Diplopia as the First Sign of Gastric Carcinoma

Orbital metastasis may be the initial manifestation of a malignancy of unknown origin. The primary locations of orbital metastasis are usually the lung, prostate, gastrointestinal tract, skin, kidney, eye, or thyroid gland. Metastasis of gastric carcinoma to an extraocular eye muscle is extremely rare. A solitary thickening in an extraocular eye muscle with no inflammatory features is suspect for a tumor. Symptoms such as diplopia, proptosis, ptosis, vision loss, or pain may be associated with an orbital malignancy. Our patient, a 67-year-old man known with radically resected prostate cancer, presented with complaints of vertigo with a tendency to fall, headache, and diplopia when looking to the right. As a coincidental finding, swelling of the rectus lateralis muscle of the left eye was observed on imaging. Extensive additional investigations showed that a gastric carcinoma with intraorbital and leptomeningeal metastasis was the cause. In conclusion, a solitary thickened extraocular eye muscle should be recognized in time and examined further

Application of NMR crystallography to highly disordered templated materials : extensive local structural disorder in the gallophosphate GaPO-34A

SEA, DMD, JEH and DM thank the ERC (EU FP7 Consolidator Grant 614290 “EXONMR”) for funding. SEA would like to thank the Royal Society and the Wolfson Foundation for a merit award. The National High Magnetic Field Laboratory is supported by National Science Foundation Cooperative Agreement DMR-1644779 and the State of Florida.We present an NMR crystallographic investigation of two as-made forms of the recently characterised gallophosphate GaPO-34A, which has an unusual framework composition with a Ga : P ratio of 7 : 6 and contains both hydroxide and fluoride anions and either 1-methylimidazolium or pyridinium as the structure-directing agent. We combine previously reported X-ray crystallographic data with solid-state NMR spectroscopy and periodic density functional theory (DFT) calculations to show that the structure contains at least three distinct types of disorder (occupational, compositional and dynamic). The occupational disorder arises from the presence of six anion sites per unit cell, but a total occupancy of these of five, leading to full occupancy of four sites and partial occupancy of the fifth and sixth (which are related by symmetry). The mixture of OH and F present leads to compositional disorder on the occupied anion sites, although the occupancy of some sites by F is calculated to be energetically unfavorable and signals relating to F on these sites are not observed by NMR spectroscopy, confirming that the compositional disorder is not random. Finally, a combination of high-field 71Ga NMR spectroscopy and variable-temperature 13C and 31P NMR experiments shows that the structure directing agents are dynamic on the microsecond timescale, which can be supported by averaging the 31P chemical shifts calculated with the SDA in different orientations. This demonstrates the value of an NMR crystallographic approach, particularly in the case of highly disordered crystalline materials, where the growth of large single crystals for conventional structure determination may not be possible owing to the extent of disorder present.PostprintPeer reviewe

Mesozoic mitogenome rearrangements and freshwater mussel (Bivalvia: Unionoidea) macroevolution

© 2019, The Author(s), under exclusive licence to The Genetics Society. Using a new fossil-calibrated mitogenome-based approach, we identified macroevolutionary shifts in mitochondrial gene order among the freshwater mussels (Unionoidea). We show that the early Mesozoic divergence of the two Unionoidea clades, Margaritiferidae and Unionidae, was accompanied by a synchronous split in the gene arrangement in the female mitogenome (i.e., gene orders MF1 and UF1). Our results suggest that this macroevolutionary jump was completed within a relatively short time interval (95% HPD 201–226 Ma) that coincided with the Triassic–Jurassic mass extinction. Both gene orders have persisted within these clades for ~200 Ma. The monophyly of the so-called “problematic” Gonideinae taxa was supported by all the inferred phylogenies in this study using, for the first time, the M- and F-type mitogenomes either singly or combined. Within Gonideinae, two additional splits in the gene order (UF1 to UF2, UF2 to UF3) occurred in the Mesozoic and have persisted for ~150 and ~100 Ma, respectively. Finally, the mitogenomic results suggest ancient connections between freshwater basins of East Asia and Europe near the Cretaceous–Paleogene boundary, probably via a continuous paleo-river system or along the Tethys coastal line, which are well supported by at least three independent but almost synchronous divergence events

