Lipopolysaccharide Downregulates Kruppel-Like Factor 2 (KLF2) via Inducing DNMT1-Mediated Hypermethylation in Endothelial Cells

Abstract

KLF2 plays a protective role in antiinflammation and endothelial function, and can be regulated by promoter methylation alteration. Lipopolysaccharide (LPS) is a mediator of inflammatory responses, which causes epigenetic change of certain genes in host cells. We thus aimed to determine whether LPS could control the KLF2 expression by inducing methylation in promoter region. DNA methylation of 16 CpG sites within KLF2 promoter region was detected by bisulfite sequencing PCR. Results showed that methylation at 12 CpG sites were significantly increased in HUVECs after exposure to LPS among the total 16 sites, and the average level was increased by 57%. The KLF2 expressions assessed by reverse transcription quantitative real-time PCR and Western blot were significantly downregulated compared that without LPS simulation. Moreover, both messenger RNA and protein levels of KLF2 in HUVEC co-treated with LPS and DNA methyltransferase (DNMT) 1 small interfering RNA were dramatically higher than that treated with LPS only. Similar result was obtained when the cells were incubated in combination with LPS and 5-aza-2′-deoxycytidine (AZA), suggesting that the reduction of KLF2 expression induced by LPS can be reversed by DNMT1 inhibition. Finally, the presence of AZA changed the expression of genes that depends on KLF2 in LPS-stimulated HUVECs, which downregulated the E-selectin and VCAM and increased the eNOS and thrombomodulin expression. Our data demonstrated that LPS exposure resulted in hypermethylation in KLF2 promoter in HUVECs, which subsequently led to downregulation of the KLF2 expression. The study suggested that epigenetic alteration is involved in LPS-induced inflammatory response and provided a new insight into atherogenesis.

http://ift.tt/2rP8T5Q

Magnetic Resonance Imaging of Hip Neuropathies: Beyond the Sciatica: A Practical Approach

Abstract

Purpose of Review

Neural entrapments in the hip area represent a challenging diagnosis due to the complexity, deep location, and variable distribution of pelvic nerves. This paper aims to perform an anatomic and pathologic review of neural entrapment syndromes involving the pudendal, obturator, lateral cutaneous femoral, and femoral nerves at the pelvis.

Recent Findings

Among the etiologies for pelvic neuropathies, besides idiopathic and expansive processes, extrinsic compression by normal anatomical structures is also frequent, which relights the importance of the critic constriction points on nerves pathway. High-field 3-Tesla (3-T) magnetic resonance neurography is considered the best image method for such imaging investigation.

Summary

At MR imaging neural disease may be appreciated by alterations in nerve signal intensity, size, and morphology. For such evaluation, three-dimensional images with isotropic volumetric data acquisition both on T1 and STIR sequences should be performed, enabling post-processing imaging on workstations, which improves the diagnostic sensibility an enables early therapeutic procedures.

http://ift.tt/2qLM0jL

Recommandations pour les cancers superficiels du tube digestif : cancer du côlon (CCR superficiels)

http://ift.tt/2rP9YuC

Acute Neuroinflammation Promotes Cell Responses to 1800 MHz GSM Electromagnetic Fields in the Rat Cerebral Cortex

Abstract

Mobile phone communications are conveyed by radiofrequency (RF) electromagnetic fields, including pulse-modulated global system for mobile communications (GSM)-1800 MHz, whose effects on the CNS affected by pathological states remain to be specified. Here, we investigated whether a 2-h head-only exposure to GSM-1800 MHz could impact on a neuroinflammatory reaction triggered by lipopolysaccharide (LPS) in 2-week-old or adult rats. We focused on the cerebral cortex in which the specific absorption rate (SAR) of RF averaged 2.9 W/kg. In developing rats, 24 h after GSM exposure, the levels of cortical interleukin-1ß (IL1ß) or NOX2 NADPH oxidase transcripts were reduced by 50 to 60%, in comparison with sham-exposed animals (SAR = 0), as assessed by RT-qPCR. Adult rats exposed to GSM also showed a 50% reduction in the level of IL1ß mRNA, but they differed from developing rats by the lack of NOX2 gene suppression and by displaying a significant growth response of microglial cell processes imaged in anti-Iba1-stained cortical sections. As neuroinflammation is often associated with changes in excitatory neurotransmission, we evaluated changes in expression and phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the adult cerebral cortex by Western blot analyses. We found that GSM exposure decreased phosphorylation at two residues on the GluA1 AMPAR subunit (serine 831 and 845). The GSM-induced changes in gene expressions, microglia, and GluA1 phosphorylation did not persist 72 h after RF exposure and were not observed in the absence of LPS pretreatment. Together, our data provide evidence that GSM-1800 MHz can modulate CNS cell responses triggered by an acute neuroinflammatory state.

http://ift.tt/2qLU1F7

Analyse chimique, activités antioxydante, anti-inflammatoire et cytotoxique d’extrait hydrométhanolique d’ Origanum glandulosum Desf.

Résumé

L'extrait hydrométhanolique des parties aériennes d'Origanum glandulosum Batt. et Trab. a été étudié pour sa composition chimique par analyse CLHP et ses activités antioxydante, anti-inflammatoire et cytotoxique. L'analyse chromatographique a révélé la présence de trois acides phénoliques et de huit flavonoïdes. Les résultats de pouvoir antioxydant qui ont été réalisé par la méthode de DPPH (2,2-diphenyl-1-picrylhydrazyl) et de β-carotène–acide linoléique indiquent que l'extrait possède une forte activité. Les résultats ont montré aussi que l'extrait de la plante a une excellente activité anti-inflammatoire dans les deux modèles in vivo (l'oedème de la patte induit par la carragénine et l'oedème de l'oreille induit par l'huile de croton). De plus, cet extrait a été trouvé comme possédant une bonne toxicité contre les larves d'Artémia (LC₅₀ = 17,64 μg/ml).

http://ift.tt/2qLYEiu

Focus on O -phosphohydroxylysine, O -phosphohydroxyproline, N 1 -phosphotryptophan and S -phosphocysteine

Abstract

The synthesis and chemistry of the lesser-known phosphoamino acids, O-phosphohydroxylysine, O-phosphohydroxyproline, N ¹-phosphotryptophan and S-phosphocysteine are described in detail. In addition, where anything at all is known, the biological synthesis, occurrence and functions of these phosphoamino acids are described. Of these phosphoamino acids, only N ¹-phosphotryptophan has not been reported to occur in proteins; however, apart from the roles of S-phosphocysteine in the sugar transporter component (EII) and in catalysis by protein phosphotyrosine phosphatase, little is currently known about the biological roles of the phosphoamino acids when they occur as post-translational modifications.

http://ift.tt/2ruOKPr

Using Simulated Data to Assess Case-Crossover Designs for Studying Less Transient Effects of Drugs

http://ift.tt/2qLZbks

Lipopolysaccharide Downregulates Kruppel-Like Factor 2 (KLF2) via Inducing DNMT1-Mediated Hypermethylation in Endothelial Cells

Abstract

KLF2 plays a protective role in antiinflammation and endothelial function, and can be regulated by promoter methylation alteration. Lipopolysaccharide (LPS) is a mediator of inflammatory responses, which causes epigenetic change of certain genes in host cells. We thus aimed to determine whether LPS could control the KLF2 expression by inducing methylation in promoter region. DNA methylation of 16 CpG sites within KLF2 promoter region was detected by bisulfite sequencing PCR. Results showed that methylation at 12 CpG sites were significantly increased in HUVECs after exposure to LPS among the total 16 sites, and the average level was increased by 57%. The KLF2 expressions assessed by reverse transcription quantitative real-time PCR and Western blot were significantly downregulated compared that without LPS simulation. Moreover, both messenger RNA and protein levels of KLF2 in HUVEC co-treated with LPS and DNA methyltransferase (DNMT) 1 small interfering RNA were dramatically higher than that treated with LPS only. Similar result was obtained when the cells were incubated in combination with LPS and 5-aza-2′-deoxycytidine (AZA), suggesting that the reduction of KLF2 expression induced by LPS can be reversed by DNMT1 inhibition. Finally, the presence of AZA changed the expression of genes that depends on KLF2 in LPS-stimulated HUVECs, which downregulated the E-selectin and VCAM and increased the eNOS and thrombomodulin expression. Our data demonstrated that LPS exposure resulted in hypermethylation in KLF2 promoter in HUVECs, which subsequently led to downregulation of the KLF2 expression. The study suggested that epigenetic alteration is involved in LPS-induced inflammatory response and provided a new insight into atherogenesis.

http://ift.tt/2rP8T5Q

Viscous dissipation effects on MHD slip flow and heat transfer in porous micro duct with LTNE assumptions using modified lattice Boltzmann method

Abstract

This paper deals with heat transfer and fluid flow in a porous micro duct under local thermal non equilibrium conditions subjected to an external oriented magnetic field. The considered sample is a micro duct filled with porous media assumed to be homogenous, isotropic and saturated. The slip velocity and the temperature jump were uniformly imposed to the wall. In modeling the flow, the Brinkmann–Forchheimer extended Darcy model was incorporated into the momentum equations. In the energy equation, the local thermal non equilibrium between the two phases was adopted. A modified axisymmetric lattice Boltzmann method was used to solve the obtained governing equation system. Attention was focused on the influence of the emerging parameters such as Knudsen number, Kn, Hartmann number, Ha, Eckert number, Ec, Biot number, Bi and the magnetic field inclination \(\gamma\) on flow and heat transfer throughout this paper.

http://ift.tt/2s3zX0X

Single breath count: a simple pulmonary function test using a mobile app

http://ift.tt/2qKmhUL

Multiple laser pulses in conjunction with an optical clearing agent to improve the curative effect of cutaneous vascular lesions

Abstract

Port-wine stains (PWSs) usually respond poorly to pulsed dye laser treatment because of the shallow penetration and light absorption of melanin in the epidermis. Multiple laser pulses (MLPs) Nd:YAG laser in conjunction with an optical clearing agent can help to reduce the total laser energy required for blood coagulation. The quantitative optical clearing effect (OCE) of glycerol was investigated by using a tissue-like phantom. Thereafter, an in vitro capillary tube experimental system and an in vivo hamster dorsal skin chamber experiment for the laser treatment of PWSs were established to visually obtain the quantitative relationship between the OCE and the blood coagulation properties under the irradiation of 1064 nm MLPs. Diffuse reflection coefficient decreases by 36.69% and transmission coefficient increases by 38.73% at 1064 nm, after applying 0.5 mL anhydrous glycerol for 10 min on the surface of the tissue-like phantom. The number of laser pulses required for blood coagulation decreases by 25% after the application of 0.5 mL anhydrous glycerol for 4 min, thrombosis appears after 10 min, and the 0.0854 clotting area completely blocks the capillary tubes in 6 pulses. For 10 min, the incident energy can be reduced by 35.09 and 29.82%. When the 0.3-mm vessel's buried depths are 1 and 0.5 mm, the pulse number can be reduced from 11 to 8 and from 6 to 4, respectively. Adding anhydrous glycerol directly on the hamster dorsal skin is an effective way to reduce the number of laser pulses from 4∼5 to 2∼3 for similar capillary tube diameter. Therefore, the MLPs of 1064 nm Nd:YAG demonstrates a substantial curative effect for large capillary tubes. In conjunction with glycerol, this approach may treat deeply buried cutaneous capillary tubes and prevent the unwanted thermal damage of normal dermal tissue.

