Smart and Multifunctional Materials Based on Electroactive Poly(vinylidene fluoride): Recent Advances and Opportunities in Sensors, Actuators, Energy, Environmental, and Biomedical Applications.

From scientific and technological points of view, poly(vinylidene fluoride), PVDF, is one of the most exciting polymers due to its overall physicochemical characteristics. This polymer can crystalize into five crystalline phases and can be processed in the form of films, fibers, membranes, and specific microstructures, being the physical properties controllable over a wide range through appropriate chemical modifications. Moreover, PVDF-based materials are characterized by excellent chemical, mechanical, thermal, and radiation resistance, and for their outstanding electroactive properties, including high dielectric, piezoelectric, pyroelectric, and ferroelectric response, being the best among polymer systems and thus noteworthy for an increasing number of technologies. This review summarizes and critically discusses the latest advances in PVDF and its copolymers, composites, and blends, including their main characteristics and processability, together with their tailorability and implementation in areas including sensors, actuators, energy harvesting and storage devices, environmental membranes, microfluidic, tissue engineering, and antimicrobial applications. The main conclusions, challenges and future trends concerning materials and application areas are also presented.

Genetic diversity goals and targets have improved, but remain insufficient for clear implementation of the post-2020 global biodiversity framework.

Genetic diversity among and within populations of all species is necessary for people and nature to survive and thrive in a changing world. Over the past three years, commitments for conserving genetic diversity have become more ambitious and specific under the Convention on Biological Diversity's (CBD) draft post-2020 global biodiversity framework (GBF). This Perspective article comments on how goals and targets of the GBF have evolved, the improvements that are still needed, lessons learned from this process, and connections between goals and targets and the actions and reporting that will be needed to maintain, protect, manage and monitor genetic diversity. It is possible and necessary that the GBF strives to maintain genetic diversity within and among populations of all species, to restore genetic connectivity, and to develop national genetic conservation strategies, and to report on these using proposed, feasible indicators.

Proteomics Reveals mRNA Regulation and the Action of Annexins in Thyroid Cancer.

Differentiated thyroid cancer is the most common malignancy of the endocrine system. Although most thyroid nodules are benign, given the high incidence of thyroid nodules in the population, it is important to understand the differences between benign and malignant thyroid cancer and the molecular alterations associated with malignancy to improve detection and signal potential diagnostic, prognostic, and therapeutic targets. Proteomics analysis of benign and malignant human thyroid tissue largely revealed changes indicating modifications in RNA regulation, a common cancer characteristic. In addition, changes in the immune system and cell membrane/endocytic processes were also suggested to be involved. Annexin A1 was considered a potential malignancy biomarker and, similarly to other annexins, it was found to increase in the malignant group. Furthermore, a bioinformatics approach points to the transcription factor Sp1 as being potentially involved in most of the alterations seen in the malignant thyroid nodules.

Peptidomics Unveils Distinct Acetylation Patterns of Histone and Annexin A1 in Differentiated Thyroid Cancer.

Thyroid cancer is a common malignancy of the endocrine system. Nodules are routinely evaluated for malignancy risk by fine needle aspiration biopsy (FNAB), and in cases such as follicular lesions, differential diagnosis between benign and malignant nodules is highly uncertain. Therefore, the discovery of new biomarkers for this disease could be helpful in improving diagnostic accuracy. Thyroid nodule biopsies were subjected to a precipitation step with both the insoluble and supernatant fractions subjected to proteome and peptidome profiling. Proteomic analysis identified annexin A1 as a potential biomarker of thyroid cancer malignancy, with its levels increased in malignant samples. Also upregulated were the acetylated peptides of annexin A1, revealed by the peptidome analysis of the supernatant fraction. In addition, supernatant peptidomic analysis revealed a number of acetylated histone peptides that were significantly elevated in the malignant group, suggesting higher gene transcription activity in malignant tissue. Two of these peptides were found to be robust malignancy predictors, with an area under the receiver operating a characteristic curve (ROC AUC) above 0.95. Thus, this combination of proteomics and peptidomics analyses improved the detection of malignant lesions and also provided new evidence linking thyroid cancer development to heightened transcription activity. This study demonstrates the importance of peptidomic profiling in complementing traditional proteomics approaches.

