Remineralization potential of varying concentrations of two plant-based extracts of Cocos nucifera on white spot lesions using SEM and EDAX analysis: An in vitro study.

Aim: To evaluate the remineralization potential of varying concentrations of two plant-based extracts of Cocos nucifera on white spot lesions using SEM and EDAX in vitro testing methods. Materials and Methods: The pulp was freshly obtained from coconut and divided into two. Then, coconut milk was obtained by blending, while the next portion was freeze-dried and lyophilized. Third molar teeth were processed into tooth slabs (N = 40) and split equally into five groups by block randomization. After demineralization, one tooth slab was taken from each, and SEM analysis was done. Remineralization was then performed among the various groups that included Group 1, which acted as a control and consisted of the remineralization solution. Groups 2 and 3 comprised 1:1 and 2:1 concentrations of the coconut milk, whereas Groups 4 and 5 consisted of 1:1 and 2:1 concentrations of the lyophilized extract. SEM and EDAX testing were done post-remineralization. Ca and phosphate values were tabulated, and statistical significance was determined for the obtained values using ANOVA. Results: Among the control and treatment groups, surface remineralization was better observed in 1:1 coconut milk and 2:1 coconut milk than in the 2:1 lyophilized coconut, control, and 1:1 lyophilized coconut. Between the control and treatment groups, Ca and phosphate percentages (P < 0.001) showed statistical differences. The lowest value of 2.3% was noted in the 2:1 lyophilized coconut group. Conclusion: Coconut extracts exhibit remineralization potential on the artificial carious lesion. Coconut milk exhibited significant improvement in the surface properties than lyophilized coconut.

Comparison of treatment effects during en-masse retraction of upper anterior teeth placed using mini-implants placed at infrazygomatic crest and interradicular sites: A randomized controlled trial.

INTRODUCTION: The objective of this prospective study was to examine the efficacy of posterior interradicular and infrazygomatic crest mini-implants for en-masse anterior retraction. METHODS: The 22 patients were divided into two groups. In group 1 (IZC n = 11), mini-implants were placed in the infrazygomatic crests and in group 2 (IR, n = 11), mini-implants were placed in the molar-premolar interradicular sites. Soft tissue, skeletal, and dental treatment effects between two groups were compared using lateral cephalometric measurements. RESULTS: The average angle between the cranial base and A point was 1.01 degrees (P = .004), and the linear distance between the upper incisor and A point was 2.67 to 5.2 millimetres (P = .00). In IZC group the maxillary incisor to the palatal plane moved upward by a mean of -5.20 mm (P = .059), whereas in IR group the incisor movement changed by -2.67 mm (P = .068). There was no significant difference between groups IZC and IR while comparing overall treatment changes on upper incisor position change, angle, and overjet. CONCLUSIONS: Mini-implants placed in between the molar and premolar as well as the infrazygomatic crest can withstand the deepening of the bite during retraction. Mini-implants in IZC are capable of causing intrusion of the anterior teeth and preventing intrusion of the molars, thereby providing absolute anchoring in all planes. Placement of the mini-implants in the infrazygomatic crest resulted in more linear retraction.

Assessment of Soft Tissue, Airway Dimension and Hyoid Bone Position in Class II Patients Treated by PowerScope Class 2 Corrector.

