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21 pages, 1375 KB  
Article
Polymeric Sustained-Release Chlorhexidine Coating on Gutta-Percha Points for Prolonged Intracanal Antimicrobial Delivery: An In Vitro Study
by Yarden Sabah, Nathanyel Sebbane, Michael Friedman, Irith Gati, Itzhak Abramovitz, Nurit Kot-Limon and Doron Steinberg
Pharmaceutics 2026, 18(4), 405; https://doi.org/10.3390/pharmaceutics18040405 (registering DOI) - 25 Mar 2026
Viewed by 277
Abstract
Background: Persistent endodontic infections involving Enterococcus faecalis and Candida albicans are a major cause of root canal treatment failure. Although conventional irrigants, such as sodium hypochlorite and chlorhexidine (CHX), exhibit strong immediate antimicrobial activity, microbes may survive and recover from the initial [...] Read more.
Background: Persistent endodontic infections involving Enterococcus faecalis and Candida albicans are a major cause of root canal treatment failure. Although conventional irrigants, such as sodium hypochlorite and chlorhexidine (CHX), exhibit strong immediate antimicrobial activity, microbes may survive and recover from the initial antimicrobial effect, hence limiting their effectiveness, especially in complex root canal anatomies and in the apical terminus of the tooth. Antibacterial dressing techniques were not proven satisfactory due to depletion of the antibacterial component or difficulty in spreading it evenly along the entire root canal. This study aimed to develop and evaluate the antimicrobial efficacy and release characteristics of a novel sustained-release device (SRD), delivering CHX via gutta-percha points coated with a sustained-release formulation used as a temporary intracanal medicament. Methods: Gutta-percha points were coated with two sustained-release CHX varnishes (CHX1 and CHX2) or a placebo and assessed in vitro. Antimicrobial activity against E. faecalis and C. albicans was evaluated using agar diffusion assays over time. Release kinetics were analyzed using Rhodamine-labeled SRD in a 3D-printed acrylic molar tooth model via fluorescence microscopy. Additionally, biofilm-infected acrylic molar teeth were treated with a placebo, a single 2% CHX irrigation, or SRD-coated gutta-percha points placed as an intracanal dressing prior to obturation. Microbial viability was quantified by colony-forming unit (CFU/mL) analysis from root canals and gutta-percha points. Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc multiple comparison test (p < 0.05). Results: SRD-coated gutta-percha points demonstrated sustained antimicrobial activity for up to 21 days against E. faecalis and 19 days against C. albicans. Fluorescence analysis, in an acrylic tooth model, confirmed continuous release for up to 15 days, with pronounced diffusion in the isthmus and palatal canals. In biofilm-infected acrylic teeth models, SRD treatment resulted in a significant reduction of 2–3 log10 CFU/mL compared to placebo groups (p < 0.001) and prevented microbial rebound over the 14-day observation period. In contrast, a single application of 2% CHX solution showed only transient reduction followed by regrowth. Conclusions: Sustained-release CHX delivery via polymer-coated gutta-percha points provided prolonged antimicrobial activity against bacterial and fungal biofilms compared to conventional single-dose CHX application in this in vitro model. These findings support the potential use of coated gutta-percha points as a removable intracanal drug delivery platform prior to final obturation, although further studies incorporating direct-release quantification and in vivo validation are required before clinical translation. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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22 pages, 5895 KB  
Article
Susceptibility of the Oral Commensal Bacterium Streptococcus sanguinis to ZnO Nanoparticles
by Raphaelle Emram, Ronit Vogt Sionov, Adi Aharoni, Sarah Gingichashvili, Noa E. Cohen, Vitaly Gutkin, Moshe Amitay, Asaf Wilensky, Doron Steinberg and Rawi Assad
Int. J. Mol. Sci. 2026, 27(6), 2782; https://doi.org/10.3390/ijms27062782 - 19 Mar 2026
Viewed by 215
Abstract
Streptococcus sanguinis (S. sanguinis) is an oral commensal and early colonizer of the tooth surface that contributes to dental biofilm homeostasis. Zinc oxide nanoparticles (ZnO NPs) are often incorporated into dental restorative materials to enhance mechanical performance and confer antibacterial properties; [...] Read more.
