Evaluation of enterovirus concentration, species identification, and cerebrospinal fluid parameters in patients of different ages with aseptic meningitis in São Paulo, Brazil.

Human enteroviruses (EV) are the most common cause of aseptic meningitis worldwide. Data on EV viral load in cerebrospinal fluid (CSF) and related epidemiological studies are scarce in Brazil. This study investigated the influence of EV viral load on CSF parameters, as well as identifying the involved species. CSF samples were collected in 2018-2019 from 140 individuals at The Hospital das Clínicas, São Paulo. The EV viral load was determined using real-time quantitative polymerase chain reaction, while EV species were identified by 5'UTR region sequencing. Median viral load was 5.72 log10 copies/mL and did not differ by subjects' age and EV species. Pleocytosis was observed in 94.3% of cases, with the highest white blood cell (WBC) counts in younger individuals. Viral load and WBC count were correlated in children (p = 0.0172). Elevated lactate levels were observed in 60% of cases and correlated with the viral load in preteen-teenagers (p = 0.0120) and adults (p = 0.0184). Most individuals had normal total protein levels (70.7%), with higher in preteen-teenagers and adults (p < 0.0001). By sequencing, 8.2% were identified as EV species A and 91.8% as species B. Age-specific variations in CSF characteristics suggest distinct inflammatory responses in each group.

Critical-size defects reconstruction with four different bone grafts associated with e-PTFE membrane: A histomorphometric experimental in vivo study.

OBJECTIVES: The goal of this study was to assess the newly formed bone and the remnant biomaterial by comparing four different bone grafts used to treat critical-size defects, associated or not with the non-resorbable membrane. MATERIALS AND METHODS: Two calvaria critical-size bone defects were created in 50 male Wistar rats. They were divided into blood (G1), autogenous (G2), bioglass (G3), hydroxyapatite (G4), and xenograft (G5) groups, associated or not with e-PTFE. The experimental periods were 15 and 45 days. Sections were prepared for histomorphometric assessment. All data were analyzed by the mixed-effects model with multiple comparisons (significance level, p < .05). RESULTS: A similar level of new bone was observed for all groups, associated with a high level of vascularization. G1 and G2 ensured sovereignty over the greater quantity of new bone. A non-significant result was reported comparing groups with and without membranes. No significant result was found between the experimental synthetic biomaterials (G3 and G4). G5L achieved 22.0% of new bone after 45 days (p > .05). All groups had a stable volume of biomaterial kept in the short term (p > .05). G2 was the best material for new bone formation and final volume of biomaterial, followed by G4 < G5 < G3. Thus, it is possible that G4 had a better degradation profile among the experimental groups. CONCLUSIONS: The best results were found in the autogenous group, with higher resorption and integration; non-significative new bone was found among the experimental groups; and the regeneration of critical bone defects using an e-PTFE barrier did not present significant results on new bone formation.

Acute disseminated encephalomyelitis following Saint Louis encephalitis virus infection.

Saint Louis encephalitis virus (SLEV) infection is an arbovirosis associated with a broad spectrum of neurological complications. We present a case of a 55-year-old man hailing from Manaus, a city situated in the heart of the Amazon Rainforest, who exhibited symptoms of vertigo, tremors, urinary and fecal retention, compromised gait, and encephalopathy 3 weeks following SLEV infection. Neuroaxis MRI revealed diffuse, asymmetric, and poorly defined margins hyperintense lesions with peripheral and ring enhancement in subcortical white matter, as well as severe spinal cord involvement. Serology for SLEV was positive both on serum and cerebrospinal fluid. To the best of our knowledge, the present report is the first to show brain lesions along with myelitis as a post-infectious complication of SLEV infection.

Minimally invasive periodontal regeneration with the buccal approach: a systematic review and meta-analysis of clinical studies.

