Prognostic value of intratumoral neutrophils in advanced gastric carcinoma in a high-risk area in northern Italy.
Several lines of evidence indicate that neutrophils act nonspecifically against tumor cells. The correlation between tumor-infiltrating neutrophils (TINs) and clinicopathological features remains unclear and deserves to be investigated. To analyze the prognostic influence of TINs in gastric carcinoma, the authors selected 273 patients with advanced gastric carcinoma who underwent gastrectomy at Cremona Hospital (Lombardia, Italy) between 1990 and 1995 and followed them for a period of 5 years. The number of TINs was assessed in a semiquantitative manner using the mean value of 20 nonoverlapping high-power fields (magnification, 400x; 0.08 mm(2)). The patients were divided into two groups: patients with a moderate or extensive amount of TINs (n = 76; >10 TINs per 20 high-power fields) and patients with a minor amount of TINs (n = 197; <or=10 TINs per 20 high-power fields). The Kaplan-Meier method and Greenwood formula were used to estimate the crude survival rates in the two groups. Multivariate analyses based on the Cox proportional hazard regression model were performed to assess the effect of the prognostic factors on survival. Among the potential prognostic factors analyzed by univariate analysis, sex, age, location of neoplasia, pTNM stage, TINs, and surgical curability were significantly associated with higher survival rate. The study of the possible interaction effects of the clinical-pathological factors with TINs reveals that female patients with a moderate or extensive amount of TINs have about a 39% reduction in their risk of mortality, whereas male patients do not seem to be affected by the level of TINs. These results suggest that women appear to have a better prognosis than men in advanced gastric carcinoma. Gender differences in some host defense mechanisms and particularly in neutrophil function may be responsible for this event. Confirmation of these findings would give valuable insights about host reaction to gastric cancer growth and, ultimately, possibly would have implications regarding the identification of low-risk patients who could be spared adjuvant therapy.


Exiles: Medieval Experiences of Isolation.
For most people alive today, the COVID-19 pandemic was our first experience of widespread isolation. However, among medieval cultures, with low population density and limited urbanisation, isolation, especially through exile, was common as a political expedient or even, as now, as a method of controlling the spread of illness. This is reflected across myriad aspects of medieval culture, from pilgrim badges to legal codes. Stories and tropes of isolation are common in medieval literature. From the immrama which often include depictions of the isolation of voyages, to images of homesickness in romances or Crusade narratives to descriptions of isolation in exile in Old English elegies and Old Norse sagas. In many instances, the literature reveals a greater fear of loneliness than death, so much so that isolation was used both as a form of punishment considered as severe as mutilation in some parts of medieval Europe, and as an important religious practice, since many people willingly distanced themselves from society in pursuit of salvation through hardship. This introductory essay introduces a dossier on medieval experiences of isolation.


Yr32 for resistance to stripe (yellow) rust present in the wheat cultivar Carstens V.
Stripe or yellow rust of wheat, caused by Puccinia striiformis f. sp. tritici, is an important disease in many wheat-growing regions of the world. A number of major genes providing resistance to stripe rust have been used in breeding, including one gene that is present in the differential tester Carstens V. The objective of this study was to locate and map a stripe rust resistance gene transferred from Carstens V to Avocet S and to use molecular tools to locate a number of genes segregating in the cross Savannah/Senat. One of the genes present in Senat was predicted to be a gene that is present in Carstens V. For this latter purpose, stripe rust response data from both seedling and field tests on a doubled haploid population consisting of 77 lines were compared to an available molecular map for the same lines using a non-parametric quantitative trait loci (QTL) analysis. Results obtained in Denmark suggested that a strong component of resistance with the specificity of Carstens V was located in chromosome arm 2AL, and this was consistent with chromosome location work undertaken in Australia. Since this gene segregated independently of Yr1, the only other stripe rust resistance gene known to be located in this chromosome arm, it was designated Yr32. Further QTLs originating from Senat were located in chromosomes 1BL, 4D, and 7DS and from Savannah on 5B, but it was not possible to characterize them as unique resistance genes in any definitive way. Yr32 was detected in several wheats, including the North American differential tester Tres.


Interactions between closely related bacterial strains are revealed by deep transcriptome sequencing.
Comparative genomics, metagenomics, and single-cell technologies have shown that populations of microbial species encompass assemblages of closely related strains. This raises the question of whether individual bacterial lineages respond to the presence of their close relatives by modifying their gene expression or, instead, whether assemblages simply act as the arithmetic addition of their individual components. Here, we took advantage of transcriptome sequencing to address this question. For this, we analyzed the transcriptomes of two closely related strains of the extremely halophilic bacterium Salinibacter ruber grown axenically and in coculture. These organisms dominate bacterial assemblages in hypersaline environments worldwide. The strains used here cooccurred in the natural environment and are 100% identical in their 16S rRNA genes, and each strain harbors an accessory genome representing 10% of its complete genome. Overall, transcriptomic patterns from pure cultures were very similar for both strains. Expression was detected along practically the whole genome albeit with some genes at low levels. A subset of genes was very highly expressed in both strains, including genes coding for the light-driven proton pump xanthorhodopsin, genes involved in the stress response, and genes coding for transcriptional regulators. Expression differences between pure cultures affected mainly genes involved in environmental sensing. When the strains were grown in coculture, there was a modest but significant change in their individual transcription patterns compared to those in pure culture. Each strain sensed the presence of the other and responded in a specific manner, which points to fine intraspecific transcriptomic modulation.


Toluidine blue staining reveals changes in chromatin stabilization of mouse spermatozoa during epididymal maturation and penetration of ova.
Sperm samples, recovered from various regions of the reproductive tract of male and female mice, were air dried, fixed for 2 min in acetic alcohol and stained with toluidine blue. Testicular sperm heads were deeply stained, while in the samples from the successive regions of caput epididymidis the proportion of stained heads gradually decreased and many of them were stained in their distal part only. Spermatozoa from the corpus and cauda epididymidis, vas deferens, uterus, oviduct and from the perivitelline space were colourless (except for one type of misshapen head). Sperm heads that had penetrated the vitellus became stained distally. Vas deferens sperm heads were fully stained after treatment with dithiothreitol for 30 min. We suggest that the inability to stain with toluidine blue is characteristic of sperm chromatin stabilized by disulphide bonds.


Diabetes and Alzheimer's Disease: Can Tea Phytochemicals Play a Role in Prevention?
Dementia and diabetes mellitus are prevalent disorders in the elderly population. While recognized as two distinct diseases, diabetes has more recently recognized as a significant contributor to risk for developing dementia, and some studies make reference to type 3 diabetes, a condition resulting from insulin resistance in the brain. Alzheimer's disease, the most common form of dementia, and diabetes, interestingly, share underlying pathological processes, commonality in risk factors, and, importantly, pathways for intervention. Tea has been suggested to possess potent antioxidant properties. It is rich in phytochemicals including, flavonoids, tannins, caffeine, polyphenols, boheic acid, theophylline, theobromine, anthocyanins, gallic acid, and finally epigallocatechin-3-gallate, which is considered to be the most potent active ingredient. Flavonoid phytochemicals, known as catechins, within tea offer potential benefits for reducing the risk of diabetes and Alzheimer's disease by targeting common risk factors, including obesity, hyperlipidemia, hypertension, cardiovascular disease, and stroke. Studies also show that catechins may prevent the formation of amyloid-β plaques and enhance cognitive functions, and thus may be useful in treating patients who have Alzheimer's disease or dementia. Furthermore, other phytochemicals found within tea offer important antioxidant properties along with innate properties capable of modulating intracellular neuronal signal transduction pathways and mitochondrial function.


Screening of potential inhibitors targeting the main protease structure of SARS-CoV-2 via molecular docking.
The novel coronavirus disease (COVID-19) caused by SARS-CoV-2 virus spreads rapidly to become a global pandemic. Researchers have been working to develop specific drugs to treat COVID-19. The main protease (Mpro) of SARS-CoV-2 virus plays a pivotal role in mediating viral replication and transcription, which makes it a potential therapeutic drug target against COVID-19. In this study, a virtual drug screening method based on the Mpro structure (Protein Data Bank ID: 6LU7) was proposed, and 8,820 compounds collected from the DrugBank database were used for molecular docking and virtual screening. A data set containing 1,545 drug molecules, derived from compounds with a low binding free energy score in the docking experiment, was established. N-1H-Indazol-5-yl-2-(6-methylpyridin-2-yl)quinazolin-4-amine, ergotamine, antrafenine, dihydroergotamine, and phthalocyanine outperformed the other compounds in binding conformation and binding free energy over the N3 inhibitor in the crystal structure. The bioactivity and ADMET properties of these five compounds were further investigated. These experimental results for five compounds suggested that they were potential therapeutics to be developed for clinical trials. To further verify the results of molecular docking, we also carried out molecular dynamics (MD) simulations on the complexes formed by the five compounds and Mpro. The five complexes showed stable affinity in terms of root mean square distance (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and hydrogen bond. It was further confirmed that the five compounds had potential inhibitory effects on SARS-CoV-2 Mpro.


Leptin corrects host defense defects after acute starvation in murine pneumococcal pneumonia.
Leptin is an adipocyte-derived hormone that declines dramatically during fasting and plays a pivotal role in the neuroendocrine response to starvation. Previously, we employed leptin-deficient (ob/ob) mice to identify an important role for leptin in the host defense against Klebsiella pneumonia. To assess the effects of fasting on the innate immune response against pneumococcal pneumonia and to determine the effects of maintaining circulating leptin levels on host defense in fasted mice. C57BL/6 mice were either fed ad libitum or fasted for 48 h and given an intraperitoneal injection of saline or recombinant leptin (1 microg/g of body weight) twice daily for 48 h before bacterial challenge. Mice were challenged with 10(5) cfu of Streptococcus pneumoniae via the intranasal route. Lung homogenate S. pneumoniae burden was nearly 20-fold greater in the fasted as compared with fed mice. The impairment in bacterial clearance observed in fasted animals was associated with reduced bronchoalveolar lavage neutrophil counts and interleukin-6 and macrophage inflammatory protein-2 levels. Alveolar macrophages from fasted animals also exhibited defective phagocytosis and killing of S. pneumoniae and reduced calcium-ionophore-stimulated leukotriene B(4) synthesis in vitro. In contrast, the provision of exogenous leptin to fasted animals restored bacterial clearance, bronchoalveolar lavage levels of neutrophils and cytokines, alveolar macrophage bacterial killing, and leukotriene B(4) synthesis. These results suggest that reduced leptin levels substantially contribute to the suppression of pulmonary antibacterial host defense during starvation and that administration of this adipokine may be of therapeutic benefit clinically.


