Increase Toll-like receptors 2 and 4 in apical periodontitis of rats with chronic liver disease.

The aim of this study was to evaluate the influence of liver fibrosis (LF) on the expression of Toll-like receptors (TLR) 2 and 4 in apical periodontitis (AP) in Wistar rats. Forty Wistar rats were allocated in the following groups (n = 10): C-control; AP-apical periodontitis; LF-liver fibrosis; AP + LF-rats with AP and LF. LF and AP were induced by established methodologies. Histological, bacteriological, and immunohistochemical analyses were performed according to pre-established scores. For comparisons between AP and AP + LF groups, the Mann-Whitney test was used (P < .05). The livers of the LF and AP + LF groups showed generalized portal inflammatory infiltrate and collagen fibers confirming the presence of LF. Histopathological analysis in the maxilla of the AP + LF group showed areas of necrosis comprising the entire dental pulp and periapical tissue surrounded by a more intense inflammatory infiltrate than observed in the AP group (P = 0.032). A significant number of specimens in the AP + LF group showed microorganisms beyond the apical foramen adhered to the extraradicular biofilm, demonstrating greater invasion compared to the AP group (P = .008). Immunohistochemical analysis showed a large number of cells immunoreactive for TLR2 and TLR4 in the AP + LF group, compared to the AP group (P < 0.05). Liver fibrosis favors the inflammation and contamination of microorganisms in apical periodontitis and triggers the expression of TLR2 and TLR4, modulating innate immunity response in periapical lesions.

Influence of melatonin supplementation on tissue response of endodontic sealers in Wistar rats.

OBJECTIVE: This study evaluated the influence of melatonin supplementation on tissue's response of endodontic sealers in Wistar rats. METHODOLOGY: Forty-eight rats received subcutaneous implants of four polyethylene tubes: one empty (control) and three filled with endodontic sealers (AH Plus, Endofill and Sealapex). Half of the animals were supplemented with melatonin (ME) and the remaining treated with water (WA) for 15 days before the implantation until euthanasia, forming the groups: control-WA, AH Plus-WA, Endofill-WA, Sealapex-WA, Control-ME, AH Plus-ME, Endofill-ME and Sealapex-ME. After 5, 15 and 30 days, (n = 8) tubes were removed and evaluated in H&E., immunohistochemistry, PSR, VK and POL. The results were statistically analyzed (p < 0.05). RESULTS: In animals treated with water, Endofill-WA evoked more intense inflammatory infiltrate compared to AH Plus-WA and Control-WA in a 30-day period (p < 0.05). In animals supplemented with melatonin, there was any difference among endodontic sealers' response in any period of analysis (p > 0.05). Comparing the individual response of each sealer, over a 30-day period, Endofill-ME and Sealapex-ME showed less inflammatory infiltrate compared to Endofill-WA and Sealapex-WA, respectively (p < 0.05). Immunostaining for IL-6 and TNF-α was less intense for all groups in animals supplemented with melatonin, in most periods, except for the Endofill sealer (p < 0.05). Furthermore, Endofill-ME at 5 days and AH-Plus-ME at 30 days showed a higher percentage of mature collagen fibers compared to the Endofill-WA and AH Plus-WA, respectively (p < 0.05). Positive structures for von Kossa staining and birefringent to polarized light were observed only for Sealapex-WA and Sealapex-ME in all periods. CONCLUSIONS: It can be concluded that melatonin influences the tissue response to endodontic sealers, modulating the inflammatory and reparative process.

Cytotoxicity, Biocompatibility, and Calcium Deposition Capacity of 45S5 Bioglass Experimental Paste and Bio-C Temp: In Vitro and In Vivo Study Using Wistar Rats.

