Oral Delivery of Liraglutide-Loaded Zein/Eudragit-Chitosan Nanoparticles Provides Pharmacokinetic and Glycemic Outcomes Comparable to Its Subcutaneous Injection in Rats.

Liraglutide (LIRA) is a glucagon-like peptide-1 (GLP-1) receptor agonist renowned for its efficacy in treating type 2 diabetes mellitus (T2DM) and is typically administered via subcutaneous injections. Oral delivery, although more desirable for being painless and potentially enhancing patient adherence, is challenged by the peptide's low bioavailability and vulnerability to digestive enzymes. This study aimed to develop LIRA-containing zein-based nanoparticles stabilized with eudragit RS100 and chitosan for oral use (Z-ERS-CS/LIRA). These nanoparticles demonstrated a spherical shape, with a mean diameter of 238.6 nm, a polydispersity index of 0.099, a zeta potential of +40.9 mV, and an encapsulation efficiency of 41%. In vitro release studies indicated a prolonged release, with up to 61% of LIRA released over 24 h. Notably, the nanoparticles showed considerable resistance and stability in simulated gastric and intestinal fluids, suggesting protection from pH and enzymatic degradation. Pharmacokinetic analysis revealed that orally administered Z-ERS-CS/LIRA paralleled the pharmacokinetic profile seen with subcutaneously delivered LIRA. Furthermore, in vivo tests on a diabetic rat model showed that Z-ERS-CS/LIRA significantly controlled glucose levels, comparable to the results observed with free LIRA. The findings underscore Z-ERS-CS/LIRA nanoparticles as a promising approach for oral LIRA delivery in T2DM management.

Prolonged polymerization of a universal adhesive in non-carious cervical lesions: 36-month double-blind randomized clinical trial.

OBJECTIVE: To evaluate the effect of prolonged (P) polymerization time of a universal adhesive system applied in etch-and-rinse (ER) or self-etch (SE) strategies on the clinical performance of restorations in non-carious cervical lesions (NCCLs), after 36 months of clinical service. METHODS: A total of 140 restorations were randomly placed in 35 subjects according to the polymerization time groups: ER (10 s); ER-P (40 s); SE (10 s); and SE-P (40 s) at 1,200 mW/cm2. Composite resin was placed incrementally. The restorations were evaluated immediately and after 6, 12, 18, and 36 months using the FDI criteria. Data were analyzed using the Kaplan-Meier survival test for retention loss, and the Kruskal-Wallis' test for secondary outcomes (α = 0.05). RESULTS: After 36 months, 19 restorations were lost: ER 6, ER-P 2, SE 9, SE-P 2. The retention rates were 82.3% for ER; 94.1 % for ER-P; 73.5 % for SE; and 94.1 % for SE-P, with a significant difference between ER vs. ER-P and SE vs. SE-P, as well as ER vs. SE-P and ER-P vs. SE (p < 0.0001). Minor defects were observed in 18 restorations for the marginal staining criteria: ER 5, ER-P 2, SE 8, SE-P 3; and in 33 restorations for the marginal adaptation criteria: ER 11, ER-P 4, SE 12, and SE-P 6 (p > 0.05). No restorations showed recurrence of caries or postoperative sensitivity. CONCLUSIONS: A prolonged polymerization time of 40 s improves the clinical performance of the universal adhesive for both adhesive strategies evaluated, even after 36 months. CLINICAL SIGNIFICANCE: Prolonging the polymerization time of a universal adhesive from 10 to 40 s has been shown to improve its clinical performance when used in NCCLs.

Genomic epidemiology unveils the dynamics and spatial corridor behind the Yellow Fever virus outbreak in Southern Brazil.

Despite the considerable morbidity and mortality of yellow fever virus (YFV) infections in Brazil, our understanding of disease outbreaks is hampered by limited viral genomic data. Here, through a combination of phylogenetic and epidemiological models, we reconstructed the recent transmission history of YFV within different epidemic seasons in Brazil. A suitability index based on the highly domesticated Aedes aegypti was able to capture the seasonality of reported human infections. Spatial modeling revealed spatial hotspots with both past reporting and low vaccination coverage, which coincided with many of the largest urban centers in the Southeast. Phylodynamic analysis unraveled the circulation of three distinct lineages and provided proof of the directionality of a known spatial corridor that connects the endemic North with the extra-Amazonian basin. This study illustrates that genomics linked with eco-epidemiology can provide new insights into the landscape of YFV transmission, augmenting traditional approaches to infectious disease surveillance and control.

