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COVID-19 is a multi-system disorder with high variability in clinical outcomes among patients who are admitted to hospital. Although some cytokines such as interleukin (IL)-6 are believed to be associated with severity, there are no early biomarkers that can reliably predict patients who are more likely to have adverse outcomes. Thus, it is crucial to discover predictive markers of serious complications.In this retrospective cohort study, we analysed samples from 455 participants with COVID-19 who had had a positive SARS-CoV-2 RT-PCR result between April 14, 2020, and Dec 1, 2020 and who had visited one of three Mayo Clinic sites in the USA (Minnesota, Arizona, or Florida) in the same period. These participants were assigned to three subgroups depending on disease severity as defined by the WHO ordinal scale of clinical improvement (outpatient, severe, or critical). Our control cohort comprised of 182 anonymised age-matched and sex-matched plasma samples that were available from the Mayo Clinic Biorepository and banked before the COVID-19 pandemic. We did a deep profiling of circulatory cytokines and other proteins, lipids, and metabolites from both cohorts. Most patient samples were collected before, or around the time of, hospital admission, representing ideal samples for predictive biomarker discovery. We used proximity extension assays to quantify cytokines and circulatory proteins and tandem mass spectrometry to measure lipids and metabolites. Biomarker discovery was done by applying an AutoGluon-tabular classifier to a multiomics dataset, producing a stacked ensemble of cutting-edge machine learning algorithms. Global proteomics and glycoproteomics on a subset of patient samples with matched pre-COVID-19 plasma samples was also done.We quantified 1463 cytokines and circulatory proteins, along with 902 lipids and 1018 metabolites. By developing a machine-learning-based prediction model, a set of 102 biomarkers, which predicted severe and clinical COVID-19 outcomes better than the traditional set of cytokines, were discovered. These predictive biomarkers included several novel cytokines and other proteins, lipids, and metabolites. For example, altered amounts of C-type lectin domain family 6 member A (CLEC6A), ether phosphatidylethanolamine (P-18:1/18:1), and 2-hydroxydecanoate, as reported here, have not previously been associated with severity in COVID-19. Patient samples with matched pre-COVID-19 plasma samples showed similar trends in muti-omics signatures along with differences in glycoproteomics profile.A multiomic molecular signature in the plasma of patients with COVID-19 before being admitted to hospital can be exploited to predict a more severe course of disease. Machine learning approaches can be applied to highly complex and multidimensional profiling data to reveal novel signatures of clinical use. The absence of validation in an independent cohort remains a major limitation of the study.Eric and Wendy Schmidt.

COVID-19 vaccines are effective, but breakthrough infections have been increasingly reported. We conducted a test-negative case-control study to assess the durability of protection against symptomatic infection after vaccination with mRNA-1273. We fit conditional logistic regression (CLR) models stratified on residential county and calendar date of SARS-CoV-2 PCR testing to assess the association between the time elapsed since vaccination and the odds of symptomatic infection, adjusted for several covariates. There were 2,364 symptomatic individuals who had a positive SARS-CoV-2 PCR test after full vaccination with mRNA-1273 (“cases”) and 12,949 symptomatic individuals who contributed 15,087 negative tests after full vaccination (“controls”). The odds of symptomatic infection were significantly higher 250 days after full vaccination compared to the date of full vaccination (Odds Ratio [OR]: 2.47, 95% confidence interval [CI]: 1.19–5.13). The odds of non-COVID-19 associated hospitalization and non-COVID-19 pneumonia (negative control outcomes) remained relatively stable over the same time interval (Day 250 ORNon-COVID Hospitalization: 0.68, 95% CI: 0.47–1.0; Day 250 ORNon-COVID Pneumonia: 1.11, 95% CI: 0.24–5.2). The odds of symptomatic infection remained significantly lower almost 300 days after the first mRNA-1273 dose as compared to 4 days after the first dose, when immune protection approximates the unvaccinated state (OR: 0.26, 95% CI: 0.17–0.39). Low rates of COVID-19 associated hospitalization or death in this cohort precluded analyses of these severe outcomes. In summary, mRNA-1273 robustly protected against symptomatic SARS-CoV-2 infection at least 8 months after full vaccination, but the degree of protection waned over this time period.

