Literature Review of Omicron: A Grim Reality Amidst COVID-19.

Coronavirus disease 2019 (COVID-19) first emerged in Wuhan city in December 2019, and became a grave global concern due to its highly infectious nature. The Severe Acute Respiratory Coronavirus-2, with its predecessors (i.e., MERS-CoV and SARS-CoV) belong to the family of Coronaviridae. Reportedly, COVID-19 has infected 344,710,576 people around the globe and killed nearly 5,598,511 persons in the short span of two years. On November 24, 2021, B.1.1.529 strain, later named Omicron, was classified as a Variant of Concern (VOC). SARS-CoV-2 has continuously undergone a series of unprecedented mutations and evolved to exhibit varying characteristics. These mutations have largely occurred in the spike (S) protein (site for antibody binding), which attribute high infectivity and transmissibility characteristics to the Omicron strain. Although many studies have attempted to understand this new challenge in the COVID-19 strains race, there is still a lot to be demystified. Therefore, the purpose of this review was to summarize the structural or virologic characteristics, burden, and epidemiology of the Omicron variant and its potential to evade the immune response.

A 'Real Life' Service Evaluation Model for Multidisciplinary Thyroid Eye Services.

Background/Aims: There is no universal consensus on the practical implementation and evaluation of the Amsterdam Declaration on Graves Orbitopathy in a Multidisciplinary Thyroid Eye Disease (MDTED) pathway. Recent recommendations from the UK TEAMeD-5 and BOPSS initiative highlight the importance of prevention, screening, and prompt referral of patients with moderate to severe and sight-threatening thyroid eye disease to multidisciplinary (MDTED) clinics and recommends annual auditing. We propose a practical service evaluation model with Key Performance Indicators (KPI) that are achievable and could be implemented across most TED pathways. Material and Methods: We conducted a service evaluation from an integrated TED pathway in London with three MDTED clinics. Data was collected retrospectively from consecutive TED patients included: 1) Patient demographics, 2) Referral to first appointment time, 3) Documented smoking cessation and selenium supplementation advice, 4) Presenting disease activity and severity, 5) Investigations and treatments, including radio-iodine, 6) Time from decision to treatment initiation, 7) Initial and subsequent thyroid status. Results: The median age was 49.0 yrs, 77.5% (183/236) were female and 49.5% (101/204) Afro-Caribbean or Asian. At their first clinic attendance, 47.6% (110/231) were biochemically euthyroid and 76.7% (79/103) at discharge. All 23.1% (52/225) current smokers received smoking cessation advice and 64.8% (153/236) received selenium supplementation advice. Intravenous methylprednisolone was given to 33.9% (80/236) patients and 12.7% (30/236) received second-line immunosuppression. All 7.2% (17/236) patients with sight-threatening disease received treatment within two weeks of diagnosis. Conclusions: This study forms a waymark for other units using TEAMeD-5 and BOPSS audit criteria. Dedicated electronic patient records with ongoing data capture, including quality of life assessments, and diagnostic coding would significantly aid future auditing, improve patient care, and facilitate a national audit of TED management. A future survey when the TED standards have become embedded would be instructive to see whether this has improved TED care.

Improvisation and Evaluation of Laterosporulin Coated Titanium Surfaces for dental Applications: An In Vitro Investigation.

Despite recent improvement in implant survival rates, there remains a significant demand for enhancing the long-term clinical efficacy of titanium (Ti) implants, particularly for the prevention of peri-implantitis. Bioactive substances such as antimicrobial peptides are emerging as effective alternatives for contemporary antimicrobial agents used in dental health care. Current research work was focused to use laterosporulins that are non-haemolytic cationic antimicrobial peptides from Brevibacillus spp. for coating commercially available Ti discs. The coated Ti surfaces were evaluated in vitro for biofilm formation by two dental plaque isolates Streptococcus gordonii strain DIGK25 and S. mutans strain DIGK119 as representatives of commensal and pathogenic streptococci respectively. The biofilm inhibition was ascertained with replicated experiments on hydroxyapatite discs and confirmed by florescence microscopy. The laterosporulin coated Ti discs showed significantly reduced biofilm formation by oral streptococci and displayed promising potential to enhance the antibacterial surface properties. Such improvised Ti surfaces may curb the menace of oral streptococcal biofilm formation on dental implants and the associated implant failures.

