Amyotrophic lateral sclerosis-motor neuron disease, monoclonal gammopathy, hyperparathyroidism, and B12 deficiency: case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Amyotrophic lateral sclerosis (the most common form of motor neuron disease) is a progressive and devastating disease involving both lower and upper motor neurons, typically following a relentless path towards death. Given the gravity of this diagnosis, all efforts must be made by the clinician to exclude alternative and more treatable entities. Frequent serology testing involves searching for treatable disorders, including vitamin B12 deficiency, parathyroid anomalies, and monoclonal gammopathies.</p> <p>Case presentation</p> <p>We present the case of a 78-year-old Caucasian man with all three of the aforementioned commonly searched for disorders during an investigation for amyotrophic lateral sclerosis.</p> <p>Conclusions</p> <p>The clinical utility of these common tests and what they ultimately mean in patients with amyotrophic lateral sclerosis is discussed, along with a review of the literature.</p

Extended [C I] and (CO)-C-13 (5 -\u3e 4) emission in M17SW

We mapped a 13 × 22 pc region in emission from 492 GHz [C I] and, for the first time, 551 GHz 13CO (5 → 4) in the giant molecular cloud M17SW. The morphologies of the [C I] and 13CO emission are strikingly similar. The extent and intensity of the [C I] and 13CO (5 → 4) emission is explained as arising from photodissociation regions on the surfaces of embedded molecular clumps. Modeling of the 13CO (5 → 4) emission in comparison to 13CO (1 → 0) indicates a temperature gradient across the cloud, peaking to at least 63 K near the M17 ionization front and decreasing to at least 20 K at the western edge of the cloud. We see no correlation between gas density and column density. The beam-averaged column density of C I in the core is 1 × 1018 cm-2, and the mean column density ratio N(C I)/N(CO) is about 0.4. The variations of N(C I)/N(CO) with position in M17SW indicate a similar clump size distribution throughout the cloud

Seasonal and Interannual Variations of the Energy Flux Equator and ITCZ. Part II: Zonally Varying Shifts of the ITCZ

The ITCZ lies at the ascending branch of the tropical meridional overturning circulation, where near-surface meridional mass fluxes vanish. Near the ITCZ, column-integrated energy fluxes vanish, forming an atmospheric energy flux equator (EFE). This paper extends existing approximations relating the ITCZ position and EFE to the atmospheric energy budget by allowing for zonal variations. The resulting relations are tested using reanalysis data for 1979–2014. The zonally varying EFE is found as the latitude where the meridional component of the divergent atmospheric energy transport (AET) vanishes. A Taylor expansion of the AET around the equator relates the ITCZ position to derivatives of the AET. To a first order, the ITCZ position is proportional to the divergent AET across the equator; it is inversely proportional to the local atmospheric net energy input (NEI) that consists of the net energy fluxes at the surface, at the top of the atmosphere, and zonally across longitudes. The first-order approximation captures the seasonal migrations of the ITCZ in the African, Asian, and Atlantic sectors. In the eastern Pacific, a third-order approximation captures the bifurcation from single- to double-ITCZ states that occurs during boreal spring. In contrast to linear EFE theory, during boreal winter in the eastern Pacific, northward cross-equatorial AET goes along with an ITCZ north of the equator. EFE and ITCZ variations driven by ENSO are characterized by an equatorward (poleward) shift in the Pacific during El Niño (La Niña) episodes, which are associated with variations in equatorial ocean energy uptake

Marked lateral deviation of the phrenic nerve due to variant origin and course of the thyrocervical trunk: a cadaveric study

Phrenic nerve impairment can often lead to serious respiratory disorders under various pathological conditions. During routine dissection of an 88-year-old Japanese male cadaver, a victim of heart failure, we recognized an extremely rare variation of the right thyrocervical trunk arising from the subclavian artery laterally to the anterior scalene muscle. In addition to that, the ipsilateral phrenic nerve was drawn and displaced remarkably laterad by this vessel. We examined all of the branches arising from subclavian arteries, phrenic nerves and diaphragm muscles. The embryological background of this arterial variation is considered. The marked displacement with prolonged strain had a potential to cause phrenic nerve impairment with an atrophic change of the diaphragm muscle. Recently many image diagnostic technologies have been developed and are often used. However, it is still possible that rare variations like this case may be overlooked and can only be recognized by intimate regional examination while keeping these rare variations in mind

