SNP-Based Genome-Wide Association Mapping of Pollen Viability Under Heat Stress in Tropical Zea mays L. Inbred Lines.
Global environmental changes with more extreme episodes of heat waves are major threats to agricultural productivity. Heat stress in spring affects the reproductive stage of maize, resulting in tassel blast, pollen abortion, poor pollination, reduced seed set, barren ears and ultimately yield loss. As an aneamophelous crop, maize has a propensity for pollen abortion under heat stress conditions. To overcome the existing challenges of heat stress and pollen abortion, this study utilized a broad genetic base of maize germplasm to identify superior alleles to be utilized in breeding programs. A panel of 375 inbred lines was morpho-physiologically screened under normal and heat stress conditions in two locations across two consecutive planting seasons, 2017 and 2018. The exposure of pollen to high temperature showed drastic decline in pollen germination percentage. The average pollen germination percentage (PGP) at 35 and 45°C was 40.3% and 9.7%, respectively, an average decline of 30.6%. A subset of 275 inbred lines were sequenced using tunable genotyping by sequencing, resulting in 170,098 single nucleotide polymorphisms (SNPs) after filtration. Genome wide association of PGP in a subset of 122 inbred lines resulted in ten SNPs associated with PGP35°C (p ≤ 10-5), nine with PGP45°C (p ≤ 10-6-10-8) and ten SNPs associated with PGP ratio (p ≤ 10-5). No SNPs were found to be in common across PGP traits. The number of favorable alleles possessed by each inbred line for PGP35°C, PGP45°C, and the PGP ratio ranged between 4 and 10, 3-13 and 5-13, respectively. In contrast, the number of negative alleles for these traits ranged between 2 and 8, 3-13 and 3-13, respectively. Genetic mapping of yield (adjusted weight per plant, AWP-1) and flowering time (anthesis-silking interval, ASI) in 275 lines revealed five common SNPs: three shared for AWP-1 between normal and heat stress conditions, one for ASI between conditions, and one SNP, CM007648.1-86615409, was associated with both ASI and AWP-1. Variety selection can be performed based on these favorable alleles for various traits. These marker trait associations identified in the diversity panel can be utilized in breeding programs to improve heat stress tolerance in maize.


Classification of breast microcalcifications: radiological-pathological correlation.
Microcalcifications play a very important role in detection of breast cancer, especially early stage breast cancer. However, ambiguity still exists in understanding the relationship between radiological and pathological characteristics of microcalcifications. The definitive indication of a biopsy has not been established. The purpose of this study is to evaluate the relationship of classification of breast microcalcifications using full-field digital mammography to the pathological characteristics. For all the women an open biopsy had been conducted. One hundred and three mammographs showing clustered microcalcifications from 98 consecutive patients were reviewed along with their pathological records. To investigate the value of each criterion for the detection of cancer, univariate and multivariate analyses were performed on the entire sample and then on morphological subgroups. Pathological examination showed 67 malignant lesions (65.05%) and 36 benign lesions (34.95%). In the univariate analysis, four radiological variables were significant: morphological type (P = 0.001), complicated by a mass (P = 0.002), number of microcalcifications per cluster (P = 0.02) and linear or triangular distribution of clusters (P = 0.009). In the multivariate analysis, two criteria remained significant: morphological type (P < 0.001) and complicated by a mass (P = 0.001). The percentage of malignancy was 37.0%, 60.0%, 78.8%, and 88.9%, respectively, for type 2 (regularly punctiform), type 3 (dusty), type 4 (irregularly punctiform) and type 5 (vermicular) microcalcifications (Le Gal's classification). The malignancy was 78.6% for microcalcifications complicated by a mass and 48.9% without a mass. The difference was significant (P < 0.05). The relationship between morphological types of microcalcifications and the pathological characteristics was also studied. In subgroups, type 3 (dusty) microcalcifications complicated by a mass (P = 0.001) or with the number of microcalcifications more than 10 (P = 0.024); and type 2 (regularly punctiform) with a diameter of the area over 20 mm (P = 0.024) or complicated by a mass (P = 0.025) were statistically significant as criteria for malignant tumour. Most cases of microcalcifications of type 4 or 5; type 3 complicated by a mass or with the number of microcalcifications more than 10; type 2 complicated by a mass or with a diameter of the area over 20 mm; are indicative of cancer. Open biopsy is recommended to acquire definitive pathological diagnosis for these cases. For the remainder of the morphological types, stereotaxic biopsy or followup should be considered.


Measuring temperature-dependent activation energy in thermally activated processes: a 2D Arrhenius plot method.
Thermally activated processes are characterized by two key quantities, activation energy (E(a)) and pre-exponential factor (nu(0)), which may be temperature dependent. The accurate measurement of E(a), nu(0), and their temperature dependence is critical for understanding the thermal activation mechanisms of non-Arrhenius processes. However, the classic 1D Arrhenius plot-based methods cannot unambiguously measure E(a), nu(0), and their temperature dependence due to the mathematical impossibility of resolving two unknown 1D arrays from one 1D experimental data array. Here, we propose a 2D Arrhenius plot method to solve this fundamental problem. Our approach measures E(a) at any temperature from matching the first and second moments of the data calculated with respect to temperature and rate in the 2D temperature-rate plane, and therefore is able to unambiguously solve E(a), nu(0), and their temperature dependence. The case study of deep level emission in a Cu(In,Ga)Se(2) solar cell using the 2D Arrhenius plot method reveals clear temperature dependent behavior of E(a) and nu(0), which has not been observable by its 1D predecessors.


The effects of cyclosporin A on V(D)J recombination activity.
V(D)J recombination is up-regulated by the protein kinase A (PKA) pathway and down-regulated by the protein kinase C (PKC) and Ca2+ pathways. When activators of the PKA and PKC pathways or the PKA and Ca2+ pathways are given at the same time, a strong reduction of the PKA effect is observed. The V(D)J recombination suppressing effect of elevated intracellular Ca2+ levels, but not that of the PKC pathway, can be abrogated by the addition of the calcineurin inhibitor cyclosporin A (CsA), indicating that the effect of Ca2+ is mediated by calcineurin. This effect is observed in a pre B cell line as well as in the V(D)J recombination competent fibroblast cell line L4, indicating that the mechanisms of the cross talk between different signalling pathways are basically the same in both cell types. In the absence of Ca2+ mobilizer CsA increases the V(D)J recombination rate in pre B cells but not in L4 cells.


A Case of Posttransplant Fibrillary Glomerulonephritis.
Fibrillary glomerulonephritis (FGN) is a rare form of glomerulonephritis, usually occurring in concurrence with other conditions such as hepatitis C, dysproteinemia, autoimmune conditions, diabetes mellitus, and malignancy. The diagnosis is made by the presence of randomly oriented fibrillar deposits with a mean diameter of 20 nm, which stain positive for IgG and C3 and are negative for congo red and thioflavin T stains. Staining for DNAJB9 (DnaJ homolog subfamily B member 9) is a recently discovered mode of diagnosis of FGN without electron microscopy. The prognosis is poor and optimal treatment is yet not clearly defined, though rituximab may be useful in FGN patients with relatively preserved renal functions. In this case report, we discuss a case of post-renal transplant patient with de novo occurrence of fibrillary glomerulonephritis.


CSI acquisition in RIS-assisted mobile communication systems.
Reconfigurable intelligent surface- (RIS) assisted mobile communication is a promising technological paradigm thanks to the attractive advantages of low cost and flexible control of electromagnetic waves. However, the low-cost features of RISs entail some fundamental challenges to the acquisition of channel state information (CSI), which is essential for the optimal RIS design. To tackle this problem, there have been extensive studies on CSI acquisition in RIS-assisted mobile communication systems, from the perspective of architectural improvement as well as specific mathematical solutions. This article aims to overview the existing works on CSI acquisition in RIS-assisted mobile communication systems.


Structural Basis of Bone Fragility in Young Subjects with Inflammatory Bowel Disease: A High-resolution pQCT Study of the SWISS IBD Cohort (SIBDC).
The onset of inflammatory bowel disease (IBD) during childhood/adolescence compromises peak bone mass acquisition and predisposes to fractures later in life. However, the structural basis for bone fragility in young adults with IBD remains unknown. One hundred two young subjects from the Swiss IBD cohort were included. Areal bone mineral density (aBMD) at distal radius, hip, and spine as well as morphometric vertebral fractures were assessed using dual-energy x-ray absorptiometry technique. Volumetric (v)BMD, trabecular, and cortical bone microstructure at the distal radius and tibia were assessed by high-resolution peripheral quantitative computed tomography. Areal, vBMD, and microstructure were compared between patients with IBD and healthy matched controls (n = 389). Multiple regression analysis was used to evaluate variables associated with bone microarchitecture and fractures. Clinical fractures were reported in 37 IBD subjects (mean age 23 yrs), mostly of the forearm; 5 subjects had morphometric vertebral fractures. After adjusting for age, sex, and height, tibia trabecular (Tb)vBMD, thickness, and distribution were significantly associated with fractures, whereas aBMD was not. After adjusting for aBMD, radius Tb distribution and tibia (Tb)vBMD and trabecular thickness still remained associated with fractures. Compared with healthy controls, patients with IBD had significantly lower aBMD at all sites, as well as alteration in (Tb)vBMD and trabecular microstructure at the distal radius and tibia, and these alterations were correlated with disease severity. Young patients with IBD have low aBMD and altered trabecular bone microarchitecture compared with healthy controls. The latter is independently associated with fractures and may predispose increased susceptibility to fragility fractures throughout life.


Central memory CD4+ T cell responses in chronic HIV infection are not restored by antiretroviral therapy.
A strong CD4(+) T cell response has been correlated with better control of HIV infection. However, the effect of HIV on the maintenance of Ag-specific memory CD4(+) T cells is not fully understood. We characterized the function and phenotype of memory CD4(+) T cells generated by mumps and influenza A or B viruses in HIV-infected individuals receiving highly active antiretroviral therapy (n = 21), HIV-infected long-term nonprogressors (n = 10), and HIV-seronegative volunteers (n = 10). We observed significantly decreased proliferation of the Ag-specific central memory CD4(+) T cell population (CD28(+)/CCR7(+)/CD45RA(-)) in the antiretroviral treated HIV-infected individuals compared with the seronegative controls. Restored CD4(+) T cell count and decreased HIV viral load while on highly active antiretroviral therapy did not result in increased proliferation, whereas nadir CD4(+) T cell count predicted the presence of Ag-specific proliferation. Our results indicate that HIV infection leads to impaired maintenance of virus-induced or vaccine-generated central memory CD4(+) T cells that is not restored by HAART.


