Hippocampal acetylcholinesterase activation induced by streptozotocin in mice is protected by an organotellurium compound without evidence of toxicity.

The cognitive deficit, which is like Alzheimer's disease and is associated with oxidative damage, may be induced by exposure to streptozotocin. This study aimed to evaluate if the tellurium-containing organocompound, 3j, 5'-arylchalcogeno-3-aminothymidine derivative, interferes with the effects of streptozotocin, as well as to investigate its toxicity in adult mice. Cognitive deficit was induced by two doses of streptozotocin (2.25 mg/kg/day, 48 h interval) intracerebroventricularly. After, the mice were subcutaneously treated with 3j (8.62 mg/kg/day) for 25 days. The effects were assessed by evaluating hippocampal and cortical acetylcholinesterase and behavioral tasks. 3j toxicity was investigated for 10 (0, 21.55, or 43.10 mg/kg/day) and 37 (0, 4.31, or 8.62 mg/kg/day) days by assessing biometric parameters and glucose and urea levels, and alanine aminotransferase activity in blood plasma. 3j exposure did not alter the behavioral alterations induced by streptozotocin exposure. On the other hand, 3j exposure normalized hippocampus acetylcholinesterase activity, which is enhanced by streptozotocin exposure. Toxicity evaluation showed that the administration of 3j for either 10 or 37 days did not cause harmful effects on the biometric and biochemical parameters analyzed. Therefore, 3j does not present any apparent toxicity and reverts acetylcholinesterase activity increase induced by streptozotocin in young adult mice.

The effect of oral dietary interventions on nutritional status and treatment tolerance in patients with hematologic neoplasms receiving chemotherapy: a systematic review.

CONTEXT: Adverse events from chemotherapy treatment affect food intake, nutritional status, and treatment tolerance in cancer patients. However, the effect of nutritional intervention in patients with hematologic neoplasms receiving chemotherapy remains unknown. OBJECTIVE: The aim of this systematic review was to evaluate the evidence on nutritional interventions on nutritional status, treatment tolerance, inflammatory markers, quality of life, and mortality in patients with hematologic neoplasms receiving chemotherapy. DATA SOURCES: The MEDLINE, LILACS, CINAHL, Web of Science, Embase, ICTRP, CENTRAL, and ClinicalTrials.gov databases were searched. Additional literature and the bibliographies of identified articles were also considered. DATA EXTRACTION: Randomized controlled trials in individuals with hematologic neoplasms receiving chemotherapy along with nutritional counseling and oral nutritional supplementation, and intake of supplementary food products, alone or in combination, were assessed as criteria of interest. The data were extracted independently by 2 researchers. The risk of bias was assessed through the Cochrane risk-of-bias tool (RoB 2). DATA ANALYSIS: Ten studies were included up to August 15, 2022 (updated in November of 2022). With regard to the outcomes, 4 studies assessed nutritional status and 2 studies showed a positive result of the intervention on some of the markers. Seven studies assessed certain markers of treatment tolerance and only 2 studies showed improvement in the outcome after the intervention. CONCLUSION: The studies that found positive results are quite different from each other in terms of intervention, study time, and design. More randomized controlled trials are needed to test different dietary interventions using placebo and blinding, when possible, and with reduced sample variability in individuals with hematologic neoplasms receiving chemotherapy. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020196765.

TACkling Cancer by Targeting Selective Protein Degradation.

Targeted protein degradation has emerged as an alternative therapy against cancer, offering several advantages over traditional inhibitors. The new degrader drugs provide different therapeutic strategies: they could cross the phospholipid bilayer membrane by the addition of specific moieties to extracellular proteins. On the other hand, they could efficiently improve the degradation process by the generation of a ternary complex structure of an E3 ligase. Herein, we review the current trends in the use of TAC-based technologies (TACnologies), such as PROteolysis TArgeting Chimeras (PROTAC), PHOtochemically TArgeting Chimeras (PHOTAC), CLIck-formed Proteolysis TArgeting Chimeras (CLIPTAC), AUtophagy TArgeting Chimeras (AUTAC), AuTophagosome TEthering Compounds (ATTEC), LYsosome-TArgeting Chimeras (LYTAC), and DeUBiquitinase TArgeting Chimeras (DUBTAC), in experimental development and their progress towards clinical applications.

Genetic Modulation of HPV Infection and Cervical Lesions: Role of Oxidative Stress-Related Genes.

Human papillomavirus (HPV) infection is a necessary but not sufficient factor for the development of invasive cervical cancer (ICC) and high-grade intraepithelial lesion (HSIL). Oxidative stress is known to play a crucial role in HPV infection and carcinogenesis. In this study, we comprehensively investigate the modulation of HPV infection, HSIL and ICC, and ICC through an exploration of oxidative stress-related genes: CßS, MTHFR, NOS3, ACE1, CYBA, HAP, ACP1, GSTT1, GSTM1, and CYP1A1. Notably, the ACE1 gene emerges as a prominent factor with the presence of the I allele offering protection against HPV infection. The association of NOS3 with HPV infection is perceived with the 4a allele showing a protective effect. The presence of the GSTT1 null mutant correlates with increased susceptibility to HPV infection, HSIL and ICC, and ICC. This study also uncovers intriguing epistatic interactions among some of the genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the BB genotype (ACP1) and DD genotype (ECA1) were shown to increase the risk of HPV infection, and the interaction between BB (ACP1) and 0.0 (GSTT1) was associated with HPV infection and cervical lesions. These findings underscore the pivotal role of four oxidative stress-related genes in HPV-associated cervical lesions and cancer development, enriching our clinical understanding of the genetic influences on disease manifestation. The awareness of these genetic variations holds potential clinical implications.

