Relaxin Inhibits the Cardiac Myofibroblast NLRP3 Inflammasome as Part of Its Anti-Fibrotic Actions via the Angiotensin Type 2 and ATP (P2X7) Receptors.

Chronic NLRP3 inflammasome activation can promote fibrosis through its production of interleukin (IL)-1ß and IL-18. Conversely, recombinant human relaxin (RLX) can inhibit the pro-fibrotic interactions between IL-1ß, IL-18 and transforming growth factor (TGF)-ß1. Here, the broader extent by which RLX targeted the myofibroblast NLRP3 inflammasome to mediate its anti-fibrotic effects was elucidated. Primary human cardiac fibroblasts (HCFs), stimulated with TGF-ß1 (to promote myofibroblast (HCMF) differentiation), LPS (to prime the NLRP3 inflammasome) and ATP (to activate the NLRP3 inflammasome) (T+L+A) or benzoylbenzoyl-ATP (to activate the ATP receptor; P2X7R) (T+L+Bz), co-expressed relaxin family peptide receptor-1 (RXFP1), the angiotensin II type 2 receptor (AT2R) and P2X7R, and underwent increased protein expression of toll-like receptor (TLR)-4, NLRP3, caspase-1, IL-1ß and IL-18. Whilst RLX co-administration to HCMFs significantly prevented the T+L+A- or T+L+Bz-stimulated increase in these end points, the inhibitory effects of RLX were annulled by the pharmacological antagonism of either RXFP1, AT2R, P2X7R, TLR-4, reactive oxygen species (ROS) or caspase-1. The RLX-induced amelioration of left ventricular inflammation, cardiomyocyte hypertrophy and fibrosis in isoproterenol (ISO)-injured mice, was also attenuated by P2X7R antagonism. Thus, the ability of RLX to ameliorate the myofibroblast NLRP3 inflammasome as part of its anti-fibrotic effects, appeared to involve RXFP1, AT2R, P2X7R and the inhibition of TLR-4, ROS and caspase-1.

MMP-9 Levels in the Gingival Crevicular Fluid of Chilean Rosacea Patients.

Rosacea is a chronic inflammatory skin disease whose prevalence rates remain unknown in Chile. Laboratory benchmark testing for this disease is not useful, therefore, we aimed to evaluate the gingival crevicular fluid (GCF) levels of extracellular metalloproteinases (MMP)-2 and MMP-9 as novel rosacea biomarkers. We designed a cross-sectional study with a control group. Participants were systemically healthy adults (n = 20) and persons with rosacea (n = 18). We performed a periodontal evaluation and collected gingival crevicular fluid to measure MMP-2 and MMP-9 levels. Analysis showed mean and standard deviation of MMP-9 concentrations in the GCF for patients with rosacea was 764.52 ± 569.83 pg/mL; for healthy patients, it was 260.69 ± 170.43 pg/mL (p < 0.05). The diagnosis of rosacea was responsible for the levels of MMP-9 in the GCF (p < 0.05), as opposed to periodontitis, smoking, and age (p > 0.05). The Area under ROC for MMP-9 was 0.869 (95%, C.I: 0.719−0.956), with a sensitivity of 72.22% and specificity of 81.58% for the diagnosis of rosacea. We conclude that the quantification of MMP-9 in the GCF could be used as a biomarker of rosacea. Also, rosacea was responsible for increasing the levels of MMP-9 in the GCF independent of periodontal status.

Academics' and students' experiences in a chilean dental school during the COVID-19 pandemic: A qualitative study.

