A phase I dose escalation and expansion trial of the next-generation oral SERD camizestrant in women with ER-positive, HER2-negative advanced breast cancer: SERENA-1 monotherapy results.

BACKGROUND: SERENA-1 (NCT03616587) is a phase I, multi-part, open-label study of camizestrant in pre- and post-menopausal women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Parts A and B aim to determine the safety and tolerability of camizestrant monotherapy and define doses for clinical evaluation. PATIENTS AND METHODS: Women aged ≥18 years with metastatic or recurrent ER+, HER2- breast cancer, refractory (or intolerant) to therapy, were assigned 25 mg up to 450 mg once daily (QD; escalation) or 75, 150, or 300 mg QD (expansion). Safety and tolerability, antitumor efficacy, pharmacokinetics, and impact on mutations in the estrogen receptor gene (ESR1m) circulating tumor (ct)DNA levels were assessed. RESULTS: By 9 March 2021, 108 patients received camizestrant monotherapy at 25-450 mg doses. Of these, 93 (86.1%) experienced treatment-related adverse events (TRAEs), 82.4% of which were grade 1 or 2. The most common TRAEs were visual effects (56%), (sinus) bradycardia (44%), fatigue (26%), and nausea (15%). There were no TRAEs grade 3 or higher, or treatment-related serious adverse events at doses ≤150 mg. Median tmax was achieved ∼2-4 h post-dose at all doses investigated, with an estimated half-life of 20-23 h. Efficacy was observed at all doses investigated, including in patients with prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and/or fulvestrant treatment, with and without baseline ESR1 mutations, and with visceral disease, including liver metastases. CONCLUSIONS: Camizestrant is a next-generation oral selective ER antagonist and degrader (SERD) and pure ER antagonist with a tolerable safety profile. The pharmacokinetics profile supports once-daily dosing, with evidence of pharmacodynamic and clinical efficacy in heavily pre-treated patients, regardless of ESR1m. This study established 75-, 150-, and 300-mg QD doses for phase II testing (SERENA-2, NCT04214288 and SERENA-3, NCT04588298).

Mathematical kinetic modelling followed by in vitro and in vivo assays reveal the bifunctional rice GTPCHII/DHBPS enzymes and demonstrate the key roles of OsRibA proteins in the vitamin B2 pathway.

BACKGROUND: Riboflavin is the precursor of several cofactors essential for normal physical and cognitive development, but only plants and some microorganisms can produce it. Humans thus rely on their dietary intake, which at a global level is mainly constituted by cereals (> 50%). Understanding the riboflavin biosynthesis players is key for advancing our knowledge on this essential pathway and can hold promise for biofortification strategies in major crop species. In some bacteria and in Arabidopsis, it is known that RibA1 is a bifunctional protein with distinct GTP cyclohydrolase II (GTPCHII) and 3,4-dihydroxy-2-butanone-4-phosphate synthase (DHBPS) domains. Arabidopsis harbors three RibA isoforms, but only one retained its bifunctionality. In rice, however, the identification and characterization of RibA has not yet been described. RESULTS: Through mathematical kinetic modeling, we identified RibA as the rate-limiting step of riboflavin pathway and by bioinformatic analysis we confirmed that rice RibA proteins carry both domains, DHBPS and GTPCHII. Phylogenetic analysis revealed that OsRibA isoforms 1 and 2 are similar to Arabidopsis bifunctional RibA1. Heterologous expression of OsRibA1 completely restored the growth of the rib3∆ yeast mutant, lacking DHBPS expression, while causing a 60% growth improvement of the rib1∆ mutant, lacking GTPCHII activity. Regarding OsRibA2, its heterologous expression fully complemented GTPCHII activity, and improved rib3∆ growth by 30%. In vitro activity assays confirmed that both OsRibA1 and OsRibA2 proteins carry GTPCHII/DHBPS activities, but that OsRibA1 has higher DHBPS activity. The overexpression of OsRibA1 in rice callus resulted in a 28% increase in riboflavin content. CONCLUSIONS: Our study elucidates the critical role of RibA in rice riboflavin biosynthesis pathway, establishing it as the rate-limiting step in the pathway. By identifying and characterizing OsRibA1 and OsRibA2, showcasing their GTPCHII and DHBPS activities, we have advanced the understanding of riboflavin biosynthesis in this staple crop. We further demonstrated that OsRibA1 overexpression in rice callus increases its riboflavin content, providing supporting information for bioengineering efforts.