Antiviral Effect of 5'-Arylchalcogeno-3-aminothymidine Derivatives in SARS-CoV-2 Infection.

The understanding that zidovudine (ZDV or azidothymidine, AZT) inhibits the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 and that chalcogen atoms can increase the bioactivity and reduce the toxicity of AZT has directed our search for the discovery of novel potential anti-coronavirus compounds. Here, the antiviral activity of selenium and tellurium containing AZT derivatives in human type II pneumocytes cell model (Calu-3) and monkey kidney cells (Vero E6) infected with SARS-CoV-2, and their toxic effects on these cells, was evaluated. Cell viability analysis revealed that organoselenium (R3a-R3e) showed lower cytotoxicity than organotellurium (R3f, R3n-R3q), with CC50 ≥ 100 µM. The R3b and R3e were particularly noteworthy for inhibiting viral replication in both cell models and showed better selectivity index. In Vero E6, the EC50 values for R3b and R3e were 2.97 ± 0.62 µM and 1.99 ± 0.42 µM, respectively, while in Calu-3, concentrations of 3.82 ± 1.42 µM and 1.92 ± 0.43 µM (24 h treatment) and 1.33 ± 0.35 µM and 2.31 ± 0.54 µM (48 h) were observed, respectively. The molecular docking calculations were carried out to main protease (Mpro), papain-like protease (PLpro), and RdRp following non-competitive, competitive, and allosteric inhibitory approaches. The in silico results suggested that the organoselenium is a potential non-competitive inhibitor of RdRp, interacting in the allosteric cavity located in the palm region. Overall, the cell-based results indicated that the chalcogen-zidovudine derivatives were more potent than AZT in inhibiting SARS-CoV-2 replication and that the compounds R3b and R3e play an important inhibitory role, expanding the knowledge about the promising therapeutic capacity of organoselenium against COVID-19.

Transferrin-Decorated PLGA Nanoparticles Loaded with an Organoselenium Compound as an Innovative Approach to Sensitize MDR Tumor Cells: An In Vitro Study Using 2D and 3D Cell Models.

Multidrug resistance (MDR) is the main challenge in cancer treatment. In this sense, we designed transferrin (Tf)-conjugated PLGA nanoparticles (NPs) containing an organoselenium compound as an alternative to enhance the efficacy of cancer therapy and sensitize MDR tumor cells. Cytotoxicity studies were performed on different sensitive tumor cell lines and on an MDR tumor cell line, and the Tf-conjugated NPs presented significantly higher antiproliferative activity than the nontargeted counterparts in all tested cell lines. Due to the promising antitumor activity of the Tf-decorated NPs, further studies were performed using the MDR cells (NCI/ADR-RES cell line) comparatively to one sensitive cell line (HeLa). The cytotoxicity of NPs was evaluated in 3D tumor spheroids and, similarly to the results achieved in the 2D assays, the Tf-conjugated NPs were more effective at reducing the spheroid's growth. The targeted Tf-NPs were also able to inhibit tumor cell migration, presented a higher cell internalization and induced a greater number of apoptotic events in both cell lines. Therefore, these findings evidenced the advantages of Tf-decorated NPs over the nontargeted counterparts, with the Tf-conjugated NPs containing an organoselenium compound representing a promising drug delivery system to overcome MDR and enhance the efficacy of cancer therapy.

Reinfection by SARS-CoV-2 by divergent Omicron sublineages, 16 days apart.

Since the beginning of the SARS-CoV-2 pandemic, studies on the variants and sublineages stand out, mainly in the cases of reinfection in a short period. In this study, we describe a case of infection by BA.1.1 sublineage in an individual from Southern Brazil. The same patient acquired reinfection with sublineage BA.2 within 16 days after the first detection. The viral extraction and RT-qPCR were performed on the samples LMM72045 (collected in May 2022) and LMM72044 (collected in June 2022). After the confirmation of SARS-CoV-2 infection, we conducted the sequencing and viral genome analysis. This case of reinfection affected a 52-year-old male patient, without comorbidities, with three doses of vaccines against COVID-19, showing symptoms on May 19. These symptoms lasted for approximately six days. The patient returned to work activities on May 30. However, on June 4, the patient felt a new round of clinical signs that lasted for approximately seven days. Analysis of the viral genomes recovered from patients' clinical samples revealed that the two COVID-19 episodes were related to two divergent VOC Omicron sublineages, namely, BA.1.1 for the first round of symptoms and BA.2 for the second infection. Based on our findings, we can say that the present case of reinfection is the shortest described so far.

