An international group of neurologists and radiologists developed revised guidelines for standardized brain and spinal cord MR imaging for the diagnosis and follow-up of MS. A brain MR imaging with ...gadolinium is recommended for the diagnosis of MS. A spinal cord MR imaging is recommended if the brain MR imaging is nondiagnostic or if the presenting symptoms are at the level of the spinal cord. A follow-up brain MR imaging with gadolinium is recommended to demonstrate dissemination in time and ongoing clinically silent disease activity while on treatment, to evaluate unexpected clinical worsening, to re-assess the original diagnosis, and as a new baseline before starting or modifying therapy. A routine brain MR imaging should be considered every 6 months to 2 years for all patients with relapsing MS. The brain MR imaging protocol includes 3D T1-weighted, 3D T2-FLAIR, 3D T2-weighted, post-single-dose gadolinium-enhanced T1-weighted sequences, and a DWI sequence. The progressive multifocal leukoencephalopathy surveillance protocol includes FLAIR and DWI sequences only. The spinal cord MR imaging protocol includes sagittal T1-weighted and proton attenuation, STIR or phase-sensitive inversion recovery, axial T2- or T2*-weighted imaging through suspicious lesions, and, in some cases, postcontrast gadolinium-enhanced T1-weighted imaging. The clinical question being addressed should be provided in the requisition for the MR imaging. The radiology report should be descriptive, with results referenced to previous studies. MR imaging studies should be permanently retained and available. The current revision incorporates new clinical information and imaging techniques that have become more available.
The promise of “personalized medicine” guided by an understanding of each individual's genome has been fostered by increasingly powerful and economical methods to acquire clinically relevant ...information. We describe the operational implementation of prospective genotyping linked to an advanced clinical decision‐support system to guide individualized health care in a large academic health center. This approach to personalized medicine entails engagement between patient and health‐care provider, identification of relevant genetic variations for implementation, assay reliability, point‐of‐care decision support, and necessary institutional investments. In one year, approximately 3,000 patients, most of whom were scheduled for cardiac catheterization, were genotyped on a multiplexed platform that included genotyping for CYP2C19 variants that modulate response to the widely used antiplatelet drug clopidogrel. These data are deposited into the electronic medical record (EMR), and point‐of‐care decision support is deployed when clopidogrel is prescribed for those with variant genotypes. The establishment of programs such as this is a first step toward implementing and evaluating strategies for personalized medicine.
Clinical Pharmacology & Therapeutics (2012); 92 1, 87–95. doi:10.1038/clpt.2011.371
Several studies have proposed that brain glutamate signaling abnormalities and glial pathology have a role in the etiology of major depressive disorder (MDD). These conclusions were primarily drawn ...from post-mortem studies in which forebrain brain regions were examined. The locus coeruleus (LC) is the primary source of extensive noradrenergic innervation of the forebrain and as such exerts a powerful regulatory role over cognitive and affective functions, which are dysregulated in MDD. Furthermore, altered noradrenergic neurotransmission is associated with depressive symptoms and is thought to have a role in the pathophysiology of MDD. In the present study we used laser-capture microdissection (LCM) to selectively harvest LC tissue from post-mortem brains of MDD patients, patients with bipolar disorder (BPD) and from psychiatrically normal subjects. Using microarray technology we examined global patterns of gene expression. Differential mRNA expression of select candidate genes was then interrogated using quantitative real-time PCR (qPCR) and in situ hybridization (ISH). Our findings reveal multiple signaling pathway alterations in the LC of MDD but not BPD subjects. These include glutamate signaling genes, SLC1A2, SLC1A3 and GLUL, growth factor genes FGFR3 and TrkB, and several genes exclusively expressed in astroglia. Our data extend previous findings of altered glutamate, astroglial and growth factor functions in MDD for the first time to the brainstem. These findings indicate that such alterations: (1) are unique to MDD and distinguishable from BPD, and (2) affect multiple brain regions, suggesting a whole-brain dysregulation of such functions.
All DNA polymerases misincorporate ribonucleotides despite their preference for deoxyribonucleotides, and analysis of cultured cells indicates that mammalian mitochondrial DNA (mtDNA) tolerates such ...replication errors. However, it is not clear to what extent misincorporation occurs in tissues, or whether this plays a role in human disease. Here, we show that mtDNA of solid tissues contains many more embedded ribonucleotides than that of cultured cells, consistent with the high ratio of ribonucleotide to deoxynucleotide triphosphates in tissues, and that riboadenosines account for three-quarters of them. The pattern of embedded ribonucleotides changes in a mouse model of Mpv17 deficiency, which displays a marked increase in rGMPs in mtDNA. However, while the mitochondrial dGTP is low in the Mpv17-/- liver, the brain shows no change in the overall dGTP pool, leading us to suggest that Mpv17 determines the local concentration or quality of dGTP. Embedded rGMPs are expected to distort the mtDNA and impede its replication, and elevated rGMP incorporation is associated with early-onset mtDNA depletion in liver and late-onset multiple deletions in brain of Mpv17-/- mice. These findings suggest aberrant ribonucleotide incorporation is a primary mtDNA abnormality that can result in pathology.