INTRODUCTION: The quick spread of COVID-19 has caused part of the world's population to adopt quarantine protocols that have limited professional activities, including dental training programmes. This study aimed to explore the experiences of students and personnel at a Chilean dental school during the COVID-19 pandemic. MATERIALS AND METHODS: This phenomenological descriptive qualitative study reported staff and students' experiences during the pandemic through in-depth, semi-structured interviews. These were recorded on audio and video with a digital platform. Three researchers then transcribed and analyzed the recordings and codified the answers into categories to determine the emerging topics until a saturation point was reached. RESULTS: The core emerging themes among the staff group were (1) change in the personal/professional life balance, (2) online learning through digital platforms, (3) staff perceptions of students' learning experiences, and (4) concerns about the future. For students, the themes were (1) changes in the learning process, (2) online learning through digital platforms, (3) interpersonal relationships, and (4) concerns about the future. CONCLUSION: The COVID-19 pandemic has been a period of learning for our dental school staff and students. Even though online learning has been a useful tool for delivering didactic (theoretical) concepts, it has been unable to replace conventional education, including skills training. Students and teachers reported being overwhelmed at the beginning of the pandemic, but they have shown remarkable adaptability and resilience during this period.

Serelaxin inhibits the profibrotic TGF-ß1/IL-1ß axis by targeting TLR-4 and the NLRP3 inflammasome in cardiac myofibroblasts.

The recombinant form of the peptide hormone relaxin, serelaxin (RLX), mediates its anti-fibrotic actions by impeding the profibrotic activity of cytokines including TGF-ß1 and IL-1ß. As IL-1ß can be produced by the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domains-containing protein 3 (NLRP3) inflammasome, this study determined whether RLX targeted the inflammasome to inhibit the profibrotic TGF-ß1/IL-1ß axis in primary human cardiac myofibroblasts (HCMFs) in vitro and in mice with isoproterenol (ISO)-induced cardiomyopathy in vivo. HCMFs stimulated with TGF-ß1 (5 ng/ml), LPS (100 ng/ml), and ATP (5 mM) (T+L+A) for 8 h, to induce the NLRP3 inflammasome, demonstrated significantly increased protein expression of markers of NLRP3 priming (NLRP3, apoptosis-associated speck-like protein containing a C-terminal caspase-recruitment domain, procaspase-1) and activity (IL-1ß, IL-18). After 72 h, there was significantly increased neuronal NOS (nNOS), TLR-4, procaspase-1, myofibroblast differentiation, and collagen-I deposition. These measures, along with interstitial TGF-ß1 expression and collagen deposition, were also increased in the left ventricle (LV) of ISO-injured mice 14 d postinjury. RLX [16.8 nM (100 ng/ml) in vitro; 0.5 mg/kg per day in vivo] inhibited T+L+A- and ISO-induced TLR-4 expression, NLRP3 priming, IL-1ß, IL-18, myofibroblast differentiation, and interstitial collagen deposition at the time points studied, via the promotion of nNOS; with the NLRP3- and IL-1ß-inhibitory effects of RLX in HCMFs being abrogated by pharmacological blockade of nNOS or TLR-4. Comparatively, the small molecule NLRP3 inhibitor, N-{[(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)amino]carbonyl}-4-(1-hydroxy-1-methylethyl)-2-furansulfonamide (1 µM in vitro, 10 mg/kg/d in vivo), inhibited components of the NLRP3 inflammasome in vitro and in vivo and ISO-induced interstitial LV fibrosis in vivo but did not affect nNOS, TLR-4, myofibroblast differentiation, or myofibroblast-induced collagen deposition. Hence, RLX can inhibit the TGF-ß1/IL-1ß axis via a nNOS-TLR-4-NLRP3 inflammasome-dependent mechanism on cardiac myofibroblasts.-Cáceres, F. T., Gaspari, T. A., Samuel, C. S., Pinar, A. A. Serelaxin inhibits the profibrotic TGF-ß1/IL-1ß axis by targeting TLR-4 and the NLRP3 inflammasome in cardiac myofibroblasts.

Determination of presence and morphometry of lingual foramina and canals in Chilean mandibles using cone-beam CT images.

