Oral Adverse Events Associated with BRAF and MEK Inhibitors in Melanoma Treatment: A Narrative Literature Review.

BACKGROUND: Melanoma cancer represents the most lethal type of skin cancer originating from the malignant transformation of melanocyte cells. Almost 50% of melanomas show the activation of BRAF mutations. The identification and characterization of BRAF mutations led to the development of specific drugs that radically changed the therapeutic approach to melanoma. METHODS: We conducted a narrative review of the literature according to a written protocol before conducting the study. This article is based on previously conducted studies. We identified articles by searching electronic databases (Medline, Google Scholar and PubMed). We used a combination of "melanoma", "Braf-Mek inhibitors", " targeted therapy" and "oral side effects". RESULTS: Eighteen studies were reported in this article showing the relationship between the use of targeted therapy in melanoma cancer and the development of oral side effects, such as mucositis, hyperkeratosis and cellular proliferation. CONCLUSION: Targeted therapy plays an important role in the treatment of melanoma cancer, showing a notable increase in response rate, prolonged progression-free survival and overall survival in BRAF-mutated melanoma patients. Oral side effects represent a common finding over the course of treatment. However, these adverse effects can be easily managed in a multidisciplinary approach involving collaboration between medical oncologists and dental doctors.

The network structure of psychopathological and resilient responses to the pandemic: A multicountry general population study of depression and anxiety.

Commonly identified patterns of psychological distress in response to adverse events are characterized by resilience (i.e., little to no distress), delayed (i.e., distress that increases over time), recovery (i.e., distress followed by a gradual decrease over time), and sustained (i.e., distress remaining stable over time). This study aimed to examine these response patterns during the COVID-19 pandemic. Anxiety and depressive symptom data collected across four European countries over the first year of the pandemic were analyzed (N = 3,594). Participants were first categorized into groups based on the four described patterns. Network connectivity and symptom clustering were then estimated for each group and compared. Two thirds (63.6%) of the sample displayed a resilience pattern. The sustained distress network (16.3%) showed higher connectivity than the recovery network (10.0%) group, p = .031; however, the resilient network showed higher connectivity than the delayed network (10.1%) group, p = .016. Regarding symptom clustering, more clusters emerged in the recovery network (i.e., three) than the sustained network (i.e., two). These results replicate findings that resilience was the most common mental health pattern over the first pandemic year. Moreover, they suggest that high network connectivity may be indicative of a stable mental health response over time, whereas fewer clusters may be indicative of a sustained distress pattern. Although exploratory, the network perspective provides a useful tool for examining the complexity of psychological responses to adverse events and, if replicated, could be useful in identifying indicators of protection against or vulnerability to future psychological distress.

Moral reasoning behind the veil of ignorance: An investigation into perspective-taking accessibility in the context of autonomous vehicles.

Perspective-taking (PT) accessibility has been recognized as an important factor in affecting moral reasoning, also playing a non-trivial role in moral investigation towards autonomous vehicles (AVs). A new proposal to deepen this effect leverages the principles of the veil of ignorance (VOI), as a moral reasoning device aimed to control self-interested decisions by limiting the access to specific perspectives and to potentially biased information. Throughout two studies, we deepen the role of VOI reasoning in the moral perception of AVs, disclosing personal and contingent information progressively throughout the experiment. With the use of the moral trilemma paradigm, two different VOI conditions were operationalized, inspired by the Original Position theory by John Rawls and the Equiprobability Model by John Harsanyi. Evidence suggests a significant role of VOI reasoning in affecting moral reasoning, which seems not independent from the order in which information is revealed. Coherently, a detrimental effect of self-involvement on utilitarian behaviours was detected. These results highlight the importance of considering PT accessibility and self-involvement when investigating moral attitudes towards AVs, since it can help the intelligibility of general concerns and hesitations towards this new technology.

Early time-course of respiratory mechanics, mechanical power and gas exchange in ARDS patients.

