Outcome Measures in UCLP: The Modified 5-Year-Olds'-Index-Development and Reliability.

OBJECTIVE: Can we reliably discriminate severity within the existing categories of the 5-Year-Olds' Index? DESIGN: Retrospective method comparison and development study. SETTING: School of Oral and Dental Science, University of Bristol. METHODS: Dental study models of 5-year-olds with unilateral cleft lip and palate (UCLP) were collected from the archives of 2 national cleft surveys (n = 351). One hundred randomly selected models were ranked to construct the modified 5-Year-Olds' Index and also scored using a visual analogue scale (VAS). Reliability testing was performed on 51 study models. Visual analogue scale scores were used to aid statistical analysis and investigate the reliability of a VAS for outcome measurement. The modified 5-Year-Olds' Index was then applied to 198 study models of 5-year-olds with UCLP. RESULTS: The modified 5-Year-Olds' Index showed excellent intra and interexaminer agreement (intraclass correlation > 0.94) and good discrimination of severity. When applied to the Cleft Care UK participants (n = 198), the modified 5-Year-Olds' Index showed good discrimination of severity within the better categories (groups 1-3) of the 5-Year-Olds' Index. Visual analogue Scale scores resulted in unacceptable variation between measurements. CONCLUSIONS: The new modified 5-Year-Olds' Index is a reliable method of assessing outcomes at 5 years of age and showed improved discriminatory power between the "better" outcome categories than the original 5-Year-Olds' Index. A VAS was found to be unsuitable for assessing outcome at 5 years of age for children with UCLP.

The Accuracy and Reproducibility of Linear Measurements Made on CBCT-derived Digital Models.

OBJECTIVE: To evaluate the accuracy and reproducibility of linear measurements made on cone-beam computed tomography (CBCT)-derived digital models. MATERIALS AND METHODS: A total of 25 patients (44% female, 18.7 ± 4 years) who had CBCT images for diagnostic purposes were included. Plaster models were obtained and digital models were extracted from CBCT scans. Seven linear measurements from predetermined landmarks were measured and analyzed on plaster models and the corresponding digital models. The measurements included arch length and width at different sites. Paired t test and Bland-Altman analysis were used to evaluate the accuracy of measurements on digital models compared to the plaster models. Also, intraclass correlation coefficients (ICCs) were used to evaluate the reproducibility of the measurements in order to assess the intraobserver reliability. RESULTS: The statistical analysis showed significant differences on 5 out of 14 variables, and the mean differences ranged from -0.48 to 0.51 mm. The Bland-Altman analysis revealed that the mean difference between variables was (0.14 ± 0.56) and (0.05 ± 0.96) mm and limits of agreement between the two methods ranged from -1.2 to 0.96 and from -1.8 to 1.9 mm in the maxilla and the mandible, respectively. The intraobserver reliability values were determined for all 14 variables of two types of models separately. The mean ICC value for the plaster models was 0.984 (0.924-0.999), while it was 0.946 for the CBCT models (range from 0.850 to 0.985). CONCLUSION: Linear measurements obtained from the CBCT-derived models appeared to have a high level of accuracy and reproducibility.

The Assessment of Digital Study Models Using the GOSLON Yardstick Index.

Objective : To investigate the reproducibility and repeatability of digital models of patients with a unilateral cleft lip and palate (UCLP) using the GOSLON yardstick. Design : Reproducibility and repeatability study. Method : Two examiners used the GOSLON yardstick to assess the intermaxillary dentoalveolar relationship of 30 consecutive UCLP patients by analyzing their 9-year (±3 months) dental study casts and digital study models. The records were rated 1 week apart to avoid bias. The process was repeated 1 month later as a measure of reproducibility. Reliability was assessed by comparing the GOSLON score achieved between the two modalities. Patient dental study casts were sent to 3M Unitek Australia to be scanned using the 3M Unitek Lava(TM) system to produce digital study models. The accuracy of the dental study cast occlusal registration was assessed by both raters prior to sending the study models for scanning. Statistical analysis : The Linear Weighted Kappa statistic and Kendall's Coefficient of Concordance statistic were used to determine the levels of agreement within and between raters. Results : The linear weighted Kappa statistic for intrarater repeatability of digital study models scores were very high (0.89 and 0.97). This compared favorably to the intrarater repeatability of study model casts scores (0.86 and 0.97). There was very good agreement for interrater digital study model scores (0.80 and 0.87) and also for the interrater study model casts scores (0.80 and 0.90). Kendall's Coefficient of Concordance statistic (0.99) and Correlation Coefficient (0.86) support the weighted Kappa results of the digital study model scores. Conclusion : Digital models can be used for GOSLON scoring with a high degree of reproducibility and repeatability.