Proteomic Identification and Time-Course Monitoring of Secreted Proteins During Expansion of Human Mesenchymal Stem/Stromal in Stirred-Tank Bioreactor.
The therapeutic potential of mesenchymal stem/stromal cells (MSC) is widely recognized for the treatment of several diseases, including acute graft-vs.-host disease (GVHD), hematological malignancies, cardiovascular, bone, and cartilage diseases. More recently, this therapeutic efficacy has been attributed to the bioactive molecules that these cells secrete (secretome), now being referred as medicinal signaling cells. This fact raises the opportunity of therapeutically using MSC-derived soluble factors rather than cells themselves, enabling their translation into the clinic. Indeed, many clinical trials are now studying the effects of MSC-secretome in the context of cell-free therapy. MSC secretome profile varies between donors, source, and culture conditions, making their therapeutic use very challenging. Therefore, identifying these soluble proteins and evaluating their production in a reproducible and scalable manner is even more relevant. In this work, we analyzed the global profile of proteins secreted by umbilical cord matrix (UCM) derived-MSC in static conditions by using mass spectrometry, enabling the identification of thousands of proteins. Afterwards, relevant proteins were chosen and monitored in the supernatant of a fully-controllable, closed and scalable system (bioreactor) by using multiple reaction monitoring (MRM) mass spectrometric technique in a time-dependent manner. The results showed that the majority of interesting proteins were enriched through time in culture, with the last day of culture being the ideal time for supernatant collection. The use of this regenerative "soup," which is frequently discarded, could represent a step toward a safe, robust and reproducible cell-free product to be used in the medical therapeutic field. The future use of chemically defined culture-media will certainly facilitate secretome production according to Good Manufacturing Practice (GMP) standards.


[Surgical protocol of velo-palatal and labio-nasal clefts].
Based on a series of 52 cases of velopalatine and labionarinal clefts treated according to the same principle of therapeutic chronology, the authors define their recent surgical protocol for the primary repair of these clefts. Satisfactory functional repair of the tongue and platysma muscles of the face determine the good anatomical results and, in particular, the development of the maxilla together with the results on speech and middle ear pathology. Pathophysiological elements argue in favour of staphylorrhaphy as the first operative stage in unilateral labiovelopalatine clefts associated, at the same time, with cheilorhinoplasty; passive orthodontia is generally performed until the secondary palatoplasty. The surgical repair technique is closely related to this therapeutic timing in terms of the muscular and periosteal detachments.


Factors Influencing Transition to Shisheh (Methamphetamine) among Young People Who Use Drugs in Tehran: A Qualitative Study.
Iran has experienced an emerging epidemic of methamphetamine use during recent years which has added to existing non-injecting and injecting opioid use in the country. This study explored factors influencing the initiation into or transition to methamphetamine use among young people who use drugs (PWUD). We conducted 42 semi-structured, in-depth interviews with young PWUD (n = 35) and health care workers (HCWs) (n = 7) between July and October 2011 in Tehran, Iran. The PWUD were purposefully recruited from different tiers of drug services and lived in geographically diverse areas of Tehran. The HCWs were substance use experts and/or service providers of treatment and harm reduction facilities. All interviews were recorded, transcribed, and coded using OpenCode 3.6 software. The predominant factors for initiation into or transition to methamphetamine use were individual domain factors. The peer domain factors were the second most frequently stated perceived factor category for transition to methamphetamine use. Other perceived factors affecting transition to stimulant use included both family and community domains. Drug prevention programs should consider targeting certain settings, including workplaces and sports clubs, for preventative interventions. Existing opioid treatment and harm reduction services should be adjusted in response to the methamphetamine use epidemic.


Nonparametric Bayesian functional selection in 1-M matched case-crossover studies.
The matched case-crossover study has been used in many areas such as public health, biomedical, and epidemiological research for humans, animals, and other subjects with clustered binary outcomes. The control information for each stratum is based on the subject's exposure experience, and the stratifying variable is the individual subject. It is generally accepted that any effects associated with the matching covariates by stratum can be removed in the conditional logistic regression model. However, when there are numerous covariates, it is important to perform variable selection to study the functional association between the variables and the relative risk of diseases or clustered binary outcomes by simultaneously adjusting effect modifications. The methods for simultaneously evaluating effect modifications by matching covariates such as time, as well as performing automatic variable and functional selections under semiparametric model frameworks, are quite limited. In this article, we propose a unified Bayesian approach due to its ability to detect both parametric and nonparametric relationships between the predictors and the relative risk of diseases or binary outcomes, accounting for potential effect modifications by matching covariates such as time, and perform automatic variable and functional selections. We demonstrate the advantages of our approach using simulation study and an epidemiological example of a 1-4 bidirectional case-crossover study.


An exploratory study on the contribution of graduate entry students personality to the diversity of medical student populations.
Studies conducted in medical education show that personality influences undergraduate medical students academic and clinical performances and also their career interests. Our aims with this exploratory study were: to assess the contribution of graduate entry students to the diversity of personality in medical student populations; to assess whether eventual differences may be explained by programme structure or student age and sex. We performed a cross-sectional study underpinned by the five-factor model of personality, with students attending three medical schools in Portugal. The five personality dimensions were assessed with the Portuguese version of the NEO-Five Factor Inventory. MANOVA and MANCOVA analyses were performed to clarify the contributions of school, programme structure, age and sex. Student personality dimensions were significantly different between the three medical schools [F (10,1026) = 3.159, p < .001, [Formula: see text] = 0.03, π = 0.987]. However, taking sex and age into account the differences became non-significant. There were institutional differences in personality dimensions. However, those were primarily accounted for by sex and age effects and not by the medical school attended. Diversifying age and sex of the admitted students will diversify the personality of the medical student population.


Homeobox oncogene activation by pan-cancer DNA hypermethylation.
Cancers have long been recognized to be not only genetically but also epigenetically distinct from their tissues of origin. Although genetic alterations underlying oncogene upregulation have been well studied, to what extent epigenetic mechanisms, such as DNA methylation, can also induce oncogene expression remains unknown. Here, through pan-cancer analysis of 4174 genome-wide profiles, including whole-genome bisulfite sequencing data from 30 normal tissues and 35 solid tumors, we discover a strong correlation between gene-body hypermethylation of DNA methylation canyons, defined as broad under-methylated regions, and overexpression of approximately 43% of homeobox genes, many of which are also oncogenes. To gain insights into the cause-and-effect relationship, we use a newly developed dCas9-SunTag-DNMT3A system to methylate genomic sites of interest. The locus-specific hypermethylation of gene-body canyon, but not promoter, of homeobox oncogene DLX1, can directly increase its gene expression. Our pan-cancer analysis followed by functional validation reveals DNA hypermethylation as a novel epigenetic mechanism for homeobox oncogene upregulation.


Bidirectional replication initiates at sites throughout the mitochondrial genome of birds.
Analysis of mitochondrial replication intermediates of Gallus gallus on fork-direction gels indicates that replication occurs in both directions around circular mitochondrial DNA. This finding was corroborated by a study of chick mitochondrial DNA on standard neutral two-dimensional agarose gels, which yielded archetypal initiation arcs in fragments covering the entire genome. There was, however, considerable variation in initiation arc intensity. The majority of initiation events map to regions flanking the major non-coding region, in particular the NADH dehydrogenase subunit 6 (ND6) gene. Initiation point mapping of the ND6 gene identified prominent free 5' ends of DNA, which are candidate start sites for DNA synthesis. Therefore we propose that the initiation zone of G. gallus mitochondrial DNA encompasses most, if not all, of the genome, with preferred initiation sites in regions flanking the major non-coding region. Comparison with mammals suggests a common mechanism of initiation of mitochondrial DNA replication in higher vertebrates.


Gradient Sensing: Engineering the Yeast Love Affair.
A new study in fission yeasts promotes the notion that transient polarity patches that wander the cell surface at the onset of mating are discrete agents of gradient sensing. This concept unexpectedly bridges the modes of gradient sensing in eukaryotes and prokaryotes.


Whey protein-derived exosomes increase protein synthesis and hypertrophy in C2-C12 myotubes.
We sought to examine potential amino acid independent mechanisms whereby hydrolyzed whey protein (WP) affects muscle protein synthesis (MPS) and anabolism in vitro. Specifically, we tested (1) whether 3-h and 6-h treatments of WP, essential amino acids, or l-leucine (Leu) affected MPS, and whether 6-h treatments with low-, medium-, or high doses of WP versus Leu affected MPS; (2) whether knockdown of the primary Leu transporter affected WP- and Leu-mediated changes in MPS, mammalian target of rapamycin (mTOR) signaling responses, or both, following 6-h treatments; (3) whether exosomes isolated from WP (WP-EXO) affected MPS, mTOR signaling responses, or both, compared with untreated (control) myotubes, following 6-h, 12-h, and 24-h treatments, and whether they affected myotube diameter following 24-h and 48-h treatments. For all treatments, 7-d post-differentiated C2C12 myotubes were examined. In experiment 1, 6-h WP treatments increased MPS compared with control (+46%), Leu (+24%), and essential amino acids (+25%). Moreover, the 6-h low-, medium-, and high WP treatments increased MPS by approximately 40 to 50% more than corresponding Leu treatments. In experiment 2 (LAT short hairpin RNA-transfected myotubes), 6-h WP treatments increased MPS compared with control (+18%) and Leu (+19%). In experiment 3, WP-EXO treatments increased MPS over controls at 12h (+18%) and 24h (+45%), and myotube diameters increased with 24-h (+24%) and 48-h (+40%) WP-EXO treatments compared with controls. The WP-EXO treatments did not appear to operate through mTOR signaling; instead, they increased mRNA and protein levels o eukaryotic initiation factor 4A. Bovine-specific microRNA following 24-h WP-EXO treatments were enriched in myotubes (chiefly miR-149-3p, miR-2881), but were not related to hypertrophic gene targets. To summarize, hydrolyzed WP-EXO increased skeletal MPS and anabolism in vitro, and this may be related to an unknown mechanism that increases translation initiation factors rather than enhancing mTOR signaling or the involvement of bovine-specific microRNA.


