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Introduction: Phosphate-solubilizing bacteria that function through acidification (organic acid synthesis) or mineralization (production of enzymes such as phytase and phosphatases) have been explored as a biotechnological alternative to enhance plant access to phosphorus (P) retained in organic and inorganic forms in agricultural soils. This study tested the hypothesis that applying a biofertilizer composed of a recognized phosphate-solubilizing bacterium ( Bacillus velezensis - endophytic strain BVPS01) and an underexplored plant growth-promoting bacterium ( Lysinibacillus fusiformis - endophytic strain BVPS02) would improve the growth and grain yield of Glycine max L. plants., Methods: Initial in vitro tests assessed the functional traits of these bacteria, and a mix of strains BVPS01 and BVPS02 was produced and tested under field conditions to evaluate its agronomic efficiency., Results: The results confirmed the hypothesis that the tested biofertilizer enhances the agronomic performance of G. max plants in the field. The B. velezensis strain (BVPS01) was found to be more effective than the L. fusiformis strain (BVPS02) in solubilizing phosphates via the phosphatase enzyme production pathway, indicated by the expression of the phoC and phoD genes. In contrast, L. fusiformis was more effective in solubilizing phosphates through organic acid and phytase-related pathways, in addition to synthesizing indole-3-acetic acid and increasing the mitotic index in the root meristem of G. max plants. These strains exhibited biological compatibility, and the formulated product based on these rhizobacteria enhanced root development and increased the number of nodules and flowers, positively affecting 1000-grain weight, grain yield, and grain P content., Discussion: Thus, the tested biofertilizer demonstrated potential to improve root growth and increase both the yield and quality of soybean crops, making it a sustainable and low-cost strategy., Competing Interests: Authors LV, ES, MO, IS, LS, and LB were employed by Simple Agro Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Vitorino, da Silva, Oliveira, Silva, Santos, Mendonça, Oliveira and Bessa.)

Background: There are concerns that airway management in patients with suspected or confirmed cervical spine injury may exacerbate an existing neurological deficit, cause a new spinal cord injury or be hazardous due to precautions to avoid neurological injury. However, there are no evidence-based guidelines for practicing clinicians to support safe and effective airway management in this setting., Methods: An expert multidisciplinary, multi-society working party conducted a systematic review of contemporary literature (January 2012-June 2022), followed by a three-round Delphi process to produce guidelines to improve airway management for patients with suspected or confirmed cervical spine injury., Results: We included 67 articles in the systematic review, and successfully agreed 23 recommendations. Evidence supporting recommendations was generally modest, and only one moderate and two strong recommendations were made. Overall, recommendations highlight key principles and techniques for pre-oxygenation and facemask ventilation; supraglottic airway device use; tracheal intubation; adjuncts during tracheal intubation; cricoid force and external laryngeal manipulation; emergency front-of-neck airway access; awake tracheal intubation; and cervical spine immobilisation. We also signpost to recommendations on pre-hospital care, military settings and principles in human factors., Conclusions: It is hoped that the pragmatic approach to airway management made within these guidelines will improve the safety and efficacy of airway management in adult patients with suspected or confirmed cervical spine injury., (© 2024 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Cancer continues to be a serious threat to human health worldwide. Lung, prostate and triple-negative breast cancers are amongst the most incident and deadliest cancers. Steroidal compounds are one of the most diversified therapeutic classes of compounds and they were proven to be efficient against several types of cancer. The epoxide function has been frequently associated with anticancer activity, particularly the 1,2-epoxide function. For this reason, three 1,2-epoxysteroid derivatives previously synthesised (EP1, EP2 and EP3) and one synthesised for the first time (oxysteride) were evaluated against H1299 (lung), PC3 (prostate) and HCC1806 (triple-negative breast) cancer cell lines. A human non-tumour cell line, MRC-5 (normal lung cell line) was also used. EP2 was the most active compound in all cell lines with IC 50 values of 2.50, 3.67 and 1.95 µM, followed by EP3 with IC 50 values of 12.65, 15.10 and 14.16 µM in H1299, PC3 and HCC1806 cells, respectively. Additional studies demonstrated that EP2 and EP3 induced cell death by apoptosis at lower doses and apoptosis/necrosis at higher doses, proving that their effects were dose-dependent. Both compounds also exerted their cytotoxicity by ROS production and by inducing double-strand breaks. Furthermore, EP2 and EP3 proved to be much less toxic against a normal lung cell line, MRC5, indicating that both compounds might be selective, and they also demonstrated suitable in silico ADME and toxicity parameters. Finally, none of the compounds induced haemoglobin release. Altogether, these results point out the extreme relevance of both compounds, especially EP2, in the potential treatment of these types of cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Assessing scientific literature about prevalence of periapical lesions in individuals with osteoporosis in comparison to those without osteoporosis. Systematic searches were conducted up to November 24th, 2023 in Cochrane Library, EMBASE, MEDLINE/PubMed, SCOPUS, Web of Science and Grey Literature Reports databases. Only observational studies were included. The ROBINS-E tool, a revised Cochrane instrument for assessing bias in nonrandomized exposure studies, was employed. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was utilized to evaluate the certainty of the evidence. From 484 studies, three were included. One of them was categorized as having an exceptionally high risk of bias, while two were deemed to have certain concerns. Two studies reported that osteoporotic patients may have more chances to present a periapical lesion compared to non-osteoporotic patients. One study reported no differences between groups. The GRADE analysis indicated a markedly low level of certainty in the evidence. The present review indicates that osteoporotic patients may present more periapical lesions compared to non-osteoporotic patients. This statement should be cautiously interpreted and further well-designed studies are needed. (EEJ-2023-09-123).

Aim: To determine the minimum dentin thickness in the mesial and distal walls of the mesiobuccal (MB) and mesiolingual (ML) canals of the mandibular first molars using cone-beam computed tomography (CBCT)., Materials and Methods: CBCT examinations of 624 mandibular first molars from an Indian subpopulation were analyzed. The mesial and distal minimum dentin thickness was evaluated in 1 mm intervals apical to the furcation area. Independent t -test was used to analyze the data ( α  = 0.05). Using Cohen's kappa coefficient, the interexaminer and intraexaminer reliability was evaluated., Results: The mesial dentin thickness was significantly higher than the distal dentin thickness for MB and ML canals ( P =0.01). The average dentin thickness in the distal and mesial plane of the MB canal was 1.15 ± 0.15 mm and 1.52 ± 0.19 mm at the 1 mm level and 0.83 ± 0.13 and 1.08 ± 0.18 at the 5 mm level, respectively. For the ML canal, the average dentin thickness in the distal plane and the mesial plane was 1.24 ± 0.18 mm and 1.44 ± 0.21 at the 1 mm level and 0.91 ± 0.16 and 1.01 ± 0.17 at the 5 mm level, respectively. Statistical analysis between the MB and ML canals showed significant differences in the dentin thickness at 4 and 5 mm levels in both the distal and the mesial planes ( P =0.01). In more than 85% of the cases, the minimum dentin thickness was seen at the 5 mm level in both the distal and mesial planes in MB and ML canals., Conclusion: The distal planes of the mesiolingual and mesiobuccal canals were thinner in most cases, making the distal surface more prone to iatrogenic perforations. Considerably, at 4 and 5 mm from the furcation, the distal wall was significantly thinner than the mesial walls. Understanding the anatomy of the danger zone in the mesial roots of the mandibular first molars may serve to minimize the risk of endodontic mishaps such as strip perforations., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Sahil Choudhari et al.)

