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1.
Front Immunol ; 15: 1406438, 2024.
Article En | MEDLINE | ID: mdl-38817611

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterised by itching, erythema, and epidermal barrier dysfunction. The pathogenesis of AD is complex and multifactorial; however,mast cell (MC) activation has been reported to be one of the crucial mechanisms in the pathogenesis of AD. The MC receptor Mas related G protein-coupled receptor-X2 (MRGPRX2) has been identified as a prominent alternative receptor to the IgE receptor in causing MC activation and the subsequent release of inflammatory mediators. The current study aimed to evaluate the therapeutic effect of a novel small molecule MRGPRX2 antagonist GE1111 in AD using in vitro and in vivo approaches. Methods: We developed an in vitro cell culture disease model by using LAD-2 MC, HaCaT keratinocytes and RAW 264.7 macrophage cell lines. We challenged keratinocytes and macrophage cells with CST-14 treated MC supernatant in the presence and absence of GE1111 and measured the expression of tight junction protein claudin 1, inflammatory cytokines and macrophage phagocytosis activity through immunohistochemistry, western blotting, RT-qPCR and fluorescence imaging techniques. In addition to this, we developed a DFNB-induced AD model in mice and evaluated the protective effect and underlying mechanism of GE1111. Results and Discussion: Our in vitro findings demonstrated a potential therapeutic effect of GE1111, which inhibits the expression of TSLP, IL-13, MCP-1, TNF-a, and IL-1ß in MC and keratinocytes. In addition to this, GE1111 was able to preserve the expression of claudin 1 in keratinocytes and the phagocytotic activity of macrophage cells. The in vivo results demonstrated that GE1111 treatment significantly reduced phenotypic changes associated with AD (skin thickening, scaling, erythema and epidermal thickness). Furthermore, immunohistochemical analysis demonstrated that GE1111 treatment preserved the expression of the tight junction protein Involucrin and reduced the expression of the inflammatory mediator periostin in the mouse model of AD. These findings were supported by gene and protein expression analysis, where GE1111 treatment reduced the expression of TSLP, IL-13, and IL-1ß, as well as downstream signalling pathways of MRGPRX2 in AD skin lesions. In conclusion, our findings provide compelling in vitro and in vivo evidence supporting the contribution of MRGPRX2-MC interaction with keratinocytes and macrophages in the pathogenesis of AD.


Cytokines , Dermatitis, Atopic , Disease Models, Animal , Keratinocytes , Receptors, G-Protein-Coupled , Receptors, Neuropeptide , Skin , Animals , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/immunology , Mice , Cytokines/metabolism , Receptors, G-Protein-Coupled/antagonists & inhibitors , Receptors, G-Protein-Coupled/metabolism , Humans , Receptors, Neuropeptide/antagonists & inhibitors , Receptors, Neuropeptide/metabolism , Skin/pathology , Skin/drug effects , Skin/metabolism , Skin/immunology , Keratinocytes/drug effects , Keratinocytes/metabolism , HaCaT Cells , Macrophages/immunology , Macrophages/metabolism , Macrophages/drug effects , Mast Cells/drug effects , Mast Cells/immunology , Mast Cells/metabolism , Nerve Tissue Proteins/antagonists & inhibitors , Nerve Tissue Proteins/metabolism , RAW 264.7 Cells , Inflammation Mediators/metabolism
2.
World J Cardiol ; 16(5): 282-292, 2024 May 26.
Article En | MEDLINE | ID: mdl-38817645