The evolution of biomaterials engineering allowed for the development of products that improve outcomes in the medical-dental field. Bioglasses have demonstrated the ability to either compose or replace different materials in dentistry. This study evaluated the cytotoxicity, biocompatibility, calcium deposition, and collagen maturation of 45S5 bioglass experimental paste and Bio-C Temp, compared to calcium hydroxide (Ca(OH)2) paste. The 45S5 bioglass and Ca(OH)2 powder were mixed with distilled water (ratio 2:1); Bio-C Temp is ready-for-use. Dental pulp cells were exposed to the materials' extracts (1:2 and 1:4 dilutions; 24, 48, and 72 h) for MTT and live/dead analyses. Polyethylene tubes filled with the pastes, or left empty (control), were implanted on the dorsum of 16 rats. After 7 and 30 days (n = 8/period), the rats were euthanized and the specimens were processed for hematoxylin-eosin (H&E), von Kossa (vK), and picrosirius red (PSR) staining, or without staining for polarized light (PL) birefringence analysis. A statistical analysis was applied (p < 0.05). There was no difference in cell viability among Ca(OH)2, 45S5 bioglass, and the control, across all periods and dilutions (p > 0.05), while Bio-C Temp was cytotoxic in all periods and dilutions compared to the control (p < 0.05). Regarding biocompatibility, there was a reduction in inflammation from 7 to 30 days for all groups, without significant differences among the groups for any period (p > 0.05). The fibrous capsules were thick for all groups at 7 days and thin at 30 days. All materials showed positive structures for vK and PL analysis. At 7 days, the control and 45S5 bioglass showed more immature collagen than the other groups (p < 0.05); at 30 days, 45S5 bioglass had more immature than mature collagen, different from the other groups (p < 0.05). In conclusion, Bio-C Temp presented cytotoxicity compared to the other materials, but the three pastes showed biocompatibility and induced calcium deposition. Additionally, the bioglass paste allowed for marked and continuous collagen proliferation. This study contributed to the development of new biomaterials and highlighted different methodologies for understanding the characteristics of medical-dental materials.

Saliva as a Biological Fluid in SARS-CoV-2 Detection.

BACKGROUND: The polymerase chain reaction of upper respiratory tract swab samples was established as the gold standard procedure for diagnosing SARS-CoV-2 during the COVID pandemic. However, saliva collection has attracted attention as an alternative diagnostic collection method. The goal of this study was to compare the use of saliva and nasopharyngeal swab (NPS) samples for the detection of SARS-CoV-2. METHODS: Ninety-nine paired samples were evaluated for the detection of SARS-CoV-2 by saliva and swab for a qualitative diagnosis and quantitative comparison of viral particles. Furthermore, the detection limits for each sample collection technique were determined. The cycle threshold (CT) values of the saliva samples, the vaccination status, and the financial costs associated with each collection technique were compared. RESULTS: The results showed qualitative equivalence in diagnosis (96.96%) comparing saliva and swab collection, although there was low quantitative agreement. Furthermore, the detection limit test demonstrated equivalence for both collection methods. We did not observe a statistically significant association between CT values and vaccination status, indicating that the vaccine had no influence on viral load at diagnosis. Finally, we observed that the use of saliva incurs lower financial costs and requires less use of plastic materials, making it more sustainable. CONCLUSIONS: These findings support the adoption of saliva collection as a feasible and sustainable alternative to the diagnosis of COVID-19.

Evaluation of the Inhibitory Potential of Synthetic Peptides Homologous to CDR3 Regions of a Monoclonal Antibody against Bothropic Venom Serine Proteases.

