Evaluation of the Positional Accuracy and Dosimetric Properties of a Three-dimensional Printed Device for Head and Neck Immobilization.
Our aim was to investigate the feasibility of a three-dimensional (3D) -printed head-and-neck (HN) immobilization device by comparing its positional accuracy and dosimetric properties with those of a conventional immobilization device (CID). We prepared a 3D-printed immobilization device (3DID) consisting of a mask and headrest with acrylonitrile-butadiene-styrene resin developed from the computed tomography data obtained by imaging a HN phantom. For comparison, a CID comprising a thermoplastic mask and headrest was prepared using the same HN phantom. We measured the setup error using the ExacTrac X-ray image system. Furthermore, using the ionization chamber and the water-equivalent phantom, we measured the changes in the dose due to the difference in the immobilization device material from the photon of 4 MV and 6 MV. The positional accuracy of the two devices were almost similar in each direction except in the vertical, lateral, and pitch directions (t-test, p<0.0001), and the maximum difference was 1 mm, and 1°. The standard deviations were not statistically different in each direction except in the longitudinal (F-test, p=0.034) and roll directions (F-test, p<0.0001). When the thickness was the same, the dose difference was almost similar at a 50 mm depth. At a 1 mm depth, the 3DID-plate had a 2.9-4.2% lower dose than the CID-plate. This study suggested that the positional accuracy and dosimetric properties of 3DID were almost similar to those of CID.


Training Regimes and Recovery Monitoring Practices of Elite British Swimmers.
Consistent prescriptions for event-specific training of swimmers are lacking, which points to likely differences in training practices and a potential gap between practice and scientific knowledge. This study aimed to analyze the distance-specific training load of elite swimmers, derive a consistent training sessions' description and reflect on the current recommendations for training and recovery. The individual training regimes of 18 elite British swimmers were documented by surveying four swim and two strength and conditioning (S&C) coaches. The annual and weekly training load and content were compared between swimmers competing in sprint, middle and long-distance events. Thematic analysis of the surveys was conducted to identify key codes and general dimensions and to define a unified classification of the swimming and S&C training sessions. Weekly training loads and content of the swim (ƞ2 - effect size; p = 0.016, ƞ2 = 0.423) and S&C (p = 0.028, ƞ2 = 0.38) sessions significantly differed between the groups. Long-distance swimmers swam significantly longer distances (mean ± SD; 58.1 ± 10.2 km vs. 43.2 ± 5.3 km; p = 0.018) weekly but completed similar number of S&C sessions compared to sprinters. The annual swimming load distribution of middle-distance specialists did not differ from that of long-distance swimmers but consisted of more S&C sessions per week (4.7 ± 0.5 vs. 2.3 ± 2.3; p = 0.04). Sprinters and middle-distance swimmers swam similar distances per week and completed similar number of S&C sessions but with different proportional content. Whereas all coaches reported monitoring fatigue, only 51% indicated implementing individualized recovery protocols. We propose a consistent terminology for the description of training sessions in elite swimming to facilitate good practice exchanges. While the training prescription of elite British swimmers conforms to the scientific training principles, recommendations for recovery protocols to reduce the risk of injury and overtraining are warranted.


Spatially resolved sampling reveals dynamic microbial communities in rising hydrothermal plumes across a back-arc basin.
Within hydrothermal plumes, chemosynthetic processes and microbe-mineral interactions drive primary productivity in deep-ocean food webs and may influence transport of elements such as iron. However, the source of microorganisms in plumes and the factors governing how these communities assemble are poorly understood, in part due to lack of data from early stages of plume formation. In this study, we examined microbial community composition of rising hydrothermal plumes from five vent fields along the Eastern Lau Spreading Center. Seafloor and plume microbial communities were significantly dissimilar and shared few phylotypes. Plume communities were highly similar to each other with significant differences in community membership only between Kilo Moana and Mariner, two vents that are separated by extremes in depth, latitude and geochemistry. Systematic sampling of waters surrounding the vents revealed that species richness and phylogenetic diversity was typically highest near the vent orifice, implying mixing of microbial communities from the surrounding habitats. Above-plume background communities were primarily dominated by SAR11, SAR324 and MG-I Archaea, while SUP05, Sulfurovum, Sulfurimonas, SAR324 and Alteromonas were abundant in plume and near-bottom background communities. These results show that the ubiquitous water-column microorganisms populate plume communities, and that the composition of background seawater exerts primary influence on plume community composition, with secondary influence from geochemical and/or physical properties of vents. Many of these pervasive deep-ocean organisms are capable of lithotrophy, suggesting that they are poised to use inorganic electron donors encountered in hydrothermal plumes.


Effects of vegetation on bacterial communities, carbon and nitrogen in dryland soil surfaces: implications for shrub encroachment in the southwest Kalahari.
Shrub encroachment is occurring in many of the world's drylands, but its impacts on ecosystem structure and function are still poorly understood. In particular, it remains unclear how shrub encroachment affects dryland soil surfaces, including biological soil crust (biocrust) communities. In this study, soil surfaces (0-1 cm depth) were sampled from areas of Grewia flava shrubs and Eragrostis lehmanniana and Schmidtia kalahariensis grasses in the southwest Kalahari during two different seasons (March and November). Our hypothesis is that the presence of different vegetation cover types (shrubs versus grasses) alters the microbial composition of soil surfaces owing to their contrasting microenvironments. The results showed that more significant differences in microclimate (light, soil surface temperatures) and soil surface microbial communities were observed between shrubs and grasses than between sampling seasons. Based on high-throughput 16S rRNA gene sequencing, our findings showed that approximately one third (33.5%) of the operational taxonomic units (OTUs) occurred exclusively in soil surfaces beneath shrubs. Soil surfaces with biocrusts in grass areas were dominated by the cyanobacteria Microcoleus steenstrupii, whereas the soil surfaces beneath shrubs were dominated by the proteobacteria Microvirga flocculans. Soil surfaces beneath shrubs are associated with reduced cyanobacterial abundance but have higher total carbon and total nitrogen contents compared to biocrusts in grass areas. These findings infer changes in the relative contributions from different sources of carbon and nitrogen (e.g. cyanobacterial and non-cyanobacterial fixation, plant litter, animal activity). The distinctive microbial composition and higher carbon and nitrogen contents in soil surfaces beneath shrubs may provide a positive feedback mechanism promoting shrub encroachment, which helps to explain why the phenomenon is commonly observed to be irreversible.


O-acetylation of glucuronoxylan in Arabidopsis thaliana wild type and its change in xylan biosynthesis mutants.
O-Acetylglucuronoxylans (AcGX) in Arabidopsis thaliana carry acetyl residues on the 2-O and/or 3-O positions of the xylopyranosyl (Xylp) units, but the distribution of different O-acetylated Xylp units is partly unclear. We studied a possible correlation of xylan acetylation and the activities of different glycosyltransferases involved in xylan biosynthesis by analyzing the distribution of O-acetyl substituents on AcGX from Arabidopsis wild-type and mutants irx7, irx9-1, irx10, irx14 and gux1gux2. The relative contents of the Xylp structural units were determined with quantitative two-dimensional heteronuclear single quantum coherence nuclear magnetic resonance spectroscopy. In the wild type, the degree of acetylation (DA) was 60%. Mono- and diacetylated Xylp units constituted 44 and 6% of the AcGX backbone, respectively; while (4-O-methyl)-glucopyranosyluronic acid (1 → 2)-linked Xylp units, most of which also carry 3-O-acetylation, represented 13%. The DA was decreased in irx7, irx9-1 and irx14 due to the decrease in monoacetylation (2-O and 3-O), indicating a relationship between acetylation and other AcGX biosynthetic processes. The possible interactions that could lead to such changes have been discussed. No change in DA was observed in irx10 and gux1gux2, but monoacetylation was nonetheless elevated in gux1gux2. This indicates that acetylation occurs after addition of GlcpA to the xylan backbone. Mass fragmentation analysis suggests that the prevalent acetylation pattern is the acetyl group added on every other Xylp unit.


Abnormalities in structure and function of limb skeletal muscle fibres of dystrophic mdx mice.
In this study we have shown that the skeletal muscle fibres from adult (older than 26 weeks) mdx mice have gross structural deformities. We have characterized the onset and age dependence of this feature in mdx mice. The three dimensional structure of these deformities has been visualized in isolated fibres and the orientation of these deformities was determined within the muscle by confocal laser scanning microscopy. We have also shown that the occurrence of morphologically abnormal fibres is greater in muscles with longer fibres (extensor digitorum longus (EDL) and soleus, 6-7.3 mm long), than in muscles with shorter fibres (flexor digitorum brevis (FDB), 0.3-0.4 mm long). A population of post-degenerative fibres, with both central and peripheral nuclei coexistent along the length of the fibre, has also been identified in the muscles studied. We showed that a mild protocol of lengthening (eccentric) contractions (the muscle was stretched by 12% during a tetanic contraction) caused a major reduction in the maximal tetanic force subsequently produced by mdx EDL muscle. In contrast, maximal tetanic force production in normal soleus, normal EDL and mdx soleus muscles was not altered by this protocol. We suggest that the deformed fast glycolytic fibres which are found in adult mdx EDL but not in adult mdx soleus muscles are the population of fibres damaged by the lengthening protocol.


Historical Perspective of Proactive and Reactive Regulations of E-cigarettes to Combat Nicotine Addiction.
Cigarettes and electronic cigarettes (e-cigarettes) are major sources of exposure to nicotine, an addictive chemical. Although these products are being regulated by the Food and Drug Administration (FDA) under the Tobacco Control Act, specifications about the nicotine content in these products have not been established yet. In e-cigarettes, nicotine concentration ranges from 0 to > 50mg/mL, and the recent e-cigarette devices provide control to change nicotine flux for higher nicotine delivery. Due to the lack of robust regulations in manufacturing, distribution and marketing, e-cigarettes have already infiltrated the market with youth appealing flavors and devices. As a result, the country is facing a youth epidemic of e-cigarette use. The unregulated nicotine levels in both cigarettes and e-cigarettes can lead to repeated and overexposure of nicotine to youth which can lead to the addiction and detrimental effects on their cognitive functions. Over the past decade, the corrective measures being taken by the FDA for cigarette and e-cigarette regulations also should focus on nicotine exposure levels. Before it is too late to prevent youth from lifetime addiction to nicotine, it is important to address the issues of nicotine concentration, nicotine flux and the e-cigarette device regulations while offering adults with smoking disorder less harmful alternatives to cigarettes.