Background: This article provides an update of the Reflective Practice Questionnaire (RPQ). The original RPQ consisted of 40-items with 10-sub-scales. In this article, the RPQ is streamlined into a 10-item single reflective practice construct, and a 30-item extended version that includes additional sub-scales of confidence, uncertainty/stress, and work satisfaction., Methods: A total of 501 university students filled out an online questionnaire that contained the original Reflective Practice Questionnaire, and two general measures of reflection: The Self-Reflection and Insight Scale, and the Rumination-Reflection Questionnaire., Results: Based on factor analysis, the RPQ was streamlined into a brief 10-item version, and an extended 30-item version. Small positive correlations were found between the RPQ reflective practice measure and the two measures of general reflection, providing discriminant validity evidence for the RPQ. The RPQ was found to be sensitive to differences among industries, whereas the general measures of reflection were not. Average reflective practice scores were higher for health and education industries compared to retail and food/accommodation industries., Competing Interests: Shane L. Rogers is an Academic Editor for PeerJ. Amit Jotangia is employed by Cygnet Health Care., (© 2024 Rogers et al.)

Objective: This study aimed to assess the effect of titanium dioxide (TiO 2 ) and silver (Ag) nanoparticles dispersed in glycerol or water, serving as optical clearing agents nanocolloids (OCAs-NC), for improving optical coherence tomography (OCT) images and highlighting incipient lesions in ex vivo human teeth., Materials and Methods: Twelve human teeth with incipient lesions were divided into seven groups according to the OCA-NC; they were subjected to G1 (air), G2 (glycerol), G3 (TiO 2 0.1%), G4 (TiO 2 0.01%), G5 (TiO 2 0.001%), G6 (AgNO 3 10%), and G7 (AgNO 3 100%). The OCA-NC was applied to the occlusal surface, and two-dimensional images of the specimens were analyzed using OCT (930 nm central wavelength; 100 nm bandwidth; 5 mW output power; axial resolution of 7/5.3 μm in water and air, respectively; lateral resolution of 8 μm; and light penetration depth of 1.6 mm inside the sample)., Results: The findings demonstrated that the utilization of OCAs-NC containing metallic or dielectric nanoparticles (AgNO 3 and TiO 2 ) led to improved differentiation between sound and demineralized enamel on occlusal surfaces. Additionally, it enhanced the depth of image penetration when analyzing this hard tissue with OCT., Clinical Relevance: In the current context of minimally invasive dentistry, the use of OCAs-NC in conjunction with OCT can provide clinicians with early diagnosis, allowing for the determination of less/more invasive therapies and consequently halting the disease before cavitation of dental tissues occurs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Guanidines are fascinating small nitrogen-rich organic compounds, which have been frequently associated with a wide range of biological activities. This is mainly due to their interesting chemical features. For these reasons, for the past decades, researchers have been synthesizing and evaluating guanidine derivatives. In fact, there are currently on the market several guanidine-bearing drugs. Given the broad panoply of pharmacological activities displayed by guanidine compounds, in this review, we chose to focus on antitumor, antibacterial, antiviral, antifungal, and antiprotozoal activities presented by several natural and synthetic guanidine derivatives, which are undergoing preclinical and clinical studies from January 2010 to January 2023. Moreover, we also present guanidine-containing drugs currently in the market for the treatment of cancer and several infectious diseases. In the preclinical and clinical setting, most of the synthesized and natural guanidine derivatives are being evaluated as antitumor and antibacterial agents. Even though DNA is the most known target of this type of compounds, their cytotoxicity also involves several other different mechanisms, such as interference with bacterial cell membranes, reactive oxygen species (ROS) formation, mitochondrial-mediated apoptosis, mediated-Rac1 inhibition, among others. As for the compounds already used as pharmacological drugs, their main application is in the treatment of different types of cancer, such as breast, lung, prostate, and leukemia. Guanidine-containing drugs are also being used for the treatment of bacterial, antiprotozoal, antiviral infections and, recently, have been proposed for the treatment of COVID-19. To conclude, the guanidine group is a privileged scaffold in drug design. Its remarkable cytotoxic activities, especially in the field of oncology, still make it suitable for a deeper investigation to afford more efficient and target-specific drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Failures in glass fiber post (GFP) retention may be associated with low adhesion achieved in root dentin., Material and Methods: 55 single-rooted premolars were endodontically treated and distributed according to different adhesion strategies (n=11): G1: RelyX ARC (3M ESPE; etch-rinse strategy); G2: Relyx Ultimate (3M ESPE; etch-rinse strategy); G3: AllCem (FGM; etch-rinse strategy); G4: Relyx Ultimate (3M ESPE; self-etching strategy); G5: RelyX U200 (3M ESPE; self-adhesive strategy). For Bonding Strength (BS) analysis, the roots were sectioned in slices (1.0mm thickness) corresponding to each root third and submitted to push-out test. The type of failure was assessed by scanning electron microscopy (SEM)., Results: The highest BS averages were found in G2 and G3. However, in the middle and apical root thirds, G3 showed statistically similar results to G4 and G5. In the cervical and middle third, G1 was statistically similar to G4 and G5. The mixed type of failure was the most common in all groups., Conclusions: Self-etching (G4) and self-adhesive resin (G5) cements, showed similar BS results of immediate bonding in the cementation of GFP compared to conventional resin cements (G1, G2, G3). Key words: Dental Cements, Dentin-Bonding Agents, Post and Core Technique, Dental Bonding., Competing Interests: Conflicts of interest The authors report no conflict of interest related to this work., (Copyright: © 2023 Medicina Oral S.L.)

The objective of this case report is to describe the treatment of a dentofacial and temporomandibular joint (TMJ) deformity by means of reconstruction with a customized TMJ prosthesis and orthognathic surgery. The article discusses the therapeutic approach and the importance of functional and esthetic rehabilitation of the patient. A 22-year-old man displayed sequelae of osteomyelitis diagnosed at 6 years of age, including facial asymmetry, laterognathism, unsatisfactory occlusion, and mandibular retrognathism. Computed tomography revealed a deformity of the left mandibular condyle, ramus, and fossa. The patient underwent 1-stage surgery that involved bimaxillary orthognathic surgery and mentoplasty in conjunction with reconstruction of the left TMJ with a customized prosthesis. Postoperatively, substantial improvement was observed in the patient's facial pattern and masticatory function, and the beneficial changes have been maintained through 2 years of follow-up. The positive outcome in this patient suggests that TMJ reconstruction using a customized prosthesis in combination with computer-guided orthognathic surgery can be a satisfactory approach to correct a mandibular defect. The advantages of 1-stage surgery for the surgeon include shorter treatment time and more predictable results, while the benefits for the patient are good esthetic and functional results and improved quality of life., Competing Interests: No conflicts of interest reported.

