High-Fat Diet Induces Disruption of the Tight Junction-Mediated Paracellular Barrier in the Proximal Small Intestine Before the Onset of Type 2 Diabetes and Endotoxemia.

BACKGROUND/AIM: A link between an impaired intestinal barrier, endotoxemia, and the pathogenesis of metabolic diseases, such as type 2 diabetes mellitus (T2DM), has been proposed. In previous work, we have demonstrated that the tight junction (TJ)-mediated intestinal barrier in ileum/colon was marginally changed in prediabetic mice; therefore, it does not seem to mainly contribute to the T2DM onset. In this study, the TJ-mediated epithelial barrier in the duodenum and jejunum was evaluated in mice during the development of type 2 prediabetes. METHODS/RESULTS: HF diet induced prediabetes after 60 days associated with a significant rise in intestinal permeability to the small-sized marker Lucifer yellow in these mice, with no histological signs of mucosal inflammation or rupture of the proximal intestine epithelium. As revealed by immunofluorescence, TJ proteins, such as claudins-1, -2, -3, and ZO-1, showed a significant decrease in junctional content in duodenum and jejunum epithelia, already after 15 days of treatment, suggesting a rearrangement of the TJ structure. However, no significant change in total cell content of these proteins was observed in intestinal epithelium homogenates, as assessed by immunoblotting. Despite the changes in intestinal permeability and TJ structure, the prediabetic mice showed similar LPS, zonulin, and TNF-α levels in plasma or adipose tissue, and in intestinal segments as compared to the controls. CONCLUSION: Disruption of the TJ-mediated paracellular barrier in the duodenum and jejunum is an early event in prediabetes development, which occurs in the absence of detectable endotoxemia/inflammation and may contribute to the HF diet-induced increase in intestinal permeability.

Knowledge on asthma, food allergies, and anaphylaxis: Assessment of elementary school teachers, parents/caregivers of asthmatic children, and university students in Uruguaiana, in the state of Rio Grande do Sul, Brazil.

INTRODUCTION: Allergic diseases have become an increasingly common reality in the last years, extending beyond the family context. OBJECTIVE: Assessing the level of knowledge on asthma, food allergies and anaphylaxis of asthmatic children's parents/caregivers (PC), elementary school teachers (EST) and university students (US) in Uruguaiana, RS, Brazil. METHOD: 577 individuals (PC - N=111; EST - N=177; US - N=299) took part in the study, answering the Newcastle Asthma Knowledge Questionnaire (validated for Portuguese) and another questionnaire on Food Allergy (FA) and anaphylaxis. RESULTS: Although PC have asthmatic children, their asthma knowledge level was average, slightly above that of EST and EU. The lack of knowledge on passive smoking, use of medications and their side effects should be highlighted. US have shown to be better informed about FA and anaphylaxis. However, even though a significant proportion of respondents know the most common symptoms of FA and anaphylaxis, few named subcutaneous adrenaline as the drug of choice for treating anaphylaxis. Although a significant number of respondents know about the possibility of anaphylactic reactions happening at school or in activities outside the school, we were surprised by the absence of conditions in schools to provide emergency care to such students. CONCLUSION: Despite the high prevalence of allergic diseases in childhood, asthmatic children's parents/caregivers, elementary school teachers and university students have inadequate levels of knowledge to monitor these patients.

Activation of the Wnt/ß-catenin pathway in pancreatic beta cells during the compensatory islet hyperplasia in prediabetic mice.

The Wnt/ß-catenin signaling pathway, also known as the canonical Wnt pathway, plays a role in cell proliferation and differentiation in several tissues/organs. It has been recently described in humans a relationship between type 2 diabetes (T2DM) and mutation in the gene encoding the transcription factor TCF7L2 associated to the Wnt/ß-catenin pathway. In the present study, we demonstrated that hyperplastic pancreatic islets from prediabetic mice fed a high-fat diet (HFD) for 60 d displayed nuclear translocation of active ß-catenin associated with significant increases in protein content and gene expression of ß-catenin as well as of cyclins D1, D2 and c-Myc (target genes of the Wnt pathway) but not of Tcf7l2 (the transcription factor). Meanwhile, these alterations were not observed in pancreatic islets from 30 d HFD-fed mice, that do not display significant beta cell hyperplasia. These data suggest that the Wnt/ß-catenin pathway is activated in pancreatic islets during prediabetes and may play a role in the induction of the compensatory beta cell hyperplasia observed at early phase of T2DM.

