Quantification of pulmonary regurgitation in patients with repaired Tetralogy of Fallot by 2D phase-contrast MRI: Differences between the standard method of velocity averaging and a pixel-wise analysis.
To compare the values of pulmonary regurgitation in patients with repaired Tetralogy of Fallot quantified from two-dimensional phase-contrast data, by using a new pixel-wise analysis and the standard velocity-averaging method. Quantitative in silico and in vivo analysis. Hospital Sótero del Río. The magnetic resonance images were acquired using a Philips Achieva 1.5T scanner. Twenty-five patients with repaired Tetralogy of Fallot who underwent cardiovascular magnetic resonance imaging requested by their referring physicians were included in this study. Using a computational fluid dynamics simulation, we validated our pixel-wise method, quantifying the error of our method in comparison with the standard method. The patients underwent a standard two-dimensional phase-contrast magnetic resonance imaging acquisition for quantifying pulmonary artery flow. Pulmonary regurgitation fraction was estimated by using our pixel-wise and the standard method. The two-dimensional flow profiles were inspected looking for simultaneous antegrade and retrograde flows in the same cardiac phase. Statistical analysis was performed with t-test for related samples, Bland-Altman plots, and Pearson correlation coefficient. Estimation of pulmonary regurgitation fraction using the pixel-wise analysis revealed higher values compared with the standard method (39 ± 16% vs. 30 ± 22%, p-value <0.01). Eight patients (32%) had a difference of more than 10% between methods. Analysis of two-dimensional flow profiles in these patients revealed simultaneous antegrade and retrograde flows through the pulmonary artery during systole-early diastole. Quantification of pulmonary regurgitation fraction in patients with repaired Tetralogy of Fallot through a pixel-wise analysis yields higher values of pulmonary regurgitation compared with the standard velocity-averaging method.


Short-term reproducibility of dipyridamole-echocardiography test.
The aim of this study was to assess the short-term reproducibility of dipyridamole-echocardiography test (DET) consisting of two-dimensional echo monitoring during dipyridamole infusion (up to 0.84 mg/kg in 10 min). The diagnostic end-point of the test is the detection of new onset or worsening regional asynergy. A group of 87 patients with rest and/or effort angina performed two DETS on two consecutive days. All 60 patients with a positive DET had a positive repeat test, and the 27 negative DETs were also negative on the following day. The timing of the asynergy was also very similar between the two tests, both in patients with angina on effort (r = .93, p less than 0.01) and at rest (r = .92, p less than 0.01). In conclusion, DET has a very high short-term reproducibility regarding the presence and timing of asynergy.


Mechanistic Insights into the Preference for Tandem Binding Sites in DNA Recognition by FOXM1.
FOXM1 is an essential proliferation-associated transcription factor that controls the activation of a number of cell cycle regulatory genes. Unlike other forkhead box (FOX) transcription factors, FOXM1 has been shown to prefer binding tandem regulatory DNA sites. However, the underlying reason for such preference is not clear. Here, we showed that the tandem DNA motif, named DIV2, is widely distributed in the promoter region of FOXM1 target genes. The binding of FOXM1 on the DIV2 site differs dramatically from other sites, which is in a highly cooperative fashion, with a much enhanced thermal stability and can be clearly detected by EMSA. The crystal structure of FOXM1 in complex with the DIV2 DNA reveals that the cooperative binding is likely to be driven by intermolecular protein-protein interactions (PPIs). Further half-site spacer insertion assays showed that FOXM1 can bind another site, DIV0, in a similar manner to the DIV2 site. Given the high occurrence of the DIV2 and DIV0 sites in FOXM1 target genes, our results suggest that FOXM1 prefers tandem DNA sites to enable cooperative DNA recognition, and such binding characteristics may further confer its specificity during transcriptional regulation.


CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications.
Osteoarthritis is a prevalent age-related disease characterized by dysregulation of extracellular matrix metabolism, lipid metabolism, and upregulation of senescence-associated secretory phenotypes. Herein, we clarify that CircRREB1 is highly expressed in secondary generation chondrocytes and its deficiency can alleviate FASN related senescent phenotypes and osteoarthritis progression. CircRREB1 impedes proteasome-mediated degradation of FASN by inhibiting acetylation-mediated ubiquitination. Meanwhile, CircRREB1 induces RanBP2-mediated SUMOylation of FASN and enhances its protein stability. CircRREB1-FASN axis inhibits FGF18 and FGFR3 mediated PI3K-AKT signal transduction, then increased p21 expression. Intra-articular injection of adenovirus-CircRreb1 reverses the protective effects in CircRreb1 deficiency mice. Further therapeutic interventions could have beneficial effects in identifying CircRREB1 as a potential prognostic and therapeutic target for age-related OA.


Ratchetaxis: Long-Range Directed Cell Migration by Local Cues.
Directed cell migration is usually thought to depend on the presence of long-range gradients of either chemoattractants or physical properties such as stiffness or adhesion. However, in vivo, chemical or mechanical gradients have not systematically been observed. Here we review recent in vitro experiments, which show that other types of spatial guidance cues can bias cell motility. Introducing local geometrical or mechanical anisotropy in the cell environment, such as adhesive/topographical microratchets or tilted micropillars, show that local and periodic external cues can direct cell motion. Together with modeling, these experiments suggest that cell motility can be viewed as a stochastic phenomenon, which can be biased by various types of local cues, leading to directional migration.


The plastome reveals new insights into the evolutionary and domestication history of peonies in East Asia.
Paeonia holds considerable value in medicinal, ornamental horticultural, and edible oil industries, but the incomplete state of phylogenetic research in this genus poses a challenge to the effective conservation and development of wild germplasm, and also impedes the practical utilization of existing cultivars. Due to its uniparental inheritance and lack of recombination, the plastome (i.e., plastid genome), which is a valuable molecular marker for phylogenetic analyses, is characterized by an appropriate rate of nucleotide evolution. In this study, 10 newly assembled data and available reported data were combined to perform a comparative genomics and phylogenetics analysis of 63 plastomes of 16 Paeonia species, primarily from East Asia, which is the origin and diversity center of Paeonia. Ranging between 152,153 and 154,405 bp, most plastomes displayed a conserved structure and relatively low nucleotide diversity, except for six plastomes, which showed obvious IR construction or expansion. A total of 111 genes were annotated in the Paeonia plastomes. Four genes (rpl22, rps3, rps19 and ycf1) showed different copy numbers among accessions while five genes (rpl36, petN, psbI, rpl33 and psbJ) showed strong codon usage biases (ENC < 35). Additional selection analysis revealed that no genes were under positive selection during the domestication of tree peony cultivars whereas four core photosynthesis-related genes (petA, psaA, psaB and rbcL) were under positive selection in herbaceous peony cultivars. This discovery might contribute to the wide adaption of these cultivars. Two types of molecular markers (SSR and SNP) were generated from the 63 plastomes. Even though SSR was more diverse than SNP, it had a weaker ability to delimit Paeonia species than SNP. The reconstruction of a phylogenetic backbone of Paeonia in East Asia revealed significant genetic divergence within the P. ostii groups. Evidence also indicated that the majority of P. suffruticosa cultivars had a maternal origin, from P. ostii. The results of this research also suggest that P. delavayi var. lutea, which likely resulted from hybridization with P. ludlowii, should be classified as a lineage within the broader P. delavayi group. Overall, this study's research findings suggest that the Paeonia plastome is highly informative for phylogenetic and comparative genomic analyses, and could be useful in future research related to taxonomy, evolution, and domestication.


