Investigation of the precision of a novel jaw tracking system in recording mandibular movements: A preliminary clinical study.

OBJECTIVES: This preliminary study aimed to clinically assess the precision of a novel optical jaw tracking system (JTS) in registering mandibular movements (MMs) of protrusion and mediotrusion. METHODS: Twenty healthy participants underwent recordings using Cyclops JTS (Itaka Way Med) for functional MMs of protrusion and laterotrusion by two trained clinicians. Each subject performed five registrations at different times according to a standardized pattern within one-month period. The angulations of protrusive and mediotrusive functional paths within the first 2 mm from the maximal intercuspal position (MIP) were calculated for each trace, using a data software for angle measurements. Descriptive statistics were used to assess the repeatability of the recordings for each participant and MM. Additionally, inferential statistics were carried out on standard deviation values obtained (α=0.05). RESULTS: The overall precision for all the patients was 7.07±3.37° for the protrusion angle, 5.24±2.24° for right laterotrusion and 5.14±3.06° for left laterotrusion angles. The protrusion angle ranged from 3.08° to 13.57°, while the right and left laterotrusion ranged from 1.82° to 9.42° and from 1.58° to 10.59°, respectively. No statistically significant differences were observed between different functional MM types and gender (p > 0.05). CONCLUSIONS: Recordings functional MMs of mediotrusion and protrusion using Cyclops JTS showed consistent repeatability, regardless of gender and functional MM type. The results revealed non-negligible variations that may be due to the patients' abilities to precisely reproduce jaw movements or to the operator's ability to consistently connect the kinesiograph. CLINICAL SIGNIFICANCE: Capturing functional MMs digitally and importing the data into dental CAD software is essential for virtual waxing in prosthetic rehabilitations to design a functionalized adapted occlusion. Establishing the repeatability of MM recordings by a JTS is a crucial step in better understanding this novel JTS in the market. This process could facilitate the interpretation of cusp angles, aid in CAD dynamic technical modeling, and enhance clinical data communication between clinicians and technicians in a modern workflow.

Systematic Review of Zinc's Benefits and Biological Effects on Oral Health.

BACKGROUND: This review was based on the following question: "What is the state-of-the-art regarding the effect of zinc exposure in the oral cavity on a population of adults and children, compared to dental products containing materials other than zinc, considering in vivo (clinical trials and observational studies) and in vitro studies?" according to a PICOS strategy format. This study aims to analyze zinc application in dental materials, with different compositions and chemical formulations, considering how mechanical and biological properties may influence its clinical applicability. METHODS: In vivo (clinical trials: controlled clinical trials (CCTs) and randomized controlled trials (RCTs); and observational studies: case control and cohort studies) trials or in vitro studies published in English or Italian during the last 10 years on children and adult patients with zinc exposure were included by three different reviewers using the MEDLINE (via PubMed), Scopus, and Web of Science electronic databases. RESULTS: Titles and abstracts were evaluated following the eligibility criteria. The full texts of eligible studies were then reviewed against the inclusion/exclusion criteria. Scientific and technical information of the 33 included studies were collected into evidence tables, reporting data on in vivo and in vitro studies. A narrative approach was adopted. CONCLUSIONS: Antibacterial activity was found to be the most studied property of zinc, but further investigations are needed to establish adjuvant zinc therapies in patients with oral disease.

Acute and chronic cannabidiol treatment: In vitro toxicological aspects on human oral cells.