OBJECTIVE: The aim of this study was to investigate clinical periodontal parameters after treatment using the Minimally Invasive Surgical Technique (MIST), Modified Minimally Invasive Surgical Technique (M-MIST), and/or any technique for papilla preservation, such as Entire Papilla Preservation (EPP), modified-papilla preservation technique (M-PPT), or simplified-papilla preservation technique (SPPT). METHODS: The focus question was "For patients with periodontal intrabony defects (P), what is the best minimally invasive regenerative approach (I), comparing MIST, M-MIST, and papilla preservation techniques' outcomes (C) to improve PD, CAL, GR, and periodontal stability (O)?" An online search was conducted on PubMed, Cochrane Library, and Embase. Only randomized clinical trials and case series with a minimum of 10 enrolled patients were included. The risk of bias was evaluated using the Critical Appraisal tools in JBI Systematic Reviews. The meta-analysis compared the data obtained for the periodontal parameters analyzed, and the heterogeneity was verified. RESULTS: After the screening, nine articles were included. Seven studies applied MIST and its modifications; two used M-PPT, one SPPT, and one approached EPP. A general statistically significant PD reduction and CAL gain were noted between the groups, comparing baseline and follow-up for all articles, independently of the technique or materials used. Also, all studies showed a non-significant increase in the gingival recession. Four studies had a low risk of bias, four had a moderate risk, and only 1 had a high risk. Moderate heterogeneity was found in one analysis for CAL (65.73%); moderate and substantial heterogeneity was found in the PD results (71.91% and 89.19%); and no heterogeneity was found within all analyses for gingival recession (0%). CONCLUSION: MIST, M-MIST, and papilla preservation techniques demonstrated their potential and efficacy to improve periodontal conditions of sites with intrabony defects with minimal morbidity.

Rehabilitation of People With Chronic Spinal Cord Injury Using a Laparoscopically Implanted Neurostimulator: Impact on Mobility and Urinary, Anorectal, and Sexual Functions.

OBJECTIVES: This study aimed to assess the impact of the laparoscopic implantation of neuromodulation electrodes (Possover-LION procedure) on mobility and on sexual, urinary, and anorectal functions of people with chronic spinal cord injury (SCI). MATERIAL AND METHODS: Longitudinal analysis of 30 patients with chronic SCI (21 ASIA impairment scale (AIS) A, eight AIS B, and one AIS C) submitted to the Possover-LION procedure for bilateral neuromodulation of femoral, sciatic, and pudendal nerves. Assessments were performed before the surgical procedure and at 3, 6, and 12 months postoperatively. The primary outcome was evolution in walking, measured by the Walking Index for Spinal Cord Injury score, preoperatively and at 12 months. Secondary outcomes were changes in overall mobility (Mobility Assessment Tool for Evaluation of Rehabilitation score), urinary function and quality of life (Qualiveen questionnaire), and bowel (time for bowel emptying proceedings and Wexner's Fecal Incontinence Severity Index [FISI]) and sexual functions (International Index of Erectile Function for men and Female Sexual Function Index for women). Surgical time, intraoperative bleeding, and perioperative complications were also recorded. RESULTS: Qualitatively, 18 of 25 (72%) patients with thoracic injury and 3 of 5 (60%) patients with cervical injury managed to establish a walker-assisted gait at one-year follow-up (p < 0.0001). A total of 11 (47.8%) have improved in their urinary incontinence (p < 0.0001), and seven (30.4%) improved their enuresis (p = 0.0156). The FISI improved from a median of 9 points preoperatively to 5.5 at 12 months (p = 0.0056). Of note, 20 of 28 (71.4%) patients reported an improvement on genital sensitivity at 12 months postoperatively (p < 0.0001), but this was not reflected in sexual quality-of-life questionnaires. CONCLUSIONS: Patients experienced improved mobility and genital sensitivity and a reduction in the number of urinary and fecal incontinence episodes. By demonstrating reproducible outcomes and safety, this study helps establish the Possover-LION procedure as an addition to the therapeutic armamentarium for the rehabilitation of patients with chronic SCI. CLINICAL TRIAL REGISTRATION: This study was registered at the WHO Clinical Trials Database through the Brazilian Registry of Clinical Trials-REBEC (Universal Tracking Number: U1111-1261-4428).

