Evaluation of Different Root Canal Sealers on Post Operative Pain in Single Visit RCT - A Comparative Study.

Aim: To evaluate and compare three different root canal sealers (Endo-Sequence BC, Bio Root RCS and Zinc Oxide Eugenol) on post operative pain in single visit root canal therapies. Material and Methodology: 60 subjects with age ranging from 18-60 years were randomly selected depending upon the inclusion criteria. The subjects were then divided into three groups with 20 patients in each. In all the patients' single visit root canal treatment was done followed by obturation using different sealers. In Group I Endo- Sequence sealer was used, in Group II Bio-Root RCS and in Group III Zinc Oxide Eugenol sealers were used respectively. Results: statistically significant results were obtained on comparing the efficacy of three groups with Group I proving to be much effect among the three. Conclusion: within the limitation of the study it can be concluded that though all the sealers were effective in reducing post-operative pain, patients with Endo Sequence BC sealers evaluated statistically significant results.

Use of Human Lung Tissue Models for Screening of Drugs against SARS-CoV-2 Infection.

The repurposing of licenced drugs for use against COVID-19 is one of the most rapid ways to develop new and alternative therapeutic options to manage the ongoing pandemic. Given circa 7817 licenced compounds available from Compounds Australia that can be screened, this paper demonstrates the utility of commercially available ex vivo/3D airway and alveolar tissue models. These models are a closer representation of in vivo studies than in vitro models, but retain the benefits of rapid in vitro screening for drug efficacy. We demonstrate that several existing drugs appear to show anti-SARS-CoV-2 activity against both SARS-CoV-2 Delta and Omicron Variants of Concern in the airway model. In particular, fluvoxamine, as well as aprepitant, everolimus, and sirolimus, has virus reduction efficacy comparable to the current standard of care (remdesivir, molnupiravir, nirmatrelvir). Whilst these results are encouraging, further testing and efficacy studies are required before clinical use can be considered.

At Least Three Doses of Leading Vaccines Essential for Neutralisation of SARS-CoV-2 Omicron Variant.

Plasma samples taken at different time points from donors who received either AstraZeneca (Vaxzevria) or Pfizer (Comirnaty) or Moderna (Spikevax) coronavirus disease-19 (COVID-19) vaccine were assessed in virus neutralization assays against Delta and Omicron variants of concern and a reference isolate (VIC31). With the Pfizer vaccine there was 6-8-fold reduction in 50% neutralizing antibody titres (NT50) against Delta and VIC31 at 6 months compared to 2 weeks after the second dose; followed by 25-fold increase at 2 weeks after the third dose. Neutralisation of Omicron was only consistently observed 2 weeks after the third dose, with most samples having titres below the limit of detection at earlier timepoints. Moderna results were similar to Pfizer at 2 weeks after the second dose, while the titres for AstraZeneca samples derived from older donors were 7-fold lower against VIC31 and below the limit of detection against Delta and Omicron. Age and gender were not found to significantly impact our results. These findings indicate that vaccine matching may be needed, and that at least a third dose of these vaccines is necessary to generate sufficient neutralising antibodies against emerging variants of concern, especially Omicron, amidst the challenges of ensuring vaccine equity worldwide.

Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice.

As existing vaccines fail to completely prevent COVID-19 infections or community transmission, there is an unmet need for vaccines that can better combat SARS-CoV-2 variants of concern (VOC). We previously developed highly thermo-tolerant monomeric and trimeric receptor-binding domain derivatives that can withstand 100 °C for 90 min and 37 °C for four weeks and help eliminate cold-chain requirements. We show that mice immunised with these vaccine formulations elicit high titres of antibodies that neutralise SARS-CoV-2 variants VIC31 (with Spike: D614G mutation), Delta and Omicron (BA.1.1) VOC. Compared to VIC31, there was an average 14.4-fold reduction in neutralisation against BA.1.1 for the three monomeric antigen-adjuvant combinations and a 16.5-fold reduction for the three trimeric antigen-adjuvant combinations; the corresponding values against Delta were 2.5 and 3.0. Our findings suggest that monomeric formulations are suitable for upcoming Phase I human clinical trials and that there is potential for increasing the efficacy with vaccine matching to improve the responses against emerging variants. These findings are consistent with in silico modelling and AlphaFold predictions, which show that, while oligomeric presentation can be generally beneficial, it can make important epitopes inaccessible and also carries the risk of eliciting unwanted antibodies against the oligomerisation domain.

Patient Perspectives on a Digital Mobile Health Application for RA.

