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Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Detection before metastasis and efficient treatment of disease significantly improve patient survival and quality of life. However, limitations in diagnosis and postoperative surveillance are associated with low CRC detection and survival rates. Thus, this project aimed to evaluate the molecular profile of patients diagnosed with CRC, as molecular biomarkers constitute a new frontier for diagnosis, treatment and prognosis. Methods and Results: 42 patients were included in the study, predominantly male (59.5%), with a median age of 63 years (SD: 10.0; min: 41; max: 83). The majority of primary tumors were located in the rectum (38.1%), in the sigmoid (33.3%) and in the ascending (21.4%) colon. We evaluated the genes KRAS, NRAS, BRAF, EGFR and TP53 using Sanger sequencing. Somatic and germline mutations were found in the KRAS, EGFR and TP53 genes, with the most common somatic alteration being rs121913529 in KRAS. This variant was also strongly associated with alcoholism (p = 0.002). Furthermore, patients with somatic mutations in TP53 had significantly higher mortality compared to those with wild-type alleles (OR: 11.2; 95% CI 1.25–2.45). Conclusions: Our findings support a relationship between alcohol consumption and the rs121913529 mutation, which is classified as pathogenic for colorectal cancer. Thus, further studies investigating the link between alcohol consumption, colorectal carcinogenesis and tumor progression ought to be conducted.

Adenoid ameloblastoma is a very rare benign epithelial odontogenic tumor characterized microscopically by epithelium resembling conventional ameloblastoma, with additional duct-like structures, epithelial whorls, and cribriform architecture. Dentinoid deposits, clusters of clear cells, and ghost-cell keratinization may also be present. These tumors do not harbor BRAF or KRAS mutations and their molecular basis appears distinct from conventional ameloblastoma but remains unknown. We assessed CTNNB1 (beta-catenin) exon 3 mutations in a cohort of 11 samples of adenoid ameloblastomas from 9 patients. Two of the 9 patients were female and 7 male and in 7/9 patients the tumors occurred in the maxilla. Tumors of 4 of these 9 patients harbored CTNNB1 mutations, specifically p.Ser33Cys, p.Gly34Arg, and p.Ser37Phe. Notably, for one patient 3 samples were analyzed including the primary tumour and two consecutive recurrences, and results were positive for the mutation in all three tumors. Therefore, 6/11 samples tested positive for the mutation. In the 6 mutation-positive samples, ghost cells were present in only 2/6, indicating beta-catenin mutations are not always revealed by ghost cell formation. Dentinoid matrix deposition was observed in 5/6 mutation-positive samples and clear cells in all 6 cases. None of the cases harbored either BRAF or KRAS mutations. Beta-catenin immunoexpression was assessed in the samples of 8 patients. Except for one wild-type case, all cases showed focal nuclear expression irrespective of the mutational status. Together with the absence of BRAF mutation, the detection of beta-catenin mutation in adenoid ameloblastomas supports its classification as a separate entity, and not as a subtype of ameloblastoma. The presence of this mutation may help in the diagnosis of challenging cases.

Treatment of cutaneous leishmaniasis depends on drugs that potentially cause serious side effects and resistance. Thus, topical therapies are attractive alternatives to the drugs currently used. 3β, 6β, 16β-trihydroxylup-20 (29)-ene is a lupane triterpene isolated from Combretum leprosum Mart. leaves (CLF-1), with reports of in vitro antileishmanial effect against L . amazonensis and to promote lesion healing in animal model. Herein, we evaluated the in vitro and in vivo antileishmanial and healing effects of CLF-1 against L . braziliensis . CLF-1 treatment showed low toxicity in macrophages and significantly reduced parasite load in vitro . CLF-1 induced higher IL-12 and TNF-α production and more discrete IL-4 and IL-10 production. For in vivo evaluation, a CLF-1 cream formulation was prepared to treat hamsters infected with L . braziliensis . CLF-1 treatment was able to reduce parasite load of the infected skin and lymph node more efficiently than the conventional treatment. Histopathological analysis indicated a strong inflammatory response accompanied by an important healing response. Data from this study indicate that topical CLF-1 treatment was effective and non-toxic in L . braziliensis infected hamsters suggesting its potential for further development as a future therapeutic intervention.

