Monomer conversion, microhardness, internal marginal adaptation, and shrinkage stress of bulk-fill resin composites.
To evaluate degree of conversion (DC), Knoop microhardness (KHN), internal marginal adaptation (IA), and polymerization shrinkage stress (PS) of one conventional and four bulk-fill composites. Bulk-fill composites tested were Surefil SDR (SDR), Filtek Bulk-Fill (FBF), Tetric EvoCeram Bulk-Fill (TEC), and EverX Posterior (EXP). The conventional composite Herculite Classic (HER) was tested using both incremental and bulk-fill insertion techniques. Standardized Class I preparations (4-mm-depth) were made in extracted molars and restored with each product system (N=5). After 1-week wet storage, restorations were cross-sectioned and DC and KHN were evaluated at four depths (1, 2, 3, and 4mm) using confocal Raman spectroscopy and KHN techniques, respectively. Epoxy resin replicas of restorations were evaluated using scanning electron microscopy for IA. PS was determined using composite bonded to acrylic rods attached to a universal testing machine (N=5). Within bulk-fill products, only SDR and FBF demonstrated similar DC at all depths, and KHN values did not statistically differ among depths, except for TEC. Neither placement method nor depth affected KHN or DC, except the DC of HER bulk-fill at 4mm. Incrementally layered HER, and bulk-fills SDR and TEC demonstrated the lowest proportion of internal gaps. Highest and lowest PS values were measured for EXP and TEC, respectively. DC with depth was not uniform among all bulk-fill materials, although no difference in KHN was found. Higher PS correlated positively with higher proportion of interfacial gaps. The incremental technique using conventional composite showed reduced gap formation.


Dual-action benefits: global (action-inherent) and local (transient) sources of action prepotency underlying inhibition failures in multiple action control.
Previous research has shown that the simultaneous execution of two actions (instead of only one) is not necessarily more difficult but can actually be easier (less error-prone), in particular when executing one action requires the simultaneous inhibition of another action. Corresponding inhibitory demands are particularly challenging when the to-be-inhibited action is highly prepotent (i.e., characterized by a strong urge to be executed). Here, we study a range of important potential sources of such prepotency. Building on a previously established paradigm to elicit dual-action benefits, participants responded to stimuli with single actions (either manual button press or saccade) or dual actions (button press and saccade). Crucially, we compared blocks in which these response demands were randomly intermixed (mixed blocks) with pure blocks involving only one type of response demand. The results highlight the impact of global (action-inherent) sources of action prepotency, as reflected in more pronounced inhibitory failures in saccade vs. manual control, but also more local (transient) sources of influence, as reflected in a greater probability of inhibition failures following trials that required the to-be-inhibited type of action. In addition, sequential analyses revealed that inhibitory control (including its failure) is exerted at the level of response modality representations, not at the level of fully specified response representations. In sum, the study highlights important preconditions and mechanisms underlying the observation of dual-action benefits.


Maneuvering for advantage: the genetics of mouse susceptibility to virus infection.
Genetic studies of host susceptibility to infection contribute to our understanding of an organism's response to pathogens at the immunological, cellular, and molecular levels. In this review we describe how the study of host genetics in mouse models has helped our understanding of host defense mechanisms against viral infection, and how this knowledge can be extended to human infections. We focus especially on the innate mechanisms that function as the host's first line of defense against infection. We also discuss the main issues that confront this field, as well as its future.


Role of PAX-8, CD5, and CD117 in distinguishing thymic carcinoma from poorly differentiated lung carcinoma.
To determine if PAX-8, CD5, and CD117 can differentiate thymic carcinoma from poorly differentiated lung carcinoma. Archived cases of thymic (n=13) and poorly differentiated lung (n=15) carcinoma were analyzed for intensity and proportion of expression of PAX-8, CD117, and CD5. PAX-8 was positive in 69.2% of thymic and 5.8% of lung carcinomas. CD117 was positive in 84% of thymic and 26.6% of lung carcinomas. A total of 53% of thymic and none of the lung carcinomas were positive for CD5. Forty-six percent, 53%, and 69% of thymic carcinomas were dual positive for combinations of CD5/PAX-8, CD117/CD5, and CD117/PAX-8, respectively. None of the lung carcinomas were dual positive. Positivity for any 2 of the 3 markers was seen in 84% of thymic and none of the lung carcinomas. Triple positivity was seen in 53% of thymic carcinomas. Adding PAX-8 to CD117 and CD5 increases the diagnostic yield for thymic carcinoma.


Ecological regime shifts enhanced the contribution of microplastics to the burial of polycyclic aromatic hydrocarbons by sediments.
Ecological regime shifts and contamination of polycyclic aromatic hydrocarbons (PAHs), and microplastics (MPs) were found in many waters. How ecological regime shifts influence the contribution of microplastics to the burial of PAHs in sediments is unclear. Sediment cores in the largest lagoon (Lagoon Pinqing) of China were used to address this issue. Regime shifted from phytoplankton dominance to macrophyte dominance in the late 1970s in Lagoon Pinqing. The factor affecting the contribution of microplastics to the burial of PAHs in sediments varied from total phosphorus to total nitrogen during the periods from 1965 to 1970s, and from 1970s to 1990s. Phytoplankton dominated from the late 1990s to 2017. The increased aromaticity of sediment organic matter induced by regime shifts enhanced this contribution in this period. This contribution varied from 0 to 67.2%, influenced by the regime shifts in different periods. This contribution for the PAHs with moderate hydrophobicity was more susceptible to regime shifts than other PAHs. Our results suggested the contribution of microplastics to the burial of PAHs by sediments could be influenced by ecological regime shifts, and driven by various factors.


The linear system theory's account of behavior maintained by variable-ratio schedules.
The mathematical theory of linear systems, which has been used successfully to describe behavior maintained by variable-interval schedules, is extended to describe behavior maintained by variable-ratio schedules. The result of the analysis is a pair of equations, one of which expresses response rate on a variable-ratio schedule as a function of the mean ratio requirement (n) that the schedule arranges. The other equation expresses response rate on a variable-ratio schedule as a function of reinforcement rate. Both equations accurately describe existing data from variable-ratio schedules. The theory accounts for two additional characteristics of behavior maintained by variable-ratio schedules; namely, the appearance of strained, two-valued (i.e., zero or very rapid) responding at large ns, and the abrupt cessation of responding at a boundary n. The theory also accounts for differences between behavior on variable-interval and variable-ratio schedules, including (a) the occurrence of strained responding on variable-ratio but not on variable-interval schedules, (b) the abrupt cessation of responding on occurrence of higher response rates on variable-ratio than on variable-interval schedules. Furthermore, given data from a series of variable-interval schedules and from a series of concurrent variable-ratio variable-interval schedules, the theory permits quantitative prediction of many properties of behavior on single-alternative variable-ratio schedules. The linear system theory's combined account of behavior on variable-interval and variable-ratio schedules is superior to existing versions of six other mathematical theories of variable-interval and variable-ratio responding.


Erodible thermogelling hydrogels for localized mitochondrial transplantation to the spinal cord.
We developed a thermal-gelling, erodible hydrogel system for localized delivery of viable mitochondria in vivo, as well as labeled transplanted mitochondria with specific dyes and/or genetically modified mitochondria tagged with red fluorescence protein (RFP). We also employed cell lines to optimize a hydrogel composed of methylcellulose and hyaluronic acid designed to preserve bioenergetics while facilitating mitochondrial release. We further investigated how transplantation of allogeneic or xenogeneic mitochondria into respective cell lines affects host cellular metabolism, as measured by MTS assay. We found that 70% of mitochondria are released from the hydrogel within 20 min at 37 °C, that the respiratory capacity of hydrogel-released mitochondria over 60 min was greater than those without gel, and that MTR-labeling of mitochondria is not indelible. RFP-tagged transgenic mitochondria isolated from modified SH-SY5Y human neuroblastoma cells showed effective uptake into both naïve SH-SY5Y cells and rat PC-12 cells, notably when released from hydrogel. The hydrogel both protected the mitochondria at physiological conditions in vitro while solidifying and diffusing within 60 min locally in situ. To assess metabolic effects, both cell lines were transplanted with different concentrations of SH-SY5Y or PC-12 cell line-derived mitochondria and all resulted in significant increases in metabolism at 6- and 24-hour after transplantation. Alternatively, transplanted mitochondria at highest concentration from rat brain and spinal cord tissues reduced metabolic activities after 24-hour. Along with hydrogel refinements, we are further investigating whether such metabolic changes are due to alterations in cell proliferation or the number of exogenous mitochondria incorporated into individual host cells.


Contaminants in two West Greenland caribou populations.
Two caribou populations in West Greenland were sampled and the kidneys, liver and muscle analyzed for contaminants, including aluminum, arsenic, cadmium, copper, lead, mercury, selenium and zinc. Although close in proximity, the two populations are topographically separated by an ice cap, which creates different climates and vegetation types in each region. Contaminant levels reflected the differing diets of the two caribou populations. To the south in the wetter lichen-rich region, caribou had significantly more aluminum, arsenic, cadmium, lead, mercury, selenium and zinc, likely due to atmospheric deposition on lichens. To the north in the dry desert steppe where grasses predominate, caribou had higher levels of copper. Cows collected in late winter had significantly less hepatic copper, lead and mercury if pregnant, indicating placental transfer of these elements. Our results suggest that hepatic copper levels <200 μg g(-1) dry weight may result in copper depletion in pregnant cows and hepatic mercury concentrations above 0.5 μg g(-1) dry weight may negatively affect fertility in caribou cows. Hepatic mercury levels were negatively correlated with cow body weight, suggesting an adverse effect on body condition. Element concentrations found in tissues from these caribou are not considered to be of a health concern for those consuming this traditional food.


Production of rhamnolipids by Pseudomonas aeruginosa.
Pseudomonas aeruginosa produces glycolipidic surface-active molecules (rhamnolipids) which have potential biotechnological applications. Rhamnolipids are produced by P. aeruginosa in a concerted manner with different virulence-associated traits. Here, we review the rhamnolipids biosynthetic pathway, showing that it has metabolic links with numerous bacterial products such as alginate, lipopolysaccharide, polyhydroxyalkanoates, and 4-hydroxy-2-alkylquinolines (HAQs). We also discuss the factors controlling the production of rhamnolipids and the proposed roles this biosurfactant plays in P. aeruginosa lifestyle.


