no conflict of interest to declare., (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/).)

Artificial intelligence has revolutionized many sectors with unparalleled predictive capabilities supported by machine learning (ML). So far, this tool has not been able to provide the same level of development in pharmaceutical nanotechnology. This review discusses the current data science methodologies related to polymeric drug-loaded nanoparticle production from an innovative multidisciplinary perspective while considering the strictest data science practices. Several methodological and data interpretation flaws were identified by analyzing the few qualified ML studies. Most issues lie in following appropriate analysis steps, such as cross-validation, balancing data, or testing alternative models. Thus, better-planned studies following the recommended data science analysis steps along with adequate numbers of experiments would change the current landscape, allowing the exploration of the full potential of ML.

Punica granatum Linn has been known for its nutritional and medicinal value since ancient times and is used in the treatment of various pathologies owing to its antibacterial properties. This review reports the results of the most recent studies on the antibacterial effects of P. granatum and its isolated compounds on bacteria of clinical interest. A search in the PubMed, Scopus, Science Direct, and Science Citation Index Expanded (Web of Science) databases was performed, which included articles that evaluated the antibacterial activity of P. granatum extracts and excluded articles that analyzed other microorganisms or nonpathogenic bacteria, as well as theses, dissertations, duplicate articles, and those not fully available. The literature suggests that P. granatum extracts can act on bacteria, such as methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), Streptococcus mutans , Escherichia coli , Pseudomonas aeruginosa , and Klebsiella pneumoniae . In addition, fruit peel was the most commonly used pharmacogen and methanol, ethanol, and water were the most common solvents for the extraction of bioactive compounds. The antibacterial potential of the methanolic extract of pomegranate peel could be attributed to the presence of active compounds, such as 5-hydroxymethylfurfural, punicic acid, gallic acid, and punicalagin. Thus, there is evidence that these plant extracts, having high polyphenol content, can disrupt the bacterial plasma membrane and inhibit the action of proteins related to antimicrobial resistance. P. granatum shows antibacterial activity against Gram-positive and Gram-negative bacteria, with great potential against multidrug-resistant strains. Further research is needed to clarify the mechanism of action related to this biological activity and investigate the isolated substances that may be responsible for the antibacterial effects., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2023 Priscila Mendonça Mendes et al.)

The aim of this study was to evaluate the antibacterial activity of nanoemulsions of Baccharis dracunculifolia essential oil. The volatile compounds of the essential oil were identified using gas chromatography-mass spectrometry. The properties of the nanoemulsions (droplet size, polydispersity index, pH, and electrical conductivity) were determined. The antibacterial activities of the essential oil and its nanoemulsions were evaluated using MIC, MBC, and disk diffusion. The microorganisms used were: Gram-positive bacteria ( Staphylococcus aureus ATCC 25923, Bacillus cereus ATCC 14579, Streptococcus mutans ATCC 25175, and Enterococcus faecalis ATCC 29212) and Gram-negative bacteria ( Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC BAA-1706, Salmonella enterica ATCC 14028, and Escherichia coli ATCC 25922). The major volatile compounds of the B. dracunculifolia essential oil were limonene (19.36%), ( E )-nerolidol (12.75%), bicyclogermacrene (10.76%), and β-pinene (9.60%). The nanoemulsions had a mean droplet size between 13.14 and 56.84 nm. The nanoemulsions presented lower and statistically significant MIC values compared to the essential oil, indicating enhancement of the bacteriostatic action. The disk diffusion method showed that both the nanoemulsions and the essential oil presented inhibition zones only for Gram-positive bacteria, while there were no results against Gram-negative bacteria, indicating that B. dracunculifolia essential oil has a better antimicrobial effect on Gram-positive microorganisms.