Streptococcus sanguinis (S. sanguinis) is an oral commensal and early colonizer of the tooth surface that contributes to dental biofilm homeostasis. Zinc oxide nanoparticles (ZnO NPs) are often incorporated into dental restorative materials to enhance mechanical performance and confer antibacterial properties; however, their effects on S. sanguinis have not been thoroughly studied. Here, we investigated the antimicrobial and antibiofilm efficacy of ZnO NPs against this bacterial species. ZnO NPs exhibited a minimal inhibitory concentration (MIC) of 100 µg/mL and caused rapid, dose-dependent suppression of intracellular ATP levels and overall metabolic activity within 2–4 h of exposure. ZnO NPs induced reactive oxygen species (ROS) production in a dose-dependent manner. The free radical scavenger α-tocopherol partly prevented the antibacterial effect of ZnO NPs, suggesting that lipid peroxidation contributes to ZnO NP-mediated toxicity, although it is not the sole mechanism involved. Short-term exposure (2 h) to ZnO NPs did not significantly affect membrane integrity or cellular morphology, whereas prolonged treatment (24 h) resulted in pronounced membrane permeabilization, membrane hyperpolarization, and cellular swelling. Computational morphometric analyses of high-resolution scanning electron microscopy (HR-SEM) images of planktonic growing bacteria after a 24 h treatment confirmed a significant, dose-dependent increase in cell surface area and surface roughness. Importantly, ZnO NPs also reduced the metabolic activity and compromised the structural integrity of mature, preformed biofilms. Collectively, these findings demonstrate that ZnO NPs exert antimicrobial and antibiofilm effects against S. sanguinis through early metabolic inhibition associated with oxidative stress followed by progressive membrane dysfunction. Full article
(This article belongs to the Special Issue Advanced Research on Antimicrobial Nanomaterials)
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34 pages, 3678 KB  
Article
Systemic Carbon Lock-In Dynamics and Optimal Sustainable Reduction Pathways for a Just Industrial Transition in South Africa
by Oliver Ibor Inah, Prosper Zanu Sotenga and Udochukwu Bola Akuru
Sustainability 2026, 18(2), 956; https://doi.org/10.3390/su18020956 - 17 Jan 2026
Viewed by 807
Abstract
South Africa’s manufacturing sector, a driving force for sustainable development, faces a profound challenge in decarbonizing without deindustrializing. This study provides an optimized, scenario-based assessment of the sector explicitly aligned with its Just Energy Transition Partnership (JETP) objectives. A novel framework is applied, [...] Read more.
South Africa’s manufacturing sector, a driving force for sustainable development, faces a profound challenge in decarbonizing without deindustrializing. This study provides an optimized, scenario-based assessment of the sector explicitly aligned with its Just Energy Transition Partnership (JETP) objectives. A novel framework is applied, integrating an extended Kaya–Logarithmic Mean Divisia Index (Kaya–LMDI) decomposition with scenario forecasting and Genetic Algorithm (GA) optimization. The decomposition disaggregates a conventional carbon intensity (CI) driver to include Electrification Share (ELE), Renewable Share (REN), and a newly defined Residual Carbon Factor (RCF) that captures direct fossil fuel use for industrial process heat. Historical analysis (2002–2022) shows that emissions growth was primarily driven by the RCF (224.1 MtCO2, 160%) and Economic Activity (187.5 MtCO2, 134%), partly offset by gains in Energy Intensity (−141.8 MtCO2, 101.35%) and REN (−202.2 MtCO2, −144.53%). Carbon emissions projections to 2040 reveal a critical sustainability trilemma: the Just Transition accelerated scenario (JTAS), despite achieving rapid renewable deployment, increases emissions by 469% as economic growth overwhelms decarbonization efforts. Conversely, the mathematically optimal (GA) pathway achieves a 90.8% reduction but only through structural contraction that implies socially unsustainable deindustrialization. This tension exposes the systemic limits of incremental decarbonization and underscores that a truly sustainable pathway requires transcending this binary choice by directly addressing the fossil fuel substrate of industrial production. Full article
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23 pages, 7558 KB  
Article
Instrumented Assessment of Gait in Pediatric Cancer Survivors: Identifying Functional Impairments After Oncological Treatment—A Pilot Study
by María Carratalá-Tejada, Diego Fernández-Vázquez, Víctor Navarro-López, Juan Aboitiz-Cantalapiedra, Francisco Molina-Rueda, Blanca López-Ibor Aliño and Alicia Cuesta-Gómez
Children 2026, 13(1), 96; https://doi.org/10.3390/children13010096 - 9 Jan 2026
Viewed by 559
Abstract
Background/Objectives: Pediatric cancer survivors frequently experience neuromuscular sequelae related to chemotherapy-induced neurotoxicity. Agents such as vincristine, methotrexate, and platinum compounds can lead to persistent gait alterations and sensorimotor deficits that impair mobility and quality of life. This study aimed to objectively assess [...] Read more.