Differential correlates of fear and anxiety in salience perception: A behavioral and ERP study with adolescents.

Anxiety disorders are the most common psychopathologies among adolescents. Their diagnostic criteria include both fear and anxiety symptomatology, although according to the literature, we can find evidence for some distinction between these two emotions. The present study contribute to this distinction, exploring the effects of trait fear and trait anxiety on behavioral and neural correlates. Thirty-two participants (aged 11-16 years) performed two experimental tasks of salient target detection, including visual stimuli that were manipulated to become salient, while reaction times and EEG were recorded. Results of both tasks revealed differential effects of trait fear and trait anxiety assessed through the Fear Survey Schedule for Children-Revised and the Youth Anxiety Measure for DSM-5 on reaction times and ERP components amplitudes. Specifically, higher symptoms from Separation Anxiety Disorder increased early neural visual processing and decreased reaction times for more salient stimuli. Also, trait fear reduced later neural visual processing of salient stimuli. These findings may provide a significant contribution to guiding psychological interventions, especially with adolescents presenting higher levels of anxiety-related symptomatology.

Localized mammary gland changes in milk composition and venous blood metabolite concentrations result from sterile subclinical mastitis.

Subclinical mastitis reduces milk yield and elicits undesirable changes in milk composition, but the mechanisms resulting in reduced milk production in affected mammary glands are incompletely understood. This study investigated the effects of sterile inflammation on mammary gland metabolism by assessing changes in milk and venous blood composition. Mid-lactation primiparous Holstein cows (n = 4) had udder halves randomly allocated to treatments; quarters of 1 udder half were infused with 2 billion cfu of formalin fixed Staphylococcus aureus (FX-STAPH) and quarters of the opposite udder half infused with saline (SAL). Blood samples were collected from the right and left subcutaneous abdominal veins in 2.6 h intervals until 40 h post challenge and analyzed for blood gas and metabolite concentrations. Milk from FX-STAPH udder halves had significantly increased SCS by first milking at 8 h post-challenge. By 16 h post-challenge, FX-STAPH udder halves had increased concentrations of protein and lactate and lower lactose concentrations than SAL udder halves. Milk fat concentrations, milk yields, energy corrected milk yields, and the ferric reducing antioxidant power of milk were not significantly different between SAL and FX-STAPH udder halves. Venous blood of FX-STAPH halves had marginally greater concentrations of saturated O2, partial pressures of O2, and glucose concentrations than SAL halves. Conversely, total and partial pressures of CO2 did not differ between udder half treatments suggesting a shift in local metabolite utilization in FX-STAPH udder halves. These results indicate that changes in milk composition resulting from mastitis are accompanied by changes in some key blood metabolite concentrations. The shift in venous blood metabolite concentrations, along with the marked increase in milk lactate, suggests that local mammary tissue and/or recruited and immune cells alters metabolite usage in mammary tissues. Future studies are needed to quantify the uptake of key milk precursors during mastitis.

Robust Photocatalytic MICROSCAFS® with Interconnected Macropores for Sustainable Solar-Driven Water Purification.