TERT Promoter Mutational Status in the Management of Cutaneous Melanoma: Comparison with Sentinel Lymph Node Biopsy.

BACKGROUND: While BRAF mutations seem important for early melanomagenesis, mutations in the TERT promoter (TERTp) are related to metastasis. Yet, in conventional melanoma management, risk stratification does not depend on molecular biomarkers that can indicate the stage of progression, but rather on clinical, pathological, sentinel lymph node (SLN), and radiologic evaluation. The aim of this work was to evaluate the frequency and prognostic impact of TERTp mutations, comparing their predictive value to those of conventional procedures in melanoma management. METHODS: Mutational analysis of a series of 91 cases was performed. The correlations between TERTp and BRAF mutational status and clinicopathological features were assessed. RESULTS: The mutation rate was 33% for TERTp and 30% for BRAF. There was 68% concordance between primary and metastatic samples for TERTp mutations and 92% for BRAF mutations. TERTp mutations are significantly associated with the presence of BRAF mutations, features of worse prognosis, and a reduced disease-free survival. Also, TERTp mutational status was similar to SLN biopsy as a predictive factor of cutaneous melanoma recurrence and metastasis. CONCLUSIONS: The predictive value of TERTp mutations may be similar to that of SLN biopsy and its integration in the management algorithm of melanoma patients should be considered.

High Performance of Metallic Thin Films for Resistance Temperature Devices with Antimicrobial Properties.

Titanium-copper alloy films with stoichiometry given by Ti1-xCux were produced by magnetron co-sputtering technique and analyzed in order to explore the suitability of the films to be applied as resistive temperature sensors with antimicrobial properties. For that, the copper (Cu) amount in the films was varied by applying different DC currents to the source during the deposition in order to change the Cu concentration. As a result, the samples showed excellent thermoresistivity linearity and stability for temperatures in the range between room temperature to 110 °C. The sample concentration of Ti0.70Cu0.30 has better characteristics to act as RTD, especially the αTCR of 1990 ×10-6°C-1. The antimicrobial properties of the Ti1-xCux films were analyzed by exposing the films to the bacterias S. aureus and E. coli, and comparing them with bare Ti and Cu films that underwent the same protocol. The Ti1-xCux thin films showed bactericidal effects, by log10 reduction for both bacteria, irrespective of the Cu concentrations. As a test of concept, the selected sample was subjected to 160 h reacting to variations in ambient temperature, presenting results similar to a commercial temperature sensor. Therefore, these Ti1-xCux thin films become excellent antimicrobial candidates to act as temperature sensors in advanced coating systems.

Global Commitments to Conserving and Monitoring Genetic Diversity Are Now Necessary and Feasible.

Global conservation policy and action have largely neglected protecting and monitoring genetic diversity-one of the three main pillars of biodiversity. Genetic diversity (diversity within species) underlies species' adaptation and survival, ecosystem resilience, and societal innovation. The low priority given to genetic diversity has largely been due to knowledge gaps in key areas, including the importance of genetic diversity and the trends in genetic diversity change; the perceived high expense and low availability and the scattered nature of genetic data; and complicated concepts and information that are inaccessible to policymakers. However, numerous recent advances in knowledge, technology, databases, practice, and capacity have now set the stage for better integration of genetic diversity in policy instruments and conservation efforts. We review these developments and explore how they can support improved consideration of genetic diversity in global conservation policy commitments and enable countries to monitor, report on, and take action to maintain or restore genetic diversity.

Tuning Properties of Cerium Dioxide Nanoparticles by Surface Modification with Catecholate-type of Ligands.

Cerium dioxide (CeO2) finds applications in areas such as corrosion protection, solar cells, or catalysis, finding increasing applications in biomedicine. This work reports on surface-modified CeO2 particles in order to tune their applicability in the biomedical field. Stable aqueous CeO2 sol, consisting of 3-4 nm in size crystallites, was synthesized using forced hydrolysis. The coordination of catecholate-type of ligands (catechol, caffeic acid, tiron, and dopamine) to the surface-Ce atoms is followed with the appearance of absorption in the visible spectral range as a consequence of interfacial charge-transfer complex formation. The spectroscopic observations are complemented with the density functional theory calculations using a cluster model. The synthesized samples were characterized by X-ray diffraction analysis, transmission electron microscopy, and nitrogen adsorption-desorption isotherms. The ζ-potential measurements indicated that the stability of CeO2 sol is preserved upon surface modification. The pristine CeO2 nanoparticles (NPs) are nontoxic against pre-osteoblast cells in the entire studied concentration range (up to 1.5 mM). Hybrid CeO2 NPs, capped with dopamine or caffeic acid, display toxic behavior for concentrations ≥0.17 and 1.5 mM, respectively. On the other hand, surface-modified CeO2 NPs with catechol and tiron promote the proliferation of pre-osteoblast cells.

