Screening and identification of 3‐aryl‐quinolin‐2‐one derivatives as antiviral agents against influenza A

alexandrossfakianakis shared this article with you from Inoreader Screening and identification of 3‐aryl‐quinolin‐2‐one derivatives as antiviral agents against influenza A via Journal of Medical Virology Abstract Quinolin-2-one represents an important and valuable chemical motif that possesses a wide variety of biological activities; however, the anti-influenza activities of quinolin-2-one-containing compounds were rarely reported. Herein we describe the screening and identification of 3-aryl-quinolin-2-one derivatives as a novel class of antiviral agents. The 3-aryl-quinolinone derivatives were synthesized via an efficient copper-catalyzed reaction cascade that we previously developed. Using this synthetic method, preliminary structure-activity relationships of this scaffold against the influenza A virus infection were systematically explored. The most potent compound 34 displayed IC50 values of 2.14 and 4.88 μM against the replication of H3N2 (A/HK/8/68) and H1N1 (A/WSN/33) strains, respectively, without apparent cytotoxicity on MDCK cells. We further demonstrated that 27 and 34 potently inhibited the plaque formation of the IAV, re ndering this scaffold attractive for pursuing novel anti-influenza agents. This article is protected by copyright. All rights reserved. View on Web

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Furcation involvement and tooth loss ‐ A registry‐based retrospective cohort study

alexandrossfakianakis shared this article with you from Inoreader Furcation involvement and tooth loss ‐ A registry‐based retrospective cohort study via Journal of Clinical Periodontology Abstract Aim This registry-based retrospective cohort study aimed to evaluate the impact of furcation status on the risk for molar loss. Material and methods Subjects with and without furcation involvement (FI) in 2010/2011 were identified in a nationwide registry in Sweden (age- and gender-matched sample: 381,450 subjects, 2,374,883 molars). Data on dental and periodontal status were extracted for the subsequent 10-year period. Impact of FI (at baseline or detected during follow-up) on molar loss (i.e. tooth extraction) was evaluated through multilevel logistic regression and survival analyses. Results FI had a significant impact on molar loss. FI degree 2 and 3 resulted in adjusted risk ratios of 1.67 (95%CI 1.63-1.71) and 3.30 (95%CI 3.18-3.43), respectively. Following first detection of deep FI (degree 2-3), estimated survival decreased by 4% at 5 years and 8% at 10 years. In addition to FI, endodontic status and probing depth were relevant risk factors for molar loss. Conclusions Furcation status had a clinically relevant impact on the risk for molar loss. Following first detection of deep FI, however, the decline in molar survival was minor. View on Web

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Association between periodontitis and chronic kidney disease by functional atherosclerosis status among older Japanese individuals: a cross‐sectional study

alexandrossfakianakis shared this article with you from Inoreader Association between periodontitis and chronic kidney disease by functional atherosclerosis status among older Japanese individuals: a cross‐sectional study via Journal of Clinical Periodontology Abstract Aims This study aimed to clarify the influence of functional atherosclerosis on the association between periodontitis and chronic kidney disease (CKD). Methods A cross-sectional study of 998 older Japanese individuals aged 60–99 years who participated in an oral health check-up was conducted. Early and advanced periodontitis were defined as periodontal pocket depth 4.0–5.9 mm and ≥6.0 mm, respectively. Functional atherosclerosis was defined as cardio-ankle vascular index (CAVI) ≥9.0. Results Of the 998 study participants, 238 (23.8%) had CKD. No significant associations between periodontitis and CKD were observed in participants without functional atherosclerosis. After adjusting for known cardiovascular risk factors, the odds ratio (OR) (95% confidence interval [CI]) was 1.31 (0.81, 2.11) for early periodontitis and 0.74 (0.41, 1.34) for advanced periodontitis. Significant positive associations were observed for participants with functional atherosclerosis; the adjusted ORs (95%CIs) were 1.76 (1.04, 3.01) for early periodontitis and 1.95 (1.05, 3.63) for advanced periodontitis, respectively. Conclusions A significant positive association between periodontitis and CKD was established for older participants with functional atherosclerosis. No significant associations were observed for those without functional atherosclerosis. These results can help clarify the influence of periodontitis on systemic circulation. View on Web