Clinical Data Element Ontology for Unified Indexing and Retrieval of Data Elements across Multiple Metadata Registries.
Classification of data elements (DEs), which is used in clinical documents is challenging, even in across ISO/IEC 11179 compliant clinical metadata registries (MDRs) due to no existence of reliable standard for identifying DEs. We suggest the Clinical Data Element Ontology (CDEO) for unified indexing and retrieval of DEs across MDRs. The CDEO was developed through harmonization of existing clinical document models and empirical analysis of MDRs. For specific classification as using data element concept (DEC), The Simple Knowledge Organization System was chosen to represent and organize the DECs. Six basic requirements also were set that the CDEO must meet, including indexing target to be a DEC, organizing DECs using their semantic relationships. For evaluation of the CDEO, three indexers mapped 400 DECs to more than 1 CDEO term in order to determine whether the CDEO produces a consistent index to a given DEC. The level of agreement among the indexers was determined by calculating the intraclass correlation coefficient (ICC). We developed CDEO with 578 concepts. Through two application use-case scenarios, usability of the CDEO is evaluated and it fully met all of the considered requirements. The ICC among the three indexers was estimated to be 0.59 (95% confidence interval, 0.52-0.66). The CDEO organizes DECs originating from different MDRs into a single unified conceptual structure. It enables highly selective search and retrieval of relevant DEs from multiple MDRs for clinical documentation and clinical research data aggregation.


Effect of surgeon experience and bony pelvic dimensions on surgical performance and patient outcomes in robot-assisted radical prostatectomy.
To evaluate the effects of surgeon experience, body habitus, and bony pelvic dimensions on surgeon performance and patient outcomes after robot-assisted radical prostatectomy (RARP). The pelvic dimensions of 78 RARP patients were measured on preoperative magnetic resonance imaging and computed tomography by three radiologists. Surgeon automated performance metrics (APMs [instrument motion tracking and system events data, i.e., camera movement, third-arm swap, energy use]) were obtained by a systems data recorder (Intuitive Surgical, Sunnyvale, CA, USA) during RARP. Two analyses were performed: Analysis 1, examined effects of patient characteristics, pelvic dimensions and prior surgeon RARP caseload on APMs using linear regression; Analysis 2, the effects of patient body habitus, bony pelvic measurement, and surgeon experience on short- and long-term outcomes were analysed by multivariable regression. Analysis 1 showed that while surgeon experience affected the greatest number of APMs (P < 0.044), the patient's body mass index, bony pelvic dimensions, and prostate size also affected APMs during each surgical step (P < 0.043, P < 0.046, P < 0.034, respectively). Analysis 2 showed that RARP duration was significantly affected by pelvic depth (β = 13.7, P = 0.039) and prostate volume (β = 0.5, P = 0.024). A wider and shallower pelvis was less likely to result in a positive margin (odds ratio 0.25, 95% confidence interval [CI] 0.09-0.72). On multivariate analysis, urinary continence recovery was associated with surgeon's prior RARP experience (hazard ratio [HR] 2.38, 95% CI 1.18-4.81; P = 0.015), but not on pelvic dimensions (HR 1.44, 95% CI 0.95-2.17). Limited surgical workspace, due to a narrower and deeper pelvis, does affect surgeon performance and patient outcomes, most notably in longer surgery time and an increased positive margin rate.


Iron, ferritin, hepatitis B surface and core antigens in the livers of Chinese patients with hepatocellular carcinoma.
Surgically resected specimens, consisting of tumor and adjacent non-neoplastic liver tissue, were obtained from 40 patients with primary liver cancer at Zhong Shan Hospital, Shanghai Medical University, the People's Republic of China, between March 1983 and July 1984. All were hepatocellular carcinomas (HCC), one being admixed with cholangiocarcinoma. The relationship of hepatitis B virus (HBV) markers with iron and ferritin was evaluated in liver tissues from patients with primary liver cancers. The serum HBsAg (Hepatitis B surface antigen) positive rate was 80.0% (32/40). Cirrhosis was observed in 97.5% (39/40). HBsAg was identified in 82.5% (33/40) of uninvolved liver, and 35.0% (14/40) of HCC tissues (P less than 0.001). HBcAg (hepatitis B core antigen) was detected in 25.0% (10/40) of liver, and 7.5% (3/40) of HCC tissues (P less than 0.05). Stainable iron was found in 65.0% (26/40) of unaffected livers, and 10.0% (4/40) of HCC tissues (P less than 0.001). Ferritin was demonstrated in 75% (30/40) of non-neoplastic liver, and 40% (16/40) of HCC tissues (P less than 0.001). Twenty-two of 33 HCC patients (66.7%) with HBsAg positive cells in their livers also showed stainable iron. Of 16 patients positive for ferritin in HCC cells, iron was found in only two. Iron was found in nine of ten patients with HBcAg in non-neoplastic hepatocytes (P = 0.056); a finding compatible with the hypothesis that iron accumulates in cells replicating HBV. The other results indicate that: immunohistologic ferritin in HCC is not due to increased stainable iron; tumor cells may produce ferritin; polyclonal antibodies to human liver ferritin react better with non-neoplastic hepatocytes than with HCC cells; the high prevalence of HBsAg and cirrhosis in HCC suggests that HBV plays a major etiologic role in hepatocarcinogenesis in China; and one case of HCC is attributed to Schistosoma japonicum infestation via cirrhosis.


Evaluating the freezing impact on the proximate composition of immature cowpea (Vigna unguiculata L.) pods: classical versus spectroscopic approaches.
Freezing represents a common conservation practice regarding vegetal foodstuffs. Since compositional features need to be monitored during storage, the development of rapid monitoring tools suitable for assessing nutritional characteristics arises as a pertinent issue. In this study, cowpea (Vigna unguiculata L.) pods, both fresh and after 6 and 9 months of freezing at -18 °C, were evaluated by high-performance liquid chromatography for their content of protein as well as of essential and nonessential amino acids, while their Fourier transform infrared spectra in the mid infrared (MIR) and near infrared (NIR) ranges were concomitantly registered to assess the feasibility of this approach for the traceability of these frozen matrices. For the NIR interval, the application of the 1st derivative to the spectral data retrieved the best results, while for lower concentrations the application of the Savitzky-Golay algorithm was indispensable to achieve quantification models for the amino acids. MIR is also suitable for this purpose, though being unable to quantify amino acids with concentrations below 0.07 mmol g-1 dry weight, irrespective of the data treatment used. The spectroscopic approach constitutes a methodology suitable for monitoring the impact of freezing on the nutritional properties of cowpea pods, allowing accurate quantification of the protein and amino acid contents, while NIR displayed better performance. © 2017 Society of Chemical Industry.


Quantitative evaluation by measurement and modeling of the variations in dose distributions deposited in mobile targets.
The objective of this study is to quantitatively evaluate variations of dose distributions deposited in mobile target by measurement and modeling. The effects of variation in dose distribution induced by motion on tumor dose coverage and sparing of normal tissues were investigated quantitatively. The dose distributions with motion artifacts were modeled considering different motion patterns that include (a) motion with constant speed and (b) sinusoidal motion. The model predictions of the dose distributions with motion artifacts were verified with measurement where the dose distributions from various plans that included three-dimensional conformal and intensity-modulated fields were measured with a multiple-diode-array detector (MapCheck2), which was mounted on a mobile platform that moves with adjustable motion parameters. For each plan, the dose distributions were then measured with MapCHECK2 using different motion amplitudes from 0-25 mm. In addition, mathematical modeling was developed to predict the variations in the dose distributions and their dependence on the motion parameters that included amplitude, frequency and phase for sinusoidal motions. The dose distributions varied with motion and depended on the motion pattern particularly the sinusoidal motion, which spread out along the direction of motion. Study results showed that in the dose region between isocenter and the 50% isodose line, the dose profile decreased with increase of the motion amplitude. As the range of motion became larger than the field length along the direction of motion, the dose profiles changes overall including the central axis dose and 50% isodose line. If the total dose was delivered over a time much longer than the periodic time of motion, variations in motion frequency and phase do not affect the dose profiles. As a result, the motion dose modeling developed in this study provided quantitative characterization of variation in the dose distributions induced by motion, which can be employed in radiation therapy to quantitatively determine the margins needed for treatment planning considering dose spillage to normal tissue.


The potential role of fecal microbiota transplantation in the treatment of inflammatory Bowel disease.
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of an unknown etiology. Its pathogenesis involves an interplay of infectious, genetic, environmental, and immunological factors. The current therapeutic options have various limitations in terms of cost, side effect profile, and the development of drug resistance and dependence. Therefore, there is a need to develop future therapeutic options which are safe and effective to control the inflammatory process. This review focuses in a method for the administration of fecal matters (which contains a mixture of various commensals) from a healthy donor to the inflamed colon called fecal microbiota transplantation (FMT) aiming to correct the underlying dysbiosis in the gut as one of the major driving force for the inflammatory process. IBD patients have reduced number of protective (e.g., clostridia and bacteroids) and increased number of pathogenic (e.g., adhesive invasive E. coli and mycobacterium avium paratuberculosis) commensals, and this method is aimed to shift these changes in the gut. Recent studies from animal models and clinical trials suggest promising effects of this method in treating patients with IBD, but more studies are urgently needed to confirm its efficacy and safety, since the etiology of this chronic inflammatory disease is not fully understood and caution should be taken when transplanting fecal matters between individuals which might transfer other infectious organisms and diseases.


[Effect of Ginkgo biloba extract on memory deficits in radial maze performance induced by some drugs in rats].
Ginkgo biloba extract is widely used as a herbal medicine or dietary supplement in Europe, since Ginkgo biloba extract is effective in facilitation of learning and recollection of memories. However, little is known about the mechanism of the action of Ginkgo biloba extract on learning and memory enhancements. On the other hand, it is well known that cholinergic, histaminergic and glutamatergic systems play a crucial role in learning and memory in animals. Therefore, in order to elucidate the mechanism of Ginkgo biloba extract on memory, we studied and clarified the effect of Ginkgo biloba extract on spatial memory deficits induced by scopolamine, diphenhydramine or MK-801 using eight-arm radial maze performance. It was found that Ginkgo biloba extract improved the spatial memory deficits induced by scopolamine. Ginkgo biloba extract also caused repair to spatial memory deficits induced by diphenhydramine. On the other hand, no significant effect was observed with MK-801-induced spatial memory deficits. These findings suggest that the effect of Ginkgo biloba extract is mediated not only by the cholinergic system but also by the histaminergic system to induce learning and memory enhancements.


