Lack of p38 activation in T cells increases IL-35 and protects against obesity by promoting thermogenesis.

Obesity is characterized by low-grade inflammation, energy imbalance and impaired thermogenesis. The role of regulatory T cells (Treg) in inflammation-mediated maladaptive thermogenesis is not well established. Here, we find that the p38 pathway is a key regulator of T cell-mediated adipose tissue (AT) inflammation and browning. Mice with T cells specifically lacking the p38 activators MKK3/6 are protected against diet-induced obesity, leading to an improved metabolic profile, increased browning, and enhanced thermogenesis. We identify IL-35 as a driver of adipocyte thermogenic program through the ATF2/UCP1/FGF21 pathway. IL-35 limits CD8+ T cell infiltration and inflammation in AT. Interestingly, we find that IL-35 levels are reduced in visceral fat from obese patients. Mechanistically, we demonstrate that p38 controls the expression of IL-35 in human and mouse Treg cells through mTOR pathway activation. Our findings highlight p38 signaling as a molecular orchestrator of AT T cell accumulation and function.

p38γ is essential for cell cycle progression and liver tumorigenesis.

The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)-cyclin protein complex1. However, control of the G0-to-G1 transition is not completely understood. Here we demonstrate that p38 MAPK gamma (p38γ) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle. p38γ shares high sequence homology, inhibition sensitivity and substrate specificity with CDK family members. In mouse hepatocytes, p38γ induces proliferation after partial hepatectomy by promoting the phosphorylation of retinoblastoma tumour suppressor protein at known CDK target residues. Lack of p38γ or treatment with the p38γ inhibitor pirfenidone protects against the chemically induced formation of liver tumours. Furthermore, biopsies of human hepatocellular carcinoma show high expression of p38γ, suggesting that p38γ could be a therapeutic target in the treatment of this disease.

Cancer is not a risk factor for severe COVID-19 in children, except in patients with recent allogeneic hematopoietic stem cell transplantation or comorbidities.

The EPICO (Spanish general registry of COVID-19 in children)-SEHOP (Spanish Society of Pediatric Hematology and Oncology) platform gathers data from children with SARS-CoV-2 in Spain, allowing comparison between children with cancer or allogeneic hematopoietic stem cell transplantation (alloHSCT) and those without. The infection is milder in the cancer/alloHSCT group than in children without comorbidities (7.1% vs. 14.7%), except in children with recent alloHSCT (less than 300 days), of which 35.7% experienced severe COVID-19. These data have been shared with the SEHOP members to support treatment and isolation policies akin to those for children without cancer, except for those with recent alloHSCT or additional comorbidities. This highlights the collaborative registries potential in managing pandemic emergencies.

Usefulness of the DN4, S-LANSS, and painDETECT screening questionnaires to detect the neuropathic pain components in people with acute whiplash-associated disorders: a cross-sectional study.

OBJECTIVE: Although the presence of neuropathic pain (NP) components has been reported in whiplash-associated disorders (WAD), no studies have analyzed the usefulness of NP screening questionnaires to detect NP components in WAD. This study aimed to assess the usefulness of 3 NP screening tools (Douleur Neuropathique 4 [DN4], self-administered Leeds Assessment of Neuropathic Symptoms and Signs [S-LANSS], and painDETECT questionnaire [PDQ]) to detect the presence of NP components in acute WAD. DESIGN: A cross-sectional study. SETTING: Hospital. SUBJECTS: Of 188 eligible individuals, 50 people (68% women, mean age = 40.3 ± 12.5 years) with acute WAD (52% Grade III) were included. METHODS: Specialized physicians initially screened participants for the presence of NP components according to clinical practice and international recommendations. After physician assessment, blinded investigators used NP screening questionnaires (DN4, S-LANSS, and PDQ) to assess participants within 2 weeks of their accident. The diagnostic accuracy of these tools was analyzed and compared with the reference standard (physicians' assessments). RESULTS: The 3 screening questionnaires showed excellent discriminant validity (area under the curve: ≥0.8), especially S-LANSS (area under the curve: 0.9; P < .001). DN4 demonstrated the highest sensitivity (87%), followed by S-LANSS (75%), while S-LANSS and PDQ showed the highest specificity (85% and 82%, respectively). These tools demonstrated a strong correlation with the reference standard (S-LANSS: rho = 0.7; PDQ: rho = 0.62; DN4: rho = 0.7; all, P < .001). CONCLUSIONS: The DN4, S-LANSS, and PDQ show excellent discriminant validity to detect the presence of NP components in acute WAD, especially S-LANSS. Initial screening with these tools might improve management of WAD.

