Modulation of the tumor microenvironment in non-muscle-invasive bladder cancer by OncoTherad® (MRB-CFI-1) nanoimmunotherapy: effects on tumor-associated macrophages, tumor-infiltrating lymphocytes, and monoamine oxidases.

Non-muscle-invasive bladder cancer (NMIBC) presents management challenges due to its high recurrence rate and a complex tumor microenvironment (TME). This study investigated the effects of OncoTherad® (MRB-CFI1) nanoimmunotherapy on the TME of BCG-unresponsive NMIBC, focusing on alterations in monoamine oxidases (MAO-A and MAO-B) and immune markers: CD163, FOXP3, CD8, and CX3CR1. A comparative analysis of immunoreactivities was made before and after OncoTherad® treatment and an immune score (IS) was established to evaluate the correlation between immunological changes and clinical outcomes. Forty bladder biopsies of twenty patients were divided into 2 groups (n = 20/group): 1 (pre-treatment biopsies); and 2 (post-treatment biopsies). Our results showed stable MAO-A levels but a significant (p < 0.05) decrease in MAO-B immunoreactivity after treatment, suggesting OncoTherad®'s efficacy in targeting the tumor-promoting and immunosuppressive functions of MAO-B. Significant (p < 0.05) reductions in CD163 and FOXP3 immunoreactivities were seen in post-treatment biopsies, indicating a decreased presence of M2 macrophages and Tregs. Corroborating with these results, we observed reductions in tumor histological grading, focality and size, factors that collectively enhanced recurrence-free survival (RFS) and pathological complete response (PCR). Moreover, elevated IFN-γ immunoreactivities in treated biopsies correlated with increased counts of CD8+ T cells and higher CX3CR1 expression, underscoring OncoTherad®'s enhancement of cytotoxic T cell functionality and overall antitumor immunity. The IS revealed improvements in immune responses post-treatment, with higher scores associated with better RFS and PCR outcomes. These findings validate OncoTherad®'s capability to modify the bladder cancer microenvironment favorably, promoting effective immune surveillance and response.

Responsible ownership and health education can reduce the time of sporotrichosis treatment in domestic cats.

Sporotrichosis is a widespread fungal infection that affects skin and subcutaneous tissues in humans and animals. In cats, it is displayed as nodules, ulcers and lesions on the nasal and respiratory mucosa. Antifungal treatment of cats is crucial but many cases are difficult, thus resulting in discontinue of the treatment, with disastrous consequences for the animal, encouraging contamination of the environment, other animals and people. The effects of responsible ownership education and health education for owners of cats with feline sporotrichosis as well as the interval between veterinary consultations on treatment outcomes for three groups of owners and their pet cats were evaluated in this study. The responsible ownership education and health education strategies consisted in videos in easy and accessible language for people with any level of education and were presented during consultations for two of the three groups included. The time between appointments was two weeks for two of the groups, and four weeks for one of the groups. The median of treatment time for the group without educational activities was 138 days, while for the other two groups it was 77.5 days and 86 days. It was found a significative reduction in the treatment time in the groups exposed to Responsible ownership education videos. There was no contamination of those responsible for home treatment, and the interval between monthly appointments did not impact on cure or death rates compared to the interval between fortnightly appointments. All these results can be applied to feline sporotrichoses treatment protocols increasing the owners treatment adherence and reducing either, the treatment discontinuation and the treatment costs and helps to control zoonotic sporotrichosis. The importance of attractive and comprehensible educational strategies as part of the feline sporotrichosis treatment protocol for the promotion of one health was highlighted.

Itraconazole in human medicine and veterinary practice.

Diagnosis and management of fungal infections are challenging in both animals and humans, especially in immunologically weakened hosts. Due to its broad spectrum and safety profile when compared to other antifungals, itraconazole (ITZ) has been widely used in the treatment and prophylaxis of fungal infections, both in human and veterinary medicine. The dose and duration of management depend on factors such as the type of fungal pathogen, the site of infection, sensitivity to ITZ, chronic stages of the disease, the health status of the hosts, pharmacological interactions with other medications and the therapeutic protocol used. In veterinary practice, ITZ doses generally vary between 3 mg/kg and 50 mg/kg, once or twice a day. In humans, doses usually vary between 100 and 400 mg/day. As human and veterinary fungal infections are increasingly associated, and ITZ is one of the main medications used, this review addresses relevant aspects related to the use of this drug in both clinics, including case reports and different clinical aspects available in the literature.