Exercise training, creatine supplementation, and bone health in ovariectomized rats.

UNLABELLED: Evidence suggests that creatine may have some beneficial effects on bone. The study aimed to investigate the effects of exercise alone or combined with creatine on bone health in ovariectomized rats. Findings show that exercise, but not creatine, has an important role in improving bone health. INTRODUCTION: The aim of this study was to investigate the effects of exercise training alone or combined with creatine supplementation on bone health parameters in ovariectomized rats. METHODS: Wistar rats were randomly allocated into one of five groups: (i) sham-operated, (ii) ovariectomized non-trained placebo-supplemented, (iii) ovariectomized non-trained creatine-supplemented, (iv) ovariectomized exercise-trained placebo-supplemented, and (v) ovariectomized exercise-trained creatine-supplemented. Downhill running training and/or creatine supplementation (300 mg/kg body weight) were administered for 12 weeks. Bone mineral content (BMC), bone mineral density (BMD), and biomechanical and histomorphometric parameters were assessed. RESULTS: No interaction effects were observed for BMC and BMD at whole body, femur, and lumbar spine (p > 0.05). Importantly, a main effect of training was detected for whole body BMC and BMD (p = 0.003 and p < 0.001, respectively), femoral BMC and BMD (p = 0.005 and p < 0.001, respectively), and lumbar spine BMC and BMD (p < 0.001 and p < 0.001, respectively), suggesting that the trained animals had higher bone mass, irrespective of creatine supplementation. Main effects of training were also observed for maximal load (p < 0.001), stiffness (p < 0.001), and toughness (p = 0.046), indicating beneficial effects of exercise training on bone strength. Neither a main effect of supplementation nor an interaction effect was detected for biomechanical parameters (p > 0.05). No main or interaction effects were observed for any of the histomorphometric parameters evaluated (p > 0.05). CONCLUSIONS: Exercise training, but not creatine supplementation, attenuated ovariectomy-induced bone loss in this rat model.

Effects of minimally invasive surgical and miniscrew-assisted rapid palatal expansion (MISMARPE) on the nasal cavity and upper airway: a comparative cohort study.

This study was performed to evaluate the impact on the upper airway and nasal cavity of a new minimally invasive surgical and miniscrew-assisted rapid palatal expansion (MISMARPE) technique for the treatment of adult patients with transverse maxillary deficiency, in comparison to surgically assisted rapid palatal expansion (SARPE). Computed tomography scans of 21 MISMARPE and 16 SARPE patients were obtained preoperatively (T0) and at the end of the activation period (T1) and analysed. Linear and volumetric measurements were performed in the dental, alveolar, nasal cavity, and oropharynx regions. Generalised estimating equations were used to consider the intervention time and surgery type, and their interaction. In both groups, measurements were increased at T1 (P < 0.001), except for oropharynx volume (P > 0.05). A greater expansion in nasal cavity floor and median palatal suture was shown for MISMARPE when compared to SARPE (P < 0.001), with the same degree of expander activation (P = 0.094). A trapezoidal (coronal plane) and 'V' shape (axial plane) expansion pattern, was observed after MISMARPE. Both surgical techniques were effective for maxillary expansion in adults. However, MISMARPE was performed without osteotomy of the pterygomaxillary suture, in an outpatient setting and with local anaesthesia.

Assessing the reaction to and efficacy of the Screener drug discovery and development board game as a pedagogical tool in postgraduate courses.