Accuracy of artificial intelligence-based segmentation of the mandibular canal in CBCT.

OBJECTIVES: To investigate the accuracy of artificial intelligence (AI)-based segmentation of the mandibular canal, compared to the conventional manual tracing, implementing implant planning software. MATERIALS AND METHODS: Localization of the mandibular canals was performed for 104 randomly selected patients. A localization was performed by three experienced clinicians in order to serve as control. Five tracings were performed: One from a clinician with a moderate experience with a manual tracing (I1), followed by the implementation of an automatic refinement (I2), one manual from a dental student (S1), and one from the experienced clinician, followed by an automatic refinement (E). Subsequently, two fully automatic AI-driven segmentations were performed (A1,A2). The accuracy between each method was measured using root mean square error calculation. RESULTS: The discrepancy among the models of the mandibular canals, between the experienced clinicians and each investigated method ranged from 0.21 to 7.65 mm with a mean of 3.5 mm RMS error. The analysis of each separate mandibular canal's section revealed that mean RMS error was higher in the posterior and anterior loop compared to the middle section. Regarding time efficiency, tracing by experienced users required more time compared to AI-driven segmentation. CONCLUSIONS: The experience of the clinician had a significant influence on the accuracy of mandibular canal's localization. An AI-driven segmentation of the mandibular canal constitutes a time-efficient and reliable procedure for pre-operative implant planning. Nevertheless, AI-based segmentation results should always be verified, as a subsequent manual refinement of the initial segmentation may be required to avoid clinical significant errors.

Accuracy of manual and artificial intelligence-based superimposition of cone-beam computed tomography with digital scan data, utilizing an implant planning software: A randomized clinical study.

OBJECTIVES: To investigate the accuracy of conventional and automatic artificial intelligence (AI)-based registration of cone-beam computed tomography (CBCT) with intraoral scans and to evaluate the impact of user's experience, restoration artifact, number of missing teeth, and free-ended edentulous area. MATERIALS AND METHODS: Three initial registrations were performed for each of the 150 randomly selected patients, in an implant planning software: one from an experienced user, one from an inexperienced operator, and one from a randomly selected post-graduate student of implant dentistry. Six more registrations were performed for each dataset by the experienced clinician: implementing a manual or an automatic refinement, selecting 3 small or 3 large in-diameter surface areas and using multiple small or multiple large in-diameter surface areas. Finally, an automatic AI-driven registration was performed, using the AI tools that were integrated into the utilized implant planning software. The accuracy between each type of registration was measured using linear measurements between anatomical landmarks in metrology software. RESULTS: Fully automatic-based AI registration was not significantly different from the conventional methods tested for patients without restorations. In the presence of multiple restoration artifacts, user's experience was important for an accurate registration. Registrations' accuracy was affected by the number of free-ended edentulous areas, but not by the absolute number of missing teeth (p < .0083). CONCLUSIONS: In the absence of imaging artifacts, automated AI-based registration of CBCT data and model scan data can be as accurate as conventional superimposition methods. The number and size of selected superimposition areas should be individually chosen depending on each clinical situation.

Accessibility to palliative care services in Colombia: an analysis of geographic disparities.