PURPOSE: To describe the clinical course of ARDS during the first three days of mechanical ventilation, to compare ventilatory setting, respiratory mechanics and gas exchange variables collected during the first three days of mechanical ventilation between patients who survived and died during intensive care unit (ICU) stay and to investigate the variables associated with mortality at ICU admission and throughout the first three days of mechanical ventilation. MATERIALS AND METHODS: Prospective observational study. Mechanically ventilated ARDS patients were studied at ICU admission and for the following three days. Univariate logistic regression models were performed for PaO2/FiO2 ratio, driving pressure and alveolar dead space fraction and for mechanical power and mechanical power ratio. RESULTS: Mechanical power ratio was higher in non survivors at ICU admission and over time; PaO2/FiO2 ratio was higher in survivors with a similar behavior over time in the two groups while alveolar dead space fraction was similar at ICU admission and over time between groups. Mechanical power ratio was the only physiological variable which remained consistently associated with ICU mortality throughout the study. CONCLUSIONS: The alteration in oxygenation, dead space, and mechanical power ratio should be assessed not at intensive care admission, but during the first days of mechanical ventilation to better predict outcome.

Treatment of Ankyloglossia: A Review.

AIM: The aim of this narrative review is to analyze and compare the current scientific evidence regarding the diagnosis and treatment of hypertrophic lingual frenulum in preschool and school-age children. The treatments considered in this review are traditional surgical therapy, laser-assisted surgical therapy, and functional rehabilitation therapy. MATERIALS AND METHODS: A comprehensive literature review was conducted using the PubMed and PubMed Central search engines, considering articles published in the English language between 1 January 2000 and 30 June 2022. The bibliographic search was performed using the following keywords as search strings: "lingual", "frenulectomy", "frenulotomy", "frenulum", "ankyloglossia", and "laser." RESULTS: A total of 14 articles were included in this review, including four prospective observational studies, one case-control study, three cross-sectional studies, four retrospective studies, and one randomized controlled trial. The data extracted from each article are summarized in a table. CONCLUSIONS: In the literature, there are still limited studies regarding the treatment of hypertrophic frenulum. No common indications for the treatment of ankyloglossia and universally used classification for lingual frenulum were found. Currently, clinicians prefer the use of a diode laser for treatment. This method offers several advantages over the use of a scalpel blade. Many studies agree on the usefulness of providing patients with myofunctional rehabilitation to improve lingual mobility, both prior to surgical therapy and in the postoperative period.

Statistical Comparison of Substructures in Pure Aluminum Before and After Creep Deformation, Based on EBSD Image Data.

Electron backscatter diffraction (EBSD) images of extruded pure aluminum were statistically analyzed to investigate creep-induced subgrain structures after applying two different levels of creep stress, corresponding to the power law (PL) and power-law breakdown (PLB) regimes. Kernel average misorientation analysis of EBSD measurements revealed 2D morphologies, which were subdivided by a multi-step segmentation procedure into subgranular arrangements. Various descriptors were employed to characterize the "subgrains" quantitatively, including their size, shape, spatial arrangement, and crystallographic orientation. In particular, the analysis of the orientations of subgrains was conducted by neglecting rotations around the loading axis. This approach facilitated the individual investigation of the {001} and {111} subgrain families with respect to the loading axis for two investigated stress levels plus a reference specimen. For the PL regime, the statistical analysis of subgrain descriptors computed from segmented image data revealed a similar degree of strain accumulation for {111} and {001} subgrains. In contrast, for the PLB regime, the analyzed descriptors indicate that {111} subgrains tend to accumulate significantly more strain than {001} ones. These observations suggest that the mechanisms leading to PLB may be associated with strain localization dependent on intergranular stress, hindering the recovery process within {111} grains.

Understanding the hot isostatic pressing effectiveness of laser powder bed fusion Ti-6Al-4V by in-situ X-ray imaging and diffraction experiments.