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Outcomes of Periodontal therapy in Rheumatoid Arthritis: the OPERA feasibility randomised trial

alexandrossfakianakis shared this article with you from Inoreader Outcomes of Periodontal therapy in Rheumatoid Arthritis: the OPERA feasibility randomised trial via Journal of Clinical Periodontology Abstract Background Periodontitis is independently associated with rheumatoid arthritis (RA); however, there are limited data on whether periodontal treatment improves overall RA disease activity. We conducted a pilot feasibility randomised controlled clinical trial to test whether intensive periodontal therapy reduces RA disease activity in patients with active RA and periodontitis. Methods The following inclusion criteria were applied: patients with RA and periodontitis, aged 18+, stable on treatment with DMARDs for ≥ 3 months, disease activity score (DAS28) ≥3.2, and DAS28 >5.1 only if patient unwilling to take biologics. Participants meeting the inclusion criteria were randomised to immediate intensive periodontal therapy or to delayed therapy (control group) administered by a dental hygienist in a secondary care setting. Data were collected at baseline, 3 and 6 months of follow-up. Participants randomised to the control group (delayed therapy) received the standard of care for the duration of the trial, including oral hygiene instructions delivered by a dental hygienist, and the same periodontal therapy as the intervention group after study completion (i.e., 6 months after randomisation). The periodontal inflammation surface area (PISA) was calculated using clinical attachment loss, periodontal probing pocket depth and bleeding on probing. Cumulative pro bing depth was also measured. We examined the effect of periodontal therapy on periodontal outcomes and on clinical markers of disease activity in RA, as measured by the DAS28-CRP score and musculoskeletal ultrasound grey scale and power Doppler scores. Results A total of 649 patients with RA were invited to participate in the study. Of these, 296 (46%) RA patients consented to participate in the screening visit. A sample of 201 were assessed for eligibility, of whom 41 (20%) did not meet RA inclusion criteria and 100 (50%) did not meet periodontal disease (PD) criteria. Amongst 60 (30%) eligible participants, 30 were randomised to immediate periodontal therapy and 30 were allocated to the control group. The loss to follow-up was 18% at the end of the trial. There were no major differences with regards to baseline characteristics between groups. Periodontal therapy was associated with reduced periodontal inflamed surface area, cumulative probing depths, RA disease activity scores and ultrasound scores over the course of the trial. There was no change in clinical attachment loss. Conclusions Overall, the trial was feasible and acceptable to study participants. Recruitment and satisfactory retention into a randomised controlled trial on the effect of periodontal treatment on RA patients is possible, albeit challenging. In this feasibility study of patients with RA and periodontitis, periodontal treatment resulted in significant improvements in periodontal disease outcomes and overall RA disease activity, although complete resolution of periodontal inflammation was difficult to achieve in some cases. This article is protected by copyright. All rights reserved. View on Web

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Subjective and objective evaluation of masticatory function in patients with bimaxillary implant‐supported prostheses

alexandrossfakianakis shared this article with you from Inoreader Subjective and objective evaluation of masticatory function in patients with bimaxillary implant‐supported prostheses via Journal of Oral Rehabilitation Abstract Background People perform poorly in masticatory function tests despite well-functioning prostheses. However, it is unclear whether there is an agreement between subjective and objective measures of mastication. Objectives To investigate the association between subjective and objective measures of masticatory function in patients with bimaxillary implant-supported prostheses. Materials and methods An experimental group (n=25, age=70.6 ±7.5 years, 8 women) with bimaxillary implant-supported fixed prostheses and a control group (n=25, age=69.0 ±5.3, 13 women) with natural dentition were recruited. The participants in the experimental group were included if they had been using the prosthesis for at least a year and had no obvious complaints with their prostheses. The control group was people with natural dentition and without any prostheses or complaints related to the masticatory system. The masticatory function was evaluated objectively with food comminution and mixing ability tests, and subjectively with jaw function limitation scale (JLFS) and oral health impact profile (OHIP). Results The experimental group performed poorly in both objective tests (P<.001). However, there was no significant differences between the two groups in total JFLS (P=0.114) and OHIP (P=0.312) scores. Though, there were certain positive correlations between the food comminution test and JFLS subdomains in the control group, and a positive correlation between food comminution test and specific subdomains of OHIP in the experimental group indicating poor correlation between the subjective and objective measures. Conclusion Although patients with implant prostheses show poor masticatory performance, there is no agreement in the objective and subjective measures of mastication. View on Web

