Obtaining 20 μm Spatial Resolution with a 2940 nm Laser by IR-MALDESI Mass Spectrometry Imaging.

High spatial resolution is a key parameter in mass spectrometry imaging (MSI), enabling a greater understanding of system biology and cellular processes. Using a novel IR laser with good Gaussian beam quality ( = 4) coupled with spatial filtering and a reflective objective, 20 μm spatial resolution was obtained by IR-MALDESI. The optical train was optimized on burn paper before demonstrating feasibility for imaging of liver tissue.

Quasi-continuous infrared matrix-assisted laser desorption electrospray ionization source coupled to a quadrupole time-of-flight mass spectrometer for direct analysis from well plates.

High-throughput screening (HTS) is a technique mostly used by pharmaceutical companies to rapidly screen multiple libraries of compounds to find drug hits with biological or pharmaceutical activity. Mass spectrometry (MS) has become a popular option for HTS given that it can simultaneously resolve hundreds to thousands of compounds without additional chemical derivatization. For this application, it is convenient to do direct analysis from well plates.

Transforming a Mid-infrared Laser Profile from Gaussian to a Top-Hat with a Diffractive Optical Element for Mass Spectrometry Imaging.

Many mass spectrometry imaging (MSI) applications such as infrared matrix-assisted electrospray ionization (IR-MALDESI) employ an infrared (IR) laser with a Gaussian profile where laser irradiance is highest in the center and decreases exponentially. To enable full ablation of a square region of interest, oversampling is often needed, which results in nonuniform ablation and leads to decreased image quality. A diffractive optical element (DOE) was integrated into the optical path to generate homogeneous intensity distributions while maintaining laser energy above the ablation threshold, to enable complete sample removal from laser pulses without oversampling.

Next-Generation Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Source for Mass Spectrometry Imaging and High-Throughput Screening.

Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is a hybrid, ambient ionization source that combines the advantages of electrospray ionization and matrix-assisted laser desorption/ionization, making it a versatile tool for both high-throughput screening (HTS) and mass spectrometry imaging (MSI) studies. To expand the capabilities of the IR-MALDESI source, an entirely new architecture was designed to overcome the key limitations of the previous source. This next-generation (NextGen) IR-MALDESI source features a vertically mounted IR-laser, a planar translation stage with computerized sample height control, an aluminum enclosure, and a novel mass spectrometer interface plate.

Improved spatial resolution of infrared matrix-assisted laser desorption electrospray ionization mass spectrometry imaging using a reflective objective.

Rationale: The level of visual detail of a mass spectrometry image is dependent on the spatial resolution with which it is acquired, which is largely determined by the focal diameter in infrared laser ablation-based techniques. While the use of mid-IR light for mass spectrometry imaging (MSI) has advantages, it results in a relatively large focal diameter and spatial resolution. The continual advancement of infrared matrix-assisted electrospray ionization (IR-MALDESI) for MSI warranted novel methods to decrease laser ablation areas and thus improve spatial resolution.

Tailoring of Versatile Surface Morphologies on Hot Dip Galvanized Steel in Wet CO: Aspects on Formation, Barrier Properties, and Utilization as a Substrate for Coatings.

Zinc carbonate and a mixed-phase zinc carbonate were precipitated selectively on hot dip galvanized steel in the presence of CO and water. The zinc carbonate was precipitated as a uniform layer with cubic superficial appearance, while the mixed-phase zinc carbonate was precipitated as nanowires. The distinct structures could be formed separately or as a dual structure with nanowires on the outermost surface.

Conditional mouse models support the role of SLC39A14 (ZIP14) in Hyperostosis Cranialis Interna and in bone homeostasis.

Hyperostosis Cranialis Interna (HCI) is a rare bone disorder characterized by progressive intracranial bone overgrowth at the skull. Here we identified by whole-exome sequencing a dominant mutation (L441R) in SLC39A14 (ZIP14). We show that L441R ZIP14 is no longer trafficked towards the plasma membrane and excessively accumulates intracellular zinc, resulting in hyper-activation of cAMP-CREB and NFAT signaling.