Snakebite accidents, neglected tropical diseases per the WHO, pose a significant public health threat due to their severity and frequency. Envenomation by Bothrops genus snakes leads to severe manifestations due to proteolytic enzymes. While the antibothropic serum produced by the Butantan Institute saves lives, its efficacy is limited as it fails to neutralize certain serine proteases. Hence, developing new-generation antivenoms, like monoclonal antibodies, is crucial. This study aimed to explore the inhibitory potential of synthetic peptides homologous to the CDR3 regions of a monoclonal antibody targeting a snake venom thrombin-like enzyme (SVTLE) from B. atrox venom. Five synthetic peptides were studied, all stable against hydrolysis by venoms and serine proteases. Impressively, four peptides demonstrated uncompetitive SVTLE inhibition, with Ki values ranging from 10-6 to 10-7 M. These findings underscore the potential of short peptides homologous to CDR3 regions in blocking snake venom toxins, suggesting their promise as the basis for new-generation antivenoms. Thus, this study offers potential advancements in combatting snakebites, addressing a critical public health challenge in tropical and subtropical regions.

Influence of systemic antibiotic therapy on the development and progression of induced apical periodontitis in Wistar rats.

The aim of this study was to investigate the influence of systemic antibiotic therapy on the development and progression of induced apical periodontitis (AP) in Wistar rats. Fifty-six rats were submitted to pulp exposure of the lower left first molar for the induction of AP. On the same day, intraperitoneal antibiotic therapy was administered once a day, for 15 days, until euthanasia. The groups were formed according to the different treatments (n = 8): C-control; GEN-treated with gentamicin (10 mg/Kg); AC-treated with amoxicillin (100 mg/Kg); MZ-treated with metronidazole (40 mg/Kg); AMP-treated with ampicillin (100 mg/Kg); AMC group-treated with amoxicillin + clavulanic acid (100 mg/kg); CLI-treated with clindamycin (60 mg/kg). After euthanasia, the jaws were collected and processed for (1) histological and histometric analysis using hematoxylin and eosin staining, (2) analysis of collagen fibers using Picrosirius Red staining and (3) bacteriological analysis using Brown-Brenn staining. The data were analyzed statistically (p < 0.05). AP induction was confirmed in all groups. The AMC group had the lower intensity of inflammatory infiltrate (p = 0.028) and less periapical bone resorption compared to control (p = 0.006). Regarding collagen maturation, PSR staining revealed a predominance of mature collagen fibers in all groups. The AC and AMC groups had the lower amount of mature fibers and the highest amount of immature fibers, compared to all other groups (p < 0.001). All groups showed bacterial contamination; however, the AC and AMC groups showed a lower extent of bacterial contamination compared to the control (p < 0.001). It can be concluded that systemic antibiotic therapy influences the development and progression of induced AP.

Factors associated to mortality in children with critical COVID-19 and multisystem inflammatory syndrome in a resource-poor setting.

SARS-CoV-2 infection in children is usually asymptomatic/mild. However, some patients may develop critical forms. We aimed to describe characteristics and evaluate the factors associated to in-hospital mortality of patients with critical COVID-19/MIS-C in the Amazonian region. This multicenter prospective cohort included critically ill children (1 mo-18 years old), with confirmed COVID-19/MIS-C admitted to 3 tertiary Pediatric Intensive Care Units (PICU) in the Brazilian Amazon, between April/2020 and May/2023. The main outcome was in-hospital mortality and were evaluated using a multivariable Cox proportional regression. We adjusted the model for pediatric risk of mortality score version IV (PRISMIV) score and age/comorbidity. 266 patients were assessed with 187 in the severe COVID-19 group, 79 included in the MIS-C group. In the severe COVID-19 group 108 (57.8%) were male, median age was 23 months, 95 (50.8%) were up to 2 years of age. Forty-two (22.5%) patients in this group died during follow-up in a median time of 11 days (IQR, 2-28). In the MIS-C group, 56 (70.9%) were male, median age was 23 months and median follow-up was 162 days (range, 3-202). Death occurred in 17 (21.5%) patients with a median death time of 7 (IQR, 4-13) days. The mortality was associated with higher levels of Vasoactive Inotropic-Score (VIS), presence of acute respiratory distress syndrome (ARDS), higher levels of Erythrocyte Sedimentation Rate, (ESR) and thrombocytopenia. Critically ill patients with severe COVID-19 and MIS-C from the Brazilian Amazon showed a high mortality rate, within 12 days of hospitalization.

