Head-to-head comparison of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 postmortem binding across the spectrum of neurodegenerative diseases.

We and others have shown that [18F]-Flortaucipir, the most validated tau PET tracer thus far, binds with strong affinity to tau aggregates in Alzheimer's (AD) but has relatively low affinity for tau aggregates in non-AD tauopathies and exhibits off-target binding to neuromelanin- and melanin-containing cells, and to hemorrhages. Several second-generation tau tracers have been subsequently developed. [18F]-MK-6240 and [18F]-PI-2620 are the two that have garnered most attention. Our recent data indicated that the binding pattern of [18F]-MK-6240 closely parallels that of [18F]-Flortaucipir. The present study aimed at the direct comparison of the autoradiographic binding properties and off-target profile of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 in human tissue specimens, and their potential binding to monoamine oxidases (MAO). Phosphor-screen and high resolution autoradiographic patterns of the three tracers were studied in the same postmortem tissue material from AD and non-AD tauopathies, cerebral amyloid angiopathy, synucleopathies, transactive response DNA-binding protein 43 (TDP-43)-frontotemporal lobe degeneration and controls. Our results show that the three tracers show nearly identical autoradiographic binding profiles. They all strongly bind to neurofibrillary tangles in AD but do not seem to bind to a significant extent to tau aggregates in non-AD tauopathies pointing to their limited utility for the in vivo detection of non-AD tau lesions. None of them binds to lesions containing ß-amyloid, α-synuclein or TDP-43 but they all show strong off-target binding to neuromelanin and melanin-containing cells, as well as weaker binding to areas of hemorrhage. The autoradiographic binding signals of the three tracers are only weakly displaced by competing concentrations of selective MAO-B inhibitor deprenyl but not by MAO-A inhibitor clorgyline suggesting that MAO enzymes do not appear to be a significant binding target of any of them. These findings provide relevant insights for the correct interpretation of the in vivo behavior of these three tau PET tracers.

First report of Colletotrichum siamense causing anthracnose in Oenocarpus bacaba in Brazil.

Bacaba (Oenocarpus bacaba Mart.) is a native palm tree from Brazilian Amazon and Cerrado biomes. This tree produces a small, rounded fruit with dark skin and approximately 1.5 mm thick pulp, extensively utilized for palm heart extraction, juices, and jellies (De Cól et al. 2021). However, several diseases can adversely impact fruit yield and quality. During the 2021 growing season, anthracnose symptoms were observed in Bacaba fruits, with a disease incidence of 58% in fruits collected from the Abreulândia (9°37'15″ S, 49°9'3″ W) and Gurupi (12°25'46" S; 49°16'42" W) municipalities in Tocantins state, Brazil. A total of 198 fruits exhibiting anthracnose symptoms, characterized by deep necrotic spots, were collected. In the laboratory, symptomatic fruits had their external surfaces sterilized for 30 seconds in 70% ethanol, 1 min in 1.5% NaOCl, and then rinsed with sterile distilled water. Sterilized pieces of the fruit tissue were transferred to PDA medium and incubated for 7 days at 28 ºC with a 12 h photoperiod. After this period, two isolates were obtained from the colonies and were identified both macroscopically and microscopically as Colletotrichum sp. The colonies grown at PDA showed a white to grey cottony mycelia, with straight and fusiform conidia, ranging from 14.0 to 21.0 (mean value of 15.8 ± 1.8) µm in length and 4.0 to 7.0 (mean value of 5.5 ± 0.7) µm in width, (n = 50). For species identification, the intergenic spacer between DNA lyase, mating-type locus MAT1-2-1 (APN2/MAT-IGS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glutamine synthetase (GS), and ß-tubulin (TUB) loci were amplified and sequenced. Resulting sequences were deposited in GenBank (OR333843, OR333844, OR333845 and OR333846). BLAST analysis of the partial APN2/MAT-IGS (99%), GAPDH (99,48%), GS (99,32%) and TUB (99,48%) sequences showed highly similarity to C. siamense isolates (IIFT223 and CBS130147). Maximum likelihood multilocus analysis placed the isolate UFTC16 within the C. siamense clade with 98% bootstrap support, clearly assigning the isolate to this species. Morphological features were consistent with the description of C. siamense (Prihastuti et al., 2009). Inoculation of Bacaba fruits and seedlings was conducted to confirm pathogenicity. The surface of uninjured Bacaba fruits was inoculated with two drops (20 µL) of conidial suspension (106 conidia mL-1). The same methodology was adopted to placed healthy leaves of 35-day-old seedlings grown in plastic tubes. Two drops of sterile distilled water were inoculated on nonwounded healthy fruits and seedlings as a negative control. The fruits and seedlings were incubated for five days in a controlled chamber at 28 °C, 70-80% humidity and a "12-h photoperiod". The experiment was conducted with five replicates (five fruits and five seedlings inoculated per isolate) and repeated once. Typical symptoms of anthracnose were observed in the fruits and leaves of Bacaba seedlings five days after inoculation. No symptoms were observed in the negative control. The pathogen was reisolated from symptomatic fruits and leaves, showing similar morphological characteristics as the original isolate, fulfilling Koch's postulates. The identification of C. siamense as the causal agent of Bacaba anthracnose helps in the diagnosis and disease control strategies of the disease. Colletotrichum siamense is a cosmopolitan species and easily found in cultivated and non-cultivated species (Batista et al. 2023). However, to the best of our knowledge, this is the first report of C. siamense causing anthracnose on Bacaba.