Sensors for detecting per- and polyfluoroalkyl substances (PFAS): A critical review of development challenges, current sensors, and commercialization obstacles.
Per- and polyfluoroalkyl substances (PFAS) are a class of compounds that have become environmental contaminants of emerging concern. They are highly persistent, toxic, bioaccumulative, and ubiquitous which makes them important to detect to ensure environmental and human health. Multiple instrument-based methods exist for sensitive and selective detection of PFAS in a variety of matrices, but these methods suffer from expensive costs and the need for a laboratory and highly trained personnel. There is a big need for fast, inexpensive, robust, and portable methods to detect PFAS in the field. This would allow environmental laboratories and other agencies to perform more frequent testing to comply with regulations. In addition, the general public would benefit from a fast method to evaluate the drinking water in their homes for PFAS contamination. A PFAS sensor would provide almost real-time data on PFAS concentrations that can also provide actionable information for water quality managers and consumers around the planet. In this review, we discuss the sensors that have been developed up to this point for PFAS detection by their molecular detection mechanism as well as the goals that should be considered during sensor development. Future research needs and commercialization challenges are also highlighted.


1,25 dihydroxyvitamin-D3 regulation of immunoglobulin production in peripheral blood mononuclear cells of patients with systemic lupus erythematosus.
Systemic Lupus Erythematosus (SLE) is a multisystem disease characterized by an increase in the secretion of autoantibodies. The mechanisms of autoantibody-induced disease have not been clarified. 1,25-Dihydroxy-vitamin D3 (1,25-D3) is known to be important in the regulation of normal human lymphocyte functions. Among its regulatory functions is the ability to inhibit mitogen-stimulated production of immunoglobulin. The experiments reported here explored the regulation of IgG production by peripheral blood mononuclear cells (PBMCs) of patients with inactive and active SLE. 1,25-Dihydroxyvitamin D3 inhibited mitogen-stimulated IgG production in cells from normal individuals and inactive SLE patients, but not spontaneous IgG production by PBMCs from active SLE patients. Addition of exogenous IL-2 (5-50 U/ml) to 1,25-D3-treated cells from all patient groups did not affect IgG production significantly under any conditions tested. The addition of IL-2 to PMBCs had no effect on IgG production in normal individuals or inactive SLE patients, but stimulated IgG production in PBMCs of active SLE patients. We conclude that the regulation of mitogen-stimulated IgG production in inactive SLE patients by 1,25-D3 and IL-2 is similar to normal individuals, but IgG production by active SLE PBMCs is unresponsive to 1,25-D3 regulation and is increased with the addition of IL-2.


Metabolic syndrome in schizophrenia - who is more to blame: FGA polypharmacy or clozapine monotherapy?
To establish the prevalence of metabolic syndrome and its parameters in group of patients with schizophrenia in polypharmacy - receiving first generation antipsychotics versus clozapine alone treated group. 48 outpatients with schizophrenia divided into two groups: the first group of 21 patients in polypharmacy with first generation antipsychotics, and the second group of 27 patients treated with clozapine alone were assessed for the presence of metabolic syndrome. We used logistic regression models to assess the relationship between metabolic syndrome and antipsychotic therapy, gender and age. Metabolic syndrome was found in 52.1% of all subjects. Compared to first generation antipsychotics polypharmacy, the monopharmacy with clozapine was associated with elevated rates of metabolic syndrome (28.6% vs. 70.4%, p=0.004). With regard to particular parameters of metabolic syndrome, the elevated plasma triglycerides were significantly more present in subjects within Clozapine group (p=0.03). Logistic regression analysis showed that female gender (p=0.004), and clozapine treatment (p=0.005) were significantly associated with metabolic syndrome. Compared to polypharmacy with first generation antipsychotics, the higher prevalence of metabolic syndrome is found in patients treated with Clozapine alone. The most prevalent metabolic disorder is dyslipidemia.


Longitudinal evaluation using the Environmental Deprivation Scale-questionnaire with felons.
The status of 32 felons was examined two years after they had completed the Environmental Deprivation Scale. Those who violated parole or probation scored significantly differently from those who remained on parole or probation or had been released. The questionnaire score could be helpful to identify which felons require additional supervision or treatment. Larger samples and extended evaluation are necessary for firm conclusions.


Reinforcement schedule thinning following functional communication training: review and recommendations.
This paper extends the Tiger, Hanley, and Bruzek (2008) review of functional communication training (FCT) by reviewing the published literature on reinforcement schedule thinning following FCT. As noted by Tiger et al. and others, schedule thinning may be necessary when the newly acquired communication response occurs excessively, to the extent that reinforcing it consistently is not practical in the natural environment. We provide a review of this literature including a discussion of each of the more commonly used schedule arrangements used for this purpose, outcomes obtained, a description of methods for progressing toward the terminal schedule, and a description of supplemental treatment components aimed at maintaining low levels of problem behavior during schedule thinning. Recommendations for schedule thinning are then provided. Finally, conceptual issues related to the reemergence of problem behavior during schedule thinning and areas for future research are discussed.


Shift from darbepoetin-α to continuous erythropoietin receptor activator decreases serum aluminium concentration in patients on hemodialysis.
The response of erythropoietic stimulating agents (ESA) in uremic patients may be associated with the changes of biochemical parameters, metal elements and inflammation status during the shift from one ESA to another. We compared changes in above mentioned factors after switching from darbepoetin-α (DPO) 20μg weekly for 10 weeks to continuous erythropoietin receptor activator (CERA) 100μg monthly for 10 weeks in uremic patients on hemodialysis. The haematocrit (Hct), metal elements and inflammation status are the primary outcome. Subjects included 54 patients without transfusion or bleeding or additional ESAs. Responders (IR, n=36) were defined as patients with an increase in Hct after the swtich. Although there was no significant difference in overall mean Hct after the switch (p=0.135), there are significantly greater mean number of red blood cells (RBC) (p=0.006), higher platelet numbers (p=0.001), larger RBCs (p=0.017) and higher creatinine (p=0.04) and total cholesterol (T-CHOL) (p=0.003) levels. Mean overall aluminium (Al) level decreased significantly (p=0.001). C-reactive protein (CRP) also decreased (p=0.016). The overall LDH increased (p=0.049) and potassium decreased significantly (p=0.036), which indicating active erythropoiesis. The calcium (Ca) level was significantly higher (p=0.034) and phosphate was significantly lower (p=0.028) after the shift. Although there was no significant increase in overall levels of parathyroid hormone (PTH) after the shift (p=0.061), but the pre-shift and post-shift PTH level was significantly higher in IRs than in non-IRs (p=0.003 and p=0.027, respectively). IRs had a significantly lower initial T-CHOL (p=0.03) and initial CRP (p=0.012) than non-responders, which may be related to lower inflammation. We found the shift from DPO to CERA results in lower Al levels, a reduced inflammatory response, and an increase in RBC number and PTH level in uremic patients on hemodialysis.