Desmoplastic stromal changes in cutaneous neural granular cell tumors: An under-recognized histopathologic feature of diagnostic and prognostic importance.

BACKGROUND: Granular cell tumors (GCTs) are uncommon mucocutaneous and soft tissue neoplasms with distinctive histopathologic appearance but controversial histogenesis. Herein, we report a variant of cutaneous GCT featuring extensive desmoplastic stroma which may result in diagnostic difficulties with mesenchymal proliferations, particularly a dermatofibroma. METHODS: Following a recent case of GCT with prominent stromal desmoplasia, we reviewed all cases diagnosed as GCT during the past 10 years accessioned at the dermatopathology unit in a tertiary university hospital. RESULTS: Three additional cases with a similar excessive connective tissue were identified out of a total of 49 GCTs. Cytoplasmic granularity was often subtle and focal, S100 expression was weak, and nuclei had a tendency to show spindling in tumor cells entrapped within the desmoplastic areas. Of note, nuclear spindling is one of the criteria used to diagnose an atypical/malignant GCT. CONCLUSION: We propose the term "desmoplastic GCT" for these tumors, which not only appropriately addresses the stromal changes but also raises an awareness of GCT being one of the cutaneous tumors which may show stromal desmoplasia. Differential diagnostic difficulties apart, awareness of this phenomenon is important so that desmoplasia and resultant spindling are not linked with potential aggressive behavior.

Magnetic Bioreactor for Magneto-, Mechano- and Electroactive Tissue Engineering Strategies.

Biomimetic bioreactor systems are increasingly being developed for tissue engineering applications, due to their ability to recreate the native cell/tissue microenvironment. Regarding bone-related diseases and considering the piezoelectric nature of bone, piezoelectric scaffolds electromechanically stimulated by a bioreactor, providing the stimuli to the cells, allows a biomimetic approach and thus, mimicking the required microenvironment for effective growth and differentiation of bone cells. In this work, a bioreactor has been designed and built allowing to magnetically stimulate magnetoelectric scaffolds and therefore provide mechanical and electrical stimuli to the cells through magnetomechanical or magnetoelectrical effects, depending on the piezoelectric nature of the scaffold. While mechanical bioreactors need direct application of the stimuli on the scaffolds, the herein proposed magnetic bioreactors allow for a remote stimulation without direct contact with the material. Thus, the stimuli application (23 mT at a frequency of 0.3 Hz) to cells seeded on the magnetoelectric, leads to an increase in cell viability of almost 30% with respect to cell culture under static conditions. This could be valuable to mimic what occurs in the human body and for application in immobilized patients. Thus, special emphasis has been placed on the control, design and modeling parameters governing the bioreactor as well as its functional mechanism.

Students' self-confidence and perceived quality of prosthodontics education: A study in the Faculty of Dental Medicine of the University of Porto.

INTRODUCTION: Oral rehabilitation with removable dentures (RDs) is still a viable choice for the edentulous population. Fostering students' confidence in prosthodontic procedures should be a major concern in dental schools. This study has three purposes: (a) to measure the self-reported confidence levels of undergraduate dental students when performing removable prosthodontic treatments; (b) to evaluate the students' perceived quality of removable prosthodontics education; and (c) to assess the students' suggestions to improve removable prosthodontics education. MATERIALS AND METHODS: An anonymous questionnaire was delivered to third-, fourth- and fifth-year students of the Faculty of Dental Medicine of the University of Porto (FMDUP) (n = 176). Data from quantitative questions were statistically analysed with IBM SPSS Statistics for Windows (V.24.0), whilst qualitative data were clustered into topics and analysed in Excel. RESULTS: With a 100% response rate, most students felt "confident" and "very confident" in RD clinical procedures. Overall, the 5th-year students had higher confidence than 4th-year ones, except when surveying diagnostic casts. Our findings also revealed that students considered the removable prosthodontics education "Good" and "Very good," and their main suggestions were related to increasing the time allocated to clinical practice. CONCLUSIONS: Students' confidence in carrying out removable prosthodontic procedures grew as they progressed through the course. Overall, the students' evaluation of the quality of prosthodontics education was positive, and their main suggestion to improve their confidence levels was increasing the clinical experience.