Direct versus indirect readout in the interaction of the trp repressor with non-canonical binding sites.
Both direct and indirect readouts are utilized when the trp repressor binds to its operators. Here, we use gel-electrophoretic methods to examine the role played by direct and indirect readouts in the interaction of the repressor with a non-canonical binding site, similar to the mtr operator, and named trpGG. The stability and affinity of the 1:1 complexes of the trp repressor with this non-canonical site are lower than those of the 1:1 complexes formed with either the natural consensus sequence or a consensus sequence found in a selection experiment. We attribute this to the inability of the trpGG target to make the same number of water-mediated hydrogen bonds as canonical trp binding sites. On the other hand, the 2:1 complex of the repressor with trpGG has high stability and affinity, similar to that of the 2:1 complex with a consensus sequence found by a selection experiment. The bend angle induced on the trpGG target by the binding of one repressor molecule is 27 degrees, which is similar to that measured in other 1:1 complexes with the repressor. The angle for the 2:1 complex is significantly larger (43 degrees versus 30 degrees in other 2:1 complexes). We present evidence suggesting that the deleterious effect of the sequence substitution in trpGG is compensated by the increased bend angle in the 2:1 complex. These observations demonstrate that indirect readout may complement for direct readout in determining the nature of the interaction between trp repressor and its binding sites.


Affective video retrieval: violence detection in Hollywood movies by large-scale segmental feature extraction.
Without doubt general video and sound, as found in large multimedia archives, carry emotional information. Thus, audio and video retrieval by certain emotional categories or dimensions could play a central role for tomorrow's intelligent systems, enabling search for movies with a particular mood, computer aided scene and sound design in order to elicit certain emotions in the audience, etc. Yet, the lion's share of research in affective computing is exclusively focusing on signals conveyed by humans, such as affective speech. Uniting the fields of multimedia retrieval and affective computing is believed to lend to a multiplicity of interesting retrieval applications, and at the same time to benefit affective computing research, by moving its methodology "out of the lab" to real-world, diverse data. In this contribution, we address the problem of finding "disturbing" scenes in movies, a scenario that is highly relevant for computer-aided parental guidance. We apply large-scale segmental feature extraction combined with audio-visual classification to the particular task of detecting violence. Our system performs fully data-driven analysis including automatic segmentation. We evaluate the system in terms of mean average precision (MAP) on the official data set of the MediaEval 2012 evaluation campaign's Affect Task, which consists of 18 original Hollywood movies, achieving up to .398 MAP on unseen test data in full realism. An in-depth analysis of the worth of individual features with respect to the target class and the system errors is carried out and reveals the importance of peak-related audio feature extraction and low-level histogram-based video analysis.


Optimized Rapeseed Oils Rich in Endogenous Micronutrients Protect High Fat Diet Fed Rats from Hepatic Lipid Accumulation and Oxidative Stress.
Micronutrients in rapeseed exert a potential benefit to hepatoprotection, but most of them are lost during the conventional refining processing. Thus some processing technologies have been optimized to improve micronutrient retention in oil. The aim of this study is to assess whether optimized rapeseed oils (OROs) have positive effects on hepatic lipid accumulation and oxidative stress induced by a high-fat diet. Rats received experiment diets containing 20% fat and refined rapeseed oil or OROs obtained with various processing technologies as lipid source. After 10 weeks of treatment, liver was assayed for lipid accumulation and oxidative stress. All OROs reduced hepatic triglyceride contents. Microwave pretreatment-cold pressing oil (MPCPO) which had the highest micronutrients contents also reduced hepatic cholesterol level. MPCPO significantly decreased hepatic sterol regulatory element-binding transcription factor 1 (SREBP1) but increased peroxisome proliferator activated receptor α (PPARα) expressions, and as a result, MPCPO significantly suppressed acetyl CoA carboxylase and induced carnitine palmitoyl transferase-1 and acyl CoA oxidase expression. Hepatic catalase (CAT) and glutathione peroxidase (GPx) activities as well as reduced glutathione (GSH) contents remarkably increased and lipid peroxidation levels decreased in parallel with the increase of micronutrients. OROs had the ability to reduce excessive hepatic fat accumulation and oxidative stress, which indicated that OROs might contribute to ameliorating nonalcoholic fatty liver induced by high-fat diet.


Cancer Resistance Is Mediated by the Upregulation of Several Anti-Apoptotic Gene Products via the Inducible Nitric Oxide Synthase/Nitric Oxide Pathway: Therapeutic Implications.
Significance: Several therapeutic strategies for cancer treatments have been developed with time, and significant milestones have been achieved recently. However, with these novel therapies, not all cancer types respond and in the responding cancer types only a subset is affected. The failure to respond is principally the result that these cancers develop several mechanisms of resistance. Thus, a focus of current research investigations is to unravel the various mechanisms that regulate resistance and identify suitable targets for new therapeutics. Recent Advances: Hence, many human cancer types have been reported to overexpress the inducible nitric oxide synthase (iNOS) and it has been suggested that iNOS/nitric oxide (NO) plays a pivotal role in the regulation of resistance. We have postulated that iNOS overexpression or NO regulates the overexpression of pivotal anti-apoptotic gene products such as B-cell lymphoma 2 (Bcl-2), B-cell lymphoma extra large (Bcl-xL), myeloid cell leukemia-1 (Mcl-1), and survivin. In this report, we describe the various mechanisms, transcriptional, post-transcriptional, and post-translational, by which iNOS/NO regulates the expression of the above anti-apoptotic gene products. Critical Issues: The iNOS/NO-mediated regulation of the four gene products is not the same with both specific and overlapping pathways. Our findings are, in large part, validated by bioinformatic analyses demonstrating, in several cancers, several direct correlations between the expression of iNOS and each of the four examined anti-apoptotic gene products. Future Directions: We have proposed that targeting iNOS may be highly efficient since it will result in the underexpression of multiple anti-apoptotic proteins and shifting the balance toward the proapoptotic gene products and reversal of resistance. Antioxid. Redox Signal. 39, 853-889.


Left-right asymmetry and the chick embryo.
Left-right (LR) asymmetry provides a fascinating example of the patterning of a major body axis during embryonic development. The chick embryo was the first system in which a molecular basis for left-right patterning was characterized, revealing that molecules known to play a role in other aspects of embryogenesis likewise are involved in the establishment of left-right asymmetry. The chick has been instrumental in the identification of a pathway of genes which regulate the sidedness of major body organs, as well as providing a basis for understanding laterality disturbances in twins. This review summarizes the advances in LR asymmetry which have been made in the chick system within the context of laterality research in general.


Quantifying risk factors for human brucellosis in rural northern Tanzania.
Brucellosis is a zoonosis of veterinary, public health and economic significance in most developing countries. Human brucellosis is a severely debilitating disease that requires prolonged treatment with a combination of antibiotics. The disease can result in permanent and disabling sequel, and results in considerable medical expenses in addition to loss of income due to loss of working hours. A study was conducted in Northern Tanzania to determine the risk factors for transmission of brucellosis to humans in Tanzania. This was a matched case-control study. Any patient with a positive result by a competitive ELISA (c-ELISA) test for brucellosis, and presenting to selected hospitals with at least two clinical features suggestive of brucellosis such as headache, recurrent or continuous fever, sweating, joint pain, joint swelling, general body malaise or backache, was defined as a case. For every case in a district, a corresponding control was traced and matched by sex using multistage cluster sampling. Other criteria for inclusion as a control included a negative c-ELISA test result and that the matched individual would present to hospital if falls sick. Multivariable analysis showed that brucellosis was associated with assisted parturition during abortion in cattle, sheep or goat. It was shown that individuals living in close proximity to other households had a higher risk of brucellosis. People who were of Christian religion were found to have a higher risk of brucellosis compared to other religions. The study concludes that assisting an aborting animal, proximity to neighborhoods, and Christianity were associated with brucellosis infection. There was no association between human brucellosis and Human Immunodeficiency Virus (HIV) serostatus. Protecting humans against contact with fluids and tissues during assisted parturition of livestock may be an important means of reducing the risk of transferring brucellosis from livestock to humans. These can be achieved through health education to the communities where brucellosis is common.


Glucagon secretion in rats with non-insulin-dependent diabetes: an in vivo and in vitro study.
Non-insulin-dependent diabetes ( NIDD ) was obtained in adult rats following a neonatal streptozotocin injection. Rats with NIDD exhibited a chronic low-insulin response to glucose in vivo, slightly elevated basal plasma glucose values (less than 2 g/l) and low pancreatic insulin stores (50% of the controls). Glucagon secretion was studied in this model, in vivo and in vitro using the isolated perfused pancreas technique. Normal basal plasma glucagon levels were observed in the fed state and were in accordance with normal basal glucagon release in vitro. The pancreatic glucagon stores were normal in the diabetics. In experiments with the perfused pancreas, the increased glucose concentration suppressed glucagon release as readily in the diabetics as in the controls. Moreover 5.5 mM glucose suppressed glucagon release stimulated by 19 mM arginine to the same extent in both groups. These data indicate that the suppression of A cell function by glucose is normal in rats with NIDD . Theophylline and isoproterenol also produced normal glucagon release in diabetics. By contrast, the glucagon secretion in response to arginine was lower in the diabetics. This was observed either in vivo (arginine infusion) or in vitro in the presence or the absence of glucose in the perfusate. But in the presence of theophylline the response to arginine was normalized in the diabetics. Impairment of A cell function of the diabetics is not limited to recognition of amino-acids, since acetylcholine evoked a lower glucagon response in the diabetics than in the controls. These defects are different from those described in their B cells.


IRAG mediates NO/cGMP-dependent inhibition of platelet aggregation and thrombus formation.
Defective regulation of platelet activation/aggregation is a predominant cause for arterial thrombosis, the major complication of atherosclerosis triggering myocardial infarction and stroke. A central regulatory pathway conveying inhibition of platelet activation/aggregation is nitric oxide (NO)/cyclic GMP (cGMP) signaling by cGMP-dependent protein kinase I (cGKI). However, the regulatory cascade downstream of cGKI mediating platelet inhibition is still unclear. Here, we show that the inositol-1,4,5-trisphosphate receptor-associated cGMP kinase substrate (IRAG) is abundantly expressed in platelets and assembled in a macrocomplex together with cGKIbeta and the inositol-1,4,5-trisphosphate receptor type I (InsP3RI). cGKI phosphorylates IRAG at Ser664 and Ser677 in intact platelets. Targeted deletion of the IRAG-InsP3RI interaction in IRAGDelta12/Delta12 mutant mice leads to a loss of NO/cGMP-dependent inhibition of fibrinogen-receptor activation and platelet aggregation. Intracellular calcium transients were not affected by DEA/NO or cGMP in mutant platelets. Furthermore, intravital microscopy shows that NO fails to prevent arterial thrombosis of the injured carotid artery in IRAGDelta12/Delta12 mutants. These findings reveal that interaction between IRAG and InsP3RI has a central role in NO/cGMP-dependent inhibition of platelet aggregation and in vivo thrombosis.