AIM: This study aims to assess the changes in the soft tissue, pharyngeal airway dimensions, and hyoid bone position in patients treated with PowerScope Class 2 corrector to correct the skeletal Class II pattern. MATERIALS AND METHODS: This study was conducted on a sample of 20 cases diagnosed with Class II malocclusion. The lateral cephalograms were taken before (T1) and after functional appliance therapy (T2) and were traced. The outcomes were compared for the mean changes in soft tissue, airway way dimension, and hyoid bone position. The paired t-test was used for the data comparisons wherein p < 0.05 was kept for statistical significance. RESULTS: The mean values before and after treatment for H angle, mentolabial angle, lower lip E-line, upper lip S-line, lower lip S-line, and lip strain were 19.88 ± 2.77 vs 17.13 ± 1.659, 94.09 ± 12.164 vs 101.75 ± 11.28, -2.47 ± 1.213 vs -1.38 ± 0.976, 3.99 ± 0.19 vs 2.64 ± 0.32, 9.01 ± 0.247 vs 9.43 ± 0.238, 10.24 ± 0.510 vs 10.64 ± 0.52, respectively, which were statistically significant (p < 0.05). All airway spaces (except for lower pharyngeal space) and hyoid bone parameters were significantly improved posttreatment. CONCLUSION: The facial convexity, upper E-line, Z-angle, nasolabial angle, and lower pharyngeal space did not show statistically significant changes. The rest of the soft tissue parameters, oropharyngeal air spaces, and hyoid positioning measured in the study showed significant improvement after treatment with the PowerScope appliance in Class II patients. CLINICAL SIGNIFICANCE: Class II malocclusion is the most common dental anomaly with a high degree of prevalence in the population. This study will help the clinician in understanding the improvement of soft tissue, airway dimension, and hyoid bone position changes on treatment with a fixed functional appliance for the correction of Class II cases, thereby ensuring the greater success of orthodontic therapy in the future.

Enamel Remineralization Efficacy of Coconut Milk and Lyophilized Coconut Extract in Different Concentrations on Demineralized Enamel Surfaces: An In-Vitro Study.

Aim The current study's objective is to determine the remineralizing efficacy of freeze-dried lyophilized coconut extract and coconut milk made from freshly grated coconut on artificial carious lesions produced by pH cycling. Materials and methods Freshly extracted coconut pulp was split into two parts. The first half was blended to obtain coconut milk, and the second part was freeze-dried and lyophilized. Tooth slabs were prepared from extracted third molar teeth. After being demineralized for 72 hours, the tooth samples were remineralized by submerging them in the appropriate remineralizing solution, which is as follows: Group 1 received 25 mL of the Remineralization solution (the control); Group 2 received 2.5 g of coconut milk and 25 mL of the solution (1:1); and Group 3 received 5 g of coconut milk and 25 mL of the solution (2:1). 2.5 g of freeze-dried, lyophilized coconut extract was given to Group 4 along with 25 mL of remineralization solution (1:1), and 5 g of freeze-dried, lyophilized coconut extract was given to Group 5 along with 25 mL of remineralization solution (2:1). Microhardness and contact angle measurements were made. An Excel spreadsheet was filled up with values from after demineralization, and after remineralization. A statistical analysis was performed using SPSS 26.0 (IBM Corp., Armonk, NY). Using descriptive statistics, the pretreatment mean values for the microhardness and contact angle of the various groups were evaluated. Post-hoc Tukey tests were utilized to compare the analytic results of the various groups. Results Among the various concentrations of freshly extracted coconut milk, the contact angle in concentrations of 1:1 was 81.22 ± 1.62 deg, and that in concentrations of 2:1 was 88.01 ± 1.85 deg. Between the two concentrations of the lyophilized coconut extract group, the contact angle in 1:1 was 75.05 ± 2.29 deg, and in 2:1 was 71.37 ± 0.85 deg. In the coconut milk group, the value of microhardness was 261 ± 6.4 kg/cm2 at a lower concentration and 322 ± 3.9 kg/cm2 at a higher concentration. In the lyophilized coconut group, the lower concentration exhibited a microhardness of 211 ± 7.2 kg/cm2, whereas in the higher concentration, it was 324 ± 4.04 kg/cm2. Conclusion Of the various concentrations of coconut milk and lyophilized coconut used, coconut milk at a higher concentration exhibits the highest contact angle, and the latter at a higher concentration exhibits the lowest contact angle. In both groups, high concentrations of the material exhibited high microhardness values compared to lower concentrations of the same.

Small-molecule screen reveals pathways that regulate C4 secretion in stem cell-derived astrocytes.