Voiding dysfunction in institutionalized elderly men: the influence of previous prostatectomy.
Voiding problems, either retention or incontinence, affect a majority of institutionalized elderly patients. Although impaired cerebral function is the dominant cause, those patients who had undergone prior transurethral prostatectomy were more vulnerable to the development of voiding dysfunction than those who had not. Moreover, the elimination of obstruction by prostatectomy did not produce the expected shift from indwelling catheterization to condom drainage.


Electron nuclear double resonance of cytochrome oxidase: nitrogen and proton ENDOR from the 'copper' EPR signal.
Proton ENDOR resonances have been found from at least two different protons with fairly large and isotropic couplings of about 12 and 19 MHz. It is possible that such protons are attached to carbons that are one bond removed from the point of ligation to copper. A number of weakly coupled protons with anisotropic couplings have also been seen. None of the protons, either weakly or strongly coupled, appears to exchange with 2H2O. We have obtained nitrogen ENDOR from at least one nitrogen with a hyperfine coupling large enough for the nitrogen to be a ligand of copper. We have not yet demonstrated experimentally ENDOR characteristic of the copper nucleus itself.


Joint state and parameter estimation of the hemodynamic model by particle smoother expectation maximization method.
In this paper, we aimed for the robust estimation of the parameters and states of the hemodynamic model by using blood oxygen level dependent signal. In the fMRI literature, there are only a few successful methods that are able to make a joint estimation of the states and parameters of the hemodynamic model. In this paper, we implemented a maximum likelihood based method called the particle smoother expectation maximization (PSEM) algorithm for the joint state and parameter estimation. Former sequential Monte Carlo methods were only reliable in the hemodynamic state estimates. They were claimed to outperform the local linearization (LL) filter and the extended Kalman filter (EKF). The PSEM algorithm is compared with the most successful method called square-root cubature Kalman smoother (SCKS) for both state and parameter estimation. SCKS was found to be better than the dynamic expectation maximization (DEM) algorithm, which was shown to be a better estimator than EKF, LL and particle filters. PSEM was more accurate than SCKS for both the state and the parameter estimation. Hence, PSEM seems to be the most accurate method for the system identification and state estimation for the hemodynamic model inversion literature. This paper do not compare its results with Tikhonov-regularized Newton-CKF (TNF-CKF), a recent robust method which works in filtering sense.


[Surgical treatment of benign, premalignant and low-risk tumors of the pancreas : Standard resection or parenchyma preserving, local extirpation].
Cystic neoplasms and neuroendocrine adenomas of the pancreas are detected increasingly more frequently and in up to 50 % as asymptomatic tumors. Intraductal papillary mucinous neoplasms, mucinous cystic neoplasms and solid pseudopapillary neoplasms are considered to be premalignant lesions with different rates of malignant transformation. The most frequent neuroendocrine adenomas are insulinomas. Neuroendocrine adenomas are considered to be potentially malignant, inherent to the lesion and development is unpredictable. Standard surgical treatment for pancreatic tumors are the Kausch-Whipple resection, left hemipancreatectomy and total pancreatectomy depending on the location; however, the application of standard surgical procedures, which are usually multiorgan resections for benign, premalignant and low-risk cancers of the pancreas have to be balanced against the risk for early postoperative morbidity, hospital mortality of 1.5-7 % and loss of endocrine and exocrine pancreatic functions in 12-30 %. Tumor enucleation, pancreatic middle segment resection and duodenum-preserving total pancreatic head (DPPHR-T/S) resection are parenchyma-preserving, local resection procedures, which are associated with a low early postoperative rate of severe complications, hospital mortality up to 1.3 % and maintenance of exocrine and endocrine pancreatic functions in more than 90 %. Tumor enucleation bears the risk of pancreatic fistulas (<33 %) and a limitation is proximity to the pancreatic main duct. The main risk for pancreatic middle segment resection is early postoperative pancreatic fistulas (up to 40 %), early postoperative intra-abdominal hemorrhage and a reintervention frequency up to 15 %. The DPPHR-T/S resection is applied for cystic neoplastic lesions in 90 %, severe postoperative complications are below 15 % and the 90-day hospital mortality is 0.5 %. Pancreatic fistulas are observed in less than 20 % with a recurrence rate of <1 %. These facts and maintenance of exocrine and endocrine pancreatic functions are advantages compared with the Kausch-Whipple resection of the pancreatic head. The use of tumor enucleation, particularly for neuroendocrine tumors and pancreatic middle segment resection as well as total DPPHR resection should replace the pancreatoduodenectomy for lesions in the pancreatic head and hemipancreatectomy for lesions in the pancreatic body and tail.


Drift-Tube Ion Mobility-Mass Spectrometry for Nontargeted 'Omics.
This chapter describes the developments in drift-tube ion mobility-mass spectrometry (DTIM-MS) that have driven application development in 'omics analyses. Harnessing the additional, orthogonal separation that DTIM provides increased confidence in compound identifications as the mass spectral complexity can be reduced and mobility-derived parameters (most prominently the collision cross section, CCS) used to support identity confirmation goals for a variety of 'omics application areas. Presented within this contribution is a methodology for improving the transmission and maintaining accurate determination of drift time-derived CCS (DTCCS) for low molecular weight compounds for a typical nontargeted 'omics (metabolomics) workflow using liquid chromatography in combination with DTIM-MS.


Influence of sleep disruption on inflammatory bowel disease and changes in circadian rhythm genes.
According to clinical investigations, sleep disruption (SD) can influence the immune system and cause inflammatory bowel disease (IBD). However, the detailed effects of sleep on IBD development and progression have not been clarified. Here, we used dextran sulfate sodium (DSS) to induce colitis in mice, and then interfered with SD (day-time 8:00 a.m. to 5:00 p.m.) to explore the influence of sleep on colitis by analyzing colon length, mouse body weight, disease activity index (DAI) score, pathology detection, and infiltration of inflammatory cells with LCA immunohistochemistry analysis. Next, we detected the mRNA levels of circadian genes and related inflammatory factors, including Bmal1, CLOCK, Cry1, Cry2, Per1, Per2, Timeless, Rev-erbα, TNF-α, IL-6, and IFN-γ. Additionally, we conducted a sleep survey in IBD patients and collected colon lesion sites to detect the mRNA levels of those eight circadian genes and three inflammatory factors. We found that SD promoted the body weight decrease, increased inflammation as shown with pathological staining of the DSS animal model, and increased expression of the clock gene Cry2 in DSS-induced colitis mice. In IBD patients with active disease, the mRNA level of circadian genes Bmal1, Cry1, Cry2, and Rev-erbα in inflammatory tissues decreased significantly compared with non-inflammatory tissues.


Treadmill exercise suppressed stress-induced dendritic spine elimination in mouse barrel cortex and improved working memory via BDNF/TrkB pathway.
Stress-related memory deficit is correlated with dendritic spine loss. Physical exercise improves memory function and promotes spinogenesis. However, no studies have been performed to directly observe exercise-related effects on spine dynamics, in association with memory function. This study utilized transcranial two-photon in vivo microscopy to investigate dendritic spine formation and elimination in barrel cortex of mice under physical constrain or naive conditions, followed by memory performance in a whisker-dependent novel texture discrimination task. We found that stressed mice had elevated spine elimination rate in mouse barrel cortex plus deficits in memory retrieval, both of which can be rescued by chronic exercise on treadmill. Exercise also elevated brain-derived neurotrophic factor (BDNF) expression in barrel cortex. The above-mentioned rescuing effects for both spinognesis and memory function were abolished after inhibiting BDNF/tyrosine kinase B (TrkB) pathway. In summary, this study demonstrated the improvement of stress-associated memory function by exercise via facilitating spine retention in a BDNF/TrkB-dependent manner.


Leveraging 31 Million Google Street View Images to Characterize Built Environments and Examine County Health Outcomes.
Built environments can affect health, but data in many geographic areas are limited. We used a big data source to create national indicators of neighborhood quality and assess their associations with health. We leveraged computer vision and Google Street View images accessed from December 15, 2017, through July 17, 2018, to detect features of the built environment (presence of a crosswalk, non-single-family home, single-lane roads, and visible utility wires) for 2916 US counties. We used multivariate linear regression models to determine associations between features of the built environment and county-level health outcomes (prevalence of adult obesity, prevalence of diabetes, physical inactivity, frequent physical and mental distress, poor or fair self-rated health, and premature death [in years of potential life lost]). Compared with counties with the least number of crosswalks, counties with the most crosswalks were associated with decreases of 1.3%, 2.7%, and 1.3% of adult obesity, physical inactivity, and fair or poor self-rated health, respectively, and 477 fewer years of potential life lost before age 75 (per 100 000 population). The presence of non-single-family homes was associated with lower levels of all health outcomes except for premature death. The presence of single-lane roads was associated with an increase in physical inactivity, frequent physical distress, and fair or poor self-rated health. Visible utility wires were associated with increases in adult obesity, diabetes, physical and mental distress, and fair or poor self-rated health. The use of computer vision and big data image sources makes possible national studies of the built environment's effects on health, producing data and results that may inform national and local decision-making.


An Rrp6-like protein positively regulates noncoding RNA levels and DNA methylation in Arabidopsis.
Rrp6-mediated nuclear RNA surveillance tunes eukaryotic transcriptomes through noncoding RNA degradation and mRNA quality control, including exosomal RNA decay and transcript retention triggered by defective RNA processing. It is unclear whether Rrp6 can positively regulate noncoding RNAs and whether RNA retention occurs in normal cells. Here we report that AtRRP6L1, an Arabidopsis Rrp6-like protein, controls RNA-directed DNA methylation through positive regulation of noncoding RNAs. Discovered in a forward genetic screen, AtRRP6L1 mutations decrease DNA methylation independently of exosomal RNA degradation. Accumulation of Pol V-transcribed scaffold RNAs requires AtRRP6L1 that binds to RNAs in vitro and in vivo. AtRRP6L1 helps retain Pol V-transcribed RNAs in chromatin to enable their scaffold function. In addition, AtRRP6L1 is required for genome-wide Pol IV-dependent siRNA production that may involve retention of Pol IV transcripts. Our results suggest that AtRRP6L1 functions in epigenetic regulation by helping with the retention of noncoding RNAs in normal cells.


[Circulating tumour DNA: Current detection methods, use in radiotherapy and future development].
Recent technological developments enable the detection and quantification of circulating tumour DNA in the blood, with potentially major clinical implications, particularly for cancers treated with curative intent. Circulating tumour DNA has a potential impact before, during and after treatment. If limitations of this approach remain, requiring further development, it is important to know the principles and applications in view of the potential impact on the clinical practice. In this review, we will discuss the current detection methods, then the place of circulating tumour DNA in oncology and more particularly in radiotherapy.