PURPOSE: To describe the presence and anatomical characteristics of lingual foramina and canals using cone-beam computed tomography (CBCT) in a sample of Chilean dry mandibles. METHODS: Cone-beam computed tomography images of 68 adult mandibles of indeterminate sex and age were analyzed. The description of number and position of lingual foramina were tabulated using a position regarding the mental spines (superior, between, and inferior to the mental spines). Area and diameter of the foramina and length of the canals found were measured. RESULTS: All the mandibles had one or more lingual foramen. The median was 3 foramina with a minimum of 1 and a maximum of 4. The most frequent positions were superior and inferior with 88% and 85% of presence, respectively. The lingual canal diameter obtained for the superior position was 1.04 ± 0.38 mm, for the between position was 1.02 ± 0.5 mm, and finally 1 ± 0.3 mm for the inferior position. The lingual canal length for the superior position was 6.38 ± 2.4 mm, for the between position 6.77 ± 1.33, and 5.38 ± 0.25 mm for the inferior position. CONCLUSIONS: All the mandibles have one or more lingual foramina. The most frequent positions were superior and inferior. Many of the lingual foramina found were over 1 mm in diameter. The lingual canal length was over 5 mm for all the positions.

Morphometry of the Greater Palatal Canal in Adult Skulls.

The purpose of this study was to evaluate in dry skulls the length and angle between the greater palatine foramen and the foramen rotundum in both the frontal and sagittal planes. In 50 human skulls from the department of morphology, the distance and angulation required to reach the foramen rotundum through the greater palatine canal were measured in the frontal and sagittal planes. A stylet was introduced up to the foramen rotundum in each greater palatine canal and fixed. The skulls were then photographed from a front and lateral view (both right and left). Finally, the stylets were photographed on graph paper. These images were analyzed with Photoshop software. In the frontal plane, mean angulations of 5.32 degrees on the right side and 6.15 degrees on the left side were obtained. In the sagittal plane, mean angulations of 61.66 degrees on the right side and 61.81 degrees on the left side were obtained. Finally, the mean length required to reach the foramen rotundum was 31.95  mm on the right side and 32.49  mm on the left side. Some of these results differ from those stated in the foreign literature (10 degrees front, 70 degrees sagittal). These differences should be considered for both clinical practice and teaching in Chile.

[Effect of VKORC1 and CYP2C9 variants on dosage of oral anticoagulants in Chilean individuals]. / Efecto de las variantes de VKORC1 y CYP2C9 sobre la dosis de anticoagulantes orales en individuos chilenos.

BACKGROUND: The dose of oral anticoagulants (OAC) shows great variability among patients. Pharmacogenetic studies have shown that common variants in genes CYP2C9 (*2 and *3) and VKORC1 (-1639G>A) are associated with lower requirements of OAC. AIM: To study the association between average maintenance doses of oral anticoagulant therapy required to maintain a stable INR and CYP2C9 and VKORC1 gene variants in Chilean adults. MATERIAL AND METHODS: Prospective study of patients on anticoagulant treatment and with a stable international normalized ratio (INR) for prothrombin time for at least three months. Patients were classified as having high or low acenocoumarol or warfarin requirements. Peripheral blood DNA genotyping was performed by polymerase chain reaction and restriction fragment polymorphism or sequencing and electrophoresis. RESULTS: The study included 185 patients, 125 on acenocoumarol and 60 on warfarin. Patients with VKORC1-1639A allele were more likely to require lower doses of both drugs than patients with the G allele (Odds ratio [OR] for acenocoumarol 9.06, and OR for warfarin = 18.7). There was no association between CYP2C9*2 and*3 and acenocoumarol or warfarin requirements. CONCLUSIONS: There is an association between VKORC1-1639A variant and anticoagulant doses.

Relationship between soluble neuropilin-1 in the gingival crevicular fluid of early pregnant women and different severities of periodontitis: A cross-sectional study.