OBJECTIVES: Due to the increase in the prevalence of non-communicable diseases and the Colombian demographic transition, the necessity of palliative care has arisen. This study used accessibility and coverage indicators to measure the geographic barriers to palliative care. METHODS: Population-based observational study focused on urban areas and adult population from Colombia, which uses three measurements of geographic accessibility to services: a) density of palliative care services per 100,000 inhabitants, b) analysis of geographic distribution by territorial nodes of the country, and c) spatial analysis of palliative care services using Voronoi diagrams. ArcGIS Pro software was used to map services' locations and identify geographic disparities. RESULTS: A total of 504 palliative care services were identified, of which 77% were primary health care services. The density of palliative care services in Colombia is 1.8 primary care services per 100,000 inhabitants and 0.4 specialized services per 100,000 inhabitants. The average palliative care coverage is 41%, two regions of the country have a coverage below 30%. Twenty-eight percent of the services provide care for a population greater than 50,000 inhabitants within their coverage area, exceeding the acceptable limit by international standards. CONCLUSIONS: Palliative care services are concentrated in three main regions (Bogotá D.C., the Center, and the Caribbean) and are limited in the Orinoquia and Amazonia nodes. Density of specialized palliative care services is extremely low and there are regions without palliative services for adults with palliative needs.

A guide for selecting the intraoral scan extension when fabricating tooth- and implant-supported fixed dental prostheses.

OBJECTIVES: To describe a new classification for intraoral scans based on the scan extension and to introduce a decision guideline to choose the scan extension for fabricating tooth- and implant-supported fixed dental prostheses (FDPs). OVERVIEW: Multiple operator- and patient-related factors have been identified that can decrease the scanning accuracy of intraoral scanners (IOSs), including scan extension. However, the decision criteria for selecting scan extension for fabricating tooth- and implant-supported restorations is unclear. Based on the extension of the intraoral digital scans, three types of scans can be defined: half-arch (anterior or posterior), extended half-arch, and complete-arch scan. Variables to consider when choosing the scan extension include the number and location of units being restored, as well as the extension and location of edentulous areas. Additionally, the accuracy of the virtual definitive cast and the accuracy of the maxillomandibular relationship captured by using IOSs should be differentiated. CONCLUSIONS: A decision tree for selecting the scan extension is presented. The decision is based on the number and location of units being restored, and the extension and location of edentulous areas. Intraoral scans with reduced scan extension are indicated when fabricating tooth- and implant-supported crowns or short-span fixed prostheses, when the patient does not have more than one missing tooth in the area of the dental arch included in the scan. For the remaining clinical conditions, complete-arch intraoral scans are recommended. CLINICAL SIGNIFICANCE: Scan extension is a clinician's decision that should be based on the number and location of units being restored and the extension and location of edentulous areas. Intraoral scans with a reduced scan extension is recommended, when possible.

An overview of the different digital facebow methods for transferring the maxillary cast into the virtual articulator.

OBJECTIVES: The purposes of this study were to classify the described digital facebow techniques for transferring the maxillary cast into the semi-adjustable virtual articulator based on the digital data acquisition technology used and to review the reported accuracy values of the different digital facebow methods described. OVERVIEW: Digital data acquisition technologies, including digital photographs, facial scanners, cone beam computed tomography (CBCT) imaging, and jaw tracking systems, can be used to transfer the maxillary cast into the virtual articulator. The reported techniques are reviewed, as well as the reported accuracy values of the different digital facebow methods. CONCLUSIONS: Digital photographs can be used to transfer the maxillary cast into the virtual articulator using the true horizontal reference plane, but limited studies have assessed the accuracy of this method. Facial scanning and CBCT techniques can be used to transfer the maxillary cast into the virtual articulator, in which the most frequently selected references planes are the Frankfort horizontal, axis orbital, and true horizontal planes. Studies analyzing the accuracy of the maxillary cast transfer by using facial scanning and CBCT techniques are restricted. Lastly, optical jaw trackers can be selected for transferring the maxillary cast into the virtual articulator by using the axis orbital or true horizontal planes, yet the accuracy of these systems is unknown. CLINICAL IMPLICATIONS: Digital data acquisition technologies, including digital photographs, facial scanning methods, CBCTs, and optical jaw tracking systems, can be used to transfer the maxillary cast into the virtual articulator. Studies are needed to assess the accuracy of these digital data acquisition technologies for transferring the maxillary cast into the virtual articulator.