Advanced oxidation processes, including photocatalysis, have been proven effective at organic dye degradation. Tailored porous materials with regulated pore size, shape, and morphology offer a sustainable solution to the water pollution problem by acting as support materials to grafted photocatalytic nanoparticles (NPs). This research investigated the influence of pore and particle sizes of photocatalytic MICROSCAFS® on the degradation of methyl orange (MO) in aqueous solution (10 mg/L). Photocatalytic MICROSCAFS® are made of binder-less supported P25 TiO2 NPs within MICROSCAFS®, which are silica-titania microspheres with a controlled size and interconnected macroporosity, synthesized by an adapted sol-gel method that involves a polymerization-induced phase separation process. Photocatalytic experiments were performed both in batch and flow reactors, with this latter one targeting a proof of concept for continuous transformation processes and real-life conditions. Photocatalytic degradation of 87% in 2 h (batch) was achieved, using a calibrated solar light simulator (1 sun) and a photocatalyst/pollutant mass ratio of 23. This study introduces a novel flow kinetic model which provides the modeling and simulation of the photocatalytic MICROSCAFS® performance. A scavenger study was performed, enabling an in-depth mechanistic understanding. Finally, the transformation products resulting from the MO photocatalytic degradation were elucidated by high-resolution mass spectrometry experiments and subjected to an in silico toxicity assessment.

Oral cancer screening outcomes in the Latin American region with special relevance to Brazil and Cuba: a systematic review.

BACKGROUND:  The Latin American region represents a hotspot for oral cancer incidence and mortality. To reduce oral cancer mortality rates, screening for early detection of subjects with suspicious or innocuous oral lesions has been promoted. A systematic review was performed to assess the outcomes of oral cancer screening in the Latin American region. MATERIAL AND METHODS:  An electronic search was conducted in eight databases and grey literature. The eligibility criteria included screening where adult participants underwent any screening test during an organized screening program. Screening programs were assessed to understand trends in oral cancer diagnosis. Rates of oral cancers diagnosed in screening programs were classified as increase, decrease, or stable based on each year assessed. RESULTS:  Following our searches, twelve studies conducted in Brazil and Cuba were included. The screening tests reported were visual oral examination (VOE) and in one study in addition light-based fluorescence testing. 13,277,608 individuals were screened and a total of 1,516 oral cancers were detected (0.01%). Only two studies aimed to screen high-risk individuals (smokers and drinkers). Oral cancer cases diagnosed during screening programs were proportionately stable over the years 1997 to 2009 but increased from 2010 to 2021. The fluorescence-associated VOE test demonstrated a sensitivity of 100% and a specificity of 90%. Similarly, the VOE test alone exhibited a sensitivity of 100%, with specificity ranging from 75% to 90%. CONCLUSIONS:  Screening studies conducted in Latin American countries had serious limitations both in methodology (lack of examiner training) and in reporting data (lack of description of clinical categories of screen positives). Capacitation of health workers to perform VOE in well-designed screening programs should be implemented.

Systemic therapies for salivary gland carcinomas: an overview of published clinical trials.

BACKGROUND: There is no consensus about effective systemic therapy for salivary gland carcinomas (sgcs). Our aim was summarized the clinical trials assessing the systemic therapies (ST) on sgcs. MATERIAL AND METHODS: Electronic searches were carried out through MEDLINE/pubmed, EMBASE, Scopus, Web of Science, and the Cochrane Library databases, and gray literature. RESULTS: Seventeen different drugs were evaluated, and the most frequent histological subtype was adenoid cystic carcinoma (n=195, 45.5%). Stable disease, observed in 11 ST, achieved the highest rate in adenoid cystic carcinoma treated with sunitinib. The highest complete (11.1%) and partial response (30.5%) rates were seen in androgen receptor-positive tumors treated with leuprorelin acetate. CONCLUSIONS: Despite all the advances in this field, there is yet no effective evidence-based regimen of ST, with all the clinical trials identified showing low rates of complete and partial responses. Further, translational studies are urgently required to characterize molecular targets and effective ST.

Translational profile of developing phellem cells in Arabidopsis thaliana roots.

