Syzygium cumini (L.) skeels mitigate diabetic nephropathy by regulating Nrf2 pathway and mitocyhondrial dysfunction: In vitro and in vivo studies.

ETHNOPHARMACOLOGICAL PREVALENCE: Hyperglycemia in diabetes increases the generation of advanced glycation end products (AGEs) through non-enzymatic reactions. The interaction between AGEs and their receptors (RAGE) leads to oxidative and inflammatory stress, which plays a pivotal role in developing diabetic nephropathy. Syzygium cumini (SC) L. (DC.) homeopathic preparations viz. 200C, 30C, and mother tincture [MT] are used to treat diabetes. This study aimed to elucidate the regulatory effects of SC preparations (200C, 30C, and MT) on the nuclear factor erythroid 2-related factor 2 (Nrf2) - nuclear factor-κB (NF-κB) pathways and mitochondrial dysfunction in mitigating diabetic nephropathy (DN). MATERIALS AND METHODS: Streptozotocin-induced diabetic rats were treated with SC preparations (200C, 30C, MT; 1:20 dilution in distilled water; 600 µL/kg body weight) and metformin (45 mg/kg body weight) twice daily for 40 days. DN was evaluated through biochemical parameters and histological examination. Renal tissue lysates were analyzed for glycation markers. Protein and gene levels of Nrf2, NF-κB, and mitochondrial dysfunctional signaling were determined via western blotting and RT-qPCR. An immunohistochemical analysis of the kidneys was performed. In vitro, human serum albumin (HSA - 10 mg/ml) was glycated with methylglyoxal (MGO - 55 mM) in the presence of SC preparations (200C, 30C, MT) for eight days. Glycated samples (400 µg/mL) were incubated with renal cells (HEK-293) for 24 h. Further reactive oxygen species production, Nrf2 nuclear translocation, and protein or gene expression of Nrf2 and apoptosis markers were analyzed by western blotting, RT-qPCR, and flow cytometry. Molecular docking of gallic and ellagic acid with the HSA-MGO complex was performed. RESULT: In vivo experiments using streptozotocin-induced diabetic rats treated with SC preparations exhibited improved biochemical parameters, preserved kidney function, and reduced glycation adduct formation in a dose-dependent manner. Furthermore, SC preparations downregulated inflammatory mediators such as RAGE, NF-κB, vascular endothelial growth factor (VEGF), and Tumor necrosis factor α (TNF-α) while upregulating the Nrf2-dependent antioxidant and detoxification pathways. They downregulated B-cell lymphoma 2 (Bcl-2) associated X-protein (BAX), C/EBP homologous protein (CHOP), Dynamin-related protein 1 (DRP1), and upregulated BCL 2 gene expression. Notably, SC preparations facilitated nuclear translocation of Nrf2, leading to the upregulation of antioxidant enzymes and the downregulation of oxidative stress markers. Molecular docking studies revealed favorable interactions between gallic (-5.26 kcal/mol) and ellagic acid (-4.71 kcal/mol) with the HSA-MGO complex. CONCLUSION: SC preparations mitigate renal cell apoptosis and mitochondrial dysfunction through Nrf2-dependent mechanisms.

Evaluation and Comparison of Dentin Thickness, Centering Ability, Canal Transportation, and Instrumentation Time of Pro AF Baby Gold and Pedoflex Files in Primary Root Canals Using a Cone Beam Computed Tomographic Analysis: An In Vitro Study.