BACKGROUND: Lipid treatment practices and levels in post-acute myocardial infarction (AMI) patients, which are crucial for secondary prevention. AIM: To evaluate the lipid treatment practices and lipid levels in post-myocardial infarction (MI) patients at a tertiary care hospital in Pakistan. METHODS: In this cross-sectional study, we analyzed patients who had experienced their first AMI event in the past 3 years. We assessed fasting and non-fasting lipid profiles, reviewed statin therapy prescriptions, and examined patient compliance. The recommended dose was defined as rosuvastatin ≥ 20 mg or atorvastatin ≥ 40 mg, with target total cholesterol levels set at < 160 mg/dL and target low-density lipoprotein cholesterol (LDL-C) at < 55 mg/dL. RESULTS: Among 195 patients, 71.3% were male, and the mean age was 57.1 ± 10.2 years. The median duration since AMI was 36 (interquartile range: 10-48) months and 60% were diagnosed with ST-segment elevation MI. Only 13.8% of patients were advised to undergo lipid profile testing after AMI, 88.7% of patients were on the recommended statin therapy, and 91.8% of patients were compliant with statin therapy. Only 11.5% had LDL-C within the target range and 71.7% had total cholesterol within the target range. Hospital admission in the past 12 months was reported by 14.4%, and the re-admission rate was significantly higher among non-compliant patients (37.5% vs 5.6%). Subsequent AMI event rate was also significantly higher among non-compliant patients (43.8% vs 11.7%). CONCLUSION: Our study highlights that while most post-AMI patients received the recommended minimum statin therapy dose, the inadequate practice of lipid assessment may compromise therapy optimization and raise the risk of subsequent events.

3.
Microsc Res Tech ; 2024 May 15.
Article En | MEDLINE | ID: mdl-38747091

The Au partially embedded nanostructure (PEN) is synthesized by ion irradiation on an Au thin film deposited on a glass substrate using a 50 keV Ar ion. Scanning electron microscopy results show ion beam-induced restructuring from irregularly shaped nanostructures (NSs) to spherical Au NSs, and further ion irradiation leads to the formation of well-separated spherical nanoparticles. Higuchi's algorithm of surface analysis is utilized to find the evolution of surface morphology with ion irradiation in terms of the Hurst exponent and fractal dimension. The Au PEN is evidenced by Rutherford backscattering spectrometry and optical studies. Also, the depth of the mechanism behind synthesized PEN is explained on the basis of theoretical simulations, namely, a unified thermal spike and a Monte Carlo simulation consisting of dynamic compositional changes (TRIDYN). Another set of plasmonic NSs was formed on the surface by thermal annealing of the Au film on the substrate. Glucose sensing has been studied on the two types of plasmonic layers: nanoparticles on the surface and PEN. The results reveal the sensing responses of both types of plasmonic layers. However, PEN retains its plasmonic behavior as the NSs are still present after washing with water, which demonstrates the potential for reusability. RESEARCH HIGHLIGHTS: Synthesis of PENs by ion irradiation Utilization of Higuchi's algorithm to explore the surface morphology. Unified thermal spike and TRIDYN simulations being used to explain the results. Glucose is only used as a test case for reusability of substrate.

4.
Asian J Neurosurg ; 19(1): 14-20, 2024 Mar.
Article En | MEDLINE | ID: mdl-38751398

Context Glioblastoma multiforme (GBM) is a malignant and aggressive primary brain tumor with a poor prognosis. This adverse prognosis is due to the tumor's tendency for advancement and recurrence caused by highly intrusive nature of the persisting GBM cells that actively escape from the main tumor mass into the surrounding normal brain tissue. On the basis of biomarker illustration, it can be classified into molecular subgroups. Aims (1) To determine the expression of IDH1, ATRX, p53, and Ki67 by immunohistochemistry, in a cohort of GBMs. (2) To determine whether altered protein expression of any of these growth-control genes in GBM will show association with patient survival. (3) To establish prognostically distinct molecular subgroups of GBM, irrespective of histopathological diagnosis. Results In this prospective observational study, 35 histologically diagnosed cases of glioblastoma were enrolled. The mean age at the time of presentation was 43.46 ± 17.25 years with a male:female ratio of 1.3:1. Of the 35 cases, microvascular proliferation was seen in 23 cases. Large foci of necrosis (>50%) were seen in 10 cases and 27 cases had mitotic count ≥ 5/high power field (HPF). Of 35 cases, 5 (14.3%) cases showed IDH1 immunopositivity and 30 (85.7%) cases were negative for IDH1. ATRX was retained in 24 (68.6%) cases, while it was lost in 11 (31.4%) cases. The p53 immunoexpression was seen in 31 (88.6%) cases, whereas p53 was negative in 4 (11.4%) cases. The overall median survival (OS) was 6 months. In two protein pairs, the three compositions were IDH1-/p53+ (74.3%), ATRX +/IDH1- (62.9%), and ATRX +/p53+ (57.1%). Combined three-protein immunohistochemical analysis revealed five different molecular variants. Also, 8.6% (3/35) of the samples had aberrant protein expression of all three proteins, i.e., ATRX-/p53 +/IDH1 + , while 11.4% (4/35) were wild-type protein expression group, i.e., ATRX +/p53-/IDH1-. Conclusion In patients with single protein expression, Kaplan-Meier survival analysis showed statistically better OS in IDH1 mutant glioblastomas. In cases with double protein pairs, IDH1/p53 revealed statistically significant association with better median OS. The survival analysis of patients with IDH1/ATRX/p53 protein combinations also denoted a better OS. Hence, GBM can be grouped into prognostically relevant subgroups using these protein expression signatures individually, as well as the combined protein expression signatures.