Cannabidiol is gaining increasing interest for its potential anti-inflammatory, immunomodulatory, and antineoplastic effects. The purpose of this study is to investigate the biological effects of acute and chronic CBD administration on gingival fibroblasts and oral keratinocytes. Viability, morphology, migration, apoptosis and cell cycle, and expression of related genes (p53, BCL2, p21, and BAX) and of endocannabinoid system receptors (CB1, CB2 and GPR55) with real-time PCR and DNA damage with phospho-γ-H2AX immunofluorescence detection were analyzed. Concentrations between 100 µM and 0.001 µM were used: 50 µM (toxic dose), 25 µM (viability promoter), and 1 µM (nontoxic), were selected for subsequent chronic analysis. Acute treatment reveals significant effects than chronic, in particular in fibroblasts: concentrations ≥50 µM are highly cytotoxic, with increased apoptosis and reduced migration. Cell death correlates with increased p53 and BAX, followed by arrest in G0/G1 phase, with elevated p21 levels, suggesting a time- and dose-dependent damage. An increase in H2AX phosphorylation was observed with 25 µM and 50 µM, while 1 µM was biocompatible. Keratinocytes showed less cytotoxic effect than fibroblasts. Induced cell damage was dose- and time-related, with less damage after chronic treatment. Further investigations are needed with longer time frames to evaluate CBD dose- and time-dependent effects to identify an effective therapeutic dose.

An evaluation of the Invisalign® Aligner Technique and consideration of the force system: a systematic review.

OBJECTIVE: Since its introduction 25 years ago, the Invisalign® system has undergone multiple digital and biomechanical evolutions and its effectiveness is often compared to traditional systems without considering the many differences which characterize them. The main aim of this systematic review is to look at the literature dealing with studies on teeth movements using the Invisalign® system and the management of these movements through digital planning and artificial intelligence. MATERIALS AND METHODS: The following electronic databases were searched: MEDLINE, Embase, the Cochrane Oral Health Group's Trials Register, and CENTRAL. Unpublished studies were searched on ClinicalTrials.gov, the National Research Register, and Pro-Quest Dissertation Abstracts and Thesis database. RESULTS: Twenty-four studies (15 retrospective, 5 prospective, 2 pilot, and 2 case-control) were included. The results of the analysis carried out on the available literature show that the Invisalign® system is recognized to be a valid alternative to conventional orthodontic treatment in no-extraction cases. The results are influenced by the methods for assessing the effectiveness of this technique and by the comparison bias of the traditional system with the innovative digital system. CONCLUSIONS: Since the introduction of SmartForce and SmartTrack material, the efficacy of the treatment has improved. There is still a shortage of high-quality evidence concerning the treatment modality. In order to make the treatment with the aligners more efficient, a correct management of the ClinCheck® software and a proper use of the biomechanics are necessary. The aligned force-driven system should be taken into account when developing the digital planning.

[Renal effects of sodium-glucose cotransporter 2 inhibitors in patients with cardiovascular disease with and without chronic kidney disease]. / Gli effetti renali degli inibitori del cotrasportatore sodio-glucosio di tipo 2 in pazienti con malattia cardiovascolare con e senza insufficienza renale cronica.

The kidney plays an important role in maintaining glucose homeostasis which is used as a metabolic substrate, generated through the mechanism of gluconeogenesis and reabsorbed in the glomerular filtrate through the action of sodium-glucose cotransporters 1 and 2 (SGLT1/2) located in the proximal tubule. Recent studies have shown that inhibition of renal glucose reabsorption, achieved through the administration of sodium-glucose cotransporter inhibitors, significantly reduces renal adverse events and exacerbations of heart failure, not only in diabetic patients, with and without confirmed cardiovascular damage, but also in patients with advanced chronic renal failure and in patients with heart failure with reduced ejection fraction regardless of the presence of diabetes. The extent of the benefit was relevant in the various clinical conditions studied, and led to a significant reduction in the major adverse cardiovascular outcomes recorded in each study. In all controlled studies, the efficacy of sodium-glucose cotransporter inhibitors was strongly associated with the reduction in progression of renal damage, as evidenced by the significant reduction in overall mortality obtained in the two studies that enrolled populations of diabetic and non-diabetic patients with advanced chronic renal failure. Both studies were stopped early at the interim analysis due to the evident superiority of the therapy in the treated arm.The purpose of this review is to examine the role of SGLT2/1 both in physiological conditions that in the course of cardio-nephropathy associated or not with type 2 diabetes mellitus and the effect of SGLT2/1 inhibition on clinical outcomes in different cardiovascular risk population enrolled in different randomized controlled clinical trials.