As of 2021 November 29, booster vaccination against SARS-CoV-2 infection has been recommended for all individuals aged 18 years and older in the United States. A key reason for this recommendation is the expectation that a booster vaccine dose can alleviate observed waning of vaccine effectiveness (VE). Although initial reports of booster effectiveness have been positive, the level of protection from booster vaccination is unclear. We conducted two studies to assess the impact of booster vaccination, with BNT162b2 or mRNA-1273, on the incidence of SARS-CoV-2 infection between August and December 2021. We first compared SARS-CoV-2 infection incidence in cohorts of 3-dose vaccine recipients to incidence in matched cohorts of 2-dose vaccine recipients (cohort size = 24,539 for BNT162b2 and 14,004 for mRNA-1273). Additionally, we applied a test-negative study design to compare the level of protection against symptomatic infection in 3-dose recipients to that observed in recent 2-dose primary vaccine series recipients. The 3-dose recipients experienced a significantly lower incidence rate of SARS-CoV-2 infection than the matched 2-dose cohorts (BNT162b2 Incidence Rate Ratio: 0.11, 95% CI: 0.09 to 0.13 and mRNA-1273 IRR: 0.11, 95% CI: 0.08 to 0.15). Results from the test-negative study showed the third vaccine dose mitigated waning of VE, with the risk of symptomatic infection in 3-dose recipients being comparable to that observed 7 to 73 days after the primary vaccine series. These results show that 3-dose vaccine regimens with BNT162b2 or mRNA-1273 are effective at reducing SARS-CoV-2 infection and support the widespread administration of booster vaccine doses.

Case reports of patients infected with COVID-19 and influenza virus (“flurona”) have raised questions around the prevalence and severity of coinfection. Using data from HHS Protect Public Data Hub, NCBI Virus, and CDC FluView, we analyzed trends in SARS-CoV-2 and influenza hospitalized coinfection cases and strain prevalences. We also characterized coinfection cases across the Mayo Clinic Enterprise from January 2020 to April 2022. We compared expected and observed coinfection case counts across different waves of the pandemic and assessed symptoms and outcomes of coinfection and COVID-19 monoinfection cases after propensity score matching on clinically relevant baseline characteristics. From both the Mayo Clinic and nationwide datasets, the observed coinfection rate for SARS-CoV-2 and influenza has been higher during the Omicron era (2021 December 14 to 2022 April 2) compared to previous waves, but no higher than expected assuming infection rates are independent. At the Mayo Clinic, only 120 coinfection cases were observed among 197,364 SARS-CoV-2 cases. Coinfected patients were relatively young (mean age: 26.7 years) and had fewer serious comorbidities compared to monoinfected patients. While there were no significant differences in 30-day hospitalization, ICU admission, or mortality rates between coinfected and matched COVID-19 monoinfection cases, coinfection cases reported higher rates of symptoms including congestion, cough, fever/chills, headache, myalgia/arthralgia, pharyngitis, and rhinitis. While most coinfection cases observed at the Mayo Clinic occurred among relatively healthy individuals, further observation is needed to assess outcomes among subpopulations with risk factors for severe COVID-19 such as older age, obesity, and immunocompromised status.

COVID-19 vaccines are effective, but breakthrough infections have been increasingly reported. We conducted a test-negative case-control study to assess the durability of protection after full vaccination with BNT162b2 against polymerase chain reaction (PCR)-confirmed symptomatic SARS-CoV-2 infection, in a national medical practice from January 2021 through January 2022. We fit conditional logistic regression (CLR) models stratified on residential county and calendar time of testing to assess the association between time elapsed since vaccination and the odds of symptomatic infection or non-COVID-19 hospitalization (negative control), adjusted for several covariates. There were 5,985 symptomatic individuals with a positive test after full vaccination with BNT162b2 (cases) and 32,728 negative tests contributed by 27,753 symptomatic individuals after full vaccination (controls). The adjusted odds of symptomatic infection were higher 250 days after full vaccination versus at the date of full vaccination (Odds Ratio [OR]: 3.62, 95% CI: 2.52 to 5.20). The odds of infection were still lower 285 days after the first BNT162b2 dose as compared to 4 days after the first dose (OR: 0.50, 95% CI: 0.37 to 0.67), when immune protection approximates the unvaccinated status. Low rates of COVID-19 associated hospitalization or death in this cohort precluded analyses of these severe outcomes. The odds of non-COVID-19 associated hospitalization (negative control) decreased with time since vaccination, suggesting a possible underestimation of waning protection by this approach due to confounding factors. In summary, BNT162b2 strongly protected against symptomatic SARS-CoV-2 infection for at least 8 months after full vaccination, but the degree of protection waned significantly over this period.