In the brain, the complement system plays a crucial role in the immune response and in synaptic elimination during normal development and disease. Here, we sought to identify pathways that modulate the production of complement component 4 (C4), recently associated with an increased risk of schizophrenia. To design a disease-relevant assay, we first developed a rapid and robust 3D protocol capable of producing large numbers of astrocytes from pluripotent cells. Transcriptional profiling of these astrocytes confirmed the homogeneity of this population of dorsal fetal-like astrocytes. Using a novel ELISA-based small-molecule screen, we identified epigenetic regulators, as well as inhibitors of intracellular signaling pathways, able to modulate C4 secretion from astrocytes. We then built a connectivity map to predict and validate additional key regulatory pathways, including one involving c-Jun-kinase. This work provides a foundation for developing therapies for CNS diseases involving the complement cascade.

Assessment of Toxicity of Green Synthesized Silver Nanoparticle-coated Titanium Mini-implants with Uncoated Mini-implants: Comparison in an Animal Model Study.

AIM: To assess the potential for systemic toxicity when silver nanoparticle-coated mini-implants were implanted in Wistar albino rats conducted as a comparative study in the animal model by assessing the blood biochemistry, liver and kidney function, and histology of the implanted site. MATERIALS AND METHODS: The surface of the mini-implant was coated with a green-mediated silver nanoparticle. Uncoated mini-implants were placed in two groups of eight Wistar albino rats, and silver nanoparticle-coated mini-implants were placed in another eight rats. The bone's general conditions, blood biochemistry assessing for ALT, AST, GPT, GOT, and histological sections using H and E stain and Masson's Trichrome stain were examined at 7, 14, and 28-day intervals. RESULTS: The creatinine, urea, ALP, and ALT showed no signs of systemic toxicity during the 28-day follow-up period in the Wistar rats both in the test and control groups. The histological evaluation, which was conducted using HE and MTS stain, revealed osteogenesis and adequate healing of the insertion site in the group where coated mini-implant was placed. The bone sample revealed no abnormalities in the control group with uncoated mini-implants. CONCLUSION: Green synthesized silver nanoparticle-coated mini-implant does not cause systemic toxicity as indicated by no abnormalities in the levels of creatinine, urea, ALT, ALP, GPT, and GOT. The bone histology indicates that the coated mini-implants placed in animal bone healed with adequate osteogenesis. CLINICAL SIGNIFICANCE: Silver nanoparticles have potential for antimicrobial activity. Mini-implants placed as temporary anchorage devices in orthodontics often fail due to inflammation and plaque. Silver nanoparticle-coated mini-implants would reduce the risk of mini-implant failure as it would have antimicrobial potential and eliminate this cause for failure of mini-implants. How to cite this article: Sreenivasagan S, Subramanian AK, Mohanraj KG, et al. Assessment of Toxicity of Green Synthesized Silver Nanoparticle-coated Titanium Mini-implants with Uncoated Mini-implants: Comparison in an Animal Model Study. J Contemp Dent Pract 2023;24(12):944-950.

Morphology and gene expression profiling provide complementary information for mapping cell state.

Morphological and gene expression profiling can cost-effectively capture thousands of features in thousands of samples across perturbations by disease, mutation, or drug treatments, but it is unclear to what extent the two modalities capture overlapping versus complementary information. Here, using both the L1000 and Cell Painting assays to profile gene expression and cell morphology, respectively, we perturb human A549 lung cancer cells with 1,327 small molecules from the Drug Repurposing Hub across six doses, providing a data resource including dose-response data from both assays. The two assays capture both shared and complementary information for mapping cell state. Cell Painting profiles from compound perturbations are more reproducible and show more diversity but measure fewer distinct groups of features. Applying unsupervised and supervised methods to predict compound mechanisms of action (MOAs) and gene targets, we find that the two assays not only provide a partially shared but also a complementary view of drug mechanisms. Given the numerous applications of profiling in biology, our analyses provide guidance for planning experiments that profile cells for detecting distinct cell types, disease phenotypes, and response to chemical or genetic perturbations.

