Analysis of Gingival Fibroblasts Behaviour in the Presence of 3D-Printed versus Milled Methacrylate-Based Dental Resins-Do We Have a Winner?

Computer-aided design and computer-aided manufacturing (CAD/CAM) techniques are based on either subtractive (milling prefabricated blocks) or additive (3D printing) methods, and both are used for obtaining dentistry materials. Our in vitro study aimed to investigate the behavior of human gingival fibroblasts exposed to methacrylate (MA)-based CAD/CAM milled samples in comparison with that of MA-based 3D-printed samples to better elucidate the mechanisms of cell adaptability and survival. The proliferation of human gingival fibroblasts was measured after 2 and 24 h of incubation in the presence of these samples using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the membrane integrity was assessed through the lactate dehydrogenase release. The level of reactive oxygen species, expression of autophagy-related protein LC3B-I, and detection of GSH and caspase 3/7 were evaluated by fluorescence staining. The MMP-2 levels were measured using a Milliplex MAP kit. The incubation with MA-based 3D-printed samples significantly reduced the viability, by 16% and 28% from control after 2 and 24 h, respectively. There was a 25% and 55% decrease in the GSH level from control after 24 h of incubation with the CAD/CAM milled and 3D-printed samples, respectively. In addition, higher levels of LC3B-I and MMP-2 were obtained after 24 h of incubation with the MA-based 3D samples compared to the CAD/CAM milled ones. Therefore, our results outline that the MA-CAD/CAM milled samples displayed good biocompatibility during 24-h exposure, while MA-3D resins are proper for short-term utilization (less than 24 h).

Exploring the Threefold Viewpoint on Children's Oral Health in a Cross-Sectional Study.

Oral health is situated within the framework of the global health agenda, addressing facets pertaining to well-being and quality of life. The research is based on the need to address variables at the community level to improve schoolchildren's oral health and promote healthy behaviors and aims to carry out an in-depth analysis from the perspective of the factors that influence children's oral health. Step 1, designed by the World Health Organization, was utilized. An easy-to-use web interface was created for data collection. The statistical analysis consisted of using multinomial and binominal logistic regression models. The level of education of the adult has a high probability of influencing the consumption of unhealthy or healthy foods, it has a significant probability of exerting influence on social or medical problems and a correlation was found between the level of academic education and the pattern of dental visits. The development of health-promoting behaviors begins in childhood and involves parents, who have an essential role in the education of their children. Oral health promotion programs in schools need to target the child-adult-teacher-dentist relationships. Taking into consideration the aforementioned, a threefold viewpoint is necessary for the development of a national program aimed at promoting the oral health of schoolchildren in Romania.

Volatility, Uncertainty, Complexity, and Ambiguity (VUCA) in Healthcare.

Our professional activity is constantly under pressure from a multitude of elements and factors that can be classified into the four components of the VUCA phenomenon-volatility, uncertainty, complexity, and ambiguity-components that define the turbulence and challenges of the external environment. Considering the general elements of this phenomenon, we designed a new VUCA dimension specific to the healthcare field within which we have identified and analyzed all the factors that can influence the main actors of the doctor-patient relationship and the effects that can occur within the healthcare system in which this relationship is born. In this context, we generated the VUCA treatment in healthcare capable of mitigating the impact of this phenomenon; this treatment involves essential elements in overcoming possible crises and vulnerabilities of the medical profession. The VUCA treatment in healthcare requires combating volatility, uncertainty, complexity, and ambiguity through vision, understanding, clarity, and agility, which are grounded in the doctor's need to acquire cross-functional competencies (soft skills). These competencies are applicable by using functional mechanisms and techniques that support the doctor in developing adaptability and anticipation skills, understanding the patient's needs and addressing them, and ensuring the functionality and efficiency of the healthcare system by transferring these elements from micro-management to macro-management levels.

Application of Common Culinary Herbs for the Development of Bioactive Materials.

Hyssop (Hyssopus officinalis L.) and oregano (Origanum vulgare L.), traditionally used for their antimicrobial properties, can be considered viable candidates for nanotechnology applications, in particular for the phytosynthesis of metal nanoparticles. The present work aims to evaluate the potential application of hyssop and oregano for the phytosynthesis of silver nanoparticles, as well as to evaluate the biological activities of their extracts and obtained nanoparticles (antioxidant potential, as well as cell viability, inflammation level and cytotoxicity in human fibroblasts HFIB-G cell line studies). In order to obtain natural extracts, two extraction methods were applied (classical temperature extraction and microwave-assisted extraction), with the extraction method having a major influence on their composition, as demonstrated by both the total phenolic compounds (significantly higher for the microwave-assisted extraction; the oregano extracts had consistently higher TPC values, compared with the hyssop extracts) and in terms of individual components identified via HPLC. The obtained nanoparticles ware characterized via X-ray diffraction (XRD) and transmission electron microscopy (TEM), with the lowest dimension nanoparticles being recorded for the nanoparticles obtained using the oregano microwave extract (crystallite size 2.94 nm through XRD, average diameter 10 nm via TEM). The extract composition and particle size also influenced the antioxidant properties (over 60% DPPH inhibition being recorded for the NPs obtained using the oregano microwave extract). Cell viability was not affected at the lowest tested concentrations, which can be correlated with the nitric oxide level. Cell membrane integrity was not affected after exposure to classic temperature hyssop extract-NPs, while the other samples led to a significant LDH increase.