How orexin signals bias action: Hypothalamic and accumbal circuits.
Survival-maximizing, well-timed actions are a key responsibility of the brain. Hypothalamic neurons containing neurotransmitters orexins/hypocretins are important players in this process. Individuals without orexin neurons display inappropriately-timed transitions between arousal states, and other behavioural abnormalities including increased risk-taking. Deciphering neural circuits through which orexin neurons control brain states and behavior thus illuminates brain mechanisms of context-appropriate actions. This review outlines and puts into broader context recent examples of orexin circuit analyses in the lateral hypothalamus (LH) and the nucleus accumbens (NAc), two brain regions clasically implicated in context-appropriate actions. In the LH, orexin neurons excite GAD65-expressing neurons. The LH(GAD65) neuron excitation induces elevated locomotor activity, while inhibition of LH(GAD65) neuron natural activity depresses voluntary locomotion. The orexin → LH(GAD65) circuit may therefore assist in creating the drive to run. In the NAc shell region, orexin axons excite D2 neurons (dopamine-inhibited neurons expressing dopamine type-2 receptor). NAc(D2) cell activation increases risk-avoidance behaviors, while NAc(D2) cell inhibition reduces risk-avoidance. The excitatory orexin → NAc(D2) circuit may thus assist in reducing risk-taking, and oppose the inhibitory VTA(dopamine) → NAc(D2) circuit during computation of risk appetite. Neural computation in these local and long-range orexin circuits may thus assist in generating risk-avoiding locomotor responses to stressors known to activate orexin neurons, such as body energy depletion or potential external threats. A model is proposed where orexin-opposing, inhibitory inputs acting on the orexin target neurons may context-specifically channel orexin-induced brain excitation towards particular sets of actions.


On scattering effects for volume sources in low-energy photon spectrometry.
In this study, different aspects of the Compton scattering inside volume sources are illustrated using experimental approach and Monte Carlo simulation. For the low-energy range (below 100 keV) scattered events represents around 30% of the whole spectrum. Influence of the source-detector geometry is discussed. The scattering effects induce strong differences in spectrum shape for different geometrical conditions. This should influence efficiency transfer factors. A new approach is proposed, including the scattered events, to avoid complex peak area determination.


5-lipoxygenase and FLAP.
The initial steps in the biosynthesis of leukotrienes from arachidonic acid are carried out by the enzyme 5-lipoxygenase (5-LO). In intact cells, the helper protein 5-LO activating protein (FLAP) is necessary for efficient enzyme utilization of endogenous substrate. The last decade has witnessed remarkable progress in our understanding of these two proteins. Here we review the molecular and cellular aspects of the expression, function, and regulation of 5-LO and FLAP.


[TOTAL KNEE ARTHROPLASTY IN YOUNG PATIENTS WITH OSTEOARTHRITIS].
To review the current situation of total knee arthroplasty (TKA) used in young patients with osteoarthritis. The recent literature in the treatment of osteoarthritis with TKA in young patients was extensively reviewed. The characteristics, curative effect, and postoperative satisfaction degree of TKA in young patients were analyzed and summarized. Young patients have longer life expectancy and higher activity, which may lead to much higher expectation of the TKA. Comparing with elderly patients, young patients obtain equal or better effectiveness after TKA, but they are likely to not be satisfied with the effects because of low survival rate of the prosthesis. At present, continuous development of implant design, prosthesis material, and operation technique are in progress to reduce wear, hence to prolong the implant survivorship so as to meet the desire of young patients. However, the studies of the big samples and long-term follow-up are required to confirm the clinical advantages of such developments. With the trend of TKA in young patients, surgeons should have a good understanding of the patients' demands, select suitable prosthesis and give appropriate preoperative


Gastric Staple Line Reinforcement With Ligation Clips for Hemostasis in Laparoscopic Sleeve Gastrectomy.
In Pakistan and worldwide, there is a lack of literature on the role of ligation clips in controlling hemostasis in laparoscopic sleeve gastrectomy. ligation clips are being used to secure hemostasis and act as staple line reinforcement to prevent intra-operative and postoperative bleeding. Data can be utilized to reflect the role of staple line reinforcement with ligation clips so as to guide surgeons about its safety and efficacy. This retrospective observational study was conducted at the Shalamar Hospital, Lahore, Pakistan, and included 120 patients. The patients' demographic parameters, BMI, intra-operative and postoperative bleeding in terms of hematemesis, melena, and fall in hemoglobin (Hb) postoperatively were compared to preoperative Hb and recorded. One hundred and twenty cases of laparoscopic sleeve gastrectomy (LSG) were included with a mean age of 44.77±12.05 years. The mean BMI was 52.06±13.85 preoperatively. The mean drop in hemoglobin was 0.04±0.26 with a p-value of 0.07, which is statistically insignificant. Among 120 cases, two (1.7%) patients reported episodes of melena, and four (3.3%) patients reported hematemesis. Postoperative hypotension was recorded in six (5%) patients and eight (6.7%) patients had postoperative tachycardia. This study shows ligation clip application along the staple line is an effective means of hemostasis similar to suture application.


Biochemical and morphological differences between CA125 isolated from healthy women and patients with epithelial ovarian cancer from Tunisian population.
Analysis of the structure of CA125 is essential for determining the physiological role of this significant tumor antigen. The objectives of this study were: (1) to identify the characteristics of the CA125 isolated from healthy and patient women with epithelial ovarian cancer; and (2) to determine the ferning structure of this antigen. The cancer-derived CA125 antigen (cCA125) purified by gel filtration and affinity chromatography (Concanavalin A) was run on SDS-PAGE and examined using light microscopy and compared with healthy-derived CA125 antigen (hCA125). Both purified antigen cCA125 and hCA125 showed a high molecular mass (> 2,000 kDa) with high mannose glycans. The ferning patterns related to cCA125 and hCA125 revealed distinct differences in the patterns of arborescence. The ferning morphology of cCA125 antigen was denser than that of hCA125 antigen making an obvious difference between cCA125 and hCA125, with respect to length, branching and distribution of crystals. The current study provides the first evidence for a potential functional link between CA125 and its structure which, in the light of a comparison between cCA125 and hCA125, might proof to be of significant biomedical importance in the future.


Microcystic adnexal carcinoma of the head and neck: Characteristics, treatment, and survival statistics.
Studies on microcystic adnexal carcinoma (MAC) survival rates have been limited. This effort examines the association of patient demographics, treatment modalities, and tumor stage with overall survival (OS) in patients with MAC of the head and neck. All cases of MAC with primary sites of the skin of the head and neck, confirmed histologically, and diagnosed from 2004 to 2016 in the National Cancer Database, were analyzed. We utilized Kaplan-Meier and Cox proportional-hazard models to analyze the characteristics and survival outcomes of the 415 cases that met the criteria. The mean age of diagnosis was 63.8 years (SD ±15.8). Mean OS was 10.8 years with 5- and 10-year OS being 81.0% and 68.0%, respectively. Women were more frequently affected (59.0%; P < .001). Stand-alone primary site surgery was the most common treatment (81.4%): 15.9% of patients were treated with postexcision radiation therapy (RT). 18.3% were treated with RT with or without surgery and/or chemotherapy. RT was independently associated with a decreased hazard of death (HR = 0.23; P = .044). MAC of the head and neck disproportionately affects whites, is more common in women, and has the potential to metastasize. Surgical excision is the commonest treatment; our study shows benefit from judicious RT.


Congenital epulis: a case report.
An unusual case of a double congenital epulis involving the alveolar mucosa of both the maxilla and mandible is reported. The authors discuss the clinical picture, histological findings, etiology and treatment of this rare lesion.


Regulation of pyruvate kinase in Reuber H35 hepatoma cells by insulin and fructose.
1. Kinetic and immunological studies as well as electrophoretic behaviour indicated that pyruvate kinase in Reuber H35 hepatoma cells is of the M2-type. 2. Addition of 0.1 microM insulin or 2 mM fructose to the incubation medium for 72 hr increased the activity of the M2-type pyruvate kinase in Reuber H35 hepatoma cells by 103 and 25% respectively. 3. Incorporation studies with [3H]leucine followed by immunoprecipitation showed that the apparent rate of synthesis of the M2-type pyruvate kinase was increased by both insulin and fructose. 4. Degradation studies indicated that the addition of insulin and fructose to the incubation medium increased the half-life of the M2-type pyruvate kinase from 4.8 to 8.6 and 6.8 hr respectively.