Exclusion of fetal ventriculomegaly with a single measurement: the width of the lateral ventricular atrium.
The ventricular atria in 100 healthy fetuses with gestational ages ranging from 14 to 38 menstrual weeks were evaluated and compared with those of 38 fetuses in whom ventriculomegaly had been diagnosed in utero. Axial sonograms of the brain through the atrium of the lateral ventricle demonstrated that the normal atrial diameter remained relatively constant throughout the gestational age range observed. The atrium had a mean diameter of 7.6 +/- 0.6 mm (standard deviation [SD]). Measurement of this structure can be quickly performed, is reproducible with low intra- and interobserver variation, and permits ventriculomegaly to be excluded. Atrial diameters exceeding 10 mm (above 4 SDs) suggest ventriculomegaly, with a low false-positive rate.


Efficient and selective capture of Au(III) from PCBs by pentaethylenehexamine-modified chloromethylated polystyrene beads.
Recycling of gold promotes solving the problems of resource waste and environmental pollution. In this work, pentaethylenehexamine (PEHA)-modified chloromethylated polystyrene beads (PEHA-CMPS) was synthesized for the recovery of Au(III) from actual printed circuits boards (PCBs) leaching solution. PEHA-CMPS exhibited excellent adsorption efficiency at a wide pH range. It was discovered that the pseudo-second-order and Langmuir model provided a superior match for the Au(III) adsorption process. The maximum adsorption capacity for Au(III) was 1186 mg/g. Furthermore, PEHA-CMPS was able to selectively capture trace Au(III) with recovery efficiencies of above 80% from the actual PCBs leaching solution. In addition, the column separation approach was utilized to better assess the practical applications for PEHA-CMPS, proving that the prepared adsorbent exhibited great prospects in industrial applications. The adsorption efficiency still maintained 95% after five adsorption-desorption cycles. The FTIR, XRD, and XPS analyses demonstrated that Au(III) uptake on PEHA-CMPS was a collaborative process involving electrostatic interaction, chelation, and oxidation-reduction. The PEHA-CMPS provided a promising strategy in Au(III) recovery and environmental remediation.


Pol3 is involved in nonhomologous end-joining in Saccharomyces cerevisiae.
Nonhomologous end joining connects DNA ends in the absence of extended sequence homology and requires removal of mismatched DNA ends and gap-filling synthesis prior to a religation step. Pol4 within the Pol X family is the only polymerase known to be involved in end processing during nonhomologous end joining in yeast. The Saccharomyces cerevisiae POL3/CDC2 gene encodes polymerase delta that is involved in DNA replication and other DNA repair processes. Here, we show that POL3 is involved in nonhomologous end joining using a plasmid-based end-joining assay in yeast, in which the pol3-t mutation caused a 1.9- to 3.2-fold decrease in the end-joining efficiency of partially compatible 5' or 3' ends, or incompatible ends, similar to the pol4 mutant. The pol3-t pol4 double mutation showed a synergistic decrease in the efficiency of NHEJ with partially compatible 5' ends or incompatible ends. Sequence analysis of the rejoined junctions recovered from the wild-type cells and mutants indicated that POL3 is required for gap filling at 3' overhangs, but not 5' overhangs during POL4-independent nonhomologous end joining. We also show that either Pol3 or Pol4 is required for simple religation of compatible or blunt ends. These results suggest that Pol3 has a generalized function in end joining in addition to its role in gap filling at 3' overhangs to enhance the overall efficiency of nonhomologous end joining. Moreover, the decreased end-joining efficiency seen in the pol3-t mutant was not due to S-phase arrest associated with the mutant. Taken together, our genetic evidence supports a novel role of Pol3 in nonhomologous end joining that facilitates gap filling at 3' overhangs in the absence of Pol4 to maintain genomic integrity.


Managing fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), with Bt maize and insecticides in southern Brazil.
Maize plants expressing insecticidal proteins of Bacillus thuringiensis are valuable options for managing fall armyworm (FAW), Spodoptera frugiperda, in Brazil. However, control failures were reported, and therefore insecticides have been used to control this species. Based on these, we evaluated the use of Bt maize and its integration with insecticides against FAW in southern Brazil. Early-planted Agrisure TL, Herculex, Optimum Intrasect and non-Bt maize plants were severely damaged by FAW and required up to three insecticidal sprays. In contrast, YieldGard VT Pro, YieldGard VT Pro 3, PowerCore, Agrisure Viptera and Agrisure Viptera 3 showed little damage and did not require insecticides. Late-planted Bt maize plants showed significant damage by FAW and required up to four sprays, with the exceptions of Agrisure Viptera and Agrisure Viptera 3. Exalt (first and second sprays); Lannate + Premio (first spray) and Avatar (second spray); and Karate + Match (first spray) and Ampligo (second spray) were the most effective insecticides against FAW larvae in Bt and non-Bt maize. Maize plants expressing Cry proteins exhibited FAW control failures in southern Brazil, necessitating insecticidal sprays. In contrast, Bt maize containing the Vip3Aa20 protein remained effective against FAW. However, regardless of the insecticide used against FAW surviving on Bt maize, grain yields were similar. © 2017 Society of Chemical Industry.


Fluid replacement strategy during a 27-Km trail run in hot and humid conditions.
We evaluated the effects of the fluid replacement strategy on core temperature, heart rate and urine osmolality during a 27-km trail run in tropical climate. 20 well-trained runners completed a 27-km trail race in tropical conditions. They were acclimatized to these conditions. Heart rate was monitored every 5 s, while core temperature and perceived thermal and comfort sensations were recorded before, at the 11(th) km, and just after the end of the race. Water intake, urine osmolality and body mass were measured before and after the race. Core temperature and the scores of perceived thermal and comfort sensations were significantly higher at the 11(th) km and at the end of the race compared to before the race, but not at the 11(th) km compared to the end of the race [corrected]. No participant exhibited dehydration as assessed by urine osmolality. The less the trail runners weighed, the greater the heat retention was. The less hot they felt at the end of the race, the more they lost water, and the better the performance was. The fastest runners were able to tolerate a greater variation in core temperature between the beginning and the end of the trail race with lower water intake.


Visual snow syndrome and its relationship with migraine.
Visual snow syndrome (VSS) is a central nervous system disorder that consists of the constant perception of small black and white dots throughout the entire visual field. VSS can present from infancy to old age, with greater prevalence in the young population, and shows no difference between sexes. The diagnostic criteria include the presence of visual snow and such other visual phenomena as palinopsia, photophobia, nyctalopia, and other persistent visual phenomena. The pathophysiology of VSS is unknown, but hyperexcitability of the visual cortex and a dysfunction in higher-order visual processing are postulated as potential mechanisms. The prevalence of migraine among patients with VSS is high, compared to the general population, and symptoms are more severe in patients presenting both conditions. No effective treatment is available, but the drug with the best results is lamotrigine, which is recommended only in selected cases with severe functional limitation. VSS is a little-known and underdiagnosed entity, but the increasing number of studies in recent years has made it possible to establish diagnostic criteria and begin studying its pathophysiology. This entity is closely related to migraine, with overlapping symptoms and probably shared pathophysiological mechanisms.


Trend of fetal echocardiography use and comparison of medical costs for congenital heart disease treatment based on fetal echocardiography use in a Korean single center.
The rate of the prenatal diagnosis of congenital heart disease is increasing along with advances in fetal echocardiography techniques. Here, we aimed to investigate the trend of the use of fetal echocardiography over time and to compare the medical costs of congenital heart disease treatment according to whether fetal echocardiography was performed. We reviewed our hospital's database, and patients who underwent the first surgery for congenital heart disease within 30 days of birth during 2005-2007, 2011-2013, and 2017-2019 were included. The severity of congenital heart disease diagnosed in each case was evaluated according to The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality Scores (STS-EACTS Mortality Scores) and Mortality Categories (STAT Mortality Categories). In total, 375 patients were analyzed, and fetal echocardiography use increased significantly after the 2010s compared with in 2005-2007 (19.1% vs. 39%, p = 0.032 in Mortality Category 1-3; 15.5% vs. 69.5%, p = 0.000 in Mortality Category 4-5). Additionally, the mean STS-EACTS Mortality Score was higher in prenatally diagnosed patients than in postnatally diagnosed patients (2.287 vs. 1.787, p = 0.001). In the recent period, there was no significant difference in hospitalization durations and medical costs according to whether or not fetal echocardiography was performed. This single center study showed the use of fetal echocardiography is increasing. Further, prenatal diagnosis with fetal echocardiography causing no differences in medical costs in recent years. Therefore, we suggest that fetal echocardiography can be applied more widely without increasing the economic burden.


Retinal and Optic Nerve Integrity Following Monocular Inactivation for the Treatment of Amblyopia.
In animal models, monocular deprivation (MD) by lid closure mimics the effects of unilateral amblyopia in humans. Temporary inactivation of one or both eyes with intraocular administration of tetrodotoxin (TTX) has recently been shown to promote recovery from the anatomical effects of MD at post-critical period ages when standard recovery strategies fail. In the current study, the retinae and optic nerves of animals subjected to 10 days of monocular retinal inactivation were assessed for pathological changes as a means of assessing the viability of this potential new amblyopia therapy. Retinal sections from both eyes were subjected to hematoxylin and eosin staining and were then examined for cell density and soma size in the ganglion cell layer (GCL). Sections of the optic nerve from each eye were examined for neurofilament protein, myelin, glial cell density, and glial fibrillary acidic protein (GFAP). Our study revealed no evidence of gross histopathological abnormalities following inactivation for 10 days, nor was there evidence of degeneration of axons or loss of myelin in the optic nerve serving inactivated eyes. On all measurements, the inactivated eye was indistinguishable from the fellow eye, and both were comparable to normal controls. We confirmed that our inactivation protocol obliterated visually-evoked potentials for 10 consecutive days, but visual responses were restored to normal after the effects of inactivation wore off. Notwithstanding the critical need for further assessment of ocular and retinal health following inactivation, these results provide evidence that retinal inactivation as a treatment for amblyopia does not produce significant retinal damage or degeneration.