Screener, a board game supplemented with online resources, was introduced and distributed by the Brazilian Society of Pharmacology and Experimental Therapeutics to postgraduate programs as an instructional tool for the process of drug discovery and development (DDD). In this study, we provided a comprehensive analysis of five critical aspects for evaluating the quality of educational games, namely: 1) description of the intervention; 2) underlying pedagogical theory; 3) identification of local educational gaps; 4) impact on diverse stakeholders; and 5) elucidation of iterative quality enhancement processes. We also present qualitative and quantitative assessments of the effectiveness of this game in 11 postgraduate courses. We employed the MEEGA+ online survey, comprising thirty-three close-ended unipolar items with 5-point Likert-type response scales, to assess student perceptions of the quality and utility of Screener. Based on 115 responses, the results indicated a highly positive outlook among students. In addition, we performed a preliminary evaluation of learning outcomes in two courses involving 28 students. Pre- and post-quizzes were applied, each consisting of 20 True/False questions directly aligned with the game's content. The analysis revealed significant improvement in students' performance following engagement with the game, with scores rising from 8.4 to 13.3 (P<0.0001, paired t-test) and 9.7 to 12.7 (P<0.0001, paired t-test). These findings underscore the utility of Screener as an enjoyable and effective tool for facilitating a positive learning experience in the DDD process. Notably, the game can also reduce the educational disparities across different regions of our continental country.

Impaired ß-cell-ß-cell coupling mediated by Cx36 gap junctions in prediabetic mice.

Gap junctional intercellular communication between ß-cells is crucial for proper insulin biosynthesis and secretion. The aim of this work was to investigate the expression of connexin (Cx)36 at the protein level as well as the function and structure of gap junctions (GJ) made by this protein in the endocrine pancreas of prediabetic mice. C57BL/6 mice were fed a high-fat (HF) or regular chow diet for 60 days. HF-fed mice became obese and prediabetic, as shown by peripheral insulin resistance, moderate hyperglycemia, hyperinsulinemia, and compensatory increase in endocrine pancreas mass. Compared with control mice, prediabetic animals showed a significant decrease in insulin-secretory response to glucose and displayed a significant reduction in islet Cx36 protein. Ultrastructural analysis further showed that prediabetic mice had GJ plaques about one-half the size of those of the control group. Microinjection of isolated pancreatic islets with ethidium bromide revealed that prediabetic mice featured a ß-cell-ß-cell coupling 30% lower than that of control animals. We conclude that ß-cell-ß-cell coupling mediated by Cx36 made-channels is impaired in prediabetic mice, suggesting a role of Cx36-dependent cell-to-cell communication in the pathogenesis of the early ß-cell dysfunctions that lead to type 2-diabetes.

Should oral chlorhexidine remain in ventilator-associated pneumonia prevention bundles?

Ventilator-associated pneumonia (VAP) is related with high mortality, duration of mechanical ventilation and costs. Recent studies have questioned the safety and effectiveness of oral chlorhexidine to prevent VAP. We sought to verify whether the adverse effects of this substance outweigh its benefits. We searched several databases and selected studies that investigated the use of oral chlorhexidine and its impact on mortality. No association between oral chlorhexidine and lower VAP rates was found on meta-analyses of double-blind randomized trials, however significant increase in mortality was reported. It is speculated that chlorhexidine can cause damage to several organic sectors and cytotoxicity. Although it still can be beneficial in specific settings, robust evidence to recommend its routine application for all mechanically ventilated patients is lacking; therefore, given the possibility of harm, it would be better to follow the principle of non-maleficence until more studies becomes available.

Oxytocin depolarizes mitochondria in isolated myometrial cells.

