Natural history of descending thoracic and thoracoabdominal aortic aneurysms

ObjectivesElucidating critical aortic diameters at which natural complications (rupture, dissection, and death) occur is of paramount importance to guide timely surgical intervention. Natural history knowledge for descending thoracic and thoracoabdominal aortic aneurysms is sparse. Our small early studies recommended repairing descending thoracic and thoracoabdominal aortic aneurysms before a critical diameter of 7.0 cm. We focus exclusively on a large number of descending thoracic and thoracoabdominal aortic aneurysms followed over time, enabling a more detailed analysis with greater granularity across aortic sizes.MethodsAortic diameters and long-term complications of 907 patients with descending thoracic and thoracoabdominal aortic aneurysms were reviewed. Growth rates (instrumental variables approach), yearly complication rates, 5-year event-free survival (Kaplan–Meier), and risk of complications as a function of aortic height index (aortic diameter [centimeters]/height [meters]) (competing-risks regression) were calculated.ResultsEstimated mean growth rate of descending thoracic and thoracoabdominal aortic aneurysms was 0.19 cm/year, increasing with increasing aortic size. Median size at acute type B dissection was 4.1 cm. Some 80% of dissections occurred below 5 cm, whereas 93% of ruptures occurred above 5 cm. Descending thoracic and thoracoabdominal aortic aneurysm diameter 6 cm or greater was associated with a 19% yearly rate of rupture, dissection, or death. Five-year complication-free survival progressively decreased with increasing aortic height index. Hazard of complications showed a 6-fold increase at an aortic height index of 4.2 or greater compared with an aortic height index of 3.0 to 3.5 (P < .05). The probability of fatal complications (aortic rupture or death) increased sharply at 2 hinge points: 6.0 and 6.5 cm.ConclusionsAcute type B dissections occur frequently at small aortic sizes; thus, prophylactic size-based surgery may not afford a means for dissection protection. However, fatal complications increase dramatically at 6.0 cm, suggesting that preemptive intervention before that criterion can save lives.     

Bending Strength of Wood Treated with Propolis Extract and Silicon Compounds

The modification of wood and its treatment with various preservatives may affect its mechanical properties, hence the knowledge of the character changes in wood caused by impregnation is of great importance. Therefore, the aim of the research was to determine the effect of impregnation, with the propolis-silane preparation (EEP-MPTMOS/TEOS) consisting of the propolis extract (EEP) and silicon compounds: 3-(trimethoxysilyl)propyl methacrylate (MPTMOS) and tetraethoxysilane (TEOS), on the bending strength of treated wood. Moreover, in the study wood treated with components of the propolis-silane formulation was used, namely 70% ethanol, the propolis extract, and silanes (MPTMOS/TEOS). In order to determine whether the impregnation of wood affects its long-term bending, creep tests were performed depending on the humidity. The impregnation of wood with the propolis extract and the propolis-silane preparation (EEP-MPTMOS/TEOS) contributed to the increase in modulus of rapture and work to maximum load values compared to the untreated wood. In dry wood condition, the wood treated with EEP and EEP-MPTMOS/TEOS was characterized by lower modulus of elasticity values than the control samples. In turn, in wet wood condition, wood treated with the propolis-silane preparation showed an increase in the MOE value. Moreover, the impregnation of wood had an influence on the wood creep process under bending loads. The treated wood was characterized by higher relative creep compliance than the untreated wood. The exception was the wood impregnated with EEP-MPTMOS/TEOS, which showed comparable relative creep compliance to the control samples. The presented results indicate that wood treated with a bio-friendly preparation based on propolis and silicon compounds can be used in various application and also in variable humidity conditions.     