This dataset contains extensive results on micromechanical behavior and microstructure of alkali-activated materials (AAM) with biomass ash (B) and silica fume (S) precursors. The data were collected at the laboratories of the Federal Center for Technological Education of Minas Gerais (CEFET-MG) in Brazil. Scanning electron microscope (SEM), optical microscopy (OM), and nanoindentation with instrumented penetration (NI) were performed from AAM in the hardened state and advanced age (1000 days). Data include loading curves, hardness, module of elasticity, and microstructure. Data may be useful for researchers and engineers in designing new alternative binders with improved durability., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Steroids and their derivatives have been the subject of extensive research among investigators due to their wide range of pharmacological properties, in which steroidal oximes are included. Oximes are a chemical group with the general formula R 1 R 2 C=N-OH and they exist as colorless crystals and are poorly soluble in water. Oximes can be easily obtained through the condensation of aldehydes or ketones with various amine derivatives, making them a very interesting chemical group in medicinal chemistry for the design of drugs as potential treatments for several diseases. In this review, we will focus on the different biological activities displayed by steroidal oximes such as anticancer, anti-inflammatory, antibacterial, antifungal and antiviral, among others, as well as their respective mechanisms of action. An overview of the chemistry of oximes will also be reported, and several steroidal oximes that are in clinical trials or already used as drugs are described. An extensive literature search was performed on three main databases-PubMed, Web of Science, and Google Scholar.

In this work, new steroidal aromatase inhibitors (AIs) were designed, synthesized, and tested. In one approach, C-ring substituted steroids namely those functionalized at C-11 position with an α or β hydroxyl group or with a carbonyl group as well as C-9/C-11 steroidal olefins and epoxides were studied. It was found that the carbonyl group at C-11 is more beneficial for aromatase inhibition than the hydroxyl group, and that the C-ring epoxides were more potent than the C-ring olefins, leading to the discovery of a very strong AI, compound 7, with an IC 50 of 0.011 μM, better than Exemestane, the steroidal AI in clinical use, which presents an IC 50 of 0.050 μM. In another approach, we explored the biological activity of A-ring C-1/C-2 steroidal olefins and epoxides in relation to aromatase inhibition and compared it with the biological activity of C-ring C-9/C-11 steroidal olefins and epoxides. On the contrary to what was observed for the C-ring olefins and epoxides, the A-ring epoxides were less potent than A-ring olefins. Finally, the effect of 7β-methyl substitution on aromatase inhibition was compared with 7α-methyl substitution, showing that 7β-methyl is better than 7α-methyl substitution. Molecular modelling studies showed that the 7β-methyl on C-7 seems to protrude into the opening to the access channel of aromatase in comparison to the 7α-methyl. This comparison led to find the best steroidal AI (12a) of this work with IC 50 of 0.0058 μM. Compound 12a showed higher aromatase inhibition capacity than two of the three AIs currently in clinical use., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: To evaluate the impact of root canal preparation in teeth with ultraconservative access cavities (UltraAC) on the development of dentinal microcracks using a nondestructive longitudinal micro-computed tomography (micro-CT) imaging experimental model. Root canal preparation in teeth with traditional access cavities (TradAC) was used as control., Methods: Forty mandibular molars were scanned in a micro-CT device, anatomically matched, and distributed into 4 groups according to the type of access cavity and instrumentation system: traditional/Reciproc (TradAC/RC), traditional/XP-endo Shaper (TradAC/XP), ultraconservative/Reciproc (UltraAC/RC), and ultraconservative/XP-endo Shaper (UltraAC/XP). After root canal preparation, the teeth were rescanned. After reconstruction and co-registration procedures, the images were screened from the furcation level to the apex to identify the presence of dentinal microcracks., Results: From a total of 15,340 cross-section images, 19.65% (3014 slices) had some dentinal microcracks. The qualitative analysis demonstrated the presence of some dentinal microcracks in 11%, 33%, 19%, and 15% of the images of cross-sections in TradAC/RC, TradAC/XP, UltraAC/RC, and UltraAC/XP groups, respectively. All dentinal microcracks observed after root canal preparation were already present in the corresponding images before canal instrumentation. Therefore, no new microcracks were detected, regardless of the access cavity and root canal instrumentation system., Conclusions: Root canal preparation with Reciproc or XP-endo Shaper under traditional or ultraconservative access cavities did not create dentinal microcracks in extracted mandibular molars., (Copyright © 2022 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Coaches can influence athlete outcomes, such as performance and personal development; yet, coaches themselves are learners in their own right, who seek to develop their coaching craft. Reflective practice is essential for coaches' development; however, coaches might engage and benefit from reflective practice in myriad ways. This study aimed to evaluate if online reflective journaling (ORJ) enhances the depth of reflection of sports coaches in a 4-week coach development programme (CDP). Participants were a convenience sample of 83 sports coaches from several sports, divided into an intervention group ( N = 42) and a control group ( N = 41). Data collection used a mixed-methods approach, examining a CDP focused on the coaches' reflective practice. The results revealed that reflection was the only dependent variable that showed significant differences over time. Participation in ORJ showed positive effects on reflection in both groups; however, only the experimental group was statistically significant. For this sample, ORJ was found to help enhance coaches' reflection towards critical reflection. All texts included in pre-, post-, and follow-up tests were coded for trustworthiness purposes. This finding supports the potential of ORJ in nurturing reflective practice, which is considered a core competency in becoming a successful sports coach.

We describe a visual algorithm to help prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contagion as well as manage COVID-19 disease according to categories of clinical severity. The algorithm is timely, with multiple countries worldwide declaring repeat surges in SARS-CoV-2 infections following the easing of lockdown measures. Its flowchart assimilates key effective interventions in a visual manner that will assist healthcare workers to manage COVID-19 disease algorithmically, and policymakers to suppress further SARS-CoV-2 waves. Importantly, we include the innovative use of topical p-menthane-3,8-diol spray by the British Army for COVID-19 Support Force personnel, which in light of its coronavirucidal properties, deserves wider dissemination. This algorithm has the potential to be updated as numerous studies are concluded globally., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 International Journal of Preventive Medicine.)

Non-cholesterol sterols are transported in plasma lipoproteins and are consequently important in cholesterol metabolism. We investigated the distribution of non-cholesterol sterol precursors of cholesterol synthesis (NCSPCS), oxysterols, and phytosterols in lipoproteins of healthy subjects differing according to HDL-Cholesterol (HDL-C) plasma levels. Elevated NCSPCS (desmosterol, lathosterol) in the High HDL group suggests that HDL exports these sterols from cells, but not the cholesterol metabolite 24-OHC which was higher in the Low HDL group than in the High HDL group. 27-hydroxycholesterol (27OH-C) plasma levels did not differ between groups. Percentage of NCSPCS and phytosterols predominates in LDL, but did not differ between groups. Thirty percent of desmosterol and lathosterol are present in HDL, with the High HDL group carrying higher percentage of these sterols. A high percentage of campesterol and sitosterol in HDL suggests that phytosterols are absorbed by enterocytes, and that HDL could be a marker of the ABCA1/ApoA1 intestinal activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nunes, da Silva, Ferreira, Assis, Cazita, Nakandakare, Zago, de Faria and Quintão.)