The prevalence and causes of visual impairment in an elderly Chinese Bai ethnic rural population: the Yunnan minority eye study.
To assess the prevalence and causes of visual impairment in the elderly Bai ethnic group in rural China. Random cluster sampling was used to identify the Bai ethnic group 50 years and older living in the Dali county of Yunnan, China. Presenting visual acuity (PVA) and best-corrected visual acuity (BCVA) were measured using the Early Treatment Diabetic Retinopathy Study visual chart. Blindness and low vision were defined according to World Health Organization criteria. The major cause of visual impairment was identified for all participants who were visually impaired. Of the 2742 eligible individuals, 2133 (77.8%) participated in the study, and 2115 (77.1%) had visual acuity data available. With the PVA, the prevalence of blindness and low vision was 3.59% and 15.22%, respectively. When the BCVA was used, these rates were reduced to 2.88% and 7.75%. Blindness and low vision were associated with older age and lack of education, but no sex difference was seen. Based on the BCVA, the predominant causes of blindness were cataract (70.5%), corneal opacity (8.2%), and glaucoma (6.6%). The majority of PVA-defined low vision cases were attributable to cataract (53.0%) and uncorrected refractive error (22.0%). A higher rate of visual impairment was seen in this Bai nationality sample than has been reported from the Han nationality population in rural China. Since potentially treatable eye disease, cataract, and uncorrected refractive error were the most important causes of visual impairment in this population, affordable provision of surgery and low-vision rehabilitation programs would help to address this problem.


Glassy dynamics and domains: explicit results for the East model.
A general matrix-based scheme for analyzing the long-time dynamics in kinetically constrained models such as the East model is presented. The treatment developed here is motivated by the expectation that slowly relaxing spin domains of arbitrary size govern the highly cooperative events that lead to spin relaxation at long times. To account for the role of large spin domains in the dynamics, a complete basis expressed in terms of domains of all sizes is introduced. It is first demonstrated that accounting for single domains of all possible sizes leads to a simple analytical result for the two-time single-spin correlation function in the East model that is in excellent quantitative agreement with simulation data for equilibrium spin-up density values c > or = 0.6. It is then shown that including also two neighboring domains leads to a closed expression that describes the slow relaxation of the system down to c approximately 0.3. Ingredients of generalizing the method to lower values of c are also provided, as well as to other models. The main advantage of this approach is that it gives explicit analytical results and that it requires neither an arbitrary closure for the memory kernel nor the construction of an irreducible memory kernel. It also allows one to calculate quantities that measure heterogeneity in the same framework, as is illustrated on the neighbor-pair correlation function, the average relaxation time, and the width of the distribution of relaxation times.


Imaging and 3D elemental characterization of intact bacterial spores by high-resolution secondary ion mass spectrometry.
We present a quantitative, imaging technique based on nanometer-scale secondary ion mass spectrometry for mapping the 3D elemental distribution present in an individual micrometer-sized Bacillus spore. We use depth profile analysis to access the 3D compositional information of an intact spore without the additional sample preparation steps (fixation, embedding, and sectioning) typically used to access substructural information in biological samples. The method is designed to ensure sample integrity for forensic characterization of Bacillus spores. The minimal sample preparation/alteration required in this methodology helps to preserve sample integrity. Furthermore, the technique affords elemental distribution information at the individual spore level with nanometer-scale spatial resolution and high (microg/g) analytical sensitivity. We use the technique to map the 3D elemental distribution present within Bacillus thuringiensis israelensis spores.


Impaired activity of plasma von Willebrand factor-cleaving protease may predict the occurrence of hepatic veno-occlusive disease after stem cell transplantation.
Hepatic veno-occlusive disease (VOD) is a life-threatening complication after stem cell transplantation (SCT), characterized by thrombus formation in hepatic venules leading to a symptom triad of hyperbilirubinemia, hepatomegaly, and ascites. Multifactorial defects in the hemostatic system may contribute to its pathogenesis, but its remains to be investigated. Unusually large VWF multimers (UL-VWFMs), produced in and released from vascular endothelial cells, are most biologically active in the interaction with platelets under a high shear stress. UL-VWFMs are cleaved and degraded into smaller VWFMs by a specific liver producing plasma protease, termed VWF-cleaving protease (VWF-CPase), which has recently been identified as a metalloprotease solely produced in liver, termed ADAMTS13. Herein, we studied the correlation between plasma VWF-CPase activity and UL-VWFMs in 21 patients who received SCT, seven patients with VOD and 14 patients without VOD. In non-VOD patients, activities (mean +/- 1s.d.) of VWF-CPase were 78 +/- 17% of the control before the conditioning regimen, 76 +/- 18% on day 0, 64 +/- 19% on day 7, 57 +/- 23% on day 14, 68 +/- 13% on day 21 and 79 +/- 19% on day 28 after SCT. The respective values in VOD patients were 32 +/- 19%, 27 +/- 15%, 18 +/- 11%, 22 +/- 18%, 26 +/- 22% and 12 +/- 4%. Thus, VWF-CPase activity was significantly reduced in VOD patients, even before the conditioning regimen, and such a difference was not found in other laboratory tests. However, despite such a clear difference, UL-VWFMs were present in plasmas of both patient groups, together with the increase of VWF antigen and ristocetin cofactor activity. These results indicate that the measurement of this enzyme activity is extremely useful in predicting the occurrence of VOD prior to a demonstration of its direct involvement in its pathogenesis.


[Ethnic factors in evaluation of drug efficacy and safety].
Ethnic difference is considered to be a major barrier in world-wide drug development. There seem to be many ethnic factors, genetic, environmental and cultural differences. There exists genetic polymorphism in drug metabolism especially for N-acetylation, debrisoquine hydroxylation and S-mephenytoin hydroxylation. The frequency of slow acetylator, poor metabolizer of debrisoquine and S-mephenytoin are 10%, less than 1% and 20% in Japanese and 50%, 10% and 5% in Caucasians respectively. Clinical responses and adverse effect of drugs are associated with these phenotypes. A retrospective study was conducted to determine whether inter-ethnic pharmacokinetic difference is larger than intra-ethnic variability. Individual pharmacokinetic parameters for most drugs were found to be extremely variable, but similarities of pharmacokinetic parameters were observed for Cmax and AUC between Japanese and other races. The results suggest that intra-ethnic variability is larger than inter-ethnic difference. The knowledge of genetic polymorphisms must find its way into clinical practice in order to achieve rational drug therapy that is more effective and safer for the benefit of the patient.


Pseudo hard-sphere viscosities from equilibrium Molecular Dynamics.
Transport coefficients like shear, bulk and longitudinal viscosities are sensitive to the intermolecular interaction potential and finite size effects when are numerically determined. For the hard-sphere (HS) fluid, such transport properties are determined almost exclusively with computer simulations. However, their systematic determination and analysis throughout shear stress correlation functions and the Green-Kubo formalism can not be done due to discontinuous nature of the interaction potential. Here, we use the pseudo hard-sphere (PHS) potential to determine pressure correlation functions as a function of volume fraction in order to compute mentioned viscosities. Simulation results are compared to available event-driven molecular dynamics of the HS fluid and also used to propose empirical corrections for the Chapman-Enskog zero density limit of shear viscosity. Moreover, we show that PHS potential is a reliable representation of the HS fluid and can be used to compute transport coefficients. The molecular simulation results of the present work are valuable for further exploration of HS-type fluids or extend the approach to compute transport properties of hard-colloid suspensions.


Comparison of two different extracorporeal circuits on cerebral embolization during cardiopulmonary bypass in children.
To compare the effect of two different extracorporeal circuits on the counts of high-intensity transient signals (HITS) during pediatric cardiopulmonary bypass (CPB). Transcranial Doppler was used to detect HITS associated with extracorporeal sources during the period of aortic crossclamping in the middle cerebral artery of children undergoing CPB. Based on body size, children were assigned one of two extracorporeal circuits (A or B). Circuit A included a D-705 oxygenator and associated reservoir, and circuit B included a Lilliput oxygenator and reservoir. Patients were further classified into two groups according to the complexity of surgical repair: single simple lesions or multiple complex lesions. We studied 109 pediatric patients. Surgery for multiple complex lesions was associated with longer periods of aortic crossclamping and CPB (p < 0.0001). The median count of extracorporeal HITS was 12 (25th, 75th percentiles: 3, 51). The type of extracorporeal circuit (p = 0.012) and the complexity of surgical repair (p < 0.0001) had an effect on the HITS counts. The use of circuit A was associated with higher HITS counts during surgery for multiple complex lesions compared to single simple lesions (p < 0.0001). Conversely, no differences were found with the use of circuit B between these two surgical groups (p > 0.25). During surgery for multiple complex lesions, patients treated with circuit A showed higher HITS counts than those with circuit B (p < 0.01), but there were no circuit-related differences in HITS counts (p = 0.30) during single simple lesions. Variations in the design characteristics of extracorporeal circuits can increase cerebral emboli during CPB in children. This may be related to the reduced ability of some circuits to remove emboli during long periods of CPB for complex congenital heart-surgery.


Autonomous Retroflexion of a Magnetic Flexible Endoscope.
Retroflexion during colonoscopy is typically only practiced in the wider proximal and distal ends of the large intestine owing to the stiff nature of the colonoscope. This inability to examine the proximal side of the majority of colon folds contributes to today's suboptimal colorectal cancer detection rates. We have developed an algorithm for autonomous retroflexion of a flexible endoscope that is actuated magnetically from the tip. The magnetic wrench applied on the tip of the endoscope is optimized in real-time with data from pose detection to compute motions of the actuating magnet. This is the first example of a completely autonomous maneuver by a magnetic endoscope for exploration of the gastrointestinal tract. The proposed approach was validated in plastic tubes of various diameters with a success rate of 98.8% for separation distances up to 50 mm. Additionally, a set of trials was conducted in an excised porcine colon observing a success rate of 100% with a mean time of 19.7 s. In terms of clinical safety, the maximum stress that is applied on the colon wall with our methodology is an order of magnitude below what would damage tissue.


