Publisher Correction: Signatures of self-organized criticality in an ultracold atomic gas.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Signatures of self-organized criticality in an ultracold atomic gas.

Self-organized criticality is an elegant explanation of how complex structures emerge and persist throughout nature1, and why such structures often exhibit similar scale-invariant properties2-9. Although self-organized criticality is sometimes captured by simple models that feature a critical point as an attractor for the dynamics10-15, the connection to real-world systems is exceptionally hard to test quantitatively16-21. Here we observe three key signatures of self-organized criticality in the dynamics of a driven-dissipative gas of ultracold potassium atoms: self-organization to a stationary state that is largely independent of the initial conditions; scale-invariance of the final density characterized by a unique scaling function; and large fluctuations of the number of excited atoms (avalanches) obeying a characteristic power-law distribution. This work establishes a well-controlled platform for investigating self-organization phenomena and non-equilibrium criticality, with experimental access to the underlying microscopic details of the system.

Dexamethasone-induced intrauterine growth restriction modulates expression of placental vascular growth factors and fetal and placental growth.

Prenatal exposure to glucocorticoids (GC) is a central topic of interest in medicine since GCs are essential for the maturation of fetal organs and intrauterine growth. Synthetic glucocorticoids, which are used in obstetric practice, exert beneficial effects on the fetus, but have also been reported to lead to intrauterine growth retardation (IUGR). In this study, a model of growth restriction in mice was established through maternal administration of dexamethasone during late gestation. We hypothesised that GC overexposure may adversely affect placental angiogenesis and fetal and placental growth. Female BALB/c mice were randomly assigned to control or dexamethasone treatment, either left to give birth or euthanised on days 15, 16, 17 and 18 of gestation followed by collection of maternal and fetal tissue. The IUGR rate increased to 100% in the dexamethasone group (8 mg/kg body weight on gestational days 14 and 15) and pups had clinical features of symmetrical IUGR at birth. Dexamethasone administration significantly decreased maternal body weight gain and serum corticosterone levels. Moreover, prenatal dexamethasone treatment not only induced fetal growth retardation but also decreased placental weight. In IUGR placentas, VEGFA protein levels and mRNA expression of VEGF receptors were reduced and NOS activity was lower. Maternal dexamethasone administration also reduced placental expression of the GC receptor, αGR. We demonstrated that maternal dexamethasone administration causes fetal and placental growth restriction. Furthermore, we propose that the growth retardation induced by prenatal GC overexposure may be caused, at least partially, by an altered placental angiogenic profile.

Analysis of the smear layer generated by different activation systems: an in vitro study.

OBJECTIVES: To evaluate via scanning electron microscopy the amount of smear layer generated during the use of sonic and ultrasonic activation systems with standardized short-term intentional contacts with the canal walls. METHODOLOGY: Seventy single-root human teeth were randomly assigned to 2 control (n = 5 each): NC (negative control), PC (positive control) and four experimental groups (n = 15 each): NC (negative control), PC (positive control), G1 (passive ultrasonic irrigation with Irrisafe), G2 (ultrasonic irrigation with EndoUltra), G3 (sonic irrigation with Endoactivator), G4 (sonic irrigation with Eddy). Samples were instrumented with ProTaper Next®. An irrigation protocol with sodium hypochlorite (NaOCl) and ethylenediaminetetraacetic acid (EDTA) was followed for both PC and the experimental groups. Standardized intentional contacts were made in the mesial walls during 5 s at WL - 2 mm in all experimental groups. Two calibrated evaluators scored the smear layer generated with an ordinal scale by scanning electron microscopy. The weighted kappa coefficient (Kw) was calculated to determine the inter-observer agreement. Post-consensus ordinal data were analyzed using the ordinal (linear) chi-square test. RESULTS: When the agitation file is in contact with dentine walls, Irrisafe® significantly generated the least amount of smear layer in the coronal third (p < 0.05). Both in the middle and apical third, activation with Irrisafe® also showed statistically significant better results than Eddy™ and EndoUltra®. Endoactivator® showed significant better results than EndoUltra® and Eddy™ in the apical third (p < 0.05). CONCLUSIONS: Irrisafe generated the least amount of smear layer in the entire canal and similar to Endoactivator in the apical third when the agitation file is in contact with dentine walls. CLINICAL RELEVANCE: The smear layer is generated during activation. It is common to apply irrigation protocols where after the removal of the smear layer using chelants, a final rinse and activation is carried out but there are no previous studies analyzing the possible creation of a new smear layer with this final activation.