There is already a societal awareness of the growing impact of nanoscience and nanotechnology, with nanomaterials (with at least one dimension less than 100 nm) now incorporated in items as diverse as mobile phones, clothes or dentifrices. In the healthcare area, nanoparticles of biocompatible materials have already been used for cancer treatment or bioimaging enhancement. Nanotechnology in dentistry, or nanodentistry, has already found some developments in dental nanomaterials for caries management, restorative dentistry and orthodontic adhesives. In this review, we present state-of-the-art scientific development in nanodentistry with an emphasis on two imaging techniques exploiting nanomaterials: optical coherence tomography (OCT) and photoacoustic imaging (PAI). Examples will be given using OCT with nanomaterials to enhance the acquired imaging, acting as optical clearing agents for OCT. A novel application of gold nanoparticles and nanorods for imaging enhancement of incipient occlusal caries using OCT will be described. Additionally, we will highlight how the OCT technique can be properly managed to provide imaging with spatial resolution down to 10's-100's nm resolution. For PAI, we will describe how new nanoparticles, namely TiN, prepared by femtosecond laser ablation, can be used in nanodentistry and will show photoacoustic microscopy and tomography images for such exogenous agents.

This article presents a case of an epidermoid cyst that mimicked a thyroglossal duct cyst in a pediatric patient. An 8-year-old boy was referred for evaluation of a volumetric increase in the median cervical region with an evolution of about 4 years. The skin in the submental region was healthy and normal colored. Palpation revealed a mobile, well-circumscribed nodular lesion of soft consistency. Computed tomography of the neck showed an expansive hypodense formation extending from the base of the tongue to the upper portion of the hyoid bone, suggesting a thyroglossal duct cyst. Considering the diagnostic hypothesis, cystic enucleation via the Sistrunk procedure was planned. However, no ductal structure was identified during the surgical procedure, and the lesion was only near, but not attached to, the hyoid bone. Simple excision of the lesion was therefore performed. At the most recent follow-up examination, about 3 months postoperatively, the patient demonstrated satisfactory clinical progress. The epidermoid cyst close to the hyoid bone presented diagnostic difficulty due to its similarity to a thyroglossal duct cyst. Computed tomography provides limited information for diagnosing this type of lesion, and ultrasonography is the preferred test. In view of the uncertain diagnosis in this case, the extent of the excision was determined during the surgery, and simple excision was a satisfactory treatment associated with a good prognosis., Competing Interests: The authors report no conflict of interest pertaining to any of the topics discussed in this article.

The study evaluated the effects of R-limonene, in sublethal concentration, on the histology, histochemistry, biochemistry, and carbohydrates and proteins levels in the third instar Aedes aegypti larvae. The R-limonene (LC50 of 27 ppm) and control groups were analyzed 12 and 24 h after the beginning of treatments. The midgut of the control larvae was composed of cylindrical and elongated cells with a spherical and central nucleus and regenerative cells with a pyramidal shape. After 12 h of treatment, columnar cells, protuberances, and cytoplasmic vacuolization were found. However, 24 h after treatment, complete disorganization of the epithelium was observed. There was a positive reaction in all treatments for the presence of glycogen. However, the midgut of larvae treated with R-limonene showed higher levels. For the total protein, positive marking occurred in all groups evaluated, with higher levels in treatments and the lowest in control 12 h. The levels of total protein and glycogen increased in the treated larvae compared to the 12 h control. Besides, a reduction in total sugar levels was observed in the treated larvae compared to controls 12 and 24 h, being more evident in the last one. Therefore, these results demonstrate that R-Limonene caused pathological changes in the epithelium of the A. aegypti midgut at histophysiological and biochemical levels., (Copyright © 2021. Published by Elsevier B.V.)

Purpose: Therapeutic efficacy of hormonal therapies to target estrogen receptor (ER)-positive breast cancer is limited by the acquisition of ligand-independent ESR1 mutations, which confer treatment resistance to aromatase inhibitors (AIs). Monitoring for the emergence of such mutations may enable individualized therapy. We thus assessed CTC- and ctDNA-based detection of ESR1 mutations with the aim of evaluating non-invasive approaches for the determination of endocrine resistance., Patients and Methods: In a prospective cohort of 55 women with hormone receptor-positive metastatic breast cancer, we isolated circulating tumor cells (CTCs) and developed a high-sensitivity method for the detection of ESR1 mutations in these CTCs. In patients with sufficient plasma for the simultaneous extraction of circulating tumor DNA (ctDNA), we performed a parallel analysis of ESR1 mutations using multiplex droplet digital PCR (ddPCR) and examined the agreement between these two platforms. Finally, we isolated single CTCs from a subset of these patients and reviewed RNA expression to explore alternate methods of evaluating endocrine responsiveness., Results: High-sensitivity ESR1 sequencing from CTCs revealed mono- and oligoclonal mutations in 22% of patients. These were concordant with plasma DNA sequencing in 95% of cases. Emergence of ESR1 mutations was correlated both with time to metastatic relapse and duration of AI therapy following such recurrence. The Presence of an ESR1 mutation, compared to ESR1 wild type, was associated with markedly shorter Progression-Free Survival on AI-based therapies (p = 0.0006), but unaltered to other non-AI-based therapies (p = 0.73). Compared with ESR1 mutant cases, AI-resistant CTCs with wild-type ESR1 showed an elevated ER-coactivator RNA signature, consistent with their predicted response to second-line hormonal therapies., Conclusion: Blood-based serial monitoring may guide the selection of precision therapeutics for women with AI-resistant ER-positive breast cancer.

Purpose: This study aimed to demonstrate the presence of dental caries through a photoacoustic imaging system with visible and near-infrared wavelengths, highlighting the differences between the 2 spectral regions. The depth at which carious tissue could be detected was also verified., Materials and Methods: Fifteen permanent molars were selected and classified as being sound or having incipient or advanced caries by visual inspection, radiography, and optical coherence tomography analysis prior to photoacoustic scanning. A photoacoustic imaging system operating with a nanosecond pulsed laser as the light excitation source at either 532 nm or 1064 nm and an acoustic transducer at 5 MHz was developed, characterized, and used. En-face and lateral (depth) photoacoustic signals were detected., Results: The results confirmed the potential of the photoacoustic method to detect caries. At both wavelengths, photoacoustic imaging effectively detected incipient and advanced caries. The reconstructed photoacoustic images confirmed that a higher intensity of the photoacoustic signal could be observed in regions with lesions, while sound surfaces showed much less photoacoustic signal. Photoacoustic signals at depths up to 4 mm at both 532 nm and 1064 nm were measured., Conclusion: The results presented here are promising and corroborate that photoacoustic imaging can be applied as a diagnostic tool in caries research. New studies should focus on developing a clinical model of photoacoustic imaging applications in dentistry, including soft tissues. The use of inexpensive light-emitting diodes together with a miniaturized detector will make photoacoustic imaging systems more flexible, user-friendly, and technologically viable., Competing Interests: Conflicts of Interest: None, (Copyright © 2021 by Korean Academy of Oral and Maxillofacial Radiology.)

