Using diffusion MRI for measuring the temperature of cerebrospinal fluid within the lateral ventricles

AIM Hypothermia is often induced to reduce brain injury in newborns, following perinatal hypoxic-ischaemic events, and in adults following traumatic brain injury, stroke or cardiac arrest. We aimed to devise a method, based on diffusion-weighted MRI, to measure non-invasively the temperature of the cerebrospinal fluid in the lateral ventricles. METHODS The well-known temperature dependence of the water diffusion constant was used for the estimation of temperature. We carried out diffusion MRI measurements on a 3T Philips Achieva Scanner involving phantoms (filled with water or artificial cerebrospinal fluid while slowly cooling from 41 to 32 degrees C) and healthy adult volunteers. RESULTS The estimated temperature of water phantoms followed that measured using a mercury thermometer, but the estimates for artificial cerebrospinal fluid were 1.04 degrees C lower. After correcting for this systematic difference, the estimated temperature within the lateral ventricles of volunteers was 39.9 degrees C. Using diffusion directions less sensitive to cerebrospinal fluid flow, it was 37.7 degrees C, which was in agreement with the literature. CONCLUSION Although further improvements are needed, measuring the temperature within the lateral ventricles using diffusion MRI is a viable method that may be useful for clinical applications. We introduced the method, identified sources of error and offered remedies for each

Study on Phylogenetic Relationships, Variability, and Correlated Mutations in M2 Proteins of Influenza Virus A

M2 channel, an influenza virus transmembrane protein, serves as an important target for antiviral drug design. There are still discordances concerning the role of some residues involved in proton transfer as well as the mechanism of inhibition by commercial drugs. The viral M2 proteins show high conservativity; about 3/4 of the positions are occupied by one residue in over 95%. Nine M2 proteins from the H3N2 strain and possibly two proteins from H2N2 strains make a phylogenic cluster closely related to 2RLF. The variability range is limited to 4 residues/position with one exception. The 2RLF protein stands out by the presence of 2 serines at the positions 19 and 50, which are in most other M2 proteins occupied by cysteines. The study of correlated mutations shows that there are several positions with significant mutational correlation that have not been described so far as functionally important. That there are 5 more residues potentially involved in the M2 mechanism of action. The original software used in this work (Consensus Constructor, SSSSg, Corm, Talana) is freely accessible as stand-alone offline applications upon request to the authors. The other software used in this work is freely available online for noncommercial purposes at public services on bioinformatics such as ExPASy or NCBI. The study on mutational variability, evolutionary relationship, and correlated mutation presented in this paper is a potential way to explain more completely the role of significant factors in proton channel action and to clarify the inhibition mechanism by specific drugs

Diagnostic and therapeutic approaches for nonmetastatic breast cancer in Canada, and their associated costs

In an era of fiscal restraint, it is important to evaluate the resources required to diagnose and treat serious illnesses. As breast cancer is the major malignancy affecting Canadian women, Statistics Canada has analysed the resources required to manage this disease in Canada, and the associated costs. Here we report the cost of initial diagnosis and treatment of nonmetastatic breast cancer, including adjuvant therapies. Treatment algorithms for Stages I, II, and III of the disease were derived by age group (< 50 or ≥ 50 years old), principally from Canadian cancer registry data, supplemented, where necessary, by the results of surveys of Canadian oncologists. Data were obtained on breast cancer incidence by age, diagnostic work-up, stage at diagnosis, initial treatment, follow-up practice, duration of hospitalization and direct care costs. The direct health care costs associated with ‘standard’ diagnostic and therapeutic approaches were calculated for a cohort of 17 700 Canadian women diagnosed in 1995. Early stage (Stages I and II) breast cancer represented 87% of all incident cases, with 77% of cases occurring in women ≥ 50 years. Variations were noted in the rate of partial vs total mastectomy, according to stage and age group. Direct costs for diagnosis and initial treatment ranged from $8014 for Stage II women ≥ 50 years old, to$10 897 for Stage III women < 50 years old. Except for Stage III women < 50 years old, the largest expenditure was for hospitalization for surgery, followed by radiotherapy costs. Chemotherapy was the largest cost component for Stage III women < 50 years old. This report describes the cost of diagnosis and initial treatment of nonmetastatic breast cancer in Canada, assuming current practice patterns. A second report will describe the lifetime costs of treating all stages of breast cancer. These data will then be incorporated into Statistics Canada's Population Health Model (POHEM) to perform cost-effectiveness studies of new therapeutic interventions for breast cancer, such as the cost-effectiveness of day surgery, or of radiotherapy to all breast cancer patients undergoing breast surgery. © 1999 Cancer Research Campaig

Geyserite in Hot-Spring Siliceous Sinter: Window on Earth’s Hottest Terrestrial (Paleo)environment and its Extreme Life