Background: Pregnancy exacerbates the periodontal inflammation; however, the biological mediators involved are not well characterized. Neuropilins (NRPs) are transmembrane glycoproteins involved in physiological and pathogenic processes such as angiogenesis and immunity but its relationship with periodontal disease in pregnant women has not been studied. Objective: To explore the soluble Neuropilin-1 (sNRP-1) levels in gingival crevicular fluid (GCF) samples during early pregnancy and its association with the periodontitis severity and periodontal clinical parameters. Methods: 80 pregnant women were recruited, and GCF samples were collected. Clinical data and periodontal clinical parameters were recorded. sNRP-1 expression was determined by ELISA assay. The relationship between sNRP-1(+) pregnant women with the severity of periodontitis and periodontal clinical parameters was determined by Kruskal-Wallis and Mann-Whitney tests. Spearman's test estimated the correlation between sNRP-1 levels and periodontal clinical parameters. Results: Periodontitis was classified as mild in 27.5% (n = 22) women, moderate in 42.5% (n = 34), and severe in 30% (n = 24). sNRP-1 expression was higher in the GCF of pregnant with severe (41.67%) and moderate (41.17%) periodontitis compared than in those with mild periodontitis (18.8%). The sNRP-1(+) pregnant had a higher BOP (76.5% v/s 57%; p = 0.0071) and PISA (1199.5 mm2 v/s 880.2 mm2; p = 0.0282) compared with sNRP-1(-). A positive correlation between sNRP-1 levels in GCF and BOP (p = 0.0081) and PISA (p = 0.0398) was observed. Conclusions: The results suggest that sNRP-1 could be involved in periodontal inflammation during pregnancy.

Umbilical KeyPort bilateral laparoscopic orchiectomy in patient with complete androgen insensitivity syndrome.

MAIN FINDINGS: A 22-year-old woman with complete androgen insensitivity syndrome (CAIS) presenting with primary amenorrhea and normal female external genitalia was referred for laparoscopic gonadectomy. She had been diagnosed several years earlier but was reluctant to undergo surgery. Case HYPOTHESIS: Diagnosis of this X-linked recessive inherited syndrome characterizes by disturbance of virilization in males with an AR mutation, XY karyotipe, female genitalia and severely undescended testis with risk of malignization. The optimal time to orchidectomy is not settled; neither the real risk of malignancy in these patients. Early surgery impacts development of a complete female phenotype, with enlargement of the breasts. Based on modern diagnostic imaging using DCE-MRI and surgical technology with single port laparoscopic access we hypothesize that the optimum time for gonadectomy is not at the time of diagnosis, but once feminization has completed. PROMISING FUTURE IMPLICATIONS: An umbilical laparoendoscopic single-site access for bilateral gonadectomy appears to be the first choice approach as leaves no visible incision and diminishes the psychological impact of surgery in a patient with CAIS absolutely reassured as female. KeyPort, a single port access with duo-rotate instruments developed by Richard Wolf facilitates this surgery and allows excellent cosmetic results.

Horizontal Bone Augmentation in the Posterior Atrophic Mandible and Dental Implant Stability Using the Tenting Screw Technique.

The aim of this study was to analyze horizontal bone augmentation using the tenting screw technique in the posterior mandible. Included subjects had a 3-mm bone width and 9-mm bone height, measured by CBCT. After the surgical approach, two to four screws were inserted, leaving 4 mm of extraosseous space; reconstruction was achieved using allogeneic biomaterial and leukocyte- and platelet-rich fibrin together with an absorbable membrane. After 4 months, a new CBCT scan was obtained to compare the bone gain and implant placement. Early and secondary stability were measured by the implant stability quotient (ISQ); prosthetic load was performed 16 weeks later. Student t test was used to compare bone gains and implant stability, with significance set at P < .05. Fourteen subjects and 27 surgical sites initially exhibited a mean bone width of 2.95 ± 0.75 mm. Four months after augmentation, the bone width was 7.15 ± 1.87 mm, confirming a significant bone gain (4.2 ± 1.26 mm). Twenty-seven implants were placed with a minimum insertion torque of 35 Ncm; the primary stability was 69.3 ± 7.16 ISQ, and the secondary stability was 75.9 ± 3.29 ISQ (P > .05). It may be concluded that the tenting screw technique is predictable in terms of bone gain and that it facilitates implant stability.

Soluble Neuropilin-1 in gingival crevicular fluid from periodontitis patients: An exploratory cross-sectional study.

