Effect of Non-Surgical Periodontal Therapy on Systemic Inflammatory Markers, Glycemic Status and Levels of Proteinuria in Type 2 Diabetic and Non-Diabetic Patients With Chronic Periodontitis.

AIMS AND OBJECTIVES:  The present study aimed to evaluate the effect of non-surgical periodontal therapy (NSPT) on systemic inflammatory markers, glycemic status, and levels of proteinuria in Type 2 diabetic and non-diabetic individuals with chronic periodontitis. METHODOLOGY: A total of 120 patients, categorized into three groups of 40 each, were included in this randomized observational study. Group 1 comprised patients with chronic periodontitis; Group 2 had chronic periodontitis with controlled diabetes; and Group 3 represented patients with chronic periodontitis with uncontrolled diabetes based on fasting blood sugar (FBS) and glycated hemoglobin (HbA1c) levels. Periodontal clinical parameters like plaque index, gingival index, bleeding on probing, pocket depth, and clinical attachment levels were evaluated. Blood samples and urine samples were collected and assessed for the levels of FBS, HbA1c, total protein, albumin, globulin, and proteinuria. All parameters recorded at baseline and three months after non-surgical periodontal therapy were analyzed for statistical significance at p <.05 using SPSS Inc. Released 2007. SPSS for Windows, Version 16.0. Chicago, SPSS Inc. RESULTS: A significant reduction in the periodontal clinical parameters within the groups, except for the clinical attachment level in Group 1 patients (p = 0.05), was observed. Glycemic status revealed a significant reduction after non-surgical periodontal therapy (p < 0.001), and on intragroup comparison, the total protein, albumin, globulin, and microprotein blood and urine levels showed significance among the evaluated groups (p < 0.001). CONCLUSION: Non-surgical periodontal treatment can effectively improve the periodontal and circulating inflammatory status. Results of our study showed improved glycemic control and a reduction in systemic inflammatory markers and proteinuria after performing non-surgical periodontal treatment in patients with type 2 diabetes.

Non-viral chimeric antigen receptor (CAR) T cells going viral.

Chimeric antigen receptor (CAR) T cell therapy has made significant strides in the treatment of B-cell malignancies, but its application in treating solid tumors still poses significant challenges. Particularly, the widespread use of viral vectors to deliver CAR transgenes into T cells comes with limitations, including high costs and regulatory restrictions, which hinder the translation of novel genetic engineering concepts into clinical applications. Non-viral methods, such as transposon/transposase and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas systems, offer promising alternatives for stable transgene insertion in CAR-T cells. These methods offer the potential to increase accessibility and efficiency in the development and delivery of CAR-T cell therapies. The main challenge in using non-viral methods, however, is their low knock-in efficiency, which leads to low transgene expression levels. In this review, we discuss recent developments in non-viral approaches for CAR-T cell production, the manufacturing requirements for clinical-grade production of non-viral CAR-T cells, and the adjustments needed in quality control for proper characterization of genomic features and evaluation of potential genotoxicity.

Effects of Non-surgical Periodontal Therapy on Saliva and Gingival Crevicular Fluid Levels of Chemerin in Periodontitis Subjects With and Without Type 2 Diabetes Mellitus.

