Convergence of inflammatory response: Salivary cytokine dynamics in coronavirus disease 2019 and periodontal disease.

Background: Periodontal disease is associated with immune dysregulation, and cytokines released can add on to the coronavirus disease 2019 (COVID-19)-associated cytokine storm, further worsening the related adverse outcomes. Specific studies investigating cytokine levels in COVID-19 patients with periodontal disease are lacking. Examining the correlation between these conditions could aid in categorizing risk categories, determining referrals, and strengthening oral hygiene protocols. The current study sought to evaluate cytokine levels in the saliva of COVID-19-positive patients with and without periodontal disease. Materials and Methods: Twenty-six COVID-19-positive patients were subjected to periodontal examination, saliva collection, and assessment of cytokine levels through cytokine bead-based multiplex assay, using fluorescence-encoded beads with flow cytometry (BD FACS LSRFortessa). Eleven cytokines were assessed (interleukin [IL] 2, 4, 6, 10, 17A, and interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-α), chemokine ligand 2 (CCL2/monocyte chemoattractant protein-1), C-X-C motif chemokine ligand (CXCL) 8/IL 8, CXCL 9/monokine-induced gamma interferon [MIG]), and CXCL 10 (chemokine IFN-gamma inducible protein 10 kDa). The cytokine levels of the recruited subjects were also compared graphically with the salivary cytokine levels reported in the literature for health, COVID-19, and periodontal disease alone. Results: Out of 26 COVID-19-positive patients, 17 had periodontal disease. Levels of all cytokines were raised in patients with both diseases when compared to values reported in literature for health, periodontal disease alone, or COVID-19 alone. However, there was no statistical difference among the recruited subjects for IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-gamma, TNF-α, CCL2, CXCL 8, and CXCL 10. MIG levels were found to be higher in periodontally healthy, COVID-19-positive subjects (P = 0.01). Conclusions: Periodontal disease might contribute to the COVID-19-induced cytokine storm, potentially amplifying its impact.

ENTEROBACTER CLOACAE CARDIAC IMPLANTABLE ELECTRONIC DEVICE INFECTION.

Enterobacter cloacae cardiac implantable electronic device infections are rare but can be associated with significant morbidity and mortality. We report an 11-year-old female with Enterobacter cloacae infection of a dual-chamber transvenous pacemaker pocket. The report is supplemented by a comprehensive review of the literature on Enterobacter cloacae cardiac implantable electronic device infections.

E-cigarettes and heated tobacco products impact on dental color parameters.

Objectives: Abstaining from tobacco smoking may not only improve general health, but also reduce teeth staining and restore teeth whiteness. Compared with conventional cigarettes, E-cigarettes (ECs) and heated tobacco products (HTPs) may offer substantial reduction in exposure to pigmented tar-like compounds of cigarette smoke. It is possible that improvements in dental color indices may be observed in those who have stopped smoking combustible cigarettes by switching to tar-free nicotine delivery products. Methods: This cross-sectional study evaluated and compared dental color parameters by digital spectrophotometry among five different groups: individuals who currently smoke ; individuals who used to smoke but have quit ; individuals who have never smoked ; exclusive users of electronic cigarettes (former smokers) ; and exclusive users of heated tobacco products (former smokers) . Results: Dental whiteness in current cigarette smokers was notably worse compared with never and former smokers, (13.38 Whiteness Index for Dentistry (WID) units vs. 19.96 and 16.79 WID units). Remarkably high WID values (i.e., whiter teeth) were also observed in ECs (16.72 WID units) and HTPs users (17.82 WID units). Compared to current smokers, difference in dental whiteness for ECs and HTPs users was visually noticeable (ΔWID difference being on average > 2.90 units). The colour differences measured as delta E*(ΔE*) were all visually detectable except for the comparison between ex-smokers and ECs users for which no perceptible color difference was observed (0.415). Conclusion: Exclusive use of ECs and HTPs is associated with better dental color measurements than current smoking, suggesting that tar-free nicotine delivery technologies are unlikely to have negative effects on dental appearance. Clinical significance: Use of alternative nicotine delivery systems may be associated with cosmetic benefits with important implications for those smokers perceiving dental aesthetics as a significant problem. For these an oral-based narrative may be a much more significant reason to refrain from smoking than the fear of developing smoking-related diseases in future.

