Severity of hyperechoic pancreas on ultrasonography as a risk factor for glycemic progression.
The aim of this study was to evaluate the association between the severity of hyperechoic pancreas (HP) on ultrasonography (US) and glycemic progression. In total, 1,386 participants who underwent abdominal US as part of health examinations between December 2008 and May 2014 were included in this retrospective study. We classified pancreatic echogenicity on a 4-point scale, and compared it using two distinct criteria: fatty pancreas (FP) 1 criterion (normal vs. ≥mild HP) and FP2 criterion (normal/mild HP vs. ≥moderate HP). According to the presence of nonalcoholic fatty liver disease (NAFLD), participants were subdivided into four groups: non-NAFLD and non-HP, isolated NAFLD, isolated HP, and HP with NAFLD. Glycemic progression was defined as progression from normoglycemia to prediabetes or diabetes or progression from prediabetes to diabetes. During the follow-up (median, 5.9 years), 262 of the 1,386 participants developed glycemic progression. Using FP2, the probability of glycemic progression across the four subgroups showed cumulative aggravation for NAFLD and HP (all P<0.05). Isolated HP showed a higher probability of glycemic progression than isolated NAFLD according to FP2 (P<0.001). The highest probability of glycemic progression was observed in patients with both NAFLD and HP (P<0.001). The hazard ratio for glycemic progression increased with the severity of HP. Increasing severity of HP on US was found to be significantly correlated with glycemic progression. Moreover, isolated HP of moderate or greater severity predicted glycemic progression independent of NAFLD.


The Poisson Index: a new probabilistic model for protein ligand binding site similarity.
The large-scale comparison of protein-ligand binding sites is problematic, in that measures of structural similarity are difficult to quantify and are not easily understood in terms of statistical similarity that can ultimately be related to structure and function. We present a binding site matching score the Poisson Index (PI) based upon a well-defined statistical model. PI requires only the number of matching atoms between two sites and the size of the two sites-the same information used by the Tanimoto Index (TI), a comparable and widely used measure for molecular similarity. We apply PI and TI to a previously automatically extracted set of binding sites to determine the robustness and usefulness of both scores. We found that PI outperforms TI; moreover, site similarity is poorly defined for TI at values around the 99.5% confidence level for which PI is well defined. A difference map at this confidence level shows that PI gives much more meaningful information than TI. We show individual examples where TI fails to distinguish either a false or a true site paring in contrast to PI, which performs much better. TI cannot handle large or small sites very well, or the comparison of large and small sites, in contrast to PI that is shown to be much more robust. Despite the difficulty of determining a biological 'ground truth' for binding site similarity we conclude that PI is a suitable measure of binding site similarity and could form the basis for a binding site classification scheme comparable to existing protein domain classification schema.


Exploration and Practice of "Internet + Maker Education" University Innovative Entrepreneurship Education Model From the Perspective of Positive Psychology.
This thesis aims to analyze the importance of psychological quality in the entrepreneurial education for undergraduates in the case of positive psychology, to explore an educational model that combines the Internet information technology with maker education, and to culture the innovative entrepreneurial capabilities of undergraduates. First, the theories of positive psychology were reviewed worldwide, and the current cultivation of entrepreneurial psychological quality for undergraduates was summarized. Second, undergraduates were taken as the survey objects. The questionnaires were distributed both online and offline to investigate the innovative entrepreneurship education (the IE education) in three different universities in Zhejiang Province, China. The current development of IE education in universities was summarized. Finally, according to the current educational status in universities, combining the Internet and maker education, the implementation strategies suitable for IE education in universities were proposed. According to the results of questionnaire survey, the proportion of college students who chose entrepreneurship was 6.1%. The innovation and entrepreneurship of contemporary college students was not optimistic, which was mainly related to the lack of systematic planning and teachers in China's current innovation and entrepreneurship education. Through the integration of Internet information technology and maker education, this study constructed a more systematic implementation scheme of innovation and entrepreneurship education in colleges and universities. It could meet the needs of students of different majors and grades. Meanwhile, teachers should give full play to the Students' subjective initiative and emphasize the student-centered learning style, thereby promoting the cultivation of students' innovative thinking. The IE education model of "Internet + Maker Education" in colleges can reform traditional college teaching methods and promote the cultivation of entrepreneurship, innovative thinking, and creative abilities, and the model can be used as a new idea and method for the development of IE education in universities.


Mo6 cluster-based compounds for energy conversion applications: comparative study of photoluminescence and cathodoluminescence.
We report the photoluminescence (PL) and cathodoluminescence (CL) properties of face-capped [Mo6Xi8La6]2- (X = Cl, Br, I; L = organic or inorganic ligands) cluster units. We show that the emission of Mo6 metal atom clusters depends not only on the nature of X and L ligands bound to the cluster and counter-cations, but also on the excitation source. Seven members of the AxMo6Xi8La6 series (A = Cs+, (n-C4H9)4N+, NH4+) were selected to evaluate the influence of counter-cations and ligands on de-excitation mechanisms responsible for multicomponent emission of cluster units. This study evaluates the ageing of each member of the series, which is crucial for further energy conversion applications (photovoltaic, lighting, water splitting, etc.).


Growth and activity of Bulgarian yogurt starter culture in iron-fortified milk.
Bulgarian yogurts were manufactured and fortified with 8, 15 and 27 mg of iron kg(-1) of yogurt. The growth and acidifying activity of the starter culture bacteria Streptococcus thermophilus 13a and Lactobacillus delbrueckii subsp. bulgaricus 2-11 were monitored during milk fermentation and over 15 days of yogurt storage at 4 degrees C. Fortifying milk with iron did not affect significantly the growth of the starter culture during manufacture and storage of yogurt. Counts of yogurt bacteria at the end of fermentation of iron-fortified milks were between 2.1 x 10(10) and 4.6 x 10(10) CFU ml(-1), which were not significantly different from numbers in unfortified yogurts. In all batches of yogurt, the viable cell counts of S. thermophilus 13a were approximately three times higher than those of L. delbrueckii subsp. bulgaricus 2-11. Greater decrease in viable cell count over 15 days of storage was observed for S. thermophilus 13a compared to L. delbrueckii subsp. bulgaricus 2-11. Intensive accumulation of lactic acid was observed during incubation of milk and all batches reached pH 4.5 +/- 0.1 after 3.0 h. At the end of fermentation process, lactic acid concentrations in iron-fortified yogurts were between 6.9 +/- 0.4 and 7.3 +/- 0.5 g l(-1). The acidifying activity of starter culture bacteria in the control and iron-fortified milks was similar. There was no increase in oxidized, metallic and bitter off-flavors in iron-fortified yogurts compared to the control. Iron-fortified yogurts did not differ significantly in their sensorial, chemical and microbiological characteristics with unfortified yogurt, suggesting that yogurt is a suitable vehicle for iron fortification and that the ferrous lactate is an appropriate iron source for yogurt fortification.


Radiologic anatomy of the inguinofemoral region: insights from MDCT.
We set out to reexamine the radiologic anatomy of the inguinofemoral region using volume data sets obtained with an MDCT scanner. We conducted a systematic prospective review of CT scans of 20 consecutively enrolled patients, 10 men and 10 women chosen retrospectively from our CT database. An experienced radiologist and a senior trainee surgeon conducted an image review to maximize recognition of relevant anatomic detail. The inferior epigastric artery and femoral canal were identified in all planes in all patients. On axial views a spur on the pubic bone was visible in 17 (85%) of the patients, but the inguinal ligament was not reliably identified in any. The round ligament or spermatic cord was visible in only 15 (75%) of 20 patients. In contrast, on coronal and sagittal views, the inguinal ligament, which is vital to reliable identification and accurate classification of groin hernias, was visible in 19 (95%) of the 20 patients. Scans in the sagittal plane best depicted the gutter-like aspect of the ligament, the canal and contents being clearly visible in 95% of the patients. On sagittal views, the internal ring was identifiable in 90% and the round ligament or spermatic cord in 95% of the patients. On coronal images, the internal ring was identified in all and the conjoint tendon in 95% of the patients. The round ligament or spermatic cord was not seen in 10% of the patients. MDCT produces images of the inguinal region in detail not possible with previous generations of scanners. In our small series, 100% identification of key anatomic structures was achieved when information from all three views was combined. We found subtle differences between imaging findings and standard anatomic teaching.


Attempt to distinguish electric signals of a dichotomous nature.
Three types of electric signals were analyzed: Ion current fluctuations in membrane channels (ICFMC), Seismic electric signals activities (SES), and "artificial" noises (AN). The wavelet transform, when applied to the conventional time domain, does not allow a classification of these signals, but does so in the "natural" time domain. A classification also becomes possible, if we study <chi(q)>-<chi>(q) versus q, where chi stands for the "natural" time. For q values approximately between 1 and 2 the signals are classified and ICFMC lies between the other two types. For q=1, the "entropy" S identical with <chilnchi>-<chi>ln<chi> of ICFMC almost equals that of a "uniform" distribution, while the AN and SES have larger and smaller S values, respectively. The recent [P. Varotsos, N. Sarlis, and E. Skordas, Phys. Rev. E 67, 021109 (2003)] finding that, in short time scales, both SES and AN (which are shown to be non-Markovian) result in comparable detrended fluctuation analysis exponents alpha in (1.0,1.5) is revisited. Even a Markovian dichotomous time series, in short time scales, leads to similar alpha exponents.


BMP and Notch Signaling Pathways differentially regulate Cardiomyocyte Proliferation during Ventricle Regeneration.
Adult mammalian hearts show limited capacity to proliferate after injury, while zebrafish are capable to completely regenerate injured hearts through the proliferation of spared cardiomyocytes. BMP and Notch signaling pathways have been implicated in cardiomyocyte proliferation during zebrafish heart regeneration. However, the molecular mechanism underneath this process as well as the interaction between these two pathways remains to be further explored. In this study we showed BMP signaling was activated after ventricle ablation and acted epistatic downstream of Notch signaling. Inhibition of both signaling pathways differentially influenced ventricle regeneration and cardiomyocyte proliferation, as revealed by time-lapse analysis using a cardiomyocyte-specific FUCCI (fluorescent ubiquitylation-based cell cycle indicator) system. Further experiments revealed that inhibition of BMP and Notch signaling led to cell-cycle arrest at different phases. Overall, our results shed light on the interaction between BMP and Notch signaling pathways and their functions in cardiomyocyte proliferation during cardiac regeneration.