Comparison of linear measurements and analyses taken from plaster models and three-dimensional images.

Digital models are an alternative for carrying out analyses and devising treatment plans in orthodontics. The objective of this study was to evaluate the accuracy and the reproducibility of measurements of tooth sizes, interdental distances and analyses of occlusion using plaster models and their digital images. Thirty pairs of plaster models were chosen at random, and the digital images of each plaster model were obtained using a laser scanner (3Shape R-700, 3Shape A/S). With the plaster models, the measurements were taken using a caliper (Mitutoyo Digimatic(®), Mitutoyo (UK) Ltd) and the MicroScribe (MS) 3DX (Immersion, San Jose, Calif). For the digital images, the measurement tools used were those from the O3d software (Widialabs, Brazil). The data obtained were compared statistically using the Dahlberg formula, analysis of variance and the Tukey test (p < 0.05). The majority of the measurements, obtained using the caliper and O3d were identical, and both were significantly different from those obtained using the MS. Intra-examiner agreement was lowest when using the MS. The results demonstrated that the accuracy and reproducibility of the tooth measurements and analyses from the plaster models using the caliper and from the digital models using O3d software were identical.

Artificial Intelligence-Based 3D Printing Strategies for Bone Scaffold Fabrication and Its Application in Preclinical and Clinical Investigations.

3D printing has become increasingly popular in the field of bone tissue engineering. However, the mechanical properties, biocompatibility, and porosity of the 3D printed bone scaffolds are major requirements for tissue regeneration and implantation as well. Designing the scaffold architecture in accordance with the need to create better mechanical and biological stimuli is necessary to achieve unique scaffold properties. To accomplish this, different 3D designing strategies can be utilized with the help of the scaffold design library and artificial intelligence (AI). The implementation of AI to assist the 3D printing process can enable it to predict, adapt, and control the parameters on its own, which lowers the risk of errors. This Review emphasizes 3D design and fabrication of bone scaffold using different materials and the use of AI-aided 3D printing strategies. Also, the adaption of AI to 3D printing helps to develop patient-specific scaffolds based on different requirements, thus providing feedback and adequate data for reproducibility, which can be improvised in the future. These printed scaffolds can also serve as an alternative to preclinical animal test models to cut costs and prevent immunological interference.

Brain Microvascular Pericytes-More than Bystanders in Breast Cancer Brain Metastasis.

Brain tissue contains the highest number of perivascular pericytes compared to other organs. Pericytes are known to regulate brain perfusion and to play an important role within the neurovascular unit (NVU). The high phenotypic and functional plasticity of pericytes make this cell type a prime candidate to aid physiological adaptations but also propose pericytes as important modulators in diverse pathologies in the brain. This review highlights known phenotypes of pericytes in the brain, discusses the diverse markers for brain pericytes, and reviews current in vitro and in vivo experimental models to study pericyte function. Our current knowledge of pericyte phenotypes as it relates to metastatic growth patterns in breast cancer brain metastasis is presented as an example for the crosstalk between pericytes, endothelial cells, and metastatic cells. Future challenges lie in establishing methods for real-time monitoring of pericyte crosstalk to understand causal events in the brain metastatic process.

Foot-and-Mouth Disease Virus: Molecular Interplays with IFN Response and the Importance of the Model.