A laboratory challenge model for evaluating enyterocytozoon hepatopenaei susceptibility in selected lines of pacific whiteleg shrimp Penaeus vannamei.
Here we report for the first time a laboratory challenge model for Enterocytozoon hepatopenaei (EHP) to determine the difference of two Specific Pathogen Free (SPF) lines of Penaeus vannamei shrimp. These lines were experimentally challenged using EHP-infected fecal strings as inoculum. Real-time PCR and histopathology assays were performed to confirm EHP infection and evaluate differences in EHP susceptibility in the two genetic lines screened. Although the histopathology of the hepatopancreas tissue showed EHP lesions in both challenged groups, the histological lesions were more pronounced in one of the SPF lines. Quantitative PCR results revealed that animals displaying less hepatocellular damage have lower EHP load compared to animals displaying more pronounced pathological changes. There was no significant difference in final survival at 36 days post-infection in these lines with survival ranging between 80 and 100%. The data showed that mortality as an endpoint metric is not a suitable parameter to determine genetic susceptibility to EHP. Instead, histopathological changes in hepatopancreas, EHP load of the same tissue, and growth retardation would be better metrics to screen EHP susceptibility in P. vannamei. The results show the feasibility of screening genetic lines of P. vannamei for EHP resistance/tolerance using fecal string as an inoculum and, assessing histopathological changes, EHP load, and weight as indicators of resistance.


Step-growth polymerization of supracolloidal chains from patchy micelles of diblock copolymers.
The formation of supracolloidal chains from the patchy micelles of diblock copolymers bears a close resemblance to traditional step-growth polymerization of difunctional monomers in many aspects, including chain-length evolution, size distribution, and initial-concentration dependence. Thus, understanding the colloidal polymerization based on the step-growth mechanism can offer potential control over the formation of supracolloidal chains in terms of chain structure and reaction rate. We analyzed the size evolution of supracolloidal chains of patchy micelles of PS-b-P4VP by investigating a large number of colloidal chains visualized in SEM images. We varied the initial concentration of patchy micelles to achieve a high degree of polymerization and a cyclic chain. To manipulate the polymerization rate, we also changed the ratio of water to DMF and adjusted the patch size by employing PS(25)-b-P4VP(7) and PS(145)-b-P4VP(40). We confirmed the step-growth mechanism for the formation supracolloidal chains from patchy micelles of PS-b-P4VP. Based on this mechanism, we were able to achieve a high degree of polymerization early in the reaction by increasing the initial concentration and form cyclic chains by diluting the solution. We also accelerated colloidal polymerization by increasing the ratio of water to DMF in the solution and patch size by using PS-b-P4VP with a larger molecular weight.


CD1a and bound lipids drive T-cell responses in human skin disease.
In addition to serving as the main physical barrier with the outside world, human skin is abundantly infiltrated with resident αβ T cells that respond differently to self, infectious, microbiome, and noxious stimuli. To study skin T cells during infection and inflammation, experimental biologists track T-cell surface phenotypes and effector functions, which are often interpreted with the untested assumption that MHC proteins and peptide antigens drive measured responses. However, a broader perspective is that CD1 proteins also activate human T cells, and in skin, Langerhans cells (LCs) are abundant antigen presenting cells that express extremely high levels of CD1a. The emergence of new experimental tools, including CD1a tetramers carrying endogenous lipids, now show that CD1a-reactive T cells comprise a large population of resident T cells in human skin. Here, we review studies showing that skin-derived αβ T cells directly recognize CD1a proteins, and certain bound lipids, such as contact dermatitis allergens, trigger T-cell responses. Other natural skin lipids inhibit CD1a-mediated T-cell responses, providing an entry point for the development of therapeutic lipids that block T-cell responses. Increasing evidence points to a distinct role of CD1a in type 2 and 22 T-cell responses, providing new insights into psoriasis, contact dermatitis, and other T-cell-mediated skin diseases.


Development and optimisation of a high-performance liquid chromatographic assay for tioconazole and its potential impurities. I. Selection of separation conditions.
Statistical mixture design techniques have been utilized to develop an isocratic high-performance liquid chromatographic separation of 1-(2- [(2-chloro-3-thienyl)-methoxy]-2-(2,4-dichlorophenyl)ethyl)- 1H-imidazole (tioconazole) and its potential impurities. By using suitable quality criteria such as reduced plate height, peak asymmetry and selectivity for the interrogation of chromatograms the variables producing best column efficiency and greatest selectivity have been identified. The optimum separation for these variables has been located by the sequential simplex approach and confirmed by response surface mapping.


Effect of parasocial relationship on tourist's destination attitude and visit intention.
Along with the rapid development of the Internet, the form of destination marketing is becoming increasingly innovative and diverse. Celebrity endorsement via social media, as an effective marketing strategy, has been widely used by various tourism companies to attract and engage with their customers. Previous studies have investigated the various aspects of such endorsement (e.g. the effect of endorser's attributes) in different contexts (e.g. Hotel, Restaurant, Airline). However, little research has focused on the influence of the tourists' parasocial relationship with endorsers on destination marketing. Accordingly, the current study aims to explore the role of parasocial relationships on tourists' destination attitude and visit intention. This study adopted quantitative method and conducted Partial Least Square-Structural Equation Modelling (PLS-SEM) for data analysis. 498 valid questionnaires were collected from Weibo (One of China's most popuar social media platforms). Results suggested that endorser's credibility positively influenced follower's parasocial relationship (p<0.001), which in turn positively influenced destination attitude and visit intention (p<0.001). Additionally, the parasocial relationship significantly mediated the relationship between credibility and destination attitude as well as visit intention (p<0.001). The emerging trend of celerbity endorsement via live-streaming makes tourism destination marketing more diverse and even effective. Through exploring the underlying mechanism of celebrity endorsement, this study can provide destination marketers with insights about how to build and strengthen the tourist's attitude and visit intention towards destiantion by developing their parasocial relationships with endorsers. This study also adds to the literature of using Partial Least Square-Structural Equation Modelling (PLS-SEM) in tourism and hospiatlity research.


Characterization and Complete Genome Sequences of Three N4-Like Roseobacter Phages Isolated from the South China Sea.
Three bacteriophages (RD-1410W1-01, RD-1410Ws-07, and DS-1410Ws-06) were isolated from the surface water of Sanya Bay, northern South China Sea, on two marine bacteria type strains of the Roseobacter lineage. These phages have an isometric head and a short tail, morphologically belonging to the Podoviridae family. Two of these phages can infect four of seven marine roseobacter strains tested and the other one can infect three of them, showing relatively broader host ranges compared to known N4-like roseophages. One-step growth curves showed that these phages have similar short latent periods (1-2 h) but highly variable burst sizes (27-341 pfu cell(-1)). Their complete genomes show high level of similarities to known N4-like roseophages in terms of genome size, G + C content, gene content, and arrangement. The morphological and genomic features of these phages indicate that they belong to the N4likevirus genus. Moreover, comparative genomic analysis based on 43 N4-like phages (10 roseobacter phages and 33 phages infecting other lineages of bacteria) revealed a core genome of 18 genes shared by all the 43 phages and 38 genes shared by all the ten roseophages. The 38 core genes of N4-like roseophages nearly make up 70 % of each genome in length. Phylogenetic analysis based on the concatenated core gene products showed that our phage isolates represent two new phyletic branches, suggesting the broad genetic diversity of marine N4-like roseophages remains.