Influence of Orientation and Radiative Heat Transfer on Aluminum Foams in Buoyancy-Induced Convection

Two differently-produced open-cell aluminum foams were compared to a commercially available finned heat sink. Further, an aluminum plate and block were tested as a reference. All heat sinks have the same base plate dimensions of four by six inches. The first foam was made by investment casting of a polyurethane preform and has a porosity of 0.946 and a pore density of 10 pores per linear inch. The second foam is manufactured by casting over a solvable core and has a porosity of 0.85 and a pore density of 2.5 pores per linear inch. The effects of orientation and radiative heat transfer are experimentally investigated. The heat sinks are tested in a vertical and horizontal orientation. The effect of radiative heat transfer is investigated by comparing a painted/anodized heat sink with an untreated one. The heat flux through the heat sink for a certain temperature difference between the environment and the heat sink’s base plate is used as the performance indicator. For temperature differences larger than 30 ^°C, the finned heat sink outperforms the in-house-made aluminum foam heat sink on average by 17%. Furthermore, the in-house-made aluminum foam dissipates on average 12% less heat than the other aluminum foam for a temperature difference larger than 40 ^°C. By painting/anodizing the heat sinks, the heat transfer rate increased on average by 10% to 50%. Finally, the thermal performance of the horizontal in-house-made aluminum foam heat sink is up to 18% larger than the one of the vertical aluminum foam heat sink.     

Vitamin D3 and Monomethyl Fumarate Enhance Natural Killer Cell Lysis of Dendritic Cells and Ameliorate the Clinical Score in Mice Suffering from Experimental Autoimmune Encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is a CD4⁺ T cell mediated inflammatory demyelinating disease that is induced in mice by administration of peptides derived from myelin proteins. We developed EAE in SJL mice by administration of PLP_139–151 peptide. The effect of treating these mice with 1α,25-Dihydroxyvitamin D₃ (vitamin D₃), or with monomethyl fumarate (MMF) was then examined. We observed that both vitamin D₃ and MMF inhibited and/or prevented EAE in these mice. These findings were corroborated with isolating natural killer (NK) cells from vitamin D₃-treated or MMF-treated EAE mice that lysed immature or mature dendritic cells. The results support and extend other findings indicating that an important mechanism of action for drugs used to treat multiple sclerosis (MS) is to enhance NK cell lysis of dendritic cells.     

From the Cover: Spatiotemporal variations of seismicity before major earthquakes in the Japanese area and their relation with the epicentral locations