Construction of a reactive surface barrier to reduce fumigant 1,3-dichloropropene emissions.
Halogenated fumigants have been used extensively in production agriculture to control soilborne pests. These types of pesticides are highly volatile and are prone to affect air quality and imperil public health. In the present study, a chemical tarp approach, termed a reactive surface barrier (RSB), was developed to reduce the emission of fumigant 1,3-dichloropropene (1,3-D) from the soil surface. The agrochemicals thiourea and allylthiourea were tested as active reagents for the construction of a RSB, where these soil amendments react with 1,3-D to form nonvolatile isothiuronium ions at the soil surface and, thereby, impede fumigant emission into the atmosphere. The feasibility of the method largely depends on the reactivity of 1,3-D and the RSB agrochemicals in soil as well as on the mobility, persistence, and toxicity of the transformation products. Therefore, the reaction kinetics and transformation mechanism of 1,3-D by thiourea and allylthiourea were studied comprehensively in aqueous solution and soil. A catalytic process occurring at the surface of soil colloids facilitated the reaction between 1,3-D and thiourea in amended soils. The rate of 1,3-D transformation in thiourea-amended soil increased with decreasing soil moisture or increasing thiourea amendment level. In a field trial, a thiourea RSB reduced cumulative 1,3-D emissions by more than 80% relative to that in bare soil surface. The present results clearly indicate that this chemical remediation technology has great potential to control the emissions of volatile halogenated organic contaminants and to mitigate atmospheric pollution.


Ethical issues arising in pharmacoepidemiologic research in a community hospital in Crete, Greece.
This paper presents the various issues encountered in planning, designing, performing, and reporting pharmacoepidemiologic research. Five hundred and fifty-one indigent patients insured by Social Care visited the Hospital Pharmacy of Chania General Hospital, and were compared with 551 patients insured under Social Security funds who visited three community pharmacies. The study had no external funding. Before we started the study, we officially sought approval from the Scientific Committee of our Hospital and from the local Pharmaceutical Association. We asked also for approval from the Medical School of the University of Crete. Patient privacy was of great concern in the design and performance of the study. The law in Greece, according to the directives of European Union, affects the way we use records in hospitals and protect patient rights. After these studies were completed, we made proposals to the authorities concerning continuous health education for both patients and health workers. Pharmacoepidemiologic research is difficult in hospitals outside universities or institutions, because of the lack of adequate funding and grants to support research staff.


Toward Understanding the Cold, Hot, and Neutral Nature of Chinese Medicines Using in Silico Mode-of-Action Analysis.
One important, however, poorly understood, concept of Traditional Chinese Medicine (TCM) is that of hot, cold, and neutral nature of its bioactive principles. To advance the field, in this study, we analyzed compound-nature pairs from TCM on a large scale (>23 000 structures) via chemical space visualizations to understand its physicochemical domain and in silico target prediction to understand differences related to their modes-of-action (MoA) against proteins. We found that overall TCM natures spread into different subclusters with specific molecular patterns, as opposed to forming coherent global groups. Compounds associated with cold nature had a lower clogP and contain more aliphatic rings than the other groups and were found to control detoxification, heat-clearing, heart development processes, and have sedative function, associated with "Mental and behavioural disorders" diseases. While compounds associated with hot nature were on average of lower molecular weight, have more aromatic ring systems than other groups, frequently seemed to control body temperature, have cardio-protection function, improve fertility and sexual function, and represent excitatory or activating effects, associated with "endocrine, nutritional and metabolic diseases" and "diseases of the circulatory system". Compounds associated with neutral nature had a higher polar surface area and contain more cyclohexene moieties than other groups and seem to be related to memory function, suggesting that their nature may be a useful guide for their utility in neural degenerative diseases. We were hence able to elucidate the difference between different nature classes in TCM on the molecular level, and on a large data set, for the first time, thereby helping a better understanding of TCM nature theory and bridging the gap between traditional medicine and our current understanding of the human body.


Simultaneous Occurrence of Cytomegalovirus Colitis and Retinitis as the Initial Presentation of Human Immunodeficiency Virus Infection in a Patient With Zero CD4 Count.
Cytomegalovirus (CMV) can be a reason for severe disease in immunocompromised patients, either via the reactivation of latent CMV infection or via the acquisition of primary CMV infection. Clinical syndromes that may be observed are retinitis, colitis, esophagitis, encephalitis, pneumonitis, hepatitis, uveitis, and graft rejection following transplantation. The simultaneous occurrence of CMV colitis and retinitis as the initial presentation of human immunodeficiency virus (HIV) infection is extremely rare. We present a case of a 42-year-old male, known to have type 2 diabetes, bronchial asthma, and allergic rhinitis, who presented to the emergency department (ED) with two weeks history of abdominal pain and watery diarrhea four to five times per day sometimes accompanied by small amounts of blood. He also had an on-and-off subjective fever for the last two months prior to presentation, loss of appetite, and weight loss of 13 kg over the last six months. Additionally, he had a history of travel outside Saudi Arabia and unprotected sex. HIV-1 serology (combination antigen/antibody immunoassay) was requested, which came out positive, with a viral load of 323141 copies/mL and decreased CD4+ T lymphocytes (0 cel/μL). CMV polymerase chain reaction (PCR) quantitative was detected and the CMV viral load was 694963 IU/mL. Given the patient's bloody diarrhea with positive CMV and HIV, the gastroenterology team was consulted and they decided to proceed with a colonoscopy and biopsy. The patient was diagnosed with CMV colitis based on the biopsy results. The patient also was found to have CMV retinitis based on ophthalmologic assessment. Multidisciplinary teams, including infectious diseases, gastroenterology, ophthalmology, and pathology, should cooperate to facilitate an accurate and fast diagnosis. Further complications can be prevented by early diagnosis andtreatment.


Current indications for ACE inhibitors and HOPE for the future.
Angiotensin-converting enzyme (ACE) inhibitors are effective in several disease states such as congestive heart failure, myocardial infarction, and diabetes. This article reviews the evidence supporting the clinical use, efficacy, and cost effectiveness of ACE inhibitors in these various disease states. With the findings of the Heart Outcomes Prevention Evaluation trial, these agents may now have a positive impact on the primary prevention of coronary artery disease. New and ongoing trials will provide more information about the role of ACE inhibitors in coronary artery disease.


[Alpha fetoprotein in non-neoplastic liver diseases].
Seric alfa-FP has been studied in acute and chronic hepatitis and in hepatocellular carcinoma. Sixty five normal subjects, 62 cirrhoses, 10 active chronic hepatitis, 12 chronic persistent hepatitis, 4 primary biliary cirrhoses and 9 hepatomas have been examined for seric alfa-FP. Abnormal seric alfa-FP (> 10 ng/ml) values agree with literature data. It is likely that hepatocellular regeneration due to viral or inflammatory disorders, can produce formation of alfa-FP and other abnormal proteins fro a depression mechanism of sue regulator gene.


Transactivation of the mouse sulfonylurea receptor I gene by BETA2/NeuroD.
The sulfonylurea receptor 1 (SUR1) plays a key role in regulation of insulin secretion in pancreatic beta-cells. In this study we investigated the mechanism for tissue-specific expression of the SUR1 gene. A -138/-20 fragment exhibited basal promoter activity while the -660/-20 fragment contained a regulatory element for tissue-specific expression of the mouse SUR1 gene. A pancreatic beta-cell-specific transcription factor, BETA2 (beta-cell E box transcription factor)/NeuroD, enhanced the promoter activity of the -660/-20 fragment in cooperation with E47. Coexpression of a dominant negative mutant of BETA2/NeuroD, BETA2(1-233), repressed the promoter activity of the -660/-20 fragment. BETA2/NeuroD bound specifically to the E3 element located at -141. The E3 sequence in a heterologous context conferred transactivation by BETA2/NeuroD in HeLa and HIT cells. Mutation of E3 eliminated the stimulatory effect of BETA2/NeuroD. Unlike BETA2/NeuroD, neurogenin 3 (ngn3) could not activate the E3 element in HeLa cells. Overexpression of ngn3 concomitantly increased expression of BETA2/NeuroD and SUR1 in HIT cells but not in HeLa cells. These results indicate that BETA2/NeuroD induces tissue-specific expression of the SUR1 gene through the E3 element. These results also suggest that E3 is specific for BETA2/NeuroD, and the stimulatory effect of ngn3 in HIT cells may require factors specifically expressed in HIT cells.


Effects of central 5,7-dihydroxytryptamine on the medical hypothalamic syndrome in rats.
The present study attempted to replicate and extend two recent studies that implicated aberrant brain 5-HT neurotransmission in the etiology of overeating and BW grain. Adult female rats received 25 mg/kg of desipramine hydrochloride 30--45 min prior to an intracisternal injection of 200 microgram (free base) of 5,7-DHT creatinine sulfate or its 1% ascorbic acid aqueous vehicle. After 7 weeks of measuring food intake, water intake, and BW change, rats from both groups received radiofrequency lesions of the MH or sham surgery. After 5 additional weeks of intake and BW measurements, all rats were tested for 24-hr acceptance of varying sucrose and quinine solutions and for 25-day acceptance of a high-fat replacement diet. While 5,7-DHT depleted brain 5-HT by 45%, it did not induce overeating and BW gain alone nor did it modify the overeating, obesity, or "finickiness" produced by hypothalamic injury. Several factors that relate to specificity, sufficiency, and compatibility with other 5-HT depletory techniques were discussed, as were factors of similarity and dissimilarity between this and the previous experiments that we attempted to replicate.


