Edible Bite Force Sensor: A Novel Approach to Measuring Bite Force in Biomedical and Dental Applications.

BACKGROUND Measurement of bite force plays a crucial role in assessment of the masticatory system. With a growing interest in detecting occlusal irregularities, bite force sensors have garnered attention in the biomedical field. This study aimed to introduce a hydrogel bite force sensor, based on hydroxyethyl-cellulose-fructose-water (HEC-F-water), for premolar and molar teeth, and to evaluate it using optical profilometry, infrared spectroscopy (FTIR), and Instron Tension testing system, with 2.5 cm (1 inch) margins at top, bottom, right, and left. MATERIAL AND METHODS We fabricated 20 HEC-F-water hydrogel samples sized with surface of 1×1 cm, with 2 different widths - 1 mm and 5 mm. The samples were characterized using optical profilometry and FTIR and their electrical characteristics were determined using an impedance analyzer. Aluminum (Al) electrodes, fabricated using Cutting Plotter, were used to form a HEC-F-water-based transducer, which was used for bite force sensing. The Instron tensile testing system was employed, utilizing 3D printed models of the upper and lower jaw, to simulate biting. Forces in the range between 40 N and 540 N were exerted upon the transducer, and the output change in the electrical signal was measured. RESULTS The study determined the transfer function between bite force and capacitance. The fabricated sensor exhibited a sensitivity of 3.98 pF/N, an input range of 500 N, output range of 2 nF, and accuracy of 95.9%. CONCLUSIONS This study introduces an edible bite force sensor employing an edible hydrogel as a dielectric, presenting a novel avenue in the development of edible sensorics in dentistry.

Sedimentation Field-Flow Fractionation: A Diagnostic Tool for Rapid Antimicrobial Susceptibility Testing.

Conventional antimicrobial susceptibility testing (AST) methods require 24-48 h to provide results, creating the need for a probabilistic antibiotic therapy that increases the risk of antibiotic resistance emergence. Consequently, the development of rapid AST methods has become a priority. Over the past decades, sedimentation field-flow fractionation (SdFFF) has demonstrated high sensitivity in early monitoring of induced biological events in eukaryotic cell populations. This proof-of-concept study aimed at investigating SdFFF for the rapid assessment of bacterial susceptibility to antibiotics. Three bacterial species were included (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) with two panels of antibiotics tailored to each bacterial species. The results demonstrate that SdFFF, when used in "Hyperlayer" elution mode, enables monitoring of antibiotic-induced morphological changes. The percentage variation of the retention factor (PΔR) was used to quantify the biological effect of antibiotics on bacteria with the establishment of a threshold value of 16.8% to differentiate susceptible and resistant strains. The results obtained with SdFFF were compared to that of the AST reference method, and a categorical agreement of 100% was observed. Overall, this study demonstrates the potential of SdFFF as a rapid method for the determination of antibiotic susceptibility or resistance since it is able to provide results within a shorter time frame than that needed for conventional methods (3-4 h vs 16-24 h, respectively), enabling earlier targeted antibiotic therapy. Further research and validation are necessary to establish the effectiveness and reliability of SdFFF in clinical settings.

Functionalized Calixarenes as Promising Antibacterial Drugs to Face Antimicrobial Resistance.

Since the discovery of polyphenolic resins 150 years ago, the study of polymeric compounds named calix[n]arene has continued to progress, and those skilled in the art perfectly know now how to modulate this phenolic ring. Consequently, calix[n]arenes are now used in a large range of applications and notably in therapeutic fields. In particular, the calix[4]arene exhibits multiple possibilities for regioselective polyfunctionalization on both of its rims and offers researchers the possibility of precisely tuning the geometry of their structures. Thus, in the crucial research of new antibacterial active ingredients, the design of calixarenes finds its place perfectly. This review provides an overview of the work carried out in this aim towards the development of intrinsically active prodrogues or metallic calixarene complexes. Out of all the work of the community, there are some excellent activities emerging that could potentially place these original structures in a very good position for the development of new active ingredients.

Ursolic Acid's Alluring Journey: One Triterpenoid vs. Cancer Hallmarks.

Cancer is a multifactorial disease characterized by various hallmarks, including uncontrolled cell growth, evasion of apoptosis, sustained angiogenesis, tissue invasion, and metastasis, among others. Traditional cancer therapies often target specific hallmarks, leading to limited efficacy and the development of resistance. Thus, there is a growing need for alternative strategies that can address multiple hallmarks concomitantly. Ursolic acid (UA), a naturally occurring pentacyclic triterpenoid, has recently emerged as a promising candidate for multitargeted cancer therapy. This review aims to summarize the current knowledge on the anticancer properties of UA, focusing on its ability to modulate various cancer hallmarks. The literature reveals that UA exhibits potent anticancer effects through diverse mechanisms, including the inhibition of cell proliferation, induction of apoptosis, suppression of angiogenesis, inhibition of metastasis, and modulation of the tumor microenvironment. Additionally, UA has demonstrated promising activity against different cancer types (e.g., breast, lung, prostate, colon, and liver) by targeting various cancer hallmarks. This review discusses the molecular targets and signaling pathways involved in the anticancer effects of UA. Notably, UA has been found to modulate key signaling pathways, such as PI3K/Akt, MAPK/ERK, NF-κB, and Wnt/ß-catenin, which play crucial roles in cancer development and progression. Moreover, the ability of UA to destroy cancer cells through various mechanisms (e.g., apoptosis, autophagy, inhibiting cell growth, dysregulating cancer cell metabolism, etc.) contributes to its multitargeted effects on cancer hallmarks. Despite promising anticancer effects, this review acknowledges hurdles related to UA's low bioavailability, emphasizing the need for enhanced therapeutic strategies.