Conbiomics: the missing approach for the conservation of freshwater bivalves

The decline of freshwater biodiversity hás reached alarming proportions. The extinction rate of freshwater biodiversity is predicted to be five times faster than ali other groups of species. The Unionidae, being the largest of the freshwater bivalve families, is among the most endangered group in the world. They are important providers of aquatic ecosystem services and are characterized by an unusual pattem of mtDNA inheritance. However, phylogeny, population genetic structure and species-level diversity remains unclear for much of the group. With an experienced and well-qualified team, the present proposal aims to define the most important freshwater mussel taxa and most criticai áreas for conservation, at European and Global leveis, to inform the most relevant policy niakers. This will be achieved by integrating a genomics approach with available distribution data, in order to determine and map global species richness, phylogenetic diversity, and weighted endemism. This complementary approach will not only help conserve this vulnerable group but will offer wider benefits to freshwater ecosystems whose billions of people depend globally. Additionally, as these animals have an extraordinary unusual pattern of mtDNA inheritance, they will be used as model-taxa to study the evolution of mtDNA and life in general.This research was developed under Project Nº NORTE-01-0145-FEDER-030286 (ConBiomics: the missing approach for the Conservation of freshwater Bivalves), co-financed by COMPETE 2020, Portugal 2020 and the European Union through the ERDF, and by FCT through national funds.info:eu-repo/semantics/publishedVersio

The crown pearl: a draft genome assembly of the European freshwater pearl mussel Margaritifera margaritifera (Linnaeus, 1758)

Since historical times, the inherent human fascination with pearls turned the freshwater pearl mussel Margaritifera margaritifera (Linnaeus, 1758) into a highly valuable cultural and economic resource. Although pearl harvesting in M. margaritifera is nowadays residual, other human threats have aggravated the species conservation status, especially in Europe. This mussel presents a myriad of rare biological features, e.g. high longevity coupled with low senescence and Doubly Uniparental Inheritance of mitochondrial DNA, for which the underlying molecular mechanisms are poorly known. Here, the first draft genome assembly of M. margaritifera was produced using a combination of Illumina Paired-end and Mate-pair approaches. The genome assembly was 2.4 Gb long, possessing 105,185 scaffolds and a scaffold N50 length of 288,726 bp. The ab initio gene prediction allowed the identification of 35,119 protein-coding genes. This genome represents an essential resource for studying this species' unique biological and evolutionary features and ultimately will help to develop new tools to promote its conservation.A.G.-d.-S. was funded by the Portuguese Foundation for Science and Technology (FCT) under the grants SFRH/BD/137935/2018, EF (CEECIND/00627/2017) and MLL (2020.03608.CEECIND). This research was developed under ConBiomics: the missing approach for the Conservation of freshwater Bivalves Project No. NORTE-01-0145-FEDER- 030286, co-financed by COMPETE 2020, Portugal 2020 and the European Union through the ERDF, and by FCT through national funds. Additional strategic funding was provided by FCT UIDB/04423/2020 and UIDP/04423/2020. Authors’ interaction and writing of the article was promoted and facilitated by the COST Action CA18239: CONFREMU—Conservation of freshwater mussels: a pan- European approach.info:eu-repo/semantics/publishedVersio

Expansion and systematics redefinition of the most threatened freshwater mussel family, the Margaritiferidae.