Simultaneous determination of seven phenolic acids in three Salvia species by capillary zone electrophoresis with β-cyclodextrin as modifier.
A capillary zone electrophoresis method was developed for the simultaneous determination of seven phenolic acids, including protocatechuic aldehyde (1), salvianolic acid C (2), rosmarinic acid (3), salvianolic acid A (4), danshensu (5), salvianolic acid B (6), and protocatechuic acid (7), in Danshen and related medicinal plants. A running buffer composed of 20 mM sodium tetraborate adjusted to pH 9.0, and containing 12 mM β-cyclodextrin as modifier. Baseline separation was achieved within 17 min running at the voltage of 20 kV, temperature of 25°C and detection wavelength of 280 nm. The relative standard deviations of migration time ranged from 0.2 to 0.7% and the peak area ranged from 1.5 to 3.7% for the seven analytes, indicating the good repeatability of the proposed method. The method was extensively validated by evaluating the linearity (R(2) ≥ 0.9992), limits of detection (0.14-0.36 μg/mL), limits of quantification (0.47-1.19 μg/mL), and recovery (96.0-102.6%). Under the optimum conditions, samples of Danshen and related medicinal plants were analyzed using the developed method with high separation efficiency.


The clinical application progress and potential of drug-induced sleep endoscopy in obstructive sleep apnea.
Background and Objective: Obstructive sleep apnoea (OSA) is characterized by nocturnal repetitive upper airway (UA) collapse. For sleep physicians, the recognition of UA collapse characteristics is critical for understanding OSA mechanisms and developing individualized treatment plans. Drug-induced sleep endoscopy (DISE) is an exam during simulated sleep that allows the dynamic assessment of the UA of individuals with OSA. The initial recognition of DISE was to locate the sites of UA obstruction and direct the surgical selection of OSA since it was introduced in the 1990s. After approximately 30 years of studies, based on advances in endoscopic operative techniques and innovative treatments of OSA, DISE had been performed to explore mechanisms and comprehensive treatments related to UA collapse. Methods: This article reviewed contemporary DISE advances, including indications and contraindications, technique of induced sleep, endoscopic operation, UA characteristics classification.Results and Conclusions: Precise selection based on the association between collapse patterns and treatment modalities, such as continuous positive airway pressure, oral appliance, positional therapy, robotic surgery and neurostimulator implanting, is the future research prospect based on DISE.Key messagesDISE provides sleep physicians with valuable information about the upper airway collapse characteristics and dynamic changes during sleep.The studies based on DISE findings improve the selectivity and efficiency of treatment modalities, including classical therapies such as continuous positive airway pressure, oral appliance, positional therapy, and innovative therapies such as neurostimulator implanting and robotic surgery, promote the advancement of OSA precision medicine.


Tight coupling of rubidium conductance and inactivation in human KCNQ1 potassium channels.
KCNQ1 K+ channels in humans are important for repolarization of cardiac action potentials and for K+ secretion in the inner ear. The pore-forming channel subunits form heteromeric complexes with small regulatory subunits of the KCNE family, in particular with KCNE1 to form channels that conduct a slow delayed rectifier K+ current, IKs. This association leads to alteration of biophysical properties, including a slowing of activation, a suppression of inactivation and an increase of the apparent single-channel conductance. In addition, inward Rb+ currents conducted by homomeric KCNQ1 channels are about threefold larger than K+ currents, whereas heteromeric KCNQ1-KCNE1 channels have smaller inward Rb+ currents compared to K+ currents. We determined inactivation properties and compared K+ vs. Rb+ inward currents for channels formed by co-assembly of KCNQ1 with KCNE1, KCNE3 and KCNE5, and for homomeric KCNQ1 channels with point mutations in the pore helix S5 or S6 transmembrane domains. Several of the channels with point mutations eliminated the apparent inactivation of KCNQ1, as described previously (Seebohm et al. 2001). We found that the extent of inactivation and the ratio of Rb+/K+ currents were positively correlated. Since the effect of Rb+ on the current size has been shown previously to be related to a fast 'flickery' process, our results suggest that inactivation of KCNQ1 channels is related to a fast flicker of the open channel. A kinetic model incorporating two open states, no explicit inactivated state and a fast flicker that is different for the two open states is able to account for the apparent inactivation and the correlation of inactivation and large Rb+ currents. We conclude that an association between KCNQ1 and KCNE subunits or removal of inactivation by mutation of KCNQ1 stabilizes the open conformation of the pore principally by altering an interaction between the pore helix and the selectivity filter and with S5/S6 domains.


[Reducing rate of macrosomia in Iceland in relation to changes in the labor induction rate].
Diabetes and prolonged pregnancy are risk factors of macrosomia. The aim was to explore the relationship between the increased rate of labor induction and macrosomia in Iceland. Changes in the incidence proportion of macrosomia was estimated by gestational age. Further, the association between labor induction and macrosomia was estimated in reference to expectant management. Data from the Iceland birth registry on 92,424 singleton births from 1997 to 2018 was used in this cohort study. Macrosomia was defined as birth weight more than 4.5 kg. The incidence proportion during three periods, 1997-2004, 2005-2011, 2012-2018, was calculated and stratified by gestational age. The relative risk reduction of macrosomia over time was calculated with log-binomial regression, using the first period as reference. The risk and relative risk of macrosomia compared with expectant management was estimated and adjusted for diabetes. The total number of macrosomic infants was 5110 and of those only 313 had a mother with diabetes. The incidence proportion of macrosomia was 6.5% during the period 1997-2004, but 4.6% during 2012-2018. A relative risk reduction of macrosomia over time was seen for deliveries after estimated due date. Labor induction decreased the risk of macrosomia, but the association persisted after adjustment for diabetes. The rate of macrosomia decreased in Iceland during the last two decades, but only a small proportion of macrosomic infants had a mother with diabetes. Labor induction decreased the risk of macrosomia, an association which seemed independent of diabetes.


Efficacy of weekly paclitaxel treatment as a single agent chemotherapy following first-line cisplatin treatment in urothelial bladder cancer.
The aim of the present study was to investigate the efficacy of paclitaxel following a first-line cisplatin regimen in patients with metastatic bladder cancer. The present study retrospectively evaluated the clinical effects and toxicities of second-line paclitaxel regimens following first-line cisplatin treatment in metastatic bladder cancer. A total of 42 patients with progressing metastatic urothelial bladder cancer following cisplatin-based chemotherapy were enrolled. The patients received weekly treatment with paclitaxel (80 mg/m2) with a median duration of 3 months. The overall response rate, disease control rate and median progression free survival were 9.5, 45.2 and 6.4 months, respectively. Weekly paclitaxel was well-tolerated with rare grade III or IV toxicities. Second-line weekly paclitaxel treatment following first-line cisplatin-based chemotherapy is an effective and well-tolerated regimen in urothelial metastatic bladder cancer.


Cornea in Marfan disease: Orbscan and in vivo confocal microscopy analysis.
To investigate corneal thickness, curvature, and morphology with the Orbscan Topography System I (Bausch & Lomb, Inc., Salt Lake City, UT) in patients with Marfan syndrome (MFS) and to study MFS with in vivo confocal microscopy. This prospective, clinical, comparative case series included 60 eyes of 31 patients with MFS and 32 eyes of 17 control subjects. First, biomicroscopic examination was conducted to search for ectopia lentis. Then, mean keratometry and ocular refractive power were calculated by the autokeratorefractometer. In each group, the Orbscan System I mean (and mean simulated) keratometry and pachymetric measurements (at the central location and at eight midperipheral locations) were obtained and compared, and correlations were established. In vivo confocal microscopy was performed to evaluate tissue morphology and Z-scan analysis of 14 thin MFS corneas compared with 14 control corneas. A significant decrease (ANOVA, P < 0.0001) of mean simulated keratometry measurement appeared in the MFS group (sim K, 40.8 +/- 1.4 D) compared with the control group (42.9 +/- 1.1 D). Pachymetry in the MFS group was significantly decreased (P < 0.0001) compared with that in the control group, in the center (respectively, 502 +/- 41.9 microm and 552 +/- 23.6 microm) and the eight midperipheral locations. Ectopia lentis was highly linked with mean keratometry and pachymetry (P < 0.0001). Confocal microscopy performed on MFS-affected thin corneas confirmed the corneal thinning and showed an opaque stromal matrix, and Z-scan profiles were abnormal with increased stromal back scattering of light. MFS is known to be associated with a flattened cornea. This study demonstrated an association with corneal thinning and described confocal microscopy findings in this syndrome.


Are doctors team players, and do they need to be?
Evidence suggests that teamwork failures contribute to poor outcomes in hospitals and that changes in healthcare delivery have at times worked against the development of effective healthcare teams. Doctors' engagement with the concept of healthcare teams, although variable, has generally been supportive and there have been several successful initiatives. However, lack of evidence on the critical components that improve the performance of healthcare teams impedes growth in our understanding and development of effective teams. In an endeavour to improve the function of healthcare teams through education and systems change, the psychology literature remains a useful framework for studying the critical components of team processes.


Interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells through PI3K/Akt/GSK3β signaling pathway activation.
Metastasis is the major cause of treatment failure in anaplastic thyroid carcinoma (ATC) patients. In the preliminary study, we demonstrated that interleukin (IL)-11 expression is positively correlated with distant metastasis in ATC. However, the mechanisms underlying remain largely unknown. Here, we found that cobalt chloride (a hypoxia mimetic) promoted IL-11 expression via HIF-1α activation. Furthermore, the resultant increase in IL-11 expression significantly induced epithelial-mesenchymal transition (EMT) in ATC cells, accompanied by Akt/GSK3β pathway activation and increased invasive and migratory abilities. Conversely, HIF-1α or IL-11 knockdown, or treating cells with a neutralizing antibody against IL-11, a PI3K inhibitor, or Akt inhibitor V, significantly suppressed the induction of EMT and counteracted the enhancements in invasive and migratory abilities. These results indicate that hypoxia increases IL-11 secretion in ATC cells via HIF-1α induction and that IL-11 then induces EMT in these cells via the PI3K/Akt/GSK3β pathway, ultimately improving their invasive and migratory potential. This study elucidates the prometastatic role played by IL-11 in ATC metastasis and indicates it as a potential target for the treatment of cancer metastasis. However, many questions remain to be explored.


A hospital play program: helping children with serious illness.
Children hospitalized with a life-threatening disease are experiencing a severely stressful situation that is often confusing, frightening, and anxiety-provoking. This paper describes a play-therapy program designed to facilitate the expression of these feelings, enhance the sense of mastery, foster adaptive behavior, and increase cooperation with medical treatment.