Characterization of Biological Properties of Individual Phenolamides and Phenolamide-Enriched Leaf Tomato Extracts.

Resistance to conventional treatments renders urgent the discovery of new therapeutic molecules. Plant specialized metabolites such as phenolamides, a subclass of phenolic compounds, whose accumulation in tomato plants is mediated by the biotic and abiotic environment, constitute a source of natural molecules endowed with potential antioxidant, antimicrobial as well as anti-inflammatory properties. The aim of our study was to investigate whether three major phenolamides found in Tuta absoluta-infested tomato leaves exhibit antimicrobial, cytotoxic and/or anti-inflammatory properties. One of them, N1,N5,N14-tris(dihydrocaffeoyl)spermine, was specifically synthesized for this study. The three phenolamides showed low to moderate antibacterial activities but were able to counteract the LPS pro-inflammatory effect on THP-1 cells differentiated into macrophages. Extracts made from healthy but not T. absoluta-infested tomato leaf extracts were also able to reduce inflammation using the same cellular approach. Taken together, these results show that phenolamides from tomato leaves could be interesting alternatives to conventional drugs.

Impact of sex on the management and outcome of aortic stenosis patients.

OBJECTIVE: The aim of this study was to assess the impact of sex on the management and outcome of patients according to aortic stenosis (AS) severity. INTRODUCTION: Sex differences in the management and outcome of AS are poorly understood. METHODS: Doppler echocardiography data of patients with at least mild-to-moderate AS [aortic valve area (AVA) ≤1.5 cm2 and peak jet velocity (VPeak) ≥2.5 m/s or mean gradient (MG) ≥25 mmHg] were prospectively collected between 2005 and 2015 and retrospectively analysed. Patients with reduced left ventricular ejection fraction (<50%), or mitral or aortic regurgitation >mild were excluded. RESULTS: Among 3632 patients, 42% were women. The mean indexed AVA (0.48 ± 0.17 cm2/m2), VPeak (3.74 ± 0.88 m/s), and MG (35.1 ± 18.2 mmHg) did not differ between sexes (all P ≥ 0.18). Women were older (72.9 ± 13.0 vs. 70.1 ± 11.8 years) and had more hypertension (75% vs. 70%; P = 0.0005) and less coronary artery disease (38% vs. 55%, P < 0.0001) compared to men. After inverse-propensity weighting (IPW), female sex was associated with higher mortality (IPW-HR: 1.91 [1.14-3.22]; P = 0.01) and less referral to valve intervention (competitive model IPW-HR: 0.88 [0.82-0.96]; P = 0.007) in the whole cohort. This excess mortality in women was blunted in concordant non-severe AS initially treated conservatively (IPW-HR = 1.03 [0.63-1.68]; P = 0.88) or in concordant severe AS initially treated by valve intervention (IPW-HR = 1.25 [0.71-2.21]; P = 0.43). Interestingly, the excess mortality in women was observed in discordant low-gradient AS patients (IPW-HR = 2.17 [1.19-3.95]; P = 0.01) where women were less referred to valve intervention (IPW-Sub-HR: 0.83 [0.73-0.95]; P = 0.009). CONCLUSION: In this large series of patients, despite similar baseline hemodynamic AS severity, women were less referred to AVR and had higher mortality. This seemed mostly to occur in the patient subset with discordant markers of AS severity (i.e. low-gradient AS) where women were less referred to AVR.

First Evidence of a Combination of Terpinen-4-ol and α-Terpineol as a Promising Tool against ESKAPE Pathogens.

Antimicrobial resistance is a major public health issue raising growing concern in the face of dwindling response options. It is therefore urgent to find new anti-infective molecules enabling us to fight effectively against ever more numerous bacterial infections caused by ever more antibiotic-resistant bacteria. In this quest for new antibacterials, essential oils (or compounds extracted from essential oils) appear to be a promising therapeutic option. In the present work, we investigate the potential antibacterial synergy between a combination of terpinen-4-ol and α-terpineol (10:1) compared to standard tea tree oil. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined. Then, time kill assays, in vitro cytotoxicity and bactericidal activity on latent bacteria (persisters) were investigated. Finally, an in silico study of the pharmacokinetic parameters of α-terpineol was also performed. Altogether, our data demonstrate that the combination of terpinen-4-ol and α-terpineol might be a precious weapon to address ESKAPE pathogens.