Oxytocin is known to play important roles in uterine contractions, mediated at least in part by increasing intracellular Ca(2+) concentration ([Ca(2+)](i)), through enhancing extracellular Ca(2+) entry and Ca(2+) release from the sarcoplasmic reticulum, processes that are intimately linked with mitochondria. This study examined the effects of oxytocin on mitochondrial function. This was achieved by measuring the ratiometric JC-1 fluorescence signal in isolated myometrial cells, which provides a relative measure of the mitochondrial membrane potential (ψ(m)), and also by loading the cells with Oregon Green BAPTA-AM to examine changes in [Ca(2+)](i). Oxytocin (1 nm) depolarized the ψ(m) to 73.8 ± 3.7% of the control value (P < 0.05; perfused for 11 min) and also caused a transient increase in [Ca(2+)](i). The depolarization of mitochondrial membrane potential was effectively reversed by 2-aminoethoxydiphenyl borate, nifedipine, Ca(2+)-free solution or oligomycin, with the ratiometric JC-1 fluorescence signal becoming no different from the control value in all cases (i.e. P > 0.05). The reduction in ψ(m) is likely to occur at least in part through the oxytocin-induced increase in [Ca(2+)](i), causing enhanced mitochondrial uptake of Ca(2+) and resultant dissipation of the mitochondrial electrochemical gradient. ATP synthase is also stimulated, which would further contribute to a decrease in ψ(m).

Stapled haemorrhoidopexy transiently decreases rectal compliance and sensitivity.

AIM: Stapled haemorrhoidopexy may damage the anorectal musculature and its sensorimotor function. Most studies have not used a barostat for the measurement of compliance. This study aimed to investigate the effect of stapled haemorrhoidopexy on rectal compliance and sensitivity. METHOD: After Ethical Committee approval, we studied 10 male patients (mean age 33.8 years) with third- or fourth-degree haemorrhoids. Rectal compliance and sensitivity were measured with a 600-ml bag and an electronic barostat. Volunteers were submitted to two consecutive rectal distension protocols, including continuous distension at 2, 4 and 6 months after stapled haemorrhoidopexy. Intraluminal volume and pressure were recorded, including the first rectal sensation, desire to defecate and onset of rectal pain. Another group of 10 male control patients (mean age 24.9 years) with pilonidal sinus and no haemorrhoids was also included in the study. RESULTS: Two months after stapled haemorrhoidopexy, rectal compliance decreased (7.1 ± 0.2 vs 5.3 ± 0.1, 6.4 ± 0.1 vs 5.1 ± 0.1 and 5.6 ± 0.2 vs 4.7 ± 0.1 ml/mmHg for first rectal sensation, desire to defecate and rectal pain, respectively; P < 0.05). The sensitivity threshold volume did not change for the first sensation but decreased significantly for the desier to defecate and pain (p <0.05) (116.8 ± 13.8 vs 148.4 ± 14.61, 251.1 ± 8.9 vs 185.8 ± 8.6 and 293.3 ± 16.6 vs 221.2 ± 6.0 ml for first rectal sensation, desire to defecate and rectal pain, respectively). Four and 6 months after surgery, rectal compliance and sensitivity returned to levels similar to those in the basal period. Muscle tissue was found in only three of the 10 resected doughnuts. Controls remained without any change in rectal compliance and sensitivity. CONCLUSION: Stapled haemorrhoidopexy transiently decreases rectal compliance and sensitivity threshold in young male patients.

Stability and surgical complications of tooth-borne and bone-borne appliances in surgical assisted rapid maxillary expansion: a systematic review.

The objective of this systematic review was to evaluate the stability and complications of tooth-borne (TB), bone-borne (BB) and hybrid (TB-BB) appliances in surgically assisted rapid maxillary expansion (SARME). Database searches were conducted (PubMed, Embase, Cochrane Library and SciELO), as well as a grey literature search (Google Scholar) and hand searches of reference lists. Forty-six articles were included after study selection (κ=0.854). After eligibility assessment, 16 articles and one article from the grey literature were processed (κ=0.866) and six articles were selected by hand searching, for a total of 23 articles included. Regarding stability, TB appliances showed width relapse rates ranging from 4 to 35% in canines, from 1 to 37% in premolars and from 0.2 to 49.5% in molars. In BB appliances, width relapse rates were 1.7-21% in canines, 1.5% in premolars and 4.6-11.5% in molars. In hybrid appliances, the width relapse rate was 14% in premolars, with a 1.8% overexpansion reported in the molar region. In TB and BB appliances, skeletal relapse rates were similar on the nasal floor (11-53% and 41.6%, respectively) and at the level of the maxilla (18% and 16%, respectively). The most common complications were bone resorption in TB appliances (18.14%) and appliance-related complications in BB appliances (17.9%). The risk of bias was high in 19 studies, medium in three studies and low in one study. The TB and BB appliances used in SARME were considered to have a high long-term stability. BB appliances appeared to have fewer relapses than TB appliances due to a more parallel distribution of forces exerted. However, relapse appears to be highly influenced by postorthodontic treatments, where arch-form coordination is achieved in the consolidation period with the purpose of overexpansion correction, alignment and final vertical adjustments. Further randomised controlled trials with long-term data and large sample sizes are needed to support evidence-based clinical decision-making and to allow meta-analytic studies of stability outcomes regarding the type of anchorage in SARME.