Using the Japan Meteorological Agency earthquake catalog, we investigate the seismicity variations before major earthquakes in the Japanese region. We apply natural time, the new time frame, for calculating the fluctuations, termed β, of a certain parameter of seismicity, termed κ₁. In an earlier study, we found that β calculated for the entire Japanese region showed a minimum a few months before the shallow major earthquakes (magnitude larger than 7.6) that occurred in the region during the period from 1 January 1984 to 11 March 2011. In this study, by dividing the Japanese region into small areas, we carry out the β calculation on them. It was found that some small areas show β minimum almost simultaneously with the large area and such small areas clustered within a few hundred kilometers from the actual epicenter of the related main shocks. These results suggest that the present approach may help estimation of the epicentral location of forthcoming major earthquakes.In this study, we investigate the evolution of seismicity shortly before main shocks in the Japanese region, N2546E125148, using Japan Meteorological Agency (JMA) earthquake catalog as in ref 1. For this, we adopted the new time frame called natural time since our previous works using this time frame made the lead time of prediction as short as a few days (see below). For a time series comprising N earthquakes (EQs), the natural time χ_k is defined as χ_k = k/N, where k means the k^th EQ with energy Q_k (Fig. 1). Thus, the raw data for our investigation, to be read from the earthquake catalog, are χ_k = k/N and pk=Qk/∑n=1NQn, where p_k is the normalized energy. In natural time, we are interested in the order and energy of events but not in the time intervals between events.Open in a separate windowFig. 1.EQ sequence in (A) conventional time and (B) natural time. In B, Q_k is given in units of the energy ε corresponding to a 3.5M_JMA EQ.We first calculate a parameter called κ₁, which is defined as follows (2, 3), from the catalog.κ1=∑k=1Npkχk2−(∑k=1Npkχk)2=〈χ2〉−〈χ〉2.[1]We start the calculation of κ₁ at the time of initiation of Seismic Electric Signals (SES), the transient changes of the electric field of Earth that have long been successfully used for short-term EQ prediction (4, 5). The area to suffer a main shock is estimated on the basis of the selectivity map (4, 5) of the station that recorded the corresponding SES. Thus, we now have an area in which we count the small EQs of magnitude greater than or equal to a certain magnitude threshold that occur after the initiation of the SES. We then form time series of seismic events in natural time for this area each time a small EQ occurs, in other words, when the number of the events increases by one. The κ₁ value for each time series is computed for the pairs (χ_k,p_k) by considering that χ_k is “rescaled” to χ_k = k/(N +1) together with rescaling pk=Qk/∑n=1N+1Qn upon the occurrence of any additional event in the area. The resulting number of thus computed κ₁ values is usually of the order 10² to 10³ depending, of course, on the magnitude threshold adopted for the events that occurred after the SES initiation until the main shock occurrence. When we followed this procedure, it was found empirically that the values of κ₁ converge to 0.07 a few days before main shocks. Thus, by using the date of convergence to 0.07 for prediction, the lead times, which were a few months to a few weeks or so by SES data alone, were made, although empirically, as short as a few days (6, 7). In fact, the prominent seismic swarm activity in 2000 in the Izu Island region, Japan, was preceded by a pronounced SES activity 2 mo before it, and the approach of κ₁ to 0.07 was found a few days before the swarm onset (8). However, when SES data are not available, which is usually the case, it is not possible to follow the above procedure. To cope with this difficulty, in the previous work (1), we investigated the time change of the fluctuation of the κ₁ values during a few preseismic months for each EQ (which we call target EQ) over the large area N2546E125148 (Fig. 2A) for the period from 1 January 1984 to 11 March 2011, the day of M9.0 Tohoku EQ. Setting a threshold M_JMA = 3.5 to assure data completeness of JMA catalog, we were left with 47,204 EQs in the concerned period of about 326 mo: ∼150 EQs per month. For calculating the β values, we chose 200 EQs before target EQs to cover the seismicity in almost one and a half months.Open in a separate windowFig. 2.(A) The 47,204 EQs with M_JMA ≥ 3.5 that occurred during the period of our study. (B) Contours of the number of EQs per month within R = 250 km. Solid diamonds show the epicenters of six shallow EQs investigated in this study. (C) Contours of the natural time window W used in each of the 12,476 areas of radius R = 250 km with offset 0.1° from one another that have at least eight EQs per month.To obtain the fluctuation β of κ₁, we need many values of κ₁ for each target EQ. For this purpose, we first took an excerpt comprised of W successive EQs just before a target EQ from the seismic catalog. The number W was chosen to cover a period of a few months. For this excerpt, we form its subexcerpts Sj={Qj+k−1}k=1,2,…,N of consecutive N = 6 EQs (since at least six EQs are needed (2) for obtaining reliable κ₁) of energy Q_j+k?1 and natural time χ_k = k/N each. Further, pk=Qj+k−1/∑k=1NQj+k−1, and by sliding S_j over the excerpt of W EQs, j=1,2,…,W−N+1 (= W − 5), we calculate κ₁ using Eq. 1 for each j. We repeat this calculation for N=7,8,…,W, thus obtaining an ensemble of [(W − 4)(W − 5)]/2 (= 1 + 2 +…+ W − 5) κ₁ values. Then, we compute the average μ(κ₁) and the SD σ(κ₁) of thus obtained ensemble of [(W − 4)(W − 5)]/2 κ₁ values. The variability β of κ₁ for this excerpt W is defined to be β ≡ σ(κ₁)/μ(κ₁) and is assigned to the (W + 1)^th EQ, i.e., the target EQ.The time evolution of the β value can be pursued by sliding the excerpt through the EQ catalog. Namely, through the same process as above, β values assigned to (W + 2)^th, (W + 3)^th, … EQs in the catalog can be obtained.We found in ref. 1 that the fluctuation β of κ₁ values exhibited minimum a few months before all of the six shallow EQs of magnitude larger than 7.6 that occurred in the study period. A minimum of β ≡ σ(κ₁)/μ(κ₁) means large average and/or small deviation of κ₁ values (e.g., see ref. 9).In the present work, we calculate the β values for small areas before the six large EQs, which showed β minima of the large area.     

