Detailed Structural Analysis of Lipids Directly on Tissue Specimens Using a MALDI-SpiralTOF-Reflectron TOF Mass Spectrometer

Direct tissue analysis using a novel tandem time-of-flight (TOF-TOF) mass spectrometer is described. This system consists of a matrix-assisted laser desorption/ionization ion source, a spiral ion trajectory TOF mass spectrometer “SpiralTOF (STOF)”, a collision cell, and an offset parabolic reflectron (RTOF). The features of this system are high precursor ion selectivity due to a 17-m flight path length in STOF and elimination of post-source decay (PSD) ions. The acceleration energy is 20 keV, so that high-energy collision-induced dissociation (HE-CID) is possible. Elimination of PSD ions allows observation of the product ions inherent to the HE-CID process. By using this tandem TOF instrument, the product ion spectrum of lipids provided detailed structural information of fatty acid residues

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Classification and clinical features of headache patients: an outpatient clinic study from China

This study aimed to analyze and classify the clinical features of headache in neurological outpatients. A cross-sectional study was conducted consecutively from March to May 2010 for headache among general neurological outpatients attending the First Affiliated Hospital of Chongqing Medical University. Personal interviews were carried out and a questionnaire was used to collect medical records. Diagnosis of headache was according to the International classification of headache disorders, 2nd edition (ICHD-II). Headache patients accounted for 19.5% of the general neurology clinic outpatients. A total of 843 (50.1%) patients were defined as having primary headache, 454 (27%) secondary headache, and 386 (23%) headache not otherwise specified (headache NOS). For primary headache, 401 (23.8%) had migraine, 399 (23.7%) tension-type headache (TTH), 8 (0.5%) cluster headache and 35 (2.1%) other headache types. Overall, migraine patients suffered (1) more severe headache intensity, (2) longer than 6 years of headache history and (3) more common analgesic medications use than TTH ones (p < 0.001).TTH patients had more frequent episodes of headaches than migraine patients, and typically headache frequency exceeded 15 days/month (p < 0.001); 22.8% of primary headache patients were defined as chronic daily headache. Almost 20% of outpatient visits to the general neurology department were of headache patients, predominantly primary headache of migraine and TTH. In outpatient headaches, more attention should be given to headache intensity and duration of headache history for migraine patients, while more attention to headache frequency should be given for the TTH ones

Tumour budding in oral squamous cell carcinoma : a meta-analysis

Background: Tumour budding has been reported as a promising prognostic marker in many cancers. This meta-analysis assessed the prognostic value of tumour budding in oral squamous cell carcinoma (OSCC). Methods: We searched OvidMedline, PubMed, Scopus and Web of Science for articles that studied tumour budding in OSCC. We used reporting recommendations for tumour marker (REMARK) criteria to evaluate the quality of studies eligible for meta-analysis. Results: A total of 16 studies evaluated the prognostic value of tumour budding in OSCC. The meta-analysis showed that tumour budding was significantly associated with lymph node metastasis (odds ratio = 7.08, 95% CI = 1.75-28.73), disease-free survival (hazard ratio = 1.83, 95% CI = 1.34-2.50) and overall survival (hazard ratio = 1.88, 95% CI = 1.25-2.82). Conclusions: Tumour budding is a simple and reliable prognostic marker for OSCC. Evaluation of tumour budding could facilitate personalised management of OSCC.Peer reviewe

Troponin elevation in acute ischemic stroke (TRELAS) - protocol of a prospective observational trial

<p>Abstract</p> <p>Background</p> <p>Levels of the cardiac muscle regulatory protein troponin T (cTnT) are frequently elevated in patients with acute ischemic stroke and elevated cTnT predicts poor outcome and mortality. The pathomechanism of troponin release may relate to co-morbid coronary artery disease and myocardial ischemia or, alternatively, to neurogenic cardiac damage due to autonomic activation after acute ischemic stroke. Therefore, there is uncertainty about how acute ischemic stroke patients with increased cTnT levels should be managed regarding diagnostic and therapeutic workup.</p> <p>Methods/Design</p> <p>The primary objective of the prospective observational trial TRELAS (TRoponin ELevation in Acute ischemic Stroke) is to investigate the frequency and underlying pathomechanism of cTnT elevation in acute ischemic stroke patients in order to give guidance for clinical practice. All consecutive patients with acute ischemic stroke admitted within 72 hours after symptom onset to the Department of Neurology at the Campus Benjamin Franklin of the University Hospital Charité will be screened for cTnT elevations (i.e. >= 0.05 μg/l) on admission and again on the following day. Patients with increased cTnT will undergo coronary angiography within 72 hours. Diagnostic findings of coronary angiograms will be compared with age- and gender-matched patients presenting with Non-ST-Elevation myocardial infarction to the Department of Cardiology. The primary endpoint of the study will be the occurrence of culprit lesions in the coronary angiogram indicating underlying co-morbid obstructive coronary artery disease. Secondary endpoints will be the localization of stroke in the cerebral imaging and left ventriculographic findings of wall motion abnormalities suggestive of stroke-induced global cardiac dysfunction.</p> <p>Discussion</p> <p>TRELAS will prospectively determine the frequency and possible etiology of troponin elevation in a large cohort of ischemic stroke patients. The findings are expected to contribute to clarify pathophysiologic concepts of co-morbid cardiac damage in ischemic stroke patients and also to provide a basis for clinical recommendations for cardiac workup of such patients.</p> <p>Trial registration</p> <p>clinicaltrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01263964">NCT01263964</a></p

How do nutrient conditions and species identity influence the impact of mesograzers in eelgrass-epiphyte systems?