Unlock the Potassium Storage Behavior of Single-Phased Tungsten Selenide Nanorods via Large Cation Insertion.
Metal chalcogenide anodes with a layered structure have been regarded as potential K-based electrochemical energy storage devices with high energy density for large-scale energy storage applications. However, their development is impeded by the slow K-ion transport kinetics and poor structural stability. In this work, the energy-storage behavior is investigated first and decisively associated them with the capacity-degradation of the promising layer-structured WSe2 from an integrated chemical and physical point of view. Then, a single-phased WSe2 with pre-intercalated high K content (SP-Kx WSe2 ) is designed to overcome the capacity-degradation issue fundamentally. Theoretical calculations clarify the beneficial effect of K-ions inside the interlayer of WSe2 on boosting its electrochemical performance, including increasing the electronic conductivity, promoting the K-ion diffusivity, and improving the structural stability. The novel design enables the K-ions pre-intercalated WSe2 anode material to exhibit a high reversible specific capacity of 211 mAh g-1 at 5 A g-1 and superior cycling stability (89.3% capacity retention after 5000 cycles at 1 A g-1 ). Especially, the K-ion hybrid capacitor, assembled from the anode of SP-Kx WSe2 and the cathode of porous activated carbon, delivers superior energy-density up to 175 Wh kg-1 , high power-density as well as exceptional cycling stability.


High-translucent yttria-stabilized zirconia ceramics are wear-resistant and antagonist-friendly.
To evaluate two-body wear of three zirconia ceramics stabilized with 3, 4 and 5mol% yttria and to compare their wear behavior with that of a lithium-disilicate glass-ceramic. Sixteen rectangular-shaped specimens made from three grades of zirconia ceramics and a lithium-disilicate glass-ceramic were polished and dynamically loaded in a chewing simulator (2kg vertical load, 2.1Hz) under water at 90°C for 1.2×106 cycles (about 7 days) in the ball-on-plate mode against steatite antagonists. Surface roughness was measured before and after wear testing. Wear tracks were scanned with a non-contact 3D profilometer and super-impositions were used to determine wear loss of the antagonists. Wear surfaces were imaged by SEM. XRD and micro-Raman spectroscopy were used to characterize phase transformation and stress status in the worn and unworn areas of the zirconia ceramics. Independent of fracture toughness, strength and aging-susceptibility, the three zirconia ceramics showed a similar and limited amount of wear (∼10μm in depth) and were more wear-resistant than the lithium-disilicate glass-ceramic (∼880μm in depth). Abrasive wear without obvious cracks was observed for all investigated zirconias, whereas the glass-ceramic with a lower fatigue threshold and high susceptibility to surface dissolution exhibited significant abrasion, fatigue and corrosion wear. All three zirconia ceramics yielded a lower antagonist wear than the glass-ceramic and no significant differences were found between the zirconia ceramics. In the context of this study, high-translucent zirconia ceramics stabilized with a higher yttria content, recently introduced in the dental field, were as wear-resistant and antagonist-friendly as conventional high-strength zirconia and suitable for monolithic restorations.


The Predictive Role of Postoperative Neutrophil to Lymphocyte Ratio for 30-Day Mortality After Intracerebral Hematoma Evacuation.
To evaluate whether the postoperative neutrophil-to-lymphocyte ratio (NLR) is a prognostic marker for patients with intracerebral hemorrhage (ICH) undergoing surgical hematoma evacuation. This retrospective cohort study was conducted to identify patients with ICH who underwent hematoma evacuation between January 2013 and December 2018. Data on demographics, clinical features, laboratory tests (admission and postoperative), and imaging information were collected. The associations between variables and 30-day mortality were assessed by multivariable logistic regression analysis. The predictive power of independent predictors was evaluated by receiver operating characteristic (ROC) curve analysis. A total of 380 patients were included. Multivariable analysis identified admission Glasgow Coma Scale score (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.53-0.70; P < 0.001) and initial hematoma volume (OR, 1.01; 95% CI, 1.01-1.02; P = 0.022) were independently associated with 30-day mortality. With regard to laboratory biomarkers, postoperative NLR (OR, 1.04; 95% CI, 1.01-1.08; P = 0.014) was independently correlated with 30-day death, but admission NLR (OR, 1.00; 95% CI, 0.97-1.03; P = 0.944) was not. The best predictive cutoff point of 12.97 for postoperative NLR (area under the ROC curve, 0.606; P = 0.006) for predicting 30-day mortality was determined by ROC analysis. In patients with ICH undergoing hematoma evacuation, admission Glasgow Coma Scale score, initial hematoma volume, and postoperative NLR were independently associated with 30-day mortality. Postoperative NLR may be a prognostic marker in surgical ICH patients, and future studies are needed to confirm this finding.


Prosodic cues for morphological complexity: the case of Dutch plural nouns.
It has recently been shown that listeners use systematic differences in vowel length and intonation to resolve ambiguities between onset-matched simple words (Davis, Marslen-Wilson, & Gaskell, 2002; Salverda, Dahan, & McQueen, 2003). The present study shows that listeners also use prosodic information in the speech signal to optimize morphological processing. The precise acoustic realization of the stem provides crucial information to the listener about the morphological context in which the stem appears and attenuates the competition between stored inflectional variants. We argue that listeners are able to make use of prosodic information, even though the speech signal is highly variable within and between speakers, by virtue of the relative invariance of the duration of the onset. This provides listeners with a baseline against which the durational cues in a vowel and a coda can be evaluated. Furthermore, our experiments provide evidence for item-specific prosodic effects.


Electrophysiologic and antiarrhythmic actions of bepridil. Comparison with verapamil and ajmaline for atrioventricular reentrant tachycardia.
Bepridil (2 mg/kg intravenously) was given to 20 patients with atrioventricular (AV) reentrant tachycardia and its effects were compared with those of verapamil (0.15 mg/kg intravenously) in 8 patients and ajmaline (0.75 mg/kg intravenously) in 12. After baseline electrophysiologic measurements, the drugs were given during sustained AV reentrant tachycardia (8 patients had dual AV nodal pathways and 12 had an accessory AV pathway). Verapamil terminated AV reentrant tachycardia in 7 patients and bepridil terminated it in 6. In 8 of the patients who received ajmaline, AV reentrant tachycardia was terminated and in 6 of this group bepridil did so. Bepridil was more successful in terminating AV reentrant tachycardia in those with dual AV nodal pathways than in those with an accessory AV pathway. Bepridil slowed sinus rate by 10% (p less than 0.0001), whereas verapamil did not change it significantly. Both verapamil and bepridil administration prolonged AV nodal conduction (39% and 44%, respectively), lengthened AV nodal effective refractory period (18% and 17% respectively) and increased the Wenckebach cycle length of the AV node (24% and 25%, respectively) to a significant degree (p less than 0.05). Bepridil also lengthened atrial and ventricular effective refractory periods (p less than 0.01) and QT interval (p less than 0.0001) in the group as a whole; in those receiving ajmaline and bepridil only atrial refractoriness was significantly altered (p less than 0.05). After treatment for 3 to 5 days with oral bepridil, 19 patients underwent repeat study.(ABSTRACT TRUNCATED AT 250 WORDS)


Habitat-specific conservation priorities of multidimensional diversity patterns of amphibians in China effectively contribute to the '3030' target.
Amphibia is the most threatened animal group among all land vertebrates in the context of anthropogenic global change. Filling the conservation gaps for this taxonomic group could help achieve the ambitious target of covering 30 % of the land by 2030 ('3030' target) set by the 15-th meeting of the Conference of the Parties (COP15). In this study, we compiled the most up-to-date occurrence records and corresponding species-specific traits and phylogenies of amphibians in China (particularly those newly described in the past decade) to explore the spatial distribution patterns of multidimensional diversity (including taxonomic, functional, and phylogenetic) for different species groups (including all, endemic and threatened). Additionally, a new conservation gap index (CGI) was proposed and applied to the analysis of multi-objective conservation strategies. The results showed that the spatial distribution of taxonomic, functional and phylogenetic diversity of amphibians in China is markedly geographically diverse, with common hotspots for all three concentrated in the humid mountainous regions of southern China. The CGI, which is independent of arbitrary threshold selection and grid cell size, showed that the conservation gap for amphibians in China is largest in biomes such as tropical and subtropical moist broadleaf forests and temperate broadleaf and mixed forests. The multi-objective conservation analysis revealed that the Yangtze River basin, Pearl River basin and Southeast Basin in China have pivotal roles in achieving the '3030' target due to their high taxonomic, phylogenetic and functional diversity, relatively high proportion of threatened and endemic species, and low coverage of existing nature reserves. Notably, sustainable management of less-protected habitats, including farmlands and grasslands, can reduce the area requirement of strict protection for reaching the '3030' conservation goal. This study provides practical strategies for guiding amphibian conservation by systematically integrating multidimensional biodiversity information, habitat features and the spatial distributions of the existing natural reserves.


A case of multiple myeloma with navicular bone involvement.
Multiple myeloma is a haematological disease caused by proliferation of malignant plasma cells in bone marrow. It frequently has lytic bone lesions. However, involvement of the small bones of the hands and feet is extremely rare. We report a unique multiple myeloma patient with first recurrence in navicular bone after allogenic stem cell transplantation.


LncRNA MIR4435-2HG functions as a ceRNA against miR-125a-5p and promotes neuroglioma development by upregulating TAZ.
Expression of the TAZ gene is closely related to the prognosis of glioma patients. We hoped to find long noncoding RNAs (lncRNAs) related to TAZ and a new target for glioma treatment. TAZ-related genes were found by dual-luciferase reporter gene assay, and the correlation of each gene was analyzed by the Pearson method. Human glioma cell lines U87 MG and U251 and glioma rats were used for cytology assays, and the related genes were transfected. We conducted immunohistochemistry, RT-qPCR, Western blotting, CCK8 test, flow cytometry, transwell assays, clone formation analysis, and tumor weight measurements to verify the above relationship. We found that miR-125a-5p was closely related to the TAZ gene, and the lncRNA MIR4435-2HG was closely related to miR-125a-5p. Both MIR4435-2HG-OE and TAZ increased the expression of the TAZ gene, activated the Wnt signaling pathway, inhibited apoptosis, and promoted migration and proliferation in glioma cells. Besides, it also increased the tumor volume of gliomas in a rat model subcutaneously inoculated with glioma cells. We also found miR-125a-5p could block the effect of MIR4435-2HG-OE and TAZ. LncRNA MIR4435-2HG obstructs the functions of miR-125a-5p and promotes neuroglioma development by upregulating the TAZ gene.