Oropharyngeal dysphagia and quality of life in elderly people in the late phase after stroke / Disfagia orofaríngea e qualidade de vida em idosos após a fase tardia do acidente vascular encefálico

ABSTRACT Purpose: to verify the correlation between oropharyngeal dysphagia and quality of life in elderly people in the late phase after stroke. Methods: a retrospective cross-sectional study, whose data were obtained by analyzing a database composed of 30 elderly people in the late phase after stroke. All participants underwent clinical and instrumental evaluation of swallowing through the fiberoptic endoscopic evaluation of swallowing. The quality of life related to swallowing was analyzed using the Quality of Life in Swallowing Disorders protocol. Data were submitted to descriptive statistical analysis and Spearman's correlation test (p ≤ 0.05). Results: the clinical evaluation showed that most individuals had mild oropharyngeal dysphagia, while the protocol applied in the instrumental evaluation showed swallowing with functional limitations. There was a positive correlation between burden, eating desire, eating duration, and mental health with the severity of oropharyngeal dysphagia, both by clinical and instrumental evaluation; and between the symptom's frequency and the severity of dysphagia by clinical evaluation. Conclusion: there was a correlation between the severity of oropharyngeal dysphagia and the quality of life of elderly people in the late phase after stroke.

RESUMO Objetivo: verificar a correlação entre disfagia orofaríngea e qualidade de vida em idosos após a fase tardia do Acidente Vascular Encefálico. Métodos: estudo transversal retrospectivo, cujos dados foram obtidos pela análise de um banco de dados, composto por 30 idosos acometidos por Acidente Vascular Encefálico, em fase tardia. Todos os participantes foram submetidos a avaliação clínica e instrumental da deglutição, por meio da videoendoscopia da deglutição. A qualidade de vida relacionada à deglutição foi analisada pelo protocolo Quality of Life in Swallowing Disorders. Os dados foram submetidos à análise estatística descritiva e ao teste de correlação de Spearman (p ≤ 0,05). Resultados: a avaliação clínica evidenciou que a maioria dos indivíduos apresentou disfagia orofaríngea leve, enquanto a escala aplicada na avaliação instrumental demonstrou deglutição com limitações funcionais. Houve correlação positiva entre fardo, desejo de se alimentar, duração da alimentação e estado mental com a gravidade da disfagia orofaríngea, tanto pela avaliação clínica quanto instrumental; e entre a frequência dos sintomas e a gravidade da disfagia pela avaliação clínica. Conclusão: houve correlação entre a gravidade da disfagia orofaríngea e a qualidade de vida de idosos após a fase tardia do Acidente Vascular Encefálico.

Brief dispersion of a putative B.1.1.28-derived SARS-CoV-2 lineage harboring additional N234P and E471Q spike protein mutations in individuals crossing the Argentina-Brazil border.

BACKGROUND: SARS-CoV-2, the virus that causes COVID-19, is constantly mutating, leading to new variants that culminate in a temporal lineages fluctuation. B.1.1.28 lineage has been evolving in Brazil since February 2020 and originated P.1 (VOC), P.2 (VOI) and other P.Xs proposed as new variants. METHODS AND RESULTS: In this study, through the Illumina platform, we performed the whole-genome sequencing of 26 positive samples of SARS-CoV-2. Employing variant calling analysis on FASTQ reads and phylogenetic inference, we report a brief dispersion of a potentially new B.1.1.28-derived variant detected between 2021 May and June in individuals crossing the border between Brazil and Argentina, and local spread to inpatients from hospitals at the Rio Grande do Sul state capital (Porto Alegre). Besides, the Rio Grande do Sul State SARS-CoV-2 genomic epidemiological data was analyzed and showed an important B.1.1.28 peak in RS at the same period (May-June), even in the presence of a major Gamma wave. CONCLUSIONS: The emergence of a putative B.1.1.28-derived lineage was identified in travelers crossing Brazil-Argentina border representing an important peak of B.1.1.28 in RS State with a decreased in Gamma variant frequency in the same period of time.

Antitumoral Activity of a CDK9 PROTAC Compound in HER2-Positive Breast Cancer.

Cyclin-dependent kinases (CDKs) are a broad family of proteins involved in the cell cycle and transcriptional regulation. In this article, we explore the antitumoral activity of a novel proteolysis-targeting chimera (PROTAC) compound against CDK9. Breast cancer cell lines from different subtypes were used. Transcriptomic mapping of CDKs in breast cancer demonstrated that the expression of CDK9 predicted a detrimental outcome in basal-like tumors (HR = 1.51, CI = 1.08-2.11, p = 0.015) and, particularly, in the luminal B subtype with HER2+ expression (HR = 1.82, CI = 1.17-2.82, p = 0.0069). The novel CDK9 PROTAC, THAL-SNS-032, displayed a profound inhibitory activity in MCF7, T47D, and BT474 cells, with less effect in SKBR3, HCC1569, HCC1954, MDA-MB-231, HS578T, and BT549 cells. The three cell lines with HER2 overexpression and no presence of ER, SKBR3, HCC1569, and HCC1954 displayed an EC50 three times higher compared to ER-positive and dual ER/HER2-positive cell lines. BT474-derived trastuzumab-resistant cell lines displayed a particular sensitivity to THAL-SNS-032. Western blot analyses showed that THAL-SNS-032 caused a decrease in CDK9 levels in BT474, BT474-RH, and BT474-TDM1R cells, and a significant increase in apoptosis. Experiments in animals demonstrated an inverse therapeutic index of THAL-SNS-032, with doses in the nontherapeutic and toxic range. The identified toxicity was mainly due to an on-target off-tumor effect of the compound in the gastrointestinal epithelium. In summary, the potent and efficient antitumoral properties of the CDK9 PROTAC THAL-SNS-032 opens the possibility of using this type of compound in breast cancer only if specifically delivered to cancer cells, particularly in ER/HER2-positive and HER2-resistant tumors.