Introduction: Our study evaluated the impact of sodium thiosulfate (ST) irrigation, subsequent to sodium hypochlorite (NaOCl) and just before root canal filling, on the filling quality (interfacial adaptation and penetration segment) of an epoxy resin-based root canal sealer., Methods and Materials: Twenty single-rooted human teeth were prepared with the ProTaper system. The specimens were then divided into the following groups: 5.25% NaOCl irrigation (NaOCl group) and 5.25% NaOCl irrigation+0.5% sodium thiosulfate (NaOCl+ST group). The root canals were filled using single-cone technique with ProTaper F3 cones and AH-Plus sealer, labeled with rhodamine B dye to allow analysis under a confocal laser scanning microscopy (CLSM). All samples were sectioned at 2, 4, and 6 mm from the apex and prepared for CLSM analysis. The percentage of voids, gaps and dentinal sealer penetration segment of the canal were calculated at the apical, middle and coronal thirds. The non-parametric Mann-Whitney statistical test was used at 5% significance level., Results: Higher percentage of gaps and voids were observed at all root thirds of the NaOCl group when compared to the NaOCl+ST group ( P <0.05). There was a significant increase in the penetration segment of NaOCl+ST group at the coronal and middle root third when compared to the NaOCl group ( P <0.05)., Conclusion: Our in vitro results showed that the use of ST as an antioxidant agent after NaOCl irrigation promoted a better interfacial adaptation and penetration of epoxy resin-based root canal fillings., Competing Interests: ‘None declared’., (© The Author(s).)

Background: Fat distribution is associated with chronic diseases and birth weight may influence fat distribution throughout life. Our aim was to compare fat distribution in children born extremely low birth weight (ELBW) and very low birth weight (VLBW). Methods: This retrospective cohort study evaluated children born ELBW and VLBW around the 7th year of life. Fat distribution was assessed by ultrasonography measurements of abdominal subcutaneous and visceral fat thickness. Multiple linear regression analysis was performed. Results: We studied 63 children. Visceral fat thickness but not subcutaneous fat thickness was significantly increased in children born ELBW compared with children born VLBW, respectively, 3.13 (±1.08) versus 1.86 (±0.76) mm. This result remained after adjustment for age, gender, and BMI; adjusted coefficient 0.118, 95% confidence interval 0.009-0.227, p  = 0.034. Conclusion: Children born ELBW seem to have increased visceral fat thickness compared with children born VLBW.

Background: To evaluate the physicochemical properties and cytotoxicity of AH Plus, MTA Fillapex and TotalFill BC Sealer. Volumetric changes were also evaluating using micro-computed tomography (micro-CT)., Material and Methods: Radiopacity and flow were evaluated in accordance with the ISO 6876, while setting time was evaluated in accordance with the ASTM- C266-08 specifications. The release of Ca2+ ions and pH were measured with spectrophotometer and pH meter, respectively, after different time intervals (1h, 3h, 24h, 72h, 168h, and 360h). Cytotoxicity was evaluated by MTT reduction assay to check 3T3 cells viability at 24, 48 and 72 hours. Volumetric change was evaluated by micro-CT, by using 30 acrylic teeth, filled with gutta-percha cones and the tested root canal sealer. The samples were evaluated after 168h, 360h and 720h of immersion in distilled water. Data were statistically analyzed by one-way ANOVA and Tukey test or by Kruskal-Wallis and Dunn tests ( P <0.05)., Results: MTA Fillapex and TotalFill BC Sealer showed lower radiopacity than AH Plus ( P <0.05). The MTA Fillapex showed the highest flow, while AH Plus showed the lowest flow ( P <0.05). The initial and final setting time of AH Plus were lower than MTA Fillapex and TotalFill BC Sealer ( P <0.05). In general, TotalFill BC Sealer presented higher Ca2+ ion release and pH than the other tested sealers. TotalFill BC Sealer also showed overall lower cytotoxicity when compared to the other sealers. Volumetric change of AH Plus and TotalFill BC Sealer was lower than MTA Fillapex ( P <0.05)., Conclusions: AH Plus, MTA Fillapex and TotalFill BC Sealer showed slight differences in the physicochemical properties and cytotoxicity, but all suitable for an endodontic sealer. However, AH Plus and TotalFill BC Sealer showed low volumetric changes when compared to MTA Fillapex. Key words: Calcium silicate, cytotoxicity, physicochemical properties, micro computed tomography., Competing Interests: Conflicts of interest The authors deny any conflict of interest., (Copyright: © 2020 Medicina Oral S.L.)