Benchmarking environmental and economic indicators of sludge management alternatives aimed at enhanced energy efficiency and nutrient recovery.

Wastewater treatment plants (WWTPs) have been developed as multifunctional systems that aim to eliminate pollutants present in wastewater, manage the sludge produced and improve energy efficiency. Specifically, sludge management accounts for the largest share in operational costs. Considering the relevant role of sludge treatment within the overall management scheme, this study aims to evaluate different alternatives and strategies for sludge management and treatment from the perspective of life cycle analysis, with special emphasis on those options that reduce environmental impacts and economic costs. Two pre-treatments (chemical or thermal) and two post-treatments (composting unit followed by land application or incineration) were evaluated to improve the eco-balance of the anaerobic digestion (AD) process in terms of operational (biogas production and digested sludge), environmental and economic indicators. According to the results obtained, both sludge pre-treatment alternatives proved to be an adequate alternative to improve biogas production without negatively affecting environmental and economic impacts. Finally, if the final disposal of the digestate is analysed, its application to the soil as a biofertiliser is recommended, since it presents a better environmental profile than incineration.

Relationship between unintentional canal overfilling and the long-term outcome of primary root canal treatments and nonsurgical retreatments: a retrospective radiographic assessment.

AIM: To determine retrospectively the long-term radiographic outcome of root canal treatments and root canal retreatments with unintentional root canal overfilling. METHODOLOGY: A total of 220 root canal treatments (143 primary/77 retreatments) with postoperative unintentional canal overfilling and performed by two endodontists during their 45 years of private practice were included in the study. Lateral condensation techniques and nine different sealers were used. Overfilling was confirmed with a postoperative periapical radiograph and patients were scheduled regularly for recall visits. Average recall time was 4.86 years (maximum = 30 years). Two calibrated observers evaluated the radiographs and determined the long-term outcome using the PAI score pooled in a 3-category scale. The persistence or resorption of the extruded material was registered. The Kappa coefficient (K) was calculated and a logistic regression was used for further analysis. Odds ratios and their 95% CI were estimated. RESULTS: The level of inter-observer agreement was 66.1%. Primary root canal treatments had a significantly (P = 0.015) greater rate of success (91.6%) than retreatments (81.8%). Tooth location (P = 0.019) was the only other factor that significantly affected the outcome. The type of extruded material, and its resorption or persistence did not relate to the outcome. Persistence of extruded material was significantly affected by tooth location and recall time after treatment. CONCLUSION: The outcome of root canal treatment with unintentional canal overfilling was not associated with the type of extruded material or its resorption or persistence. The persistence of extruded material did not relate to a favourable or unfavourable outcome.

Suitability of different tooth replicas for endodontic training: perceptions and detection of common errors in the performance of postgraduate students.