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Implant deformation and implant–abutment fracture resistance after standardized artificial aging: An in vitro study

alexandrossfakianakis shared this article with you from Inoreader Implant deformation and implant–abutment fracture resistance after standardized artificial aging: An in vitro study via Clinical Implant Dentistry and Related Research Abstract Background and purpose Zirconia abutments have been widely adopted in clinical implant practice. The unique mechanical properties of zirconia may significantly affect the long-term prognosis of implant treatments. The purpose of this study was to investigate the influence of abutment material on implant deformation and fracture resistance of internal conical connection implant–abutment complexes of two diameters after standardized artificial aging. Materials and methods Thirty original abutments (one-piece titanium, one-piece zirconia, zirconia with alloy base) with two diameters (regular, narrow) were connected to internal conical connection implants and subjected to a standardized artificial aging process consisting of thermal cycling and mechanical cyclic loading. Microcomputed tomography (μCT) scans of implant bodies were performed before and after aging. 3-dimensional images of implant bodies were generated from the μCT scans and aligned for before and after aging to calculate the volumetric deformation amount. Finally, fracture resistance was measured using a mechanical static loading test for the surviving aged and 30 brand-new specimens. Results All specimens survived artificial aging. No significant difference in implant deformation was found in the regular groups (p = 0.095). In narrow groups, the one-piece zirconia group showed significantly less deformation (p < 0.0001). For fracture resistance, no significant decrease was observed after aging in any group (p > 0.05). One-piece zirconia abutments showed significantly lower strength than the other two materials for both diameters (p < 0.0001). Conclusions In the regular diameter system, abutment material had no significant influence on the tested mechanical property degradation after simulated long-term oral use. The mechanical performance of narrow diameter one-piece zirconia abutments differed from the other two materials. For optimal performance, one-piece zirconia abutments should be adopted only in anterior regions. View on Web

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Characterization of FA1654: a putative DPS protein in Filifactor alocis

alexandrossfakianakis shared this article with you from Inoreader Characterization of FA1654: a putative DPS protein in Filifactor alocis via Molecular Oral Microbiology Abstract The survival/adaptation of Fillifactor alocis, a fastidious gram positive asaccharolytic anaerobe, to the inflammatory environment of the periodontal pocket requires an ability to overcome oxidative stress. Moreover, its pathogenic characteristics are highlighted by its capacity to survive in the oxidative-stress microenvironment of the periodontal pocket and a likely ability to modulate the microbial community dynamics. There is still a significant gap in our understanding of its mechanism of oxidative stress resistance and its impact on the virulence and pathogenicity of the microbial biofilm. Coinfection of epithelial cells with F.alocis and P.gingivalis, resulted in the upregulation of several genes including HMPREF0389_01654(FA1654). Bioinformatics analysis indicates that FA1654 has a "di-iron binding domain", and could function as a DNA Starvation and Stationary Phase Protection (DPS) protein. We have further characterized the FA1654 protein to deter mine its role in oxidative stress resistance in F.alocis. In the presence of hydrogen peroxide induced oxidative stress there was a ∼1.3 fold upregulation of the FA1654 gene in F.alocis. Incubation of the purified FA1654 protein with DNA in the presence of hydrogen peroxide and iron resulted in the protection of the DNA from Fenton-mediated degradation. Circular Dichroism (CD) and Differential Scanning Flourimetry (DSF) studies have documented the intrinsic ability of rFA1654 protein to bind iron, however the rFA1654 protein is missing the intrinsic ability to reduce hydrogen peroxide. Collectively, the data may suggest that FA1654 in F.alocis is involved in oxidative stress resistance via an ability to protect against Fenton-mediated oxidative stress-induced damage. This article is protected by copyright. All rights reserved View on Web