Potential Impact of Prosthetic Biomaterials on the Periodontium: A Comprehensive Review.

The success of a prosthetic treatment is closely related to the periodontal health of the individual. The aim of this article was to review and present the importance of prosthetic restorative materials on the condition of the periodontium, the changes that occur in the composition of the subgingival microbiota and the levels of inflammatory markers in gingival crevicular fluid. Articles on the influence of different prosthetic restorative materials on subgingival microbiota and proinflammatory cytokines were searched for using the keywords "prosthetic biomaterials", "fixed prosthesis", "periodontal health", "subgingival microbiota", "periodontal biomarkers" and "gingival crevicular fluid" in PubMed/Medline, Science Direct, Scopus and Google Scholar. The type of material used for prosthesis fabrication together with poor marginal and internal fit can result in changes in the composition of the subgingival microbiota, as well as increased accumulation and retention of dentobacterial plaque, thus favoring the development of periodontal disease and prosthetic treatment failure. Biological markers have helped to understand the inflammatory response of different prosthetic materials on periodontal tissues with the main purpose of improving their clinical application in patients who need them. Metal-free ceramic prostheses induce a lower inflammatory response regardless of the fabrication method; however, the use of CAD/CAM systems is recommended for their fabrication. In addition, it is presumed that metal-ceramic prostheses cause changes in the composition of the subgingival microbiota producing a more dysbiotic biofilm with a higher prevalence of periodontopathogenic bacteria, which may further favor periodontal deterioration.

Investigating the impact of diameters and thread designs on the Biomechanics of short implants placed in D4 bone: a 3D finite element analysis.

BACKGROUND: Dental implants emerge as a dependable and efficacious alternative for patients experiencing partial or complete tooth loss. The stability of these implants is influenced by surface topography and macro-level design. In cases where the height of the maxillary posterior region is diminished, employing short implants can prove advantageous. With the aim of examining the distribution of von Mises stress, strain, and micromovement in D4 bone quality surrounding platform-switched short implants, measuring 6 mm in length and featuring diameters ranging from 4 to 6 mm, as well as different thread designs, an in-depth finite element analysis was conducted under immediate loading conditions. METHODOLOGY: A 3D finite element model was constructed to simulate maxillary molar crowns, incorporating an implant with a length of 6 mm and varying diameters and thread designs. The diameters utilized were 4/3.6 mm, 5/4 mm, and 6/4.8 mm, while the thread designs included buttress, square, and triangle patterns. Each model underwent analysis with a 100 N force applied in two directions: vertical and oblique, relative to the long axis of the implant. Stress, strain, and micromovement in the peri-implant region were recorded, employing the Ansys Workbench R v.18.1 software for modelling and analysis. RESULTS: When comparing all three diameters, the wide diameter (6 mm threads) exhibited the lowest values of peri-implant von Mises stresses (3.3 MPa and 35.1 MPa), strains (194 Ɛ and 484 Ɛ), and micromovements (0.7 µm and 1.3 Ɛ) subjected to axial and non-axial loading of a 100 N force. Notably, square microthreads yielded the most favorable stress parameters among the different thread shapes, manifesting the minimum values of stress, strains, and micromovements in their vicinity. CONCLUSION: For the treatment of atrophic ridges or in scenarios necessitating extensive surgical preparation of the implant site, a combination of short implants, wide diameters, and platform switching can be employed. In situations with reduced bone height and the requirement for an implant-supported prosthesis to replace a missing permanent maxillary molar, the utilization of wide-diameter platform-switched short implants measuring 6 mm in length, featuring a square thread design, should be taken into consideration.

Neurocysticercosis: diagnosis via metagenomic next-generation sequencing.