International audienceSiliceous hot-spring deposits, or sinters, typically form in active, terrestrial (on land), volcanic terrains where magmatically heated waters circulating through the shallow crust emerge at the Earth's surface as silica-charged geothermal fluids. Geyserites are sinters affiliated with the highest temperature (~ 75–100 °C), natural geothermal fluid emissions, comprising localized, lithologically distinctive, hydrothermal silica precipitates that develop around geysers, spouters and spring-vents. They demarcate the position of hot-fluid upflow zones useful for geothermal energy and epithermal mineral prospecting. Near-vent areas also are “extreme environment” settings for the growth of microbial biofilms at near-boiling temperatures. Microbial biosignatures (e.g., characteristic silicified microbial textures, carbon isotopes, genetic material, lipid biomarkers) may be extracted from modern geyserite. However, because of strong taphonomic filtering and subsequent diagenesis, fossils in geyserite are very rare in the pre-Quaternary sinter record which, in and of itself, is patchy in time and space back to about 400 Ma. Only a few old examples are known, such as geyserite reported from the Devonian Drummond Basin (Australia), Devonian Rhynie cherts (Scotland), and a new example described herein from the spectacularly well-preserved, Late Jurassic (150 Ma), Yellowstone-style geothermal landscapes of Patagonia, Argentina. There, geyserite is associated with fossil vent-mounds and silicified hydrothermal breccias of the Claudia sinter, which is geologically related to the world-class Cerro Vanguardia gold/silver deposit of the Deseado Massif, a part of the Chon Aike siliceous large igneous province. Tubular, filament-like micro-inclusions from Claudia were studied using integrated petrographic and laser micro-Raman analysis, the results of which suggest a biological origin. The putative fossils are enclosed within nodular geyserite, a texture typical of subaerial near-vent conditions. Overall, this worldwide review of geyserite confirms its significance as a mineralizing geological archive reflecting the nature of Earth's highest temperature, habitable terrestrial sedimentary environment. Hot-spring depositional settings also may serve as analogs for early Earth paleoenvironments because of their elevated temperature of formation, rapid mineralization by silica, and morphologically comparable carbonaceous material sourced from prokaryotes adapted to life at high temperatures

Correlation between phenotypic antibiotic susceptibility and the resistome in Pseudomonas aeruginosa

Genetic determinants of antibiotic resistance (AR) have been extensively investigated. High-throughput sequencing allows for the assessment of the relationship between genotype and phenotype. A panel of 672 Pseudomonas aeruginosa strains was analysed, including representatives of globally disseminated multidrug-resistant and extensively drug-resistant clones; genomes and multiple antibiograms were available. This panel was annotated for AR gene presence and polymorphism, defining a resistome in which integrons were included. Integrons were present in >70 distinct cassettes, with In5 being the most prevalent. Some cassettes closely associated with clonal complexes, whereas others spread across the phylogenetic diversity, highlighting the importance of horizontal transfer. A resistome-wide association study (RWAS) was performed for clinically relevant antibiotics by correlating the variability in minimum inhibitory concentration (MIC) values with resistome data. Resistome annotation identified 147 loci associated with AR. These loci consisted mainly of acquired genomic elements and intrinsic genes. The RWAS allowed for correct identification of resistance mechanisms for meropenem, amikacin, levofloxacin and cefepime, and added 46 novel mutations. Among these, 29 were variants of the oprD gene associated with variation in meropenem MIC. Using genomic and MIC data, phenotypic AR was successfully correlated with molecular determinants at the whole-genome sequence level

Genetic epidemiology of motor neuron disease-associated variants in the Scottish population

Genetic understanding of motor neuron disease (MND) has evolved greatly in the past 10 years, including the recent identification of association between MND and variants in TBK1 and NEK1. Our aim was to determine the frequency of pathogenic variants in known MND genes and to assess whether variants in TBK1 and NEK1 contribute to the burden of MND in the Scottish population. SOD1, TARDBP, OPTN, TBK1, and NEK1 were sequenced in 441 cases and 400 controls. In addition to 44 cases known to carry a C9orf72 hexanucleotide repeat expansion, we identified 31 cases and 2 controls that carried a loss-of-function or pathogenic variant. Loss-of-function variants were found in TBK1 in 3 cases and no controls and, separately, in NEK1 in 3 cases and no controls. This study provides an accurate description of the genetic epidemiology of MND in Scotland and provides support for the contribution of both TBK1 and NEK1 to MND susceptibility in the Scottish population

Chronic migraine plus medication overuse headache: two entities or not?

Chronic migraine (CM) represents migraine natural evolution from its episodic form. It is realized through a chronicization phase that may require months or years and varies from patient to patient. The transition to more frequent attacks pattern is influenced by lifestyle, life events, comorbid conditions and personal genetic terrain, and it often leads to acute drugs overuse. Medication overuse headache (MOH) may complicate every type of headache and all the drugs employed for headache treatment can cause MOH. The first step in the management of CM complicated by medication overuse must be the withdrawal of the overused drugs and a detoxification treatment. The goal is not only to detoxify the patient and stop the chronic headache but also to improve responsiveness to acute or prophylactic drugs. Different methods have been suggested: gradual or abrupt withdrawal; home treatment, hospitalization, or a day-hospital setting; re-prophylaxes performed immediately or at the end of the wash-out period. Up to now, only topiramate and local injection of onabotulinumtoxinA have shown efficacy as therapeutic agents for re-prophylaxis after detoxification in patients with CM with and without medication overuse. Although the two treatments showed similar efficacy, onabotulinumtoxinA is associated with a better adverse events profile. Recently, the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program proved that patients with CM, even those with MOH, are the ones most likely to benefit from onabotulinumtoxinA treatment. Furthermore, it provided an injection paradigm that can be used as a guide for a correct administration of onabotulinumtoxinA