Effect of yeast supplementation on performance, rumination time, and rumen pH of dairy cows in commercial farm environments.
The aims of the present study were to evaluate the effects of live yeast supplementation (Vistacell MUCL 39855, AB Vista, Marlborough, UK) on performance, rumination time, and rumen pH on dairy cows in commercial farm environments. Three trials were carried out, the trials lasted 12 (trial 1), 15 (trial 2), and 19 wk (trial 3). In each trial, 14 multiparous Holstein dairy cows were allocated to 2 groups that received (trial 1) a standard diet plus yeast, (trial 2) an acidogenic diet plus yeast, and (trial 3) grazing pasture plus yeast. Milk production, milk chemical characteristics, body weight and body condition score, rumination time, and rumen pH were monitored for each group throughout the 3 trials. No statistically significant differences were observed in any of the 3 trials for any of the recorded variables. In contrast, an effect of time (period or days in milk) on rumen pH was observed in all 3 of the trials, as time spent under the acidotic thresholds increased across the experimental periods; however the differences were not associated with live yeast supplementation. No effect of live yeast supplementation was observed in any of the 3 trials reported. Further research should include studies on animals at different stages of lactation (with emphasis on transition period and early lactation), consuming more challenging diets (higher level of inclusion of concentrates or starch), or under different environments such as grazing of succulent forages. Such studies might be required to elucidate any possible effect of live yeast supplementation of dairy cows when the rumen environment is under challenge.


Decision Tree Algorithm-Generated Single-Nucleotide Polymorphism Barcodes of rbcL Genes for 38 Brassicaceae Species Tagging.
DNA barcode sequences are accumulating in large data sets. A barcode is generally a sequence larger than 1000 base pairs and generates a computational burden. Although the DNA barcode was originally envisioned as straightforward species tags, the identification usage of barcode sequences is rarely emphasized currently. Single-nucleotide polymorphism (SNP) association studies provide us an idea that the SNPs may be the ideal target of feature selection to discriminate between different species. We hypothesize that SNP-based barcodes may be more effective than the full length of DNA barcode sequences for species discrimination. To address this issue, we tested a ribulose diphosphate carboxylase (rbcL) SNP barcoding (RSB) strategy using a decision tree algorithm. After alignment and trimming, 31 SNPs were discovered in the rbcL sequences from 38 Brassicaceae plant species. In the decision tree construction, these SNPs were computed to set up the decision rule to assign the sequences into 2 groups level by level. After algorithm processing, 37 nodes and 31 loci were required for discriminating 38 species. Finally, the sequence tags consisting of 31 rbcL SNP barcodes were identified for discriminating 38 Brassicaceae species based on the decision tree-selected SNP pattern using RSB method. Taken together, this study provides the rational that the SNP aspect of DNA barcode for rbcL gene is a useful and effective sequence for tagging 38 Brassicaceae species.


Non-communicable diseases and maternal health: a scoping review.
Non-communicable diseases [NCDs] are leading causes of ill health among women of reproductive age and an increasingly important cause of maternal morbidity and mortality worldwide. Reliable data on NCDs is necessary for accurate measurement and response. However, inconsistent definitions of NCDs make reliable data collection challenging. We aimed to map the current global literature to understand how NCDs are defined, operationalized and discussed during pregnancy, childbirth and the postnatal period. METHODS: For this scoping review, we conducted a comprehensive global literature search for NCDs and maternal health covering the years 2000 to 2020 in eleven electronic databases, five regional WHO databases and an exhaustive grey literature search without language restrictions. We used a charting approach to synthesize and interpret the data. RESULTS: Only seven of the 172 included sources defined NCDs. NCDs are often defined as chronic but with varying temporality. There is a broad spectrum of conditions that is included under NCDs including pregnancy-specific conditions and infectious diseases. The most commonly included conditions are hypertension, diabetes, epilepsy, asthma, mental health conditions and malignancy. Most publications are from academic institutions in high-income countries [HICs] and focus on the pre-conception period and pregnancy. Publications from HICs discuss NCDs in the context of pre-conception care, medications, contraception, health disparities and quality of care. In contrast, publications focused on low- and middle-income countries discuss NCDs in the context of NCD prevention. They take a life cycle approach and advocate for integration of NCD and maternal health services. Standardising the definition and improving the articulation of care for NCDs in the maternal health setting would help to improve data collection and facilitate monitoring. It would inform the development of improved care for NCDs at the intersection with maternal health as well as through a woman's life course. Such an approach could lead to significant policy and programmatic changes with the potential corresponding impact on resource allocation.


Priming effects of triethylene glycol and triethylene glycol monomethacrylate on dentin bonding.
The objective of this study was to evaluate the effects of triethylene glycol (TEG) and triethylene glycol monomethacrylate (TEGMA) solutions as dentin primers on dentin bonding. To this end, wall-to-wall polymerization contraction gap width of a resin composite in a cylindrical dentin cavity and shear bond strength to a flat dentin surface were measured. Dentin was pretreated with an experimental dentin bonding system - consisting of 0.5 M ethylenediaminetetraacetic acid conditioner, TEG or TEGMA primer, and Clearfil Photo Bond bonding agent - prior to resin composite filling. When the cavity was primed with an aqueous solution of 35 vol% TEG, 35 or 45 vol% TEGMA for a few seconds, contraction gap formation was prevented completely. Then, among these three gap-free groups, there were no significant differences in shear bond strength. It was thus shown that both TEG and TEGMA were highly effective dentin primers, completely preventing contraction gap formation even when they were applied for only a few seconds.


Head and neck MR angiography in pediatric patients: a pictorial essay.
Magnetic resonance (MR) angiography is a new, noninvasive imaging method with well-known uses in adults for the evaluation of carotid disease in the neck and cerebral vasculopathy. MR angiography examinations were prospectively studied in 126 children to evaluate the usefulness of MR angiography of the head and neck in children, as well as to correlate its findings with those of conventional angiography. Eleven patients underwent conventional angiography in addition to MR angiography. MR angiography was performed with commercially available pulse sequences and included two- and three-dimensional time-of-flight and phase-contrast techniques. Indications for MR angiography included evaluation of pathologic conditions (aneurysms and arteriovenous malformations, infarcts, venous sinus thrombosis, brain tumors, and cerebritis), screening examinations in sickle cell disease, and follow-up of extracorporeal membrane oxygenation. MR angiography was found to be a useful, noninvasive diagnostic and screening examination for head and neck and cerebral vascular abnormalities in children and had excellent correlation with conventional angiography.


Management of UTIs during pregnancy.
This article summarizes the pathophysiology, patient presentation, diagnostic testing, and current treatment modalities for pregnant women presenting with urinary tract symptoms in pregnancy. Urinary tract infection is a common health problem, affecting millions of people each year. However, this seemingly benign condition may have serious consequences if it occurs during the course of a woman's pregnancy, and if untreated could lead to pyelonephritis, preterm labor, or Group B Streptococcal infection in the newborn. Thus, the prevention, early detection, and prompt treatment of urinary tract infections in pregnancy have become essential components of prenatal care.


Identification of a New Inhibitor That Stabilizes Interleukin-2-Inducible T-Cell Kinase in Its Inactive Conformation.
Interleukin-2-inducible T-cell kinase (ITK) plays an important role in T-cell signaling and is considered a promising drug target. As the ATP binding sites of protein kinases are highly conserved, the design of selective kinase inhibitors remains a challenge. Targeting inactive kinase conformations can address the issue of kinase inhibitor selectivity. It is important for selectivity considerations to identify compounds that stabilize inactive conformations from the primary screen hits. Here we screened a library of 390,000 compounds with an ADP-Glo assay using dephosphorylated ITK. After a surface plasmon resonance (SPR) assay was used to filter out promiscuous inhibitors, 105 hits were confirmed. Next, we used a fluorescent biosensor to enable the detection of conformational changes to identify inactive conformation inhibitors. A single-cysteine-substituted ITK mutant was labeled with acrylodan, and fluorescence emission was monitored. Using a fluorescent biosensor assay, we identified 34 inactive conformation inhibitors from SPR hits. Among them, one compound was bound to a site other than the ATP pocket and exhibited excellent selectivity against a kinase panel. Overall, (1) biochemical screening using dephosphorylated kinase, (2) hit confirmation by SPR assay, and (3) fluorescent biosensor assay that can distinguish inactive compounds provide a useful platform and offer opportunities to identify selective kinase inhibitors.


[The use of a new analogue DGlu-Octagastrin in scintigraphy of medullary thyroid carcinoma].
Medullary thyroid carcinomas (MTC) reveal overexpression of several peptide receptors particularly of gastrin and cholecystokinin 2 (CCK2). Experimental studies of various CCK-2/gastrin analogues found that a C-terminal, 8-aminoacid peptide, (D)Glu-octagastrin, has optimal properties. Thus, the aim of our studies was to prepare (99m)Tc-labelled HYNIC-octagastrin, to evaluate its biologic tolerance in animals and introduce for scintigraphy in patients with MTC. HYNIC-(D)Glu-octagastrin was from piCHEM (Graz, Austria), (99m)Tc generator from Amersham (Health), other reagents were purchased from Sigma. Labelling of the peptide was performed in phosphate buffer of pH 6.0 for 10 minutes at 100(o)C using EDDA and tricine as coligands. The labeling yields were high (above 95%); the specific activity amounted to 1200 to 1430 microCi/microg. Radiochemical purity on SepPak cartridge and ITLC ranged from 94 to 98%. No adverse effects were observed in mice after administration of 10 to 50 times greater doses that those used in patients. Clinical studies comprised 20 patients with MTC and high serum calcitonin. (99m)Tc-EDDA/HYNIC-(D)Glu-octagastrin, 500 to 700 MBq, was administered iv and whole body scintigraphy was performed using a double head gamma-camera (Varicam, Elscint) 2 and 4 hours later. Increased accumulation of the tracer in foci of MTC and its metastases was found in 8 patients. Scintigraphy with a new gastrin analogue ((D)Glu-octagastrin) makes it possible to detect MTC with overexpression of CCK-2/gastrin receptors and to select patients for receptor-mediated radiopeptide therapy using DOTA-gastrin analogues labelled with (177)Lu and (90)Y.