5.
Proc Natl Acad Sci U S A ; 121(21): e2314604121, 2024 May 21.
Article En | MEDLINE | ID: mdl-38748581

We developed a significantly improved genetically encoded quantitative adenosine triphosphate (ATP) sensor to provide real-time dynamics of ATP levels in subcellular compartments. iATPSnFR2 is a variant of iATPSnFR1, a previously developed sensor that has circularly permuted superfolder green fluorescent protein (GFP) inserted between the ATP-binding helices of the ε-subunit of a bacterial F0-F1 ATPase. Optimizing the linkers joining the two domains resulted in a ~fivefold to sixfold improvement in the dynamic range compared to the previous-generation sensor, with excellent discrimination against other analytes, and affinity variants varying from 4 µM to 500 µM. A chimeric version of this sensor fused to either the HaloTag protein or a suitable spectrally separated fluorescent protein provides an optional ratiometric readout allowing comparisons of ATP across cellular regions. Subcellular targeting the sensor to nerve terminals reveals previously uncharacterized single-synapse metabolic signatures, while targeting to the mitochondrial matrix allowed direct quantitative probing of oxidative phosphorylation dynamics.


Adenosine Triphosphate , Green Fluorescent Proteins , Adenosine Triphosphate/metabolism , Green Fluorescent Proteins/metabolism , Green Fluorescent Proteins/genetics , Humans , Biosensing Techniques/methods , Animals , Oxidative Phosphorylation , Proton-Translocating ATPases/metabolism , Proton-Translocating ATPases/genetics
6.
Nanotechnology ; 35(32)2024 May 24.
Article En | MEDLINE | ID: mdl-38710165

For deep ultraviolet (UV-C) photodetectors, gallium oxide (Ga2O3) is a suitable candidate owing to its intrinsic ultra-wide band gap and high stability. However, its detection is limited within the UV-C region, which restricts it to cover a broad range, especially in visible and near-infrared (NIR) region. Therefore, constructing a heterostructure of Ga2O3with an appropriate material having a narrow band gap is a worthwhile approach to compensate for it. In this category, PtS2group-10 transitional metal dichalcogenide stands at the top owing to its narrow band gap (0.25-1.65 eV), high mobility, and stability for heterostructure synthesis. Moreover, heterostructure with Ga2O3sensing in UV and PtS2broad response in visible and IR range can broaden the spectrum from UV to NIR and to build broadband photodetector. In this work, we fabricated a 2D-3D PtS2-x/Ga2O3heterostructure based broadband photodetector with detection from UV-C to NIR region. In addition, the PtS2-x/Ga2O3device shows a high responsivity of 38.7 AW-1and detectivity of 4.8 × 1013Jones under 1100 nm light illumination at 5 V bias. A fast response of 90 ms/86 ms illustrates the device's fast speed. An interface study between the PtS2-xand Ga2O3was conducted using x-ray photoelectron spectroscopy and ultraviolet photoelectron spectroscopy (UPS) which confirmed type-I band alignment. Finally, based on their band alignment study, a carrier transport mechanism was proposed at the interface. This work offers a new opportunity to fabricate large-area high-performance 2D-3D heterostructures based photodetectors for future optoelectronics devices.