Characterization of a novel miniaturized burst-mode infrared laser system for IR-MALDESI mass spectrometry imaging.

Laser systems are widely used in mass spectrometry as sample probes and ionization sources. Mid-infrared lasers are particularly suitable for analysis of high water content samples such as animal and plant tissues, using water as a resonantly excited sacrificial matrix. Commercially available mid-IR lasers have historically been bulky and expensive due to cooling requirements.

IR-MALDESI Mass Spectrometry Imaging at 50 Micron Spatial Resolution.

High spatial resolution in mass spectrometry imaging (MSI) is crucial to understanding the biology dictated by molecular distributions in complex tissue systems. Here, we present MSI using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) at 50 μm resolution. An adjustable iris, beam expander, and an aspherical focusing lens were used to reduce tissue ablation diameters for MSI at high resolution.

Genetic polymorphisms in UDP-glucuronosyltransferase 1A6 and 1A7 and the risk for benign Warthin's tumors of the parotid gland.

Background: Warthin's tumors of the parotid gland are associated with smoking, whereas pleomorphic adenomas are not. Genetic polymorphisms in biotransformation enzymes, involved in detoxification of toxins and carcinogens in cigarette smoke, might modify the corresponding enzyme activity and influence detoxifying capacity. We hypothesize that these genetic polymorphisms may influence the individual risk for Warthin's tumor, but not for pleomorphic adenomas.

Late-onset systemic lupus erythematosus in Latin Americans: a distinct subgroup?

Objective: To examine the characteristics of patients who developed late onset systemic lupus erythematosus (SLE) in the GLADEL (Grupo Latino Americano de Estudio del Lupus) cohort of patients with SLE.

Methods: Patients with SLE of less than two years of disease duration, seen at 34 centers of nine Latin American countries, were included. Late-onset was defined as >50 years of age at time of first SLE-related symptom.

Optimising the pre-treatment process before mobile ear surgery for chronic suppurative otitis media in Wolisso and Attat, Ethiopia.

Background: Chronic suppurative otitis media is a major cause of long-standing hearing impairment in many Sub-Saharan African countries.

Methods: Attempts were made to optimise the pre-treatment process before mobile ear surgery for chronic suppurative otitis media in Wolisso, a semi-urban community in the Oromia region, and in Attat, a rural community in the Gurage region, both in the south-west of Ethiopia, between 2008 and 2010. This included special training for ENT nurses, and the use of a strict scheduling regime and improved topical treatment.

Chromosome instability predicts progression of premalignant lesions of the larynx.

The histopathology of premalignant laryngeal lesions does not provide reliable information on the risk of malignant transformation, hence we examined new molecular markers which can easily be implemented in clinical practice. Dual-target fluorescence in situ hybridisation (FISH) for chromosome 1 and 7 centromeres was performed on tissue sections of laryngeal premalignancies in 69 patients. Chromosome instability was indicated by numerical imbalances and/or polysomy for chromosomes 1 and 7.

Sclerosing bone dysplasias with involvement of the craniofacial skeleton.

In this review we provide a complete overview of the existing sclerosing bone dysplasias with craniofacial involvement. Clinical presentation, disease course, the craniofacial symptoms, genetic transmission pattern and pathophysiology are discussed. There is an emphasis on radiologic features with a large collection of CT and MRI images.

Localization of the gene for hyperostosis cranialis interna to chromosome 8p21 with analysis of three candidate genes.

Hyperostosis cranialis interna (HCI) is a rare autosomal dominant disorder characterized by intracranial hyperostosis and osteosclerosis, which is confined to the skull, especially the calvarium and the skull base. The rest of the skeleton is not affected. Progressive bone overgrowth causes nerve entrapment that leads to recurrent facial nerve palsy, disturbance of the sense of smell, hearing and vision impairments, impairment of facial sensibility, and disturbance of balance due to vestibular areflexia.