The in situ population of jaguars in the Caatinga is less than 250 individuals, subdivided into five subpopulations, and is classified as endangered regarding its risk of extinction. Luisa, a 15-year-old female weighing 36 kg, was the last known ex situ jaguar from this biome. Her reproductive evaluation is detailed in this manuscript. Luisa was subjected to both a clinical and laparoscopic evaluation of her reproductive system. After 45 days of reproductive investigation, she died unexpectedly, and skin fragments were taken to establish the postmortem fibroblast lineage. At the clinical evaluation, Luisa had small, undeveloped mammary gland and a small vulva, characteristic of a nulliparous female, with no mammary gland nodules, edema, or abnormal masses. By laparoscopy, normal-appearing bladder and bowel loops were observed, as were uterine horns with standard color, shape, and length with no striae. Ovaries and uterine horns seem free of fibrinous adhesions. Both ovaries showed a yellowish color, a fibrous consistency, a decreased size (atrophied), and no follicles, hemorrhagic corpus, corpus luteum, luteal scars, or other abnormal structures. We may assume that this jaguar female was infertile based on Luisa's mature age and the absence of birthing or ovarian activity signs. The harsh conditions of the Caatinga biome, which included low food availability and frequent conflicts with humans, may have impacted both the pregnancy and lactation of Luisa's mother and her development after birth., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare.

Chronic diseases such as cystic fibrosis, inflammatory bowel diseases, rheumatoid arthritis, and cardiovascular illness have been linked to a decrease in selenium levels and an increase in oxidative stress. Selenium is an essential trace element that exhibits antioxidant properties, with selenocysteine enzymes like glutathione peroxidase being particularly effective at reducing peroxides. In this study, a series of synthetic organoselenium compounds were synthesized and evaluated for their potential antioxidant activities. The new selenohydantoin molecules were inspired by selenoneine and synthesized using straightforward methods. Their antioxidant potential was evaluated and proven using classical radical scavenging and metal-reducing methods. The selenohydantoin derivatives exhibited glutathione peroxidase-like activity, reducing hydroperoxides. Theoretical calculations using Density Functional Theory (DFT) revealed the selenone isomer to be the only one occurring in solution, with selenolate as a possible tautomeric form in the presence of a basic species. Cytocompatibility assays indicated that the selenohydantoin derivatives were non-toxic to primary human aortic smooth muscle cells, paving the way for further biological evaluations of their antioxidant activity. The results suggest that selenohydantoin derivatives with trifluoro-methyl (-CF 3 ) and chlorine (-Cl) substituents have significant activities and could be potential candidates for further biological trials. These compounds may contribute to the development of effective therapies for chronic diseases such cardiovascular diseases., 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 Ltd. All rights reserved.)

In recent years, cold atmospheric plasma (CAP) is used for surface disinfection. However, little is known about its ability to improve biocompatibility of metallic surfaces when compared to thermal plasma methods. In this context, the study aimed to evaluate the response of human endothelial cells (Ea.hy926) on titanium surfaces treated by non-thermal plasma method and thermal plasma method under nitriding atmosphere. The wettability was characterized by the sessile drop method, the topography and roughness were evaluated by atomic force microscopy (AFM), and the microstructure by grazing angle X-ray diffraction (GIXRD). Endothelial cells were cultured and evaluated for morphology by scanning electron microscopy and viability by an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. CAP treatment reduced the contact angle of the Ti surface (13.43° ± 1.48; p<0.05), increasing hydrophilicity. Rz roughness was higher on the nitrided surface (220.44±20.30; p< 0.001) compared to the CAP treated surfaces (83.29 ± 11.61; p< 0.001) and polished (75.98 ±34.21a); p<0.001). The different applied plasma treatments created different titanium surfaces improving the biocompatibility of endothelial cells, however CAP results demonstrate its potential for biomedical applications, considering the low cost and ease of use of the technique, allowing surface treatments before clinical procedures.

C-H bond functionalization generates molecular complexity in single-step transformation. However, the activation of C-H bonds requires expensive metals or stoichiometric amounts of oxidizing/reducing species. In many cases, they often require pre-functionalization of starting molecules. Such pre-activating measures cause waste generation and their separation from the final product is also troublesome. In such a scenario, reactions activating elements generating from renewable energy resources such as electricity and light would be more efficient, green, and cost-effective. Further, incorporation of growing flow technology in chemical transformation processes will accelerate the safer accesses of valuable products. Arenes & heteroarenes are ubiquitous in pharmaceuticals, natural products, medicinal compounds, and other biologically important molecules. Herein, we discussed enabling tools and technologies used for the recent C-H bonds functionalization of arenes and heteroarenes., (© 2023 The Authors. The Chemical Record published by The Chemical Society of Japan and Wiley-VCH GmbH.)

