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Shikonin and Alkannin inhibit ATP synthase and impede the cell growth in Escherichia coli
Naturally occurring naphthoquinones, shikonin and alkannin, are important ingredients of traditional Chinese medicine Zicao. These constituents are reported to have many therapeutic uses, such as wound healing; scar treatment; and anti-inflammation, anti-acne, anti-ulcer, anti-HIV, anticancer, and antibacterial properties. The primary objective of this investigation was to explore the effect of shikonin and alkannin on Escherichia coli ATP synthase and its cell growth. Shikonin caused complete (100 %) inhibition, and alkannin caused partial (79 %) inhibition of wild-type E. coli ATP synthase. Both caused partial (4 %–27 %) inhibition of ATP synthase with genetically modified phytochemical binding site. The growth inhibition of strains expressing normal, deficient, and mutant ATP synthase by shikonin and alkannin, corroborated the inhibition observed in isolated normal wild-type and mutant ATP synthase. Trivial inhibition of mutant enzymes indicated αR283D, αE284R, βV265Q, and γT273A are essential for formation of the phytochemical binding site where shikonin and alkannin bind. Further, shikonin was a potent inhibitor of ATP synthase than alkannin. The antimicrobial properties of shikonin and alkannin were tied to the binding at phytochemical site of microbial ATP synthase. Selective targeting of bacterial ATP synthase by shikonin and alkannin may be an advantageous alternative to address the antibiotic resistance issue
A Rare Presentation of Self-Resolving Purple Fingers
Achenbach syndrome is a rare, benign, self-limiting, syndrome of unknown etiology. Here, we report a 66-year-old female who presented to the dermatology clinic with waxing and waning non-palpable purpura for the last year on the volar aspect of her hands bilaterally. The patient admitted to tingling prior to the onset of the purpura and mild tenderness following presentation. The purpura would spontaneously resolve without discoloration or scarring after 2-7 days. The patient stated these episodes can occur anywhere from a few times a month to every 1-2 months. Evaluation and work-up performed by her primary care physician and rheumatologist did not reveal an explanation for her symptoms. Two punch biopsies were performed and revealed a perivascular lymphocytic infiltrate with extravasted erythrocytes and pigmented macrophages consistent with a pigmented purpuric dermatosis. Immunofluorescence was negative. The diagnosis of Achenbach syndrome was made by diagnosis of exclusion. Reassurance was provided to the patient and she was given DerMend Bruise formula cream, which contains retinol, glycolic acid, arnica oil, ceramides, niacinamide, and phytonadione, to monitor for improvement of her symptoms. It is important for healthcare providers to be aware of the benign nature of this syndrome to be able to provide reassurance to patients and avoid an unnecessary, more invasive evaluation
Editorial: Gut Physiology—Microbes and Inflammatory Diseases
Editorial on the Research Topic Gut physiology—microbes and inflammatory disease
The ability of different formulations of artificial saliva to protect dentin from erosive wear
Objective: Evaluate the protective effect of artificial saliva formulations associated or not with mucin on dentin. Materials and Methods: Bovine dentin specimens were randomly allocated to 10 groups (n = 20) according to the artificial saliva tested and the presence or absence of mucin: Amaechi et al. (1998); Klimek et al. (1982); Vieira et al. (2005) and Eisenburger et al. (2001) and deionized water (control). Samples were submitted to an erosive cycle consisting of two immersions of 120 min in the saliva, followed by 1 min in hydrochloric acid solution, and new storage in saliva for 120 min. Surface loss (μm) was measured before and after the cycle. Data were analyzed using 2-way ANOVA and Tukey’s test (p \u3c 0.05). Results: A significant difference was observed for the saliva formulation but not for the presence of mucin. The deionized water provided the highest surface loss and the Eisenburger’s saliva formulation the lowest. The groups testing the Amaechi, Klimek, and Vieira saliva did not present significant differences. Conclusion: Eisenburger’s saliva formulation provides a higher protective effect against dentin erosion. The presence of mucin did not increase the erosion-preventive effect of artificial saliva formulations