Interferons are key cytokines acting on pancreatic islets in type 1 diabetes.

AIMS/HYPOTHESIS: The proinflammatory cytokines IFN-α, IFN-γ, IL-1ß and TNF-α may contribute to innate and adaptive immune responses during insulitis in type 1 diabetes and therefore represent attractive therapeutic targets to protect beta cells. However, the specific role of each of these cytokines individually on pancreatic beta cells remains unknown. METHODS: We used deep RNA-seq analysis, followed by extensive confirmation experiments based on reverse transcription-quantitative PCR (RT-qPCR), western blot, histology and use of siRNAs, to characterise the response of human pancreatic beta cells to each cytokine individually and compared the signatures obtained with those present in islets of individuals affected by type 1 diabetes. RESULTS: IFN-α and IFN-γ had a greater impact on the beta cell transcriptome when compared with IL-1ß and TNF-α. The IFN-induced gene signatures have a strong correlation with those observed in beta cells from individuals with type 1 diabetes, and the level of expression of specific IFN-stimulated genes is positively correlated with proteins present in islets of these individuals, regulating beta cell responses to 'danger signals' such as viral infections. Zinc finger NFX1-type containing 1 (ZNFX1), a double-stranded RNA sensor, was identified as highly induced by IFNs and shown to play a key role in the antiviral response in beta cells. CONCLUSIONS/INTERPRETATION: These data suggest that IFN-α and IFN-γ are key cytokines at the islet level in human type 1 diabetes, contributing to the triggering and amplification of autoimmunity.

Effects of probiotic supplementation on chronic inflammatory process modulation in colorectal carcinogenesis.

The current study investigated the potential effects of probiotic supplementation on colorectal carcinogenesis chemically induced with 1,2-dimethylhydrazine (DMH) and treated with 5-fluorouracil (5FU)-based chemotherapy in mice. Animals were randomly allocated in five different groups: Control: which not receive any treatment throughout the experimental course; Colitis model group (DMH): treated with DMH; DMH+ 5FU: animals received I.P. (intraperitoneal) dose of chemotherapy on a weekly basis; DMH+PROB: animals received daily administrations (via gavage) of probiotics (Lactobacillus: acidophilus and paracasei, Bifidobacterium lactis and bifidum); and DMH+ PROB+ 5FU: animals received the same treatment as the previous groups. After ten-week treatment, mice's large intestine was collected and subjected to colon length, histopathological, periodic acid-schiff (PAS) staining and immunohistochemistry (TLR2, MyD88, NF-κB, IL-6, TLR4, TRIF, IRF-3, IFN-γ, Ki-67, KRAS, p53, IL-10, and TGF-ß) analyzes. Variance (ANOVA) and Kruskal-Wallis tests were used for statistical analysis, at significance level p 0.05. Probiotics' supplementation has increased the production of Ki-67 cell-proliferation marker, reduced body weight, and colon shortening, as well as modulated the chronic inflammatory process in colorectal carcinogenesis by inhibiting NF-κB expression and mitigating mucin depletion. Thus, these findings lay a basis for guide future studies focused on probiotics' action mechanisms in tumor microenvironment which might have implications in clinical practice.

OncoTherad® (MRB-CFI-1) Nanoimmunotherapy: A Promising Strategy to Treat Bacillus Calmette-Guérin-Unresponsive Non-Muscle-Invasive Bladder Cancer: Crosstalk among T-Cell CX3CR1, Immune Checkpoints, and the Toll-Like Receptor 4 Signaling Pathway.