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals with a significant socioeconomic impact. One of the issues related to this disease is the ability of its etiological agent, foot-and-mouth disease virus (FMDV), to persist in the organism of its hosts via underlying mechanisms that remain to be elucidated. The establishment of a virus-host equilibrium via protein-protein interactions could contribute to explaining these phenomena. FMDV has indeed developed numerous strategies to evade the immune response, especially the type I interferon response. Viral proteins target this innate antiviral response at different levels, ranging from blocking the detection of viral RNAs to inhibiting the expression of ISGs. The large diversity of impacts of these interactions must be considered in the light of the in vitro models that have been used to demonstrate them, some being sometimes far from biological systems. In this review, we have therefore listed the interactions between FMDV and the interferon response as exhaustively as possible, focusing on both their biological effect and the study models used.

The Effectiveness of In-house Clear Aligners and Traditional Fixed Appliances in Achieving Good Occlusion in Complex Orthodontic Cases: A Randomized Control Clinical Trial.

OBJECTIVE: To compare the effectiveness and efficiency of the in-house clear aligners with the traditional fixed appliances in treating premolar-extraction-based complex cases. MATERIALS AND METHODS: A single-centered, 2-arm parallel-group randomized controlled clinical trial was conducted on thirty-six (12 males, 24 females; mean age: 21.24 ± 2.33) patients with severe crowding who required orthodontic treatment with four first premolars extraction. The patients were equally and randomly divided into two groups: The in-house clear aligners (CA) group and the fixed appliances (FA) group. All the measurements were made on the pre-and post-treatment dental cast models. The effectiveness was evaluated using Little's irregularity index (LII) and the Peer Assessment Rating index (PAR). The efficiency was evaluated by studying the treatment duration. Two sample t-tests and chi-square tests were used to test for significant differences between the two groups. Bonferroni correction was applied, and the adjusted alpha level was set at 0.006.  Results: Before treatment, there were no significant differences between the two groups regarding LII in the upper and lower jaws (p˃0.006). After treatment, the mean LII decreased in both groups, with no significant differences between the two studied groups (p˃0.006). There were no significant differences in all studied PAR domains between the two groups (p˃0.006). The mean score reduction in the CA group was 28.39 (±8.51) points, whereas it was 26.39 (±5.76) points in the FA group, with no significant differences between the two groups. All the patients in this study were improved. However, a great improvement was achieved in 88.9% of the patients in the CA group and 91.7% in the FA group, with no significant differences between them (p=0.674). The average treatment duration in the CA group was 23.27 (±5.28) months, whereas the average was 26.20 (±5.27) in the FA group, with no significant difference between the two groups. CONCLUSION: In-house clear aligners can be effective as fixed appliances in achieving good occlusion when treating complex orthodontic cases when suitable teeth movement protocol is used.

Comparison of dental arch forms created from assessment of teeth, alveolar bone, and the overlying soft tissue.

OBJECTIVE: The objective of this study was to determine whether there are differences among the arch forms created from assessments of tooth surfaces, alveolar bone, and overlying soft tissue. MATERIALS AND METHODS: This study included 18 individuals who presented with a class I malocclusion, mild crowding, and a cone beam computed tomography (CBCT) image of good diagnostic quality. The facial axis point was chosen to create the arch form from teeth, the Bowman-Kau (BK) point was used to establish the arch form from alveolar bone, and the WALA ridge was used to calculate the soft tissue arch form. A predetermined algorithm was then used to create five separate arch forms per patient. These arch forms were categorized according to shape and were superimposed. The distances between the tooth-, bone-, and soft tissue-derived arch forms were calculated. RESULTS: The calculated distances between all arch forms were significantly different. The distances between the tooth- and bone-derived arch forms were larger for the mandible compared to the maxilla (mean 3.30 vs. 2.48 mm, respectively). The larger distances seemed to be located more posteriorly in the arch than anteriorly. The distance between tooth- and soft tissue-derived arch forms was largest for the second premolar (2.35 ± 1.59 mm), first molar (2.86 ± 0.63 mm), and second molar (3.25 ± 0.87 mm). There were no significant differences in the distance between the tooth- and either bone- or soft tissue-derived arch forms with regard to sex. CONCLUSIONS: The arch form shapes obtained from the teeth, alveolar bone, and soft tissue are correlated and show the same general shape. Although future large-scale studies are needed for confirmation, our results suggest that evaluating the easily visualized external features, including the WALA ridge, can adequately predict the underlying bone shape, and thus the desired arch form. Nevertheless, the shapes vary significantly between patients, so the final treatment plan should be individualized rather than relying on over-simplified general wire shapes.