The emergence of highly transmissible SARS-CoV-2 variants and vaccine breakthrough infections globally mandated the characterization of the immuno-evasive features of SARS-CoV-2. Here, we systematically analyzed 2.13 million SARS-CoV-2 genomes from 188 countries/territories (up to June 2021) and performed whole-genome viral sequencing from 102 COVID-19 patients, including 43 vaccine breakthrough infections. We identified 92 Spike protein mutations that increased in prevalence during at least one surge in SARS-CoV-2 test positivity in any country over a 3-month window. Deletions in the Spike protein N-terminal domain were highly enriched for these 'surge-associated mutations' (Odds Ratio = 14.19, 95% CI 6.15-32.75, p value = 3.41 × 10

Recent reports on waning of COVID-19 vaccine-induced immunity have led to the approval and rollout of additional doses and booster vaccinations. Individuals at increased risk of SARS-CoV-2 infection are receiving additional vaccine doses in addition to the regimen that was tested in clinical trials. Risks and adverse event profiles associated with additional vaccine doses are currently not well understood.To evaluate the safety of third-dose vaccination with US Food and Drug Administration (FDA)-approved COVID-19 mRNA vaccines.This cohort study was conducted using electronic health record (EHR) data from December 2020 to October 2021 from the multistate Mayo Clinic Enterprise. Participants included all 47 999 individuals receiving 3-dose COVID-19 mRNA vaccines within the study setting who met study inclusion criteria. Participants were divided into 2 cohorts by vaccine brand administered and served as their own control groups, with no comparison made between cohorts. Data were analyzed from September through November 2021.Three doses of an FDA-authorized COVID-19 mRNA vaccine, BNT162b2 or mRNA-1273.Vaccine-associated adverse events were assessed via EHR report. Adverse event risk was quantified using the percentage of study participants who reported the adverse event within 14 days after each vaccine dose and during a 14-day control period, immediately preceding the first vaccine dose.Among 47 999 individuals who received 3-dose COVID-19 mRNA vaccines, 38 094 individuals (21 835 [57.3%] women; median [IQR] age, 67.4 [52.5-76.5] years) received BNT162b2 (79.4%) and 9905 individuals (5099 [51.5%] women; median [IQR] age, 67.7 [59.5-73.9] years) received mRNA-1273 (20.6%). Reporting of severe adverse events remained low after the third vaccine dose, with rates of pericarditis (0.01%; 95% CI, 0%-0.02%), anaphylaxis (0%; 95% CI, 0%-0.01%), myocarditis (0%; 95% CI, 0%-0.01%), and cerebral venous sinus thrombosis (no individuals) consistent with results from earlier studies. Significantly more individuals reported low-severity adverse events after the third dose compared with after the second dose, including fatigue (2360 individuals [4.92%] vs 1665 individuals [3.47%]; P .001), lymphadenopathy (1387 individuals [2.89%] vs 995 individuals [2.07%]; P .001), nausea (1259 individuals [2.62%] vs 979 individuals [2.04%]; P .001), headache (1185 individuals [2.47%] vs 992 individuals [2.07%]; P .001), arthralgia (1019 individuals [2.12%] vs 816 individuals [1.70%]; P .001), myalgia (956 individuals [1.99%] vs 784 individuals [1.63%]; P .001), diarrhea (817 individuals [1.70%] vs 595 individuals [1.24%]; P .001), fever (533 individuals [1.11%] vs 391 individuals [0.81%]; P .001), vomiting (528 individuals [1.10%] vs 385 individuals [0.80%]; P .001), and chills (224 individuals [0.47%] vs 175 individuals [0.36%]; P = .01).This study found that although third-dose vaccination against SARS-CoV-2 infection was associated with increased reporting of low-severity adverse events, risk of severe adverse events remained comparable with risk associated with the standard 2-dose regime. These findings suggest the safety of third vaccination doses in individuals who were eligible for booster vaccination at the time of this study.