In Vivo Regulation of Active Matrix Metalloproteinase-8 (aMMP-8) in Periodontitis: From Transcriptomics to Real-Time Online Diagnostics and Treatment Monitoring.

BACKGROUND: This study investigated in vivo regulation and levels of active matrix metalloproteinase-8 (aMMP-8), a major collagenolytic protease, in periodontitis. METHODS: Twenty-seven adults with chronic periodontitis (CP) and 30 periodontally healthy controls (HC) were enrolled in immunohistochemistry and transcriptomics analytics in order to assess Treponema denticola (Td) dentilisin and MMP-8 immunoexpression, mRNA expression of MMP-8 and its regulators (IL-1ß, MMP-2, MMP-7, TIMP-1). Furthermore, the periodontal anti-infective treatment effect was monitored by four different MMP-8 assays (aMMP-8-IFMA, aMMP-8-Oralyzer, MMP-8-activity [RFU/minute], and total MMP-8 by ELISA) among 12 CP (compared to 25 HC). RESULTS: Immunohistochemistry revealed significantly more Td-dentilisin and MMP-8 immunoreactivities in CP vs. HC. Transcriptomics revealed significantly elevated IL-1ß and MMP-7 RNA expressions, and MMP-2 RNA was slightly reduced. No significant differences were recorded in the relatively low or barely detectable levels of MMP-8 mRNAs. Periodontal treatment significantly decreased all MMP-8 assay levels accompanied by the assessed clinical indices (periodontal probing depths, bleeding-on-probing, and visual plaque levels). However, active but not total MMP-8 levels persisted higher in CP than in periodontally healthy controls. CONCLUSION: In periodontal health, there are low aMMP-8 levels. The presence of Td-dentilisin in CP gingivae is associated with elevated aMMP-8 levels, potentially contributing to a higher risk of active periodontal tissue collagenolysis and progression of periodontitis. This can be detected by aMMP-8-specific assays and online/real-time aMMP-8 chair-side testing.

Transcriptome analysis of Huh7 cells upon Chikungunya virus infection and capsid transfection reveals regulation of distinct cellular and metabolic pathways.

Chikungunya virus (CHIKV) causes persistent arthritis and neurological problems imposing a huge burden globally. The present study aims to understand the interaction mechanism of Chikungunya virus and CHIKV-capsid in Huh7 cells. The RNA-sequencing and qRT-PCR method was used for the transcript and gene profiles of CHIKV virus and CHIKV capsid alone. Transcriptional analysis showed capsid induced 1114 and 956 differentially expressed genes (DEGs) to be upregulated and downregulated respectively, while in virus, 933 genes were upregulated and 956 were downregulated. Total 202 DEGs were common in both capsid and virus; and nine were validated using qRT-PCR. Identified DEGs were found to be associated with metabolic pathways such as Diabetes, cardiac disease, and visual impairment. Further, knock-down study on one of the DEGs (MafA) responsible for insulin regulation showed low viral proteins expression suggesting a reduction in virus-infection. Thus, the study provides insight into the interplay of the virus-host factors assisting virus replication.

Active Matrix Metalloproteinase-8 (aMMP-8) Versus Total MMP-8 in Periodontal and Peri-Implant Disease Point-of-Care Diagnostics.