Uncommon Pigmented Carcinoma In Situ: Case Report and Brief Review.

Pigmented lesions of the oral mucosa encompass several benign and malignant conditions that may be a matter of concern under both clinical and histopathological views. We reported a case of a 62-year-old woman, presenting with an asymptomatic, deeply pigmented lesion on the soft palate. On examination, it appeared asymmetrical, with irregular borders and an area of ulceration. A biopsy, taken to rule out melanoma, revealed a pigmented carcinoma in situ. Throughout the tumor thickness, numerous interspersed melanocytes were found that did not extend to neighboring epithelium. These were large, richly dendritic, and presented abundance of melanin granules and small nuclei. Mild melanin incontinence was found. Scanty transfer of pigment to dysplastic epithelial cells was found through Fontana Masson staining. On immunohistochemical analyses, there were pancytokeratin-stained tumor epithelial cells; increased cell proliferation throughout the entire thickness of the tumor was emphasized by Ki-67 immunomarking. P16 was negative. The dendritic cells were selectively stained for S-100, HMB45 and Melan A. Wide spectrum in situ hybridization for human papillomavirus (HPV) was negative. Unfortunately, following diagnosis, the patient refused any treatment option. Pigmented squamous cell carcinoma with melanocyte colonization must be taken into account in the differential diagnosis of pigmented lesions of the oral cavity.

The Brazilian version of the SCOFF questionnaire to screen eating disorders in young adults: cultural adaptation and validation study in a university population.

OBJECTIVE: This study translated, culturally adapted, and validated a Brazilian Portuguese version (SCOFF-BR) of the Sick, Control, One Stone, Fat, Food Questionnaire (SCOFF) to screen eating disorders in young adults. METHODS: This study used back-translation to culturally adapt the questionnaire according to International Society of Pharmacoeconomics and Outcome Research principles. The SCOFF-BR validation process involved a sample of men and women aged 18-32 years from a university community. After the participants completed the SCOFF-BR questionnaire, pre-trained researchers interviewed them with the Mini International Neuropsychiatric Interview (MINI). The presence of eating disorders was determined according to DSM-5 criteria. RESULTS: Of the 361 subjects, 9.7% had an eating disorder (2.2% anorexia nervosa, 5% bulimia nervosa, and 2.5% binge-eating disorder). Using a cutoff point of two positive responses, we obtained a sensitivity of 80% and a specificity of 71.5%, with an accuracy of 72.3%. The positive and negative predictive values were 23.1% and 97.1%, respectively. CONCLUSION: This study demonstrated that the Brazilian version of the SCOFF questionnaire presents satisfactory accuracy and reliability to screen eating disorders among young adults in the Brazilian university community.

Panax ginseng metabolite (GIM-1) modulates the effects of monobutyl phthalate (MBP) on the GPR30/GPER1 canonical pathway in human Sertoli cells.

This study was performed to evaluate the effect of monobutyl phthalate (MBP) on GPR30-activated pathways in Sertoli cells. Additionally, we tested if GIM-1 (Panax ginseng metabolite) modulates MBP action. Human Sertoli cells (HSeC lineage) were exposed to MBP and/or GIM-1 for 30 min, 1, 12, and 48 h. Four experimental treatments were performed: control (DEMEM/F12 medium), MBP, GIM-1, and MBP + GIM-1. The results indicate that MBP activates GPR30, PKA, Src, EGFR, and the ERK1/2 proteins, while GIM-1 inhibits PKA, Src, ERK1/2, and the AKT pathway. MBP also enhances Cofilin expression, decreasing F-actin intensity on the cell surface in a short time. The combined exposure demonstrated a functional antagonism between compounds. Collectively, these data show that MBP activates GPR30 in Sertoli cells, and GIM-1 modulates this response, playing a protective role in Sertoli cells exposed to MBP.

Isolation and Genetic Identification of Endophytic Lactic Acid Bacteria From the Amazonian Açai Fruits: Probiotics Features of Selected Strains and Their Potential to Inhibit Pathogens.