A multi-omic analysis of MCF10A cells provides a resource for integrative assessment of ligand-mediated molecular and phenotypic responses.

The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods ( synapse.org/LINCS_MCF10A ). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.

Cephalometric Analysis in Orthodontics Using Artificial Intelligence-A Comprehensive Review.

Artificial intelligence (AI) is a branch of science concerned with developing programs and computers that can gather data, reason about it, and then translate it into intelligent actions. AI is a broad area that includes reasoning, typical linguistic dispensation, machine learning, and planning. In the area of medicine and dentistry, machine learning is currently the most widely used AI application. This narrative review is aimed at giving an outline of cephalometric analysis in orthodontics using AI. Latest algorithms are developing rapidly, and computational resources are increasing, resulting in increased efficiency, accuracy, and reliability. Current techniques for completely automatic identification of cephalometric landmarks have considerably improved efficiency and growth prospects for their regular use. The primary considerations for effective orthodontic treatment are an accurate diagnosis, exceptional treatment planning, and good prognosis estimation. The main objective of the AI technique is to make dentists' work more precise and accurate. AI is increasingly being used in the area of orthodontic treatment. It has been evidenced to be a time-saving and reliable tool in many ways. AI is a promising tool for facilitating cephalometric tracing in routine clinical practice and analyzing large databases for research purposes.

Comparative Assessment of pH and Degree of Surface Roughness of Enamel When Etched with Five Commercially Available Etchants: An In Vitro Study.

AIM: To evaluate the pH and degree of surface roughness caused by five commercially and readily available etchants on tooth enamel. MATERIALS AND METHODS: Five different etchants were chosen. An electric pH meter was utilized to test the pH of the etchants employed. Fifteen maxillary bicuspids that had been extracted were cleansed and stored in thymol solution. The samples were sorted into five groups of three each. A noncontact profilometer was employed to assess the microsurface changes of the pre-etched enamel. The teeth were then etched for 30 seconds with respect to the group to which they belonged before being cleaned and dried. The surface roughness after etching was analyzed, measured and values were tabulated. Descriptive statistics and paired t-test were done. RESULTS: The pH of the etchants and surface roughness of the enamel are varied across the five groups, though they have the same composition of 37% orthophosphoric acid. Etchant from Group C was found to be most acidic while the one manufactured by Group E was least acidic. Ivoclar, DPI, and DTECH showed a statistically significant value in surface roughness parameter post-etching (p <0.05). A statistical difference that was significant was observed with the Kruskal-Wallis test for surface roughness parameter (p <0.05). CONCLUSION: All five etchants had varied pH and the amount of surface roughness was also varied though the composition was the same. Further elemental analysis of these etchants has to be done to validate the results obtained. CLINICAL SIGNIFICANCE: Etchants of the same composition should ideally produce the same effect on the tooth enamel surface, but etchants from different manufacturers produce different levels of surface roughness which could be due to differences in the composition of the prepared etchant. The study was conducted to assist in making an educated selection about the most cost-effective but efficient etchant for clinical application.

The World Wide Web of orthodontics- A comprehensive narrative on teledentistry pertaining to the orthodontics of the 21st century.