The phellem is a specialized boundary tissue providing the first line of defense against abiotic and biotic stresses in organs undergoing secondary growth. Phellem cells undergo several differentiation steps, which include cell wall suberization, cell expansion, and programmed cell death. Yet, the molecular players acting particularly in phellem cell differentiation remain poorly described, particularly in the widely used model plant Arabidopsis thaliana. Using specific marker lines we followed the onset and progression of phellem differentiation in A. thaliana roots and further targeted the translatome of newly developed phellem cells using translating ribosome affinity purification followed by mRNA sequencing (TRAP-SEQ). We showed that phellem suberization is initiated early after phellogen (cork cambium) division. The specific translational landscape was organized in three main domains related to energy production, synthesis and transport of cell wall components, and response to stimulus. Novel players in phellem differentiation related to suberin monomer transport and assembly as well as novel transcription regulators were identified. This strategy provided an unprecedented resolution of the translatome of developing phellem cells, giving a detailed and specific view on the molecular mechanisms acting on cell differentiation in periderm tissues of the model plant Arabidopsis.

Patritumab deruxtecan in untreated hormone receptor-positive/HER2-negative early breast cancer: final results from part A of the window-of-opportunity SOLTI TOT-HER3 pre-operative study.

BACKGROUND: Patritumab deruxtecan (HER3-DXd) is a human epidermal growth factor receptor 3 (HER3)-directed antibody-drug conjugate composed of a fully human anti-HER3 monoclonal antibody (patritumab) covalently linked to a topoisomerase I inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. TOT-HER3 is a window-of-opportunity study designed to assess the biological activity, measured by CelTIL score [= -0.8 × tumor cellularity (in %)  + 1.3  × tumor-infiltrating lymphocytes (TILs) (in %)], and clinical activity of HER3-DXd during short-term (21 days) pre-operative treatment in patients with primary operable HER2-negative early breast cancer. PATIENTS AND METHODS: Patients with previously untreated hormone receptor-positive/HER2-negative tumors were allocated to one of four cohorts according to baseline ERBB3 messenger RNA expression. All patients received one dose of HER3-DXd 6.4 mg/kg. The primary objective was to evaluate change from baseline in CelTIL score. RESULTS: Seventy-seven patients were evaluated for efficacy. A significant change in CelTIL score was observed, with a median increase from baseline of 3.5 (interquartile range, -3.8 to 12.7; P = 0.003). Among patients assessable for clinical response (n = 62), an overall response rate of 45% was observed (tumor measurement by caliper), with a trend toward an increase in CelTIL score among responders compared with non-responders (mean difference, +11.9 versus +1.9). Change in CelTIL score was independent of baseline ERBB3 messenger RNA and HER3 protein levels. Genomic changes occurred, including switching toward a less proliferative tumor phenotype based on PAM50 subtypes, suppression of cell proliferation genes, and induction of genes associated with immunity. Treatment-emergent adverse events were observed in 96% of patients (14% grade ≥3); most common were nausea, fatigue, alopecia, diarrhea, vomiting, abdominal pain, and neutrophil count decrease. CONCLUSIONS: A single dose of HER3-DXd was associated with clinical response, increased immune infiltration, suppression of proliferation in hormone receptor-positive/HER2-negative early breast cancer, and a tolerable safety profile consistent with previously reported results. These findings support further study of HER3-DXd in early breast cancer.

Reversible down-regulation of photosystems I and II leads to fast photosynthesis recovery after long-term drought in Jatropha curcas.