Active matrix metalloproteinase-8 (aMMP-8) is a promising biomarker candidate for the modern periodontal and peri-implant disease diagnostics utilizing the chairside/point-of-care oral fluid technologies. These rapid biomarker analysis technologies utilize gingival crevicular fluid (GCF), peri-implant sulcular fluid (PISF), or mouth rinse as the oral fluid matrices that can be collected patient-friendly and non-invasively without causing bacteremia. aMMP-8, but not total or latent proMMP-8, has been shown to be a relevant biomarker to be implemented to the latest 2017 classification system of periodontitis and peri-implantitis. Thus, aMMP-8 point-of-care-testing (POCT)-but not total or latent proMMP-8-can be conveniently used as an adjunctive and preventive diagnostic tool to identify and screen the developing and ongoing periodontal and peri-implant breakdown and disease as well as predict its episodic progression. Similarly, aMMP-8 POCT provides an important tool to monitor the treatment effect of these diseases, but also other diseases such as head and neck cancer, where it can identify and predict the rapid tissue destructive oral side-effects during and after the radiotherapy. Additionally, recent studies support aMMP-8 POCT benefitting the identification of periodontitis and diabetes as the escalating risk diseases for COVID-19 infection. Overall, aMMP-8 POCT has launched a new clinical field in oral medicine and dentistry, i.e., oral clinical chemistry.

Study to Determine Concordance between High-Risk Human Papilloma Virus DNA Detection in Self Collected First Voided Urine Samples and Health-Care Worker Collected Cervical Samples in a Subset of Women with Proven Histopathological Precancerous and Cancerous Lesions of the Cervix.

Objective: The objective of our study was to assess whether urinary samples for human papilloma virus (HPV) detection are a good predictive marker of cervical cancerous and precancerous lesions, by comparing against results from cervical scrapings as the gold standard test. Materials and Methods: The study is a hospital-based cross-sectional study wherein symptomatic women were screened at the colposcopy clinic. Paired samples-cervical scrapings/washings and urine samples were tested for hr-HPV for women who were found to harbor premalignant and malignant lesions of the cervix in histopathological lesions, by multiplex real-time polymerase chain reaction and HPV genotyping. Diagnostic accuracy was tested by calculating concordance with Cohen's kappa with hr-HPV detection in cervical samples as the gold standard. Results: A total of 295 patients undergoing colposcopy were recruited in the study, out of which 54 had histopathological-proven premalignant and malignant lesions of the cervix. Overall, positivity rate in urinary samples for both HPV 16 and 18 combined is 64.81%, whereas for cervical samples is 68.51%. HPV 16 was seen in 30 (55.5%) and 32 (59.3%) cervical and urinary samples, respectively, whereas HPV 18 was seen in 7 (12.9%) and 6 (11.1%) samples, respectively. There was substantial concordance between the cervical samples and first-void urinary samples results with Cohen's k: 0.6988 (95% confidence interval: From 0.507 to 0.891). There was 85.96% agreement among all the tests that were performed with only 14.04% disagreement. Conclusions: The study showed that HPV DNA detection from the urine and cervical samples showed significant agreeability for the detection of precancerous and cancerous lesions of the cervix among women with abnormal histology results. Thus, urinary sampling can be done as a potential replacement for cervical sampling methods with the added benefit as it can be used in females reluctant to provide cervical samples, if there is no availability of skilled workforce for collecting samples, for mass screening, and for the follow-up of vaccination programs.

Infective Endocarditis at a Referral Children's Hospital During 19-Year Period: Trends and Outcomes.

BACKGROUND: We noted a recent increase in cases of infective endocarditis (IE) at our institution. The purpose of the study is to examine the incidence, risk factors, microbiology and outcome of IE in our pediatric population. METHODS: Retrospective review of IE cases during 2002-2020 at Children's Hospital of Michigan, Detroit. RESULTS: 68 patients with IE were identified. There was a 2-fold increase in incidence during the 2012-2020 (late period) compared to the 2002-2011 (early period). The most common predisposing conditions were congenital heart disease (CHD) in 39 (57.4%) and central venous catheter (CVC) in 19 (27.9%). CHD was more frequent in the late period (29/43, 67.4%) compared to early period (10/25, 40.0%) (p = 0.042). In CHD patients, palliative or corrective cardiac surgery was performed prior to IE diagnosis in 4/25 (16%) in early period and 23/43 (53.5%) in the late period (p = 0.004). S. aureus was the most common causative organism (35.3%) followed by streptococci (22.1%). Valve replacement or valvuloplasty was performed in 22.1% of patients. Complications occurred in 20 (29.4%). Mortality occurred in 7 (10.3%): 3 had CHD, 3 had CVC and underlying conditions and 1 had fulminant MRSA infection. CONCLUSION(S): The higher incidence of IE during the late period is likely due to an increase in patients with CHD who had undergone prior cardiac surgery. S. aureus was the predominant pathogen in all patients including those with CHD, followed by streptococci. IE in children continues to be associated with high rates of morbidity and mortality.