Teledentistry has proven effective in practically all dental fields. It also allows access to inaccessible and underdeveloped locations. Better treatment outcomes were documented in patients treated by an orthodontist supervised by teledentistry than by a general dentist with minimal orthodontic experience alone. It may also help to focus referrals to specialists and weed out those who do not need them. But, on a critical note, a doctor-patient relationship is much more than a business transaction. A face-to-face initial consultation instills trust that a remote session cannot. Teledentistry includes professional networking of doctors. This contact includes digital information exchange, CPD programs, case discussions, and analysis that bring dentists from all around the world together to improve patient care. Teledentistry has not only spanned the distance between dentists worldwide, but has also served as a conduit between customer (patient) and manufacturer. This spawned Direct to Consumer (DTC) dentistry, sparking substantial debate among dentists worldwide. In DTC dentistry, inadequately trained customers conduct complex procedures on themselves with minimal guidance of a dentist. One of the major issues today is the general availability of clear aligners to patients without the requirement for an intermediary skilled orthodontist. The American Association of Orthodontists (AAO) has publicly questioned the validity of Smile Direct Club, a private firm that dominates the DTC industry. European Federation of Orthodontic Specialists Association, on the other hand, has sponsored a joint declaration with the representative orthodontic associations in Europe to highlight and alert patients about the potential risks of DTC products. Unfortunately, public shaming hasn't slowed commercialization of DTC firms. Teledentistry has been a boon for healthcare, but a nightmare for our profession, raising fundamental questions like what is the difference between a customer and a patient? Is dentistry a just another discipline of cosmetics? Is teledentistry making us less connected with our patients?

In vitro anti-inflammatory activity of silymarin/hydroxyapatite/chitosan nanocomposites and its cytotoxic effect using brine shrimp lethality assay.

Silymarin, a bioactive compound, is one of the most prominent drugs used in liver diseases. Chitosan and hydroxyapatite (HAP) are the major materials used employed in many biomedical processes like drug delivery, osteointegration, etc. The nanoparticles and nanocomposites are advanced materials with many biomedical applications in diagnosis and therapeutics. In this study, HAP and chitosan were used as a polymeric material, silymarin as a bioactive compound, and other nanoparticle based combinations. The prepared individual materials and nanocomposites were used for the anti-inflammatory activity and brine shrimp lethality assay. The results clearly show that the nanocomposites are good anti-inflammatory agents with lower toxicity.

Translating in vitro CFTR rescue into small molecule correctors for cystic fibrosis using the Library of Integrated Network-based Cellular Signatures drug discovery platform.

Cystic fibrosis (CF) is a lethal autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The common ΔF508-CFTR mutation results in protein misfolding and proteasomal degradation. If ΔF508-CFTR trafficks to the cell surface, its anion channel function may be partially restored. Several in vitro strategies can partially correct ΔF508-CFTR trafficking and function, including low-temperature, small molecules, overexpression of miR-138, or knockdown of SIN3A. The challenge remains to translate such interventions into therapies and to understand their mechanisms. One approach for connecting such interventions to small molecule therapies that has previously succeeded for CF and other diseases is via mRNA expression profiling and iterative searches of small molecules with similar expression signatures. Here, we query the Library of Integrated Network-based Cellular Signatures using transcriptomic signatures from previously generated CF expression data, including RNAi- and low temperature-based rescue signatures. This LINCS in silico screen prioritized 135 small molecules that mimicked our rescue interventions based on their genomewide transcriptional perturbations. Functional screens of these small molecules identified eight compounds that partially restored ΔF508-CFTR function, as assessed by cAMP-activated chloride conductance. Of these, XL147 rescued ΔF508-CFTR function in primary CF airway epithelia, while also showing cooperativity when administered with C18. Improved CF corrector therapies are needed and this integrative drug prioritization approach offers a novel method to both identify small molecules that may rescue ΔF508-CFTR function and identify gene networks underlying such rescue.

Pain Perception Associated with Mini-Implants and Interventions for Pain Management: A Cross-Sectional Questionnaire-Based Survey.