Background/Objectives: Pediatric cancer survivors frequently experience neuromuscular sequelae related to chemotherapy-induced neurotoxicity. Agents such as vincristine, methotrexate, and platinum compounds can lead to persistent gait alterations and sensorimotor deficits that impair mobility and quality of life. This study aimed to objectively assess gait in pediatric cancer survivors after the completion of oncological pharmacological treatment to identify specific spatiotemporal, kinematic, and kinetic alterations and characterize neuromechanical patterns associated with neurotoxic exposure. Methods: A cross-sectional observational study was conducted including pediatric cancer survivors (6–18 years) who had completed chemotherapy and age- and sex-matched healthy controls. Gait was analyzed using a Vicon®3D motion capture system, with reflective markers placed on standardized anatomical landmarks. Spatiotemporal, kinematic, and kinetic variables were compared between groups using parametric tests and statistical parametric mapping (SPM) with Holm–Bonferroni correction (α = 0.05). Results: Pediatric cancer survivors showed slower gait velocity (Mean Difference (MD) = 0.17, p = 0.018, Confidence Interval CI95% = 0.04; 0.4), shorter step (MD = 0.1, p = 0.015, CI95% = 0.01; 0.19) and stride length (MD = 0.17, p = 0.018, CI95% = 0.03; 0.31), as well as reduced single support time (MD = 0.1, p = 0.043, CI95% = 0.01; 0.19), along with significant alterations in pelvic, hip, knee, and ankle kinematics compared with controls. Increased pelvic elevation (MD = 0.92, p = 0.018, CI95% = 0.25; 1.58), reduced hip extension during stance (MD = −2.99, p = 0.039, CI95% = −5.19; −0.74), knee hyperextension in mid-stance (MD = −3.84, p < 0.001, CI95% = −6.18; −0.72), and limited ankle dorsiflexion (MAS MD = −4.04, p < 0.001, CI95% = −6.79; −0.86, LAS MD = −3.16, p < 0.001) and plantarflexor moments in terminal stance (MAS MD = −149.65, p = 0.018, CI95% = −259.35; −48.25, LAS MD = −191.81, p = 0.008, CI95% = −323.81; −57.31) were observed. Ground reaction force peaks during loading response (MAS MD = −16.86, p < 0.001, CI95% = −26.12; −0.72 LAS MD = −11.74, p = 0.001, CI95% = −19.68; −3.94) and foot-off (MAS MD = 10.38, p = 0.015, CI95% = 0.41; 20.53, LAS MD = 11.88, p = 0.01, CI95% = 3.15; 22.38) were also reduced. Conclusions: Children who have completed chemotherapy present measurable gait deviations reflecting persistent neuromechanical impairment, likely linked to chemotherapy-induced neurotoxicity and deconditioning. Instrumented gait analysis allows early detection of these alterations and may support the design of targeted rehabilitation strategies to optimize functional recovery and long-term quality of life in pediatric cancer survivors. Full article
(This article belongs to the Special Issue Movement Disorders in Children: Challenges and Opportunities)
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18 pages, 2075 KB  
Article
A Spatial Framework for Assessing Irrigation Water Use in Overexploited Mediterranean Aquifers
by Esther López-Pérez, Juan Manzano-Juarez, Miguel Angel Jiménez-Bello, Alberto García-Prats, Carles Sanchis-Ibor, Adrià Rubio-Martín, Fatima Zahrae Boubekri, Abdellah Kajji, Paolo Tufoni, Luís Miguel Nunes and Manuel Pulido-Velazquez
Remote Sens. 2025, 17(24), 4019; https://doi.org/10.3390/rs17244019 - 12 Dec 2025
Cited by 1 | Viewed by 635
Abstract
Irrigated agriculture in Mediterranean semi-arid regions is increasingly constrained by aquifer depletion and climate change. Enhancing water use efficiency in the irrigation of perennial crops is essential for long-term agricultural sustainability. This study introduces a Spatial Irrigation Adequacy Index (SIAI), a normalized index [...] Read more.
Irrigated agriculture in Mediterranean semi-arid regions is increasingly constrained by aquifer depletion and climate change. Enhancing water use efficiency in the irrigation of perennial crops is essential for long-term agricultural sustainability. This study introduces a Spatial Irrigation Adequacy Index (SIAI), a normalized index expressing the deviation between actual evapotranspiration (ETa) and Crop Water Requirements (CWR). The framework was applied to assess irrigation performance in grapevine (Vitis vinifera), apple orchards (Malus domestica) and citrus tress (Citrus sinensis) across three groundwater-dependent systems: Requena-Utiel (Spain), Ain Timguenai (Morocco), and Campina de Faro (Portugal). ETa was estimated using Landsat 8 and 9 imageries processed with the SSEBop model, while crop water demand was calculated with the FAO-56 dual crop coefficient method incorporating site-specific agroclimatic data. Results revealed distinct crop-specific irrigation patterns: grapevines achieved near-optimal water use, apple orchards were generally over-irrigated, and citrus groves experienced persistent deficits. The framework enables scalable, transferable assessments of irrigation performance, supporting sustainable water management and adaptive irrigation under climate variability, with potential applications in digital farm management systems, water authority decision-making, and corporate ESG reporting frameworks. Full article
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23 pages, 3274 KB  
Article
Mechanism of Action of Zinc Oxide Nanoparticles as an Antibacterial Agent Against Streptococcus mutans
by Raphaelle Emram, Ronit Vogt Sionov, Vitaly Gutkin, Asaf Wilensky, Doron Steinberg and Rawi Assad
Biomolecules 2025, 15(12), 1660; https://doi.org/10.3390/biom15121660 - 27 Nov 2025
Viewed by 1611
Abstract
Oral microbial biofilms play a critical role in the development of various oral infectious diseases, including periodontitis and tooth caries, with Streptococcus mutans recognized as a key biofilm-forming bacterium due to its strong adhesion and acidogenic capacity. Zinc oxide nanoparticles (ZnO NPs) have [...] Read more.