Altered reverse impression method involving extraoral digitalization of a verification jig for the fabrication of implant-supported prosthesis by using a complete-digital workflow.

The reverse impression method involves the extraoral digitalization of the interim implant-supported prostheses and intraoral digitalization of antagonist arch and maxillomandibular relationship. This technique allows the fabrication of implant-supported prostheses by using a complete-digital workflow. The scan analogs make the reverse impression method feasible. However, this method may not be recommended if the interim polymethyl methacrylate prosthesis does not have passive fit. The present manuscript describes an altered reverse impression technique that involves the extraoral digitalization of a conventional verification jig, which has attached scan analogs. With this technique modification, the implant positions captured using the verification jig are used to obtain the virtual definitive implant cast and fabricate the definitive implant-supported prosthesis.

A biologically oriented preparation technique (BOPT) for immediate posterior implant placement, immediate provisionalization, and definitive implant crown fabrication: A complete digital workflow.

OBJECTIVE: Immediate implants and immediate alveolar sealing have been a widely utilized treatment with high predictability and biological advantages. The improvement in technology has made it possible to simplify clinical processes. The aim of the present report was to describe the complete digital workflow of the Biologically oriented preparation technique for immediate posterior implant, immediate provisionalization and fabrication of definitive implant crowns. CLINICAL CONSIDERATIONS: The surgical process and prosthetic management to preserve the gingival contours of the extracted natural tooth during immediate implant placement and provisionalization are described. Additionally, during the same clinical intervention, the definitive intraoral digital implant scans for capturing the implant position, peri-implant tissue contours, adjacent and antagonist dentition, and profile emergence of the interim implant crown are captured for the fabrication of the definitive crown. CONCLUSIONS: Based on the technique described, the immediate implant placement and provisionalization in the posterior area provides biological and clinical advantages, reducing the number of abutment-implant disconnections and the number of clinical appointments, as well as increases patient comfort. CLINICAL SIGNIFICANCE: The present article describes a technique for an immediate implant placement and provisionalization in the posterior region for maintaining the gingival architecture of the extracted tooth. During the same appointment, the implant position, peri-implant tissue contours, and adjacent and antagonist dentition, and profile emergence of the interim implant crown are captured by using an intraoral scanner and used for the fabrication of the definitive crown. This technique aims to reduce the number of abutment-implant disconnections and clinical appointments.

An overview of artificial intelligence based applications for assisting digital data acquisition and implant planning procedures.

OBJECTIVES: To provide an overview of the current artificial intelligence (AI) based applications for assisting digital data acquisition and implant planning procedures. OVERVIEW: A review of the main AI-based applications integrated into digital data acquisitions technologies (facial scanners (FS), intraoral scanners (IOSs), cone beam computed tomography (CBCT) devices, and jaw trackers) and computer-aided static implant planning programs are provided. CONCLUSIONS: The main AI-based application integrated in some FS's programs involves the automatic alignment of facial and intraoral scans for virtual patient integration. The AI-based applications integrated into IOSs programs include scan cleaning, assist scanning, and automatic alignment between the implant scan body with its corresponding CAD object while scanning. The more frequently AI-based applications integrated into the programs of CBCT units involve positioning assistant, noise and artifacts reduction, structures identification and segmentation, airway analysis, and alignment of facial, intraoral, and CBCT scans. Some computer-aided static implant planning programs include patient's digital files, identification, labeling, and segmentation of anatomical structures, mandibular nerve tracing, automatic implant placement, and surgical implant guide design.

Recommendations for successful virtual patient-assisted esthetic implant rehabilitation: A guide for optimal function and clinical efficiency.