Development and validation of a liquid chromatography-tandem mass spectrometry for the determination of BPR0L075, a novel antimicrotuble agent, in rat plasma: application to a pharmacokinetic study.
A rapid and sensitive liquid chromatography-tandem mass spectrometric method (LC-MS/MS) had been developed and validated to determine the concentrations of BPR0L075 in rat plasma. After a simple protein precipitation of plasma samples by acetonitrile, BPR0L075 was analyzed on a C(8) column at a flow rate of 0.5 mL/min. The mobile phase consisted of a mixture of 10 mM ammonium acetate containing 0.1% formic acid and acetonitrile (20:80, v/v). Both BPR0L075 (analyte) and the internal standard (BPR0L092) were determined using electro-spray ionization and the MS data acquisition was via multiple reactions monitoring (MRM) in positive scanning model. The MS/MS ion transitions monitored are m/z 342.2/195.2 and 312.5/165.2 for BPR0L075 and BPR0L092, respectively. The low limit of quantitation was 0.5 ng/mL. Each plasma sample was chromatographed within 5 min. The method was validated with respect to linearity, accuracy, precision, recovery, and stability. A good linear relationship was observed over the concentration range of 0.5-1000 ng/mL (r>0.9994). Absolute recoveries ranged from 63.45 to 68.34% in plasma at the concentrations of 2, 40, 400, and 800 ng/mL. The intra- and inter-day accuracy ranged from 92.04 to 111.80%. Intra- and inter-day relative standard deviations were 1.08-3.29% and 1.96-5.46%, respectively. This developed and validated assay method had been successfully applied to a pharmacokinetic study after intravenous injection of BPR0L075 in rats at a dose of 5mg/kg.


Symptomatic subacute subdural hematoma associated with cerebral hemispheric swelling and ischemia.
A 55-year-old man with traumatic acute subdural hematoma (SDH) was managed nonsurgically because of having isolated mild headache that resolved within a week. However, the patient developed an acute onset of amnestic aphasia 12 days post-trauma. Although the SDH itself did not increase in volume, remarkable swelling of the ipsilateral cerebral hemisphere was observed on CT scanning. Craniotomy was required since the main component of the SDH was solid and partially organized. Post-operative recovery from his speech disturbance was delayed, necessitating speech therapy for more than two months. Additionally, decreased cerebral blood flow on the affected side was observed even 3 months after injury. Symptomatic subacute SDH exclusively presenting as focal neurological deficits, though very rare,is worthwhile to be kept in mind as a pitfall in nonsurgical management of acute SDH.


Multilayered nano-prism vertex tips for tip-enhanced Raman spectroscopy and imaging.
We presented a scalable fabrication method for the preparation of multilayered nano-prism vertex (NV)-tips whose dimensions can be controlled for tip-enhanced Raman spectroscopy (TERS). The NV-tip had sharp vertices (diameter ~20 nm) originated from the chemical lift-off process after the angle-grinding process, enabling high resolution imaging. TERS measurements were performed on brilliant cresyl blue (BCB) molecules using a Ag/Au NV-tip, revealing the enhanced field localization at the vertices of the NV-tip. Furthermore, we could observe the polarization effect of the NV-tip. Our NV-tips should be a powerful tool for basic research on TERS experiments and SPM applications.


A new approach to electron-beam reference dosimetry.
A new approach is proposed for electron-beam dosimetry under reference conditions and data necessary to use this approach are presented. The approach has the following features; it uses ion chambers and starts from an absorbed-dose calibration factor for 60Co to be consistent with the present proposal for the new AAPM photon-beam protocol; it uses R50 to specify the beam quality and the reference depth, dref = 0.6R50 - 0.1 (all quantities in cm), recommended by Burns et al. [Med. Phys. 23, 383-388 (1996)]; it has a formalism which is parallel to the kQ formalism for photon-beam dosimetry; it fully accounts for the impact on stopping-power ratios of realistic electron beams; it allows an easy transition to using primary standards for absorbed dose to water in electron beams when these are available. The equation for dose to water under reference conditions is; DWQ = MPionPgrQk'R50kecalND,w60Co. The term PgrQ is not needed with plane-parallel chambers but corrects for gradient effects with cylindrical chambers and is measured in the user's beam. The parameter kecal is associated with converting the 60Co absorbed-dose calibration factor into one for an electron beam of quality Qe and contains most of the chamber to chamber variation. Calculated values of kecal are presented as well as Monte Carlo calculated Pwall values for plane-parallel chambers in a water phantom irradiated by a 60Co beam since these are needed to calculate kecal. The factor k'R50 is a function of R50 and converts the absorbed-dose calibration factor to that for the electron-beam quality of interest. Two analytical expressions are presented which are close to universal expressions for all cylindrical Farmer-like chambers and for well-guarded plane-parallel chambers respectively. Calculated values are presented graphically for electron beams with energies between 5 and 50 MeV.


Effects of elevated CO2 concentrations and fly ash amended soils on trace element accumulation and translocation among roots, stems and seeds of Glycine max (L.) Merr.
The carbon dioxide (CO(2)) levels of the global atmosphere and the emissions of heavy metals have risen in recent decades, and these increases are expected to produce an impact on crops and thereby affect yield and food safety. In this study, the effects of elevated CO(2) and fly ash amended soils on trace element accumulation and translocation in the root, stem and seed compartments in soybean [Glycine max (L.) Merr.] were evaluated. Soybean plants grown in fly ash (FA) amended soil (0, 1, 10, 15, and 25% FA) at two CO(2) regimes (400 and 600 ppm) in controlled environmental chambers were analyzed at the maturity stage for their trace element contents. The concentrations of Br, Co, Cu, Fe, Mn, Ni, Pb and Zn in roots, stems and seeds in soybeans were investigated and their potential risk to the health of consumers was estimated. The results showed that high levels of CO(2) and lower concentrations of FA in soils were associated with an increase in biomass. For all the elements analyzed except Pb, their accumulation in soybean plants was higher at elevated CO(2) than at ambient concentrations. In most treatments, the highest concentrations of Br, Co, Cu, Fe, Mn, and Pb were found in the roots, with a strong combined effect of elevated CO(2) and 1% of FA amended soils on Pb accumulation (above maximum permitted levels) and translocation to seeds being observed. In relation to non-carcinogenic risks, target hazard quotients (TQHs) were significant in a Chinese individual for Mn, Fe and Pb. Also, the increased health risk due to the added effects of the trace elements studied was significant for Chinese consumers. According to these results, soybean plants grown for human consumption under future conditions of elevated CO(2) and FA amended soils may represent a toxicological hazard. Therefore, more research should be carried out with respect to food consumption (plants and animals) under these conditions and their consequences for human health.


Effect of emergency department crowding on time to antibiotics in patients admitted with community-acquired pneumonia.
We hypothesize that emergency department (ED) volume and increased patient complexity are associated with lower quality of care, as measured by time to antibiotics for patients being admitted with community-acquired pneumonia. This was a cross-sectional study at a university tertiary care hospital ED. Community-acquired pneumonia patients admitted from the ED and discharged between January 2004 and June 2005 were reviewed by our institution for The Joint Commission's antibiotic timing core measure. Medical records were abstracted for patient age, sex, race, mode of transport, arrival time, triage acuity, inpatient level of care, and arrival-to-antibiotic-administration times. Controlling for patient characteristics, multivariate logistic regression determined association of antibiotic administration within 4 hours of arrival, with total ED volume at the time of the community-acquired pneumonia patient's arrival, and with number of ED patients requiring admission at the time of arrival. Four hundred eighty-six patients were eligible for the study; antibiotic administration time was available for 405. Sixty-one percent of patients received antibiotics within 4 hours. Antibiotic administration within 4 hours was less likely with a greater number of patients (odds ratio 0.96 per additional patient; 95% confidence interval 0.93 to 0.99) and a greater number of patients ultimately admitted (odds ratio 0.93 per patient; 95% confidence interval 0.88 to 0.99) in the ED. The effect of additional patients was present below total ED capacity. As ED volume increases, ED patients with community-acquired pneumonia are less likely to receive timely antibiotic therapy. The effect of additional patients appears to occur even at volumes below the maximum bed capacity. Measures to ensure that quality targets are met in the ED should consider the impact of ED volume.


Caregiving as a dyadic process: perspectives from caregiver and receiver.
Most family caregiving research has relied on the perspective of the caregiver but has not systematically examined the views and opinions of the elder who is receiving care. The present study examined 63 caregiving dyads to determine how the responses of each member had an impact on the well-being of the other member of the dyad. Caregiver relationship strain predicted his or her own depression and negative health, but no significant association was found between caregiver and care recipient outcomes. Multilevel modeling was used to assess the level of dyadic discrepancy over the care recipient's needs and appraisal of caregiving difficulties. Results indicate that there is little disagreement over the care recipient's needs, but a significant amount of variation in how much the care recipient and caregiver agree on their appraisals of caregiving difficulties. Relationship strain perceived by the caregiver, but not the care recipient, was significantly associated with this disagreement.


Accepted standards on how to give a Medical Research Presentation: a systematic review of expert opinion papers.
Background: This systematic review aimed to extract recommendations from expert opinion articles on how to give a medical research presentation on a scientific conference and to determine whether the experts agree on what makes an effective or poor presentation. Methods: Presentation-related terms were searched within article titles listed in PubMed, restricting the search to English-language articles published from January 1975 to July 2015. Recommendations were extracted from the articles, grouped by content, and analyzed for frequency. Ninety-one articles were included. Among 679 different recommendations, 29 were given in more than 20% of articles each. The five most frequent recommendations were to keep slides simple, adjust the talk to the audience, rehearse, not read the talk from slides or a manuscript, and make eye contact. Results: No article gave advice that was the complete opposite of the 29 most frequent recommendations with the exception of whether a light or dark background should be used for slides. Conclusions: Researchers should comply with these widely accepted standards to be perceived as effective presenters.


Repurposing of nucleoside- and nucleobase-derivative drugs as antibiotics and biofilm inhibitors.
There is an urgent need for new antibacterial drugs that are robust against the development of resistance. Drug repurposing is a cost-effective strategy to fast-track the drug development process. Here we examine why the nucleoside and nucleobase analogue drugs in particular present an attractive class for repurposing. Some of these drugs have already been evaluated for their potential as antibacterial agents. In addition to inhibiting bacterial growth and survival, some also act synergistically with antibiotics, and as such can enhance the therapeutic spectrum of currently available antibiotics. Furthermore, nucleoside and nucleobase analogue drugs can inhibit bacterial virulence and biofilm formation. Biofilms are known to impart antibiotic tolerance and are associated with chronic infections. Targeting biofilm formation thus renders pathogens more susceptible to antibiotic treatment and host immune defences. Moreover, specific analogues have properties that make them less susceptible to the development of resistance. Thus, nucleoside and nucleobase analogue drugs ought to be considered as new weapons in our fight against pathogenic bacteria.