Identification of Urine Metabolic Markers of Stroke Risk Using Untargeted Nuclear Magnetic Resonance Analysis.

Stroke remains the second leading cause of mortality worldwide, and the third leading cause of death and morbidity combined, affecting more than 12 million people every year. Stroke pathophysiology results from complex interactions of several risk factors related to age, family history, gender, lifestyle, and the presence of cardiovascular and metabolic diseases. Despite all the evidence, it is not possible to fully prevent stroke onset. In recent years, there has been an exploration of innovative methodologies for metabolite analysis aimed at identifying novel stroke biomarkers. Utilizing Nuclear Magnetic Resonance (NMR) spectroscopy, we investigated small molecule variations in urine across different stages of stroke risk. The Framingham Stroke Risk Score was used in people over 63 years of age living in long-term care facilities (LTCFs) to calculate the probability of suffering a stroke: low stroke risk (LSR, control), moderate stroke risk (MSR), and high stroke risk (HSR). Univariate statistical analysis showed that urinary 4-hydroxyphenylacetate levels increased while glycolate levels decreased across the different stroke risk groups, from the LSR to the HSR groups. Trimethylamine N-oxide (TMAO) had average concentration values that were significantly higher in elderly people in the HSR group, while trigonelline levels were significantly lower in the MSR group. These metabolic markers can be used for early detection and to differentiate stages of stroke risk more efficiently.

Exploring the Larvicidal and Adulticidal Activity against Aedes aegypti of Essential Oil from Bocageopsis multiflora.

This study investigates the chemical composition of the essential oil obtained from the leaves of Bocageopsis multiflora (Mart.) R.E.Fr (Annonaceae), examining its effectiveness in combating both the larvae and adult forms of Aedes aegypti mosquitoes. Additionally, for a deeper understanding of the insecticidal activity, toxicity properties and molecular docking calculations were conducted using the main compounds of this essential oil. GC/MS analysis revealed the presence of 26 constituents, representing 95.2% of the essential oil, with the major components identified as the sesquiterpenes α-selinene, ß-selinene, and ß-elemene. Larvicidal assays demonstrated potent activity of this essential oil with significant LC50 values of 40.8 and 39.4 µg/mL at 24 and 48 h, respectively. Adulticidal assessments highlighted strong efficacy with LC50 of 12.5 µg/mL. Molecular docking analysis identified optimal interaction activities of α-selinene and ß-selinene with key Aedes proteins. The in silico studies comparing synthetic insecticides with the major sesquiterpenes of the essential oil revealed that ß-selinene exhibited a significantly higher binding affinity compared to the other two sesquiterpenes. Also, ADMET studies of the three main sesquiterpenes indicated acceptable drug-like properties. In these findings, safety evaluations showed low toxicity and skin sensitization for the main sesquiterpenes, contrasting with commercial synthetic insecticides. Therefore, in silico analyses suggest promising interactions with Aedes proteins, indicating its potential as an effective alternative to conventional insecticides These results show the larvicidal and adulticidal potential of the essential oil from Bocageopsis multiflora against Aedes aegypti, supported by its predominant constituents, α-selinene, ß-selinene and ß-elemene.