Genome trees and the nature of genome evolution.
Genome trees are a means to capture the overwhelming amount of phylogenetic information that is present in genomes. Different formalisms have been introduced to reconstruct genome trees on the basis of various aspects of the genome. On the basis of these aspects, we separate genome trees into five classes: (a) alignment-free trees based on statistic properties of the genome, (b) gene content trees based on the presence and absence of genes, (c) trees based on chromosomal gene order, (d) trees based on average sequence similarity, and (e) phylogenomics-based genome trees. Despite their recent development, genome tree methods have already had some impact on the phylogenetic classification of bacterial species. However, their main impact so far has been on our understanding of the nature of genome evolution and the role of horizontal gene transfer therein. An ideal genome tree method should be capable of using all gene families, including those containing paralogs, in a phylogenomics framework capitalizing on existing methods in conventional phylogenetic reconstruction. We expect such sophisticated methods to help us resolve the branching order between the main bacterial phyla.


Recombinant VP1 protein of duck hepatitis virus 1 expressed in Pichia pastoris and its immunogenicity in ducks.
The VP1 gene of duck hepatitis virus type 1 (DHV-1) strain VJ09 was amplified by reverse transcription PCR from the liver of a duckling with clinical symptoms of viral hepatitis. The resulting VP1 cDNA was 720 bp in length and encoded a 240-amino-acid protein. In VP1 gene-based phylogenetic analysis, the VJ09 strain grouped with DHV-1 genotype C. The VP1 gene was inserted into the expression vector pPICZαA and expressed in Pichia pastoris. The expressed VP1 protein was purified and identified by western blot analysis. To evaluate the recombinant VP1's immunogenic potential in ducklings, the antibodies raised in the immunized ducklings were titrated by ELISA, and lymphocyte proliferation and virus neutralization assays were performed. The results show that the recombinant VP1 protein induced a significant immune response in ducklings and this could be a candidate for the development of a subunit vaccine against DHV-1 genotype C.


Identification of the expression of farnesoid X receptor in astrocytes.
Recently, we have identified a functional expression of farnesoid X receptor (FXR) in neurons in vitro and in vivo. However, whether the FXR is expressed in astrocytes remains unclear. In the present study, we addressed this issue by using an array of experimental methods such as immunofluorescence and western blot. Results showed that the FXR mRNA and protein were expressed in mouse brain primary cultured astrocytes. In mouse primary cultured astrocytes in vitro the FXR was predominantly localized in the nucleus with an obvious punctuate distribution property. Unlike its expressional characteristic in cultured astrocytes, the FXR was not detected in astrocytes in the mouse hippocampus and prefrontal cortex, suggesting that the FXR is not expressed in astrocytes at conditions in vivo. Functional studies in vitro showed that activation of the FXR in primary cultured astrocytes by chenodeoxycholic acid or GW4064 induced a marked increase in expression levels of small heterodimer partner mRNA and protein. Taken together, these findings show a differential expression of FXR in astrocytes at conditions in vitro but not in vivo, and in mouse primary cultured astrocytes the FXR can be activated by its ligands.


Characterisation of unessential genes required for survival under conditions of DNA stress.
Genomic instability is a hallmark of cancer. Cancer progression depends on the development and amplification of mutations that alter the cellular response to threats to the genome. This can lead to DNA replication stress and the potential loss of genetic integrity of the newly formed cells. This study utilised fission yeast to map the interactions occurring in some of the most crucial pathways in both DNA replication and checkpoint monitoring involving Rad4, the Schizosaccharomyces pombe (S. pombe) TopBP1 homologue. We have modelled conditions of replication stress in the genetically tractable fission yeast, S. pombe using the hypomorphic rad4-116 allele. Synthetic genetic analysis was used to identify processes required for cell survival under conditions of DNA replication stress. With the aim of mapping the genetic interactions of rad4 and its mutant allele, rad4-116, several genes that could have an interaction with rad4 during replication stress have emerged as attractive. Interactions with genes involved in chromatin remodelling, such as hip1, and replication fork stalling resolution, such as mrc1, swi1 and swi3 were explored and confirmed. The interactions of Rad4 with each of the genes provided separate and distinct tumour formation pathways, as evident in the synthetically lethal interactions. Even within the same complex, rad4-116 double mutants behaved differently proving that Rad4 interacts at different levels and functions with the same proteins. Results from this study provide a novel view of the rad4 interactions, the association of Rad4 with the replisome. The study also provides the groundwork on a theoretical and practical level for the exploration and separation of interactions of TopBP1 with the histone chaperone family and the replisome.


Chemotherapy of metastatic hepatoid adenocarcinoma: Literature review and two case reports with cisplatin etoposide.
Hepatoid adenocarcinoma (HAC) is a rare and aggressive cancer subtype with a poor prognosis under metastatic conditions. Currently, there is no specific chemotherapy treatment protocol for advanced stages of the disease. This review evaluates two cases of HAC of gastric cardia with synchronous liver metastasis, which were successfully treated by chemotherapy with cisplatin (25 mg/m2 each day) (day 1 to day 3) and etoposide (100 mg/m2) (day 1 to day 3), every three weeks. A structured literary evaluation and reviewed pertinent articles are additionally presented to analyse the different approaches for the treatment of metastatic HAC (mHAC). The two described case reports demonstrated good partial responses to treatment and one of the two patients exhibited a good prognosis after a 9-year follow-up. A total of 20 case reports concerning the use of chemotherapy in mHAC were presented in the literature, 11 of which were regarding gastric HACs. The two aforementioned cases result in a total of 22 reports, 11 of which exhibited objective responses to chemotherapy, 8 patients demonstrated a partial response and 3 a complete response. The cisplatin-based regimen concerned 55% (12/22) patients and enabled 9 (75%) to exhibit a partial or complete response. A total of three patients exhibited a good prognosis in the long-term follow-up, all of them treated with a cisplatin-based regimen. It was demonstrated that the usual digestive regimens were not efficient in the treatment of HAC. In the absence of prospective trials, it may be hypothesized that cisplatin-based chemotherapy may be the most efficient first-line treatment in mHAC, with a 75% patient response, in accordance with the literature and follow-up cases.


[Forebrain regionalization mechanisms].
Where do the regions of the forebrain come from? The paradigm that has come to light in the last ten years is that of a neural plate subdivided by soluble factors which (through the formation of gradients or of a molecular framework) transmits positional information to the neural stem cells. Some of those soluble factors are Fgf8, Sonic hedgehog and proteins of the BMP family. The neural stem cells interpret positional information in terms of the expression of combinations of certain transcription factors. Such combinations would finally be responsible for the formation of specific neural lineages (cortical, thalamic, etc.) from specific neuroepithelial regions. In addition, this primary positional information can make certain regions of the neural primordium (secondary organizers) secrete new soluble factors. These would in turn give rise to new positional information, spatially more restricted, so that the whole process would repeat itself to confer detail to a certain area. This wealth of new knowledge is already helping us to understand the cause of some brain malformations, and maybe we will soon be able to apply it to the early diagnosis and the prevention of such conditions.


Sequential ctDNA whole-exome sequencing in advanced lung adenocarcinoma with initial durable tumor response on immune checkpoint inhibitor and late progression.
Despite prolonged tumor response to immune checkpoint inhibitors (ICIs) for a subset of patients with advanced non-small cell lung cancer (NSCLC), a secondary resistance will occur for a majority of these patients. The understanding of late progression mechanisms with ICIs is important to improve future treatment strategies. We performed whole-exome sequencing (WES) on circulating tumor DNA and compared molecular profiles between the beginning of ICI treatment and tumor progression in patients with advanced NSCLC treated with ICIs and who had initial and prolonged tumor response with secondary progression, after at least 6 months of treatment. We identified eight patients who experienced initial and durable tumor response, and secondary tumor progression after 6 months of treatment, with available paired blood samples (diagnosis and progression). All had lung adenocarcinoma, three had programmed-death ligand-1 expression ≥50% in immunohistochemistry and all presented low blood tumor mutational burden (bTMB). Seven patients received nivolumab in second-line or more, and one received pembrolizumab as first-line treatment. WES at progression showed clonal selection with molecular alterations of Wnt pathway-related genes, increase of copy number aberrations in cancer-related genes and loss of tumor-suppressor genes (such as PTEN) or of genes associated with immune response (such as B2M). No difference in term of bTMB was observed at progression. This is the first study describing putative molecular mechanisms associated with late progression under ICI in lung cancer. Studies on treatment strategies adapted to these mechanisms are needed.


[New research progress of the safety of human papillomavirus vaccine].
Human papillomavirus infection is the main pathogenic factor leading to cervical cancer. About 630 000 new cancers are caused by HPV infection every year, among which cervical cancer accounts for the highest proportion (83%). The burden of cervical cancer is serious in China. Research data shows that there were nearly 110 000 new cases and nearly 50 000 deaths of cervical cancer in China in 2018, accounting for about 20 percent and 16 percent of the global total of cases and deaths, respectively. The World Health Organization's position paper clearly states that HPV vaccination can effectively prevent the occurrence of HPV-related diseases. Across clinical studies and real world data from around the world, HPV vaccines have shown good efficacy and safety. As of October 2019, 98 countries and regions around the world have included HPV vaccine in their national immunization program. However, with the increase of vaccination coverage and indications, the safety of HPV vaccine has become a global public health issue of high concern. Since the launch of HPV vaccine in 2006, many authorities around the world and countries have conducted long-term monitoring of the safety of HPV vaccine after its launch, and accumulated a large number of safety data, which showed that the HPV vaccine was safe and supported the use of HPV vaccine. In this paper, the safety data related to HPV vaccine in the world and mainland China will be combed to provide reference for the HPV vaccination in China.