Pineocytoma with neuronal differentiation--case report.
The authors describe a case of pineocytoma studied by light and electron microscopy and the immunoperoxidase method. The tumor consisted of two types of cells bearing either chromatin-rich or pale nuclei. These cells were arranged in rosettes and contained pale, eosinophilic material at the center, or in lobular patterns with thin connective tissue and a few blood vessels. Bodian silver staining disclosed a delicate tangle of argyrophilic fibers and processes with small, club-like terminations. These findings are characteristic of pineocytoma. On ultrastructural examination, the tumor cells were found to be closely packed, in clumps separated by numerous fine or expanded, interlacing processes, some of which contained microtubules. A few dense core vesicles and clusters of clear vesicles similar to synaptic vesicles were seen, the latter being aggregated around desmosome-like thickenings in the cellular membrane, suggestive of a synaptic complex. Some tumor cells were positive for neuron-specific enolase and S-100 protein. Only a few cells positive for glial fibrillary acidic protein were distributed in the tumor tissue, but it was not ascertained if they were tumor cells or normal, pre-existing astrocytes. The tumor was diagnosed as a pineocytoma with neuronal differentiation.


Toll-like receptors and radiation protection.
Exposure to ionizing radiation (IR) causes severe injuries to the human body, and normal tissue toxicity also limits the further application of cancer radiotherapy. However, current clinically used radioprotective agents are difficult to produce satisfactory effects. Toll-Like receptor (TLR) is a kind of pattern recognition receptor (PRR) that has been extensively studied for radioprotection in recent years. Several TLR family members are closely related to radioprotection. In cultured cells, TLR2, TLR5 or TLR9 agonist was proved to inhibit radiation-induced apoptosis and increase cell survival. TLR5 ligand CBLB502 was reported to alleviate bone marrow and intestinal injuries in mice and rhesus monkeys. Activation of TLR4 by its agonist LPS can protect bone marrow damage and lower mice mortality after irradiation. TLR9 ligand also exhibited protective effects on mid jejunum. Moreover, some kinds of TLR agonists, such as TLR2/6 co-agonist CBLB613, were reported to be more effective in radioprotection than single TLR agonist. In conclusion, TLRs and their ligands provide novel strategies for radiation protection in nuclear accidents as well as protection of normal tissues during cancer radiotherapy.


[Syndrome dopamine dysregulation and deep brain stimulation of the subthalamic nucleus in Parkinson's disease].
Dopamine dysregulation syndrome (DDS) is a complication of the dopaminergic therapy in Parkinson's disease (PD); it is manifested as a compulsive medication use and may have negative impact on patients' social, psychological, and physical functioning. An effect of deep brain stimulation in the subthalamic nucleus (DBS STN) on DDS is not fully understood. Therefore, the degree of DDS during DBS STN in PD patients was evaluated in the study. The main group included 15 patients with DDS symptoms in the preoperative period. The comparison group consisted of 15 patients without DDS symptoms and the control group consisted of 15 patients who did not undergo surgery. The severity of motor disturbances in the surgery groups has decreased significantly (by 45%). Motor complications during DBS STN in patients with DDS have decreased by 50%; a decrease in the reduction of doses of dopaminergic preparations was noted as well.


Chelate ring size variations and their effects on coordination chemistry and catechol dioxygenase reactivity of iron(III) complexes.
The catechol dioxygenase reactivity of iron(III) complexes using tripodal ligands was investigated. Increasing, as well as decreasing, chelate ring sizes in the highly active complex [Fe(tmpa)(dbc)]B(C6H5)4 (tmpa = tris[(2-pyridyl)methyl]amine; dbc = 3,5-di-tert-butylcatecholate dianion), using related ligands, only resulted in decreased reactivity of the investigated compounds. A detailed low-temperature stopped-flow investigation of the reaction of dioxygen with [Fe(tmpa)(dbc)]B(C6H5)4 was performed, and activation parameters of DeltaH++ = 23 +/- 1 kJ mol(-1) and DeltaS++ = -199 +/- 4 J mol(-1) K(-1) were obtained. Crystal structures of bromo-(tetrachlorocatecholato-O,O')(bis((2-pyridyl)methyl)-2-pyridylamine-N,N',N'')-iron(III), (mu-oxo)-bis(bromo)(bis((2-pyridyl)methyl)-2-pyridylamine-N,N',N' ',N''')-diiron(III), dichloro-((2-(2-pyridyl)ethyl)bis((2-pyridyl)methyl)amine-N,N',N' ',N''')-iron(III) and (tetrachlorocatecholato-O,O')((2-(2-pyridyl)ethyl)bis((2-pyridyl)methyl)amine-N,N',N' ',N''')-iron(III) are reported.


[Arthroscopic options for regenerative treatment of cartilage defects in the shoulder].
Chondral or osteochondral lesions of the shoulder may lead to premature osteoarthritis of the glenohumeral joint as regeneration of damaged articular cartilage is lacking. Rising health awareness, increasingly active populations and improvements in medical techniques have increased the application of cartilage regenerative minimally invasive approaches for glenohumeral joint preservation or delayed prosthetic replacement. In contrast to the conclusive and mostly convincing mid-term results of cartilage regenerative techniques known for the knee, clinical results of innovative therapeutic approaches with glenohumeral cartilage defects are more or less absent. Current techniques include procedures for mesenchymal stem cell recruitment, such as microfracturing, (autologous) osteochondral transplantation, (matrix-associated) autologous chondrocyte transplantation and biological resurfacing, addressing focal chondral defects up to massive structural osteochondral defects. With increasing arthroscopic applicability, they evolve to important tools in the armamentarium of the shoulder surgeon. Future clinical data will determine evidence-based applicability, enabling standardized treatment selection.


Synthesis of 2,4-dihydroxychalcone derivatives as potential antidepressant effect.
In this study, twelve 2,4-dihydroxychalcone derivatives were synthesized and evaluated for antidepressant activities using the forced swimming test (FST). The pharmacological test showed that 6 compounds significantly reduced the immobility times in the FST at a dose of 10 mg/kg, indicative of antidepressant activity. Among the derivatives, compounds designated 3d and 3 h exhibited the best antidepressant activity, with reduced immobility time by 32.05% and 34.33%, respectively. In the 5-hydroxytryptophan-induced head-twitch test and yohimbine-induced mortality test, compounds 3d and 3 h increased head-twitch and increased the mortality rate. The mechanisms of the antidepressant effects of compounds 3d and 3 h may be related with the 5-HTP and NE nervous system.


[Optogenetics: A Therapeutic Option for Advanced Retinal Dystrophies].
Optogenetics refers to the genetic modification of cells to express light-sensitive proteins, which mediate ion flow or secondary signalling cascades upon light exposure. Channelrhodopsin, the most famous example, is an unselective cation channel, which opens when exposed to blue light, thus mediating the depolarisation of the expressing cell. Along with other light-sensitive proteins such as the chloride pump eNpHR, which mediates light-activated hyperpolarisation, the optogenetic toolset offers a wide range of non-invasive single cell manipulations. Due to the direct modulation of the membrane potential, the in-vivo and in-vitro application of optogenetics in neuronal cells seemed to be of outstanding interest. Soon it became evident that these tools are well-suited to treat retinas of patients suffering from photoreceptor degeneration, independently of the underlying mutation. The ectopic expression of channelrhodopsin or eNpHR may cause inactive photoreceptors or other, intact cells of the retina to become sensitive to light. Thus, the most basic function of the retina, the perception of light, can be restored. This review gives a short overview of the retinal structure as well as its physiological and pathological function as the primary light-perceiving tissue. We will focus on different optogenetic strategies to restore visual function in previously blind retinas.


The importance of early bonding on the long-term mental health and resilience of children.
Human babies are born very dependent on their parents. They undergo huge brain development, growth and neuron pruning in the first two years of life. The brain development of infants (as well as their social, emotional and cognitive development) depends on a loving bond or attachment relationship with a primary caregiver, usually a parent. There is increasing evidence from the fields of development psychology, neurobiology and animal epigenetic studies that neglect, parental inconsistency and a lack of love can lead to long-term mental health problems as well as to reduced overall potential and happiness. In this paper, the authors consider the evidence for this claim across several disciplines and conclude that the support of babies and their parents in the first two years of life to be a crucial aim of public health groups in the community.


Primary parotid gland Hodgkin's lymphoma.
Hodgkin's lymphoma with its primary manifestation in the parotid gland is an exceedingly rare entity and is not usually suspected in the initial evaluation of a parotid mass. Because it is not suspected, the results of fine-needle aspiration cytology are often misleading, and parotidectomy is needed for a definitive diagnosis. The most common subtype encountered is lymphocyte-predominant. The prognosis is favorable; the 5-year survival rate exceeds 90%. Treatment consists of chemotherapy, radiotherapy, or both. A case of primary parotid gland Hodgkin's lymphoma is presented along with a review of the literature and a discussion of the evaluation and management of this rare entity.


Efficient Assessment of Developmental, Surgical and Pathological Lymphangiogenesis Using a Lymphatic Reporter Mouse and Its Embryonic Stem Cells.
Several lymphatic reporter mouse lines have recently been developed to significantly improve imaging of lymphatic vessels. Nonetheless, the usage of direct visualization of lymphatic vessels has not been fully explored and documented. Here, we characterized a new Prox1-tdTomato transgenic lymphatic reporter mouse line, and demonstrated how this animal tool enables the researchers to efficiently assess developmental, surgical and pathological lymphangiogenesis by direct visualization of lymphatic vessels. Moreover, we have derived embryonic stem cells from this reporter line, and successfully differentiated them into lymphatic vessels in vivo. In conclusion, these experimental tools and techniques will help advance lymphatic research.


Extraordinary optical transmission in the ultraviolet region through aluminum hole arrays.
We investigated the extraordinary optical transmission phenomenon in the UV range by fabricating large-area, free-standing aluminum hole arrays using extreme UV interference lithography and shadow thermal evaporation. Transmission spectra show strong peaks in the UV region resulting from both surface plasmon polariton and localized surface plasmon excitations. The results indicate that the high plasmon frequency of Al is directly responsible for the presence of strong resonance peaks in the UV region, which supports the role of plasmonic phenomena in the extraordinary transmission. The simple fabrication method enables large-area production of such structures for research and industrial production purposes.


