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Danielle Cristinne Azevedo Feio,1 Nayara Cristina Lima de Oliveira,1 Edmundo Luis Rodrigues Pereira,1 Aleksandra Tiemi Morikawa,2 José Augusto Pereira Carneiro Muniz,3 Raquel Carvalho Montenegro,1 Ana Paula Negreiros Nunes Alves,4 Patrícia Danielle Lima de Lima,5 Raul Cavalcante Maranhão,2 Rommel Rodríguez Burbano1 1Human Cytogenetics Laboratory, Institute of Biological Sciences, Federal University of Pará, Belem, 2Heart Institute, University of Sao Paulo Medical School Hospital, Sao Paulo, 3Evandro Chagas Institute, Primate National Center, Ananindeua, 4Department of Clinical Dentistry, Health Sciences Center, Federal University of Ceará, Fortaleza, 5Molecular Biology Laboratory, Post Graduate Program of Amazon Parasitic Biology, Biological and Health Sciences Center, State University of Pará, Belem, Brazil Abstract: Lipid-based nanoparticle systems have been used as vehicles for chemotherapeutic agents in experimental cancer treatments. Those systems have generally been credited with attenuating the severe toxicity of chemotherapeutic agents. This study aimed to investigate the effects of associating paclitaxel (PTX) with a lipid-based nanoparticle system on a nonhuman primate, Cebus apella, documenting the toxicity as measured by serum biochemistry, which is a detailed analysis of blood and tissue. Eighteen C. apella were studied: three animals were treated with cholesterol-rich nanoemulsion (LDE) only, without PTX, administered intravenously every 3 weeks, during six treatment cycles; six animals were treated with PTX associated with LDE at the same administration scheme, three with lower (175 mg/m2) and three with higher (250 mg/m2) PTX doses; and six animals were treated with commercial PTX, three with the lower and three with the higher doses. In the LDE-PTX group, no clinical toxicity appeared, and the weight–food consumption curve was similar to that of the controls. Two animals treated with commercial PTX presented weight loss, nausea and vomiting, diarrhea, skin flaking, 70% loss of body hair, and decreased physical activity. The use of LDE as a carrier at both lower and higher doses reduced the toxicity of the drug in this species, which is closely related to human subjects. This was observed not only by clinical, biochemical, and hematological profiles but also by the histopathological analysis. The results of this study support the assumption that lipid-based nanoparticle systems used as drug carriers can serve as valuable tools to decrease the toxicity and increase the safety of chemotherapeutic agents. Keywords: nanoparticles, LDE, paclitaxel, toxicity, Cebus apella

PURPOSE: The aim of this prospective observational study was to evaluate the incidence of postoperative bleeding after dental extraction in candidates for liver transplantation and the efficacy of the association of tranexamic acid and absorbable hemostatic sponges. PATIENTS AND METHODS: All individuals referred for oral health evaluation requiring extraction were considered in this study. Patients were included in the analysis when the blood examinations showed a platelet count of 30,000/mm(3) or greater and an international normalized ratio (INR) of 3.0 or less. In group 1 local pressure was applied by use of gauze soaked with tranexamic acid, and in group 2 gauze without tranexamic acid was used. Absorbable hemostatic sponges and cross sutures were used as a standard hemostatic measure. RESULTS: In the 23 patients included in this study, 84 simple extractions were performed during 35 dental surgical procedures. The main preoperative blood tests found the following: a mean hematocrit level of 34.54% (SD, 5.84%; range, 21.7%-44.4%), platelet counts from 31,000/mm(3) to 160,000/mm(3), and a mean INR of 1.50 (SD, 0.39; range, 0.98-2.59). Postoperative bleeding occurred during only 1 procedure (2.9%), and local pressure with gauze was effective for achieving hemostasis. No statistically significant difference in the time to hemostasis was found between the 2 groups. CONCLUSIONS: This study found a low risk of bleeding for tooth extractions in patients with liver cirrhosis, INRs of 2.50 or less, and platelet counts of 30,000/mm(3) or greater. Blood transfusions were not needed, and in the case of postoperative bleeding, the use of local hemostatic measures was satisfactory. [ABSTRACT FROM AUTHOR]

Purpose: Incisional hernia is one of the most common post-operative complications. Previous studies showed that prophylactic mesh placement in laparotomy closure is safe and reduces the incidence of incisional hernia. We aimed to perform a meta-analysis comparing post-operative complications after the use of prophylactic permanent mesh placement versus primary closure in patients undergoing elective or emergency laparotomies., Methods: A systematic review of Cochrane Central Register of Controlled Trials, Embase and PubMed was performed in April 2024. Only randomized clinical trials were included. 1,234 studies were imported for screening. 280 were duplicated reports, 923 were excluded for irrelevancy and 16 were excluded after full-text review. Data were extracted in accordance with PRISMA guidelines and pooled by a random-effects model. The primary outcome was incidence of incisional hernia. Secondary outcomes included post-operative complications and period of hospitalization., Results: Fifteen studies and 2,108 patients were included. Incisional hernia incidence was different between groups (risk ratio [RR] 0.30; 95% CI 0.21-0.43; p < 0.00001; I²=39%). This finding was confirmed in a subgroup analysis of elective (RR 0.29; 95% CI 0.18-0.46; p < 0.00001; I²=48%) versus emergency laparotomies (RR 0.28; 95% CI 0.19-0.43; p = 0.0001; I²=0%). There was no significant difference in incisional hernia incidence by locals of mesh placement. Secondary outcomes had shown no statistically significant difference between groups, except for seroma wherein primary closure had lower events (RR 1.80; CI 95% 1.21-2.68; p = 0.38; I²=7%)., Conclusion: In patients undergoing laparotomy, prophylactic permanent mesh placement is associated with a significant reduction on incidence of incisional hernia as compared to primary closure., Competing Interests: Declarations Conflict of interest The authors Ana Paula Valério-Alves, Caio Leonardo dos Santos Saggin, João Marcos Escórcio de Aguiar Portela, Patricia Viana, Gabriela Branquinho Guerra, Camila Mariana de Paiva Reis and Rafael Morriello, declare they have no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

To improve the biocompatibility and bioactivity of biodegradable iron-based materials, nanostructured surfaces formed by metal oxides offer a promising strategy for surface functionalization. To explore this potential, iron oxide nanotubes were synthesized on pure iron (Fe) using an anodic oxidation process (50 V-30 min, using an ethylene glycol solution containing 0.3% NH 4 F and 3% H 2 O, at a speed of 100 rpm). A nanotube layer composed mainly of α-Fe 2 O 3 with diameters between 60 and 70 nm was obtained. The effect of the Fe-oxide nanotube layer on cell viability and morphology was evaluated by in vitro studies using a human osteosarcoma cell line (SaOs-2 cells). The results showed that the presence of this layer did not harm the viability or morphology of the cells. Furthermore, cells cultured on anodized surfaces showed higher metabolic activity than those on non-anodized surfaces. This research suggests that growing a layer of Fe oxide nanotubes on pure Fe is a promising method for functionalizing and improving the cytocompatibility of iron substrates. This opens up new opportunities for biomedical applications, including the development of cardiovascular stents or osteosynthesis implants.