A STEPwise Approach for Oral Hygiene Behavior of Schoolchildren in Romania.

This research analyzes the dental hygiene habits of schoolchildren from parents' perspectives, using the STEPS approach recommended by the World Health Organization. The key points of oral health care in children include the role of the family in encouraging and maintaining proper oral hygiene practices. This study aimed to assess the oral hygiene practices of schoolchildren with on-site dentists in Romania. Additionally, it sought to establish correlations between these behaviors and the educational levels of the adults with whom they live with. The participants were selected from the zero grade to the eighth grade, totaling 3843students. Statistical analysis involved the application of Fisher's Exact Test and Z-tests with Bonferroni correction. Multinominal and binominal logistic regression models were employed to predict the impact of parents' education on children's oral health status and behavior. The oral health status of children evaluated by parents as poor was more frequent in children whose parents had a primary or gymnasium education (p < 0.001). Female adults with a university education evaluated the gum health of their children as very good to a much greater extent (41.7%, p < 0.001). Regarding the use of auxiliary means, the majority of parents with a university education mentioned that their children use dental floss (26.4% females/27.4% males) (p < 0.001), compared to those with primary education, where the percentage was only (1.2% males/3.5% females) (p < 0.001). The results of this study highlight that the education level of the adults with whom the children live with influences the perception of the teeth and gums health status, the frequency of oral hygiene, the use of fluoride toothpaste, and auxiliary brushing aids.

Collateral Victims of Defensive Medical Practice.

This paper analyzes the phenomenon of defensive medical practice, starting from the doctor-patient relationship, and the behavioral and professional factors that can influence the proper functioning of this relationship and the healthcare system. We analyze medical malpractice, given the increase in the number of accusations, as an essential factor in triggering the defensive behavior of doctors, together with other complementary factors that emphasize the need for protection and safety of doctors. The possible consequences for the doctor-patient relationship that defensive practice can generate are presented and identified by analyzing the determining role of the type of health system (fault and no-fault). At the same time, we investigate the context in which overspecialization of medical personnel can generate a form of defensive practice as a result of the limiting effect on the performance of a certain category of operations and procedures. The increase in the number of malpractice accusations impacts the medical community-"the stress syndrome induced by medical malpractice"-turning doctors into collateral victims who, under the pressure of diminishing their reputational safety, practice defensively to protect themselves from future accusations. This type of defensive behavior puts pressure on the entire healthcare system by continuously increasing costs and unresolved cases, which impact patients by limiting access to medical services in the public and private sectors.

The Yin and Yang dualistic features of autophagy in thermal burn wound healing.

Burn healing should be regarded as a dynamic process consisting of two main, interrelated phases: (a) the inflammatory phase when neutrophils and monocytes infiltrate the injury site, through localized vasodilation and fluid extravasation, and (b) the proliferative-remodeling phase, which represents a key event in wound healing. In the skin, both canonical autophagy (induced by starvation, oxidative stress, and environmental aggressions) and non-canonical or selective autophagy have evolved to play a discrete, but, essential, "housekeeping" role, for homeostasis, immune tolerance, and survival. Experimental data supporting the pro-survival roles of autophagy, highlighting its Yang, luminous and positive feature of this complex but insufficient explored molecular pathway, have been reported. Autophagic cell death describes an "excessive" degradation of important cellular components that are necessary for normal cell function. This deadly molecular mechanism brings to light the darker, concealed, Yin feature of autophagy. Autophagy seems to perform dual, conflicting roles in the angiogenesis context, revealing once again, its Yin-Yang features. Autophagy with its Yin-Yang features remains the shadow player, able to decide quietly whether the cell survives or dies.

Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects.

