Orthodontic correction of a skeletal Class II malocclusion with severe gummy smile by total intrusion of the maxillary dentition.

A 22-year-old woman visited the hospital complaining of lip protrusion, crowded teeth, and a gummy smile. The clinical examination showed a convex profile with a hyperdivergent mandible and a severe gummy smile in both anterior and posterior regions. The unstable mandible position was considered during treatment planning, and a targeted mechanic system was carefully designed. Temporary skeletal anchorage devices in the posterior dental region and a transpalatal arch were introduced as anchorage for the intrusion of the entire maxillary dentition and controlled retraction of the anterior teeth. Based on effective and simple mechanisms, we successfully eliminated the severe gummy smile and improved the facial aesthetics with the aid of conventional appliances. This approach provided an alternative option to orthognathic surgery or bulky invasive miniscrews for treatment of skeletal Class II malocclusion with severe gummy smile.

A Novel Leucyl-tRNA Synthetase Inhibitor, MRX-6038, Expresses Anti-Mycobacterium abscessus Activity In Vitro and In Vivo.

Therapeutic options for Mycobacterium abscessus infections are extremely limited, and new drugs are needed. The anti-M. abscessus activity of MRX-6038, a new leucyl-tRNA synthetase inhibitor, was evaluated in vitro and in vivo. Antimicrobial susceptibility testing was performed on 12 nontuberculosis mycobacteria (NTM) reference strains and 227 clinical NTM isolates. A minimum bactericidal concentration assay was conducted to distinguish the bactericidal versus bacteriostatic activity of MRX-6038. The synergy between MRX-6038 and 12 clinically important antibiotics was determined using a checkerboard assay. The activity of MRX-6038 against M. abscessus residing inside macrophages was also evaluated. Finally, the potency of MRX-6038 in vivo was determined in a neutropenic mouse model that mimicked a pulmonary M. abscessus infection. MRX-6038 exhibited high anti-M. abscessus activity against extracellular M. abscessus in culture, with a MIC50 of 0.063 mg/L and a MIC90 of 0.125 mg/L. Fifty percent of the activity was bactericidal, and fifty percent was bacteriostatic. A synergy between MRX-6038 and clarithromycin or azithromycin was found in 25% of strains. No antagonism was evident between MRX-6038 and 12 antibiotics commonly used to treat NTM infections. MRX-6038 also exhibited activity against intracellular NTM, which caused a significant reduction in the bacterial load in the lungs of M. abscessus-infected neutropenic mice. In conclusion, MRX-6038 was active against M. abscessus in vitro and in vivo, and it represents a potential candidate for incorporation into strategies by which M. abscessus infections are treated.

Discovery of Antibacterial Contezolid Acefosamil: Innovative O-Acyl Phosphoramidate Prodrug for IV and Oral Therapies.

New oral antibiotic contezolid (CZD) is effective against Gram-positive infections but unsuitable for intravenous (IV) administration due to its modest solubility. To address the medical need for an IV form of CZD, its isoxazol-3-yl phosphoramidate derivatives have been explored, and contezolid acefosamil (CZA, 8), the first representative of a novel O-acyl phosphoramidate prodrug class, has been identified. CZA exhibits high aqueous solubility (>200 mg/mL) and good hydrolytic stability at media pH suitable for IV administration. CZA rapidly converts into the active drug CZD in vivo. In a pharmacokinetic (PK) rat model, the exposure of active drug CZD after IV administration of the prodrug CZA was similar to or higher than that from the IV administration of CZD. The prodrug CZA is bioequivalent to or better than CZD in several preclinical infection models. CZA is likewise active upon its oral administration. To date, CZA has been evaluated in Phase 1 and Phase 2 clinical trials in the USA. It is advancing into further clinical studies including step-down therapy with in-hospital intravenous CZA administration followed by outpatient oral CZD treatment.

Fabrication of oxidized sodium alginate-collagen heterogeneous bilayer barrier membrane with osteogenesis-promoting ability.