Molecular dysregulations underlying the pathogenesis of endometriosis.

Endometriosis is a crippling disease characterized by the presence of endometrium-like tissue or scar outside the uterine cavity, commonly confined to the peritoneal and serosal surfaces of the pelvic organs. 10-15% of women in reproductive age are estimated to be affected by endometriosis. Most of these patients present with infertility and suffer from pelvic pain. The benign disease rarely progresses to malignancy. Regardless of its high prevalence, the pathogenesis of the disease is not fully understood. Treatment options for endometriosis are limited and are often based on a symptomatic approach. The unavailability of proper diagnostic approaches, fewer therapeutic options, and sparse understanding of molecular alterations are responsible for the continued disease burden. Exploring the molecular elements causing the pathogenesis of endometriosis may lead to a number of breakthroughs in the treatment of the illness, such as the discovery of new biomarkers for diagnosis and therapeutic targets that can be a guide to better prognosis and reduced recurrence. The goal of this review is to provide the reader a critical understanding of the disease by summarizing the genetic, immunological, hormonal, and epigenetic deregulations that support the molecular basis for development of endometriotic cyst, with a special focus on the study models needed to analyze these changes in the endometriotic microenvironment.

Comparison of reliability, validity, and accuracy of linear measurements made on pre- and posttreatment digital study models with conventional plaster study models.

OBJECTIVES: To compare the accuracy of the linear measurements made on pre- and posttreatment three-dimensional (3D) scanned digital models with conventional plaster study models. MATERIALS AND METHODS: The study was conducted on pre- and posttreatment study models of 132 patients. A 3D model scanner was used to scan the plaster models to form 3D digital models. The measurements were made on the plaster models using digital Vernier calipers, and the 3D digital models were assessed for similar measurement using a software of the model scanner. The intraclass correlation for intraoperator error showed good correlations between the measurements made on conventional plaster models and digital models. RESULTS: Although the comparison of the linear measurements made by conventional and digital methods on both pre- and posttreatment study models using intraclass coefficient showed a good correlation, analysis of variance showed significant mean differences in the measurements of multiple variables in both the groups. The number of variables showing significant differences was more in the pretreatment group. The measurements obtained by Vernier calipers were generally higher than those of scanned pre- and posttreatment study models. CONCLUSION: The linear measurements made by conventional and digital methods showed statistically significant mean differences. The accuracy of recording can be affected by the severity of pretreatment malocclusion, but the deviations were not large enough to contradict the use of the digital models for orthodontic records.

Comparison of transverse maxillary dental arch width changes with self-ligating and conventional brackets in patients requiring premolar extraction - A randomised clinical trial.

OBJECTIVE: The purpose of this study was to evaluate, the change in the transverse maxillary arch dimensions, in patients requiring all first premolar extractions when using Active and Passive Self-ligating brackets, and comparing them with Conventional brackets. MATERIALS AND METHODS: This study was a non-blinded randomised clinical trial, which consisted of 42 patients (21 males and 21 females) within the age group of 16-25 years, having bimaxillary protrusion. They were divided into three groups with 14 patients each. In Group 1 - Conventional brackets (3M Unitek), in Group 2 - Passive Self-ligation brackets: Smart Clip (3M Unitek), and in Group 3 - Active Self-ligation brackets: Empower AO (American Orthodontics) were bonded. All brackets had MBT prescription and 0.02" slot size. Dental study models were taken before the start of treatment and after six months of retraction. Inter-canine and intermolar widths were measured in all the three groups in the above mentioned stages. RESULTS: As compared to Conventional brackets, Self-ligating brackets (Passive and Active) showed greater increase in the transverse arch widths. Furthermore, between Passive and Active Self-ligating brackets, Passive Self-ligating brackets - Smart Clip (Group 2) showed a greater increment in the transverse arch dimensions, with an increase of 4.89mm in the inter-canine width and 3.4mm in intermolar width. CONCLUSION: Significant difference was found between Self-ligating brackets and the Conventional bracket system regarding maxillary arch width dimensional changes. Passive Self-ligating brackets - Smart Clip (Group 2) showed the highest and inter-molar width increase.

