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.

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.

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.

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.

Assessing the Influence of Maternal Age in Bovine Embryos and Oocytes: A Model for Human Reproductive Aging.

In the first weeks after fertilization, embryo mortality in cattle is significantly higher. It is well known that the age of the dam is one of the crucial factors affecting the quality of embryos and oocytes in many mammalian species. In older cattle, there are several evidences that embryo quality decreases, due to a decrease in ovarian reserve, a decrease in mtDNA and ATP, a decrease in progesterone levels, and due to susceptibility to genetic mutations. Herein, we intend to provide an updated summary of recent research on the effects of maternal age on embryos and oocytes of domestic cattle which are a widely used model species for human oocytes and early embryonic development.

Clinical Characteristics of Genuine Acute Autoimmune Hepatitis.

Introduction: Autoimmune hepatitis (AIH) has a spectrum of symptoms ranging from asymptomatic disease to acute severe hepatitis, chronic hepatitis, and decompensated cirrhosis. The acute presentation is not rare and could represent genuine acute AIH (GAAIH) or acute exacerbation of chronic autoimmune hepatitis. We aimed to identify the prevalence, clinical features, and prognostic factors associated with GAAIH and compare these cases with acute exacerbation of chronic AIH. Methods: This cross-sectional observational study evaluated patients with acute AIH presentation, defined as total bilirubin >5 times the upper limit of normality (xULN) and/or alanine aminotransferase >10 xULN, and no prior history of liver disease. Histology findings of acute disease defined GAAIH. Bivariate analyses were performed to identify factors associated with the GAAIH, when compared with acute exacerbation of chronic AIH. Results: Seventy-two patients with acute presentation of AIH were included and six (8.3%) of them presented GAAIH. Comparative analysis between patients with GAAIH and patients with acute exacerbation of chronic AIH revealed that prothrombin activity (96% [74-100] vs. 61% [10-100]; p = 0.003) and albumin levels (3.9 ± 0.2 g/dL vs. 3.4 ± 0.5 g/dL; p < 0.001) were higher in patients with GAAIH. The International Autoimmune Hepatitis Group score was higher in patients with acute exacerbation of chronic AIH (18.5 [8-23] vs. 16.5 [15-17]; p = 0.010). Compared to 15.2% of acute exacerbation of chronic AIH, complete therapeutic response to treatment was achieved in 67.7% of cases with GAAIH (p = 0.018). Conclusions: GAAIH was rare (8.3%), and patients with this presentation exhibited more preserved liver function tests, suggesting that most cases presenting with loss of function are acute exacerbation of chronic AIH. Additionally, patients with GAAIH had a better complete therapeutic response, suggesting a more preserved liver function at presentation, and early diagnosis has a positive therapeutic implication.

Introdução: A hepatite autoimune (HAI) apresenta um espectro de sintomas que varia de doença assintomática a hepatite aguda grave, hepatite crónica e cirrose descompensada. A apresentação aguda não é rara e pode representar hepatite autoimune aguda genuína (HAIAG) ou exacerbação aguda de hepatite autoimune crónica (EAHAIC). O nosso objetivo foi identificar a prevalência, caraterísticas clínicas e fatores prognósticos associados à HAIAG, e comparar esses casos com EAHAIC. Métodos: Estudo observacional, transversal, incluindo doentes com apresentação aguda de HAI, definida como bilirrubina total > 5 vezes o limite superior da normalidade (xLSN) e/ou ALT > 10 xLSN, e sem história prévia de doença hepática. HAIAG foi definida pela presença de achados histológicos de doença aguda. Análises bivariadas foram realizadas para identificar fatores associados à HAIAG, quando comparado com o EAHAIC. Resultados: Foram incluídos setenta e dois doentes com apresentação aguda de HAI, dos quais seis (8.3%) com HAIAG. A análise comparativa entre doentes com HAIAG e doentes com EAHAIC mostrou que a atividade de protrombina (96% (74-100) versus 61% (10-100; p=0.003) e os níveis de albumina (3,9 ± 0,2 g/dL vs. 3,4 ± 0,5 g/dL; p < 0,001) foram significativamente mais elevados em pacientes com HAIAG. O score do Grupo Internacional de Hepatite Autoimune foi mais elevado em doentes com EAHAIC (18.5 (8-23) versus 16.5 (15-17); p=0.010). A resposta terapêutica completa ao tratamento foi alcançada em 66.7% dos casos de HAIAG (vs. 15,2% na EAHAIC, p=0,018). Conclusões: A HAIAG é rara (8.3%), e os doentes com esta apresentação mostraram testes de função hepática mais preservados, sugerindo que a maioria dos casos com perda de função são EAHAIC. Além disso, os doentes com HAIAG tiveram maior taxa de resposta terapêutica completa, sugerindo que uma função hepática mais preservada na apresentação e o diagnóstico precoce tem uma implicação terapêutica positiva.

Endophytic species of Colletotrichum associated with cashew tree in northeastern Brazil.

