Review and case report of the treatment in a young girl with primary failure of eruption

Any localized non‐eruption of teeth can be attributed to myriad of factors. A failure of a permanent tooth to erupt or cessation of initial eruption with no obvious local/systemic causative factor is said to be primary failure of eruption (PFE). The etio‐pathogenesis of PFE is due to the mutation of PTH1R gene. Clinical features such as infra‐occluded teeth, posterior open bite, lack of any cause or habit are usually attributed to diagnosing the condition, and a confirmatory diagnosis is done by the gene analysis of PTH1R gene. Treatment of such a condition is tricky as any application of orthodontic traction to teeth affected by PFE will not be successful and may cause ankylosis. This correspondence reviews and demonstrates the treatment of a case of PFE to restore function and esthetics to the best possible outcome.     

Rational selection of bioactive principles for wound healing applications: Growth factors and antioxidants

Wound healing is a complex process of communication between growth factors, reactive species of oxygen, cells, signalling pathways, and cytokines in the extracellular matrix, in which growth factors are the key regulators. In humans, the main regulators of the cellular responses in wound healing are five growth factors, namely EGF, bFGF, VEGF, and TGF-β1. On the other hand, antioxidants such as astaxanthin, beta-carotene, epigallocatechin gallate, delphinidin, and curcumin have been demonstrated to stimulate cell proliferation, migration and angiogenesis, and control inflammation, to suggest a practical approach to design new strategies to treat non-healing cutaneous conditions. Based on the individual effects of growth factors and antioxidants, it may be envisioned that the use of both types of bioactives in wound healing formulations may have an additive or synergistic effect on the healing potential. This review addresses the effect of growth factors and antioxidants on wound healing-related processes. Furthermore, a prospective on their potential additive or synergistic effect on wound healing formulations, based on their individual effects, is presented. This may serve as a guide for the development of a new generation of wound healing formulations.     

Meta-analysis of head-to-head clinical trials comparing incretin-based glucose-lowering medications and basal insulin: An update including recently developed glucagon-like peptide-1 (GLP-1) receptor agonists and the glucose-dependent insulinotropic polypeptide/GLP-1 receptor co-agonist tirzepatide

Objective

To assess comparative efficacy, safety and tolerability of injectable incretin-based glucose-lowering medications (IBGLMs) versus basal insulin treatment in patients with type 2 diabetes.

Research Design and Methods

We performed an updated meta-analysis of randomized clinical trials of head-to-head comparisons of IBGLMs (short- and long-acting glucagon-like peptide-1 [GLP-1] receptor agonists [GLP-1RAs] and glucose-dependent insulinotropic polypeptide [GIP]/GLP-1 receptor co-agonist tirzepatide) versus basal insulin using a PubMed database search (April 2022). The primary endpoint was difference in reduction of glycated haemoglobin (HbA_1c) versus baseline between pooled IBGLMs (fixed-effects meta-analysis) and their subgroups (random-effects meta-analysis) versus basal insulin treatment (mean differences). Secondary endpoints were fasting plasma glucose, body weight, HbA_1c target achievement, hypoglycaemia, blood pressure and lipids. Risk of bias assessment was performed using Jadad scores and the Risk of Bias tool 2.0.

Results

In all, 20 studies, representing 47 study arms and 11 843 patients, were eligible. Compared with basal insulin, IGBLMs lowered HbA_1c by 0.48 (0.45-0.52)% more than did basal insulin treatment. This effect was driven by pooled long-acting GLP-1RAs (ΔHbA_1c −0.25 [−0.38; −0.11]%) and the only GIP/GLP-1 receptor co-agonist, tirzepatide (pooled doses; ΔHbA_1c −0.90 [−1.06; −0.75]%), while short-acting GLP-1RAs were equally effective compared with basal insulin (P = 0.90). All IBGLM subgroups achieved significantly lower body weight versus insulin treatment (−4.6 [−4.7; −4.4] kg), in particular tirzepatide (−12.0 [−13.8; −10.1] kg). IBGLMs significantly reduced hypoglycaemia and blood pressure and improved lipid variables. Risk of bias was low. IBGLM treatment was associated with more nausea, vomiting and diarrhoea and study medication discontinuation.

Conclusions

Recently introduced, highly effective IBGLMs were superior to basal insulin treatment, reinforcing the recommendation that IBGLMs should be considered as the first injectable treatment for most patients with type 2 diabetes.     

Inhibition of cartilage proteoglycan release by a specific inactivator of cathepsin b and an inhibitor of matrix metalloproteinases. evidence for two converging pathways of chondrocyte-mediated proteoglycan degradation

Objective. To investigate mechanisms of cartilage matrix destruction by a study of the effects of a specific inactivator of cathepsin B and an inhibitor of several matrix metalloproteinases (MMP) on cartilage proteoglycan release. Methods. Cartilage explants were treated with either recombinant human interleukin-1α (rHuIL-1α) or retinoic acid in the presence or absence of the inhibitors, and proteoglycan release was quantitated. Tests for nonspecific effects of the inhibitors included reversibility, rates of protein synthesis and glycolysis, and effects on other rHuIL-1α–mediated events. Results. The cathepsin B inactivator inhibited rHuIL-1α–stimulated proteoglycan release at nanomolar concentrations, but failed to significantly inhibit retinoic acid–stimulated proteoglycan release. An inhibitor of MMP was inhibitory to both rHuIL-1α–stimulated release and retinoic acid–stimulated release. Conclusion. Cathepsin B is implicated in rHuIL-1α–stimulated loss of cartilage proteoglycan. Its lack of involvement in retinoic acid–stimulated proteoglycan release suggests the existence of at least 2 pathways of cartilage proteoglycan breakdown, which may converge at the activation of a matrix prometalloproteinase.     

Alcohol,place conditioning,and male rats: A systematic review of outcome prediction

Although Place Conditioning (PC) has been used to study the motivational effects of alcohol for almost 50 years, variables and situations in which alcohol induces PC in rats are still unclear, especially for short PC protocols (up to 10 conditioning trials). The aim of this systematic review was to predict primary outcomes (namely, conditioning failure, conditioned place aversion (CPA), and conditioned place preference (CPP)) of alcohol-induced PC with male outbred rats. We sought relevant records in PUBMED and two other sources. Two reviewers independently assessed records for eligible articles (those meeting all inclusion criteria), selected alcohol-induced PC experiments (those meeting no exclusion criteria) from eligible articles, extracted data, and assessed the quality of included studies. We then conducted a predictive analysis of outcomes by examining procedure-outcome relations according to variables known to affect associative learning, alcohol interventions in rats, and PC interventions themselves. We selected 192 experiments (133 short protocols, 27 long protocols, and 32 protocols with alcohol pre-exposure) from 62 articles to compose the review. Rates of conditioning failure are mainly predicted by interactions of alcohol dose and the number of habituation sessions and conditioning trials. Different conditions (housing systems) and characteristics (age and weight) of animals predict CPA and CPP: higher rates of CPA are predicted by single-housed, older, and heavier animals, while higher rates of CPP are predicted by group-housed, younger, and lighter animals. We recommend settings for CPP induction in short protocols, discuss the broad theoretical and translational consequences of the predictive analysis for the use of PC in alcohol research, and specify variables needing more careful investigation. This review could improve our understanding of the results of alcohol-induced PC with rats, refine our understanding of the motivational function of alcohol and alcohol-seeking behavior triggered by environmental contexts, and open new avenues of research on their neurobiological basis.