Background Evidence had shown a bi-directional link between diabetes mellitus and periodontitis. Chemerin, an adipose tissue-specific adipokine plays a significant role in adipocyte initiation and differentiation that directly influences glucose metabolism, lipid metabolism, and inflammatory mediators. Non-surgical periodontal therapy (NSPT) for patients with periodontitis and diabetes mellitus improves the periodontal condition and regulates glycemic level. Aims and objectives To assess the impact of chemerin on periodontal disease and diabetes mellitus pathogenesis and to analyze the impact of NSPT on saliva and gingival crevicular fluid (GCF) chemerin levels in patients with periodontitis with and without type 2 diabetes mellitus (T2DM). Materials and methods A total of 60 patients were divided into four groups: Group I: Systemically and periodontally healthy subjects (n=15), Group II: Systemically healthy subjects with periodontitis (n=15), Group III: Subjects with periodontitis and T2DM (n=15), Group IV: Periodontally healthy subjects with T2DM (n=15). Indices and parameters like plaque index (PI), gingival index (GI), periodontal probing depth (PPD), and clinical attachment level (CAL) were assessed at baseline in all four groups and six weeks after NSPT in Group II and Group III. A glycated hemoglobin (HbA1c) test was taken to assess the patient's blood glucose level. Fasting blood sugar (FBS) level was taken at baseline in all the groups and six weeks after NSPT in Group II and Group III subjects. Saliva and GCF chemerin levels were assessed at baseline in all four groups and six weeks after NSPT in Group II and Group III subjects. Results A statistically significant difference was observed in comparing chemerin levels at baseline with all four groups (p < 0.001). After NSPT, there was a reduction in clinical parameters, FBS, and chemerin levels in Group II and Group III. A positive correlation was observed between salivary chemerin and FBS in Group II, GCF chemerin, PI, and FBS in Group II, and PPD and FBS in Group III. A negative correlation was observed between salivary chemerin and all parameters in Group II and between salivary chemerin and GCF chemerin in Group III. Conclusion Based on the observed relationship between chemerin and the parameters, their utility as a dual biomarker for diagnosis and prognosis in periodontal disease seems promising. However, further studies with a larger sample size on the role of chemerin in health and various states of diseases are required to substantiate the result of the study.

Ethnic-Guided Soft Tissue Cephalometric Analysis on Lambani Indian Inhabitants for Forensic Facial Reconstruction.

BACKGROUND: Forensic craniofacial reconstruction is a combination of both scientific technique and artistic skill that assist facial soft tissue approximation on the skull to obtain an image of an individual that varies in the different ethnic groups depending on genetic and environmental factors such as soft tissue norms. OBJECTIVES: The present study was aimed to evaluate the soft tissue norms for Lambani Indian tribes spread across the state of Karnataka in India and compare them with the local inherent ethnolinguistic Kannadiga population. MATERIAL AND METHODS: Forty healthy individuals encompassing 20 Lambanis and 20 Kannadigas were selected using demographic information. Lateral cephalograms obtained were analyzed for various soft tissue landmarks that include facial angle, upper lip curvature, skeletal convexity, H angle, nose tip to H-line, upper sulcus depth, lower sulcus depth, upper lip thickness, upper lip strain, lower lip to H line, soft tissue chin thickness, and glabella. RESULTS: It was observed that glabella thickness, upper sulcus depth, and lower lip to H line showed a significant difference between Lambani and Kannadiga populations. Lambani's have a higher facial angle than the Kannadiga group though not statistically significant. Gender-wise comparison had shown a significant difference in variables on upper sulcus depth, glabella among females, and lower lip to H line, glabella among males. CONCLUSION: The differences obtained between the two ethnic groups in this study clearly suggest the need for separate soft tissue thickness norms for distinctive populations that could be vital in the facial reconstruction of an individual in the field of forensic investigation to narrow down the identification process.

A Comparative Study of Mast Cells Count in Different Histological Grades of Oral Squamous Cell Carcinoma by Using Toluidine Blue Stain.

Background Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide accounting for 90% of all malignant oral lesions with high mortality and a five-year survival rate of about 50%. Various studies have shown mast cells regulate carcinogenesis by immunosuppression, angiogenesis enhancement, and promotion of tumor cell mitosis. Aim Hence, the present study was aimed to compare mast cell counts in normal oral mucosa with histological grades of oral squamous cell carcinoma by using toluidine blue stain. Methodology Sixty formalin-fixed, paraffin-embedded tissue samples included 15 well-differentiated, 15 moderately differentiated, and 15 poorly differentiated OSCC, as well as 15 cases of the normal oral mucosa (control), were sectioned and stained with 1% toluidine blue. Results We observed that the mean mast cell (MMC) count was comparatively more in normal mucosa than in various grades of OSCC. It was higher in low-grade OSCC. However, the differences between grades were not statistically significant. Conclusion In the present study, according to the results obtained, the MMC count was significantly decreased in OSCC in comparison with normal oral mucosa. Therefore, it can be assumed that mast cells could serve as an indicator of tumor progression.

