Unlocking the complete blood count as a risk stratification tool for breast cancer using machine learning: a large scale retrospective study.

Optimizing early breast cancer (BC) detection requires effective risk assessment tools. This retrospective study from Brazil showcases the efficacy of machine learning in discerning complex patterns within routine blood tests, presenting a globally accessible and cost-effective approach for risk evaluation. We analyzed complete blood count (CBC) tests from 396,848 women aged 40-70, who underwent breast imaging or biopsies within six months after their CBC test. Of these, 2861 (0.72%) were identified as cases: 1882 with BC confirmed by anatomopathological tests, and 979 with highly suspicious imaging (BI-RADS 5). The remaining 393,987 participants (99.28%), with BI-RADS 1 or 2 results, were classified as controls. The database was divided into modeling (including training and validation) and testing sets based on diagnostic certainty. The testing set comprised cases confirmed by anatomopathology and controls cancer-free for 4.5-6.5 years post-CBC. Our ridge regression model, incorporating neutrophil-lymphocyte ratio, red blood cells, and age, achieved an AUC of 0.64 (95% CI 0.64-0.65). We also demonstrate that these results are slightly better than those from a boosting machine learning model, LightGBM, plus having the benefit of being fully interpretable. Using the probabilistic output from this model, we divided the study population into four risk groups: high, moderate, average, and low risk, which obtained relative ratios of BC of 1.99, 1.32, 1.02, and 0.42, respectively. The aim of this stratification was to streamline prioritization, potentially improving the early detection of breast cancer, particularly in resource-limited environments. As a risk stratification tool, this model offers the potential for personalized breast cancer screening by prioritizing women based on their individual risk, thereby indicating a shift from a broad population strategy.

Biochemical phenotyping of paroxysmal nocturnal hemoglobinuria reveals solute carriers and ß-oxidation deficiencies.

INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal disease of hematopoietic cells with a variable clinical spectrum characterized by intravascular hemolysis, high risk of thrombosis, and cytopenias. To understand the biochemical shifts underlying PNH, this study aimed to search for the dysfunctional pathways involved in PNH physiopathology by comparing the systemic metabolic profiles of affected patients to healthy controls and the metabolomic profiles before and after the administration of eculizumab in PNH patients undergoing treatment. METHODS: Plasma metabolic profiles, comprising 186 specific annotated metabolites, were quantified using targeted quantitative electrospray ionization tandem mass spectrometry in 23 PNH patients and 166 population-based controls. In addition, samples from 12 PNH patients on regular eculizumab maintenance therapy collected before and 24 hours after eculizumab infusion were also analyzed. RESULTS: In the PNH group, levels of the long-chain acylcarnitines metabolites were significantly higher as compared to the controls, while levels of histidine, taurine, glutamate, glutamine, aspartate and phosphatidylcholines were significantly lower in the PNH group. These differences suggest altered acylcarnitine balance, reduction in the amino acids participating in the glycogenesis pathway and impaired glutaminolysis. In 12 PNH patients who were receiving regular eculizumab therapy, the concentrations of acylcarnitine C6:1, the C14:1/C6 ratio (reflecting the impaired action of the medium-chain acyl-Co A dehydrogenase), and the C4/C6 ratio (reflecting the impaired action of short-chain acyl-Co A dehydrogenase) were significantly reduced immediately before eculizumab infusion, revealing impairments in the Acyl CoA metabolism, and reached levels similar to those in the healthy controls 24 hours after infusion. CONCLUSIONS: We demonstrated significant differences in the metabolomes of the PNH patients compared to healthy controls. Eculizumab infusion seemed to improve deficiencies in the acyl CoA metabolism and may have a role in the mitochondrial oxidative process of long and medium-chain fatty acids, reducing oxidative stress, and inflammation.

Plasma metabolomics of oral squamous cell carcinomas based on NMR and MS approaches provides biomarker identification and survival prediction.