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

On Hemangioblasts in Chicken

Hemangioblasts are bi-potential precursors for blood and endothelial cells (BCs and ECs). Existence of the hemangioblast in vivo by its strict definition, i.e. a clonal precursor giving rise to these two cell types after division, is still debated. Using a combination of mitotic figure analysis, cell labeling and long-term cell tracing, we show that, in chicken, cell division does not play a major role during the entire ventral mesoderm differentiation process after gastrulation. One eighth of cells do undergo at least one round of division, but mainly give rise to daughter cells contributing to the same lineage. Approximately 7% of the dividing cells that contribute to either the BC or EC lineage meet the criteria of true hemangioblasts, with one daughter cell becoming a BC and the other an EC. Our data suggest that hemangioblast-type generation of BC/EC occurs, but is not used as a major mechanism during early chicken development. It remains unclear, however, whether hemangioblast-like progenitor cells play a more prominent role in later development

Genomic Tools for Evolution and Conservation in the Chimpanzee: Pan troglodytes ellioti Is a Genetically Distinct Population

In spite of its evolutionary significance and conservation importance, the population structure of the common chimpanzee, Pan troglodytes, is still poorly understood. An issue of particular controversy is whether the proposed fourth subspecies of chimpanzee, Pan troglodytes ellioti, from parts of Nigeria and Cameroon, is genetically distinct. Although modern high-throughput SNP genotyping has had a major impact on our understanding of human population structure and demographic history, its application to ecological, demographic, or conservation questions in non-human species has been extremely limited. Here we apply these tools to chimpanzee population structure, using ∼700 autosomal SNPs derived from chimpanzee genomic data and a further ∼100 SNPs from targeted re-sequencing. We demonstrate conclusively the existence of P. t. ellioti as a genetically distinct subgroup. We show that there is clear differentiation between the verus, troglodytes, and ellioti populations at the SNP and haplotype level, on a scale that is greater than that separating continental human populations. Further, we show that only a small set of SNPs (10–20) is needed to successfully assign individuals to these populations. Tellingly, use of only mitochondrial DNA variation to classify individuals is erroneous in 4 of 54 cases, reinforcing the dangers of basing demographic inference on a single locus and implying that the demographic history of the species is more complicated than that suggested analyses based solely on mtDNA. In this study we demonstrate the feasibility of developing economical and robust tests of individual chimpanzee origin as well as in-depth studies of population structure. These findings have important implications for conservation strategies and our understanding of the evolution of chimpanzees. They also act as a proof-of-principle for the use of cheap high-throughput genomic methods for ecological questions

Compounds from Silicones Alter Enzyme Activity in Curing Barnacle Glue and Model Enzymes

Background: Attachment strength of fouling organisms on silicone coatings is low. We hypothesized that low attachment strength on silicones is, in part, due to the interaction of surface available components with natural glues. Components could alter curing of glues through bulk changes or specifically through altered enzyme activity. Methodology/Principal Findings: GC-MS analysis of silicone coatings showed surface-available siloxanes when the coatings were gently rubbed with a cotton swab for 15 seconds or given a 30 second rinse with methanol. Mixtures of compounds were found on 2 commercial and 8 model silicone coatings. The hypothesis that silicone components alter glue curing enzymes was tested with curing barnacle glue and with commercial enzymes. In our model, barnacle glue curing involves trypsin-like serine protease(s), which activate enzymes and structural proteins, and a transglutaminase which cross-links glue proteins. Transglutaminase activity was significantly altered upon exposure of curing glue from individual barnacles to silicone eluates. Activity of purified trypsin and, to a greater extent, transglutaminase was significantly altered by relevant concentrations of silicone polymer constituents. Conclusions/Significance: Surface-associated silicone compounds can disrupt glue curing and alter enzyme properties

Development of the Pulmonary Vein and the Systemic Venous Sinus: An Interactive 3D Overview

Knowledge of the normal formation of the heart is crucial for the understanding of cardiac pathologies and congenital malformations. The understanding of early cardiac development, however, is complicated because it is inseparably associated with other developmental processes such as embryonic folding, formation of the coelomic cavity, and vascular development. Because of this, it is necessary to integrate morphological and experimental analyses. Morphological insights, however, are limited by the difficulty in communication of complex 3D-processes. Most controversies, in consequence, result from differences in interpretation, rather than observation. An example of such a continuing debate is the development of the pulmonary vein and the systemic venous sinus, or “sinus venosus”. To facilitate understanding, we present a 3D study of the developing venous pole in the chicken embryo, showing our results in a novel interactive fashion, which permits the reader to form an independent opinion. We clarify how the pulmonary vein separates from a greater vascular plexus within the splanchnic mesoderm. The systemic venous sinus, in contrast, develops at the junction between the splanchnic and somatic mesoderm. We discuss our model with respect to normal formation of the heart, congenital cardiac malformations, and the phylogeny of the venous tributaries