The açai palm (Euterpe oleracea) is native to the Amazon basin, a humid tropical forest. High levels of total mesophilic bacteria with high diversity have been consistently reported in açai fruits. As local consumers have few digestive problems, the results of the present study reveal the lactic acid bacteria (LAB) recovered from açai fruits with characteristics that suggest they are possible candidates for probiotics and antagonistic potential against pathogens for the first time. Açai fruits were sampled from five different locations in the Eastern Amazonia floodplains. Sixty-six isolates were recovered from fruits and tested for some probiotic characteristics following FAO/WHO guidelines. Approximately 65% of the isolates showed no catalase or oxidase activity, Gram-positive staining or cocci and bacilli cell morphology. Furthermore, 48% of the isolates demonstrated preliminary characteristics that suggest safety for use, as they presented no coagulase enzyme activity or gamma-hemolysis. These strains were identified as belonging to the genera Lactiplantibacillus and Pediococcus, and 32 strains also presented resistance to vancomycin, ciprofloxacin and streptomycin. In addition, 28 isolates showed a survival rate, expressed as log cycle reduction, higher than 0.9 under gastric conditions (pH 2). All strains tested positive in bile salts deconjugation tests and showed a survival rate higher than 0.8 in the presence of this salt. Regarding antimicrobial activity against pathogens, all strains were able to inhibit Salmonella Typhimurium (ATCC® 14028TM) and 97% were capable of inhibiting Escherichia coli (ATCC® 25922TM). Concerning the results of in vitro antagonistic assays, three isolates (B125, B135, and Z183 strains) were selected for antagonistic tests using açai juice contaminated with these two pathogens. All tested LAB strains were able to inhibit pathogen growth in açai juice. In summary, açai fruits are a potential source of LAB isolates to be investigated as probiotics.

Arsenic exposure during prepuberty alters prostate maturation in pubescent rats.

Arsenic is a widely dispersed chemical compound in the environment and has been associated with the development of some diseases and different types of cancer. Little is known about the action of arsenic compounds on prostate development during prepuberty and puberty. This study evaluated prostate morphophysiology after sodium arsenite exposure during prepubertal period in rats. Male Wistar rats at PND23 were randomly distributed into three experimental groups (n = 10/group). The Ctrl group (filtered drinking water); As1 group (0.01 mg/L of NaAsO2); As2 group (10.0 mg/L of NaAsO2) that received the diluted solution in drinking water from PND23 to PND53. Histological and molecular analyzes showed developmental delay in the As1 group and important morphophysiological alterations in As2 group. The results showed that exposure to NaAsO2 during prepuberty compromised structural and functional maturation of the prostate in pubertal rats at both doses evaluated in this study.

Panax ginseng methabolit (GIM-1) prevents oxidative stress and apoptosis in human Sertoli cells exposed to Monobutyl-phthalate (MBP).

This study evaluated oxidative stress markers in Human Sertoli cells cultivated on Geltrex® and exposed to Monobutyl Phthalate (MBP), and the potential cytoprotective role of GIM-1 on the antioxidant response. Exposure was performed at 30 min, 1, 12 and 48 h into 4 groups: control, MBP (10µM), GIM-1 (0,05µM) and MBP + GIM-1. Morphology was evaluated. Antioxidant enzymes were analyzed by colorimetric method; NRF-2, SIRT-1, 8- OHdG and Cleaved Caspase-3 by Western Blot. Larger spaces between cells were shown in MBP treatment; GIM-1 was similar to Control and MBP + GIM-1 showed an intermediate aspect. MBP reduced enzymatic activity of all enzymes and NRF-2 expression, increasing cleaved Caspase-3 expression; while GIM-1 increased antioxidants markers alone and attenuated MPB effects in MBP + GIM-1. MBP induced deleterious effects on Sertoli cells, increasing the oxidative stress, apoptosis and modifying their distribution in culture; however, GIM-1 acted as an important cytoprotective agent reversing our attenuating MBP effects.

Raloxifene decreases cell viability and migratory potential in prostate cancer cells (LNCaP) with GPR30/GPER1 involvement.