TERT promoter mutations are associated with poor prognosis in cutaneous squamous cell carcinoma.

BACKGROUND: Telomerase reverse transcriptase gene (TERT) promoter (TERTp) mutations have been reported as potential predictors of poor prognosis in several cancers, but the prognostic value of TERTp mutations for cutaneous squamous cell carcinoma (cSCC) has not been determined. OBJECTIVE: To evaluate the frequency of TERTp mutations and correlate it with clinicopathologic features and patient outcome. METHODS: We performed genetic profiling of TERTp mutations in a retrospective series of cSCCs. The predictive value of TERTp mutations and clinicopathologic parameters were assessed by using logistic regression models. RESULTS: A total of 152 cSCCs from 122 patients were analyzed for TERTp mutations; the mutation rate was 31.6% (48 of 152), and it was higher in invasive cSCC (42 of 121 [34.7%]) than in in situ cSCC (6 of 31 [19.4%]). Age older than 75 years (odds ratio [OR], 14.84; P = .013] and TERTp mutation (OR, 8.11; P = .002) were independent predictors of local recurrence. TERTp mutation (OR, 15.89; P = .022) was independently associated with higher risk of lymph node metastasis. LIMITATIONS: The restricted number of metastatic cases. CONCLUSION: TERTp mutations may prove to be a molecular biomarker with prognostic significance in invasive cSCC, but larger studies are needed.

Bottom-up Layer-by-Layer Assembling of Antibacterial Freestanding Nanobiocomposite Films.

In this study, freestanding nanobiocomposite films were obtained by the sequential deposition of biopolymer-capped silver nanoparticles (AgNPs) and hyaluronic acid (HA). At first, dispersions of AgNPs decorated with chitosan (CS) or aminocellulose (AC) were synthesized by applying high intensity ultrasound. These polycationic nanoentities were layer-by-layer assembled with the HA polyanion to generate stable 3D supramolecular constructs, where the biopolymer-capped AgNPs play the dual role of active agent and structural element. SEM images of the assemblies revealed gradual increase of thickness with the number of deposited bilayers. The composites of ≥50 bilayers were safe to human cells and demonstrated 100% antibacterial activity against Staphylococcus aureus and Escherichia coli. Moreover, the films containing CSAgNPs brought about the total prevention of biofilm formation reducing the cells surface adherence by up to 6 logs. Such nanobiocomposites could serve as an effective barrier to control bacterial growth on injured skin, burns, and chronic wounds.

Is the femoral lateral condyle's bone morphology the trochlea of the ACL?

PURPOSE: The purpose of this study was to investigate the association of different osteoarticular femoral and tibial morphology and morphometric parameters with the risk of anterior cruciate ligament (ACL) rupture. METHODS: Thirty-six patients (29 male and 7 female) with an ACL rupture (<6 months) and 36 age and sex-matched controls were included. The anatomomorphological parameters and morphometrics of the distal epiphysis of the femur and proximal epiphysis of the tibia were measured through conventional lateral radiography of the knee. RESULTS: It was found statistically significant smaller heights of femur's lateral condyle, AP distances of the tibial plateaus and smaller XY and WX distances, as well as, higher XY/AB and B/AB ratios (p < 0.05). In turn, women had smaller AP distances of the femur's lateral condyle, AP distances of the femur's diaphysis, AP distances of the tibial plateaus and heights of femur's lateral condyle, as well as, higher values of XY/AB (Porto ratio) and B/AB ratios (p < 0.05). CONCLUSIONS: Several femoral and tibial bone morphological parameters were identified as potential risk factors for sustaining an ACL injury. These parameters are clinically relevant to identify individuals with higher risk of ACL injury, decide between conservative or surgical treatment and identify individuals who may benefit from preventive neuromuscular programs. LEVEL OF EVIDENCE: Case-control study, Level III.

