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This study was aimed at analysing the mechanical characteristics of different mandibular extraction modes using a clear aligner. Three experimental schemes of different extraction patterns were designed to treat mandibular crowding, including extraction of one mandibular central incisor, bilateral first premolars, and bilateral second premolars. The stress distribution during the space closing was analysed using the finite element method. When a central incisor was extracted, a significant retraction force was found in the anterior region, in line with the design expectation. The posterior teeth, which were designed to move mesially, acted as anchorage for anterior retraction, and were subjected to a mesial force. The anterior teeth were retracted when the bilateral first premolars were extracted. The lateral incisors and canines were subjected to a significant distal force and moment, while the central incisors and canines were subjected to lingual forces and moments. Additionally, the canines were subjected to a non-designated intruding force. The molars were designed to move mesially when the bilateral second premolars were extracted. All molars were subjected to a significant mesial force, while the lingual force on the front teeth was slight. The bilateral second molars were subjected to non-design mesial moment and extrusive force. The bilateral first molars were subjected to a non-designated mesial moment, and the bilateral first premolars on both sides were subjected to non-designated intrusive force and distal moment. When one incisor was extracted, attachments on the anterior teeth had a controlling effect on the tooth axis, but the anterior teeth still tended to tilt. When the bilateral first premolars were extracted, the anterior teeth showed a tendency for lingual inclination. The risk of distal inclination of the canines and lingual inclination of the central incisor increased. When the bilateral second premolars were extracted and the posterior teeth were designed to move mesially, the teeth on both sides of the extraction sites showed an obvious bowing effect.

Discovering novel uses for existing drugs, through drug repurposing, can reduce the time, costs, and risk of failure associated with new drug development. However, prioritizing drug repurposing candidates for downstream studies remains challenging. Here, we present a high-throughput approach to identify and validate drug repurposing candidates. This approach integrates human gene expression, drug perturbation, and clinical data from publicly available resources. We apply this approach to find drug repurposing candidates for two diseases, hyperlipidemia and hypertension. We screen >21,000 compounds and replicate ten approved drugs. We also identify 25 (seven for hyperlipidemia, eighteen for hypertension) drugs approved for other indications with therapeutic effects on clinically relevant biomarkers. For five of these drugs, the therapeutic effects are replicated in the All of Us Research Program database. We anticipate our approach will enable researchers to integrate multiple publicly available datasets to identify high priority drug repurposing opportunities for human diseases., Prioritizing drug repurposing candidates for downstream studies remains challenging. Here, the authors present a high-throughput approach to identify and validate drug repurposing candidates, integrating human gene expression, drug perturbation, and clinical data from publicly available resources.

The purpose of this work was to evaluate the effects of several surface treatment methods on the shear bond strengths of metal brackets bonded to a silica-based ceramic with a light-cured adhesive. Silica-based ceramic (IPS Classic®) with glazed surfaces was cut into discs that were used as substrates. A total of 80 specimens were randomly divided into four groups according to the method used: 9.6 % hydrofluoric acid (group 1), 9.6 % hydrofluoric acid (HF) + silane coupling agent (group 2), sandblasting (aluminum trioxide, 50 μm) + silane (group 3), and tribochemical silica coating (CoJet™ sand, 30 μm) + silane (group 4). Brackets were bonded to the treated specimens with a light-cure adhesive (Transbond XT, 3 M Unitek). Shear bond strength was tested after bracket bonding, and the Adhesive Remnant Index (ARI) scores were quantified after debonding. Group 4 showed the highest bond strength (12.3 ± 1.0 MPa), which was not significantly different from that of group 3 (11.6 ± 1.2 MPa, P > 0.05); however, the bond strength of group 4 was substantially higher than that of group 2 (9.4 ± 1.1 MPa, P

The ω-hydroxylase CYP4A11 catalyzes the transformation of epoxyeicosatrienoic acids (EETs) to ω-hydroxylated EETs, endogenous peroxisome proliferator-activated receptor-α (PPARα) agonists. PPARα activation increases high-density lipoprotein cholesterol (HDL-C). A cytosine-for-thymidine (T8590C) variant of CYP4A11 encodes for an ω-hydroxylase with reduced activity. This study examined the relationship between CYP4A11 T8590C genotype and metabolic parameters in the Framingham Offspring Study and in a clinical practice-based biobank, BioVU. In women in the Framingham Offspring Study, the CYP4A11 8590C allele was associated with reduced HDL-C concentrations (52.1±0.5 mg dl(-1) in CYP4A11 CC- or CT-genotype women versus 54.8±0.5 mg dl(-1) in TT women at visit 2, P=0.02), and with an increased prevalence of low HDL-C, defined categorically as 50 mg dl(-1) (odds ratio 1.39 (95% CI 1.02-1.90), P=0.04). In the BioVU cohort, the CYP4A11 8590C allele was also associated with low HDL-C in women (odds ratio 1.69 (95% CI 1.03-2.77, P=0.04)). There was no relationship between genotype and HDL-C in men in either cohort.

Type 1 cannabinoid receptor blockers increase high-density lipoprotein cholesterol levels. Although genetic variation in the type 1 cannabinoid receptor--encoded by the CNR1 gene--is known to influence high-density lipoprotein cholesterol level as well, human studies conducted to date have been limited to genetic markers such as haplotype-tagging single nucleotide polymorphisms. Here we identify rs806371 in the CNR1 promoter as the causal variant. We re-sequence the CNR1 gene and genotype all variants in a DNA biobank linked to comprehensive electronic medical records. By testing each variant for association with high-density lipoprotein cholesterol level in a clinical practice-based setting, we localize a putative functional allele to a 100-bp window in the 5'-flanking region. Assessment of variants in this window for functional impact on electrophoretic mobility shift assay identifies rs806371 as a novel regulatory binding element. Reporter gene assays confirm that rs806371 reduces gene expression, thereby linking CNR1 gene variation to high-density lipoprotein cholesterol level in humans.