The novel arylindolylmaleimide PDA-66 displays pronounced antiproliferative effects in acute lymphoblastic leukemia cells.
Prognosis of adult patients suffering from acute lymphoblastic leukemia (ALL) is still unsatisfactory. Targeted therapy via inhibition of deregulated signaling pathways appears to be a promising therapeutic option for the treatment of ALL. Herein, we evaluated the influence of a novel arylindolylmaleimide (PDA-66), a potential GSK3β inhibitor, on several ALL cell lines. ALL cell lines (SEM, RS4;11, Jurkat and MOLT4) were exposed to different concentrations of PDA-66. Subsequently, proliferation, metabolic activity, apoptosis and necrosis, cell cycle distribution and protein expression of Wnt and PI3K/Akt signaling pathways were analyzed at different time points. PDA-66 inhibited the proliferation of ALL cells significantly by reduction of metabolic activity. The 72 h IC50 values ranged between 0.41 to 1.28 μM PDA-66. Additionally, caspase activated induction of apoptosis could be detected in the analyzed cell lines. PDA-66 influenced the cell cycle distribution of ALL cell lines differently. While RS4;11 and MOLT4 cells were found to be arrested in G2 phase, SEM cells showed an increased cell cycle in G0/1 phase. PDA-66 displays significant antileukemic activity in ALL cells and classifies as candidate for further evaluation as a potential drug in targeted therapy of ALL.


Au quantum dots engineered room temperature crystallization and magnetic anisotropy in CoFe2O4 thin films.
For the first time, this work presents a novel room temperature time-effective concept to manipulate the crystallization kinetics and magnetic responses of thin films grown on amorphous substrates. Conventionally, metal-induced crystallization is adopted to minimize the crystallization temperature of the upper-layer thin film. However, due to the limited surface area of the continuous metal under-layer, the degree of crystallization is insufficient and post-annealing is required. To expose a large surface area of the metal under-layer, we propose a simple and novel approach of using an Au nanodots array instead of a continuous metallic under-layer to obtain crystallization of upper-layer thin films. Spinel cobalt ferrite (CFO) thin film as a 'model' was deposited on an Au nano-dots array to realize this methodology. Our findings revealed that the addition of quantum-sized Au nano-dots as a metal under-layer dramatically enhanced the crystallization of the cobalt ferrite upper layer at room temperature. The appearance of major X-ray diffraction peaks with high intensity and well-defined crystallized lattice planes observed via transmission electron microscopy confirmed the crystallization of the CFO thin film deposited at room temperature on 4 nm-sized Au nano-dots. This crystallized CFO thin film exhibits 18-fold higher coercivity (Hc = 4150 Oe) and 4-fold higher saturation magnetization (Ms = 262 emu cm-3) compared to CFO deposited without the Au under-layer. The development of this novel concept of room-temperature crystallization without the aid of additives and solvents represents a crucial breakthrough that is highly significant for exploring the green and energy-efficient synthesis of a variety of oxide and metal thin films.


Genetic and genomic approaches to develop rice germplasm for problem soils.
Soils that contain toxic amounts of minerals or are deficient in essential plant nutrients are widespread globally and seriously constrain rice production. New methods are necessary to incorporate the complex adaptive traits associated with tolerance of these abiotic stresses, while simultaneously retaining the high yield potential of rice varieties when conditions are favorable. Significant progress in the genetic characterization of stress response pathways and recent advances in genomics have provided powerful tools for in-depth dissection of tolerance mechanisms. Additionally, tolerance of most of these abiotic stresses in rice is controlled by a few QTLs with large effects despite the intricacy of the numerous traits involved. Genetic dissection of these QTLs and their incorporation into high-yielding varieties will significantly enhance and stabilize rice productivity in these problem soils. Current efforts at IRRI and in rice breeding programs worldwide are seeking to explore diverse germplasm collections and genetically dissect the causal mechanisms of tolerance to facilitate their use in breeding. This review focuses on salinity and P and Zn deficiency as the major problems encountered in rice soils, and examines current understanding of the mechanisms involved and efforts toward germplasm improvement.


Dynamics of oxytetracycline, sulfamerazine, and ciprofloxacin and related antibiotic resistance genes during swine manure composting.
Understanding the dynamics of veterinary antibiotic and related antibiotic resistance genes (ARGs) during swine manure composting is crucial in assessing the environmental risk of antibiotics, which could effectively reduce their impact in natural environments. This study investigated the dissipation of oxytetracycline (OTC), sulfamerazine (SM1) and ciprofloxacin (CIP) as well as the behaviour of their corresponding ARGs during swine manure composting. These antibiotics were added at two concentration levels and two different methods of addition (single/mixture). The results indicated that the removal efficiency of antibiotics by composting were ≥85%, except for the single-SM1 treatment. The tetracycline resistance genes (TRGs) encoding ribosomal protection proteins (RPP) and efflux pump (EFP) and fluoroquinolone resistance genes (FRGs) could be effectively removed after 42 days. On the contrary, the TRGs encoding enzymatic inactivation (EI) and sulfonamide resistance genes (SRGs) were enriched up to 31-fold (sul 2 in single-low-SM1). Statistical analyses indicated that the behaviour of these class antibiotics and ARGs were controlled by microbial activity and significantly influenced by environmental factors (mainly C/N, moisture and pH) throughout the composting process.


Direct-write 3D printing and characterization of a GelMA-based biomaterial for intracorporeal tissue.
We develop and characterize a biomaterial formulation and robotic methods tailored for intracorporeal tissue engineering (TE) via direct-write (DW) 3D printing. Intracorporeal TE is defined as the biofabrication of 3D TE scaffolds inside of a living patient, in a minimally invasive manner. A biomaterial for intracorporeal TE requires to be 3D printable and crosslinkable via mechanisms that are safe to native tissues and feasible at physiological temperature (37 °C). The cell-laden biomaterial (bioink) preparation and bioprinting methods must support cell viability. Additionally, the biomaterial and bioprinting method must enable the spatially accurate intracorporeal 3D delivery of the biomaterial, and the biomaterial must adhere to or integrate into the native tissue. Current biomaterial formulations do not meet all the presumed intracorporeal DW TE requirements. We demonstrate that a specific formulation of gelatin methacryloyl (GelMA)/Laponite®/methylcellulose (GLM) biomaterial system can be 3D printed at physiological temperature and crosslinked using visible light to construct 3D TE scaffolds with clinically relevant dimensions and consistent structures. Cell viability of 71%-77% and consistent mechanical properties over 21 d are reported. Rheological modifiers, Laponite® and methylcellulose, extend the degradation time of the scaffolds. The DW modality enables the piercing of the soft tissue and over-extrusion of the biomaterial into the tissue, creating a novel interlocking mechanism with soft, hydrated native tissue mimics and animal muscle with a 3.5-4 fold increase in the biomaterial/tissue adhesion strength compared to printing on top of the tissue. The developed GLM biomaterial and robotic interlocking mechanism pave the way towards intracorporeal TE.


Effect of antisense oligonucleotides on the expression of hepatocellular bile acid and organic anion uptake systems in Xenopus laevis oocytes.
A Na(+)-dependent bile acid (Na+/taurocholate co-transporting polypeptide; Ntcp) and a Na(+)-independent bromosulphophthalein (BSP)/bile acid uptake system (organic-anion-transporting polypeptide; oatp) have been cloned from rat liver by using functional expression cloning in Xenopus laevis oocytes. To evaluate the extent to which these cloned transporters could account for overall hepatic bile acid and BSP uptake, we used antisense oligonucleotides to inhibit the expression of Ntcp and oatp in Xenopus laevis oocytes injected with total rat liver mRNA. An Ntcp-specific antisense oligonucleotide co-injected with total rat liver mRNA blocked the expression of Na(+)-dependent taurocholate uptake by approx. 95%. In contrast, an oatp-specific antisense oligonucleotide when co-injected with total rat liver mRNA had no effect on the expression of Na(+)-dependent taurocholate uptake, but it blocked Na(+)-independent uptake of taurocholate by approx. 80% and of BSP by 50%. Assuming similar expression of hepatocellular bile acid and organic anion transporters in Xenopus laevis oocytes, these results indicate that Ntcp and oatp respectively represent the major, if not the only, Na(+)-dependent and Na(+)-independent taurocholate uptake systems in rat liver. By contrast, the cloned oatp accounts for only half of BSP transport, suggesting that there must be additional, non-bile acid transporting organic anion uptake systems in rat liver.


Energies, structures, and harmonic frequencies of small water clusters from the direct random phase approximation.
The binding energies, structures, and vibrational frequencies of water clusters up to 20 molecules are computed at the direct random phase approximation (RPA) level of theory and compared to theoretical benchmarks. Binding energies of the WATER27 set, which includes neutral and positively and negatively charged clusters, are predicted to be too low in the complete basis set limit by an average of 7 kcal/mol (9%) and are worse than the results from the best density functional theory methods or from the Møller-Plesset theory. The RPA shows significant basis set size dependence for binding energies. The order of the relative energies of the water hexamer and dodecamer isomers is predicted correctly by the RPA. The mean absolute deviation for angles and distances for neutral clusters up to the water hexamer are 0.2° and 0.6 pm, respectively, using quintuple-ζ basis sets. The relative energetic order of the hexamer isomers is preserved upon optimization. Vibrational frequencies for these systems are underestimated by several tens of wavenumbers for large basis sets, and deviations increase with the basis set size. Overall, the direct RPA method yields accurate structural parameters but systematically underestimates binding energies and shows strong basis set size dependence.