Jatropha curcas is a drought-tolerant plant that maintains its photosynthetic pigments under prolonged drought, and quickly regains its photosynthetic capacity when water is available. It has been reported that drought stress leads to increased thermal dissipation in PSII, but that of PSI has been barely investigated, perhaps due to technical limitations in measuring the PSI absolute quantum yield. In this study, we combined biochemical analysis and spectroscopic measurements using an integrating sphere, and verified that the quantum yields of both photosystems are temporarily down-regulated under drought. We found that the decrease in the quantum yield of PSII was accompanied by a decrease in the core complexes of PSII while light-harvesting complexes are maintained under drought. In addition, in drought-treated plants, we observed a decrease in the absolute quantum yield of PSI as compared with the well-watered control, while the amount of PSI did not change, indicating that non-photochemical quenching occurs in PSI. The down-regulation of both photosystems was quickly lifted in a few days upon re-watering. Our results indicate, that in J. curcas under drought, the down-regulation of both PSII and PSI quantum yield protects the photosynthetic machinery from uncontrolled photodamage.

Phenotypic heterogeneity in 22q11.2 deletion syndrome: Copy Number Variants as genetic modifiers for congenital heart disease in a Brazilian cohort.

The clinical heterogeneity in 22q11.2 deletion syndrome (22q11.2DS) underlies complex genetic mechanisms including variants in other regions of the genome, known as genetic modifiers. Congenital heart disease (CHD) is one of the most relevant phenotypes in the syndrome and copy number variants (CNVs) outside the 22q11.2 region could play a role in its variable expressivity. Since those described loci account for a small proportion of the variability, the CNV analysis in new cohorts from different ancestry-based populations constitutes a valuable resource to identify a wider range of modifiers. We performed SNP-array in 117 Brazilian patients with 22q11.2DS, with and without CHD, and leveraged genome-wide CNV analysis. After quality control, we selected 50 CNVs in 38 patients for downstream analysis. CNVs' genetic content and implicated biological pathways were compared between patients with and without CHD. CNV-affected genes in patients with CHD were enriched for several functional terms related to ubiquitination, transcription factor binding sites and miRNA targets, highlighting the complexity of the phenotype's expressivity. Cardiac-related genes were identified in both groups of patients suggesting that increasing risk and protective mechanisms could be involved. These genes and enriched pathways could indicate new modifiers to the cardiac phenotype in 22q11.2DS patients.

Coffee by-products: An underexplored source of prebiotic ingredients.

Consumers' demand for foods with high nutritional value and health benefits has fueled the development of prebiotic foods. In coffee industry, cherries transformation into roasted beans generates a large amount of waste/by-products (pulp/husks, mucilage, parchment, defective beans, silverskin and spent coffee grounds) that usually end up in landfills. The possibility to use coffee by-products as relevant sources of prebiotic ingredients is herein ascertained. As a prelude to this discussion, an overview of pertinent literature on prebiotic action was conducted, including on biotransformation of prebiotics, gut microbiota, and metabolites. Existing research indicates that coffee by-products contain significant levels of dietary fiber and other components that can improve gut health by stimulating beneficial bacteria in the colon, making them excellent candidates for prebiotic ingredients. Oligosaccharides from coffee by-products have lower digestibility than inulin and can be fermented by gut microbiota into functional metabolites, such as short-chain fatty acids. Depending on the concentration, melanoidins and chlorogenic acids may also have prebiotic action. Nevertheless, there is still a lack of in vivo studies to validate such findings in vitro. This review shows how coffee by-products can be interesting for the development of functional foods, contributing to sustainability, circular economy, food security, and health.

Coffee by-product oligosaccharides increase short-chain fatty acid levels.Melanoidins and chlorogenic acids promote the growth of lactobacillus and bifidobacteria.Coffee by-products show prebiotic potential, but further in vivo studies are required.

Artificial Intelligence Agents for Materials Sciences.