Guided bone regeneration technique is an effective approach to repair bone defects, in which a barrier membrane is essential. However, the collagen barrier membranes commonly used lose stability quickly, leading to connective tissue invasion and failure of osteogenesis. Herein, we presented an oxidized sodium alginate (OSA)-collagen heterogeneous bilayer barrier membrane with well-controlled pore size and osteogenesis-promoting ability. The OSA crosslinking significantly improved the structural stability, compressive strength, swelling behavior, and slowed down the biodegradation rate of collagen membranes. Meanwhile, the collagen-based membranes exhibited superior cytocompatibility, osteogenesis-promotion, and barrier function against fibroblasts. Especially, the osteogenic differentiation was most promoted on the membrane with a large pore size (240-310 µm), while the barrier function was most improved on the membrane with a small pore size (30-60 µm). Then the above two membranes were combined together to obtain a heterogeneous bilayer membrane. This bilayer barrier membrane showed excellent osteogenesis-promoting ability in rats.

Nonsurgical treatment of a hyperdivergent skeletal Class III patient with mini-screw-assisted mandibular dentition distalization and flattening of the occlusal plane.

Treatment of hyperdivergent skeletal Class III malocclusion is challenging for orthodontists, and orthognathic-orthodontic treatment is usually required. This report presents the successful nonsurgical treatment of a 20-year-old man who had a skeletal Class III malocclusion with anterior open bite, anterior and posterior crossbite, hyperdivergent growth pattern, steep occlusal plane, early loss of three first molars, and an uncommon convex profile with a retruded chin. An orthodontic camouflage treatment plan was chosen based on the etiology and the patient's complaints. Tooth #37 was extracted. Miniscrews were used for uprighting and intruding of the lower molars, distalization of the lower dentition, and flattening of the occlusal plane. After 34 months of active treatment, Class I relationships, proper anterior overjet and overbite, flat occlusal plane, and an esthetic facial profile were achieved. The results demonstrated that the biomechanics involved in the nonsurgical treatment assisted with miniscrews to distalize the mandibular dentition and flatten the occlusal plane while keeping the mandibular plane stable was effective for treating this hyperdivergent skeletal Class III patient with a convex profile and anterior open bite.

A Novel Oxazolidinone, Contezolid (MRX-I), Expresses Anti-Mycobacterium abscessus Activity In Vitro.

An evaluation of the anti-Mycobacterium abscessus activity expressed by a novel oxazolidinone, contezolid (MRX-I), toward 12 reference strains and 194 clinical isolates was conducted. Contezolid was active against M. abscessus in vitro, with effects comparable to the anti-M. abscessus effects of linezolid both extracellularly and intracellularly. Contezolid did not antagonize the most frequently used anti-M. abscessus drugs, and preexposure to contezolid did not induce drug resistance. These results provide a novel approach to treating M. abscessus infections.

Rodent incisor and molar dental follicles show distinct characteristics in tooth eruption.

OBJECTIVE: Rodent incisors and molars show different eruption patterns. Dental follicles and their interaction with dental epithelia play key roles in tooth eruption. However, little is known about the differences between incisor dental follicle (IF) and molar dental follicle (MF) during tooth eruption of rodents. This study aimed to investigate the differences between IF and MF during tooth eruption under induction with cervical-loop cells (CLC) and Hertwig's epithelial root sheath (HERS) cells of rats. MATERIALS AND METHODS: CLC, HERS, IF, MF cells were isolated from 10 postnatal day 7 rats and identified by immunofluorescence staining. CLC or HERS cells-derived conditioned medium (CM) was obtained to induce IF and MF cells. Cell proliferation, mineralization, gene and protein expression related to tooth eruption were detected, and histological analysis was also performed. RESULTS: The osteogenic differentiation and mineralization abilities of IF cells were stronger than those of MF cells. Both CLC and HERS cells-derived CM enhanced these abilities of IF cells, whereas they showed the opposite effect on MF cells. At 7, 10, and 15 d after birth, IF cells expressed more OPG and less RANKL than MF cells. CONCLUSIONS: IF and MF cells present distinct characteristics in tooth eruption, CLC and HERS cells have significant inductive effects on them.

High intensity focused ultrasound treatment of adenomyosis: a comparative study.