X-ray diffraction analysis of MTA mixed and placed with various techniques.
The aim of this study was to evaluate the effect of various mixing techniques as well as the effect of ultrasonic placement on hydration of mineral trioxide aggregate (MTA) using X-ray diffraction (XRD) analysis. One gram of ProRoot MTA and MTA Angelus powder was mixed with a 0.34-g of distilled water. Specimens were mixed either by mechanical mixing of capsules for 30 s at 4500 rpm or by manual mixing followed by application of a compaction pressure of 3.22 MPa for 1 min. The mixtures were transferred into the XRD sample holder with minimum pressure. Indirect ultrasonic activation was applied to half of the specimens. All specimens were incubated at 37 °C and 100% humidity for 4 days. Samples were analyzed by XRD. Phase identification was accomplished by use of search-match software utilizing International Centre for Diffraction Data (ICDD). All specimens comprised tricalcium silicate, calcium carbonate, and bismuth oxide. A calcium hydroxide phase was formed in all ProRoot specimens whereas among MTA Angelus groups, it was found only in the sample mixed mechanically and placed by ultrasonication. Mechanical mixing followed by ultrasonication did not confer a significant disadvantage in terms of hydration characteristics of MTA. Clinicians vary in the way they mix and place MTA. These variations might affect their physical characteristics and clinical performance. For ProRoot MTA, the mixing and placement methods did not affect its rheological properties, whereas for MTA Angelus, mechanical mixing combined with ultrasonic placement enhanced the calcium hydroxide phase formation.


Transcriptional control of KIT gene expression during germ cell development.
The characterization of the mechanisms that regulate KIT expression in germ cells at different times of their development is important not only in the field of reproduction, but also for a better understanding of the biology of testicular germ cell tumors (TGCTs). Indeed this tyrosine kinase receptor, besides being essential for the survival and proliferation of primordial germ cells (PGCs) and for postnatal spermatogenesis and oogenesis, is also frequently overexpressed or constitutively active due to activating mutations in carcinoma in situ of the testis and in seminomas. In this review, I will summarize available data about the transcriptional mechanisms involved in the control of Kit expression in the germline. Variable mechanisms, involving different germ cell-specific transcription factors, are operating in the various developmental stages: SOX2 and SOHLH1/2 act as direct positive regulators in PGCs and in postnatal spermatogonia, respectively, whereas PLZF suppresses KIT expression in spermatogonial stem cells. DMRT1, acting through indirect mechanisms, suppresses KIT transcription in fetal gonocytes, while activating it in differentiating spermatogonia.


Nonessential tRNA and rRNA modifications impact the bacterial response to sub-MIC antibiotic stress.
Antimicrobial resistance develops as a major problem in infectious diseases treatment. While antibiotic resistance mechanisms are usually studied using lethal antibiotic doses, lower doses allowing bacterial growth are now considered as factors influencing the development and selection of resistance. Starting with a high-density Tn insertion library in Vibrio cholerae and following its evolution by TN-seq in the presence of subinhibitory concentrations of antibiotics, we discovered that RNA modification genes can have opposite fates, being selected or counter-selected. We, thus have undertaken the phenotypic characterization of 23 transfer RNA (tRNA) and ribosomal RNA (rRNA) modifications deletion mutants, for which growth is globally not affected in the absence of stress. We uncover a specific involvement of different RNA modification genes in the response to aminoglycosides (tobramycin and gentamicin), fluoroquinolones (ciprofloxacin), β-lactams (carbenicillin), chloramphenicol, and trimethoprim. Our results identify t/rRNA modification genes, not previously associated to any antibiotic resistance phenotype, as important factors affecting the bacterial response to low doses of antibiotics from different families. This suggests differential translation and codon decoding as critical factors involved in the bacterial response to stress.


Changes in composition of spider orb web sticky droplets with starvation and web removal, and synthesis of sticky droplet compounds.
The sticky spiral of araneoid spider orb webs consists of silk fibers coated with adhesive droplets. The droplets contain a variety of low-molecular-mass compounds (LMM). Within a species, a fairly consistent ratio of LMM is often observed, but substantial variability can exist. To gain insight into factors influencing LMM composition, spiders of three araneid species were starved and LMM from their webs were analyzed for changes in composition. To determine if these changes were consistent with the spider's ability to synthesize the different organic LMM, synthetic capacities were estimated following the feeding of radiolabeled metabolites. Some changes in droplet composition were broadly consistent with differing synthetic capacities: molar percentages of less readily synthesized compounds (e.g. choline, isethionate, N-acetyltaurine) typically declined with starvation, at least during a portion of the imposed fast, while more readily synthesized compounds (e.g. GABamide, glycine) tended to increase. Most striking was the apparent partial substitution of N-acetylputrescine by the more readily synthesized GABamide in fasting Argiope trifasciata. However, departures from expected compositional shifts demonstrated that synthetic capacity alone does not adequately predict sticky droplet compositional shifts with starvation. Moreover, feeding controls exhibited some changes in composition similar to starving spiders. As the webs of both feeding and starving spiders were removed for chemical analysis and could not be recycled, the loss of LMM contained in these webs likely contributed to similarities between treatments. In addition, feeding spiders molted, oviposited and/or built heavier webs. The added metabolic demands of these activities may have contributed to changes in composition similar to those resulting from starvation.


Pickled vegetables and the risk of oesophageal cancer: a meta-analysis.
Ecological and experimental studies have suggested a relationship between Asian pickled vegetable consumption and oesophageal squamous cell carcinoma (OSCC), but the results of epidemiological studies investigating the association have been inconsistent. We conducted a meta-analysis of observational studies of this association to evaluate the existing evidence. We searched the PubMed, ISI-Web of Science, J-EAST, IndMed, Vip Chinese Periodical, and China National Knowledge Infrastructure databases for all studies published in English or Chinese languages. Pooled results for all studies combined and for several study subgroups were computed. A total of 34 studies were included in this analysis. The overall random effects odds ratio (OR) and 95% confidence interval (CI) for pickled vegetable consumption was 2.08 (1.66-2.60), but the results were heterogeneous across studies. After excluding the three most influential studies, the respective numbers were 2.32 (1.92-2.81). Similar to the overall association, the majority of subgroup analyses showed a statistically significant association between consuming pickled vegetables and OSCC risk. There were only three prospective studies. Our results suggest a potential two-fold increased risk of oesophageal cancer associated with the intake of pickled vegetables. However, because the majority of data was from retrospective studies and there was a high heterogeneity in the results, further well-designed prospective studies are warranted.


Frequency and type of adverse analytical findings in athletics: Differences among disciplines.
Athletics is a highly diverse sport that contains a set of disciplines grouped into jumps, throws, races of varying distances, and combined events. From a physiological standpoint, the physical capabilities linked to success are quite different among disciplines, with varying involvements of muscle strength, muscle power, and endurance. Thus, the use of banned substances in athletics might be dictated by physical dimensions of each discipline. Thus, the aim of this investigation was to analyse the number and distribution of adverse analytical findings per drug class in athletic disciplines. The data included in this investigation were gathered from the Anti-Doping Testing Figure Report made available by the World Anti-Doping Agency (from 2016 to 2018). Interestingly, there were no differences in the frequency of adverse findings (overall,~0.95%, range from 0.77 to 1.70%) among disciplines despite long distance runners having the highest number of samples analysed per year (~9812 samples/year). Sprinters and throwers presented abnormally high proportions of adverse analytical findings within the group of anabolic agents (p < 0.01); middle- and long-distance runners presented atypically high proportions of findings related to peptide hormones and growth factors (p < 0.01); racewalkers presented atypically high proportions of banned diuretics and masking agents (p = 0.05). These results suggest that the proportion of athletes that are using banned substances is similar among the different disciplines of athletics. However, there are substantial differences in the class of drugs more commonly used in each discipline. This information can be used to effectively enhance anti-doping testing protocols in athletics.


Individual oocysts of Isospora (Apicomplexa: Coccidia) parasites from avian feces: from photo to sequence.
Numerous microscopic studies of coccidian oocysts from avian feces have become the basis for species identification. In contrast, molecular studies of wild birds' Coccidia are still in their infancy and are mostly based on DNA extracted from the blood stages of these parasites. Linking microscopic and molecular data requires a method that reliably extracts DNA from single oocysts with parallel detailed morphological examination of the same cell. We offer a thorough manual of isolating, photographing, and trapping single oocysts from avian feces, followed by extraction of parasite DNA and amplification of mitochondrial DNA from the same cells. In 39 single oocysts from 6 wild blackcaps, we combined microscopic studies of individual cells with studies on their mitochondrial haplotype. In 72% of the single oocysts sampled, we detected unambiguous sequences. From feces and blood of investigated birds, we obtained 6 different haplotypes of Isospora sp. (iSAT1-iSAT 6), finding both the same haplotype in different host individuals and various haplotypes in the same host individual. Our described methodology enables linking the huge amount of morphological data with innovative gene analysis. This method expands the scope of genetic studies conducted on Isospora species, including routine molecular analysis of single oocysts isolated from fecal samples.


Measurement of the wave front of a pulsed dye laser using an integrated-optics sensor with 200-nsec temporal resolution.
We report the use of an integrated-optics wave-front measurement sensor to measure with 200-nsec temporal resolution the phase and intensity at the aperture of a high-power (3.5-MW peak power) flash-lamp-pumped pulsed dye laser. The measurements reveal large fluctuations of the dye-laser wave front during the 2-microsec duration of the laser pulse. The fluctuations and the resulting poor beam quality are attributed to inhomogeneous heating of the dye during the pulse. These high-temporal-resolution measurements, which are not possible with other state-of-the-art wave-front analyzers, explain the previously measured poor beam quality of the laser.


Unsupervised spatial event detection in targeted domains with applications to civil unrest modeling.
Twitter has become a popular data source as a surrogate for monitoring and detecting events. Targeted domains such as crime, election, and social unrest require the creation of algorithms capable of detecting events pertinent to these domains. Due to the unstructured language, short-length messages, dynamics, and heterogeneity typical of Twitter data streams, it is technically difficult and labor-intensive to develop and maintain supervised learning systems. We present a novel unsupervised approach for detecting spatial events in targeted domains and illustrate this approach using one specific domain, viz. civil unrest modeling. Given a targeted domain, we propose a dynamic query expansion algorithm to iteratively expand domain-related terms, and generate a tweet homogeneous graph. An anomaly identification method is utilized to detect spatial events over this graph by jointly maximizing local modularity and spatial scan statistics. Extensive experiments conducted in 10 Latin American countries demonstrate the effectiveness of the proposed approach.