Primary epithelioid sarcoma of the hard palate. A case report.
A case of primary epithelioid sarcoma of the hard palate is described with no evidence of metastases. Review of the literature revealed no other reported cases of epithelioid sarcoma at this site. The patient, a 20-year-old male negro, returned with 2 local recurrences after initial excision but with no evidence of metastases. He remains well with no evidence of disease at present. This report records a unique primary site for this tumour, and illustrates the diagnostic difficulties, both clinical and histological, which this tumour may present.


Cardiovascular and body weight regulation changes in transgenic mice overexpressing thyrotropin-releasing hormone (TRH).
Thyrotropin-releasing hormone (TRH) plays several roles as a hormone/neuropeptide. Diencephalic TRH (dTRH) participates in the regulation of blood pressure in diverse animal models, independently of the thyroid status. The present study aimed to evaluate whether chronic overexpression of TRH in mice affects cardiovascular and metabolic variables. We developed a transgenic (TG) mouse model that overexpresses dTrh. Despite having higher food consumption and water intake, TG mice showed significantly lower body weight respect to controls. Also, TG mice presented higher blood pressure, heart rate, and locomotor activity independently of thyroid hormone levels. These results and the higher urine noradrenaline excretion observed in TG mice suggest a higher metabolic rate mediated by sympathetic overflow. Cardiovascular changes were impeded by siRNA inhibition of the diencephalic Trh overexpression. Also, the silencing of dTRH in the TG mice normalized urine noradrenaline excretion, supporting the view that the cardiovascular effects of TRH involve the sympathetic system. Overall, we show that congenital dTrh overexpression leads to an increase in blood pressure accompanied by changes in body weight and food consumption mediated by a higher sympathetic overflow. These results provide new evidence confirming the participation of TRH in cardiovascular and body weight regulation.


Contemporary use and effectiveness of N-acetylcysteine in preventing contrast-induced nephropathy among patients undergoing percutaneous coronary intervention.
The aim of this study was to examine the use of and outcomes associated with use of N-acetylcysteine (NAC) in real-world practice. The role of NAC in the prevention of contrast-induced nephropathy (CIN) is controversial, leading to widely varying recommendations for its use. Use of NAC was assessed in consecutive patients undergoing nonemergent percutaneous coronary intervention from 2006 to 2009 in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium, a large multicenter quality improvement collaborative. We examined the overall prevalence of NAC use in these patients and then used propensity matching to link its use with clinical outcomes, including CIN, nephropathy-requiring dialysis, and death. Of the 90,578 percutaneous coronary interventions performed during the study period, NAC was used in 10,574 (11.6%) procedures, with its use steadily increasing over the study period. Patients treated with NAC were slightly older and more likely to have baseline renal insufficiency and other comorbidities. In propensity-matched, risk-adjusted models, we found no differences in outcomes between patients treated with NAC and those not receiving NAC for CIN (5.5% vs. 5.5%, p = 0.99), nephropathy-requiring dialysis (0.6% vs. 0.6%, p = 0.69), or death (0.6% vs. 0.8%, p = 0.15). These findings were consistent across many prespecified subgroups. Use of NAC is common and has steadily increased over the study period but does not seem to be associated with improved clinical outcomes in real-world practice.


Hemin stimulation of cAMP production in human lymphocytes.
Hemin stimulates cAMP production in human peripheral blood mononuclear cells (PBMC). The kinetics are similar to that of hormone-induced cAMP generation, namely a rapid effect followed by a desensitization phase. Several experimental findings suggest that prostaglandins do not mediate this effect. First, macrophage depleted T and B cells purified by erythrocyte-rosetting were as responsive as unfractionated PBMC to hemin. Second, indomethacin, an inhibitor of prostaglandin synthesis, and meclofenamate, a prostaglandin E2 receptor antagonist, had no effect on hemin stimulated cAMP production. In addition, propranolol, a beta-adrenergic receptor antagonist, had no effect on hemin-stimulated cAMP production. We also examined structural analogues of hemin. Among the metalloporphyrins (Fe, Ni, Co, Zn and Sn) and protoporphyrin IX tested only hemin (Fe-protoporphyrin) was active in stimulating cAMP production. No correlation was found between the ability of metalloporphyrins to stimulate cAMP production and their ability to generate H2O2. The data indicate that hemin stimulates cAMP production by directly affecting lymphocytes and that prostaglandins do not mediate this effect.


Enrichment and separation of chlorogenic acid from the extract of Eupatorium adenophorum Spreng by macroporous resin.
A simple and efficient chromatographic method for separation of chlorogenic acid from Eupatorium adenophorum Spreng extract was developed. The adsorption properties of nine macroporous resins were evaluated. NKA-II resin showed much better adsorption/desorption properties. The adsorption of chlorogenic acid on NKA-II resin at 25°C was well fitted to Langmuir isotherm model and pseudo-second-order kinetic model. The dynamic adsorption and desorption experiments were carried out on columns packed with NKA-II resin to optimize the separation process. The content of chlorogenic acid in the product increased to 22.17%, with a recovery yield of 82.41%.


Is obesity a risk factor in acute pancreatitis? A meta-analysis.
Obesity has been associated with a worse prognosis in acute pancreatitis. According to some authors, obesity favours the development of local complications, while according to other reports obese patients presented more frequently systemic complications. Few studies find a relationship between obesity and mortality in acute pancreatitis. We conducted a meta-analysis of several reports that evaluate the relationship between obesity and the outcome of acute pancreatitis in order to assess its prognostic role in this disease. A MEDLINE search was conducted from 1965 to December 2002 with search terms including obesity, body mass index (BMI) and pancreatitis. A total of 12 reports were identified. Of these, only four studies included patients with mild and severe acute pancreatitis and measured obesity by BMI. The end points of the meta-analysis were the severity of acute pancreatitis, local complications, systemic complications and mortality. Obesity was defined when BMI was > or =30 kg/m2. Pooled odds ratio (OR) and confidence intervals (CI) were calculated according to the Mantel-Haenszel method, and heterogeneity was assessed by the multiplicative inverse variance method. A total of 607 patients were evaluated. There was no heterogeneity for the variables severity, systemic complications, local complications and mortality among the included studies. Severe AP was significantly more frequent in obese patients (OR 2.6, 95% CI 1.5-4.6). Furthermore, those patients developed significantly more systemic (OR 2.0, 95% CI 1.1-4.6) and local complications (OR 4.3, 95% CI 2.4-7.9). Mortality in obese patients was only slightly higher (OR 1.3, 95% CI 0.5-3.6). Obesity is a prognostic factor favouring the development of systemic and local complications in this disease. Therefore, it should be used routinely as part of the initial assessment of the severity of a case of acute pancreatitis.


Opsoclonus in a patient with increased titers of anti-GAD antibody provides proof for the conductance-based model of saccadic oscillations.
Paucity in gamma-amino butyric acid (GABA) due to blockage in the action of glutamic acid decarboxylase (GAD), as seen in the syndrome of anti-GAD antibody, causes adult onset cerebellar ataxia, muscle rigidity, and episodic spasms. Downbeat nystagmus, saccadic dysmetria, impaired ocular pursuit, and impaired cancelation of vestibular ocular reflex are typical ocular motor deficits in patients with syndrome of anti-GAD antibody. We describe opsoclonus, in addition to downbeat nystagmus, in a patient with increased titers of anti-GAD antibody. Paucity in GABA leading to disinhibition to Purkinje target neurons at deep cerebellar and vestibular nuclei might have caused downbeat nystagmus in our patient. Anti-GAD antibody can also increase levels of glutamate the precursor of GABA and the substrate for the action of GAD. We propose that opsoclonus might be due to increased levels of glutamate and subsequent hyperexcitability of excitatory and inhibitory burst neurons leading to reverberation in their reciprocally innervating circuit.


Evolutionary pattern of protein architecture in mammal and fruit fly genomes.
Mutations, which can alter amino acid constitution, contribute greatly to protein evolution. However, little is reported of their pattern during protein structural evolution. We investigated the distribution of non-synonymous single nucleotide polymorphisms (nsSNPs) and insertions/deletions (indels) along mammal and fruit fly proteins. We found the nsSNPs (and d(N)) and indels increased in protein boundary regions, and this pattern is inversely correlated with the distribution of protein domain density. Additionally, synonymous substitutions (and d(S)) are reduced in 5' and 3' regions, indicating more variable protein boundaries, compared with central interior. All evidence suggests that the inner part of coding sequences (CDSs) is comparatively conserved, whereas the 5' and 3' regions, with higher evolution rates, are more variable. We assumed that due to greater frequencies of nsSNPs and indels in adaptive regions of CDSs it could be easier to ultimately alter, gain, or lose amino acids, thus becoming the front line of protein evolution.


Middle ear implantation: its place in the immunohistophysiology of lymphoid tissue.
The concept of immunotolerance in otological tissue grafting is presented against the background of some fundamental aspects of immunohistophysiology. Available experimental and clinical data on tympanoplasty with allografts are evaluated in relation to this phenomenon of abolished immune reactivity.


ELF1-activated FOXD3-AS1 promotes the migration, invasion and EMT of osteosarcoma cells via sponging miR-296-5p to upregulate ZCCHC3.
Osteosarcoma (OS) is a malignant carcinoma often occurring in adolescents. The critical function of long non-coding RNAs (lncRNAs) in cancer arouses increasing attention. Nevertheless, the specific function of FOXD3 Antisense RNA 1 (FOXD3-AS1) in OS has not been understood yet. In this research, FOXD3-AS1 showed strengthened level in OS specimens and cell lines, and its deficiency restrained cell migration, invasion and epithelial-to-mesenchymal transition (EMT) in OS. Then, we confirmed the interaction of FOXD3-AS1 with microRNA-296-5p (miR-296-5p) and that miR-296-5p overexpression blocked OS cell migration, invasion and EMT. Besides, miR-296-5p targeted zinc finger CCHC-type containing 3 (ZCCHC3), and FOXD3-AS1 released ZCCHC3 via sequestering miR-296-5p. Moreover, rescue assays delineated that ZCCHC3 upregulation neutralized the inhibitory effect of FOXD3-AS1 depletion on in vitro behaviors and in vivo tumorigenesis in OS. In addition, E74 like ETS transcription factor 1 (ELF1) stimulated FOXD3-AS1 transcription, and ELF1 silence-suppressed malignant phenotypes of OS cells were offset by FOXD3-AS1 upregulation. Overall, present work elucidated that ELF1-activated FOXD3-AS1 aggravated cell migration, invasion and EMT in OS via absorbing miR-296-5p to augment ZCCHC3 expression, which might provide potential guidance for researchers to find effective targets for OS treatment.