Although pancreatic cancer (PC) was considered in the past an orphan cancer type due to its low incidence, it may become in the future one of the leading causes of cancer death. Pancreatic ductal adenocarcinoma (PDAC) is the most frequent type of PC, being a highly aggressive malignancy and having a 5-year survival rate of less than 10%. Non-modifiable (family history, age, genetic susceptibility) and modifiable (smoking, alcohol, acute and chronic pancreatitis, diabetes mellitus, intestinal microbiota) risk factors are involved in PC pathogenesis. Chronic inflammation induced by various factors plays crucial roles in PC development from initiation to metastasis. In multiple malignant conditions such as PC, cytokines, chemokines, and growth factors activate the class I phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) (PI3K/AKT/mTOR) signaling pathway, which plays key roles in cell growth, survival, proliferation, metabolism, and motility. Currently, mTOR, AKT, and PI3K inhibitors are used in clinical studies. Moreover, PI3K/mTOR dual inhibitors are being tested in vitro and in vivo with promising results for PC patients. The main aim of this review is to present PC incidence, risk factors, tumor microenvironment development, and PI3K/AKT/mTOR dysregulation and inhibitors used in clinical, in vivo, and in vitro studies.

Autophagy Plays Multiple Roles in the Soft-Tissue Healing and Osseointegration in Dental Implant Surgery-A Narrative Review.

Dental endo-osseous implants have become a widely used treatment for replacing missing teeth. Dental implants are placed into a surgically created osteotomy in alveolar bone, the healing of the soft tissue lesion and the osseointegration of the implant being key elements to long-term success. Autophagy is considered the major intracellular degradation system, playing important roles in various cellular processes involved in dental implant integration. The aim of this review is an exploration of autophagy roles in the main cell types involved in the healing and remodeling of soft tissue lesions and implant osseointegration, post-implant surgery. We have focused on the autophagy pathway in macrophages, endothelial cells; osteoclasts, osteoblasts; fibroblasts, myofibroblasts and keratinocytes. In macrophages, autophagy modulates innate and adaptive immune responses playing a key role in osteo-immunity. Autophagy induction in endothelial cells promotes apoptosis resistance, cell survival, and protection against oxidative stress damage. The autophagic machinery is also involved in transporting stromal vesicles containing mineralization-related factors to the extracellular matrix and regulating osteoblasts' functions. Alveolar bone remodeling is achieved by immune cells differentiation into osteoclasts; autophagy plays an important and active role in this process. Autophagy downregulation in fibroblasts induces apoptosis, leading to better wound healing by improving excessive deposition of extracellular matrix and inhibiting fibrosis progression. Autophagy seems to be a dual actor on the scene of dental implant surgery, imposing further research in order to completely reveal its positive features which may be essential for clinical efficacy.

Compressive and Flexural Strength of 3D-Printed and Conventional Resins Designated for Interim Fixed Dental Prostheses: An In Vitro Comparison.

A provisionalization sequence is essential for obtaining a predictable final prosthetic outcome. An assessment of the mechanical behavior of interim prosthetic materials could orient clinicians towards selecting an appropriate material for each clinical case. The aim of this study was to comparatively evaluate the mechanical behavior-with compressive and three-point flexural tests-of certain 3D-printed and conventional resins used to obtain interim fixed dental prostheses. Four interim resin materials were investigated: two 3D-printed resins and two conventional resins (an auto-polymerized resin and a pressure/heat-cured acrylic resin). Cylindrically shaped samples (25 × 25 mm/diameter × height) were obtained for the compression tests and bar-shaped samples (80 × 20 × 5 mm/length × width × thickness) were produced for the flexural tests, observing the producers' recommendations. The resulting 40 resin samples were subjected to mechanical tests using a universal testing machine. Additionally, a fractographic analysis of failed samples in bending was performed. The results showed that the additive manufactured samples exhibited higher elastic moduli (2.4 ± 0.02 GPa and 2.6 ± 0.18 GPa) than the conventional samples (1.3 ± 0.19 GPa and 1.3 ± 0.38 GPa), as well as a higher average bending strength (141 ± 17 MPa and 143 ± 15 MPa) when compared to the conventional samples (88 ± 10 MPa and 76 ± 7 MPa); the results also suggested that the materials were more homogenous when produced via additive manufacturing.

Hypoxia-Inducible Factors and Burn-Associated Acute Kidney Injury-A New Paradigm?

O2 deprivation induces stress in living cells linked to free-radical accumulation and oxidative stress (OS) development. Hypoxia is established when the overall oxygen pressure is less than 40 mmHg in cells or tissues. However, tissues and cells have different degrees of hypoxia. Hypoxia or low O2 tension may be present in both physiological (during embryonic development) and pathological circumstances (ischemia, wound healing, and cancer). Meanwhile, the kidneys are major energy-consuming organs, being second only to the heart, with an increased mitochondrial content and O2 consumption. Furthermore, hypoxia-inducible factors (HIFs) are the key players that orchestrate the mammalian response to hypoxia. HIFs adapt cells to low oxygen concentrations by regulating transcriptional programs involved in erythropoiesis, angiogenesis, and metabolism. On the other hand, one of the life-threatening complications of severe burns is acute kidney injury (AKI). The dreaded functional consequence of AKI is an acute decline in renal function. Taking all these aspects into consideration, the aim of this review is to describe the role and underline the importance of HIFs in the development of AKI in patients with severe burns, because kidney hypoxia is constant in the presence of severe burns, and HIFs are major players in the adaptative response of all tissues to hypoxia.