Thoroughly analyzing the sperm and exploring the information obtained using artificial intelligence (AI) could be the key to improving fertility estimation. Artificial neural networks have already been applied to calculate zootechnical indices in animals and predict fertility in humans. This method of estimating the results of reproductive biotechnologies, such as in vitro embryo production (IVEP) in cattle, could be valuable for livestock production. This study was developed to model IVEP estimates in Senepol animals based on various sperm attributes, through retrospective data from 290 IVEP routines performed using 38 commercial doses of semen from Senepol bulls. All sperm samples that had undergone the same procedure during sperm selection for in vitro fertilization were evaluated using a computer-assisted sperm analysis (CASA) system to define sperm subpopulations. Sperm morphology was also analyzed in a wet preparation, and the integrity of the plasma and acrosomal membranes, mitochondrial potential, oxidative status, and chromatin resistance were evaluated using flow cytometry. A previous study identified three sperm subpopulations in such samples and the information used in tandem with other sperm quality variables to perform an AI analysis. AI analysis generated models that estimated IVEP based on the season, donor, percentage of viable oocytes, and 18 other sperm predictor variables. The accuracy of the results obtained for the three best AI models for predicting the IVEP was 90.7, 75.3, and 79.6%, respectively. Therefore, applying this AI technique would enable the estimation of high or low embryo production for individual bulls based on the sperm analysis information., Competing Interests: SN was employed by Senepol 3G. AB was employed In Vitro Brasil at the time of the study and is currently employed by Salt Biotechnology. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Campanholi, Garcia Neto, Pinheiro, Nogueira, Rocha, Losano, Siqueira, Nichi, Assumpção, Basso, Monteiro and Gimenes.)

The toxic effects of venlafaxine (VLX) on aquatic organisms have already been verified and therefore are a proven matter of concern. Herein, we evaluated zebrafish embryos/adults after acute exposure to VLX. Embryos/larvae were exposed to different concentrations of VLX (100-1000 mg/L; 1.33 as a dilution factor), to evaluate mortality/developmental changos and to analyze biomarkers (0.002-100 mg/L). For adults, mortality, genotoxicity, and biomarkers were assessed in five different concentrations of VLX (1-100 mg/L). The median lethal concentration (LC50-168h) was 274.1 mg/L for embryos/larvae, and >100 mg/L for adults (LC50-96h). VLX decreased the heart rate frequency and caused premature hatching and lack of equilibrium in embryos/larvae exposed to different concentrations ranging from 100 to 562.5 mg/L. The activity of acetylcholinesterase (AChE) was inhibited in larvae exposed to 1, 25 and 100 mg/L. Glutathione-S-transferase (GST) activity was reduced in both larvae and adults after exposure to different concentrations, mainly at 25 mg/L. For both larvae and adults, lactate dehydrogenase (LDH) activity increased after 100 mg/L of VLX exposure. No DNA damage was observed in peripheral erythrocytes. Exposure to VLX may cause adverse effects on zebrafish in their early and adult life stages, interfering with embryo-larval development, and can induce physiological disturbances in adults.

The Metropolitan Area of São Paulo (MASP) is among the largest urban areas in the Southern Hemisphere. Vehicular emissions are of great concern in metropolitan areas and MASP is unique due to the use of biofuels on a large scale (sugarcane ethanol and biodiesel). In this work, tunnel measurements were employed to assess vehicle emissions and to calculate emission factors (EFs) for heavy-duty and light-duty vehicles (HDVs and LDVs). The EFs were determined for particulate matter (PM) and its chemical compounds. The EFs obtained for 2018 were compared with previous tunnel experiments performed in the same area. An overall trend of reduction of fine and coarse PM, organic carbon (OC), and elemental carbon (EC) EFs for both LDVs and HDVs was observed if compared to those observed in past years, suggesting the effectiveness of vehicular emissions control policies implemented in Brazil. A predominance of Fe, Cu, Al, and Ba emissions was observed for the LDV fleet in the fine fraction. Cu presented higher emissions than two decades ago, which was associated with the increased use of ethanol fuel in the region. For HDVs, Zn and Pb were mostly emitted in the fine mode and were linked with lubricating oil emissions from diesel vehicles. A predominance in the emission of three- and four-ring polycyclic aromatic hydrocarbons (PAHs) for HDVs and five-ring PAHs for LDVs agreed with what was observed in previous studies. The use of biofuels may explain the lower PAH emissions for LDVs (including carcinogenic benzo[a]pyrene) compared to those observed in other countries. The tendency observed was that LDVs emitted higher amounts of carcinogenic species. The use of these real EFs in air quality modeling resulted in more accurate simulations of PM concentrations, showing the importance of updating data with real-world measurements., 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. Published by Elsevier Ltd.)