Capacity Assessment Instrument - Health: Pilot Study of a New Tool for Adults with Dementia.

OBJECTIVES: This research comprises a pilot study of the CAI-Health, a new tool for the evaluation of decision-making capacity in healthcare. It aims to analyze the instrument's indicators of reliability and internal validity to conclude its final version. METHODS: A total of 89 participants were included, of which 22 had Alzheimer's Disease; 32 had mild cognitive impairment, and 35 were controls. Cronbach's alpha and the intercorrelation matrix were used as indicators of reliability and internal validity as well as to identify items for elimination. Repeated-measures ANOVA allowed for the analysis of differences between the vignettes that comprise CAI-Health. RESULTS: The internal consistency results were acceptable, and no items were proposed for elimination. A repeated-measures ANOVA revealed that the vignettes were unexpectedly equivalent. Despite the procedures used to develop clinical vignettes with increased levels of complexity in assessing decision-making capacity, this study showed no differences in the vignettes' level of demand. CONCLUSIONS: The extensive application of CAI-Health compromises its clinical usefulness and viability. To reduce its length while maintaining a thorough assessment of each ability, it was decided to eliminate two vignettes and retain all interview items. The final version of the CAI-Health comprises a clinical vignette and a capacity interview. CLINICAL IMPLICATIONS: CAI-Health was designed for the assessment of medical decision-making capacity in older adults.

Would it really be necessary to use metronidazole as an adjunct in the surgical treatment of periodontitis?

DESIGN: Prospective, parallel, randomized, double-blind, clinical trial. CASE SELECTION: Participants were at least 30 years old, who were systemically healthy, with stages III-IV, grades B-C periodontitis. DATA ANALYSIS: Of the 50 eligible individuals for the study, 40 were divided into 2 equal groups. The test group received doses of 500 mg of metronidazole, while the control group received a placebo, both administered three times a day for 7 days, commencing immediately after periodontal surgery. All patients were followed up at 3-, 6-, 9-, and 12-months post-surgery. The study utilized probing depth, clinical attachment level, bleeding on probing, and plaque index as parameters for determining the outcomes at each assessment. Microbiological samples were collected for the detection and quantification of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Tannerella forsythia DNA. In order to analyze quantitative variables in a comparison between the test and control groups, Student's t-tests or Mann-Whitney U tests were utilized. For categorical results, chi-square or Fisher tests were employed. For both probing depth and clinical attachment level, repeated measures ANOVA was used. The statistical significance level was set at p ≤ 0.05. RESULTS: The study found statistically significant differences for probing depth (mean difference, MD = 0.31 mm, 95% confidence interval, CI [0.13; 0.49]; p = 0.001) and clinical attachment level (MD = 0.64 mm, 95% CI [0.02; 1.27]; p = 0.044) only 3 months after surgery, with a reduction observed in the test group. However, despite being statistically significant, these results lack clinical relevance. CONCLUSIONS: Although the study found statistically significant results for clinical attachment level (MD = 0.66 mm, 95% CI [0.01; 1.31]; p = 0.045) and probing depth (MD = 0.28 mm, 95% CI [0.09; 0.46]; p = 0.004), these findings do not represent clinically significant gains. Therefore, no evidence was demonstrated to support the use of systemic metronidazole as adjunctive therapy to periodontal surgery.

What is the potential of antibacterial, antiviral and antifungal photodynamic therapy in dentistry?

DESIGN: A review of the principal clinical applications of antimicrobial photodynamic therapy (aPDT) in dentistry. AIM: To provide an overview of clinical applications and future perspectives of aPDT in dentistry. METHODS: A comprehensive search was conducted on PubMed, Web of Science, Scopus, and Embase up to September 2022, where only data from randomized clinical trials were included. In vitro studies, animal studies, literature reviews, and duplicate articles were excluded from the review. Out of a total of 1042 references initially identified, only 89 studies were included in the review. Six main oral conditions for which aPDT has been used were identified: periodontal and peri-implant diseases, endodontics, bacterial plaque, caries, and fungal and viral infections. RESULTS: The review suggests that aPDT can be used as an effective complementary treatment for reducing pathogenic microorganisms in bacterial plaque; carious lesions; and periodontal, peri-implant, endodontic, fungal, and viral infections. CONCLUSIONS: Despite the efficacy of aPDT against different types of microorganisms, there are no specific irradiation parameters for its respective photosensitizers due to the significant heterogeneity of clinical trials. Therefore, more studies are needed to determine irradiation protocols and development of new photosensitizers to improve the safety and efficacy of aPDT.