BACKGROUND: Soluble Neuropilin-1 (sNRP-1) is a glycoprotein with angiogenic and immune regulatory functions, which correspond to processes deeply involved with periodontal diseases. This study's objective was to determine the concentration of sNRP-1 in gingival crevicular fluid (GCF) samples of severe periodontitis (stages III-IV) compared to mild-moderate (stages I-II) periodontitis patients. MATERIALS AND METHODS: An exploratory cross-sectional study was conducted, including 36 adults subjected to a complete periodontal exam, which recorded the following periodontal parameters: periodontal probing depth (PPD), clinical attachment loss (CAL), bleeding on probing (BOP), gingival index (GI) and periodontal inflamed surface area (PISA). Periodontitis was defined by two periodontists using the case definition proposed by the 2017 World Workshop for periodontal diseases. GCF samples were collected to determine the levels of sNRP-1 via ELISA. The results were analyzed using descriptive statistics, Mann-Whitney, Kruskal Wallis, and Spearman tests. RESULTS: The levels of sNRP-1 in patient's GCF with periodontitis in stages III-IV showed a median of 38.385 â€‹ng/mL (iqr 30.98), in comparison with 20.085 â€‹ng/mL (iqr 12.74) for stages I-II (p â€‹= â€‹0.202). Regardless of the periodontitis stage, we observed a positive correlation between the levels of sNRP-1 in BOP (Rho: 0.45; p â€‹= â€‹0.0048), PISA (Rho: 0.50; p â€‹= â€‹0.0019), PD (Rho: 0.3; p â€‹= â€‹0.015) and GI (Rho: 0.37; p â€‹= â€‹0.02). CONCLUSIONS: The GCF-sNRP-1 concentration was positively related to periodontal clinical inflammatory parameters and probably could be involved in pro-inflammatory and angiogenic mechanisms observed in periodontitis. Additional studies are necessary to confirm these preliminary results.

Effect of macro-design in the primary stability of short and extra-short implants using resonance frequency analysis. An ex vivo study.

OBJECTIVE: This study aimed to determine the effect of macro design in the primary stability of short and extra-short implants using resonance frequency analysis (RFA). MATERIAL AND METHODS: On an ex-vivo model using pig's ribs, we inserted 80 short and extra-short dental implants (20 implants per brand): Biohorizons®(B) 4.6 × 6mm; Intralock®(I) 4.75 × 6.5 mm; Straumann®(S) 4.1 × 4mm; and Tixos®(T) 5 × 5mm. Primary implant stability was measured using an RFA device. We compared mean ISQ values through ANOVA test. RESULTS: Mean ISQ values: B = 73.36 (±3.39); I = 75.13 (±3.88); S = 65.38 (±8.38); T = 72.13 (±11). B and I showed higher ISQ than S (p-value < 0.001). Short (I) showed higher ISQ than extra-short (B,S,T) implants (p-value = 0.001). Tapered (B,I) had higher ISQ than parallel (S,T) implants (p-value < 0.001). There was a moderate positive correlation between ISQ and length (r = 0.52), and a weak correlation with diameter (r = 0.33). DISCUSSION: The final result is a combination of implant design, length, and diameter. Tapered design (B and I) and larger implants (I) showed better primary stability in terms of ISQ values. This information could be beneficial at implant selection in a severely reabsorbed low-quality bone, privileging length (as long as it is safe), and conical walls design.

Effects of osseodensification protocol on insertion, removal torques, and resonance frequency analysis of BioHorizons® conical implants. An ex vivo study.

OBJECTIVE: Quantify the effect of the osseodensification Densah® protocol on the insertion torque, ISQ, and the removal torque of conical BioHorizons® implants. MATERIALS AND METHODS: An ex vivo model over fresh pig tibia bone was used. Test group (TG) included 50 osteotomies using Densah® osseodensification protocol, and the control group (CG), 50 osteotomies using BioHorizons®'s recommended procedure. Conical BioHorizons® implants (3.8 × 10.5 mm) were implanted, verifying the insertion torque with a manual torque meter. ISQ values were registered with Ostell® device. Finally, implants were removed with manual reverse torque registering the values. Results were analyzed and compared with the Mann-Whitney test and t-test. RESULTS: Median and interquartile range per group were as follows: insertion torque, CG: 26 (12) Ncm; TG: 42 (26) Ncm, removal torque, CG: 25 (20) Ncm; TG: 40 (28) Ncm, ISQ value, CG: 69.25 (5.5); TG: 71.5 (4). All variables were significantly higher (p ≤ 0.05) in the osseodensification group. CONCLUSIONS: The Osseodensification technique may improve primary stability in the clinical scenario on tapered implants. Further human RCTs are necessary to validate this.