[The mechanisms mediating the favorable effects of sodium-glucose cotransporter 2 inhibitors on cardiorenal function]. / I meccanismi d'azione degli inibitori del cotrasportatore sodio-glucosio di tipo 2 ed i loro effetti benefici sull'assetto funzionale di cuore e rene.

In several clinical investigations performed in patients with type 2 diabetes mellitus and in diabetic and non-diabetic patients with heart failure or chronic kidney disease, sodium-glucose cotransporter 2 inhibitors (SGLT2i) proved their benefit on cardiac and renal adverse outcomes. Although there is clear evidence regarding the clinical benefits achieved, the pathophysiological mechanisms underlying their efficacy are still poorly understood. Some favorable mechanisms are likely related to the induced glycosuria and natriuresis. Both have been observed since the early stages of the molecule action and can drive beneficial hemodynamic changes, resulting in a decline of glomerular hyperfiltration and activation of the renin-angiotensin-aldosterone system. In addition to the improvement of cardiocirculatory regimen and renal performance, SGLT2i have an important role in cardio-renal protection by improving the metabolism of cardiomyocytes, carrying out anti-fibrotic and anti-inflammatory action and increasing the expression of cardio-protective adipokines. Further studies are needed to better understand the molecular mechanisms underlying the favorable effects of these drugs in diabetic and non-diabetic patients. The purpose of this review article is to analyze the molecular mechanisms underlying the cardiovascular benefits of SGLT2i in each of the main organs involved in the cardio-renal axis. Furthermore, the manuscript aims to analyze the extent of the beneficial effects of SGLT2i on heart failure in the different populations investigated in the most recent clinical studies.

In Vitro effects of alternative smoking devices on oral cells: Electronic cigarette and heated tobacco product versus tobacco smoke.

OBJECTIVE: To investigate the biological effects of electronic cigarette (e-cigarette) and heated tobacco product extracts respect to tobacco smoke extract on human gingival fibroblasts and human oral keratinocytes analysing cell viability, morphology, migration, apoptosis, cell cycle and epithelial-mesenchymal transition (EMT). DESIGN: Human gingival fibroblasts and human oral keratinocytes viability was analysed by MTT assay, cell morphology using scanning electron microscope (SEM) and cell migration by Scratch assay, a method that mimics the cell migration during wound healing in vivo. Apoptosis and cell cycle were analysed with flow cytometry and the related-gene expression of TP53, BCL2, CDKN2A and CDKN1A was indagated using real-time polymerase chain reaction. EMT process was analysed through expression of specific markers: CDH1, SNAI2, TWIST1, MMP2, FN1 and VIM. All investigations were evaluated after 24 h an in vitro exposure. RESULTS: Undiluted tobacco smoke extract induced significant inhibition of cell viability and cell migration, caused morphological alterations and induced an increase in cell death. No alterations or damage were observed after treatment with e-cigarette extracts. Heated tobacco product extract induced proliferation as highlighted by an increase of cell viability, cell migration and alterations of cycle analysis. CONCLUSIONS: Comparing the different cigarette extracts, tobacco smoke turns out to be the most harmful, e-cigarette did not determine morphological and functional alterations and heated tobacco product must be carefully investigated for its possible clinical effects on oral cell populations.

Estimating the 18-Year Threshold with Third Molars Radiographs in the Southern Italy Population: Accuracy and Reproducibility of Demirjian Method.