In the present study, in-situ observation of Hot Isostatic Pressure (HIP) procedure of laser powder bed fusion manufactured Ti-6Al-4V parts was performed to quantitatively estimate the densification rate of the material and the influence of the defect initial size and shape on such rate. The observations were performed in-situ using the Ultrafast Tomography Paris-Edinburgh Cell and the combination of fast phase-contrast synchrotron X-ray tomography and energy dispersive diffraction. With this strategy, we could quantify how the effectiveness of HIP depends on the characteristics of a defect. Smaller defects showed a higher densification rate, while the defect shape did not have significant effect on such rate.

A new Bayesian procedure for the estimation of the referees' decision thresholds and agreement. The case of professional handball refereeing.

In double refereeing, agreement between referees is fundamental for the achievement of a flawless and smooth refereeing activity. Nonetheless, the agreeement can be affected by several external and internal factors, with a negative impact on the consistency of the refereeing and the fluidity of the game. The referee's Decision Threshold (DT) is the limit above which the evidence of a foul results in the call of an infraction by the referee. It represents the individual refereeing style, and it is one of the factors that can contribute to low agreement between the referees. We present an application of a new Bayesian procedure to estimate referee's DT in a typical refereeing task. To this end, 56 italian professional handball (FIGH) referees were asked to evaluate 96 potential foul plays, belonging to four different infraction types: 7-m throw, passive play, offensive foul, disciplinary sanctions. The proposed method provides information about: (i) referee's individual DT; (ii) the agreement between pairs of referees (i.e., one-to-one); (iii) the agreement between each referee and all the other referees (i.e., one-to-total); (iv) the agreement between each referee and a reference referee (i.e., one-to-expert); (v) the proportion of agreement between the referees and a reference referee for each potential foul play. Sport federations would profit by this procedure in different ways: by using the information about the DT to train referees, by detecting referees with a low agreement with their colleagues or with the reference referee, by focusing training on specific plays to improve the arbitration class internal consistency.

New Potential Biological Limiters of the Main Esca-Associated Fungi in Grapevine.

The strains Trichoderma harzianum TH07.1-NC (TH), Aphanocladium album MX95 (AA), Pleurotus eryngii AL142PE (PE) and Pleurotus ostreatus ALPO (PO) were tested as biological limiters against Fomitiporia mediterranea Fme22.12 (FM), Phaeoacremonium minimum Pm22.53 (PM) and Phaeomoniella chlamydospora Pc22.65 (PC). Pathogens were obtained from naturally Esca-affected 'Nero di Troia' vines cropped in Grumo Appula (Puglia region, Southern Italy). The antagonistic activity of each challenge organism was verified in a dual culture. TH and PO completely overgrew the three pathogens. Partial replacement characterized PE-FM, PE-PM, PE-PC and AA-PC interactions. Deadlock at mycelial contact was observed in AA-FM and AA-PM cultures. The calculated antagonism index (AI) indicated TH and PE as moderately active antagonists (10 < AI < 15), while AA and PO were weakly active (AI < 10). The maximum value of the re-isolation index (s) was associated with deadlock among AA-PM, AA-PC and PE-FM dual cultures. The tested biological limiters were always re-isolated when PO and TH completely replaced the three tested pathogens. TH and AA confirmed their efficiencies as biological limiters when inoculated on detached canes of 'Nero di Troia' in dual combination with FM, PC and PM. Nevertheless, additional experiments should be performed for a solid conclusion, along with validation experiments in the field.

Texture-based residual stress analysis of laser powder bed fused Inconel 718 parts.

Although layer-based additive manufacturing methods such as laser powder bed fusion (PBF-LB) offer an immense geometrical freedom in design, they are typically subject to a build-up of internal stress (i.e. thermal stress) during manufacturing. As a consequence, significant residual stress (RS) is retained in the final part as a footprint of these internal stresses. Furthermore, localized melting and solidification inherently induce columnar-type grain growth accompanied by crystallographic texture. Although diffraction-based methods are commonly used to determine the RS distribution in PBF-LB parts, such features pose metrological challenges in their application. In theory, preferred grain orientation invalidates the hypothesis of isotropic material behavior underlying the common methods to determine RS. In this work, more refined methods are employed to determine RS in PBF-LB/M/IN718 prisms, based on crystallographic texture data. In fact, the employment of direction-dependent elastic constants (i.e. stress factors) for the calculation of RS results in insignificant differences from conventional approaches based on the hypothesis of isotropic mechanical properties. It can be concluded that this result is directly linked to the fact that the {311} lattice planes typically used for RS analysis in nickel-based alloys have high multiplicity and less strong texture intensities compared with other lattice planes. It is also found that the length of the laser scan vectors determines the surface RS distribution in prisms prior to their removal from the baseplate. On removal from the baseplate the surface RS considerably relaxes and/or redistributes; a combination of the geometry and the scanning strategy dictates the sub-surface RS distribution.

