Neuroinflammation and white matter alterations in occupational manganese exposure assessed by diffusion basis spectrum imaging.

OBJECTIVE: To evaluate in-vivo neuroinflammation and white matter (WM) microstructural integrity in occupational manganese (Mn) exposure. METHODS: We assessed brain inflammation using Diffusion Basis Spectrum Imaging (DBSI) in 26 Mn-exposed welders, 17 Mn-exposed workers, and 26 non-exposed participants. Cumulative Mn exposure was estimated from work histories and the Unified Parkinson's Disease Rating Scale motor subsection 3 (UPDRS3) scores were completed by a movement specialist. Tract-based Spatial Statistics allowed for whole-brain voxel-wise WM analyses to compare WM DBSI-derived measures between the Mn-exposed and non-exposed groups. Exploratory grey matter region of interest (ROI) analyses examined the presence of similar alterations in the basal ganglia. We used voxelwise general linear modeling and linear regression to evaluate the association between cumulative Mn exposure, WM or basal ganglia DBSI metrics, and UPDRS3 scores, while adjusting for age. RESULTS: Mn-exposed welders had higher DBSI-derived restricted fraction (DBSI-RF), higher DBSI-derived nonrestricted fraction (DBSI-NRF), and lower DBSI-derived fiber fraction (DBSI-FF) in multiple WM tracts (all p < 0.05) in comparison to less-exposed workers and non-exposed participants. Basal ganglia ROI analyses revealed higher average caudate DBSI-NRF and DBSI-derived radial diffusion (DBSI-RD) values in Mn-exposed welders relative to non-exposed participants (p < 0.05). Caudate DBSI-NRF was also associated with greater cumulative Mn exposure and higher UPRDS3 scores. CONCLUSIONS: Mn-exposed welders demonstrate greater DBSI-derived indicators of neuroinflammation-related cellularity (DBSI-RF), greater extracellular edema (DBSI-NRF), and lower apparent axonal density (DBSI-FF) in multiple WM tracts suggesting a neuroinflammatory component in the pathophysiology of Mn neurotoxicity. Caudate DBSI-NRF was positively associated with both cumulative Mn exposure and clinical parkinsonism, indicating a possible dose-dependent effect on extracellular edema with associated motor effects.

Evolved gas composition monitoring by repetitive injection gas chromatography.

Performance characteristics and applications of a small volume gas chromatograph oven are described. Heating and cooling properties of the apparatus are evaluated and examples are given illustrating the advantages of greatly reducing the air bath volume surrounding fused silica columns. Fast heating and cooling of the oven permit it to be employed for repetitive injection analyses. By using fast gas chromatography separations to achieve short assay cycle times, the apparatus can be employed for on-line species-specific gas stream composition monitoring when volatile species concentrations vary on time scales of a few minutes or longer. This capability facilitates repeated sampling and fast gas chromatographic separations of volatile product mixtures produced during thermal analyses. Applications of repetitive injection gas chromatography-mass spectrometry evolved gas analyses to monitoring purge gas effluent streams containing volatile acid catalyzed polymer cracking products are described. The influence of thermal analysis and chromatographic experimental parameters on effluent sampling frequency are delineated.

Risk factors for posttreatment edema in patients treated with stereotactic radiosurgery for meningiomas.

BACKGROUND: Peritumoral edema is a recognized complication following stereotactic radiosurgery (SRS). OBJECTIVE: To evaluate the risk of posttreatment peritumoral edema following SRS for intracranial meningiomas and determine predictive factors. METHODS: Between 2002 and 2008, 173 evaluable patients underwent CyberKnife or Gamma Knife SRS for meningiomas. Eighty-four patients (49%) had prior surgical resections, 13 patients had World Health Organization grade II (atypical) meningiomas, and 117 patients had a neurological deficit before SRS. Sixty-two tumors were in parasagittal, parafalcine, and convexity locations. The median tumor volume was 4.7 mL (range, 0.1-231.8 mL). The median prescribed dose and median prescribed biologically equivalent dose were 15 Gy (range, 9-40 Gy) and 67 Gy (range, 14-116 Gy), respectively. Ninety-seven patients were treated with single-fraction SRS, 74 received 2 to 5 fractions, and 2 received >5 fractions. RESULTS: The median follow-up was 21.0 months. Thirteen patients (8%) developed symptomatic peritumoral edema, with a median onset time of 4.5 months (range, 0.2-9.5 months). The 3-, 6-, 12-, and 24-month actuarial symptomatic edema rates were 2.9%, 4.9%, 7.7%, and 8.5%, respectively. The crude tumor control rate was 94%. On univariate analysis, large tumor volume (P = .01) and single-fraction SRS (P = .04) were predictive for development of posttreatment edema. CONCLUSION: SRS meningioma treatment demonstrated a low incidence of toxicity; however, large tumor volumes and single-fraction SRS treatment had an increased risk for posttreatment edema. Risk factors for edema should be considered in meningiomas treatment.

Metabolic footprinting of the anaerobic bacterium Fusobacterium varium using 1H NMR spectroscopy.