Pharyngeal bulb prosthesis and speech outcome in patients with cleft palate / Obturador faríngeo e resultados de fala em pacientes com fissura palatina

Abstract Introduction: Individuals with cleft palate can present with velopharyngeal dysfunction after primary palatoplasty and require a secondary treatment due to insufficiency. In these cases, the pharyngeal bulb prosthesis can be used temporarily while awaiting secondary surgery. Objective: This study aimed to investigate the outcome of treatment of hypernasality with pharyngeal bulb prosthesis in patients with history of cleft palate presenting with velopharyngeal insufficiency after primary palatal surgery. We hypothesized that the use of the pharyngeal bulb prosthesis is an effective approach to eliminate hypernasality related to velopharyngeal insufficiency in patients with cleft palate. Methods: Thirty speakers of Brazilian Portuguese (15 males and 15 females) with operated cleft palate, ages ranging from 6 to 14 years (mean: 9 years; SD = 1.87 years), participated in the study. All patients were fitted with a pharyngeal bulb prosthesis to manage velopharyngeal insufficiency while they were awaiting corrective surgery to be scheduled. Auditory-perceptual analysis of speech recorded in the conditions with and without pharyngeal bulb prosthesis were obtained from three listeners who rated the presence or absence of hypernasality for this study. Results: Seventy percent of the patients eliminated hypernasality while employing the pharyngeal bulb prosthesis, while 30% still presented with hypernasality. The comparison was statistically significant (p < 0.001). Conclusion: The use of the pharyngeal bulb prosthesis is an effective approach to eliminate hypernasality related to velopharyngeal insufficiency.

Resumo Introdução: Indivíduos com fissura palatina podem apresentar disfunção velofaríngea após a palatoplastia primária e necessitam de um secundário devido à insuficiência velofaríngea. Nesses casos, o obturador faríngeo pode ser usado temporariamente enquanto se aguarda uma cirurgia secundária. Objetivo: Investigar o resultado do tratamento da hipernasalidade com o uso de obturador faríngeo em pacientes com histórico de fissura palatina que apresentam insuficiência velofaríngea após a palatoplastia primária. Nossa hipótese é que o uso do obturador faríngeo seja uma abordagem eficaz para eliminar a hipernasalidade relacionada à insuficiência velofaríngea em pacientes com fissura palatina Método: Participaram do estudo 30 indivíduos falantes do Português Brasileiro (15 homens e 15 mulheres) com fissura palatina operada, de 6 a 14 anos de idade (média: 9 anos; DP = 1,87 anos). Todos os pacientes receberam obturador faríngeo para o tratamento da insuficiência velofaríngea, enquanto aguardavam vaga para a cirurgia secundária. A análise perceptivo-auditiva da fala, realizada nas condições com e sem obturador faríngeo, foi realizada por três ouvintes, quanto à presença e ausência da hipernasalidade. Resultados: 70% dos pacientes eliminaram a hipernasalidade de fala com o uso do obturador faríngeo, enquanto 30% não eliminaram. A comparação foi estatisticamente significante (p < 0,001). Conclusão: O uso temporário do obturador faríngeo é uma abordagem efetiva para eliminar a hipernasalidade decorrente da insuficiência velofaríngea.

Pharyngeal bulb prosthesis and speech outcome in patients with cleft palate.

INTRODUCTION: Individuals with cleft palate can present with velopharyngeal dysfunction after primary palatoplasty and require a secondary treatment due to insufficiency. In these cases, the pharyngeal bulb prosthesis can be used temporarily while awaiting secondary surgery. OBJECTIVE: This study aimed to investigate the outcome of treatment of hypernasality with pharyngeal bulb prosthesis in patients with history of cleft palate presenting with velopharyngeal insufficiency after primary palatal surgery. We hypothesized that the use of the pharyngeal bulb prosthesis is an effective approach to eliminate hypernasality related to velopharyngeal insufficiency in patients with cleft palate. METHODS: Thirty speakers of Brazilian Portuguese (15 males and 15 females) with operated cleft palate, ages ranging from 6 to 14 years (mean: 9 years; SD = 1.87 years), participated in the study. All patients were fitted with a pharyngeal bulb prosthesis to manage velopharyngeal insufficiency while they were awaiting corrective surgery to be scheduled. Auditory-perceptual analysis of speech recorded in the conditions with and without pharyngeal bulb prosthesis were obtained from three listeners who rated the presence or absence of hypernasality for this study. RESULTS: Seventy percent of the patients eliminated hypernasality while employing the pharyngeal bulb prosthesis, while 30% still presented with hypernasality. The comparison was statistically significant (p < 0.001). CONCLUSION: The use of the pharyngeal bulb prosthesis is an effective approach to eliminate hypernasality related to velopharyngeal insufficiency.