Metabolomics has proven to be an important omics approach to understand the molecular pathways underlying the tumour phenotype and to identify new clinically useful markers. The literature on cancer has illustrated the potential of this approach as a diagnostic and prognostic tool. The present study aimed to analyse the plasma metabolic profile of patients with oral squamous cell carcinoma (OSCC) and controls and to compare patients with metastatic and primary tumours at different stages and subsites using nuclear magnetic resonance and mass spectrometry. To our knowledge, this is the only report that compared patients at different stages and subsites and replicates collected in diverse institutions at different times using these methodologies. Our results showed a plasma metabolic OSCC profile suggestive of abnormal ketogenesis, lipogenesis and energy metabolism, which is already present in early phases but is more evident in advanced stages of the disease. Reduced levels of several metabolites were also associated with an unfavorable prognosis. The observed metabolomic alterations may contribute to inflammation, immune response inhibition and tumour growth, and may be explained by four nonexclusive views-differential synthesis, uptake, release, and degradation of metabolites. The interpretation that assimilates these views is the cross talk between neoplastic and normal cells in the tumour microenvironment or in more distant anatomical sites, connected by biofluids, signalling molecules and vesicles. Additional population samples to evaluate the details of these molecular processes may lead to the discovery of new biomarkers and novel strategies for OSCC prevention and treatment.

Previous gut microbiota has an effect on postprandial insulin response after intervention with yacon syrup as a source of fructooligosaccharides: a randomized, crossover, double-blind clinical trial.

OBJECTIVES: The use of prebiotics has an effect on postprandial glucose and insulin concentrations; however, the interaction between the previous profile of the intestinal microbiota and the effect of supplementation with prebiotics is not clear. Our objective was to evaluate the effect of previous intestinal microbiota profile on the postprandial insulin response to yacon syrup, used as a source of fructooligosaccharides (FOSs), in young women. The product presents high levels of FOS. METHODS: In this double-blind, crossover, randomized clinical trial, 40 adult women were allocated to receive a breakfast containing 40 g of yacon syrup (14 g FOS, intervention A) or a breakfast containing 40 g of placebo (intervention B). On each intervention day, after 12 h of fasting, an aliquot of blood was collected for insulin analysis at 0, 15, 30, 45, 60, 90, and 120 min. The fecal sample was collected before the beginning of the interventions, and the DNA was extracted and quantified, with subsequent amplification of the 16S region, next-generation sequencing, and analysis of sequencing data. RESULTS: The glucose and insulin concentrations were reduced after ingestion of yacon syrup compared with placebo, specifically at the 30 min to insulin. After the receiver operating characteristic analysis, six volunteers who did not respond to the yacon consumption intervention were identified. The abundance of the phylum Actinobacteria (P = 0.021) and the order Bifidobacteriales (P = 0.013) were positively associated with better insulin response. Other main phyla were not associated with intervention response. CONCLUSIONS: The previous profile of the intestinal microbiota has an effect on the postprandial insulin response to FOSs, mainly in the phylum Actinobacteria and Bifidobacteriales order.

Metabolomic profile in patients with primary warm autoimmune haemolytic anaemia.

Autoimmune haemolytic anaemia (AIHA) is a rare clinical condition with immunoglobulin fixation on the surface of erythrocytes, with or without complement activation. The pathophysiology of AIHA is complex and multifactorial, presenting functional abnormalities of T and B lymphocytes that generate an imbalance between lymphocyte activation, immunotolerance and cytokine production that culminates in autoimmune haemolysis. In AIHA, further laboratory data are needed to predict relapse and refractoriness of therapy, and thus, prevent adverse side-effects and treatment-induced toxicity. The metabolomic profile of AIHA has not yet been described. Our group developed a cross-sectional study with follow-up to assess the metabolomic profile in these patients, as well as to compare the metabolites found depending on the activity and intensity of haemolysis. We analysed the plasma of 26 patients with primary warm AIHA compared to 150 healthy individuals by mass spectrometry. Of the 95 metabolites found in the patients with AIHA, four acylcarnitines, two phosphatidylcholines (PC), asymmetric dimethylarginine (ADMA) and three sphingomyelins were significantly increased. There was an increase in PC, spermine and spermidine in the AIHA group with haemolytic activity. The PC ae 34:3/PC ae 40:2 ratio, seen only in the 12-month relapse group, was a predictor of relapse with 81% specificity and 100% sensitivity. Increased sphingomyelin, ADMA, PC and polyamines in patients with warm AIHA can interfere in autoantigen and autoimmune recognition mechanisms in a number of ways (deficient action of regulatory T lymphocytes on erythrocyte recognition as self, negative regulation of macrophage nuclear factor kappa beta activity, perpetuation of effector T lymphocyte and antibody production against erythrocyte antigens). The presence of PC ae 34:3/PC ae 40:2 ratio as a relapse predictor can help in identifying cases that require more frequent follow-up or early second-line therapies.