Azathioprine-induced lymphoma in a patient with Takayasu arteritis: A case report from Iraq.
Azathioprine, used for vasculitis and connective tissue diseases, carries long-term cancer risks. This case report raises awareness among healthcare providers about such risks and emphasizes the need for taking necessary precautions to avoid them while treating such diseases. We present an Azathioprine-induced lymphoma case in a 51-year-old male patient with Takayasu arteritis who presented with painless cervical swelling, itching, weight loss, and decreased appetite. This case report aims to increase awareness of the potential long-term cancer risks associated with azathioprine use in the treatment of chronic diseases.


Primary vitrectomy for rhegmatogenous retinal detachment in pseudophakic eyes: 20-gauge versus 25-gauge vitrectomy.
To report anatomical and functional outcome of 20-gauge versus 25-gauge primary pars plana vitrectomy for management of complex rhegmatogenous retinal detachment in pseudophakic eyes. Prospective single-centre randomized comparative pilot trial. Fifty patients with retinal detachment (RD) not complicated by proliferative vitreoretinopathy grade B or C, who cannot be treated with a single meridional sponge, were randomized (1:1) from November 2006 to January 2010 to either 20-gauge or 25-gauge vitrectomy as first surgical intervention and followed up over a 12-month period, evaluating change in best-corrected visual acuity, anatomical success and intraocular pressure dysregulation. Mean visual acuity improved by 0.88 (SD 0.67) from 1.22 logMAR (SD 0.63) to 0.34 logMAR (SD 0.31) in the 20-gauge group and by 0.53 (SD 0.91) from 0.86 logMAR (SD 0.73) to 0.34 logMAR (SD 0.46) in the 25-gauge group. Final anatomical success rate was 100% and primary success rate was 69% at 6 months of follow-up. In the 20-gauge group, the retina was attached after one single procedure in 18 eyes (72%) and in 21 eyes (84%) of the 25-gauge group. Two patients in the 25-gauge group had hypotony at the first postoperative day which normalized within 6 weeks. In our series, transconjunctival sutureless 25-gauge and 20-gauge vitrectomy showed comparable results in pseudophakic RD not suitable for single sponge surgery with respect to visual outcome and retinal reattachment. Postoperative hypotony does not seem to be a significant problem of transconjunctival sutureless vitrectomy.


Use of benzodiazepines, depressive symptoms and cognitive function in old age.
Benzodiazepine use is more frequently observed in depressive and cognitively impaired subjects. The temporal relation behind this association is unknown. Here, we studied whether benzodiazepine use is associated with depressive symptoms and cognitive function and what the temporal relation underlying the associations is. Within the Leiden 85-plus Study, a prospective population based study of 599 subjects aged 85 years at baseline, we assessed benzodiazepine use, depressive symptoms, and cognitive function annually during a 5-year follow-up period. Benzodiazepine users were more likely to be female, be institutionalized, and have a low education. Benzodiazepine users scored 0.76 points higher on the 15-item Geriatric Depression Scale than non-users (95% CI: 0.27-1.25, p = 0.002). They were 1.6-fold more likely to develop new depressive symptoms in 1 year when compared to non-users (95% CI: 1.05-2.55, p = 0.028). Benzodiazepine use did not associate with cognitive function, but discontinued benzodiazepine users had a 4.0 points lower Mini Mental State Examination (MMSE) score in the year before discontinuation than continued benzodiazepine users (95% CI: 1.31-6.73, p = 0.004). In old age the use of benzodiazepines is associated with depressive symptoms and the use of benzodiazepines may precede the development of depressive symptoms. Treating physicians seem to be aware of the detrimental effects of benzodiazepines on cognitive function. However, they should be cautious in prescribing a new benzodiazepine in old age and monitor elderly benzodiazepine users for development of depressive symptoms.


Clinical comparison between paclitaxel liposome (Lipusu®) and paclitaxel for treatment of patients with metastatic gastric cancer.
To compare the efficacy and safety of paclitaxel liposome (Lipusu®) with paclitaxel in combination with tegafur and oxaliplatin in treating patients with advanced gastric cancer. Patients with advanced gastric cancer receiving chemotherapy were retrospectively collected, and divided into two groups. Patients in group A received paclitaxel liposomes at a dose of 135 mg/m2 on day 1 of each cycle, and patients in group B were given paclitaxel at the same dose with the same timing. All patients received tegafur at a dose of 500 mg mg/m2 on days 1-5, and oxaliplatin at a dose of 80-100 mg/m2 on day 1 for 2 cycles (each cycle was 21 d in total). Fifty-eight patients could be evaluated for efficacy. The overall response rate was 47% in group A (14/30), and 46% in group B (13/28). Disease control rate was 73% in group A (22/30), and 71% in group B (20/28) (P>0.05). No significant differences were detected in hematologic and neurologic toxicities between the two groups (P>0.05). However, nausea, vomiting and hypersensitive reactions were significantly lower in group A than in group B (P<0.05). Paclitaxel liposomes are as effective as paclitaxel when combined with tegafur and oxaliplation in treating patients with advanced gastric cancer, but adverse reactions with paclitaxel liposomes are less common.


Management of Thygeson's superficial punctate keratitis.
Four patients had Thygeson's superficial punctate keratitis of one to 16 years' duration. One patient was completely unresponsive to topical corticosteroids, and the remaining three patients had only partial resolution of signs or symptoms while using topical corticosteroids. In all cases, rapid resolution of the epithelial lesions occurred with symptomatic relief after patching for 24 hours or after the use of therapeutic soft contact lenses. Three of the four patients have tolerated daily or extended wear of soft contact lenses accompanied by relief of both signs and symptoms. The use of therapeutic soft contact lenses may provide an alternative to topical corticosteroids in the treatment of Thygeson's superficial punctate keratitis.


Pure and doped carbon quantum dots as fluorescent probes for the detection of phenol compounds and antibiotics in aquariums.
The resulting antibiotic residue and organic chemicals from continuous climatic change, urbanization and increasing food demand have a detrimental impact on environmental and human health protection. So, we created a unique B, N-CQDs (Boron, Nitrogen doping carbon quantum dots) based fluorescent nanosensor to investigate novel sensing methodologies for the precise and concentrated identification of antibiotics and phenol derivatives substances to ensure that they are included in the permitted percentages. The as-prepared highly fluorescent B, N-CQDs had a limited range of sizes between 1 and 6 nm and average sizes of 2.5 nm in our study. The novel B, N-CQDs showed high sensitivity and selectivity for phenolic derivatives such as hydroquinone, resorcinol, and para aminophenol, as well as organic solvents such as hexane, with low detection limits of 0.05, 0.024, 0.032 and 0.013 µM respectively in an aqueous medium. The high fluorescence B, N-CQDs probes were examined using transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and UV/VIS spectroscopy. The outcomes were compared to carbon quantum dots (CQDs) previously generated from Urea.


Creating a Blueprint for the Future: Lessons Learned From Public Health Laboratories in the COVID-19 Response.
Public health laboratories have played a central role in the US response to COVID-19. Since the earliest days, myriad issues have impeded the laboratory community's ability to keep pace with the overwhelming demand for effective tests. In this article, the Association of Public Health Laboratories and a subset of its members examine the response to date and evaluate lessons learned from 4 main categories: testing surges, supplies, staffing, and regulations and policy. Within these categories, the authors offer recommendations intended both to improve the ongoing COVID-19 response and to strengthen planning for future outbreaks.


Uncertainty analysis in probabilistic design of detention rockfill dams using Monte-Carlo simulation model and probabilistic frequency analysis of stability factors.
The detention rockfill dams are of promising importance in flood control projects, due to their minimal technical requirement, low cost, minimal environmental side effects, and self-automotive operation process. However, due to the complexity of Non-Darcian flow interactions with stability and uncertainties of dam, the reliable design is a challenging topic. This study aimed to examine the effects of uncertainties in probabilistic design of these dams. We proposed a reliable design framework for detention rockfill dams with a focus on the importance of stability analysis. The effects of design uncertainty sources on the stability of dam, safety factors of overturning, sliding and bearing, along with the hydraulic performance of the dam were examined. The results of the model revealed that the uncertainties in input parameters can effectively regenerate uncertainties in the hydraulic performance ranges from - 53.54 to + 110.11%. The safety factor against the sliding (SFS) has maximum dependencies with the uncertainties ranging - 32.63 to + 87.81%. The Monte-Carlo Simulation (MCS) and fitting probability distribution functions to the safety factor histograms, and uncertainty quantifications results in 88.3%in increasing the safety factors as a reliable methodology for stability design of detention rockfill dams. Thus, the study calls for reliable, certain, and safe design of flood protection rockfill ponds. The ecological evaluation and applying more advanced uncertainty assessment methods remains a future research direction of the current study. The developed framework can be used to acquire future detention rockfill dam design/modeling requirements for reliability-based design optimization as a simulation-optimization model coupled whit MCS.


Electronic consultation accessibility influence on patient assessments: A case-control study with user-generated tags of physician expertise.
In online health communities (OHCs), patients often list their physicians' expertise by user-generated tags based on their consulted diseases. These expertise tags play an essential role in recommending the match of physicians to future patients. However, few studies have examined the impact of the accessibility of e-consults on patient assessments using marking of the physicians' expertise in OHCs. This study aims to investigate what are the patient assessments of the physicians' expertise if they have e-consult accessibility. Through a case-control study, this article examined the effect of e-consult accessibility on patient-generated tags of physician expertise in OHCs. With data collected from the Good Doctor website, the samples consisted of 9841 physicians from 1255 different hospitals widely distributed in China. The breadth of voted expertise (BE) is measured by the number of consulted disease-related labels marked by a physician's served patients (SP). The volume of votes (VV) is measured by the number of a physician's votes given by the SP. The degree of voted diversity (DD) is measured by the information entropy of each physician's service expertise (labeled and voted by patients). The data analysis of e-consult accessibility is conducted by estimating the average treatment effect on the DD of physicians' expertise. For the BE, its mean was 7.305 for the case group of physicians with e-consults accessible (photo and text queries), while the mean was 9.465 for the control for physicians without e-consults. For the VV, its mean was 39.720 for the case group, while the mean was 84.565 for the control. For the DD, its mean on patient-generated tags was 2.103 for the case group, which is 0.413 lower than the control group. The availability of e-consults increases the concentration on physician expertise in the patient-generated tags. e-Consults reinforce the increment of the already-received physician expertise (reflected in tags), reducing the tag information diversity.