Targeting the NLRP3 inflammasome to treat cardiovascular fibrosis.

Cardiovascular fibrosis refers to the scar tissue that develops in the injured heart and blood vessels from an aberrant wound healing response to organ injury or insult. Established fibrosis becomes a hallmark of chronic disease progression and a key contributor to tissue stiffness and dysfunction, which ultimately leads to heart failure. As wound healing and fibrotic responses to myocardial injury are multifactorial processes, current therapies that only target specific contributing factors to disease pathogenesis offer limited overall anti-fibrotic efficacy. As such, recent attention has turned to targeting the body's immune system, which orchestrates the wound healing response to tissue injury. This review focuses on the increasing body of work that has identified the NLRP3 inflammasome, a multiprotein oligomer complex responsible for activation of inflammatory responses via its production of IL-1ß and IL-18, as an immune system-initiated facilitator of cardiovascular healing, but also an important contributor to tissue scarring following its persistent activation. The review summarises the factors that can elicit priming and activation of the inflammasome complex, how the activated inflammasome complex contributes to cardiovascular pathophysiology and fibrosis progression, and the molecular mechanisms involved from various cell culture and animal model studies that have utilised genetic deletion or pharmacological inhibition of specific components of the inflammasome. Finally, it outlines currently known and previously unrecognised cardiovascular receptors that may be pharmacologically targeted to ablate the contribution of the NLRP3 inflammasome to cardiovascular diseases characterised by fibrosis, by compounds that may be developed as effective adjunct therapies to current standard of care medication.

Methodological Issues in First-Principle Calculations of CH3NH3PbI3 Perovskite Surfaces: Quantum Confinement and Thermal Motion.

Characterization and control of surfaces and interfaces are critical for photovoltaic and photocatalytic applications. In this work, we propose CH3NH3PbI3 (MAPI) perovskite slab models whose energy levels, free of quantum confinement, explicitly consider the spin-orbit coupling and thermal motion. We detail methodological tools based on the density functional theory that allow achieving these models at an affordable computational cost, and analytical corrections are proposed to correct these effects in other systems. The electronic state energies with respect to the vacuum of the static MAPI surface models, terminated in PbI2 and MAI atomic layers, are in agreement with the experimental data. The PbI2-terminated slab has in-gap surface states, which are independent of the thickness of the slab and also of the orientation of the cation on the surface. The surface states are not useful for alignments in photovoltaic devices, while they could be useful for photocatalytic reactions. The energy levels calculated for the MAI-terminated surface coincide with the widely used values to estimate the MAPI alignment with the charge transport materials, i.e., -5.4 and -3.9 eV for valence band maximum and conduction band minimum, respectively. Our study offers these slab models to provide guidelines for optimal interface engineering.

Enseñanza histológica e histopatológica a través de microscopía virtual, una oportunidad en odontología / Virtual microscopy in histological and histopathological teaching, an opportunity in dentistry

RESUMEN La microscopía virtual (MV) está siendo ampliamente implementada en educación y podría llevar a reemplazar a la microscopía óptica (MO). Objetivo: Proporcionar una revisión de la literatura a partir de las preguntas ¿Cuál es la percepción de académicos y estudiantes? y ¿Cuál es el desempeño de los estudiantes? respecto a la enseñanza de histología y/o histopatología con MV en odontología. Material y métodos: Se consultaron las bases de datos: Pubmed, Scielo, Science Direct y Scopus, y 10 artículos fueron seleccionados. Resultados: La totalidad de estudios que evaluaron percepción y desempeño académico obtuvieron resultados a favor de la MV. Conclusiones: La MV tiene un futuro prometedor, pero más estudios con metodologías similares y que consideren la percepción de los académicos son requeridos.