Oral microbial biofilms play a critical role in the development of various oral infectious diseases, including periodontitis and tooth caries, with Streptococcus mutans recognized as a key biofilm-forming bacterium due to its strong adhesion and acidogenic capacity. Zinc oxide nanoparticles (ZnO NPs) have demonstrated antibacterial properties against various bacteria. This study investigated the antibacterial and antibiofilm properties of ZnO NPs on S. mutans and elucidated their mode of action. Bacterial cultures were exposed to increasing concentrations of ZnO NPs, and planktonic growth, biofilm biomass and biofilm metabolic activity were measured. Complementary assays assessed bacterial ATP content, pH shift in the media, reactive oxygen species (ROS) production, membrane integrity (SYTO 9/PI live/dead staining) and membrane potential. Morphological changes were examined by high-resolution scanning electron microscopy (HR-SEM), while gene expression was analyzed by real-time qPCR. We observed that ZnO NPs inhibited S. mutans growth and biofilm formation in a dose-dependent manner, with both the minimum inhibitory and biofilm inhibitory concentration of 0.5 mg/mL. ZnO NP treatment disrupted bacterial membranes, caused cytoplasmic leakage, and induced ROS production. EPS production determined by Congo Red staining was significantly reduced. Gene expression analysis revealed significant upregulation of vicR, luxS, wapA, gtpB, nox and ftsZ, and downregulation of spaP, gtpC and atpB. In conclusion, ZnO NPs compromise S. mutans viability and biofilm development through oxidative stress and membrane disruption, highlighting their potential use as bioactive materials in oral healthcare. Full article
(This article belongs to the Section Chemical Biology)
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14 pages, 3857 KB  
Article
Coating Doyle Nasal Silicone Splints with a Sustained Release Varnish Containing Antibiotics Provides Long-Term Protection from Staphylococcus aureus: An In Vitro Study
by Ahmad Siag, Ronit Vogt Sionov, Irith Gati, Michael Friedman, Doron Steinberg and Menachem Gross
Pharmaceuticals 2025, 18(11), 1746; https://doi.org/10.3390/ph18111746 - 17 Nov 2025
Viewed by 1239
Abstract
Background/Objectives: Doyle nasal silicone splints are commonly used in nasal surgeries to maintain the shape of the nasal passage and prevent scar tissue formation. However, these implants are prone to bacterial colonization, particularly by Staphylococcus aureus, which is associated with severely [...] Read more.
Background/Objectives: Doyle nasal silicone splints are commonly used in nasal surgeries to maintain the shape of the nasal passage and prevent scar tissue formation. However, these implants are prone to bacterial colonization, particularly by Staphylococcus aureus, which is associated with severely recurrent and recalcitrant cases of infected sinonasal cavities. The aim of this study was to develop a sustained-release varnish (SRV) with antibacterial properties that can be applied to Doyle splints to provide an antibacterial environment for an extended period. Methods: Doyle nasal splints (1 cm × 1 cm segments) were coated with SRV containing one of the three antibiotics: augmentin, ciprofloxacin, or chloramphenicol. A placebo varnish without antibiotics served as a control. The coated splints were exposed daily to a fresh culture of S. aureus, and antibacterial activity was assessed by monitoring bacterial growth. Antibiofilm activity was determined using an MTT metabolic assay. Antibacterial activity was further studied by the kinetic disk diffusion assay, where the stents were transferred daily to new, freshly coated S. aureus plates. Biofilm formation on the coated splints was visualized by high-resolution scanning electron microscopy (HR-SEM). Results: Doyle segments coated with augmentin, ciprofloxacin, or chloramphenicol effectively inhibited S. aureus planktonic growth for 9 ± 1, 18 ± 1, and 21 ± 1 days, respectively. Biofilm formation was prevented for 10 ± 1, 18 ± 1, and 21 ± 1 days, and bacterial clearance occurred for 14 ± 1, 52 ± 1, and >65 days, respectively. HR-SEM images showed the prevention of biofilm formation on the coated segments. Conclusions: Our findings demonstrate that coating Doyle nasal silicon splints with SRV containing augmentin, ciprofloxacin, or chloramphenicol provides long-term antibacterial and antibiofilm activity, with SRV–chloramphenicol being superior. Further studies are needed to confirm the in vivo efficacy of this approach. Full article
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19 pages, 2575 KB  
Article
Anandamide Alters Glycolytic Activity in Streptococcus mutans: Metabolomics and Stable Isotope Labeling Study
by Goldie Wolfson, Doron Steinberg, Alexandra Eliassaf, Anna Morshina, César Jessé Enríquez-Rodríguez, Itzhack Polacheck, Maya Korem and Ori Shalev
Int. J. Mol. Sci. 2025, 26(17), 8401; https://doi.org/10.3390/ijms26178401 - 29 Aug 2025
Cited by 1 | Viewed by 1213
Abstract
Streptococcus mutans (S. mutans) is a cariogenic bacterium in the oral cavity that plays a significant role in plaque formation and dental caries. In previous research by our group, we showed that the endocannabinoid anandamide (AEA) has anti-bacterial and anti-biofilm activities against S. [...] Read more.