http://ift.tt/2ruKxeG

Reply to Comment on “The Impact of Psychological Support on Weight Loss Post Weight Loss Surgery: a Randomised Control Trial” Ratcliffe et al.

http://ift.tt/2sztYNZ

Association mapping to discover significant marker-trait associations for resistance against fusarium wilt variant 2 in pigeonpea [ Cajanus cajan (L.) Millspaugh] using SSR markers

Abstract

Pigeonpea production is severely constrained by wilt disease caused by Fusarium udum. In the current study, we discover the putative genomic regions that control resistance response to variant 2 of fusarium wilt using association mapping approach. The association panel comprised of 89 diverse pigeonpea genotypes including seven varieties, three landraces and 79 germplasm lines. The panel was screened rigorously for 3 consecutive years (2013–14, 2014–15 and 2015–2016) against variant 2 in a wilt-sick field. A total of 65 pigeonpea specific hypervariable SSR markers (HASSRs) were screened representing seven linkage groups and 29 scaffolds of the pigeonpea genome. A total of 181 alleles were detected, with average values of gene diversity and polymorphism information content (PIC) of 0.55 and 0.47, respectively. Further analysis using model based (STRUCTURE) and distance based (clustering) approaches separated the entire pigeonpea collection into two distinct subgroups (K = 2). The marker trait associations (MTAs) were established based on three-year wilt incidence data and SSR dataset using a unified mixed linear model. Consequently, six SSR markers were identified, which were significantly associated with wilt resistance and explained up to 6% phenotypic variance (PV) across the years. Among these SSRs, HASSR18 was found to be the most stable and significant, accounting for 5–6% PV across the years. To the best of our knowledge, this is the first report of identification of favourable alleles for resistance to variant 2 of Fusarium udum in pigeonpea using association mapping. The SSR markers identified here will greatly facilitate marker assisted resistance breeding against fusarium wilt in pigeonpea.

http://ift.tt/2sztBmK

High opioids tolerance due to transmucosal fentanyl abuse

http://ift.tt/2ruyL3O

Laboratory and field studies on a new sensor for dissolved N 2 O

Abstract

Nitrous oxide (N₂O) is a strong greenhouse gas, whose atmospheric concentration has been continuously increasing for more than 200 years. One major source is wastewater treatment plants (WWTPs), where N₂O emissions should either be minimized or pushed to levels where exploitation in biogas combustion engines becomes efficient. Both these strategies require online control of the N₂O concentrations in the liquid as well as in the gas phase. For this purpose, we propose a system for membrane extraction of the gas from the liquid phase, which then allows for a subsequent gas-phase analysis, which we perform by photoacoustic spectroscopy. We compare different theoretical calculations of the extraction efficiency, based either on a straightforward mathematical model or on a finite element simulation. The comparison of results with measurements produced on a well-defined model system shows good accordance. Based on the outcome, a field probe was developed and tested on a WWTP, yielding results comparable to the one achieved by GC reference analysis.

Graphical abstract

Gas extraction from liquids, e.g. from a wastewater treatment plant, for online gas monitoring

http://ift.tt/2rPjhdP

Size-exclusion chromatography of xylan derivatives—the critical evaluation of macromolecular data

Abstract

Hydroxypropyl xylans with varying degrees of substitution were characterized by size-exclusion chromatography. Molar masses of the samples were determined using two approaches: by conventional calibration with molar mass standards and by a multi-detection method that utilizes the combination of static light scattering, viscometry, and differential refractive index detection. The molar mass results obtained by the multi-detection method were accurate, but required the determination of separate refractive index increments for each structurally different sample. The column calibration approach with standard pullulan samples gave biased results due to the differences in hydrodynamic volumes between pullulans and hydroxypropyl xylans with similar molar masses. The degree of hydroxypropylation affected the chain conformation and compactness of the polymer chains. Mark-Houwink parameters and persistence length values suggested that the hydroxypropyl substituents reduced the flexibility of the xylan chain and made the polymer chain more extended.

http://ift.tt/2rPaCby

A rare case of poorly differentiated thyroid carcinoma probably arising from a nodular goiter

Abstract

Background

Some poorly differentiated thyroid carcinomas (PDTC) arise from pre-existing, well-differentiated carcinomas of follicular cell origin; however, others most likely arise de novo. The case of a PDTC adjacent to a pre-existing nodular goiter is very rare.

Case presentation

A patient had a PDTC, a widely invasive, cellular tumor with cells that lacked the nuclear features of a papillary thyroid carcinoma. Carcinoma cells were arranged in trabecular, solid, and microfollicular histological patterns and displayed high mitotic activity. A nodule partially encapsulated in a thick fibrous capsule was found adjacent to the PDTC. The nodule was composed of small or dilated follicles, without papillary carcinoma-like nuclear features, that were consistent with a nodular goiter. The PDTC showed a high Ki-67 labeling index and an NRAS gene mutation (codon 61, Q61K).

Conclusion

These results support our diagnosis of a PDTC, probably arising from a nodular goiter.

http://ift.tt/2s3jCcP

Light-emitting diode modulates carbohydrate metabolism by pancreatic duct regeneration

Abstract

Pancreatic lesions can produce metabolic disorders. Light-emitting diode (LED) has been used as a safe and effective phototherapy for cell proliferation and regeneration. We investigate the effects of phototherapy using LED irradiation on the pancreas after the injection of streptozotocin (STZ) to induce experimental diabetes and evaluate that the β cells can regenerate in the pancreas in an in vivo model and observe its implications on the control of carbohydrate metabolism. Twenty Wistar rats were randomized into three groups: non-diabetic control, diabetic control, and diabetic treated with LED. Except for the non-diabetic control group, all were induced to diabetes type I by streptozotocin injection. Treated groups were irradiated by LED: λ = 805 nm; 40 mW, 22 s; spot diameter 5 mm, spot area 0.196 cm², 0.88 J that it was applied on pancreas projection area for 5 consecutive days and monitored for 30 days. Diabetic group treated with LED showed regeneration of islets and ducts (p = 0.001) on the pancreas. Intraperitoneal insulin tolerance test showed differences between the diabetic control and diabetic treated groups (p = 0.03). In diabetic control group, the hepatic glycogen content was 296% lower when compared with diabetic treated with LED. Furthermore, in the diabetic control group, the glycogen content of the gastrocnemius muscle was 706% smaller when compared with diabetic treated with LED. This study shows that LED was able to modify morphological and metabolic features and also altered carbohydrate metabolism on irradiated pancreas in experimental model of diabetes.

http://ift.tt/2rP0rn9

Effect of dynamic curing time on thermal, mechanical and rheological behavior of organoclay-containing nanocomposite based on ethylene-octene copolymer

Abstract

Ethylene-octene copolymer (EOC)/organoclay nanocomposite was cured by peroxide in an internal mixer for different time periods. Low angle x-ray diffraction and transmission electron microscopy results revealed that the clay platelets were appeared as large parallel tactoids in the uncross-linked nanocomposite whereas the layers arranged in thinner tactoids in the cross-linked counterpart. Tensile experiments indicated that although the tensile modulus and yield stress were increased for the samples cross-linked for 6 min in comparison with that of the uncross-linked nanocomposite, the values decreased for the samples cross-linked for extra time. The results obtained from the Cole-Cole and tanδ against angular frequency plots showed that the over-cured samples had lower relaxation time and higher damping values, respectively. The average molecular weight between cross-links for different samples was also estimated using James-Guth theory and the results showed that the molecular weight was increased for the samples cross-linked dynamically for longer than 6 min.

http://ift.tt/2qJGuKi

Miscibility and toughness improvement of poly(lactic acid)/poly(3-Hydroxybutyrate) blends using a melt-induced degradation approach

Abstract

Biodegradable polymer blends of high-molecular-weight poly(3-hydroxybutyrate) (PHB) and poly(lactic acid) (PLA) are not miscible in general. Yet, by decreasing the molecular weight of PHB, the low-molecular-weight PHB could have improved miscibility with the PLA. In this study, a melt-induced degradation process of PLA/PHB blends was therefore implemented, termed the in-situ self-compatibilization approach, to produce low-molecular-weight PHB during melt blending process. The solution blends of PLA and oligomer PHB (PLA/OPHB) were also prepared as a basis to understand the role of low-molecular-weight PHB to improve its miscibility with PLA in PLA/PHB blends. Only one single glass transition temperature (T_g) was found for the resulting PLA/PHB blends at compositions of 95/05 to 80/20, proving that the miscibility was greatly improved by decreasing molecular weight of PHB. Because the degraded PHB had a relatively lower T_g, it thus provided plasticization effect to the PLA and resulted in the decreased crystallization temperature. Moreover, with increasing PHB content to 20% in the blend, the elongation at break increased significantly from 7.2% to 227%, more than 30-fold. The extensive shear yielding and necking behavior were observed during tensile testing for the blend of 80/20. The localized plasticization within PLA/PHB matrix with the reduction of local yield stress and the well-dispersed PHB crystallites were the major contributing factors to trigger shear yielding phenomenon. Moreover, initial modulus decreased only 20%, from 1.68 to 1.35 GPa. A common problem of severely reduced stiffness from the added plasticizer encountered in the plasticized PLA blends was therefore not perceived here.

http://ift.tt/2s3ucAy

The Content of As and Heavy Metals in TSP and PM 10 Near Copper Smelter in Bor, Serbia

Abstract

The content of As and heavy metals (Pb, Cd, Ni, and Cu) in total suspended particulate (TSP) and PM₁₀ at 3 locations (Park, Institute, and Jugopetrol) near the copper smelter in Bor (Serbia) has been analyzed within the period 2004 to 2015 with the aim of investigating the seasonal and spatial changes of those pollutants in the suspended particles. The content of As in TSP and PM₁₀ was over the annual EU limit value at all measuring points during the entire period of observation, while contents of Cd and Pb were periodically above the annual EU limits. There were no statistically significant seasonal changes between mean levels of the observed elements in the cold (October–March) and warm (April–September) periods during the year. A strong and moderate positive correlation was detected between the concentrations of each particular element (except Ni) at all measuring points. Additionally, Cd was the most enriched element followed by Pb, As, and Cu, while Ni was low-enriched. The constant air pollution with As particles, sometimes in concentrations even 20 times higher than the permitted annual value, requires urgent undertaking of concrete actions in order to reduce anthropogenic emission of suspended particles in Bor.

http://ift.tt/2soebCu

Nucleotide polymorphisms of candidate genes of adaptive significance in the ural populations of Larix sibirica Ledeb.

