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BACKGROUND: Uromodulin, the most abundant protein excreted in normal urine, plays major roles in kidney physiology and disease. The mechanisms regulating the urinary excretion of uromodulin remain essentially unknown.METHODS: We conducted a meta-analysis of genome-wide association studies for raw (uUMOD) and indexed to creatinine (uUCR) urinary levels of uromodulin in 29,315 individuals of European ancestry from 13 cohorts. We tested the distribution of candidate genes in kidney segments and investigated the effects of keratin-40 (KRT40) on uromodulin processing.RESULTS: Two genome-wide significant signals were identified for uUMOD: a novel locus ( P 1.24E-08) over the KRT40 gene coding for KRT40, a type 1 keratin expressed in the kidney, and the UMOD-PDILT locus ( P 2.17E-88), with two independent sets of single nucleotide polymorphisms spread over UMOD and PDILT. Two genome-wide significant signals for uUCR were identified at the UMOD-PDILT locus and at the novel WDR72 locus previously associated with kidney function. The effect sizes for rs8067385, the index single nucleotide polymorphism in the KRT40 locus, were similar for both uUMOD and uUCR. KRT40 colocalized with uromodulin and modulating its expression in thick ascending limb (TAL) cells affected uromodulin processing and excretion. CONCLUSIONS: Common variants in KRT40, WDR72, UMOD, and PDILT associate with the levels of uromodulin in urine. The expression of KRT40 affects uromodulin processing in TAL cells. These results, although limited by lack of replication, provide insights into the biology of uromodulin, the role of keratins in the kidney, and the influence of the UMOD-PDILT locus on kidney function.

We evaluated the accuracy of a new scale of surgical difficulty for the extraction of impacted mandibular third molars, which includes consideration of previously underestimated variables. Two hundred patients with impacted third molars were enrolled, and a preoperative clinical and radiographic assessment of difficulty was made by an oral surgeon using the new index. Five oral surgeons with similar degrees of experience then evaluated the surgical difficulty during operation. The kappa test and weighted kappa were used to evaluate the level of agreement between the preoperative and postoperative evaluations. This was 0.73, which indicated a substantial concordance between the preoperative and postoperative assessments of difficulty indicated by the new scale. The linear weight of kappa was 0.8 and the quadratic weight 0.87. We recommend this new scale of surgical difficulty for the extraction of impacted third molars for use in clinical practice.

To compare corneal thickness (CT) measurements obtained with SP3000P specular microscope and Pentacam in eyes screened to undergo refractive surgery (RS).In this prospective study, a non-randomized consecutive series of 73 healthy eyes (age range: 14-78 years; mean=38.4±14.9) underwent CT measurement with both Oculus Pentacam and Topcon SP3000P specular microscope to assess their suitability to undergo corneal RS.CT measurements with SP3000P ranged from 451 to 609 μs (mean 523.1±34.4 μs). The measurements obtained with Pentacam ranged at the corneal apex from 477 to 672 μs (mean 558.9±38.9 μs), at the pupil center from 477 to 672 μs (mean 557.9±38.9 μs) and at the thinnest point from 474 to 669 μs (mean 551.1±39.4 μs). CT measurements showed a good correlation but a statistically significant difference at the pupil center (mean -34.9±14.6 μs, R(2)=0.860, p0.001), at the apex (mean -35.9±14.9 μs, R(2)=0.856, p0.001) and at the thinnest point (mean -32±14.8 μs, R(2)=0.862, p0.001). The calculated regression formulas were: y=0.816x+66.94 for the apex, y=0.819x+66.07 for the pupil center and y=0.810x+73.13 for the thinnest point; where y is the CT measured with the SP3000P and x is the measurement obtained with the Oculus Pentacam.Our results suggest that SP3000P measures thinner corneas compared to the Pentacam and that the correcting factor we identified should be applied to make comparisons between these two devices.

Purpose The aim of this study was to assess the anatomy of the mandibular lingual foramen (MLF) and its linked canals (mandibular lingual vascular canals – MLVC), describing their frequency, diameter, location, and course. Materials and methods One hundred and fourteen computed tomography (CT) images of the mandible (57 male and 57 female; mean age 44.70 ± 12.53; age range 13–75 years, were evaluated. The CT sections were obtained on axial plane by using a bone reconstruction algorithm and then processed with dedicated software (Dentascan), with a standard protocol. Results 103 patients (90.35%) had at least one lingual vascular canal and 52 (45.61%) had multiple (two or three) canals. The typical locations of MLVC were the midline of the mandible (median lingual canal [MLC]). The mean diameter of the lingual canals in the midline (MLC) was 0.8 mm ± 0. The direction of MLC progresses in an anterior and slightly caudal sense. Conclusions Dental CT examination easily demonstrates the presence, position, direction and size of the lingual foramen and of the lingual vascular canals of the mandible. Radiologists and oral surgeons should be aware of these canals and their importance, in order to prevent bleeding complications during implants placement and other surgical procedures.