A pilot study testing the genetic polymorphism of N-acetyltransferase 2 as a risk factor in lung cancer.
NAT2 as phase II enzyme is involved in the detoxification/activation of various drugs, environmental substances and carcinogenic compounds. A genotyping approach has been used to investigate NAT2 genotype with putative relevance in lung cancer in population of 110 Slovak-Caucasians patients and 167 non-malignant individuals from the same region. Slow acetylation was not observed to be a significant risk factor of lung cancer development (OR=1.19; 95% CI: 0.71-1.99). However, one genotype responsible for slow acetylation (NAT2*5B/*6) was observed significantly more frequently in lung cancer patients with squamous cell carcinoma compared with control subjects (OR=2.24; 95% CI: 1.14-4.34). Stratified analysis showed an increasing impact of the specific allelic combination NAT2*5B/*6 in non-smokers (OR=6.5; 95% CI: 1.25-15.08). In the case of squamous lung carcinoma an analysis revealed a tendency to adversely affect cancer risk in the individuals with the mentioned genotype in younger than 60 years (OR=3.14; 95% CI: 0.98-9.72) non-smokers (OR=10.40; 95% CI: 1.35-118.89) and in females (OR=4.25; 1.08-16.25). Additional studies are needed to confirm the results we observed and to assess the impact of other effects (specific allelic combinations, sex differences and histological subtype of lung cancer) on NAT2 susceptibility in lung carcinogenesis.


Gambogic acid potentiates the chemosensitivity of colorectal cancer cells to 5-fluorouracil by inhibiting proliferation and inducing apoptosis.
Chemotherapy using 5-fluorouracil (5-FU) for colorectal cancer (CRC) has low specificity and response rates, leading to severe side effects. Gambogic acid (GA), a traditional Chinese medicine, has multi-targeted anticancer effects, including growth inhibition and apoptosis induction. However, it is unclear whether a combination of 5-FU and GA has synergistic anticancer effects in CRC cells. In this study, SW480 and HCT116 human CRC cells and human intestinal epithelial cells (IECs) were treated with different concentrations of 5-FU, GA or 5-FU+GA. A Cell Counting kit-8 assay was conducted to quantify cell proliferation. The combination index (CI) was calculated and the median-effect principle was applied to analyze the interaction between 5-FU and GA. Flow cytometry was used to determine the percentage of cells undergoing apoptosis. Reverse transcription-quantitative polymerase chain reaction and western blotting were applied to measure P53, survivin and thymidylate synthase (TS) mRNA and protein levels. It was found that 5-FU+GA more pronouncedly inhibited cell growth and induced apoptosis, compared with either monotherapy. CI values <1 indicated the synergistic effects of the drugs. 5-FU+GA further decreased P53, survivin and TS mRNA and protein levels in the two CRC cell lines compared with single drugs, whereas increased P53 protein levels were observed in HCT116 cells. Moreover, 5-FU+GA did not increase cytotoxicity to IECs. These results demonstrate that GA enhances the anticancer effects of 5-FU on CRC cells. Combined treatment with 5-FU and GA is effective and safe for CRC cells, and may become a promising chemotherapy treatment.


Effects of lipoxygenase and cyclooxygenase inhibitors on the induction of ornithine decarboxylase by 12-O-tetradecanoylphorbol-13-acetate and isoproterenol in mouse tissues in vivo.
I.p. administration of 12-O-tetradecanoylphorbol-13-acetate (TPA) (400 micrograms/kg) caused a remarkable increase in ornithine decarboxylase (ODC) activity in CD-1 mouse liver (8.3-fold), spleen (17.8-fold), kidney (4-fold), lung (7.7-fold) and brain (2.7-fold). TPA induced an increase in ODC activity in liver, spleen and kidney in a dose-dependent manner (100-800 micrograms/kg). The putrescine contents of these tissues were also increased by TPA injection. BW755C, an inhibitor of cyclooxygenase and lipoxygenase, prevented the TPA-induced increase in ODC activity in liver, spleen and kidney in a dose-dependent manner. AA861-a selective lipoxygenase inhibitor, also showed the inhibition of TPA-induced increase in ODC activity in these tissues. Significant inhibition was observed either by BW755C or AA861 at the dose of 30 mg/kg. On the other hand, indomethacin, a selective cyclooxygenase inhibitor, enhanced the TPA-induced increase in ODC activity in these tissues dose-dependently. Significantly enhancement was observed at 3 mg/kg for liver and spleen and 1 mg/kg for kidney. The subcutaneous administration of isoproterenol (1 mg/kg) caused an increase in ODC activity in both liver (11-fold) and spleen (3.4-fold). Both AA861 and BW755C failed to inhibit the isoproterenol-induced increase in ODC activity in these tissues. These results indicate that product(s) of lipoxygenase pathway play an important role in ODC induction caused by TPA in liver, spleen and kidney, while the lipoxygenase pathway does not play an essential role in the isoproterenol-induced increase in ODC activity.


Guidelines and evaluation: improving the quality of consultation-liaison psychiatry.
Previous research has shown that residents in the consultation-liaison unit of Geneva University Hospital did not meet proposed guidelines on three counts: quickness of response to emergency situations, reporting cases to supervisors, and consulting with supervisors on major issues. The introduction of daily meetings between residents and supervisors improved the level of compliance with guidelines, from 69.2% to 82.6% for quickness of response, from 57.6% to 97.3% for reporting cases to supervisors, and from 25.0% to 98.0% for consulting with supervisors on major issues. Periodical evaluation would thus appear to enhance performance.


Utilization of youth-friendly reproductive health service and associated factors among youth in Aleta Wondo town, southern Ethiopia, 2020.
Youth faces various sexual and reproductive health problems in developing countries like Ethiopia. Major health problems like unintended pregnancy, unsafe abortion, and sexually transmitted infections are common among youth in Ethiopia. This study aimed to determine the level of utilization of youth-friendly reproductive health services and associated factors among youth in Aleta Wondo town, southern Ethiopia, from 20 to 30 June 2020. A community-based cross-sectional study was conducted among youths of Aleta Wondo town from 20 to 30 June 2020. A total of 421 study participants were selected from households of selected kebeles in the town by using a systematic random sampling method. Data were collected using structured pretested face-to-face interviewer-administered questionnaires. The data were entered using Epi-data version 4.4.2 and exported to SPSS version 25 for analysis. Bivariate and multivariate logistic regression models were used to determine factors significantly associated with the utilization of youth-friendly reproductive health services. Adjusted odds ratio and 95% confidence interval with p value of <0.05 were considered to declare statistical significance. The level of utilization of youth-friendly reproductive health services was 32.8% (95% confidence interval = 28.0%-37.0%). Youth-friendly service utilization was significantly associated with being female gender (adjusted odds ratio = 2.20, 95% confidence interval = 1.34-3.62), living alone (adjusted odds ratio = 2.99, 95% confidence interval = 1.48-5.77), who had not ever discussed with their parents (adjusted odds ratio = 0.46, 95% confidence interval = 0.27-0.81), have visited service required and missed service (adjusted odds ratio = 1.96, 95% confidence interval = 1.19-3.24), and have sexual partner (adjusted odds ratio = 4.52, 95% confidence interval = 2.75-7.44). Youth-friendly reproductive health service utilization among youth Aleta Wondo town was low. Factors like gender, current living place, have ever discussed in reproductive health issues with their parents, have visited health facility and missed service, and having sexual partner were predictors of youth-friendly service utilization. It is better to work in collaboration with youth clubs and schoolteachers to scale up youth-friendly service.


Male reproductive effects of octylphenol and estradiol in Fischer and Wistar rats.
4-tert-Octylphenol is a non-ionic surfactant used as a detergent, emulsifier and wetting agent. It is generally accepted that it acts as a weak estrogenic substance when evaluated in in vitro and in vivo short-term screening assays. The sensitivity of animal species (mouse versus rat), strain (inbred versus outbred) has been a matter of concern when selecting assay type for testing of estrogenicity of chemicals. The present study was designed to investigate whether the choice of different animal strain, could affect the outcomes of studies. Fischer and Wistar adult male rats were exposed to vehicle or 400 mg/kg bw of 4-tert-octylphenol administrated orally by gavage. Estradiol benzoate, at a dose of 40 microg/kg bw, was used as positive control agent. Treatment with estradiol benzoate decreased serum levels of testosterone, LH, FSH, inhibin and increased prolactin. Additionally, estradiol benzoate decreased the weight of all investigated reproductive organs, decreased sperm production and increased seminiferous tubular degeneration in both strains. More progressive effects on testis weight and histopathology were observed in the Fischer rats. Oral administration of octylphenol at 400 mg/kg bw to both rat strains increased prolactin levels but had no effect on LH, FSH, testosterone or inhibin. In the octylphenol-treated Fischer rats the weights of the seminal vesicles and the levator ani/bulbocavernosus muscle were significantly decreased, whereas only the levator ani/bulbocavernosus muscle was affected in Wistar rats. The weights of all other reproductive organs and sperm count were unaffected. It is concluded that there might be an organ specific difference in sensitivity between the two strains with the Fischer rat being the most sensitive rat model as demonstrated mainly by the more progressive effects on testis weight and histopathology in estradiol benzoate-treated Fischer rats but also by the decrease in seminal vesicle weight in octylphenol-treated rats.


Comparative interaction of few antihypertensive drugs with cyclosporine-A in rats.
The maximal endothelial dependent relaxation of isolated aortic rings to cumulative doses of acetylcholine was significantly decreased in the Cyclosporine-A (CSA, 20 mg kg(-1) day(-1)) treated animals compared to olive oil (CSA vehicle) treated control. Administration of antihypertensive drugs like diltiazem, enalapril or propranolol to CSA treated animals augmented the endothelial damage induced by CSA. These drugs also increased the bioavailability of CSA. However, administration of losartan to CSA treated animals produced a significant increase in endothelial dependent relaxation as compared to CSA treated control but did not affect the bioavailability of CSA significantly. The results suggest that losartan is safer compared to other antihypertensives for the treatment of CSA induced hypertension.


[The development of database system of electrocardiographic information].
An ECG information database system was established with 1297 ECG information records and clinical informations. The data and the analysis software in this database can be shared with the international physiological signal databases such as MIT-BIH Arrhythmia. The establishment of this database will facilitate the clinical interpretation, diagnosis and prediction of cardiovascular diseases, especially the cardiac sudden death (SCD).