Experiências e perspectivas dos homens sobre sua participação na gestação: um estudo de abordagem qualitativa / Men's experiences and perspectives on their involvement in pregnancy: a qualitative approach study

OBJETIVO: Compreender a percepção masculina sobre sua própria participação durante a gestação. MÉTODO: Pesquisa descritiva de abordagem qualitativa. As informações foram coletadas por meio de entrevistas semiestruturadas com dez homens acompanhantes de puérperas em Alojamento Conjunto, e submetidas a análise temática. RESULTADOS: De maneira geral, a participação do homem no pré-natal ocorreu no acompanhamento nas consultas, em exames e no suporte na realização das tarefas domésticas. Algumas limitações foram a rotina de trabalho e aspectos jurídicos relacionados a questões trabalhistas. Os entrevistados apontaram sugestões para maior incentivo na sua participação e na inclusão na vivência da gestação e do pré-natal. CONCLUSÃO: Os profissionais da área devem dar voz aos pais, e devem inseri-los como alvo das ações em saúde, tornando-o também protagonista neste momento, e assim reforçando as boas práticas assistenciais determinadas por políticas governamentais.

OBJECTIVE: To understand men's experiences and perceptions of their involvement in pregnancy. METHOD: A descriptive, qualitative research approach was used. Information was collected through semi-structured interviews with ten male partners of postpartum women in a shared accommodation setting and subjected to thematic analysis. RESULTS: Overall, men's involvement in prenatal care included attending medical appointments, being present during examinations, and assisting with household tasks. Some limitations included work routines and legal aspects related to work issues. Respondents suggested ways to encourage greater involvement and inclusion in the experience of pregnancy and prenatal care. CONCLUSION: Health professionals should give fathers a voice and include them as targets of health initiatives, making them active participants during this period and reinforcing good health practices set by government policies.

Blockage of the fractalkine pathway reduces hyperalgesia and prevents morphological glial alterations-Comparison between inflammatory and neuropathic orofacial pain in male rats.

This study aimed to evaluate the effects of inhibitors of the fractalkine pathway in hyperalgesia in inflammatory and neuropathic orofacial pain in male rats and the morphological changes in microglia and satellite glial cells (SGCs). Rats were submitted to zymosan-induced arthritis of the temporomandibular joint or infraorbital nerve constriction, and treated intrathecally with a P2 X7 antagonist, a cathepsin S inhibitor or a p-38 mitogen-activated protein kinase (MAPK) inhibitor. Mechanical hyperalgesia was evaluated 4 and 6 h following arthritis induction or 7 and 14 days following nerve ligation. The expression of the receptor CX3 CR1 , phospho-p-38 MAPK, ionized calcium-binding adapter molecule-1 (Iba-1), and glutamine synthetase and the morphological changes in microglia and SGCs were evaluated by confocal microscopy. In both inflammatory and neuropathic models, untreated animals presented a higher expression of CX3 CR1 and developed hyperalgesia and up-regulation of phospho-p-38 MAPK, which was prevented by all drugs (p < .05). The number of microglial processes endpoints and the total branch length were lower in the untreated animals, but the overall immunolabeling of Iba-1 was altered only in neuropathic rats (p < .05). The mean area of SGCs per neuron was significantly altered only in the inflammatory model (p < .05). All morphological alterations were reverted by modulating the fractalkine pathway (p < .05). In conclusion, the blockage of the fractalkine pathway seemed to be a possible therapeutic strategy for inflammatory and neuropathic orofacial pain, reducing mechanical hyperalgesia by impairing the phosphorylation of p-38 MAPK and reverting morphological alterations in microglia and SGCs.

Nature-Based Interventions Targeting Elderly People's Health and Well-Being: An Evidence Map.