aMMP-8 point-of-care - diagnostic methods and treatment modalities in periodontitis and peri-implantitis.

INTRODUCTION: When collected in a standardized fashion, oral fluid analysis can refine the diagnosis of periodontal and peri-implant disease. In practice, dental professionals can perform active matrix metalloproteinase (aMMP-8) analysis chairside. AREAS COVERED: Periodontal tissues are mainly made up of type I collagen, and collagen breakdown is one of the main events in periodontal and peri-implantitis destructive lesions. In addition to traditional measurements, their diagnosis can be refined with tests utilizing oral fluids. The active matrix metalloproteinase-8 (aMMP-8) is possible to be determined from the gingival crevicular fluid (GCF), peri-implant sulcus fluid (PISF), and other oral fluids such as mouth rinse and saliva. We also investigated the applicability of aMMP-8 chair-side test kits in the evaluation of oral health benefits of different adjunctive host-modulating periodontal therapies including fermented lingonberry mouthwash (FLJ) and antibacterial photodynamic therapy (aPDT). EXPERT OPINION: The aMMP-8 levels can more reliably detect early activation of periodontal and peri-implant disease as compared to traditional diagnostic methods that assess the experienced health status or past disease, rather than the present or future pathology. Novel therapies like, fermented lingonberry juice as a mouthrinse or aPDT, are potential host-modulating adjunctive treatments to reduce the signs of oral inflammation and infection.

Association between periodontitis and cognitive impairment in adults.

DESIGN: To summarize the data on association between periodontal diseases and cognitive impairment in adults this systematic review scrutinized various observational studies till September 2021. This review was carried out in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA 2020) guidelines. The authors used PECO framework question,: population-Adults (18 years or older), exposure-adults suffering from periodontitis, comparator-adult group without periodontitis, outcome-adults at high risk for cognitive impairment. CASE/CONTROL SELECTION: Search for the literature was conducted on PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Search was limited to human studies with no limitation to year of publication prior to September 2021. Search terms used were related to gingiva, oral bacteria like Porphyromonas gingivalis, gum inflammation, periodontitis, dementia, neuroinflammation, cognitive impairment, Alzheimer's disease, Parkinson disease. Following research, all the studies providing association between periodontal diseases and neurodegenerative diseases with quantitative measures were included in the study. Non-human studies, studies on patients below 18 year old, studies related to influence of treatment and in subjects already suffering from neurological disease were excluded. After removing duplicates, eligible studies were identified and data extracted by two reviewers to make ensure inter examiner reliability and to prevent data entry errors. Data from the studies were tabulated as study design, sample characteristics, diagnosis, exposure biomarkers/measures, outcomes and results. DATA ANALYSIS: Methodological quality of studies was assessed by adapted Newcastle-Ottawa scale. Selection of study groups, comparability and exposure/outcome were used as parameters. Case-control and cohort studies were considered as high-quality studies if six or more stars were awarded out of nine maximum stars and four or more stars for cross-sectional studies out of six stars. Comparability among the groups was studied by taking into account primary factors for Alzheimer's disease such as age and sex and secondary factors like hypertension, osteoarthritis, depression, diabetes mellitus, and cerebrovascular disease. For cohort studies, 10 year follow up and dropout of <10% was considered to be successful. RESULTS: A total of 3693 studies were identified by two independent reviewers and finally 11 studies were included in the final analysis. Six cohort studies, three cross-sectional and two case-control studies were included after excluding remaining studies. Bias in studies was assessed by adapted Newcastle-Ottawa Scale. All included studies were of high methodological quality. Association between periodontitis and cognitive impairment was determined by using different criteria like International classification of disease, clinical measurement of periodontitis subjects, inflammatory biomarkers, microbes and antibodies. It was suggested that subjects with chronic periodontitis since 8 years or more, are at a higher risk of having dementia. Clinical measures of periodontal disease like probing depth, clinical attachment loss, alveolar bone loss were found to be positively associated with cognitive impairment. Inflammatory biomarkers and pre-existing elevated levels of serum IgG specific to periodontopathogens was reported to be associated with cognitive impairment. Within the limitations of the study, the authors concluded that though the patients with long-standing periodontitis are at greater risk for developing cognitive impairment by neurodegenerative diseases, the mechanism by which periodontitis can lead to cognitive impairment is still vague. CONCLUSIONS: Evidence suggests a strong association between periodontitis and cognitive impairment. Still further studies should be done to explore the mechanism involved.