Could light be a broad-spectrum antimicrobial?

DESIGN: A review on antimicrobial resistance mechanisms discussing the main light-based antimicrobial approaches including ultraviolet light (UV), antimicrobial photodynamic therapy (aPDT), and antimicrobial blue light (aBL). AIM: To describe antimicrobial resistance mechanisms and to present potential light-based alternatives to conventional antimicrobials. METHODS: The paper was divided into different topics, starting with an approach to antimicrobial resistance mechanisms. Subsequently, emphasis was placed on innovative light-based antimicrobials approaches, including aBL, UV, and aPDT. RESULTS: The review suggests that blue light (400-470 nm) acts on endogenous porphyrins with peak absorption at 405 nm, thus not requiring the administration of photosensitizers, to trigger antimicrobial effects. In this regarding, the direct effect of aBL could be attributed to both the generation of reactive oxygen species (ROS), which induces microbicidal effects, and the inactivation of bacterial defense mechanisms. In turn, blue light combined with curcumin has been used in the treatment of dental infections. Otherwise, green light (495-570 nm) associated with the photosensitizer Rose Bengal has shown promising results both in wound closure due to the induction of additional collagen cross-link formation and in reducing the viability of Pseudomonas aeruginosa. Red light (620-750 nm) is the wavelength most commonly used in aPDT, presenting superior tissue penetration capability compared to blue and green light. Both red and infrared light act directly as photobiomodulation agents, promoting tissue repair with greater penetration depth for the infrared spectrum. Conversely, red light combined with methylene blue is the most commonly used technique in the treatment of localized infections. Meanwhile, infrared light associated with indocyanine green acts as a photothermal and photosensitizing agent, promoting thermal damage and production of ROS. Ultraviolet lights UVA, UVB, and UVC (200-400 nm) have antimicrobial potential related to inducing changes in DNA and generating both ROS and singlet oxygen. Furthermore, light can enhance the efficacy of traditional antimicrobial agents by deactivating microbial resistance, both through increasing the permeability of the cell membrane and by inhibiting the efflux pump and ß-lactamases of the bacteria. CONCLUSIONS: The antimicrobial potential of light is extensive; however, there is a limitation regarding the depth of penetration of certain wavelengths into infected areas. Furthermore, there is a need for additional studies to determine the safety and efficacy of various approaches using light at its different wavelengths.

How safe is off-label use of imiquimod in oral lesions?

DATA SOURCES: A comprehensive search was conducted on PubMed and Embase, adhering to the principles outlined in the PRISMA Extension for Scoping Reviews (PRISMA-ScR). The search strategy was subsequently registered on PROSPERO. STUDY SELECTION: Articles were chosen based on an analysis of titles and abstracts, with no restrictions on publication date, language, or participant age. In vitro studies, animal studies, and literature reviews were excluded from consideration. DATA EXTRACTION AND SYNTHESIS: Clinical trials in humans, case reports, or case series that reported the use of imiquimod for treating conditions in the oral or labial mucosa were included in this study. Results from duplicate articles were excluded from the analysis. RESULTS: Out of a total of 601 references initially identified, only 28 studies were included in the review. These studies were classified based on the use of imiquimod into three groups: potentially malignant disorders and oral cancer, lesions related to HPV, and autoimmune conditions. In all cases presented in the article, there is an occurrence of both local and systemic side effects. CONCLUSIONS: The study elucidated the off-label use of imiquimod in oral pathologies, whether potentially malignant, cancerous, autoimmune, or associated with HPV infection. However, it was observed that further research is warranted for the development of a specific formulation for the oral mucosa, ensuring the drug's sustained presence at its active site of action without interference from saliva and minimizing potential side effects.

What is the science underpinning the prescription of antibiotics in dentistry?