BACKGROUND: Healthy aging encompasses more than the absence of disease, emphasizing the preservation of functional abilities for enhanced well-being and quality of life. Nature-based interventions are scientifically proven contributors to healthy aging. OBJECTIVE: To develop an evidence map showcasing nature-based interventions targeting older individuals' health and well-being. METHODS: The evidence map was developed through critical analysis of systematic reviews and clinical trials utilizing the tools AMSTAR2 and CONSORT. A systematic search spanning the past decade was conducted across databases: Cochrane, SCOPUS, PubMed, Web of Science, Embase, and LILACS. RESULTS: Twelve articles met the eligibility criteria. Nature-based interventions such as forest bathing, hiking, therapeutic gardens, virtual reality, and forest sounds were identified. Outcomes were categorized into physical aspects (cardiovascular and pulmonary; neuro-immuno-endocrinological) and mental/behavioral aspects. The final map integrated interventions, outcomes, and quality assessments. CONCLUSIONS: The survey highlights the positive impact of nature-based interventions on the health of the elderly. This study provides insights across various domains, fostering the development of programs and policies in management to promote healthy aging. Regarding healthcare, it encourages discourse among professionals regarding the integration of nature-based practices for equitable care in both individual and group settings. Furthermore, it underscores the need for research in the Southern Hemisphere, particularly in Brazil, where the study was conducted.

Adsorption of aflatoxin B1 by different antimycotoxin additives: bentonite, clinoptilolite, and beta-glucans extracted from yeast cell wall.

The present study aims to evaluate and compare antimycotoxin additives (AMAs) composed of bentonite (AMA 1), clinoptilolite (AMA 2), and beta-glucans extracted from yeast cell wall (AMA 3), with respect to their ability to bind Aflatoxin B1 (AFB1) using the isothermal models of Freundlich, Langmuir, and BET. The additives were submitted to an in vitro adsorption experiment with AFB1 (0.05-4 mg L-1), using solutions of pH 3 and pH 6, with an inclusion rate of 0.5%, and analyzed by HPLC-MS/MS. At pH 3, for the seven concentrations evaluated, AMA 1 obtained adsorption rates (99.69 to 99.98%) higher (p < 0. 05) than the other AMAs, which were from 82.97 to 88.72% (AMA 2) and from 79.43 to 89.32% (AMA 3). At pH 6, in concentrations of 1, 2, and 4 mg L-1 of AFB1, AMA 1 obtained higher (p < 0.05) adsorption results (97.86 to 99.86%) than AMA 2 (91.98 to 96.12%) and AMA 3 (87.56 to 93.50%). The Freundlich model best fitted the AMA 1 adsorption data. For the other additives, the Langmuir model obtained the best fit, demonstrating qm of 8.6 mg g-1 at pH 3 and 2.3 mg g-1 at pH 6 for AMA 2; and for AMA 3, with qm of 3.4 mg g-1 at pH 3 and 2.3 mg g-1 at pH 6. The isotherm models work as an effective tool to describe the adsorption process whereas the AMA adsorption capacity varies as a function of product composition, pH, and mycotoxin content.

Evaluation of the inhibitory potential of synthetic peptides homologous to CDR3 regions of a monoclonal antibody against Bothropic venom serine proteases

Snakebite accidents, neglected tropical diseases per the WHO, pose a significant public health threat due to their severity and frequency. Envenomation by Bothrops genus snakes leads to severe manifestations due to proteolytic enzymes. While the antibothropic serum produced by the Butantan Institute saves lives, its efficacy is limited as it fails to neutralize certain serine proteases. Hence, developing new-generation antivenoms, like monoclonal antibodies, is crucial. This study aimed to explore the inhibitory potential of synthetic peptides homologous to the CDR3 regions of a monoclonal antibody targeting a snake venom thrombin-like enzyme (SVTLE) from B. atrox venom. Five synthetic peptides were studied, all stable against hydrolysis by venoms and serine proteases. Impressively, four peptides demonstrated uncompetitive SVTLE inhibition, with Ki values ranging from 10−6 to 10−7 M. These findings underscore the potential of short peptides homologous to CDR3 regions in blocking snake venom toxins, suggesting their promise as the basis for new-generation antivenoms. Thus, this study offers potential advancements in combatting snakebites, addressing a critical public health challenge in tropical and subtropical regions.

