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Bacillus thuringiensis (Bt) is one of the most promising biological control agents used commercially. Its products can contribute to reducing ecological and environmental problems associated with the use of chemical pesticides. Among the limiting factors of using Bt as bioinsecticide are the costs and ensuring its biological activity, which may vary according to the strain and culture conditions. This systematic review aimed to collect state-of-the-art information on the production of Bt endotoxins and to score the methodological feasibility of the data obtained, thus highlighting possible incoherencies. In order to consolidate recent findings and guide future studies, a total of 47 original articles from the last 10 years was analysed, with special attention being given to corroborating data, identifying inconsistencies and suggesting future adjustments so as to increase data reliability. With a maximum score of 8 points, three production parameters were classified on the following scale: preferable (score: 2), adequate (score: 1) and inadequate (score: 0), and another two parameter were classified as adequate (score: 1) or inadequate (score: 0). No article scored more than 6 out of the maximum of 8, thus reflecting the need for more detailed studies regarding Bt endotoxin production. The lack of standardization of methods and units of measurement also have made a comparison of results and an overall analysis difficult. Standards are suggested in the present study. The inclusion of bioassays and quantifying toxin via alkaline dilution are strongly recommended for studies of this nature, along with LC50 expressed in mg/L. Sixteen articles (34%) did not use either of these suggested methods, which indicates the need for further supporting studies. These findings reinforce the need for robust studies in this area, which could include the development of more affordable and effective bioinsecticides, thus increasing their competitiveness against insecticides derived from unsustainable sources.

Phenolic compounds are thought to be important to prevent neurodegenerative diseases (ND). Parkinson’s Disease (PD) is a neurodegenerative disorder known for its typical motor features, the deposition of α-synuclein (αsyn)-positive inclusions in the brain, and for concomitant cellular pathologies that include oxidative stress and neuroinflammation. Neuroprotective activity of fisetin, a dietary flavonoid, was evaluated against main hallmarks of PD in relevant cellular models. At physiologically relevant concentrations, fisetin protected SH-SY5Y cells against oxidative stress overtaken by tert-butyl hydroperoxide (t-BHP) and against methyl-4-phenylpyridinuim (MPP+)-induced toxicity in dopaminergic neurons, the differentiated Lund human Mesencephalic (LUHMES) cells. In this cellular model, fisetin promotes the increase of the levels of dopamine transporter. Remarkably, fisetin reduced the percentage of cells containing αsyn inclusions as well as their size and subcellular localization in a yeast model of αsyn aggregation. Overall, our data show that fisetin exerts modulatory activities toward common cellular pathologies present in PD; remarkably, it modulates αsyn aggregation, supporting the idea that diets rich in this compound may prove beneficial.

Chlorella vulgaris is a microalga which contains a variety of bioactive compounds. Chlorella has been used in different fields for several years and proved attractive to the pharmaceutical and cosmetic industry. The present study aimed to evaluate the wound-healing activity of a hydrogel-based C. vulgaris extract in in vivo assay. A hydrogel formulation containing different concentrations of extracts of C. vulgaris grown under autotrophic (AE) or mixotrophic (ME) condition was developed and applied for 12 days on excisional wounds in mice. Macroscopic analyses and histomorphometric studies were performed to investigate tissue repair. Extracts were evaluated for protein concentration, phytochemical profile, hemagglutinating activity, antioxidant activity using DPPH assay, and antibacterial activity. The wound-healing assay suggested that animals treated with hydrogel containing 25% of ME exhibited a higher presence of collagen deposition, a decrease of fibroblast and inflammatory cells, strong evidence of skin appendages, and evidence of basal laminae. Results showed that ME has 1.174 mg mL−1 of total proteins and hemagglutinating activity ≥ to 248 against rabbit erythrocytes and ≥ to 224 against human type B blood. The phytochemical profile of the extract demonstrated the presence of steroids, triterpenes, saponins, and sugars. In addition, ME had the highest values of antioxidant activity (54.64%) and antibacterial activity against Klebsiella pneumoniae, Enterococcus faecalis, and Escherichia coli. This first report of a hydrogel formulation containing microalgae extracts for wound healing showed that C. vulgaris cell extracts from mixotrophic cultivation have pro-healing and anti-inflammatory properties, which accelerated the wound healing process.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity symptoms. Neuroimaging studies have revealed a delayed cortical and subcortical development pattern in children diagnosed with ADHD. This study followed up on the development in vitro of frontal cortical neurons from Spontaneously hypertensive rats (SHR), an ADHD rat model, and Wistar-Kyoto rats (WKY), control strain, over their time in culture, and in response to BDNF treatment at two different days in vitro (DIV). These neurons were also evaluated for synaptic proteins, brain-derived neurotrophic factor (BDNF), and related protein levels. Frontal cortical neurons from the ADHD rat model exhibited shorter dendrites and less dendritic branching over their time in culture. While pro- and mature BDNF levels were not altered, the cAMP-response element-binding (CREB) decreased at 1 DIV and SNAP-25 decreased at 5 DIV. Different from control cultures, exogenous BDNF promoted less dendritic branching in neurons from the ADHD model. Our data revealed that neurons from the ADHD model showed decreased levels of an important transcription factor at the beginning of their development, and their delayed outgrowth and maturation had consequences in the levels of SNAP-25 and may be associated with less response to BDNF. These findings provide an alternative tool for studies on synaptic dysfunctions in ADHD. They may also offer a valuable tool for investigating drug effects and new treatment opportunities.