Two Unionida (freshwater mussel) families are present in the Northern Hemisphere; the Margaritiferidae, representing the most threatened of unionid families, and the Unionidae, which include several genera of unresolved taxonomic placement. The recent reassignment of the poorly studied Lamprotula rochechouartii from the Unionidae to the Margaritiferidae motivated a new search for other potential species of margaritiferids from members of Gibbosula and Lamprotula. Based on molecular and morphological analyses conducted on newly collected specimens from Vietnam, we here assign Gibbosula crassa to the Margaritiferidae. Additionally, we reanalyzed all diagnostic characteristics of the Margaritiferidae and examined museum specimens of Lamprotula and Gibbosula. As a result, two additional species are also moved to the Margaritiferidae, i.e. Gibbosula confragosa and Gibbosula polysticta. We performed a robust five marker phylogeny with all available margaritiferid species and discuss the taxonomy within the family. The present phylogeny reveals the division of Margaritiferidae into four ancient clades with distinct morphological, biogeographical and ecological characteristics that justify the division of the Margaritiferidae into two subfamilies (Gibbosulinae and Margaritiferinae) and four genera (Gibbosula, Cumberlandia, Margaritifera, and Pseudunio). The systematics of the Margaritiferidae family is re-defined as well as their distribution, potential origin and main biogeographic patterns

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants

Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition

The effect of crystalloid versus medium molecular weight colloid solution on post-operative nausea and vomiting after ambulatory gynecological surgery - a prospective randomized trial.

UNLABELLED: ABSTRACT: BACKGROUND: Intravenous fluid is recommended in international guidelines to improve patient post-operative symptoms, particularly nausea and vomiting. The optimum fluid regimen has not been established. This prospective, randomized, blinded study was designed to determine if administration of equivolumes of a colloid (hydroxyethyl starch 130/0.4) reduced post operative nausea and vomiting in healthy volunteers undergoing ambulatory gynecologic laparoscopy surgery compared to a crystalloid solution (Hartmann\u27s Solution). METHODS: 120 patients were randomized to receive intravenous colloid (N = 60) or crystalloid (N = 60) intra-operatively. The volume of fluid administered was calculated at 1.5 ml.kg-1 per hour of fasting. Patients were interviewed to assess nausea, vomiting, anti-emetic use, dizziness, sore throat, headache and subjective general well being at 30 minutes and 2, 24 and 48 hours post operatively. Pulmonary function testing was performed on a subgroup. RESULTS: At 2 hours the proportion of patients experiencing nausea (38.2 % vs 17.9%, P = 0.03) and the mean nausea score were increased in the colloid compared to crystalloid group respectively (1.49 ± 0.3 vs 0.68 ± 0.2, P = 0.028). The incidence of vomiting and anti-emetic usage was low and did not differ between the groups. Sore throat, dizziness, headache and general well being were not different between the groups. A comparable reduction on post-operative FVC and FEV-1 and PEFR was observed in both groups. CONCLUSIONS: Intra-operative administration of colloid increased the incidence of early postoperative nausea and has no advantage over crystalloid for symptom control after gynaecological laparoscopic surgery

A new perspective of the climatological features of upper-level cut-off lows in the Southern Hemisphere

This study presents a detailed view of the seasonal variability of upper-level cut-off lows (COLs) in the Southern Hemisphere. The COLs are identified and tracked using data from a 36-year period of the European Centre for Medium Range Weather Forecast reanalysis (ERA-Interim). The objective identification of the COLs uses a new approach, which is based on 300 hPa relative vorticity minima, and three restrictive criteria of the presence of a cold-core, stratospheric potential vorticity intrusion, and cut-off cyclonic circulation. The highest COL activity is in agreement with previous studies, located near three main continental areas (Australia, South America, and Africa), with maximum frequencies usually observed in the austral autumn. The COL mean intensity values show a marked seasonal and spatial variation, with maximum (minimum) values during the austral winter (summer), a unique feature that has not been observed previously in studies based on the geopotential. The link between intensity and lysis is examined, and finds that weaker systems are more susceptible to lysis in the vicinity of the Andes Cordillera, associated with the topographic Rossby wave. Lysis and genesis regions are close to each other, confirming that COLs are quasi-stationary systems. Also, COLs tend to move eastward and are faster over the higher latitudes. The mean growth/decay rates coincide with the major genesis and lysis density regions, such as the significant decay values across the Andes all year. As a consequence of using vorticity for the tracking method a longer lifetime of COLs is detected than in other studies, but this does not affect the total frequency of occurrence. Comparisons with other studies suggest that the differences in seasonality are due to uncertainties in the reanalyses and the methods used to identify COLs