Exogenous Nitric Oxide Alleviates Water Deficit and Increases the Seed Production of an Endemic Amazonian Canga Grass.

Open pit mining can cause loss in different ecosystems, including damage to habitats of rare and endemic species. Understanding the biology of these species is fundamental for their conservation, and to assist in decision-making. Sporobolus multiramosus is an annual grass endemic to the Amazon canga ecosystems, which comprise rocky outcrop vegetation covering one of the world's largest iron ore reserves. Here, we evaluated whether nitric oxide aids S. multiramosus in coping with water shortages and examined the physiological processes behind these adaptations. nitric oxide application improved the water status, photosynthetic efficiency, biomass production, and seed production and germination of S. multiramosus under water deficit conditions. These enhancements were accompanied by adjustments in leaf and root anatomy, including changes in stomata density and size and root endodermis thickness and vascular cylinder diameter. Proteomic analysis revealed that nitric oxide promoted the activation of several proteins involved in the response to environmental stress and flower and fruit development. Overall, the results suggest that exogenous nitric oxide has the potential to enhance the growth and productivity of S. multiramosus. Enhancements in seed productivity have significant implications for conservation initiatives and can be applied to seed production areas, particularly for the restoration of native ecosystems.

Overview of nursing ethics teaching in Brazilian public higher education institutions.

OBJECTIVES: to outline the teaching of ethics in undergraduate Nursing programs in Brazilian public higher education institutions. METHODS: descriptive and exploratory study, carried out through the documentary analysis of pedagogical projects of undergraduate Nursing programs in Brazil. RESULTS: 153 active undergraduate Nursing programs were found, of which 106 provide the pedagogical project. In addition to deontological teaching, the teaching of ethics was identified in a transversal way associated with themes such as Social Context, Hospital and Community Care, Pharmacology, Systematization of Nursing Care, Surgical Nursing, Epidemiology, Palliative Care, Management in Nursing, Diversity, Women's, Children's, Adolescent's, Adult's and Older People's Health, and Mental Health. FINAL CONSIDERATIONS: the challenge in teaching nursing ethics is its integration with each action of caring, teaching and managing.

Fluorotic Enamel Susceptibility to Dental Erosion and Fluoride Treatment.

The purpose of this in vitro study was to test the hypothesis that fluoride treatment can prevent dental erosion on fluorotic enamel of different severities. It followed a 3×2 factorial design, considering a) fluorosis severity: sound (TF0, Thylstrup-Fejerskov Index), mild (TF1-2), moderate (TF3-4); and b) fluoride treatment: 0 (negative control) and 1150ppmF. Human molars with the three fluorosis severities (n=16, each) were selected and randomly assigned to the two fluoride treatments (n=8). Enamel blocks (4×4mm) were prepared from each tooth and subjected to a dental erosion cycling model, for 10 days. The daily cycling protocol consisted of erosive challenges (1% citric acid, pH 2.4), interspersed by periods of immersion in artificial saliva, and three 2-minute treatments with either 0 or 1150ppm F. The enamel volume loss (mm3) was calculated by subtracting values obtained by microtomography before and after cycling. Two-Way ANOVA showed no significant interaction between fluorosis severity and fluoride treatment (p=0.691), and no significant effect for either fluorosis severity (TF0 mean±standard-deviation: 13.5(10-2±0.42(10-2, TF1-2: 1.50(10-2±0.52(10-2, TF3-4: 1.24(10-2±0.52(10-2, p=0.416) or treatment (0ppmF: 1.49(10-2±0.53(10-2; 1150ppmF: 1.21(10-2±0.42(10-2; p=0.093), when evaluated independently. Considering the limitations of this in vitro study, the presence and severity of fluorosis in enamel do not appear to affect its susceptibility to dental erosion. Fluoride treatment was not effective in preventing the development of dental erosion in both sound and fluorotic enamel substrates under our experimental conditions.