Application of the multivariate and univariate analyses to estimate the feed efficiency in beef cattle

This study aimed to compare the univariate analyses (relationship between dry matter intake (DMI) and average daily gain (ADG), Kleiber ratio, and residual feed intake) and multivariate analysis (bionutritional index [BNI]) to determine feed efficiency. Were used a total of 160 cattle (individual data) and the analyzed variables were dry matter intake, weight gain, and body weight of the animals. We used five methods to evaluate feed efficiency, the BNI, FE, corrected feeding efficiency (corFE), Kleiber ratio (KR), and residual feed intake (RFI). Study 1 demonstrated that only the FE (p=0.0472) was significant, although the FE after the transformation of Box-Cox (corFE) (p=0.0642) showed a statistical trend. In studies 2, 3, and 5, we observed that BNI was the best biological efficiency indicator. In the study 4, we observed that the best indicators were FE (0.110; p=0.0281), corFE (0.380; p=0.0429), and RFI (0.465; p=0.0340) for the genders. However, corFE decreased the coefficient of variation in all studies. In conclusion, the use of the Box-Cox transformation is as efficient as the multivariate analysis in discriminating experimental groups (genetic groups, different levels of concentrate in the diet, and genders) concerning the other univariate analyzes.

Prevalence of bruxism among college students: what are the associated factors? A cross-sectional study

Evaluate the prevalence of bruxism and to analyze what are the possible associated factors with this condition in students of a Brazilian university. Methods: This was a cross-sectional study, with a sample of 230 students randomly selected among undergraduate courses at a university center. The dependent variable was the presence of awake bruxism and sleep bruxism. The independent variables were sociodemographic factors, smoking, alcohol consumption, oral habits and stress perception (Perceived Stress Scale- PSS 14). Descriptive statistics and bivariate analysis were used. Results: The prevalence of awake bruxism was 28.7% and was associated with the independent variables: course (degree program), gum chewing habits, chin hand placing, facedown sleeping and one-side biting. Sleep bruxism had a 7.0% prevalence and displayed association with gum chewing, pens/pencils/objects biting, tongue/lips/cheeks biting, nails biting and one-side biting. Perceived stress was not associated with either type of bruxism. Conclusion: Bruxism has an important prevalence among university students, especially when distinguishing between awake bruxism and sleep bruxism

Relationship between Resilience and the Impostor Phenomenon among Undergraduate Medical Students.

Introduction: Impostor Phenomenon (IP) is the inability to internalize success and a tendency to attribute success to external causes. Social and institutional support are strategies to avoid the problem, but only partially successful. Resilience has been considered protective against mental health disorders in medical students. This study aims to investigate the association between IP and resilience in undergraduate medical students. Methods: Using Clance Impostor Phenomenon Scale (CIPS), Connor-Davidson Resilience Scale (CD-RISC), and a socio-demographic questionnaire, we conducted a cross-sectional, quantitative study with undergraduate medical students. Results: The study included 425 pre-clerkship medical students of average age of 23.03 years. The prevalence of IP was 47.76% (CIPS ≥ 62 score, as recommended in prior literature.) and there were no differences among age, gender, current semester, religion. The majority student's CD-RISC score was 68.57 ± 14.66 and there was no statistical difference in resilience scale among age, gender, religion and training semester. "Other religions" group was associated with a higher resilience score when compared to "Catholic" or "Non-religious" students. We found an inverse correlation between the level of resilience by CD-RISC and the level of symptoms related to IP by CIPS (ρ = -0.409; p-value < .001). Conclusions: Findings from this study suggest that higher levels of resilience are likely protective against IP among undergraduate medical students. Furthermore, the non-inclusion of medical internship students and the cross-sectional design of this study are restraining aspects noticed within the project, suggesting the need for further studies to adjust those limitations.

Towards risk stratification and prediction of disease severity and mortality in COVID-19: Next generation metabolomics for the measurement of host response to COVID-19 infection.