This work dealt with the study of growth parameters, pigments production, and bioenergetic aspects of the microalga Dunaliella tertiolecta in different culture media. For this purpose, cultures were carried out in Erlenmeyer flasks containing F/2 medium, Bold’s Basal medium, or an alternative medium made up of the same constituents of the Bold’s Basal medium dissolved in natural seawater instead of distilled water. D. tertiolecta reached the highest dry cell concentration (Xmax = 1223 mgDM·L−1), specific growth rate (µmax = 0.535 d−1), cell productivity (PX = 102 mgDM·L−1·d−1), and photosynthetic efficiency (PE = 14.54%) in the alternative medium, while the highest contents of carotenoids (52.0 mg·g−1) and chlorophyll (108.0 mg·g−1) in the biomass were obtained in Bold’s Basal medium. As for the bioenergetic parameters, the biomass yield on Gibbs energy dissipation was higher and comparable in both seawater-based media. However, the F/2 medium led to the highest values of moles of photons absorbed to produce 1 C-mol of biomass (nPh), total Gibbs energy absorbed by the photosynthesis (ΔGa) and released heat (Q), as well as the lowest cell concentration, thus proving to be the least suitable medium for D. tertiolecta growth. On the other hand, the highest values of molar development of O2 and consumption of H+ and H2O were obtained in the alternative medium, which also ensured the best kinetic parameters, thereby allowing for the best energy exploitation for cell growth. These results demonstrate that composition of culture medium for microalgae cultivation has different effects on pigments production, growth kinetics, and bioenergetics parameters, which should be taken into consideration for any use of biomass, including as raw material for biofuels production.

Automatic Item Generation (AIG) refers to the process of using cognitive models to generate test items using computer modules. It is a new but rapidly evolving research area where cognitive and psychometric theory are combined into digital framework. However, assessment of the item quality, usability and validity of AIG relative to traditional item development methods lacks clarification. This paper takes a top-down strong theory approach to evaluate AIG in medical education. Two studies were conducted: Study I—participants with different levels of clinical knowledge and item writing experience developed medical test items both manually and through AIG. Both item types were compared in terms of quality and usability (efficiency and learnability) ; Study II—Automatically generated items were included in a summative exam in the content area of surgery. A psychometric analysis based on Item Response Theory inspected the validity and quality of the AIG-items. Items generated by AIG presented quality, evidences of validity and were adequate for testing student’s knowledge. The time spent developing the contents for item generation (cognitive models) and the number of items generated did not vary considering the participants' item writing experience or clinical knowledge. AIG produces numerous high-quality items in a fast, economical and easy to learn process, even for inexperienced and without clinical training item writers. Medical schools may benefit from a substantial improvement in cost-efficiency in developing test items by using AIG. Item writing flaws can be significantly reduced thanks to the application of AIG's models, thus generating test items capable of accurately gauging students' knowledge.

Dopamine directly acts in the liver and white adipose tissue (WAT) to regulate insulin signaling, glucose uptake, and catabolic activity. Given that dopamine is secreted by the gut and regulates insulin secretion in the pancreas, we aimed to determine its regulation by nutritional cues and its role in regulating glucagon-like peptide 1 (GLP-1) action in WAT. Solutions with different nutrients were administered to Wistar rats and postprandial dopamine levels showed elevations following a mixed meal and glucose intake. In high-fat diet-fed diabetic Goto-Kakizaki rats, sleeve gastrectomy upregulated dopaminergic machinery, showing the role of the gut in dopamine signaling in WAT. Bromocriptine treatment in the same model increased GLP-1R in WAT, showing the role of dopamine in regulating GLP-1R. By contrast, treatment with the GLP-1 receptor agonist Liraglutide had no impact on dopamine receptors. GLP-1 and dopamine crosstalk was shown in rat WAT explants, since dopamine upregulated GLP-1-induced AMPK activity in mesenteric WAT in the presence of the D2R and D3R inhibitor Domperidone. In human WAT, dopamine receptor 1 (D1DR) and GLP-1R expression were correlated. Our results point out a dietary and gut regulation of plasma dopamine, acting in the WAT to regulate GLP-1 action. Together with the known dopamine action in the pancreas, such results may identify new therapeutic opportunities to improve metabolic control in metabolic disorders.