BACKGROUND: Orthodontists use mini-implants temporarily as an effective mode of skeletal anchorage devices. The placement of mini-implants can cause pain and discomfort to the patients. Patients often develop swelling, and the pain could interfere with their daily activities. Practitioners tend to prescribe antibiotics and pain medication for management. OBJECTIVES: The main objectives of this study are to evaluate the pain perception and discomfort due to mini-implant placement experienced by the patient and evaluate the interventions for pain management commonly practiced among orthodontists. MATERIALS AND METHODS: The study was designed as a questionnaire-based cross-sectional study. A total of 271 patients were assessed, for whom 625 mini-implants (ranging from 1.2 to 2 mm diameter and length 8-14 mm) were placed. Pain scores were assessed using the VAS and the "Faces" pain rating scale to collect data about discomfort in daily activity and function. Data was collected from 244 patients. A total of 155 orthodontists were questioned regarding the prescription of medications and the interventions for managing pain and adverse effects. RESULTS: Average pain score among female subjects was 16.71 and among men was 13.5. The highest pain scores were recorded for palatal mini-implants with an average score of 36.29 and the least for interradicular mini-implants with an average score of 9.02. Among the subjects, 47.9% of them took analgesics, and the most commonly prescribed analgesics were paracetamol (39%). Swelling at the site is where the mini-implants were placed, and ulceration due to implants were commonly dealt with the excision of the surrounding soft tissue, composite placement, and palliative care with oral analgesic gels. CONCLUSION: Female subjects had more mini-implants placed, and female subjects had also given more pain scores than their male counterparts. Palatal mini-implants caused the highest pain, followed by mini-implants placed at the infrazygomatic crest and the buccal shelf region. Palatal mini-implants caused maximum discomfort during speech and eating, followed by the mini-implant in the buccal shelf and the infrazygomatic crest region that also caused difficulty in yawning and laughing. Infiltration anesthesia was commonly given for the placement of interradicular implants and extra-alveolar mini-implants. Paracetamol was the most prescribed by the orthodontists, and more than half the doctors did not regularly prescribe antibiotics.

Assessment of Wettability and Contact Angle of Bonding Agent with Enamel Surface Etched by Five Commercially Available Etchants: An In Vitro Study.

BACKGROUND: The quantity and quality of the etching pattern produced by acids play a significant role in the wettability and contact angle of the adhesive with the enamel surface in orthodontics. The better the etch pattern, the more the surface energy of the enamel, better the penetration of the adhesive, which ultimately results in better bond strength. The present study aimed to evaluate the contact angle of the bonding agent with the enamel surface etched by five commercially available etchants and check if any difference existed between the five. MATERIALS AND METHODS: Twenty-five human maxillary and mandibular central incisors and premolars extracted for orthodontic or dental purposes were used in this study as samples. The teeth were allocated into five groups based upon the etchant used to etch the enamel surface. After the samples were etched, a hard tissue microtome was used to create thin slices of the enamel surface. The samples were then exposed to bonding agent Ormco Enlight. The bonding agent was released in the form of droplets onto the enamel slices mounted on a contact angle goniometer. The contact angle values were tabulated, and statistical analysis using the one-way ANOVA test was carried out. RESULTS: The contact angle measurements of the etchant group, DPI, were the lowest, while D-tech has the highest contact angle values. However, statistical analysis revealed no statistically significant difference between the contact angle measurements of the five groups included in the study. CONCLUSION: No statistically significant difference existed between the five etchant groups included in the study. However, commercially available etchant DPI showed lesser contact angle and thus better wettability in comparison to other groups. Further elemental analysis and surface analysis are required to validate these results.

The Exponential Rise of Teledentistry and Patient-Oriented Protective Measures in Southeast Asian Dental Clinics: Concerns, Benefits, and Challenges.

In the Southeast Asian region, various policies have been advocated by health regulatory bodies that entail protective measures such as face masks, gloves, maintaining distance in public areas, and more. These protective measures are aimed at helping reverse the growth rate of the coronavirus. Dentists in this region have incorporated several changes to their practices to help minimize risks of person-to-person transmission inside dental offices. This narrative review aimed to provide an in-depth overview of the current situation in the Southeast Asian region regarding the use of teledentistry during the pandemic. Teledentistry involves the transfer of patient information across remote distances for online consultation and treatment planning. A few years back, it used to be a lesser-known entity but has seen an exponential rise in its incorporation into dental practices all around the Association of Southeast Nations (ASEAN) region. Many clinics in the Southeast Asian region have started using online consultations to ensure that patients can be diagnosed or followed up during their treatment. Teledentistry is the clear answer in the coming months as it will help reduce the risk of virus transmission and help patients get access to oral healthcare and dentists to see their patients. This article reviews the current pandemic situation in the ASEAN region, the recent evidence, and the scope of teledentistry. It also provides recommendations for the future and sheds light on the different types of teledentistry and how it can be incorporated into practices by regulatory authorities in this region.