Introduction: Pediatric rotary systems have the advantage of improved canal centricity and conservative canal preparation with better obturation quality. Pro AF Baby Gold and Pedoflex files are two exclusive pediatric rotary file systems that were introduced in recent times. Aim and objective: The aim of the present study is to compare and evaluate the dentine thickness, centering ability, canal transportation, and instrumentation time of Pro AF Baby Gold and Pedoflex files using cone beam computed tomography (CBCT). Materials and methods: A total of 40 extracted human primary molar teeth with a minimum 7 mm root length were included in the study and randomly divided into two groups: group I, Pro AF Baby Gold; group II, Pedoflex files. Teeth were imaged preoperatively with CBCT, then root canal preparation was done in both groups with respective files, followed by postoperative CBCT imaging to evaluate the dentin thickness, centering ability, and canal transportation of both groups. Instrumentation time was noted using a stopwatch. Results: There is a statistically significant difference in the instrumentation time; Pedoflex took a shorter time when compared to Pro AF Baby Gold files. Regarding canal transportation, there was no significant difference between the two files, with Pedoflex showing a better value than the other files. Regarding centering ability, there was no significant difference between the two files, with Pro AF Baby Gold having a better value than the other files (p < 0.001). Conclusion: From the findings of our present study, it was found that both systems were able to effectively shape curved root canals in terms of canal transportation and centering ability. How to cite this article: Busi S, PJ N, Deoghare A, et al. Evaluation and Comparison of Dentin Thickness, Centering Ability, Canal Transportation, and Instrumentation Time of Pro AF Baby Gold and Pedoflex Files in Primary Root Canals Using a Cone Beam Computed Tomographic Analysis: An In Vitro Study. Int J Clin Pediatr Dent 2024;17(8):892-897.

Exploring the glycation association with dyslipidaemia: Novel approach for diabetic nephropathy.

The transcription factor known as sterol regulatory element-binding protein (SREBP) and the glycation pathways, specifically the formation of Advanced Glycation End Products (AGEs), have a significant and deleterious impact on the kidney. They alter renal lipid metabolism and promote glomerulosclerosis, mesangial cell expansion, tubulointerstitial fibrosis, and inflammation, leading to diabetic nephropathy (DN) progression. Although several pieces of scientific evidence are reported for potential causes of glycation and lipotoxicity in DN, the underlying mechanism of renal lipid accumulation still needs to be fully understood. We provide a rationalized view on how AGEs exert multiple effects that cause SREBP activation and inflammation, contributing to DN through Receptor for AGEs (RAGE) signaling, AGE-R1-dependent downregulation of Sirtuin 1 (SIRT-1), and increased SREBP Cleavage Activating Protein (SCAP) glycosylation. This review emphasizes the association between glycation and the SREBP pathway and how it affects the onset of DN associated with obesity. Finally, we discuss the correlation of glycation and the SREBP pathway with insulin resistance (IR), oxidative stress, endoplasmic reticulum stress, inflammation, and existing and emerging therapeutic approaches toward better controlling obesity-related DN.

Guidance of Erupting First Permanent Molar in Complex Clinical Scenarios: A Case Series.

Aim: The aim of this current case series is to propose various design modifications of the conventional distal shoe space maintainers in relation to complex clinical scenarios. Background: Primary dentition plays a significant role in preserving space for underlying unerupted permanent teeth; early childhood caries (ECC) is a serious public health problem in both developing and developed countries, and it is often left untreated. Its consequences can have an immediate and long-term impact on the child's quality of life and overall health. Premature loss of primary dentition can result in loss of arch length, thereby hampering the eruption of the succeedaneous tooth, which can further lead to malalignment, crowding, rotation, and impaction of the permanent teeth. Space maintainers are advocated in cases where extraction of primary molars is inevitable. In the early loss of the second primary molar, a distal-shoe space maintainer is advocated to guide the eruption, as well as prevent mesial migration of the first permanent molar (FPM) during the eruption. In clinical scenarios where multiple losses of deciduous molars occur bilaterally, obtaining adequate anchorage is questionable and futile. The following clinical modifications, however, are useful in overcoming the problems related to the same. The following case series intends to project various modifications of distal shoes in complex scenarios. Case description: Various modifications of the distal shoe have been proposed in our current case series. The appliances were adjusted individually on a case-to-case basis depending on the clinical scenario. A 1-year clinical follow-up was carried out on all the patients. Conclusion: All the clinical modifications were successful in guiding the eruption of a FPM; there were no complications during any follow-up visit. Clinical significance: In cases where the traditional design is not indicated, certain modifications in distal shoes by adding new components to the appliance will allow the appliance to be placed and the space to be maintained effectively. Along with this, reinforcement of parents and the child for oral hygiene maintenance will maintain the remaining healthy tooth structure and increase the success of treatment. How to cite this article: Gunjal PY, Chauhan RS, Tirupathi S, et al. Guidance of Erupting First Permanent Molar in Complex Clinical Scenarios: A Case Series. Int J Clin Pediatr Dent 2024;17(3):362-367.