A 68-year-old Brazilian woman had 3 months of progressive fatigue, difficulty walking and 18 kg weight loss. On examination, there was gait apraxia and executive dysfunction. MR scan of brain showed communicating hydrocephalus and a cerebrospinal fluid showed 105 white cells/µL (≤5), predominantly lymphocytes, protein of 1.35 g/L (0.15-0.45) and the glucose content of 0.06 mmol/L (3.3-4.4). We suspected an infective cause and used of metagenomic next-generation sequencing to diagnose neurocysticercosis. This case highlights the challenge of diagnosing chronic meningitis and the relevance of genetic approaches in diagnosing neurological infections.

The Interference of Age and Gender on Smile Characterization Analyzed on Six Parameters: A Clinical-Photographic Pilot Study.

Background and Objective: This study aimed to evaluate six smile-esthetic parameters (deviation of the upper dental midline from the facial midline, upper lip curvature, smile line, smile arch, smile width, and shape of the maxillary central incisors), correlating them with age and gender. Materials and methods: Caucasian individuals (N = 114) were grouped by gender (male and female) and age (group I-18 to 30 years old; group II-31 to 50 years old; and group III-over 50 years old). Using a digital camera, extra and intraoral pictures were taken to analyze the variables above-mentioned. The data were statistically evaluated, considering a significance level of p < 0.05. Results: Most participants found deviations of the upper dental midline, straight upper lip curvature, and the medium smile line coincided with the facial midline. The parallel smile arch exposing 9 to 11 upper teeth, the absence of exposure of lower teeth when smiling, and oval upper incisors were prevalent parameters. Regarding gender, significant results were found for the curvature of the upper lip (p = 0.049), the smile arch (p = 0.001), and the shape of the upper central incisors (p = 0.004). For age, the association with the curvature of the upper lip (p = 0.032), the smile line (p = 0.001), the smile arch (p = 0.007), the width of the smile exposing lower teeth (p = 0.002), and the shape of the upper central incisors (0.012) were significant. Conclusions: Within this study's limitations, gender and age affect the anterior teeth shape and upper lip curves; gender and age did not influence the coincidence between dental and facial midlines.

Evaluation of Behavior of Castable versus Machined Solid Abutments for Morse Tapper Implant Connection: A Clinical Retrospective Study.

Objective: The primary objective of the present retrospective clinical study was to evaluate and compare the clinical performance presented by castable abutments developed for the MT system versus intermediate machined abutments, specifically regarding prosthetic or implant fractures/loss; the secondary objective was to verify the looseness of the abutments and the behavior of the peri-implant soft tissues. Methods: This clinical retrospective study was conducted on patients rehabilitated between 2019 and 2020. Inclusion criteria were patients in good general health, with an implants-supporting single crown; with solid machined abutments (control group) or castable UCLA abutments; with a connection portion (base) machined in cobalt-chrome (test group) over Morse taper DuoCone implants in the posterior mandible area; and at least two years in function. Clinical assessment was carried out by the same professional, considering the following parameters: (A) prosthetic: (i) loosening of the fixation screw, (ii) fracture of the screw and (iii) the number of times the patient had some type of complication after the installation of the prostheses were evaluated; (B) biological: (i) without keratinized mucosa (KM), (ii) 1 mm or less, (iii) between 1 and 2 mm and (iv) greater than 2 mm of KM width; and the presence or absence of mucositis. Furthermore, radiographic evaluation was performed in order to assess the marginal bone loss. These evaluations permitted to compare the groups analyzed and patients enrolled. Data were statistically analyzed, with the level of significance set at α = 0.05. Results: 79 patients with 120 MT implants were evaluated (80 castable UCLA abutments and 40 machined solid abutments). The follow-up was from 2 to 4 years. There was a 100% implant survival rate. Therefore, the control group showed two fractured abutments (5%) and no abutment loosening (95% for prosthetic survival rate), whereas the test group showed no abutment fracture but nine loosening screws (11.3%) (100% for prosthetic survival rate). Keratinized mucosa was considered thin or absent in 19 implants in the control group (47.5%) and 42 in the test group (52.5%). Mucositis was found in 11 implants in the control group (27.5%) and 27 in the test group (33.8%). A positive correlation was observed between the width of keratinized mucosa and mucositis (r = 0.521, p = 0.002). The mean marginal bone loss was 2.3 mm, ranging from 1.1 to 5.8 mm. No correlation was observed when considering marginal bone loss versus the three parameters (implant diameter, implant length and time of the prosthesis in function). Conclusions: The results suggest that UCLA-type abutments are a viable option for rehabilitating implants with Morse taper connections, suggesting lower fracture risk. Further research is necessary to confirm these findings and thoroughly evaluate the clinical performance and long-term outcomes.