In Vitro Approaches for Investigating the Influence of MIF on Leukocyte-Endothelial Cell Interactions Under Flow Conditions.
The exit of leukocytes from the bloodstream into inflamed sites involves a sequence of interactions with vascular endothelial cells, in which leukocytes, moving rapidly in flowing blood, first tether and roll on the endothelial surface before arresting and then transmigrating across the endothelial barrier. Examining the mechanisms of these interactions in human systems has involved the use of in vitro flow chamber assays, using a variety of cells and immobilized molecules as adhesive substrata. Here we describe how to perform these assays using human umbilical vein endothelial cells and human leukocytes.


Antenatal Phenotype of Desbuquois Dysplasia.
Desbuquois dysplasia (DBQD) is an uncommon, autosomal recessive disorder with multiple joint dislocations. It is caused by pathogenic variants in CANT1 (calcium-activated nucleotidase 1) [NM_001159773.2]. This study adds to the scant data of nine reported antenatal phenotypes of DBQD. The present paper describes two unrelated consanguineous families with antenatal features of lethal skeletal dysplasia. The defining radiological changes were identified in only one patient who presented in the late second and third trimesters. Solo exome sequencing was performed and two previously reported homozygous variants c.896C>T (p.Pro299Leu) in patient 1 and c.902_906dup (p.Ser303fs*20) in patient 2 were identified. This study highlights the fetal presentations in DBQD and adds to its phenotypic spectrum. A complete clinical workup, including fetal autopsy and radiographs is essential to confirm the diagnosis of lethal skeletal dysplasia. Molecular diagnosis remains the diagnostic modality to define the causative variant. A definitive diagnosis is essential to inform management and offer reproductive care.


Blunted HPA Axis Activity in Suicide Attempters Compared to those at High Risk for Suicidal Behavior.
Studies looking at the relationship of the hypothalamic-pituitary-adrenal (HPA) axis to suicidal behavior and its risk factors, such as depression, childhood abuse, and impulsive aggression, report inconsistent results. These studies also do not always differentiate between subjects who go on to attempt suicide, suicidal subjects who never attempted suicide, and non-suicidal subjects with psychiatric disorders. In this study, we examined cortisol responses to an experimental stressor, the Trier Social Stress Test (TSST), in 208 offspring of parents with mood disorder. Offspring suicide attempters showed lower total cortisol output (β=-0.47, 95% CI (-0.83, -0.11), p=0.01) compared with offspring with suicide-related behavior (SRB) but never attempted, non-suicidal offspring, and a healthy control group. The result remained significant even after controlling for sex, age, race, ethnicity, site, socio-economic status, and hour of the day when the TSST was conducted. Suicide attempters also showed lower baseline cortisol before the TSST (β=-0.45, 95% CI (-0.74, -0.17), p=0.002). However, there were no significant differences between the groups on cortisol reactivity to stress (β=4.5, 95% CI (-12.9, 22), p=0.61). Although subjects with suicide attempt and SRB have similar clinical and psychosocial characteristics, this is the first study to differentiate them biologically on HPA axis indices. Blunted HPA axis activity may increase risk for suicide attempt among individuals with psychopathology by reducing their ability to respond adaptively to ongoing stressors. These results may help better identify subjects at high risk for suicidal behavior for targeted prevention and intervention efforts.


Kappa-opioid receptor binding varies inversely with tumor grade in human gliomas.
Opioid agonists can inhibit cell proliferation in various neural tumor cell lines, including rat gliomas. Because opioid antimitogenic effects are mediated by opioid receptors, it was of interest to the authors to determine opioid receptor levels in human brain tumors. Specimens obtained at craniotomy from 30 patients with glioma and nonneoplastic brain disorders were evaluated for their kappa-opioid receptor binding. Kd and Bmax values were estimated from homologous competition binding curves with the kappa1-selective radioligand [3H]U69,593. Receptor binding density was greatest in nonneoplastic brain tissue, less in Grade 2 and 3 astrocytoma, and least in glioblastoma multiforme. These results suggest that opioid receptor-based stratification of grade may have clinical utility in distinguishing glioblastoma multiforme from lower grade astrocytomas, and thereby may facilitate diagnosis and treatment.


Stakeholder engagement in the development of an upper extremity outcome measure for children with rare musculoskeletal conditions.
Upper extremity (UE) involvement is prevalent in 73% of individuals with arthrogryposis multiplex congenita (AMC), yet no AMC-specific outcome measure exists. When developing a measure specific to a population with a rare musculoskeletal condition, clinicians' and patients' perspectives and involvement is a crucial and necessary step. This study sought to determine the most clinically useful items for an outcome measure of UE function for children with AMC as defined by caregivers and clinicians. To ensure the perspectives and needs of caregivers of children with AMC and clinicians were considered in the development of the UE measure for AMC, a Nominal Group technique (NGT) with caregivers of children with AMC (phase 1) followed by a three-round survey with clinicians (phase 2) were carried out. Phase 1: Eleven individuals participated in the nominal group technique and identified 32 items. The most important items were Picking up an object (n = 11), Eating (n = 10), Reaching mouth (n = 10), Getting out of bed (n = 10). Phase 2: Invitations to participate to an online survey was sent to 47 experts in the field of AMC, 20 participants completed round 1, 15 completed round 2 and 13 completed round 3. Throughout the survey, participants were asked about movement required to screen the UE, essential domains to be included in the measure, establishing a scoring guide and identifying tasks associated with joint motion and position. A preliminary version of an UE AMC-specific outcome measure was developed with the help of caregivers' perspectives and expert opinions.


Procalcitonin and C-reactive Protein Levels as Biomarkers to Determine Gastrointestinal Involvement in Adult Henoch-Schönlein Purpura Patients.
To investigate the association of procalcitonin (PCT) and C-reactive protein (CRP) levels with gastrointestinal (GI) involvement in adult HSP patients. A retrospective study using clinical data and serum PCT and CRP levels from 121 adult HSP patients was performed. The proportion of male HSP patients with GI involvement was significantly higher compared to patients without GI involvement. PCT and CRP levels in adult HSP patients with GI involvement were higher compared to patients without GI involvement (P < 0.05); Among the patients with GI involvement, those with GI hemorrhage had significant higher PCT and CRP levels (P < 0.05); the median PCT value was lower compared to the threshold value for systemic infection. There was a positive correlation between PCT and CRP levels in HSP patients with GI involvement and GI bleeding (P < 0.05). ROC curve analysis demonstrated that the PCT and CRP cutoff levels of 0.07 ng/ml and 29.35 mg/L respectively had optimal diagnostic efficacy for GI bleeding in adult HSP patients. Elevated serum PCT and CRP levels were significantly associated with GI involvement in adult HSP patients, especially for GI bleeding. PCT levels correlated well with CRP levels.


Effect of cell isolation methods and drug concentration on the use of the Differential Staining Cytotoxicity (DiSC) assay with solid tumours.
The Differential Staining Cytotoxicity (DiSC) in vitro drug sensitivity assay has been tested in solid tumours obtained from surgery. Various enzyme cocktails have been used for disaggregating cells for times ranging from 1-72 h. Collagenase (0.5%) plus DNase (0.002%) was chosen as producing the best results when incubated for 3 h at 37°C. This cocktail was also used for 24, 48 and 72 h incubations. Cell suspensions so produced were sometimes cleaned up by centrifugation on a Nycodenz gradient. Breast tumours were more often successfully cultured (67%) compared to gastrointestinal (43%) or other tumours (34%). Results with 6 drugs tested in 10 or more tumours suggested that in general, higher drug concentrations should be used when testing solid tumours as opposed to leukaemias in the DiSC assay.


Simultaneous high-performance liquid chromatographic analysis of free carotenoids and carotenoid esters.
High-performance liquid chromatography using a non-aqueous reversed phase with gradient elution on C18 columns is a powerful tool for investigating the carotenoid composition of natural samples, e.g., flower petals, and for the simultaneous detection of carotenoids of the widest possible polarity range (xanthophylls, diones, hydrocarbons and carotenoid esters). The comparison of sample extracts submitted or not to saponification allows the presence of carotenoid esters to be revealed through the appearance of the corresponding free hydroxycarotenoids. The gas chromatographic analysis of the fatty acids after alkaline hydrolysis of esters provides further confirmation. In most cases, peaks of various carotenoids were identified by comparison with standards. The wavelengths of the visible absorbance maxima of the chromatographed carotenoids as obtained on-line by the stop-flow method in the eluent system and off-line in carbon disulphide are reported. The esters appear to constitute the main carotenoid fraction in flower petals.


Emergency department medication history taking: current inefficiency and potential for a self-administered form.
Emergency Departments (EDs) struggle with obtaining accurate medication information from patients. Our aim was to estimate the proportion of urban ED patients who are able to complete a self-administered medication form and record patient observations of the medication information process. In this cross-sectional study, we consecutively sampled ED patients during various shifts between 8 AM and 10 PM. We created a one-page medication questionnaire that included a list of 49 common medications, categorized by general indications. We asked patients to circle any medications they took and write the names of those not on the form in a dedicated area on the bottom of the page. After their visit, we asked patients to recall which providers had asked them about their medications. Research staff approached 354 patients; median age was 45 years (interquartile range 29-53 years). Two hundred and forty-nine (70%) completed a form, 61 (17%) were too ill, 19 (5%) could not read it, and 25 (7%) refused to participate. Excluding refusals, 249 of 329 (76%; 95% confidence interval 70-80%) were able to complete the form. Of 209 patients recalling their visit, 180 (86%) indicated that multiple providers took a history, including 103 in which every provider did so, and 9 (4%) indicated that no provider took a medication history. The process of ED medication information transfer often involves redundant efforts by the health care team. More than 70% of patients presenting for Emergency care were able to complete a self-administered medication information form.