Prevalence and Cause of Mini-Implant Failure Encountered by Orthodontic Residents.

This study was designed to increase understanding of mini-implants as well as causes of mini-implant complications and failure in orthodontic patients. Orthodontic case sheets were evaluated to identify retraction in mini-implant cases. Samples were taken and tabulated to determine causes and sites of mini-implant failure. The overall success rate of mini-implants over a period of 3 months postplacement follow-up was 83.5%, indicating that screw implants can be used for orthodontic anchorage. To minimize failure, clinicians should attempt to reduce inflammation around screw implants.

A human liver cell-based system modeling a clinical prognostic liver signature for therapeutic discovery.

Chronic liver disease and hepatocellular carcinoma (HCC) are life-threatening diseases with limited treatment options. The lack of clinically relevant/tractable experimental models hampers therapeutic discovery. Here, we develop a simple and robust human liver cell-based system modeling a clinical prognostic liver signature (PLS) predicting long-term liver disease progression toward HCC. Using the PLS as a readout, followed by validation in nonalcoholic steatohepatitis/fibrosis/HCC animal models and patient-derived liver spheroids, we identify nizatidine, a histamine receptor H2 (HRH2) blocker, for treatment of advanced liver disease and HCC chemoprevention. Moreover, perturbation studies combined with single cell RNA-Seq analyses of patient liver tissues uncover hepatocytes and HRH2+, CLEC5Ahigh, MARCOlow liver macrophages as potential nizatidine targets. The PLS model combined with single cell RNA-Seq of patient tissues enables discovery of urgently needed targets and therapeutics for treatment of advanced liver disease and cancer prevention.

Assessment of Insertion Torque of Mini-implant and Its Correlation with Primary Stability and Pain Levels in Orthodontic Patients.

AIM: The aim of this study was to assess the insertion torque of the mini-implant used in orthodontic patients and to assess the correlation between the insertion torque, primary stability, and perception of pain in patients undergoing orthodontic therapy with mini-implant-augmented anchorage. MATERIAL AND METHODS: Among the patients undergoing orthodontic therapy, 31 samples who required mini-implant for anchorage purpose were selected. A total of 59 mini-implants were placed in these patients. This included interradicular mini-implants and extra-alveolar mini-screws. Immediately after placement, the insertion torque in all these was measured using a digital torque meter and primary stability was assessed by identifying any mobility of the implant placed. Primary stability was noted at two time intervals immediate post-placement and 1 week after that. All the mini-implants that were considered in this study were immediately loaded. Patients were asked to record any pain experienced on the visual analog scale (VAS) score sheet at 24 hours and 1 week post-placement. RESULTS: Among the mini-implants placed, those with 2 mm diameter needed higher placement torque, i.e., infrazygomatic crest mini-implants and buccal shelf mini-implants were placed with average placement torque of 10.08 and 10.25 N cm, respectively. Extra-alveolar screws caused more pain, especially higher in the mandible than the maxilla. Decrease in pain scores was noted from T0 to T1 in almost all the cases. CONCLUSION: Thicker mini-implant needed more insertion torque and highest insertion torque was recorded with extra-alveolar screws. No direct correlation could be obtained with the pain levels experienced by the patients and with the primary stability of the mini-implants. CLINICAL SIGNIFICANCE: Mini-implants placed with an insertion torque above the recommended range tend to fail and break more often. Patients placed with extra-alveolar bone screws reported more pain than that of the smaller-dimension mini-implant.