Association of Other Autoimmune Diseases With Thyroid Eye Disease.

Background: Thyroid eye disease (TED) is a potentially disfiguring and sight-threatening autoimmune (AI) orbitopathy, affecting up to 400,000 people in the UK. There are no accurate early predictors of TED severity. Although polyautoimmunity has been shown to affect AI disease severity, its influence on TED severity has never been investigated. The prevalence of polyautoimmunity among TED patients is also unclear, with discordant results reported in the literature. This study evaluates the prevalence of non-thyroid/"other" AI (OAI) conditions in an ethnically diverse TED cohort and assesses how polyautoimmunity affects TED severity and activity. Methods: A retrospective study of patients presenting to multidisciplinary TED clinics across three North-West London hospitals between 2011 and 2019. Data collected included: 1) demographics; 2) OAI conditions and management; 3) endocrine management of thyroid dysfunction; 4) details of TED and clinical activity score at presentation. Results: Two hundred and sixty-seven patients with a median age of 46 (35-54) years were included, 79.4% were female and 55% were Black, Asian and minority ethnic (BAME). Thirty-seven patients (13.9%) had OAI conditions, with rheumatoid arthritis (3.7%), vitiligo (3.0%) and psoriasis (3.0%) among the most prevalent. Of patients with OAI conditions, 43.2% (16/37) required immunosuppression prior to TED onset. Non-immunosuppressed patients with OAI conditions had a significantly higher clinical activity score at presentation than TED-only and previously immunosuppressed patients (p=0.02). No significant differences were observed in thyroid receptor antibody titers between these groups. Conclusions: This study finds a 13.9% prevalence of OAI conditions among TED patients. Patients with OAI conditions overall have a tendency for more severe and significantly more clinically active TED than those without OAI conditions. Larger, prospective studies are warranted to further evaluate polyautoimmunity as an early predictor of TED severity.

Evaluation of the efficacy of subgingival irrigation in patients with moderate-to-severe chronic periodontitis otherwise indicated for periodontal flap surgeries.

BACKGROUND: In certain medically and physically compromised; and terminally ill patients, periodontal surgery may not be feasible. They need special attention and assistance for their daily plaque control regimens for the management and maintenance of periodontal conditions. Subgingival irrigation home care devices with antiplaque agents may serve as useful tools in such specific patient populations. AIMS: The aim of this study was to evaluate of the efficacy of sub-gingival irrigation in patients with moderate-to-severe chronic periodontitis otherwise indicated for periodontal flap surgeries. SETTINGS AND DESIGN: Randomized comparative parallel group interventional clinical trial. MATERIALS AND METHODS: Forty adults with moderate-to-severe periodontitis, divided inot Group A and B, were subjected to the use of subgingival home irrigations using 0.06% chlorhexidine (CHX) and mouth-rinsing with 15 ml of 0.12% CHX twice daily, respectively after Phase I therapy. Clinical parameters, i.e., gingival index, oral hygiene index simplified, and bleeding on probing scores were assessed at baseline, 2 weeks, 4 weeks, and 12 weeks' postphase I therapy, whereas clinical attachment level (CAL), probing depth (PD), and stain assessment at baseline and 12 weeks following Phase I therapy. STATISTICAL ANALYSIS USED: Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, USA version 15.0 for Windows). RESULTS: A statistically significant difference was seen with the use of 0.06% CHX irrigations in PD (P = 0.004) and CAL (P = 0.002) as compared to the use of mouth rinsing with 0.12% CHX. Similar differences were observed in both intensity (P = 0.014) and area (P = 0.034) of lingual surface staining with greater staining with CHX mouth rinsing. CONCLUSION: The adjunctive use of subgingival home irrigations using 0.06% CHX has a promising potential to maintain the oral health and results in lesser staining compared to CHX mouth rinsing. The regimen may further obviate the need of periodontal surgery in medically compromised subjects.