Understanding plant responses to saline waterlogging: insights from halophytes and implications for crop tolerance.

MAIN CONCLUSION: Saline and wet environments stress most plants, reducing growth and yield. Halophytes adapt with ion regulation, energy maintenance, and antioxidants. Understanding these mechanisms aids in breeding resilient crops for climate change. Waterlogging and salinity are two abiotic stresses that have a major negative impact on crop growth and yield. These conditions cause osmotic, ionic, and oxidative stress, as well as energy deprivation, thus impairing plant growth and development. Although few crop species can tolerate the combination of salinity and waterlogging, halophytes are plant species that exhibit high tolerance to these conditions due to their morphological, anatomical, and metabolic adaptations. In this review, we discuss the main mechanisms employed by plants exposed to saline waterlogging, intending to understand the mechanistic basis of their ion homeostasis. We summarize the knowledge of transporters and channels involved in ion accumulation and exclusion, and how they are modulated to prevent cytosolic toxicity. In addition, we discuss how reactive oxygen species production and cell signaling enhance ion transport and aerenchyma formation, and how plants exposed to saline waterlogging can control oxidative stress. We also address the morphological and anatomical modifications that plants undergo in response to combined stress, including aerenchyma formation, root porosity, and other traits that help to mitigate stress. Furthermore, we discuss the peculiarities of halophyte plants and their features that can be leveraged to improve crop yields in areas prone to saline waterlogging. This review provides valuable insights into the mechanisms of plant adaptation to saline waterlogging thus paving the path for future research on crop breeding and management strategies.

Comparing Traditional and Toxin-Oriented Approaches towards Antivenom Production against Bitis arietans Snake Venom.

Accidents with snakes are responsible for about 32,000 deaths annually in sub-Saharan Africa, caused mostly by snakes from the genus Bitis, in particular Bitis arietans. B. arietans venom is composed of a complex mixture of toxins, mainly metalloproteases, serine proteases, phospholipases, lectins, and disintegrins. In this work, we compared two approaches to anti-B. arietans antivenom production: immunization with crude snake venom ("traditional approach") and immunization with selected key toxins isolated from the snake venom ("toxin oriented" approach). Fractions from B. arietans venom were isolated by size exclusion chromatography. Crude venom and samples containing serine proteases or metalloproteases were selected for the immunization of BALB/c mice. Anti-B. arietans and anti-serine proteases plasmas showed a similar recognition profile and higher titers and affinity than the anti-metalloproteases plasma. Cross-recognition of other Bitis venoms was observed, but with low intensity. Although the plasma of all experimental groups inhibited the enzymatic activity of B. arietans venom in vitro, in vivo protection was not achieved. Our results have shown limitations in both approaches considered. Based on this, we proposed a model of polyclonal, species-specific, monovalent antivenoms that could be used as a base to produce customizable polyvalent sera for use in sub-Saharan Africa.

Susceptibility of fluorotic enamel to dental erosion-abrasion.