Aim: To evaluate the response measures in continuing an image-guided intervention service in two tertiary-level musculoskeletal oncology centres during the COVID-19 pandemic., Materials and Methods: This study was a retrospective review of all patients undergoing image-guided intervention in the computed tomography (CT) and normal ultrasound (US) rooms from 24 March 2020 to 24 May 2020 (during the COVID-19 pandemic peak) at Royal National Orthopaedic Hospital, London, and Royal Orthopaedic Hospital, Birmingham, UK. Measures were put in place to address air pressures, airflow direction, aerosol generation, and the safe utilisation of existing scanning rooms and work lists for interventional procedures., Results: Three hundred and thirty-one patients (164 at Royal National Orthopaedic Hospital and 167 at Royal Orthopaedic Hospital) underwent image-guided procedures at both sites in the CT and US rooms. At the Royal National Orthopaedic Hospital, 40% of all procedures were performed under general anaesthesia. These consisted of 47 CT biopsies, 7 CT radiofrequency ablations (RFAs), and 12 US biopsies. At the Royal Orthopaedic Hospital, 86% of all procedures were performed under local anaesthetic, with no general anaesthetic procedures. These consisted of 61 CT biopsies and 83 US biopsies. All 256 patients having procedures in the CT room had no post-procedural complications or COVID-19-related symptoms and morbidity on follow-up., Conclusion: By adopting a pragmatic approach with meticulous planning, a limited, but fully functional image-guided interventional list can be run without any adverse patient outcomes., (Copyright © 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Functional group modification is one of the main strategies used in drug discovery and development. Despite the controversy of being identified for many years as a biologically hazardous functional group, the introduction of an epoxide function in a structural backbone is still one of the possible modifications being implemented in drug design. In this manner, it is our intention to prove with this work that epoxides can have significant interest in medicinal chemistry, not only as anticancer agents, but also as important drugs for other pathologies. Thus, this revision paper aims to highlight the biological activity and the proposed mechanisms of action of several epoxide-containing molecules either in preclinical studies or in clinical development or even in clinical use. An overview of the chemistry of epoxides is also reported. Some of the conclusions are that effectively most of the epoxide-containing molecules referred in this work were being studied or are in the market as anticancer drugs. However, some of them in preclinical studies, were also associated with other different activities such as anti-malarial, anti-arthritic, insecticidal, antithrombotic, and selective inhibitory activity of FXIII-A (a transglutaminase). As for the epoxide-containing molecules in clinical trials, some of them are being tested for obesity and schizophrenia. Finally, drugs containing epoxide groups already in the market are mostly used for the treatment of different types of cancer, such as breast cancer and multiple myeloma. Other diseases for which the referred drugs are being used include heart failure, infections and gastrointestinal disturbs. In summary, epoxides can be a suitable option in drug design, particularly in the design of anticancer agents, and deserve to be better explored. However, and despite the promising results, it is imperative to explore the mechanisms of action of these compounds in order to have a better picture of their efficiency and safety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Introduction: The aim of this study was to evaluate the cyclic fatigue resistance of 3 replicalike rotary instruments compared with their original brand systems using continuous rotation and optimum torque reverse (OTR) kinematics., Methods: New F1 rotary instruments (n = 20 per group) from ProTaper Universal (Dentsply Maillefer, Ballaigues, Switzerland) and ProTaper Gold (Dentsply Maillefer) original brand systems were compared with 3 replicalike instruments (U-File [Dentmark, Ludhiana, India], Super Files [Shenzhen Flydent Medical, Shenzhen, China], and Super Files Blue [Shenzhen Flydent Medical]) regarding cyclic fatigue resistance. In each group, the selected instruments were randomly distributed into 2 subgroups (n = 10) according to the kinematics. In the rotary group (ROT), the instruments were activated with a continuous clockwise rotation (300 rpm, 1.5 Ncm), whereas in the OTR group, asymmetric oscillatory motion was performed setting the OTR function at 300 rpm and adjusting the torque limit at the minimum level using the TriAuto ZX2 motor (J Morita, Kyoto, Japan). The time to fracture was recorded and statistically compared according to the kinematics (ROT × OTR) and the instrument type (replicalike × original brand) using the independent sample t test (α = 0.05). Additionally, the metal alloy characterization of each system was performed by differential scanning calorimetry and energy-dispersive X-ray spectroscopy., Results: Statistical analysis revealed significantly higher time to fracture for all rotary systems tested in OTR motion compared with continuous rotation (P < .05) with a mean percentage increase ranging from 52.1% (ProTaper Gold) to 156.7% (U-File). The replicalike instruments showed a significantly higher time to fracture compared with the respective original brand instruments in either ROT or OTR motion (P < .05). Replicas presented austenitic temperatures above the ones displayed by the original brands and an almost equiatomic ratio between nickel and titanium elements., Conclusions: OTR motion significantly improved the fatigue resistance of both original and replicalike systems. The replicas showed higher cyclic fatigue resistance than original brand instruments and higher transition temperatures to the austenitic phase., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

This investigation aimed to refine the operational parameters of the Fenton process, to compare Fenton-treated and non-treated leachate with respect to physicochemical variables and toxicity towards Daphnia magna , and to characterize the sludge. The optimal conditions for the Fenton treatment involved the use of a reagent containing 12 g Fe 2+  L -1 , H 2 O 2 /Fe 2+ molar ratio of 9 and pH 2.0, with oxidation, flocculation and sedimentation times of 30, 10 and 15 min, respectively. Under these conditions, the values of the majority of parameters, including chemical oxygen demand (COD), biochemical oxygen demand, dissolved organic carbon, true color (TC), carbohydrates, proteins, phosphorus, total solids, total volatile solids, dissolved volatile solids, Kjeldahl nitrogen, N-NH 3 and iron, were reduced significantly after treatment. However, sludge production rate remained somewhat high (98 kg m -3 of treated leachate), although the specific resistance to filtration of the sludge was moderate (12 × 10 9  cm g -1 ). While the Fenton process achieved a satisfactory removal of COD (87%) and TC (91%), the treated leachate contained organic compounds that were resistant to oxidation and remained toxic towards D. magna . Hence we conclude that the Fenton process alone is not appropriate for treatment of leachate, because it could negatively affect the ecosystem in receiving water bodies, but it could represent a viable alternative for the pretreatment of landfill leachate.

Introduction: The purpose of this study was to perform a quality assessment and provide a scientific-based checklist for prevalence studies on root and root canal anatomy by appraising the methodological quality of in vivo studies using cone-beam computed tomographic (CBCT) imaging as the assessment tool., Methods: A systematic assessment of the literature was conducted, and 211 studies were selected and submitted to a methodological evaluation. Data were grouped into categories such as journal impact factor, open access availability, language, study origin, journal publisher, sample size, and CBCT settings. Interrater agreement was calculated by applying the Holsti method and Cohen kappa. The Kruskal-Wallis test and Pearson correlation coefficient were undertaken to assess the different variables (α = 0.05)., Results: The included studies (N = 211) reported data on 247,616 teeth from 41 countries. The maxillary first molar was the most studied tooth (n = 69) and the second mesiobuccal canal the most investigated anatomic feature. The highest scores were associated with high-impact journals (r = 0.482, P < .05), large sample sizes (r = 0.374, P < .05), non-open access availability (P < .05), and English-based language (P < .05), but geographic region and journal publisher also had an impact on quality scores. The identified methodological gaps were used to formulate a scientific-based checklist for this type of study., Conclusions: Although a small improvement in the global quality of the studies was observed over the years, only less than half of the studies correctly addressed the participant recruitment and frame and had an adequate sample size or provided sufficient CBCT imaging settings. The proposed checklist highlights the most pertinent points to guide researchers throughout the experimental design and the implementation of epidemiological cross-sectional studies of this nature., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: Very-low-birth-weight (VLBW) preterm neonates are vulnerable to patent ductus arteriosus (PDA), which might be related to high-resistance flow in the superior mesenteric artery (SMA), with decreased diastolic flow in situations of marked intestinal hypoperfusion. No previous studies have evaluated the portal vein and superior mesenteric vein (SMV) parameters to assess the PDA hemodynamic repercussions., Objective: To assess mesenteric and portal flow in VLBW preterm neonates with or without PDA using serial Doppler ultrasonography (US)., Materials and Methods: We conducted a prospective longitudinal study on 61 VLBW preterm neonates submitted to 161 Doppler US exams, from 2 days to 20 days of age., Results: All infants exhibited a progressive daily increase in the mean of the SMA diameter and systolic velocity, the portal vein diameter, the peak velocity, the mean velocity and the flow volume and of SMV diameter (P<0.05). The incidence of PDA was 37.7% (n=23) and infants with the disease revealed a smaller diameter, greater systolic velocity, lower diastolic velocity, and higher resistivity and pulsatility indices on SMA compared to those without PDA (P<0.05). Additionally, 47.8% (n=11) of infants with PDA exhibited absent or reversed end-diastolic flow in the SMA, and its resolution was seen among 54.5% (n=6) of these. Infants with PDA also exhibited lower values of portal vein diameter and flow volume and of SMV diameter (P<0.01)., Conclusion: Doppler US enhances the understanding of mesenteric and portal flow, including the effects of PDA. The study of SMV and portal vein flow is proposed as a new parameter in PDA evaluation.