BACKGROUND: Emerging evidence suggests that patients are increasingly willing to use digital mobile health applications for rheumatoid arthritis (RA apps). The development and diffusion of RA apps open the possibility of improved management of the disease and better physician-patient interactions. However, adoption rates among apps have been lower than hoped, and research shows that many available RA apps lack key features. There is little research exploring patient preferences for RA apps or patients' habits and preferences for app payment, which are likely key factors affecting adoption of this technology. This study seeks to understand characteristics of RA patients who have adopted RA apps, their preferences for app features, and their willingness to pay for, and experiences with app payment. METHODS: Data for this study come from a 33-question online survey of patients with RA in Canada and the United States (N=30). Information on demographics, diagnosis and management of RA, current use and desired features of RA apps, and prior experience with and willingness to pay for an app was collected. Descriptive statistics are reported, and bivariate analyses (chi-square, point-biserial correlation, and ANOVA) were performed to understand relationships between variables. RESULTS: Respondents showed a clear preference for certain app features, namely symptom tracking, scheduling appointments, and reminders. Physician recommendation for an app and patient tracking of symptoms with an app were significantly related to patient adoption of an RA app. Years since diagnosis with RA, physician recommendation for an RA app, and current use of a non-RA health tracking app were significantly related to patients' willingness to pay a subscription for an RA app. CONCLUSION: RA patients appear to prefer task support features in an RA app, notably symptom tracking, appointment scheduling, and reminders, over other features such as those related to dialogue support and social support. The choice of whether an RA app will be free or based on a subscription, pay-per-service, or one-time purchase model may also play a role in eventual adoption. Similarly, physician recommendation appears to influence patients' decision to use an RA app as well as their willingness to pay a subscription for an app.

Efficacy and tolerability of DPP4 inhibitor, teneligliptin, on autonomic and peripheral neuropathy in type 2 diabetes: an open label, pilot study.

BACKGROUND: Diabetic neuropathy increases risk of cardiovascular disease, peripheral artery disease, foot amputation and overall mortality. Not only hyperglycaemia induced nerve damage is harder to repair using currently approved medications, but also, the use of these agents is often limited by the extent of pain relief provided and side effects. METHODOLOGY: In this prospective, open-label, pilot study, 20 type-2 diabetes mellitus patients (male/female=13/7, mean age- 56.1±8.04 years), meeting inclusion/exclusion criteria, were treated with dipeptidyl peptidase-4 (DPP-4) inhibitor, Teneligliptin, 20mg once a day for three months. Efficacy parameters: Sudomotor function (Sudoscan score); parasympathetic dysfunction assessed using Ewing's criteria i.e. heart rate response to -standing (HRS), -valsalva (HRV) and -deep breath (HRD); sympathetic dysfunction assessed as blood pressure response to -standing (BPS) and -handgrip (BPH); ankle brachial index (ABI), vibration perception threshold (VPT), C-reactive protein, glycemic profile and health related quality of life (HRQoL); and, tolerability parameters: complete blood count, liver function tests, serum creatinine, thyroid stimulating hormone, QT- interval and serum vitamin B12 levels, were measured. RESULTS: There was no statistical difference in BMI, SBP, DBP, HRD, BPH and all safety parameters. After 12 weeks treatment, there was improvement in HRS (p<0.01) and HRV (p<0.01), but not in HRD (p=0.12). BPS was significantly lowered (p <0.01), but not the BPH (p =0.06). Sudoscan score was increased, while VPT was significantly decreased (both p<0.01). CONCLUSION: Teneligliptin not only improves the glycemic status but also improves sudomotor function, peripheral and autonomic neuropathy, and reduces vascular inflammation in type 2 diabetes.

Association of sudomotor function with peripheral artery disease in type 2 diabetes.

Peripheral artery disease (PAD) is the major risk factor for cardiovascular disease and lower extremity amputation in patients with diabetes. Autonomic neuropathy is a risk factor for cardiovascular-related morbidity and mortality. Sudomotor dysfunction is well established in type 2 diabetes mellitus (T2DM) and reflects small fibre neuropathy, cardiovascular autonomic neuropathy and peripheral sympathetic autonomic neuropathy. However, the relationship between sudomotor dysfunction and PAD remains unexplored. Therefore, the aim of present study was to explore the association of sudomotor function with ankle-brachial index (ABI) and C-reactive protein (CRP) in T2DM. In this cross-sectional study, we recruited 36 consecutive type 2 diabetes patients and 20 age- and sex-matched healthy controls. Sudomotor function was assessed using Sudoscan (Sudoscan-Impeto Medical Device, EZS 01750010193, Paris, France), which detects sweat gland function through measurement of electrochemical skin conductance of both hands and feet. Measurement of ankle-brachial ABI was carried out with sphygmomanometer and Doppler device (Hadeco Bidop ES-100V3). Glycated haemoglobin (HbA1c), fasting plasma glucose, and inflammatory marker CRP were also measured. Type 2 diabetic patients had significantly impaired sudomotor function (48.14 ± 8.28 vs. 76.48 ± 6.72 µs), lower ABI (0.89 ± 0.25 vs. 1.15 ± 0.11) and elevated CRP (5.32 ± 2.41 vs. 2.45 ± 1.11 mg/l) as compared to healthy controls, respectively (p < 0.01). Sudoscan scores were found to be inversely correlated with CRP and HbA1c, and directly correlated with ABI (p < 0.05) in the patients. Sudomotor dysfunction is associated with significant peripheral artery disease, vascular inflammation and impaired glycaemic status.