This study has innovative aspects related to the use of sequential inoculation technique in the coffee bean fermentation process: the inoculation of Lactiplantibacillus plantarum followed by Saccharomyces cerevisiae, in the fermentation of coffee fruit for the production of specialty natural coffees. The objective was to evaluate the effect of this technique and of the total fermentation time on the sensory attributes of the coffee beverage and on the organic acid profile, bioactive compounds, and fatty acid profile of the beans. The fermentation of coffee fruit with sequential inoculation resulted in greater acidity of the beverage and contributed to increases of up to 2 points in coffee fermented. The total fermentation time was directly related to the organic acid content, and the longer the total fermentation time was, the greater the organic acid content. The fatty acid content and bioactive compound content showed little variation among treatments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the role of induced nitric oxide synthase (iNOS) in nociception/orofacial discomfort in rats submitted to tooth whitening with hydrogen peroxide (H₂O₂)., Design: Wistar rats were divided into three groups (n = 24/group): a sham group not submitted to whitening treatment, a saline group submitted to whitening treatment, and a test group submitted to whitening treatment and blockade of iNOS with aminoguanidine 50 mg/kg/day. After 24 and 48 h, and 7 days, the animals were euthanized to collect trigeminal ganglia and maxillae to histomorphometric analysis (size of neuronal bodies and percentage of pulp area filled by vessels) and behavior/nociception (Grimace scales, scratching and biting counting, weight loss and nociception assay). ANOVA-1- or - 2-way tests were used (p < 0.05, GraphPadPrism 5.0)., Results: The aminoguanidine-treated group showed a reduction in nociceptive threshold in the masseteric region (p < 0.001), Grimace scale scores (p < 0.001), number of scratching (p = 0.011) and body mass loss (p = 0.007). After 24 and 48 h of tooth bleaching, the saline group showed a significant increase in the mean area of the blood vessels (p = 0.020) and iNOS immunostaining in odontoblasts (p = 0.002) and non-odontoblasts cells (p = 0.025). Aminoguanidine reversed both increases. Tooth bleaching reduced the mean area of neuronal bodies, and aminoguanidine significantly reversed it (p = 0.019), but an increase in GFAP immunostaining in neuronal bodies did not reduce after seven-days or after aminoguanidine treatment (p = 0.003)., Conclusion: iNOS blockage by aminoguanidine plays an important role in nociception and orofacial discomfort by control of inflammation in dental pulp after tooth bleaching with hydrogen peroxide (H₂O₂) 35%., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The increased fish consumption by the growing human population in the world translates into an increase in fish waste. The reintroduction of these fish by-products into food and feed chains presents economic benefits and contributes to counteracting their negative environmental impact. Under this context, the present study aimed to evaluate the effects of the dietary inclusion of fish hydrolysate and oil obtained from fish waste (experimental diet) in substitution of shrimp hydrolysate and salmon oil (control diet) mainly imported from third countries on palatability, apparent total tract digestibility, fecal characteristics and metabolites, blood fatty acid profile, flatulence, and coat quality of adult dogs. A two-bowl test was performed to evaluate palatability by the pairwise comparison between the two diets. A feeding trial was conducted according to a crossover design with two diets (control and experimental diets), six adult Beagle dogs per diet, and two periods of 6 weeks each. The replacement of shrimp hydrolysate and salmon oil with fish hydrolysate and oil did not affect the first diet approach and taste, as well as the intake ratio. Generally, the digestibility of dry matter, nutrients, and energy was not affected by diet, but the intake of digestible crude protein (CP) and ether extract was higher, respectively, with the control and the experimental diet. The higher intake of eicosapentaenoic acid and docosahexaenoic acid with the experimental diet was reflected in a higher content of these long-chain polyunsaturated fatty acids and the omega-3 index of red blood cells, but it did not affect coat quality. The significantly higher intake of digestible CP with the control diet might have contributed to the higher fecal ammonia-N and valerate concentrations. Daily fecal output and characteristics were similar between diets. Overall, results suggest that fish hydrolysate and oil from the agrifood industry might constitute sustainable functional ingredients for dog feeding while adding value for wild fisheries, aquaculture, and fish farming under a circular economy approach and reducing dependence on imports from third countries with a high carbon footprint., Competing Interests: TA was employed by SORGAL, Sociedade de Óleos e Rações S.A. AR was employed by SEBOL, Comércio e Indústria de Sebo, S.A., AA and RM were employed by Indústria Transformadora de Subprodutos, S.A. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cabrita, Maia, Alves, Aires, Rosa, Almeida, Martins and Fonseca.)

Background: Collagen is a component of Pyogenic Granuloma (PG) and Peripheral Ossifying Fibroma (POF) and performs different functions in these lesions. The objective of this study is to evaluate the role of collagen and immunostaining for Transforming Growth Factor beta (TGF-β) in the clinical and microscopic findings of PG and POF., Material and Methods: PG (n=20) and POF (n=20) were selected for clinical evaluation (sex, age, localization, size and evolution time) and microscopic analysis (picrosirius red staining for collagen analysis and immunohistochemistry for TGF-β) performed in the superficial and deep areas of the two lesions. ANOVA/Bonferroni and t-test, Pearson correlation and χ2 were used to compare the sites and parameters analyzed (p<0.05, GraphPad Prism 5.0)., Results: The depth of PG presented the highest amount of collagen (p<0.001), and its surface showed the lowest amount of type 1 collagen (yellow-red strong birefringence). Type 1 collagen gradually increased in depth of PG, surface and depth of POF (p<0.001). The number of TGF-β+ cells was lower on the surface of PG compared with the depth of PG and the two areas of POF (p<0.001). Sex and localization did not affect these parameters, but the profile of collagen and immunostaining for TGF-β suffered from modifications by the time of evolution and the size of the lesion., Conclusions: Although PG and POF are reactive gingival lesions, the expression of TGF-β and its role in collagen showed different biological behaviors in these lesions, suggesting different biological origins for its components.