AIM: To compare the perceptions of students when using five different tooth replicas and to detect common errors in the performance of students that might be attributed to a specific type of tooth replica. METHODOLOGY: Five groups (n = 10 each) of artificial first maxillary molars (DEPT, DRSK, Nissin, DENTALIKE and TrueTooth) were used. All 50 teeth were mounted individually in opaque containers, distributed in 10 packages containing a sample from each with an assigned random order for students to perform root canal treatments. Ten postgraduate students each performed a root canal treatment on the five replicas, in the assigned order, and completed a satisfaction questionnaire. Three trained and calibrated endodontic educators, each with more than 15 years of experience, evaluated their performance using a grading rubric and completed a questionnaire to detect common errors attributed to a specific tooth replica. Inter-rater reliability was calculated with the interclass correlation coefficient for both consistency and absolute agreement. A two-way related measures anova was used to assess the interaction amongst evaluators and tooth groups on the average scores of students. Post hoc T3 Dunnet was used to compare groups. The perceptions of students amongst groups were compared with chi-square and linear-by-linear association tests. RESULTS: Inter-rater reliability was very high for both consistency (ICCC = 0.939; 95% confidence interval (CI) 0.902-0.964) and absolute agreement (ICCA = 0.940; 95% CI 0.904-0.965). No significant differences were found amongst the ratings of evaluators; however, students performed differently when using the various tooth replicas (P < 0.05). Overall, 60% of students preferred the DRSK replica for root canal treatment training purposes, followed by DENTALIKE (30%). The least preferred was TrueTooth (70% responses) due to its complex anatomy and poor resistance to instruments and heat pluggers. Evaluators detected several common errors in specific tooth replicas and preferred tooth replicas manufactured based on microCT scans of natural teeth. CONCLUSIONS: Tooth replicas manufactured based on microCT scans of natural teeth (TrueTooth and DENTALIKE) had much better acceptance amongst evaluators, although students rated and performed less well in TrueTooth replicas due to their greater level of difficulty.

Positive and negative pressure irrigation in oval root canals with apical ramifications: a computational fluid dynamics evaluation in micro-CT scanned real teeth.

AIM: To compare using computational fluid dynamics (CFD) the flow pattern, irrigant velocity, apical pressure and shear stress produced by negative (MiC) and positive pressure with different types of needles (side-vented (SV), front-vented (FV) and notched (N)) at two insertion depths in the apical ramification of oval root canals. METHODOLOGY: The micro-CT of a mandibular molar with an oval root canal with an apical ramification was used for computational analysis after preparation and geometric reconstruction. Geometries with the needles in two positions (1 and 3 mm from WL) were created to run the simulations. Key parameters of irrigation were displayed with CFD and compared. RESULTS: The penetration depth of the needle in the root canal strongly influenced shear stress and apical pressure. The three needles revealed that the highest shear stress, velocity and apical pressure were 1 mm from the WL and generated medium velocities. In N simulations, the fluid flow did not reach the apical ramification and the lowest shear stress values for positive pressure needles were found. The predominant axial component for FV revealed a different pattern of irrigation with high shear stress values and higher apical pressures than those exerted by other needles. SV simulations had generalized fluid flow in most of the main canal, the highest shear stress values and lower apical pressure than the threshold determined for risk of extrusion. MiC was associated with low velocity, shear stress and apical pressure. CONCLUSION: The SV needle demonstrated a combination of low positive pressure and high shear stress; while N had the lowest shear stress and FV the highest apical pressure. MiC generated fluid flow in part of the apical ramification with negative apical pressure values but low shear stress and velocity.

Realization of a Rydberg-Dressed Ramsey Interferometer and Electrometer.

We present the experimental realization and characterization of a Ramsey interferometer based on optically trapped ultracold potassium atoms, where one state is continuously coupled by an off-resonant laser field to a highly excited Rydberg state. We show that the observed interference signals can be used to precisely measure the Rydberg atom-light coupling strength as well as the population and coherence decay rates of the Rydberg-dressed states with subkilohertz accuracy and for Rydberg state fractions as small as one part in 10^{6}. We also demonstrate an application for measuring small, static electric fields with high sensitivity. This provides the means to combine the outstanding coherence properties of Ramsey interferometers based on atomic ground states with a controllable coupling to strongly interacting states, thus expanding the number of systems suitable for metrological applications and many-body physics studies.

Does exercise during pregnancy impact on maternal weight gain and fetal cardiac function? A randomized controlled trial.

