NMR-Verified Dearomatization of 5,7-Substituted Pyrazolo[1,5-a]pyrimidines.

Tetrahydropyrazolo[1,5-a]pyrimidine (THPP) is an attractive scaffold for designing biologically active compounds. The most obvious way to obtain such compounds is to reduce pyrazolopyrimidines with complex hydrides, because the pyrimidine ring is reduced in the preference over the pyrazole ring. The presence of substituents at positions five and seven of pyrazolo[1,5-a]pyrimidines complicates the set of reaction products but makes it more attractive for medicinal chemistry because four possible stereoisomers can be formed during reduction. However, the formation of only syn-isomers has been described in the literature. This article is the first report on the formation of anti-configured isomers along with syn-isomers in the reduction of model 5,7-dimethylpyrazolo[1,5-a]pyrimidine, which was confirmed by NMR. The bicyclic core in the syn-configuration was shown to be conformationally stable, which was used to estimate the long-range interproton distances using NOESY data. At the same time, long-range dipole-dipole interactions corresponding to a distance between protons of more than 6 Å were first registered and quantified. In turn, the bicyclic core in the trans-configuration represents a conformationally labile system. For these structures, an analysis of conformations observed in solutions was carried out. Our results indicate the significant potential of trans-configured tetrahydropyrazolo[1,5-a]pyrimidines for the development of active small molecules. While possessing structural lability due to the low energy of the conformational transition, they have the ability to adjust to the active site of the desired target.

EPA-coated titanium implants promote osteoconduction in white New Zealand rabbits.

OBJECTIVES: To investigate the effect of eicosapentaenoic acid (EPA)-coated Ti implants on osteoconduction in white New Zealand rabbit mandibles. MATERIAL AND METHODS: Sandblasted and cleansed planar titanium specimens with a size of 5 × 5 × 1 mm were coated on one side with 0.25 vol% eicosapentaenoic acid (EPA). The other side of the specimens was kept highly polished (the control side). These specimens were inserted in rabbit mandibles. Twelve rabbits were randomly assigned into three study groups (n = 4). The rabbits were sacrificed at 4, 8, and 12 weeks. The harvested specimens with the implants were assessed for new bone formation on both sides of the implant using CBCT, conventional radiographs, and the biaxial pullout test. The results were statistically analyzed by a nonparametric Kruskal-Wallis test and Friedman's test as multiple comparisons and by Brunner-Langer nonparametric mixed model approach (R Software). RESULTS: A significant osteoconductive bone formation was found on the EPA-coated Ti implant surface (P < 0.05) at 8 weeks when compared to the polished surface (control). Biaxial pullout test results showed a significant difference (P < 0.05) after 8 and 12 weeks with a maximum force of 243.8 N, compared to 143.25 N after 4 week. CONCLUSION: EPA implant coating promoted osteoconduction on the Ti implant surfaces, enhancing the anchorage of the implant to the surrounding bone in white New Zealand rabbits.

The influence of experimental silane primers on dentin bond strength and morphology: a laboratory and finite element analysis study.

STATEMENT OF PROBLEM: The inconsistency of dentin bonding affects retention and microleakage. PURPOSE: The purpose of this laboratory and finite element analysis study was to investigate the effects on the formation of a hybrid layer of an experimental silane coupling agent containing primer solutions composed of different percentages of hydroxyethyl methacrylate. MATERIAL AND METHODS: A total of 125 sound human premolars were restored in vitro. Simple class I cavities were formed on each tooth, followed by the application of different compositions of experimental silane primers (0%, 5%, 25%, and 50% of hydroxyethyl methacrylate), bonding agents, and dental composite resins. Bond strength tests and scanning electron microscopy analyses were performed. The laboratory experimental results were validated with finite element analysis to determine the pattern of stress distribution. Simulations were conducted by placing the restorative composite resin in a premolar tooth by imitating simple class I cavities. The laboratory and finite element analysis data were significantly different from each other, as determined by 1-way ANOVA. A post hoc analysis was conducted on the bond strength data to further clarify the effects of silane primers. RESULTS: The strongest bond of hybrid layer (16.96 MPa) was found in the primer with 25% hydroxyethyl methacrylate, suggesting a barely visible hybrid layer barrier. The control specimens without the application of the primer and the primer specimens with no hydroxyethyl methacrylate exhibited the lowest strength values (8.30 MPa and 11.78 MPa) with intermittent and low visibility of the hybrid layer. These results were supported by finite element analysis that suggested an evenly distributed stress on the model with 25% hydroxyethyl methacrylate. CONCLUSIONS: Different compositions of experimental silane primers affected the formation of the hybrid layer and its resulting bond strength.