DESIGN: A critical review on the use of antimicrobials in dentistry. AIM: To provide a general overview of the use of antimicrobials in dentistry. METHODS: The paper was divided into different topics, starting with an approach to understanding both commensal and pathogenic oral microbiota. Subsequently, emphasis was placed on the main categories of antibiotics used in dentistry (ß-lactams, tetracyclines, macrolides, lincosamides, nitroimidazoles and quinolones), and the basis for their prescription. Finally, the implications between systemic diseases and the use of orally-administered antibiotics are presented. RESULTS: The study suggests that an adequate medical history can minimize the risk of systemic adverse effects, unwanted drug interactions, and allergies related to the use of antibiotics. In this regard, when facing a potential history of allergy to a particular group of antibiotics, the prescription of a different group is mandatory. In most indications, ß-lactam antibiotics represent the first-choice in dentistry. Moreover, a short-term prescription of antibiotics when treating acute oral infections is recommended. The use should be extended for 2 to 3 days following the resolution of the infection, with an average duration of 6 days in order to prevent the development of antibiotic resistance. CONCLUSIONS: Oral infections should be managed with interventions aiming at the elimination/reduction of the associated pathogens. Furthermore, inadequate prescription of antibiotics can lead to potential risks to the patient such as allergy, adverse effects, and development of microbial resistance.

Eating disorders prevention programs in Latin American countries: A systematic review.

OBJECTIVE: This systematic review evaluates and summarizes existing eating disorder (ED) prevention programs in Latin American countries. METHODS: A systematic literature search was conducted using the Cochrane Controlled Trial Register, PubMed, and Virtual Health Library databases up to and including July 31, 2022. All ED prevention studies published in English, Spanish or Portuguese were eligible, regardless of the study design, sample characteristics, and type of prevention programs. The Cochrane Collaboration Risk of Bias criteria were used to evaluate the quality of the included studies. RESULTS: Twenty-two studies were included. Most were pilot studies that were nonrandomized, had a high risk of bias, were from Mexico and Brazil, and employed selective interventions. Dissonance-based programs and social cognitive theory were the commonly used approaches in interventions, and most of them were tested in adolescent girls and women. Short follow-ups were used, varying from 1 to 6 months. Many found significant decreases after the intervention and/or at follow-up in ED/disordered eating risk behaviors/symptoms, negative affect, body-ideal internalization, and body image disturbances. CONCLUSIONS: This review highlights promising efforts to prevent EDs among Latin American countries. Some barriers in conducting research include funding restrictions, laws that do not allow remuneration or compensation for participants, and high costs of training. Nonetheless, the outcomes of the programs developed and evaluated so far are positive enough to merit further work on ED prevention. Efforts for future researchers should recruit samples with diverse characteristics, use robust designs and data analysis techniques, and expand the accessibility of prevention programs. PUBLIC SIGNIFICANCE STATEMENT: The development of effective eating disorder (ED) prevention programs that can be broadly implemented is a public health priority. Nevertheless, there is limited evidence regarding the characteristics of ED prevention programs and their efficacy among Latin American countries. In the present study, we reviewed existing ED prevention programs adopted in Latin America, described their characteristics and outcomes, noted the limitations of available programs, and discussed the implications of these findings for efforts to prevent the development of EDs in Latin America. The outcomes of the programs developed and evaluated so far are positive enough to merit the development and rigorous evaluation of future programs and their broad dissemination in Latin American countries. PROSPERO registration number CRD42021275245.

OBJETIVO: Esta revisión sistemática evalúa y resume los programas de prevención de trastornos de la conducta alimentaria (TCA) existentes en los países de América Latina. MÉTODOS: Se realizó una búsqueda bibliográfica sistemática utilizando las bases de datos del Registro Cochrane de Ensayos Controlados (Cochrane Controlled Trial Register), PubMed y Virtual Health Library hasta el 31 de julio de 2022 inclusive. Todos los estudios de prevención de TCA publicados en inglés, español o portugués fueron elegibles, independientemente del diseño del estudio, las características de la muestra y el tipo de programas de prevención. Se utilizaron los Criterios de Riesgo de Sesgo de la Colaboración Cochrane para evaluar la calidad de los estudios incluidos. RESULTADOS: Se incluyeron veintidós estudios. La mayoría eran estudios piloto no aleatorizados, tenían un alto riesgo de sesgo, eran de México y Brasil, y empleaban intervenciones selectivas. Los programas basados en la disonancia y la teoría cognitiva social fueron los enfoques comúnmente utilizados en las intervenciones, y la mayoría de ellos se probaron en niñas y mujeres adolescentes. Se utilizaron seguimientos cortos, que variaron de uno a 6 meses. Muchos encontraron disminuciones significativas después de la intervención y / o en el seguimiento en los síntomas de TCA/Conductas Alimentarias de Riesgo, afecto negativo, internalización de la figura ideal y trastornos de la imagen corporal. CONCLUSIONES: Esta revisión destaca los esfuerzos prometedores para prevenir los TCA entre los países de América Latina. Algunas barreras en la realización de investigaciones incluyen restricciones de financiamiento, leyes que no permiten la remuneración o compensación para los participantes y los altos costos de capacitación. No obstante, los resultados de los programas desarrollados y evaluados hasta ahora son lo suficientemente positivos como para merecer un mayor trabajo en la prevención de los TCA. Los esfuerzos para futuros investigadores deben reclutar muestras con características diversas, utilizar diseños robustos y técnicas de análisis de datos, y ampliar la accesibilidad de los programas de prevención.