To evaluate the impact of a quality improvement project (QI) on reducing proven late-onset sepsis (LOS) in centers of the Brazilian Network Neonatal Research (BNNR). An interventional study conducted in 12 BNNR centers from 2021 to 2023. Included preterm infants (PT) born at 22–36 weeks' gestational age, weighing 400–1499 grams, without malformations, and admitted to the NICU for > 72 h. QI tools were used and four process indicators were defined: central catheter complication (≤ 20 %); antibiotic discontinuation ≤48 h in non-infected infants (≥ 80 %); breast milk expression within the first 48 h and enteral feeding within the first 24 h of life (≥ 80 %); full enteral feeding without parenteral nutrition by day 11 (≥ 70 %). The outcome was the proportional reduction of LOS according to each center’s baseline (2020). Indicators were analyzed descriptively across three periods. A total of 1993 PT < 1500 grams were included. Half of the centers achieved the target for umbilical catheter complications, and 92 % for percutaneous catheters. Antibiotics were discontinued within 48 h in 67 % of non-infected infants. Early breast milk expression and enteral feeding were achieved in 44 % and 75 % of cases, respectively. 58 % achieved full enteral nutrition without parenteral support by day 11. LOS incidence declined in 67 % of centers, and half met their targets, with an overall 18.5 % reduction. The project reduced LOS in most centers, although some clinical practices still need improvement. It demonstrates a reproducible, low-cost strategy with the potential to guide other neonatal units facing high sepsis incidence.

Parkinson’s Disease (PD) is a common neurodegenerative disorder affecting millions of people worldwide for which there are only symptomatic therapies. Small molecules able to target key pathological processes in PD have emerged as interesting options for modifying disease progression. We have previously shown that a (poly)phenol-enriched fraction (PEF) of Corema album L. leaf extract modulates central events in PD pathogenesis, namely α-synuclein (αSyn) toxicity, aggregation and clearance. PEF was now subjected to a bio-guided fractionation with the aim of identifying the critical bioactive compound. We identified genipin, an iridoid, which relieves αSyn toxicity and aggregation. Furthermore, genipin promotes metabolic alterations and modulates lipid storage and endocytosis. Importantly, genipin was able to prevent the motor deficits caused by the overexpression of αSyn in a Drosophila melanogaster model of PD. These findings widens the possibility for the exploitation of genipin for PD therapeutics. In this work, the authors identify Genipin as a small iridoid able to prevent alpha-synuclein aggregation and toxicity by affecting endocytosis, metabolism and lipid storage.

Background: This study investigated effects of rapid high-intensity light-curing (3 s) on increasing transdentinal temperature and cell viability. Methods: A total of 40 dentin discs (0.5 mm) obtained from human molars were prepared, included in artificial pulp chambers (4.5 × 5 mm), and subjected to four light-curing protocols (n = 5), with a Valo Grand light curing unit: (i) 10 s protocol with a moderate intensity of 1000 mW/cm2 (Valo-10 s); (ii) 3 s protocol with a high intensity of 3200 mW/cm2 (Valo-3 s); (iii) adhesive system + Filtek Bulk-Fill Flow bulk-fill composite resin in 10 s (FBF-10 s); (iv) adhesive system + Tetric PowerFlow bulk-fill composite resin in 3 s (TPF-3 s). Transdentinal temperature changes were recorded with a type K thermocouple. Cell viability was assessed using the MTT assay. Data were analyzed using one-way ANOVA and Tukey tests for comparison between experimental groups (p < 0.05). Results: The 3 s high-intensity light-curing protocol generated a higher temperature than the 10 s moderate-intensity standard (p < 0.001). The Valo-10 s and Valo-3 s groups demonstrated greater cell viability than the FBF-10s and TPF-3 s groups and statistical differences were observed between the Valo-3 s and FBF-10 s groups (p = 0.023) and Valo-3 s and TPF-3 s (p = 0.025), with a potential cytotoxic effect for the FBF-10 s and TPF-3 s groups. Conclusions: The 3 s rapid high-intensity light-curing protocol of bulk-fill composite resins caused a temperature increase greater than 10 s and showed cell viability similar to and comparable to the standard protocol.