OBJECTIVE: To evaluate the association between physical exercise during pregnancy and maternal gestational weight gain and fetal cardiac function. METHODS: This was a randomized controlled trial of women with a singleton pregnancy managed from the first trimester at the Hospital de Torrejón, Madrid, between November 2014 and June 2015. Women were randomized to either follow a supervised physical conditioning program, consisting of a 60-min session 3 days per week for the duration of pregnancy, or not attend any exercise program (controls). The primary outcome was maternal weight gain during pregnancy. Secondary outcomes included fetal cardiac function parameters evaluated at 20, 28 and 36 weeks' gestation, Cesarean section, preterm delivery, induction of labor and birth weight. A sample size of 45 in each group was planned to detect differences in maternal weight gain of at least 1 kg, with a power of > 80% and α of 0.05. RESULTS: During the study period, 120 women were randomized into the exercise (n = 75) and control (n = 45) groups. Following exclusions, the final cohort consisted of 42 women in the exercise group and 43 in the control group. Baseline characteristics (maternal age, prepregnancy body mass index, parity, conception by in-vitro fertilization, Caucasian ethnicity, physical exercise prior to pregnancy and smoker) were similar between the two groups. No differences were found between the groups in maternal weight at 20, 28, 36 and 38 weeks' gestation or in weight gain at 38 weeks. However, the proportion of women with weight loss ≥ 9 kg at 6 weeks postpartum was higher in the exercise compared with the control group (68.2% vs 42.8%; relative risk 1.593; P = 0.02). The ductus arteriosus pulsatility index (DA-PI) at 20 weeks (2.43 ± 0.40 vs 2.26 ± 0.33, P < 0.05) and the ejection fraction (EF) at 36 weeks (0.85 ± 0.13 vs 0.81 ± 0.11, P < 0.05) were higher in the exercise compared with the control group. All other evaluated fetal cardiac function parameters were similar between the two groups. CONCLUSIONS: Performing exercise during pregnancy is not associated with a reduction in maternal weight gain but increases weight loss at 6 weeks postpartum. Physical exercise during pregnancy is associated with increased fetal DA-PI at 20 weeks and EF at 36 weeks, which could reflect adaptive mechanisms. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Hepatic Metal and Metallothionein Levels in a Potential Sentinel Teleost, Dulesauriga, from a Southeastern Brazilian Estuary.

The identification of estuarine sentinel species is of paramount importance. The potential of the species Dules auriga sampled from Guanabara Bay, Brazil regarding metal contamination was assessed. Hepatic metallothionein (MT) and Fe, Zn, Cu, Mn, Cd and Ag concentrations were determined in cytosolic fractions (S50 and HT S50) by polarography and ICP-OES, respectively. HT S50 Fe, Mn and Zn were lower than in the S50 fraction, indicating MT-detoxification. MT was correlated to HT S50 Zn, indicating Zn homeostasis. Zn was negatively correlated to weight (TW) and length (TL), suggesting environmental Zn influence. A moderate negative correlation between HT S50 Cu and the condition factor (CF) was observed, indicating that increasing environmental Cu concentrations may decrease D. auriga CF. Several inter-elemental correlations were observed. No MT, TW and TL correlations were found. Thus, MT variability is probably linked to environmental metal concentrations. D. auriga fulfills most sentinel requisites, and MT may be an adequate metal contamination biomarker in this species.

Persistently altered liver test results in hepatitis C patients after sustained virological response with direct-acting antivirals.

Guidelines recommend evaluating persistent alteration of liver tests in HCV-infected patients after sustained virological response (SVR) and its influence on liver disease progression. We studied the prevalence, etiology, associated factors and evolutionary implications of persistent alteration of liver tests in HCV patients after direct-acting antivirals (DAA)-induced SVR. This was a prospective study of HCV-infected patients and SVR after DAA. Those with another previously diagnosed liver disease were excluded. Persistent alteration of liver tests was defined as any increase in ALT, AST or GGT at SVR12 and SVR24. Causes were determined according to standard clinical practice, including liver biopsy and follow-up transient elastography. A total of 1112 patients were included (70.8% males, median age 53 years, 38.8% cirrhosis, 34.9% interferon-experienced, 56.8% HIV-coinfected). Persistent alteration of liver tests was detected in 130/1112 patients (11.7% [95%CI: 9.7-13.6]). Its frequency differed between HCV-monoinfected (45/480: 9.4% [95%CI: 6.7-12.1]) and HIV-coinfected (85/632: 13.5% [95%CI: 10.7-16.2]) (P = .046). In multivariable analysis, cirrhosis (OR 2.12; 95%CI: 1.28-3.53; P = .004) and baseline transient elastography values (OR 1.03; 95%CI: 1.01-1.04; P = .000) were associated with persistent alteration of liver tests. The main etiologies were clinical diagnosis suggestive of nonalcoholic fatty liver disease in 47 (36.2%), alcohol in 30 (23.1%) and drug consumption in 19 (14.6%). Baseline and follow-up transient elastography was performed in 594 patients and showed a significantly different decrease in patients who did or did not have a persistent alteration of liver tests (-21.1% vs -30%, respectively; P = .003), independently of sex, HIV status or baseline TE value. In conclusion, persistent alteration of liver tests is not infrequent after SVR. It is associated with cirrhosis and baseline transient elastography, and the main cause is fatty liver. According to transient elastography changes, persistent alteration of liver tests seems to affect the course of liver disease.