Trace metals as markers for historical anthropogenic contamination: Evidence from the Peshawar Basin, Pakistan.
Trace element concentrations in the youngest Holocene sedimentary archives, historical mining, and archaeological sites are reliable indicators for historical anthropogenic contamination. The Pleistocene-Holocene strata and the overlying archaeological sites of the Peshawar Basin, NW Pakistan provide sedimentary archives to explore historical anthropogenic controls on the distributions of trace elements. The basin with 2500 y of human civilization was sampled using archaeological trenches at Gor Khuttree and Hund, and six sections of youngest Pleistocene-Holocene strata along river banks. Geochemical analysis of high-resolution samples were conducted for both the lacustrine-floodplain sediments and archaeological sites. Results from various horizons of the archaeological sites provide signals for anthropogenic control on the distribution of As, Zn, Cu, Mo, Pb, Hg, Ag, and Au during the Meghalayan Stage of Holocene that gain progressive strength since the 18th century. The geochemical proxies negate direct mining of Cu-Pb and Zn in the area. The consistent, anthropogenic Ag and Au contribution to the system throughout the basin's archaeological history is a significant finding. When correlated against the anthropogenic mercury contamination, it appears that Hund was a major silver-gold panning site throughout its known history whereas Gor Khuttree was the major silver-gold processing center. The Peshawar Basin anthropogenic signals contribute to widespread European early Anthropocene signals at around 2000 BP related to the Greek and Roman mining. Signals during the Hindu Shahi period correlate well with the Medieval period mining and smelting peak signals observed in Europe and China. Hg, Ag, and Au concentrations in the area since the start of the 19th century CE correlates to the start of industrialisation. During the mid-20th century, these geochemical signals from the Gor Khuttree reflect anthropogenic contributions to the local system and correlate to the suggested base of a formalised Anthropocene.


N-acetylcysteine for the prevention of contrast-induced nephropathy in patients with pre-existing renal insufficiency or diabetes: a systematic review and meta-analysis.
To identify benefit of N-acetylcysteine (NAC) on patients with pre-existing renal insufficiency or diabetes. NAC administration is a common method for prevention of contrast-induced nephropathy (CIN). Nevertheless, its benefit on patients with pre-existing renal insufficiency or diabetes remains uncertain and controversial. Randomized controlled trials (RCTs) to evaluate the efficacy of NAC for the prevention of CIN in patients with pre-existing renal insufficiency or diabetes were searched from the databases of MEDLINE, EMBASE, and Cochrane library. Pooled odds ratio (OR) with 95% confidence interval (95% CI) were calculated using fixed-effects model by the Mantel-Haenszel test. Twenty RCTs involving 3466 subjects (1756 assigned to NAC and 1710 assigned to the control) were included in the pre-existing renal dysfunction group. Pooled analysis suggested a significant reduction in CIN among this group (OR, 0.76; 95% CI, 0.61-0.93; p = 0.008). However, the nine trials comparing NAC versus control among patients with diabetes (NAC, 367 subjects; control, 358 subjects) showed no benefit of NAC for prevention of CIN (OR = 0.87; 95% CI, 0.58-1.30; p = 0.50). No significant heterogeneity was detected (p = 0.07; I2 = 34% for the group of pre-existing renal dysfunction; p = 0.40; I2 = 5% for the group of diabetes). Our results suggest that NAC decreases the incidence of contrast-induced nephropathy among patients with pre-existing renal insufficiency. The benefit was not existed in patients with diabetes.


Tennessee antigen: the predictive value of preoperative and postoperative assays in large-bowel cancer.
Twenty-nine of 31 patients bearing resectable colorectal cancers had elevated levels of serum Tennessee antigen in comparison with only eight of 31 patients for carcinoembryonic antigen. This high detection rate is, however, of limited value since the level of serum Tennessee antigen is not specific for the presence of malignancy. There appeared to be no relationship between the level of preoperative serum Tennessee antigen and subsequent prognosis. Furthermore, in only nine of 31 patients did the serum Tennessee antigen level fall after removal of all macroscopic cancer. There also appeared to be no relationship between the level of serum TennaGen at three months after resection and subsequent prognosis. These findings are in contrast to estimations of serum carcinoembryonic antigen.


The transfer of maternal IgE and other immunoglobulins specific for Trichostrongylus colubriformis larval excretory/secretory product to the neonatal lamb.
The transference of immunoglobulins from six New Zealand Romney ewes to their lambs was examined. Immunoglobulin levels were determined in ewe plasma, colostrum and lamb plasma shortly after birth and before the lambs fed, in lamb plasma 2 days after birth, and lamb plasma, ewe plasma and milk 30 days after parturition. Levels of total IgE, and IgE, IgG1, IgG2, IgM, and IgA with specificity for Trichostronglus colubriformis third stage larval secretory/excretory products (TcL3E/S) were determined. Mean levels of total IgE were three times higher in colostrum than in parturient ewe plasma while only trace amounts were detected in milk at 30 days after birth (107.7, 34.3, and 0.2U ml(-1), respectively, differences between means P< or =0.01). Mean total IgE in lamb plasma rose from being undetectable before suckling to levels comparable to those of the ewes by 2 days after birth (21.7U ml(-1)) and then declined to low levels by 30 days (0.4U ml(-1)). Total IgE levels in lamb plasma were significantly correlated with levels in ewe plasma and colostrum (r=0.91, P< or =0.01; r=0.96, P< or =0.003, respectively). The transference of TcL3E/S-specific IgE, IgG1 and IgA was substantial with mean levels of these antibodies in lamb plasma at 2 days comparable to that in parturient ewe plasma (absorbance levels in lamb plasma of 0.283, 0.537, and 0.334, respectively). Proportionally less maternal IgM and IgG2 appeared to be transferred to the lambs (absorbance of 0.112 and 0.081, respectively). Levels of TcL3E/S-specific IgE and IgG1 in lamb plasma at 2 days were significantly correlated with levels in parturient ewe plasma and colostrum (r=0.89 and 0.82, 0.85 and 0.96; all P< or =0.05, respectively). These results indicate that IgE is concentrated in ewe colostrum and that substantial amounts of maternal IgE are transferred to lambs via colostrum. Further, the results suggest that humoral immunity against gastro-intestinal nematode parasites and potentially other parasites in colostrum-fed lambs may approximate that of the ewe. The implications of the transference of humoral immunity through colostrum in ruminants for the passive protection and the development of active immunity against parasites remains to be fully explored.


Pharmacokinetics of chloroquine: saliva and plasma levels relationship.
The use of saliva levels as an alternative to plasma levels in monitoring chloroquine therapy was studied in five healthy volunteers. Subjects took two (250 mg) tablets of chloroquine diphosphate (300 mg chloroquine base) with 200 ml of water. Saliva and blood samples were collected at intervals over 6 days. Plasma was separated from blood samples after centrifugation while saliva samples were centrifuged to remove mucoid sediments. Both the plasma and saliva samples were analysed for chloroquine by a combination of thin-layer chromatography and spectrophotometry. Regression analysis was used to determine the correlation between saliva and plasma chloroquine levels. A significant correlation (r = 0.97, p less than 0.05) was observed between saliva and plasma levels of chloroquine. The saliva: plasma concentrations ratio was found to be 0.53. From the saliva: plasma relationship, the extent of chloroquine binding to plasma proteins was estimated to be 47%. The Cmax and AUC0-6 day values obtained from saliva data was about half those from plasma, while the Tmax obtained from both fluids remained the same. The saliva clearance rate (Cls/F) of chloroquine was about twice the plasma clearance rate (Cl/F). (Cls/F: 0.46 +/- 0.051/day/kg; 0.27 +/- 0.021/day/kg). However, the predicted Cl/F (0.27 +/- 0.031/day/kg) from saliva data was in agreement with Cl/F from plasma data. This was also true of the volume of distribution. The collection of saliva for measuring chloroquine levels provides a painless, non-invasive alternative to plasma sampling, and it is useful in predicting chloroquine pharmacokinetics.