C-H activation on a diphosphine and hydrido-bridged diiridium complex: generation and detection of an active IrII-IrII species [(Cp*Ir)2(micro-dmpm)(micro-H)]+.
Reaction of [Cp*Ir(micro-H)](2) (5) (Cp* = eta(5)-C(5)Me(5)) with bis(dimethylphosphino)methane (dmpm) gives a new neutral diiridium complex [(Cp*Ir)(2)(micro-dmpm)(micro-H)(2)] (3). Treatment of 3 with methyl triflate at -30 degrees C results in the formation of [(Cp*Ir)(H)(micro-dmpm)(micro-H)(Me)(IrCp*)][OTf] (6). Warming a solution of above 0 degrees C brings about predominant generation of 32e(-) Ir(II)-Ir(II) species [(Cp*Ir)(micro-dmpm)(micro-H)(IrCp*)][OTf] (7). Further heating of the solution of 7 up to 30 degrees C for 14 h leads to quantitative formation of a new complex [(Cp*Ir)(H)(micro-Me(2)PCH(2)PMeCH(2))(micro-H)(IrCp*)][OTf] (8), which is formed by intramolecular oxidative addition of the methyl C-H bond of the dmpm ligand. Intermolecular C-H bond activation reactions with 7 are also examined. Reactions of 7 with aromatic molecules (benzene, toluene, furan, and pyridine) at room temperature result in the smooth sp(2) C-H activation to give [(Cp*Ir)(H)(micro-dmpm)(micro-H)(Ar)(IrCp*)][OTf] (Ar = Ph (9); Ar = m-Tol (10a) or p-Tol (10b); Ar = 2-Fur (11)) and [(Cp*Ir)(H)(micro-dmpm)(micro-C(5)H(4)N)(H)(IrCp*)][OTf] (12), respectively. Complex also reacts with cyclopentene at 0 degrees C to give [(Cp*Ir)(H)(micro-dmpm)(micro-H)(1-cyclopentenyl)(IrCp*)][OTf] (13). Structures of 3, 8 and 12 have been confirmed by X-ray analysis.


The Complete Genome Sequence of the San Miguel Sea Lion Virus-8 Reveals that It Is Not a Member of the Vesicular Exanthema of Swine Virus/San Miguel Sea Lion Virus Species of the Caliciviridae.
The complete genome sequence of the San Miguel sea lion virus-8 (SMSV-8) was determined in this study. A comparison of this sequence to other calicivirus sequences in GenBank showed that this virus is genetically distinct from the vesicular exanthema of swine virus/San Miguel sea lion virus (VESV/SMSV) strains and belongs to a novel clade within the Vesivirus genus.


Kinematic, muscular, and metabolic responses during exoskeletal-, elliptical-, or therapist-assisted stepping in people with incomplete spinal cord injury.
Robotic-assisted locomotor training has demonstrated some efficacy in individuals with neurological injury and is slowly gaining clinical acceptance. Both exoskeletal devices, which control individual joint movements, and elliptical devices, which control endpoint trajectories, have been utilized with specific patient populations and are available commercially. No studies have directly compared training efficacy or patient performance during stepping between devices. The purpose of this study was to evaluate kinematic, electromyographic (EMG), and metabolic responses during elliptical- and exoskeletal-assisted stepping in individuals with incomplete spinal cord injury (SCI) compared with therapist-assisted stepping. Design A prospective, cross-sectional, repeated-measures design was used. Participants with incomplete SCI (n=11) performed 3 separate bouts of exoskeletal-, elliptical-, or therapist-assisted stepping. Unilateral hip and knee sagittal-plane kinematics, lower-limb EMG recordings, and oxygen consumption were compared across stepping conditions and with control participants (n=10) during treadmill stepping. Exoskeletal stepping kinematics closely approximated normal gait patterns, whereas significantly greater hip and knee flexion postures were observed during elliptical-assisted stepping. Measures of kinematic variability indicated consistent patterns in control participants and during exoskeletal-assisted stepping, whereas therapist- and elliptical-assisted stepping kinematics were more variable. Despite specific differences, EMG patterns generally were similar across stepping conditions in the participants with SCI. In contrast, oxygen consumption was consistently greater during therapist-assisted stepping. Limitations Limitations included a small sample size, lack of ability to evaluate kinetics during stepping, unilateral EMG recordings, and sagittal-plane kinematics. Despite specific differences in kinematics and EMG activity, metabolic activity was similar during stepping in each robotic device. Understanding potential differences and similarities in stepping performance with robotic assistance may be important in delivery of repeated locomotor training using robotic or therapist assistance and for consumers of robotic devices.


Safe medication use based on knowledge of information about contraindications concerning cross allergy and comprehensive clinical intervention.
An investigation of safety issues regarding information on contraindications related to cross allergy was conducted to promote clinical awareness and prevent medical errors in a 2200-bed tertiary care teaching hospital. Prescribing information on contraindications concerning cross allergy was collected from an information system and package inserts. Data mining and descriptive analysis were performed. A risk register was used for project management and risk assessment. A Plan, Do, Check, Act cycle was used as part of continuous quality improvement. Records of drug counseling and medical errors were collected from an online reporting system. A pharmacist-led multidisciplinary team initiated an intervention program on cross allergy in August 2008. Four years of risk management at our hospital achieved successful outcomes, ie, the number of medical errors related to cross allergies decreased by 97% (10 cases monthly before August 2008 versus three cases yearly in 2012) and risk rating decreased significantly [initial risk rating: 25(high-risk) before August 2008 versus final risk rating:6 (medium-risk) in December 2012]. We conclude that comprehensive clinical interventions are very effective through team cooperation. Medication use has potential for safety risks if sufficient attention is not paid to contraindications concerning cross allergy. The potential for cross allergy involving drugs which belong to completely different pharmacological classes is easily overlooked and can be dangerous. Pharmacists can play an important role in reducing the risk of cross allergy as well as recommending therapeutic alternatives.


The fluorinated (10, 0) boron nitride nanotube: a computational nuclear magnetic resonance and nuclear quadrupole resonance study.
Quantum chemical calculations at the level of density functional theory (DFT) were carried out to investigate the influence of fluorination boron and nitrogen nuclear magnetic resonance (NMR) and also nuclear quadrupole resonance (NQR) parameters in the (10, 0) single-wall boron nitride nanotube (SWBNNT). To achieve this aim three models of (10, 0) boron nitride nanotubes (BNNTs), raw and two F-attached (exohedral and endohedral) derivatives were studied. The results of calculations showed that while the boron atom chemically bonded to F atom has the largest chemical shielding isotropy (CSI); it has the smallest quadrupole coupling constant (CQ) value among the other boron nuclei.


Validation of Thiosemicarbazone Compounds as P-Glycoprotein Inhibitors in Human Primary Brain-Blood Barrier and Glioblastoma Stem Cells.
P-glycoprotein (Pgp) is highly expressed on blood-brain barrier (BBB) and glioblastoma (GB) cells, particularly on cancer stem cells (SC). Pgp recognizes a broad spectrum of substrates, limiting the therapeutic efficacy of several chemotherapeutic drugs in eradicating GB SC. Finding effective and safe inhibitors of Pgp that improve drug delivery across the BBB and target GB SC is open to investigation. We previously identified a series of thiosemicarbazone compounds that inhibit Pgp with an EC50 in the nanomolar range, and herein, we investigate the efficacy of three of them in bypassing Pgp-mediated drug efflux in primary human BBB and GB cells. At 10 nM, the compounds were not cytotoxic for the brain microvascular endothelial hCMEC/D3 cell line, but they markedly enhanced the permeability of the Pgp-substrate doxorubicin through the BBB. Thiosemicarbazone derivatives increased doxorubicin uptake in GB, with greater effects in the Pgp-rich SC clones than in the differentiated clones derived from the same tumor. All compounds increased intratumor doxorubicin accumulation and consequent toxicity in GB growing under competent BBB, producing significant killing of GB SC. The compounds crossed the BBB monolayer. The most stable derivative, 10a, had a half-life in serum of 4.2 h. The coadministration of doxorubicin plus 10a significantly reduced the growth of orthotopic GB-SC xenografts, without eliciting toxic side effects. Our work suggests that the thiosemicarbazone compounds are able to transform doxorubicin, a prototype BBB-impermeable drug, into a BBB-permeable drug. Bypassing Pgp-mediated drug efflux in both BBB and GB SC, thiosemicarbazones might increase the success of chemotherapy in targeting GB SC, which represent the most aggressive and difficult components to eradicate.


A life course perspective on retirement, gender, and well-being.
The existing research literature on the links between retirement and physical and psychological health is examined. This synthesis characterizes the complexity of the relationship between retirement and health; points out potential gender differences in the nature, experience, and implications of retirement; and develops a life course model of the pathways through occupational career and retirement leading to health. Such a life course model suggests a research agenda that can produce important insights on the dynamics and consequences of the retirement transition, including the mechanisms and conditions linking withdrawal from employment to changes in health and well-being.


The contribution of motor efficiency to drawing performance of older people with and without signs of cognitive decline.
In clinical practice, different drawing tests are used for the assessment of cognitive efficiency in the geriatric population. However, so far, the contribution of motor skills to drawing performance has not been sufficiently examined in the late adult life span. This study was aimed at disentangling the role played by motor functioning in three well-known drawing tests that in the clinical field are commonly used to detect some signs of cognitive impairment of older individuals. One hundred and forty-nine community dwellers (Mage = 77.4 years, SD = 5.9 years) completed a battery of tests assessing global cognitive efficiency, drawing skills (i.e., Clock Drawing, Visuo-spatial Drawing ACE-R, Copy Figures Tests), handgrip muscular strength (HGS), and functional mobility (assessed through the Timed-Up-and-Go test). Significant relationships were found among those measures. Moreover, handgrip strength and functional mobility explained 12-19% of the variance in each drawing condition. Finally, participants exhibiting poorer HGS performed worse the drawing tasks and were successively recognized as cognitively deteriorated. In conclusion, these findings highlight that motor skills can significantly impact the assessment of cognitive efficiency in late adulthood. Therefore, in clinical practice, the concurrent assessment of basic motor functions (in terms of muscular strength and functional mobility) and cognitive efficiency of the geriatric population at risk for cognitive decline should be encouraged.