The artificial intelligence (AI) tools based on large-language models may serve as a demonstration that we are reaching a groundbreaking new paradigm in which machines themselves will generate knowledge autonomously. This statement is based on the assumption that the ability to master natural languages is the ultimate frontier for this new paradigm and perhaps an essential step to achieving the so-called general artificial intelligence. Autonomous knowledge generation implies that a machine will be able, for instance, to retrieve and understand the contents of the scientific literature and provide interpretations for existing data, allowing it to propose and address new scientific problems. While one may assume that the continued development of AI tools exploiting large-language models, with more data used for training, may lead these systems to learn autonomously, this learning can be accelerated by devising human-assisted strategies to deal with specific tasks. For example, strategies may be implemented for AI tools to emulate the analysis of multivariate data by human experts or in identifying and explaining patterns in temporal series. In addition to generic AI tools, such as Chat AIs, one may conceive personal AI agents, potentially working together, that are likely to serve end users in the near future. In this perspective paper, we discuss the development of this type of agent, focusing on its architecture and requirements. As a proof-of-concept, we exemplify how such an AI agent could work to assist researchers in materials sciences.

Genetic factors underlying insomnia and ovarian insufficiency.

Premature ovarian insufficiency (POI) is characterized by a loss of regular hormone production and egg release in women below the age of 40 years, which often leads to infertility, vaginal dryness and dysfunctional sleep. Acknowledging the common co-occurrence of insomnia and POI, we tested the overlap between POI and insomnia-associated genes, which were implicated in previous large-scale populational genetics efforts. Among the 27 overlapping genes, three pathways were found as enriched: DNA replication, homologous recombination and Fanconi anemia. We then describe biological mechanisms, which link these pathways to a dysfunctional regulation and response to oxidative stress. We propose that oxidative stress may correspond to one of the convergent cellular processes between ovarian malfunction and insomnia pathogenic etiology. This overlap might also be driven by cortisol release associated with dysregulated DNA repair mechanisms. Benefiting from the enormous advances in populational genetics studies, this study provides a novel outlook on the relationship between insomnia and POI. The shared genetic factors and critical biological nodes between these two comorbidities may lead to identification of putative pharmacological and therapeutical targets, which can leverage novel approaches to treat or alleviate their symptoms.

Isolation and Characterization of a Serratia rubidaea from a Shallow Water Hydrothermal Vent.

Microbial life present in the marine environment has to be able to adapt to rapidly changing and often extreme conditions. This makes these organisms a putative source of commercially interesting compounds since adaptation provides different biochemical routes from those found in their terrestrial counterparts. In this work, the goal was the identification of a marine bacterium isolated from a sample taken at a shallow water hydrothermal vent and of its red product. Genomic, lipidomic, and biochemical approaches were used simultaneously, and the bacterium was identified as Serratia rubidaea. A high-throughput screening strategy was used to assess the best physico-chemical conditions permitting both cell growth and production of the red product. The fatty acid composition of the microbial cells was studied to assess adaptation at the lipid level under stressful conditions, whilst several state-of-the-art techniques, such as DSC, FTIR, NMR, and Ultra-High Resolution Qq-Time-of-Flight mass spectrometry, were used to characterize the structure of the pigment. We hypothesize that the pigment, which could be produced by the cells up to 62 °C, is prodigiosin linked to an aliphatic compound that acts as an anchor to keep it close to the cells in the marine environment.

The administration of methyl and butyl parabens interferes with the enzymatic antioxidant system and induces genotoxicity in rat testis: possible relation to male infertility.