This study assessed the safety and efficacy of OncoTherad® (MRB-CFI-1) nanoimmunotherapy for non-muscle invasive bladder cancer (NMIBC) patients unresponsive to Bacillus Calmette-Guérin (BCG) and explored its mechanisms of action in a bladder cancer microenvironment. A single-arm phase I/II study was conducted with 44 patients with NMIBC who were unresponsive to BCG treatment. Primary outcomes were pathological complete response (pCR) and relapse-free survival (RFS). Secondary outcomes comprised response duration and therapy safety. Patients' mean age was 65 years; 59.1% of them were refractory, 31.8% relapsed, and 9.1% were intolerant to BCG. Moreover, the pCR rate after 24 months reached 72.7% (95% CI), whereas the mean RFS reached 21.4 months. Mean response duration in the pCR group was 14.3 months. No patient developed muscle-invasive or metastatic disease during treatment. Treatment-related adverse events occurred in 77.3% of patients, mostly grade 1-2 events. OncoTherad® activated the innate immune system through toll-like receptor 4, leading to increased interferon signaling. This activation played a crucial role in activating CX3CR1+ CD8 T cells, decreasing immune checkpoint molecules, and reversing immunosuppression in the bladder microenvironment. OncoTherad® has proved to be a safe and effective therapeutic option for patients with BCG-unresponsive NMIBC, besides showing likely advantages in tumor relapse prevention processes.

A novel therapeutic strategy for non-muscle invasive bladder cancer: OncoTherad® immunotherapy associated with platelet-rich plasma.

Patients with non-muscle invasive bladder cancer (NMIBC) that are unresponsive to Bacillus Calmette-Guérin (BCG) have historically had limited treatment options. A new perspective is represented by OncoTherad® (MRB-CFI-1) immunotherapy, a nanostructured inorganic phosphate complex associated with glycosidic protein, developed by the University of Campinas in Brazil. Previous studies have shown that Platelet-Rich Plasma (PRP) also acts on immune activation and exerts antitumor effects. This study characterized the effects of the OncoTherad® associated with PRP in the treatment of NMIBC chemically induced in mice. When treated intravesically with PRP only, mice showed 28.6% of tumor progression inhibition rate; with OncoTherad® 85.7%; and with OncoTherad®+PRP 71.4%. Intravesical treatments led to distinct activation of Toll-like Receptors (TLRs) 2 and 4-mediated innate immune system in the interleukins (canonical) and interferons (non-canonical) signaling pathways. OncoTherad® isolated or associated with PRP upregulated TLR4 and its downstream cascade mediators as well as increased interleukins 6 (IL-6) and 1ß (IL-1ß), and interferon-γ (IFN-γ). In this way, the NMIBC microenvironment was modulated to a cytotoxic profile correlated with the IL-1ß increase by stimulating immune pathways for IFN-γ production and consequent cytotoxic T lymphocytes (as CD8+ T-cells) activation and regulatory T-cells (Tregs) reduction. In addition, PRP did not trigger carcinogenic effects through the biomarkers evaluated. Considering the possibility of personalizing the treatment with the PRP use as well as the antitumor properties of OncoTherad®, we highlight this association as a potential new therapeutic strategy for NMIBC, mainly in cases of relapse and/or resistance to BCG.

Genomic Surveillance of SARS-CoV-2 in Healthcare Workers: A Critical Sentinel Group for Monitoring the SARS-CoV-2 Variant Shift.

SARS-CoV-2 genome surveillance is important for monitoring risk groups and health workers as well as data on new cases and mortality rate due to COVID-19. We characterized the circulation of SARS-CoV-2 variants from May 2021 to April 2022 in the state of Santa Catarina, southern Brazil, and evaluated the similarity between variants present in the population and healthcare workers (HCW). A total of 5291 sequenced genomes demonstrated the circulation of 55 strains and four variants of concern (Alpha, Delta, Gamma and Omicron-sublineages BA.1 and BA.2). The number of cases was relatively low in May 2021, but the number of deaths was higher with the Gamma variant. There was a significant increase in both numbers between December 2021 and February 2022, peaking in mid-January 2022, when the Omicron variant dominated. After May 2021, two distinct variant groups (Delta and Omicron) were observed, equally distributed among the five Santa Catarina mesoregions. Moreover, from November 2021 to February 2022, similar variant profiles between HCW and the general population were observed, and a quicker shift from Delta to Omicron in HCW than in the general population. This demonstrates the importance of HCW as a sentinel group for monitoring disease trends in the general population.

Analysis of false positive PI-RADS 4 lesions: experience from a single nonacademic center using cognitive fusion.