Neurophysiologic, audiometric and vestibular function tests in patients with hyperostosis cranialis interna.

Objective: Hyperostosis cranialis interna (HCI) is an autosomal dominant sclerosing bone dysplasia affecting the skull base and the calvaria, characterized by cranial nerve deficits due to stenosis of neuroforamina. The aim of this study is to describe the value of several neurophysiological, audiometric and vestibular tests related to the clinical course of the disorder.

Methods: Ten affected subjects and 13 unaffected family members were recruited and tested with visual evoked potentials, masseter reflex, blink reflex, pure tone and speech audiometry, stapedial reflexes, otoacoustic emissions, brainstem evoked response audiometry and electronystagmography.

Combined effect of genetic polymorphisms in phase I and II biotransformation enzymes on head and neck cancer risk.

Background: Combinations of genetic polymorphisms in biotransformation enzymes might modify the individual risk for head and neck cancer.

Methods: Blood from 432 patients with head and neck cancer and 437 controls was investigated for genetic polymorphisms in 9 different phase I and II biotransformation enzymes. Analysis of the risk-modifying effect was performed according to predicted enzyme activities, based on genetic polymorphisms in the corresponding genes.

Versatile method for achieving 1% speckle contrast in large-venue laser projection displays using a stationary multimode optical fiber.

We propose a method based on quantitative theoretical analysis for achieving speckle contrast of 1% or less in images created by a full-frame laser projection display system. The method employs a stationary multimode optical fiber to achieve the effect of using a rapidly moving diffuser, but without moving the fiber or any other system component. When a suitably large projector lens is used, low-speckle illumination light delivered through the fiber acts in conjunction with wavelength diversity at the projection screen to achieve speckle contrast of 1% in viewed images.

Imaging features and progression of hyperostosis cranialis interna.

Background And Purpose: HCI is a unique autosomal-dominant sclerosing bone dysplasia affecting the skull base and the calvaria, characterized by cranial nerve deficits due to stenosis of neuroforamina, whereby the mandible is affected to a lesser extent. The aim of this study is to describe the specific radiologic characteristics and course of the disorder.

Materials And Methods: CT scans of affected individuals within 1 family were analyzed and compared with scans of their unaffected family members and with an age- and sex-matched control group.

A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls.

Genetic polymorphism in the conjugating enzyme UGT1A1 and the risk of head and neck cancer.

UDP-glucuronosyltransferase 1A1 (UGT1A1) is an enzyme which catalyses not only the glucuronidation of tobacco smoke carcinogens like benzopyrene, but also of the endogenous substrate bilirubin. Bilirubin for a long time was considered to be only a toxic waste product of hemoglobin degradation, but recent findings have shown that bilirubin is a potent antioxidant, which may play a protective role against cancer. We investigated whether a genetic polymorphism in UGT1A1 (UGT1A1*28), associated with a reduced UGT1A1 enzyme activity, may have a risk-modifying effect on head and neck carcinogenesis.

A sex-specific association between a 15q25 variant and upper aerodigestive tract cancers.

Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.

Bone metabolic activity in hyperostosis cranialis interna measured with 18F-fluoride PET.

Purpose: (18)F-Fluoride PET/CT is a relatively undervalued diagnostic test to measure bone metabolism in bone diseases. Hyperostosis cranialis interna (HCI) is a (hereditary) bone disease characterised by endosteal hyperostosis and osteosclerosis of the skull and the skull base. Bone overgrowth causes entrapment and dysfunction of several cranial nerves.

Shared care for hearing complaints: guideline effects on patient flow.

Rationale, Aims And Objectives: A national guideline was proposed to enable shared care in hearing complaints and therefore to change patient flows. In this study the effect of this guideline is evaluated.

Methods: From a total of 3500 patients with hearing complaints, consulting the Ear Nose and Throat Department of a large non-university hospital in the Netherlands in 2002, a random sample of 1000 patients was selected.