Absolute Configuration of Alkaloids from Uncaria longiflora through Experimental and Computational Approaches.
The structure elucidation of three new alkaloids named isoformosaninol (1), formosaninol (2), and longiflorine (3), isolated from the leaves of Uncaria longiflora var. pteropoda (Miq.) Ridsdale, along with their biosynthetic pathways are discussed. Their absolute structures were determined through a combination of physical data interpretation and quantum chemical calculations using the time-dependent density functional theory (TDDFT) method.


Plasma levels of 8-methoxypsoralen after bath-PUVA for psoriasis: relationship to disease severity.
Plasma levels of 8-methoxypsoralen (8-MOP) were determined by high-pressure liquid chromatography in 19 patients with psoriasis who were receiving bath-PUVA treatment, at different time points after the psoralen bath. The levels of 8-MOP varied between < 5 ng/ml (lower limit of detection) and 34 ng/ml, and we found a relationship between the plasma psoralen levels and the severity of the disease.


Evaluating Pharmacist's Patient Care Process in Shiraz, using a newly-validated questionnaire: The First Report from Iran.
The Pharmacists' Patient Care Process (PPCP) as one of many inter-related foundations for the delivery of evidence-based and outcomes-focused patient care has a positive trend in academic literatures in the world. Unfortunately, PPCP has not been establish well in community pharmacies in Iran, yet. This study was performed to explore the current status of the provision and perception toward patient care services and finally evaluate professional competency of pharmacists about PPCP implementation, in both patients and pharmacist's perspectives. A cross-sectional study was conducted using two self-administrated Likert-based questionnaires_ one for pharmacists and another one for patients. In total, 121 pharmacists and 479 patients participated to the study. Questionnaires were distributed and collected in the Shiraz during the Oct 2017 till Jun 2018. Obtained data were analyzed through the statistical package for social sciences (SPSS) version 25. In addition, the competency to PPCP implementation was classified to three groups _good, moderate, and weak _ based on achieving ≥75%, 50%-75%, and <50% of the dimensions' total score, respectively. The pharmacist's age range was 23-76 years (mean age: 40.61±12.85 years). Their Competency to PPCP implementation was good (43.8%), moderate (52%), and just 4% weak. Patient's response to PPCP was 11.2% good, 50.7% moderate and 35.6% weak. Besides promotion of public awareness about PPCP, improvement of pharmacists' motivation toward these services seems necessary. In addition, the introduced instrument may be useful for practice of pharmacists, but it should be used cautiously until it is tested among clients of pharmacies known to provide all levels of pharmacy care within pharmacy stores.


TAKE10: A community approach to teaching compression-only CPR to high-risk zip codes.
Bystander cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrest (OHCA) has the ability to improve patient survival. However, the rates at which CPR occurs are suboptimal. We hypothesized that targeted CPR training in neighborhoods with low bystander CPR and high incidence of cardiac arrests would increase the incidence of bystander CPR for adult OHCA. This study is a descriptive observation and analysis of the TAKE 10 program, which recruited City of Austin and Travis County residents to teach fellow community members compression-only CPR. Twelve zip codes in Austin and Travis County were identified as "high-risk," based on low bystander CPR rates and high incidences of cardiac arrest. Data was collected on bystander CPR for OHCA over the study period of July 2008 to September 2013. Incidence of cardiac arrest and bystander CPR were calculated yearly and overall. Over the study period, a total of 11,242 community members completed compression-only CPR training. While there was no significant difference in the number of individuals trained in high-risk zip codes compared to the other zip codes (High-Risk [n±sd] 263±235; General 212±193; p-value 0.46), the amount of people trained in the high-risk zip codes did trend upwards over the study period. Additionally, there was an increase in percent of bystander CPR per eligible cardiac arrest in the high-risk zip codes (2009: [n±sd] 0.28±0.34 to 2013: 0.39±0.28). Targeted compression-only CPR training in high-risk neighborhoods may be associated with increased bystander CPR rates over time.


Recombinant proteins that trigger production of antibodies recognizing botulinum neurotoxin while not possessing sequences of this toxin.
Sequences mimicking epitopes of pathogens can be used as effective tools for fast development and characterization of pathogen-specific antibodies. To demonstrate this, we used phage displays and isolated a number of short peptides mimicking epitopes of botulinum neurotoxin serotype A (BoNT/A). Presented data suggest that some of these peptides mimic linear epitopes while others mimic structural epitopes of BoNT/A. All tested peptides retained their ability to be recognized by BoNT/A-specific antibodies even when transferred into new carrier proteins. We demonstrated how such new hybrids can be used for fast conversion of pathogen-specific serums into panels of mono-epitope specific antibodies. We also demonstrated that hybrid proteins carrying multiple isolated peptides can be used as a substitute for BoNT/A in immunization studies and triggers production of BoNT/A-specific antibodies.


Manganese porphyrin given at symptom onset markedly extends survival of ALS mice.
Mice that overexpress the human Cu,Zn superoxide dismutase-1 mutant G93A develop a delayed and progressive motor neuron disease similar to human amyotrophic lateral sclerosis (ALS). Most current studies of therapeutics in these mice to date have involved administration of agents long before onset of symptoms, which cannot currently be accomplished in human ALS patients. We examined the effects of the manganese porphyrin AEOL 10150 (manganese [III] tetrakis[N-N'-diethylimidazolium-2-yl]porphyrin) given at symptom onset and found, in three separate studies, that it extended the survival after onset up to 3.0-fold. Immunohistochemical analysis of spinal cord for SMI-32, an abundant protein in motor neurons, indicated better preservation of motor neuron architecture, less astrogliosis (glial fibrillary acidic protein), and markedly less nitrotyrosine and malondialdehyde in porphyrin-treated spinal cords relative to vehicle-treated mice. These results show that the catalytic antioxidant AEOL 10150 provides a pronounced therapeutic benefit with onset administration and is, therefore, a promising agent for the treatment of ALS.


The ketogenic diet in two paediatric patients with refractory myoclonic status epilepticus.
We describe two patients with refractory myoclonic status epilepticus treated with the ketogenic diet. Between May 1, 2014 and January 1, 2015, two patients who met the diagnostic criteria for refractory myoclonic status epilepticus, seen at our department, were placed on the ketogenic diet and followed for a minimum of six months. One patient with myoclonic epilepsy of unknown aetiology had a 75-90% seizure reduction, and the other with progressive encephalopathy associated with myoclonic epilepsy had a 50% seizure reduction. Both patients retained good tolerability for the diet. At the last control, one patient had isolated myoclonias and EEG showed occasional generalized spike-and-polyspike waves; the patient is now successfully attending kindergarten. The quality of life of the second patient improved significantly. In both cases, the number of antiepileptic drugs was reduced. The ketogenic diet is an effective and well-tolerated treatment option for patients with refractory myoclonic status epilepticus and should be considered earlier in the course of treatment.


Scrotal masses caused by meconium peritonitis: prenatal sonographic diagnosis.
Although uncommon, meconium peritonitis can present with a scrotal mass. Usually calcified, this mass may be the initial or only sign of meconium peritonitis. We detected such a scrotal mass prenatally with ultrasound.


Bone Mineral Density as a Predictor of Subsequent Wrist Fractures: Findings From the Women's Health Initiative Study.
Wrist fractures are common among postmenopausal women. Associations of bone mineral density (BMD) and 10-year predicted risk of major osteoporotic fracture (MOF) with wrist fractures are poorly characterized. The objective was to examine associations between the Fracture Risk Assessment Tool (FRAX)-predicted risk of MOF, BMD, BMD change, and wrist fracture. This was a prospective observational study with a mean follow-up of 8.5 years. This study included 40 US centers. A total of 11 392 participants from the Women's Health Initiative BMD Cohort aged 50-79 years at baseline were included in this study. None. The goal was to measure incident wrist fracture. A FRAX-predicted MOF risk ≥9.3% identified 17% of the women aged <65 years who subsequently experienced wrist fracture. Each one standard deviation lower BMD was associated with higher wrist fracture risk, with adjusted hazard ratio (95% confidence interval) of 1.66 (1.42-1.93) for femoral neck (FN) BMD and 1.45 (1.28-1.64) for lumbar spine BMD. Compared with FN BMD T score ≥ -1.0, wrist fracture adjusted hazard ratios (95% confidence interval) were: 1.51 (1.06-2.16) for a T score between -1.01 and -1.49; 1.93 (1.36-2.72) for T score between -1.50 and -1.99; 2.52 (1.77-3.60) for a T score between -2.00 and -2.49; and 2.65 (1.78-3.95) for a T score ≤ -2.5. Decrease in FN BMD between baseline and year 3 was associated with increased risk of subsequent wrist fracture; however, change in lumbar spine BMD was not. Lumbar spine and femoral neck BMDs were associated with incident wrist fracture, but the FRAX threshold recommended to identify screening candidates did not identify the majority of women who subsequently experienced wrist fracture. Improved understanding of determinants of wrist fractures is warranted.


Production of intergeneric somatic hybrids between round kumquat (Fortunella japonica Swingle) and 'Morita navel' orange (Citrus sinensis Osbeck).
Intergeneric somatic hybrids between embryogenic callus-derived protoplasts of round kumquat (Fortunella japonica Swingle) and 'Morita navel' orange (Citrus sinensis Osbeck) were produced by electrofusion. Among the eight different fusion strains obtained, six showed normal morphology, whereas the remaining two showed malformation. All the regenerated plants were intermediate in leaf morphology and had thick and round leaves, which are typical characteristics of polyploids. Ploidy analyses by flow cytometry and chromosome counting in root-tip cells revealed that these plants are amphidiploid (2n=4x=36). Hybridity of the fusion products was confirmed by random amplified polymorphic DNA and cleaved amplified polymorphic sequence (CAPS) analyses. Furthermore, analyses of chloroplast (cp) and mitochondrial (mt) DNA by CAPS showed that these somatic hybrids contained cp- and mt-DNA of round kumquat without recombination in the regions analyzed.


Signalling by O2-. and NO.: how far can either radical, or any specific reaction product, transmit a message under in vivo conditions?
With regard to the stability of the NO. radical as a chemical entity, it is without doubt able to serve as an intra- as well as an intercellular messenger. The radical O2-., in contrast, does not seem to be suited to far-range signalling in the vascular system. Its short chemical half-life, which is limited by the presence of various reactive blood constituents to below 50 ms, results in a free diffusion path length of less than 40 microns, i.e. only the distance between just a few cells. While accelerated 'downstream' transport by arterial blood may help to extend the action sphere, there is no possibility for O2-. to serve as a signal in an upstream direction. The estimates presented, however, do not invalidate arguments for a possible role of superoxide anions in intra- or pericellular signalling phenomena. Cross-talk between NO.- and O2-.-dependent signal routes, e.g. by peroxynitrite formation, is unlikely to be a relevant process under the conditions which prevail in the vascular system.