Abstract

The objectives of conservation and sustainable forest management require in depth study of genomes of woody plants and definition of their intraspecific genetic diversity. In recent years, an approach was developed based on the study of "candidate genes" that can potentially be involved in the formation of adaptive traits. In this study, we investigated nucleotide polymorphism of several adaptive candidate genes in the populations of Siberian larch (Larix sibirica Ledeb.) in the Urals. Representatives of this genus are among the most valuable and widely distributed forest tree species in Russia. From ten selected gene loci in the genome of L. sibirica, we isolated and investigated three loci, one of which (ABA-WDS) was sequenced in L. sibirica for the first time. The total length of the analyzed sequence in each individual amounted to 2865 bp. The length of locus alignment was from 360 bp to 1395 bp. In total, we identified 200 polymorphic positions. The most conservative is locus 4CL1-363, and the most polymorphic is locus sSPcDFD040B03103-274. The studied populations of L. sibirica are characterized by a high level of nucleotide polymorphism in comparison with other species and genuses (Picea, Pinus, Pseudotsuga, Abies) conifers plants (Hd = 0.896; π = 0.007; θ_W = 0.015). The most selectively neutral polymorphism (D _T =–0.997) was attributed to locus 4CL1-363, and polymorphism with high probability of adaptability (D _T =–1.807) was determined for the ABA-WDS locus. We identified 54 SNP markers, only five of which were nonsynonymous (9.26%) replacements. The average frequency of SNPs in the three studied loci of L. sibirica was one SNP in 53 bp. We detected unique SNP markers for eight populations, which could potentially be used to identify populations. Populations that are characterized by the highest number of unique SNP markers can be recommended for selection in order to preserve the gene pool of the species.

http://ift.tt/2rOOvlp

Genetic diversity of invasive populations of the florida crab ( Rhithropanopeus harrisii (Gould, 1841): (Decapoda, Panopidae))

Abstract

The variability of the mtDNA locus COI in the Florida crab (Rhithropanopeus harrisii) of coastal populations of the northern Black Sea is studied. The introduction of this crab species is demonstrated to originate from European populations, most likely the Netherlands. The studied populations experienced a strong decline in the level of genetic variability based on the haplotype diversity, but to a lesser extent based on the nucleotide diversity. Analysis of the structure of decapod community of Crimea makes it possible to discuss the reasons underlying invasive success of the Florida crab in the region.

http://ift.tt/2so8HHV

Evolutionary conservation of recombination proteins and variability of meiosis-specific proteins of chromosomes

Abstract

A comparison of amino acid sequences is performed for orthologs to the meiosis-specific proteins in humans and seven other species, including animals, fungi, and plants that serve as models for the study of molecular mechanisms of meiosis. It is demonstrated that the RAD51 recombination mediator protein is the most conserved of the studied proteins. Its meiotic homolog DMC1 is less conserved, like the MHL1 mismatch-repair protein. The meiosis-specific SPO11 endonuclease is the least conserved among the studied meiotic enzymes. Structural proteins of meiotic chromosomes are poorly conserved. REC8 meiotic cohesin has 6 times lower similarity in the organisms from different kingdoms than its somatic homolog RAD21. The intermediate conservation level is characteristic of the synaptonemal complex proteins containing HORMA domain. Two functional domains of SPO11 endonuclease and MutL Trans_MLH1 domain of MLH1 enzyme are equally or even less conserved than the whole proteins. HORMA functional domain of a number of synaptonemal complex proteins is only 2–3 times more conserved than the whole molecule. Thus, among the key meiotic proteins, the most conserved are proteins responsible for the accuracy of meiotic recombination. Cohesins, synaptonemal complex proteins, and meiosis-specific SPO11 endonuclease are less conserved even within their functional domains. Obviously, the meiosis-specific proteins have undergone independent evolution in different phylogenetic lineages of eukaryotes.

http://ift.tt/2rOCHj3

The influence of late pleistocene mountain glaciations on the genetic differentiation of long-tailed ground squirrel ( Urocitellus undulatus )

Abstract

Long-tailed ground squirrel (Urocitellus undulatus) is a polytypic species with a wide distribution from the Tien Shan to the Amur River region. Previously, considerable genetic differentiation between eastern and western populations of this species was demonstrated. Moreover, the greatest differences were observed in the western part of the range located in Central Asia, the region that was subjected to repeated glaciations in the past and represents one of the centers of the ground squirrel secondary diversification. The analysis of polymorphism of the mitochondrial DNA control region was carried out on long-tailed ground squirrels living in the northern part of Central Asia, on the territory of the Altai Mountains (45 individuals from 23 localities). The presence of two genetically differentiated (7.7% differences) and geographically separated lineages (western and eastern) was revealed. The data obtained disprove the hypothesis on unidirectional, from west to east, colonization of the Altai Mountains after the end of the last glacial maximum and show the two pathways of the ground squirrel colonization of the Altai, from both western and eastern refugia.

http://ift.tt/2soklma

Genetic differentiation in the polyploid complex of Suaeda corniculata (C.A. Mey.) Bunge in Eastern Siberia

Abstract

Data on differentiation of the polyploid complex of Suaeda corniculata (C.A. Mey.) Bunge in East Siberia based on variability of morphological characteristics, karyological analysis, and genetic polymorphism in inter simple sequence repeat (ISSR) markers were given for the first time. It was established that the samples studied belonged to three cytotypes: diploids (2n = 2x = 18), tetraploids (2n = 4x = 36) and hexaploids (2n = 6x = 54). The analysis of variability of morphological characteristics by the method of principal coordinates showed division of the samples into three separate groups. On the basis of morphological and molecular-genetic methods, a genetically differentiated diploid population was revealed in Yakutia.

http://ift.tt/2rOOIFf

Genetic diversity in collection of cultivars and varieties of Triticum durum Desf. from Azerbaijan

Abstract

AFLP analysis of 144 samples of tetraploid wheat species, including cultivars and landraces of Triticum durum from Azerbaijan, was conducted. We obtained 249 fragments, 189 (76%) of which were polymorphic. The Dice genetic similarity index ranged from 0.67 to 0.99. Principal coordinate analysis revealed clear differences between the group of wheat with A^uA^uBB genome and the group of wheat with A^bA^bGG genome. Within the group of wheat with A^uA^uBB genome, differentiation was less pronounced, and this group was not divided into separate subclusters. It was shown that the Azerbaijani varieties of durum wheat were fairly similar to each other and with other species of Triticum durum.

http://ift.tt/2sos7fG

The role of molecular genetic alterations in genes involved in folate and homocysteine metabolism in multifactorial diseases pathogenesis

Abstract

The molecular genetic modifications in multiple genes involved in folate and homocysteine metabolism play the pivotal role in the development of hyperhomocysteinemia. Hyperhomocysteinemia is observed in 5% of patients worldwide and accompanies various multifactorial diseases, including neurodegenerative, autoimmune and vascular disorders and tumors. It should be noted that increased homocysteine level itself may point to some imbalance in the organism and represent a diagnostic marker of the development of some pathology. The present review describes the role of molecular-genetic modifications in one carbon metabolism accompanying different multifactorial diseases, including congenital birth defects, vascular disorders, diabetes, and hormone-dependent cancers such as breast and ovarian cancer. Data of the association between the SNPs in functionally significant genes involved in the one carbon metabolism and pathologies mentioned above were demonstrated. In addition, we firstly represent the data of the involvement of epigenetic factors (hypermethylation and miRNA) in regulation of these genes in multifactorial diseases. The section devoted to the role of molecular-genetic impairments in the genes involved in homocysteine metabolism associated with breast and ovarian cancer includes worldwide findings and our own results.

http://ift.tt/2rOOLRr

AFLP, RAPD, and ISSR analysis of intraspecific polymorphism and interspecific differences of allotetraploid species Aegilops kotschyi Boiss. and Aegilops variabilis Eig

Abstract

To evaluate genetic variation, 27 accessions of allotetraploid species Aegilops kotschyi and Ae. variabilis with the US genome were analyzed using the AFLP, RAPD, and ISSR methods. A total of 316 polymorphic RAPD fragments, 750 polymorphic AFLP fragments, and 234 polymorphic ISSR fragments were obtained. It was demonstrated that the analyzed species were characterized by a considerable level of nuclear genome variation. According to the data of ISSR and RAPD analysis, the average value of the Jaccard similarity coefficient for the accessions of Ae. variabilis from different geographical regions was slightly lower than that for the accessions of Ae. kotschyi. At the same time, AFLP analysis showed no considerable differences in the levels of intraspecific variation of the studied species. Analysis of the summarized RAPD, ISSR, and AFLP marking data in the Structure software program showed that most of the analyzed accessions with high degree of probability could be assigned to one of two groups, the first of which corresponded to Ae. kotschyi and the second corresponded to Ae. variabilis, thereby confirming the species independence of Ae. kotschyi and Ae. variabilis. Accessions k900, k907, k908, and v90 could not with a sufficiently high degree of probability be assigned to one of the species, which possibly was the result of interspecific hybridization. Analysis of the species diversity using different molecular markers made it possible to identify the accessions that were notably different from other accessions of its species.

http://ift.tt/2sos2IU

Genetic and morphological heterogeneity of Lake Baikal endemic gastropod Benedictia fragilis (Dybowski, 1875)

Abstract

Baikal endemic Benedictia fragilis gastropods distributed in a wide range of depths (from sublittoral to abyssal) of three lake basins are studied. The analysis of the nucleotide sequence of the COI mitochondrial gene fragment and internal transcribed nuclear DNA spacer (ITS1) demonstrates that the studied gastropods are represented in Lake Baikal by three genetic groups. The results of the studies on genetic diversity, phenotypic traits, and distribution allow us to assume that the detected groups are incipient allopatric (geographical) species. On the basis of the data obtained and geological and climatic history of Baikal, possible pathways of the B. fragilis resettlement in the lake and the emergence of three genetic groups are hypothesized.

http://ift.tt/2rOOhus

Molecular genetic polymorphism of soil yeasts of the genus Williopsis from Taiwan Island

Abstract

Comparative molecular genetic study of Williopsis yeasts isolated in different world regions reveals some peculiarities of species content in Taiwan. Some Williopsis yeasts may represent novel species. In Taiwan, four of the five known Williopsis species are documented: W. saturnus, W. suaveolens, W. mrakii, and W. subsufficiens. The W. saturnus yeasts predominate in Taiwanese soils, while W. suaveolens is more frequently isolated in Europe.

http://ift.tt/2so7eBr

Genetic aspects of keratoconus development

Abstract

Keratoconus (KC) is the most common form of keratoectasia characterized by changes in corneal topography and its thinning, stretching, and protrusion. The hereditary or genetic theory of keratoconus development is widely recognized. To date, a large number of candidate genes have been investigated in patients with KC. One of the most important of them are the gene encoding a homeodomain-containing protein that belongs to the subfamily of paired-like homeodomain proteins (VSX1), superoxidedismutase 1 (SOD1) gene, and the gene of lysyloxidase (LOX). The linkage analysis reveals over 17 chromosomal regions mutations in which can lead to the development of KC. In families with a hereditary form of keratoconus by GWAS analysis, the association of central corneal thickness (CCT) with a number of genetic loci is revealed. Thus, diverse results of genetic studies and a large number of identified chromosomal regions associated with keratoconus, firstly, show marked genetic heterogeneity of the disease and, secondly, are associated with challenges in DNA diagnosis of this disease. However, there are prerequisites that keratoconus belongs to both hereditary and genetically caused diseases and identified genetic variants are specific both to individual populations and to certain ethnic groups in general.

http://ift.tt/2rOJyZM

Importance of DNA methylation in the inheritance of radiation-induced aberrant expression of microRNA

Abstract

We studied microRNA gene expression in HeLa cells following exposure for 6 h and 8 days to Co⁶⁰ gamma rays at a dose of 4 Gy using an approach of large-scale parallel DNA sequencing. We identified 12 microRNAs with aberrant expression which were maintained in cell generations. The analysis of radiation-induced aberrant expression of pre-microRNAs made it possible to assess the importance of nuclear and cytoplasmic stages of microRNA biogenesis for preservation of its aberrant expression. On cell treatment by 5-azacytidine, aberrant expression was maintained only in two microRNAs: miR-21-3p and miR-422a, which demonstrated an increase in expression. Radiation-induced decrease in expression in ten examined microRNAs was dependent on DNA demethylation. At the same time, expression in a microRNA set, which demonstrated inheritable alteration of the expression after gamma-radiation exposure in the untreated cells, was not dependent or was weakly dependent on DNA methylation. The obtained results suggest that ionizing radiation induces aberrant DNA methylation, which affects inherited expression changes in microRNAs in cell generations after exposure to the mutagen.