Breathing pattern, orthognathic surgery and head posture in dentofacial deformity / Padrão respiratório, cirurgia ortognática e postura de cabeça na deformidade dentofacial

Abstract Introduction: Dentofacial deformity (DFD) and the breathing mode can change the head posture. However, head posture changes after orthognathic surgery are controversial, and no studies were found on the relationship between the head posture and breathing mode in adults with DFD. Objective: To identify the main head posture changes in young adults affected by DFD, to verify if orthognathic surgery modifies the breathing mode and head posture, and if the breathing mode is associated with the head posture. Methods: Twenty-five young adults were assessed and divided in dentofacial deformity group (DFD; n = 15; x̅ = 28 years) and control group with dentofacial harmony (CG; n = 10; balanced by gender and age with the study group). Breathing mode was evaluated according to the orofacial myofunctional evaluation protocol, and biophotogrammetry was used in the head posture analyses. For the DFD group, the evaluations were performed pre and post the orthognathic surgery (pre- and post-DFD). Results: For the DFD group, the breathing mode modified after orthognathic surgery (p = 0.003), but with difference from GC (p = 0.027). No changes were found in head posture after orthognathic surgery, but significant difference was seen between post-DFD and GC for head inclination (p = 0.017). No relationship was observed between breathing mode and head posture (p > 0.05). Conclusion: After orthognathic surgery, a spontaneous improvement of breathing was seen in the sample. It was not possible to verify changes in head posture and association with breathing mode and head posture.

Resumo Introdução: A deformidade dentofacial (DDF) e o modo respiratório podem alterar a postura de cabeça. Entretanto as modificações da postura de cabeça após a cirurgia ortognática são controversas e não foram encontrados estudos que apontassem relação entre a postura de cabeça e o modo respiratório em adultos com DDF. Objetivo: Identificar as principais alterações na postura de cabeça em adultos jovens com DDF, verificar se a cirurgia ortognática altera o modo respiratório e a postura de cabeça e se o modo respiratório está associado com a postura de cabeça. Métodos: Foram avaliados 25 jovens adultos, os quais foram divididos no grupo deformidade dentofacial (DDF; n = 15; x̅ = 28 anos) e grupo controle com harmonia dentofacial (GC; n = 10; equilibrados por gênero e idade com o grupo de estudo). O modo respiratório foi analisado de acordo com o protocolo de avaliação miofuncional orofacial e a postura de cabeça foi avaliada por meio da biofotogrametria. Para o grupo DDF, as avaliações foram realizadas antes e após a cirurgia ortognática (pré e pós-DDF). Resultados: Para o grupo DDF, o modo respiratório se modificou após a cirurgia ortognática (p = 0,003), porém com diferença em relação ao GC (p = 0,027). Não houve modificação na postura de cabeça após a cirurgia ortognática, porém observou-se diferença significativa entre os grupos pós-DDF e GC para a inclinação de cabeça (p = 0,017). Não observou-se relação entre o modo respiratório e a postura de cabeça (p > 0,05). Conclusão: Após a cirurgia ortognática, notou-se melhora espontânea da respiração na amostra estudada. Não foi possível verificar modificações na postura de cabeça e associação entre modo respiratório e postura de cabeça.

Pathogenic Microenvironment from Diabetic-Obese Visceral and Subcutaneous Adipocytes Activating Differentiation of Human Healthy Preadipocytes Increases Intracellular Fat, Effect of the Apocarotenoid Crocetin.

In diabetes mellitus type 2 (DM2), developed obesity is referred to as diabesity. Implementation of a healthy diet, such as the Mediterranean, prevents diabesity. Saffron is frequently used in this diet because of its bioactive components, such as crocetin (CCT), exhibit healthful properties. It is well known that obesity, defined as an excessive accumulation of fat, leads to cardiometabolic pathology through adiposopathy or hypertrophic growth of adipose tissue (AT).This is related to an impaired adipogenic process or death of adipocytes by obesogenic signals. We aimed to evaluate the effect of the pathogenic microenvironment and CCT, activating differentiation of healthy preadipocytes (PA). For this, we used human cryopreserved PA from visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) depots obtained from healthy and obese-DM2 donors. We studied the effect of a metabolically detrimental (diabesogenic) environment, generated by obese-DM2 adipocytes from VAT (VdDM) or SAT (SdDM), on the viability and accumulation of intracellular fat of adipocytes differentiated from healthy PA, in the presence or absence of CCT (1 or 10 µM). Intracellular fat was quantified by Oil Red O staining. Cytotoxicity was measured using the MTT assay. Our results showed that diabesogenic conditions induce cytotoxicity and provide a proadipogenic environment only for visceral PA. CCT at 10 µM acted as an antiadipogenic and cytoprotective compound.

Overcoming MDR by Associating Doxorubicin and pH-Sensitive PLGA Nanoparticles Containing a Novel Organoselenium Compound-An In Vitro Study.