OBJECTIVES: This study evaluated raloxifene (ral) effects on LNCaP prostate tumour cells modulating the activity of GPER1/GPR30 receptors. METHODS: LNCaP cells were submitted for 40/120 min and 12 h to the following treatments: C: RPMI + DMSO; R: RPMI + Ral; G: RPMI + Ral + G15 (GPER1 antagonist). Trypan blue staining measured cell viability. Migratory potential (12 h) was measured by transwell migration test in translucent inserts, which were then stained with DAPI and analysed under a fluorescence microscope for quantification. Cells from 40- and 120-min treatments were subjected to protein extraction to the study of AKT, pAKT, ERK, pERK, ERß and SIRT1. KEY FINDINGS: There is a reduction in cellular viability in R compared to C at all evaluated times, and an increased cell viability in G when compared to R; cell viability was similar in C and G in all times studied. The migration assay demonstrated a significant decrease in migration potential of tumour cells in R compared to C and G. Ral treatment reduced pERK expression and increased pAKT in the treated groups after 40 min, pointing out to an antiproliferative and apoptotic effect in the GPER1-controlled rapid-effect pathways. CONCLUSIONS: Raloxifene was able to modulate GPER1 in LNCaP prostate tumour cells, decreasing cell viability and their migratory potential.

Is there a role for cannabidiol in psychiatry?

OBJECTIVES: Understanding whether cannabidiol (CBD) is useful and safe for the treatment of psychiatric disorders is essential to empower psychiatrists and patients to take good clinical decisions. Our aim was to conduct a systematic review regarding the benefits and adverse events (AEs) of CBD in the treatment of schizophrenia, psychotic disorders, anxiety disorders, depression, bipolar disorder and substance-use disorders. METHODS: We conducted a literature search in PubMed, Scielo, and Clinicaltrials.gov databases. Evidence was classified according to the WFSBP task forces standards. RESULTS: Bibliographic research yielded 692 records. After analysis, we included six case reports and seven trials, comprising 201 subjects. Most the studies published presented several drawbacks and did not reach statistical significance. We have not found evidence regarding major depressive and bipolar disorders. The level of evidence for cannabis withdrawal is B; cannabis addiction is C2; treatment of positive symptoms in schizophrenia and anxiety in social anxiety disorder is C1. Discrete or no AEs were reported. The most frequently reported AEs are sedation and dizziness. CONCLUSIONS: The evidence regarding efficacy and safety of CBD in psychiatry is still scarce. Further larger well-designed randomised controlled trials are required to assess the effects of CBD in psychiatric disorders.

Assessment of the accuracy of a new tool for the screening of smartphone addiction.

OBJECTIVE: To translate, adapt and validate the Smartphone Addiction Inventory (SPAI) in a Brazilian population of young adults. METHOD: We employed the translation and back-translation method for the adaptation of the Brazilian version SPAI (SPAI-BR). The sample consisted of 415 university students. Data was collected through an electronic questionnaire, which consisted of the SPAI-BR and the Goodman Criteria (gold standard). The retests were carried out 10-15 days after the initial tests with 130 individuals. RESULTS: The SPAI-BR maintained semantic, idiomatic and conceptual equivalences from the original scale. The Confirmatory Factor Analysis confirmed the One-factor model of the SPAI with good fit indexes (x2 = 767.861, CFI = 0.913, TLI = 0.905, RMSE = 0.061, WRMR = 1.465). The Kuder-Richardson Coefficient showed good internal consistency. The analysis of the ROC curve established an area under the curve of 86.38%. The Intraclass-Correlation Coefficient of 0.926 between the test and the retest demonstrated an excellent temporal stability. The high correlation between SPAI-BR and the Goodman Criteria (rs = 0.750) established the convergent validity. CONCLUSION: The SPAI-BR is a valid and reliable tool for the detection of Smartphone Addiction in Brazilian university students.

In Situ Melanoma of the Gingiva Associated with Dense Inflammation and Pigment Deposition: A Potential Diagnostic Pitfall in Evaluating Stromal Invasion.

Melanoma is a highly aggressive neoplasm in which the neoplastic cells display melanocytic differentiation. Less than 1 % of all melanomas arise in the mucosal surfaces of the oral cavity, with purely in situ lesions being exceedingly rare tumors, but with a favorable prognosis compared with invasive lesions. We describe the clinical, histopathological and immunohistochemical findings in an uncommon case of in situ mucosal melanoma of the oral cavity with intense tumor-associated pigment deposition and inflammation complicating the morphological assessment of infiltrative areas.