Effect of Different Iron Supplements on Color Stability of Nanocomposite Restorative Materials.

Physical development and growth are significantly influenced by adequate nutrition. Enamel, dentin, and dental pulp are among the tissues that contain iron, which is regarded as a necessary element for human health. The disadvantages of the available iron drops include bad taste and black discoloration of primary teeth. In areas that are decalcified and hypomineralized, this discoloration is more noticeable. Therefore, efforts are being made to create iron drops that have a more pleasant taste and minimal adverse effects (i.e., no or minimal tooth discoloration). Liposomes are minuscule vesicles made of the bilayer of phospholipids that can encase both hydrophilic and hydrophobic drugs to boost their effectiveness and lessen side effects (color staining). Therefore, the goal of the study is to compare the color stability of cosmetic materials with that of pediatric liposomal iron supplements and regular pediatric iron supplements. How to cite this article: Lokhande RS, PJ N, Deoghare A,et al. Effect of Different Iron Supplements on Color Stability of Nanocomposite Restorative Materials. Int J Clin Pediatr Dent 2024;17(3):274-278.

Evolving Trends in the Diagnosis and Management of Keratoconus Over 3 Decades.

PURPOSE: To report the trends in the clinical presentation, diagnosis, and management of keratoconus (KC) in patients presenting to a multitier hospital network over 33 years. METHODS: This retrospective study included patients with KC presenting from 1987 to 2020. Patients with KC in at least 1 eye were included. The data of 20,576 patients included in this study were retrieved from the electronic medical record database. Data on patient demographics, ocular diagnosis, contact lens usage, and surgical history were collected and exported for analysis. Descriptive statistics and chi square test were used for statistical analysis. RESULTS: A total of 20,576 KC cases were seen from 1987 to 2020. Mean age at diagnosis reduced from 29.3 years (1987-1991) to 22.2 years (2016-2020). Adults (76.64%) were commonly affected with a majority being male (61.25%). Use of contact lenses increased from 4.34% (2002-2006) to 11.23% (2016-2020). Of the total number of surgical interventions, collagen crosslinking (CXL) constituted more than 1/5th (22.28%) between 2007 and 2011, which increased to more than half between 2012 and 2016 (53.61%) and almost 3/4th (72.53%) between 2017 and 2020. Advances in lamellar surgery have led to more patients undergoing deep anterior lamellar keratoplasty (DALK) as compared with penetrating keratoplasty. In the last 8 years, 17.2% patients underwent surgery and the most common was CXL (14.77%) followed by DALK (1.72%) and penetrating keratoplasty (1.04%). CONCLUSIONS: We report the trends in the clinical presentation and management of KC over 3 decades. In the last 33 years, advances in diagnostics have helped diagnose KC earlier. Contact lenses and advances in CXL have reduced the number of keratoplasties in KC, DALK being more common.

Quantum dots in noninvasive imaging of oral squamous cell carcinomas: A scoping literature review.

ABSTRACT: The current scoping review's objective was to outline existing applications, recent breakthroughs, and quantum dots' applicability in imaging of oral squamous cell cancer. Quantum dots are nanometric semiconductor crystals with customizable optical characteristics and intense, stable fluorescence suited for bioimaging and labeling. We used the Preferred reporting items for systematic reviews and meta-analyses (PRISMA) recommendations for conducting our systematic search. An analysis of the properties and applications of quantum dots in noninvasive detection of oral squamous cell cancer is presented in this study, which comprehensively explores the available evidence. Following searches in the databases PubMed, Ovid SP, and Cochrane using the search terms quantum dots AND oral squamous cell cancer, 55 published publications were chosen for this review. The review identified a total of eight papers that met the criteria. In noninvasive detection of oral squamous cell carcinoma, quantum dots have the potential to offer an array of therapeutic and diagnostic applications. Furthermore, quantum dots emit near-infrared and visible light, which is advantageous in biological imaging since it reduces light dispersion and absorption of tissue. The future may see quantum dots become a popular noninvasive imaging technique for oral squamous cell cancer. The number of studies accessible is quite limited, and further research is required.