In this study, we developed PLGA nanoparticles (NPs) as an effective carrier for 5'-Se-(phenyl)-3-(amino)-thymidine (ACAT-Se), an organoselenium compound, nucleoside analogue that showed promising antitumor activity in vitro. The PLGA NPs were prepared by the nanoprecipitation method and modified with a pH-responsive lysine-based surfactant (77KL). The ACAT-Se-PLGA-77KL-NPs presented nanometric size (around 120 nm), polydispersity index values < 0.20 and negative zeta potential values. The nanoencapsulation of ACAT-Se increased its antioxidant (DPPH and ABTS assays) and antitumor activity in MCF-7 tumor cells. Hemolysis study indicated that ACAT-Se-PLGA-77KL-NPs are hemocompatible and that 77KL provided a pH-sensitive membranolytic behavior to the NPs. The NPs did not induce cytotoxic effects on the nontumor cell line 3T3, suggesting its selectivity for the tumor cells. Moreover, the in vitro antiproliferative activity of NPs was evaluated in association with the antitumor drug doxorubicin. This combination result in synergistic effect in sensitive (MCF-7) and resistant (NCI/ADR-RES) tumor cells, being especially able to successfully sensitize the MDR cells. The obtained results suggested that the proposed ACAT-Se-loaded NPs are a promising delivery system for cancer therapy, especially associated with doxorubicin.

Validation of the MBGR orofacial myofunctional assessment protocol for adults with temporomandibular disorders with disc displacement with reduction. / Validação do protocolo de avaliação miofuncional orofacial MBGR para adultos com disfunção temporomandibular com deslocamento de disco com redução.

PURPOSE: This study aimed at validating the MBGR Orofacial Myofunctional Assessment Protocol (MBGR Protocol) for adults with Temporal Mandibular Disorders (TMD). METHODS: The study sample was composed of 30 adults: 15 with TMD (disc displacement with reduction according to the Research Diagnostic Criteria for Temporomandibular Disorders) and 15 control individuals. The validation process encompassed the content, criterion, and construct of the protocol, as well as its inter- and intra-rater agreement levels and sensitivity and specificity values, considering a 5% statistical significance level. RESULTS: The following validities were confirmed: of content, as the MBGR Protocol covers all functional issues present in patients with TMD; of criterion, with significant correlations between the MBGR and Orofacial Myofunctional Evaluation with Scores (OMES) protocols; of construct, differentiating individuals with and without Orofacial Myofunctional Disorders (OMD) as for pain on palpation and mandible range of motion, with significant correlation between the MBGR clinical evaluation and that using a digital algometer, as well as confirmation of the instrumental assessment for the breathing mode classification. Agreement ranged from poor to very good and from reasonable to very good for the inter- and intra-rater power analyses, respectively. High sensitivity and specificity values were observed. CONCLUSION: The MBGR Protocol proved to be valid for use in adults presented with TMD with disc displacement with reduction and controls, covering all aspects that enable the analysis of OMD in these individuals.

OBJETIVO: Este estudo visou validar o Protocolo de Avaliação Miofuncional Orofacial MBGR para adultos com DTM. MÉTODO: Participaram 30 adultos, sendo 15 com DTM (deslocamento de disco com redução segundo o Research Diagnostic Criteria for Temporomandibular Disorders) e 15 Controles. O processo de validação envolveu a validade de conteúdo, de critério e de construto, além da concordância inter e intra-avaliador, sensibilidade e especificidade. Considerou-se nível de significância de 5%. RESULTADOS: Foram confirmadas as validades de conteúdo, visto que o Protocolo MBGR abarca todas as questões funcionais presentes em indivíduos com DTM; de critério, com correlações significantes entre o MBGR e AMIOFE; e de construto, diferenciando indivíduos com e sem DMO quanto à dor à palpação e mobilidade mandibular, com correlação significante entre a avaliação clínica do MBGR e o uso do algômetro digital, bem como confirmação do exame instrumental para a classificação do modo respiratório. A força de concordância variou de pobre a muito boa para a análise interavaliador e de razoável a muito boa para intra-avaliador. Os valores de sensibilidade e especificidade foram elevados. CONCLUSÃO: O Protocolo MBGR mostrou-se válido para aplicação em adultos com DTM com deslocamento de disco com redução e controles, contemplando todos os aspectos que possibilitam a análise das condições oromiofuncionais nesses indivíduos.

Tongue function and swallowing in individuals with temporomandibular disorders.

BACKGROUND: The tongue participates in the oral phase of swallowing by pushing the food bolus toward the oropharynx. This relationship between tongue function and swallowing is little addressed addressed in individuals with temporomandibular dysfunction (TMD). OBJECTIVE: To analyze the association of functional tongue conditions on swallowing in individuals with TMD. METHODOLOGY: After approval by the Institutional Review Board, the study was conducted on 30 individuals of both sexes, aged 18 to 28 years, with TMD, and not treated for the disorder. Tongue function was assessed as to the mobility, pressure, and oral motor control. Swallowing was analyzed by clinical assessment during ingestion of solid (wafer biscuit) and liquid (water). Data regarding mobility and swallowing were collected using the orofacial myofunctional evaluation protocol. Tongue pressure was measured by the Iowa Oral Performance Instrument, during elevation, protrusion, swallowing, and resistance test. The oral motor control was assessed by the oral diadochokinesis (DDK) test by rapid and repeated emissions of syllables "ta" and "ka". Data were statistically analyzed by the Spearman correlation coefficient, at a significance level of 5%. RESULTS: Relationships were found between tongue function and swallowing for the following aspects: mobility (r=0.741), pressure in protrusion (r=-0.366), swallowing of saliva (r=-0.499), mean DDK rate in emissions "ta" (r=-0.424) and "ka" (r=-0.446), and mean DDK period in emissions "ta" (r=0.424) and "ka" (r=0.446). Thus, the greater the change in tongue mobility, the lower the tongue pressure in protrusion and swallowing of saliva, the lower the emissions per second, the longer the mean time between vocalizations, and the worse the swallowing of individuals with TMD. CONCLUSION: The functional conditions of the tongue regarding mobility, pressure, and oral DDK were associated with swallowing in individuals with TMD.