"Even if I Don't Remember, I Feel Better". A Qualitative Study of Patients with Early-Stage Non-Small Cell Lung Cancer Undergoing Stereotactic Body Radiotherapy or Surgery.
While surgical resection is recommended for most patients with early stage lung cancer according to the National Comprehensive Cancer Network guidelines, stereotactic body radiotherapy is increasingly being used. Provider-patient communication regarding the risks and benefits of each approach may be a modifiable factor leading to improved patient-centered outcomes. To qualitatively describe the experiences of patients undergoing either surgery or stereotactic body radiotherapy for early stage non-small cell lung cancer. We qualitatively evaluated and used content analysis to describe the experiences of 13 patients with early clinical stage non-small cell lung cancer before undergoing treatment in three health care systems in the Pacific Northwest, with a focus on knowledge obtained, communication, and feelings of distress. Although most participants reported rarely having been told about other options for treatment and could not readily recall many details about specific risks of recommended treatment, they were satisfied with their care. The patients paradoxically described clinicians as displaying caring and empathy despite not explicitly addressing their concerns and worries. We found that the communication domains that underlie shared decision making occurred infrequently, but that participants were still pleased with their role in the decision-making process. We did not find substantially different themes based on where the participant received care or the treatment selected. Patients were satisfied with all aspects of their care, despite reporting little knowledge about risks or other treatment options, no direct elicitation of worries from providers, and a lack of shared decision making. While the development of effective communication strategies to address these gaps is warranted, their effect on patient-centered outcomes, such as distress and decisional conflict, is unclear.


The amphioxus genome and the evolution of the chordate karyotype.
Lancelets ('amphioxus') are the modern survivors of an ancient chordate lineage, with a fossil record dating back to the Cambrian period. Here we describe the structure and gene content of the highly polymorphic approximately 520-megabase genome of the Florida lancelet Branchiostoma floridae, and analyse it in the context of chordate evolution. Whole-genome comparisons illuminate the murky relationships among the three chordate groups (tunicates, lancelets and vertebrates), and allow not only reconstruction of the gene complement of the last common chordate ancestor but also partial reconstruction of its genomic organization, as well as a description of two genome-wide duplications and subsequent reorganizations in the vertebrate lineage. These genome-scale events shaped the vertebrate genome and provided additional genetic variation for exploitation during vertebrate evolution.


Malaria Policy Advisory Committee to the WHO: conclusions and recommendations of March 2013 meeting.
The Malaria Policy Advisory Committee to the World Health Organization met in Geneva, Switzerland from 13 to 15 March, 2013. This article provides a summary of the discussions, conclusions and recommendations from that meeting.Meeting sessions included: a review of the efficacy of artemisinin-based combination therapy in Guyana and Suriname; the outcomes from a consultation on non-malaria febrile illness; the outcomes from the second meeting of the Evidence Review Group on malaria burden estimation; an update on the review of the WHO Guidelines for the Treatment of Malaria; an update regarding progress on the constitution of the vector control Technical Expert Group; updates on the RTS, S/AS01 vaccine and the malaria vaccine technology roadmap; financing and resource allocation for malaria control; malaria surveillance and the need for a surveillance, monitoring and evaluation Technical Expert Group; criteria and classification related to malaria elimination; the next meeting of the Evidence Review Group on Intermittent Preventive Treatment in pregnancy; an update on the soon-to-be launched Elimination Scenario Planning Tool; and an update on the process for the Global Technical Strategy for Malaria Control and Elimination (2016-2025).Policy statements, position statements, and guidelines that arise from the MPAC meeting conclusions and recommendations will be formally issued and disseminated to World Health Organization Member States by the World Health Organization Global Malaria Programme.


Preterm birth and structural brain alterations in early adulthood.
Alterations in cortical development and impaired neurodevelopmental outcomes have been described following very preterm (VPT) birth in childhood and adolescence, but only a few studies to date have investigated grey matter (GM) and white matter (WM) maturation in VPT samples in early adult life. Using voxel-based morphometry (VBM) we studied regional GM and WM volumes in 68 VPT-born individuals (mean gestational age 30 weeks) and 43 term-born controls aged 19-20 years, and their association with cognitive outcomes (Hayling Sentence Completion Test, Controlled Oral Word Association Test, Visual Reproduction test of the Wechsler Memory Scale-Revised) and gestational age. Structural MRI data were obtained with a 1.5 Tesla system and analysed using the VBM8 toolbox in SPM8 with a customized study-specific template. Similarly to results obtained at adolescent assessment, VPT young adults compared to controls demonstrated reduced GM volume in temporal, frontal, insular and occipital areas, thalamus, caudate nucleus and putamen. Increases in GM volume were noted in medial/anterior frontal gyrus. Smaller subcortical WM volume in the VPT group was observed in temporal, parietal and frontal regions, and in a cluster centred on posterior corpus callosum/thalamus/fornix. Larger subcortical WM volume was found predominantly in posterior brain regions, in areas beneath the parahippocampal and occipital gyri and in cerebellum. Gestational age was associated with GM and WM volumes in areas where VPT individuals demonstrated GM and WM volumetric alterations, especially in temporal, parietal and occipital regions. VPT participants scored lower than controls on measures of IQ, executive function and non-verbal memory. When investigating GM and WM alterations and cognitive outcome scores, subcortical WM volume in an area beneath the left inferior frontal gyrus accounted for 14% of the variance of full-scale IQ (F = 12.9, p < 0.0001). WM volume in posterior corpus callosum/thalamus/fornix and GM volume in temporal gyri bilaterally, accounted for 21% of the variance of executive function (F = 9.9, p < 0.0001) and WM in the posterior corpus callosum/thalamus/fornix alone accounted for 17% of the variance of total non-verbal memory scores (F = 9.9, p < 0.0001). These results reveal that VPT birth continues to be associated with altered structural brain anatomy in early adult life, although it remains to be ascertained whether these changes reflect neurodevelopmental delays or long lasting structural alterations due to prematurity. GM and WM alterations correlate with length of gestation and mediate cognitive outcome.


Trichlorination of a Teicoplanin-Type Glycopeptide Antibiotic by the Halogenase StaI Evades Resistance.
Glycopeptide antibiotics (GPAs) include clinically important drugs used for the treatment of infections caused by Gram-positive pathogens. These antibiotics are specialized metabolites produced by several genera of actinomycete bacteria. While many GPAs are highly chemically modified, A47934 is a relatively unadorned GPA lacking sugar or acyl modifications, common to other members of the class, but which is chlorinated at three distinct sites. The biosynthesis of A47934 is encoded by a 68-kb gene cluster in Streptomyces toyocaensis NRRL 15009. The cluster includes all necessary genes for the synthesis of A47934, including two predicted halogenase genes, staI and staK In this study, we report that only one of the halogenase genes, staI, is necessary and essential for A47934 biosynthesis. Chlorination of the A47934 scaffold is important for antibiotic activity, as assessed by binding affinity for the target N-acyl-d-Ala-d-Ala. Surprisingly, chlorination is also vital to avoid activation of enterococcal and Streptomyces VanB-type GPA resistance through induction of resistance genes. Phenotypic assays showed stronger induction of GPA resistance by the dechlorinated compared to the chlorinated GPA. Correspondingly, the relative expression of the enterococcal vanA resistance gene was shown to be increased by the dechlorinated compared to the chlorinated compound. These results provide insight into the biosynthesis of GPAs and the biological function of GPA chlorination for this medically important class of antibiotic.


Physical environment, diet quality, and body weight in a group of 12-year-old children from four public schools in Puerto Rico.
Physical environment influences diet and has been proposed as a determinant of childhood obesity. This cross-sectional study explored physical environment and its associations with diet quality and weight status in a sample of 114 12-year-old children from 4 public schools in the metropolitan area of San Juan, PR. Physical environment was assessed by asking questions regarding the availability and accessibility of healthy and unhealthy foods and food outlets as well as of recreational and sports facilities and equipment. Food intake was determined using a 24-hour diet-recall questionnaire, with the gathered data being used to assess diet quality and calculate the Healthy Eating Index (HEI)-2010. The HEI includes 12 components that are used to determine the compliance of a given diet with federal guidelines. HEI-2010 total score ranges from 0 to 100 and is divided into the following classifications: poor (< or = 50), needs improvement (51-80), and good (> 80). Body mass index was computed using measured weight and height and categorized according to the CDC Growth Charts. Thirty-six percent of the participating children were overweight or obese. Nearly 57% had poor diet quality. The lowest HEI-2010 component scores were found for total fruits, whole fruits, total vegetables, whole grains, seafood and plant proteins, and fatty acids. However, diet quality was not associated with weight status or physical environment factors. Compared to the other children in the study, overweight or obese children reported having a significantly (p < 0.05) lower availability of unhealthy foods and the highest access to recreational and sports facilities at home but also lower utilization of recreational and sports facilities at school and reduced participation in the school breakfast program. This study showed that some home- and school-environment factors influenced body weight in the children in this sample. However, these same factors did not appear to affect diet quality.


Molecular changes in lobular breast cancers in response to endocrine therapy.
Invasive lobular carcinoma (ILC) accounts for approximately 10% to 15% of breast carcinomas, and although it responds poorly to neoadjuvant chemotherapy, it appears to respond well to endocrine therapy. Pre- and on-treatment (after 2 weeks and 3 months) biopsies and surgical samples were obtained from 14 postmenopausal women with estrogen receptor-positive (ER(+)) histologically confirmed ILC who responded to 3 months of neoadjuvant letrozole and were compared with a cohort of 14 responding invasive ductal carcinomas (IDC) matched on clinicopathologic features. RNA was extracted and processed for whole human genome expression microarray. Dynamic clinical response was assessed using periodic three-dimensional ultrasound measurements performed during treatment and defined as a reduction of >70% in tumor volume by 3 months. Pretreatment profiles of ILC and IDC tumors showed distinctive expression of genes associated with E-cadherin signaling, epithelial adhesion, and stromal rearrangement. The changes in gene expression in response to letrozole were highly similar between responding ILC and IDC tumors; genes involved in proliferation were downregulated and those involved with immune function and extracellular matrix remodeling were upregulated. However, molecular differences between the histologic subtypes were maintained upon treatment. This is the first study of molecular changes in ILC in response to endocrine therapy to date. The genes that change on letrozole are highly consistent between ILC and IDC. Differences in gene expression between ILC and IDC at diagnosis are maintained at each time point on treatment.