ABSTRACT Virtual microscopy (VM) is being widely implemented in education and could lead to the replacement of light microscopy (LM). Objective: To provide a review of the literature based on the questions: What is the perception of academics and students? and What is the performance of students? regarding the teaching of histology and/or histopathology with VM in dentistry. Material and methods: The following databases were consulted: Pubmed, Scielo, Science Direct and Scopus, and 10 articles were selected. Results: All the studies that evaluated perception and academic performance obtained results in favor of VM. Conclusions: VM has a promising future, but more studies with similar methodologies and that consider the perception of academics are required.

Patient experience and non-surgical periodontal therapy in a postgraduate periodontal training program: A qualitative study

ABSTRACT: Objective: To explore patient experience for non-surgical periodontal therapy using phenomenography. Methods: This qualitative study was performed in a postgraduate specialist training program in periodontics. Patients reported their experiences through in-depth interviews in order to recognize the impact of non-surgical periodontal therapy on their quality of life and their satisfaction. A homogeneous sampling procedure was used, establishing redundancy after the fifteenth interview. Interviews were audio recorded, transcribed and analyzed by three researchers who codified the answers into categories to determine the emerging topics. Results: The core emerging themes were: (i) lack of information about periodontal disease; (ii) experience during treatment; (iii) treatment implications; and (iv) clinician-patient relationship. Conclusions: Patients seem to have limited knowledge about periodontal diseases. Reasons for attendance mainly include bleeding gums, tooth mobility, and aesthetic problems. Therapy can generate pain, fear, and is considered invasive, whereas dentine hypersensitivity may occur post-operatively. Despite this, patients would be willing to undergo treatment again and were generally satisfied with the level of care and treatment received.

Expression and function of toll-like receptor 4 and inflammasomes in cardiac fibroblasts and myofibroblasts: IL-1ß synthesis, secretion, and degradation.

UNLABELLED: Cardiac inflammation can be produced by pathogen-associated molecular patterns (PAMPs), from parasitic, bacterial or viral origin; or by danger-associated molecular patterns (DAMPs), released from dead cells after cardiac tissue damage, for example by cardiac infarction. Both, PAMPS and DAMPS activate TLR4 on resident immune cells and heart tissue cells, triggering an inflammatory process necessary to begin the wound healing process. Cardiac fibroblasts (CF) are the most abundant cells in the heart and are critical to wound healing, along with cardiac myofibroblasts (CMF), which are differentiated from CF through a TGF-ß1-mediated process. While TLR4 and the inflammasome complex are known to play important roles in CF function, the effects of TGF-ß1 on TLR4 and inflammasome expression and activity remain unknown. To elucidate this important point, we evaluated the effect of TGF-ß1 on TLR4, and the inflammasome protein expression and activity through activation by LPS, mimicking a myocarditis condition by bacterial origin. We found that TGF-ß1 increased TLR4 expression in CF and that the process was mediated by the TGFßRI and p38 signaling pathways. In both CF and CMF, LPS triggered ERK1/2, PI3K-Akt, and p65-NF-κB phosphorylation. All of these effects were blocked by TAK-242, a TLR4 signaling pathway inhibitor. LPS increased pro-IL-1ß levels, which were dependent on the ERK1/2, PI3K-Akt, and NF-κB signaling pathways, and levels were higher in CF than CMF. NLRP3 and ASC levels were similar in CF and CMF, while pro-caspase-1 levels and caspase-1 activity were higher in CMF. LPS+ATP treatment induced inflammasome complex assembly and activation, triggering the release of IL-1ß in both CMF and CF. Finally, the unsecreted pro-IL-1ß in the CF was degraded by autophagy. CONCLUSION: TGF-ß1 increases TLR4 expression in CF. Despite different pro-IL-1ß and caspase-1 activity levels in CF versus CMF, the two cell types secreted similar levels of IL-1ß after LPS+ATP treatment. These findings suggest that both cell types are active participants in inflammation.

Two-port laparoscopic radical cystectomy with reusable umbilical system: a feasibility study.