OBJECTIVE: To compare the treatment efficacy and safety of high intensity focused ultrasound (HIFU) on its own, HIFU combined with levonorgestrel-releasing intrauterine system (LNG-IUS) and HIFU combined with gonadotropin-releasing hormone agonist (GnRHa). METHOD: Seventy-eight patients with adenomyosis who underwent HIFU treatment were retrospectively analyzed. Among them, 45 patients were treated only with HIFU, 15 patients were treated with HIFU combined with LNG-IUS and 18 patients were treated with HIFU combined with GnRHa. Dysmenorrhea scores, menstrual blood volumes, uterine volumes and adenomyotic lesion volumes were evaluated 1, 6 and 12 months after HIFU. RESULT: After treatment, dysmenorrhea score, menstrual blood volume, uterine volume and adenomyotic lesion volume significantly decreased in all three groups (p < 0.05). No significant difference was observed among the HIFU group, HIFU with LNG-IUS group and HIFU with GnRHa group 1 month after HIFU. However, 6 and 12 months after HIFU, dysmenorrhea score, menstrual blood volume, uterine volume and adenomyotic lesion volume decreased significantly more in the HIFU with LNG-IUS group and HIFU with GnRH-a group than in the group treated with HIFU on its own (p < 0.05). CONCLUSION: HIFU can be effectively used in the management of adenomyosis. Based on the results of this study with a limited number of patients, our study suggested that combining HIFU with LNG-IUS or GnRHa may provide a superior clinical effect compared to HIFU treatment on its own.

Optimized fan-shaped chiral metamaterial as an ultrathin narrow-band circular polarizer at visible frequencies.

Chiral metamaterials have the great ability to manipulate the circular polarizations of light, which can be utilized to build ultrathin circular polarizers. Here we build a narrow-band circular polarizer at visible frequencies based on plasmonic fan-shaped chiral nanostructures. In order to achieve the best optical performance, we systematically investigate how different fabrication factors affect the chiral optical response of the fan-shaped chiral nanostructures, including incident angle of vapor depositions, nanostructure thickness, and post-deposition annealing. The optimized fan-shaped nanostructures show two narrow bands for different circular polarizations with the maximum extinction ratios 7.5 and 6.9 located at wavelength 687 nm and 774 nm, respectively.

Switchable reflection/transmission utilizing polarization on a plasmonic structure consisting of self-assembly polystyrene spheres with silver patches.

We report a plasmonic structure for switchable reflection and transmission by polarization. The structure is composed of a hexagonal-packed polystyrene sphere array with silver patches on them. Simulations and experiments demonstrated that the conversions between reflected beams and transmitted ones can be performed when the polarization directions of incident beams vary from 0° to 90°. A switchable reflection and transmission at a given wavelength can be obtained, as long as sizes of PS spheres and azimuthal angles are properly chosen. Such a patchy plasmonic structure serving as a switch between reflection and transmission have potential applications in photoelectric control devices.

In-plane displacement measurement using optical vortex phase shifting.

In this paper, we propose a new method for in-plane displacement measurement by application of phase shifting based on an optical vortex. The phase shifts are obtained by displaying computer-generated fork holograms on the screen of a liquid-crystal spatial light modulator (LC-SLM). Furthermore, the vortex beam that is generated by the LC-SLM can be used as a reference light in the experiment. Eight speckle patterns with phase-shift increments of 0, π/2, π, and 3π/2 were captured by a CCD camera before and after the deformation. The displacement of the deformed object was obtained by unwrapping. Experimental results demonstrated the efficacy of the proposed method for in-plane displacement measurement.

Application of annular centrifugal contactors in the hot test of the improved total partitioning process for high level liquid waste.

High level liquid waste (HLLW) produced from the reprocessing of the spent nuclear fuel still contains moderate amounts of uranium, transuranium (TRU) actinides, (90)Sr, (137)Cs, etc., and thus constitutes a permanent hazard to the environment. The partitioning and transmutation (P&T) strategy has increasingly attracted interest for the safe treatment and disposal of HLLW, in which the partitioning of HLLW is one of the critical technical issues. An improved total partitioning process, including a TRPO (tri-alkylphosphine oxide) process for the removal of actinides, a CESE (crown ether strontium extraction) process for the removal of Sr, and a CECE (calixcrown ether cesium extraction) process for the removal of Cs, has been developed to treat Chinese HLLW. A 160-hour hot test of the improved total partitioning process was carried out using 72-stage 10-mm-dia annular centrifugal contactors (ACCs) and genuine HLLW. The hot test results showed that the average DFs of total α activity, Sr and Cs were 3.57 × 10(3), 2.25 × 10(4) and 1.68 × 10(4) after the hot test reached equilibrium, respectively. During the hot test, 72-stage 10-mm-dia ACCs worked stable, continuously with no stage failing or interruption of the operation.

