Amelanotic melanocytoma of the cervicomedullary junction.

A 64-year-old female with a 1-year history of gait difficulties and right-sided dysesthesias was found to have an intra-axial left-sided exophytic cervicomedullary enhancing mass. Microscopic, immunohistochemical, and ultrastructural findings demonstrated an amelanotic melanocytic neoplasm. Next-generation sequencing with a targeted exomic oncopanel identified a variant of functional significance in the GNA11 gene, thus confirming the diagnosis of a primary amelanotic melanocytoma. The crucial distinction from a melanoma was possible by correlating all of these studies that utilize different technologies.

Iatrogenic embolization following cardiac intervention: postmortem analysis of 110 cases.

INTRODUCTION: Iatrogenic embolization following cardiac investigative procedures may result from hydrophilic polymer emboli (HPE) from catheter valve and vessel wall calcifications, and air embolism from open heart surgery. This retrospective clinical pathologic analysis was undertaken to ascertain the frequency and extent of these potentially fatal complications. METHODS: This retrospective clinical pathologic autopsy analysis with premortem diagnostic imaging correlation identified 110 individuals who had undergone endovascular procedures between 2010 and 2016 within 90 days of death and followed by hospital autopsy. Clinical outcomes, radiologic studies, and autopsy materials were reviewed. RESULTS: Iatrogenic emboli were assessed as causing death in 9/110 autopsy cases (8.2%) and 9/34 (26.5%) cases with proven iatrogenic emboli. Iatrogenic emboli caused strokes in 10/110 (9.1%) autopsy cases including calcified emboli (CE, n=6), HPE (n=2), cardiac valvular tissue (n=1), and air embolism (n=1). Seven cases of calcified emboli complicating endovascular procedures were identified: four of the CE were thought to be the cause of death due to fatal strokes (n=2) and fatal myocardial (n=1) and colonic infarction (n=1). The CE likely originated from calcified aortic valves and atherosclerotic aortic plaques. Histologic evidence of HPE was found in 23% (25/110) of cases; 54% (26/48) showed evidence of infarction in postprocedural imaging, with radiologic evidence of infarction in 32% (8/25) of cases with HPE histology. Endovascular aortic repair was associated with the greatest density/distribution of HPE. HPE material showed degradation with time and was often associated with an inflammatory response. HPE directly contributed to death in three cases. One fatal air embolism followed open heart surgery, and one cardiac tissue embolus resulted in a major stroke. CONCLUSIONS: We advocate for greater awareness of these underrecognized and occasionally fatal complications of endovascular procedures. Targeted postprocedural imaging has a role in the identification of iatrogenic embolic infarcts.

Decreased skeletal muscle mitochondrial DNA in patients with statin-induced myopathy.

Statins are widely used to treat hyperlipidemia and lower cardiovascular disease risk. While statins are generally well tolerated, some patients experience statin-induced myopathy (SIM). Statin treatment has been associated with mitochondrial dysfunction and mitochondrial DNA (mtDNA) depletion. In this retrospective study, skeletal muscle biopsies from patients diagnosed with SIM were studied. These were compared with biopsies from patients clinically assessed as having statin-unrelated myopathy but whose biopsy showed no or negligible pathology. For each biopsy sample, mtDNA was quantified relative to nuclear DNA (mtDNA content) by qPCR, mtDNA deletions were investigated by long-template PCR followed by gel densitometry, and mtDNA oxidative damage was quantified using a qPCR-based assay. For a subset of matched samples, mtDNA heteroplasmy and mutations were investigated by cloning/sequencing. Skeletal muscle mtDNA content was significantly lower in SIM patients (N=23, mean±SD, 2036±1146) than in comparators (N=24, 3220±1594), p=0.006. There was no difference in mtDNA deletion score or oxidative mtDNA damage between the two groups, and no evidence of increased mtDNA heteroplasmy or somatic mutations was detected. The significant difference in skeletal muscle mtDNA suggests that SIM or statin treatments are associated with depletion of skeletal muscle mtDNA or that patients with an underlying predisposition to SIM have lower mtDNA levels. If statins induce mtDNA depletion, this would likely reflect decreased mitochondria biogenesis and/or increased mitochondria autophagy. Further work is necessary to distinguish between the lower mtDNA as a predisposition to SIM or an effect of SIM or statin treatment.