BACKGROUND: We evaluated pathological findings in targeted biopsies of PI-RADS4 and PI-RADS5 lesions, and clinical data that could predict those patients with benign findings. MATERIALS AND METHODS: A retrospective study was conducted to summarize the experience from a single nonacademic center using cognitive fusion and a 1.5 or 3.0 Tesla scanner. RESULTS: We found a false positive rate of 29 and 3.7% for any cancer in PI-RADS 4 and 5 lesions, respectively. Diverse histologic patterns were observed among target biopsies. At multivariate analysis, size ≤ 6 mm and previous negative biopsy were independent predictors of false positive PI-RADS4 lesions. The small number of false PI-RADS5 lesions precluded further analyses. CONCLUSION: Benign findings are common in PI-RADS4 lesions and most of them do not show obvious glandular or stromal hypercellularity as expected in hyperplastic nodules. Size ≤ 6 mm and previous negative biopsy predict a higher probability of false positive results in patients with PI-RADS 4 lesions.

Topical hydrophilic gel with itraconazole-loaded polymeric nanomicelles improves wound healing in the treatment of feline sporotrichosis.

Sporotrichosis is a superficial fungal disease that can affect animals and humans. The high number of infected cats has been associated with zoonotic transmission and contributed to sporotrichosis being considered by the World Health Organization as one of the main neglected tropical fungal diseases for 2021-2030. Oral administration of itraconazole (ITZ) is the first choice for treatment, but it is expensive, time-consuming, and often related to serious adverse effects. As a strategy to optimize the treatment, we proposed the development of a hydrophilic gel with nanomicelles loaded with ITZ (HGN-ITZ). The HGN-ITZ was developed using an I-optimal design and characterized for particle size, Zeta potential, drug content, microscopic aspects, viscosity, spreadability, in vitro drug release, in vitro antifungal activity, and clinical evaluation in cats. The HGN-ITZ showed a high content of ITZ (97.3 ± 2.1 mg/g); and characteristics suitable for topical application (viscosity, spreadability, globules size, Zeta potential, controlled drug release). In a pilot clinical study, cats with disseminated sporotrichosis were treated with oral ITZ or HGN-ITZ + oral ITZ. A mortality rate of 21.3% was observed for the oral ITZ group compared to 5.3% for the HGN-ITZ + oral ITZ group. In a cat with a single lesion, topical treatment alone (HGN-ITZ) provided complete healing of the lesion in 45 days. No signs of topical irritation were observed during the treatments, suggesting that HGN-ITZ can be a promising strategy in the treatment of sporotrichosis.

OncoTherad® is an immunomodulator of biological response that downregulate RANK/RANKL signaling pathway and PD-1/PD-L1 immune checkpoint in non-muscle invasive bladder cancer.

INTODUCTION: Bladder cancer is the second most common urinary tract cancer. Above 70% of the occurrence of bladder cancer is superficial (pTis, pTa, and pT1), non-muscle invasive tumor (NMIBC), and the incidence of invasive disease is occasional. Treatments for NMIBC consist of transurethral resection (TUR) and subsequently intravesical immunotherapy with Bacillus Calmette-Guérin (BCG), intending to prevent tumor progression and decrease recurrence. However, 20-30% of these tumors have progression, and 70% have a recurrence after exclusive TUR treatment. The immunomodulator of biological response, OncoTherad®, is an attractive potential to revolutionize cancer therapy. In our previous studies with mice, the results showed that treatment with OncoTherad® reduced 100% of tumor progression in NMIBC through the activation of Toll-Like Receptors' non-canonical pathway. MATERIALS AND METHODS:  In the present study, 36 female C57Bl/6J mice were divided into 6 groups (n = 6/group): Control, Cancer, Cancer + BCG, Cancer + OncoTherad® (MRB-CFI-1), Cancer + P14-16 and Cancer + CFI-1. NMIBC was chemically induced and the treatments were followed for 6 weeks. A week after the last dose of treatment, animals were euthanized, the bladder was collected and routinely processed for immunohistochemical analyses of RANK, RANKL, FOXP3, and PD-1/PD-L1, such as PD-1/PD-L1 western blotting. CONCLUSION: The immunohistochemical results showed that OncoTherad® reduced RANK and RANKL immunoreactivities compared to the cancer group, which indicates a good prognosis. Immunohistochemical and western blotting analyses confirmed that OncoTherad® modulated PD-1/PD-L1 immune checkpoint.