http://ift.tt/2son7rh

Nanostructured TiO 2 and ZnO prepared by using pressurized hot water and their eco-toxicological evaluation

Abstract

The eco-toxicological effects of unconventionally prepared nanostructured TiO₂ and ZnO were evaluated in this study, since both oxides are keenly investigated semiconductor photocatalysts in the last three decades. Unconventional processing by pressurized hot water was applied in order to crystallize oxide materials as an alternative to standard calcination. Acute biological toxicity of the synthesized oxides was evaluated using germination of Sinapis alba seed (ISO 11269-1) and growth of Lemna minor fronds (ISO 20079) and was compared to commercially available TiO₂ Degussa P25. Toxicity results revealed that synthesized ZnO as well as TiO₂ is toxic contrary to commercial TiO₂ Degussa P25 which showled stimulation effect to L. minor and no toxicity to S. alba. ZnO was significantly more toxic than TiO₂. The effect of crystallite size was considered, and it was revealed that small crystallite size and large surface area are not the toxicity-determining factors. Factors such as the rate of nanosized crystallites aggregation and concentration, shape and surface properties of TiO₂ nanoparticles affect TiO₂ toxicity to both plant species. Seriously, the dissolution of Ti⁴⁺ ions from TiO₂ was also observed which may contribute to its toxicity. In case of ZnO, the dissolution of Zn²⁺ ions stays the main cause of its toxicity.

Graphical abstract

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http://ift.tt/2qLxZCC

Ketones 2-heptanone, 2-nonanone, and 2-undecanone inhibit DnaK-dependent refolding of heat-inactivated bacterial luciferases in Escherichia coli cells lacking small chaperon IbpB

Abstract

Many bacteria, fungi, and plants produce volatile organic compounds (VOCs) emitted to the environment. Bacterial VOCs play an important role in interactions between microorganisms and in bacterial-plant interactions. Here, we show that such VOCs as ketones 2-heptanone, 2-nonanone, and 2-undecanone inhibit the DnaKJE-ClpB bichaperone dependent refolding of heat-inactivated bacterial luciferases. The inhibitory activity of ketones had highest effect in Escherichia coli ibpB::kan cells lacking small chaperone IbpB. Effect of ketones activity increased in the series: 2-pentanone, 2-undecanone, 2-heptanone, and 2-nonanone. These observations can be explained by the interaction of ketones with hydrophobic segments of heat-inactivated substrates and the competition with the chaperones IbpAB. If the small chaperone IbpB is absent in E. coli cells, the ketones block the hydrophobic segments of the polypeptides and inhibit the action of the bichaperone system. These results are consistent with the data on inhibitory effects of VOCs on survival of bacteria. It can be suggested that the inhibitory activity of the ketones indicated is associated with different ability of these substances to interact with hydrophobic segments in proteins.

http://ift.tt/2qQ35Eg

Heavy metal accumulation by Saccharomyces cerevisiae cells armed with metal binding hexapeptides targeted to the inner face of the plasma membrane

Abstract

Accumulation of heavy metals without developing toxicity symptoms is a phenotype restricted to a small group of plants called hyperaccumulators, whose metal-related characteristics suggested the high potential in biotechnologies such as bioremediation and bioextraction. In an attempt to extrapolate the heavy metal hyperaccumulating phenotype to yeast, we obtained Saccharomyces cerevisiae cells armed with non-natural metal-binding hexapeptides targeted to the inner face of the plasma membrane, expected to sequester the metal ions once they penetrated the cell. We describe the construction of S. cerevisiae strains overexpressing metal-binding hexapeptides (MeBHxP) fused to the carboxy-terminus of a myristoylated green fluorescent protein (myrGFP). Three non-toxic myrGFP-MeBHxP (myrGFP-H6, myrGFP-C6, and myrGFP-(DE)3) were investigated against an array of heavy metals in terms of their effect on S. cerevisiae growth, heavy metal (hyper) accumulation, and capacity to remove heavy metal from contaminated environments.

http://ift.tt/2rl2Vsa

Is sedation administration strategy and analysis during drug-induced sedation endoscopy objective and systematic?

http://ift.tt/2rAYY2U

Totally laparoscopic right colectomy versus laparoscopically assisted right colectomy: a propensity score analysis

Abstract

Introduction

The aim of this study is to compare short- and long-term outcomes of totally laparoscopic right colectomy (TLRC) and laparoscopically assisted right colectomy (LARC), using propensity score matching (PSM) analysis.

Materials and methods

A retrospective analysis of patients who underwent laparoscopic right colectomy between January 2006 and July 2016 was conducted. PSM analysis was performed to overcome patient selection bias between the two surgical techniques.

Results

A total of 116 patients were reviewed. After PSM, 54 patients for the TLRC group and 54 patients for the LARC group were compared. TLRC was associated with shorter post-operative hospital stay (6.81 vs. 4.79 days; p < 0.001) with no difference in 30-day morbidity and mortality. A lower incidence of long-term incisional hernia was observed in the TLRC group (1.9 vs. 21.2%; p = 0.002). TLRC showed better oncological accuracy as demonstrated by a greater number of lymph node achieved (19.21 vs. 15.19; p = 0.001) and higher vascular pedicle length (131.81 vs. 114.76 mm; p = 0.014).

Discussion

TLRC is a safe and feasible technique with similar results of LARC in terms of short-term morbidity and mortality. Major advantages related to TLRC are represented by shorter post-operative hospital stay and lower incidence of long-term incisional hernias. Further investigations are needed to assess the oncological outcomes for this technique.

http://ift.tt/2s39i4t

Protective effect of gallic acid in experimental model of ketamine-induced psychosis: possible behaviour, biochemical, neurochemical and cellular alterations

Abstract

Gallic acid has been reported to possess a number of psychopharmacological activities. These activities are attributed to the antioxidant potential due to the presence of phenolic moeity. The present study was carried out to investigate the protective effects of gallic acid in an experimental model of ketamine-induced psychosis in mice. Ketamine (50 mg/kg, i.p.) was used to induce stereotyped psychotic behavioural symptoms in mice. Behavioural studies (locomotor activity, stereotype behaviour, immobility duration and memory retention) were carried out to investigate the protective of gallic acid on ketamine-induced psychotic symptoms, followed by biochemical and neurochemical changes and cellular alterations in the brain. Chronic treatment with gallic acid for 15 consecutive days significantly attenuated stereotyped behavioural symptoms in mice. Biochemical estimations revealed that gallic acid reduced the lipid peroxidation and restored the total brain proteins. Furthermore, gallic acid remarkably reduced the dopamine levels, AChE activity and inflammatory surge (serum TNF-α), and increased the levels of GABA and increased glutathione in mice. The study revealed that gallic acid could ameliorate psychotic symptoms and biochemical changes in mice, indicating protective effects in psychosis.

http://ift.tt/2qKkKSC

Tumor infiltrating lymphocytes in acral lentiginous melanoma: a study of a large cohort of cases from Latin America

Abstract

Purpose

Acral lentiginous melanoma (ALM) is a poor prognosis subtype and is the most prevalent in non-Caucasian populations. The presence of tumor infiltrating lymphocytes (TILs) has been associated with poor prognosis in melanoma. A large cohort of ALM cases was studied to determine status of TIL and its association with outcome.

Methods

All patients with cutaneous melanoma presenting from 2005 to 2012 at Instituto Nacional de Enfermedades Neoplasicas in Peru were retrospectively identified. Clinicopathological information was obtained from the medical charts. A prospective evaluation of TIL was performed. Analysis of association between ALM and clinicopathological features including TIL as well as survival analysis compared the outcome of ALM to whole group and extremity NALM was performed.

Results

537 ALM from a total of 824 cutaneous melanoma cases were studied. Older age (p = 0.022), higher Breslow (p = 0.008) and ulceration (p < 0.001) were found to be more frequent in ALM. Acral had worse overall survival (OS) compared with the whole group (p = 0.04). Clinical stage (CS) I–II patients had a median OS of 5.3 (95% CI 4.3–6.2) for ALM and 9.2 (95% CI 5.0–7.0) for extremity NALM (p = 0.016). Grade 0 (absence of TIL), I, II and III were found in 7.5, 34.5, 32.1, and 25.9%, respectively. Lower TIL grade was associated with larger tumor size (p = 0.003), higher Breslow (p = 0.001), higher Clark level (p = 0.007), higher CS (p = 0.002), extremity location (p = 0.048), histological subtype ALM (p = 0.024) and better OS (p = 0.001).

Conclusions

ALM is highly prevalent in Peru and carries poor outcome. Lower TIL levels were associated with poor outcome and ALM.

http://ift.tt/2rtdAiM

Dysregulation of lysophosphatidic acids in multiple sclerosis and autoimmune encephalomyelitis

Abstract

Bioactive lipids contribute to the pathophysiology of multiple sclerosis. Here, we show that lysophosphatidic acids (LPAs) are dysregulated in multiple sclerosis (MS) and are functionally relevant in this disease. LPAs and autotaxin, the major enzyme producing extracellular LPAs, were analyzed in serum and cerebrospinal fluid in a cross-sectional population of MS patients and were compared with respective data from mice in the experimental autoimmune encephalomyelitis (EAE) model, spontaneous EAE in TCR¹⁶⁴⁰ mice, and EAE in Lpar2 ^-/- mice. Serum LPAs were reduced in MS and EAE whereas spinal cord LPAs in TCR¹⁶⁴⁰ mice increased during the 'symptom-free' intervals, i.e. on resolution of inflammation during recovery hence possibly pointing to positive effects of brain LPAs during remyelination as suggested in previous studies. Peripheral LPAs mildly re-raised during relapses but further dropped in refractory relapses. The peripheral loss led to a redistribution of immune cells from the spleen to the spinal cord, suggesting defects of lymphocyte homing. In support, LPAR2 positive T-cells were reduced in EAE and the disease was intensified in Lpar2 deficient mice. Further, treatment with an LPAR2 agonist reduced clinical signs of relapsing-remitting EAE suggesting that the LPAR2 agonist partially compensated the endogenous loss of LPAs and implicating LPA signaling as a novel treatment approach.

Graphical abstract

Graphical summary of lysophosphatidic signaling in multiple sclerosis

http://ift.tt/2rOc1yO

Long-term use of proton pump inhibitors among community-dwelling persons with and without Alzheimer’s disease

Abstract

Purpose

The aim of this study is to determine the prevalence of use and long-term use (≥180 days) of proton pump inhibitors (PPIs) and associated factors among community-dwellers with and without Alzheimer's disease (AD).

Methods

MEDALZ cohort encompassed all persons who received a verified diagnosis of AD in Finland during the years 2005–2011 and their age-, sex-, and region of residence-matched comparison persons, including 69,353 persons with and 69,353 persons without AD. Data was derived from several Finnish administrative registers. A mathematical modelling method, PRE2DUP, was used for converting dispensing data to drug use periods (when regular PPI use started and ended). Morbid conditions and concomitant drugs associated with use and long-term use of PPIs were assessed with logistic regression models.