Consumer acceptability and fragrance quality differentiate on of Mogiana coffee types using the Check-All-That-Apply (CATA) method.

Coffee, one of the most produced and consumed beverage in the world, has a range of variability in its quality. The aim of this work was to evaluate the consumer capacity to perceive the coffee quality through their fragrance and to verify the influence of previous information about quality on this perception using hedonic scale and Check All That Apply (CATA) sensory tests. The sensory tests were performed in two stages, one without and the other with quality related information of Mogiana coffee samples (Rio, Hard and Soft), and a traditional coffee sample. CATA attributes frequency of occurrence shows that samples discrimination could be done with specific attributes. For Soft coffee the attributes with more occurrence were sweet, caramel, brown sugar, and smooth. The Hard coffee sample was described by the attributes peanut, buttery, and chocolate. While for Rio coffee, the descriptive attributes most often mentioned were strong and burnt. The traditional sample stood out among consumers for its characteristics of old, medicine, sour, burnt, unpleasant and spicy. Therefore, the use of coffee powder fragrance can be alternative to differentiate the quality of the product and its function can be enhanced by passing on information on quality attributes to consumers.

Antileishmanial Screening, Cytotoxicity, and Chemical Composition of Essential Oils: A Special Focus on Piper callosum Essential Oil.

Leishmania amazonensis is the etiological agent of tegumentary leishmaniasis, a disease characterized by the emergence of cutaneous and mucocutaneous ulcerated lesions that can evolve into severe destruction of skin tissue. Treatment of the disease is often accompanied by high toxicity and variable efficacy. Essential oils stand out for having diverse pharmacological properties. Here, we screened a panel of fourteen essential oils for their anti-L. amazonensis activity, cytotoxicity, and chemical profile. Lippia sidoides (LSEO) and Piper callosum (PCEO) oils displayed the best anti-promastigote and anti-amastigote activities with IC50 of 31 and 21 µg/ml, respectively. PCEO was the safest oil with a desirable selectivity index >10. In addition, PCEO showed no cytotoxicity against the VERO line and erythrocytes. PCEO-treated amastigotes displayed mitochondrial membrane depolarization and high levels of intracellular ROS. Safrole (54.72 %) was the main component of PCEO. The results described here highlight the use of essential oils to combat tegumentary leishmaniasis.

Searching for Metabolic Markers of Stroke in Human Plasma via NMR Analysis.

More than 12 million people around the world suffer a stroke every year, one every 3 s. Stroke has a variety of causes and is often the result of a complex interaction of risk factors related to age, genetics, gender, lifestyle, and some cardiovascular and metabolic diseases. Despite this evidence, it is not possible to prevent the onset of stroke. The use of innovative methods for metabolite analysis has been explored in the last years to detect new stroke biomarkers. We use NMR spectroscopy to identify small molecule variations between different stages of stroke risk. The Framingham Stroke Risk Score was used in people over 63 years of age living in long-term care facilities (LTCF) to calculate the probability of suffering a stroke. Using this parameter, three study groups were formed: low stroke risk (LSR, control), moderate stroke risk (MSR) and high stroke risk (HSR). Univariate statistical analysis showed seven metabolites with increasing plasma levels across different stroke risk groups, from LSR to HSR: isoleucine, asparagine, formate, creatinine, dimethylsulfone and two unidentified molecules, which we termed "unknown-1" and "unknown-3". These metabolic markers can be used for early detection and to detect increasing stages of stroke risk more efficiently.