The estimation of the age of the majority of living subjects is widely required nowadays due to the presence of unidentifiable individuals, without documents and general information, involved in migration or legal procedures. Dental age estimation (DAE) is a valid method for investigating the age of subjects. The aim of this study was to evaluate the accuracy of the Demirjian method in a limited age group (16-24 years) in differentiating between older and younger than 18 years. From an initial sample of 17,594 radiographs, 460 were selected meeting the inclusion criteria. Two dentists provided the age estimate according to the Demirjian method, with a simplified approach based on the development of the third molars. The presence of a developmental stage of H for at least one third molar allowed to establish the major age if the other third molars, inferior or superior, have reached a stage equal or superior to F, with an accuracy of 90.2% and a predictive positive value of 91.6%. Thirty-three patients showed the development of at least one third molar (Stage H) before the age of 18 years while six patients showed the development of all four third molars with root completion (stage H) before the age of 18 years. When all third molars reached stage H an individual was over 18 years old in 97.4% of cases. In presence of one third molar on stage H and a stage equal or superior to F for the other third molars the probability of being of major age was 91.6%.

Mechanical properties of 3D-printed prosthetic materials compared with milled and conventional processing: A systematic review and meta-analysis of in vitro studies.

STATEMENT OF PROBLEM: Three-dimensional (3D) additive manufacturing (AM) is an evolving technology in dentistry, proposed as an alternative to subtractive milling manufacture (MM) or conventional processing. However, a systematic review of the use of AM technology instead of milling or conventional processing is lacking. PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate the mechanical properties of 3D-printed prosthetic materials compared with MM and conventional techniques. MATERIAL AND METHODS: An electronic search of the literature was conducted on the MEDLINE (via PubMed), Scopus, and Web of Science databases. The inclusion criteria were in vitro studies published in the last 5 years, in English or Italian, and with 3D AM printed dental prosthetic materials. Data extraction was focused on dental prosthetic materials (ceramics, polymers, and metals) and their mechanical properties: flexural strength, fracture load, hardness, roughness, removable partial denture (RPD) fit accuracy, trueness, marginal discrepancy, and internal fit. Data considered homogenous were subjected to meta-analysis using the Stata17 statistical software program (95% confidence interval [CI]; α=.05). Since all variables were continuous, the Hedge g measure was calculated. A fixed-effects model was used for I2=0%, while the statistical analysis was conducted using a random-effects model with I2>0%. RESULTS: From a total of 3624 articles, 2855 studies were selected, and 76 studies included after full-text reading. The roughness of AM-printed ceramics generally increased compared with that of conventional processing while the marginal discrepancy was comparable both for ceramics and polymers. The flexural strength, hardness, and fracture load of AM-printed polymers were statistically lower than those of the conventional group (P<.05). No significant difference was detected in terms of hardness, roughness, marginal discrepancy, fracture load, trueness, or internal fit between the AM and MM techniques (P>.05). Milling techniques showed significantly higher values of flexural strength (Hedge g=-3.88; 95% CI, -7.20 to -0.58; P=.02), also after aging (Hedge g=-3.29; 95% CI, -6.41 to -0.17; P=.04), compared with AM printing. CONCLUSIONS: AM is comparable with MM in terms of mechanical properties, in particular with polymeric materials. The flexural strength of AM-printed prostheses is lower than with conventional and MM techniques, as are the parameters of hardness and fracture load, while the marginal discrepancy is similar to that of MM and conventional techniques. AM prostheses are commonly used for interim crowns and fixed partial dentures, as their rigidity and fracture resistance cannot support mastication forces for extended periods. More comparative studies are needed.

Biological effects of cannabidiol on human cancer cells: Systematic review of the literature.