Magnetic nanoparticles: recent developments in drug delivery system.
Nanostructured functional materials have demonstrated their great potentials in medical applications, attracting increasing attention because of the opportunities in cancer therapy and the treatment of other ailments. This article reviews the problems and recent advances in the development of magnetic NPs for drug delivery.


Molecular cloning of human interferon cDNA.
A hybrid plasmid, TpIF319, has been shown to contain the sequence for human fibroblast interferon mRNA [Taniguchi, T., Sakai, M., Fujii-Kuriyama, Y., Muramatsu, M., Kobayashi, S. & Sudo, T. (1979) Proc. Jpn. Acad. 55, Ser. B, 464-469]. This conclusion was confirmed by a hybridization-translation assay, using rabbit globin mRNA and its cDNA-containing plasmid as a control. Plasmid TpIF319 was used as probe and another recombinant plasmid, TpIF319-13, whose cDNA insert consists of about 800 base pairs, was isolated. Nucleotide sequence analysis of the cDNA revealed that the DNA in fact codes for human fibroblast interferon.


Prognostic Impact of Sarcopenia in Patients With Biliary Tract Cancer Undergoing Chemotherapy.
Sarcopenia affects the treatment of various cancer types but its impact on chemotherapy efficacy and prognosis in biliary tract cancer remains unclear. Thus, we evaluated whether sarcopenia independently affects the outcome of chemotherapy for biliary tract cancer. Data of 50 patients who underwent chemotherapy for biliary tract cancer at two affiliated centres were retrospectively analysed. The association of clinical factors, including sarcopenia, with overall survival and time to treatment failure was analysed. Sarcopenia was an independent factor negatively influencing overall survival and time to treatment failure in univariate and multivariate analyses (median overall survival, sarcopenic vs. non-sarcopenic patients: 10.6 vs. 16.6 months; hazard ratio=2.19, p=0.018; time to treatment failure: 5.3 vs. 13.1 months, hazard ratio=2.50, p=0.019). Sarcopenia may affect the efficacy of chemotherapy and prognosis in biliary tract cancer. Thus, improving sarcopenia may improve the prognosis of patients with biliary tract cancer undergoing chemotherapy.


The splanchnic syndrome. Diagnosis and indications for treatment.
The typical chronic splanchnic syndrome is characterized by upper abdominal pain usually provoked by a meal, the finding of an epigastric bruit and weight loss in conjunction with haemodynamically significant stenosis of two or more of the splanchnic arteries. Diagnosis of chronic splanchnic syndrome depends mainly on a strong clinical suspicion. Usually the classical triad is incomplete or absent. Therefore chronic splanchnic syndrome should be considered, in every patient with chronic abdominal discomfort, after exclusion of other more common causes of upper abdominal discomfort. Findings from nonvasive and invasive diagnostic tests support the presence of chronic splanchnic syndrome. However, until now, the diagnosis of chronic splanchnic syndrome has usually only been made retrospectively if all the symptoms disappeared after technically successful reconstructive surgery. A variety of surgical techniques has been advocated to repair the splanchnic arteries. The choice of the technique is usually based on the preference and experience of the surgeon.


Outcomes of corneal crosslinking for central and paracentral keratoconus.
The aim of the study was to compare the therapy of corneal collagen crosslinking (CXL) for central and paracentral keratoconus. 64 eyes of 43 central keratoconus patients whose highest power of the cornea located in the central 3 mm zone and 24 eyes of 16 paracentral keratoconus patients whose highest power located out of the central 3 mm zone received standard corneal CXL were included. Maximum keratometry (Kmax) and astigmatism according to topography, uncorrected distant visual acuity (UDVA), corrected distant visual acuity (CDVA) were studied preoperatively and 2 years postoperatively. Central group: Preoperative UDVA and CDVA were 0.9 ± 0.4 and 0.5 ± 0.4 logMAR, respectively. At 2 years, UDVA and CDVA significantly improved to 0.8 ± 0.4 and 0.4 ± 0.3 logMAR(P < 0.01). Preoperative Kmax and astigmatism were 61.5 ± 14.7 diopter (D) and 4.0 ± 2.9 D, respectively. At 2 years, Kmax and astigmatism significantly decreased to 57.0 ± 10.4 and 3.0 ± 2.2 D (P < 0.01). Paracentral group: preoperative UDVA and CDVA were 0.8 ± 0.7 and 0.2 ± 0.4 logMAR, respectively. At 2 years, UDVA significantly improved to 0.4 ± 0.4 logMAR(P < 0.01), whereas CDVA remained 0.2 ± 0.3 logMAR(P > 0.05). Preoperative Kmax and astigmatism were 50.3 ± 5.3 and 2.4 ± 1.7 D, respectively. At 2 years, Kmax significantly decreased to 48.8 ± 4.6 (P < 0.01), whereas astigmatism remained 2.2 ± 1.8 D (P > 0.05). This study indicated that CXL was more effective for central keratoconus than paracentral keratoconus.


Differences in fruit and vegetable intake and determinants of intakes between children of Dutch origin and non-Western ethnic minority children in the Netherlands - a cross sectional study.
Fruit and vegetable consumption is low in the Netherlands and a key target in healthy diet promotion. However, hardly any information is available on differences in fruit and vegetable consumption between Dutch children and ethnic minority children. Therefore, the aim of present study was to determine differences in usual fruit and vegetable intake between native Dutch and non-Western ethnic minority children and to study differences in and mediating effects of potential psychosocial and environmental determinants. Ethnicity, usual fruit and vegetable consumption, psychosocial and environmental determinants and mothers' educational level were measured with a self-administered questionnaire during school hours in primary schools in Rotterdam, the Netherlands. Complete data was available for 521 10-11 year-old-children, of which 50.5% of non-Western origin. Differences between the groups regarding potential determinants and fruit and vegetable intake were assessed with Mann Whitney tests or multiple regression analyses. Multiple regression analyses were also conducted to assess mediating effects. Ethnic minority girls ate fruit more frequently (1.41 +/- 1.0 times/day) than Dutch girls (1.03 +/- 0.82 times/day); no differences in frequency of intake were found for vegetables or among boys. Ethnic differences were found for almost all potential determinants. The Dutch children reported lower scores on these determinants than the ethnic minority children, except for perceived self-efficacy and barriers to eat fruit and vegetables. Knowledge of recommendations and facilitating behaviors of the parents mediated the association between ethnicity and fruit consumption among girls. Ethnic minority girls in the Netherlands appear to have more favorable fruit intakes than Dutch girls, and ethnic minority children in general show more positive prerequisites for fruit and vegetable consumption. Interventions addressing multi-ethnic populations of children must take such differences into account.


A mixed method observational study of strategies to promote adoption and usage of an application to support asthma self-management.
Apps can potentially support asthma self-management, however attracting downloads and encouraging on-going adherence is challenging. We observed the impact of different recruitment strategies and app features on adoption and continued use. Practice nurses in five practices in Lothian/Oxford approached adults with active asthma to try out a prototype app. We also advertised the app via social media (Asthma UK; AUK Centre for Applied Research). We observed patients' download and retention rates and sent pre- and post-trial questionnaires. We sampled 15 patients for interviews before and after using our app for one month to explore motivations, triggers and barriers to adoption and usage. Interviews were transcribed and analysed thematically with reference to the Fogg behaviour model. Social media attracted 87 users, but only 15 (17%) used the app for 30 days. Practices recruited 24 patients, 13 (54%) continued for 30 days. Successful adoption was dependent on ease of downloading and sufficient motivation. Some patients needed technological assistance with downloading the app and starting to use the features. Adherence was dependent on motivation derived from a sense that the healthcare professional and/or researcher was interested in the results, and that using an app to support their self-management could improve their asthma control. Social media attracted more downloads in a short time. However, most patients stopped using the app within a month. Practices recruited fewer patients, but patents adhered longer to the app. Dual promotion strategies (social media with practice support) may be the optimal approach to encourage adoption and adherence to telehealth.


Contrasting Community Composition of Active Microbial Eukaryotes in Melt Ponds and Sea Water of the Arctic Ocean Revealed by High Throughput Sequencing.
Melt ponds (MPs), form as the result of thawing of snow and sea ice in the summer, have lower albedo than the sea ice and are thus partly responsible for the polar amplification of global warming. Knowing the community composition of MP organisms is key to understanding their roles in the biogeochemical cycles of nutrients and elements. However, the community composition of MP microbial eukaryotes has rarely been studied. In the present study, we assessed the microbial eukaryote biodiversity, community composition, and assembly processes in MPs and surface sea water (SW) using high throughput sequencing of 18S rRNA of size-fractionated samples. Alpha diversity estimates were lower in the MPs than SW across all size fractions. The community composition of MPs was significantly different from that of SW. The MP communities were dominated by members from Chrysophyceae, the ciliate classes Litostomatea and Spirotrichea, and the cercozoan groups Filosa-Thecofilosea. One open MP community was similar to SW communities, which was probably due to the advanced stage of development of the MP enabling the exchange of species between it and adjacent SW. High portions of shared species between MPs and SW may indicate the vigorous exchange of species between these two major types of environments in the Arctic Ocean. SW microbial eukaryote communities are mainly controlled by dispersal limitation whereas those of MP are mainly controlled by ecological drift.


Plant-Based Nano-Emulsions as Edible Coatings in the Extension of Fruits and Vegetables Shelf Life: A Patent Review.
Fresh fruits and vegetables are important sources of minerals, vitamins, fibers, and antioxidants, essential for human well-being. However, some fruits and vegetables are highly perishable with a very short shelf life during storage. Serious consumer concern over the use of chemical preservatives for this purpose has led to a green revolution and a sustainable era where the design and fabrication of edible coatings have attracted considerable interest. In recent years, scientific communities have paid great attention to the development of bio-based edible coatings to extend the postharvest shelf life of fruits and vegetables. Furthermore, nanotechnology has been distinguished as a great strategy for improving coating properties, including a better water barrier and better mechanical, optical, and microstructural properties, as well as gradual and controlled release of bioactive compounds. In this work, patent articles on plant-based nano-emulsions as edible coatings in the extension of fruit and vegetable shelf life were reviewed. The Patentscope search service and Espacenet portal were used, applying a query strategy composed of mesh terms and inclusion criteria. Through database searching, a total of 16 patent documents met the inclusion criteria. Further, to demonstrate the innovation trends in this topic, all relevant patents are described at the end of the study, along with the components, technology, application, and advantages of developed preparations.