Plant-necrotroph co-transcriptome networks illuminate a metabolic battlefield.
A central goal of studying host-pathogen interaction is to understand how host and pathogen manipulate each other to promote their own fitness in a pathosystem. Co-transcriptomic approaches can simultaneously analyze dual transcriptomes during infection and provide a systematic map of the cross-kingdom communication between two species. Here we used the Arabidopsis-B. cinerea pathosystem to test how plant host and fungal pathogen interact at the transcriptomic level. We assessed the impact of genetic diversity in pathogen and host by utilization of a collection of 96 isolates infection on Arabidopsis wild-type and two mutants with jasmonate or salicylic acid compromised immunities. We identified ten B. cinereagene co-expression networks (GCNs) that encode known or novel virulence mechanisms. Construction of a dual interaction network by combining four host- and ten pathogen-GCNs revealed potential connections between the fungal and plant GCNs. These co-transcriptome data shed lights on the potential mechanisms underlying host-pathogen interaction.


Effect of individualised dietary advice for weight loss supplemented with walnuts on blood pressure: the HealthTrack study.
In addition to weight-loss, healthy dietary patterns and lower sodium intakes can help reduce blood pressure (BP), but individualised dietary advice may be necessary to achieve these effects. This study aimed to examine the impact of individualised dietary advice on BP in the intensive phase of a weight-loss trial. Secondary analysis of baseline and 3-month data from the HealthTrack randomised controlled trial (n = 211). Participants were randomly assigned to one of three dietary advice groups: general advice (control), individualised advice (intervention group, I), or intervention group supplemented with 30 g walnuts/day (IW). Resting BP and 24-h urine sodium and potassium were measured. Dietary intake was evaluated through diet history interviews. Unadjusted SBP reduced significantly in all groups (IW and I groups P < 0.001; control group P = 0.002) and DBP in IW and I groups (P < 0.001). Compared to controls, the reductions in BP were 3-4 mmHg greater in the I and IW groups, but this only reached significance for DBP in the I group (-3.3 mmHg; P = 0.041). After controlling for age, sex, medication, weight-loss, physical activity and smoking, only the IW group showed a significant association between SBP reduction and increased urinary potassium (β = -0.101, P = 0.044), decreased sodium:potassium ratio (β = 2.446, P = 0.037) and increased consumption of seed and nut products and dishes (β = -0.108, P = 0.034). Dietary patterns with distinctive foods and lower sodium:potassium ratios may enhance the effects of weight-loss on BP. The patterns were best achieved with individualised dietary advice and food supplements.


Synthetic and immunological studies on trimeric MUC1 immunodominant motif antigen-based anti-cancer vaccine candidates.
Therapeutic vaccines have been regarded as a very promising treatment modality against cancer. Tumor-associated MUC1 is a promising antigen for the design of antitumor vaccines. However, body's immune tolerance and low immunogenicity of MUC1 glycopeptides limited their use as effective antigen epitopes of therapeutic vaccines. To solve this problem, we chose the immune dominant region of MUC1 VNTRs. We designed and synthesized its linear trivalent glycopeptide fragments and coupled the fragments with BSA. Immunological evaluation indicated that the antibodies induced by glycosylated MUC1 based vaccine 11 had a stronger binding than non-glycosylated 10. The novel constructed antigen epitopes have the potential to overcome the weak immunogenicity of natural MUC1 glycopeptides and deserve further research.


The causal role of the dorsolateral prefrontal cortex in the modification of attentional bias: evidence from transcranial direct current stimulation.
A pattern of attentional bias for threatening information is thought to be involved in the etiology of anxiety. Consistent with this idea, cognitive training techniques directly targeting such patterns of biased attention have been shown to reduce symptoms of anxiety. Research seeking to establish the neurologic underpinnings of change in the attentional bias for threat have implicated, but not confirmed, the role of lateral prefrontal regions. The current study sought to confirm experimentally the causal role of lateral prefrontal areas in the modification of attentional bias by delivering targeted cortical stimulation during attention bias modification training to assess the consequent effects on attentional bias change. While completing either an "attend threat" or "avoid threat" attention bias modification task, 77 volunteers (17-22 per group) received either active transcranial direct current stimulation of the left dorsolateral prefrontal cortex or a sham stimulation control condition. Participants receiving active stimulation showed greater evidence of attentional bias acquisition in the targeted direction (toward or away from threat) compared with participants in the sham stimulation condition. Our findings provide the first experimental evidence that increasing activity in the dorsolateral prefrontal cortex leads to greater evidence of attention bias modification. This evidence confirms the role of these areas in facilitating change in the allocation of attention to threat. We believe this study provides a critical step in the translation of neuroimaging findings to novel neuromodulatory interventions capable of enhancing the treatment of emotional pathology.


Evidence of B Cell Clonality and Investigation Into Properties of the IgM in Patients With Schnitzler Syndrome.
The Schnitzler Syndrome (SchS) is an acquired, autoinflammatory condition successfully treated with IL-1 inhibition. The two main defining features of this late-onset condition are neutrophilic urticarial dermatoses (NUD) and the presence of an IgM monoclonal component. While the former aspect has been extensively studied in this disease setting, the enigmatic paraproteinaemia and its potential consequential effects within SchS, has not previously been thoroughly addressed. Previous studies analyzing clonal B cell repertoires have largely focused on autoimmune disorders such as Systemic Lupus Erythematous (SLE) and hematological malignancies such as Chronic Lymphocytic Leukaemia (CLL), where B-cell clonality is central to disease pathology. The present study uses next-generation sequencing to provide detailed insight into aspects of B cell VDJ recombination and properties of the resulting immunoglobulin chains. An overview of IgH regional dynamics in 10 SchS patients, with a particular focus on CDR3 sequences and VDJ gene usage is reported, highlighting the presence of specific B cell expansions. Protein microarray detected a substantial proportion of autoreactive IgM to nuclear target proteins, though a single universal target was not identified. Together, these genetic and functional findings impart new understanding into this rare disorder.


Clinical features and management of individuals admitted to hospital with monkeypox and associated complications across the UK: a retrospective cohort study.
The scale of the 2022 global mpox (formerly known as monkeypox) outbreak has been unprecedented. In less than 6 months, non-endemic countries have reported more than 67 000 cases of a disease that had previously been rare outside of Africa. Mortality has been reported as rare but hospital admission has been relatively common. We aimed to describe the clinical and laboratory characteristics and outcomes of individuals admitted to hospital with mpox and associated complications, including tecovirimat recipients. In this cohort study, we undertook retrospective review of electronic clinical records and pathology data for all individuals admitted between May 6, and Aug 3, 2022, to 16 hospitals from the Specialist and High Consequence Infectious Diseases Network for Monkeypox. The hospitals were located in ten cities in England and Northern Ireland. Inclusion criteria were clinical signs consistent with mpox and MPXV DNA detected from at least one clinical sample by PCR testing. Patients admitted solely for isolation purposes were excluded from the study. Key outcomes included admission indication, complications (including pain, secondary infection, and mortality) and use of antibiotic and anti-viral treatments. Routine biochemistry, haematology, microbiology, and virology data were also collected. Outcomes were assessed in all patients with available data. 156 individuals were admitted to hospital with complicated mpox during the study period. 153 (98%) were male and three (2%) were female, with a median age of 35 years (IQR 30-44). Gender data were collected from electronic patient records, which encompassed full formal review of clincian notes. The prespecified options for data collection for gender were male, female, trans, non-binary, or unknown. 105 (71%) of 148 participants with available ethnicity data were of White ethnicity and 47 (30%) of 155 were living with HIV with a median CD4 count of 510 cells per mm3 (IQR 349-828). Rectal or perianal pain (including proctitis) was the most common indication for hospital admission (44 [28%] of 156). Severe pain was reported in 89 (57%) of 156, and secondary bacterial infection in 82 (58%) of 142 individuals with available data. Median admission duration was 5 days (IQR 2-9). Ten individuals required surgery and two cases of encephalitis were reported. 38 (24%) of the 156 individuals received tecovirimat with early cessation in four cases (two owing to hepatic transaminitis, one to rapid treatment response, and one to patient choice). No deaths occurred during the study period. Although life-threatening mpox appears rare in hospitalised populations during the current outbreak, severe mpox and associated complications can occur in immunocompetent individuals. Analgesia and management of superimposed bacterial infection are priorities for patients admitted to hospital. None.


Novel therapeutic strategies targeting vascular redox in human atherosclerosis.
It is now widely accepted that redox signaling is a key feature in vascular homeostasis. Reactive oxygen species are generated by a wide range of enzymatic systems located in both vascular endothelium and vascular wall. Further, to their role as cytotoxic molecules produced by immune system, free radicals play critical signaling roles in the vascular wall. By regulating several redox-sensitive transcription pathways, free radicals play a key role in the synthesis of inflammatory mediators in both vascular endothelium and vascular wall, with important role in the overall vascular dysfunction. The well-established role of redox state in vascular disease mandates that development of newer therapeutic strategies should be able to alter redox-sensitive intracellular signaling events. Widely used cardiovascular agents like statins or angiotensin receptor blockers have well documented beneficial effects on vascular redox state, reflected also in clinical outcome improvement. Newer promising strategies along with recent patented inventions may also include thiazolidinediones, folates, tetrahydrobiopterin, cyclopentone prostaglandins and aldose reductase inhibitors with well known effects on vascular redox, but with still unclear results on clinical outcome. Better understanding of redox-sensitive intracellular signaling pathways could indicate the critical steps to intervene with newer agents to reverse vascular dysfunction, inhibiting atherosclerosis progression and potentially improve clinical outcome.