Antibiotic prophylaxis in orthognathic surgery: an overview of systematic reviews.

The purpose of this overview was to assess different antibiotic regimens used in orthognathic surgery and to establish an evidence-based protocol so that beneficial and adverse effects can be determined. A comprehensive literature search for systematic reviews and/or meta-analyses was conducted in MEDLINE (PubMed), EMBASE, and the Cochrane Library until March 2020. Grey literature was investigated in Google Scholar, and a manual search was done of references lists. Two meta-analyses and four systematic reviews met the inclusion criteria. The AMSTAR-2-tool was used to ascertain the potential risk of bias in the included studies, which presented moderate to high methodological quality. Lower infection rates were associated with long-term therapies of penicillin, cefazolin-cephalexin, and amoxicillin-clavulanic-acid, with rates varying from 0% - 3.13%. Higher rates were reported in placebo groups (52.6%) and short-term penicillin therapy (60%). Side effects were reported with cefazolin, clindamycin, and penicillin therapies, including nausea, pain, swelling, headache, vomiting, and skin rash. Evidence suggests that long-term antibiotics can reduce the risk of a surgical site infection (SSI) in orthognathic surgery, but there is uncertainty regarding the effects of one dose of antibiotics preoperatively versus short-term antibiotics. In the same way, intravenous penicillin, cefazolin, clindamycin, and amoxicillin-clavulanic acid kept the infection rates associated with bimaxillary procedures under 3.5%.

Should oral chlorhexidine remain in ventilator-associated pneumonia prevention bundles?

Ventilator-associated pneumonia (VAP) is related with high mortality, duration of mechanical ventilation and costs. Recent studies have questioned the safety and effectiveness of oral chlorhexidine to prevent VAP. We sought to verify whether the adverse effects of this substance outweigh its benefits. We searched several databases and selected studies that investigated the use of oral chlorhexidine and its impact on mortality. No association between oral chlorhexidine and lower VAP rates was found on meta-analyses of double-blind randomized trials, however significant increase in mortality was reported. It is speculated that chlorhexidine can cause damage to several organic sectors and cytotoxicity. Although it still can be beneficial in specific settings, robust evidence to recommend its routine application for all mechanically ventilated patients is lacking; therefore, given the possibility of harm, it would be better to follow the principle of non-maleficence until more studies becomes available.

Minimally invasive intraoral proportional condylectomy with a three-dimensionally printed cutting guide.

The aim of this study was to describe the steps of a minimally invasive surgical technique used to perform a proportional intraoral condylectomy with a three-dimensionally (3D) printed cutting guide. The technique consists of two steps: virtual surgical planning and intraoral condylectomy. During virtual surgical planning, the mandibular ramus was measured bilaterally, the height of the proportional condylectomy was planned virtually, and a cutting guide was 3D printed. In the intraoral condylectomy, the mandibular condyle was approached intraorally, the 3D printed cutting guide was positioned in the sigmoid notch, and the proportional condylectomy was performed. The protocol reported in this technical note is the sum of knowledge acquired from a series of studies published previously by the authors, who have jointly developed a surgical technique that is both minimally invasive and accurate for the treatment of condylar hyperplasia.

Nasolabial soft tissue effects of segmented and non-segmented Le Fort I osteotomy using a modified alar cinch technique-a cone beam computed tomography evaluation.