Streptococcus mutans (S. mutans) is a cariogenic bacterium in the oral cavity that plays a significant role in plaque formation and dental caries. In previous research by our group, we showed that the endocannabinoid anandamide (AEA) has anti-bacterial and anti-biofilm activities against S. mutans. Here, we aimed to investigate its effects on S. mutans through metabolomics analyses. S. mutans was cultivated in the absence or presence of AEA at a sub-minimum inhibitory concentration (MIC), and changes in metabolites and metabolic pathways were assessed through liquid chromatography–mass spectrometry (LC-MS). Treatment of S. mutans using AEA at 10 µg/mL significantly disturbed the glycolytic flux in the bacteria, which was indicated by a reduced glucose uptake into the cell, suppression of key glycolytic intermediates, reduced acid production into the media, imbalance of NAD+/NADH, and decreased adenosine triphosphate (ATP) production. The disruption of carbohydrate metabolism impacts critical cellular processes, including energy production, redox balance, and biosynthetic pathways, leading to metabolic stress and impaired cellular function. These results highlight the mode of action of AEA as an antimicrobial agent. Altogether, these findings suggest that AEA has potential as a novel antimicrobial agent in the development of therapeutics against S. mutans. Full article
(This article belongs to the Special Issue Antimicrobial Materials: Molecular Developments and Applications)
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9 pages, 599 KB  
Article
Sugar Content of Children’s Breakfast Foods in Mediterranean Diet Patterns
by Clara Guinot-Barona, Giorgia Tumino, Marta Ibor-Miguel, Carla Borrell-García, Juan-Ignacio Aura-Tormos, Esther García-Miralles and Laura Marqués-Martínez
Nutrients 2025, 17(17), 2717; https://doi.org/10.3390/nu17172717 - 22 Aug 2025
Viewed by 1409
Abstract
Background: Breakfast habits in Mediterranean countries often include processed products with hidden sugars, which may compromise children’s oral and general health. Objectives: This study assessed the sugar content of breakfast foods commonly consumed by children using °Brix refractometry and examined its implications for [...] Read more.
Background: Breakfast habits in Mediterranean countries often include processed products with hidden sugars, which may compromise children’s oral and general health. Objectives: This study assessed the sugar content of breakfast foods commonly consumed by children using °Brix refractometry and examined its implications for dental caries and obesity. Methods: Forty-nine breakfast food samples (processed products, homemade alternatives, and fresh fruits) were analysed using a digital °Brix refractometer to quantify soluble sugar concentrations. Comparative statistical analyses were performed to evaluate differences among food categories. Results: Processed foods consistently exhibited significantly higher °Brix values (mean ± SD: 14.1 ± 4.9), reflecting greater levels of extrinsic sugars, compared with homemade preparations (10.9 ± 1.1) and fresh fruits (10.7 ± 5.2) (p < 0.01). Processed items contained on average 25% more sugar than the other categories. Fresh fruits and homemade options demonstrated moderate °Brix levels, with no added sugars, whereas processed products—despite some being marketed as “no added sugars”—frequently contained substantial sugar content. Conclusions: The findings highlight the urgent need for educational strategies and clearer labelling to reduce sugar intake during childhood breakfasts. Promoting natural and homemade alternatives could be a key preventive approach to lowering the risk of dental caries, obesity, and other diet-related conditions. Full article
(This article belongs to the Special Issue Diet and Oral Health)
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16 pages, 3137 KB  
Systematic Review
Correction of Anterior Open Bite Using Temporary Anchorage Devices: A Systematic Review and Meta-Analysis
by Patricia Burgos-Lancero, Marta Ibor-Miguel, Laura Marqués-Martínez, Paula Boo-Gordillo, Esther García-Miralles and Clara Guinot-Barona
J. Clin. Med. 2025, 14(14), 4958; https://doi.org/10.3390/jcm14144958 - 13 Jul 2025
Cited by 1 | Viewed by 4656
Abstract
Background/Objectives: Anterior open bite (AOB) is a complex malocclusion characterized by the lack of vertical overlap between the upper and lower teeth during maximum intercuspation. It often results in functional impairments and aesthetic concerns. Traditional treatments for adult patients, including orthognathic surgery, are [...] Read more.