To improve survival during storage and exposure to adverse conditions, Bacillus subtilis was microencapsulated with oat β-glucan by spray-drying technology. The characterisation of the microcapsules was designed to compare free and microencapsulated cells through exposure to simulated gastric fluids (SGF) throughout storage for 90 days at different temperatures. The characterisation included analysis of efficiency, morphology, moisture, water activity, hygroscopicity, particle size, and zeta potential. The microcapsules presented a particle size of 1.5 ± 0.34 μm and an encapsulation efficiency of 77.9 ± 3.06%. After SGF, the survival of microencapsulated cells was 8.4 ± 0.07 log CFU mL -1 while that of free cells was 7.6 ± 0.06 log CFU mL -1 . After 90 days of storage, only microencapsulated cells remained above 6 log-unit of viability. In conclusion, spray-drying technique combined with the addition of oat β-glucan proved to be an efficient method to protect B. subtilis under storage and SGF with potential application in fish feed.

Low-grade myofibroblastic sarcoma (LGMS) represents an atypical tumor composed of myofibroblasts with a variety of histological patterns and with a high tendency to local recurrence and a low probability of distant metastases. LGMS has predilection for the head and neck regions, especially the oral cavity. This study aimed to report 13 new cases of LGMS arising in the oral and maxillofacial region. This study included LGMS cases from five oral and maxillofacial pathology laboratories in four different countries (Brazil, Peru, Guatemala, and South Africa). Their clinical, radiographic, histopathological, and immunohistochemical findings were evaluated. In this current international case series, most patients were females with a mean age of 38.7 years, and commonly presenting a nodular lesion in maxilla. Microscopically, all cases showed a neoplasm formed by oval to spindle cells in a fibrous stroma with myxoid and dense areas, some atypical mitoses, and prominent nucleoli. The immunohistochemical panel showed positivity for smooth muscle actin (12 of 13 cases), HHF35 (2 of 4 cases), β-catenin (3 of 5 cases), desmin (3 of 11 cases), and Ki-67 (range from 5 to 50%). H-caldesmon was negative for all cases. The diagnosis of LGMS was confirmed in all cases. LGMS shows predominance in young adults, with a slight predilection for the female sex, and maxillary region. LGMS should be a differential diagnosis of myofibroblastic lesions that show a proliferation of spindle cells in a fibrous stroma with myxoid and dense areas and some atypical mitoses, supporting the diagnosis with a complementary immunohistochemical study. Complete surgical excision with clear margins is the treatment of choice. However, long-term follow-up information is required before definitive conclusions can be drawn regarding the incidence of recurrence and the possibility of metastasis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The mechanisms of pathogenesis of acute kidney injury (AKI) in snakebites is multifactorial and involves hemodynamic disturbances, with release of free radical causing cytotoxic effects. The phosphodiesterase-3 (PDE3) inhibitor, Cilostazol, has been reported to provide protection against renal oxidative stress., Objective: We evaluated the protective effects of cilostazol against Bothrops alternatus snake venom (BaV)-induced nephrotoxicity., Methods: Wistar rat kidneys (n = 6, 260-300 g) were isolated and perfused with Krebs-Henseleit solution containing 6 g/100 mL of bovine serum albumin. After 30 min, the kidneys were perfused with BaV to a final concentration of 1 and 3 μg/mL, and subsequently evaluated for perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR), and percentage of electrolyte tubular sodium and chloride transport (%TNa + , %TCl - ). Oxidative stress and renal histological analyses were performed., Results: BaV caused a reduction in all the evaluated renal parameters (PP, RVR, GFR, UF, %TNa + , and %TCl - ). Although only the effects on PP and UF were reversed with cilostazol treatment, the decrease in the malondialdehyde levels, without changes in glutathione levels, further reduced the venom-induced renal tissue changes., Conclusion: Our data suggest that PDE3 is involved in BaV-induced nephrotoxicity, as cilostazol administration significantly ameliorated these effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Purpose: The purpose of this study was to investigate the vascular effects of photobiomodulation using a light-emitting diode on the chorioallantoic embryonic membrane of chicken eggs grouped into different times of exposure and to detect the morphological changes induced by the light on the vascular network architecture using quantitative metrics., Methods: We used a phototherapy device with light-emitting diode (670 nm wavelength) as the source of photobiomodulation. We applied the red light at a distance of 2.5 cm to the surface of the chorioallantoic embryonic membrane of chicken eggs in 2, 4, or 8 sessions for 90 s and analyzed the vascular network architecture using AngioTool software (National Cancer Institute, USA). We treated the negative control group with 50 μl phosphate-buffered-saline (pH 7.4) and the positive control group (Beva) with 50 μl bevacizumab solution (Avastin, Produtos Roche Químicos e Farmacêuticos, S.A., Brazil)., Results: We found a decrease in total vessel length in the Beva group (24.96% ± 12.85%) and in all the groups that received 670 nm red light therapy (2× group, 34.66% ± 8.66%; 4× group, 42.42% ± 5.26%; 8× group, 38.48% ± 6.96%), compared with the negative control group. The fluence of 5.4 J/cm2 in 4 sessions (4×) showed more regular vessels. The number of junctions in the groups that received a higher incidence of 670 nm red light (4× and 8×) significantly decreased (p<0.0001)., Conclusion: Photo-biomodulation helps reduce vascularization in chorioallantoic embryonic membrane of chicken eggs and changes in the network architecture. Our results open the possibility of future clinical studies on using this therapy in patients with retinal diseases with neovascular components, especially age-related macular degeneration.