This study investigated the association between COVID-19 infection and host metabolic signatures as prognostic markers for disease severity and mortality. We enrolled 82 patients with RT-PCR confirmed COVID-19 infection who were classified as mild, moderate, or severe/critical based upon their WHO clinical severity score and compared their results with 31 healthy volunteers. Data on demographics, comorbidities and clinical/laboratory characteristics were obtained from medical records. Peripheral blood samples were collected at the time of clinical evaluation or admission and tested by quantitative mass spectrometry to characterize metabolic profiles using selected metabolites. The findings in COVID-19 (+) patients reveal changes in the concentrations of glutamate, valeryl-carnitine, and the ratios of Kynurenine/Tryptophan (Kyn/Trp) to Citrulline/Ornithine (Cit/Orn). The observed changes may serve as predictors of disease severity with a (Kyn/Trp)/(Cit/Orn) Receiver Operator Curve (ROC) AUC = 0.95. Additional metabolite measures further characterized those likely to develop severe complications of their disease, suggesting that underlying immune signatures (Kyn/Trp), glutaminolysis (Glutamate), urea cycle abnormalities (Cit/Orn) and alterations in organic acid metabolism (C5) can be applied to identify individuals at the highest risk of morbidity and mortality from COVID-19 infection. We conclude that host metabolic factors, measured by plasma based biochemical signatures, could prove to be important determinants of Covid-19 severity with implications for prognosis, risk stratification and clinical management.

May critical molecular cross-talk between indoleamine 2,3-dioxygenase (IDO) and arginase during human aging be targets for immunosenescence control?

BACKGROUND: This study aimed to identify novel plasma metabolic signatures with possible clinical relevance during the aging process. A biochemical quantitative phenotyping platform, based on targeted electrospray ionization tandem mass spectrometry technology, was used for the identification of any eventual perturbed biochemical pathway by the aging process in prospectively collected peripheral blood plasma from 166 individuals representing the population of São Paulo city, Brazil. RESULTS: Indoleamine 2,3-dioxygenase (IDO) activity (Kyn/Trp) was significantly elevated with age, and among metabolites most associated with elevations in IDO, one of the strongest correlations was with arginase (Orn/Arg), which could also facilitate the senescence process of the immune system. Hyperactivity of IDO was also found to correlate with increased blood concentrations of medium-chain acylcarnitines, suggesting that deficiencies in beta-oxidation may also be involved in the immunosenescence process. Finally, our study provided evidence that the systemic methylation status was significantly increased and positively correlated to IDO activity. CONCLUSIONS: In the present article, besides identifying elevated IDO activity exhibiting striking parallel association with the aging process, we additionally identified increased arginase activity as an underlying biochemical disturbance closely following elevations in IDO. Our findings support interventions to reduce IDO or arginase activities in an attempt to preserve the functionality of the immune system, including modulation of myeloid-derived suppressor cells (MDSCs), T cells, macrophages, and dendritic cells' function, in old individuals/patients.

Burning in southwestern Brazilian Amazonia, 2016-2019.

Fire is one of the most powerful modifiers of the Amazonian landscape and knowledge about its drivers is needed for planning control and suppression. A plethora of factors may play a role in the annual dynamics of fire frequency, spanning the biophysical, climatic, socioeconomic and institutional dimensions. To uncover the main forces currently at play, we investigated the area burned in both forested and deforested areas in the outstanding case of Brazil's state of Acre, in southwestern Amazonia. We mapped burn scars in already-deforested areas and intact forest based on satellite images from the Landsat series analyzed between 2016 and 2019. The mapped burnings in already-deforested areas totalled 550,251 ha. In addition, we mapped three forest fires totaling 34,084 ha. Fire and deforestation were highly correlated, and the latter occurred mainly in federal government lands, with protected areas showing unprecedented forest fire levels in 2019. These results indicate that Acre state is under increased fire risk even during average rainfall years. The record fires of 2019 may continue if Brazil's ongoing softening of environmental regulations and enforcement is maintained. Acre and other Amazonian states must act quickly to avoid an upsurge of social and economic losses in the coming years.