OBJECTIVE: To describe the technique and report outcomes of laparoscopic radical cystectomy using 2 ports (2-port LRC) for muscle-invasive bladder cancer. PATIENTS AND METHODS: Prospective study was performed between November 2011 and October 2012 to standardize 2-port LRC, lymph node dissection, and urinary diversion. Twenty patients were intervened (8 ileal conduit, 12 neobladder) and followed up for >1 yr. Median follow-up was 75.5 weeks (interquartile range, 65.2-86 weeks). A reusable system placed through the umbilicus and laparoscopic curved instruments with double rotation, plus one 10-mm extra port placed in the right iliac fossa were used. Neobladder or conduit was performed extracorporeally. Preoperative, perioperative, and pathologic outcomes and long-term security data are presented. RESULTS: Median age was 69.5 years; body mass index, 27.4 kg/m(2); operative time, 335 minutes; estimated blood loss, 337 mL; hospital stay, 9 days; intraoperative transfusion rate, 10%; and visual analog pain score, 3 at day 3. Surgical margin was positive in a case (5%); 3 (15%) were pT0, 2 (10%) pT1, 5 (25%) pT2, 6 (30%) pT3a, 3 (15%) pT3b, and 1 (5%) pT4. The number of nodes removed was 18.5 (interquartile range, 16-29.2), 4 (20%) positive. Complications were major in 2 (10%; fecal peritonitis and urinary sepsis) and minor in 4 (20%; ileus and 3 postoperative transfusion) cases. No case required additional analgesia. Incision was totally hidden in the umbilicus. Continence rate in neobladders was 91.7% at daytime and 75% at nighttime. Study limitation was the absence of a comparative cohort. CONCLUSION: Umbilical 2-port LRC is feasible with good oncologic and functional outcomes, low postoperative pain, and absence of abdominal wall complications. Difficulties have slowed laparoendoscopic single-site radical cystectomy, but umbilical 2-port LRC is a very acceptable alternative for minimally invasive surgery of muscle-invasive bladder cancer.

Umbilical laparoendoscopic urological surgery with a novel reusable device.

OBJECTIVE: The aims of this study were to present cumulative experience with umbilical laparoendoscopic urological surgery using a reusable device and to evaluate outcomes and complications in the first 100 patients. MATERIAL AND METHODS: Patients undergoing umbilical surgery with the KeyPort system and DuoRotate instruments (Richard Wolf, Knittlingen, Germany) were evaluated prospectively. Demographic, intraoperative and postoperative data were assessed. RESULTS: Between October 2011 and July 2012, 79 pelvic (66 radical prostatectomy, 10 radical cystectomy, one diverticulectomy, one bilateral orchiectomy, one ureter reimplantation) and 21 renal (seven radical nephrectomy, six partial nephrectomy, five nephroureterectomy, two pyeloplasty, one pyelolithotomy) surgeries were performed through the umbilicus using this platform. Follow-up was 56.7 ± 12.6 weeks (mean ± SD). Mean age was 64.3 ± 10.3 years, body mass index 29 ± 4.6 kg/m(2), operative time 232 ± 106 min and estimated blood loss 260 ± 95 ml. Conversion to standard multiport laparoscopy was not necessary. An accessory port was used in 87 cases to facilitate suturing and conduct drainage extraction. Postoperative complications occurred in 24 cases (six Clavien grade I, 12 grade II, one grade IIIa, two grade IIIb, two grade IVa, one grade IVb). Mean hospital stay was 4.2 ± 4 days. Total transfusion rate was 10%. Mean visual analogue pain scale at day 2 was 2.1 ± 1.3 (0-10). Visual analogue wound satisfaction scale at month 1 was 9.2 ± 0.6 (0-10). No cancer-related events occurred during follow-up. Late complications (4%) were not related to the surgical approach. CONCLUSIONS: Umbilical KeyPort surgery is technically feasible for a great variety of procedures, both ablative and reconstructive. This access offers adequate surgical outcomes, scarce postoperative pain and security for the patient in the short term. Its reusable nature implies a noticeable economic advantage.