Characterization of management and outcomes of patients with acromegaly in Vancouver over 30 years.

PURPOSE: The purpose of this study was to characterize the management and outcomes of patients with acromegaly seen in single center in Vancouver, British Columbia, Canada over a 30 year period. METHODS: The study involved retrospective data collection from charts of patients diagnosed with acromegaly since 1980: 130 patients (63 male and 67 female) were included in the analysis, with a mean age at diagnosis of 43 years (male) and 47 years (female). RESULTS: The most common presenting features included acral enlargement, coarse facial features, sweating/oily skin and headache. All cases were caused by pituitary adenomas, of which 58.5% were macroadenomas and of these, 30.8% were invasive. The most common co-morbidities were hypertension 31.5%, arthralgia 28%, diabetes 27.7% and sleep apnea 23.8%. The vast majority (88.5%) of patients was treated surgically and of these patients, 21.5% also received radiotherapy and 66.9% received medical therapy. When stringent cure criteria were applied (based on latest growth hormone (GH) and IGF-1 results) the outcomes were 35.4% cured or controlled, 30% remained active, 15.4 discordant results and 19.2 % with no results reported. Twenty eight percent of patients who underwent surgery and 32% of patients who underwent radiotherapy were not cured but symptoms were moderately well controlled with medical therapy. CONCLUSION: Based on the size of population studied, this study showed a prevalence of acromegaly of 29 per million. The cure rate was low following surgery but with adjuvant medical treatment disease control was achieved in most individuals.

Enhanced π-conjugation and emission via icosahedral carboranes: synthetic and spectroscopic investigation.

The ability of ortho-, meta- and para-carboranes to enhance the emission intensity has been compared. For this purpose a series of carborane-appended 1,3,5-triphenylbenzene (TB) and 1,3,5- tris(biphenyl-4-yl)benzene (TBB) containing three ortho-, meta- and para-carborane clusters directly attached to the conjugated cores have been synthesized employing Suzuki, Heck, and trimerization reactions. The incorporation of the icosahedral carboranes was associated with a red shift in the UV absorption spectrum of up to 13 nm as well as enhancements of the emission intensities of up to 154%. The presence of ortho-carboranes showed the maximum red shift in the UV spectrum whereas the maximum enhancement of the emission intensity was observed in the presence of meta-carborane clusters. The order of π-conjugation extension is found to be ortho > meta ≈ para. A comparative thermal analysis indicated o-carborane-appended trimers to be the most thermally stable in the series. Proton NMR spectra of reported carborane-appended trimers indicated that ortho- and meta-carborane cages have benzenelike characteristics.

Carboranylpyrroles: a synthetic investigation.

The unusual reactivity of carborane mono- and dialdehydes with pyrroles in the presence of acid catalysts leads to the formation of a new class of carboranyl mono- and dipyrro derivatives.

Application of cycloaddition reactions to the syntheses of novel boron compounds.

This review covers the application of cycloaddition reactions in forming the boron-containing compounds such as symmetric star-shaped boron-enriched dendritic molecules, nano-structured boron materials and aromatic boronic esters. The resulting boron compounds are potentially important reagents for both materials science and medical applications such as in boron neutron capture therapy (BNCT) in cancer treatment and as drug delivery agents and synthetic intermediates for carbon-carbon cross-coupling reactions. In addition, the use of boron cage compounds in a number of cycloaddition reactions to synthesize unique aromatic species will be reviewed briefly.

Advances in the metallacarborane chemistry of f-block elements.

The role of carborane clusters in organometallic chemistry is diverse. A number of carborane cage systems such as C(2)B(4), C(2)B(9) and C(2)B(10) clusters have been extensively used for the synthesis of numerous metallacarboranes of s, p, d and f-block elements. An introduction to the chemistry of metallacarboranes is provided with an emphasis on the recent advances on the metallacarboranes of f-block elements.