Parabens are esters of p-hydroxybenzoic acid, used for decades as a preservative in many products, including agrochemicals, pharmaceuticals, foods and cosmetics. Concerns regarding parabens toxicity include adverse effects on endocrine activity, carcinogenesis, infertility, spermatogenesis, and adipogenesis. The present study aimed to investigate the in vivo administration of methyl and butylparaben at concentrations of 100 and 200 mg/kg body weight, by subcutaneous injection, in variable murinometric measurements, antioxidant systems and genotoxicity. The administration of parabens did not affect the consumption of water and food. However, there was a decrease in the weight of the testes and the seminal vesicle (p < 0.05). The administration of parabens caused an increase in superoxide dismutase for methylparaben (200 mg/kg) and both concentrations of butylparaben (p < 0.05). Catalase showed increased activity in all groups treated with parabens. In contrast, glutathione reductase and glutathione S-transferase suffered a decrease in the groups treated with both parabens. These results show that parabens, especially butyl, can affect the rat testis enzymatic antioxidant system, decreasing the cellular antioxidant capacity, which was confirmed by the decrease in the glutathione reducing power, expressed by the reduced glutathione/oxidized glutathione ratio. Therefore, an increase in lipid peroxidation was observed, which was significant in the case of butyl. Genetic Damage Indicator values show that butylparaben treatments displayed significantly higher values than the control. This study shows for the first time that parabens can induce genotoxicity in the rat male reproductive organ.

Evaluation of the masking efficacy of caries infiltration in post-orthodontic initial caries lesions: 1-year follow-up.

OBJECTIVES: This study aimed to qualitatively and quantitatively assess the masking efficacy and color stability of resin infiltration on post-orthodontic ICL after 1 year. MATERIALS AND METHODS: In 17 adolescents, 112 ICL (ICDAS-1: n = 1; ICDAS-2: n = 111) in 112 teeth were treated by resin infiltration (Icon, DMG) 3 to 12 months after bracket removal. The etching procedure was performed up to 3 times. Standardized digital images were taken before treatment (T0), 7 days (T7) and 12 months (T365) after treatment. Outcomes included the evaluation of the color differences between infiltrated and healthy enamel at T0, T7, and T365 by quantitative (colorimetric analysis (ΔE), ICDAS scores) and qualitative methods (5-point Likert scale (deteriorated (1), unchanged (2), improved, but not satisfying (3), improved and no further treatment required (4), completely masked (5)).) Differences between time points were analyzed by using Friedman test (ΔΕ) and chi-square tests (ICDAS). RESULTS: The median color difference (25th/75th percentiles) between carious and healthy enamel at baseline (ΔΕ0) was 10.2(7.7/13.6). A significant decrease was observed 7 days after treatment (ΔΕ7 = 3.1(1.8/5.0); p < 0.001; ICDAS; p < 0.001). No significant changes based on ΔΕ (p = 1.000), and ICDAS grade (p = 0.305) were observed between T7 and T365 (ΔΕ12 = 3.4 (1.8/4.9)). Furthermore, at T365 four experienced dentists classified 55% and 39% of the lesions as "improved and no further treatment required" and "completely masked," respectively (Fleiss kappa: T365 = 0.851 (almost perfect)). CONCLUSION: Resin infiltration efficaciously masked post-orthodontic ICL 7 days and 12 months after treatment. These results for most of the teeth could not only be observed by quantitative but also by qualitative analysis. CLINICAL RELEVANCE: Resin infiltration efficaciously masks post-orthodontic initial carious lesions. The optical improvement can be observed directly after treatment and remains stable for at least 12 months.

Effects of vitrification techniques on the formation of skin cryobank of the ocelot (Leopardus pardalis).

BACKGROUND: Skin cryobanks represent important tools for the conservation of the maximum genetic representation of a population, especially those with a certain degree of threat to extinction, such as the ocelot. A relevant step towards the proper establishment of these banks is the definition of adequate cryopreservation techniques for the conservation of the skin. OBJECTIVE: We evaluated the effects of two different techniques [direct vitrification in cryovials (DVC) and solid-surface vitrification (SSV)] for the preservation of ear skin derived from ocelot. MATERIALS & METHODS: For both techniques, we vitrified the ear skin using Dulbeccos modified Eagles medium with 3.0 M dimethyl sulfoxide, 0.25 M sucrose, and 10% fetal bovine serum. Non-cryopreserved tissues were used as control (control group). All tissues were analyzed for their morphometric characteristics by conventional histology and morphological / functional analysis by cell ability during the culture. RESULTS: While tissues cryopreserved by DVC showed similar values for dermis thickness and number of perinuclear halos to the control, tissues cryopreserved by SSV showed similarities to the control regarding the number of melanocytes, percentage of collagen fibers, and numbers of viable cells by apoptosis analysis. Additionally, none of the vitrification techniques affected stratum corneum thickness, number of keratinocytes, tissue proliferative activity, cell viability, or metabolism. CONCLUSION: Both vitrification techniques (DVC and SSV) can be used for the conservation of ocelot skin; however, SSV guarantees a higher cellular quality after in vitro tissue culture in most of the parameters evaluated, such as viability, metabolism, and apoptosis analysis. doi.org/10.54680/fr23110110412.