Assessment Methods for Marginal and Internal Fit of Partial Crown Restorations: A Systematic Review.

BACKGROUND: Different methods are used for the analysis of marginal and internal fit of partial crowns, but not all of them are applicable for in vivo studies. The aim of this review is to search the available methods, described in the current literature, to assess marginal and internal fit in partial crowns. METHODS: an electronic search was performed on Pubmed and Web of Science databases to find studies published from 1 January 2017 up to 2 March 2023, following PRISMA guidelines and Cochrane handbook for systematic reviews. The search strategy applied was: "(marginal) AND (fit OR gap OR adaptation OR discrepancy) AND (inlay OR onlay OR partial crown)". In vitro studies which evaluated marginal and internal fit on CAD CAM or 3D printed partial crowns were included in this review. Quality of the studies was assessed by using Quality Assessment Tool For In Vitro Studies (QUIN tool). RESULTS: 22 studies were included. Among conventional methods, direct view with microscope, indirect view on resin replicas, and silicone replica technique (SRT) were used. Considering new digital methods, micro-CT, SRT 3D and triple scan technique (TST) were applied. CONCLUSIONS: Among 2D methods, direct view technique is the most used marginal fit analysis. For a more comprehensive evaluation, a 3D digital analysis is suggested. SRT and indirect view are the only 2D methods available for in vivo analysis. A protocol for the application of TST for assessment in vivo is now available, but no studies are reported in literature yet.

Management of the Pediatric Patient with Suspected Diagnosis of Obstructive Sleep Apnea Syndrome.

AIM: The aim of this paper is to describe the multidisciplinary management pathway for pediatric patients with suspected obstructive sleep apnea syndrome (OSAS) conducted by the Pediatric and Orthodontic Department of the Dental Clinic of Padua. MATERIALS AND METHODS: All pediatric subjects undergo a comprehensive medical history, including the completion of the Pediatric Sleep Questionnaire (PSQ), and a physical examination. Patients with suspected OSAS are placed on a waiting list for home respiratory polygraphy testing. The respiratory polygraphy examination is conducted over two consecutive nights and interpreted by a neurologist. Additionally, patients diagnosed with OSAS undergo a case study involving intraoral and extraoral photography, as well as radiographic evaluation. RESULTS: Between September 2021 and May 2023, a total of 134 subjects (including 76 males), with an average age of 9.2 years, were identified as diagnostic suspects. Among these, 38 patients (28.3%) tested positive based on respiratory polygraphic results. Depending on the severity and etiopathogenetic characteristics of the disease, the positive cases were referred to various specialists. CONCLUSION: In the daily clinical practice of dentistry, particularly in orthodontics and pedodontics, the establishment of a defined management pathway for pediatric patients with OSAS is crucial. The collaboration of a multidisciplinary team with a shared objective of achieving accurate diagnosis and implementing targeted treatment in a timely manner is essential. Regular re-evaluation of patients through clinical and instrumental examinations is recommended.

On the dependence of creep-induced dislocation configurations on crystallographic orientation in pure Al and Al-Mg.

The peak broadening in neutron diffraction experiments on tensile specimens of pure Al (99.8%) and an Al-Mg alloy pre-deformed at different creep strains is analysed. These results are combined with the kernel angular misorientation of electron backscatter diffraction data from the creep-deformed microstructures. It is found that differently oriented grains possess different microstrains. These microstrains vary with creep strain in pure Al, but not in the Al-Mg alloy. It is proposed that this behaviour can explain the power-law breakdown in pure Al and the large creep strain observed in Al-Mg. The present findings further corroborate a description of the creep-induced dislocation structure as a fractal, predicated on previous work.