Regulatory and junctional proteins of the blood-testis barrier in human Sertoli cells are modified by monobutyl phthalate (MBP) and bisphenol A (BPA) exposure.

The blood-testis barrier (BTB) is responsible for providing a protected environment and coordinating the spermatogenesis. Endocrine disruptors (EDs) might lead to infertility, interfering in the BTB structure and modulation. This study aimed to correlate the actions of two EDs, monobutyl phthalate (MBP) and bisphenol A (BPA) in different periods of exposure, in a low toxicity dose to the human Sertoli cells (HSeC) and its effects on the proteins of the BTB and regulatory proteins involved in its modulation. HSeC cells were exposed to MBP (10µM) and BPA (20µM) for 6 and 48h. Western Blot assay indicated that MBP was able to reduce the expression of occludin, ZO-1, N-cadherin and Androgen Receptor (AR), while BPA leads to a reduction of occludin, ZO-1, ß-catenin and AR. TGF-ß2 and F-actin were not modified. Phalloidin and Hematoxylin and Eosin assay revealed phenotically disruption in Sertoli cells adhesion, without changes in F-actin expression or localization. Our data suggested both EDs present potential for disrupting the structure and maintenance of the human BTB by AR dependent pathway.

Preemptive Analgesia with Acupuncture Monitored by c-Fos Expression in Rats.

Pain behavior and awareness are characterized by heightened alertness and anxiety, which begin to disappear as soon as the curative process starts. The present study aimed to quantify c-fos expression in rat spinal cords and brains after a surgical stimulus and with preoperative or postoperative acupuncture. Animals were randomly divided into preoperative and postoperative groups and were then further divided into control, manual acupuncture (MA), or electroacupuncture (EA) groups. Expression of c-fos was quantified using immunohistochemistry. The collected data were analyzed using the t test at a 5% probability level. Presurgery and postsurgery spinal cord c-fos expressions were similar in all of the treatment groups. In the control rats, c-fos expression was higher before surgery than after surgery, contradicting the expected outcome of acupuncture and preemptive analgesia. After treatment, the expression of c-fos in the brains of the rats in the MA and the EA groups was reduced compared with that of the rats in the control group. These findings suggest that acupuncture used as preemptive analgesia in rats is a useful model for studying its application in human treatment.

Effects of chin advancement surgery in hyoid bone and tongue positions and in the dimension of the oropharynx.

INTRODUCTION: Advancement genioplasty has been increasingly indicated for the correction of anterior mandibular deficiency as it balances the patient's profile and generates functional changes. OBJECTIVE: Thus, the aim of this study was to assess the effects of advancement genioplasty in the oropharyngeal size and in the position of the hyoid bone and tongue. METHODS: The sample comprised 22 lateral cephalometric radiographs of 11 individuals who had undergone advancement genioplasty alone. Eleven of these radiographs depicted the immediate preoperative period (T0) and the other 11 the postoperative period after at least four months (T1). The radiographs were scanned and exported to the Radiocef Studio 2.0® software (Radio Memory Ltda., Belo Horizonte, MG, Brazil). The landmarks were then identified and automatically measured by the program. RESULTS: The results showed statistically significant differences between the horizontal position of the hyoid bone and tongue and in the oropharyngeal size. The hyoid bone and tongue were repositioned anteriorly after surgery (p = 0.01), thereby increasing the dimension of the oropharyngeal airspace (p = 0.01). CONCLUSIONS: The oropharyngeal dimension increased as the tongue base and hyoid bone were repositioned more anteriorly.

Calcium oxalate crystals in eucalypt ectomycorrhizae: morphochemical characterization.

Ectomycorrhizal fungi are ubiquitous in forest ecosystems, benefitting plants principally by increasing the uptake of water and nutrients such as calcium from the soil. Previous work has demonstrated accumulation of crystallites in eucalypt ectomycorrhizas, but detailed morphological and chemical characterization of these crystals has not been performed. In this work, cross sections of acetic acid-treated and cleared ectomycorrhizal fragments were visualized by polarized light microscopy to evaluate the location of crystals within cortical root cells. Ectomycorrhizal sections were also observed by scanning electron microscopy (SEM) coupled with energy dispersive x-ray (EDS) microprobe analysis. The predominant forms of crystals were crystal sand (granules) and concretions. Calcium, carbon and oxygen were detected by EDS as constituent elements and similar elemental profiles were observed between both crystal morphologies. All analyzed crystalline structures were characterized as calcium oxalate crystals. This is the first report of the stoichiometry and morphology of crystals occurring in eucalypt ectomycorrhizas in tropical soils. The data corroborates the role of ectomycorrhizae in the uptake and accumulation of calcium in the form of calcium oxalate crystals in hybrid eucalypt plants.