Discovery of a novel amino acid racemase through exploration of natural variation in Arabidopsis thaliana

Plants produce diverse low-molecular-weight compounds via specialized metabolism. Discovery of the pathways underlying production of these metabolites is an important challenge for harnessing the huge chemical diversity and catalytic potential in the plant kingdom for human uses, but this effort is often encumbered by the necessity to initially identify compounds of interest or purify a catalyst involved in their synthesis. As an alternative approach, we have performed untargeted metabolite profiling and genome-wide association analysis on 440 natural accessions of Arabidopsis thaliana. This approach allowed us to establish genetic linkages between metabolites and genes. Investigation of one of the metabolite–gene associations led to the identification of N-malonyl-d-allo-isoleucine, and the discovery of a novel amino acid racemase involved in its biosynthesis. This finding provides, to our knowledge, the first functional characterization of a eukaryotic member of a large and widely conserved phenazine biosynthesis protein PhzF-like protein family. Unlike most of known eukaryotic amino acid racemases, the newly discovered enzyme does not require pyridoxal 5′-phosphate for its activity. This study thus identifies a new d-amino acid racemase gene family and advances our knowledge of plant d-amino acid metabolism that is currently largely unexplored. It also demonstrates that exploitation of natural metabolic variation by integrating metabolomics with genome-wide association is a powerful approach for functional genomics study of specialized metabolism.Plants have the ability to create over 200,000 small compounds known as secondary or specialized metabolites (1). These chemically diverse compounds help mediate plant adaptation to their environment and play important roles in plant defense mechanisms, pigmentation, and development. In addition, many of these metabolites are desirable to humans as medicinal and nutritional compounds. Therefore, furthering our understanding of plant specialized metabolism will have profound impacts on various applications from crop improvement to human health.To date, only a small fraction of the chemical and catalytic space in plant specialized metabolism has been explored. Even in the best-studied model plant Arabidopsis thaliana, there are still many uncharacterized metabolites, and the vast majority of genes encoding enzymes implied to be involved in specialized metabolism do not have known associations with any metabolites. Several studies of Arabidopsis natural accessions (individuals collected from wild populations) revealed considerable qualitative and quantitative variation in the accumulation of various compounds such as glucosinolates, terpenoids, and phenylpropanoids (2–4). This extensive metabolite variation can be attributed to genetic variation in genes encoding enzymes and regulatory factors of the pathways involved; quantitative trait locus (QTL) mapping has successfully uncovered several genes involved in the production of these metabolites (3–7). Liquid chromatography–mass spectrometry (LC-MS)–based untargeted metabolic profiling has further extended such analysis to unknown metabolites, finding genetic contribution to the variation in at least three-fourths of detected mass peaks (8).Here we describe an integrated transdisciplinary platform, combining metabolomics, genetics, and genomics, to exploit the biochemical and genetic diversity of natural accessions of the model plant A. thaliana to uncover associations between genes and metabolites. Using this platform, we linked a differentially accumulating metabolite, identified through chemical analysis as N-malonyl-d-allo-isoleucine (NMD-Ile), to a previously uncharacterized gene identified as an amino acid racemase through reverse genetics and biochemical analysis.Amino acids exist in two forms; l-amino acids, the proteogenic form, and their enantiomorphs, d-amino acids. d-amino acids also play important structural and physiological roles in diverse life systems. In bacteria, d-amino acids confer cell-wall protease resistance and regulate cell-wall remodeling (9–11). d-amino acids were also found to be involved in signaling mechanisms in animal nervous systems and plant pollination (12, 13). Enzymes that catalyze the conversion of l-amino acids to d-amino acids are a class of isomerases known as amino acid racemases (14). Amino acid racemases are categorized into pyridoxal 5′ phosphate (PLP)-dependent and PLP-independent families. PLP-dependent racemases include AlaR, SerR, ArgR, and AspR and are found in both bacteria and eukaryotes, including mammals and plants. PLP-independent amino acid racemases include bacterial ProR, GluR, AspR, and diaminopimelate (DAP) epimerase. Except for DAP epimerase, which is required for the biosynthesis of Lys in bacteria and plants, ProR in Trypanosoma cruzi, the protozoan parasite responsible for Chagas disease, has been the only known eukaryotic PLP-independent racemase (15). The Arabidopsis amino acid racemase that we describe in this paper is a new member of the PLP-independent family, making its identification a significant addition to this class of enzymes.     