Chitinolytic Enzymes of the Hyperparasite Fungus Aphanocladium album: Genome-Wide Survey and Characterization of A Selected Enzyme.

The filamentous fungus Aphanocladium album is known as a hyperparasite of plant pathogenic fungi; hence, it has been studied as a possible agent for plant protection. Chitinases secreted by A. album have proven to be essential for its fungicidal activity. However, no complete analysis of the A. album chitinase assortment has been carried out, nor have any of its chitinases been characterized yet. In this study, we report the first draft assembly of the genome sequence of A. album (strain MX-95). The in silico functional annotation of the genome allowed the identification of 46 genes encoding chitinolytic enzymes of the GH18 (26 genes), GH20 (8 genes), GH75 (8 genes), and GH3 (4 genes) families. The encoded proteins were investigated by comparative and phylogenetic analysis, allowing clustering in different subgroups. A. album chitinases were also characterized according to the presence of different functional protein domains (carbohydrate-binding modules and catalytic domains) providing the first complete description of the chitinase repertoire of A. album. A single chitinase gene was then selected for complete functional characterization. The encoded protein was expressed in the yeast Pichia pastoris, and its activity was assayed under different conditions of temperature and pH and with different substrates. It was found that the enzyme acts mainly as a chitobiosidase, with higher activity in the 37-50 °C range.

Correlation between Malocclusions, Tonsillar Grading and Mallampati Modified Scale: A Retrospective Observational Study.

AIM: to investigate the correlation between growth tendency and different patient malocclusion, tonsillar grading, and tongue size (Mallampati index). MATERIALS AND METHODS: The sample is composed of 64 males and 40 females; patients aged between 6 and 16 years (median age 11 years, IQR 9-13) were included. The final sample is therefore 104 patients. After the first orthodontic visit, all the children underwent a collection of documentation (photographs, digital arch models, and X-rays). Patients were classified according to their malocclusion, palatal conformation, tonsillar grading, and Mallampati index. Group comparisons were performed using Fisher's test. A p-value less than 0.05 was considered statistically significant. RESULTS: The narrow palate was more frequent in those with Angle class III (p = 0.04), while the other variables considered (tonsillar grading, Mallampati, and lingual frenulum) were not significantly associated with dental class (p > 0.05). Furthermore, a different distribution of tonsillar grading was observed between subjects with normal palate and subjects with narrow palate, while no statistically significant association was found between the palatal shape and Mallampati index (p = 0.88). CONCLUSIONS: This study found that children with higher tonsillar grading had a higher prevalence of crossbite or narrow palate compared to other children at the same developmental stage. However, we did not observe any association between tonsil hyperplasia and the prevalence of class II malocclusion, anterior open bite, or patient divergence in this sample. Furthermore, no correlation was found between the Mallampati index and patients' dental class, narrow palate, or divergence in this study.

Comparison of microbiological profile of enterotoxigenic Bacteroides fragilis (ETBF) isolates from subjects with colorectal cancer (CRC) or intestinal pre-cancerous lesions versus healthy individuals and evaluation of environmental factors involved in intestinal dysbiosis.