Integrity of the blood-testis barrier in healthy men after suppression of spermatogenesis with testosterone and levonorgestrel.

STUDY QUESTION: Do exogenous male hormonal contraceptives that suppress intratesticular testosterone and spermatogenesis interfere with the blood-testis barrier integrity in men? SUMMARY ANSWER: When spermatogenesis was suppressed by testosterone alone or combined with levonorgestrel (LNG) treatment in men, the structural appearance of Sertoli cell tight junctions remained intact in the human testis. WHAT IS ALREADY KNOWN: Testosterone promotes the integrity of the blood-testis barrier. Intratesticular androgen deprivation induced by exogenous testosterone plus a progestin to suppress spermatogenesis in a contraceptive regimen may disturb the structural and functional integrity of the blood-testis barrier. STUDY DESIGN, SIZE AND DURATION: Testicular biopsies were obtained from a sub-study of a randomized clinical trial of 36 healthy Chinese men who were treated for 18 weeks and followed for at least a 12-week recovery period. PARTICIPANTS/MATERIAL, SETTING, METHODS: Healthy Chinese male volunteers (27-48 years) were randomized to two treatment groups (n = 18/group) for 18 weeks: (1) testosterone undecanoate (TU) 1000 mg i.m. injection followed by a 500 mg injection every 6 weeks and (2) TU + LNG 250 µg orally daily. Blood samples were obtained from all participants before and during treatment and at the end of the recovery phase. Open testicular biopsies for this study were obtained from four men before treatment and from four men in each of the TU and TU + LNG groups at 2 and 9 weeks of treatment. The presence of antisperm antibodies was checked in the archived serum samples of the subjects at baseline, during treatment and at the end of the recovery period. Stored testicular biopsy samples from cynomolgus monkeys treated with either sub-cutaneous testosterone or placebo for 12 weeks were used for additional protein expression studies. MAIN RESULTS AND ROLE OF THE CHANCE: Expression of blood-testis barrier associated proteins quantified by immunohistochemistry (claudin 3, claudin 11, junctional adhesion molecule-A, zonula occludens-1) remained unchanged despite a significant decrease in the numbers of pachytene spermatocytes and round spermatids in the seminiferous tubules at 9 weeks in the TU + LNG group. This was confirmed by immunoblots showing a lack of quantitative change in these tight junction proteins in monkeys after testosterone treatment. There were no increases in serum antisperm antibodies in the volunteers during the study. LIMITATIONS/REASONS FOR CAUTION: The duration of the study was short and the long-term effects of male hormonal contraceptive treatments on the integrity of the blood-testis barrier remain to be determined. WIDER IMPLICATIONS OF THE FINDINGS: This study supports the safety of male hormonal contraceptive treatment and does not corroborate the previous findings of disturbed immunological integrity of the blood-testis barrier from animal studies such as androgen receptor knockout mice and exogenous hormonal treatment in rats. STUDY FUNDING/COMPETING INTEREST: The study was supported by grants from the Contraceptive Research and Development Program and the Mellon Foundation (MFG-02-64, MFG-03-67), Endocrine, Metabolism and Nutrition Training Grant (T32 DK007571), the Clinical and Translational Science Institute at Los Angeles Biomedical and Harbor-UCLA Medical Center (UL1RR033176 and UL1TR000124) and the Los Angeles Biomedical Research Institute Summer High School Student Program.

Proteomic analysis of testis biopsies in men treated with transient scrotal hyperthermia reveals the potential targets for contraceptive development.