ILs and MMPs Levels in Inflamed Human Dental Pulp: A Systematic Review.

A wide range of mediators are released from the pulp tissue because of bacterial invasion which causes inflammation. Interleukins (ILs) and matrix metalloproteinases (MMPs) have a leading role in initiating and spreading of inflammation because of their synergic action. Biomarkers such as ILs and MMPs can be identified via several methods, establishing the inflammatory response of the dental pulp. The aim of this systematic review is to evaluate the levels of ILs and/or MMPs in human dental pulp. PubMed, OVID, Cochrane, Scopus, Web of Science and Wiley online library databases were searched for original clinical studies. After applying inclusion and exclusion criteria, a quality assessment of studies was performed based on a modified Newcastle-Ottawa scale. In the review were included articles that evaluated the presence of ILs and/or MMPs in pulp tissue using enzyme-linked immunosorbent assay (ELISA) or western blot or multiplex assay. Six articles were included in the present synthesis. Although various diagnostic methods were used, statistically significant higher levels of ILs and/or MMPs were mostly found in the experimental groups compared to healthy pulp samples. The biomarkers studied can be a promising tool to evaluate pulp tissue health or even in pulpitis treatment.

Lutein Treatment Effects on the Redox Status and Metalloproteinase-9 (MMP-9) in Oral Cancer Squamous Cells-Are There Therapeutical Hopes?

Carotenoids loaded in nanoparticles should be regarded as a promising way to increase the availability in healthy cells and to induce apoptosis in cancer. Lutein is a carotenoid that, in contrast to beta-carotene, has no known toxicities. Oral cancer represents one of the most frequent types of cancer world-wide with an incidence rate of about 9% of all types of cancer. Almost 95% of all oral cancers are represented by squamous cell carcinomas (OSCC). The aim of this study was to review and analyse the effects of lutein and Poly(d,l-lactide-co-glycolide) (PLGA) Nps containing lutein (Lut Nps) on oxidative stress biomarkers (OXSR-1, FOXO-3, TAC) and collagen degradation biomarker-MMP-9, in human cells BICR10 of buccal mucosa squamous carcinoma. Lut Nps were prepared by the emulsion-solvent evaporation method. MMP, OXSR-1, TAC, FOXO-3 and MMP-9 were measured in tumour cell lysates by the ELISA technique. Our results have shown that in Lut 100 cells and Lut Nps the OXSR1 (p < 0.001, p < 0.001) and TAC (p < 0.001, p < 0.001) values were significantly higher than in control cells. The Lut 100 and Lut Nps FOXO-3 levels revealed no significant differences versus the control. MMP-9 levels were significantly reduced (p < 0.001) in the Lut Nps cells versus control cells. In our study conditions, lutein and lutein Nps did not trigger an oxidative stress by ROS induction. However, lutein Nps treatment seemed to have a positive effect, by downregulating the MMP-9 levels. Loaded in Nps, lutein could be regarded as a protective factor against local invasiveness, in whose molecular landscape MMPs, and especially MMP-9 are the main actors.

Glucose Metabolism in Burns-What Happens?

Severe burns represent an important challenge for patients and medical teams. They lead to profound metabolic alterations, trigger a systemic inflammatory response, crush the immune defense, impair the function of the heart, lungs, kidneys, liver, etc. The metabolism is shifted towards a hypermetabolic state, and this situation might persist for years after the burn, having deleterious consequences for the patient's health. Severely burned patients lack energy substrates and react in order to produce and maintain augmented levels of glucose, which is the fuel "ready to use" by cells. In this paper, we discuss biological substances that induce a hyperglycemic response, concur to insulin resistance, and determine cell disturbance after a severe burn. We also focus on the most effective agents that provide pharmacological modulations of the changes in glucose metabolism.

Molecular Interactions between Saliva and Dental Composites Resins: A Way Forward.

Dentin and enamel loss related to trauma or especially caries is one of the most common pathological issues in dentistry that requires restoration of the teeth by using materials with appropriate properties. The composite resins represent dental materials with significant importance in today's dentistry, presenting important qualities, including their mechanical behavior and excellent aesthetics. This paper focuses on the saliva interactions with these materials and on their biocompatibility, which is continuously improved in the new generations of resin-based composites. Starting from the elements involved on the molecular landscape of the dental caries process, the paper presents certain strategies for obtaining more advanced new dental composite resins, as follows: suppression of oral biofilm acids formation, promotion of remineralization process, counteraction of the proteolytic attack, and avoidance of cytotoxic effects; the relation between dental composite resins and salivary oxidative stress biomarkers is also presented in this context.