Hyderabad Rheumatology Center

Shared enzymatic targets between azoles used in agriculture as fungicides and clinical antifungals are hypothesized to have led to the drift of resistant fungal isolates from field to clinic, reducing efficacy of azoles in infectious disease treatment. Recent discovery of a novel herbicide, tetflupyrolimet, and a potential clinical antifungal, olorofim, both targeting dihydroorotate dehydrogenase (DHODH), raises concern that widespread use of tetflupyrolimet may similarly cause clinical resistance to olorofim in Aspergillus isolates migrating from agricultural settings. Using minimum inhibitory concentration analysis on Aspergillus subspecies, enzymatic assays of recombinant DHODH, and a series of DHODH knockout yeast strains complemented with various DHODH orthologs, we demonstrate that tetflupyrolimet is highly selective for plant DHODH over Aspergillus DHODH. Based on the inability of tetflupyrolimet to inhibit Aspergillus DHODH or hinder growth of various Aspergillus species, the data demonstrate that risk of olorofim resistance developing in Aspergillus due to agrochemical use of the herbicide tetflupyrolimet is minimal.

ABSTRACTBackground:The surgical extraction of impacted mandibular 3rd molars is a common procedure in oral surgery. Choosing an appropriate incision technique significantly influences postoperative outcomes.Objective:This research evaluates the outcomes of different incision types in terms of postoperative complications, healing, and patient satisfaction.Materials and Methods:A comparative research was conducted involving 120 patients undergoing impacted mandibular 3rd molar extraction. Patients were divided into three groups based on incision type: triangular flap, envelope flap, and modified triangular flap. Postoperative pain, swelling, healing, and complications were assessed over two weeks.Results:The triangular flap showed faster healing and fewer complications, while the envelope flap resulted in less immediate postoperative pain. Modified triangular flaps demonstrated a balance between outcomes.Conclusion:Selecting an incision should be tailored to patient-specific needs and surgeon expertise, considering the nuances of each technique.

The objective of the present study was to evaluate the marginal fit of three most commonly used veneers in dentistry. A maxillary central incisor was embedded in a self-cure acrylic resin block, with the crown and 2 mm of the root exposed to facilitate standardized tooth preparation. Following the preparation, 30 elastomeric impressions were made to produce master casts. These working dies were then randomly allocated to three experimental groups, each consisting of 15 samples. Group I comprised indirect composite veneers (ICV), fabricated using laboratory composite resin. Group II included pressable ceramic veneers (PCV), manufactured using heat-pressed lithium disilicate. Group III consisted of computer-aided designing (CAD)/computer-aided manufacturing (CAM) ceramic veneers, fabricated through digital milling of lithium disilicate blocks. All veneers were fabricated in accordance with the respective manufacturer's guidelines and were carefully repositioned on the prepared tooth to evaluate the marginal discrepancy using a stereomicroscope. Three pre-designated points-mesio-labial, mid-labial, and disto-labial and mesio-palatal, mid-palatal, and disto-palatal on the labial and palatal margins-were measured. The values were recorded and analyzed with one-way ANOVA and Tukey's post-hoc test using SPSS software. ICV showed more variation with mean discrepancy of 189.24 ± 25.17 µm at cervical margin and 79.01 ± 11.68 µm at palatal area. PCV showed less variation with mean discrepancy of 48.2 ± 8.35 µm and 40.58 ± 9.47 µm at cervical and palatal areas, respectively. CAD/CAM-fabricated ceramic veneers showed mean discrepancy of 94.24 ± 9.00 µm at cervical and 52.72 ± 16.33 µm at palatal areas. Pressable ceramic veneers showed the best marginal fit at both cervical and palatal margins followed by CAD/CAM veneers. Indirect composite veneers showed poorest marginal fit. The marginal discrepancy values were within the clinically acceptable range for PCV and CAD/CAM ceramic veneers. It is of paramount importance that the dentist should choose wisely the veneer material taking the marginal fit into account.

The morbidity of type 2 diabetes mellitus (T2DM) is rising dramatically both at the national and international levels. In recent years, many novel medications are developed or in development for better management of hyperglycemia in people with T2DM. Focusing on the new promising molecules, here we aim to present the opinion of experts and their consensus on the use of imeglimin for the treatment of T2DM in India. Multiple advisory board meetings were conducted with six leading key opinion leaders (KOLs) in endocrinology and diabetes specialty across India to share their experiences, understand and discuss the real-world imeglimin treatment strategies, its effectiveness and safety in patients with T2DM. A novel oral antidiabetic drug (ADD), imeglimin, a tetrahydrotriazine compound of the "glimin" family, is currently being used in the treatment of T2DM. Its mode of action is unique when compared to other types of ADDs as it has a dual mode of action, which includes (1) improving the action of insulin and (2) reversing pancreatic β-cell dysfunction. Additionally, imeglimin has been associated with reduced hepatic steatosis, protection from β-cell apoptosis and stimulation of skeletal muscle glucose absorption. Efficacy and safety of imeglimin as a monotherapy is well demonstrated in treatment-naive patients when metformin is contraindicated or in patients who are intolerant to metformin, metformin failure, or as an add-on/combination with other oral antidiabetic drugs (OADs), mainly DPP4i, SGLT2i or insulin. The clinical efficacy of imeglimin is dose dependent, and it is observed that the efficacy of imeglimin 1,000 mg BID is >500 mg BID. This consensus paper presents the experts' opinion of their real-world clinical experiences on imeglimin treatment, its clinical efficacy, safety and their recommendations for better management of T2DM.

A male in early adolescence presented with a sudden drop in vision in the emergency clinic. At the presentation, visual acuity was counting fingers in both eyes. Clinical evaluation revealed severe conjunctival congestion, sterile corneal melt and acute severe aqueous deficiency (Schirmer values 0 mm at 5 min) in both eyes. He had a history of fever, body ache, large joint swelling and oral and urogenital ulcers of 20 days duration. Laboratory investigations revealed positive Human Leucocyte Antigen (HLA) B27, strongly positive Dense Fine Speckled (DFS)70, elevated C-reactive protein (CRP), raised erythrocyte sedimentation rate (ESR), increased serum ferritin levels and pus cells on urine examination, corroborative with the clinical diagnosis of reactive arthritis. He was managed with emergency tarsorrhaphy, frequent artificial tear supplements, systemic antibiotics and immune modulators. The corneal epithelial defect healed rapidly with restoration of visual acuity to 20/20 in both eyes. Acute lacrimal gland insufficiency leading to corneal melts should be promptly diagnosed and managed to prevent vision-threatening complications.