Mild testicular heating safely and reversibly suppresses spermatogenesis. In this study, we attempted to clarify the underlying molecular mechanism(s) involved in heat-induced spermatogenesis suppression in human testis. We conducted global proteomic analyses of human testicular biopsies before, and at 2 and 9 wk after heat treatment. Thirty-one and Twenty-six known proteins were identified with significant differential expression at 2 and 9 wk after heat treatment, respectively. These were used to characterize the cellular and molecular events in the testes when seminiferous epithelia became damaged (2 wk) and recovered (9 wk). At 2 wk post-treatment, the changed expression of a series of proteins could promote apoptosis or suppress proliferation and cell survival. At 9 wk post-treatment, the changed expression of proteins mainly promoted cell proliferation, differentiation and survival, but resisted cell apoptosis. Among those heat-regulated proteins, HNRNPH1 was selected for the further functional study. We found that HNRNPH1 was an anti-apoptosis protein that could regulate the expression of other heat-induced proteins. In conclusion, heat-induced reversible suppression of spermatogenesis occurred by modulating the expression of proteins related to proliferation, differentiation, apoptosis and cell survival pathways. These differentially expressed proteins were found to be key molecular targets affecting spermatogenesis after heat treatment.

Anatomy of the transversus nuchae muscle and its relationship with the superficial musculoaponeurotic system.

BACKGROUND: Previous studies have proved the existence of muscle fibers in the superficial musculoaponeurotic system (SMAS) of the parotid and masseter region; however, no studies have investigated the origination of the muscle fibers in the SMAS. Theoretically speaking, the muscle fibers within the SMAS in the parotid and masseter region might originate from a certain muscle with a definite origin and insertion. Based on this hypothesis, the authors' study investigated the origination of the muscle fibers in the SMAS of the parotid and masseter region to provide anatomical evidence that can improve our understanding of the SMAS. METHODS: An anatomical study was performed on 20 halves of seven fixed and three fresh adult cadavers (seven male and three female cadavers). A traditional bilateral face-lift incision was designed in each cadaver, and the muscle fibers within the SMAS in the parotid and masseter region, along with the origin and insertion, were investigated, dissected, analyzed, and photographed. RESULTS: The transversus nuchae muscle can be divided into two sections according to the origin of its tendons. The muscular fasciculi of the two sections run transversely across the sternocleidomastoid muscle, insert into the superficial fascia above the parotidomasseteric fascia, and terminate in the zygomatic region. The muscle fibers within the SMAS in the parotid and masseter region come from the transversus nuchae muscle. CONCLUSIONS: The authors' study first investigated the transversus nuchae muscle combined with the SMAS and clarified the issue that has been neglected by previous studies for more than 30 years. The authors hope this will unify their understanding of the SMAS and offer plastic surgeons and readers a brief insight into the SMAS.

[A study on population-based prenatal screening and diagnosis of Down's syndrome in Jiangsu province].

OBJECTIVE: To screen and diagnose Down's syndrome during mid-term pregnancy to reduce the number of babies with Down's syndrome. METHODS: With the multi-level of stratified cluster sampling, twenty thousand and eight hundred and three women at 15-20 weeks gestation were screened by maternal serum AFP and beta-hCG using the time resolved fluoroimmunoassay (TRFIA). Then the screened high-risk women were diagnosed by amniocentesis, cell culture and chromosome analyses. The born children were diagnosed by follow-up and peripheral blood chromosome analyses. RESULTS: Six fetuses were diagnosed by serum screening and amniotic fluid chromosome analyses, and 3 born children were diagnosed by follow-up and peripheral blood chromosome analyses. Nine cases of Down's syndrome were detected in total, with the positive prenatal screen rate being 67% (6/9). CONCLUSION: The prenatal screening and diagnosis can reduce the birth of Down's syndrome patients and improve the population quality. However, the diagnosis accuracy still needs to be improved to further reduce the false negative rate and prevent misdiagnosis.

(3S,4R)-3-Ethyl-4-hydr-oxy-3-(3-methoxy-phen-yl)-1-methyl-azepanium (2R,3R)-2,3-bis-(benzo-yloxy)-3-carboxy-propionate.

The crystal structure of the title compound, C(16)H(26)NO(2) (+)·C(18)H(13)O(8) (-), is stabilized by an extensive network of classical N-H⋯O and O-H⋯O hydrogen bonding. The crystal structure also shows an ammonium-driven diastereo-isomerism.

Highly selective and potent mu opioid ligands by unexpected substituent on morphine skeleton.

Unexpected substituent on the well-known morphine skeleton is described to be account for highly selective and potent mu opioid ligands, which is strongly connected to substituted aromatic groups on this omitted 8alpha-position.