Third molar maturity index (I3M) assessment according to different geographical zones: a large multi-ethnic study sample.

Identification of living undocumented individuals highlights the need for accurate, precise, and reproducible age estimation methods, especially in those cases involving minors. However, when their country of origin is unknown, or it can be only roughly estimated, it is extremely difficult to apply assessment policies, procedures, and practices that are accurate and child-sensitive. The main aim of this research is to optimize the correct classification of adults and minors by establishing new cut-off values for four different continents (Africa, America, Asia, and Europe). For this purpose, a vast sample of 10,701 orthopantomographs (OPTs) from four continents was evaluated. For determination and subsequent validation of the new third molar maturity index (I3M) cut-off values by world regions, a cross-validation by holdout method was used and contingency tables (confusion matrices) were generated. The lower third molar maturity indexes, from both left and right side (I3ML and I3MR) and the combination of both sides (I3ML_I3MR) were calculated. The new cut-off values, that aim to differentiate between a minor and an adult, with more than 74.00% accuracy for all populations were as follows (I3ML; I3MR; I3ML_I3MR, respectively): Africa = (0.10; 0.10; 0.10), America = (0.10; 0.09; 0.09), Asia = (0.15; 0.17; 0.14), and Europe = (0.09; 0.09; 0.09). The higher sensitivity (Se) was detected for the I3ML for male African people (91%) and the higher specificity (Sp) of all the parameters (I3ML; I3MR; I3ML_I3MR) for Europeans both male and female (> 91%). The original cut-off value (0.08) is still useful, especially in discriminating individuals younger than 18 years old which is the goal of the forensic methods used for justice.

The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease.

BACKGROUND: Patients with primary sclerosing cholangitis associated with inflammatory bowel disease (PSC-IBD) have a very high risk of developing colorectal neoplasia. Alterations in the gut microbiota and/or gut bile acids could account for the increase in this risk. However, no studies have yet investigated the net result of cholestasis and a potentially altered bile acid pool interacting with a dysbiotic gut flora in the inflamed colon of PSC-IBD. AIM: The aim of this study was to compare the gut microbiota and stool bile acid profiles, as well as and their correlation in patients with PSC-IBD and inflammatory bowel disease alone. METHODS: Thirty patients with extensive colitis (15 with concomitant primary sclerosing cholangitis) were prospectively recruited and fresh stool samples were collected. The microbiota composition in stool was profiled using bacterial 16S rRNA sequencing. Stool bile acids were assessed by high-performance liquid chromatography tandem mass spectrometry. RESULTS: The total stool bile acid pool was significantly reduced in PSC-IBD. Although no major differences were observed in the individual bile acid species in stool, their overall combination allowed a good separation between PSC-IBD and inflammatory bowel disease. Compared with inflammatory bowel disease alone, PSC-IBD patients demonstrated a different gut microbiota composition with enrichment in Ruminococcus and Fusobacterium genus compared with inflammatory bowel disease. At the operational taxonomic unit level major shifts were observed within the Firmicutes (73%) and Bacteroidetes phyla (17%). Specific microbiota-bile acid correlations were observed in PSC-IBD, where 12% of the operational taxonomic units strongly correlated with stool bile acids, compared with only 0.4% in non-PSC-IBD. CONCLUSIONS: Patients with PSC-IBD had distinct microbiota and microbiota-stool bile acid correlations as compared with inflammatory bowel disease. Whether these changes are associated with, or may predispose to, an increased risk of colorectal neoplasia needs to be further clarified.

Antigenic response to CT-P13 and infliximab originator in inflammatory bowel disease patients shows similar epitope recognition.

AIM: To test the cross-immunogenicity of anti-CT-P13 IBD patients' sera to CT-P13/infliximab originator and the comparative antigenicity evoked by CT-P13/infliximab originator sera. METHODS: Sera of patients with IBD with measurable anti-CT-P13 antibodies were tested for their cross-reactivity to 5 batches of infliximab originator and CT-P13. Anti-drug antibody positive sera from treated patients were used to compare antigenic epitopes. RESULTS: All 42 anti-CT-P13 and 37 anti-infliximab originator IBD sera were cross-reactive with infliximab originator and CT-P13 respectively. Concentration of anti-drug antibodies against infliximab originator or CT-P13 were strongly correlated both for IgG1 and IgG4 (P < 0.001). Anti-CT-P13 sera of patients with IBD (n = 32) exerted similar functional inhibition on CT-P13 or infliximab originator TNF binding capacity and showed reduced binding to CT-P13 in the presence of five different batches of CT-P13 and infliximab originator. Anti-CT-P13 and anti-infliximab originator IBD sera selectively enriched phage-peptides from the VH (CDR1 and CDR3) and VL domains (CDR2 and CDR3) of infliximab. Sera reactivity detected major infliximab epitopes in these regions of infliximab in 60%-79% of patients, and no significant differences were identified between CT-P13 and infliximab originator immunogenic sera. Minor epitopes were localised in framework regions of infliximab with reduced antibody reactivity shown, in 30%-50% of patients. Monoclonal antibodies derived from naïve individuals and ADA-positive IBD patients treated with CT-P13 provided comparable epitope specificity to five different batches of CT-P13 and infliximab originator. CONCLUSIONS: These results strongly support a similar antigenic profile for infliximab originator and CT-P13, and point toward a safe switching between the two drugs in anti-drug antibody negative patients.