Selective inhibition of cyclooxygenase (COX)-2 enzyme is an important achievement when looking for potent anti-inflammatory agents, with fewer gastrointestinal side effects. In this work, a new series of cinnamic acid derivatives, namely hexylamides, have been designed, synthesized and evaluated in human blood for their inhibitory activity of COX-1 and COX-2 enzymes. From this, new structure-activity relationships were built, showing that phenolic hydroxyl groups are essential for both COX-1 and COX-2 inhibition. Furthermore, the presence of bulky hydrophobic di-tert-butyl groups in the phenyl ring strongly contributes for selective COX-2 inhibition. In addition, a correlation with the theoretical log P has been carried out, showing that lipophilicity is particularly important for COX-2 inhibition. Further, a plasma protein binding (PPB) prediction has been performed revealing that PPB seems to have no influence in the activity of the studied compounds. From the whole study, effective selective inhibitors of COX-2 were found, namely compound 9 (IC 50  = 3.0 ± 0.3 μM), 10 (IC 50  = 2.4 ± 0.6 μM) and 23 (IC 50  = 1.09 ± 0.09 μM). Those can be considered starting point hit compounds for further optimization as potential non-steroidal anti-inflammatory drugs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Fuel and lubricating oil leaks produce an oily wastewater that creates an environmental problem for industries. Dissolved air flotation (DAF) has been successfully employed for the separation of oily contaminants. Collectors constitute an auxiliary tool in the DAF process that enhances the separation efficiency by facilitating the adhesion of the contaminant particles. The use of biosurfactants as collectors is a promising technology in flotation processes, as these biomolecules are biodegradable and non-toxic. In the present study, a biosurfactant was produced from the bacteria Pseudomonas aeruginosa UCP 0992 cultivated in 0.5% corn steep liquor and 4.0% vegetable oil residue in a bioreactor at 225 rpm for 120 h, resulting in a surface tension of 26.5 mN/m and a yield of 26 g/L. The biosurfactant demonstrated stability when exposed to different temperatures, heating times, pH values and salt and was characterised as a glycolipid with a critical micelle concentration of 600 mg/L. A central composite rotatable design was used to evaluate the effect of the crude biosurfactant added to a laboratory DAF prototype on the removal efficiency of motor oil. The isolated and formulated forms of the biosurfactant were also tested in the prototype after the optimisation of the operational conditions. The results demonstrated that all forms of the biosurfactant increased the oil separation efficiency of the DAF process by 65 to 95%. In conclusion, the use of biosurfactants is a promising alternative as an auxiliary tool in flotation processes for the treatment of oily waters generated by industrial activities.

C-6α and C-7α androstanes were studied to disclose which position among them is more convenient to functionalize to reach superior aromatase inhibition. In the first series, the study of C-6 versus C-7 methyl derivatives led to the very active compound 9 with IC 50 of 0.06 μM and K i = 0.025 μM (competitive inhibition). In the second series, the study of C-6 versus C-7 allyl derivatives led to the best aromatase inhibitor 13 of this work with IC 50 of 0.055 μM and K i = 0.0225 μM (irreversible inhibition). Beyond these findings, it was concluded that position C-6α is better to functionalize than C-7α, except when there is a C-4 substituent simultaneously. In addition, the methyl group was the best substituent, followed by the allyl group and next by the hydroxyl group. To rationalize the structure-activity relationship of the best inhibitor 13, molecular modeling studies were carried out.

The need to remediate areas contaminated by petroleum products has led to the development of novel technologies for treating such contaminants in a non-conventional manner, that is, without the use of chemical or physical methods. Biosurfactants are amphipathic biomolecules produced by microorganisms that can be used in bioremediation processes in environments contaminated by petroleum products due to their excellent tensioactive properties. The aim of the present study was to produce a biosurfactant from Pseudomonas aeruginosa UCP 0992 cultivated in 0.5% corn steep liquor and 4.0% vegetable oil residue in a 1.2-L bioreactor employing a central composite rotatable design to optimize the cultivation conditions for maximum yield. The best results were achieved with aeration rate of 1.0 vvm and 3.0% inoculum at 225 rpm for 120 h, resulting in a surface tension of 26.5 mN/m and a biosurfactant yield of 26 g/L. Kinetic and static assays were then performed with the biosurfactant for the removal of motor oil adsorbed to sand, with removal rates around 90% and 80%, respectively, after 24 h. Oil degradation experiments with the bacterium and the combination of the bacterium and biosurfactant were also conducted to simulate the bioremediation process in sand and seawater samples (duration: 75 and 30 days, respectively). In both cases, oil degradation rates were higher than 90% in the presence of the biosurfactant and the producing species, indicating the potential of the biomolecule as an adjuvant in petroleum decontamination processes in the marine environment., (Copyright © 2018. Published by Elsevier B.V.)

The aim of the present study was to investigate the separation of oil from water using a bench-scale DAF prototype with the addition of biosurfactants isolated from Pseudomonas cepacia CCT6659 and Bacillus cereus UCP1615. The best operating conditions for the DAF prototype were determined using a central composite rotatable design. The results demonstrated that the biosurfactants from P. cepacia and B. cereus increased the oil separation efficiency from 53.74% (using only microbubbles) to 94.11 and 80.01%, respectively. The prediction models for both DAF-biosurfactant systems were validated, showing an increase in the efficiency of the DAF process from 53.74% to 98.55 and 70.87% using the formulated biosurfactants from P. cepacia and B. cereus, respectively. The biosurfactant from P. cepacia was selected as the more promising product and used for the treatment of oily effluent from a thermoelectric plant, achieving removal rates ranging between 75.74 (isolated biosurfactant) and 95.70% (formulated biosurfactant), respectively.

The multiplicity of new therapies for breast cancer presents a challenge for treatment selection. We describe a 17-gene digital signature of breast circulating tumor cell (CTC)-derived transcripts enriched from blood, enabling high-sensitivity early monitoring of response. In a prospective cohort of localized breast cancer, an elevated CTC score after three cycles of neoadjuvant therapy is associated with residual disease at surgery ( P = 0.047). In a second prospective cohort with metastatic breast cancer, baseline CTC score correlates with overall survival ( P = 0.02), as does persistent CTC signal after 4 weeks of treatment ( P = 0.01). In the subset with estrogen receptor (ER)-positive disease, failure to suppress ER signaling within CTCs after 3 weeks of endocrine therapy predicts early progression ( P = 0.008). Drug-refractory ER signaling within CTCs overlaps partially with presence of ESR1 mutations, pointing to diverse mechanisms of acquired endocrine drug resistance. Thus, CTC-derived digital RNA signatures enable noninvasive pharmacodynamic measurements to inform therapy in breast cancer. Significance: Digital analysis of RNA from CTCs interrogates treatment responses of both localized and metastatic breast cancer. Quantifying CTC-derived ER signaling during treatment identifies patients failing to respond to ER suppression despite having functional ESR1. Thus, noninvasive scoring of CTC-RNA signatures may help guide therapeutic choices in localized and advanced breast cancer. Cancer Discov; 8(10); 1286-99. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 1195 ., (©2018 American Association for Cancer Research.)