Background/Objectives: Anterior open bite (AOB) is a complex malocclusion characterized by the lack of vertical overlap between the upper and lower teeth during maximum intercuspation. It often results in functional impairments and aesthetic concerns. Traditional treatments for adult patients, including orthognathic surgery, are effective but invasive. Temporary anchorage devices (TADs) have emerged as a minimally invasive alternative. The aim of this systematic review and meta-analysis was to evaluate the effectiveness of TADs for molar intrusion in the correction of AOB. Methods: A systematic review was conducted according to the PRISMA 2020 guidelines. An electronic search was performed in PubMed and Scopus until March 2025. The inclusion criteria comprised clinical studies in humans published in English or Spanish in the last 10 years. The risk of bias was assessed using RoB 2, ROBINS-I, and the Joanna Briggs Institute tools. A random-effects meta-analysis was carried out to estimate pooled intrusion values, and heterogeneity was evaluated using Cochran’s Q test and the I2 statistic. Results: Twelve studies were included. Molar intrusion using TADs achieved significant overbite improvements, with a pooled mean intrusion of 1.70 mm (95% CI: 0.53–2.87 mm). The heterogeneity among studies was high (I2 = 88.5%). Despite variability in force magnitude and TAD type, lighter forces were generally associated with similar outcomes and fewer adverse effects. Conclusions: TADs offer a predictable and less invasive alternative to orthognathic surgery for AOB correction. When appropriately indicated and biomechanically managed, they provide effective vertical control and short- to medium-term stability in adult patients. Full article
(This article belongs to the Special Issue Latest Advances in Orthodontics)
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22 pages, 460 KB  
Article
Quality of Life and Experience of Patients with Heart Failure with Preserved Ejection Fraction and Their Caregivers
by Raül Rubio, Beatriz Palacios, Luis Varela, Martín Gutiérrez Ibañez, Selene Camargo Correa, Elena Calvo Barriuso, Nuria José, Sergi Yun Viladomat, María Teresa Soria Gómez, Esther Montero Hernández, Encarna Hidalgo, Cristina Enjuanes, Yolanda Rueda, Maite San Saturnino, Paloma Garcimartín, Jorge V. López-Ibor, Javier Segovia-Cubero and Josep ComínColet
J. Clin. Med. 2025, 14(13), 4715; https://doi.org/10.3390/jcm14134715 - 3 Jul 2025
Viewed by 2349
Abstract
Background/Objectives: Evidence of patient experiences with heart failure with preserved ejection fraction (HFpEF) and disease impact on quality of life (QoL) is scarce. This study explored perceived impacts on QoL and healthcare experiences of HFpEF patients and their caregivers. Methods: This [...] Read more.
Background/Objectives: Evidence of patient experiences with heart failure with preserved ejection fraction (HFpEF) and disease impact on quality of life (QoL) is scarce. This study explored perceived impacts on QoL and healthcare experiences of HFpEF patients and their caregivers. Methods: This was a mixed-methods study with HFpEF patients, ≥40 years, New York Heart Association functional classes I-IV in Spain. Qualitative data were collected through semi-structured interviews with patients (n = 19) and caregivers (n = 17). The EuroQoL 5D-5L, Patient Global Impression of Severity, and Kansas City Cardiomyopathy Questionnaire were used to collect QoL measures. Results: The themes were as follows. (1) Impact of HFpEF on QoL; (2) new roles of informal caregiving; and (3) the increasing value of multidisciplinary care. Qualitative data were supported by a trend of worsening QoL on quantitative measures as HF progressed, despite quantitative measures not fully capturing the burden. Qualitative data further captured discrepancies of QoL perceptions. Conclusions: The impact of HFpEF on patients and their caregivers was similar to the HFrEF population’s. Insights from discrepancies between PROMs data and interviews could help with tailoring QoL questionnaires to capture the broader impact of HFpEF, identify unmet needs, and customize care. Full article
(This article belongs to the Special Issue Patient-Oriented Treatments for Heart Failure)
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15 pages, 2618 KB  
Article
Pulsed Blue Light and Phage Therapy: A Novel Synergistic Bactericide
by Amit Rimon, Jonathan Belin, Ortal Yerushalmy, Yonatan Eavri, Anatoly Shapochnikov, Shunit Coppenhagen-Glazer, Ronen Hazan and Lilach Gavish
Antibiotics 2025, 14(5), 481; https://doi.org/10.3390/antibiotics14050481 - 9 May 2025
Cited by 2 | Viewed by 1996
Abstract
Background: Antibiotic-resistant Pseudomonas aeruginosa (P. aeruginosa) strains are an increasing cause of morbidity and mortality. Pulsed blue light (PBL) enhances porphyrin-induced reactive oxygen species and has been clinically shown to be harmless to the skin at low doses. Bacteriophages, viruses that [...] Read more.