Analyses of typical bacterial clusters in humans named enterotypes may facilitate understanding the host differences in the cardiometabolic profile. It stills unknown whether the three previously described enterotypes were present in populations living below the equator. We examined how the identification of enterotypes could be useful to explain the dietary associations with cardiometabolic risk factors in Brazilian subjects. In this cross-sectional study, a convenience sample of 268 adults (54.2% women) reported their dietary habits and had clinical and biological samples collected. In this study, we analyzed biochemical data and metagenomics of fecal microbiota (16SrRNA sequencing, V4 region). Continuous variables were compared using ANOVA, and categorical variables using chi-square test. Vsearch clustered the operational taxonomic units, and Silva Database provided the taxonomic signatures. Spearman coefficient was used to verify the correlation between bacteria abundances within each enterotype. One hundred subjects were classified as omnivore, 102 lacto-ovo-vegetarians, and 66 strict vegetarians. We found the same structure as the three previously described enterotypes: 111 participants were assigned to , 55 to , and 102 to enterotype. The cluster contained higher amount of strict vegetarians individuals than the other enterotypes (40.0 vs. 20.7 and 20.6, = 0.04). Subjects in this enterotype had a similar anthropometric profile but a lower mean LDL-c concentration than the enterotype (96 ± 23 vs. 109 ± 32 mg/dL, = 0.04). We observed significant correlations between bacterial abundances and cardiometabolic risk factors, but coefficients differed depending on the enterotype. In enterotype, (r BMI = -0.33, = 0.03, and r HDL-c = 0.33, = 0.04), (r 2h glucose = -0.35, = 0.02), (r BMI = -0.36, = 0.02 and r waist = -0.36, = 0.02), and (r insulin = -0.35, = 0.02) abundances were associated to better cardiometabolic profile. The three enterotypes previously described are present in Brazilians, supporting that those bacterial clusters are not population-specific. Diet-independent lower LDL-c levels in subjects from than in other enterotypes suggest that a protective bacterial cluster in the former should be driving this association. Enterotypes seem to be useful to understand the impact of daily diet exposure on cardiometabolic risk factors. Prospective studies are needed to confirm their utility for predicting phenotypes in humans.

Aims To describe the abundance of major phyla and some genera in the gut microbiota of individuals according to dietary habits and examine their associations with inflammatory markers, insulin resistance, and cardiovascular risk profile. Methods A total of 268 non-diabetic individuals were stratified into groups of dietary types (strict vegetarians, lacto-ovo-vegetarians, and omnivores). The taxonomic composition and phylogenetic structure of the microbiota were obtained through the analysis of the 16S rRNA gene. Samples were clustered into operational taxonomic units at 97% similarity using GreenGenes 13.5 database. Clinical, biochemical, and circulating inflammatory markers were compared by ANOVA or Kruskal–Wallis test. Results The sample (54.2% women, mean age 49.5 years) was composed of 66 strict vegetarians, 102 lacto-ovo-vegetarians and 100 omnivores. Considering the entire sample, the greatest abundant phyla were Firmicutes (40.7 ± 15.9%) and Bacteroidetes (39.5 ± 19.9%), and no difference in abundances was found between individuals with normal and excess weight. Stratifying by dietary types, the proportion of Firmicutes was lower and of Bacteroidetes was higher in strict vegetarians when compared to lacto-ovo-vegetarians and omnivores. At the genus level, strict vegetarians had a higher Prevotella abundance and Prevotella/Bacteroides ratio than the other groups. They also had a lower proportion of Faecalibacterium than lacto-ovo-vegetarians, and both vegetarian groups had higher proportions than did omnivores. Succinivibrio and Halomonas from the Proteobacteria phylum were overrepresented in omnivores. The omnivorous group showed higher values of anthropometric data, insulin, HOMA-IR, and a worse lipid profile. Inflammatory markers exhibited a gradual and significant increase from the vegetarians and lacto-ovo-vegetarians to the omnivorous group. Conclusions There are differences in gut microbiota composition of individuals with distinct dietary habits, who differ according to their inflammatory and metabolic profiles. Based on the findings relative to bacteria abundances and on their recognized actions in the metabolism, we suggest that exposure to animal foods may favor an intestinal environment which could trigger systemic inflammation and insulin resistance-dependent metabolic disorders.