This systematic review examine the biological effects of CBD, a major component of therapeutic Cannabis, on human pathological and cancer cell populations of integumentary, gastro-intestinal, genital and breast, respiratory, nervous, haematopoietic and skeletal districts in terms of cell viability, proliferation, migration, apoptosis, inflammation, metastasis, and CBD receptor expression. The included studies were in English, on human cell lines and primary culture from non-healthy donors with CBD exposure as variable and no CBD exposure as control. Quality assessment was based on ToxRtool with a reliability score ranging from 15 to 18. Following the PRISMA statement 4 independent reviewers performed an electronic search using MEDLINE via PubMed, Scopus and Web of Science. From 3974 articles, 83 studies have been selected. Data showed conflicting results due to different concentration exposure, administrations and time points. CBD inhibited cell viability and proliferation in most cellular districts except the integumentary apparatus. Also a significant inhibition of migration was observed in all cell types, while an increase in apoptosis at both high and low doses (greater and less than 10 µM respectively). Considering inflammation, CBD caused an anti-inflammatory effect on nervous cells at low doses and on gastro-intestinal cells at high doses, while metastatic power was reduced even at low doses, but in a skeletal cell line there was an increased angiogenesis. CB1 receptor has been related to viability effects, CB2 to apoptosis and TRPV1 to inflammation and invasiveness. A detailed insight into these aspects would allow therapeutic use of this substance without possible side effects.

Systematic Review of the Literature on Dental Caries and Periodontal Disease in Socio-Economically Disadvantaged Individuals.

Dental caries and periodontal disease represent a health problem and a social cost for the entire population, and in particular for socio-economically disadvantaged individuals who are less resistant to disease. The aim of this review is to estimate the prevalence and severity of the two dental pathologies, caries and periodontal disease, in the different classes of socio-economically disadvantaged subjects and to understand which of them are most affected. A systematic search of the literature was performed in MEDLINE (via PubMed), EMBASE and Web of Science after establishing a suitable search strategy for each database, using keywords related to socio-economically vulnerable classes and health outcomes. Socio-economically disadvantaged individuals are more susceptible to tooth decay and periodontal disease (with relative tooth loss) than non-vulnerable people. Additionally, when multiple vulnerabilities are combined in the same subject, these oral diseases worsen. There is no type of vulnerability more affected by caries and periodontitis than others, since overall they all have severe disease indices. The data from this systematic literature review might be useful for health policy makers looking to allocate more resources and services to socially disadvantaged individuals, resulting in making them more resilient to oral disease due to their social marginalization.

Use of the Er:YAG Laser in Conservative Dentistry: Evaluation of the Microbial Population in Carious Lesions.

The aim of this study is to investigate the Erbium:Yttrio-Aluminum-Granate (Er:YAG) laser photothermal and mechanical effects on cariogenic species concentration and on the microbial load composition of therapeutic cavities, in order to evaluate the possible micro-organisms reduction and make a comparison with manual and rotating conventional therapy (CT). A clinical trial was designed, including adults with active deep carious lesions on permanent teeth who were divided into two groups, i.e., control group and intervention group treated with CT and Er:YAG therapy, respectively. Before and after any conservative treatment, two oral samples were collected using a small sterile microbrush scrubbed within the base of the dentinal cavity tissue. The percentage of reduction and the colony-forming units (CFUs) count after Er:YAG and conventional treatments were compared for total microorganisms, including Candida spp., Streptococcus spp., and Lactobacillus spp. The microbial reduction varied from 90.2% to 100% and was significantly observed for total microorganisms and Streptococcus spp. (p < 0.05). The Er:YAG laser shows the potential for clinical applications, especially with paediatric and complicated patients, thanks to its minimally invasive properties and its effect on the reduction of microbial load.

Heat-not-burn tobacco (IQOS), oral fibroblasts and keratinocytes: cytotoxicity, morphological analysis, apoptosis and cellular cycle. An in vitro study.