Repeatability of dental plaque quantitation by light induced fluorescence technology in current, former, and never smokers.

BACKGROUND: The effects of smoking on the accumulation of dental plaque have not been studied in depth. We compared dental plaque quantitation obtained with a novel light induced fluorescence technology among current, former, and never smokers and verified measurements' repeatability. METHODS: Dental plaque quantitation was objectively assessed by quantitative light induced fluorescence (QLF) technology on three separate study visits in current, former, and never smokers: baseline (day 0), day 7, day 30. Increase in the fluorescence intensity of at least 30% (ΔR30) and 120% (ΔR120) together with the simple oral hygiene (SOH) scoring were considered for analysis. RESULTS: The QLF parameters were highly repeatable in each study group (p < 0.0001, by regression analyses). All QLF parameters showed a significant difference between never smokers and current smokers (p = 0.041 for ΔR30; p = 0.027 for ΔR120; p = 0.04 for SOH). No significant differences were observed between never and former smokers and between current and former smokers except for ΔR120 (p = 0.033). CONCLUSION: Dental plaque measurements by QLF technology were highly reproducible and showed greater plaque formation among current smokers compared to non-smokers. Objective and reproducible quantitation of dental plaque can be a valuable clinical and regulatory science endpoint to investigate the effect of smoking cessation medications, combustion-free tobacco products, and consumer care products on oral health. CLINICAL RELEVANCE: There is a need to objectively evaluate the relationship between smoking and plaque build-up as well as maturation. Current smokers demonstrated greater and more mature plaque buildup when compared to never and former smokers. Differences in plaque build-up and maturation between current, former and non-smokers may be utilized as an effective tool for patient motivation, identifying therapeutic end-points, translational research as well as prognostication. TRIAL REGISTRATION: The study is a pilot study parts of a larger project with registration ID: NCT04649645. As preliminary study, the pilot study referred into this paper started before the larger study registered in ClinicalTrials.gov.

Evidence that the catalytic mechanism of heme a synthase involves the formation of a carbocation stabilized by a conserved glutamate.

In eukaryotes and many aerobic prokaryotes, the final step of aerobic respiration is catalyzed by an aa3-type cytochrome c oxidase, which requires a modified heme cofactor, heme a. The conversion of heme b, the prototypical cellular heme, to heme o and ultimately to heme a requires two modifications, the latter of which is conversion of a methyl group to an aldehyde, catalyzed by heme a synthase (HAS). The N- and C-terminal halves of HAS share homology, and each half contains a heme-binding site. Previous reports indicate that the C-terminal site is occupied by a heme b cofactor. The N-terminal site may function as the substrate (heme o) binding site, although this has not been confirmed experimentally. Here, we assess the role of conserved residues from the N- and C-terminal heme-binding sites in HAS from prokaryotic (Shewanella oneidensis) and eukaryotic (Saccharomyces cerevisiae) species - SoHAS/CtaA and ScHAS/Cox15, respectively. A glutamate within the N-terminal site is found to be critical for activity in both types of HAS, consistent with the hypothesis that a carbocation forms transiently during catalysis. In contrast, the residue occupying the analogous C-terminal position is dispensable for enzyme activity. In SoHAS, the C-terminal heme ligands are critical for stability, while in ScHAS, substitutions in either heme-binding site have little effect on global structure. In both species, in vivo accumulation of heme o requires the presence of an inactive HAS variant, highlighting a potential regulatory role for HAS in heme o biosynthesis.