Allergic Reactions in Orthodontic Patients: A Review / Reacciones Alérgicas en Pacientes de Ortodoncia: Una Revisión

Allergic reactions are host immune responses to endogenous or exogenous antigens, which can result in local and systemic problems. Among the main allergens are the dental materials used in orthodontics, which faces some challenges with regard to biocompatibility with oral tissues.This study aimed to analyze in the literature which materials used in orthodontics are related to the appearance of oral and perioral allergic reactions, as well as to investigate the most prevalen t manifestations.An integrative review was carried out with articles published between 2010 and 2020 on the PubMed, Embase, and ScienceDirect on-line database. For this, MeSH descriptors and synonyms were used following two semantic fields: "Hypersensitivity" in association with "Orthodontic Appliances", the selection of studies counted with the stages of identifica tion, screening, eligibility and inclusion. Randomized clinical trials, cross-sectional or cohort clinical trials; Patients with alle rgic reactions affecting the oral or perioral region due to contact with orthodontic material, were included in the review.From a to tal of 549 articles only 04 were selected for the study. In accordance with what has been analyzed in the evidence of these studies, periodontal changes such as gingival inflammation as well as erythema, edema, papules and blisters were the main reactions described. Furthermore, in all articles there was an association with nickel and in only one with chromium. It is possible to i nfer that inflammatory lesions are frequent manifestations on the use of nickel in orthodontic patients.

Las reacciones alérgicas son respuestas inmunes del huésped a antígenos endógenos o exógenos, los cuales pueden provocar problemas locales y sistémicos. Entre los principales alérgenos se encuentran los materiales dentales utilizados en la ortodoncia, la cual se enfrenta a algunos desafíos respecto a la biocompatibilidad de los tejidos orales. Este estudio tuvo como objetivo analizar en la literatura que materiales utilizados en ortodoncia están relacionados con la aparición de reacciones alérgicas orales y periorales, así como investigar las manifestaciones más prevalentes. Se llevó a cabo una revisión con artículos publicados entre 2010 y 2020 en las bases de datos PubMed, Embase y ScienceDirect. Para ello, se utilizaron descriptores y sinónimos de MeSH siguiendo dos campos semánticos: "Hipersensibilidad" en asociación con "Aparatos de Ortodoncia", la selección de estudios contó con las etapas de identificación, cribado, elegibilidad e inclusión. Ensayos clínicos aleatorizados, ensayos clínicos transversales o de cohortes; en la revisión se incluyeron pacientes con reacciones alérgicas que afectaron a la regiones oral o perioral debido al contacto con material de ortodoncia. De un total de 549 artículos sólo cuatro fueron seleccionados para el estudio. De acuerdo con lo que se analizó en la evidencia, las principales reacciones descritas fueron cambios periodontales, como inflamación gingival, eritema, edema, pápulas y ampollas. Además, en todos los artículos hubo una asociación con níquel y solamente en uno con cromo. Es posible inferir que las lesiones inflamatorias son manifestaciones frecuentes sobre el uso de níquel en pacientes de ortodoncia.

Plasma metabolomics are associated with metabolic syndrome: A targeted approach.

OBJECTIVES: Advances in metabolomic tools have allowed us to gain a more comprehensive understanding of metabolic syndrome (MetS). The aim of this study was to evaluate the association between plasma metabolomic profiles and MetS. METHODS: For this study, adults without diabetes, chronic kidney disease, stroke, heart disease, or cancer and with full metabolomics, biochemical, and dietetic data available, representing a subsample of the Health Survey of Sao Paulo study (ISA-Capital; N = 130), were included. The joint interim statement consensus criteria were used for diagnosing MetS. Absolute quantification (µmol/L) of blood metabolites was achieved by targeted quantitative profiling of annotated metabolites by electrospray ionization tandem mass spectrometry in plasma samples. Mean differences in the compounds for MetS were evaluated by linear regression adjusted for confounding factors. RESULTS: Serine was inversely associated with MetS (ß = -15.04; P = 0.014). In glycerophospholipids with acyl-alkyl bonds, there was an inverse association with MetS, including phosphatidylcholine (PC) ae C42:5 (ß = -0.15; P = 0.040), PC ae C44:5 (ß = -0.15; P = 0.046), PC ae C40:4 (ß = -0.21; P = 0.014) and PC ae C44:4 (ß = -0.04; P = 0.032). CONCLUSION: Plasma metabolomic profiles were associated with MetS, especially the amino acid serine and some acyl-alkyl PCs.