Anthracnose caused by Colletotrichum is the most severe and widely occurring cashew disease in Brazil. Colletotrichum species are commonly found as pathogens, endophytes and occasionally as saprophytes in a wide range of hosts. The endophytic species associated with cashew trees are poorly studied. In this study, we report the Colletotrichum endophytic species associated with cashew trees in two locations in the state of Pernambuco, their prevalence in different plant organs (leaves, veins, branches and inflorescences), and compare the species in terms of pathogenicity and aggressiveness using different inoculation methods (wounded × unwounded). Six species of Colletotrichum were identified according to multilocus phylogenetic analyses, including Colletotrichum asianum, Colletotrichum chrysophilum, Colletotrichum karsti, Colletotrichum siamense, Colletotrichum theobromicola, and Colletotrichum tropicale. There were differences in the percentage of isolation in relation to the prevalence of colonized tissues and collection locations. C. tropicale was the prevalent species in both geographic areas and plant tissues collected, with no pattern of distribution of species between areas and plant tissues. All isolates were pathogenic in injured tissues of cashew plants. The best method to test the pathogenicity of Colletotrichum species was utilizing the combination of leaves + presence of wounds + conidial suspension, as it better represents the natural infection process. C. siamense was the most aggressive species.

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.

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.

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.

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.

COVID-19 in a Portuguese whole blood donor population.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leading to pneumonia and acute respiratory distress syndrome. The COVID-19 pandemic had a major impact on the stock of blood banks worldwide. This study aims to assess the prevalence of COVID-19 in a population of whole blood donors and analyze the possible association between blood group and susceptibility to the disease and the impact of adopting preventive measures against SARS-CoV-2 infection. Material and methods: This retrospective study included all whole blood donors from a Portuguese hospital between July and September 2021. A self-assessment questionnaire was used to collect data on COVID-19 infection, vaccination, and preventive measures. Statistical analysis was performed using Chi-square and Mann-Whitney U tests. Results: The prevalence of COVID-19 in the donor population was 11.96% (n = 97), with only 2 cases of serious illness requiring hospitalization. No association was found between blood group and disease susceptibility. Older men were less likely to adopt preventive measures. The vaccination rate was high, with 84.26% of donors having received at least one dose of the vaccine. Seven donors declined COVID-19 vaccination. Preventive measures did not differ based on COVID-19 infection status or vaccination. Discussion: Although there was a higher frequency of COVID-19 in group A donors, the blood group was not associated with susceptibility to infection. The donor population consisted of young individuals without comorbidities, showing a COVID-19 prevalence like the general population and few severe cases. The high vaccination rate and adoption of preventive measures likely contributed to these findings.

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.

Somatic evolution of marine transmissible leukemias in the common cockle, Cerastoderma edule.

Transmissible cancers are malignant cell lineages that spread clonally between individuals. Several such cancers, termed bivalve transmissible neoplasia (BTN), induce leukemia-like disease in marine bivalves. This is the case of BTN lineages affecting the common cockle, Cerastoderma edule, which inhabits the Atlantic coasts of Europe and northwest Africa. To investigate the evolution of cockle BTN, we collected 6,854 cockles, diagnosed 390 BTN tumors, generated a reference genome and assessed genomic variation across 61 tumors. Our analyses confirmed the existence of two BTN lineages with hemocytic origins. Mitochondrial variation revealed mitochondrial capture and host co-infection events. Mutational analyses identified lineage-specific signatures, one of which likely reflects DNA alkylation. Cytogenetic and copy number analyses uncovered pervasive genomic instability, with whole-genome duplication, oncogene amplification and alkylation-repair suppression as likely drivers. Satellite DNA distributions suggested ancient clonal origins. Our study illuminates long-term cancer evolution under the sea and reveals tolerance of extreme instability in neoplastic genomes.

Nutritional and chemical composition of Alpinia zerumbet leaves, a traditional functional food.

Alpinia zerumbet, a species of the Zingiberaceae family, is a common plant in tropical and subtropical areas used in traditional medicine to treat various diseases and also included as food in the traditional Okinawan diet (Japan). The leaves and rhizomes of this plant are used as spice and flavoring in foods such as rice, meats, and pasta. Studies of the chemical and nutritional characteristics of fresh leaves and of leaves submitted to thermal treatments such as boiling and steaming are lacking. In the current study, the leaves of A. zerumbet were subjected to boiling or steaming for 10, 20, and 30 min as part of the thermal treatments. The study also provides noteworthy results regarding the proximate composition, physical-chemical data, minerals, phenolic compounds, antioxidant activity, volatile compounds, and LC-MS chromatographic profiles of the extracts produced with fresh leaves and with thermal treatments. The carbohydrate content of A. zerumbet leaves improved during the thermal treatments, showing an increase after steaming (18.86 to 19.79%) and boiling for 30 min (25.85%). After boiling treatment for 20 min, a significant amount of protein was found (6.79%) and all heat treatments resulted in low content of lipid (<1.0%). The boiling treatment for 10 min (BT10) resulted in the highest concentrations of total phenolic components (TPC), 339.5 mg/g, and flavonoids (TF), 54.6 mg/g, among the three thermal treatments (BT10, BT20 and BT30). The results of the steaming treatments (ST 10, 20, and 30 min) differed, with ST20 leading to higher TPC (150.4 mg/g) and TF (65.0 mg/g). The quantity of total phenolics and flavonoids, as well as the antioxidant activity, were significantly affected by the cooking method and the length of time of sample exposure to heat. The samples boiled for 30 and 10 min had higher concentrations of antioxidant activity as measured by the phosphomolybdenum and DPPH methods (151.5 mg/g of extract and 101.5 µg/mL, respectively). Thirty-eight volatile organic compounds (VOCs) were identified by chromatographic analysis of fresh and thermally treated leaves of A. zerumbet. Terpenoids were the predominant class of volatile compounds in the fresh leaves and in all thermal treatments. p-Cymene, 1,8-cineole, 4-terpineol, linalool, α-copaene and ß-bisabolene have the greatest impact on overall aroma perception, with odor activity values (OAV) greater than five. Among the phenolic compounds identified by LC-HRMS in the extracts of fresh and thermally treated leaves were proanthocyanidins, (+) catechin, (-) epicatechin, quercetin-3-O-glucoronide, isorhamnetin-3-O-glucoronide, kaempferol-3-O-rutinoside, pinocembrin, alpinetin, pinostrobin, and other compounds. The present results support the traditional use of this plant as a potential food with properties that certainly contribute to health improvement.