Inhibition of Myeloperoxidase Pro-Fibrotic Effect by Noscapine in Equine Endometrium.

Myeloperoxidase is an enzyme released by neutrophils when neutrophil extracellular traps (NETs) are formed. Besides myeloperoxidase activity against pathogens, it was also linked to many diseases, including inflammatory and fibrotic ones. Endometrosis is a fibrotic disease of the mare endometrium, with a large impact on their fertility, where myeloperoxidase was shown to induce fibrosis. Noscapine is an alkaloid with a low toxicity, that has been studied as an anti-cancer drug, and more recently as an anti-fibrotic molecule. This work aims to evaluate noscapine inhibition of collagen type 1 (COL1) induced by myeloperoxidase in equine endometrial explants from follicular and mid-luteal phases, at 24 and 48 h of treatment. The transcription of collagen type 1 alpha 2 chain (COL1A2), and COL1 protein relative abundance were evaluated by qPCR and Western blot, respectively. The treatment with myeloperoxidase increased COL1A2 mRNA transcription and COL1 protein, whereas noscapine was able to reduce this effect with respect to COL1A2 mRNA transcription, in a time/estrous cycle phase-dependent manner (in explants from the follicular phase, at 24 h of treatment). Our study indicates that noscapine is a promising drug to be considered as an anti-fibrotic molecule to prevent endometrosis development, making noscapine a strong candidate to be applied in future endometrosis therapies.

Delving into the Mechanisms of Sponge-Associated Enterobacter against Staphylococcal Biofilms.

Staphylococci are one of the most common causes of biofilm-related infections. Such infections are hard to treat with conventional antimicrobials, which often lead to bacterial resistance, thus being associated with higher mortality rates while imposing a heavy economic burden on the healthcare system. Investigating antibiofilm strategies is an area of interest in the fight against biofilm-associated infections. Previously, a cell-free supernatant from marine-sponge-associated Enterobacter sp. inhibited staphylococcal biofilm formation and dissociated the mature biofilm. This study aimed to identify the chemical components responsible for the antibiofilm activity of Enterobacter sp. Scanning electron microscopy confirmed that the aqueous extract at the concentration of 32 µg/mL could dissociate the mature biofilm. Liquid chromatography coupled with high-resolution mass spectrometry revealed seven potential compounds in the aqueous extract, including alkaloids, macrolides, steroids, and triterpenes. This study also suggests a possible mode of action on staphylococcal biofilms and supports the potential of sponge-derived Enterobacter as a source of antibiofilm compounds.

Is there evidence that e-cigarettes promote an increased risk of dental caries?

DATA SOURCES: This study was conducted on a sample of patients who attended the dental clinic at Tufts University School of Dental Medicine, between January 1, 2019 and January 1, 2022. Ethical approval was obtained before commencing the research. STUDY SELECTION: This cross-sectional study was carried out through an electronic search of electronic records. It includes patients aged over 16 years, both electronic cigarette (e-cigarettes) users and non-users, with recorded caries risk assessments. Patients with a history of recreational drug use or lacking a caries diagnosis were excluded. The Caries Management by Risk Assessment (CAMBRA) was utilized to indicate and classify caries risk. DATA EXTRACTION AND SYNTHESIS: Descriptive statistics, multivariate and bivariate analyzes were used to assess the relationship between use of e-cigarettes and caries risk level. SPSS software, Version 26 (IBM) was used in the analysis with significance level set at α = 0.05. RESULTS: Out of a total of 13,216 patients included in the research, 13,080 (99.3%) self-declared as non-users of e-cigarettes, and 136 (0.69%) were e-cigarette users. There was a statistically significant difference (P < 0.001) in caries risk levels between e-cigarette users (6.6% low, 14.3% moderate, and 79.1% high caries risk level) and control group (14.5% low, 25.9% moderate, and 59.6% high caries risk level). CONCLUSIONS: The study provides evidence supporting the notion that e-cigarette users exhibit a high level of caries risk.

Electronic nicotine delivery systems (ENDS): a strategy for smoking cessation or a new risk factor for oral health?