World Federation of Orthodontists guidelines for postgraduate orthodontic education
Advanced dental education programs in orthodontics and dentofacial orthopedics require an extensive and comprehensive evidence-based experience, which must be representative of the current didactic and technical advancements. Over the past 25 years, the World Federation of Orthodontists (WFO) has placed emphasis in the support for the recognized orthodontic specialty training programs in every region of the world. In its early years, the WFO developed general principles for specialty education that culminated in the first comprehensive curriculum recommendations, i.e., the WFO Guidelines for Postgraduate Orthodontic Education, which was published in February 2009. In view of the significant changes in the specialty of orthodontics, the WFO has revised and updated its previous document to reflect the expanded scope and demands of current orthodontic education and practice. The members of the task force participated in a thorough revision of the guidelines and created a new document that takes into consideration the didactic, clinical, and the appropriate physical facilities to provide clinical care, study, and research areas. Although it is recognized that there will be variations in teaching and faculty assets, as well as facilities, access to materials, and equipment, the aim of the WFO Educational Guidelines is to provide the minimum program requirements necessary to provide orthodontic specialty residents the educational experience that prepares them to deliver the best level of orthodontic treatment for their patients. It is recommended that these guidelines be used universally by orthodontic specialty program educators and related educational, scientific, and administrative institutions to evaluate and compare their curriculum to a world standard
Does e-cigarette use affect response to non-surgical periodontal therapy?
Design: Cross-sectional study Case selection: Consecutive patient charts (n = 220) at Guy’s Dental Hospital between April 2018 and April 2020 were included. The inclusion criteria were adults ≥18 years with a diagnosis of periodontitis (localized or generalized, all stages and grades) and who have received professional mechanical plaque removal (PMPR) by periodontology graduate students. Data of periodontal indices before and after PMPR (6–20 weeks) were also needed to be available. Exclusion criteria included uncontrolled diabetes, pregnancy, medications attributed to drug induced overgrowth, among others. Data analysis: This retrospective study evaluated the response to periodontal treatment in e-cigarette users and they compared the outcomes to non-smokers, former and current smokers. The primary outcome to evaluate the response to periodontal therapy was ‘need for surgery’. This was defined by the authors as the number of sextants with ≥2 non-adjacent sites with probing depth (PD) ≥ 5 mm after PMPR. Secondary outcomes included periodontal parameters such as number of sextants with ≥1 site with PD ≥ 5 mm, PD, clinical attachment level (CAL), bleeding on probing, recession, and plaque scores. Results: E-cigarette users and current smokers had similar poorer clinical response to periodontal therapy. Analysis revealed e-cigarette users had more sextants with ‘need for surgery’ as the primary outcome. Pocket closure outcome (PD ≤ 4 mm with no bleeding on probing) were highest in nonsmokers (77.1%), followed by former smokers (74.9%), current smokers (69.4%), and e-cigarette users (66.6%). Conclusions: E-cigarette users showed less than beneficial response to periodontal therapy compared to non-smokers, who had the best outcome overall
Fracture Resistance of Chairside CAD/CAM Molar Crowns Fabricated with Different Lithium Disilicate Ceramic Materials