OBJECTIVES: The aim of this work is to investigate the biological effects of IQOS smoking on human gingival fibroblasts and human keratinocytes analysing cell viability, morphology, migration, apoptosis and cell cycle. BACKGROUND: Electronic cigarettes and tobacco heating systems have been marketed to reduce smoking damages caused by combustion. METHODS: Human gingival fibroblasts and human keratinocytes viability was determined by a colorimetric assay measuring mitochondrial dehydrogenase activity (MTT assay); after an in vitro exposure of 24 h, cell morphology was analysed with scanning electron microscope and cell migration was tested by Scratch assay, a method to mimic the migration of the cells during wound healing in vivo. Apoptosis and cell cycle were analysed with flow cytometry, and the expression of related genes (p53, Bcl2, p16 and p21) was indagated using real-time polymerase chain reaction. RESULTS: IQOS extracts increased both cell viability (23%-41% with fibroblasts and 30%-79% with keratinocytes) and migration. No morphological alterations were observed. IQOS extracts did not induced an increase in cell death, but rose the number of S- and G2/M-phase cells. IQOS extracts also significantly increased p53 expression by fibroblasts (undiluted and 6.25% dilution, 2- and 3.6-fold higher, respectively) and reduced both Bcl2 (about two- and fivefold, respectively) and p21 expressions (about twofold with both extracts), while on keratinocytes both undiluted and 6.25% dilution extracts increased Bcl2 expression (about four- and threefold higher, respectively) and reduced p53 expression (about two- and fivefold, respectively). CONCLUSION: IQOS smoke seemed to induce proliferation as highlighted by a viability assay, and migration and cell cycle analysis. The increased cell proliferation induced by IQOS devices must be carefully investigated for its possible clinical effects on oral cell populations.

Bio-mechanical characterization of a CAD/CAM PMMA resin for digital removable prostheses.

OBJECTIVE: To compare the mechanical and biological features of a polymethylmethacrylate (PMMA) disc for CAD/CAM prostheses (test samples, TG) with a traditional resin (control samples, CG). METHODS: Mechanical analysis was performed using Dynamic Mechanical Analysis (DMA) and Brillouin's micro-spectroscopy. Human keratinocyte morphology and adhesion were analyzed by scanning electronic microscopy (SEM), cytotoxicity by the MTT assay, apoptosis by flow cytometry and p53, p21 and bcl2 gene expression by real time PCR. RESULTS: TG exhibited a higher elastic modulus than CG (range 5100-5500 ± 114.3 MPa vs 3000-3300 ± 99.97 MPa). The Brillouin frequency was found at ωB= (15.50 ± 0.05) GHz for TG and at ωB_1 = (15.50 ± 0.05) GHz and ωB_2 = (15.0 ± 0.1) GHz for CG where two peaks were always present independently of the sample point. SEM analysis revealed that keratinocytes on TG disks appeared to be flattened with lamellipodia. Keratinocytes on CG disks rose above the substrate with cytoplasmatic filaments. MTT viability data at 3 h and 24 h showed TG was significantly less cytotoxic than CG (p < 0.001). No significant differences emerged in apoptosis on CG and TG. Real-time PCR showed p53 expression increased after 3 h by about 9-fold in keratinocytes on TG (p < 0.001) and about 5-fold in those on CG (p < 0.001). High p53 expression persisted after 24 h on both disks. No significant variations were observed in p21 and bcl2 expression at any time-point. SIGNIFICANCE: PMMA resins, as used in CAD/CAM technology, displayed suitable biocompatible and mechanical properties for removable prostheses.

Morpho-functional effects of different universal dental adhesives on human gingival fibroblasts: an in vitro study.