SpikeSegNet-a deep learning approach utilizing encoder-decoder network with hourglass for spike segmentation and counting in wheat plant from visual imaging.

BACKGROUND: High throughput non-destructive phenotyping is emerging as a significant approach for phenotyping germplasm and breeding populations for the identification of superior donors, elite lines, and QTLs. Detection and counting of spikes, the grain bearing organs of wheat, is critical for phenomics of a large set of germplasm and breeding lines in controlled and field conditions. It is also required for precision agriculture where the application of nitrogen, water, and other inputs at this critical stage is necessary. Further, counting of spikes is an important measure to determine yield. Digital image analysis and machine learning techniques play an essential role in non-destructive plant phenotyping analysis. RESULTS: In this study, an approach based on computer vision, particularly object detection, to recognize and count the number of spikes of the wheat plant from the digital images is proposed. For spike identification, a novel deep-learning network, SpikeSegNet, has been developed by combining two proposed feature networks: Local Patch extraction Network (LPNet) and Global Mask refinement Network (GMRNet). In LPNet, the contextual and spatial features are learned at the local patch level. The output of LPNet is a segmented mask image, which is further refined at the global level using GMRNet. Visual (RGB) images of 200 wheat plants were captured using LemnaTec imaging system installed at Nanaji Deshmukh Plant Phenomics Centre, ICAR-IARI, New Delhi. The precision, accuracy, and robustness (F1 score) of the proposed approach for spike segmentation are found to be 99.93%, 99.91%, and 99.91%, respectively. For counting the number of spikes, "analyse particles"-function of imageJ was applied on the output image of the proposed SpikeSegNet model. For spike counting, the average precision, accuracy, and robustness are 99%, 95%, and 97%, respectively. SpikeSegNet approach is tested for robustness with illuminated image dataset, and no significant difference is observed in the segmentation performance. CONCLUSION: In this study, a new approach called as SpikeSegNet has been proposed based on combined digital image analysis and deep learning techniques. A dedicated deep learning approach has been developed to identify and count spikes in the wheat plants. The performance of the approach demonstrates that SpikeSegNet is an effective and robust approach for spike detection and counting. As detection and counting of wheat spikes are closely related to the crop yield, and the proposed approach is also non-destructive, it is a significant step forward in the area of non-destructive and high-throughput phenotyping of wheat.

Combined immunosuppression and radiotherapy in thyroid eye disease (CIRTED): a multicentre, 2 × 2 factorial, double-blind, randomised controlled trial.