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Role of Natural mTOR Inhibitors in Treatment of Diabetes Mellitus

alexandrossfakianakis shared this article with you from Inoreader Role of Natural mTOR Inhibitors in Treatment of Diabetes Mellitus via Fundamental & Clinical Pharmacology Abstract Diabetes mellitus is one of the most common and complex problems in today's society and is responsible for many socio-economic problems. Type 1 diabetes is due to a defect in insulin secretion caused by a destruction of pancreatic β cells. In contrast, the pathogenesis of type 2 diabetes is associated with the development of insulin resistance in the liver and peripheral tissues, a decrease in β-cell mass, and a defect in insulin secretion. Various factors such as inflammation, stress, obesity, and lifestyle are involved in diabetes. Long-term or chronic increase in glucose in these patients is the leading causes of secondary disorders such as micro- and macro-angiopathy, weakness of the antioxidant defense system as well as metabolic disorders and altered lipid profile. The above conditions lead to short-term and long-term complications. These complications cause damage to the physical and physiological function of diverse orga ns of the body and threaten human health. Late complications of diabetes, including nephropathy, retinopathy, cardiovascular complications, neuropathy, hypertension, and weight gain are common and more research has been done on them. Numerous drugs such as Meglitinides, Biguanides, and Thiazolidinedione have been proposed to reduce high blood sugar, but due to the lack of complete cure of this disease with the use of existing drugs, the tendency to use alternative and traditional therapies has increased. In the meantime, the role of herbs with hypoglycemic properties in the treatment of diabetic patients cannot be ignored. The consumption of herbs by people with diabetes has become widespread even in Western countries. The use of herbs could be considered when conventional therapies cannot control the disease, and the patient needs to be prescribed insulin. The mammalian target of rapamycin, mTOR, plays a significant role in regulating cell growth, cellular metabolic status in respo nse to nutrients, many extracellular cues and growth factors. Impaired insulin secretion can lead to altered mTOR signaling. The mTOR pathway has shown different behaviors depending on the situation. It has been shown that mTOR can regulate the adaptation of β cells to blood sugar but also chronic inhibition of the mTOR pathway can also induce diabetes. Here, we have reviewed recent findings on the role of mTOR in major metabolic organs, such as the liver, pancreas, brain, and adipose tissue and muscle, and discussed its potential as a diabetes-related drug target. View on Web

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Study on the Use of Ozone Water as a Chemical Decontamination Agent for Antineoplastic Drugs in Clinical Settings

alexandrossfakianakis shared this article with you from Inoreader Study on the Use of Ozone Water as a Chemical Decontamination Agent for Antineoplastic Drugs in Clinical Settings via Annals of Work Exposures and Health Advance Access Abstract The exposure of healthcare workers to antineoplastic drugs in hospitals has been recognized to be harmful. To minimize the risk of exposure, the removal of these drugs from work environments, such as compounding facilities, has been recommended. In our previous paper, the degradation and inactivation efficacy of ozone water, which is being introduced into Japanese hospitals as a chemical decontamination agent, was reported for its effects on typical antineoplastic drugs (gemcitabine, irinotecan, paclitaxel). This article aims to further investigate the efficacy of ozone water for eight antineoplastic drugs to clarify its application limitations. A small amount (medicinal ingredient: typically ca. 1.5 μmol) of formulation containing 5-fluorouracil, pemetrexed, cisplatin, oxaliplatin, cyclophosphamide, ifosfamide, doxorubicin, or docetaxel was mixed with 50 mL of ozone water (~8 mg/L), and the resulting solu tions were analyzed by high-performance liquid chromatography over time to observe the degradation. Consequently, the ozonation was overall effective for the degradation of the drugs, however this varied depending on the chemical structures of the drugs and additives in their formulations. In addition, after the parent drugs were completely degraded by the ozonation, the degradation mixtures were subjected to 1H nuclear magnetic resonance spectroscopy and evaluated for mutagenicity against Salmonella typhimurium strains and cytotoxicity against human cancer cells. The degradation mixtures of cisplatin and ifosfamide were mutagenic while those of the other drugs were non-mutagenic. Further, the ozonation resulted in clear decreases of cytotoxicity for 5-fluorouracil, oxaliplatin, and doxorubicin, but increases of cytotoxicity for pemetrexed, cisplatin, cyclophosphamide, and ifosfamide. These results suggest that the ozone water shoul d be restrictedly used according to the situation of contamination in clinical settings because the ozonation enhances toxicity depending on the drug even if degradation is achieved. View on Web

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An HPV-Vaccinated Patient With Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma

alexandrossfakianakis shared this article with you from Inoreader An HPV-Vaccinated Patient With Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma via JAMA Otolaryngology–Head & Neck Surgery Online First This case report describes an extremely early-onset case of hu man papillomavirus–positive oropharyngeal squamous cell carcinoma in a Norwegian woman in her early 20s. View on Web

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