Sysmex UF-1000i flow cytometer to screen urinary tract infections: the URISCAM multicentre study.

The new Sysmex UF-1000i analyzer - which incorporates bacteria morphology distinction - allows to automatically screen samples to be cultured at microbiology laboratories. We have evaluated the feasibility and accuracy of Sysmex UF-1000i to screen urinary tract infections (UTIs). A total amount of 2468 urine samples from six Spanish hospitals were analysed. Demographic and clinical data such as age, gender, source and sample type, preserving conditions, cytometer parameters (bacteria, leucocytes and bacteria morphology) as well as urine culture results (gold standard) were recorded. After applying data mining techniques, the variables of age, bacteria count and rod morphology were defined as predictive variables of UTIs. By using the UF-1000i in combination with a predictive algorithm of three decision rules, we could identify 94·9 and 47·4% positive and negative urine samples, respectively, with a negative predictive value of 97 and only 1·17% diagnostic error. This error was reduced down to 0·4% when contaminated samples were excluded. Our results show that flow cytometry parameters together with age, by means of a predictive algorithm model, can be used to screen UTIs. Its implementation would avoid culturing 38% of urine samples, and therefore, would reduce time to diagnosis with a discrete false negative ratio. SIGNIFICANCE AND IMPACT OF THE STUDY: Fluorescent flow cytometry performance has recently spread for urine screening. However, controversy about cytometer results can be drawn from medical literature. This study shows the diagnosis accuracy of Sysmex UF-1000i analyzer by means of a group of decision rules encompassing both demographic variables (age) and cytometer parameters (bacteria, leucocytes and bacteria morphology). After applying the predictive algorithm, the UF-1000i could optimally identify 95% urinary tract infections with high negative predictive value and low diagnostic error. Implementation of UF-1000i would avoid culturing almost 38% of urine samples, thus reducing time to diagnosis, unnecessary antibiotic treatments and consequently improving cost-effectiveness.

Lateral and axial cutting efficiency of instruments manufactured with conventional nickel-titanium and novel gold metallurgy.

AIM: To isolate the effect of metallurgy in lateral and axial cutting efficacy against plastic and bovine dentine substrates by comparing two rotary systems with identical design but manufactured with either conventional nickel-titanium or heat-treated gold alloy. METHODOLOGY: A total of 258 ProTaper Universal (PTU) and ProTaper Gold (PTG) Shaping instruments were used. Bending behaviour was assessed to determine the appropriate displacement associated with a 2 N force in lateral cutting. Ten instruments of each type were used in lateral action for 60 s against bovine dentine or plastic substrates four consecutive times producing four notches in each specimen. Ten further instruments of each type were used in on axial action in four standardized simulated root canals fabricated from 4-mm thick plastic or dentine discs. Both tests were performed at 300 rpm in a computer-controlled testing platform. Notch area and torsional load were compared with Student's t-tests. Repeated measures ANOVA was used to compare cutting efficiency across the four different time-points. Pearson correlation coefficients between substrates were also determined. RESULTS: For lateral action, all three PTG instruments cut significantly more effectively (P < 0.05) than PTU on the plastic substrate. S1 and S2 PTG cut significantly more after 120 and 180 s (P < 0.05) on bovine dentine substrate. For axial action, S1 and S2 PTG were significantly more efficient in cutting at 180 s on plastic and 120 s on bovine dentine (P < 0.05). CONCLUSION: Instruments made from heat-treated nickel-titanium gold alloy had equal or greater cutting efficiency when compared to those made from conventional nickel-titanium.