Results

Use of PPIs was more common among comparison persons than persons with AD (39.0 and 35.8%, respectively, p < 0.001), whereas long-term use of PPIs was more frequent among persons with than without AD (20.3 and 17.9%, respectively, p < 0.001). Factors related to long-term use of PPIs were female sex, history of gastrointestinal bleedings, AD, rheumatoid arthritis, cardiovascular disease, asthma/COPD and use of bisphosphonates, SSRIs and antithrombotic agents. Median follow-up time was 2.6 years among persons with AD and 3.5 years among persons without AD. Median duration of the first long-term PPI use was similar in both groups (1.4 years).

Conclusion

Long-term use of PPIs was common among persons with and without AD. Due to possible adverse events associated with the long-term use of PPIs, need for PPIs should be assessed regularly.

http://ift.tt/2s20fAB

A step function density profile model for the convective stability of CO $$_2$$ 2 geological sequestration

Abstract

The convective stability associated with carbon sequestration is usually investigated by adopting an unsteady diffusive basic profile to account for the space and time development of the carbon-saturated boundary layer instability. The method of normal modes is not applicable due to the time dependence of the nonlinear base profile. Therefore, the instability is quantified either in terms of critical times at which the boundary layer instability sets in or in terms of long-time evolution of initial disturbances. This paper adopts an unstably stratified basic profile having a step function density with top heavy carbon-saturated layer (boundary layer) overlying a lighter carbon-free layer (ambient brine). The resulting configuration resembles that of the Rayleigh–Taylor problem with buoyancy diffusion at the interface separating the two layers. The discontinuous reference state satisfies the governing system of equations and boundary conditions and pertains to an unstably stratified motionless state. Our model accounts for anisotropy in both diffusion and permeability and chemical reaction between the carbon dioxide-rich brine and host mineralogy. We consider two cases for the boundary conditions, namely an impervious lower boundary with either a permeable (one-sided model) or poorly permeable upper boundary. These two cases possess neither steady nor unsteady unstably stratified equilibrium states. We proceed by supposing that the carbon dioxide that has accumulated below the top cap rock forms a layer of carbon-saturated brine of some thickness that overlies a carbon-free brine layer. The resulting stratification remains stable until the thickness, and by the same token, the density, of the carbon-saturated layer is sufficient to induce the fluid to overturn. The existence of a finite threshold value for the thickness is due to the stabilizing influence of buoyancy diffusion at the interface between the two layers. With this formulation for the reference state, the stability calculations will be in terms of critical boundary layer thickness instead of critical times, although the two formulations are homologous. This approach is tractable by the classical normal-mode analysis. Even though it yields only conservative threshold instability conditions, it offers the advantage for an analytically tractable study that puts forth expressions for the carbon concentration convective flux at the interface and explores the flow patterns through both linear and weakly nonlinear analyses.

http://ift.tt/2rsM6K9

Formation of Aldehydes and Carboxylic Acids in Humic Acid Ozonation

Abstract

The purpose of this study was to determine the different kinds and concentrations of intermediates, and investigate on the effects of contact time and ozone (O₃) doses on the removal of humic acid (HA), which is served as the main disinfection by-product (DBP) precursor. Based on that, the knowledge gap of DBPs generated was made up. The results showed that HA was the major precursor material for aldehydes and carboxylic acids. The concentrations of aldehydes increased as contact time and O₃ doses, and reached up maximum at 2~10 min but approached a plateau at the higher O₃ doses. The concentrations of formic and acetic acids increased as contact time and O₃ doses. However, aromatic acids, including protocatechuic, 3-hydroxybenzoic, and benzoic acids, declined rapidly at longer reaction time and higher O₃ doses. It was worth mentioning that aromatic acids had been rarely reported. Besides, a possible formation pathway was proposed: (a) HA was degraded into fulvic acid (FA)-like compounds; (b) FA-like compounds were further converted into aromatic acids; (c) aromatic acids were transformed into low-molecular-weight organic matters; (d) chlorine reacted with aldehydes and/or carboxylic acids by addition, hydrolysis, and decarbonylation reactions, leading to DBP formation. Furthermore, not only HA were the main DBPs precursors, but also the oxidation intermediates of HA could be the DBPs precursors, and they gave a certain amount of DBPs. Consequently, aldehydes and carboxylic acids should be under control in drinking water treatment plants.

http://ift.tt/2rNh0jh

Single Analyzer Precursor Ion Scans in a Linear Quadrupole Ion Trap Using Orthogonal Double Resonance Excitation

Abstract

Reported herein is a simple method of performing single analyzer precursor ion scans in a linear quadrupole ion trap using orthogonal double resonance excitation. A first supplementary AC signal applied to the y electrodes is scanned through ion secular frequencies in order to mass-selectively excite precursor ions while, simultaneously, a second fixed-frequency AC signal is applied orthogonally on the x electrodes in order to eject product ions of selected mass-to-charge ratios towards the detector. The two AC signals are applied orthogonally so as to preclude the possibility of (1) inadvertently ejecting precursor ions into the detector, which results in artifact peaks, and (2) prevent beat frequencies on the x electrodes from ejecting ions off-resonance. Precursor ion scans are implemented while using the inverse Mathieu q scan for easier mass calibration. The orthogonal double resonance experiment results in single ion trap precursor scans with far less intense artifact peaks than when both AC signals are applied to the same electrodes, paving the way for implementation of neutral loss scanning in single ion trap mass spectrometers.

Graphical Abstract

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http://ift.tt/2rt3Kxz

Revolutions and Reconstructions in the Philosophy of Science: Mary Hesse (1924–2016)

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Treatment of fifth metacarpal neck fractures with antegrade single elastic intramedullary nailing

Abstract

Background

The aim of this study was to investigate clinical outcomes of fifth metacarpal neck fractures using antegrade single elastic nail and to explore ideal puncture point to avoid iatrogenic ulnar nerve injury.

Methods

A single elastic nail with suitable diameter was used in 27 cases of fifth metacarpal neck fractures with dorsal angulation over 45°. An initial entry point was perforated at the ulnar-dorsal base of the metacarpal. The nail was inserted in an antegrade approach. The nail was usually removed at about 5 weeks postoperatively.

Results

At final follow up, all fractures proceeded to bony union. The mean total passive motion was 285° and the mean total active motion (TAM) was 270°. The mean angulation decreased from 50.2 ± 6.3° preoperatively to 7.4 ± 2.3° postoperatively (p < 0.001). The mean DASH-Score was 2.1 ± 3.6 points after surgery. Two cases of skin irritation and one case of the dorsal cutaneous branch of the ulnar nerve (DCBUN) injury were observed. Superficial wound infections were not observed.

Conclusions

Collectively, antegrade single elastic intramedullary nailing was a minimally invasive and reliable fixation technique for fifth metacarpal neck fractures with dorsal angulation over 45°. Appropriate puncture position helped to reduce nerve damage.

http://ift.tt/2smsvvf

Consultation patterns of children and adolescents with knee pain in UK general practice: analysis of medical records

Abstract

Background

Knee problems are common in children and adolescents. Despite this, little is known about the epidemiology of knee problems in children and adolescents who consult in general practice. The aim of this study was to describe consultations by children and adolescents about knee problems in general practice, and examine patterns of patient presentations and consultations by age group, sex and area of socio-economic deprivation.

Methods

Consultations records specific to the knee region were extracted from a general practice consultation database (CiPCA) over a one year period. Knee consultation codes were organised into 'symptom' or 'diagnosis' (sub-categorised: 'trauma', 'non-trauma') categories. Descriptive statistics were used to describe patient presentations and number of consultations overall, and stratified analysis carried out on age group, sex, and area of socio-economic deprivation.

Results

Out of all musculoskeletal consultations, knee problems were the fourth most common patient presentation, responsible for the second highest number of consultations. Patient presentations and consultations increased up to age 12–15 years and then stabilised. Symptoms codes e.g. 'knee pain' were used more commonly than diagnosis codes e.g. 'knee sprain' overall. However, symptom code use declined as age increased, more symptom codes were used in girls compared to boys, and more diagnosis codes were used in patients from areas of high socio-economic deprivation.

Conclusions

This study provides insight into the epidemiology of knee problems in children and adolescents in general practice. Future research is needed to improve our understanding of the knee problems encountered by GPs, and the influence socio-economic deprivation has on consultations.

http://ift.tt/2sm6nB7

RBM20, a potential target for treatment of cardiomyopathy via titin isoform switching

Abstract

Cardiomyopathy, also known as heart muscle disease, is an unfavorable condition leading to alterations in myocardial contraction and/or impaired ability of ventricular filling. The onset and development of cardiomyopathy have not currently been well defined. Titin is a giant multifunctional sarcomeric filament protein that provides passive stiffness to cardiomyocytes and has been implicated to play an important role in the origin and development of cardiomyopathy and heart failure. Titin-based passive stiffness can be mainly adjusted by isoform switching and post-translational modifications in the spring regions. Recently, genetic mutations of TTN have been identified that can also contribute to variable passive stiffness, though the detailed mechanisms remain unclear. In this review, we will discuss titin isoform switching as it relates to alternative splicing during development stages and differences between species and muscle types. We provide an update on the regulatory mechanisms of TTN splicing controlled by RBM20 and cover the roles of TTN splicing in adjusting the diastolic stiffness and systolic compliance of the healthy and the failing heart. Finally, this review attempts to provide future directions for RBM20 as a potential target for pharmacological intervention in cardiomyopathy and heart failure.

http://ift.tt/2rzs8zr

Interferometric study of the effect of laser intensity and polarization on the cold-drawing of virgin polypropylene fibres

Abstract

With the aid of the Mach–Zehnder interferometer, the drawability of polypropylene fibres (PP) was optically studied. The effect of varying the intensity of He–Ne laser on PP opto-mechanical properties was investigated. The state of polarization of the used laser was found to influence the optical and mechanical properties of PP fibres, such as the refractive index, elongation at break, work of rupture and the stress–strain curves. As a key finding, it is found that the PP fibres break at different draw ratios when the state of polarization is changed from 0° to 90°.

http://ift.tt/2qIt1CE

Predisposing factors for recurrence of chronic posttraumatic osteomyelitis: a retrospective observational cohort study from a tertiary referral center in Brazil

Abstract

Background

The incidence of posttraumatic osteomyelitis (PTO) is increasing despite new treatment strategies. Assessment of patients' outcomes following PTO is challenging due to multiple variables. The study goals are to determine the frequency of recurrence following PTO treatment and identify factors predisposing patients to treatment failure.

Methods

Between August 01, 2007 to August 30, 2012, a single-center retrospective cohort study was performed among 193 patients diagnosed with PTO following orthopedic surgery for fracture care. Bone and soft tissues were collected for cultures and PTO was defined according to CDC/NHSN criteria. Patient, injury, surgery-associated variables, and microbiological records were reviewed for risk factors associated to recurrence of PTO. Univariate and multivariable analyses using logistic regression were performed, with p <0.05 considered significant.

Results

Thirty-eight patients (20%) of 192 diagnosed and treated for PTO failed their treatment. Factors associated with recurrence were age between 61 and 80 years [hazard ratio (HR) = 6.086, 95% confidence interval (CI) = 2.459;15.061, p = <0.001], age above 80 years [HR = 9.975 (95% CI = 3.591;27.714), p = <0.001], intraoperative blood transfusion [HR = 2.239 (95% CI = 1.138;4.406), p = 0.020], and positive culture for Pseudomonas aeruginosa [HR = 2.700 (95% CI = 1.370;5.319), p = 0.004].