OBJECTIVE: Complete arch implant rehabilitation necessitates meticulous treatment planning and high-level collaboration between surgical and prosthetic dental teams. Emerging virtual technologies hold considerable promise in streamlining this process. The aim of this article is to extend recommendations to clinicians venturing into the virtual patient-assisted esthetic implant rehabilitation workflow. OVERVIEW: This article summarizes recommendations for virtual patient-assisted esthetic implant rehabilitation in the following five aspects: three-dimensional data handling and superimposition, occlusion and virtual articulator integration in creating virtual patients, streamlined face- and prosthetic-driven surgical planning, reuse of presurgical data ("Copy & Paste"), and final impression for passive fitting of final restoration. To illustrate these principles, a case with complete-mouth implant rehabilitation completed within six visits using this virtual patient workflow is presented. CONCLUSION: The virtual patient workflow serves as an invaluable tool to perform treatment planning, enhance efficiency, and ensure predictable outcomes in esthetic complete arch implant rehabilitation. CLINICAL SIGNIFICANCE: Virtual workflows are increasingly prevalent in esthetic implant rehabilitation. Nevertheless, these workflows necessitate a distinct set of knowledge and tools divergent from conventional dentistry practices. This article offers guidelines and recommendations for dental clinicians who are new to this field.

Virtual implant scan body switch by using computer-aided design programs avoiding the need of obtaining a new intraoral implant digital scan: A novel protocol.

OBJECTIVE: The present manuscript describes a technique to virtually switch an implant scan body eliminating the need of obtaining a new intraoral implant digital scan. CLINICAL CONSIDERATIONS: Implant scan bodies assist on transferring the 3-dimensional position of the implants into the virtual definitive implant cast. However, if a different implant part is desired during the designing procedures of the implant restoration such as selecting a different implant abutment of varying height, angulation, or manufacturer, a new intraoral implant digital scan with the specific implant scan body is required. CONCLUSIONS: This novel protocol aims to reduce possible complications that require capturing a new intraoral implant digital scan, facilitate prostheses design modifications after the obtention of the definitive intraoral implant digital scan, and to ease the manufacturing procedures. CLINICAL SIGNIFICANCE: The novel technique may provide a solution for virtually switch implant scan bodies for fabricating implant-supported single crowns or short-span prostheses. Additional studies are needed before its clinical implementation.

Cephalometric analysis performance discrepancy between orthodontists and an artificial intelligence model using lateral cephalometric radiographs.

PURPOSE: The purpose of the present clinical study was to compare the Ricketts and Steiner cephalometric analysis obtained by two experienced orthodontists and artificial intelligence (AI)-based software program and measure the orthodontist variability. MATERIALS AND METHODS: A total of 50 lateral cephalometric radiographs from 50 patients were obtained. Two groups were created depending on the operator performing the cephalometric analysis: orthodontists (Orthod group) and an AI software program (AI group). In the Orthod group, two independent experienced orthodontists performed the measurements by performing a manual identification of the cephalometric landmarks and a software program (NemoCeph; Nemotec) to calculate the measurements. In the AI group, an AI software program (CephX; ORCA Dental AI) was selected for both the automatic landmark identification and cephalometric measurements. The Ricketts and Steiner cephalometric analyses were assessed in both groups including a total of 24 measurements. The Shapiro-Wilk test showed that the data was normally distributed. The t-test was used to analyze the data (α = 0.05). RESULTS: The t-test analysis showed significant measurement discrepancies between the Orthod and AI group in seven of the 24 cephalometric parameters tested, namely the corpus length (p = 0.003), mandibular arc (p < 0.001), lower face height (p = 0.005), overjet (p = 0.019), and overbite (p = 0.022) in the Ricketts cephalometric analysis and occlusal to SN (p = 0.002) and GoGn-SN (p < 0.001) in the Steiner cephalometric analysis. The intraclass correlation coefficient (ICC) between both orthodontists of the Orthod group for each cephalometric measurement was calculated. CONCLUSIONS: Significant discrepancies were found in seven of the 24 cephalometric measurements tested between the orthodontists and the AI-based program assessed. The intra-operator reliability analysis showed reproducible measurements between both orthodontists, except for the corpus length measurement. CLINICAL SIGNIFICANCE: The artificial intelligence software program tested has the potential to automatically obtain cephalometric analysis using lateral cephalometric radiographs; however, additional studies are needed to further evaluate the accuracy of this AI-based system.