Randomized Clinical Trial Comparing Insertion Torque and Implant Stability of Two Different Implant Macrogeometries in the Initial Periods of Osseointegration.

Objectives: The present study compared two implants with different macrogeometries placed in healed alveolar sites, evaluating the insertion torque (ITV) and implant stability quotient (ISQ) values at three different periods. Methods: Seventy patients with a total of 100 dental implants were allocated into two groups (n = 50 per group): DuoCone implants (DC group) that included 28 implants in the maxilla and 22 in the mandible, and Maestro implants (MAE group) that included 26 in the maxilla and 24 in the mandible. The ITV was measured during the implant placement, and the ISQ values were measured immediately at implant placement (baseline) and after 30 and 45 days. Results: The mean and standard deviations of the ITV were statistically significant (p < 0.0001), 56.4 ± 6.41 Ncm for the DC group and 29.3 ± 9.65 Ncm for the MAE group. In the DC group, the ISQs ranged between 61.1 ± 3.78 and 69.8 ± 3.86, while the MAE group presented similar values compared with the other group, ranging between 61.9 ± 3.92 and 72.1 ± 2.37. Conclusions: The value of implant insertion torque did not influence the ISQ values measured immediately after implant placement. However, the ITV influenced the ISQ values measured in the two initial periods of osseointegration, with implants installed with lower torques presenting higher ISQ values.

Association of genomic profiles and survival in early onset and screening-age colorectal cancer patients with liver metastases resected over 15 years.

BACKGROUND: This study explores whether genomic profiles of colorectal liver metastasis (CRLM) patients with early onset (EO, < 50 years old) and screening age (SA) primary diagnosis are associated with overall survival (OS). METHODS: All patients undergoing hepatectomy between 2002 and 2017 were identified and tumor specimens with next-generation sequencing data were cataloged. Gene and signaling-level alterations were checked for association with OS from primary diagnosis accommodating for left-truncated survival. RESULTS: Of 1822 patients, 333 were sequenced-127 (38%) EO-CRLM and 206 (62%) SA-CRLM patients. More aggressive features presented in EO-CRLM patients-synchronous metastatic presentation (83% vs. 75%, p < 0.001) and primary node-positive disease (71% vs. 61%, p < 0.001). The median OS from primary diagnosis was 11.8 years (95% confidence interval = 7.94-NA). Five-year OS did not differ by age (p = 0.702). On multivariable analysis, altered APC (EO-CRLM: [hazard ratio [HR] = 0.37, p = 0.018] vs. SA-CRLM:[HR = 0.61, p = 0.260]), BRAF (EO-CRLM:[HR = 4.38, p = 0.007] vs. SA-CRLM:[HR = 4.78, p = 0.032]), and RAS-TP53 (EO-CRLM:[HR = 2.82, p = 0.011] vs. SA-CRLM:[HR = 2.35, p = 0.003]) associated with OS. CONCLUSIONS: Despite bearing more aggressive features, EO-CRLM patients had similar genomic profiles and survival as SA-CRLM patients. Better performance status in younger patients leading to increased treatment tolerance may partly explain this. As screening and treatment strategies from older patients are applied to younger patients, genomic predictors of biology identified historically in older cohorts could apply to EO patients.