Impact of Patient Education Formats on Treatment Adherence and Denture Hygiene in Edentulous Patients: A Comparative Study.

BACKGROUND Effective communication and patient education are important in geriatric dental care. Memory decline complicates patient adherence. This study aimed to compare verbal, audio, and video patient education material (PEM) and adherence to dental prosthetic management in edentulous patients. MATERIAL AND METHODS 90 completely/partially edentulous patients (aged 40 to 70 years), were divided (simple random) into three groups (Gp) of 30 each . A total of 68 instructions were organized into 9 learning categories. For GpVi, a 20 minute video was shot using a Sony camera (PD170), with two actors depicting related PEM information. Patients were recalled after 1 day and 7days, to recall the PEM instructions. A Denture plaque Index (DPI) determined the efficiency of the instructions at both time intervals. Frequencies, means and standard deviations were derived for each group and then compared using Chi square, paired and unpaired t test and a Neuman-Keul post hoc pairwise test. All significant differences were kept at probability t value of ≤0.05. RESULTS PEM instructions related to patient individuality, proper tongue position and miscellaneous showed poor patient recall. At 1 day interval, audio was found to have better recall than video and verbal in 5 PEM instruction categories. At 7 day interval, video showed better recall than other two groups (P≤0.05). Despite improvements in patients recall, DPI revealed better denture hygiene maintenance in patients receiving instructions through video format (P≤0.05). CONCLUSIONS For all categories, no single media was considered to be sufficient, audio produced early better recall while video influenced long term recall and better denture hygiene maintenance.

Alleviation of albumin glycation-induced diabetic cardiomyopathy by L-Arginine: Insights into Nrf-2 signaling.

In hyperglycemia, accelerated glycation and oxidative stress give rise to many diabetic complications, such as diabetic cardiomyopathy (DCM). Glycated human serum albumin (GHSA) has disturbed structural integrity and hampered functional capabilities. When GHSA accumulates around cardiac cells, Nrf-2 is dysregulated, aiding oxidative stress. L-Arginine (L-Arg) is prescribed to patients with diabetes and cardiovascular diseases. This research contributes to the mechanistic insights on antiglycation and antioxidant potential of L-Arg in alleviating DCM. HSA was glycated with methylglyoxal in the presence of L-Arg (20-640 mM). Structural and functional modifications of HSA were studied. L-Arg and HSA, GHSA interactions, and thermodynamics were determined by steady-state fluorescence. H9c2 cardiomyocytes were given treatments of GHSA-L-Arg along with the inhibitor of the receptor of AGEs. Cellular antioxidant levels, detoxification enzyme activities were measured. Gene, protein expressions, and immunofluorescence data examined the activation and nuclear translocation of Nrf-2 during glycation and oxidative stress. L-Arg protected HSA from glycation-induced structural and functional modifications. The binding affinity of L-Arg was more towards HSA (104 M-1). L-Arg, specifically at lower concentration (20 mM), upregulated Nrf-2 gene, protein expressions and facilitated its nuclear translocation by activating Nrf-2 signaling. The study concluded that L-Arg can be of therapeutic advantage in glycation-induced DCM and associated oxidative stress.

The Eyes Absent family members EYA4 and EYA1 promote PLK1 activation and successful mitosis through tyrosine dephosphorylation.

The Eyes Absent proteins (EYA1-4) are a biochemically unique group of tyrosine phosphatases known to be tumour-promoting across a range of cancer types. To date, the targets of EYA phosphatase activity remain largely uncharacterised. Here, we identify Polo-like kinase 1 (PLK1) as an interactor and phosphatase substrate of EYA4 and EYA1, with pY445 on PLK1 being the primary target site. Dephosphorylation of pY445 in the G2 phase of the cell cycle is required for centrosome maturation, PLK1 localization to centrosomes, and polo-box domain (PBD) dependent interactions between PLK1 and PLK1-activation complexes. Molecular dynamics simulations support the rationale that pY445 confers a structural impairment to PBD-substrate interactions that is relieved by EYA-mediated dephosphorylation. Depletion of EYA4 or EYA1, or chemical inhibition of EYA phosphatase activity, dramatically reduces PLK1 activation, causing mitotic defects and cell death. Overall, we have characterized a phosphotyrosine signalling network governing PLK1 and mitosis.