Association between Tumor Necrosis Factor- α-308 G/A Polymorphism and Multiple Sclerosis: A Systematic Review and Meta-Analysis.
Multiple sclerosis (MS) is a complex polygenic disease in which gene-environment interactions are important. A number of studies have investigated the association between tumor necrosis factor-α (TNF-α) -308 G/A polymorphism (substitution G→A, designated as TNF1 and TNF2) and MS susceptibility in different populations, but the results of individual studies have been inconsistent. Therefore, performing a systematic review and meta-analysis of the published studies is desirable. We sought to quantitatively summarize the association between TNF-α-308 G/A polymorphism and MS. The Medline and Scopus databases were searched to identify potentially relevant case-control studies published in English journals up to January 2010. A meta-analysis of these studies was performed. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under fixed and random effects models. Twenty-one eligible studies, comprising 2880 patients with MS and 3579 controls, were included in the meta-analysis. The overall pooled ORs (95%CI) for TNF2 versus TNF1 and TNF2 carriers (2/2+2/1) versus non-carriers (1/1) were 1.02 (0.86-1.21) and 0.99 (0.8-1.24), respectively. In the European populations, the pooled ORs (95%CI) for TNF 2/1 versus 1/1 were 0.85 (0.73-0.98), which was statistically significant. However, the other results did not support this finding. The pooled ORs (95%CI) for TNF 2/1 versus 1/1 and TNF 2/2 versus 2/1 were not statistically significant in the overall population. In addition, the pooled ORs for TNF2/2 versus TNF2/1+1/1 and TNF2/2 versus TNF1/1 were not statistically significant. Our meta-analysis does not support the role of TNF-α -308 G/A polymorphism in developing MS.


Differential Expression Analysis of Olfactory Genes Based on a Combination of Sequencing Platforms and Behavioral Investigations in Aphidius gifuensis.
Aphidius gifuensis Ashmead is a dominant endoparasitoid of aphids, such as Myzus persicae and Sitobion avenae, and plays an important role in controlling aphids in various habitats, including tobacco plants and wheat in China. A. gifuensis has been successfully applied for the biological control of aphids, especially M. persicae, in green houses and fields in China. The corresponding parasites, as well as its mate-searching behaviors, are subjects of considerable interest. Previous A. gifuensis transcriptome studies have relied on short-read next-generation sequencing (NGS), and the vast majority of the resulting isotigs do not represent full-length cDNA. Here, we employed a combination of NGS and single-molecule real-time (SMRT) sequencing of virgin females (VFs), mated females (MFs), virgin males (VMs), and mated males (MMs) to comprehensively study the A. gifuensis transcriptome. Behavioral responses to the aphid alarm pheromone (E-β-farnesene, EBF) as well as to A. gifuensis of the opposite sex were also studied. VMs were found to be attracted by female wasps and MFs were repelled by male wasps, whereas MMs and VFs did not respond to the opposite sex. In addition, VFs, MFs, and MMs were attracted by EBF, while VMs did not respond. According to these results, we performed a personalized differential gene expression analysis of olfactory gene sets (66 odorant receptors, 25 inotropic receptors, 16 odorant-binding proteins, and 12 chemosensory proteins) in virgin and mated A. gifuensis of both sexes, and identified 13 candidate genes whose expression levels were highly consistent with behavioral test results, suggesting potential functions for these genes in pheromone perception.


Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects.
Phenotypic heterogeneity in sporadic Creutzfeldt-Jakob disease (sCJD) is well documented, but there is not yet a systematic classification of the disease variants. In a previous study, we showed that the polymorphic codon 129 of the prion protein gene (PRNP), and two types of protease-resistant prion protein (PrP(Sc)) with distinct physicochemical properties, are major determinants of these variants. To define the full spectrum of variants, we have examined a series of 300 sCJD patients. Clinical features, PRNP genotype, and PrP(Sc) properties were determined in all subjects. In 187, we also studied neuropathological features and immunohistochemical pattern of PrP(Sc) deposition. Seventy percent of subjects showed the classic CJD phenotype, PrP(Sc) type 1, and at least one methionine allele at codon 129; 25% of cases displayed the ataxic and kuru-plaque variants, associated to PrP(Sc) type 2, and valine homozygosity or heterozygosity at codon 129, respectively. Two additional variants, which included a thalamic form of CJD and a phenotype characterized by prominent dementia and cortical pathology, were linked to PrP(Sc) type 2 and methionine homozygosity. Finally, a rare phenotype characterized by progressive dementia was linked to PrP(Sc) type 1 and valine homozygosity. The present data demonstrate the existence of six phenotypic variants of sCJD. The physicochemical properties of PrP(Sc) in conjunction with the PRNP codon 129 genotype largely determine this phenotypic variability, and allow a molecular classification of the disease variants.


[Translated article] Immune-Mediated Skin Reactions to Tumor Necrosis α Inhibitors: A Review of 30 Cases.
Tumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions. Retrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain. We collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution. Paradoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases.


The rheology of liquids: a comparison of clinicians' subjective impressions and objective measurement.
Texture-modified diets are commonly prescribed for patients with dysphagia; it is therefore important to demonstrate that clinicians form accurate impressions of the rheological (flow) properties of the items that they recommend for their clients. We explored the correlation between objective rheological measurement and clinicians' subjective impressions of liquid consistency, rated on the bases of product labeling and sampling. Ten liquids, ranging from thin through nectar-thick and honey-thick to spoon-thick consistencies, were selected for study. Rheological analysis was conducted using a CarriMed CSL Controlled Stress Rheometer. Fifty speech-language pathologists ranked the liquids in order of perceived viscosity, based on their interpretation of the product packaging and label. Product nomenclature proved insufficient to accurately represent the consistency class to which each liquid belonged. A second group of 16 speech-language pathologists rated the perceived relative viscosity and density of nectar-thick and honey-thick juice items in blinded two-point discrimination tests of stirring-resistance, oral manipulation, and vessel weight. Physical sampling of these two products enabled clinicians to reliably perceive relative viscosity and density differences between the nectar- and honey-thick items.


Recent analytical methods for cephalosporins in biological fluids.
Since 1980, RP chromatography has been the principal analytical technique used for cephalosporins. This technology offers selectivity, accuracy, and ease of use. Most of the methods rely on protein precipitation and, to a lesser extent, solid-phase isolation or extraction procedures. The proper selection of a method depends on the analytical constraints imposed by the overall objective of the study. For example, pharmacokinetic datum interpretation mandates that the method be validated and provide specific and accurate results. LC is the preferred technique, since it not only meets these specifications but may also distinguish between the drug and metabolites. Those chromatographic methods which quantify several different cephalosporins are not desirable for pharmacokinetic datum interpretation, since accuracy and precision are usually compromised in order that many different drugs may be quantified in a single analysis. The proper selection of sample preparation method is dependent on the presence of potential interferences and the acceptable lower limit of quantitation. Protein precipitation methods offer ease of sample preparation but may suffer from nonselectivity. Solid-phase isolation and extraction procedures may increase selectivity and improve the limit of quantitation. Although LC provides specific and accurate results, clinical laboratories may prefer to use the less specific methods for therapeutic drug monitoring. In this case, microbiological, enzymatic, and fluorimetric methods offer improved sample throughput but less specificity. However, these methods should not be used for drugs that may have a low margin of safety or if the patient is on multiple-antibiotic therapy. Future methods may involve incorporating solid-phase isolation columns to enhance the specificity of chromatographic, microbiological, enzymatic, and fluorescence methods. Advancements in microbore column technology may allow improvements in the selectivity and sensitivity of LC methods. Many investigators prefer to use simple protein precipitation procedures for sample preparation because of sample throughput constraints. However, advances in robotic sample preparation may allow the more cumbersome solid-phase isolation or extraction techniques to be used to improved sample throughput and specificity.


Concordant association of insulin degrading enzyme gene (IDE) variants with IDE mRNA, Abeta, and Alzheimer's disease.
The insulin-degrading enzyme gene (IDE) is a strong functional and positional candidate for late onset Alzheimer's disease (LOAD). We examined conserved regions of IDE and its 10 kb flanks in 269 AD cases and 252 controls thereby identifying 17 putative functional polymorphisms. These variants formed eleven haplotypes that were tagged with ten variants. Four of these showed significant association with IDE transcript levels in samples from 194 LOAD cerebella. The strongest, rs6583817, which has not previously been reported, showed unequivocal association (p = 1.5x10(-8), fold-increase = 2.12,); the eleven haplotypes were also significantly associated with transcript levels (global p = 0.003). Using an in vitro dual luciferase reporter assay, we found that rs6583817 increases reporter gene expression in Be(2)-C (p = 0.006) and HepG2 (p = 0.02) cell lines. Furthermore, using data from a recent genome-wide association study of two Croatian isolated populations (n = 1,879), we identified a proxy for rs6583817 that associated significantly with decreased plasma Abeta40 levels (ss = -0.124, p = 0.011) and total measured plasma Abeta levels (b = -0.130, p = 0.009). Finally, rs6583817 was associated with decreased risk of LOAD in 3,891 AD cases and 3,605 controls. (OR = 0.87, p = 0.03), and the eleven IDE haplotypes (global p = 0.02) also showed significant association. Thus, a previously unreported variant unequivocally associated with increased IDE expression was also associated with reduced plasma Abeta40 and decreased LOAD susceptibility. Genetic association between LOAD and IDE has been difficult to replicate. Our findings suggest that targeted testing of expression SNPs (eSNPs) strongly associated with altered transcript levels in autopsy brain samples may be a powerful way to identify genetic associations with LOAD that would otherwise be difficult to detect.


Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes.
Diabetes confers an increased risk of adverse cardiovascular and renal events. In the EMPA-REG OUTCOME trial, empagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduced the risk of major adverse cardiovascular events in patients with type 2 diabetes at high risk for cardiovascular events. We wanted to determine the long-term renal effects of empagliflozin, an analysis that was a prespecified component of the secondary microvascular outcome of that trial. We randomly assigned patients with type 2 diabetes and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m(2) of body-surface area to receive either empagliflozin (at a dose of 10 mg or 25 mg) or placebo once daily. Prespecified renal outcomes included incident or worsening nephropathy (progression to macroalbuminuria, doubling of the serum creatinine level, initiation of renal-replacement therapy, or death from renal disease) and incident albuminuria. Incident or worsening nephropathy occurred in 525 of 4124 patients (12.7%) in the empagliflozin group and in 388 of 2061 (18.8%) in the placebo group (hazard ratio in the empagliflozin group, 0.61; 95% confidence interval, 0.53 to 0.70; P<0.001). Doubling of the serum creatinine level occurred in 70 of 4645 patients (1.5%) in the empagliflozin group and in 60 of 2323 (2.6%) in the placebo group, a significant relative risk reduction of 44%. Renal-replacement therapy was initiated in 13 of 4687 patients (0.3%) in the empagliflozin group and in 14 of 2333 patients (0.6%) in the placebo group, representing a 55% lower relative risk in the empagliflozin group. There was no significant between-group difference in the rate of incident albuminuria. The adverse-event profile of empagliflozin in patients with impaired kidney function at baseline was similar to that reported in the overall trial population. In patients with type 2 diabetes at high cardiovascular risk, empagliflozin was associated with slower progression of kidney disease and lower rates of clinically relevant renal events than was placebo when added to standard care. (Funded by the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance; EMPA-REG OUTCOME ClinicalTrials.gov number, NCT01131676.).


Our flesh is here but our soul stayed there: A qualitative study on resource loss due to war and displacement among internally-displaced women in the Republic of Georgia.
Losses experienced by conflict-affected civilians in low and middle income countries is a relatively unexplored area. The aim of our paper is to explore the concept of resource loss in the accounts of internally displaced women in Georgia. We use Hobfoll's Conservation of Resources (COR) theory to guide our approach by examining the loss of objects, personal characteristics, conditions, and energies. Semi-structured interviews were conducted on 42 purposively-selected Georgian women residing in internally displaced persons settlements during fieldwork in Georgia from December 2012 to February 2013. Line-by-line open-coding was conducted on translated and transcribed interviews using Nvivo. The conservation of resources theory was utilised to guide the 'mapping' of the relationships between losses which occurred in the post-conflict period. War-related trauma led to the loss of property, which caused the loss of livelihood and subsequent loss of social networks and mental and physical health. The mental and physical health losses, along with the loss of livelihood, constituted a loss spiral in which losses in one area perpetuated on-going losses in the other areas. Interventions at supporting livelihoods are needed in order to address the cascade of losses resulting from war.


The relationship between depression level and smoking motives in college smokers.
While the link between cigarette smoking and depression symptomatology has been well established, more research is needed to determine how smoking motives are related to depression levels in smokers. Specifically, smoking motives related to the friendship-like attachment to smoking (i.e., affiliative attachment) may play an important role in individuals reporting depressive symptomatology. The present study examined the relationship between three smoking motives and depression levels in a sample of 79 mildly nicotine-dependent, college student cigarette smokers. A hierarchical multiple regression analysis was conducted with depression as the dependent variable and gender and cigarettes per day as the independent variables (Step 1), positive and negative reinforcement motives (Step 2), and affiliative attachment motives (Step 3). Results of regression analyses indicated that affiliative attachment motives explained significant variance in participant depression level above and beyond that explained by positive and negative reinforcement motives. These findings suggest that smokers with elevated depression should be assessed for social functioning and affiliative attachment smoking motives, and future research should be conducted to determine if individuals with high levels of affiliative attachment may benefit from smoking cessation treatment programs with an enhanced social support component.


Association between maternal use of traditional healer services and child vaccination coverage in Pont-Sonde, Haiti.
Child vaccination is one of the public health interventions that are responsible for the relatively low child morbidity and mortality in developed nations compared to the developing world. We carried out this study to examine the association between mothers' use of traditional healer services and vaccination among Haitian children. Our hypothesis was that children whose mothers used the services of traditional healers were less likely to be vaccinated compared to children whose mothers did not use the services of traditional healers. A two-stage stratified sampling method was used to select 720 mothers from the population of Pont-Sonde, Haiti. Of these mothers, 691 (96%) completed the survey by responding to a standardized questionnaire on vaccination giving unadjusted odds ratios (OR) and adjusted odds ratios (AOR) and 95% confidence intervals (CI) and use of traditional healers. Bivariate and multivariate logistic regression analyses were performed to estimate the effect of explanatory variables on vaccination (the main outcome). Mother's use of traditional healer services was negatively associated with vaccination after controlling for maternal age, education, religion, and distance from the nearest health care facility. For those children whose mothers often or always used the services of traditional healers, we found a 53% decrease in the odds of vaccination (AOR = 0.47; 95% CI [0.27, 0.83]) compared against children whose mothers never used the services of the traditional healers. There were negative associations between practice of Vodou and vaccination (AOR = 0.56; 95% CI [0.35, 0.92]), and distance from the nearest health care service facility and vaccination (AOR = 0.53; 95% CI [0.29, 0.97] and AOR = 0.34; 95% CI [0.20, 0.59] at 46-60 and more than 60 minutes walk time, respectively). We found that mother's use of traditional healer services was negatively associated with vaccination of Haitian children. Findings from this study underscore the potential to enlist the support of traditional healers in promoting child health by educating, mentoring them (the traditional healers) in supporting vaccination efforts.


Cryptotrichosporon siamense sp. nov., a ballistoconidium-forming yeast species in Trichosporonales isolated in Thailand.
Two strains, which formed pink colonies and produced ballistoconidia and represented a novel anamorphic yeast species, were isolated from peat (DMKU-SPS1-2) and fern leaf (ST-145) collected in Thailand. Analysis of the sequences of the D1/D2 domains of the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) regions showed that the two strains were identical to the sequences of the D1/D2 domains of the LSU rRNA gene and differed by two nucleotide substitutions in the ITS regions. Phylogenetic analysis based on the combined sequences of the ITS and the D1/D2 regions confirmed that the two strains represented a single species in the genus Cryptotrichosporon that was distinct from the other known species of the genus. Cryptotrichosporon argae (CBS 14376T) was the most closely related species, but with 2.2 % nucleotide substitutions in the D1/D2 domains of the LSU rRNA gene, and 6.8-8.0 % nucleotide substitutions in the ITS regions. Therefore, the two strains were assigned as a novel species, for which we propose the name Cryptotrichosporon siamense sp. nov. The type is DMKU-SPS1-2T. The MycoBank number of the novel species is MB82336.


Small Extracellular Vesicle Enrichment of a Retrotransposon-Derived Double-Stranded RNA: A Means to Avoid Autoinflammation?
Small extracellular vesicles (SEVs) such as exosomes are released by multiple cell types. Originally believed to be a mechanism for selectively removing unwanted cellular components, SEVs have received increased attention in recent years for their ability to mediate intercellular communication. Apart from proteins and lipids, SEVs contain RNAs, but how RNAs are selectively loaded into SEVs remains poorly understood. To address this question, we profiled SEV RNAs from mouse dendritic cells using RNA-Seq and identified a long noncoding RNA of retroviral origin, VL30, which is highly enriched (>200-fold) in SEVs compared to parental cells. Bioinformatic analysis revealed that exosome-enriched isoforms of VL30 RNA contain a repetitive 26-nucleotide motif. This repeated motif is itself efficiently incorporated into SEVs, suggesting the likelihood that it directly promotes SEV loading. RNA folding analyses indicate that the motif is likely to form a long double-stranded RNA hairpin and, consistent with this, its overexpression was associated with induction of a potent type I interferon response. Taken together, we propose that preferential loading into SEVs of the VL30 RNA containing this immunostimulatory motif enables cells to remove a potentially toxic RNA and avoid autoinflammation. In this way, the original notion of SEVs as a cellular garbage bin should not be entirely discounted.


Thymopentin nanoparticles engineered with high loading efficiency, improved pharmacokinetic properties, and enhanced immunostimulating effect using soybean phospholipid and PHBHHx polymer.
Formulation of protein and peptide drugs with sustained release properties is crucial to enhance their therapeutic effect and minimize administration frequency. In this study, immunomodulating polymeric systems were designed by manufacturing PHBHHx nanoparticles (NPs) containing thymopentin (TP5). The release profile of the drug was studied over a period of 7 days. The PHBHHx NPs containing TP5-phospholipid (PLC) complex (TP5-PLC) displayed a spherical shape with a mean size, zeta potential, and encapsulation efficiency of 238.9 nm, -32.0 mV, and 72.81%, respectively. The cytotoxicity results showed the PHBHHx NPs had a relatively low toxicity in vitro. TP5 entrapped in the NPs could hardly release in vitro, while the NPs had longer than 7 days release duration after a single subcutaneous injection in Wistar rats. The immunodepression rat model was built to evaluate the immunomodulating effects of TP5-PLC-NPs in vivo. The results of T-lymphocyte subsets (CD3(+), CD4(+), CD8(+), and CD4(+)/CD8(+) ratio) analysis and superoxide dismutase (SOD) values suggested that TP5-PLC-NPs had stronger immunoregulation effects than TP5 solution. In conclusion, an applicable approach to markedly enhancing the loading of a water-soluble peptide into a hydrophobic polymer matrix has been introduced. Thus, TP5-PLC-NPs are promising nanomedicine systems for sustained release effects of TP5.