Transcervical fat injection laryngoplasty for unilateral vocal fold paralysis: an easy way to do the job.
Unilateral vocal fold paralysis resulting in glottic incompetence can cause impairment of laryngeal functions, including airway protection and phonation. The objective of this study is to present an easy new technique for harvesting and injection of abdominal fat into the vocal fold for patients with unilateral vocal fold paralysis. This is a retrospective study of patients carried out on 16 patients suffering from unilateral vocal fold paralysis resulting from different etiologies. All patients were subjected to the protocol of voice assessment pre- and postoperatively. All patients were subjected to fat injection of the paralyzed vocal fold. There was a statistically significant difference between the pre- and postoperative grade of voice parameters. Vocal fold injection using fat medializes a paralyzed vocal fold by increasing vocal fold volume. Fat injections are safe and easily mastered; and in the absence of the standard settings for fat harvesting and injection, it could be performed with minimal equipment that are readily available in any operating room.


A new case of envenomation by neotropical opisthoglyphous snake Philodryas olfersii (Lichtenstein, 1823) in Recife, State of Pernambuco, Brazil.
Human envenomation by the snakes Colubridae and Dipsadidae are reported in Brazil, and envenomation by the Opisthoglyphous snake Philodryas olfersii could be dangerous. Here, we present the second record of an envenomation by Philodryas olfersii in Pernambuco, northeast Brazil. The male victim presented with mild erythema pain, paraesthesia, local numbness, and swollen lymph nodes. The symptoms were similar to those of a pit viper bite, and disappeared completely after 15 days.


Co-designing implementation strategies for the WALK-Cph intervention in Denmark aimed at increasing mobility in acutely hospitalized older patients: a qualitative analysis of selected strategies and their justifications.
Selecting appropriate strategies to target barriers to implementing interventions represents a considerable challenge in implementation research and practice. The aim was to investigate what categories of implementation strategies were selected by health care practitioners and their managers in a co-design process and how they justified these strategies aimed at facilitating the implementation of the WALK-Cph intervention. The study used a qualitative research design to explore what implementation strategies were selected and the justifications for selecting these strategies. Workshops were used because this qualitative method is particularly well suited for studying co-design processes that involve substantial attention to social interaction and the context. Data were 1) analyzed deductively based on the Proctor et al. taxonomy of implementation strategies, 2) categorized in accordance with the ERIC compilation of implementation strategies by Powell et al., and 3) analyzed to examine the justification for the selected strategies by the Proctor et al. framework for justifications of implementation strategies. Thirteen different types of implementation strategies were chosen across two hospitals. The deductive analysis showed that selection of implementation strategies was based on pragmatic and theoretical justifications. The contents of the two types of justifications were thematized into nine subthemes. This study contributes with knowledge about categories and justification of implementation strategies selected in a co-design process. In this study, implementation strategies were selected through pragmatic and theoretical justifications. This points to a challenge in balancing strategies based on practice-based and research-based knowledge and thereby selection of strategies with or without proven effectiveness.


Thymus-independent type 2 antigen induces a long-term IgG-related network memory.
Thymus-independent type 2 (TI-2) antigens occasionally induce long-lasting IgM memory, but do not prime for typical secondary IgG responses. However, contrary to current understanding, we detected several TI-2-induced long-term memory effects in subsequent thymus-dependent (TD) responses to the hapten 2-phenyloxazolone coupled to a protein carrier. The early primary TD response, even 3 months after TI-2 immunization, included non-mutated IgM as well as IgG antibodies exhibiting higher affinities than the Ox1 idiotype which dominates and has highest affinity in sole TD responses. The secondary exclusive IgG response 8 weeks later contained major hitherto non-observed clones. Somatic hypermutation on the normally dominant V(H)Ox1 gene was largely silenced while the associated VkappaOx1 exhibited the classical affinity-enhancing mutations, thus suggesting a separate regulation of this process for V(H) and V(L) genes. Mutations accumulated in genes which normally are rarely or non-expressed or non-mutating. First evidence is presented that receptor revision by V(H) replacement may occur during immune maturation in genetically non-engineered wildtype mice. We conclude that the TI-2 antigen-induced altered selection of TD Ag-inducible clones and its severe gene-specific influence on further somatic mutations and affinity maturation represents a network memory, which we hypothesize to be mediated by anti-idiotypic regulatory T cells.


On-site colorimetric food spoilage monitoring with smartphone embedded machine learning.
Real-time and on-site food spoilage monitoring is still a challenging issue to prevent food poisoning. At the onset of food spoilage, microbial and enzymatic activities lead to the formation of volatile amines. Monitoring of these amines with conventional methods requires sophisticated, costly, labor-intensive, and time consuming analysis. Here, anthocyanins rich red cabbage extract (ARCE) based colorimetric sensing system was developed with the incorporation of embedded machine learning in a smartphone application for real-time food spoilage monitoring. FG-UV-CD100 films were first fabricated by crosslinking ARCE-doped fish gelatin (FG) with carbon dots (CDs) under UV light. The color change of FG-UV-CD100 films with varying ammonia vapor concentrations was captured in different light sources with smartphones of various brands, and a comprehensive dataset was created to train machine learning (ML) classifiers to be robust and adaptable to ambient conditions, resulting in 98.8% classification accuracy. Meanwhile, the ML classifier was embedded into our Android application, SmartFood++, enabling analysis in about 0.1 s without internet access, unlike its counterpart using cloud operation via internet. The proposed system was also tested on a real fish sample with 99.6% accuracy, demonstrating that it has a great advantage as a potent tool for on-site real-time monitoring of food spoilage by non-specialized personnel.


Production enhancement of the extracellular lipase LipA in Bacillus subtilis: Effects of expression system and Sec pathway components.
Lipases are among the most versatile biocatalysts, and are used in a range of industrially relevant bioconversion reactions. However, the production of LipA in recombinant Bacillus subtilis is still limited, due to unresolved issues surrounding the regulation of the expression and secretion systems. In this study, the gene encoding LipA from B. subtilis 168 was expressed in BNA under the control of the P43 and the PAE promoter. The extracellular lipase activity of the resulting strains BNACL and BNAAL was 7.8 U ml-1 and 12.6 U ml-1, respectively. To further enhance the expression of LipA, pHP13L was constructed by inserting the PAE-lip into the shuttle vector pHP13, which produced an extracellular lipase activity of 180.5 U ml-1 of BNA/pHP13L. The strain BNAY8 described in Supplement data which lacks eight extracellular proteins was constructed and the deletion a few of the much weaker secreting proteins had no significant effect on the secretion of LipA. Moreover, the four Sec pathway components, secA-prfB, secDF, secYEG, prsA, were individually overexpressed in BNA. The overexpression of secDF and prsA enhanced the production of LipA by 28% and 49%, respectively. Furthermore, the co-overexpression of secDF with prsA improved the extracellular amount of LipA by 59% over that of BNA/pHP13L, reaching 287.8 U ml-1. It can therefore be said that both regulatory elements and secretion pathway had an impact on the production of secreted LipA. Their optimization and modification is a useful strategy to improve the homologous overproduction of other extracellular proteins in B. subtilis.