The aim of this study was to verify soft tissues changes and the effect of a minimally invasive surgical technique in the nasolabial region after segmented and non-segmented Le Fort I osteotomy, using cone beam computed tomography (CBCT) evaluation of three-dimensional (3D) volume surfaces. Two groups were evaluated: group 1, bimaxillary surgery with maxillary segmentation (n=40); group 2, bimaxillary surgery without maxillary segmentation (n=40). In both groups, a specific alar cinching technique was used to control nasal base broadening. CBCT evaluation was performed at three different treatment time points: T0, 1 month before surgery; T1, 1 month after surgery; T2, 1year after surgery. The results showed statistically significant differences in the nasolabial area (P<0.001). For group 1, the mean change in alar base width (Alinf-Alinf) was 1.31±1.40mm at T1 and 0.93±1.77mm at T2; for group 2 these values were 1.12±2.01mm at T1 and 0.54±1.54mm at T2. For group 1, the mean changes in inter-alar width (Al-Al) were 1.68±1.46mm at T1 and 1.49±1.33mm at T2; for group 2, they were 2.22±1.93mm at T1 and 1.34±1.79mm at T2. The alar cinch technique proposed here appears to be effective in controlling nasolabial soft tissue widening.

Preclinical toxicity of innovative molecules: In vitro, in vivo and metabolism prediction.

The lack of predictivity of animal's models has increased the failure rate of drug candidates. Thus, the reversion of this scenario using preliminary in vitro assays and metabolism prediction can reduce the unnecessary use of animals, as well as predict toxic effects at preclinical and clinical stages. The present study aimed to evaluate safety of four biologically active molecules (RN104, RI78, ICH, PCH) with potential therapeutic applications synthesized in our laboratory. Initially, we used MTT cytotoxicity against A549, H9C2, HepG2, LLC-PK1 and NEURO-2 cell lines. RN104 showed the lowest cytotoxicity and further studies were conducted with it. The neutral red (NR) test was performed according to OECD-129 and then acute toxicity test (OECD-423). According to NR results we administered at 300 mg/kg on animals; however, no toxic effect was observed, while 2,000 mg/kg resulted in the death of one animal per group. After, metabolism prediction studies, performed using both ligand-based and structure-based, suggests three potential metabolites. In silico results suggested that potential metabolites could be fast eliminated and, then, this could be an explanation for lower observed toxicity in in vivo experiments. The results showed limitations of the NR as a predictor of the initial dose for the acute toxicity study, which may be related to metabolism. Therefore, the combination of theoretical and experimental studies is relevant to a general understanding of new molecule's toxicity.

Intestinal luminal content from high-fat-fed prediabetic mice changes epithelial barrier function in vitro.

AIMS: Evidence suggests that administration of a high-fat diet (HFD) results in changes in the intestinal lumen environment. Gut dysbiosis associated with intestinal barrier disruption may be involved in type 2 diabetes mellitus (T2DM) development through increased intestinal permeability, which would trigger an inflammatory response leading to peripheral insulin resistance state and ultimately T2DM. In this study, we investigated the effect of the intestinal luminal content isolated from control or HFD-fed prediabetic mice upon the tight junction (TJ)-mediated epithelial barrier in Caco-2 and MDCK epithelial cell lines. METHODS/KEY FINDINGS: Exposure to small intestine luminal content (SI) isolated from HFD-fed prediabetic mice induced a more significant decrease in transepithelial electrical resistance (TEER), associated with higher paracellular flux in Caco-2 and MDCK cells after 6 h and 4 h respectively, as compared to the SI obtained from control mice. Such changes were accompanied by a significant decrease in TJ content of claudins, occludin, and ZO-1, indicative of disruption of the TJ barrier. Meanwhile, large intestine luminal content from control (Ctrl-LI) and prediabetic (HFD-LI) animals did not change TEER significantly, however, paracellular flux was significantly increased after 24 h, accompanied by a decrease in ZO-1 (after HFD-LI exposure) in Caco-2 and significant changes in the junctional distribution of claudins-1, -2, occludin and ZO-1 proteins in MDCK, particularly after HFD-LI exposure. SIGNIFICANCE: Luminal components of intestinal content, altered by HFD exposure, induce impairment of the TJ structure and function in vitro, corroborating the idea of a role of the intestinal paracellular barrier in the obesity-related T2DM pathogenesis.