Once-daily antiretroviral therapy: Spanish Consensus Statement.
Administration of antiretroviral therapy (ART) once daily is creating extraordinary interest among the members of the scientific community and also among those who receive the therapy. However, in clinical practice, some doubts remain about its use. This document examines the characteristics and possibilities of treatment administered once daily. Consensus of 248 Spanish experts in the field. Once-daily dosing is considered an added value which could favour adherence and, therefore, efficacy, as well as the quality of life of certain patients, however, the objective of adequate adherence in the long term is often difficult to achieve regardless of the treatment used. In theory, any patient can receive once-daily therapy, although some patients could particularly benefit from it, e.g. those with unfavourable social or personal circumstances, including drug users, patients whose treatment must be supervised, patients receiving multiple medications, or those who need rescue therapy after multiple treatment failures. At present, it is possible to design once-daily ART using some of the combinations of drugs considered as first-choice in national and international recommendations for antiretroviral therapy, but the options are still limited. The marketing of new drugs with this characteristic could allow us to increase the number and types of patient who can benefit from once-daily regimens, including those patients who need rescue therapy. Once-daily ART is a good alternative to regimens administered several times each day when a potent combination of active drugs is available.


Arabidopsis KLU homologue GmCYP78A72 regulates seed size in soybean.
Soybean (Glycine max) is one of the most important crops in the world, and its yield is largely determined by grain weight and grain size. However, the genes that regulate soybean seed size have not been identified. CYP78A, which is highly conserved within terrestrial plants, regulates organ development. In Arabidopsis, AtCYP78A5/KLU has been shown to determine seed size. In the present study, soybean CYP78A72 (GmCYP78A72), one of the orthologs of KLU, was over-expressed in both Arabidopsis and soybean to examine its function in plant development. GmCYP78A72 heterologous expression in Arabidopsis resulted in enlarged sepals, petals, seeds and carpel. Over-expression of GmCYP78A72 in soybean resulted in increased pea size, which is an extremely desirable trait for enhancing productivity. Moreover, knock-down of GmCYP78A72 does not reduce grain size. However, silencing of GmCYP78A57, GmCYP78A70 and GmCYP78A72 genes in triplet reduces the seed size significantly indicating functional redundancy of these three GmCYP78A genes. In conclusion, we investigated the role of CYP78A in soybean seed regulation, and our strategy can be effectively used to engineer large seed traits in soybean varieties as well as other crops.


Metagenomic Characterization of Gut Microbiota of Carriers of Extended-Spectrum Beta-Lactamase or Carbapenemase-Producing Enterobacteriaceae Following Treatment with Oral Antibiotics and Fecal Microbiota Transplantation: Results from a Multicenter Randomized Trial.
Background: The R-GNOSIS (Resistance in Gram-Negative Organisms: Studying Intervention Strategies) WP3 study was the first multicenter randomized clinical trial systematically investigating fecal microbiota transplantation (FMT) for intestinal decolonization of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Here, we characterized the temporal dynamics of fecal microbiota changes in a sub-cohort of the R-GNOSIS WP3 participants before and after antibiotics/FMT using whole metagenome shotgun sequencing. Methods: We sequenced fecal DNA obtained from 16 ESBL-E/CPE carriers having received oral colistin/neomycin followed by FMT and their corresponding seven donors. Ten treatment-naïve controls from the same trial were included. Fecal samples were collected at baseline (V0), after antibiotics but before FMT (V2) and three times after FMT (V3, V4 and V5). Results: Antibiotic treatment transiently decreased species richness and diversity and increased the abundance of antibiotic resistance determinants (ARDs). Bifidobacterium species, together with butyrate- and propionate-producing species from Lachnospiraceae and Ruminococcaceae families were significantly enriched in post-FMT microbiota of treated carriers. After FMT, the proportion of Enterobacteriaceae was lower compared to baseline but without statistical significance. Conclusions: Combined antibiotic and FMT treatment resulted in enrichment of species that are likely to limit the gut colonization by ESBL-E/CPE.


Differential plastic changes in synthesis and binding in the mouse somatostatin system after electroconvulsive stimulation.
Electroconvulsive therapy (ECT) is regularly used to treat patients with severe major depression, but the mechanisms underlying the beneficial effects remain uncertain. Electroconvulsive stimulation (ECS) regulates diverse neurotransmitter systems and induces anticonvulsant effects, properties implicated in mediating therapeutic effects of ECT. Somatostatin (SST) is a candidate for mediating these effects because it is upregulated by ECS and exerts seizure-suppressant effects. However, little is known about how ECS might affect the SST receptor system. The present study examined effects of single and repeated ECS on the synthesis of SST receptors (SSTR1-4) and SST, and SST receptor binding ([125I]LTT-SST28) in mouse hippocampal regions and piriform/parietal cortices. A complex pattern of plastic changes was observed. In the dentate gyrus, SST and SSTR1 expression and the number of hilar SST immunoreactive cells were significantly increased at 1 week after repeated ECS while SSTR2 expression was downregulated by single ECS, and SSTR3 mRNA and SST binding were elevated 24 h after repeated ECS. In hippocampal CA1 and parietal/piriform cortices, we found elevated SST mRNA levels 1 week after repeated ECS and elevated SST binding after single ECS and 24 h after repeated ECS. In hippocampal CA3, repeated ECS increased SST expression 1 week after and SST binding 24 h after. In the parietal cortex, SSTR2 mRNA expression was downregulated after single ECS while SSTR4 mRNA expression was upregulated 24 h after repeated ECS. Considering the known anticonvulsant effects of SST, it is likely that these ECS-induced neuroplastic changes in the SST system could participate in modulating neuronal excitability and potentially contribute to therapeutic effects of ECT.


Assessment of Cardiac Autonomic Function in Women With Polycystic Ovary Syndrome Through Ewing's Battery, Heart Rate Variability Analysis, and Composite Autonomic Symptom Score-31 Scale.
Introduction Polycystic ovary syndrome (PCOS) is a frequently occurring endocrine condition prevalent in women of reproductive age characterized by chronic anovulation, hyperandrogenism, insulin resistance, and a low-grade inflammatory state. Patients with PCOS are more vulnerable to developing cardiac and metabolic co-morbidities. Sympathetic overactivity is also reported in PCOS patients. Objective This study aimed to assess cardiac autonomic function in PCOS by Heart Rate Variability Analysis, Ewing's Test, and Composite Autonomic Symptom Scale-31 (COMPASS-31). Methods Thirty female PCOS patients and 30 age-matched control females were enrolled in the study. Both cases and controls were subdivided into sub-groups based on body mass index (BMI) and waist-to-hip ratio (WHR). The cardiac autonomic functions were assessed by the COMPASS-31 questionnaire, Ewing's battery tests, and short-term heart rate variability analysis. Results There was no significant difference in age, BMI, and WHR of both groups. Additionally, cases had a significantly higher low frequency to high frequency (LF/HF) ratio and COMPASS-31 score and also reported more derangement in Ewing's battery test, indicating cardiac autonomic dysfunction in PCOS patients. Conclusion Patients with PCOS are more prone to developing cardiac and metabolic co-morbidities. Early assessment of cardiac autonomic function can prevent future complications with timely interventions. Altered autonomic function in PCOS patients can be due to hyperandrogenism and insulin resistance.


Predicting MCI to AD Conversation Using Integrated sMRI and rs-fMRI: Machine Learning and Graph Theory Approach.
Graph theory and machine learning have been shown to be effective ways of classifying different stages of Alzheimer's disease (AD). Most previous studies have only focused on inter-subject classification with single-mode neuroimaging data. However, whether this classification can truly reflect the changes in the structure and function of the brain region in disease progression remains unverified. In the current study, we aimed to evaluate the classification framework, which combines structural Magnetic Resonance Imaging (sMRI) and resting-state functional Magnetic Resonance Imaging (rs-fMRI) metrics, to distinguish mild cognitive impairment non-converters (MCInc)/AD from MCI converters (MCIc) by using graph theory and machine learning. With the intra-subject (MCInc vs. MCIc) and inter-subject (MCIc vs. AD) design, we employed cortical thickness features, structural brain network features, and sub-frequency (full-band, slow-4, slow-5) functional brain network features for classification. Three feature selection methods [random subset feature selection algorithm (RSFS), minimal redundancy maximal relevance (mRMR), and sparse linear regression feature selection algorithm based on stationary selection (SS-LR)] were used respectively to select discriminative features in the iterative combinations of MRI and network measures. Then support vector machine (SVM) classifier with nested cross-validation was employed for classification. We also compared the performance of multiple classifiers (Random Forest, K-nearest neighbor, Adaboost, SVM) and verified the reliability of our results by upsampling. We found that in the classifications of MCIc vs. MCInc, and MCIc vs. AD, the proposed RSFS algorithm achieved the best accuracies (84.71, 89.80%) than the other algorithms. And the high-sensitivity brain regions found with the two classification groups were inconsistent. Specifically, in MCIc vs. MCInc, the high-sensitivity brain regions associated with both structural and functional features included frontal, temporal, caudate, entorhinal, parahippocampal, and calcarine fissure and surrounding cortex. While in MCIc vs. AD, the high-sensitivity brain regions associated only with functional features included frontal, temporal, thalamus, olfactory, and angular. These results suggest that our proposed method could effectively predict the conversion of MCI to AD, and the inconsistency of specific brain regions provides a novel insight for clinical AD diagnosis.


[Reproduction studies of carboplatin (II)--Intravenous administration to rats during the period of fetal organogenesis].
Carboplatin, an oncostatic drug, was administered intravenously to pregnant Crj: CD (Sprague-Dawley) rats from day 7 through 17 of gestation at dose levels of 1, 2 and 4 mg/kg/day. The summarized results obtained are as follows: 1. Carboplatin 4 mg/kg suppressed the maternal body weight gains from day 13 through 20 of gestation. 2. Uterine weights were reduced in F0 dams at term at carboplatin 4 mg/kg. 3. Carboplatin 4 mg/kg brought the inhibition of fetal growth accompanied by the lowered values in fetal weights, crown-rump distances and tail lengths. Furthermore, the elevated incidences of unossified 5th and 6th sternum , as well as retarded ossification of sacrococcygeal vertebrae were also noted in this dose level. 4. The birth rate was reduced in neonates (F1) at carboplatin 4 mg/kg. 5. Body weight gains in male F1 rats were suppressed at carboplatin 4 mg/kg from 4 to 8 weeks of age. 6. Carboplatin 4 mg/kg decreased the brain weights on an absolute basis in female F1 rats, but failed to affect their postnatal differentiations, early behavioral developments, learning ability, motor activity or emotional development. 7. Reproductive ability in F1 rats of both sexes were not affected by carboplatin. 8. Influences on prenatal development were not apparently observed for F2 fetuses derived from F1 rats whose dams had ever received carboplatin during the organogenetic period. Based on these results, the no-effect dose level of carboplatin under the present experimental condition was estimated to be 2 mg/kg/day against dams and their offspring.