Classification of geographical origin of kimchi by volatile compounds analysis using an electronic nose.
Food authenticity is one of the largest concerns in recent days. As kimchi has been a global food, its production origin has been important issue, particularly due to the large import from China. Among the potential methods, electronic nose which can measure volatile compounds in foods is considered to be a powerful device for identifying country of production. This study is to classify 69 kinds of kimchi produced in South Korea (39) and China (30) by analyzing volatile compounds in kimchi using electronic nose-mass spectrometry. Two widely used multivariate analyses, discriminant function analysis and principal component analysis, were used. Results showed that both multivariate analyses can completely separate Korean and Chinese kimchi using 10 kinds of molecular weights among 10-160 amu. The results indicate that the volatile compounds in kimchi are a suitable target to determine the geographical origin of kimchi.


Increased suicide rate in cancer patients. A cohort study based on the Swedish Cancer-Environment Register.
Using the Swedish Cancer-Environment Register, 424,127 cancer patients were followed in the national cause-of-death register with the aim of analyzing the suicide rate among cancer patients compared with the general population. The overall Standardized Mortality Ratio (SMR) in suicide was 1.9 (95% confidence interval 1.8-2.1) for males and 1.6 (1.5-1.8) for females. The suicide rate was highest during the first year after cancer diagnosis, with an SMR of 16.0 (13.5-18.9) in males and 15.4 (11.2-20.6) in females. There were no substantial differences in suicide rate between different sites of tumor, although higher suicide rates were observed in patients with cancer in the lungs and upper airways (both sexes) and with gastro-intestinal tumors (males). Our results corroborate previous findings of an increased suicide rate among cancer patients, and indicate a need for further attention to social and psychological aspects of the care and treatment of cancer patients.


Machine learning applications in RNA modification sites prediction.
Ribonucleic acid (RNA) modifications are post-transcriptional chemical composition changes that have a fundamental role in regulating the main aspect of RNA function. Recently, large datasets have become available thanks to the recent development in deep sequencing and large-scale profiling. This availability of transcriptomic datasets has led to increased use of machine learning based approaches in epitranscriptomics, particularly in identifying RNA modifications. In this review, we comprehensively explore machine learning based approaches used for the prediction of 11 RNA modification types, namely, m 1 A , m 6 A , m 5 C , 5 hmC , ψ , 2 ' - O - Me , ac 4 C , m 7 G , A - to - I , m 2 G , and D . This review covers the life cycle of machine learning methods to predict RNA modification sites including available benchmark datasets, feature extraction, and classification algorithms. We compare available methods in terms of datasets, target species, approach, and accuracy for each RNA modification type. Finally, we discuss the advantages and limitations of the reviewed approaches and suggest future perspectives.


Astragaloside IV-loaded nanoparticle-enriched hydrogel induces wound healing and anti-scar activity through topical delivery.
This study aims to investigate the novel preparation of solid lipid nanoparticle-enriched hydrogel (SLN-gel) for the topical delivery of astragaloside IV and to determine the effects of astragaloside IV-based SLN-gel on wound healing and anti-scar formation. Solid lipid nanoparticles (SLNs) were prepared through the solvent evaporation method. The particle size, polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), drug release, and morphological properties of the SLNs were characterized. The optimized SLNs were incorporated in carbomer hydrogel to form an SLN-enriched gel (SLN-gel) carrier. The effects of astragaloside IV-enriched SLNs on wound healing were determined using the wound scratch test, and their uptake by skin cells was tested in vitro. With the rat full-skin excision model, the in vivo regulation of astragaloside IV-based SLN-gel in the wound stages of re-epithelization, angiogenesis, and extracellular matrix remodeling was investigated. The best formulation of astragaloside IV-based SLNs had high EE (93% ± 5%) and ZP (-23.6 mV ± 1.5 mV), with a PDI of 0.18 ± 0.03 and a drug loading percentage of 9%. Astragaloside IV-based SLNs and SLN-gel could release drug sustainably. Astragaloside IV-based SLNs enhanced the migration and proliferation of keratinocytes and increased drug uptake on fibroblasts in vitro (P<0.01) through the caveolae endocytosis pathway, which was inhibited by methyl-β-cyclodextrin. Astragaloside IV-based SLN-gel strengthened wound healing and inhibited scar formation in vivo by increasing wound closure rate (P<0.05) and by contributing to angiogenesis and collagen regular organization. SLN-enriched gel is a promising topical drug delivery system. Astragaloside IV-loaded SLN-enriched gel was proven as an excellent topical preparation with wound healing and anti-scar effects.


Wind-driven development and transport of Gymnodinium catenatum blooms along the coast of Fujian, China.
Gymnodinium catenatum is a cosmopolitan, bloom-forming dinoflagellate known to produce a suite of potent paralytic shellfish poisoning (PSP) toxins. Here, we revisit two major blooms of G. catenatum along the Fujianese Coast, China, in 2017 and 2018. The impact area of the 2017 bloom was larger than that of the 2018 event. Field sampling and remote satellite sensing revealed that alongshore transport driven by the southwest wind, as well as physical accumulation driven by the northeast wind, played important roles in the development and distribution of the two bloom events. The relationship between wind-induced hydrodynamic conditions and the unprecedented HAB events established in this study adds greatly to our understanding of algal bloom dynamics along the Fujianese coast. These results improve our ability to detect, track, and forecast G. catenatum blooms, thereby potentially minimizing the negative impacts of future HAB events.


Prognostic impacts of geriatric nutritional risk index in patients with ischemic heart failure after percutaneous coronary intervention.
Malnutrition has been proven to be associated with increased risk of poor prognosis in a series of diseases. This study explored the association between poor nutritional status and prognosis in patients with ischemic heart failure (IHF) undergoing percutaneous coronary intervention (PCI). The study enrolled 1745 patients with IHF undergoing PCI. The mean follow-up time was 28.7 months. Nutritional status was assessed by geriatric nutritional risk index (GNRI). All patients were divided into four groups according to GNRI quartiles (median and interquartile range: 103.8, 99.9-107.7). The primary endpoint was major adverse cardiovascular events (MACE), and the secondary endpoints were each component of the primary endpoint as follows: all-cause mortality, non-fatal myocardial infarction (MI), and any revascularization. The Kaplan-Meier survival analyses were performed to evaluate the incidence of the endpoints among 4 groups. The multivariate Cox proportional hazards analysis confirmed the independent effect of GNRI on the primary endpoint and secondary endpoints. The restricted cubic spline (RCS) was performed to evaluate the non-linear association of GNRI with MACE. The negative correlation of the GNRI with MACE (Log-rank P < 0.001), all-cause mortality (Log-rank P < 0.001) and any revascularization (Log-rank P < 0.001) was confirmed through the Kaplan-Meier curves. Multivariate analysis showed that the decreased GNRI was independently related to increased risk of MACE (Quartile 1 versus Quartile 4: HR, 95% CI: 2.66, 2.01-3.51, P < 0.001), all-cause mortality (Quartile 1 versus Quartile 4: HR, 95% CI: 2.33, 1.54-3.50, P < 0.001) and any revascularization (Quartile 1 versus Quartile 4: HR, 95% CI: 3.42, 2.22-5.27, P < 0.001). In addition, the non-linear association of GNRI with MACE was shown through RCS and the risk of MACE decreased as the GNRI increased in general (Non-linear P < 0.001). Decreased GNRI was an independent risk factor of MACE in IHF patients undergoing PCI.