OBJECTIVE: The aim of this study was to analyze enterotoxigenic Bacteroides fragilis (ETBF) isolates from colorectal biopsies of subjects with a histological analysis positive for colorectal cancer (CRC), pre-cancerous lesions (pre-CRC) or with a healthy intestinal tissue and to evaluate the environmental factors that may not only concur to CRC development but may also affect gut microbiota composition. METHODS: ETBF isolates were typed using the ERIC-PCR method, while PCR assays were performed to investigate the bft alleles, the B. fragilis pathogenicity island (BFPAI) region and the cepA, cfiA and cfxA genes. Susceptibility to antibiotics was tested using the agar dilution method. Environmental factors that could play a role in promoting intestinal dysbiosis were evaluated throughout a questionnaire administered to the subjects enrolled. RESULTS: Six different ERIC-PCR types were identified. The type denominated C in this study was the most prevalent, in particular among the biopsies of subjects with pre-CRC, while an isolate belonging to a different type, denominated F, was detected in a biopsy from a subject with CRC. All the ETBF isolates from pre-CRC or CRC subjects had a B. fragilis pathogenicity island (BFPAI) region pattern I, while those from healthy individuals showed also different patterns. Furthermore, 71% of isolates from subjects with pre-CRC or CRC were resistant to two or more classes of antibiotics vs 43% of isolates from healthy individuals. The B. fragilis toxin BFT1 was the most frequently detected in this study, confirming the constant circulation of this isoform strains in Italy. Interestingly, BFT1 was found in 86% of the ETBF isolates from patients with CRC or pre-CRC, while the BFT2 was prevalent among the ETBF isolates from healthy subjects. No substantial differences based on sex, age, tobacco and alcohol consumption were observed between healthy and non-healthy individuals included in this study, while most of the subjects with CRC or pre-CRC lesions were subjected to pharmacological therapy (71%) and showed a body mass index (BMI) that falls within the overweight range (86%). CONCLUSIONS: Our data suggest that some types of ETBF seem to better adapt and colonize the human gut and that the selective pressure exerted by factors related to lifestyle, such as pharmacological therapy and weight, could facilitate their persistence in the gut and their possible involvement in CRC development.

A New Validation of Montreal Cognitive Assessment on a Large Sample of Elderly Patients Undergoing Elective Orthopedic Surgery.

Objective: The hip and knee arthroplasties are reliable and suitable surgical procedures aimed at restoring the patients' functioning. The most representative age range for these replacement surgeries is between 65 and 84 years for females. With aging, the likelihood of developing cognitive deficits increases, and there is evidence that elderly patients undergoing surgery orthopedic are at higher risk of developing cognitive problems in the postoperative phase. The Montreal Cognitive Assessment (MoCA) is often used for cognitive evaluation, but different cut-offs and validations are available in the literature. Given the importance of the problem, in this work we studied a hospitalized population candidate for orthopedic surgery to determine a new specific validation of the MoCA to assess the risk of MCI. Method: We applied MoCA and Mini-Mental State Examination (MMSE) to a sample of 492 (333 women) hospitalized patients for knee (74%) or hip surgery. A non-parametric receiver operating characteristic (ROC) curve analysis was conducted to investigate the predictive accuracy of the MoCA to assess cognitive impairment, using MMSE as the gold standard. Results: A score of 22.52 gives a sensitivity of 70% and a specificity of 78%. This value is providing a more coherent diagnosis with the MMSE as compared to the other cut-offs presented in the other available validations. No differences were found between patients in terms of age and gender, suggesting a general uniformity of the selected sample. Conclusions: Deepening the coherence in MCI diagnosis between MMSE and the other MoCA's scoring considered, our new cut-off seems reasonably better than previous Italian validation on an elderly population in matching MMSE classification.

Pain during Rapid Maxillary Expansion: A Systematic Review.

AIM: The aim of the present systematic review is to evaluate the pain perceived by patients during rapid maxillary expansion (RME) in relation to factors such as demographic characteristics, appliance type, activation protocol, and the eventual use of medication or pain management strategies. MATERIALS AND METHODS: An electronic search of available articles on the subject was conducted on three electronic databases, using predefined keywords. Sequential screenings based on pre-established eligibility criteria were performed. RESULTS: Ten studies were ultimately included in this systematic review. The main data of the reviewed studies were extracted according to the PICOS approach. CONCLUSIONS: Pain is a common effect of RME treatment that tends to decrease over time. Gender and age differences in pain perception are not clear. Perceived pain is influenced by the expander design and expansion protocol used. Some pain management strategies can be useful for reducing RME-associated pain.

Influence of New Technology in Dental Care: A Public Health Perspective.

The advent of new technology has caused significant changes in the field of dentistry, enabling dentists and orthodontists to provide more efficient and effective treatments to their patients [...].