Evaluating the Surface Characteristics of Stainless Steel, TMA, Timolium, and Titanium-niobium Wires: An in vivo Scanning Electron Microscope Study.

BACKGROUND: Recent metallurgical research and advancement in material science has benefited orthodontists in the selection of an appropriate wire size and alloy type, which is necessary to provide an optimum and predictable treatment results. The purpose of the study was to clinically evaluate and compare the surface characteristics of 16 x 22 stainless steel, Titanium molybdenum alloy, timolium, and titanium-niobium before and after placing them in a patient's mouth for 3 months using a scanning electron microscope (SEM). MATERIALS AND METHODS: The total sample size was 40, which were divided into four groups (group 1 - stainless steel wires, 10 samples, group 2 - TMA wires, 10 samples, group 3 - timolium wires, 10 samples, and group 4 - titanium-niobium wires, 10 samples), and these were further subdivided into 5 each. The first subgroup of five samples was placed in the patient's mouth and was evaluated under SEM, and another subgroup of five samples was directly subjected to the SEM. RESULTS: Scanning electron microscopic evaluation of surface characteristics of unused 16 x 22 rectangular stainless steel wire under 500 x magnification showed an overall smooth surface. Stainless steel wire samples placed in the patient's mouth showed black hazy patches, which may be interoperated as areas of stress. TMA unused wires showed multiple small voids of areas and small craters with fewer elevated regions. The TMA wire samples placed in the patient's mouth showed black hazy patches and prominent ridges, making the wire rougher. Timolium unused archwires showed heavy roughness and voids, whereas wires tested in the patient's mouth showed homogeneous distribution of deep cracks and craters. Unused titanium-niobium archwires showed uniform prominent striations and ridges with occasional voids, whereas wires used in the patient's mouth showed prominent huge voids that could be interpreted as maximum stress areas. CONCLUSION: Stainless steel (group 1) used and unused wires showed smooth surface characteristics when compared with all the other three groups followed by timolium, which was superior to titanium-niobium wires and TMA wires. CLINICAL SIGNIFICANCE: Timolium wires are superior to titanium-niobium wires and TMA wires.

Early prevention and intervention of Class II division 1 in growing patients.

Early screening and diagnosis help in preventing and intercepting the severity of the malocclusion which helps in addressing the esthetic and functional concerns. Growth modulation such as mandibular advancement has been an effective procedure in orthodontics. Mandibular growth advancer (MGA) and PowerScope are gaining popularity recently as these are effective in achieving the mandibular advancement and ease of fabrication, placement, and wear. MGA was fabricated by making the upper and lower splints separately and are placed in the oral cavity by joining the two splints in the new construction bite using cold cure, MGA when worn during growth phase helps in condylar remodeling in the temporomandibular joint thus helps in advancement of the mandible. The proclination of the upper anteriors in Class II division 1 can be moved lingually by activating the labial bow in the splint. Dr. Andy Hayes worked in conjunction with American orthodontics developed PowerScope. PowerScope delivers Class II correction with a combination of patient comfort and ease of use that was unmatched among other appliances. This ready to use chairside solution required no laboratory setup, making for a much quicker, and easier installation process and appointment. PowerScopes high quality, fixed one-piece design requires no patient compliance. These superior qualities of PowerScope help in correction of Class II skeletal growing patient in conjunction with fixed orthodontic therapy. MGA and PowerScope were chosen as a functional appliance for this study, which shows decreased ANB angle and effective mandible length was increased.

Clinical Utilization of M Spring for the Space Closure of Midline Diastema - Clinical Case Reports.

People approach orthodontist mainly for aesthetic purpose, midline diastema is one of the condition which causes aesthetic compromise. The midline diastema can be caused by various reasons such as high frenal attachment, midline pathology, etc. In the field of orthodontics, relapse rate is high while treating midline diastema. This relapse can be reduced only when there is bodily movement of the incisors in mesial direction. In this article, two cases of midline diastema are selected. Both the cases were treated using "M" spring which has three coils; two at periphery and one at the center and each coil was of 3mm diameter. "M" spring was fabricated using round 0.018" AJ Wilcock wire for one case and 0.017 X 0.025 TMA for another case. For both cases the duration of treatment was for six weeks. IOPA was taken after six weeks, the case in which rectangular wire was used; there was bodily movement of the central incisor in mesial direction. Whereas in round wire technique, predominantly tipping type of tooth movement was seen. The rectangular wire has two point contacts, because of which bodily movement was obtained. This technique of using rectangular wire to fabricate "M" spring has less inventory and chair side time.