Hábitos associados à mordida aberta anterior em crianças: uma revisão integrativa / Habits associated to preceding open bite in children: an integrative revie

Objetivo: Analisar na literatura quais são os hábitos associados à mordida aberta anterior em crianças. Métodos: Realizou-se uma pesquisa bibliográfica referente aos artigos publicados de 2015 a 2020 nos bancos de dados on-line PubMed, Embase, SciELO, LILACS e BBO utilizando descritores e sinônimos MeSH, DeCS e Emtree com as seguintes etapas: identificação, triagem, elegibilidade e inclusão. Foram incluídos estudos observacionais, transversais ou de coorte, e artigos que demonstrassem hábitos associados à mordida aberta anterior em crianças de 2 a 12 anos de idade. Relatos de caso, revisões da literatura e outros tipos de estudos que não estavam de acordo com os critérios foram excluídos. Os artigos foram analisados por dois pesquisadores independentes e os estudos selecionados foram avaliados quanto à qualidade metodológica. Resultados: De um total de 462 artigos encontrados apenas 9 foram selecionados para o estudo. Desses, 8 (88,9%) apresentaram alta ou moderada qualidade metodológica, sendo apenas 1 (11,1%), dentre os artigos, de baixa qualidade. Mediante à análise dos estudos inclusos, observou-se que a manutenção de hábitos orais como sucção digital (66,6% dos artigos) e de chupeta (77,7%), bem como uso de mamadeira (33,3%) e duração do tempo de aleitamento materno (22,2%) pode ocasionar alterações na oclusão, fala, respiração, crescimento craniofacial, afetando diretamente a qualidade de vida da criança. Conclusão:Uma vez que a infância é a fase adequada para a implementação de novos hábitos saudáveis e tratamentos, é imprescindível que o cirurgião-dentista conheça essa associação, e adote medidas terapêuticas e preventivas.

Aim: To perform an analysis of in the literature regarding which habits are associated with anterior open bite in children. Methods:This was a bibliographic study conducted using articles published from 2015 to 2020 in the PubMed, Embase, SciELO, LILACS, and BBO online databases, using MeSH, DeCS, and Emtree descriptors and synonyms with the following steps: identification, screening, eligibility, and inclusion. Observational, cross-sectional, or cohort studies, as well as and articles demonstrating habits associated with anterior open bite in children aged 2 to 12 years, were included. Case reports, literature reviews, and other types of studies that were not in accordance with the criteria were excluded. The articles were evaluated by two independent researchers, and the selected studies were evaluated for methodological quality. Results:Of a total of 462 articles found, only nine were selected for the study. Of these, eight (88.9%) presented high or moderate methodological quality, with only 1 (11.1%) of the articles presenting a low quality. Through the analysis of the included studies, it was observed that the maintenance of oral habits, such as finger sucking (66.6% of the articles) and pacifiers (77.7%), as well as the use of a bottle (33.3%) and the duration of breastfeeding time (22.2%), may cause changes in occlusion, speech, breathing, and craniofacial growth, directly affecting the child's quality of life. Conclusion: Since childhood is the appropriate phase for the implementation of new healthy habits and treatments, it is essential for the dentist to understand this association and adopt therapeutic and preventive measures.

Biochemical phenotyping of multiple myeloma patients at diagnosis reveals a disorder of mitochondrial complexes I and II and a Hartnup-like disturbance as underlying conditions, also influencing different stages of the disease.

The aim of this study was to identify novel plasma metabolic signatures with possible relevance during multiple myeloma (MM) development and progression. A biochemical quantitative phenotyping platform based on targeted electrospray ionization tandem mass spectrometry technology was used to aid in the identification of any eventual perturbed biochemical pathway in peripheral blood plasma from 36 MM patients and 73 healthy controls. Our results showed that MM cases present an increase in short and medium/long-chain species of acylcarnitines resembling Multiple AcylCoA Dehydrogenase Deficiency (MADD), particularly, associated with MM advanced International Staging System (ISS). Lipids profile showed lower concentrations of phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and sphingomyelins (SM) in the MM patients and its respective ISS groups. MM cases were accompanied by a drop in the concentration of essential amino acids, especially tryptophan, with a significant inverse correlation between the progressive drop in tryptophan with the elevation of ß2-microglobulin, with the increase in systemic methylation levels (Symmetric Arginine Dimethylation, SDMA) and with the accumulation of esterified carnitines in relation to free carnitine (AcylC/C0). Serotonin was significantly elevated in cases of MM, without a clear association with ISS. Kynurenine/tryptophan ratio demonstrates that the activity of dioxigenases is even higher in the cases classified as ISS 3. In conclusion, our study showed that MM patients at diagnosis showed metabolic disorders resembling both mitochondrial complexes I and II and Hartnup-like disturbances as underlying conditions, also influencing different stages of the disease.