Mining the transcriptome of target tissues of autoimmune and degenerative pancreatic ß-cell and brain diseases to discover therapies.

Target tissues of autoimmune and degenerative diseases show signals of inflammation. We used publicly available RNA-seq data to study whether pancreatic ß-cells in type 1 and type 2 diabetes and neuronal tissue in multiple sclerosis and Alzheimer's disease share inflammatory gene signatures. We observed concordantly upregulated genes in pairwise diseases, many of them related to signaling by interleukins and interferons. We next mined these signatures to identify therapies that could be re-purposed/shared among the diseases and identified the bromodomain inhibitors as potential perturbagens to revert the transcriptional signatures. We experimentally confirmed in human ß-cells that bromodomain inhibitors I-BET151 and GSK046 prevent the deleterious effects of the pro-inflammatory cytokines interleukin-1ß and interferon-γ and at least some of the effects of the metabolic stressor palmitate. These results demonstrate that key inflammation-induced molecular mechanisms are shared between ß-cells and brain in autoimmune and degenerative diseases and that these signatures can be mined for drug discovery.

Effects of combined OncoTherad immunotherapy and probiotic supplementation on modulating the chronic inflammatory process in colorectal carcinogenesis.

This study evaluated the effects of combined OncoTherad immunotherapy and probiotic supplementation on colorectal carcinogenesis chemically induced with 1,2-dimethylhydrazine (DMH) in mice. The animals were randomly allocated in five groups: Control, DMH: did not receive any treatment; DMH + OncoTherad: received weekly I.P. (intraperitoneal) dose of OncoTherad; DMH + Probiotic: received daily administrations via gavage of the functional food (Lactobacillus: acidophilus and paracasei, Bifidobacterium: lactis and bifidum) and DMH + Probiotic + OncoTherad: received the same treatment than the previous groups. After ten weeks of treatment, the large intestine was collected for immunohistochemical analysis of TLR4, MyD88, NF-κB, IL-6, TLR2, TRIF, IRF-3, IFN-γ, Ki-67, KRAS, IL-10, and TGF-ß. For the statistical analysis, the variance tests (ANOVA) and Kruskal-Wallis were used and significance set at p < 0.05. Probiotic supplementation associated with the OncoTherad were able to modulate weight loss, stimulate the canonical signaling pathway TLR2/TLR4 (MyD88-dependent), reduce the non-canonical signaling pathway (TRIF-dependent), attenuate the proliferative pathway mediated by Ki-67 and KRAS oncogene, and stimulate the production of IL-10 and TGF-ß cytokines. Thus, the association of OncoTherad and probiotic supplementation has shown important immudomulatory effects and could be considered a potential new therapeutic approach for colorectal cancer after further investigations.

Blueberry Consumption and Changes in Obesity and Diabetes Mellitus Outcomes: A Systematic Review.

Low-grade inflammation and oxidative stress are key mechanisms involved in obesity and related disorders. Polyphenols from blueberry (BB) and bilberries (BiB) might protect against oxidative damage and inflammation. To summarize the effects of BiB or BB consumption in parameters related to obesity and its comorbidities, a search of the literature was performed in PubMed, Embase, and Cochrane Library repositories to identify all studies that evaluated associations of whole BB or BiB with obesity and associated disorders. Thirty-one studies were eligible for inclusion in this review: eight clinical trials and 23 animal studies. In humans, BB consumption only consistently decreased oxidative stress and improved endothelial function. In rodents, BB or BiB consumption caused positive effects on glucose tolerance, nuclear factor-kappa B (Nf-κb) activity, oxidative stress, and triglyceride (TG) content in the liver and hepatic steatosis. The high content of anthocyanins present in BB and BiB seems to attenuate oxidative stress. The decrease in oxidative stress may have a positive impact on glucose tolerance and endothelial function. Moreover, in rodents, these berries seem to protect against hepatic steatosis, through the decreased accumulation of hepatic TGs. BB and BiB might also attenuate inflammation by decreasing Nf-κb activity and immune cell recruitment into the adipose tissue.

Association between healthy food environment and metabolic syndrome, waist circumference, and systolic blood pressure in older adults in Southern Brazil.