Estruturação de currículo baseado em competências e atividades profissionais confiáveis para formação do Especialista em pneumologia da Santa Casa de Belo Horizonte / Structuring a curriculum based on competencies and entrustable professional activities for the training of pulmonology specialists at Santa Casa de Belo Horizonte

O programa de especialização em Pneumologia da Santa Casa de Belo Horizonte (SCBH), criado em 1984, propôs ter bem estabelecidas as competências que caracterizam o médico pneumologista ali formado, assim como as atividades profissionais a ele confiadas. O presente trabalho teve como propósito estruturar um currículo baseado em atividades profissionais confiáveis (EPA - entrustable professional activities) para formação do médico especialista em pneumologia da Santa Casa de Belo Horizonte. O estudo envolveu elaboração de uma matriz de competências essenciais à formação de um especialista a partir do perfil almejado para o egresso do programa de especialização em pneumologia. Esta matriz de competência foi embasada na matriz de competências de Pneumologia publicada pela Comissão Nacional de Residência Médica do Ministério da Educação do Brasil (CNRM/MEC), no programa educacional baseado em competências desenvolvido pela Unidade de Ensino e Pesquisa da SCBH e na matriz do Royal College of Physicians and Surgeons of Canada (CanMeds). As competências foram agrupadas em seis grandes domínios: 1. Autogestão do Conhecimento; 2. Comunicação; 3. Expertise Técnica; 4. Liderança Colaborativa; 5. Profissionalismo; 6. Responsabilidade Social. Posteriormente, foram definidas e elaboradas as Atividades Profissionais Confiáveis (EPA ­ entrustable professional activities) que foram usadas para a formação do espectro de construção e atuação do especialista em pneumologia da SCBH. Em um segundo momento, as EPAs elaboradas foram discutidas e aprimoradas com um comitê de especialistas em pneumologia. Obteve-se uma matriz de competências com 143 objetivos educacionais distribuídos pelos seis domínios: autogestão do conhecimento (4%), comunicação (17%), expertise técnica (64%), liderança colaborativa (4%), profissionalismo (5%) e responsabilidade social (5%). A partir desta matriz, foram elaboradas 11 EPAs: 1 ­ Cuidado clínico ao paciente com problemas respiratórios em qualquer cenário; 2 ­ Registro em prontuário médico; 3 ­ Prescrição médica do paciente com problemas respiratórios; 4 ­ Solicitação e interpretação de exames complementares; 5 ­ Cuidado ao paciente com insuficiência respiratória; 6 ­ Interconsulta e cuidado ambulatorial de pacientes com problemas respiratórios complexos; 7 ­ Cuidado ao paciente crítico; 8 ­ Manejo dos testes de função pulmonar; 9 ­ Análise diagnóstica do tórax pela imagem; 10 ­ Condução na alta responsável; 11 ­ Procedimento em situação de óbito. A obtenção do currículo baseado em EPAs para formação do especialista em pneumologia da Santa Casa BH favorecerá a avaliação dos especializandos no cenário do serviço e contribuirá para a excelência do cuidado aos portadores de doenças respiratórias

The specialization program in Pulmonology at Santa Casa de Belo Horizonte (SCBH), created in 1984, needed to have well-established skills that characterize the pulmonologists trained there, as well as the professional activities entrusted to them. This work aimed at structuring a curriculum based on entrustable professional activities (EPA) for the training of the pulmonology specialists at Santa Casa de Belo Horizonte. This is a study applied to the reality of the health service, which involved the organization of a matrix of essential competencies for the formation of a specialist in pulmonology from the desired profile of the egress of the pulmonology specialization program, using as reference the matrix of competencies of Pulmonology published by the National Commission of Medical Residency of the Brazilian Ministry of Education (CNRM/MEC - Comissão Nacional de Residência Médica do Ministério da Educação do Brasil), the competency-based educational program developed by the Teaching and Research Unit of SCBH, and the matrix of the Royal College of Physicians and Surgeons of Canada (CanMeds). The competencies were grouped into six major domains: 1. Self-Management of Knowledge; 2. Communication; 3. Technical Expertise; 4. Collaborative Leadership, 5. Professionalism; 6. Social Responsibility. Sequentially, the Entrustable Professional Activities (EPA) were defined and elaborated, characterizing the spectrum of training and practice of specialists in pulmonology by the SCBH. The elaborated EPAs were then discussed and improved by a committee of specialists in pulmonology. A competency matrix was obtained with 143 educational objectives distributed across the six domains: self-management of knowledge (4%), communication (17%), technical expertise (64%), collaborative leadership (4%), professionalism (5%) and social responsibility (5%). From the matrix, 11 EPAs were developed: 1 - Clinical care for patients with respiratory problems in any scenario; 2 - Data entry in medical records; 3 - Medical prescription for the patient with respiratory problems; 4 - Request and interpretation of complementary tests; 5 - Care of the patient with respiratory failure; 6 - Referral and outpatient care of patients with complex respiratory problems; 7 - Care of the critically ill patient; 8 - Management of pulmonary function tests; 9 - Diagnostic image analysis of the thorax; 10 - Responsible discharge; 11 - Procedure in the event of death. The development of the curriculum based on EPAs in the formation of pulmonology specialists at SCBH will favor the evaluation of future specialists in the service scenario and contribute to the excellent care of those with respiratory diseases