Background: The human Amniotic Membrane (hAM) has been studied as a potential therapeutic option in cancer, namely in hepatocellular carcinoma. Previously, our research group evaluated the effect of human Amniotic Membrane Protein Extracts (hAMPE) in cancer therapy, demonstrating that hAMPE inhibit the metabolic activity of human hepatocellular carcinoma cell lines: Hep3B2.1-7, HepG2 and Huh7. Therefore, and considering the close relationship between metabolic activity and oxidative stress, the aim of this study was to evaluate the effect of hAMPE treatment in glucose metabolism and its role in oxidative stress of hepatocellular carcinoma., Methods and Results: Glucose uptake and lactate production was assessed by 1 H-NMR, and the expression of several mediators of the glycolytic pathway was evaluated by Western blot or fluorescence. Total antioxidant capacity (TAC) and biomarkers of oxidative stress effects in proteins were detected. Our results showed that hAMPE treatment increased glucose consumption on Hep3B2.1-7, HepG2, and Huh7 through the increase of GLUT1 in Hep3B2.1-7 and Huh7, and GLUT3 in HepG2 cells. It was observed an increased expression of 6-phosphofrutokinase (PFK-1L) in all cell lines though glucose was not converted to lactate on HepG2 and Huh7 cells, suggesting that hAMPE treatment may counteract the Warburg effect observed in carcinogenesis. In Hep3B2.1-7, hAMPE treatment induced an increase in expression of lactate dehydrogenase (LDH) and monocarboxylate transporter isoform 4 (MCT4). We further detected that hAMPE enhances the TAC of culture media after 2 and 8 h. This was followed by a degree of protection against proteins nitration and carbonylation., Conclusions: Overall, this work highlights the potential usefulness of hAMPE as anticancer therapy through the modulation of the glycolytic and oxidative profile in human hepatocellular carcinoma., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: This study aimed to analyze whether immunohistochemistry (IHC) is more sensitive than hematoxylin-eosin (H&E) staining for identifying perineural invasion (PNI) or lymphovascular invasion (LVI) in oral squamous cell carcinoma (OSCC)., Material and Methods: In this systematic review and meta-analysis (Prospective Register of Systematic Reviews - CRD 42021256515), data were obtained from six databases (PubMed, Scopus, LILACS, Web of Science, EBSCO, LIVIVO, Embase) and the grey literature. Cross-sectional observational studies of the diagnostic sensitivity of IHC for PNI and LVI were included. Studies were selected in two phases: first collection and reference retrieval. The Quality Assessment of Diagnostic Accuracy Studies-2 tool assessed study quality, while the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach assessed evidence quality. The meta-analysis (random effects model) was performed using MedCalc 18.2.1 software (MedCalc®) (p<0.05)., Results: Four studies (560 patients with 295 biopsies) were analyzed. The combined sensitivity was 76% (95% confidence interval [CI], 44.30-97.19%) and specificity was 42% (95% CI, 23.40-62.02%). The positive predictive value (PPV) and negative predictive value (NPV) were 61% (95% CI, 49.78-71.53%) and 70% (95% CI, 37.63-94.43%). The overall accuracy was 58% (95% CI, 45.17-70.65%). The risk of bias was low, and GRADE analysis showed a very low certainty of evidence., Conclusions: Our data suggest that IHC staining to highlight PNI/LVI may be useful in cases in which H&E analysis results in a negative decrease in the prevalence of false-negative cases and underestimated treatment.

Yellow fever virus (YFV) is the causative agent of yellow fever (YF), a hemorrhagic and viscerotropic acute disease. Severe YF has been described in approximately 15-25% of YF patients, with 20-50% of severe YF cases being fatal. Here we analyzed cerebrospinal fluid (CSF) samples collected during the YF outbreak in Brazil in 2018, aiming to investigate CNS neuroinvasion in fatal YFV cases. YFV RNA was screened by RT-qPCR targeting the 3'UTR region of the YFV genome in CSF. CSF samples were tested for the presence of anti-YFV IgM and neutralizing antibodies, coupled with routine laboratory examinations. Among the 13 patients studied, we detected anti-YFV IgM in CSF from eight patients and YFV RNA in CSF from five patients. YFV RNA genomic load in CSF samples ranged from 1.75×103 to 5.42×103 RNA copies/mL. We genotyped YFV from three CSF samples that grouped with other YFV samples from the 2018 outbreak in Brazil within the South-American I genotype. Even though descriptions of neurologic manifestations due to wild type YFV (WT-YFV) infection are rare, since the last YF outbreak in Brazil in 2017-2018, a few studies have demonstrated WT-YFV RNA in CSF samples from YF fatal cases. Serological tests indicated the presence of IgM and neutralizing antibodies against YFV in CSF samples from two patients. Although the presence of viral RNA, IgM and neutralizing antibodies in CSF samples could indicate neuroinvasiveness, further studies are needed to better elucidate the role of YFV neuroinvasion and possible impacts in disease pathogenesis., Competing Interests: Conflict of interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Objectives: To investigate physicochemical properties, dentin bonding, cytotoxicity, and in vivo pulp response of experimental self-adhesive composites tailored to direct pulp capping., Materials and Methods: Experimental composites were prepared with beta-tricalcium phosphate and hydroxyapatite nanoparticles adsorbed with simvastatin and glutathione added at 0% (control resin), 1 wt% (Res 1%), and 10 wt% (Res 10%). A commercial light-curable calcium hydroxide (Ca(OH) 2 ) (Ultra-Blend Plus) was used as control material. The physicochemical properties investigated were flexural strength and modulus, calcium release, and degree of conversion. Dentin bonding was assessed by the push-out test. Proliferation and cell counting assays were performed to evaluate in vitro cytotoxicity using fluorescence microscopy. In vivo pulp capping was performed on molars of Wistar rats, which were euthanized after 14 days and evaluated by histological analysis., Results: No statistical difference was observed in flexural strength and cell viability ( p > 0.05). Res 10% presented higher modulus than control resin and Ca(OH) 2 . Also, Res 10% attained statistically higher degree of conversion when compared to other experimental composites. Ca(OH) 2 showed higher calcium release after 28 and 45 days of storage, with no statistical difference at 45 days to Res 10%. All experimental composites achieved significantly higher bond strength when compared to Ca(OH) 2 . While no significant difference was observed in the cell proliferation rates, resins at lower concentrations showed higher cell viability. In vivo evaluation of pulp response demonstrated no pulp damage with experimental composites., Conclusions: The experimental composite investigated in this study achieved adequate physicochemical properties with minor in vivo pulpal inflammation and proved to be a valuable alternative for direct pulp capping., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Julianne Coelho Silva et al.)

Objective: To evaluate the short-term result of retinal functional behavior in patients with dry age-related macular degeneration (AMD) corrected by photobiomodulation (PBM) with 670 nm light-emitting diode (LED) light. Materials and methods: Ten patients with dry AMD underwent a treatment consisting of nine PBM sessions with LED light of 670 nm with two cycles of 50 mW/cm 2 , producing 4 J/cm 2 per dose in 88 sec. The studied eye was compared with the baseline (before therapy), and after nine PBM sessions, the following aspects were evaluated: best-corrected visual acuity (VA), retinal sensitivity, and characteristics of the correction area by the fundus automated perimetry using the Compass system. A functional and structural assessment of the retina was also performed using the multifocal electroretinography (ERG), optical coherence tomography (OCT), fluorescence retinography (FR), and autofluorescence (AF). All examinations were performed 1, 4, and 16 weeks after the therapy. The Chi-square and Student's t -tests were used for comparisons. The analyses followed the 95% confidence level ( p -value ≤0.05). Results: The BCVA significantly improved, from an average of 1.1 to 0.98 LogMAR ( p  = 0.01). The visual field examination, according to the parameters of mean deviation, standard deviation, and index of deviation of background perimeter, showed a significant improvement of -12.6% to -10.6%, 10.54% to 9.89%, and 56% to 60%, respectively ( p  = 0.02, 0.03, and 0.02, respectively). No participant had an adverse effect during the follow-up period; neither did any participant experience abnormalities in OCT, ERG, FR, and AF findings. Conclusions: In this short-term study, the PBM technique in patients with dry AMD showed the potential to improve VA and macular perimetry without causing significant adverse events. A larger number of patients and a longer follow-up will be necessary to further assess the success of this technique in these patients.