Dimensional analysis of the parietal bone in areas of surgical interest and relationship between parietal thickness and cephalic index.

PURPOSE: The aim of this study was to determine the thickness of the parietal bone in bone graft donor sites and to study the relationship between parietal bone thickness and gender or cephalic index. MATERIALS AND METHODS: We studied 300 parietal bones from 150 human skulls (84 male and 66 female) from individuals aged 18 to 60 years at the time of death. On each parietal bone, 9 areas were drawn by use of reference anatomic landmarks (bregma, lambda, asterion, and pterion), and bone thickness was determined in the areas adjoining the sagittal suture--superior-anterior (Sa), superior-medial (Sm), and superior-posterior (Sp). RESULTS: Mean thickness measurements ranged from 2.30 to 11.25 mm in the Sa area, from 3.08 to 13.32 mm in the Sm area, and from 2.88 to 12.26 in the Sp area. Smaller mean measurements were observed in the Sa area, with the smallest mean thickness being found in brachycephalic female specimens. The largest mean thickness was also found in female specimens in the Sm area. Statistically significant differences between genders were found only in the Sa area in dolichocephalic and mesocephalic specimens. CONCLUSION: Although the best bone graft donor site surgically is different in individuals of different genders and with different cephalic indexes, our findings suggest that harvesting from the anterosuperior area of the parietal bone should not be performed.

Effect of gene therapy with vascular endothelial growth factor after abdominoplasty on TRAM flap viability in a rat model.

BACKGROUND: The transverse rectus abdominis musculocutaneous (TRAM) flap may develop necrosis, especially in patients with risk factors such as previous abdominoplasty, caused by damage to perforating vessels during surgical procedures. This study was designed from the perspective of using vascular endothelial growth factor (VEGF) gene therapy with plasmid vector after abdominoplasty to stimulate neovascularization of the TRAM flap, thus increasing flap viability. METHODS: Thirty-two Wistar rats were divided into four groups (n = 8). A right inferiorly based TRAM flap was constructed in all animals and was the only procedure performed in group I (TRAM flap). Animals from groups II (abdominoplasty) and III (plasmid) underwent abdominoplasty and were injected intramuscularly with physiologic saline solution and empty plasmid, respectively. Group IV (VEGF) received intramuscular injection of naked plasmid DNA encoding VEGF-165 during abdominoplasty. The TRAM flap was created 30 days after abdominoplasty. RESULTS: The mean necrosis was 24.65 +/- 18.13 percent in group I, 62.49 +/- 28.06 percent in group II, 57.80 +/- 25.43 percent in group III, and 18.33 +/- 16.20 percent in group IV. The number of vessels in the TRAM flap was determined by immunohistochemistry using the antibody human heart factor. Groups I and IV had a similar number of vessels, as did groups II and III. Groups I and IV had greater viability and number of vessels than groups II and III. CONCLUSION: VEGF gene therapy increased viability and vessel number in the TRAM flap created after abdominoplasty in a rat model.

Russell body apical periodontitis: an unusual case report.

Russell bodies (RBs) changes in chronic apical lesions have rarely been reported in the literature. We describe a case of a periapical lesion abundantly and extensively composed of RB. Microscopic examination showed accumulation of plasma cells containing globular, spherical, polygonal, and eosinophilic structures against fibrous connective tissue. Initial diagnostic considerations based on a smaller magnification included hypersecretory plasmocytoma, although there was no evidence of infiltrative growth, mitotic activity, nuclear atypia, or cellular pleomorphism. Then, a panel of immunohistochemical markers was applied and the cells showed positivity with both kappa and lambda chains demonstrating their polyclonal origin. The extensive accumulation of RBs involving the periapical region represents an unreported and significant histologic change, as it was mimicking a malignant neoplasm.