Recent studies suggest that the association of antigens in microparticles increases the anti- Leishmania vaccine immunogenicity. This study aims to investigate the in situ effect of the adjuvant performance consisting of chitosan-coated poly( D , L -lactic) acid submicrometric particles (SMP) and analyze the inflammatory profile and toxicity. Two formulations were selected, SMP 1 , containing poly( D , L -lactide) (PLA) 1% wt / v and chitosan 1% wt / v ; and SMP 2 , containing PLA 5% wt / v and chitosan 5% wt / v . After a single dose of the unloaded SMP 1 or SMP 2 in mice, the SMPs promoted cell recruitment without tissue damage. In addition, besides the myeloperoxidase (MPO) activity having demonstrated similar results among the analyzed groups, a progressive reduction in the levels of N-acetyl- β- D -glucosaminidase (NAG) until 72 h was observed for SMPs. While IL-6 levels were similar among all the analyzed groups along the kinetics, only the SMPs groups had detectable levels of TNF-α. Additionally, the Leishmania braziliensis antigen was encapsulated in SMPs (SMP 1 Ag and SMP 2 Ag), and mice were vaccinated with three doses. The immunogenicity analysis by flow cytometry demonstrated a reduction in NK (CD3 - CD49 + ) cells in all the SMPs groups, in addition to impairment in the T cells subsets (CD3 + CD4 + ) and CD3 + CD8 + ) and B cells (CD19 + ) of the SMP 2 group. The resulting data demonstrate that the chitosan-coated SMP formulations stimulate the early events of an innate immune response, suggesting their ability to increase the immunogenicity of co-administered Leishmania antigens.

A transition-metal free methodology for the chemoselective reduction of benzylidene thiazolidine-2,4-diones and similar heterocycles is described, allowing the preparation of a broad scope of the corresponding reduced derivatives in up to 90% yield. The protocol has a simple and safe experimental setup, in which water was employed as the hydrogen source. To further demonstrate the synthetic utility of this transformation, the antidiabetic API Pioglitazone was prepared in 81% yield. To the best of our knowledge, this is the first hydride and transition-metal free protocol for the synthesis of Pioglitazone, highlighting its potential utility as a greener alternative in both academic and industrial synthesis.

Introduction: Although the administration of drugs on the skin is a safe and noninvasive therapeutic alternative, producing formulations capable of disrupting the cutaneous barriers is still a challenge. In this scenario, extrusion-based techniques have emerged as disruptive technologies to ensure unique drug-excipient interactions that facilitate drug skin diffusion for systemic or local effect and even mean the key to obtain viable industrial products., Areas Covered: This article presents a comprehensive overview of extrusion-based techniques in developing pharmaceutical dosage forms for topical or transdermal drug delivery. First, the theoretical basis of how extrusion-based techniques can optimize the permeation of drugs through the skin is examined. Then, the current state-of-the-art of drug products developed by extrusion-based techniques, specifically by hot-melt extrusion (HME) and fused deposition modeling (FDM) 3D printing, are discussed and contrasted with the current pharmaceutical processes., Expert Opinion: A wide variety of pharmaceutical products can be obtained using HME and FDM 3D printing, including new dosage forms designed for a perfect anatomical fit. Despite the limitations of pharmaceutical products produced with HME and FDM 3D printing regarding thermal stability and available excipients, the advantages in industrial adaptability and improved bioavailability allied with patient-match devices certainly deserve full attention and investment.