Distal root curvatures in mandibular molars: analysis using digital panoramic X-rays.

BACKGROUND: The aim of this study was to describe the degree of curvature in distal roots in the first and second permanent mandibular molars in a Chilean patient sample. A cross-sectional descriptive study was conducted in which digital panoramic X-rays were analysed. MATERIALS AND METHODS: Examinations of patients under 18 years, with signs of distortion or alteration in the contrast or the presence of pathologies that affected visualisation of the roots and pulp-chamber floor of the teeth to be analysed were excluded. Using the AutoCad software, an angle was drawn to represent the curve of the root in its different thirds, drawing lines inside the root canal from the pulp-chamber floor to the dental apex. Using the classic definition of dilaceration (root curvature > 90°), its prevalence was established. 412 teeth and roots were analysed, finding a dilaceration prevalence of 0.73% (n = 3). 84.72% of the roots presented some type of curvature. RESULTS: The middle third had the highest percentage of curvatures and the greatest average of angular curvature, whereas the cervical third was the straightest. No significant differences were found between the degree of curvature and the gender of the subjects, except for the apical third of tooth 3.6. The analysis of curvature by root third offers to the clinician a better perspective of the directional change of the roots and does not limit it to just the presence of curves in the apical third. CONCLUSIONS: The report of the angular degree of the curvatures, in addition to the prevalence of dilacerations, informs to the clinicians about the likelihood of finding difficulties when treating root canals. (Folia Morphol 2018; 77, 1: 131-137).

Prevalence and morphometric analysis of idiopathic osteosclerosis in a Chilean population.

BACKGROUND: The aim of this study was to analyse the prevalence and morpho-metric parameters of idiopathic osteosclerosis (IO) in a Chilean population. IO is an intraosseous growth of compact, benign, unilocular, non-expandable bone that is referred to as an anatomical variation. MATERIALS AND METHODS: A cross-sectional study was performed using 1000 digital panoramic radiographs of adults in which data on the location (maxillary/ mandibular, right/left hemiarcades), shape, position to the dental apex, and the prevalence of IOs were observed in relation to gender and age. The morphometric parameters evaluated were area, height, width, and the linear distances of the IO up to the midline and at the base of the mandible. RESULTS: The overall prevalence was 2.8% (27 individuals), with the majority of cases in women (66.7%) in the second, third, and fifth decades of life, but without significant differences. All cases were present in the mandible (100%), usually in the left hemiarcade (59.3%), molar (48.2%) and premolar (44.4%) regions; at the height of the dental apices (65.5%), with an irregular shape (40.7%) and round (37%). The area of the IOs was 33.9 ± 20.1 mm2, with a height of 7.7 ± ± 3.1 mm, width of 6.6 ± 3.1 mm, and the distance from the IO to the mandible median line was 26.6 ± 10.7 mm and 9.7 ± 3.7 mm to the mandibular base. CONCLUSIONS: All the data observed corroborate with previous studies; the IO does not present a large difference in the Chilean population evaluated compared to pre-vious studies carried out in other populations. (Folia Morphol 2018; 77, 2: 272-278).

Bilateral bifid mandibular canal: a case report using cone beam computed tomography.

The mandibular canal (MC) originates in the mandibular foramen and runs bilaterally through the mandibular ramus and body, ending in the mental foramen. One of the most common anatomical variations is bifid MC, the configurations of which have been classified into four categories and sub-categories. The prevalence of these variations depends on the imaging method used. Studies carried out in panoramic X-rays and cone beam computed tomography (CBCT) show prevalences varying between 1% and 20%. In this case report we present the finding of a bilateral bifid MC by CBCT examination; we describe its location and morphological characteristics. The variation found was a type 1 bilateral bifid MC, which consists in an accessory canal originating from a single mandibular foramen and extending to the third molar or its immediate surroundings. In this report we discuss the importance of detecting these anatomical variations, as well as their implications in clinical practice.