Conclusions

Risk factors associated with recurrence of PTO are difficult to measure. The present study revealed that elderly patients, intraoperative blood transfusions, and infection due to P. aeruginosa were independently associated with recurrence of PTO. These factors should warn clinicians of a higher failure rate following treatment of PTO. Trial registration: ISRCTN71648577. Registered 18 May 2017. Retrospectively registered.

http://ift.tt/2qK5EN4

Unstimulated salivary flow, pH, proteins and oral health in patients with Juvenile Idiopathic Arthritis

Abstract

Background

There have been inconsistent conclusions regarding salivary abnormalities and their effect on oral health of Juvenile Idiopathic Arthritis (JIA) patients. The purpose of the study was to evaluate the flow rate and selected biochemical parameters of unstimulated whole saliva in correlation to oral health in JIA children.

Methods

Thirty-four JIA patients and 34 age- and sex-matched controls not affected by JIA (C) were divided into two groups: with mixed and permanent dentition. DMFT/dmft, gingival and simplified oral hygiene indices were evaluated. Salivary flow rate, pH, lysozyme, lactoferrin, salivary protein concentrations and peroxidase activity were assessed.

Results

The salivary flow rate was significantly lower in the total JIA group (0.41 ml/min) as compared with the C (0.51 ml/min) and in the permanent dentition of JIA children (0.43 ml/min) as compared with the C (0.61 ml/min). A significantly lower pH was observed in total (6.74), mixed (6.7) and permanent (6.76) dentition of JIA groups in comparison to the C (7.25, 7.21, 7.28 respectively). The specific activity of peroxidase was significantly higher in JIA patients (total 112.72 IU/l, mixed dentition 112.98 IU/l, permanent dentition 112.5 IU/l) than in the C group (total 70.03 IU/l, mixed dentition 71.83 IU/l, permanent dentition 68.61 IU/l). The lysozyme concentration in JIA patients (total and permanent dentition groups) was significantly higher than in the C group. There were no significant differences in lactoferrin and salivary protein concentrations. There were no statistically significant differences in oral status between JIA patients and C, respectively: DMFT = 5.71, dmft = 3.73, OHI-S = 0.95, GI = 0.25 and DMFT 5.71, dmft = 3.73, OHI-S = 0.85, GI = 0.24. The specific activity of peroxidase in the unstimulated whole saliva was inversely correlated with the GI index, whereas the salivary lysozyme concentration was inversely correlated with the dmft index in JIA patients.

Conclusion

In the course of JIA occur a reduction of the resting salivary flow rate and a decrease of saliva pH. In spite of this, no differences in the clinical oral status between the JIA children population and the control group were found. The mobilisation of salivary peroxidase and lysozyme contributes to the maintenance of healthy oral tissues.

http://ift.tt/2rMYisk

Epidemiology and time trends of distal forearm fractures in adults - a study of 11.2 million person-years in Sweden

Abstract

Background

A distal forearm fracture is a very common injury causing both suffering and substantial health care costs. The incidence of this fracture type seemed to increase worldwide until the middle 1980's, but thereafter most reports have shown stable or decreasing rates. As few large studies have been presented lately we aimed to describe recent epidemiology and time trends of distal forearm fractures in adults. We paid special attention to fractures in working ages as they present challenges in terms of treatment and costs for sick-leave, and have not previously been thoroughly investigated.

Methods

By use of population data from Statistics Sweden and official in- and out-patient register data of men and women (≥17 years) in Sweden (Skåne region), we ascertained distal forearm fractures and estimated age- and sex-specific rates and time-trends from year 1999 to 2010 (11.2 million person-years (py)).

Results

The total incidence rate was 278 per 100,000 py (31,233 fractures) with 23% higher annual numbers 2010 compared with 1999. An increase in the annual age standardized incidence was found in men, +0.7% per annum (95% confidence interval (CI) 0.1, 1.4), and women, +0.9% (95% CI 0.5, 1.3), driven mainly by an increasing incidence in working ages (17–64 years). Also, expected demographic changes including a 25% population increase may result in 38% more fractures until 2050, compared to 2017.

Conclusions

The incidence of distal forearm fractures in adults in southern Sweden is increasing, mainly driven by an increase in working ages. In combination with expected demographic changes these findings may present substantial challenges for the future.

http://ift.tt/2s1pYcH

Effect of personal exposure to black carbon on changes in allergic asthma gene methylation measured 5 days later in urban children: importance of allergic sensitization

Abstract

Background

Asthma gene DNA methylation may underlie the effects of air pollution on airway inflammation. However, the temporality and individual susceptibility to environmental epigenetic regulation of asthma has not been fully elucidated. Our objective was to determine the timeline of black carbon (BC) exposure, measured by personal sampling, on DNA methylation of allergic asthma genes 5 days later to capture usual weather variations and differences related to changes in behavior and activities. We also sought to determine how methylation may vary by seroatopy and cockroach sensitization and by elevated fractional exhaled nitric oxide (FeNO).

Methods

Personal BC levels were measured during two 24-h periods over a 6-day sampling period in 163 New York City children (age 9–14 years), repeated 6 months later. During home visits, buccal cells were collected as noninvasive surrogates for lower airway epithelial cells and FeNO measured as an indicator of airway inflammation. CpG promoter loci of allergic asthma genes (e.g., interleukin 4 (IL4), interferon gamma (IFNγ), inducible nitric oxide synthase (NOS2A)), arginase 2 (ARG2)) were pyrosequenced at the start and end of each sampling period.

Results

Higher levels of BC were associated with lower methylation of IL4 promoter CpG⁻⁴⁸ 5 days later. The magnitude of association between BC exposure and demethylation of IL4 CpG⁻⁴⁸ and NOS2A CpG⁺⁵⁰⁹⁹ measured 5 days later appeared to be greater among seroatopic children, especially those sensitized to cockroach allergens (RR [95% CI] 0.55 [0.37–0.82] and 0.67 [0.45–0.98] for IL4 CpG⁻⁴⁸ and NOS2A CpG⁺⁵⁰⁹⁹, respectively), compared to non-sensitized children (RR [95% CI] 0.87 [0.65–1.17] and 0.95 [0.69–1.33] for IL4 CpG⁻⁴⁸ and NOS2A CpG⁺⁵⁰⁹⁹, respectively); however, the difference was not statistically different. In multivariable linear regression models, lower DNA methylation of IL4 CpG⁻⁴⁸ and NOS2A CpG⁺⁵⁰⁹⁹ were associated with increased FeNO.

Conclusions

Our results suggest that exposure to BC may exert asthma proinflammatory gene demethylation 5 days later that in turn may link to airway inflammation. Our results further suggest that seroatopic children, especially those sensitized to cockroach allergens, may be more susceptible to the effect of acute BC exposure on epigenetic changes.

http://ift.tt/2rMTFye

Ideal T1 laminar screw fixation based on computed tomography morphometry

Abstract

Background

The application of laminar screws is an alternative fixation for the first thoracic vertebra (T1). This paper is to determine the anatomical characteristics for adequate laminar screw fixation, and present a modified method of sagittal reconstruction of T1 to provide more accurate measurements.

Methods

Computed tomography (CT) images of 62 patients (32 males, 30 females) were used for the analysis. The following parameters of the T-1 lamina were measured using Mimics software: lamina length, axis angle, minimal outer cortical width, cancellous width, minimal outer cortical height, cancellous height, and spinous process height. Right or left modified sagittal reconstructions (parallel to right or left screws) were innovatively used for measurement.

Results

There were no significant differences between the left and right sides for each measurement performed (P > 0.05), but significant differences were detected between males and females (P < 0.05). The mean length of the T1 lamina was 32.8 mm of the T1 minimal outer cortical width was 7.4 mm, and 3.8% of males had a minimal outer cortical width < 5 mm, while 8.6% of females had a minimal outer cortical width < 5 mm. The mean minimal outer cortical height was 10.8 mm, and 1.9% of males had a minimal outer cortical height < 9 mm, while 7.7% of females had a minimal outer cortical height < 9 mm.

Conclusion

This study suggests there are no anatomical limitations for T1 laminar screw placement in most people. The modified sagittal reconstruction method described allows for easy and precise measurement to aid in the insertion of laminar screws in T1, and gives good visualization of laminar screw insertion direction.

http://ift.tt/2qIjtas

Consultation patterns of children and adolescents with knee pain in UK general practice: analysis of medical records

Abstract

Background

Knee problems are common in children and adolescents. Despite this, little is known about the epidemiology of knee problems in children and adolescents who consult in general practice. The aim of this study was to describe consultations by children and adolescents about knee problems in general practice, and examine patterns of patient presentations and consultations by age group, sex and area of socio-economic deprivation.

Methods

Consultations records specific to the knee region were extracted from a general practice consultation database (CiPCA) over a one year period. Knee consultation codes were organised into 'symptom' or 'diagnosis' (sub-categorised: 'trauma', 'non-trauma') categories. Descriptive statistics were used to describe patient presentations and number of consultations overall, and stratified analysis carried out on age group, sex, and area of socio-economic deprivation.

Results

Out of all musculoskeletal consultations, knee problems were the fourth most common patient presentation, responsible for the second highest number of consultations. Patient presentations and consultations increased up to age 12–15 years and then stabilised. Symptoms codes e.g. 'knee pain' were used more commonly than diagnosis codes e.g. 'knee sprain' overall. However, symptom code use declined as age increased, more symptom codes were used in girls compared to boys, and more diagnosis codes were used in patients from areas of high socio-economic deprivation.

Conclusions

This study provides insight into the epidemiology of knee problems in children and adolescents in general practice. Future research is needed to improve our understanding of the knee problems encountered by GPs, and the influence socio-economic deprivation has on consultations.

http://ift.tt/2sm6nB7

Tangeretin inhibits neurodegeneration and attenuates inflammatory responses and behavioural deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease dementia in rats

Abstract

Our aim was to investigate whether tangeretin, a citrus flavonoid, was able to prevent neuroinflammation and improve dementia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rodent model of Parkinson's disease (PD). MPTP-HCl was infused into the substantia nigra pars compacta of male Sprague–Dawley rats. Tangeretin (50, 100 or 200 mg/kg body weight) was administered orally starting 3 days prior to MPTP injection and was continued for 20 days following injection. MPTP-lesioned rats revealed motor dysfunction in bar test and rota rod tests. Deficits in working memory and object recognition function were also observed following MPTP induction. Tangeretin treatment significantly attenuated the memory deficits and improved motor functions and cognition. Immunohistochemical analysis reveals the protective effects of tangeretin against MPTP lesion-induced dopaminergic degeneration and hippocampal neuronal loss. Tangeretin reduced expression of inflammatory mediators—COX-2, iNOS—as well reduced the levels of cytokines—interleukins (IL)—IL-1β, IL-6 and IL-2. The experimental data suggest tangeretin as an effective candidate drug with potential for prevention and treatment of neuroinflammation and dementia associated with PD.

http://ift.tt/2smCtNk

Survival and quality of life in incident systemic sclerosis-related pulmonary arterial hypertension

Abstract

Background

Pulmonary arterial hypertension (PAH) is a leading cause of mortality in systemic sclerosis (SSc). We sought to determine survival, predictors of mortality, and health-related quality of life (HRQoL) related to PAH in a large SSc cohort with PAH.