Etiologia e fatores associados à halitose: uma revisão integrativa da literatura / Etiology and factors associated with halitosis: an integrative literature review

Objetivo: avaliar quais as possíveis causas e quais são os fatores associados ao surgimento da halitose. Métodos: foi realizada uma revisão nos bancos de dados PubMed e SciELO, utilizando os descritores e sinônimos MeSH organizados em lógica booleana: 'Halitosis' AND 'Risk Factors' OR 'Association' OR 'Etiologies', com as seguintes etapas: identificação dos artigos, triagem, elegibilidade e inclusão. Apenas artigos publicados entre os anos de 2015-2020, ensaios clínicos randomizados, estudos transversais ou de coorte foram incluídos na revisão. Foram excluídos protocolos de estudos e os artigos que não estavam nos critérios e objetivo desta revisão. Resultados: de 240 artigos encontrados, 22 foram inclusos. Desses, 50% demonstraram que a falta ou a deficiência dos hábitos de higiene oral se relacionam com a halitose. Ainda, 40,9% deles se referem à saburra lingual como um forte fator etiológico e 36,4% demonstram que a doença periodontal está diretamente associada com o mau hálito. Além disso, em relação a outras condições locais e sistêmicas, xerostomia (13,6%), doença gastrointestinal e refluxo laringofaríngeo (9,1%), rinite e diabetes (4,5%) também demonstraram associação. Considerações finais: a halitose pode estar associada com higiene bucal, saburra lingual, doença periodontal, alguns hábitos e quadros sistêmicos.(AU)

Objective: to evaluate the possible causes and what are the factors associated with the onset of halitosis. Methods: a review was performed in the PubMed and SciELO databases, using the descriptors and synonyms MeSH organized in Boolean logic: 'Halitosis' AND 'Risk Factors' OR 'Association' OR 'Etiologies', with the following steps: identification of articles, screening, eligibility and inclusion. Only articles published between 2015- 2020; randomized clinical trials; cross-sectional or cohort studies were included in the review. Study protocols and articles that were not in the criteria and objective of this review were excluded. Results: Of 240 articles found, 22 were included. Of those, 50% showed that the lack or deficiency of oral hygiene habits are related to halitosis. Furthermore, 40.9% of them refer to tongue coating as a strong etiological factor and 36.4% demonstrate that periodontal disease is directly associated with bad breath. Moreover, in relation to other local and systemic conditions, xerostomia (13.6%), gastrointestinal disease and laryngeal reflux (9.1%), rhinitis and diabetes (4.5%) also demonstrated an association. Final considerations: Halitosis may be associated with oral hygiene, lingualcoating, periodontal disease, some habits and systemic conditions.(AU)

Contemporary human papillomavirus genotyping and correlations to peniscopy, cytology, and histopatology on over 1000 males.

OBJECTIVES: To explore male human papillomavirus (HPV) contemporary genotyping epidemiology and correlations to peniscopy, cytology, and histopatology. METHODS: Medical records of patients who had been submitted to HPV infection screening with genotyping, peniscopy, cytology, and histopathology in a period of 2 years were reviewed. Frequency analysis and correlations between the diagnostic tools were established. RESULTS: Genotype of 1132 men resulted in 69.2% (784) positivity for HPV DNA, 78% classified as high risk of oncogenesis. Co-infections occurred in 429 (54.7%) and the most frequently identified types were HPV-6, HPV-42, and HPV-16, in 133 (17%), 94 (12%), and 86 (11%) patients, respectively. Positive/negative predictive values of peniscopy, cytology, and histopathology were 83/31%, 92/32%, and 87/33%, respectively. As a result, though significant, the correlations between genotype and non-molecular tests were poor. CONCLUSIONS: In the current contemporary representative male cohort, over two thirds are positive for human HPV DNA, 78% of high risk and with over half co-infections. Though significant, its correlation with non-molecular tests is poor and while the positive predictive values of peniscopy, cytology, and histopatology are between 83% and 92%, their negative predictive values are as low as 31% to 33%.

Distinct pattern of one-carbon metabolism, a nutrient-sensitive pathway, in invasive breast cancer: A metabolomic study.