Purpose: To compare the fracture resistance of five different groups of chairside CAD/ CAM molar crowns fabricated from various lithium disilicate ceramic materials (LDC): one conventional precrystallized CAD/CAM LDC, two novel precrystallized LDCs, and one fully crystallized LDC tested both with and without optional sintering. Materials and Methods: A total of 60 chairside CAD/CAM lithium disilicate molar crowns (n = 12 per group) with 1.5-mm occlusal thickness and a 1.0-mm chamfer finish were designed and fabricated with a chairside CAD/CAM system (CEREC, Dentsply Sirona). The restorations were divided into five groups: (1) IPS e.max CAD; (2) Amber Mill; (3) Straumann n!ce; (4) Straumann n!ce with optional sintering; and (5) Supreme CAD. Restorations were cemented using conventional resin luting cement and primer system to 3D-printed resin dies. Bonded restorations were loaded for 100,000 cycles with 275-N force, and the load at break (LB) and peak load (PL) until fracture were measured. SEM images of fracture surfaces on the printed dies were obtained. Results: Fracture resistance was significantly different depending on the material. Supreme CAD showed the highest fracture resistance (LB: 1,557.2 N; PL: 1,785.8 N), followed by Amber Mill (LB: 1,393.0 N; PL: 1,604.2 N) and IPS e.max CAD (LB: 1,315.7 N; PL: 1,461.9 N). Straumann n!ce without (LB: 862.4 N; PL: 942.9 N) and with the optional sintering (LB: 490.4 N; PL: 541.0 N) showed significantly lower fracture resistance than the others. Conclusion: The fracture resistance of chairside CAD/CAM lithium disilicate molar crowns varied depending on the material, and the novel materials did not perform as well as the conventional equivalents. Fully crystallized lithium disilicate ceramic block materials showed lower fracture resistance than precrystallized counterparts and should be used with caution in the clinic, especially with optional sintering. Int J Prosthodont 2023;36:722–729. doi:10.11607/ijp.780
Scattered Crypt Intestinal Epithelial Cell Apoptosis Induces Necrotizing Enterocolitis Via Intricate Mechanisms
Abstract
Background & aims: Necrotizing enterocolitis (NEC) is a life-threatening disease affecting mostly the ileum of preemies. Intestinal epithelial cell (IEC) apoptosis contributes to NEC pathogenesis. However, how scattered crypt IEC apoptosis leads to NEC with excessive villus epithelial necrosis remains unclear.
Methods: A novel triple-transgenic mouse model, namely, 3xTg-iAPcIEC (inducible apoptosis phenotype in crypt-IEC), was developed to induce IEC-specific overexpression of Fasl transgene using doxycycline (Dox)-inducible tetO-rtTA system and villin-cre technology. The 3-days-old neonatal 3xTg-iAPcIEC mice and their littermate controls were subcutaneously (s.c.) challenged with a single dose of Dox. Intestinal tissues were processed at different time points to examine scattered crypt IEC apoptosis-mediated NEC development. Gene knockout technology, antibody-mediated cell depletion, and antibiotic-facilitated Gram-positive bacteria depletion were used to study mechanisms.
Results: Treatment of 3xTg-iAPcIEC mouse pups with Dox induces scattered crypt IEC apoptosis followed by crypt inflammation and excessive villous necrosis resembling NEC. This progression correlated with elevated Ifng, Rip3, CD8+ T cells, and Gram-positive bacteria in the ileum. Mechanistically, IFN-γ and RIP3-activated signals mediate the effect of scattered crypt IEC apoptosis on the induction of intestinal crypt inflammation and villous necrosis. Meanwhile, pathophysiological events of CD8+ T cell infiltration and dysbiosis with Gram-positive bacteria primarily contribute to excessive villous inflammation and necrosis. Notably, blocking any of these events protects against NEC development in 3xTg-iAPcIEC mouse pups, underlining their central roles in NEC pathogenesis.
Conclusions: Scattered crypt IEC apoptosis induces NEC in mouse pups via IFN-γ, RIP3, CD8+ T cells, and Gram-positive bacteria-mediated comprehensive pathophysiological events. Our findings may advance knowledge in the prevention and treatment of NEC
Piecing together the subtle clues of common variable immunodeficiency
Abstract
Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder that results in decreased immunity and increased infection risk. This multisystem disorder often presents as recurrent, prolonged respiratory tract infections. Other manifestations include chronic lung disease, systemic granulomatous disease, malignancies, enteropathy, splenomegaly, and autoimmune disease including cytopenias. Diagnosis often is delayed, affecting patient quality of life, morbidity, and mortality. This article reviews the presentation, diagnosis, and management of patients with CVID