Homeopathic Formulations of Syzygium jambolanum Alleviate Glycation-Mediated Structural and Functional Modifications of Albumin: Evaluation through Multi-Spectroscopic and Microscopic Approaches.

BACKGROUND: The growing interest in identifying the mode of action of traditional medicines has strengthened its research. Syzygium jambolanum (Syzyg) is commonly prescribed in homeopathy and is a rich source of phytochemicals. OBJECTIVE: The present study aims to shed light on the anti-glycation molecular mechanism of Syzyg mother tincture (MT), 30c, and 200c on glycated human serum albumin (HSA) by multi-spectroscopic and microscopic approaches. METHODS: The phytochemicals and antioxidant potential of the Syzyg formulations were estimated by the high-performance liquid chromatography and spectroscopic technique, respectively. Glycation was initiated by incubating HSA with methylglyoxal, three Syzyg formulations, and the known inhibitor aminoguanidine in separate tubes at 37°C for 48 hours. The formation of glycation adducts was assessed by spectrofluorometer and affinity chromatography. The structural modifications were analyzed through circular dichroism, Fourier transform infrared spectroscopy, turbidity, 8-anilinonapthalene-1-sulfonic acid fluorescence, and nuclear magnetic resonance. Further, the formation of the aggregates was examined by thioflavin T, native-polyacrylamide gel electrophoresis, and transmission electron microscopy. Additionally, the functional modifications of glycated HSA were determined by esterase-like activity and antioxidant capacity. The binding analysis of Syzyg formulations with glycated HSA was evaluated by surface plasmon resonance (SPR). RESULTS: Syzyg formulations MT, 30c, and 200c contained gallic acid and ellagic acid as major phytochemicals, with concentrations of 16.02, 0.86, and 0.52 µg/mL, and 227.35, 1.35, and 0.84 µg/mL, respectively. Additionally, all three formulations had remarkable radical scavenging ability and could significantly inhibit glycation compared with aminoguanidine. Further, Syzyg formulations inhibited albumin's structural and functional modifications. SPR data showed that Syzyg formulations bind to glycated HSA with an equilibrium dissociation constant of 1.10 nM. CONCLUSION: Syzyg formulations inhibited the glycation process while maintaining the structural and functional integrity of HSA.

Mechanistic role of Syzygium cumini (L.) Skeels in glycation induced diabetic nephropathy via RAGE-NF-κB pathway and extracellular proteins modifications: A molecular approach.

ETHNOPHARMACOLOGY RELEVANCE: Syzygium cumini (L.) Skeels (SC), an ancient medicinal plant, is used as a complementary and alternative medicine for treating diabetes mellitus and its associated complications, such as diabetic nephropathy (DN). Phytochemicals present in SC homeopathic formulations possess anti-glycemic, anti-glycation, anti-inflammatory, and antioxidant properties. Additionally, the non-enzymatic formation of advanced glycation end products (AGEs) increases during hyperglycemia in diabetes. AGEs interaction with their receptor of AGEs (RAGE) promotes inflammation via Nuclear Factor-κB (NF-κB) and the accumulation of Extracellular Matrix (ECM) proteins, contributing to the renal dysfunction in DN. However, the molecular mechanism through which SC formulations interact with the AGEs-RAGE-NF-κB pathway has not yet been investigated. AIM: This study aims to examine the impact of SC formulations on the RAGE-NF-κB pathway and ECM protein modifications in glycation-induced DN using a molecular approach. MATERIALS AND METHODS: Human serum albumin (10 mg/ml) was glycated with MGO (55 mM) in the presence of SC formulations - Mother tincture (MT), 30C, 200C for 7 days. Glycated samples were added to renal cells (HEK 293) for 24 h. Subsequently, cellular gene and protein expressions of RAGE, NF-κB, vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), collagen IV (Col IV), and fibronectin were determined using RT-qPCR and Western blot analysis. The immunofluorescence, luciferase assay, and chromatin immunoprecipitation techniques were employed to gain insights into glycation-induced NF-κB nuclear translocation, transcriptional activity, and its effect on RAGE promoter activity in SC-treated cells. RESULTS: SC formulations significantly downregulated glycation-induced elevated levels of RAGE and NF-κB. Mechanistically, SC formulations prevented NF-κB nuclear translocation, transcriptional activity, and RAGE promoter activity. Also, SC formulations significantly attenuated glycation-enhanced expressions of inflammatory cytokines (IL-6, TNF-α, and VEGF) and ECM proteins (Col IV and fibronectin). CONCLUSION: Our findings enlighten the molecular mechanism of SC in DN by targeting the AGEs-RAGE-NF-κB signaling pathway, inflammatory responses, and ECM accumulation. Hence, the study validates the protective role of SC formulations and signifies its novel potential for treating DN.