Increased apoptosis and decreased proliferation of colorectal cancer cells using insulin-like growth factor binding protein-4 gene delivered locally by gene transfer.
Insulin-like growth factor (IGF)-I induces proliferation of transformed cells. Its binding proteins (IGFBP) are involved in local regulation of IGF. This study assessed the effects of overexpression of IGFBP-4 on the development of cancer in vivo. Nude mice were subcutaneously inoculated with HT-29 colorectal cancer cells (3 x 10(6)). When the tumour became visible (1 week after inoculation), animals received either 150 microg of mammalian expression vector containing IGFBP-4 cDNA or vector alone (n = 6 each) by peritumoural injection. Tumour size was measured during the growth. After 3 weeks of IGFBP-4 induction, animals were killed and tumour tissue samples were collected for examining the level of IGFBP-4 expression. Tumour mitotic activities were determined by counting numbers of mitotic cells on the tissue section. Apoptosis was investigated by terminal deoxynucleotidyl transferase-mediated dUDP nick end labelling assay. Following IGFBP-4 treatment, tumour showed large necrotic areas, significantly increased numbers of apoptotic cells (36.67 +/- 7.36 vs 7.07 +/- 1.91, P < 0.01 vs control), decreased cells undergoing mitosis (2.31 +/- 0.32 vs 3.61 +/- 0.27, P < 0.01 vs control) and higher expression of IGFBP-4 (P < 0.05 vs control). IGFBP-4 gene transfer increased apoptosis and decreased mitosis, but tumour volume was not significantly altered possibly due to cellular debris filling the centre of tumours.


Successful treatment of two individual cases of generalized granuloma annulare with amoxicillin/clavulanic acid and a combination of doxycycline and pentoxifylline.
Granuloma annulare is a benign inflammatory skin disease potentially related to a delayed hypersensitivity reaction to the dermis. Generalized granuloma annulare (GGA) manifests as diffuse skin-colored to erythematous annular or nummular plaques affecting at least the trunk and either upper or lower extremities, or both. GGA is resistant to many therapeutic modalities, making it difficult to treat. Different therapeutic approaches to GGA have been attempted but definitive treatment for this disease remains elusive. This article focuses on the use of amoxicillin/clavulanic acid and a combination of doxycycline and pentoxifylline therapy as treatment options for GGA in two patients with histopathology-proven interstitial GGA. Both amoxicillin/clavulanic acid and doxycycline inhibit bacterial cell growth, raising the possibility that a bacterial pathogenesis may be of significance in GGA. This is the first reported case of successful treatment of GGA with these regimens.


Social mobility and personal satisfaction: evidence from ten countries.
This paper examines survey data relating class mobility to satisfaction and dissatisfaction with seven different domains of everyday life among nationally representative samples of men and women living in ten industrialized nations. The evidence is set against competing pessimistic and optimistic accounts of the mobility experience found in earlier literature. Results show that individuals who move from working-class origins to middle-class destinations are no more likely to be systematically satisfied or dissatisfied with life than are the socially immobile or even those downwardly mobile from advantaged backgrounds into the working class. Indeed, in all nations, the overall association between class experience and satisfaction with life is both weak and uneven across the different life-domains. The study also serves to illustrate an important principle of research methodology more generally.


Development of hepatocellular carcinoma (HCC) in a patient 17 years after recovery from chronic hepatitis B and seroconversion to anti-HBs.
A 63-year-old man was admitted to hospital in 2003 for treatment of a hepatocellular carcinoma (HCC). He was negative for HBs antigen (HBsAg) and anti-HCV antibody, and positive for anti-HBs. He had a past history of chronic hepatitis B. In 1986, HBsAg had become negative with the development of anti-HBs. In 2003, an HCC was detected and liver resection was carried out. Histological examination revealed moderately differentiated HCC and slightly fibrotic liver. It is suggested that a diagnosis of HCC, combined with negativity for HBsAg and anti-HCV antibody, may include cases of past recovery from chronic hepatitis B, such as this case.


Study Design of the Microcirculatory Shock Occurrence in Acutely Ill Patients (microSOAP): an International Multicenter Observational Study of Sublingual Microcirculatory Alterations in Intensive Care Patients.
Objective. Sublingual microcirculatory alterations are associated with an adverse prognosis in several critical illness subgroups. Up to now, single-center studies have reported on sublingual microcirculatory alterations in ICU patient subgroups, but an extensive evaluation of the prevalence of these alterations is lacking. We present the study design of an international multicenter observational study to investigate the prevalence of microcirculatory alterations in critically ill: the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Methods. 36 ICU's worldwide have participated in this study aiming for inclusion of over 500 evaluable patients. To enable communication and data collection, a website, an Open Clinica 3.0 database, and image uploading software have been designed. A one-session assessment of the sublingual microcirculation using Sidestream Dark Field imaging and data collection on patient characteristics has been performed in every ICU patient >18 years, regardless of underlying disease. Statistical analysis will provide insight in the prevalence and severity of sublingual alterations, its relation to systemic hemodynamic variables, disease, therapy, and outcome. Conclusion. This study will be the largest microcirculation study ever performed. It is expected that this study will also establish a basis for future studies related to the microcirculation in critically ill.


Eye manifestations in the NSUN2 intellectual disability syndrome.
The NSUN2-intellectual disability syndrome is a rare disorder of the cellular transcriptome that prevents proper t-RNA splicing. This disorder interrupts cellular function and leads to an accumulation of RNA fragments, producing a constellation of symptoms including dysmorphic facies, hypotonia, microcephaly, and short stature. Eye manifestations have been reported but not well characterized. Our study presents a new case involving a 4-year-old boy with novel NSUN2 variants and clinical features consistent with the syndrome. In addition, through a systemic review, we discuss the 24 previously reported cases of the syndrome with an emphasis on the eye and ocular adnexa clinical features.


Analysis of TET expression/activity and 5mC oxidation during normal and malignant germ cell development.
During mammalian development the fertilized zygote and primordial germ cells lose their DNA methylation within one cell cycle leading to the concept of active DNA demethylation. Recent studies identified the TET hydroxylases as key enzymes responsible for active DNA demethylation, catalyzing the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine. Further oxidation and activation of the base excision repair mechanism leads to replacement of a modified cytosine by an unmodified one. In this study, we analyzed the expression/activity of TET1-3 and screened for the presence of 5 mC oxidation products in adult human testis and in germ cell cancers. By analyzing human testis sections, we show that levels of 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine are decreasing as spermatogenesis proceeds, while 5-methylcytosine levels remain constant. These data indicate that during spermatogenesis active DNA demethylation becomes downregulated leading to a conservation of the methylation marks in mature sperm. We demonstrate that all carcinoma in situ and the majority of seminomas are hypomethylated and hypohydroxymethylated compared to non-seminomas. Interestingly, 5-formylcytosine and 5-carboxylcytosine were detectable in all germ cell cancer entities analyzed, but levels did not correlate to the 5-methylcytosine or 5-hydroxymethylcytosine status. A meta-analysis of gene expression data of germ cell cancer tissues and corresponding cell lines demonstrates high expression of TET1 and the DNA glycosylase TDG, suggesting that germ cell cancers utilize the oxidation pathway for active DNA demethylation. During xenograft experiments, where seminoma-like TCam-2 cells transit to an embryonal carcinoma-like state DNMT3B and DNMT3L where strongly upregulated, which correlated to increasing 5-methylcytosine levels. Additionally, 5-hydroxymethylcytosine levels were elevated, demonstrating that de novo methylation and active demethylation accompanies this transition process. Finally, mutations of IDH1 (IDH1 (R132)) and IDH2 (IDH2 (R172)) leading to production of the TET inhibiting oncometabolite 2-hydroxyglutarate in germ cell cancer cell lines were not detected.


Surgical Management of Mandibular Angle Fractures.
The study proposed to determine the superiority between different fixation methods in the mandibular angle fractures (MAFs) and to evaluate best option for surgeon and patient. A systematic review was conducted according to PRISMA guidelines, examining Medline-Ovid, Embase, and Pubmed databases. The quality of studies was assessed, and the odds risk (OR) with its corresponding 95% confidence interval (CI) was assessed to measure the effect size. Subgroup analyses by different fracture regions and different miniplate sizes were performed. Publication bias was measured by a funnel plot. Twenty-one articles were enrolled in this review: 8 randomized controlled trials , 2 controlled clinical trials, and 11 retrospective studies. There were significant advantages for 3-dimensional (3D) miniplate (OR = 0.48, P = 0.003, 95% CI, 0.35-0.67) and 1 miniplate (OR 0.38, 95% CI 0.25-0.58, P < 0.00001). The cumulative OR for locking miniplate was 0.45, showing that the utilizing of locking mini-plate in management of MAFs decreases postoperative complications risk by 55% over the use of nonlocking mini-plate. The results of this review indicated that the use of 3D miniplate, locking plate, and 1 plate were more advanced to 2 miniplates technique in low incidence of postoperative complications in the treatment of MAFs.


Environment-dependent vibrational heat transport in molecular junctions: Rectification, quantum effects, vibrational mismatch.
Vibrational heat transport in molecular junctions is a central issue in different contemporary research areas such as chemistry, materials science, mechanical engineering, thermoelectrics, and power generation. Our model system consists of a chain of molecules which are sandwiched between two solids that are maintained at different temperatures. We employ a quantum self-consistent reservoir model, which is built on a generalized quantum Langevin equation, to investigate quantum effects and far from equilibrium conditions on thermal conduction at nanoscale. The present self-consistent reservoir model can easily mimic the phonon-phonon scattering mechanisms. Different thermal environments are modeled as (i) Ohmic, (ii) sub-Ohmic, and (iii) super-Ohmic environments, and their effects are demonstrated for the thermal rectification properties of the system with spring graded or mass graded features. The behavior of heat current across molecular junctions as a function of chain length, temperature gradient, and phonon scattering rates are studied. Further, our analysis reveals the effects of vibrational mismatch between the solids phonon spectra on heat transfer characteristics in molecular junctions for different thermal environments.


Contraceptive use among migrant, second-generation migrant and non-migrant women seeking abortion care: a descriptive cross-sectional study conducted in Sweden.
The objective of this study was to compare ever-in life contraception use, use of contraception at current conception, and planned use of contraception after an induced abortion, among three groups of women: migrants, second-generation migrants and non-migrant women, and to compare the types of contraception methods used and intended for future use among the three groups of women. The cross-sectional study administered a questionnaire face-to-face to women aged 18 years and older who were seeking abortion care at one of six abortion clinics in Stockholm County from January to April 2015. The analysis included 637 women. Migrants and second-generation migrants were less likely to have used contraception historically, at the time of the current conception, and to plan to use contraception after their induced abortion compared with non-migrant women. Historically, non-migrants had used pills (89%) and withdrawal (24%) while migrants had used the copper intrauterine device (24%) to a higher extent compared to the other two groups of women. Both the migrants (65%) and second-generation migrants (61%) were more likely than the non-migrants (48%) to be planning to use long-acting reversible contraception. Lower proportions of contraception use were found in migrants and second-generation migrants than in non-migrants. In addition, there were significant differences in the types of contraception methods used historically and intended for future use.