Cell membrane deformation is an important feature that occurs during many physiological processes, and its study has been put to good use to investigate cardiomyocyte function. Several methods have been developed to extract information on cardiomyocyte contractility. However, no existing computational framework has provided, in a single platform, a straightforward approach to acquire, process, and quantify this type of cellular dynamics. For this reason, we develop CONTRACTIONWAVE, high-performance software written in Python programming language that allows the user to process large data image files and obtain contractility parameters by analyzing optical flow from images obtained with videomicroscopy. The software was validated by using neonatal, adult-, and human-induced pluripotent stem-cell-derived cardiomyocytes, treated or not with drugs known to affect contractility. Results presented indicate that CONTRACTIONWAVE is an excellent tool for examining changes to cardiac cellular contractility in animal models of disease and for pharmacological and toxicology screening during drug discovery., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Purpose: Our objective was to evaluate the influence of pretreatment with tocilizumab (TCZ) in bone healing after tooth extraction in rats., Methods: Wistar male rats were equally divided into sham (ie, nonoperated), saline (both treated with 0.1 ml/kg saline), and six TCZ groups treated with 1, 2, 4, 8, 16, and 32 mg/kg TCZ (TCZ1 to TCZ32, respectively). Twenty-four hours after administration of vehicle or TCZ, exodontia of the first lower left molar was performed, and the animals were euthanized three days later for hematological analysis and organ (liver, spleen, and kidney mass indexes, and histological evaluation), gingiva (myeloperoxidase [MPO] assay), and mandible (radiographic, histomorphometric analysis, and IL-6 immunostaining) evaluation. Analysis of variance/Bonferroni test (statistical significance, P < .05) was performed using GraphPad Prism version 5.0 (GraphPad Inc, San Diego, CA, USA)., Results: There was no difference in radiographic results; however, leukopenia (P = .039) and neutropenia (P < .001) were statistically significant in the TCZ16 and TCZ32 groups. Weight loss (P < .001) and reduced liver index (P = .001) were significantly dose-dependent; however, no histological alterations were observed in the other organs. Osteoclast counts were reduced in groups TCZ4 to TCZ32 (P < .001), and IL-6 immunostaining increased in the TCZ8 to TCZ32 groups (P < .001). Alveolar infection rates increased in groups TCZ4 to TCZ32 (P < .001), and MPO had a biphasic response, exhibiting a reduction in groups TCZ2 and TCZ4, and an increase in group TCZ32 (P = .004)., Conclusion: TCZ-induced immunosuppression led to a reduction in osteoclast function, an increase in alveolar infection, and compensatory neutrophil infiltration., (Copyright © 2020 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Plasma membrane repair (PMR) is an important process for cell homeostasis, especially for cells under constant physical stress. Repair involves a sequence of Ca 2+ -dependent events, including lysosomal exocytosis and subsequent compensatory endocytosis. Cholesterol sequestration from plasma membrane causes actin cytoskeleton reorganization and polymerization, increasing cell stiffness, which leads to exocytosis and reduction of a peripheral pool of lysosomes involved in PMR. These changes in mechanical properties are similar to those observed in cells exposed to oxidized Low Density Lipoprotein (oxLDL), a key molecule during atherosclerosis development. Using a human umbilical vein endothelial cell line (EAhY926) we evaluated the influence of mechanical modulation induced by oxLDL in PMR and its effect in endothelial fragility. Similar to MβCD (a drug capable of sequestering cholesterol) treatment, oxLDL exposure led to actin reorganization and de novo polymerization, as well as an increase in cell rigidity and lysosomal exocytosis. Additionally, for both MβCD and oxLDL treated cells, there was an initial increase in endocytic events, likely triggered by the peak of exocytosis induced by both treatments. However, no further endocytic events were observed, suggesting that constitutive endocytosis is blocked upon treatment and that the reorganized cytoskeleton function as a mechanical barrier to membrane traffic. Finally, the increase in cell rigidity renders cells more prone to mechanical injury. Together, these data show that mechanical modulation induced by oxLDL exposure not only alters membrane traffic in cells, but also makes them more susceptible to mechanical injury, which may likely contribute to the initial steps of atherosclerosis development., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare pulmonary condition characterized by diffuse proliferation of neuroendocrine cells in the epithelium of the bronchial wall. DIPNECH may be easily missed in daily clinical practice and diagnosis is often delayed, which may impair prognosis since this condition is considered a pre-invasive lesion for lung carcinoid tumours. We report a clinical case of DIPNECH in order to discuss the diagnostic and therapeutic approach for this entity, the management of which is not yet well established in the literature., Learning Points: DIPNECH is a poorly understood lung condition characterized histologically by diffuse proliferation of pulmonary neuroendocrine cells in the bronchial wall, clinically by obstructive respiratory symptoms and radiologically by small airway disease features and pulmonary nodules.DIPNECH is considered to be a preneoplastic lesion within the spectrum of pulmonary neuroendocrine tumours.Treatment is usually guided by the symptoms and prognosis is highly variable., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interest, (© EFIM 2020.)