Keratoconus in India: Clinical presentation and demographic distribution based on big data analytics.

PURPOSE: This paper aims to describe the clinical presentation and demographic distribution of keratoconus (KCN) in India by analyzing the electronic medical records (EMR) of patients presenting at a multitier ophthalmology hospital network. METHODS: This cross-sectional hospital-based study included the data of 2,384,523 patients presenting between January 2012 and March 2020. Data were collected from an EMR system. Patients with a clinical diagnosis of KCN in at least one eye were included in this study. Univariate analysis was performed to identify the prevalence of KCN. A multiple logistic regression analysis was performed using R software (version 3.5.1), and the odds ratios are reported. RESULTS: Data were obtained for 14,749 (0.62%) patients with 27,703 eyes diagnosed with KCN and used for the analysis. The median age of the patients was 22 (inter-quartile range (IQR): 17-27). In total, 76.64% of adults (odds ratio = 8.77; P = <0.001) were affected the most. The majority of patients were male (61.25%), and bilateral (87.83%) affliction was the most common presentation. A significant proportion of the patients were students (63.98%). Most eyes had mild or no visual impairment (<20/70; 61.42%). Corneal signs included ectasia (41.35%), Fleischer ring (44.52%), prominent corneal nerves (45.75%), corneal scarring (13.60%), Vogts striae (18.97%), and hydrops (0.71%). Only 7.85% showed an association with allergic conjunctivitis. A contact lens clinic assessment was administered to 47.87% of patients. Overall, 10.23% of the eyes affected with KCN underwent a surgical procedure. the most common surgery was collagen cross-linking (8.05%), followed by deep anterior lamellar keratoplasty (1.13%) and penetrating keratoplasty (0.88%). CONCLUSION: KCN is usually bilateral and predominantly affects males. It commonly presents in the second and third decade of life, and only a tenth of the affected eyes require surgical treatment.

Lateral Cephalometric Landmark Annotation Using Histogram Oriented Gradients Extracted from Region of Interest Patches.

Introduction: Two-dimensional cephalometric image analysis plays a crucial role in orthodontic diagnosis and treatment planning. While deep learning-based algorithms have emerged to automate the laborious task of anatomical landmark annotation, their effectiveness is hampered by the challenges of acquiring and labelling clinical data. In this study, we propose a model that leverages conventional machine learning techniques to enhance the accuracy of landmark detection using limited dataset. Materials and methods: Our methodology involves coarse localization through region of interest (ROI) extraction and fine localization utilizing histogram-oriented gradient (HOG) feature. The image patch containing landmark pixels is classified using the light gradient boosting machine (LGBM) algorithm. To evaluate our model's performance, we conducted rigorous tests on the ISBI Cephalometric dataset and Dental Cepha dataset, aiming to achieve accuracy within a 2 mm radial precision range. We also employed cross-validation to assess our approach, providing a robust evaluation. Results: Our model's performance on the ISBI Cephalometric dataset showed an accuracy rate of 77.11% within the desired 2 mm radial precision range. The cross-validation results further confirmed the effectiveness of our approach, yielding a mean accuracy of 78.17%. Additionally, we applied our model to the Dental Cepha dataset, where we achieved a remarkable landmark detection accuracy of 84%. Conclusion: The results demonstrate that traditional machine learning techniques can be effective for accurate landmark detection in cephalometric images, even with limited data. Our findings highlight the potential of these techniques for clinical applications, where large datasets of labelled images may not be available.