Natural attenuation processes during in situ capping.
Chlorinated solvents are common groundwater contaminants that threaten surface water quality and benthic health when present in groundwater seeps. Aquatic sediments can act as natural biobarriers to detoxify chlorinated solvent plumes via reductive dechlorination. In situ sediment capping, a remedial technique in which clean material is placed at the sediment-water interface, may alter sedimentary natural attenuation processes. This research explores the potential of Anacostia River sediment to naturally attenuate chlorinated solvents under simulated capping conditions. Results of microcosm studies demonstrated that intrinsic dechlorination of dissolved-phase PCE to ethene was possible, with electron donor availability controlling microbial activity. A diverse microbial community was present in the sediment, including multiple Dehalococcoides strains indicated by the amplification of the reductive dehalogenases tceA, vcrA, and bvcA. An upflow column simulating a capped sediment bed subject to PCE-contaminated groundwater seepage lost dechlorination activity with time and only achieved complete dechlorination when microorganisms present in the sediment were provided electron donor. Increases in effluent chloroethene concentrations during the period of biostimulation were attributed to biologically enhanced desorption and the formation of less sorptive dechlorination products. These findings suggest that in situ caps should be designed to account for reductions in natural biobarrier reactivity and for the potential breakthrough of groundwater contaminants.


TRAIL-induced apoptosis of HL60 leukemia cells: two distinct phenotypes of acquired TRAIL resistance that are accompanied with resistance to TNFalpha but not to idarubicin and cytarabine.
TNF-related apoptosis-inducing ligand (TRAIL) is a proapoptotic cytokine implicated in cancer cell surveillance. A potential of TRAIL as a cancer-specific therapeutic agent has been proposed, either as a single agent or in combination with chemotherapy. Prolonged exposure of TRAIL-sensitive leukemia cell line, wild-type (WT) HL60 cells to recombinant soluble TRAIL or to cytostatic agents, cytarabine and idarubicin, resulted in the establishment of resistant subclones with distinct phenotypic features. The TRAIL resistant HL60 subclones were characterized by decreased expression of TRAIL and TNFalpha death receptors. These resistant subclones had impaired activation of caspases 8 and 10 in response to TRAIL and TNFalpha, decreased TRAIL-induced nuclear translocation of NFkappaB RelA/p65, and dysregulation of the expression of several apoptosis regulators. Among the TRAIL resistant HL60 subclones we identified two separate phenotypes that differed in the expression of CD14, osteoprotegerin, and several apoptosis regulators. Both these TRAIL resistant HL60 subclones were resistant to TNFalpha, suggesting disruption of the extrinsic apoptotic pathway, but not to cytostatic agents, cytarabine and idarubicin. The concurrently derived HL60 subclones were cytarabine and idarubicin-resistant but remained sensitive to TRAIL-induced apoptosis. We identified distinct pathways for the development of HL60 leukemia cell resistance to apoptosis induction. These findings are relevant for the design of more effective strategies for leukemia therapy.


High prevalence of infections in non-COVID-19 patients admitted to the Emergency Department with severe lymphopenia.
In the Emergency Department (ED), early and accurate recognition of infection is crucial to prompt antibiotic therapy but the initial presentation of patients is variable and poorly characterized. Lymphopenia is commonly associated with bacteraemia and poor outcome in intensive care unit patients. The objective of this retrospective study was to assess the prevalence of community-acquired infection in a cohort of unselected patients admitted to the ED with undifferentiated symptoms and severe lymphopenia. This is a retrospective single-center study conducted over a 1 year-period before the COVID-19 pandemic. Consecutive adult patients admitted to the ED with severe lymphopenia (lymphocyte count < 0.5 G/L) were studied. Patients with hematological or oncological diseases, HIV infection, hepato-cellular deficiency, immunosuppression, or patients over 85 years old were excluded. Diagnoses of infection were validated by an independent adjudication committee. The association between various parameters and infection was assessed using a multivariate logistic regression analysis. Of 953 patients admitted to the ED with severe lymphopenia, 245 were studied (148 men; mean age: 63 ± 19 years). Infection was confirmed in 159 patients (65%) (bacterial: 60%, viral: 30%, other: 10%). Only 61 patients (25%) were referred to the ED for a suspected infection. In the univariate analysis, SIRS criteria (OR: 5.39; 95%CI: 3.04-9.70; p < 0.001) and temperature ≥ 38.3 °C (OR: 10.95; 95%CI: 5.39-22.26; p < 0.001) were strongly associate with infection. In the multivariate analysis, only SIRS criteria (OR: 2.4; 95%CI: 1.48-3.9; p < 0.01) and fever (OR: 3.35; 95%CI: 1.26-8.93; p = 0.016) were independently associated with infection. The prevalence of underlying infection is high in patients admitted to the ED with lymphopenia, irrespective of the reason for admission. Whether lymphopenia could constitute a valuable marker of underlying infection in this clinical setting remains to be confirmed prospectively in larger cohorts. No registration required as this is a retrospective study.


Cancer incidence in North West Algeria (Mascara) 2000-2010: results from a population-based cancer registry.
Cancer is a leading cause of death worldwide accounting for 7.4 million deaths. Cancer has become a major public health concern in Algeria. The aim of the present study was to estimate cancer incidence in Mascara Province based on the population-based cancer registry. We analyzed data from the cancer registry of Mascara covering all cancer cases diagnosed by all methods and included in the registry from 1(st) January 2000 to 31(st) December 2010. The results are presented as incidence rates of cases by site, sex, age, and crude rate. Age-standardized rates per 100,000 person-years (ASRs) were calculated, using the direct method of standardization to the world population. A total of 1875 cases of invasive cancer were recorded. The mean age of diagnosis for all cancers was 52.66 ± 0.5 in men and 59.18 ± 0.6 in women. The ASR for all cancers in females was 27.8 per 100,000, and that for males was 23.6 per 100,000. The most important finding of the present study was the high incidence of liver cancer among males and females in Mascara. Among females, breast cancer was the most frequently reported followed by Cervix uteri, liver and colon. The most frequent cancer types in males were lung, colon, esophagus and stomach and liver. Cancer incidence in Mascara province was lower than that reported in other national and regional registries. Findings of the present study revealed high incidence of liver cancer in the province, the highest in Algeria, suggesting high prevalence of risk factors.


Why clinical ethics consultants might not want to be educators.
... Perhaps we should make explicit that clinical ethics consultants' work is to encourage and to assist others to think about the nature of their profession and reflect on their own behaviors, rather than to change behavior directly. Clinical ethics consultants' work is thus made more difficult, but it should be difficult. They should be continually challenged in their work (as teaching in that setting will do) because it will keep them from succumbing to their titles, from believing that they do know what is best, that they are ethics experts. Furthermore, clinical ethics consultants should be doing something very different from what other people in the healthcare environment are doing; they should acknowledge themselves as outsiders and should cherish that status because only then will they be able to ask the difficult questions that psychological proximity to and practical involvement in healthcare obscure. True education, of course, is the most dangerous activity, but the danger posed by such education is considerably more appealing than the danger posed by clinical ethics consultants who pursue and exert power in healthcare under cover of implicit claims and false beliefs about their expertise.


Extreme mountain bike challenges may induce sub-clinical myocardial damage.
The relationship between extreme exercise and coronary artery disease is not well understood, and the information available is contradictory. The aim of the present study was to determine whether strenuous endurance exercise, performed under conditions in which the partial pressure of environmental oxygen varies constantly, can induce myocardial cell injury. Plasma urea, creatinine, creatine kinase, myoglobin and cardiac troponin I (cTnI) concentrations were measured the day before and immediately after a mountain bike challenge (distance 95 km, cumulative altitude difference 2340 m) in eleven amateur male cyclists. All biochemical markers of muscle cell damage increased significantly after exercise. Although cTnI concentrations also increased significantly, they remained below the threshold (0.5 microg/L) indicative of acute myocardial infarction. In male, amateur mountain bikers, this kind of strenuous exercise may induce sub-clinical myocardial injury.


Biochemical markers in patients with familial colonic neoplasia.
Many potential markers, including biochemical markers, have been studied in an attempt to identify the presence of early colorectal neoplasia or risk of neoplasia, particularly in those families with hereditary colonic neoplasia syndromes. Unfortunately, most of these markers are useless in screening or diagnosis. Nevertheless, such markers as carcinoembryonic antigen (CEA) and CA 19-9 may have a role in pretherapeutic and posttherapeutic monitoring of disease or recurrence. The newer tumor markers, including the carbohydrate markers, ornithine decarboxylase (ODC) and the polyamines, are of great interest as potential tumor markers; ODC and the polyamines may also have a future potential as therapeutic targets. However, further studies are needed to determine their true sensitivity and specificity in hereditary colonic neoplasia syndromes, as well as in patients without genetic syndromes who are at risk for colorectal cancer.


Discrimination of human leukemia subtypes by flow cytometric analysis of cellular DNA and RNA.
A newly developed flow cytometry technique for simultaneous measurements of three features of individual cells--DNA, RNA, and nuclear diameter--using acridine orange as a fluorescent metachromatic dye, has been applied to cell-cycle analysis. DNA stemline determination, and to classification of 102 cases of human leukemias in adults. Acute lymphoblastic leukemia (L1-2) was characterized by moderately increased RNA of G0/1 cells as compared to normal lymphocytes; acute nonlymphoblastic leukemia (M 1-5) by very high RNA of G0/G1 cells. Both had either diploid or aneuploid DNA stemlines. Chronic lymphocytic leukemia showed diploid DNA, very low proliferation, and low RNA, similar to that found by use to be typical for normal B cells. In chronic myelogenous leukemia, two cell populations were distinguished, one with high RNA, the other with very low RNA and elongated nuclear diameter due to stripped, unfolded nuclei of polymorphonuclear leukocytes. The number of leukemic blast cells, identified by aneuploid DNA values, correlates well with conventional microscopy counts and could be followed during the course of treatment. Thus, acridine orange flow cytometry can be used to discriminate subtypes of human leukemias, to determine cell cycle stages, and to detect and monitor aneuploid leukemia stemlines.