The aim of this study was to investigate the association between healthy food outlet proximity, metabolic syndrome (MS), and two of its components, waist circumference (WC) and systolic blood pressure (SBP), in older adults (63-107 years old, median age 73 years) living in Florianópolis, South Brazil in 2013-2014. This is a cross-sectional analysis of the second wave of the EpiFloripa Aging Cohort Study. Individual-level data on MS, WC, SBP, and socio-demographic and health-related characteristics were collected from face to face interviews. The healthy food environment was assessed via the number and types of establishments present. The residences of older adult participants were georeferenced using Geographical Information System (GIS) software. The number of each type of food establishment in a 500 m buffer around the each residence was determined. Multivariate linear regression was used to test association between food outlet proximity and continuous outcomes (SBP and WC), and multiple logistic regression was used to examine the relations between the predictor variables and the dichotomous outcome of MS (yes/no). The study revealed that greater frequency of supermarkets and restaurants in the neighborhood was associated with a lower likelihood of having MS. WC was lower in individuals living in places with greater availability of greengrocers' shops and restaurants. The results demonstrated that the number of establishments in a neighborhood is associated with cardiometabolic outcomes, and the likelihood of MS and increased WC is lower for older adults who live in neighborhoods with more access to establishments that sell foundational components of a healthy diet.

In-office bleaching protocols using violet LED: A split mouth case report.

A new LED wavelength, violet LED (VL) with a wavelength between 405 - 410 nm was recently introduced to be used for in-office dental bleaching. In comparison to the blue LED system (440 to 485 nm), the shorter wavelength has more energy carried in its photons and also corresponds to the absorption peak of the stained particles, which lead to whitening utilizing a physical process. Considering the need to suggest and develop new protocols with this new technology, this article reports 2 different dental bleaching protocols developed in a split-mouth model using VL. A 25-year-old male patient was submitted to in-office dental bleaching. On the teeth from the left side, the bleaching gel (35% H2O2) was renewed 3 times (every 8 mins), and on the right side, the gel was maintained without renewal during the bleaching session. The irradiation with Violet LED Light (405 nm ± 10 nm) was performed with the following protocol: 1 min of irradiation with 30 s light off until 8 min of total time. A total of 3 cycles were performed (total time of 24 min). Two bleaching sessions were performed with an interval of 7 days between sessions. Based on the results of this split-mouth case report, there was no visible difference in the final color outcome and sensitivity between both bleaching protocols tested.

A functional genomic approach to identify reference genes for human pancreatic beta cell real-time quantitative RT-PCR analysis.

Exposure of human pancreatic beta cells to pro-inflammatory cytokines or metabolic stressors is used to model events related to type 1 and type 2 diabetes, respectively. Quantitative real-time PCR is commonly used to quantify changes in gene expression. The selection of the most adequate reference gene(s) for gene expression normalization is an important pre-requisite to obtain accurate and reliable results. There are no universally applicable reference genes, and the human beta cell expression of commonly used reference genes can be altered by different stressors. Here we aimed to identify the most stably expressed genes in human beta cells to normalize quantitative real-time PCR gene expression.We used comprehensive RNA-sequencing data from the human pancreatic beta cell line EndoC-ßH1, human islets exposed to cytokines or the free fatty acid palmitate in order to identify the most stably expressed genes. Genes were filtered based on their level of significance (adjusted P-value >0.05), fold-change (|fold-change| <1.5) and a coefficient of variation <10%. Candidate reference genes were validated by quantitative real-time PCR in independent samples.We identified a total of 264 genes stably expressed in EndoC-ßH1 cells and human islets following cytokines - or palmitate-induced stress, displaying a low coefficient of variation. Validation by quantitative real-time PCR of the top five genes ARF1, CWC15, RAB7A, SIAH1 and VAPA corroborated their expression stability under most of the tested conditions. Further validation in independent samples indicated that the geometric mean of ACTB and VAPA expression can be used as a reliable normalizing factor in human beta cells.

The rs2304256 Polymorphism in TYK2 Gene Is Associated with Protection for Type 1 Diabetes Mellitus.