Pigmented hepatocellular adenoma with ß-catenin activation: case report and literature review.

 Hepatocellular adenomas (HCAs) are benign liver tumors recently characterized into 4 different types according to genetic, pathological and clinical features. The prognosis is not well established yet and malignant transformation has been recently associated with ß-catenin activation. We aimed to describe a case of a pigmented HCA with ß-catenin nuclear expression and inflammatory features and to review the cases of pigmented HCAs in the literature. We report a case of a young female patient without contraceptive use, with a liver tumor diagnosis. Liver biopsy revealed diffuse expression of ß-catenin and a partial hepatic resection was performed. The histologic analysis revealed a hepatocellular tumor composed of uniform trabeculae of hepatocytes and solid areas, the later with a significant amount of black pigment highlighted by Masson-Fontana stain. Immunohistochemistry showed co-expression of C-reactive protein and serum amyloid A in the tumor. Literature review revealed that pigmented HCAs, previously reported as dark adenomas, are rare tumors. In HCAs, the presence of ß-catenin activation should be searched for due to the higher risk of malignant transformation in hepatocarcinoma. We describe a pigmented HCA with ß-catenin nuclear expression and inflammatory features being the fifth case reported so far.

Escherichia coli and Pseudomonas aeruginosa eradication by nano-penicillin G.

The transformation of penicillin G into nano/micro-sized spheres (nanopenicillin) using sonochemical technology was explored as a novel tool for the eradication of Gram-negative bacteria and their biofilms. Known by its effectiveness only against Gram-positive microorganisms, the penicillin G spherization boosted the inhibition of the Gram-negative Pseudomonas aeruginosa 10-fold (from 0.3 to 3.0 log-reduction) and additionally induced 1.2 log-reduction of Escherichia coli growth. The efficient penetration of the spheres within a Langmuir monolayer sustained the theory that nanopenicillin is able to cross the membrane and reach the periplasmic space in Gram-negative bacteria where they inhibit the ß-lactam targets: the transferases that build the bacteria cell wall. Moreover, it considerably suppressed the growth of both bacterial biofilms on a medically relevant polystyrene surface, leaving majority of the adhered cells dead compared to the treatment with the non-processed penicillin G. Importantly, nanopenicillin was found innocuous towards human fibroblasts at the antibacterial-effective concentrations.

Enzyme multilayer coatings inhibit Pseudomonas aeruginosa biofilm formation on urinary catheters.

Bacteria use a signaling mechanism called quorum sensing (QS) to form complex communities of surface-attached cells known as biofilms. This protective mode of growth allows them to resist antibiotic treatment and originates the majority of hospital-acquired infections. Emerging alternatives to control biofilm-associated infections and multidrug resistance development interfere with bacterial QS pathways, exerting less selective pressure on bacterial population. In this study, biologically stable coatings comprising the QS disrupting enzyme acylase were built on silicone urinary catheters using a layer-by-layer technique. This was achieved by the alternate deposition of negatively charged enzyme and positively charged polyethylenimine. The acylase-coated catheters efficiently quenched the QS in the biosensor strain Chromobacterium violaceum CECT 5999, demonstrated by approximately 50% inhibition of violacein production. These enzyme multilayer coatings significantly reduced the Pseudomonas aeruginosa ATCC 10145 biofilm formation under static and dynamic conditions in an in vitro catheterized bladder model. The quorum quenching enzyme coatings did not affect the viability of the human fibroblasts (BJ-5ta) over 7 days, corresponding to the extended useful life of urinary catheters. Such enzyme-based approach could be an alternative to the conventional antibiotic treatment for prevention of biofilm-associated urinary tract infections.

Sonochemically processed cationic nanocapsules: efficient antimicrobials with membrane disturbing capacity.