Investigation of Nanoparticle Metallic Core Antibacterial Activity: Gold and Silver Nanoparticles against Escherichia coli and Staphylococcus aureus.

Multidrug-resistant (MDR) bacteria constitute a global health issue. Over the past ten years, interest in nanoparticles, particularly metallic ones, has grown as potential antibacterial candidates. However, as there is no consensus about the procedure to characterize the metallic nanoparticles (MNPs; i.e., metallic aggregates) and evaluate their antibacterial activity, it is impossible to conclude about their real effectiveness as a new antibacterial agent. To give part of the answer to this question, 12 nm gold and silver nanoparticles have been prepared by a chemical approach. After their characterization by transmission electronic microscopy (TEM), Dynamic Light Scattering (DLS), and UltraViolet-visible (UV-vis) spectroscopy, their surface accessibility was tested through the catalytic reduction of the 4-nitrophenol, and their stability in bacterial culture medium was studied. Finally, the antibacterial activities of 12 nm gold and silver nanoparticles facing Staphylococcus aureus and Escherichia coli have been evaluated using the broth microdilution method. The results show that gold nanoparticles have a weak antibacterial activity (i.e., slight inhibition of bacterial growth) against the two bacteria tested. In contrast, silver nanoparticles have no activity on S. aureus but demonstrate a high antibacterial activity against Escherichia coli, with a minimum inhibitory concentration of 128 µmol/L. This high antibacterial activity is also maintained against two MDR-E. coli strains.

Antioxidant and Polyphenol-Rich Ethanolic Extract of Rubia tinctorum L. Prevents Urolithiasis in an Ethylene Glycol Experimental Model in Rats.

Treatment of kidney stones is based on symptomatic medications which are associated with side effects such as gastrointestinal symptoms (e.g., nausea, vomiting) and hepatotoxicity. The search for effective plant extracts without the above side effects has demonstrated the involvement of antioxidants in the treatment of kidney stones. A local survey in Morocco has previously revealed the frequent use of Rubia tinctorum L. (RT) for the treatment of kidney stones. In this study, we first explored whether RT ethanolic (E-RT) and ethyl acetate (EA-RT) extracts of Rubia tinctorum L. could prevent the occurrence of urolithiasis in an experimental 0.75% ethylene glycol (EG) and 2% ammonium chloride (AC)-induced rat model. Secondly, we determined the potential antioxidant potency as well as the polyphenol composition of these extracts. An EG/AC regimen for 10 days induced the formation of bipyramid-shaped calcium oxalate crystals in the urine. Concomitantly, serum and urinary creatinine, urea, uric acid, phosphorus, calcium, sodium, potassium, and chloride were altered. The co-administration of both RT extracts prevented alterations in all these parameters. In the EG/AC-induced rat model, the antioxidants- and polyphenols-rich E-RT and EA-RT extracts significantly reduced the presence of calcium oxalate in the urine, and prevented serum and urinary biochemical alterations together with kidney tissue damage associated with urolithiasis. Moreover, we demonstrated that the beneficial preventive effects of E-RT co-administration were more pronounced than those obtained with EA-RT. The superiority of E-RT was associated with its more potent antioxidant effect, due to its high content in polyphenols.

Cell biology of microbes and pharmacology of antimicrobial drugs explored by Atomic Force Microscopy.

Antimicrobial molecules have been used for more than 50 years now and are the basis of modern medicine. No surgery can nowdays be imagined to be performed without antibiotics; dreadful diseases like tuberculosis, leprosis, siphilys, and more broadly all microbial induced diseases, can be cured only through the use of antimicrobial treatments. However, the situation is becoming more and more complex because of the ability of microbes to adapt, develop, acquire, and share mechanisms of resistance to antimicrobial agents. We choose to introduce this review by briefly drawing the panorama of antimicrobial discovery and development, but also of the emergence of microbial resistance. Then we describe how Atomic Force Microscopy (AFM) can be used to provide a better understanding of the mechanisms of action of these drugs at the nanoscale level on microbial interfaces. In this section, we will address these questions: (1) how does drug treatment affect the morphology of single microbes?; (2) do antimicrobial molecules modify the nanomechanical properties of microbes, or do the nanomechanical properties of microbes play a role in antimicrobial activity and efficiency?; and (3) how are the adhesive abilitites of microbes affected by antimicrobial drugs treatment? Finally, in a second part of this review we focus on recent studies aimed at changing the paradigm of the single molecule/cell technology that AFM typically represents. Recent work dealing with the creation of a microbe array which can be explored by AFM will be presented, as these developments constitute the first steps toward transforming AFM into a higher throughput technology. We also discuss papers using AFM as NanoMechnanicalSensors (NEMS), and demonstrate the interest of such approaches in clinical microbiology to detect quickly and with high accuracy microbial resistance.