Hierarchy of surgical stability in orthognathic surgery: overview of systematic reviews.

The purpose was to perform an overview of systematic reviews in order to create a hierarchical scale of stability in orthognathic surgery with the aid of the highest level of scientific evidence. The systematic search was conducted in the PubMed, Embase, and Cochrane Library databases. The grey literature was investigated in Google Scholar and a manual search was done of the references lists of included studies. Fifteen studies were included in the final sample, of which eight were systematic reviews and seven were meta-analyses. These were assessed for methodological quality using the AMSTAR 2 tool and all were considered to be of medium to high methodological quality. The clinical studies included in the 15 reviews and meta-analyses were classified by the review authors as having a moderate to high potential for risk of bias. The hierarchical pyramid of stability in orthognathic surgery was established, with two surgical procedures considered highly unstable: (1) maxillary expansion with semi-rigid internal fixation evaluated at the dental level in the posterior region, and (2) clockwise rotation of the mandible with rigid internal fixation of bicortical screws in the sagittal direction.

Assessing the reaction to and efficacy of the Screener drug discovery and development board game as a pedagogical tool in postgraduate courses

Screener, a board game supplemented with online resources, was introduced and distributed by the Brazilian Society of Pharmacology and Experimental Therapeutics to postgraduate programs as an instructional tool for the process of drug discovery and development (DDD). In this study, we provided a comprehensive analysis of five critical aspects for evaluating the quality of educational games, namely: 1) description of the intervention; 2) underlying pedagogical theory; 3) identification of local educational gaps; 4) impact on diverse stakeholders; and 5) elucidation of iterative quality enhancement processes. We also present qualitative and quantitative assessments of the effectiveness of this game in 11 postgraduate courses. We employed the MEEGA+ online survey, comprising thirty-three close-ended unipolar items with 5-point Likert-type response scales, to assess student perceptions of the quality and utility of Screener. Based on 115 responses, the results indicated a highly positive outlook among students. In addition, we performed a preliminary evaluation of learning outcomes in two courses involving 28 students. Pre- and post-quizzes were applied, each consisting of 20 True/False questions directly aligned with the game's content. The analysis revealed significant improvement in students' performance following engagement with the game, with scores rising from 8.4 to 13.3 (P<0.0001, paired t-test) and 9.7 to 12.7 (P<0.0001, paired t-test). These findings underscore the utility of Screener as an enjoyable and effective tool for facilitating a positive learning experience in the DDD process. Notably, the game can also reduce the educational disparities across different regions of our continental country.

Involvement of the Helicobacter pylori plasticity region and cag pathogenicity island genes in the development of gastroduodenal diseases.

Infection by Helicobacter pylori is associated with the development of several gastroduodenal diseases, including gastritis, peptic ulcer disease (gastric ulcers and duodenal ulcers), and gastric adenocarcinoma. Although a number of putative virulence factors have been reported for H. pylori, there are conflicting results regarding their association with specific H. pylori-related diseases. In this work, we investigated the presence of virB11 and cagT, located in the left half of the cag pathogenicity island (cagPAI), and the jhp917-jhp918 sequences, components of the dupA gene located in the plasticity zone of H. pylori, in Brazilian isolates of H. pylori. We also examined the association between these genes and H. pylori-related gastritis, peptic ulcer disease, and gastric and duodenal ulcers in an attempt to identify a gene marker for clinical outcomes related to infection by H. pylori. The cagT gene was associated with peptic ulcer disease and gastric ulcers, whereas the virB11 gene was detected in nearly all of the samples. The dupA gene was not associated with duodenal ulcers or any gastroduodenal disease here analyzed. These results suggest that cagT could be a useful prognostic marker for the development of peptic ulcer disease in the state of São Paulo, Brazil. They also indicate that cagT is associated with greater virulence and peptic ulceration, and that this gene is an essential component of the type IV secretion system of H. pylori.