Novel Method for Superposing 3D Digital Models for Monitoring Orthodontic Tooth Movement.

Quantitative three-dimensional analysis of orthodontic tooth movement (OTM) is possible by superposition of digital jaw models made at different times during treatment. Conventional methods rely on surface alignment at palatal soft-tissue areas, which is applicable to the maxilla only. We introduce two novel numerical methods applicable to both maxilla and mandible. The OTM from the initial phase of multi-bracket appliance treatment of ten pairs of maxillary models were evaluated and compared with four conventional methods. The median range of deviation of OTM for three users was 13-72% smaller for the novel methods than for the conventional methods, indicating greater inter-observer agreement. Total tooth translation and rotation were significantly different (ANOVA, p < 0.01) for OTM determined by use of the two numerical and four conventional methods. Directional decomposition of OTM from the novel methods showed clinically acceptable agreement with reference results except for vertical translations (deviations of medians greater than 0.6 mm). The difference in vertical translational OTM can be explained by maxillary vertical growth during the observation period, which is additionally recorded by conventional methods. The novel approaches are, thus, particularly suitable for evaluation of pure treatment effects, because growth-related changes are ignored.

A pilot study to assess the feasibility and accuracy of using haptic technology to occlude digital dental models.

OBJECTIVES: The use of haptic technology as an adjunct to clinical teaching is well documented in medicine and dentistry. However its application in clinical patient care is less well documented. The aim of this pilot study was to determine the feasibility and accuracy of using a haptic device to determine the occlusion of virtual dental models. METHODS: The non-occluded digital models of 20 pre-treatment individuals were chosen from the database of Faculty of Dentistry, The University of Hong Kong. Following minimal training with the haptic device (Geomagic(®) Touch™), the upper model was occluded with the lower model until a stable occlusion was achieved. Seven landmarks were placed on each of the corners of the original and haptically aligned upper model bases. The absolute distance between the landmarks was calculated. Intra- and inter-operator errors were assessed. RESULTS: The absolute distance between the 7 landmarks for each original and corresponding haptically aligned model was 0.54 ± 0.40 mm in the x-direction (lateral), 0.73 ± 0.63 mm in the y-direction (anterior-posterior) and 0.55 ± 0.48 mm in the z-direction (inferior-superior). CONCLUSION: Based on initial collision detection to prevent interpenetration of the upper and lower digital model surfaces, and contact form resistance during contact, it is possible to use a haptic device to occlude digital study models. CLINICAL SIGNIFICANCE: The use of 3D digital study models is routine, but new problems arise, such as the lack of "touch" in a virtual environment. Occluding study models requires the sense of touch. For the first time, using haptic technology, it is possible to occlude digital study models in a virtual environment.

Puesta a punto de la técnica de Ussing Chamber para estudios de permeabilidad intestinal en tejido de cerdo / Optimization of the Ussing Chamber Technique for studies of intestinal permeability in pig tissue

El Sistema de Clasificación Biofarmacéutica es un marco científico para clasificar ingredientes farmacéuticos activos en base a su solubilidad acuosa y su permeabilidad intestinal, que cuando se combina con la disolución del producto toma en cuenta los tres factores principales que gobiernan la velocidad y el alcance de la absorción de un fármaco a partir de formas posológicas orales sólidas de liberación inmediata. Cuando los fármacos cumplen con determinados criterios biofarmacéuticos este sistema permite reemplazar los estudios in vivo de biodisponibilidad / bioequivalencia por estudios in vitro. La permeabilidad intestinal de los IFAs puede ser estudiada por diferentes métodos, uno de ellos es la técnica de Ussing Chamber que utiliza una porción de tejido intestinal. La ventaja de esta técnica es que permite conservar las capacidades funcionales de los tejidos. En la puesta a punto de esta nueva técnica se obtuvieron datos concordantes con bibliografía. Se evaluó la permeabilidad de ibuprofeno, metoprolol y atenolol (drogas de alta y baja permeabilidad) utilizando Ussing Chamber con intestino delgado de cerdo. Contar con esta técnica en el Departamento de Farmacología representa un valioso complemento a las metodologías ya utilizadas: estudios in vitro (células Caco-2 y MDCK) e in situ (perfusión intestinal en rata).