7.
PLoS One ; 19(5): e0303787, 2024.
Article En | MEDLINE | ID: mdl-38758754

BACKGROUND: Advances in Next Generation Sequencing have made rapid variant discovery and detection widely accessible. To facilitate a better understanding of the nature of these variants, American College of Medical Genetics and Genomics and the Association of Molecular Pathologists (ACMG-AMP) have issued a set of guidelines for variant classification. However, given the vast number of variants associated with any disorder, it is impossible to manually apply these guidelines to all known variants. Machine learning methodologies offer a rapid way to classify large numbers of variants, as well as variants of uncertain significance as either pathogenic or benign. Here we classify ATP7B genetic variants by employing ML and AI algorithms trained on our well-annotated WilsonGen dataset. METHODS: We have trained and validated two algorithms: TabNet and XGBoost on a high-confidence dataset of manually annotated, ACMG & AMP classified variants of the ATP7B gene associated with Wilson's Disease. RESULTS: Using an independent validation dataset of ACMG & AMP classified variants, as well as a patient set of functionally validated variants, we showed how both algorithms perform and can be used to classify large numbers of variants in clinical as well as research settings. CONCLUSION: We have created a ready to deploy tool, that can classify variants linked with Wilson's disease as pathogenic or benign, which can be utilized by both clinicians and researchers to better understand the disease through the nature of genetic variants associated with it.


Copper-Transporting ATPases , Deep Learning , Genetic Variation , Hepatolenticular Degeneration , Hepatolenticular Degeneration/genetics , Hepatolenticular Degeneration/pathology , Humans , Copper-Transporting ATPases/genetics , Algorithms , High-Throughput Nucleotide Sequencing/methods
9.
J Neurosci Rural Pract ; 15(2): 217-226, 2024.
Article En | MEDLINE | ID: mdl-38746514

Objectives: In developing nations such as India, a disparity exists between the available resources for stroke rehabilitation and the substantial burden of stroke cases. Consequently, the provision of cost-effective and multidisciplinary post-stroke rehabilitation care to stroke survivors becomes of paramount importance. The utilization of mobile applications (apps) for stroke care has been on the rise, offering a personalized and pragmatic solution with the potential for wider reach in settings constrained by limited resources. To address the unmet needs in the prevention and management of post-stroke complications, we conceptualized a strategy known as a mobile application-based post-stroke care strategy for both survivors and their caregivers. Materials and Methods: The scope of the app's focus was determined based on the incidence of post-stroke complications within a prospective cohort of stroke patients, in conjunction with existing literature. An initial "web-based mobile app" prototype was crafted to align with the identified focus area. Before the development of the final app version, a feasibility study was conducted involving 30 participant dyads (comprising a patient and a caregiver). Content validity was evaluated by a panel of 20 stroke experts encompassing neurologists, nurses, physiotherapists, and psychologists. Results: The "Stroke Home Care" (SHC) mobile app was conceived as a web-based educational tool aimed at preventing and managing post-stroke complications. It seeks to train caregivers of immobile stroke patients in the administration of preventive and therapeutic care procedures, thereby potentially enhancing survivors' quality of life and alleviating caregivers' burden. The feasibility and validity studies indicated "high satisfaction" levels among most caregivers and experts (>75%), with the remainder expressing "satisfaction" and no "dissatisfaction" regarding app utilities. Stroke experts unanimously deemed the app "appropriate", with consensus on contents, video quality, video length, and voice clarity. Caregivers reported "satisfactory" user experiences, encountering no issues during app installation or operation. Suggestions from both caregivers and experts were integrated into the final app version. Conclusion: The "SHC" app represents a feasible and well-received innovation tailored for the use by caregivers of stroke survivors. Consequently, the initial feasibility of the developed app serves as a precursor to a randomized controlled clinical trial aimed at substantiating its effectiveness within the post-stroke survivor and caregiver population. Notably, within resource-constrained contexts, this app has the potential to be a pivotal tool for post-stroke care.