Methods

We studied consecutive SSc patients with newly diagnosed (incident) World Health Organization (WHO) Group 1 PAH enrolled in a prospective cohort between 2009 and 2015. Survival methods were used to determine age and sex-adjusted standardised mortality ratio (SMR) and years of life lost (YLL), and to identify predictors of mortality. HRQoL was measured using the Short form 36 (SF-36) instrument.

Results

Among 132 SSc-PAH patients (112 female (85%); mean age 62 ± 11 years), 60 (45.5%) died, with a median (±IQR) survival time from PAH diagnosis of 4.0 (2.2–6.2) years. Median (±IQR) follow up from study enrolment was 3.8 (1.6–5.8) years. The SMR for patients with SSc-PAH was 5.8 (95% CI 4.3–7.8), with YLL of 15.2 years (95% CI 12.3–18.1). Combination PAH therapy had a survival advantage (p < 0.001) compared with monotherapy, as did anticoagulation compared with no anticoagulation (p < 0.003). Furthermore, combination PAH therapy together with anticoagulation had a survival benefit compared with monotherapy with or without anticoagulation and combination therapy without anticoagulation (hazard ratio 0.28, 95% CI 0.1–0.7). Older age at PAH diagnosis (p = 0.03), mild co-existent interstitial lung disease (ILD) (p = 0.01), worse WHO functional class (p = 0.03) and higher mean pulmonary arterial pressure at PAH diagnosis (p = 0.001), and digital ulcers (p = 0.01) were independent predictors of mortality.

Conclusions

Despite the significant benefits conferred by advanced PAH therapies suggested in this study, the median survival in SSc PAH remains short at only 4 years.

http://ift.tt/2rMXgN0

Treatment of fifth metacarpal neck fractures with antegrade single elastic intramedullary nailing

Abstract

Background

The aim of this study was to investigate clinical outcomes of fifth metacarpal neck fractures using antegrade single elastic nail and to explore ideal puncture point to avoid iatrogenic ulnar nerve injury.

Methods

A single elastic nail with suitable diameter was used in 27 cases of fifth metacarpal neck fractures with dorsal angulation over 45°. An initial entry point was perforated at the ulnar-dorsal base of the metacarpal. The nail was inserted in an antegrade approach. The nail was usually removed at about 5 weeks postoperatively.

Results

At final follow up, all fractures proceeded to bony union. The mean total passive motion was 285° and the mean total active motion (TAM) was 270°. The mean angulation decreased from 50.2 ± 6.3° preoperatively to 7.4 ± 2.3° postoperatively (p < 0.001). The mean DASH-Score was 2.1 ± 3.6 points after surgery. Two cases of skin irritation and one case of the dorsal cutaneous branch of the ulnar nerve (DCBUN) injury were observed. Superficial wound infections were not observed.

Conclusions

Collectively, antegrade single elastic intramedullary nailing was a minimally invasive and reliable fixation technique for fifth metacarpal neck fractures with dorsal angulation over 45°. Appropriate puncture position helped to reduce nerve damage.

http://ift.tt/2smsvvf

RANK/RANKL/OPG system in the intervertebral disc

Abstract

Background

The receptor activator of NF-κB ligand (RANKL), a member of the TNF ligand superfamily, is known to regulate bone metabolism. The expression of each component of the RANK/RANKL/osteoprotegerin (OPG) system in the intervertebral disc (IVD) has not been examined in detail. The purposes of this study were to examine the expression of the RANK/RANKL/OPG system and to evaluate the function of RANKL in the matrix metabolism of the rat IVD.

Methods

Sprague-Dawley, 12-week-old, male rats were used in this study. Anulus fibrosus (AF), nucleus pulposus (NP) and cartilaginous endplate (CEP) cells isolated from dissected thoracolumbar discs were monolayer-cultured. RANK/RANKL/OPG expression in rat IVDs was examined using real-time polymerase chain reaction (PCR) and immunohistochemical analysis (cultured cells and IVD tissues). To examine the effect of interleukin-1β (IL-1β) stimulation on the mRNA levels of RANK, RANKL and OPG, the cells were cultured with or without recombinant human IL-1β (rhIL-1β). To evaluate the effect of RANKL on the mRNA expression of catabolic factors (IL-1β, matrix metalloproteinase-3 (MMP-3) and MMP-13), the cells were cultured with RANKL in the presence or absence of rhIL-1β. The immunohistochemical expression of this system was also evaluated using human IVD tissues with different grades of degeneration.

Results

mRNA expression levels of RANK, RANKL, and OPG were clearly identified in AF, NP and CEP cells. Immunoreactivity to RANK, RANKL and OPG was distributed in the cell membranes and/or cytoplasm of the three types of cells. The mRNA level of RANKL was significantly upregulated by treatment with rhIL-1β of the three types of cells. Treatment with RANKL without rhIL-1β did not induce significant effects on the mRNA expression of catabolic factors by AF, NP and CEP cells. However, the expression was significantly upregulated by stimulation with RANKL in the presence of rhIL-1β. There was a general trend for more RANK/RANKL/OPG-positive cells in human IVD tissues in an advanced stage of degeneration compared to an early stage.

Conclusions

Our study showed the possibility that the RANK/RANKL/OPG system may play a part in the process of intervertebral disc degeneration.

http://ift.tt/2rN9vJe

Change in child mortality patterns after injuries in Sweden: a nationwide 14-year study

Abstract

Introduction

Sweden has one of the world's lowest child injury mortality rates, but injuries are still the leading cause of death among children. Child injury mortality in the country has been declining, but this decline seems to decrease recently. Our objective was therefore to further examine changes in the mortality of children's death from injury over time and to assess the contribution of various effects on mortality. The underlying hypothesis for this investigation is that the incidence of lethal injuries in children, still is decreasing and that this may be sex specific.

Patients and methods

We studied all deaths from injury in Sweden under-18-year-olds during the 14 years 1999–2012. We identified those aged under 18 whose underlying cause of death was recorded as International Classification of Diseases, 10th Revision (ICD-10) diagnosis from V01 to X39 in the Swedish cause of death, where all dead citizens are registered.

Results

From the 1 January 1999 to 31 December 2012, 1213 children under the age of 18 died of injuries in Sweden. The incidence declined during this period (r = −0.606, p = 0.02) to 3.3 deaths/100,000 children-years (95 % CI 2.6–4.2). Death from unintentional injury was more common than that after intentional injury (p < 0.0001). There was a reduction in the incidence of unintentional injuries during the study period (r = −0.757, p = 0.03). The most common causes of death were injury to the brain (n = 337, 41 %), followed by drowning (n = 109, 13 %). The number of deaths after intentional injury increased (r = 0.585, p = 0.03) and at the end of the period was 1.5 deaths/100,000 children-years. The most common causes of death after intentional injuries were asphyxia (n = 177, 45 %), followed by injury to the brain (n = 76, 19 %).

Discussion

Mortality patterns in injured children in Sweden have changed from being dominated by unintentional injuries to a more equal distribution between unintentional and intentional injuries as well as between sexes and the overall rate has declined further. These findings are important as they might contribute to the preventive work that is being done to further reduce mortality in injured children.

http://ift.tt/2rNdfum

Intraperitoneal rupture of hydatid cysts

Abstract

Purpose

Hydatid cyst rupture into abdominal cavity is a rare but a serious complication. The rupture can occur after a trauma, or spontaneously as a result of increased intracystic pressure. It is a surgical emergency with high morbidity and mortality rates. Early diagnosis and appropriate surgical management of this complication can be life saving. The objective of the current paper is to evaluate the clinical, and radiographic findings and surgical treatment of this complication.

Methods

A retrospective study on 12 patients operated in our department for intraperitoneal rupture of hydatid cyst between January 1990 and May 2015. We reviewed age, gender, imaging findings, surgical treatment procedures, mortality, morbidity and recurrence.

Results

Our study includes 12 cases of intraperitoneal rupture of hydatid cysts; eight of the patients were men, and four were women. Four patients had a history of abdominal trauma and the other ruptures occurred spontaneously. All the patients had peritoneal irritation signs at presentation. All them underwent ultrasonography and CT scan. Imaging showed intraabdominal free fluid in all of cases. In 11 cases the cyst was unique and only in one case an associated mesenteric hydatid cyst was noted. Ruptured cysts were located in the right lobe of the liver in nine cases, in the left lobe in the other three cases. All the patients underwent emergency surgery after imaging. The procedure applied was conservative associated with drainage in all the cases. Some associated procedures were performed during the same operation. In only one case total pericystectomy for intraperitoneal cyst was performed. There were no post operative deaths. A total of five morbidities developed in three patients (one case of evisceration, three cases of biliary fistula and a case of pulmonary infection).

Conclusions

Hydatid cyst rupture in peritoneal cavity is a rare complication. Imaging assessment has an important role in diagnosis but clinical signs are mandatory. A quick diagnosis and emergency surgery can decrease postoperative death. Surgery and postoperative care constitute the basis of treatment.

http://ift.tt/2smku9s

Pathological Findings of the Antral and Pyloric Smooth Muscle in Patients with Gastroparesis-Like Syndrome Compared to Gastroparesis: Similarities and Differences

Abstract

Background

Gastroparesis (GP)-like syndrome presents with the symptoms of GP but without delayed gastric emptying (GE). Whether GP-like syndrome is part of a spectrum of GP is not clear. This study aimed to compare the histopathological features of antral and pyloric smooth muscle tissue in GP and GP-like syndrome.

Methods

Full-thickness antral and/or pyloric biopsies were obtained from 37 GP and 18 GP-like syndrome patients who underwent abdominal surgery to place a gastric electrical stimulator or jejunal feeding tube and/or pyloroplasty. The tissues were stained with H&E, C-Kit, and trichrome. Based on previous control data, an interstitial cells of Cajal (ICC) count of <10 per high power field in the antrum and/or pylorus was considered depletion. Baseline total symptom score (TSS) was recorded.

Results

Twenty-four GP and 7 GP-like patients had pyloric biopsies. Pyloric ICC loss was observed in 20/24 (83.3%) GP and 2/7 (28.6%) GP-like patients (p < 0.01). Fibrosis was detected in the pyloric tissue of 20/24 (83.3%) GP and 2/7 (28.6%) GP-like patients who had pyloric trichrome staining (p < 0.01). Seventeen out of 24 (70.8%) GP patients with pyloric biopsies had concomitant pyloric ICC loss and fibrosis, while only one GP-like patient had ICC loss and simultaneous pyloric fibrosis. GP patients had a greater TSS compared to GP-like patients. In GP patients, those with pyloric ICC loss had a greater TSS compared to those with normal ICC. GP patients with pyloric fibrosis had a higher TSS compared to those without pyloric fibrosis.

Conclusions

Compared to GP-like patients, the pyloric histopathological findings of ICC loss and fibrosis are common in GP and predict a greater symptom score. These pathological findings might be considered as markers of "pyloric dysfunction" and explain delayed GE in GP.

http://ift.tt/2sxqXOj

Association of endometrial hyperplasia and cancer with a history of gestational diabetes

Abstract

Purpose

Excess circulating insulin may contribute to endometrial cancer (EC) development; studies suggest increased risk of EC associated with type 2 diabetes. We investigated whether gestational diabetes is associated with increased risk of EC and its precursor, endometrial hyperplasia (EH).