Two consecutive cruises in the Weddell Sea, Antarctica, in winter 2013 provided the first direct observations of sea salt aerosol (SSA) production from blowing snow above sea ice, thereby validating ...a model hypothesis to account for winter time SSA maxima in the Antarctic. Blowing or drifting snow often leads to increases in SSA during and after storms. For the first time it is shown that snow on sea ice is depleted in sulfate relative to sodium with respect to seawater. Similar depletion in bulk aerosol sized ∼0.3–6 µm above sea ice provided the evidence that most sea salt originated from snow on sea ice and not the open ocean or leads, e.g. >90 % during the 8 June to 12 August 2013 period. A temporally very close association of snow and aerosol particle dynamics together with the long distance to the nearest open ocean further supports SSA originating from a local source. A mass budget estimate shows that snow on sea ice contains even at low salinity (<0.1 psu) more than enough sea salt to account for observed increases in atmospheric SSA during storms if released by sublimation. Furthermore, snow on sea ice and blowing snow showed no or small depletion of bromide relative to sodium with respect to seawater, whereas aerosol was enriched at 2 m and depleted at 29 m, suggesting that significant bromine loss takes place in the aerosol phase further aloft and that SSA from blowing snow is a source of atmospheric reactive bromine, an important ozone sink, even during winter darkness. The relative increase in aerosol concentrations with wind speed was much larger above sea ice than above the open ocean, highlighting the importance of a sea ice source in winter and early spring for the aerosol burden above sea ice. Comparison of absolute increases in aerosol concentrations during storms suggests that to a first order corresponding aerosol fluxes above sea ice can rival those above the open ocean depending on particle size. Evaluation of the current model for SSA production from blowing snow showed that the parameterizations used can generally be applied to snow on sea ice. Snow salinity, a sensitive model parameter, depends to a first order on snowpack depth and therefore was higher above first-year sea ice (FYI) than above multi-year sea ice (MYI). Shifts in the ratio of FYI and MYI over time are therefore expected to change the seasonal SSA source flux and contribute to the variability of SSA in ice cores, which represents both an opportunity and a challenge for the quantitative interpretation of sea salt in ice cores as a proxy for sea ice.
SATELLITE AND IN SITU SALINITY Boutin, J.; Chao, Y.; Asher, W. E. ...
Bulletin of the American Meteorological Society,
08/2016, Letnik:
97, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Remote sensing of salinity using satellite-mounted microwave radiometers provides new perspectives for studying ocean dynamics and the global hydrological cycle. Calibration and validation of these ...measurements is challenging because satellite and in situ methods measure salinity differently. Microwave radiometers measure the salinity in the top few centimeters of the ocean, whereas most in situ observations are reported below a depth of a few meters. Additionally, satellites measure salinity as a spatial average over an area of about 100 × 100 km². In contrast, in situ sensors provide pointwise measurements at the location of the sensor. Thus, the presence of vertical gradients in, and horizontal variability of, sea surface salinity complicates comparison of satellite and in situ measurements. This paper synthesizes present knowledge of the magnitude and the processes that contribute to the formation and evolution of vertical and horizontal variability in near-surface salinity. Rainfall, freshwater plumes, and evaporation can generate vertical gradients of salinity, and in some cases these gradients can be large enough to affect validation of satellite measurements. Similarly, mesoscale to submesoscale processes can lead to horizontal variability that can also affect comparisons of satellite data to in situ data. Comparisons between satellite and in situ salinity measurements must take into account both vertical stratification and horizontal variability.