One of the prevalent medical issues that deserve global attention is adverse pregnancy outcomes and preterm low birth weight deliveries which have a significant impact on neonatal health. Periodontitis has been implicated as a significant risk factor for adverse effects in pregnancy. Elevated levels of periodontal pathogenic bacteria and proinflammatory cytokines which are pathognomonic features of periodontitis are believed to cause placental infection and premature rupture of the amniotic membrane consequently leading to preterm delivery. The role of CD14+CD16+ monocytes as a causal link between periodontitis and adverse pregnancy outcomes has not been researched so far, although an elevation of these cells has been independently demonstrated in both conditions. With the available background information, this hypothesis attempts to derive a mechanistic link between periodontitis and adverse pregnancy outcomes through the participation of CD14+CD16+ monocytes.

Introduction Osteoporotic patients require particular attention to their implant site bone quality as an indication of prognosis and may require modified surgical technique Insertion Torque (IT). Aim It is the purpose of this study to test whether IT is significantly correlated with bone density or not, as assessed by the cone-beam computed tomography (CBCT) in a group of osteopenic and osteoporotic patients. Materials and methods A total of 30 patients were included in the study. The mandibular second premolar region was chosen as the site of investigation to prevent variability in surgical implant placement technique in different locations affecting bone mineral density (BMD). Partially, edentulous female patients between 51 and 60 years of age who were scheduled to receive implant placement were recruited for the study. CBCT (Master Series 3D Dental Imaging) was used for preoperative evaluation of the jaws for each patient. Materialise's Interactive Medical Image Control System (MIMICS) was used to process stacks of 2D images from CBCT. Finite element analysis were carried out on bone using Ansys software. Maximum displacement and maximum stress—strain patterns were compared in normal, osteoporotic, and osteopenic groups. Results The difference in mean bone density in all three groups were statistically significant (p < 0.05) (Table 1). FEA at 32, 36, 40 N in all 3 groups was statistically significant. (Table 2). Conclusion Within the limitations of the study, the amount of stress—strain that exhibits at 40 N load in normal bone will be almost the same stress—strain given at 32 N load in osteoporotic bone. Normal IT load analysis exhibits more stress/strain in osteoporotic patients when compared with other groups, showing that IT must be achieved to an optimum level to avoid further complication and failures. How to cite this article Venkatakrishnan CJ, Bhuminathan S, Chandran CR. Implant Insertion Torque Load Analysis for Mandible using CBCT Images. World J Dent 2017;8(3):183-189.

G-protein-coupled receptors (GPCRs) mediate a wide variety of physiological functions and are a rich source of drug targets. In response to activation by extracellular stimuli, GPCRs trigger cytoplasmic signalling pathways through intracellular partners such as G-proteins and arrestins. This chapter provides a general overview of the molecular mechanisms of GPCR activation gleaned from crystal structures, biophysical experiments, and computational analyses. Furthermore, existing challenges and unresolved mechanistic questions about GPCR signalling are highlighted.

Dopamine receptors are implicated in the pathogenesis and treatment of nearly every neuropsychiatric disorder. Although thousands of drugs interact with these receptors, our molecular understanding of dopaminergic drug selectivity and design remains clouded. To illuminate dopamine receptor structure, function, and ligand recognition, we determined crystal structures of the D4 dopamine receptor in its inactive state bound to the antipsychotic drug nemonapride, with resolutions up to 1.95 angstroms. These structures suggest a mechanism for the control of constitutive signaling, and their unusually high resolution enabled a structure-based campaign for new agonists of the D4 dopamine receptor. The ability to efficiently exploit structure for specific probe discovery-rapidly moving from elucidating receptor structure to discovering previously unrecognized, selective agonists-testifies to the power of structure-based approaches.

G-protein-coupled receptors (GPCRs) pose challenges for drug discovery efforts because of the high degree of structural homology in the orthosteric pocket, particularly for GPCRs within a single subfamily, such as the nine adrenergic receptors. Allosteric ligands may bind to less-conserved regions of these receptors and therefore are more likely to be selective. Unlike orthosteric ligands, which tonically activate or inhibit signalling, allosteric ligands modulate physiologic responses to hormones and neurotransmitters, and may therefore have fewer adverse effects. The majority of GPCR crystal structures published to date were obtained with receptors bound to orthosteric antagonists, and only a few structures bound to allosteric ligands have been reported. Compound 15 (Cmpd-15) is an allosteric modulator of the β2 adrenergic receptor (β2AR) that was recently isolated from a DNA-encoded small-molecule library1. Orthosteric β-adrenergic receptor antagonists, known as beta-blockers, are amongst the most prescribed drugs in the world and Cmpd-15 is the first allosteric beta-blocker. Cmpd-15 exhibits negative cooperativity with agonists and positive cooperativity with inverse agonists. Here we present the structure of the β2AR bound to a polyethylene glycol-carboxylic acid derivative (Cmpd-15PA) of this modulator. Cmpd-15PA binds to a pocket formed primarily by the cytoplasmic ends of transmembrane segments 1, 2, 6 and 7 as well as intracellular loop 1 and helix 8. A comparison of this structure with inactive- and active-state structures of the β2AR reveals the mechanism by which Cmpd-15 modulates agonist binding affinity and signalling.