Although the exact mechanism of the pathogenesis of COVID-19 is not fully understood, oxidative stress and the release of pro-inflammatory cytokines have been highlighted as playing a vital role in the pathogenesis of the disease. In this sense, alternative treatments are needed to reduce the inflammation caused by COVID-19. Therefore, this study aimed to investigate the potential effect of red PBM as an attractive therapy to downregulate the cytokine storm caused by COVID-19 from a zebrafish model. RT-PCR analyses and protein-protein interaction prediction among SARS-CoV-2 and Danio rerio proteins showed that rSpike was responsible for generating systemic inflammatory processes with significantly increased pro-inflammatory (il1b, il6, tnfa, and nfkbiab), oxidative stress (romo1) and energy metabolism (slc2a1a, coa1) mRNA markers, with a pattern like those observed in COVID-19 cases in humans. On the other hand, PBM treatment decreased the mRNA levels of these pro-inflammatory and oxidative stress markers compared with rSpike in various tissues, promoting an anti-inflammatory response. Conversely, PBM promotes cellular and tissue repair of injured tissues and significantly increases the survival rate of rSpike-inoculated individuals. Additionally, metabolomics analysis showed that the most impacted metabolic pathways between PBM and the rSpike-treated groups were related to steroid metabolism, immune system, and lipids metabolism. Together, our findings suggest that the inflammatory process is an incisive feature of COVID-19, and red PBM can be used as a novel therapeutic agent for COVID-19 by regulating the inflammatory response. Nevertheless, the need for more clinical trials remains, and there is a significant gap to overcome before clinical trials.

ABSTRACT Objectives: to understand the values attributed by nurses and physicians working in obstetric care for abortion. Methods: this is a phenomenological study based on Max Scheler’s theory of values, with 19 semi-structured online interviews with healthcare professionals working in legal abortion, using the snowball sampling recruitment technique. The collected data were transcribed in full and submitted to content analysis. Results: it was evident from healthcare professionals’ statements that abortion has a vital, moral and ethical professional value. Furthermore, the lack of value given to abortion by physicians and nurses was demonstrated as well as the vital value attributed to women’s lives by public health. Final Considerations: in order to understand the values attributed by nurses and physicians, there was the need to advance the values of health, rights, dignity and respect for women in the face of abortion. RESUMEN Objetivos: comprender los valores atribuidos por enfermeras y médicos que actúan en la atención del aborto obstétrico. Métodos: se trata de un estudio fenomenológico basado en la teoría de valores de Max Scheler, con 19 entrevistas semiestructuradas en línea a profesionales de la salud que trabajan en el aborto legal, utilizando la técnica de reclutamiento por muestreo de bola de nieve. Los datos recopilados fueron transcritos en su totalidad y sometidos a análisis de contenido. Resultados: se evidenció, a partir de las declaraciones de los profesionales de la salud, que el aborto tiene un valor ético vital, moral y profesional. Además, quedó demostrada la infravaloración del aborto por parte de médicos y enfermeras, así como el valor vital que la salud pública atribuye a la vida de las mujeres. Consideraciones Finales: para comprender los valores atribuidos por enfermeras y médicos, se mostró la necesidad de avanzar en los valores de salud, derechos, dignidad y respeto a las mujeres frente al aborto. RESUMO Objetivos: compreender os valores atribuídos pelos enfermeiros e médicos atuantes na assistência obstétrica ao abortamento. Métodos: trata-se de estudo fenomenológico fundamentado no referencial da teoria dos valores de Max Scheler, com 19 entrevistas semiestruturadas online com profissionais de saúde atuantes no abortamento legal, por meio da técnica de recrutamento snowball sampling. Os dados coletados foram transcritos na íntegra e submetidos à análise de conteúdo. Resultados: evidenciou-se, pelos depoimentos dos profissionais de saúde, que o abortamento possui um valor vital, moral e ético profissional. Além disso, mostrou-se o desvalor do abortamento por parte de médicos e enfermeiros, e ainda o valor vital para a vida das mulheres atribuído pela saúde pública. Considerações Finais: com a finalidade da compreensão dos valores atribuídos por enfermeiros e médicos, mostrou-se a necessidade do avanço para os valores à saúde, ao direito, à dignidade e ao respeito das mulheres diante do abortamento.