BACKGROUND: Standard treatment for thyroid eye disease is with systemic corticosteroids. We aimed to establish whether orbital radiotherapy or antiproliferative immunosuppression would confer any additional benefit. METHODS: CIRTED was a multicentre, double-blind, randomised controlled trial with a 2 × 2 factorial design done at six centres in the UK. Adults with active moderate-to-severe thyroid eye disease associated with proptosis or ocular motility restriction were recruited to the trial. Patients all received a 24 week course of oral prednisolone (80 mg per day, reduced to 20 mg per day by 6 weeks, 10 mg per day by 15 weeks, and 5 mg per day by 21 weeks) and were randomly assigned via remote computerised randomisation to receive either radiotherapy or sham radiotherapy and azathioprine or placebo in a 2 × 2 factorial design. Randomisation included minimisation to reduce baseline disparities in potential confounding variables between trial interventions. Patients and data analysts were masked to assignment, whereas trial coordinators (who monitored blood results), pharmacists, and radiographers were not. The radiotherapy dose was 20 Gy administered to the retrobulbar orbit in ten to 12 fractions over 2 to 3 weeks. Azathioprine treatment was provided for 48 weeks at 100-200 mg per day (dispensed as 50 mg tablets), depending on bodyweight (100 mg for <50 kg, 150 mg 50-79 kg, 200 mg for ≥80 kg). The primary outcomes were a binary composite clinical outcome score and an ophthalmopathy index at 48 weeks, and a clinical activity score at 12 weeks. The primary analysis was based on the intention-to-treat allocation and safety was assessed in all participants. This study is registered with ISRCTN, number 22471573. FINDINGS: Between Feb 15, 2006, and Oct 3, 2013, 126 patients were recruited and randomly assigned to groups: 31 patients to radiotherapy plus azathioprine, 31 to sham radiotherapy and azathioprine, 32 to radiotherapy and placebo, and 32 to sham radiotherapy and placebo. Outcome data were available for 103 patients (54 for sham radiotherapy vs 49 for radiotherapy and 53 for placebo vs 50 for azathioprine), of whom 84 completed their allocated treatment of radiotherapy or sham radiotherapy and 57 continued to take azathioprine or placebo up to 48 weeks. There was no interaction betweeen azathioprine and radiotherapy (pinteraction=0·86). The adjusted odds ratio (ORadj) for improvement in the binary clinical composite outcome measure was 2·56 (95% CI 0·98-6·66, p=0·054) for azathioprine and 0·89 (0·36-2·23, p=0·80) for radiotherapy. In a post-hoc analysis of patients who completed their allocated therapy the ORadj for improvement was 6·83 (1·66-28·1, p=0·008) for azathioprine and 1·32 (0·30-4·84, p=0·67) for radiotherapy. The ophthalmopathy index, clinical activity score, and numbers of adverse events (161 with azathioprine and 156 with radiotherapy) did not differ between treatment groups. In both groups, the most common adverse events were mild infections. No patients died during the study. INTERPRETATION: In patients receiving oral prednisolone for 24 weeks, radiotherapy did not have added benefit. We also did not find added benefit for addition of azathioprine in the primary analysis; however, our conclusions are limited by the high number of patients who withdrew from treatment. Results of post-hoc analysis of those who completed the assigned treatment suggest improved clinical outcome at 48 weeks with azathioprine treatment. FUNDING: National Eye Research Centre, Above and Beyond, and Moorfields Eye Charity.

Arylalkyl ketones, benzophenones, desoxybenzoins and chalcones inhibit TNF-α induced expression of ICAM-1: structure-activity analysis.

The interaction between leukocytes and the vascular endothelial cells (EC) via cellular adhesion molecules plays an important role in the pathogenesis of various inflammatory and autoimmune diseases. Small molecules that block these interactions have been targeted as potential therapeutic agents against acute and chronic inflammatory diseases. In an effort to identify potent intercellular cell adhesion molecule-1 (ICAM-1) inhibitors, a large number of arylalkyl ketones, benzophenones, desoxybenzoins and chalcones and their analogs (54 in total) have been synthesized and screened for their ICAM-1 inhibitory activity. The structure-activity relationship studies of these compounds identified three potent chalcone derivatives and also demonstrated the possible mechanism for their ICAM-1 inhibitory activities. The most active compound was found to be 79.

Diabetes and periodontitis.

The main aim of this review is to update the reader with practical knowledge concerning the relationship between diabetes mellitus and periodontal diseases. Exclusive data is available on the association between these two chronic diseases till date. Articles published on this relationship often provide the knowledge of definitions of diabetes mellitus and periodontal diseases, prevalence, extent, severity of periodontal disease, complications of diabetes along with the possible underlying mechanisms. The authors reviewed human epidemiological studies, cross-sectional observations and longitudinal cohort, case control that evaluated variables exclusively over the past 30 years and the predominant findings from the "certain" articles are summarized in this review. This review clarifies certain queries such as 1) Do periodontal diseases have an effect on the metabolic control of diabetes? 2) Does diabetes act as a risk factor of periodontitis? 3) What are the possible underlying mechanisms relating the connection between these two chronic diseases? 4) What is the effect of periodontal intervention on metabolic control of diabetes? After a thorough survey of literature, it was observed that diabetes acts as a risk factor in development of periodontitis as periodontitis is significantly aggravated in patients suffering from diabetes having long term hyperglycemia. Different mechanisms underlying the association between the accelerated periodontal disease and diabetes are emerging but still more work is required. Major efforts are required to elucidate the impact of periodontal diseases on diabetes. At the same time, patients are needed to be made aware of regular periodontal maintenance schedule and oral hygiene.

Protocol for the combined immunosuppression & radiotherapy in thyroid eye disease (CIRTED) trial: a multi-centre, double-masked, factorial randomised controlled trial.