ABSTRACT
We present Atacama Large Millimeter/Sub-millimeter Array observations of the candidate jet–ISM interaction zones near the black hole X-ray binaries GRS 1758−258 and 1E 1740.7−2942. Using ...these data, we map the molecular line emission in the regions, detecting emission from the HCN J = 1−0, HCO+ J = 1−0, SiO J = 2−1, CS J = 2−1, 13CO J = 1−0, C18O J = 1−0, HNCO J = 40,4−30,3, HNCO J = 50,5−40,4, and CH3OH J = 21,1−11,0 molecular transitions. Through examining the morphological, spectral, and kinematic properties of this emission, we identify molecular structures that may trace jet-driven cavities in the gas surrounding these systems. Our results from the GRS 1758−258 region in particular, are consistent with recent work, which postulated the presence of a jet-blown cocoon structure in deep radio continuum maps of the region. Using these newly discovered molecular structures as calorimeters, we estimate the time averaged jet power from these systems, finding $(1.1{\!-\!}5.7)\times 10^{36}{\rm erg\, s}^{-1}$ over 0.12−0.31 Myr for GRS 1758−258 and $(0.7{\!-\!}3.5)\times 10^{37}{\rm erg\, s}^{-1}$ over 0.10−0.26 Myr for 1E 1740.7−2942. Additionally, the spectral line characteristics of the detected emission place these molecular structures in the central molecular zone of our Galaxy, thereby constraining the distances to the black hole X-ray binaries to be 8.0 ± 1.0 kpc. Overall, our analysis solidifies the diagnostic capacity of molecular lines, and highlights how astro-chemistry can both identify jet–ISM interaction zones and probe jet feedback from Galactic X-ray binaries.
The identification and quantification of micro and nanoplastics (MPs and NPs respectively) requires the development of standardised analytical methods. Thermal analysis methods are generally not ...considered a method of choice for MPs analysis, especially in aqueous samples due to limited sample size introduction to the instrument, decreasing the detection levels. In this article, pyrolysis - Gas chromatography time of flight mass spectrometry (Py-GCToF) is used as a method of choice for detection of MPs and NPs due to its unprecedented detection capabilities, in combination with PTFE membranes as sample support, allow for smaller particle sizes (>0.1 μm) in water samples to be identified. The utilisation of these widely used membranes and the identification of several and specific (marker) ions for the three plastics in study (polypropylene (PP), polystyrene (PS) and polyvinyl chloride (PVC)), allows for the extraction of individual plastics from complex signals at trace levels. The method was validated against a number of standards, containing known quantities of MPs. Detection levels were then determined for PVC and PS and were found to be below <50 μg/L, with repeatable data showing good precision (%RSD <20%). Further verification of this new method was achieved by the analysis of a complex sample, sourced from a river. The results were positive for the presence of PS with a semi-quantifiable result of 241.8 μg/L. Therefore PY-GCToF seems to be a fit for purpose method for the identification of MPs and NPs from complex mixtures and matrices which have been deposited on PTFE membranes.
•Py-GCToF presented as a standard methodology for identification and semi-quantification of micro and nanoplastics.•Fast sample preparation and obtainment of repeatable results even in real environmental aqueous samples.•Use of PTFE membranes as a sample support; an affordable, common and broadly applied material in the industry.
Abnormalities in L-glutamic acid (glutamate) and GABA signal transmission have been postulated to play a role in depression, but little is known about the underlying molecular determinants and neural ...mechanisms. Microarray analysis of specific areas of cerebral cortex from individuals who had suffered from major depressive disorder demonstrated significant down-regulation of SLC1A2 and SLC1A3, two key members of the glutamate/neutral amino acid transporter protein family, SLC1. Similarly, expression of L-glutamate-ammonia ligase, the enzyme that converts glutamate to nontoxic glutamine was significantly decreased. Together, these changes could elevate levels of extracellular glutamate considerably, which is potentially neurotoxic and can affect the efficiency of glutamate signaling. The astroglial distribution of the two glutamate transporters and L-glutamate-ammonia ligase strongly links glia to the pathophysiology of depression and challenges the conventional notion that depression is solely a neuronal disorder. The same cortical areas displayed concomitant up-regulation of several glutamate and GABAA receptor subunits, of which $GABA_A\alpha1$ and $GABA_A\beta 3$ showed selectivity for individuals who had died by suicide, indicating their potential utility as biomarkers of suicidality. These findings point to previously undiscovered molecular underpinnings of the pathophysiology of major depression and offer potentially new pharmacological targets for treating depression.
Several recent works show structurally and functionally dynamic contacts between mitochondria, the plasma membrane, the endoplasmic reticulum, and other subcellular organelles. Many cellular ...processes require proper cooperation between the plasma membrane, the nucleus and subcellular vesicular/tubular networks such as mitochondria and the endoplasmic reticulum. It has been suggested that such contacts are crucial for the synthesis and intracellular transport of phospholipids as well as for intracellular Ca
2+ homeostasis, controlling fundamental processes like motility and contraction, secretion, cell growth, proliferation and apoptosis. Close contacts between smooth sub-domains of the endoplasmic reticulum and mitochondria have been shown to be required also for maintaining mitochondrial structure. The overall distance between the associating organelle membranes as quantified by electron microscopy is small enough to allow contact formation by proteins present on their surfaces, allowing and regulating their interactions. In this review we give a historical overview of studies on organelle interactions, and summarize the present knowledge and hypotheses concerning their regulation and (patho)physiological consequences.
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