DATA SOURCES: A search was conducted in PubMed and Cochrane Library databases for articles published in English between January 2012 and October 2022. STUDY SELECTION: Articles were selected using both the term "electronic nicotine delivery system" (ENDS), as per the Medical Subject Heading (MeSH), in conjunction with specific oral domains. In vitro studies, animal models, unregistered clinical trials, and articles with conflicts of interest were excluded. DATA EXTRACTION AND SYNTHESIS: Clinical and public health studies comparing ENDS users, smokers, and non-smokers in the context of oral-related diseases were included. Results from duplicate articles were not considered. RESULTS: The study indicates a potential carcinogenic effect due to cytogenotoxicity from intrinsic components of ENDS. However, this does not establish ENDS as an independent risk factor for oral cancer. ENDS use may alter the oral microbiome, leading to increased biofilm adhesion and potential associations with caries, periodontal disease, and peri-implantitis. The wide variety of flavors available in the ENDS market is a significant factor influencing initiation and long-term use by young people. CONCLUSIONS: ENDS users are susceptible to periodontal disease, caries, soft tissue injuries, and changes in tooth and prosthesis coloration. The chemical components in ENDS can induce cellular changes associated with a potential risk of oral cancer. However, more long-term studies are required to fully understand the impact of ENDS use on oral health.

Impacts of smoking on oral health-what is the role of the dental team in smoking cessation?

DATA SOURCES: Electronic searches were conducted on databases (PubMed, EMBASE, and Google Scholar). In addition, websites of national organisations (US Food and Drug Administration, National Cancer Institute, Centres for Disease Control and Prevention, American Dental Association, Office of Disease Prevention and Health Promotion, National Institute on Drug Abuse, Agency for Healthcare Research and Quality) were also searched. STUDY SELECTION: To achieve the objectives of the study, systematic reviews, controlled clinical trials, and observational studies published between October 2021 and February 2022 were considered. DATA EXTRACTION AND SYNTHESIS: This narrative review included articles which investigated the role of Dentistry professionals and their impact on smoking cessation and the effects resulting from tobacco use on oral health. RESULTS: The review revealed that smokers have a significantly higher likelihood of developing oral cancer (95% CI: 3.19-6.77) compared to non-smokers. Passive smokers also have an increased risk (1.51 times) of developing oral cancer (95% CI: 1.20-1.91). Additionally, smokers have an 80% increased risk of periodontitis (RR = 1.82; 95% CI: 1.43-2.31), an 85% worsened periodontal condition (RR = 1.85; 95% CI: 1.5-2.2), and a 36.6% increase in caries prevalence (OR = 1.84; 95% CI: 1.64-2.07). Smoking is also associated with a higher potential for dental implant failure in a dose-dependent manner. Brief educational interventions by the dental team resulted in a smoking cessation rate of 74/1000 individuals versus 27/1000 individuals in the control group. When combined with pharmacological therapy, these interventions may lead to an additional 50 to 70% increase in long-term smoking abstinence. CONCLUSIONS: Smoking is strongly linked to an increased risk of oral cancer, dental caries, implant failure, and periodontal disease. Dental teams play a vital role in identifying and addressing oral pathologies related to smoking and providing necessary care for smoking cessation. Brief educational interventions, either alone or in combination with pharmacotherapy, offer valuable approaches for the dental team to support smoking cessation. However, establishing a comprehensive training and continuing education program is crucial to integrate dental professionals into a multidisciplinary smoking cessation program.

MEX3A regulates Lgr5+ stem cell maintenance in the developing intestinal epithelium.

Intestinal stem cells (ISCs) fuel the lifelong self-renewal of the intestinal tract and are paramount for epithelial repair. In this context, the Wnt pathway component LGR5 is the most consensual ISC marker to date. Still, the effort to better understand ISC identity and regulation remains a challenge. We have generated a Mex3a knockout mouse model and show that this RNA-binding protein is crucial for the maintenance of the Lgr5+ ISC pool, as its absence disrupts epithelial turnover during postnatal development and stereotypical organoid maturation ex vivo. Transcriptomic profiling of intestinal crypts reveals that Mex3a deletion induces the peroxisome proliferator-activated receptor (PPAR) pathway, along with a decrease in Wnt signalling and loss of the Lgr5+ stem cell signature. Furthermore, we identify PPARγ activity as a molecular intermediate of MEX3A-mediated regulation. We also show that high PPARγ signalling impairs Lgr5+ ISC function, thus uncovering a new layer of post-transcriptional regulation that critically contributes to intestinal homeostasis.