Strategies to Decrease the Prevalence of Soil-Transmitted Helminths in Central India.

Background Intestinal parasites are a major public health problem in tropical countries. Over 1.5 billion people are infected with soil-transmitted helminths (STH), of which 225 million are in India. Parasitic infections are associated with poor sanitation, lack of safe potable water, and improper hygiene. Materials and Methods The study was undertaken to ascertain the impact of control strategies, namely open-defecation free drive and mass drug administration of single dose albendazole. Stool samples received at AIIMS Bhopal Microbiology laboratory, across all age groups, were studied for protozoan trophozoites/cysts and helminthic ova. Results Out of 4,620 stool samples, 389 (8.41%) were positive either for protozoal or helminthic infections. Protozoan infections were more common than helminthic infections with Giardia duodenalis infection being the most common, 201 (51.67%), followed by Entamoeba histolytica , 174 (44.73%). The helminthic infections constituted 14 (3.5%) of the positive stool samples with Hookworm ova in 6 (1.5%) cases. Conclusion This study proves that strategies, namely "Swachh Bharat Abhiyan" and "National Deworming Day" started in 2014 and 2015 led to significant reduction of intestinal parasite infections in Central India, with a higher reduction of STH compared with protozoan parasite infection being ascribed to the activity spectrum of albendazole.

Plasmonic nanoparticle's anti-aggregation application in sensor development for water and wastewater analysis.

Colorimetric sensors have emerged as a powerful tool in the detection of water pollutants. Plasmonic nanoparticles use localized surface plasmon resonance (LSPR)-based colorimetric sensing. LSPR-based sensing can be accomplished through different strategies such as etching, growth, aggregation, and anti-aggregation. Based on these strategies, various sensors have been developed. This review focuses on the newly developed anti-aggregation-based strategy of plasmonic nanoparticles. Sensors based on this strategy have attracted increasing interest because of their exciting properties of high sensitivity, selectivity, and applicability. This review highlights LSPR-based anti-aggregation sensors, their classification, and role of plasmonic nanoparticles in these sensors for the detection of water pollutants. The anti-aggregation based sensing of major water pollutants such as heavy metal ions, anions, and small organic molecules has been summarized herein. This review also provides some personal insights into current challenges associated with anti-aggregation strategy of LSPR-based colorimetric sensors and proposes future research directions.

Photochemistry and Photophysics of Cholesta-5,7,9(11)-trien-3ß-ol in Ethanol.

Cholesta-5,7,9(11)-trien-3ß-ol (9,11-dehydroprovitamin D3, CTL) is used as a fluorescent probe to track the presence and migration of cholesterol in vivo. We recently described the photochemistry and photophysics of CTL in degassed and air-saturated tetrahydrofuran (THF) solution, an aprotic solvent. The zwitterionic nature of the singlet excited state, 1CTL* is revealed in ethanol, a protic solvent. In ethanol, the products observed in THF are accompanied by ether photoadducts and by photoreduction of the triene moiety to four dienes, including provitamin D3. The major diene retains the conjugated s-trans-diene chromophore and the minor is unconjugated, involving 1,4-addition of H at the 7 and 11 positions. In the presence of air, peroxide formation is a major reaction channel as in THF. X-ray crystallography confirmed the identification of two of the new diene products as well as of a peroxide rearrangement product.