Background: Antibiotic-resistant Pseudomonas aeruginosa (P. aeruginosa) strains are an increasing cause of morbidity and mortality. Pulsed blue light (PBL) enhances porphyrin-induced reactive oxygen species and has been clinically shown to be harmless to the skin at low doses. Bacteriophages, viruses that infect bacteria, offer a promising non-antibiotic bactericidal approach. This study investigates the potential synergism between low-dose PBL and phage therapy against P. aeruginosa in planktonic cultures and preformed biofilms. Methods: We conducted a factorial dose–response in vitro study combining P. aeruginosa-specific phages with PBL (457 nm, 33 kHz) on both PA14 and multidrug-resistant PATZ2 strains. After excluding direct PBL effects on phage titer or activity, we assessed effectiveness on planktonic cultures using growth curve analysis (via growth_curve_outcomes, a newly developed, Python-based tool available on GitHub) , CFU, and PFU. Biofilm efficacy was evaluated using CFU post-sonication, crystal violet staining, and live/dead staining with confocal microscopy. Finally, we assessed reactive oxygen species (ROS) as a potential mechanism using the nitro blue tetrazolium reduction assay. ANOVA or Kruskal–Wallis tests with post hoc Tukey or Conover–Iman tests were used for comparisons (n = 5 biological replicates and technical triplicates). Results: The bacterial growth lag phase was significantly extended for phage alone or PBL alone, with a synergistic effect of up to 144% (p < 0.001 for all), achieving a 9 log CFU/mL reduction at 24 h (p < 0.001). In preformed biofilms, synergistic combinations significantly reduced biofilm biomass and bacterial viability (% Live, median (IQR): Control 80%; Phage 40%; PBL 25%; PBL&Phage 15%, p < 0.001). Mechanistically, PBL triggered transient ROS in planktonic cultures, amplified by phage co-treatment, while a biphasic ROS pattern in biofilms reflected time-dependent synergy. Conclusions: Phage therapy combined with PBL demonstrates a synergistic bactericidal effect against P. aeruginosa in both planktonic cultures and biofilms. Given the strong safety profile of PBL and phages, this approach may lead to a novel, antibiotic-complementary, safe treatment modality for patients suffering from difficult-to-treat antibiotic-resistant infections and biofilm-associated infections. Full article
(This article belongs to the Special Issue Antibiofilm Activity against Multidrug-Resistant Pathogens)
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29 pages, 11382 KB  
Article
The Incorporation of CBD into Biodegradable DL-Lactide/Glycolide Copolymers Creates a Persistent Antibacterial Environment: An In Vitro Study on Streptococcus mutans and Staphylococcus aureus
by Ronit Vogt Sionov, Ahmad Siag, Emma Theresa Mersini, Natalya M. Kogan, Tatiana Alkhazov, Igor Koman, Praveen Rowlo, Vitaly Gutkin, Menachem Gross and Doron Steinberg
Pharmaceutics 2025, 17(4), 463; https://doi.org/10.3390/pharmaceutics17040463 - 2 Apr 2025
Cited by 3 | Viewed by 1377
Abstract
Background: Cannabidiol (CBD) is a natural compound from the Cannabis sativa L. plant, which has anti-inflammatory, anti-nociceptive, neuroprotective, and antibacterial activities. Objective: The aim of this study was to develop a sustained-release device of CBD that can provide an antibacterial effect [...] Read more.
Background: Cannabidiol (CBD) is a natural compound from the Cannabis sativa L. plant, which has anti-inflammatory, anti-nociceptive, neuroprotective, and antibacterial activities. Objective: The aim of this study was to develop a sustained-release device of CBD that can provide an antibacterial effect against the Gram-positive bacteria Streptococcus mutans and Staphylococcus aureus for extended periods of time. Methods: CBD was incorporated into the biodegradable PURASORB 5010 or PURASORB 7510 DL-lactide/glycolide polymers using either dimethylsulfoxide (DMSO) or acetone as the solvent, and the dried polymer scaffolds were exposed daily to a fresh culture of bacteria. The bacterial growth was determined daily by optical density, and the metabolic activity of biofilms was determined using the MTT assay. Biofilm formation on the polymer scaffolds was visualized by HR-SEM. Its anti-inflammatory effect was determined by measuring the IL-6 release from LPS-stimulated RAW 264.7 macrophages by ELISA. Cell cytotoxicity on normal Vero epithelial cells was determined by the MTT assay. The daily release of CBD was determined by gas chromatography–mass spectrometry (GC-MS). Results: PURASORB 5010/CBD scaffolds had antibacterial activity against S. mutans UA159, S. aureus ATCC25923, and a clinical isolate of a multidrug-resistant S. aureus (MDRSA CI-M) strain for the tested period of up to 17 days. PURASORB 7510/CBD scaffolds also had antibacterial activity, but overall, it was less effective than PURASORB 5010/CBD over time. The addition of PEG400 to the copolymers significantly increased the antibacterial activity of PURASORB 7510/CBD but not of PURASORB 5010/CBD. The daily release of CBD from the polymer scaffolds was sufficient to reduce the LPS-induced IL-6 secretion from RAW 264.7 macrophages, and importantly, it was not cytotoxic to either RAW 264.7 macrophages or Vero epithelial cells. The daily release of CBD was found to be between 1.12 and 9.43 µg/mL, which is far below the cytotoxic dose of 25 µg/mL. Conclusions: The incorporation of CBD into the biodegradable PURASORB 5010 can be used to prepare sustained-release devices for medical purposes where combined antibacterial and anti-inflammatory activities are desirable. Full article
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15 pages, 4037 KB  
Article
Computational Analysis of Morphological Changes in Lactiplantibacillus plantarum Under Acidic Stress
by Athira Venugopal, Doron Steinberg, Ora Moyal, Shira Yonassi, Noga Glaicher, Eliraz Gitelman, Moshe Shemesh and Moshe Amitay
Microorganisms 2025, 13(3), 647; https://doi.org/10.3390/microorganisms13030647 - 12 Mar 2025
Cited by 2 | Viewed by 2349
Abstract
Shape and size often define the characteristics of individual microorganisms. Hence, characterizing cell morphology using computational image analysis can aid in the accurate, quick, unbiased, and reliable identification of bacterial morphology. Modifications in the cell morphology of Lactiplantibacillus plantarum were determined in response [...] Read more.