Diaminothiazoles evade multidrug resistance in cancer cells and xenograft tumour models and develop transient specific resistance: understanding the basis of broad-spectrum versus specific resistance.

Acquired drug resistance poses a challenge in cancer therapy. Drug efflux is the most common mechanism of resistance displayed by hydrophobic drugs beyond a certain size. However, target specific changes and imbalance between the pro- and anti-apoptotic proteins are also found quite often in many tumours. A number of small antimitotic agents show high potential for multidrug resistant tumours, mainly because they are able to evade the efflux pumps. However, these compounds are also likely to suffer from resistance upon prolonged treatment. Thus, it is important to find out agents that are sensitive to resistant tumours and to know the resistance mechanisms against small molecules so that proper combinations can be planned. In this report, we have studied the efficiency of diaminothiazoles, a novel class of tubulin targeting potential anticancer compounds of small size, in multidrug resistant cancer. Studies in model cell lines raised against taxol and the lead diaminothiazole, DAT1 [4-amino-5-benzoyl-2-(4-methoxy phenyl amino) thiazole], and the xenograft tumours derived from them, show that diaminothiazoles are highly promising against multidrug resistant cancers. They were able to overcome the expression of efflux protein MDR1 and certain tubulin isotypes, could sensitize improper apoptotic machinery and ablated checkpoint proteins Bub1 and Mad2. Further, we have found that the resistance against microtubule binding compounds with higher size is broad-spectrum and emerges due to multiple factors including overexpression of transmembrane pumps. However, resistance against small molecules is transient, specific and is contributed by target specific changes and variations in apoptotic factors.

Curcumin is an inhibitor of calcium/calmodulin dependent protein kinase II.

Calcium/calmodulin dependent protein kinase II (CaMKII) is involved in the mechanisms underlying higher order brain functions such as learning and memory. CaMKII participates in pathological glutamate signaling also, since it is activated by calcium influx through the N-methyl-d-aspartate type glutamate receptor (NMDAR). In our attempt to identify phytomodulators of CaMKII, we observed that curcumin, a constituent of turmeric and its analogs inhibit the Ca(2+)-dependent and independent kinase activities of CaMKII. We further report that a heterocyclic analog of curcumin I, (3,5-bis[ß-(4-hydroxy-3-methoxyphenyl)ethenyl]pyrazole), named as pyrazole-curcumin, is a more potent inhibitor of CaMKII than curcumin. Microwave assisted, rapid synthesis of curcumin I and its heterocyclic analogues is also reported.

Diaminothiazoles inhibit angiogenesis efficiently by suppressing Akt phosphorylation.

The prevention of neovessel formation or angiogenesis is a recent popular strategy for limiting and curing cancer. Diaminothiazoles are a class of compounds that have been reported to show promise in the treatment of cancer by inhibiting cancer cell proliferation and inducing apoptosis, because of their effects on microtubules and as inhibitors of cyclin-dependent kinases. Many microtubule-targeting agents are being studied for their antiangiogenic activity, and a few have shown promising activity in the treatment of cancer. Here, we report that diaminothiazoles can be highly effective as antiangiogenic agents, as observed in the chick membrane assay. The lead compound, 4-amino-5-benzoyl-2-(4-methoxyphenylamino)thiazole (DAT1), inhibits endothelial cell processes such as invasion, migration, and tubule formation, which require a functional cytoskeleton. DAT1 also decreases the expression of cell adhesion markers. The antiangiogenic activities of DAT1 occur at concentrations that are not cytotoxic to the normal endothelium. Analysis of intracellular signaling pathways shows that DAT1 inhibits Akt phosphorylation, which is actively involved in the angiogenic process. The antiangiogenic properties of diaminothiazoles, in addition to their promising antimitotic and cytotoxic properties in cancer cell lines, give them an extra advantage in the treatment of cancer.