True horizontal or gravity plane for transferring the maxillary cast into the virtual articulator by using an optical jaw tracking system.

Different techniques of transferring the maxillary cast into the analog semi-adjustable articulator by using the true horizontal or gravity reference plane have been reported. However, procedures are required for recording this reference plane and transferring the maxillary cast into the virtual semi-adjustable articulator. In the present manuscript, a technique is described for registering the true horizontal or gravity plane in relationship to the natural head position of the patient by using an optical jaw tracking system. Additionally, the recorded true horizontal plane is used to transfer the maxillary cast into the virtual semi-adjustable articulator by using a dental computer-aided design program. This technique facilitates the maxillary cast transfer into the virtual articulator by using the true horizontal plane recorded with an optical jaw tracking system, maximizing the functionality of the optical jaw tracking device.

Implementing an optical jaw tracking system to locate centric occlusion: A dental technique.

Optical jaw tracking systems are designed to record the static maxillomandibular relationship and the mandibular motion of a patient, including excursive movements and mastication pattern. This digital data acquisition technology can be integrated into diagnostic and treatment planning procedures, as well as into designing dental prostheses. A step-by-step protocol to record a patient's digital data, including the repeatable reference position of the jaw or centric relation, by using an intraoral scanner, Kois deprogrammer, and optical jaw tracking system is described. The data are then processed in the software program of the jaw tracking system to locate centric occlusion.

Integrating the repeatable reference position and excursive movements of the mandible acquired using a jaw tracker into the design procedures of an occlusal device: A technique.

Jaw tracking systems can record mandibular movement such as the repeatable reference position and excursive movements of the mandible. A technique for integrating the recorded repeatable reference position of the mandible and excursive movements captured using an optical jaw tracking system into the design procedures of an occlusal device is described. The mandibular motion of the patient is directly used to design the occlusal device, replacing the virtual articulator. The described technique aims to reduce the delivery time by incorporating the recorded motion of the patient into the virtual design of the occlusal device.

Digital diagnostic occlusal equilibration combining an intraoral scanner, optical jaw tracking system, and dental design program: A dental technique.

Patients with aberrant occlusal patterns, including constricted mastication patterns or occlusal dysfunction, may require occlusal equilibration. Conventional diagnostic procedures involve diagnostic stone casts mounted in the articulator. During diagnostic procedures, occlusal equilibration methods are simulated on mounted stone casts to analyze the amount of dental structure that may need to be removed. A technique to virtually simulate an occlusal equilibration procedure is described. Digital data acquisition procedures include diagnostic casts acquired using an intraoral scanner and the repeatable reference position of the mandible or centric relation, excursive movements, and the mastication pattern captured using an optical jaw tracking system. The jaw tracker and dental design programs are used to simulate the occlusal equilibration.

Intraoral scanners as tracking devices: A dental protocol for assessing volumetric changes between intraoral scans.

Intraoral scanners (IOSs) are digital data acquisition technologies that ease the recording of virtual diagnostic casts. Some IOSs have a specific software tool to assess volumetric changes between 2 scans acquired on the patient at different times. The scans are superimposed and volumetric differences between both meshes are reported. However, these software tools may be limited to scans captured only by the IOS of the same manufacturer. The present manuscript describes a protocol for comparing volumetric changes between 2 scans recorded using any IOS. Additionally, 1 of the scans is divided into 3 sections to minimize the alignment distortion and maximize the evaluation of the volumetric changes.