The science and art employed in the profession of dentistry can play an important role in the fabrication of an orbital prosthesis. Anophthalmia (the loss of an eye) not only impairs patient's vision but also create a noticeable deformity on facial appearance and esthetics. The condition is a psychological distress for the patient interrupting his routine work. A prosthodontist as an integral member of the craniofacial rehabilitation team can help raise the spirits and ease the mind of the affected. Mutilation of a portion of a face can cause a heavy impact on the self image and personality of an individual. Acceptable cosmetic results usually can be obtained with a orbital prosthesis. This paper describes prosthetic rehabilitation of a 30-year-old female patient having a left and right ocular defect. A technique to modify stock eye with heat polymerizing polymethyl methacrylate is illustrated. The resultant prosthesis was structurally durable and esthetically acceptable with satisfactory retention. The importance of meticulous treatment planning to tackle the challenges faced in fabricating an ocular prosthesis is explained with the relevant literature. How to cite this article Venkatakrishnan CJ, Jain AR, Pradeep R, Philip JM, Narasimman M. Prosthetic Rehabilitation of Patient with Ocular Defect using Acrylic Stock Eyes. Int J Prosthodont Restor Dent 2013;3(4):143-147.

Bibliometric study of a subject will help administrators and policy makers to frame policies for the growth of the subject. Prosthodontics is an integral part of dental sciences and no bibliometric study has been done on Indian prosthodontics publications. Publications from Indian Dental establishments during 1996–2007 were collected from Medline and data were collected. First author’s affiliations were only considered. Publications by prosthodontists were considered for this study. Predictor variables: year, number of author, state Outcome variables: type and reach of journal, type of article. There were 43 articles fulfilling the criteria. Prosthodontist from nine different states published in 12 different journals. Thirteen (30.2 %) were case reports, 23 (53.5 %) were research, 4 (9.3 %) were reviews and 3 (7 %) were technical note. The inter-annual variation between the type and reach of article and type of articles is presented. The growth trend analysis was performed and predictions are presented. Prosthodontist exhibited a trend to publish in general dental journals, publish case reports, in international journals. The mean numbers of authors in each type are discussed. The potential use of this data are discussed.

Restoration of a long span partially edentulous maxilla with tooth supported prosthesis is challenging because of inherent anatomic limitations and unfavourable biomechanics present after the loss of teeth. A tooth supported fixed-removable prosthesis is a treatment option for restoration of such long span partially edentulous maxillary arches. This prosthesis meets the requirements for esthetics, phonetics, comfort, and hygiene, as well as favourable biomechanical stress distribution to the remaining natural tooth abutments. This article presents a procedure for fabrication of a fixed-removable prosthesis that has cement-retained custom cast bar metal substructure and a ball attachment retained removable superstructure prosthesis.

Skin graft vestibuloplasty has long been popularized in increasing the depth of the vestibule. An unusual case of vestibuloplasty for correction of vestibule depth due to previous surgery is presented. Conventional methods of graft-stent fixation are traumatic, effortful and carry substantial risk. An altered method for rehabilitation of the present case by using graft-vestibuloplasty is described with underlying physiology of the process.

Monocytes are immune cells that form an important bridge between the innate and adaptive immune response. These cells exist in various phenotypes based on cell surface marker expression and participate in the pathobiology of many systemic diseases. Periodontitis is an inflammatory condition of the tooth attachment apparatus caused by microbial assault from the dental plaque biofilm. It is noteworthy that monocytes play a key role in mediating tissue destruction in periodontitis. The CD14+ CD16+ monocytes that bear both the surface markers are especially involved and upregulated in periodontitis and produce increased amounts of proinflammatory cytokines following microbial challenge. In this context and exploring the available literature, the present chapter aims to unravel the role of CD14+ CD16+ monocytes in periodontitis and systemic disease and also aims to elucidate the possible pathways by which periodontitis could be a key risk factor for systemic disease based on monocyte selection and participation.