Tau Oligomer-Containing Synapse Elimination by Microglia and Astrocytes in Alzheimer Disease.

Importance: Factors associated with synapse loss beyond amyloid-ß plaques and neurofibrillary tangles may more closely correlate with the emergence of cognitive deficits in Alzheimer disease (AD) and be relevant for early therapeutic intervention. Objective: To investigate whether accumulation of tau oligomers in synapses is associated with excessive synapse elimination by microglia or astrocytes and with cognitive outcomes (dementia vs no dementia [hereinafter termed resilient]) of individuals with equal burdens of AD neuropathologic changes at autopsy. Design, Setting, and Participants: This cross-sectional postmortem study included 40 human brains from the Massachusetts Alzheimer Disease Research Center Brain Bank with Braak III to IV stages of tau pathology but divergent antemortem cognition (dementia vs resilient) and cognitively normal controls with negligible AD neuropathologic changes. The visual cortex, a region without tau tangle deposition at Braak III to IV stages, was assessed after expansion microscopy to analyze spatial relationships of synapses with microglia and astrocytes. Participants were matched for age, sex, and apolipoprotein E status. Evidence of Lewy bodies, TDP-43 aggregates, or other lesions different from AD neuropathology were exclusion criteria. Tissue was collected from July 1998 to November 2020, and analyses were conducted from February 1, 2022, through May 31, 2023. Main Outcomes and Measures: Amyloid-ß plaques, tau neuropil thread burden, synapse density, tau oligomers in synapses, and internalization of tau oligomer-tagged synapses by microglia and astrocytes were quantitated. Analyses were performed using 1-way analysis of variance for parametric variables and the Kruskal-Wallis test for nonparametric variables; between-group differences were evaluated with Holm-Sídák tests. Results: Of 40 included participants (mean [SD] age at death, 88 [8] years; 21 [52%] male), 19 had early-stage dementia with Braak stages III to IV, 13 had resilient brains with similar Braak stages III to IV, and 8 had no dementia (Braak stages 0-II). Brains with dementia but not resilient brains had substantial loss of presynaptic (43%), postsynaptic (33%), and colocalized mature synaptic elements (38%) compared with controls and significantly higher percentages of mature synapses internalized by IBA1-positive microglia (mean [SD], 13.3% [3.9%] in dementia vs 2.6% [1.9%] in resilient vs 0.9% [0.5%] in control; P < .001) and by GFAP-positive astrocytes (mean [SD], 17.2% [10.9%] in dementia vs 3.7% [4.0%] in resilient vs 2.7% [1.8%] in control; P = .001). In brains with dementia but not in resilient brains, tau oligomers more often colocalized with synapses, and the proportions of tau oligomer-containing synapses inside microglia (mean [SD] for presynapses, mean [SD], 7.4% [1.8%] in dementia vs 5.1% [1.9%] resilient vs 3.7% [0.8%] control; P = .006; and for postsynapses 11.6% [3.6%] dementia vs 6.8% [1.3%] resilient vs 7.4% [2.5%] control; P = .001) and astrocytes (mean [SD] for presynapses, 7.0% [2.1%] dementia vs 4.3% [2.2%] resilient vs 4.0% [0.7%] control; P = .001; and for postsynapses, 7.9% [2.2%] dementia vs 5.3% [1.8%] resilient vs 3.0% [1.5%] control; P < .001) were significantly increased compared with controls. Those changes in brains with dementia occurred in the absence of tau tangle deposition in visual cortex. Conclusion and Relevance: The findings from this cross-sectional study suggest that microglia and astrocytes may excessively engulf synapses in brains of individuals with dementia and that the abnormal presence of tau oligomers in synapses may serve as signals for increased glial-mediated synapse elimination and early loss of brain function in AD.

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.

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.

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.