Objective: To describe a McIndoe procedure technique for surgical management of Mayer-Rokitansky-Kuster-Hauser syndrome with the use of Nile tilapia skin as a scaffold for the proliferation of new vaginal epithelium., Design: Surgical video article. Local Institutional Review Board approval and written permission from the patient were obtained. There were no conflicts of interest., Setting: University hospital., Patient(s): A 17-year-old woman who presented at our gynecology department with the complaint of primary amenorrhea. At physical examination, she had a phenotypically normal vulva with no vaginal canal. Magnetic resonance imaging of the abdomen and pelvis revealed normal ovaries and absence of uterus and vaginal canal. No other congenital malformations were found. Karyotype was 46,XX., Intervention(s): The McIndoe procedure involved only a vaginal approach. Labia minora were separated, and a transverse midline incision of 3 cm was made. The vesicorectal space was progressively dissected. Blunt dissection was performed initially with digital separation of tissues. The neovagina was then inspected with the introduction of a vaginal speculum, allowing for review of hemostasis. Blunt dissection was continued with the aid of the speculum, to reach the appropriate vaginal dimensions. Subsequently, a vaginal acrylic mold covered with two pieces of processed and sterilized tilapia fish skin was inserted and accommodated into the newly created cavity. The external side of the tilapia skin, which maintained its grayish coloration after the removal of the scales, stayed in contact with the acrylic mold, while the white internal side of the tilapia skin, which was previously attached to the fish's muscle, stayed in contact with the walls of the neocavity. The mold was held in position by four multifilament polyglactin 1.0 sutures in the labia majora, thus preventing expulsion., Main Outcome Measure(s): Anatomic data, such as measurement of the final canal length, and histomorphologic analysis, 180 days after surgery., Result(s): The patient remained on bed rest for 9 days, after which the tilapia fish skin had been partially reabsorbed. After this time, the acrylic mold was removed. A larger plastic mold was then inserted and the patient was advised to wear it day and night for the first postoperative month. The vaginal mold had to be worn each night until normal sexual intercourse was possible. The final canal length 180 days after surgery was between 8 and 9 cm. For the histopathologic analysis, fragments of the lateral vaginal wall were removed 180 days after surgery and showed the presence of stratified squamous epithelium with five cell layers, ectasic blood vessels, and occasional desquamated epithelial cells., Conclusion(s): The procedure described offered this patient an anatomic and functional neovagina by means of a simple, safe, easy, effective, quick, and minimally invasive procedure. Limitations include the experimental nature of this study, based on a single case report with no long-term outcome results. The tilapia fish skin is a low-cost and widely available biomaterial., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Hepatocellular carcinoma (HCC) is the most frequently detected primary malignant liver tumor, representing a worldwide public health problem due to its high morbidity and mortality rates. The HCC is commonly detected in advanced stage, precluding the use of treatments with curative intent. For this reason, it is crucial to find effective therapies for HCC. Cancer cells have a high dependence of glycolysis for ATP production, especially under hypoxic environment. Such dependence provides a reliable possible strategy to specifically target cancer cells based on the inhibition of glycolysis. HCC, such as other cancer types, presents a clinically well-known upregulation of several glycolytic key enzymes and proteins, including glucose transporters particularly glucose transporter 1 (GLUT1). Such enzymes and proteins constitute potential targets for therapy. Indeed, for some of these targets, several inhibitors were already reported, such as 2-Deoxyglucose, Imatinib or Flavonoids. Although the inhibition of glycolysis presents a great potential for an anticancer therapy, the development of glycolytic inhibitors as a new class of anticancer agents needs to be more explored. Herein, we propose to summarize, discuss and present an overview on the different approaches to inhibit the glycolytic metabolism in cancer cells, which may be very effective in the treatment of HCC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: The aim of the present study was to analyze the epidemiological data of digital panoramic radiographs revealing suggestive images of carotid artery calcifications (CAC) from a Northeast Brazilian population., Material and Methods: A cross-sectional retrospective study was conducted with 2,500 digital panoramic radiographs obtained from a single imaging reference center in Northeast Brazil. Images from individuals of both sexes and older than 18 years were included and those that did not cover the region of cervical vertebrae or presented low radiographic quality were excluded. Data were analyzed regarding prevalence, location (bilateral, right or left), sex, and age using the Chi-square test at the significance level of 5%., Results: An amount of 96 (4%) patients presented suggestive images of CAC. The female sex (p=0.003) and individuals aged up to 70 years (p=0.002) were statically significant. 40.4% were found bilaterally, 37.6% on the right side (p<0.001) and 22% on the left side., Conclusions: In conclusion, this study showed a low prevalence of suggestive images of CAC in digital panoramic radiographs from a Northeast Brazilian population. It was observed a higher prevalence of CAC associated with female sex, older patients, and right side location.

This manuscript describes the experimental observation of vasculogenesis in chick embryos by means of network analysis. The formation of the vascular network was observed in the area opaca of embryos from 40 to 55 h of development. In the area opaca endothelial cell clusters self-organize as a primitive and approximately regular network of capillaries. The process was observed by bright-field microscopy in control embryos and in embryos treated with Bevacizumab (Avastin ® ), an antibody that inhibits the signalling of the vascular endothelial growth factor (VEGF). The sequence of images of the vascular growth were thresholded, and used to quantify the forming network in control and Avastin-treated embryos. This characterization is made by measuring vessels density, number of cell clusters and the largest cluster density. From the original images, the topology of the vascular network was extracted and characterized by means of the usual network metrics such as: the degree distribution, average clustering coefficient, average short path length and assortativity, among others. This analysis allows to monitor how the largest connected cluster of the vascular network evolves in time and provides with quantitative evidence of the disruptive effects that Avastin has on the tree structure of vascular networks., Competing Interests: We declare we have no competing interests.

Estradiol (E 2 ) prevents cardiac hypertrophy, and these protective actions are mediated by estrogen receptor (ER)α and ERβ. The G protein-coupled estrogen receptor (GPER) mediates many estrogenic effects, and its activation in the heart has been observed in ischemia and reperfusion injury or hypertension models; however, the underlying mechanisms need to be fully elucidated. Herein, we investigated whether the protective effect of E 2 against cardiomyocyte hypertrophy induced by endothelin-1 (ET-1) is mediated by GPER and the signaling pathways involved. Isolated neonatal female rat cardiomyocytes were treated with ET-1 (100 nmol/l) for 48 h in the presence or absence of E 2 (10 nmol/l) or GPER agonist G-1 (10 nmol/l) and GPER antagonist G-15 (10 nmol/l). ET-1 increased the surface area of cardiomyocytes, and this was associated with increased expression of atrial and brain natriuretic peptides. Additionally, ET-1 increased the phosphorylation of extracellular signal-related protein kinases-1/2 (ERK1/2). Notably, E 2 or G-1 abolished the hypertrophic actions of ET-1, and that was reversed by G-15. Likewise, E 2 reversed the ET-1-mediated increase of ERK1/2 phosphorylation as well as the decrease of phosphorylated Akt and its upstream activator 3-phosphoinositide-dependent protein kinase-1 (PDK1). These effects were inhibited by G-15, indicating that they are GPER dependent. Confirming the participation of GPER, siRNA silencing of GPER inhibited the antihypertrophic effect of E 2 . In conclusion, E 2 plays a key role in antagonizing ET-1-induced hypertrophy in cultured neonatal cardiomyocytes through GPER signaling by a mechanism involving activation of the PDK1 pathway, which would prevent the increase of ERK1/2 activity and consequently the development of hypertrophy.