An antisense oligonucleotide targeting TGF-ß2 inhibits lung metastasis and induces CD86 expression in tumor-associated macrophages.

BACKGROUND: The transforming growth factor (TGF)-ß pathway is a well-described inducer of immunosuppression and can act as an oncogenic factor in advanced tumors. Several preclinical and clinical studies show that the TGF-ß pathway can be considered a promising molecular target for cancer therapy. The human genome has three TGF-ß isoforms and not much is known about the oncogenic response to each of the isoforms. Here, we studied the antitumor response to ISTH0047, a recently developed locked nucleic acid-modified antisense oligonucleotide targeting TGF-ß2. MATERIALS AND METHODS: We have studied the anticancer response to ISTH0047 using gymnotic delivery in tumor cell cultures and in in vivo preclinical orthotopic mouse models for primary tumors (breast and kidney tumors) and lung metastasis. RESULTS: We observed that ISTH0047 is able to significantly reduce TGF-ß2 mRNA and protein levels without altering the levels of TGF-ß1 and TGF-ß3. ISTH0047 prevented lung metastasis in syngeneic orthotopic renal cell carcinoma (RENCA) and breast cancer (4T1) tumor models. In addition, using an orthotopic xenograft model of a lung cancer cell line (CRL5807) that mainly expresses TGF-ß2, we observed that ISTH0047 had an important effect on the lung microenvironment inhibiting the growth of lung lesions. ISTH0047 treatment re-educated macrophages in the lung parenchyma to express the tumor-suppressive factor, CD86. CONCLUSION: Overall, our data point to TGF-ß2 as a therapeutic target and ISTH0047 as a novel anticancer drug to prevent lung metastasis by impacting on the tumor niche, in part, through the induction of CD86 in tumor-associated macrophages.

New curricular design in biostatistics to prepare residents for an evidence-based practice and lifelong learning education: a pilot approach.

AIM: To develop, implement and evaluate an innovative curriculum in biostatistics in response to the need to foster critical thinking in graduate healthcare education for evidence-based practice and lifelong learning education. METHODOLOGY: The curriculum was designed for first-year residents in a postgraduate endodontic programme using a six-step approach to curriculum development to provide sufficient understanding to critically evaluate biomedical publications, to design the best research strategy to address a specific problem and to analyse data by appropriate statistical test selection. Multiple learner-centred instructional methods and formative and summative assessments (written tasks, simulation exercises, portfolios and pre-post knowledge tests) were used to accomplish the learning outcomes. The analysis of the achievement of the group of students and a satisfaction survey for further feedback provided to the residents at the end of the curriculum were used for curriculum evaluation. RESULTS: All residents demonstrated competency at the end of the curriculum. The correct answer rate changed from 36.9% in the pre-test to 79.8% in the post-test. No common errors were detected in the rest of the assessment activities. All participants completed the questionnaire demonstrating high satisfaction for each independent category and with the overall educational programme, instruction and course in general. CONCLUSIONS: The curriculum was validated by the assessment of students' performance and a satisfaction survey, offering an example of a practical approach to the teaching of statistics to prepare students for a successful evidence-based endodontic practice and lifelong learning education as practicing clinicians.

Injection in temporomandibular joint of rats. Description of technical protocol.

The development of animal models for research has been very diffused. Osteoarthritis is a joint degenerative pathology that induces cartilage erosion, chondrocyte proliferation and osteophyte formation. The aim of this paper is to present a technical procedure to perform the injection of monosodium iodine acetate in the temporomandibular joints of rats to generate osteoarthritis and to contribute to future research analysis related to pathology progression and proper treatment performance. The use of rat models may be a complex process because of their size, but they can be compared to the human temporomandibular joint due to the similar characteristics and the possibility of performing diagnosis and treatment protocols in order to detect this pathology.