Gingival recession treatment with enamel matrix derivative associated with coronally advanced flap and subepithelial connective tissue graft: a split-mouth randomized controlled clinical trial with molecular evaluation.

OBJECTIVES: The goal of this study was to evaluate the impact of enamel matrix derivative (EMD) on periodontal healing after root coverage (RC) surgery, involving CAF in combination with SCTG, and to assess the molecular profile, verifying the inflammation level in early stage (1 and 2 weeks). MATERIALS AND METHODS: Thirty-two recessions (RT1) were submitted to periodontal surgery with (test) or without (control) EMD. The clinical parameters analyzed on the day of surgery and 6 months after the surgical procedure were as follows: recession height and width, keratinized tissue height, percentual root coverage, and the gingival thickness of keratinized tissue. Moreover, the main inflammatory biomarkers and growth factors (IL-1ß, IL-6, IL-8, FGF, MIP-1α and ß, PDGF, TNF-α, and VEGF) were evaluated at baseline, 7, and 14 days after procedures. RESULTS: The average root coverage was significantly higher in the test group as compared to the control group (86% vs. 66%, p = 0.008). The test side had significantly lesser final RH compared to the control side (p = 0.01). Also, there was a significant reduction of RW in both groups, with more significant results in the test group. KTH and GT were not significantly different at any time and group. After 14 days, the immunological analysis showed an increase of VEGF (p = 0.03) on the test group compared to the control side. CONCLUSION: The use of EMD in RC surgeries resulted in a significantly higher RC, as well as a significant increase in VEGF expression, suggesting that EMD may contribute to the angiogenic and healing process. CLINICAL RELEVANCE: EMD provided better results in root coverage treatment when associated with CAF and SCTG, beyond a greater releasing of angiogenic growth factor (VEGF), which enhanced the result.

Biomolecular and Biochemical Aspects of the Oral Cavity.

Recent advances in science, especially innovations in the field of biochemistry and materials science, greatly contribute to improvements in the prevention, diagnosis, and treatment of oral diseases [...].

Prokaryotic diversity and biogeochemical characteristics of field living and laboratory cultured stromatolites from the hypersaline Laguna Interna, Salar de Atacama (Chile).

Stromatolites are organo-sedimentary structures found principally in seas and saline lakes that contain sheets of sediments and minerals formed by layers of microbial communities, which trap sediments and induce the precipitation of minerals.A living stromatolite from the alkaline Laguna Interna in the Salar de Atacama was collected and one of the fragments was deposited in an experimental aquarium for 18 months. We used Illumina sequencing of PCR-amplified V4 regions of 16S rRNA genes from total extracted DNA to identify the microbial populations. The chemical structure was studied using X-Ray Diffraction (XRD) and bench chemical methods. We found that members belonging to the Proteobacteria, Planctomycetes, Chloroflexi and Bacteroidetes phyla dominated the bacterial communities of the living and aquarium cultured samples. The potential metabolic functionality of the prokaryotic community reveals that sulfur, nitrogen, methane and carbon fixation metabolism functions are present in the samples. This study is the first to provide new insights into the prokaryotic community composition from this unusual aquatic desert site. Further studies will be helpful to obtain a better understanding of the biotic and abiotic mechanisms residing in stromatolites from Laguna Interna, as well as to have better knowledge about the formation of these biosignatures.

Novel potent (dihydro)benzofuranyl piperazines as human histamine receptor ligands - Functional characterization and modeling studies on H3 and H4 receptors.