Coastal eutrophication is thought to cause excessive growth of epiphytes in eelgrass beds, threatening the health and survival of these ecologically and economically valuable ecosystems worldwide. Mesograzers, small crustacean and gastropod grazers, have the potential to prevent seagrass loss by grazing preferentially and efficiently on epiphytes. We tested the impact of three mesograzers on epiphyte biomass and eelgrass productivity under threefold enriched nutrient concentrations in experimental indoor mesocosm systems under summer conditions. We compared the results with earlier identical experiments that were performed under ambient nutrient supply. The isopod Idotea baltica, the periwinkle Littorina littorea, and the small gastropod Rissoa membranacea significantly reduced epiphyte load under high nutrient supply with Rissoa being the most efficient grazer, but only high densities of Littorina and Rissoa had a significant positive effect on eelgrass productivity. Although all mesograzers increased epiphyte ingestion with higher nutrient load, most likely as a functional response to the quantitatively and qualitatively better food supply, the promotion of eelgrass growth by Idotea and Rissoa was diminished compared to the study performed under ambient nutrient supply. Littorina maintained the level of its positive impact on eelgrass productivity regardless of nutrient concentrations

The prevalence of waterpipe tobacco smoking among the general and specific populations: a systematic review

Abstract Background The objective of this study was to systematically review the medical literature for the prevalence of waterpipe tobacco use among the general and specific populations. Methods We electronically searched MEDLINE, EMBASE, and the ISI the Web of Science. We selected studies using a two-stage duplicate and independent screening process. We included cohort studies and cross sectional studies assessing the prevalence of use of waterpipe in either the general population or a specific population of interest. Two reviewers used a standardized and pilot tested form to collect data from each eligible study using a duplicate and independent screening process. We stratified the data analysis by country and by age group. The study was not restricted to a specific context. Results Of a total of 38 studies, only 4 were national surveys; the rest assessed specific populations. The highest prevalence of current waterpipe smoking was among school students across countries: the United States, especially among Arab Americans (12%-15%) the Arabic Gulf region (9%-16%), Estonia (21%), and Lebanon (25%). Similarly, the prevalence of current waterpipe smoking among university students was high in the Arabic Gulf region (6%), the United Kingdom (8%), the United States (10%), Syria (15%), Lebanon (28%), and Pakistan (33%). The prevalence of current waterpipe smoking among adults was the following: Pakistan (6%), Arabic Gulf region (4%-12%), Australia (11% in Arab speaking adults), Syria (9%-12%), and Lebanon (15%). Group waterpipe smoking was high in Lebanon (5%), and Egypt (11%-15%). In Lebanon, 5%-6% pregnant women reported smoking waterpipe during pregnancy. The studies were all cross-sectional and varied by how they reported waterpipe smoking. Conclusion While very few national surveys have been conducted, the prevalence of waterpipe smoking appears to be alarmingly high among school students and university students in Middle Eastern countries and among groups of Middle Eastern descent in Western countries

LRIG1 regulates cadherin-dependent contact inhibition directing epithelial homeostasis and pre-invasive squamous cell carcinoma development.

Epidermal growth factor receptor (EGFR) pathway activation is a frequent event in human carcinomas. Mutations in EGFR itself are, however, rare, and the mechanisms regulating EGFR activation remain elusive. Leucine-rich immunoglobulin repeats-1 (LRIG1), an inhibitor of EGFR activity, is one of four genes identified that predict patient survival across solid tumour types including breast, lung, melanoma, glioma, and bladder. We show that deletion of Lrig1 is sufficient to promote murine airway hyperplasia through loss of contact inhibition and that re-expression of LRIG1 in human lung cancer cells inhibits tumourigenesis. LRIG1 regulation of contact inhibition occurs via ternary complex formation with EGFR and E-cadherin with downstream modulation of EGFR activity. We find that LRIG1 LOH is frequent across cancers and its loss is an early event in the development of human squamous carcinomas. Our findings imply that the early stages of squamous carcinoma development are driven by a change in amplitude of EGFR signalling governed by the loss of contact inhibition

Elucidation of the Mode of Action of a New Antibacterial Compound Active against Staphylococcus aureus and Pseudomonas aeruginosa.

Nosocomial and community-acquired infections caused by multidrug resistant bacteria represent a major human health problem. Thus, there is an urgent need for the development of antibiotics with new modes of action. In this study, we investigated the antibacterial characteristics and mode of action of a new antimicrobial compound, SPI031 (N-alkylated 3, 6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol), which was previously identified in our group. This compound exhibits broad-spectrum antibacterial activity, including activity against the human pathogens Staphylococcus aureus and Pseudomonas aeruginosa. We found that SPI031 has rapid bactericidal activity (7-log reduction within 30 min at 4x MIC) and that the frequency of resistance development against SPI031 is low. To elucidate the mode of action of SPI031, we performed a macromolecular synthesis assay, which showed that SPI031 causes non-specific inhibition of macromolecular biosynthesis pathways. Liposome leakage and membrane permeability studies revealed that SPI031 rapidly exerts membrane damage, which is likely the primary cause of its antibacterial activity. These findings were supported by a mutational analysis of SPI031-resistant mutants, a transcriptome analysis and the identification of transposon mutants with altered sensitivity to the compound. In conclusion, our results show that SPI031 exerts its antimicrobial activity by causing membrane damage, making it an interesting starting point for the development of new antibacterial therapies