Shape and size often define the characteristics of individual microorganisms. Hence, characterizing cell morphology using computational image analysis can aid in the accurate, quick, unbiased, and reliable identification of bacterial morphology. Modifications in the cell morphology of Lactiplantibacillus plantarum were determined in response to acidic stress, during the growth stage of the cells at a pH 3.5 compared to a pH of 6.5. Consequently, we developed a computational method to sort, detect, analyze, and measure bacterial size in a single-species culture. We applied a deep learning methodology composed of object detection followed by image classification to measure bacterial cell dimensions. The results of our computational analysis showed a significant change in cell morphology in response to alterations of the environmental pH. Specifically, we found that the bacteria existed as a long unseparated cell, with a dramatic increase in length of 41% at a low pH compared to the control. Bacterial width was not altered in the low pH compared to the control. Those changes could be attributed to modifications in membrane properties, such as increased cell membrane fluidity in acidic pH. The integration of deep learning and object detection techniques, with microbial microscopic imaging, is an advanced methodology for studying cellular structures that can be projected for use in other bacterial species or cells. These trained models and scripts can be applied to other microbes and cells. Full article
(This article belongs to the Special Issue Bacterial Motility)
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27 pages, 7343 KB  
Article
Cannabidiol (CBD) Acts as an Antioxidant on Gardnerella vaginalis, Resulting in Reduced Metabolic Activity, Loss of Survivability, and Elimination of Biofilms
by Ronit Vogt Sionov, Maya Korem, Itzhack Polacheck and Doron Steinberg
Antibiotics 2025, 14(2), 136; https://doi.org/10.3390/antibiotics14020136 - 1 Feb 2025
Cited by 5 | Viewed by 3789
Abstract
Background: Gardnerella vaginalis is a natural inhabitant of the vagina, but when an imbalance occurs in the vaginal microbiota, this bacterium can cause vaginosis, a condition that must be treated when symptomatic and prior to a gynecological intervention. Cannabidiol (CBD) is an [...] Read more.
Background: Gardnerella vaginalis is a natural inhabitant of the vagina, but when an imbalance occurs in the vaginal microbiota, this bacterium can cause vaginosis, a condition that must be treated when symptomatic and prior to a gynecological intervention. Cannabidiol (CBD) is an anti-inflammatory compound that also has antibacterial activities against several Gram-positive and certain Gram-negative bacteria. Objectives: Since G. vaginalis is an opportunistic pathogenic Gram-variable bacterium, we investigated its response to CBD. Methods: The antibacterial activity of CBD was studied by broth dilution assay, changes in intracellular ATP levels, and the ability of bacteria to recover on chocolate agar plates. The antibiofilm activity was investigated by MTT metabolic assay, crystal violet staining, and HR-SEM. Flow cytometric analyses were performed to measure changes in membrane potential, membrane perforation, and metabolic activity. Reactive oxygen species (ROS) production was analyzed using the nitro blue tetrazolium (NBT) reagent. Gene expression was determined by semi-quantitative real-time PCR, while protein composition was determined by LC-MS/MS analysis. Results: We observed that G. vaginalis clinical isolates exhibited high susceptibility to CBD with a minimum inhibitory concentration (MIC) of 2.5 µg/mL CBD. CBD induced rapid membrane hyperpolarization and caused cytoplasmic leakage of ATP without increasing propidium iodide uptake. This was accompanied by reduced metabolic activity and loss of survivability. Proteomic analysis revealed decreased expression of some ribosomal-associated proteins. CBD exhibited antioxidant activity by reducing intracellular ROS levels in a dose-dependent manner. The antibacterial effect was neutralized by the free radical scavenger α-tocopherol, suggesting the involvement of radicals in executing the antibacterial effect. Importantly, CBD not only prevented the biofilm formation of G. vaginalis but also reduced the metabolic activity and biofilm biomass of preformed, mature biofilms. Real-time PCR analysis of G. vaginalis treated with CBD for 6 h showed an increase in the expression of biofilm-associated genes, suggesting that the antibiofilm activity of CBD is mainly due to its antibacterial effect. CBD did not alter the ability of G. vaginalis to adhere to HeLa cervical carcinoma cells and CBD-treated bacteria were still phagocytosed by RAW264.7 macrophages. Conclusions: Our study shows that CBD exhibits antibacterial and antibiofilm activities against G. vaginalis clinical isolates and is thus a potential drug for the treatment of vaginosis caused by this bacterium. Full article
(This article belongs to the Special Issue Antimicrobial and Antibiofilm Activity by Natural Compounds)
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