Patient and healthcare provider perspectives on adherence with antihypertensive medications: an exploratory qualitative study in Tanzania.
Poor medication adherence is an extraordinarily common problem worldwide that contributes to inadequate control of many chronic diseases, including Hypertension (HT). Globally, less than 14% of the estimated 1.4 billion patients with HT achieve optimal control. A myriad of barriers, across patient, healthcare provider, and system levels, contributes to poor medication adherence. Few studies have explored the reasons for poor medication adherence in Tanzania and other African countries. A qualitative study applying grounded theory principles was conducted in the catchment area of two semi-urban clinics in Dar es Salaam, Tanzania, to determine the perceived barriers to HT medication adherence. Ten key informant interviews were conducted with healthcare providers who manage HT patients. Patients diagnosed with HT (SBP ≥ 140 and DBP ≥ 90), were randomly selected from patient registers, and nine focus group discussions were conducted with a total 34 patients. Inductive codes were developed separately for the two groups, prior to analyzing key thematic ideas with smaller sub-categories. Affordability of antihypertensive medication and access to care emerged as the most important barriers. Fee subsidies for treatment and medication, along with health insurance, were mentioned as potential solutions to enhance access and adherence. Patient education and quality of physician counseling were mentioned by both providers and patients as major barriers to medication adherence, as most patients were unaware of their HT and often took medications only when symptomatic. Use of local herbal medicines was mentioned as an alternative to medications, as they were inexpensive, available, and culturally acceptable. Patient recommendations for improving adherence included community-based distribution of refills, SMS text reminders, and family support. Reliance on religious leaders over healthcare providers emerged as a potential means to promote adherence in some discussions. Effective management of hypertensive patients for medication adherence will require several context-specific measures. These include policy measures addressing financial access, with medication subsidies for the poor and accessible distribution systems for medication refill; physician measures to improve health provider counseling for patient centric care; and patient-level strategies with reminders for medication adherence in low resource settings.


Anomalies in a waterlike model confined between plates.
Using molecular dynamic simulations we study a waterlike model confined between two fixed hydrophobic plates. The system is tested for density, diffusion, and structural anomalous behavior and compared with the bulk results. Within the range of confining distances we had explored and observed that in the pressure-temperature phase diagram the temperature of maximum density (TMD line) and the temperature of maximum and minimum diffusion occur at lower temperatures when compared with the bulk values. For distances between the two layers below a certain threshold, d ≤ dc, only two layers of particles are formed, for d ≥ dc three or more layers are formed. In the case of three layers the central layer stays liquid while the contact layers crystallize. This result is in agreement with simulations for atomistic models.


Excitonic condensation in a symmetric electron-hole bilayer.
Using diffusion Monte Carlo simulations we have investigated the ground state of a symmetric electron-hole bilayer and determined its phase diagram at T = 0. We find clear evidence of an excitonic condensate, whose stability however is affected by an in-layer electronic correlation. This stabilizes the electron-hole plasma at large values of the density or interlayer distance, and the Wigner crystal at low density and large distance. We have also estimated pair correlation functions and low-order density matrices to give a microscopic characterization of correlations as well as to try and estimate the condensate fraction.


Isolation of mutants of Caulobacter crescentus deficient in ATP-dependent deoxyribonuclease activity.
Caulobacter crescentus mutants sensitive to UV radiation, mitomycin C and methyl methane-sulfonate were isolated and tested for ATP-dependent deoxyribonuclease activity. Two mutants were identified of which one had less than 5 per cent of the wild-type level of the nuclease activity. This mutant in cross with another auxotrophic partner gave highly reproducible two-fold reduction in number of recombinants compared to a control cross. The suggested causes for reduced recombination frequency when one of the partners has residual ATP-dependent deoxyribonuclease activity are discussed.


Cardiovascular and pulmonary responses to breath-hold diving in humans.
Cardiovascular and pulmonary responses to breath-hold diving (breath holding, submersion, and compression) were investigated. In addition, the effects of transitions between dry conditions and head-out immersion during eupnea were studied. Surface breath holds at a large lung volume with relaxed respiratory muscles resulted in a positive esophageal (transthoracic) pressure and a reduced cardiac output. In contrast, the esophageal pressure (relative to ambient pressure) was decreased, and cardiac output was at least partially restored, when lung gas volume was reduced by compression during breath-hold diving. The increased cardiac output that accompanied eupneic transition from dry to immersed conditions was associated with a short-lasting increase of alveolar gas exchange, whereas the decreased cardiac output during immersion-to-dry transition was associated with a long-lasting decrease of alveolar gas exchange, both reflecting changes in the tissue gas stores of the body. Surface breath holds were associated with a decreased O2 uptake from the lung to the blood, and breath-hold dives were associated with a large transient increase of O2 uptake at depth which resulted in a restoration of the time-averaged O2 uptake to the eupneic control level: these changes reflected changes in tissue O2 stores. Compared to surface breath holds, breath-hold dives were associated with larger tissue retention of CO2 during breath holds, and prolonged recovery for CO2 elimination after breath holds. The distribution of pulmonary perfusion, as indicated by expirograms obtained immediately after breath holds, was made more homogeneous by submersion and the distribution was further improved by compression during breath-hold dives. All of these different effects on the gas exchange in breath-hold diving and in eupneic headout immersion can to a large extent be explained by associated changes in cardiac output in combination with redistributions of peripheral blood flow and venous blood volume. Thus, the different components of breath-hold diving have profound cardiovascular and pulmonary effects. Changes in the intrathoracic pressure and in the distribution of venous blood volume induce changes in cardiac output. All of these changes affect the temporal and spatial distributions of pulmonary perfusion and peripheral blood flow. Also, the circulatory changes affect the temporal and spatial distributions of alveolar gas exchange and of tissue gas stores of the body.


[The role of NADPH-oxidase in paracrine and autocrine regulation of platelet functional activity].
NADPH-oxidase (NOX) is a novel transmembrane enzyme that appears to have pivotal role in the control of platelet signal pathways. The NOX activity in platelets is controlled by agonist receptors activation, which, in turn are modulated by NOX. This review focuses on participation of NOX in autocrine and paracrine regulation of platelet activation, aggregation secretion, protein synthesis and cell recruitment processes during thrombus formation. Possible involving of NOX in the cell-to-cell communication and coordination in response to trombogenic stimulus is discussed.


[The influence of the packaging on the storage qualities of the volatile substances].
The objective of the present study was to evaluate the storage qualities of the acetone and ethanol aqueous solutions kept in the polyethylene flasks, polypropylene and glass tubes that were stored under different environmental temperature. It was shown that the acetone aqueous solution better retained its properties when stored in glass vials at room temperature as well as at 0° C and 4° C. The most pronounced decrease of acetone concentrations (from 70 up to 95%) was documented after its storage in the polyethylene flasks. The ethanol concentration fell down by 40% when stored in polyethylene flasks at room temperature.


Effects of confidentiality limitations on the psychotherapeutic process.
This review article examines the impact of confidentiality limitations on the psychotherapeutic process. Findings from analogue studies with nonpatienis indicate that perceived confidentiality limitations will deter people from seeking therapy and will inhibit self-disclosures once they are in treatment. However these findings da not hold up in research with actual therapy patients. A methodological issue is whether the subject pool for clinical studies is primarily persons at risk for only mild to moderate social injury if their communications are repeated to others. In the few studies of persons at risk for serious sociolegal consequences, warnings of mandatory reporting served as a barrier to therapeutic disclosure or entry into treatment.


Abstainers and Drinkers - Two Sides of the Same Coin?
This commentary discusses a recently published literature review focussing on the growing trend of young people abstaining from drinking alcohol. Despite the recent increase in research on the decline in youth drinking, the review only identified 10 papers that explicitly examined abstainers. The inclusion criteria used thus excluded and overlooked the vast literature available on the decline in youth drinking. This commentary discusses the implications of this and raises the issue of how the adolescent abstainer should be viewed in research; is it a distinct social phenomenon with unique determinants or are abstainers merely the flip side of drinkers?


Sweat monitoring beneath garments using passive, wireless resonant sensors interfaced with laser-ablated microfluidics.
Sweat loss can help determine hydration status of individuals working in harsh conditions, which is especially relevant to those who wear thick personal protective equipment (PPE) such as firefighters. A wireless, passive, conformable sweat sensor sticker is described here that can be worn under and interrogated through thick clothing to simultaneously measure sweat loss volume and conductivity. The sticker consists of a laser-ablated, microfluidic channel and a resonant sensor transducer. The resonant sensor is wirelessly read with a handheld vector network analyzer coupled to two, co-planar, interrogation antennas that measure the transmission loss. A sweat proxy is used to fill the channels and it is determined that the sensor can orthogonally determine the sweat conductivity and volume filled in the channel via peak transmission loss magnitude and frequency respectively. A four-person study is then used to determine level of sensor variance caused by local tissue dielectric heterogeneity and sensor-reader orientation.


Clinicopathological Profile and Malignant Transformation in Oral Lichen Planus: A Retrospective Study.
The aim of this study was to analyze the histopathologically diagnosed cases of oral lichen planus (OLP) in terms of age, gender, clinical variant, site, hyperpigmentation, systemic illness, grade of dysplasia, and associated malignant transformation. This study also intended to do a review of reported cases of OLP with malignant transformation. One hundred and forty-three cases of histopathologically diagnosed OLP between 2010 and 2016 were retrospectively reviewed. Demographic and clinicopathological data including malignant transformation were obtained. The data obtained were analyzed using the Statistical Package for the Social Sciences (SPSS) software for Windows version 20.0 (IBM SPSS, SPSS Inc., Chicago, IL, USA). A review of published literature on OLP with malignant transformation was also done from 1988 to 2017 and tabulated. OLP in this study showed a male predilection with most of the patients in the third decade. The buccal mucosa (bilateral presentation) was the most common site (79.72%), and reticular type was the most common clinical type (79.02%) followed by erosive type (20.98%). The majority (92.31%) of cases were diagnosed with OLP without dysplasia. The rest (7.69%) of dysplastic cases were predominantly seen in the buccal mucosa of 58 years and above, female patients manifesting mainly as erosive type. Two patients (1.4%) previously diagnosed clinically and histopathologically as OLP developed oral squamous cell carcinoma. The present investigation revealed the predominance of OLP among middle-aged male population and the prevalence of bilateral involvement of buccal mucosa. Two of our cases showed malignant transformation over an average period of 3.5 years. The outcome of this study emphasizes the role of clinical follow-up of patients with OLP.