Outcomes of reimplantation of a new Glaucoma Drainage Device after explantation of an older implant from exposure-related complications.

Purpose: To describe the clinical outcome of a series of seven eyes with an explanation of an original Glaucoma Drainage Device (GDD) arising from the complication of plate exposure and consequent reimplantation of another GDD at a second setting. Methods: This was a retrospective, interventional, and non-comparative study at two tertiary eye care hospitals in eastern and southern India. Electronic medical record data of the seven eyes where a GDD was explanted and a 2nd GDD was reimplanted over October 2010 and May 2021 was analyzed. Statistical analysis was done by SPSS (ver. 26). Results: The first GDD survived for a mean of 168 days only till the plate got exposed and thereby got explanted. Possible predisposing factors noted were conjunctival and scleral thinning, ischemic conjunctiva, etc., The reimplantation surgery was technically easy in the absence of hypotony-opposite to what is reported in the literature. The final IOP (mean +/- SD) values (mm Hg) were 18.9 (+/-7.9), range = 10-30. The mean number of glaucoma medications reduced from 3.9 (+/-1.2; range, 2 to 5) after the explanation to 3.1 (+/-0.7; range, 2 to 4) after the 2nd GDD implantation, in the final follow-up. The second GDD was found to be stable till the last follow-up (mean = 1149 days). No other significant intraoperative or postoperative complications were seen. Conclusions: Reimplantation of a second GDD in a separate setting after explanations of an original implant due to exposure-related complication is both a safe and effective method.

IGF-1R targeting in cancer - does sub-cellular localization matter?

The insulin-like growth factor receptor (IGF-1R) was among the most intensively pursued kinase targets in oncology. However, even after a slew of small-molecule and antibody therapeutics reached clinical trials for a range of solid tumors, the initial promise remains unfulfilled. Mechanisms of resistance to, and toxicities resulting from, IGF-1R-targeted drugs are well-catalogued, and there is general appreciation of the fact that a lack of biomarker-based patient stratification was a limitation of previous clinical trials. But no next-generation therapeutic strategies have yet successfully exploited this understanding in the clinic.Currently there is emerging interest in re-visiting IGF-1R targeted therapeutics in combination-treatment protocols with predictive biomarker-driven patient-stratification. One such biomarker that emerged from early clinical trials is the sub-cellular localization of IGF-1R. After providing some background on IGF-1R, its drugging history, and the trials that led to the termination of drug development for this target, we look more deeply into the correlation between sub-cellular localization of IGF-1R and susceptibility to various classes of IGF-1R - targeted agents.

Crosstalk between Aldosterone and Glycation through Rac-1 Induces Diabetic Nephropathy.

Background: Advanced glycation end products (AGEs) interaction with its receptor (RAGE) and aldosterone (Aldo) through the mineralocorticoid receptor (MR) activates Rac-1 and NF-κB independently in diabetic nephropathy (DN). However, the crosstalk of Aldo with AGEs-RAGE is still unresolved. Our study examined the impact of the AGEs-Aldo complex on renal cells and its effect on the RAGE-MR interaction. Methods and results: Glycation of human serum albumin (HSA) (40 mg/mL) with methylglyoxal (10 mM) in the presence of Aldo (100 nM) and aminoguanidine (AG) (100 nM) was performed. Glycation markers such as fructosamine and carbonyl groups and fluorescence of AGEs, pentosidine, and tryptophan followed by protein modification were measured. Renal (HEK-293T) cells were treated with the glycated HSA-Aldo (200 µg/mL) along with FPS-ZM1 and spironolactone antagonists for RAGE and Aldo, respectively, for 24 h. Glycation markers and esRAGE levels were measured. Protein and mRNA levels of RAGE, MR, Rac-1, and NF-κB were estimated. Glycation markers were enhanced with Aldo when albumin was only 14-16% glycated. AGEs-Aldo complex upregulated RAGE, MR, Rac-1 and NF-κB expressions. However, FPS-ZM1 action might have activated the RAGE-independent pathway, further elevating MR, Rac-1, and NF-κB levels. Conclusion: Our study concluded that the presence of Aldo has a significant impact on glycation. In the presence of AGEs-Aldo, RAGE-MR crosstalk exerts inflammatory responses through Rac-1 in DN. Insights into this molecular interplay are crucial for developing novel therapeutic strategies to alleviate DN in the future.