Evaluation of the antinociceptive properties from Brillantaisia palisotii Lindau stems extracts.
Brillantaisia palisotii Lindau is a plant belonging to Acanthaceae family and it is widely found in tropical regions. Some species of this family are used in the folk medicine to treat several disorders, mainly those that involve analgesic processes. In this work it was evaluated antinociceptive activities of dichloromethane, ethyl acetate and n-butanol extracts obtained from Brillantaisia palisotii stems in peripheral (acetic acid-induced writhing) and central (tail flick and hot plate) analgesic models. All three extracts significantly inhibited the total number of writhing in a dose dependent manner. A spinal antinociceptive effect was observed with all three extracts and with similar patterns to all doses (1-30 mg/kg). Although ethyl acetate extract did not demonstrate supra-spinal activity, the effects observed with dichloromethane extract showed analgesic effect with all doses. The n-butanolic extract had activity only with the lowest dose (1 mg/kg). Our results indicate that all extracts from Brillantaisia palisotti stems develop peripheral and spinal analgesic activity, being the dichloromethane extract the only one with supra-spinal analgesic effect.


Synthesis and antiproliferative activity of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing the 1,8-naphthyridin-2-one moiety.
A series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing the 1,8-naphthyridin-2-one moiety were designed, synthesized and evaluated for their biological activities. The target compounds exhibited moderate to high antiproliferative activity against three cancer cell lines (A549, HepG2 and MCF-7) and several compounds (25, 27, 33, 37, 41, 43, 49 and 53) were evaluated for the activity against c-Met kinase. The most promising compound 33 (IC50 c-Met = 2.36 nM) showed excellent activity against A549, HepG2 and MCF-7 cell lines with IC50 values of 0.23 μM, 0.42 μM and 0.21 μM, respectively, which was 1.5-2.1 times of the positive control. Furthermore, compound 33 was evaluated for the activity against Flt3, PDGFR-α, PDGFR-β, c-Kit, Flt4, ALK and EGFR kinase. Structure activity relationship studies indicated that mono-EWGs (such as R2 = F) at 4-position of moiety C was a key factor in improving the antitumor activity. In addition, further research on compound 33 was mainly including concentration dependence, apoptosis (acridine orange staining), apoptosis result analyzing and molecular docking.


Potentially avoidable perinatal deaths in Denmark, Sweden and Lithuania as classified by the Nordic-Baltic classification.
To analyse which subgroups of perinatal deaths contribute most to the perinatal mortality rate in Lithuania compared with Denmark/Sweden. Comparison of all perinatal deaths in Denmark/Sweden 1991 and Lithuania 1993-1994 by the common Nordic-Baltic perinatal death classification, based on information from the medical records. The doubled perinatal mortality in Lithuania compared with Denmark/Sweden is mainly explained by a threefold increase of intrapartum and two- to fivefold increase in neonatal deaths of nonmalformed infants. The higher rate of malformed infants is partly explained by a four times higher mortality from neural tube defects. The use of a common perinatal death classification has identified categories mainly responsible for the higher rate of perinatal mortality, but further investigation of potentially avoidable factors requires further study.


Systematic Review of Interventions to Reduce Suicide Risk in Transgender and Gender Diverse Youth.
Transgender youth experience high rates of suicidal ideation and suicide attempts. This systematic review sought to examine interventions for suicide prevention in transgender children and adolescents. Literature related to suicide in the transgender population was systematically collected in accordance with PRISMA criteria. Searches identified studies with at least one suicide prevention method for participants ages 24 years or younger with gender identity and sex clearly defined. Primary outcomes include suicide-related thoughts and behaviors. A total of 1558 citations were identified with 17 articles meeting inclusion criteria. Interventions with potential effectiveness included a gender-affirming crisis hotline, medical care via interdisciplinary gender clinics, online media-based outreach, safety and connectedness in schools, and family system-based interventions. In the included studies, the overall quality of evidence was low and the risk of bias high. Further high-quality studies are needed.


Clinical application of human β-defensin and CD14 gene polymorphism in evaluating the status of chronic inflammation.
Periodontitis is a common disease that affects the periodontal tissue supporting the teeth. This disease is attributed to multiple risk factors, including diabetes, cigarette smoking, alcohol, pathogenic microorganisms, genetics and others. Human beta-defensin-1 (hBD-1) is a cationic antimicrobial peptide with cysteine-rich ß-sheets and broad-spectrum antimicrobial activity. CD14 is a protein involved in the detection of bacterial lipopolysaccharide (LPS) and has also been associated with periodontitis. This study investigates the single nucleotide polymorphic (SNP) region, -1654(V38I), of the human beta-defensin-1 (hBD-1) gene as well as the -159 region of the CD14 gene in subjects with chronic periodontitis. Blood samples from periodontally healthy subjects and periodontitis patients were obtained. DNA was extracted from the blood and was used to perform restriction digest at the polymorphic G1654A site of DEFB1 with the enzyme HincII. The polymorphic site 159TT of CD14 was digested with the enzyme AvaII. Enzyme-linked immunosorbent assay (ELISA) was performed on soluble samples to determine the protein expressions. The control and patient groups expressed 35% and 38% 1654 A/A genotype of DEFB1, respectively. The A allele frequency of the control group was 40%, while the patient blood group was 54%. The mean hBD-1 protein levels of the control and patient samples were 102.83 pg/mL and 252.09 pg/mL, respectively. The genotype distribution of CD14 in healthy subjects was 16% for C/C, 26% for T/T and 58% for C/T. The genotype frequencies of CD14 in periodontitis patients were 10% for C/C, 43% for T/T and 47% for C/T. The CD14 protein expression determined by ELISA showed a mean protein level of the control samples at 76.28ng/mL and the patient blood samples at 179.27ng/mL with a p value of 0.001.Our study demonstrated that patients suffering from chronic periodontitis present more commonly with the 1654A/A genotype on the DEFB1 gene and the 159T/T genotype on the CD14 gene. This study purely investigated the association between periodontitis and one polymorphic site on both DEFB1 and CD14 gene, with the purpose of expanding knowledge for the future development in diagnostic markers or therapeutic interventions to combat this disease.


Efficient immobilization of mushroom tyrosinase utilizing whole cells from Agaricus bisporus and its application for degradation of bisphenol A.
A simple and efficient procedure for preparation and immobilization of tyrosinase enzyme was developed utilizing whole cells from the edible mushroom Agaricus bisporus, without the need for enzyme purification. Tyrosinase activity in the cell preparation remained constant during storage at 21 °C for at least six months. The cells were entrapped in chitosan and alginate matrix capsules and characterized with respect to their resulting tyrosinase activity. A modification of the alginate with colloidal silica enhanced the activity due to retention of both cells and tyrosinase from fractured cells, which otherwise leached from matrix capsules. The observed activity was similar to the activity that was obtained with immobilized isolated tyrosinase in the same material. Mushroom cells in water were susceptible to rapid inactivation, whereas the immobilized cells maintained 73% of their initial activity after 30 days of storage in water. Application in repeated batch experiments resulted in almost 100% conversion of endocrine disrupting bisphenol A (BPA) for 11 days, under stirring conditions, and 50-60% conversion after 20 days, without stirring under continuous usage. The results represent the longest yet reported application of immobilized tyrosinase for degradation of BPA in environmental water samples.


Cell Viability and Immunogenic Function of T Cells Loaded with Nanoparticles for Spatial Guidance in Magnetic Fields.
Immune cell therapies, such as adoptive T cell therapies, are an innovative and powerful treatment option for previously non-treatable diseases. Although immune cell therapies are thought to be very specific, there is still the danger of developing severe to life-threatening side effects due to the unspecific distribution of the cells throughout the body (on-target/off-tumor effects). A possible solution for the reduction of these side effects and the improvement of tumor infiltration is the specific targeting of the effector cells (e.g., T cells) to the desired destination (e.g., tumor region). This can be achieved by the magnetization of cells with superparamagnetic iron oxide nanoparticles (SPIONs) for spatial guidance via external magnetic fields. A prerequisite for the use of SPION-loaded T cells in adoptive T cell therapies is that cell viability and functionality after nanoparticle loading are preserved. Here, we demonstrate a protocol to analyze cell viability and functionality such as activation, proliferation, cytokine release, and differentiation at a single cell level using flow cytometry.


Biomass accumulation and resource utilization in co-occurring grassland annuals.
Mediterranean-climate annuals growing on serpentine soils in central California differ greatly in their life spans and reproductive periods dependent on their access to soil moisture. The longer-lived annuals accumulate a greater lifetime biomass, have a higher total, but lower proportional, reproductive output, and produce leaves with a higher C/N ratios at the time of reproduction.


Publisher Correction: Fatty acid synthase, a novel poor prognostic factor for acute lymphoblastic leukemia which can be targeted by ginger extract.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Association study of genetic variants of the ANGPTL3 gene and susceptibility to ischemic stroke.
Stroke ranks as the third-leading cause of years of life lost worldwide. ANGPTL3 plays important roles in lipid metabolism, atherosclerosis, and occurrence of stroke. The purpose of this study was to evaluate associations of genetic variants in the ANGPTL3 gene with ischemic stroke (IS) risk. A case-control study was conducted to evaluate the associations of tag single-nucleotide polymorphisms (SNPs) of the ANGPTL3 gene and risk of IS, as well as serum lipid levels. Dual-luciferase reporter assays in the HEK293T cell line was conducted to evaluate the promoter activity of ANGPTL3 rs6690733. We found rs6690733 (C vs A: OR 1.34, 95% CI 1.13-1.59; P=0.001) and rs12563308 (C vs T: OR 0.77, 95% CI 0.64-0.93, P=0.007) were significantly associated with susceptibility to IS. Even corrected for Bonferroni adjustment, the two variants were still significant (0.007×4=0.028). Carriers of the minor allele of SNP rs6690733 had significantly higher levels of TC and LDL-C, while carriers of the minor allele of SNP rs12563308 had significantly lower levels of TC and LDL-C (all P<0.05). For rs6690733, the luciferase assay showed that promoter activity was significantly increased by 67% of plasmids containing the minor C allele compared with the major A allele in HEK293 cells. Our study revealed genetic variants of the ANGPTL3 gene could contribute to susceptibility to IS through participating in the regulation of lipid metabolism.