Histamine acts through four different receptors (H1R-H4R), the H3R and H4R being the most explored in the last years as drug targets. The H3R is a potential target to treat narcolepsy, Parkinson's disease, epilepsy, schizophrenia and several other CNS-related conditions, while H4R blockade leads to anti-inflammatory and immunomodulatory effects. Our group has been exploring the dihydrobenzofuranyl-piperazines (LINS01 series) as human H3R/H4R ligands as potential drug candidates. In the present study, a set of 12 compounds were synthesized from adequate (dihydro)benzofuran synthons through simple reactions with corresponding piperazines, giving moderate to high yields. Four compounds (1b, 1f, 1g and 1h) showed high hH3R affinity (pKi > 7), compound 1h being the most potent (pKi 8.4), and compound 1f showed the best efficiency (pKi 8.2, LE 0.53, LLE 5.85). BRET-based assays monitoring Gαi activity indicated that the compounds are potent antagonists. Only one compound (2c, pKi 7.1) presented high affinity for hH4R. In contrast to what was observed for hH3R, it showed partial agonist activity. Docking experiments indicated that bulky substituents occupy a hydrophobic pocket in hH3R, while the N-allyl group forms favorable interactions with hydrophobic residues in the TM2, 3 and 7, increasing the selectivity towards hH3R. Additionally, the importance of the indole NH in the interaction with Glu5.46 from hH4R was confirmed by the modeling results, explaining the affinity and agonistic activity of compound 2c. The data reported in this work represent important findings for the rational design of future compounds for hH3R and hH4R.

Closing the knowledge gap in pelvic neuroanatomy: assessment of a cadaveric training program.

BACKGROUND: The objective of this study is to characterize participants in a laparoscopic cadaveric neuroanatomy course and assess knowledge of pelvic neuroanatomy before and after this course. METHODS: This is a survey-based cohort study with a setting in a university educational facility. The participants are surgeons in a multiday laparoscopic cadaveric pelvic neuroanatomy course. Participants completed a precourse survey, including demographics and comfort with laparoscopic surgery. They then completed an identical precourse and postcourse anatomic knowledge test. Main outcomes are scores on the anatomic knowledge test precourse and postcourse. RESULTS: 44 respondents were included: 25 completed fellowship, 15 completed residency, 2 were residents, and 2 were fellows. Participants were on average 11.09 years post training, with an average of 8.67 years from training if they completed fellowship and 18.62 years if they completed residency only. 22 of 42 respondents strongly agreed or agreed they are comfortable performing complex laparoscopic hysterectomies. The average precourse score was 32.18/50 points and the mean difference score (MDS, defined as mean of Postcourse scores minus Precourse scores) was 9.80, showing significant improvement (p <  0.001). Precourse and MDS scores were not significantly different when comparing country of practice, level of training, or time since training. CONCLUSION: Baseline knowledge of pelvic neuroanatomy was similar among groups when comparing fellowship status, place of training, or time since training. There was significant improvement in knowledge after training in this dissection method. This course garnered interest from surgeons with broad training backgrounds.

Efficacy of Essential Oil Mouthwashes With and Without Alcohol on the Plaque Formation: A Randomized, Crossover, Double-Blinded, Clinical Trial.

BACKGROUND: Essential oil (EO) mouthwash has been considered as one of the effective chemical agents as an adjunct to mechanical plaque control, without adverse effects compared with chlorhexidine (pigmentation, changes of taste, and formation of supragingival calculus), which limits its continuous use. New EO alcohol-based has emerged with questions regarding contraindications for its daily use. OBJECTIVE: To compare the efficacy of EO mouthwashes with and without alcohol on the early supragingival and subgingival plaque formation using a plaque-free zone score system. METHODS: This study was a crossover, randomized, double-blind clinical trial. Eleven participants, totaling 396 sites of evaluation, remained 4 days with no mechanical oral hygiene control and only used EO mouthwash with (control) and without alcohol (test) during this period. The presence of the plaque-free zone was recorded every 24 hours. Friedman and Wilcoxon tests were used with a 5% significance level. RESULTS: The control group showed a more significant number of buccal surfaces free of plaque at 48, 72, and 96 hours compared with the test group. Both groups presented satisfactory efficacy up to 72 hours with a significant difference in favor of the control group. The presence of subgingival plaque on both the proximal and free surfaces was significantly higher in the test group. CONCLUSION: EO with alcohol presented better results in retarding the early supragingival and subgingival plaque formation compared with EO without alcohol.