BACKGROUND: Medical management of thyroid eye disease remains controversial due to a paucity of high quality evidence on long-term treatment outcomes. Glucocorticoids are known to be effective initially but have significant side-effects with long-term use and recrudescence can occur on cessation. Current evidence is conflicting on the efficacy of radiotherapy and non-steroid systemic immunosuppression, and the majority of previous studies have been retrospective, uncontrolled, small or poorly designed.The Combined Immunosuppression and Radiotherapy in Thyroid Eye Disease (CIRTED) trial was designed to investigate the efficacy of radiotherapy and azathioprine in combination with a standard course of oral prednisolone in patients with active thyroid eye disease. METHODS/DESIGN: Patients with active thyroid eye disease will be randomised to receive (i) azathioprine or oral placebo and (ii) radiotherapy or sham-radiotherapy in this multi-centre, factorial randomised control trial. The primary outcome is improvement in disease severity (assessed using a composite binary measure) at 12 months and secondary end-points include quality of life scores and health economic measures. DISCUSSION: The CIRTED trial is the first study to evaluate the role of radiotherapy and azathioprine as part of a long-term, combination immunosuppressive treatment regime for Thyroid Eye Disease. It will provide evidence for the role of radiotherapy and prolonged immunosuppression in the management of this condition, as well as pilot data on their use in combination. We have paid particular attention in the trial design to establishing (a) robust placebo controls and masking protocols which are effective and safe for both radiotherapy and the systemic administration of an antiproliferative drug; (b) constructing effective inclusion and exclusion criteria to select for active disease; and (c) selecting pragmatic outcome measures. TRIAL REGISTRATION: Current controlled trials ISRCTN22471573.

Inferior oblique schwannoma: diagnosis and management.

INTRODUCTION: Orbital schwannoma accounts for less than 5% of orbital tumours and few cases arising in the superior orbit are reported in the literature. PURPOSE: To present, to our knowledge, the first report of inferior oblique-associated orbital schwannoma. METHODS: Interventional case report with clinical photographs, MRI imaging, intra-operative photographs and histology. RESULTS: A 68 year-old man presented with decreased right vision and double vision in downgaze. Examination revealed a right 3 mm ptosis, hypertropia and limitation of depression. Exploration and excision, via anterior orbitotomy, and histological examination confirmed a schwannoma located within the right inferior oblique muscle. Vision normalised post-operatively and there has been no clinical or radiological recurrence of the lesion at 2 years. CONCLUSIONS: This rare case highlights that schwannoma may occur in association with the inferior oblique complex and we suggest that schwannomas should now be considered in the differential diagnosis when patients present with a clinically-suspected or radiologically-proven orbital mass.

Clinical features and visual outcome of intermediate uveitis in children.

PURPOSE: To determine the presentation, course, treatment and outcome of idiopathic intermediate uveitis in children. METHODS: The records of all patients under the age of 16 presenting with idiopathic intermediate uveitis under the care of one consultant (SL) between 1990 and 2001 were reviewed. The case notes were analysed with respect to presenting symptoms, associated conditions, ocular signs, change in visual acuity, treatment and complications. All patients with systemic disease were specifically excluded from the study. RESULTS: Twenty-six patients (45 eyes) were identified with intermediate uveitis from 114 cases of childhood uveitis seen. The mean age at presentation was 10 years (range 7-13 years) and the average follow-up time was 3 years (range 0-7 years). All patients had varying degrees of vitritis, 28 eyes had snowbanks and 5 had cystoid macular oedema at presentation. Six patients required no treatment, five received topical treatment only, five were managed with orbital floor steroids alone and a further two were managed with orbital floor steroids and oral prednisolone. Systemic steroids were required in eight patients, four of whom also required cyclosporin. Six of these children had successful disease control and maintained a visual acuity of 6/9 in at least one affected eye. CONCLUSION: Idiopathic intermediate uveitis is a relatively uncommon condition in children but can have severe effects on vision. With careful management, vision can be preserved in at least one eye. This study describes the course of the disease in a relatively large series. The variation in disease severity prompts the use of individually tailored immunosuppressive regimens.