The Biopharmaceutical Classification System is a scientific framework for classifying Active Pharmaceutical Ingredients based on their aqueous solubility and their intestinal permeability which, when combined with the dissolution of the product takes into account the three main factors that govern the absorption speed and extent of a drug from immediate-release solid oral dosage form. When drugs meet certain biopharmaceutical criteria, this system allows in vivo bioavailability / bioequivalence studies to be replaced by in vitro studies. The intestinal permeability of APIs can be studied by different methods, one of them is the Ussing Chamber technique that uses a portion of intestinal tissue. The advantage of this technique is that it allows to conserve the functional capacities of tissues. In the development of this new technique, concordant data with bibliography was obtained. The permeability of ibuprofen, metoprolol and atenolol (high and low permeability drugs) was evaluated utilizing the Ussing Chamber Technique with pig small intestine. To have this technique in the Department of Pharmacology represents a valuable complement to the methodologies already used; both in vitro (Caco-2 and MDCK cells) and in situ (intestinal perfusion in rat) studies.

Síndrome de respuesta inflamatoria sistémica y disfunción orgánica en urgencias pediátricas / Association between systemic inflammatory response and organ dysfunction in paediatric emergencies

En las salas de Emergencias Pediátricas la gravedad o el riesgo de fallecer es un hecho de especial importancia. La gravedad de una enfermedad es difícil de definir, para esto, se han desarrollado escalas de riesgo de muerte. Para optimizar la preparación del departamento de emergencia en el manejo de niños con enfermedades graves necesitamos conocer las características del paciente y su enfermedad. Objetivo: Evaluar relación entre síndrome de respuesta inflamatoria sistémica y disfunción orgánica en niños Metodología: Cohorte prospectiva. Niños con enfermedad aguda grave, admitidos en forma consecutiva al departamento de urgencias, evaluación de variables clínicas y fisiológicas. Análisis del efecto de variables sobre el riesgo de disfunción orgánica múltiple o mortalidad Resultados: Riesgo de enfermedad aguda grave, 70/105 niños <12 años; edad mediana 0,9 (0,3-3,9) años; síndrome de disfunción orgánica múltiple, 14 (24,1%) de 58; tasa de mortalidad observada 6,9%. Riesgo de muerte en niños con disfunción multiorgánica 3/14 (21,4%) contra 1(2,3%) de 44 niños sin disfunción multiorgánica (RR 9,4; χ2 6,1; p 0,04) Conclusión: En niños con enfermedad aguda grave el riesgo de muerte esta positivamente asociado con el riesgo de disfunción orgánica múltiple.

In pediatric emergency rooms, the risk of dying is a fact of particular importance. The severity of a disease is difficult to define, for this reason, risk of death scales have been developed. To optimize the preparation of emergency departments in the management of children with serious diseases we need to know the characteristics of the patient and his illness. Goal: To assess the relationship between systemic inflammatory response syndrome and organ dysfunction in children Methodology: Prospective cohort. Children with serious acute illness, admitted consecutively to the Emergency Department, evaluation of clinical and physiological variables. Analysis of the effect of variables on the risk of mortality and multiple organ dysfunction Results: Serious risk of acute illness, 70/105 children < 12 years; age median 0.9 (0, 3-3, 9) years; multiple organ dysfunction syndrome, 14 (24.1%) 58; rate 6.9% observed mortality. Risk of death in children with dysfunction multi-organ 3/14 (21.4%) against 1(2,3%) of 44 children without multiple organ dysfunction (RR 9.4; ) χ2 ( 6.1; p 0.04) Conclusion: In children with acute and severe illnesses, the risk of death is positively associated with the risk of multiple organ dysfunction.