Effect of proper oral rehabilitation on general health of mandibulectomy patients.

Here, we aimed to assess whether postoperative oral rehabilitation for mandibulectomy patients is necessary to improve patients' general health in terms of health-related quality of life.

"High Frequency/Small Tidal Volume Differential Lung Ventilation": A Technique of Ventilating the Nondependent Lung of One Lung Ventilation for Robotically Assisted Thoracic Surgery.

With the introduction of new techniques and advances in the thoracic surgery fields, challenges to the anesthesia techniques had became increasingly exponential. One of the great improvements that took place in the thoracic surgical field was the use of the robotically assisted thoracic surgical procedure and minimally invasive endoscopic thoracic surgery. One lung ventilation technique represents the core anesthetic management for the success of those surgical procedures. Even with the use of effective one lung ventilation, the patient hemodynamics and respiratory parameters could be deranged and could not be tolerating the procedure that could compromise the end result of surgery. We are presenting our experience in managing one patient who suffered persistent hypoxia and hemodynamic instability with one lung ventilation for robotically assisted thymectomy procedure and how it was managed till the completion of the surgery successfully.

Effect of experimental silane-based primers with various contents of 2-hydroxyethyl methacrylate on the bond strength of orthodontic adhesives.

AIM: To evaluate in vitro the effect of different concentrations of 2-hydroxyethyl methacrylate (HEMA) in experimental silane-based primers on shear bond strength of orthodontic adhesives. METHODS: Different volume percentages of HEMA were tested in four experimental silane-based primer solutions (additions of HEMA: 0, 5.0 vol%, 25.0 vol% and 50.0 vol%). An experimental silane blend (primer) of 1.0 vol% 3-isocyanatopropyltrimethoxysilane (ICMS) + 0.5% bis-1,2-(triethoxysilyl) ethane (BTSE) was prepared and used. The experimental primers together with the control group were applied onto acid-etched premolars for attachment of orthodontic brackets. After artificial aging by thermocycling the shear-bond strength was measured. The fractured surfaces of all specimens were examined under scanning electron microscopy (SEM) to evaluate the failure mode on the enamel surface. RESULTS: The experimental primers showed the highest shear-bond strength of 21.15 MPa (SD ± 2.70 MPa) and with 25 vol% showed a highly significant increase (P < 0.05) in bond strength. The SEM images showed full penetration of adhesive agents when using silane-based primers. In addition, the SEM images suggested that the predominant failure type was not necessarily the same as for the failure propagation. CONCLUSIONS: This preliminary study suggested that nonacidic silane-based primers with HEMA addition might be an alternative to for use as adhesion promoting primers.

Human abdomen recognition using camera and force sensor in medical robot system for automatic ultrasound scan.

Physicians use ultrasound scans to obtain real-time images of internal organs, because such scans are safe and inexpensive. However, people in remote areas face difficulties to be scanned due to aging society and physician's shortage. Hence, it is important to develop an autonomous robotic system to perform remote ultrasound scans. Previously, we developed a robotic system for automatic ultrasound scan focusing on human's liver. In order to make it a completely autonomous system, we present in this paper a way to autonomously localize the epigastric region as the starting position for the automatic ultrasound scan. An image processing algorithm marks the umbilicus and mammary papillae on a digital photograph of the patient's abdomen. Then, we made estimation for the location of the epigastric region using the distances between these landmarks. A supporting algorithm distinguishes rib position from epigastrium using the relationship between force and displacement. We implemented these algorithms with the automatic scanning system into an apparatus: a Mitsubishi Electric's MELFA RV-1 six axis manipulator. Tests on 14 healthy male subjects showed the apparatus located the epigastric region with a success rate of 94%. The results suggest that image recognition was effective in localizing a human body part.