Altered cell metabolism is a hallmark of cancer and critical for its development. Particularly, activation of one-carbon metabolism in tumor cells can sustain oncogenesis while contributing to epigenetic changes and metabolic adaptation during tumor progression. We assessed whether increased one-carbon metabolism activity is a metabolic feature of invasive ductal carcinoma (IDC). Differences in the metabolic profile between biopsies from IDC (n = 47) and its adjacent tissue (n = 43) and between biopsies from different breast cancer subtypes were assessed by gas spectrometry in targeted (Biocrates Life Science ® ) and untargeted approaches, respectively. The metabolomics data were statistically treated using MetaboAnalyst 4.0, SIMCA P+ (version 12.01), Statistica 10 software and t test with p < 0.05. The Cancer Genome Atlas breast cancer dataset was also assessed to validate the metabolomic profile of IDC. Our targeted metabolomics analysis showed distinct metabolomics profiles between IDC and adjacent tissue, where IDC displayed a comparative enrichment of metabolites involved in one-carbon metabolism (serine, glycine, threonine, and methionine) and a predicted increase in the activity of pathways that receive and donate carbon units (i.e., folate, methionine, and homocysteine). In addition, the targeted and untargeted metabolomics analyses showed similar metabolomics profiles between breast cancer subtypes. The gene set enrichment analysis identified different transcription-related functions between IDC and non-tumor tissues that involved one-carbon metabolism. Our data suggest that one-carbon metabolism may be a central pathway in IDC and even in general breast tumors, representing a potential target for its treatment and prevention.

STUDY OF LIPID BIOMARKERS OF PATIENTS WITH POLYPS AND COLORECTAL CÂNCER.

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer worldwide. Early diagnostic methods using serum biomarkers are required. The study of omics, most recently lipidomics, has the purpose of analyzing lipids for a better understanding of human lipidoma. The evolution of mass spectrometry methods, such as MALDI-MS technology, has enabled the detection and identification of a wide variety of lipids with great potential to open new avenues for predictive and preventive medicine. OBJECTIVE: To determine the lipid profile of patients with colorectal cancer and polyps. METHODS: Patients with stage I-III CRC, adenomatous polyps and individuals with normal colonoscopy were selected. All patients underwent peripheral blood collection for lipid extraction. The samples were analyzed by MALDI-MS technique for lipid identification. STATISTICAL ANALYSIS: Univariate and multivariate (principal component analysis [PCA] and discriminant analysis by partial least squares [PLS-DA]) analyses workflows were applied to the dataset, using MetaboAnalyst 3.0 software. The ions were identified according to the class of lipids using the online database Lipid Maps (http://www.lipidmaps.org). RESULTS: We included 88 individuals, 40 with CRC, 12 with polyps and 32 controls. Boxplot analysis showed eight VIP ions in the three groups. Differences were observed between the cancer and control groups, as well as between cancer and polyp, but not between polyps and control. The polyketide (810.1) was the lipid represented in cancer and overrepresented in polyp and control. Among the patients with CRC we observed differences between lipids with lymph node invasion (N1-2) compared to those without lymph node invasion (N). CONCLUSION: Possible lipid biomarkers were identified among cancer patients compared to control and polyp groups. The polyketide lipid (810.1) was the best biomarker to differentiate the cancer group from control and polyp. We found no difference between the biomarkers in the polyp group in relation to the control.

Multiple sclerosis has a distinct lipid signature in plasma and cerebrospinal fluid.

OBJECTIVE: The diagnosis of multiple sclerosis (MS) has changed over the last decade, but remains a composite of clinical assessment and magnetic resonance imaging to prove dissemination of lesions in time and space. The intrathecal synthesis of immunoglobulin may be a nonspecific marker and there are no plasma biomarkers that are useful in the diagnosis of MS, presenting additional challenges to their early detection. METHODS: We performed a preliminary untargeted qualitative lipidomics mass spectrometry analysis, comparing cerebrospinal fluid (CSF) and plasma samples from patients with MS, other inflammatory neurological diseases and idiopathic intracranial hypertension. RESULTS: Lipid identification revealed that fatty acids and sphingolipids were the most abundant classes of lipids in the CSF and that glycerolipids and fatty acids were the main class of lipids in the plasma of patients with MS. The area under the curve was 0.995 (0.912-1) and 0.78 (0.583-0.917), respectively. The permutation test indicated that this ion combination was useful for distinguishing MS from other inflammatory diseases (p < 0.001 and 0.055, respectively). CONCLUSION: This study concluded that the CSF and plasma from patients with MS bear a unique lipid signature that can be useful as a diagnostic biomarker.