Dental hard tissue conditions can be of pre- or post-eruptive nature, such as enamel fluorosis and erosive tooth wear (ETW), respectively. Dental enamel fluorosis is caused by the chronic and excessive intake of fluoride during enamel development, leading to increased fluoride concentration and increased porosity. ETW has become a common clinical condition and often impairs dental function and aesthetics. This in vitro study tested the hypothesis that fluorotic enamel presents different susceptibility to dental erosion-abrasion. It consisted of a 3×3×2 factorial design, considering a) fluorosis severity: sound (TF0), mild (TF1-2), moderate (TF3-4); b) abrasive challenge: low, medium, and high; and c) erosive challenge: yes or no. A total of 144 human teeth were selected according to the three fluorosis severity levels (n=48), and subdivided into six groups (n = 8) generated by the association of the different erosive and abrasive challenges. Enamel blocks (4×4 mm) were prepared from each tooth and their natural enamel surfaces subjected to an erosion-abrasion cycling model. After cycling, the depth of the lesions in enamel was assessed by profilometry. ANOVA showed that the three-way and two-way interactions among the factors were not significant (p > 0.20). Enamel fluorosis level (p=0.638) and abrasion level (p = 0.390) had no significant effect on lesion depth. Acid exposure caused significantly more enamel surface loss than water (p < 0.001). Considering the limitations of this in vitro study, fluorosis did not affect the susceptibility of enamel to dental erosion-abrasion.

Design, Synthesis and Phenotypic Profiling of Simplified Gedatolisib Analogues.

Targeted antitumour therapy has revolutionized the treatment of several types of tumours. Among the validated targets, phosphatidylinositol-3 kinase (PI3K) deserves to be highlighted. Several PI3K inhibitors have been developed for the treatment of cancer, including gedatolisib (4). This inhibitor was elected as a prototype and molecular modifications were planned to design a new series of simplified gedatolisib analogues (5a-f). The analogues were synthesised, and the comparative cytotoxic activity profile was studied in phenotypic models employing solid and nonadherent tumour cell lines. Compound 5f (LASSBio-2252) stood out as the most promising of the series, showing good aqueous solubility (42.38 µM (pH = 7.4); 39.33 µM (pH = 5.8)), good partition coefficient (cLogP = 2.96), cytotoxic activity on human leukemia cell lines (CCRF-CEM, K562 and MOLT-4) and an excellent metabolic stability profile in rat liver microsomes (t1/2 = 462 min; Clapp = 0.058 mL/min/g). The ability of 5f to exert its cytotoxic effect through modulation of the PI3K pathway was demonstrated by flow cytometry analysis in a comparative manner to gedatolisib.

A two-year study on the occurrence and concentration of mycotoxins in corn varieties with different endosperm textures.

BACKGROUND: Mycotoxin monitoring in cereal grains has great importance in the food and feed industries. This study evaluated mycotoxin contamination in corns with different endosperm textures in 2 years of cultivation. Samples of dent, semi-dent, flint and semi-flint corns from field experiments were analyzed by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). RESULTS: Occurrences of fumonisins B1 (FB1 ) and B2 (FB2 ) in 2020 were 45.72% (mean 270 µg kg-1 ) and 35.89% (94.97 µg kg-1 ), respectively, and 68.98% (446 µg kg-1 ) and 45.83% (152 µg kg-1 ) in 2021. Occurrence of aflatoxin B1 was 11.96% (0.16 µg kg-1 ) in 2020 and 11.11% (0.13 µg kg-1 ) in 2021. In 2020, deoxynivalenol (DON) and zearalenona (ZEA) presented occurrences of 1.28% and 1.70%, with means of 4.08 and 2.45 µg kg-1 , respectively. In 2021, results were 8.33% (31.00 µg kg-1 ) for DON and 8.79% (4.38 µg kg-1 ) for ZEA. Citrinin, diacetoxyscirpenol and fusarenon-X did not occur in 2020 but presented 1.66%, 0.83%, and 2.50% positive rates in 2021, respectively. In 2020, flint corn presented the lowest concentration of FB1 whereas dent corn presented the highest concentration of FB1 and FB2 (P < 0.05). In 2021, dent corn presented the highest means of FB1 , FB2 and diacetoxyscirpenol (P < 0.05). Dent and semi-dent presented the highest concentration of nivalenol (P < 0.05). CONCLUSION: The endosperm texture influenced mycotoxin contamination in corn grains, especially FB1 and FB2 , which had the highest concentration in dent corn in the 2 years of this study. © 2023 Society of Chemical Industry.