Posterior Surgical Treatment of Cervical Spondylotic Myelopathy: Review Article

Background

Cervical spondylosis is now recognised as the leading cause of myelopathy and spinal cord dysfunction worldwide. Chronic spinal cord compression results in chronic inflammation, cellular apoptosis, and microvacular insufficiency, which are thought to the biologic basis for cervical spondylotic myelopathy (CSM).

Questions/Purposes

Our purpose was to address the key principles of CSM, including natural history and presentation, pathogenesis, optimal surgical approach, results and complication rates of posterior surgical approaches for CSM so that the rationale for addressing CSM by a posterior approach can be fully understood.

Methods

We conducted a systematic search of PubMed/MEDLINE and the Cochrane Collaboration Library for literature published through February 2014 to identify articles that evaluated CSM and its management. Reasons for exclusion included patients with ossification of the posterior longitudinal ligament (OPLL), patients with degenerative disc disease without CSM, and patients with spine tumor, trauma and infection. Meeting abstracts/proceedings, white articles and editorials were additionally excluded.

Results

The search strategy yielded 1,292 articles, which was reduced to 52 articles, after our exclusion criteria were introduced. CSM is considered to be a surgical disorder due to its progressive nature. There is currently no consensus in the literature whether multilevel spondylotic compression is best treated via an anterior or posterior surgical approach.

Conclusion

Multilevel CSM may be safely and effectively treated using a posterior approach, either by laminoplasty or with a laminectomy and fusion technique.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-014-9425-5) contains supplementary material, which is available to authorized users.     

Residual C‐peptide in type 1 diabetes: what do we really know?

Connecting peptide, or C‐peptide, is a protein that joins insulin's α and B chains in the proinsulin molecule. During insulin synthesis, C‐peptide is cleaved from proinsulin and secreted in an equimolar concentration to insulin from the β cells. Because C‐peptide experiences little first‐pass clearance by the liver, and because levels are not affected by exogenous insulin administration, it may be used as a marker of endogenous insulin production and a reflection of β‐cell function. Residual β‐cell function, as measured by C‐peptide in those with type 1 diabetes (T1D), has repeatedly been demonstrated to be clinically important. The Eisenbarth model of type 1 diabetes postulated immune‐mediated linear loss of β cells, with clinical diagnosis occurring when there was insufficient insulin secretion to meet glycemic demand. Moreover, the model also implied that all individuals with T1D rapidly and inevitably progressed to absolute insulin deficiency. Correspondingly, it was assumed that most people with longstanding T1D would show little to no residual C‐peptide secretion. While more than a quarter century of data confirms that this model remains largely true and appropriately serves as the basis for prevention studies, accumulating evidence suggests that the natural history of β‐cell function before, during and after diagnosis is more complex. In this review, we discuss the clinical benefits of residual insulin secretion and present recent data about the natural history of insulin secretion in those with, or at risk for T1D.