AimsTo evaluate the relationship between social determinants, health care insurance status and occurrence of diabetes-related chronic complications (DRCC) in Brazilian patients with type 1 diabetes.MethodsA multicenter cross-sectional study conducted between August 2011 and August 2014 in 14 public clinics in 10 Brazilian cities. Data were obtained from 1760 patients, aged 29.9 ± 11.9 years, with diabetes duration of 15.5 ± 9.3 years; 55.9% female, 54.5% Caucasians, 69.7% were attended exclusively by the public Brazilian National Health Care System (BNHCS) and 30.3% had also private health care insurance. Patients’ information was obtained through a questionnaire and a chart review form.ResultsThe social determinants associated with having both private and public health care insurance were being employed, belonging to medium or high socioeconomic status, having more years of school attendance and having younger age. Regarding DRCC, patients that had private and public health care had lower rates of diabetic retinopathy and of any other DRCC. Chronic kidney disease was not associated with health care coverage status after adjusting for classical clinical risk factors.ConclusionsBrazilian patients with type 1 diabetes had better clinical control and lower rates of DRCC, mainly retinopathy, when also having private health care insurance. These patients presented less frequently predictors of chronic complications such as high levels of HbA1c and blood pressure. BNHCS should change the approach for screening DRCC such as diabetic retinopathy, using methods such as telemedicine that would lead to earlier diagnosis, better outcomes and will be cost-effective sometime after its implementation.

The aim of this study was to investigate if grape or apple juices are able to protect bone tissue of rats exposed to cadmium. For this purpose, histopathological analysis and immunohistochemistry for RUNX-2 and RANK-L were investigated in this setting. A total of 20 adult Wistar rats were distributed into four groups ( n  = 5), as follows: control group, cadmium group, cadmium and grape juice group, and Cadmium and apple juice group. Control group received a single intraperitoneal (i.p.) water injection. Cadmium group received a single i.p. injection of cadmium chloride (1.2 mg/kg body weight) diluted in water. Cadmium and grape juice and cadmium and apple juice groups received a single i.p. injection of cadmium chloride (1.2 mg/kg body), and after 15 days, the rats were treated with grape or apple juices for 15 days, by gavage. All animals were euthanized 30 days after the beginning of experiment. Histopathological analysis in rat femur revealed extensive bone loss in rats intoxicated with cadmium. Grape or apple juices were able to increase bone formation. Cadmium inhibited RUNX-2 immunoexpression whereas cadmium increased RANK-L immunoexpression in rat bone cells. Grape or apple juices increased RUNX-2 and decreased RANK-L immunoexpression after cadmium intoxication. Taken together, our results demonstrate that grape or apple juices are able to exert therapeutic activity following cadmium intoxication in rat bone tissue as result of stimulatory effect of bone formation by RUNX-2 upregulation and RANK-L downregulation.