Aim: Considering the epidemiology of leishmaniasis, the emergence of resistant parasites to the approved drugs, and severe clinical manifestations, the development of novel leishmanicidal molecules has become of considerable importance., Results: In this work, three commercially available and 19 synthesized quinoline derivatives were evaluated against promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. In addition, structural parameters and molecular electrostatic potentials were obtained by theoretical calculations, allowing statistical (principal component analyses and hierarchical cluster analyses) and comparative (molecular electrostatic potentials vs leishmanicidal activities) studies, respectively., Conclusion: Principal component analyses and hierarchical cluster analyses suggested volume and polar surface area as possible structural descriptors for the leishmanicidal activity. Furthermore, a comparison between molecular electrostatic potentials and leishmanicidal activities afforded a reasonable structure-activity relationship.

Background: Topotecan (TPT) is a water-soluble derivate of camptothecin, which undergoes ring-opening hydrolysis in neutral solutions, leading to stability loss and poor cellular uptake. Lipid nanoencapsulation can improve TPT stability, and polymer-lipid hybrid nanoparticles (PLN) are interesting alternatives to improve TPT nanoencapsulation., Objective: This study seeks to prepare complexes between the cationic TPT and the negatively charged dextran sulfate (DS) with a view of improving drug loading, chemical stability and release control., Methods: The optimum ionic molar ratio in DS-TPT complexation was determined, and the selected complex was characterized by FTIR and solid-state 13C NMR. TPT solubility in the free and complexed forms was also assayed. TPT-PLN was then obtained via a microemulsion technique, and particle size, zeta potential, encapsulation efficiency, drug loading and drug recovery were determined. Additionally, the TPT stability and in vitro release were determined from PLN and compared with free TPT, TPT-DS complex and TPT encapsulated in nanostructured lipid carriers (NLC) of similar composition., Results: TPT-DS complexation was confirmed by FTIR and NMR. TPT solubility in the complex was drastically decreased when compared to free TPT. TPT-PLN had high encapsulation efficiency (97%) and drug loading capacity (5.5%). Additionally, TPT-PLN showed a mean diameter, polidispersivity index e zeta potential of 140 nm, 0.2 and -22 mV, respectively. The TPT chemical stability and release from PLN were observed to be superior when compared to NLC., Conclusion: PLN has shown to be a more effective nanosystem for TPT nanoencapsulation because TPT loading, stability and release were superior when compared to TPT-NLC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The majority of breast cancer cases are estrogen receptor positive (ER + ). Although, third-generation aromatase inhibitors (AIs) are used as first-line treatment in post-menopausal women, they cause endocrine resistance and bone loss, which limits their success. Therefore, there is a demand to discover new potent molecules, with less toxicity that can circumvent these drawbacks. Our group has previously demonstrated that new 7α-substituted steroidal molecules, 7α-(2ξ,3ξ-epoxypropyl)androsta-1,4-diene-3,17-dione (3), 7α-allylandrost-4-ene-3,17-dione (6), 7α-allylandrost-4-en-17-one (9), 7α-allyl-3-oxoandrosta-1,4-dien-17β-ol (10) and 7α-allylandrosta-1,4-diene-3,17-dione (12) are potent AIs in placental microsomes. In this work, it was investigated their anti-aromatase activity and in vitro effects in sensitive and resistant breast cancer cells. All the steroids efficiently inhibit aromatase in breast cancer cells, allowing to establish new structure-activity relationships for this class of compounds. Moreover, the new AIs can inhibit breast cancer cell growth, by causing cell cycle arrest and apoptosis. The effects of AIs 3 and 12 on sensitive cells were dependent on aromatase inhibition and androgen receptor (AR), while for AI 9 and AI 10 were AR- and ER-dependent, respectively. In addition, it was shown that all the AIs can sensitize resistant cancer cells being their behavior similar to the sensitive cells. In summary, this study contributes to the understanding of the structural modifications in steroidal scaffold that are translated into better aromatase inhibition and anti-tumor properties, providing important information for the rational design/synthesis of more effective AIs. In addition, allowed the discovery of new potent 7α-substituted androstane molecules to inhibit tumor growth and prevent endocrine resistance., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aim: To evaluate, using a novel micro-CT approach, the solubility and dimensional changes of an MTA-based sealer inside the root canal system after a solubility challenge. The MTA-based material (MTA Fillapex) was compared to a gold standard epoxy-based endodontic sealer (AH Plus)., Methodology: Ten human mandibular premolars with a single canal were divided randomly into two groups (n = 5) according to the sealer used. The canals were instrumented using the Reciproc System (VDW) with a R40 file and filled with R40 gutta-percha cones and one of the sealers. The filled canals were immediately scanned in a micro-CT, and after that, the teeth were immersed in 20 mL phosphate-buffered saline (PBS) at 37 °C for 7 days, when they were removed and rescanned. Final image stacks were registered against the initial stacks and the numerical difference between the initial and final volume of the filling material was obtained. Calculations were performed to identify dimensional changes of the filling material. All image stacks were 3D rendered to disclose areas of dislocation of the filling material inside or outside the root canal. The Shapiro-Wilk's test revealed that data were normally distributed; thus, the Student's t-test was used to detect statistically significant changes, assuming a 5% α-error., Results: No significant changes were seen for the percentage volume of material lost after the solubility challenge for both AH Plus and MTA Fillapex groups (1.44% and 1.16%, respectively). A significant difference was, however, found for the volume of filling material which revealed dimensional changes after the solubility test (6.68% for MTA Fillapex and 1.09% for AH Plus). In fact, observation of 3D models disclosed that MTA Fillapex was associated with material extrusion through the foramen in all but one sample. In AH Plus filled samples, no material extrusion was detected., Conclusions: Although the solubility of both sealers was similar using this novel micro-CT approach, MTA Fillapex was associated with significant dimensional changes related to material extrusion through the apex after PBS storage compared to AH Plus., (© 2016 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Introduction: The aim of the present study was to evaluate the percentage frequency of dentinal micro-cracks observed after root canal preparation with TRUShape and Self-Adjusting File (SAF) systems by means of micro-computed tomography imaging analysis. A conventional full-sequence rotary system (BioRace) and a single-file reciprocation system (Reciproc) were used as reference techniques for comparison because of their known assertive cutting efficiency., Methods: Forty anatomically matched mandibular incisors were selected, scanned at a resolution of 14.25 μm, and assigned to 4 experimental groups (n = 10), according to the preparation protocol: TRUShape, SAF, BioRace, and Reciproc systems. After the experimental procedures, the specimens were scanned again, and the registered preoperative and postoperative cross-section images of the roots (n = 70,030) were screened to identify the presence of dentinal micro-cracks., Results: Overall, dentinal defects were observed in 28,790 cross-section images (41.11%). In the TRUShape, SAF, BioRace, and Reciproc groups, dentinal micro-cracks were visualized in 56.47% (n = 9842), 42.38% (n = 7450), 32.90% (n = 5826), and 32.77% (n = 5672) of the slices, respectively. All dentinal defects observed in the postoperative data sets were already present in the corresponding preoperative images., Conclusions: None of the preparation systems induced the formation of new dentinal micro-cracks., (Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)