Bacterial-mediated diseases are a major healthcare concern worldwide due to the rapid spread of antibiotic-resistant bacteria. One strategy to manage the bacterial infections while avoiding the emergence of resistant strains implies specific targeting and disruption of bacteria membranes. This work evaluates the potential of nanostructured biopolymer derivatives, nanocapsules (NCs), to disrupt the bacteria cell walls and effectively kill planktonic microorganisms. Two biopolymers, chitosan and cellulose, were chemically modified to synthesize derivatives with improved cationic character (thiolated chitosan and aminocellulose) prior to their processing into nanocapsules via a one-step sonochemical process. The interactions of NCs, displaying an average size of around 250 nm, with bacteria membrane were evaluated using two membrane models: Langmuir monolayers and liposome bilayers composed of a l-α-phosphatidylglycerol phospholipid extracted from Escherichia coli. NCs possessed improved membrane disturbing capacity in comparison to the nonprocessed biopolymer derivatives, by drastically increasing the monolayer fluidity and inducing more than 50% leakage of a dye inserted in the bilayered liposomes. In addition, membrane disturbance was directly proportional to the NCs cationic charge. Whereas evidence showed that thiolated chitosan and aminocellulose interacted with the bacteria membrane through a "carpet model", the NCs were found to induce larger surface defects and high local perturbance through a "detergent model". Importantly, the degree of disruption caused by the biopolymer derivatives and NCs correlated well with the antimicrobial capacity against Escherichia coli, selectively killing bacteria cells without imparting toxicity to human fibroblasts.

A 3D-Printed Portable UV and Visible Photoreactor for Water Purification and Disinfection Experiments.

Water scarcity and contamination are urgent issues to be addressed. In this context, different materials, techniques, and devices are being developed to mitigate contemporary and forthcoming water constraints. Photocatalysis-based approaches are suitable strategies to address water contamination by degrading contaminants and eliminating microbes. Photoreactors are usually designed to perform photocatalysis in a scalable and standardised way. Few or none have been developed to combine these characteristics with portability, flexibility, and cost effectiveness. This study reports on designing and producing a portable (490 g), low-cost, and multifunctional photoreactor that includes adjustable radiation intensity and two types of wavelengths (UV-A and visible), including combined agitation in a compact mechanism produced through 3D printing technology. The mechanical, electrical, and optical subsystems were designed and assembled into a robust device. It is shown that it is possible to apply radiations that can reach 65 mW/cm2 and 110 mW/cm2 using the installed visible and UV LEDs and apply mechanical agitation up to 200 rpm, all under a ventilated system. Regarding functionality, the photoreactor proof of concept indicated the ability to degrade ~80% and 30% ciprofloxacin under UV and visible irradiation of TiO2 and Ag/TiO2 nanoparticles. The device also showed the ability to eliminate E. coli bacteria, recurring to radiation set-ups and nanoparticles. Therefore, the originally designed and constructed photoreactor concept was characterised and functionally validated as an exciting and flexible device for lab-scaled or outdoor experiments, assuring standardised and comparable results.

Accuracy of Silicone Impressions and Stone Models Using Two Laboratory Scanners: A 3D Evaluation.

PURPOSE: To evaluate the in vitro accuracy of impressions obtained with two silicone and corresponding stone models using two laboratory scanners. MATERIALS AND METHODS: A master model with synthetic resin teeth with two single-unit crown preparations was created and scanned using a 12-megapixel scanner. Five conventional impressions of the physical model were prepared with different silicone impression systems (Zhermack and Coltene) using the double-mix technique and poured with gypsum. The impressions and stone models obtained were scanned using two extraoral scanning systems (Identica T500, Medit; S600 ARTI, Zirkonzahn). All best-fit superimpositions of the teeth areas were conducted between the master model and the scans of the impressions and models obtained with the two scanners. A P < .05 level was considered significant. RESULTS: The Identica T500 Medit scanner showed an accuracy of 102.34 (89.67, 115.01) µm for Coltene silicone and 79.51 (67.82, 91.21) µm for Zhermack silicone, while the S600 ARTI Zirkonzhan scanner presented 110.79 (98.24, 123.33) µm and 91.91 (81.29, 102.54) µm, respectively, with significant differences between scanners for Zhermack silicone (P = .008) and for the corresponding stone models (P = .002). Zhermack silicone presented overall discrepancies lower than Coltene silicone, with statistically significant differences in both scanners analyzed (P < .001; P = .017). However, the discrepancies found were within clinically acceptable values. With the Zirkonzahn scanner, discrepancies found in the Zhermack impressions were lower than in the corresponding stone models (P < .001). CONCLUSIONS: The direct digitization of silicone impressions with laboratory scanners presented comparable results to conventional techniques with stone models.