Parosteal lipoma with hyperostosis: report of two pathologically proven cases evaluated by magnetic resonance imaging.
The authors describe two cases of parosteal lipoma, an infrequent benign tumour, associated with hyperostosis. The first patient presented with a mass in the posterior neck, the other with one in the proximal forearm. Radiologic diagnosis was facilitated by magnetic resonance imaging (MRI). The MRI images showed the characteristic features of a parosteal lipoma, as well as hyperostotic areas that remained of low signal intensity in both T1-weighted and T2-weighted sequences. MRI is both sensitive and specific for diagnosing these lesions and provides excellent depiction of the anatomic features before surgery.


Maternal endothelial function, circulating endothelial cells, and endothelial progenitor cells in pregnancies conceived with or without in vitro fertilization.
In women who conceived with or without assisted reproduction, we evaluated endothelial function by EndoPAT [reactive hyperemia index (RHI)], circulating numbers of endothelial cells (CEC) and endothelial progenitor cells (EPC), and their function before during and after pregnancy. In vitro fertilization (IVF) pregnancies were stratified by method of conception and corpus luteum (CL) number-controlled ovarian stimulation (>1 CL) or programmed (0 CL) cycles and spontaneous singleton pregnancies (1 CL). We observed 1) comparable gestational decline of RHI in the three participant groups secondary to gestational rise of baseline preocclusion pulse-wave amplitude (PWA) incorporated into the RHI calculation by EndoPAT software; 2) progressive rise in "normalized" RHI throughout pregnancy (calculated by substituting prepregnancy baseline preocclusion PWA into the RHI equation), greater in spontaneous conception vs. IVF cohorts; 3) similar gestational increase of maximum PWA and time to maximum PWA after the ischemia stimulus among the three participant groups; 4) modest gestational increase of ischemia response (reactive hyperemia) in the spontaneous conception group and no change or significant decline, respectively, in women who conceived using programmed or controlled ovarian stimulation cycles; 5) enhanced basal nitric oxide production by early (primitive) outgrowth EPC during pregnancy in women who conceived spontaneously, but not through IVF; and 6) gestational increase in CEC in all three participant cohorts, more pronounced in women who conceived by IVF using programmed cycles. On balance, the evidence supported enhanced endothelial function during pregnancy in spontaneous conceptions but less so in IVF pregnancies using either controlled ovarian stimulation or programmed cycles.


Feasibility of catheter ablation renal denervation in "mild" resistant hypertension.
Renal denervation (RDN) has been proposed as a novel interventional antihypertensive technique. However, existing evidence was mainly from patients with severe resistant hypertension. The authors aimed to evaluate the efficacy of RDN in patients with resistant hypertension with mildly elevated blood pressure (BP). Studies of RDN in patients with mild resistant hypertension (systolic office BP 140-160 mm Hg despite treatment with three antihypertensive drugs including one diuretic, or mean systolic BP by 24-hour ambulatory BP measurement [ABPM] 135-150 mm Hg) were included. Two observational and one randomized cohort were identified (109 patients in the RDN group and 36 patients in the control group). Overall, the mean age of patients was 62±10 years, and 69.7% were male. Before-after comparison showed that RDN significantly reduced ABPM as compared with the baseline systolic ABPM, from 146.3±13 mm Hg at baseline to 134.6±14.7 mm Hg at 6-month follow-up and diastolic ABPM from 80.8±9.4 mm Hg at baseline to 75.5±9.8 mm Hg at 6-month follow up (both P<.001). This significant effect was not observed in the control group. Between-group comparison showed a greater change in ABPM in the RDN group as compared with that in the control group (change in systolic ABPM: -11.7±9.9 mm Hg in RDN vs -3.5±9.6 mm Hg in controls [P<.001]; change in diastolic ABPM: -5.3±6.3 mm Hg in RDN vs -2.1±5.5 mm Hg in control [P=.007]). RDN was also associated with a significantly decreased office systolic/diastolic BP and reduced number of antihypertensive medications. No severe adverse events were found during follow-up. RDN seems feasible to treat patients with mild resistant hypertension.


The impact of early hyperglycaemia on children with traumatic brain injury.
Hyperglycaemia is common amongst children with traumatic brain injury (TBI). We aim to investigate the association between early hyperglycaemia and poor clinical outcomes in children with moderate to severe TBI. We performed a retrospective study in a tertiary paediatric hospital between May 2012 and October 2014 of all patients with TBI who were aged <16 years with a Glasgow Coma Scale (GCS) of ≤13. The primary outcome was death. Secondary outcomes were 14 ventilation-free, 14 paediatric intensive care unit (PICU)-free and 28 hospital-free days. We defined hyperglycaemia as glucose >11.1 mmol/L (200 mg/dL). There were 109 patients with a median age of 54 months [inter-quartile range (IQR): 17-82]. Median glucose on arrival was 6.1 mmol/L (IQR: 5.2-9.8). Median GCS in our cohort was 8 (IQR: 6-12). Multivariate logistic regression demonstrated that initial hyperglycaemia [odds ratio (OR): 15.23; 95% confidence interval (CI): 3.74-62.00; P < 0.001], and GCS <8 (OR: 13.02; 95% CI: 2.31-73.33; P = 0.004) were risk factors for mortality. Multivariate linear regression showed that initial hyperglycaemia was a risk factor for reduced ventilation-free, PICU-free and hospital-free days. Early hyperglycaemia predicts for in-hospital mortality, reduced ventilation-free, PICU-free and hospital-free days in children with moderate to severe TBI.


Martius repair in urethrovaginal defects.
To repair a urethrovaginal defect in childhood is a challenge for a pediatric surgeon. Martius fat-pad flap repair is being used in women successfully. Here, we report 2 girls who had Martius repair for their urethrovaginal defects. Topical estriol and asiaticoside perineally were administered for preoperative 3 weeks to reinforce the tissues. Martius repair was done using 1-sided labial fat-pad flap. Urethral and bladder catheters were inserted. Urethral catheter was removed on postoperative day 14 and bladder catheter on day 21 after controlling residual urine. Patient 1, a 6-year-old girl, had lipomeningocele repair at the age of 18 months and had an iatrogenic urethrovaginal fistula that is caused by catheter insertion. She developed urinary incontinence, and 3 primary repair attempts were unsuccessful. Patient 2 is a 5-year-old girl who had pouch colon with persistent cloacal malformation and had posterior anorectovaginourethroplasty. The urethrovaginal septum did not heal, and she was incontinent. One attempt of primary repair was unsuccessful. The urethrovaginal wall was completely open at the time of Martius repair in both patients. Urethral wall was completely healed after Martius repair in both patients. Martius fat-pad flap repair can be used to repair urethrovaginal fistulas in girls. It has both functionally and cosmetically good results, and neourethra is easily catheterizable.


Cognitive Path Planning With Spatial Memory Distortion.
Human path-planning operates differently from deterministic AI-based path-planning algorithms due to the decay and distortion in a human's spatial memory and the lack of complete scene knowledge. Here, we present a cognitive model of path-planning that simulates human-like learning of unfamiliar environments, supports systematic degradation in spatial memory, and distorts spatial recall during path-planning. We propose a Dynamic Hierarchical Cognitive Graph (DHCG) representation to encode the environment structure by incorporating two critical spatial memory biases during exploration: categorical adjustment and sequence order effect. We then extend the "Fine-To-Coarse" (FTC), the most prevalent path-planning heuristic, to incorporate spatial uncertainty during recall through the DHCG. We conducted a lab-based Virtual Reality (VR) experiment to validate the proposed cognitive path-planning model and made three observations: (1) a statistically significant impact of sequence order effect on participants' route-choices, (2) approximately three hierarchical levels in the DHCG according to participants' recall data, and (3) similar trajectories and significantly similar wayfinding performances between participants and simulated cognitive agents on identical path-planning tasks. Furthermore, we performed two detailed simulation experiments with different FTC variants on a Manhattan-style grid. Experimental results demonstrate that the proposed cognitive path-planning model successfully produces human-like paths and can capture human wayfinding's complex and dynamic nature, which traditional AI-based path-planning algorithms cannot capture.


Identification of anti-TNFalpha peptides with consensus sequence.
Phage displayed peptide library was used to select tumor necrosis factor alpha (TNFalpha) binding peptides. After three sequential rounds of biopanning, some linear TNFalpha-binding peptides were identified from a 12-mer peptide library. A consensus sequence (L/M)HEL(Y/F)(L/M)X(W/Y/F), where X might be variable residue, was deduced from sequences of these peptides. The phages bearing these peptides showed specific binding to immobilized TNFalpha, with over 80% of phages bound being competitively eluted by free TNFalpha. To confirm the binding activity and to explore further functional properties, three peptides with typical structure were selected and expressed as GST-fused protein. These recombinant peptides effectively competed for [125I]TNFalpha binding to TNFR1 in a dose-dependent manner, with IC(50) from 10 to 160 microM. Furthermore, the GST-fused derivatives showed inhibitory effects on TNFalpha-induced cytotoxicity. Taken together, these data demonstrate that the TNFalpha-binding peptides are effective antagonists of TNFalpha and the deduced motif might be useful in development of novel low molecular weight anti-TNFalpha drugs.


Rubicon deficiency enhances cardiac autophagy and protects mice from lipopolysaccharide-induced lethality and reduction in stroke volume.
: Rubicon has been suggested to suppress autophagosome maturation by negatively regulating PI3KC3/Vps34 activity. However, the physiological function of Rubicon remains elusive. We hypothesized that Rubicon deficiency enhances autophagic flux in the heart and affects cardiac function. Rubicon knockout (KO) mice were generated by piggyBac transposition. Loss of Rubicon was demonstrated at both mRNA and protein levels. Rubicon KO mice were born in Mendelian ratios. Autophagic flux, assessed by bafilomycin A1-induced changes in LC3 II protein abundance, was enhanced in the heart of Rubicon KO mice compared with wild-type (WT) controls. Hematoxylin-eosin staining and picrosirius red staining showed that Rubicon KO mice exhibited normal baseline cardiac morphology. Echocardiography revealed that ejection fraction and fractional shortening, 2 indices of cardiac function, were comparable between Rubicon KO mice at 2, 8, and 12 months of age (n = 6-8 for each age group) and the corresponding WT controls (n = 6-8 for each age group). In a mouse model of lipopolysaccharide (LPS)-induced sepsis, the survival time of LPS-treated Rubicon KO mice (n = 10) was prolonged compared with LPS-treated WT controls (n = 11). Echocardiography revealed that Rubicon deficiency partially normalized LPS-induced reduction in stroke volume and cardiac output 12 hours after LPS administration compared with LPS-treated WT controls (n = 6 for each group). Autophagic flux was enhanced in Rubicon-deficient hearts 12 hours after LPS treatment compared with LPS-treated WT controls. Real-time quantitative polymerase chain reaction suggested that proinflammatory cytokine expression was not significantly different between LPS-treated Rubicon KO mice and WT controls (n = 3 for each group). Our data demonstrate for the first time that Rubicon deficiency enhances autophagic flux in the heart and protects mice from lethality and reduction in stroke volume induced by LPS.