11.
ACS Omega ; 9(12): 14604-14612, 2024 Mar 26.
Article En | MEDLINE | ID: mdl-38559966

Early detection and viral concentration monitoring of human immunodeficiency virus in resource-poor settings are important to control disease spread and reduce mortality. Nucleic acid amplification tests are expensive for low-resource settings. Lateral flow antibody tests are not sensitive if testing is performed within 7-10 days, and these tests are not quantitative. We describe a signal enhancement technique based on fluorescent silica nanoparticles and bioorthogonal chemistries for the femtomolar detection of the HIV-1 p24 antigen. We developed a magnetic bead-based assay, wherein we used fluorescent-dye-encapsulated silica nanoparticles as reporters. The number of reporters was increased by using bioorthogonal chemistry to provide signal enhancement. The limit and range of detection of the sandwich immunoassay using alternating multiple layers for p24 in human serum were found to be 46 fg/mL (1.84 fM) and 46 fg/mL to 10 ng/mL, respectively. This simple assay was 217-fold higher in sensitivity compared to that of commercial enzyme-linked immunoassays (limit of detection of 10 pg/mL).

12.
Front Neurol ; 15: 1305514, 2024.
Article En | MEDLINE | ID: mdl-38562429

Purpose: Despite the diagnostic and etiological significance of in-patient MRI in ischemic stroke (IS), its utilization is considered resource-intensive, expensive, and thus limiting feasibility and relevance. This study investigated the utilization of in-patient MRI for IS patients and its impact on patient and healthcare resource utilization outcomes. Methods: This retrospective registry-based study analyzed 1,956 IS patients admitted to Halifax's QEII Health Centre between 2015 and 2019. Firstly, temporal trends of MRI and other neuroimaging utilization were evaluated. Secondly, we categorized the cohort into two groups (MRI vs. No MRI; in addition to a non-contrast CT) and investigated adjusted differences in patient outcomes at admission, discharge, and post-discharge using logistic regression. Additionally, we analyzed healthcare resource utilization using Poisson log-linear regression. Furthermore, patient outcomes significantly associated with MRI use underwent subgroup analysis for stroke severity (mild stroke including transient ischemic attack vs. moderate and severe stroke) and any acute stage treatment (thrombolytic or thrombectomy or both vs. no treatment) subgroups, while using an age and sex-adjusted logistic regression model. Results: MRI was used in 40.5% patients; non-contrast CT in 99.3%, CT angiogram in 61.8%, and CT perfusion in 50.3%. Higher MRI utilization was associated with male sex, younger age, mild stroke, wake-up stroke, and no thrombolytic or thrombectomy treatment. MRI use was independently associated with lower in-hospital mortality (adjusted OR, 0.23; 95% CI, 0.15-0.36), lower symptomatic neurological status changes (0.64; 0.43-0.94), higher home discharge (1.32; 1.07-1.63), good functional outcomes at discharge (mRS score 0-2) (1.38; 1.11-1.72), lower 30-day stroke re-admission rates (0.48; 0.26-0.89), shorter hospital stays (regression coefficient, 0.92; 95% CI, 0.90-0.94), and reduced direct costs of hospitalization (0.90; 0.89-0.91). Subgroup analysis revealed significantly positive association of MRI use with most patient outcomes in moderate and severe strokes subgroup and non-acutely treated subgroup. Conversely, outcomes in mild strokes (including TIAs) subgroup and acute treatment subgroup were comparable regardless of MRI use. Conclusion: A substantial proportion of admitted IS patients underwent MRI, and MRI use was associated with improved patient outcomes and reduced healthcare resource utilization. Considering the multifactorial nature of IS patient outcomes, further randomized controlled trials are suggested to investigate the role of increased MRI utilization in optimizing in-patient IS management.