Prediction of the COVID-19 spread in African countries and implications for prevention and control: A case study in South Africa, Egypt, Algeria, Nigeria, Senegal and Kenya.
COVID-19 (Corona Virus Disease 2019) is globally spreading and the international cooperation is urgently required in joint prevention and control of the epidemic. Using the Maximum-Hasting (MH) parameter estimation method and the modified Susceptible Exposed Infectious Recovered (SEIR) model, the spread of the epidemic under three intervention scenarios (suppression, mitigation, mildness) is simulated and predicted in South Africa, Egypt, and Algeria, where the epidemic situations are severe. The studies are also conducted in Nigeria, Senegal and Kenya, where the epidemic situations are growing rapidly and the socio-economic are relatively under-developed, resulting in more difficulties in preventing the epidemic. Results indicated that the epidemic can be basically controlled in late April with strict control of scenario one, manifested by the circumstance in the South Africa and Senegal. Under moderate control of scenario two, the number of infected people will increase by 1.43-1.55 times of that in scenario one, the date of the epidemic being controlled will be delayed by about 10 days, and Algeria, Nigeria, and Kenya are in accordance with this situation. In the third scenario of weak control, the epidemic will be controlled by late May, the total number of infected cases will double that in scenario two, and Egypt is in line with this prediction. In the end, a series of epidemic controlling methods are proposed, including patient quarantine, close contact tracing, population movement control, government intervention, city and county epidemic risk level classification, and medical cooperation and the Chinese assistance.


Delusional (paranoid) disorders.
The group of paranoid or delusional disorders, although not nearly as common as the mood and schizophrenic disorders, may be much more frequent than has usually been thought. DSM-IIIR has made a decisive step in recognizably defining at least one group of them. Interestingly, this change partly came about because the advent of an effective treatment helped to define that group more clearly. Nevertheless, DSM-IIIR's classification is too restrictive, and it was wrong to exclude the diagnosis of paraphrenia. Cases fitting this description will have to be consigned to the category of Psychotic Disorder NOS, which will inevitably be a grab-bag of mixed diagnoses. Also, DSM-IIIR does not emphasize the link between the delusional disorders and paranoid schizophrenia, and the somewhat less well defined overlap with affective disorders, both of which give rise to much diagnostic confusion and inappropriate treatment. Precise history taking and mental status examination and, above all, an up-to-date knowledge of their existence are essential to the recognition and appropriate treatment of the delusional disorders.


Preventing Severe Asthma Exacerbations in Children. A Randomized Trial of Mite-Impermeable Bedcovers.
Allergen exposure in sensitized individuals with asthma interacts with viruses to increase the risk of asthma exacerbation. To evaluate the use of house dust mite-impermeable bedding and its impact on severe asthma exacerbations in children. We randomized mite-sensitized children with asthma (ages 3-17 yr) after an emergency hospital attendance with an asthma exacerbation to receive mite-impermeable (active group) or control (placebo group) bed encasings. Over a 12-month intervention period, the occurrence of severe asthma exacerbations was investigated. Of 434 children with asthma who consented, 286 (mean age, 7.7 yr; male sex, 65.8%) were mite sensitized, and 284 were randomized (146 to the active group and 138 to the placebo group). At 12 months, significantly fewer children in the active group than in the placebo group had attended the hospital with an exacerbation (36 [29.3%] of 123 vs. 49 [41.5%] of 118; P = 0.047). In the multivariable analysis, the risk of emergency hospital attendance was 45% lower in the active group (hazard ratio, 0.55; 95% confidence interval [CI], 0.36-0.85; P = 0.006) than in the placebo group. The annual rate of emergency hospital attendance with exacerbations was 27% lower in the active group than in the placebo group, but this did not reach significance (estimated marginal mean [95% CI], active, 0.38 [0.26-0.56] vs. placebo, 0.52 [0.35-0.76]; P = 0.18). No difference between the groups in the risk of prednisolone use for exacerbation was found (hazard ratio, 0.82; 95% CI, 0.58-1.17; P = 0.28). Mite-impermeable encasings are effective in reducing the number of mite-sensitized children with asthma attending the hospital with asthma exacerbations but not the number requiring oral prednisolone. This simple measure may reduce the health care burden of asthma exacerbations in children. Clinical trial registered with www.isrctn.com (ISRCTN 69543196).


Treatment of Whole Blood With Riboflavin and UV Light: Impact on Malaria Parasite Viability and Whole Blood Storage.
Sub-Saharan African countries utilize whole blood (WB) to treat severe anemia secondary to severe blood loss or malaria on an emergency basis. In many areas with high prevalence of transfusion-transmissible agents, blood safety measures are insufficient. Pathogen reduction technology applied to WB might considerably improve blood safety. Whole blood from 40 different donors were treated with riboflavin and UV light (pathogen reduction technology) in order to inactivate malaria parasite replication. The extent of parasite inactivation was determined using quantitative polymerase chain reaction methods and was correlated to studies evaluating the replication of malaria parasites in culture. Products were also stored for 21 days at +4°C and monitored for cell quality throughout storage. Plasmodium amplicon was present in 21 samples (>100 copies/mL), doubtful in four (10-100 genome equivalents [gEq]/mL), and negative in 15 U. The majority of asymptomatic parasitemic donors carried low parasite levels, with only six donors above 5,000 copies/mL (15%). After treatment with riboflavin and UV light, these six samples demonstrated a 0.5 to 1.2 log reduction in quantitative polymerase chain reaction amplification. This correlated to equal to or greater than 6.4 log reductions in infectivity. In treated WB units, cell quality parameters remained stable; however, plasma hemoglobin increased to 0.15 g/dL. All markers behaved similarly to published data for stored, untreated WB. Pathogen reduction technology treatment can inactivate malaria parasites in WB while maintaining adequate blood quality during posttreatment cold storage for 21 days.


[Biologics and infections in rheumatic diseases].
The successful use of a chimeric monoclonal antibody targeting TNF alpha (infliximab) to treat rheumatoid arthritis (RA) two decades ago, ushered in a new era of therapy with the so-called biopharmaceuticals, commonly referred to as "biologics". Their use rapidly spread to other indications such as Crohns disease, and their commercial success led to rapid extension of the concept using other forms of monoclonal antibodies and receptor recombinant molecules with specificities to other cytokines, growth factors and immune cell subsets. Soon after their introduction into the clinic, the first indications of increased risk of infection appeared in the form of reactivation of tuberculosis, mostly in the first months after treatment and often extrapulmonary. It was later recognised that an overall increased risk of bacterial infection under TNF-alpha blockade exists with a relative increased risk of around 2 - 3, and that classical symptoms of infection may be masked by cytokine blockade. Biologics against other cytokines such as IL-6, co-stimulatory molecules, and anti B cells seem less associated with infection, though this may be in part related to more careful patient monitoring. Increasing experience led to guidelines concerning pre-treatment screening, vaccination and perioperative advice, as well as the use of biologics in the presence of chronic viral infection, e. g. HIV, hepatitis B and C. Biologics have changed the outcome for patients with RA and other autoimmune diseases, but this success should not lead to complacency when assessing potential infectious complications of treatment in individual patients.


PROCLEIX West Nile virus assay based on transcription-mediated amplification.
The PROCLEIX West Nile virus (WNV) assay is based on transcription-mediated amplification and is the most sensitive nucleic acid test commercially available today for blood screening. Since 2003, in the USA, the assay has been used for year-round screening of blood donations in minipools of 16 and in an individual-donation testing format, when appropriate triggering guidelines for such switch become effective. The test can be run on the semiautomated PROCLEIX modular platform or the fully-automated PROCLEIX TIGRIS System. This assay and the corresponding platforms have been developed and are manufactured by San Diego-based Gen-Probe, Inc., while they are marketed and distributed by Chiron, a Novartis business. This review covers some of the epidemiological and virological aspects of WNV, as well as clinical questions and technological assessment of the transcription-mediated amplification and alternative technologies used in WNV blood screening.


Identification of key genes for carcinogenic pathways associated with colorectal adenoma-to-carcinoma progression.
Colorectal adenomas form a biologically and clinically distinct intermediate stage in development of colorectal cancer (CRC) from normal colon epithelium. Only 5% of adenomas progress into adenocarcinomas, indicating that malignant transformation requires other biological alterations than those involved in adenoma formation. The present study aimed to explore which cancer-related biological processes are affected during colorectal adenoma-to-carcinoma progression and to identify key genes within these pathways that can serve as tumor markers for malignant transformation. The activity of 12 cancer-related biological processes was compared between 37 colorectal adenomas and 31 adenocarcinomas, using the pathway analysis tool Gene Set Enrichment Analysis. Expression of six gene sets was significantly increased in CRCs compared to adenomas, representing chromosomal instability, proliferation, differentiation, invasion, stroma activation, and angiogenesis. In addition, 18 key genes were identified for these processes based on their significantly increased expression levels. For AURKA and PDGFRB, increased mRNA expression levels were verified at the protein level by immunohistochemical analysis of a series of adenomas and CRCs. This study revealed cancer-related biological processes whose activities are increased during malignant transformation and identified key genes which may be used as tumor markers to improve molecular characterization of colorectal tumors.


The modified Ross Reversal operation: a new approach for preserving the autograft wall.
The Ross Reversal operation is a breakthrough strategy first reported by Flynn et al. in 2007. In a reoperation for pulmonary autograft dysfunction after the Ross operation, an excised autograft can be preserved by reusing it in a native pulmonary position. We report a case wherein we used a new approach to excise the autograft valve with less invasion. The patient underwent a modified Ross Reversal operation concomitant with aortic root replacement and recovered without any complications. Our new approach enables a safer operation with improved valve function.