Insights into the thermal and chemical stability of multilayered V2CTx MXene.

We report on the thermal stability of multilayered V2CTx MXenes under different atmospheres by combining in situ Raman spectroscopy with ex situ X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM) in order to elucidate and monitor the molecular, electronic, and structural changes of both the surface and bulk of the V2CTx MXene which has recently received much attention. The MXene samples were heated up to 600 °C in inert (N2), oxidative (CO2, air), and reductive (H2) environments under similar conditions. In situ Raman showed that the V[double bond, length as m-dash]O vibration for two-dimensional vanadia is preserved up to 600 °C under N2, while its intensity reduces under H2. When heated above 300 °C under either CO2 or air, V2CTx slightly oxidizes or transforms into V2O5, respectively. Furthermore, SEM revealed the presence of an accordion-like layered structure for the MXene under N2 and H2, while under CO2 and air the layered structure collapses and forms VO2 (V4+) and V2O5 (V5+) crystals, respectively. XPS reveals that, regardless of the gas, surface V species oxidize above 300 °C during the dehydration process. Finally, we demonstrated that the partial dehydration of V2CTx results in the partial oxidation of the material, and the total dehydration is achieved once 700 °C is reached. We believe that our methodology is a unique alternative to tune the dehydration, oxidation, and properties of V2CTx, which allows for the expansion of applications of MXenes.

Chronic fibrosing osteomyelitis of the jaws: an important cause of recalcitrant facial pain. A clinicopathologic study of 331 cases in 227 patients.

OBJECTIVE: This was a retrospective and follow-up analysis of 331 cases of chronic fibrosing osteomyelitis of the jaws (CFOJ) in 227 patients. STUDY DESIGN: Demographic, clinical, surgical, and microscopic characteristics were tabulated for all patients. A follow-up mail survey was used to determine the degree of symptom relief experienced after surgery. RESULTS: The female to male ratio approached 7:1, and mean age of patients was 53 years. The most common sites were the mandibular posterior region, followed by the maxillary posterior region. Consistent clinical findings included intractable jaw pain mimicking that of odontogenic origin but unresponsive to usual therapies, minimal or undetectable radiographic abnormalities on plain films but dramatic radiolucencies detected on cone beam computed tomography, and large cavities that were either empty or filled with blood mixed with lipid globules encountered at surgery. The most common histomorphologic findings were vital lamellar bone, prominent resting and reversal lines, microshards and splaying of trabeculae, rounded trabeculae, marrow fibrosis, and pools of erythrocytes and lipid globules, often together. Moderate to complete relief of symptoms for periods up to 108 months after surgery were reported by 83% of the 70 patients who returned the survey. CONCLUSIONS: On the basis of the findings of this study, CFOJ can be considered a unique entity with consistent clinicopathologic features. Its features suggest a pathogenesis based on bone marrow ischemia. CFOJ can be treated on a rational basis with a justifiable expectation of success and probable cure.

Morton's neuroma.

Morton neuroma is a common source of forefoot pain. This condition is more correctly termed as interdigital nerve compression and is not a true neuroma. Although Morton neuroma is a common diagnosis, debate exists as to the best surgical and nonsurgical treatments. This article discusses the pathogenesis, diagnosis, nonsurgical and surgical management, and surgical complications of this common disorder.

Discovery of 6-({4-[2-(4-tert-butylphenyl)-1H-benzimidazol-4-yl]piperazin-1-yl}methyl)quinoxaline (WAY-207024): an orally active antagonist of the gonadotropin releasing hormone receptor (GnRH-R).

A potent, highly insoluble, GnRH antagonist with a 2-phenyl-4-piperazinylbenzimidazole template and a quinoxaline-2,3-dione pharmacophore was modified to maintain GnRH antagonist activity and improve in vitro pharmaceutical properties. Structural changes to the quinoxaline-2,3-dione portion of the molecule resulted in several structures with improved properties and culminated in the discovery of 6-([4-[2-(4-tert-butylphenyl)-1H-benzimidazol-4-yl]piperazin-1-yl] methyl)quinoxaline (WAY-207024). The compound was shown to have excellent pharmacokinetic parameters and lowered rat plasma LH levels after oral administration.

Design, synthesis, and SAR of new pyrrole-oxindole progesterone receptor modulators leading to 5-(7-fluoro-3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)-1-methyl-1H-pyrrole-2-carbonitrile (WAY-255348).

We have continued to explore the 3,3-dialkyl-5-aryloxindole series of progesterone receptor (PR) modulators looking for new agents to be used in female healthcare: contraception, fibroids, endometriosis, and certain breast cancers. Previously we reported that subtle structural changes with this and related templates produced functional switches between agonist and antagonist properties ( Fensome et al. Biorg. Med. Chem. Lett. 2002, 12, 3487; 2003, 13, 1317 ). We herein report a new functional switch within the 5-(2-oxoindolin-5-yl)-1 H-pyrrole-2-carbonitrile class of compounds. We found that the size of the 3,3-dialkyl substituent is important for controlling the functional response; thus small groups (dimethyl) afford potent PR antagonists, whereas larger groups (spirocyclohexyl) are PR agonists. The product from our optimization activities in cell-based systems and also for kinetic properties in rodents and nonhuman primates was 5-(7-fluoro-3,3-dimethyl-2-oxo-2,3-dihydro-1 H-indol-5-yl)-1-methyl-1 H-pyrrole-2-carbonitrile 27 (WAY-255348), which demonstrated potent and robust activity on PR antagonist and contraceptive end points in the rat and also in cynomolgus and rhesus monkeys including ovulation inhibition, menses induction, and reproductive tract morphology.