Regorafenib in Combination with First-Line Chemotherapy for Metastatic Esophagogastric Cancer.

BACKGROUND: Angiogenesis is critical to gastroesophageal adenocarcinoma growth and metastasis. Regorafenib is a multikinase inhibitor targeting angiogenic and stromal receptor tyrosine kinases. We evaluated whether regorafenib augments the antitumor effect of first-line chemotherapy in metastatic esophagogastric cancer. MATERIALS AND METHODS: Patients with previously untreated metastatic gastroesophageal adenocarcinoma received 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) every 14 days and regorafenib 160 mg daily on days 4 to 10 of each 14-day cycle. The primary endpoint was 6-month progression-free survival (PFS). To identify predictive biomarkers of outcome, we examined correlations between genomic characteristics of sequenced pretreatment tumors and PFS. RESULTS: Between August 2013 and November 2014, 36 patients with metastatic esophagogastric cancer were accrued to this single-center phase II study (NCT01913639). The most common grade 3-4 treatment-related adverse events were neutropenia (36%), leucopenia (11%) and hypertension (8%). The 6-month PFS was 53% (95% confidence interval [CI], 38%-71%), the objective response rate was 54% (95% CI, 37%-70%), and the disease control rate was 77% (95% CI, 67%-94%). Next-generation sequencing did not identify any genomic alterations significantly correlated with response, and there was no association between homologous recombination deficiency and PFS with platinum-based chemotherapy. CONCLUSION: Regorafenib (one week on-one week off schedule) is well tolerated in combination with first-line FOLFOX but does not improve 6-month PFS relative to historical control. IMPLICATIONS FOR PRACTICE: Prognosis for metastatic esophagogastric cancer remains poor despite modern systemic therapy regimens. This phase II trial indicates that the combination of regorafenib and FOLFOX is well tolerated but does not add to the efficacy of first-line chemotherapy in metastatic esophagogastric cancer. Notably, recently reported data suggest potential synergy between regorafenib and the PD-1 inhibitor nivolumab. As this study demonstrates that regorafenib plus FOLFOX is safe, and combined chemotherapy and immunotherapy show favorable toxicity profiles, future studies combining immunotherapy with regorafenib and chemotherapy may be feasible.

The Novel H4R Antagonist 1-[(5-Chloro-2,3-Dihydro-1-Benzofuran-2-Yl)Methyl]-4-Methyl-Piperazine (LINS01007) Attenuates Several Symptoms in Murine Allergic Asthma.

BACKGROUND/AIMS: Histamine is an important chemical transmitter involved in inflammatory processes, including asthma and other chronic inflammatory diseases. Its inflammatory effects involve mainly the histamine H4 receptor (H4R), whose role in several studies has already been demonstrated. Our group have explored the effects of 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazines as antagonists of H4R, and herein the compounds LINS01005 and LINS01007 were studied with more details, considering the different affinity profile on H4R and the anti-inflammatory potential of both compounds. METHODS: We carried out a more focused evaluation of the modulatory effects of LINS01005 and LINS01007 in a murine asthma model. The compounds were given i.p. (1-7 mg/kg) to ovalbumin sensitized BALB/c male mice (12 weeks old) 30 min before the antigen challenging, and after 24 h the cell analysis from the bronchoalveolar lavage fluid (BALF) was performed. The lung tissue was used for evaluation by western blot (COX-2, 5-LO, NF-κB and STAT3 expressions) and histological analysis. RESULTS: Treatment with the more potent H4R antagonist LINS01007 significantly decreased the total cell count and eosinophils in BALF at lower doses when compared to LINS01005. The expression of COX-2, 5-LO, NF-κB and STAT3 in lung tissue was significantly reduced after treatment with LINS01007. Morphophysiological changes such as mucus and collagen production and airway wall thickening were significantly reduced after treatment with LINS01007. CONCLUSION: These results show important down regulatory effect of novel H4R antagonist (LINS01007) on allergic lung inflammation.