To analyze the effects of four universal adhesives (Optibond Solo Plus-OB, Universal Bond-UB, Prime&Bond Active-PBA, FuturaBond M + -FB) on human gingival fibroblasts in terms of cytotoxicity, morphology and function. After in vitro exposure for up to 48 h, fibroblast viability was determined by the MTT assay determined, morphology by phase-contrast microscopy and migration by the scratch wound assay. Expression levels of IL1ß, IL6, IL8, IL10, TNFα and VEGF genes were assessed by RT-PCR and their protein production by Western blot analysis. Apoptosis and cell cycle were analyzed by flow cytometry. OB and UB induced early morphological changes on fibroblasts (3 h) with extended cell death at 24 h/48 h. Gene expression of collagen type I and fibronectin increased fivefold compared with controls, elastin disappeared and elastase increased threefold, indicating gingival tissue tended to become fibrotic. Only UB and OB increased gene expression of inflammatory markers: IL1ß at 3 and 48 h (up to about three times), IL6 and IL8 at 3 h (up to almost four times) which corresponded to the increase of the activated form NF-kB. All adhesives showed an effect on the functionality of fibroblasts with cytotoxic effect time and concentration dependent. Among all the OB and UB adhesives, they showed the greatest cell damage. The in-depth analysis of the effects of universal adhesives and possible functional effects represents an important information for the clinician towards choosing the most suitable adhesive system.

Biological effects of Cannabidiol on normal human healthy cell populations: Systematic review of the literature.

A systematic review was performed to evaluate the biological effects of Cannabidiol (CBD), one of the major components of Cannabis Sativa, on normal human healthy cell populations in terms of cell viability, proliferation, migration, apoptosis and inflammation. Inclusion criteria were: studies on cell lines and primary cell culture from healthy donors, CBD exposure as variable, no CBD exposure as control and published in English language. Quality assessment was based on ToxR tool, with a score of reliability ranging from 15 to 18.Following the PRISMA statement, three independent reviewers performed both a manual and an electronic search using MEDLINE via PubMed, Scopus, Web of Science and Cochrane. From a total of 9437eligible articles, 29 studies have been selected. The average quality assessment score was 16.48.Theresults showed heterogeneous CBD concentration exposure (0.01-50 µM or 0.1 nmol/mL-15 mg/mL). The definition of a threshold limit would allow the identification of specific effects on expected outcomes. From the data obtained CBD resulted to inhibit cell viability in a dose-dependent manner above 2 µM, while in oral cell populations the inhibitory concentration is higher than 10 µM. Moreover, it was observed a significantly inhibition of cell migration and proliferation. On the contrary, it was highlighted a stimulation of apoptosis only at high doses (from 10 µM).Finally, CBD produced an anti-inflammatory effect, with a reduction of the pro-inflammatory cytokine gene expression and secretion. CBD down-regulated ROS production, although at high concentrations (16 µM) increased ROS-related genes expression. The diffusion of CBD for therapeutic and recreational uses require a precise definition of its potential biological effects. A thorough knowledge of these aspects would allow a safe use of this substance without any possible side effects.

A new pressure guided management tool for epidural space detection: feasibility assessment in a clinical scenario.

BACKGROUND: The detection of epidural space is usually performed by the technique of loss of resistance (LOR) without technological support, although there are few commercial options. In this work, we aimed to assess the feasibility of a new, non-invasive, mechatronic system for LOR detection in clinical settings. The system allows monitoring the pressure exerted on the syringe plunger by the clinician during the puncture. The LOR is related to the mentioned pressure. METHODS: Pressure exerted on the syringe plunger by an expert anesthesiologist was monitored using the proposed system. 58 epidural punctures were performed on 34 patients using six configurations with different sensitivities and ranges of measurements. The system capability in LOR detection was evaluated comparing the LOR detected by the system with the feedback provided by the clinician. The procedure time was estimated using the system and without its use. RESULTS: The detection of LOR is strongly related to the system configuration; it ranged from 93.3% to 27.7%, while 3 configurations never detected it. The procedure time showed a non-significant increase (p=0.56) using the proposed system (average time 71 s vs. 62 s). CONCLUSIONS: The proposed mechatronic system successfully detected the LOR in the large part of cases using the configurations characterized by the best trade-off between system sensitivity and range of measurements. A non-significant increment of the procedure time is related to the use of the system.