BACKGROUND: Tyrosine kinase 2 (TYK2) is a candidate gene for type 1 diabetes mellitus (T1DM) since it plays an important role in regulating apoptotic and pro-inflammatory pathways in pancreatic ß-cells through modulation of the type I interferon signaling pathway. The rs2304256 single nucleotide polymorphism (SNP) in TYK2 gene has been associated with protection for different autoimmune diseases. However, to date, only two studies have evaluated the association between this SNP and T1DM, with discordant results. This study thus aimed to investigate the association between the TYK2 rs2304256 SNP and T1DM in a Southern Brazilian population. METHODS: This case-control study comprised 478 patients with T1DM and 518 non-diabetic subjects. The rs2304256 (C/A) SNP was genotyped by real-time polymerase chain reaction technique using TaqMan minor groove binder (MGB) probes. RESULTS: Genotype and allele frequencies of the rs2304256 SNP differed between T1DM patients and non-diabetic subjects (P<0.0001 and P=0.001, respectively). Furthermore, the A allele was associated with protection against T1DM under recessive (odds ratio [OR], 0.482; 95% confidence interval [CI], 0.288 to 0.806) and additive (OR, 0.470; 95% CI, 0.278 to 0.794) inheritance models, adjusting for human leukocyte antigen (HLA) DR/DQ genotypes, gender, and ethnicity. CONCLUSION: The A/A genotype of TYK2 rs2304256 SNP is associated with protection against T1DM in a Southern Brazilian population.

-866G/A and Ins/Del polymorphisms in UCP2 gene are associated with reduced short-term weight loss in patients who underwent Roux-en-Y gastric bypass.

BACKGROUND: Uncoupling protein 2 (UCP2) plays an important role in energy expenditure regulation. Previous studies have associated the common -866G/A (rs659366) and Ins/Del polymorphisms in the UCP2 gene with metabolic and obesity-related phenotypes. However, it is still unclear whether these polymorphisms influence weight loss after bariatric surgery. OBJECTIVES: To investigate whether UCP2 -866G/A and Ins/Del polymorphisms are associated with weight loss outcomes after bariatric surgery. SETTING: Longitudinal study in a university hospital. METHODS: We retrospectively evaluated 186 patients who underwent Roux-en-Y gastric bypass (RYGB) surgery for clinical and laboratory characteristics in the preoperative period, 6, 12, and 18 months after RYGB. The -866G/A (rs659366) polymorphism was genotyped using real-time PCR, while the Ins/Del polymorphism was genotyped by direct separation of PCR products in 2.5% agarose gels. RESULTS: Patients with the -866A/A genotype showed higher body mass index (BMI) after 6, 12, and 18 months of surgery and excess body weight after 6 and 12 months compared with G/G patients. They also showed lower excess weight loss (EWL%) after 6 and 12 months of surgery. Ins allele carriers (Ins/Ins + Ins/Del) had lower delta (Δ) BMI 12 months after surgery compared with Del/Del patients. Accordingly, patients carrying haplotypes with ≥2 risk alleles of these polymorphisms had higher BMI and excess weight and lower EWL% during follow-up. CONCLUSION: UCP2 -866A/A genotype is associated with higher BMI and excess weight and lower EWL% during an 18-month follow-up of patients who underwent RYGB, while the Ins allele seems to be associated with lower ΔBMI 12 months after surgery. Further studies are needed to confirm the associations of the -866G/A and Ins/Del polymorphisms with weight loss after bariatric surgery.

Factors associated with preschool children's sleep bruxism.

Objective: To evaluate the prevalence of sleep bruxism, related factors, and quality of life of preschool children and their families.Method: The sample was 475 children between 4 and 5 years old enrolled in schools in the city of Bauru-Brazil. Parents/legal guardians answered two questionnaires, one to assess the presence of bruxism and related factors and another that was the validated Brazilian version of the Early Childhood Oral Health Impact Scale (B-ECOHIS). Intraoral clinical examination was performed by two trained examiners (Kappa = 0.82) within the school environment. The data were analyzed using statistics and the Mann-Whitney, Kruskal-Wallis, and Spearman correlation coefficient. The significance level was p < 0.05.Results:The prevalence of sleep bruxism was 47.4%. The highest prevalence was related to Class I canines and marked overjet, oral habits, such as nail biting, lip biting, chewing gum, and mouth breathing. Children with agitated sleep, reports of headache, and those considered aggressive, anxious, and/or shy were also more related.Conclusion: In the studied sample, sleep bruxism prevalence was high and related to important oral and general factors. Data also indicated SB as the main factor that interfered in the OHRQoL of children and their families.