The Association between Molar-Incisor Hypomineralization and Dental Caries with Socioeconomic Status as an Explanatory Variable in a Group of Finnish Children

The aim of this study was to investigate if a developmental enamel defect known as Molar-Incisor Hypomineralization (MIH) is associated with dental caries. Socioeconomic status (SES) was examined as a confounding factor between caries and MIH. In this cross-sectional study, 636 children, aged 8 to 13 years, from three towns (two rural areas and one urban area) in Finland were examined for MIH in line with the criteria of the European Academy of Paediatric Dentistry. Caries status for permanent teeth was recorded as decayed, missing and filled teeth (DMFT). Caries experience (DMFT > 0) in the first permanent molars (FPMs) was set as an outcome. SES was determined using a questionnaire completed by parents. The prevalence of MIH was 18.1%. The mean DMFT in FPMs for children with MIH was higher than for their peers, 1.03 +/- 1.25 vs. 0.32 +/- 0.80 (p = 0.000, Mann-Whitney U test). In a multivariate analysis using the generalized linear mixed model where locality, SES, age and MIH were taken into account as caries risk indicators, MIH was the strongest risk indicator of caries in FPMs (Odds Ratio: 6.60, 95% Confidence Interval: 3.83-11.39, p = 0.000). According to the study results, children with MIH have a higher risk for dental caries than children without MIH.Peer reviewe

Exotoxin-Targeted Drug Modalities as Antibiotic Alternatives

The paradigm of antivirulence therapy dictates that bacterial pathogens are specifically disarmed but not killed by neutralizing their virulence factors. Clearance of the invading pathogen by the immune system is promoted. As compared to antibiotics, the pathogen-selective antivirulence drugs hold promise to minimize collateral damage to the beneficial microbiome. Also, selective pressure for resistance is expected to be lower because bacterial viability is not directly affected. Antivirulence drugs are being developed for stand-alone prophylactic and therapeutic treatments but also for combinatorial use with antibiotics. This Review focuses on drug modalities that target bacterial exotoxins after the secretion or release-upon-lysis. Exotoxins have a significant and sometimes the primary role as the disease-causing virulence factor, and thereby they are attractive targets for drug development. We describe the key pre-clinical and clinical trial data that have led to the approval of currently used exotoxin-targeted drugs, namely the monoclonal antibodies bezlotoxumab (toxin B/TcdB, Clostridioides difficile), raxibacumab (anthrax toxin, Bacillus anthracis), and obiltoxaximab (anthrax toxin, Bacillus anthracis), but also to challenges with some of the promising leads. We also highlight the recent developments in pre-clinical research sector to develop exotoxin-targeted drug modalities, i.e., monoclonal antibodies, antibody fragments, antibody mimetics, receptor analogs, neutralizing scaffolds, dominant-negative mutants, and small molecules. We describe how these exotoxin-targeted drug modalities work with high-resolution structural knowledge and highlight their advantages and disadvantages as antibiotic alternatives