Background: Transgenic maize (Zea mays L.) event TC1507 (Herculex ® I insect protection), expressing Cry1F δ-endotoxin derived from Bacillus thuringiensis var. aizawai, was commercialized in 2003 in the Americas. Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) susceptibility to Cry1F was monitored annually across several regions in Argentina using diagnostic concentration bioassays. Reduced performance of TC1507 maize against S. frugiperda was reported in 2013. A resistant population was established in the laboratory and the dominance of Cry1F resistance was characterized., Results: During 2012-2015, high-survivorship of several populations was observed in the resistance monitoring program. Reciprocal crosses of a Cry1F-resistant population with a Cry1F-susceptible population were evaluated to calculate effective dominance (D ML ) based on mortality levels observed at 100 µg/ml Cry1F. Two additional dominance levels (D LC and D EC ) were calculated using lethal (LC 50 ) or effective concentration (EC 50 ) derived from concentration-response bioassays. Estimates indicated that Cry1F resistance in S. frugiperda in Argentina was either highly recessive (D ML = 0.005) or incompletely recessive (D LC < 0.26 and D EC < 0.19)., Conclusion: This study is the first documented confirmation and characterization of S. frugiperda Cry1F field-evolved resistance in Argentina. The resistance to Cry1F in S. frugiperda populations collected in Argentina, is autosomal and incompletely recessive similar to the resistance reported in Brazil. © 2017 The Authors. Pest Management Science published by John Wiley © Sons Ltd on behalf of Society of Chemical Industry., (© 2017 The Authors. Pest Management Science published by John Wiley © Sons Ltd on behalf of Society of Chemical Industry.)

Bacillus thuringiensis (Bt) corn producing the Cry1F protein was the first highly efficacious Bt corn deployed against the fall armyworm Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) in Brazil, but reduced efficacy of this technology against the fall armyworm has been reported in some regions of the country. Here, we surveyed Cry1F resistance allele frequency and susceptibility of eight S. frugiperda populations collected in 2013 from non-Bt fields in different regions of Brazil. In F1 screen experiments, the overall frequency of the Cry1F resistance alleles in Brazilian populations was estimated at 0.24, with 95% credibility interval between 0.18 and 0.25. In concentration-response bioassays, five of the eight populations surveyed exhibited significant resistance levels, which were over 32 times higher than that of the standard susceptible laboratory strain. The estimates of Cry1F resistance allele frequency were positively correlated with those of median effective or lethal concentrations (i.e., EC50 or LC50). These results show that the allelic frequency and the magnitude of Cry1F resistance are high in field populations of S. frugiperda in Brazil, indicating a challenging situation for resistance management., (© The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The presence of fitness costs of resistance to Bacillus thuringiensis (Bt) insecticidal proteins in insect populations may delay or even reverse the local selection of insect resistance to Bt transgenic crops, and deserves rigorous investigation. Here we assessed the fitness costs associated with Cry1Fa resistance in two strains of fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), derived from field collections in different Brazilian regions and further selected in the laboratory for high levels of resistance to Cry1Fa using leaves of TC1507 corn., Results: Fitness components were compared using paired resistant and susceptible strains with similar genetic backgrounds and F 1 generations from reciprocal crosses, all of them reared on non-transgenic corn leaves. No apparent life history costs in the larval stage were observed in the Bt-resistant strains. Moreover, the resistance remained stable for seven generations in the absence of selection, with no decrease in the proportion of resistant individuals. Larval respiration rates were also similar between resistant and susceptible homozygotes, and heterozygotes displayed respiration rates and demographic performance equal or superior to those of susceptible homozygotes., Conclusion: In combination, these results indicate the lack of strong fitness costs associated with resistance to Cry1Fa in the fall armyworm strains studied. These findings suggest that Cry1Fa resistance in S. frugiperda populations is unlikely to be counterselected in Cry1Fa-free environments. © 2016 Society of Chemical Industry., (© 2016 Society of Chemical Industry.)

Antiphospholipid syndrome (APS) is a prothrombotic autoimmune disease that may be classified as primary or secondary. Treatment consists of oral anticoagulant, antiplatelet, and/or immunosuppressant drugs. This report describes the dental treatment of 2 women with APS and multiple dental concerns, including periodontal disease, caries, and missing teeth. The invasive dental procedures were performed in an outpatient setting with hematologic monitoring and use of local hemostatic measures. Neither interruption of anticoagulant medications nor administration of blood products was necessary. All of the procedures were performed without complications. To date, no recommendations for the dental care of patients with APS have been established, demonstrating a need to investigate the risks for bleeding and infection, among other concerns, during dental treatment of these patients.

Acute graft-versus-host disease (aGVHD) is the main complication of allogeneic hematopoietic stem cell transplantation, and many efforts have been made to overcome this important limitation. We showed previously that G-CSF treatment generates low-density splenic granulocytes that inhibit experimental aGVHD. In this article, we show that aGVHD protection relies on incoming IL-10 + neutrophils from G-CSF-treated donor spleen (G-Neutrophils). These G-Neutrophils have high phagocytic capacity, high peroxide production, low myeloperoxidase activity, and low cytoplasmic granule content, which accounts for their low density. Furthermore, they have low expression of MHC class II, costimulatory molecules, and low arginase1 expression. Also, they have low IFN-γ, IL-17F, IL-2, and IL-12 levels, with increased IL-10 production and NO synthase 2 expression. These features are in accordance with the modulatory capacity of G-Neutrophils on regulatory T cell (Treg) generation. In vivo, CD25 + Treg depletion shortly after transplantation with splenic cells from G-CSF-treated donors blocks suppression of aGVHD, suggesting Treg involvement in the protection induced by the G-Neutrophils. The immunocompetence and specificity of the semiallogeneic T cells, long-term after the bone marrow transplant using G-Neutrophils, were confirmed by third-party skin graft rejection; importantly, a graft-versus-leukemia assay showed that T cell activity was maintained, and all of the leukemic cells were eliminated. We conclude that G-CSF treatment generates a population of activated and suppressive G-Neutrophils that reduces aGVHD in an IL-10- and Treg-dependent manner, while maintaining immunocompetence and the graft versus leukemia effect., (Copyright © 2016 by The American Association of Immunologists, Inc.)