Synthesis and properties of carborane-appended C(3)-symmetrical extended pi systems.

A series of C(3)-symmetric pi-conjugated compounds containing three to six o-carborane clusters have been synthesized by employing palladium-catalyzed Suzuki coupling reactions and palladium-catalyzed acetylation reactions, followed by silicon tetrachloride mediated trimerization reactions. Carborane-containing extended trimers were found to emit blue light. Incorporation of o-carborane clusters into extended pi-conjugated systems led to 22-70% enhancement of their relative fluorescence quantum yields. Decapitation of o-carborane clusters made these extended trimers water soluble, and their aqueous solutions were also found to be fluorescent, but with a reduced fluorescence intensity. The carborane-appended pi-conjugated compounds are found to be extremely thermally stable, and for some of these compounds only 10% mass loss occurred at temperatures close to 500 degrees C. The DSC thermograms of smaller C(cage)-appended trimers indicate the occurrence of solid-solid phase transitions.

Boron-enriched star-shaped molecule via cycloaddition reaction.

The facile synthesis of a thermally stable carborane appended symmetrical star-shaped molecule having six bulky o-carborane clusters on the periphery, thereby containing sixty boron atoms was accomplished via a cobalt-catalyzed [2+2+2] cycloaddition reaction.

Boron atoms as spin carriers in two- and three-dimensional systems.

Paramagnetic compounds with at least partially boron-centered electron spin can be constructed using either the prototypically electron-accepting boron atoms bridged by planar pi-conjugated organic systems, or by taking advantage of the three-dimensional delocalized bonding in oligonuclear borane, haloborane, or carborane clusters. The concept of mixed valency can thus be transferred from organic and transition-metal chemistry to main-group-element molecules, and density functional theory is capable of reproducing the variable spin distribution.

Meningiomas in 2009: controversies and future challenges.

Meningiomas are the most common intracranial primary neoplasm in adults. Over recent years, interest in this clinically diverse group of tumors has intensified, bringing new questions and challenges to the fore, particularly in the fields of epidemiology, radiology, pathology, genetics, and treatment. Interest in modern meningioma research has been stimulated by the high tumor prevalence and the advances in technology. The incidence of meningiomas is climbing, and may indicate increased exposure to environmental risk factors or more sensitive diagnostic modalities. Technological advances have dramatically improved radiologic imaging and radiotherapy treatments, and further refinements are under investigation. Furthermore, the current era of tumor genetics and molecular biology is challenging translational researchers to discover new, targeted, therapeutic agents. This review is an update on the recent advances in the understanding of meningiomas and their management, and highlights pertinent research questions to be addressed in the future.

Intestinal and renal effects of low-volume phosphate and sulfate cathartic solutions designed for cleansing the colon: pathophysiological studies in five normal subjects.

OBJECTIVES: Ingestion of a concentrated low-volume phosphate solution produces copious diarrhea, which cleanses the colon, but it occasionally causes renal failure due to calcium phosphate precipitation in renal tubules. We hypothesized that a concentrated low-volume sulfate solution would be an equally effective cathartic, and that urine produced after sulfate would have less tendency to precipitate calcium salts than urine produced after phosphate. METHODS: Hydrated subjects ingested 75 ml of phosphosoda or an equimolar dose of sulfate salts in a small volume of solution. Four liters of PEG (polyethylene glycol) lavage solution was the control. All solutions were administered in split doses, 10 h apart. Propensity of urine to precipitate at pH 6.4 (the pH of renal tubular fluid) was assessed by determining the minimal calcium concentration that caused precipitation. RESULTS: Average diarrheal stool weight was 2,004 g after phosphate, 2,854 g after sulfate, and 3,021 g after PEG (P<0.001). Average calcium concentration (in mg/dl) required to induce urine precipitation at pH 6.4 was 43 after PEG, 10 after PO(4), and 187 after SO(4) (P=0.009). CONCLUSIONS: (i) In equimolar doses, sulfate produced 42% more diarrheal stool weight than phosphate. (ii) Phosphate increased the propensity for calcium salt precipitation in urine at pH 6.4, whereas sulfate did not. (iii) These results suggest that a hypertonic low-volume sulfate solution would be an effective cathartic for colon cleansing and that sulfate-induced catharsis would be less likely than phosphate catharsis to produce calcium salt deposition in renal tubules.