Personalized group cognitive behavioural therapy for obesity: a longitudinal study in a real-world clinical setting.

PURPOSE: Severe obesity is difficult to treat, and non-surgical treatment is not supported by robust evidence. The aim of the present study was to establish the immediate and longer-term outcomes following "personalized" form of group cognitive behavioural therapy for obesity (CBT-OB)-a new treatment designed to address specific cognitive processes that have been associated with attrition, weight loss, and weight maintenance in previous studies. METHODS: Sixty-seven adult patients with obesity (body mass index (BMI) ≥ 30 kg/m2) were recruited from consecutive referrals to an Italian National Health Service obesity clinic. Each patient was offered 22 group sessions of CBT-OB (14 in the 6-month weight-loss phase and 8 in the subsequent 12-month weight-maintenance phase). RESULTS: 76.2% patients completed the treatment, with an average weight loss of 11.5% after 6 months (10% in the intention-to-treat analysis) and 9.9% (7.5% in the intention-to-treat analysis) after 18 months. Weight loss was associated with a significant reduction in cardiovascular risk factors, anxiety, depression, and eating disorder psychopathology, and an improvement in obesity-related quality of life. CONCLUSIONS: These findings provide strong preliminary support for the use of CBT-OB for obesity in standard clinical settings, and justify its further evaluation in randomized controlled trials. LEVEL OF EVIDENCE: Level III, longitudinal cohort study.

Injection pressures measuring for a safe peripheral nerve block.

The performance of a precise and safe peripheral nerve blockade (PNB) can currently rely on the aid of the ultrasounds and nerve stimulators. The injection pressure monitoring may be beneficial to perform a safer procedure. This review focuses on the pressures measured during PNB among studies conducted on animal, and human models. From a deep research among the PubMed/MEDLINE database for all reports published in English between January 2004 and November 2018, we selected 15 original papers. We excluded those that were reviews, case-reports, recommendations and correspondences, that did not match with object of our study. We highlighted the available systems for monitoring injection pressures and classified the reports on the basis of the model used for the respective study (animals, humans, in vitro). Intraneural injections were associated with lower pressures than perineural ones. High injection pressures registered at the needle tip were associated with an increased risk of nerve damage. To date, a precise cut-off pressure value has not yet emerged from the literature for a safe PNBs, but based on the recent literature, it can be stated that the threshold of 15 psi is an acceptable value under which a perineural injection can be performed during a PNB to achieve a safer procedure. So it is desirable to make further studies in order to assess them. In the future, the monitoring of the pressure could allow the use of a minimal quantity of anesthetic, empowering the safety of the nerve blocks. Moreover, the sensitive system should not be invasive and it should not hinder the job of the anesthetists.

Constitutive STAT3 activation in epidermal keratinocytes enhances cell clonogenicity and favours spontaneous immortalization by opposing differentiation and senescence checkpoints.

STAT3, a pleiotropic transcription factor acting downstream of cytokines and growth factors, is known to enhance proliferation, migration, invasion and aerobic glycolysis in tumors upon aberrant activation. In the murine epidermis, STAT3 is necessary for experimentally induced carcinogenesis. Skin tumorigenesis is conversely enhanced by overexpression in keratinocytes of the constitutively active STAT3C mutant, which also induces robust, psoriasis-like epidermal hyperplasia. We show here that STAT3C expression at physiological levels in knock-in mice leads to mild epidermal hyperplasia and attenuated expression of terminal differentiation markers. Altered differentiation is confirmed in isolated primary epidermal keratinocytes in vitro, correlating with enhanced proliferative and clonogenic potential, attenuated senescence and, strikingly, high-frequency spontaneous immortalization. These results suggest that moderate levels of continuous STAT3 activation, which closely resemble those triggered by chronic inflammation or persistent growth factor stimulation, may establish a preneoplastic state in part by promoting the escape of epidermal progenitor cells from differentiation and senescence checkpoints.