Metabolic footprinting of the anaerobic bacterium Fusobacterium varium demonstrated the accumulation of six carboxylic acids as metabolic end-products and revealed specific growth requirements and utilization capabilities towards amino acids. Guided by (1)H NMR determinations of residual amino acids in spent medium, a modified chemically defined minimal medium (CDMM*) was developed by minimizing the amino acid composition while satisfying nutritional requirements to support abundant growth of F. varium. Quantitative determinations of carboxylate salts and residual substrates were readily performed by (1)H NMR analysis of lyophilized residues from CDMM* cultures without interference from initial medium components. Only small concentrations of alanine, arginine, glycine, isoleucine, leucine, methionine, proline and valine were required to support growth of F. varium, whereas larger quantities of aspartate, asparagine, cysteine, glutamine, glutamate, histidine, lysine, serine and threonine were utilized, most likely as energy sources. Both bacterial growth and the distribution of carboxylate end-products depended on the composition of the chemically defined medium. In cultures provided with glucose as the primary energy source, the accumulation of butyrate and lactate correlated with growth, consistent with the regeneration of reduced coenzyme formed by the oxidative steps of glucose catabolism.

Multiplex protein assays based on real-time magnetic nanotag sensing.

Magnetic nanotags (MNTs) are a promising alternative to fluorescent labels in biomolecular detection assays, because minute quantities of MNTs can be detected with inexpensive giant magnetoresistive (GMR) sensors, such as spin valve (SV) sensors. However, translating this promise into easy to use and multilplexed protein assays, which are highly sought after in molecular diagnostics such as cancer diagnosis and treatment monitoring, has been challenging. Here, we demonstrate multiplex protein detection of potential cancer markers at subpicomolar concentration levels and with a dynamic range of more than four decades. With the addition of nanotag amplification, the analytic sensitivity extends into the low fM concentration range. The multianalyte ability, sensitivity, scalability, and ease of use of the MNT-based protein assay technology make it a strong contender for versatile and portable molecular diagnostics in both research and clinical settings.

Volatile mixture analysis by repetitive injection fast gas chromatography/mass spectrometry.

An apparatus designed for repetitive sampling and characterization of evolved gas mixtures generated during thermal analysis is described. The apparatus combines fast temperature ramp gas chromatography separations with mass spectrometric detection to selectively monitor volatile mixture component concentration changes as a function of sample temperature. The apparatus was tested by using it to repetitively sample and analyze the volatile products generated when poly(styrene) was catalytically cracked by an HY zeolite solid acid catalyst by heating the polymer/catalyst mixture in an inert helium atmosphere. Eleven mixture components contained in the gas stream were separated and detected at 90-s intervals when the polymer/catalyst sample was heated from 200 to 400 degrees C. Mass spectral extracted ion chromatograms were employed to generate species-specific evolution temperature profiles, which provided insight into thermal reaction mechanisms.

Giant magnetoresistive biochip for DNA detection and HPV genotyping.

A giant magnetoresistive (GMR) biochip based on spin valve sensor array and magnetic nanoparticle labels was developed for inexpensive, sensitive and reliable DNA detection. The DNA targets detected in this experiment were PCR products amplified from Human Papillomavirus (HPV) plasmids. The concentrations of the target DNA after PCR were around 10 nM in most cases, but concentrations of 10 pM were also detectable, which is demonstrated by experiments with synthetic DNA samples. A mild but highly specific surface chemistry was used for probe oligonucleotide immobilization. Double modulation technique was used for signal detection in order to reduce the 1/f noise in the sensor. Twelve assays were performed with an accuracy of approximately 90%. Magnetic signals were consistent with particle coverage data measured with Scanning Electron Microscopy (SEM). More recent research on microfluidics showed the potential of reducing the assay time below one hour. This is the first demonstration of magnetic DNA detection using plasmid-derived samples. This study provides a direct proof that GMR sensors can be used for biomedical applications.

Phase III quality-of-life study results: impact on patients' quality of life to reducing xerostomia after radiotherapy for head-and-neck cancer--RTOG 97-09.

PURPOSE: To determine whether prevention of hyposalivation after curative radiotherapy (RT) to the head and neck improves patients' quality of life (QOL). METHODS AND MATERIALS: Patients were to receive at least 50 Gy to 50% of the volume of the major salivary glands, provide unstimulated and stimulated saliva samples, and complete the University of Washington head-and-neck QOL tool before RT and 3 and 6 months after RT. Patients were randomized to receive pilocarpine 5 mg or placebo q.i.d. RESULTS: A total of 249 patients was randomized between March 1998 and January 2000. Of these, 214 were eligible for QOL analysis. Patients were evenly distributed between arms by race, gender, tobacco use, tumor site, T stage (50% T2-T3), and salivary function. A Karnofsky performance status of 90% was more common in the pilocarpine arm. Twenty percent of the patients on the pilocarpine arm and 29% of the patients on the placebo arm were taking nutritional supplements. The placebo arm patients had greater mouth pain and chewing difficulties. Compliance for the QOL tool at 3 and 6 months was 65% and 50%, respectively. Despite statistically significant (p = 0.047 and p = 0.049, respectively) preservation of salivary function in the pilocarpine arm, patients on the pilocarpine arm reported difficulties with swallowing (75%), activity (80%), hyposalivation (64%), and taste (81%). No difference was noted between arms at 3 months in mucositis scores, with both arms demonstrating increased requirement for oral nutrients. CONCLUSION: Objective prevention of hyposalivation did not affect patients' assessment of salivary function or QOL because of the greater impact mucositis plays in QOL after RT.