FROGS: a powerful tool to analyse the diversity of fungi with special management of internal transcribed spacers.
Fungi are present in all environments. They fulfil important ecological functions and play a crucial role in the food industry. Their accurate characterization is thus indispensable, particularly through metabarcoding. The most frequently used markers to monitor fungi are ITSs. These markers are the best documented in public databases but have one main weakness: polymerase chain reaction amplification may produce non-overlapping reads in a significant fraction of the fungi. When these reads are filtered out, traditional metabarcoding pipelines lose part of the information and consequently produce biased pictures of the composition and structure of the environment under study. We developed a solution that enables processing of the entire set of reads including both overlapping and non-overlapping, thus providing a more accurate picture of fungal communities. Our comparative tests using simulated and real data demonstrated the effectiveness of our solution, which can be used by both experts and non-specialists on a command line or through the Galaxy-based web interface.


Rivaroxaban or apixaban in fragile patients with acute venous thromboembolism.
The efficacy and safety of the direct oral anticoagulants (DOACs) in fragile patients (age ≥ 75 years and/or creatinine clearance [CrCl] levels ≤50 mL/min and/or body weight ≤50kg) with venous thromboembolism (VTE) have not been consistently compared. We used the RIETE database to compare the rates of the composite of VTE recurrences or major bleeding during anticoagulation in fragile patients with VTE, according to the use of rivaroxaban or apixaban for initial and long-term therapy. From January 2013 to October 2019, 36,889 patients were recruited, of whom 14,831 (40%) were fragile. Overall, 999 fragile patients (15%) received DOACs starting within the first 48 h: rivaroxaban 711 and apixaban 288. Median duration of therapy was: 113 vs. 111 days. A substantial amount of patients in both subgroups (25% vs. 40%) received non-recommended doses of DOACs. During anticoagulation, 13 patients developed VTE recurrences, 18 had major bleeding and 36 died. When only considering patients receiving recommended doses (n = 705), there were no differences between drugs in the rate of the composite outcome (rate ratio [RR]: 1.08; 95%CI: 0.35-3.30) or all-cause death (RR: 0.99; 95%CI: 0.32-3.08). On multivariable analysis, patients receiving rivaroxaban or apixaban at recommended doses had a similar risk for the composite outcome (hazard ratio: 1.34; 95%CI: 0.35-5.06). The use of rivaroxaban or apixaban at recommended doses in fragile patients with VTE was associated with a similar risk for VTE recurrences or major bleeding.


[Comparison of polarity profiles by novelty filters].
The present study compares the ability of humans with the ability of neural networks to determine similarities between several graphic patterns. The simulated neural network was designed as a novelty filter. The stimulus material consisted of 8 different polarity profiles which were judged for their similarity under different conditions: (1) simultaneous presentation and (2) serial presentation. The judgments were collected by using the method of paired comparisons. The profile patterns were fed into the neural network to calculate novelty (similarity) values. As a further criterion for the correspondence of the profiles, a correlation coefficient (Q-coefficient) was taken. The comparison of the resulting similarity matrices shows that the performance of the novelty filter is in a good competition with the performance of a human observer. Furthermore, in both conditions the correspondence between the similarity-judgments of the subjects and the novelty values was higher than the correspondence between the judgments and the Q-coefficient. Despite this advantage the standardization of the novelty values raises some methodological problems.


Targeted Gene Expression Profiling of Human Myeloid Cells From Blood and Lung Compartments of Patients With Tuberculosis and Other Lung Diseases.
Myeloid-derived suppressor cells (MDSC) have been identified in the peripheral blood and granulomas of patients with active TB disease, but their phenotype-, function-, and immunosuppressive mechanism- spectrum remains unclear. Importantly, the frequency and signaling pathways of MDSC at the site of disease is unknown with no indication how this compares to MDSC identified in peripheral blood or to those of related myeloid counterparts such as alveolar macrophages and monocytes. Most phenotypic and functional markers have been described in oncological studies but have not yet been validated in TB. Using a panel of 43 genes selected from pathways previously shown to contribute to tumor-derived MDSC, we set out to evaluate if the expression of these additional functional markers and properties may also be relevant to TB-derived MDSC. Differential expression was investigated between MDSC, alveolar macrophages and monocytes enriched from bronchoalveolar lavage fluid and peripheral blood of patients with active TB, patients with other lung diseases (OLD). Results demonstrated that anatomical compartments may drive compartment-specific immunological responses and subsequent MDSC immunosuppressive functions, demonstrated by the observation that MDSC and/or monocytes from PB alone can discriminate, via hierarchical clustering, between patients with active TB disease and OLD. Our data show that the gene expression patterns of MDSC in peripheral blood and bronchoalveolar lavage fluid do not cluster according to disease states (TB vs OLD). This suggests that MDSC from TB patients may display similar gene expression profiles to those found for MDSC in cancer, but this needs to be validated in a larger cohort. These are important observations for TB research and may provide direction for future studies aimed at repurposing and validating cancer immunotherapies for use in TB.


Evaluation of Health-Related Quality of Life among Tuberculosis Patients in Two Cities in Yemen.
The health-related quality of life (HRQoL) of Tuberculosis (TB) patients is important because it directly influences the outcome of TB patients in several aspects. The current study aims to evaluate and to find the factors influencing the HRQoL of TB patients in two major TB-prevalent cities (Taiz and Alhodidah) in Yemen. A prospective study was conducted, and all TB patients meeting the HRQoL criteria were asked to complete the HRQoL SF-36 survey. The records of TB patients were examined for disease confirmation, and a follow-up was consequently performed for patients during treatment between March 2013 and February 2014 in Taiz and Alhodidah Cities. HRQol scores were calculated by using QM scoring software version 4.5, in which the physical component score (PCS) and mental component score (MCS) were obtained. The scores obtained between 47-53 normal based score (NBS) were considered equivalent to the US normal score. Low scores indicate the poor health situation of TB patients. A total of 243 TB patients enrolled in the study at the beginning of the treatment. A total of 235 and 197 TB patients completed the questionnaire at the end of the intensive phase (I.P.) and continuation phase (C.P.), respectively. The final dropout rate was 16.2%. The mean PCS and MCS scores at the beginning of treatment were low, thus showing the poor health situation of TB patients. The mean PCS scores at the beginning of treatment, end of I.P., and end of treatment were (36.1), (44.9), and (48), respectively. Moreover, the mean MCS score at the beginning of treatment, end of I.P., and end of treatment were (35.1), (42.2), and (44.3), respectively. The result shows that significant increases are observed at the end of I.P. for PCS and MCS because of the treatment and slight changes at the end of C.P. Despite this finding, the MCS score remains below the normal range (47), thus indicating a significant risk of depression among TB patients. Furthermore, general linear repeated measure ANOVA was performed for selected variables, to examine the changes of PCS and MCS over time. It was found that Alhodiah city, chewing khat habit, stigmatization, and duration of treatment more than six months were greatly associated with low mean MCS score of TB patient, indicating great risk of depression which may result in poor treatment outcome. TB patients in Yemen were found to have poor QoL, with a significant likelihood of depression. Highly risk depression was found among TB patients in Alhodiah city, khat chewers, stigmatization and having a duration of treatment more than 6 months. Therefore, additional efforts should be made to improve their QoL because it may affect the final clinical outcome of patients.


Functional Optimization of Broadly Neutralizing HIV-1 Antibody 10E8 by Promotion of Membrane Interactions.
The 10E8 antibody targets a helical epitope in the membrane-proximal external region (MPER) and transmembrane domain (TMD) of the envelope glycoprotein (Env) subunit gp41 and is among the broadest known neutralizing antibodies against HIV-1. Accordingly, this antibody and its mechanism of action valuably inform the design of effective vaccines and immunotherapies. 10E8 exhibits unusual adaptations to attain specific, high-affinity binding to the MPER at the viral membrane interface. Reversing the charge of the basic paratope surface (from net positive to net negative) reportedly lowered its neutralization potency. Here, we hypothesized that by increasing the net positive charge in similar polar surface patches, the neutralization potency of the antibody may be enhanced. We found that an increased positive charge at this paratope surface strengthened an electrostatic interaction between the antibody and lipid bilayers, enabling 10E8 to interact spontaneously with membranes. Notably, the modified 10E8 antibody did not gain any apparent polyreactivity and neutralized virus with a significantly greater potency. Binding analyses indicated that the optimized 10E8 antibody bound with a higher affinity to the epitope peptide anchored in lipid bilayers and to Env spikes on virions. Overall, our data provide a proof of principle for the rational optimization of 10E8 via manipulation of its interaction with the membrane element of its epitope. However, the observation that a similar mutation strategy did not affect the potency of the first-generation anti-MPER antibody 4E10 shows possible limitations of this principle. Altogether, our results emphasize the crucial role played by the viral membrane in the antigenicity of the MPER-TMD of HIV-1.IMPORTANCE The broadly neutralizing antibody 10E8 blocks infection by nearly all HIV-1 isolates, a capacity which vaccine design seeks to reproduce. Engineered versions of this antibody also represent a promising treatment for HIV infection by passive immunization. Understanding its mechanism of action is therefore important to help in developing effective vaccines and biologics to combat HIV/AIDS. 10E8 engages its helical MPER epitope where the base of the envelope spike submerges into the viral membrane. To enable this interaction, this antibody evolved an unusual property: the ability to interact with the membrane surface. Here, we provide evidence that 10E8 can be made more effective by enhancing its interactions with membranes. Our findings strengthen the idea that to elicit antibodies similar to 10E8, vaccines must reproduce the membrane environment where these antibodies perform their function.