13.
Front Cell Infect Microbiol ; 14: 1346349, 2024.
Article En | MEDLINE | ID: mdl-38628551

Efficient precision vaccines against several highly pathogenic zoonotic viruses are currently lacking. Proteolytic activation is instrumental for a number of these viruses to gain host-cell entry and develop infectivity. For SARS-CoV-2, this process is enhanced by the insertion of a furin cleavage site at the junction of the spike protein S1/S2 subunits upstream of the metalloprotease TMPRSS2 common proteolytic site. Here, we describe a new approach based on specific epitopes selection from the region involved in proteolytic activation and infectivity for the engineering of precision candidate vaccinating antigens. This approach was developed through its application to the design of SARS-CoV-2 cross-variant candidates vaccinating antigens. It includes an in silico structural analysis of the viral region involved in infectivity, the identification of conserved immunogenic epitopes and the selection of those eliciting specific immune responses in infected people. The following step consists of engineering vaccinating antigens that carry the selected epitopes and mimic their 3D native structure. Using this approach, we demonstrated through a Covid-19 patient-centered study of a 500 patients' cohort, that the epitopes selected from SARS-CoV-2 protein S1/S2 junction elicited a neutralizing antibody response significantly associated with mild and asymptomatic COVID-19 (p<0.001), which strongly suggests protective immunity. Engineered antigens containing the SARS-CoV-2 selected epitopes and mimicking the native epitopes 3D structure generated neutralizing antibody response in mice. Our data show the potential of this combined computational and experimental approach for designing precision vaccines against viruses whose pathogenicity is contingent upon proteolytic activation.


COVID-19 , Viral Vaccines , Humans , Animals , Mice , SARS-CoV-2/genetics , COVID-19/prevention & control , Viral Vaccines/genetics , Epitopes/genetics , Antibodies, Neutralizing , Antibodies, Viral
14.
J Transl Med ; 22(1): 370, 2024 Apr 18.
Article En | MEDLINE | ID: mdl-38637842

JAK-STAT signalling pathway inhibitors have emerged as promising therapeutic agents for the treatment of hair loss. Among different JAK isoforms, JAK3 has become an ideal target for drug discovery because it only regulates a narrow spectrum of γc cytokines. Here, we report the discovery of MJ04, a novel and highly selective 3-pyrimidinylazaindole based JAK3 inhibitor, as a potential hair growth promoter with an IC50 of 2.03 nM. During in vivo efficacy assays, topical application of MJ04 on DHT-challenged AGA and athymic nude mice resulted in early onset of hair regrowth. Furthermore, MJ04 significantly promoted the growth of human hair follicles under ex-vivo conditions. MJ04 exhibited a reasonably good pharmacokinetic profile and demonstrated a favourable safety profile under in vivo and in vitro conditions. Taken together, we report MJ04 as a highly potent and selective JAK3 inhibitor that exhibits overall properties suitable for topical drug development and advancement to human clinical trials.


Drug Development , Hair , Mice , Animals , Humans , Mice, Nude , Drug Discovery , Janus Kinase 3
15.
J Am Heart Assoc ; 13(8): e034118, 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38563374

BACKGROUND: In the wake of pandemic-related health decline and health care disruptions, there are concerns that previous gains for cardiovascular risk factors may have stalled or reversed. Population-level excess burden of drug-treated diabetes and hypertension during the pandemic compared with baseline is not well characterized. We evaluated the change in incident prescription claims for antihyperglycemics and antihypertensives before versus during the pandemic. METHODS AND RESULTS: In this retrospective, serial, cross-sectional, population-based study, we used interrupted time series analyses to examine changes in the age- and sex-standardized monthly rate of incident prescriptions for antihyperglycemics and antihypertensives in patients aged ≥66 years in Ontario, Canada, before the pandemic (April 2014 to March 2020) compared with during the pandemic (July 2020 to November 2022). Incident claim was defined as the first prescription filled for any medication in these classes. The characteristics of patients with incident prescriptions of antihyperglycemics (n=151 888) or antihypertensives (n=368 123) before the pandemic were comparable with their pandemic counterparts (antihyperglycemics, n=97 015; antihypertensives, n=146 524). Before the pandemic, monthly rates of incident prescriptions were decreasing (-0.03 per 10 000 individuals [95% CI, -0.04 to -0.01] for antihyperglycemics; -0.14 [95% CI, -0.18 to -0.10] for antihypertensives). After July 2020, monthly rates increased (postinterruption trend 0.31 per 10 000 individuals [95% CI, 0.28-0.34] for antihyperglycemics; 0.19 [95% CI, 0.14-0.23] for antihypertensives). CONCLUSIONS: Population-level increases in new antihyperglycemic and antihypertensive prescriptions during the pandemic reversed prepandemic declines and were sustained for >2 years. Our findings are concerning for current and future cardiovascular health.