Photophysics associated with site selectively templated and tagged xerogel sensor platforms.
The analytical signal produced from a site selectively templated and tagged xerogel (SSTTX) based sensor is more completely elucidated. In an SSTTX, target analyte (TA) binding sites are created within a xerogel and a fluorescent reporter molecule (e.g., nitrobenzo-2-oxa-1,3-diazole, NBD) is covalently and selectively positioned within the template site. TA binding modulates the NBD cybotactic region, yielding a TA concentration-dependent change in the NBD reporter fluorescence. Our results reveal that there are two NBD sub-populations within the SSTTX. One sub-population is associated with misformed template sites that bind TA poorly and the NBD reporter molecules are heavily quenched by an adjacent amine residue that is intentionally positioned within close proximity to the NBD reporter molecule. The second NBD sub-population is associated with a properly formed template site that binds TA; the adjacent amine is still present but it is not as close to the NBD in comparison to the misformed site. When TA is present, the TA-responsive site binds TA, the TA disrupts the adjacent amine-NBD interaction (dequenching), and the NBD fluorescence increases. All NBD quenching occurs via photo-induced electron transfer (PET) from the adjacent amines to the excited NBD reporter molecules. As the mole fraction ratio of n-octyltrimethoxysilane (C(8)-TMOS) to tetramethoxysilane (TMOS) within an SSTTX increases, the misformed site mole fraction decreases and the dissociation constant (K(d)) for TA binding to the TA-responsive site decreases by 13-fold.


The efficacy of vitamin E and melatonin as antioxidants against lipid peroxidation in rat retinal homogenates.
Free radical-induced oxidation can cause severe cell damage in biological systems. Melatonin, a pineal secretory product, is a recently identified antioxidant that protects cells from the damaging effects of free radicals. We compared the effect of melatonin and vitamin E, another antioxidant, against lipid peroxidation (LPO) in rat retinal homogenates. The aim was to characterize the antioxidative efficacy of melatonin in retina, a tissue highly susceptible to oxidative damage. The LPO product, malondialdehyde (MDA), was determined to provide an index of cell damage in vitro. After the incubation with iron(II) ions, the free radical scavenging effectiveness of four different concentrations (i.e., 0.5, 1.0, 2.0, and 4.0 mM) of vitamin E and melatonin were determined by comparing the final levels of MDA. Lipid peroxidation product levels were significantly reduced in a dose-response manner by all concentrations of vitamin E. Melatonin, in concentrations of either 2.0 or 4.0 mM, also significantly reduced LPO. Statistical analysis of the data showed that vitamin E treatment always yielded a lower level of LPO products than did the same concentration of melatonin. The concentrations of each agent required to inhibit 50% of the lipid damage (IC50) were 0.69 mM and 4.98 mM for vitamin E and melatonin, respectively. Both vitamin E and melatonin protect the retina against LPO in a dose-dependent manner. Although the IC50 value for melatonin is about 7.2 times higher than that of vitamin E, melatonin's pharmacological and physiological role in the treatment and/or prevention of certain retinal diseases in vivo should be further investigated.


Effects of pelvic tilt angles and forced vital capacity in healthy individuals.
[Purpose] The purpose of this study was to investigate the effect of pelvic tilt angles and lung function in participants performing pelvic tilts on a ball. [Subjects and Methods] Eighteen subjects participated in this study. While they performed pelvic tilt on sitting at a ball, the peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) were measured at 10 degrees of anterior and posterior pelvic tilt, respectively, and neutral position. The repeated measure ANOVA was performed, and the Bonferroni correction was used for post-hoc analysis. [Results] The PEF of the participants was significantly higher at neutral position, compared with an anterior pelvic tilt at 10 degrees. The FEV1 was also higher in neutral position, compared with anterior and posterior pelvic tilt. [Conclusion] This study underlines the need for the standardization of the FVC testing protocol for positioning the pelvic angle in a neutral position in patients with respiratory disorders to promote reliable interpretation of intervention outcomes.


Early enteral nutrition and outcomes of critically ill patients treated with vasopressors and mechanical ventilation.
To determine the effect of early enteral feeding on the outcome of critically ill medical patients whose hemodynamic condition is unstable. Prospectively collected data in a multi-institutional medical intensive care unit database were analyzed retrospectively. A total of 1174 patients were identified who required mechanical ventilation for more than 2 days and were treated with vasopressor agents to support blood pressure. The patients were divided into 2 groups: those who received enteral nutrition (n = 707) within 48 hours of the start of mechanical ventilation, termed the early enteral nutrition group, and those who did not (n = 467), termed the late enteral nutrition group. The primary end points were overall intensive care unit and hospital mortality. Subgroup analyses were used to evaluate potential confounding variables. The data were also analyzed after adjustments for confounding by matching for propensity score. Intensive care unit and hospital mortality were lower in the early enteral nutrition group than in the late enteral group: 22.5% vs 28.3%; P = 03; and 34.0% vs 44.0%; P < .001, respectively. The beneficial effect of early feeding was more evident in the sickest patients, that is, those treated with multiple vasopressors (odds ratio, 0.36; 95% confidence interval, 0.15-0.85) and those without early improvement (odds ratio, 0.59; 95% confidence interval, 0.39-0.90). When adjustments were made for confounding by matching for propensity score, early feeding was associated with decreased hospital mortality. Early enteral nutrition may be associated with reduced intensive care unit and hospital mortality in patients whose hemodynamic condition is unstable.


Socialization characteristics in patients with psychogenic nonepileptic seizures (PNES).
The purpose of this study was to describe social behaviors and preferences in adults with psychogenic nonepileptic seizures (PNES) including self-reported use of various socialization mediums (face-to-face and indirect communication) as well as perceived social barriers. One hundred forty-one consecutive patients with a diagnosis of PNES that was later confirmed through inpatient video-EEG monitoring were administered a questionnaire on the day of their first outpatient appointment. The questionnaire was designed to assess preferences in socialization practices, frequency of interpersonal contact, use of social media, and perceived barriers to socialization. The survey was developed to gain a better understanding of the socialization behaviors and preferences of our patients for the future development of customized activities in our wellness program. Contrary to prevalent assumptions that patients with PNES tend to be socially isolated, our responders reported that they were in fact quite socially connected (72.2% reported daily communication with friends and family via telephone, 68.54% saw relatives in person weekly, 65.28% saw friends weekly, and 51.2% reported using the computer daily to socialize). Facebook was the preferred online social media. Indoor/solitary activities were most common with 57.44% stating that they watch TV/read/use the computer. The primary barriers to socialization that respondents endorsed were driving prohibition and medication side effects. Respondents expressed the greatest interest in online support groups or educational programs (29.46%), office-based support groups (28.57%), and volunteering (23.21%). Although it has been speculated that social isolation is a significant problem for patients with PNES, considerable participation in social activities was reported. Characteristics of socialization practices may be more nuanced than first believed. When addressing therapeutic interventions with this group of patients in the future, it might be beneficial to offer both distance-based options as well as face-to-face options for treatment and support depending on age and personal preference.


Development and Validation of an Older Occupant Finite Element Model of a Mid-Sized Male for Investigation of Age-related Injury Risk.
The aging population is a growing concern as the increased fragility and frailty of the elderly results in an elevated incidence of injury as well as an increased risk of mortality and morbidity. To assess elderly injury risk, age-specific computational models can be developed to directly calculate biomechanical metrics for injury. The first objective was to develop an older occupant Global Human Body Models Consortium (GHBMC) average male model (M50) representative of a 65 year old (YO) and to perform regional validation tests to investigate predicted fractures and injury severity with age. Development of the GHBMC M50 65 YO model involved implementing geometric, cortical thickness, and material property changes with age. Regional validation tests included a chest impact, a lateral impact, a shoulder impact, a thoracoabdominal impact, an abdominal bar impact, a pelvic impact, and a lateral sled test. The second objective was to investigate age-related injury risks by performing a frontal US NCAP simulation test with the GHBMC M50 65 YO and the GHBMC M50 v4.2 models. Simulation results were compared to the GHBMC M50 v4.2 to evaluate the effect of age on occupant response and risk for head injury, neck injury, thoracic injury, and lower extremity injury. Overall, the GHBMC M50 65 YO model predicted higher probabilities of AIS 3+ injury for the head and thorax.


Recent progress in live cell mRNA/microRNA imaging probes based on smart and versatile nanomaterials.
RNAs play important roles in various biological processes. Imaging of intracellular microRNAs (miRNAs) and messenger RNAs (mRNAs) not only helps us to better understand the formation and transcription of mRNAs, but also provides vital information for disease diagnosis and treatment. Recently, many efforts have been focused on the development of high-performance RNA imaging probes that directly monitor endogenous miRNAs and mRNAs inside living cells without special treatment. Such real-time and in situ monitoring of the intracellular RNA expression level offers dynamic distribution information of target RNA in living cells that promotes target mRNA/miRNA functional research. With the breakthrough in smart cell delivery techniques, efficient live cell RNA imaging probes greatly expand our knowledge of life processes and improve cancer detection accuracy. In this review, we summarize different classes of state-of-the-art live cell miRNA/mRNA optical imaging probes based on smart and versatile nanomaterials that have been reported in recent years. By featuring the designs and performance for the probes of interest, we compare advanced RNA imaging probes, provide guidance for better utilization of the existing imaging probes and suggest the design of future advanced live cell RNA imaging probes.


Functional correlation between cell adhesive properties and some cell surface proteins.
The adhesive properties of Chinese hamster V79 cells were analyzed and characterized by various cell dissociation treatments. The comparisons of aggregability among cells dissociated with EDTA, trypsin + Ca2+, and trypsin + EDTA, revealed that these cells have two adhesion mechanisms, a Ca2+-independent and a Ca2+-dependent one. The former did not depend on temperature, whereas the latter occurred only at physiological temperatures. Both mechanisms were trypsin sensitive, but the Ca2+-dependent one was protected by Ca2+ against trypsinization. In morphological studies, the Ca2+-independent adhesion appeared to be a simple agglutination or flocculation of cells, whereas the Ca2+-dependent adhesion seemed to be more physiological, being accompanied by cell deformation resulting in the increase of contact area between adjacent cells. Lactoperoxidase-catalyzed iodination of cell surface proteins revealed that several proteins are more intensely labeled in cells with Ca2+-independent adhesiveness than in cells without that property. It was also found that a cell surface protein with a molecular weight of approximately 150,000 is present only in cells with Ca2+-dependent adhesiveness. The iodination and trypsinization of this protein were protected by Ca2+, suggesting its reactivity to Ca2+. Possible mechanisms for each adhesion property are discussed, taking into account the correlation of these proteins with cell adhesiveness.