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm of the hematopoietic stem cell characterized by presence of the oncoprotein BCR-ABL1, which have constitutive tyrosine kinase activity. BCR-ABL1 activation induces aurora kinase A (AURKA) and aurora kinase B (AURKB) expression, which are serine-threonine kinases that play an important function in chromosome alignment, segregation and cytokinesis during mitosis. Acquisition of resistance to tyrosine kinase inhibitors has emerged as a problem for CML patients and the identification of novel targets with an important contribution for CML phenotype is of interest. In the present study, we explored the cellular effects of reversine, an AURKA and AURKB inhibitor, in the BCR-ABL1+ K562 cells. Our results indicate that reversine reduces AURKA and AURKB expression, leads to reduction of cell viability and increased apoptosis in a dose- and time-dependent manner, as well as, induces mitotic catastrophe in K562 cells. Our preclinical study establishes that reversine presents an effective antileukemia activity against K562 cells and provide new insights on anticancer opportunities for CML., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Denosumab, an anti-resorptive agent, IgG2 monoclonal antibody for human Receptor activator of nuclear factor-kappa B ligand (RANKL), has been related to the occurrence of osteonecrosis of the jaws. Thus, the aim of this study was to review the literature from clinical case reports, regarding the type of patient and the therapeutic approach used for osteonecrosis of the jaws induced by chronic use of Denosumab., Material and Methods: For this, a literature review was performed on PubMed, Medline and Cochrane databases, using the keywords "Denosumab" "anti-RANK ligand" and "Osteonecrosis of jaw". To be included, articles should be a report or a serie of clinical cases, describing patients aged 18 years or over who used denosumab therapy and have received any therapy for ONJ., Results: Thirteen complete articles were selected for this review, totaling 17 clinical cases. The majority of ONJ cases, patients receiving Denosumab as treatment for osteoporosis and prostate cancer therapy. In most cases, patients affected by ONJ were women aged 60 or over and posterior mandible area was the main site of involvement. Diabetes pre-treatment with bisphosphonates and exodontia were the most often risk factors related to the occurrence of this condition. Systemic and local antibiotic therapy with or without surgical debridement was the most used treatment for ONJ resolution., Conclusions: It is concluded that the highest number of ONJ cases caused by the use of anti-RANKL agents occurred in female patients, aged 60 years or older, under treatment for osteoporosis and cancer metastasis, and the most affected region was the mandible posterior.

Aim: To evaluate the relationship between mononuclear inflammatory infiltrate and the expression of a proliferative immunomarker (Ki-67) as well as to evaluate basement membrane and extracellular matrix proteins (laminin and collagen type IV) in radicular cysts and dentigerous cysts (DC)., Methodology: Immunohistochemical analyses were performed in heavily inflamed radicular cysts (HIRC), slightly inflamed radicular cysts (SIRC) and DC (n = 20) using Ki-67 (Dako(®) , 1 : 50), anticollagen type IV (DBS(®) , 1 : 40) and antilaminin (DBS(®) , 1 : 20). The data were analysed using anova/Tukey's test (Ki-67) and Kruskal-Wallis/Dunn's test (collagen type IV and laminin) (P < 0.05)., Results: The immunoexpression of Ki-67 was significantly greater in the SIRC group compared with the HIRC and DC (P = 0.0040). Likewise, the immunoexpression of collagen type IV in the basement membrane of the SIRC group was significantly more continuous (P = 0.0475) than in the HIRC group. DC had significantly less collagen type IV in extracellular matrix immunoexpression than HIRC and SIRC (P = 0.0246). Laminin was absent in the basement membrane in the SIRC and DC groups, and the extracellular matrix of the HIRC was weak and punctate., Conclusion: The presence of inflammatory factors in the radicular cyst wall modified the expression of proliferation factors in the epithelial lining and the expression of collagen type IV and laminin in the basement membrane, but did not modify extracellular matrix behaviour in radicular cysts., (© 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Objective: to evaluate the influence of Tumor Necrosis Factor alpha (TNF-α) and apoptosis in rats with DM treated with chamomile extract or triamcinolone., Material and Methods: Wistar male rats (210.0±4.2 g) were divided into five groups: negative control group (NCG) without diabetes; positive control group (PCG) with DM (alloxan, 45 mg/kg); and groups treated with chamomile extract (normoglycemic= NCG group and diabetic= DCG group) and with triamcinolone (TG). Traumatic ulcers were performed on all animals that received topical triamcinolone, chamomile extract or saline 12/12 hours for ten days., Results: On days five and ten the animals were euthanized and the ulcers were analyzed by light microscopy, TUNEL assay, and immunohistochemically (TNF-α). The NCG (p=0.0062), PCG (p=0.0285), NCG (p=0.0041), and DCG (p<0.0001) groups were completely healed on the 10th day, however, there was no healing on the TG (p=0.5127) group. The TNF-α expression showed a significant reduction from the 5th to the 10th day in NCG (p=0.0266) and DCG (p=0.0062). In connective tissue, the TUNEL assay showed a significant reduction in the number of positive cells in NCG (p=0.0273) and CNG (p=0.0469) and in the epithelium only in CDG (p=0.0320)., Conclusions: Chamomile extract can optimize the healing of traumatic oral ulcers in diabetic rats through the reduction of apoptosis in the epithelium and TNF-α expression., Competing Interests: AND SOURCE OF FUNDING The authors declare no sources of funding and conflicts of interest.

Several Bt maize events expressing various insecticidal Cry protein genes have been commercialized for management of western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae). We used high efficacy (>99.7%) experimental maize events that express mCry3A for selections under laboratory conditions to develop a western corn rootworm colony resistant to mCry3A at higher levels than published results. The resistance ratio (RR) to mCry3A was >97-fold based on LC 50 values in diet-based bioassays after six generations of selections when compared to that of an unselected Control colony. Using a sublethal seedling assay (SSA) method, we confirmed that the colony had no cross-resistance to maize event DAS-59122-7, which expresses Cry34/35Ab. Reciprocal crosses between the mCry3A-resistant colony and the susceptible colony were performed to test the inheritance of resistance. Larval survival and development evaluated by the SSA method indicated that resistance to mCry3A was inherited autosomally and was incompletely recessive (h = 0.23-0.25). Specific binding of mCry3A to brush border membrane vesicles of midgut tissue revealed reduced binding in the resistant colony when compared to binding in the susceptible colony. This is the first report where resistance in western corn rootworm has been shown to involve reduced binding of a Cry3-class protein in midgut tissue., (© The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Refuge is mandated in the United States where genetically modified maize (Zea mays L.) expressing insecticidal proteins derived from Bacillus thuringiensis Berliner (Bt) are cultivated. Currently, refuge is deployed in different ways including blocks, field strips, or seed blends containing Bt and non-Bt maize. Seed blends provide practical advantages for refuge implementation. However, concerns related to the movement of insect larvae, potential differential survival of heterozygous resistant larvae, reduction in insect production, and cross-pollination of ears resulting in sublethal selection, have delayed seed blend use for Lepidoptera in the southern United States, where maize plantings are used as refuge for Helicoverpa zea (Boddie). In this study, we evaluated the relative survival of H. zea in Bt events and in seed blends compared with pure stand refuge and the relative survival of H. zea on the individual components of the pyramid 1507xMON810xMIR162. The results showed variation on the production of H. zea in refuge plants from seed blends compared with pure stand refuge plants. The relative survival of H. zea on the events 1507, MON810, MIR162, and 1507xMON810xMIR162 ranked similarly across the three locations tested. These results can be used in computer simulation modeling efforts to evaluate the feasibility of seed blends as a refuge deployment strategy with the pyramid 1507xMON810xMIR162. Because the reduction on survival of H. zea due to blending was variable, a sensitivity analysis that includes all possible scenarios of reduction in survival should be considered., (© The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)