Antihypertensive Agents , Hypoglycemic Agents , Humans , Antihypertensive Agents/therapeutic use , Hypoglycemic Agents/therapeutic use , Retrospective Studies , Cross-Sectional Studies , Drug Prescriptions , Ontario/epidemiology
16.
Dental Press J Orthod ; 29(1): e2423133, 2024.
Article En | MEDLINE | ID: mdl-38567922

OBJECTIVE: This study aimed to assess the frequency with which orthodontic patients decided to shift to another type of orthodontic appliance, among conventional metal brackets, ceramic brackets, lingual brackets and clear aligner, based on their personal experiences of pain, ulcers, bad breath, hygiene issues and social difficulties. MATERIAL AND METHODS: This study comprises of patients seeking orthodontic treatment. The sample (n = 500; age group = 19-25 years) was divided equally into four groups based on the treatment modality: conventional metal brackets, ceramic brackets, lingual brackets and clear aligner. Patients rated the questionnaire using a visual analogue scale, to assess variables (such as pain, ulcer etc) that impact various treatment modalities. Subsequently, patients from all groups provided feedback regarding their treatment experiences, and expressed their preference for an alternative modality. Intergroup comparison among the four groups was done using one-way analysis of variance with Tukey's HSD post-hoc test (p ≤ 0.05). RESULTS: Patients who received lingual brackets reported higher levels of pain and ulceration, as compared to those who received clear aligners. All four groups showed statistically significant differences for ulcers during treatment (p ≤ 0.05). Of the 125 patients who received conventional metal brackets, 28% expressed a preference for clear aligner therapy, while 20% preferred ceramic brackets. In the lingual group, 56% of 125 patients preferred clear aligner therapy, and 8% preferred ceramic brackets to complete their treatment. In the ceramic group, 83% did not want to switch, whereas 17% desired to switch to clear aligner, while in aligner group no patient desired to switch. CONCLUSIONS: A higher percentage of patients from lingual brackets group chose to shift to clear aligners, followed by conventional metal brackets group and by ceramic brackets group, in this descending order. The clear aligner group demonstrated fewer issues than the other treatment modalities.


Orthodontic Brackets , Ulcer , Humans , Young Adult , Adult , Orthodontic Appliances , Ceramics , Pain
17.
Biopolymers ; : e23578, 2024 Apr 05.
Article En | MEDLINE | ID: mdl-38577865

Ocular drug delivery is constrained by anatomical and physiological barriers, necessitating innovative solutions for effective therapy. Natural polymers like hyaluronic acid, chitosan, and gelatin, alongside synthetic counterparts such as PLGA and PEG, have gained prominence for their biocompatibility and controlled release profiles. Recent strides in polymer conjugation strategies have enabled targeted delivery through ligand integration, facilitating tissue specificity and cellular uptake. This versatility accommodates combined drug delivery, addressing diverse anterior (e.g., glaucoma, dry eye) and posterior segment (e.g., macular degeneration, diabetic retinopathy) afflictions. The review encompasses an in-depth exploration of each natural and synthetic polymer, detailing their individual advantages and disadvantages for ocular drug delivery. By transcending ocular barriers and refining therapeutic precision, these innovations promise to reshape the management of anterior and posterior segment eye diseases.