Phytocannabinoids: Chromatographic Screening of Cannabinoids and Loading into Lipid Nanoparticles.

Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) are receiving increasing interest as an approach to encapsulate natural extracts to increase the physicochemical stability of bioactives. Cannabis extract-derived cannabidiol (CBD) has potent therapeutic properties, including anti-inflammatory, antioxidant, and neuroprotective properties. In this work, physicochemical characterization was carried out after producing Compritol-based nanoparticles (cSLN or cNLC) loaded with CBD. Then, the determination of the encapsulation efficiency (EE), loading capacity (LC), particle size (Z-Ave), polydispersity index (PDI), and zeta potential were performed. Additionally, the viscoelastic profiles and differential scanning calorimetry (DSC) patterns were recorded. As a result, CBD-loaded SLN showed a mean particle size of 217.2 ± 6.5 nm, PDI of 0.273 ± 0.023, and EE of about 74%, while CBD-loaded NLC showed Z-Ave of 158.3 ± 6.6 nm, PDI of 0.325 ± 0.016, and EE of about 70%. The rheological analysis showed that the loss modulus for both lipid nanoparticle formulations was higher than the storage modulus over the applied frequency range of 10 Hz, demonstrating that they are more elastic than viscous. The crystallinity profiles of both CBD-cSLN (90.41%) and CBD-cNLC (40.18%) were determined. It may justify the obtained encapsulation parameters while corroborating the liquid-like character demonstrated in the rheological analysis. Scanning electron microscopy (SEM) study confirmed the morphology and shape of the developed nanoparticles. The work has proven that the solid nature and morphology of cSLN/cNLC strengthen these particles' potential to modify the CBD delivery profile for several biomedical applications.

Valorization of Pumpkin Peel as a Source of Bioactive Compounds: Optimization of Heat- and Ultrasound-Assisted Extraction.

The peels from three pumpkin genotypes cultivated in Greece were assessed for their phenolic content and bioactive properties to obtain extracts with a high preservative capacity. The optimization of the extraction was performed through response surface methodology (RSM) based on a Box-Behnken experimental design after applying two extraction techniques: heat-assisted (HAE) and ultrasound-assisted (UAE) extraction. The implemented independent variables were time, solvent concentration, and temperature/power (for HAE/UAE), while as dependent variables the dry residue (DR), reducing power (RP), and total phenolic content (TP) were considered. In general, HAE was the most effective technique for 'TL' (75 min; 30 °C; 24% ethanol) and 'Voutirato' (15 min; 30 °C; 10% ethanol), while UAE was more effective for 'Leuka Melitis' (5 min; 400 W; 0% ethanol). The extracts obtained in the global optimum conditions for each genotype peel were then assessed for their phenolic profile, by HPLC-DAD-ESI/MS, and bioactive potential. Seven phenolic compounds were detected, including four flavonoids, two phenolic acids, and one flavan-3-ol. The extracts presented high antioxidant, antibacterial, and antifungal potential, with no cytotoxicity for non-tumor cells. The optimized conditions for the extraction of preservative compounds from bioresidues were defined, allowing the acquisition of antioxidant and antimicrobial extracts and proving their potential for food application.