Modifying Whole Health Services for Successful Telehealth Delivery: Lessons from Veterans Health Administration's Rapid Transition During the COVID-19 Pandemic.

Introduction: The Veterans Health Administration (VHA) is shifting care from a disease-oriented to health-creating approach that aims to provide whole person care. This Whole Health (WH) system combines person-centered care with delivery of WH services (e.g., health coaching, well-being education and skill-building classes, and evidence-based complementary and integrative health therapies), alongside conventional medical services. During the COVID-19 pandemic, WH services were modified for delivery through telehealth (teleWH). This article characterizes modifications to WH services made to maintain continuity during the transition to telehealth formats. Materials and methods: We conducted semistructured qualitative interviews with a purposive sample of 51 providers delivering teleWH services at 10 VHA medical centers. We examined WH service modifications as well as facilitators and barriers to those modifications using rapid coding and directed content analysis. Results: Modifications were driven by (1) preparing for teleWH service delivery and (2) improving teleWH service delivery. To prepare for teleWH services, modifications were prompted by access, readiness, and setting and resources. Modifications to improve the delivery of teleWH services were motivated by engagement, community-building, safety, and content for a teleWH environment. One-on-one teleWH services required the fewest modifications, while more significant modifications were needed for well-being, skill-building, and movement-based groups, and reconfiguration of manual therapies. Discussion: Findings highlighted the need for modifications to ensure that teleWH services are accessible and safe and support interpersonal relationships between patients and providers, as well as in group-based classes. Successfully delivering teleWH services requires proactive preparation that considers access, readiness, and the availability of resources to engage in teleWH services. Tailoring strategies and considering the unique needs of different teleWH services are critical. Conclusions: The COVID-19 pandemic catalyzed teleWH service implementation, utilization, and sustainment. The challenges faced and modifications made during this transition provide lessons learned for other health care systems as they attempt to implement teleWH services.

Comparative Evaluation of Fluoride Release from Four Commercially Available Pediatric Dental Restorative Materials.

Objectives: The aim of this study was to evaluate the fluoride-releasing abilities of commercially available restorative materials such as-Activa™ BioActive-restorative™ material, Zirconomer (Shofu Inc), Beautifil® II (Shofu Inc), GC Gold Label 9 high strength posterior restorative glass ionomer cement (GIC Corp). Materials and methods: A total of 40 disk specimens (10 of each material) were placed into distilled/deionized (DI) water and the fluoride release was measured for 30 days. Fluoride ion measurement was performed at the end of the 1st, 3rd, 7th, 15th, and 30th day under normal atmospheric conditions by fluoride ion selective electrode (F-ISE) (Orion 9609 BNWP, Ionplus SureFlow fluoride electrode, Thermo Scientific, United States of America) coupled to a benchtop analyzer (Hachsen Ion+). Results: All the materials included in the study exhibited fluoride release. Although there were differences in the amounts of fluoride released between Activa™, Zirconomer, and GC Gold Label 9 the mean difference between these three groups was not found to be statistically significant. Beautifil® II showed low amounts of fluoride released at all time intervals. Conclusion: Among the above-compared materials Activa™ and Zirconomer exhibit both improved mechanical properties as well as they have fluoride-releasing ability so can be preferred over conventional glass ionomer restorations. How to cite this article: Dhumal RS, Chauhan RS, Patil V, et al. Comparative Evaluation of Fluoride Release from Four Commercially Available Pediatric Dental Restorative Materials. Int J Clin Pediatr Dent 2023;16(S-1):S6-S12.