18.
J Pharm Bioallied Sci ; 16(Suppl 1): S684-S686, 2024 Feb.
Article En | MEDLINE | ID: mdl-38595430

Background: Sodium hypochlorite serves as the most efficient root canal irrigating fluid. Objectives: This study's goal was to assess the replenished NaOCl's capacity to dissolve the tissue of pulp when combined with 9% tetrasodic etidronate (Na4HEBP), 18% tetrasodic etidronate (Na4HEBP), and 17% disodic ethylenediaminetetraacetate (Na2EDTA) under continuous controlled administration. Materials and Methods: Hundred and twenty complete undamaged teeth of the anterior mandible extracted due to periodontal problems within forty-eight hours were taken as a source of the pulp tissue. Results: It was found that there was a decrease in the weight of pulp tissue in all groups except negative control. Conclusion: NaOCl's potential to dissolve tissue with chelating agents like EDTA and HEBP inside the root canal was unaffected when there was controlled administration of EDTA and HEBP.

19.
J Pharm Bioallied Sci ; 16(Suppl 1): S443-S445, 2024 Feb.
Article En | MEDLINE | ID: mdl-38595459

Background: This randomized controlled trial aimed to assess and compare postoperative swelling and pain in patients undergoing alveolar ridge preservation using RidgeMax Pro and AlveoGraft Plus. Methods: A total of 20 patients requiring tooth extraction were enrolled in this study and randomly assigned to two groups: Group A received alveolar ridge preservation with RidgeMax Pro and Group B with AlveoGraft Plus. Postoperative swelling was evaluated by measuring facial dimensions using standardized facial photographs at baseline and at 24, 48, and 72 hours postoperatively. Pain was assessed using a visual analog scale (VAS) at the same time points. Statistical analysis was performed using t-tests and repeated measures ANOVA. Results: Both RidgeMax Pro and AlveoGraft Plus demonstrated effective alveolar ridge preservation without any reported complications. In terms of postoperative swelling, Group A (RidgeMax Pro) exhibited significantly lower facial swelling compared to Group B (AlveoGraft Plus) at all time points (P < 0.05). The mean pain scores on the VAS were consistently lower in Group A than in Group B across the assessment time points (P < 0.05). The trend of reduced swelling and pain in Group A persisted throughout the 72-hour follow-up period. Conclusion: Alveolar ridge preservation with RidgeMax Pro (Trade Name: RidgeMax Pro) resulted in significantly reduced postoperative swelling and pain compared to AlveoGraft Plus (Trade Name: AlveoGraft Plus).

20.
J Pharm Bioallied Sci ; 16(Suppl 1): S446-S448, 2024 Feb.
Article En | MEDLINE | ID: mdl-38595602

Background: This randomized controlled trial aimed to compare the aesthetic outcome and patient perception of immediate versus DL of implant-supported single crowns. Methods: A total of 60 patients with a single missing tooth were enrolled and randomly assigned to two groups: immediate loading (IL) and delayed loading (DL). Each group consisted of 30 patients with a total of 30 implants. In the IL group, crowns were loaded onto implants immediately after placement, while in the DL group, a healing period of 3 months was observed before crown placement. Aesthetic outcome was assessed using the Pink Esthetic Score (PES) for soft tissue and the White Esthetic Score (WES) for the crown. Patient perception was evaluated through a visual analog scale (VAS) for satisfaction, comfort, and overall experience. Results: The IL group demonstrated comparable aesthetic outcomes to the DL group, with mean PES and WES scores of 10.2 ± 1.5 and 8.7 ± 1.2, respectively, in the IL group, and 10.5 ± 1.3 and 8.5 ± 1.4 in the DL group. Patient perception in terms of satisfaction, comfort, and overall experience was similarly high in both groups, with VAS scores above 8 for each parameter. Conclusion: This randomized controlled trial suggests that both IL and DL of implant-supported single crowns result in favorable aesthetic outcomes and high levels of patient satisfaction.

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