Catalytic phenylborylation reaction by iridium(0) nanoparticles produced from hydridoiridium carborane.

Well-dispersed iridium(0) nanoparticles stabilized with the ionic liquid, trihexyltetradecylphosphonium methylsulfonate, [THTdP][MS], have been successfully prepared by reduction of the precursor hydridoiridium carborane, (Ph 3P) 2Ir(H)(7,8- nido-C 2B 9H 11). The iridium nanoparticles were found to be active catalysts for arylborylation, forming boric acids. The activity of the catalyst has been investigated as a function of the activating base, and reaction conditions. The highest yield of 91% was achieved in a microwave reactor using the base, tetra-2-pyridinylpyrazine, in the presence of [THTdP][MS]. The catalytic system could be recycled at least six times with less than a 0.5% loss of activity.

Synthesis of a new class of carborane-containing star-shaped molecules via silicon tetrachloride promoted cyclotrimerization reactions.

Symmetrical star-shaped molecules with carborane clusters on the periphery have been synthesized in good yields via silicon tetrachloride mediated cyclotrimerization reactions of 9-benzyl derivatives of carboranes with acetyl group substitution on the benzene ring. Facile functionalization of these symmetrical core structures with 1-iodoheptane and trivinylchlorosilane produce compounds which could be used as liquid crystalline substances and precursors for synthesis of higher order carbosilane dendrons.

Latest developments in the catalytic application of nanoscaled neutral group 8-10 metals.

In the last few decades, the synthesis and catalytic application of nanoscaled particles prepared from Group 8-10 (formerly Group VIIIB) elements have been widely explored and have achieved promising results. The innovative use of these nanoparticle catalysts may provide new opportunities in the efficient combination of conventionally used homogenous and heterogeneous catalysts. Conventional homogeneous catalysts pose extraction and recycling difficulties when dealing with metal complexes and/or ligands, whereas heterogeneous catalysts generally require more pressing experimental conditions, such as high temperatures and high pressures, to be effective. Therefore, to solve these problems, the synthesis and use of nanoparticle catalysts as replacements for conventional catalytic systems is a breakthrough owing to their improved handling and environmental and economic aspects. This Focus Review primarily addresses the catalytic applications of neutral Group 8-10 nanoparticles with an average size of less than 10 nm, and also includes a discussion of commonly used synthetic methodology.

[η-2,3-Bis(trimethylsilyl)-2,3-dicarba-nido-hexaborane(2-)]chlorido(N,N,N',N'-tetramethylethylenediamine)dysprosium(III).

The structure of the title compound, [Dy(C(8)H(22)B(4)Si(2))Cl(C(6)H(16)N(2))], reveals that a center of symmetry exists within the dimeric half-sandwich units. Within each half-sandwich, the Dy(III) ion is coordinated by the five-membered ring of the carborane, tetramethylethyl-enediamine and the chloride ion.

Ruthenium(0) nanoparticle-catalyzed isotope exchange between 10B and 11B nuclei in decaborane(14).

Well dispersed ruthenium(0) nanoparticles, stabilized in the ionic liquid agent, trihexyltetradecylphosphonium dodecylbenzenesulfonate, have been successfully prepared via a reduction reaction of the precursor [CpRuCp*RuCp*]PF6 (Cp* = C5Me5). The ruthenium(0) nanoparticles were shown to catalyze the isotope exchange reaction between 10B enriched diborane and natural abundant B10H14 to produce highly 10B enriched (approximately 90%) decaborane(14) products. The ruthenium(0) nanoparticles were characterized by TEM, XRD, and XPS. The 10B enriched decaborane(14) has been analyzed by Raman spectroscopy, NMR, and high-resolution MS.