Tongue function and swallowing in individuals with temporomandibular disorders

Abstract The tongue participates in the oral phase of swallowing by pushing the food bolus toward the oropharynx. This relationship between tongue function and swallowing is little addressed addressed in individuals with temporomandibular dysfunction (TMD). Objective: To analyze the association of functional tongue conditions on swallowing in individuals with TMD. Methodology: After approval by the Institutional Review Board, the study was conducted on 30 individuals of both sexes, aged 18 to 28 years, with TMD, and not treated for the disorder. Tongue function was assessed as to the mobility, pressure, and oral motor control. Swallowing was analyzed by clinical assessment during ingestion of solid (wafer biscuit) and liquid (water). Data regarding mobility and swallowing were collected using the orofacial myofunctional evaluation protocol. Tongue pressure was measured by the Iowa Oral Performance Instrument, during elevation, protrusion, swallowing, and resistance test. The oral motor control was assessed by the oral diadochokinesis (DDK) test by rapid and repeated emissions of syllables "ta" and "ka". Data were statistically analyzed by the Spearman correlation coefficient, at a significance level of 5%. Results: Relationships were found between tongue function and swallowing for the following aspects: mobility (r=0.741), pressure in protrusion (r=-0.366), swallowing of saliva (r=-0.499), mean DDK rate in emissions "ta" (r=-0.424) and "ka" (r=-0.446), and mean DDK period in emissions "ta" (r=0.424) and "ka" (r=0.446). Thus, the greater the change in tongue mobility, the lower the tongue pressure in protrusion and swallowing of saliva, the lower the emissions per second, the longer the mean time between vocalizations, and the worse the swallowing of individuals with TMD. Conclusion: The functional conditions of the tongue regarding mobility, pressure, and oral DDK were associated with swallowing in individuals with TMD.

Herramientas evaluadoras de calidad de la investigación de las medicinas no convencionales / Quality assessing tools for unconventional medicine research

Introducción: El uso de las medicinas no convencionales (MNC) crece en la población; sin embargo, los médicos tienen un bajo nivel de conocimiento acerca de ellas, a pesar de su interés, debido a las preguntas que reciben de sus pacientes con respecto a sus riesgos y beneficios. No obstante, se desconoce cuántos y cuáles son los instrumentos que evalúan la calidad de la investigación de estas medicinas. Objetivo: Identificar las herramientas que se utilizan para evaluar la calidad de la investigación en medicinas no convencionales a fin de conocer sus avances y origen de sus limitaciones. Método: Se realizó una búsqueda de información en bases de datos científicas; acopiándose un total de 200 de estos, solo 75 fueron considerados adecuados; aunque, solo 12 respondieron a la pregunta de investigación. El análisis acogió algunas de las recomendaciones PRISMA. Resultados: Se encontraron 12 instrumentos que guían y evalúan la calidad de la investigación en medicinas no convencionales, 9 de ellas son extensiones CONSORT. China, Corea del Sur y la India son los países que promueven la estandarización de su medicina tradicional, la cual representa gran parte de las medicinas alternativas y complementarias de otras partes del mundo. Conclusiones: Se requiere seguir procedimientos específicos para la evaluación de la calidad de la investigación en medicinas no convencionales con el fin de encontrar los criterios más apropiados para la evaluación de su eficacia y seguridad(AU)

Introduction: The use of unconventional medicine grows in the population; but doctors have low level of knowledge of them, despite their interest, due to the questions from their patients regarding their risks and benefits. Yet, it is unknown what the instruments are and how many are they to assess the quality of research on these medications. Objective: To identify and to describe the tools used to assess the quality of research in unconventional medicine in order to know progress and origin of limitations. Method: An information search was carried out in scientific databases; collecting a total of 200, only 75 were considered adequate; although, only 12 answered the research question. The analysis comprised some of PRISMA recommendations. Results: Twelve instruments were found that guide and evaluate the quality of research in non-conventional medicine, nine of them are CONSORT extensions. China, South Korea and India are the countries that promote standardization of their traditional medicine, which represents a large part of alternative and complementary medicine from other parts of the world. Conclusions: It is required to follow specific procedures for assessing the quality of research in non-conventional medicine in order to find the most appropriate criteria for evaluating their efficacy and safety(AU)