Methods

We conducted a population-based, case–control study of women in Washington State. Cases were women with a hospital discharge record indicating the presence of EH/EC who could be linked to a prior delivery hospitalization or birth record from 1987 to 2013 (n = 593). Controls were randomly selected from remaining deliveries, frequency matched 10:1 on delivery year and maternal age at delivery (n = 5,743). Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results

After adjustment for race/ethnicity, maternal age at delivery, and delivery year, EH/EC was associated with a history of gestational diabetes (OR 1.73, 95% CI 1.27–2.35). This association was present for both EH and EC (OR 1.61, 95% CI 1.00–2.60 and OR 1.80, 95% CI 1.22–2.65, respectively). After adjustment for prepregnancy body mass index, the OR for EH/EC was attenuated and became statistically non-significant (OR 1.22, 95% CI 0.87–1.72), except in women <50 years old at the time of case ascertainment (OR 1.49, 95% CI 1.00–2.20). Associations were slightly stronger for EC than EH.

Conclusions

We observed an association between EH/EC and a history of gestational diabetes specific to younger women. Future studies focusing on the relationships between gestational diabetes, obesity, and EC, including age at diagnosis, are warranted.

http://ift.tt/2qO3Fm3

Cost minimization analysis of treatment with intravenous or subcutaneous trastuzumab in patients with HER2-positive breast cancer in Spain

Abstract

Purpose

To describe healthcare professional (HCP) and patient time and related costs associated with trastuzumab intravenous infusion (IV) and trastuzumab subcutaneous (SC) formulations in patients with HER2-positive early breast cancer.

Methods

This prospective, observational time, and motion study in three Spanish centers was run as a substudy of the PrefHer trial. We recorded active HCP time for trastuzumab SC and IV-related tasks and calculated HCP time as the mean sum of task times over 154 administrations (80 IV, 74 SC). We calculated mean patient infusion chair time and treatment room time. Staff costs were calculated using fully loaded salary costs based on Spanish salaries (€ 2012).

Results

The transition from trastuzumab IV to SC led to a 50% reduction in active HCP time [27.2 min (95% CI 21.8–32.6) vs. 13.2 min (95% CI 8.9–17.5) per cycle]. Time savings resulted from avoiding IV catheter installation and removal, line flushing, and drug reconstitution. SC administration led to a fivefold reduction (78–85%) in chair time and a fourfold reduction (59–81%) in patient treatment room time, resulting in 24 h free-up time in the total treatment course (18 cycles). Total estimated direct costs were € 29,431.75 and € 28,452.12 for IV and SC, respectively, a saving of € 979.60 over a full treatment course.

Conclusions

Trastuzumab SC provided substantial time savings for HCP and patients, and reduced staff costs vs. trastuzumab IV. Reducing the use of hospital facilities may result in further savings and improved quality of medical care.

http://ift.tt/2rMYIir

Regenerative properties of collagenated porcine bone grafts in human maxilla: demonstrative study of the kinetics by synchrotron radiation microtomography and light microscopy

Abstract

Objectives

Recently, it has been reported that heterologous biomaterials, where the collagen matrix is preserved, seem to facilitate blood clotting and the subsequent invasion of repairing and regenerative cells. This study aimed at evaluating the healing of human extraction sockets grafted with a collagenated cortico-cancellous porcine bone (mp3®, OsteoBiol®, Tecnoss®, Giaveno, Italy) by synchrotron radiation X-ray microtomography (microCT) and histology in order to have a 3D quantitative characterization over time.

Materials and methods

Ridge preservation with porcine bone and collagen membrane was performed on 21 patients using a flapless approach and a secondary soft tissue closure. At the time of implant placement, six bone samples were harvested, two in the 3-month group, two in the 6-month group, one in the 12-month group post-surgery, and one spontaneously healed control, and evaluated by microCT and histology.

Results

MicroCT revealed that in the grafted sites there were a greater number of trabeculae, although they appeared thinner than in the control sites; these trabeculae homogenously filled the defects, suggesting an improved strength of the socket. Histology showed that over time, the amount of biomaterial decreased and the newly formed bone increased, while less dense bone with wider marrow spaces was detected in the control sample, supporting synchrotron findings.

Conclusions

The morphometric data converge to indicate the suitability of porcine bone for the preservation of post-extraction sockets.

Clinical relevance

The use of mp3 is encouraged to preserve and heal sockets.

http://ift.tt/2rsywGN

Multi-level deep supervised networks for retinal vessel segmentation

Abstract

Purpose

Changes in the appearance of retinal blood vessels are an important indicator for various ophthalmologic and cardiovascular diseases, including diabetes, hypertension, arteriosclerosis, and choroidal neovascularization. Vessel segmentation from retinal images is very challenging because of low blood vessel contrast, intricate vessel topology, and the presence of pathologies such as microaneurysms and hemorrhages. To overcome these challenges, we propose a neural network-based method for vessel segmentation.

Methods

A deep supervised fully convolutional network is developed by leveraging multi-level hierarchical features of the deep networks. To improve the discriminative capability of features in lower layers of the deep network and guide the gradient back propagation to overcome gradient vanishing, deep supervision with auxiliary classifiers is incorporated in some intermediate layers of the network. Moreover, the transferred knowledge learned from other domains is used to alleviate the issue of insufficient medical training data. The proposed approach does not rely on hand-crafted features and needs no problem-specific preprocessing or postprocessing, which reduces the impact of subjective factors.

Results

We evaluate the proposed method on three publicly available databases, the DRIVE, STARE, and CHASE_DB1 databases. Extensive experiments demonstrate that our approach achieves better or comparable performance to state-of-the-art methods with a much faster processing speed, making it suitable for real-world clinical applications. The results of cross-training experiments demonstrate its robustness with respect to the training set.

Conclusions

The proposed approach segments retinal vessels accurately with a much faster processing speed and can be easily applied to other biomedical segmentation tasks.

http://ift.tt/2rMKQEC

Suche nach Risikogenen bei der Alzheimer-Erkrankung

Zusammenfassung

Die Alzheimer-Erkrankung („Alzheimer's disease", AD) ist die häufigste Form der neurodegenerativen Demenz. Die Suszeptibilität für die AD wird durch eine komplexe Interaktion zwischen genetischen, epigenetischen und Umweltfaktoren bestimmt. Generell beträgt das Risiko, welches genetischen Faktoren zugeordnet werden kann, ca. 80 %. Obwohl die meisten AD-Fälle sporadisch sind, gibt es jedoch auch Familien mit seltenen voll penetranten Mutationen in APP, PSEN1 und PSEN2. Diese sind jedoch sehr selten und kaum mit sporadischen Fällen assoziiert. Über 20 Jahre lang war das APOE-ε4-Allel der einzige bekannte genetische Risikofaktor der sporadischen AD, der die Suszeptibilität zur AD in etwa dreifach erhöht. Durch die Entwicklung der genomweiten Assoziationsstudien wurde die Suche nach zusätzlichen genetischen Faktoren vorangetrieben und führte zur Identifizierung 26 neuer Risikovarianten. Bei genauerer Betrachtung lassen sich diese Gene in verschiedene Gruppen einordnen, die maßgeblich in bestimmten biologischen Signalwegen zusammengefasst werden können, wie Cholesterol- und Lipidmetabolismus, Immunantwort sowie endozytotische Transportvorgänge; u. a. mithilfe neuer Sequenziermethoden wurden zudem neue Impulse in der Risikogensuche gesetzt. Durch die Exomsequenzierung wurden Assoziationen zwischen der AD und seltenen kodierenden Varianten bei TREM2, SORL1 und ABCA1 aufgedeckt (geringere Allelfrequenz <1 %). Somit hat der Fortschritt der genetischen Forschung maßgeblich zum Verständnis der Krankheitsmechanismen beigetragen. Doch obwohl unser Wissen über die Genetik der AD deutlich vorangeschritten ist, ist es noch weit davon entfernt, vollständig zu sein. Um jedoch die genaue Architektur der AD zu vervollständigen, muss weitere intensive Forschung betrieben werden.

http://ift.tt/2rz5Xt8

The effectiveness of creatine treatment for Parkinson’s disease: an updated meta-analysis of randomized controlled trials

Abstract

Background

The effectiveness of creatine in treating Parkinson's disease (PD) has not been conclusively determined. Therefore, we performed a meta-analysis to address this issue.

Methods

The Cochrane Central Register of Controlled Trials, PUBMED, EMBASE, and other databases were searched, and outcomes measured by the Total Unified Parkinson's Disease Rating Scale (UPDRS) and the Schwab & England Scale were analyzed.

Results

Five randomized controlled trials (RCTs) were selected, and 1339 participants were included in the analysis. There were no significant differences between the control and treatment groups in the total, mental, activities of daily living (ADL), or motor UPDRS scores, but an improvement in Schwab & England Scale scores was observed.

Conclusions

Creatine has no observed benefit in PD patients, although more correlated studies are still needed.

http://ift.tt/2smeA8t

A combined experimental and molecular dynamics simulation study on the miscibility of Eucommia ulmoides gum with butadiene rubber

Abstract

The miscibility of Eucommia ulmoides gum (EUG) blended with butadiene rubber (BR) was investigated by atomistic molecular dynamics (MD), mesoscopic dynamics (MesoDyn) simulations and melt-mixing in an open two-roll mill at 80°C and 50 rpm. Seven EUG/BR blends (with weight ratios of 80/20, 70/30, 50/50, 30/70, and 20/80), as well as pure EUG and BR, were examined. Flory Huggins parameters, phase diagrams, the radial distribution function, free energy, and order parameters were computed for different blends using atomistic simulations to predict blend miscibility. The simulation results showed that all the EUG/BR blends have good miscibility. However, the mechanical properties of the vulcanized EUG/BR blends improved with the addition of EUG into BR matrix, and scanning electron microscopy (SEM) micrographs of the fractured surface had also revealed that the phase separation was not found, but which indicated EUG/BR had good miscibility. All the simulation results are qualitatively consistent with the experimental results, which demonstrates that the modeling strategies in this study may provide a powerful tool for predicting the miscibility and mesoscopic morphology of polymer blends.

http://ift.tt/2rsyuyG

Ideal T1 laminar screw fixation based on computed tomography morphometry

Abstract

Background

The application of laminar screws is an alternative fixation for the first thoracic vertebra (T1). This paper is to determine the anatomical characteristics for adequate laminar screw fixation, and present a modified method of sagittal reconstruction of T1 to provide more accurate measurements.

Methods

Computed tomography (CT) images of 62 patients (32 males, 30 females) were used for the analysis. The following parameters of the T-1 lamina were measured using Mimics software: lamina length, axis angle, minimal outer cortical width, cancellous width, minimal outer cortical height, cancellous height, and spinous process height. Right or left modified sagittal reconstructions (parallel to right or left screws) were innovatively used for measurement.

Results

There were no significant differences between the left and right sides for each measurement performed (P > 0.05), but significant differences were detected between males and females (P < 0.05). The mean length of the T1 lamina was 32.8 mm of the T1 minimal outer cortical width was 7.4 mm, and 3.8% of males had a minimal outer cortical width < 5 mm, while 8.6% of females had a minimal outer cortical width < 5 mm. The mean minimal outer cortical height was 10.8 mm, and 1.9% of males had a minimal outer cortical height < 9 mm, while 7.7% of females had a minimal outer cortical height < 9 mm.

Conclusion

This study suggests there are no anatomical limitations for T1 laminar screw placement in most people. The modified sagittal reconstruction method described allows for easy and precise measurement to aid in the insertion of laminar screws in T1, and gives good visualization of laminar screw insertion direction.

http://ift.tt/2qIjtas