The opposite effect of isotype-selective monoamine oxidase inhibitors on adipogenesis in human bone marrow mesenchymal stem cells.
Adiponectin production during adipocyte differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) can be used to evaluate the pharmacological activity of anti-diabetic drugs to improve insulin sensitivity. Monoamine oxidase (MAO) inhibitors such as phenelzine and pargyline inhibit adipogenesis in murine pre-adipocytes. In this study, however, we found that selective MAO-A inhibitors, moclobemide and Ro41-1049, and a selective MAO-B inhibitor, selegiline, promoted adiponectin production during adipocyte differentiation in hBM-MSCs, which suggested the anti-diabetic potential of these drugs. In contrast, non-selective MAO inhibitors, phenelzine and tranylcypromine, inhibited adipocyte differentiation of hBM-MSCs. Concomitant treatments of MAO-A and MAO-B selective inhibitors did not change the stimulatory effect on adiponectin production in hBM-MSCs. Taken together, the opposite effects of isotype-selective MAO inhibitors on adiponectin production during adipogenesis in hBM-MSCs may not be directly associated with the inhibitory effects of MAO, suggested that the structure of MAO inhibitors may contain a novel anti-diabetic pharmacophore.


Retinitis pigmentosa: problems associated with genetic classification.
Genetic classification of retinitis pigmentosa (RP) can be problematic, due to a large number of isolated cases, reduced penetrance, and considerable variation in expressivity. Another confounder is a high proportion of affected female carriers in X-linked RP. Based on the genetic definitions of five different authors, a reclassification experiment was conducted with 350 Danish families. Agreement existed about a small "nucleus" of familial cases. Most definitions favored autosomal dominant inheritance at the expense of X-linked. The experiment revealed that methodological differences to a large extent might explain the considerable variation among reported genetic frequencies of retinitis pigmentosa.


Comparative analysis between cytomorphology and flow cytometry methods in central nervous system infiltration assessment in oncohematological patients.
Oncohematological patients require the evaluation for possible infiltration of the central nervous system (CNS) by neoplastic cells at diagnosis and/or during the monitoring of the chemotherapeutic treatment. Morphological analysis using conventional microscopy is considered the method of choice to evaluate the cerebrospinal fluid (CSF) samples, despite technical limitations. This study aimed to compare the performance of the cytomorphology and flow cytometric immunophenotyping (FC) in the detection of CNS infiltration. We evaluated 520 CSF samples collected from 287 oncohematological patients for whom the detection of neoplastic cells was simultaneously requested by cytomorphology and FC. Laboratory analyses revealed 435/520 (83.7%) conclusive results by the two methods evaluated, among which 385 (88.5%) were concordant. Discordance between the methods was observed in 50/435 (11.5%) samples, 45 (90%) being positive by FC. Furthermore, the FC defined the results in 69/72 (95.8%) inconclusive samples by cytomorphology. The positivity of FC was particularly higher among hypocellular samples. Among 431 samples with a cell count of < 5/μL, the FC identified neoplastic cells in 75 (17.4%), while the cytomorphology reported positive results in 26 (6%). Among the samples that presented adequate cell recovery for evaluation by both methods (506/520), the comparative analysis between FC and cytomorphology revealed a Kappa coefficient of 0.45 (CI: 0.37-0.52), interpreted as a moderate agreement. The data showed that the CSF analysis by FC helps in the definition of CNS infiltration by neoplastic cells, particularly in the cases with dubious morphological analysis or in the evaluation of samples with low cellularity.


Expression of multidrug resistance-associated protein (MRP) in thyroid cancers.
It was found that the mechanism of anti-cancer drug resistance in anaplastic carcinoma of the thyroid was not explicable only in terms of expression of mdr1 and its gene product, P-glycoprotein. The multidrug resistance-associated protein (MRP), another member of the mdr gene family, may be involved in anti-cancer drug resistance of this carcinoma. The MRP expression was examined immunohistochemically in 8 cell lines and 73 thyroid cancer tissues; its frequency in anaplastic carcinoma (52%) was significantly higher than that in other thyroid cancer types.


The effect of a one-piece competition speedsuit on swimming performance and thermoregulation during a swim-cycle trial in triathletes.
This study investigated the thermoregulatory response to wearing a one-piece competition speedsuit during the swim-cycle aspect of a sprint-distance triathlon. Eight highly trained, male triathletes completed a graded-exercise test, and two swim-cycle trials including a 750 m swimming time trial followed by 30 min of cycling at 95% lactate threshold. Cycling was conducted inside a climate regulated chamber set to 30.0+/-0.3 degrees C and 60.3+/-0.3% humidity. Throughout each swim-cycle testing session, the athletes wore either standard swimming bathers only (BATHERS), or a competition speedsuit (SPEEDSUIT). During the swim-cycle trial, the athletes core temperature (T(c)) and skin temperature (T(sk)) were recorded via a telemetric temperature pill and a series of skin thermistors, respectively. Blood lactate concentration (BLa), heart rate (HR) and ratings of perceived thermal sensation (RPTS) were collected at the conclusion of the swim and during cycling. The SPEEDSUIT swim time (590+/-20s) was significantly faster (3.2%, p<0.01) than the BATHERS trial (609+/-24s). This time improvement incurred no between group differences in T(c), BLa or RPTS (SPEEDSUIT: 38.4+/-0.2 degrees C, 8.3+/-0.9 mmol L(-1), 15+/-1, BATHERS: 38.2+/-0.1 degrees C, 8.4+/-1.1 mmol(-1), 15+/-1, respectively) (p>0.05). During the 30 min cycle, there were not significant differences between the mean values for power output, T(c), T(sk), HR, BLa or RPTS (SPEEDSUIT: 289+/-13W, 38.65+/-0.27 degrees C, 34.30+/-0.71 degrees C, 7.8+/-1.1 mmol L(-1), 17+/-1, BATHERS: 288+/-14W, 38.35+/-0.10 degrees C, 33.50+/-0.57 degrees C, 7.1+/-0.9 mmol L(-1), 17+/-1, respectively) (p>0.05). The use of a competition speedsuit improved the triathletes' swim time without effecting temperature regulation during a laboratory-based swim-cycle trial.


Shatavari Supplementation in Postmenopausal Women Improves Handgrip Strength and Increases Vastus lateralis Myosin Regulatory Light Chain Phosphorylation but Does Not Alter Markers of Bone Turnover.
Shatavari has long been used as an Ayurvedic herb for women's health, but empirical evidence for its effectiveness has been lacking. Shatavari contains phytoestrogenic compounds that bind to the estradiol receptor. Postmenopausal estradiol deficiency contributes to sarcopenia and osteoporosis. In a randomised double-blind trial, 20 postmenopausal women (68.5 ± 6 years) ingested either placebo (N = 10) or shatavari (N = 10; 1000 mg/d, equivalent to 26,500 mg/d fresh weight shatavari) for 6 weeks. Handgrip and knee extensor strength were measured at baseline and at 6 weeks. Vastus lateralis (VL) biopsy samples were obtained. Data are presented as difference scores (Week 6-baseline, median ± interquartile range). Handgrip (but not knee extensor) strength was improved by shatavari supplementation (shatavari +0.7 ± 1.1 kg, placebo -0.4 ± 1.3 kg; p = 0.04). Myosin regulatory light chain phosphorylation, a known marker of improved myosin contractile function, was increased in VL following shatavari supplementation (immunoblotting; placebo -0.08 ± 0.5 a.u., shatavari +0.3 ± 1 arbitrary units (a.u.); p = 0.03). Shatavari increased the phosphorylation of Aktser473 (Aktser473 (placebo -0.6 ± 0.6 a.u., shatavari +0.2 ± 1.3 a.u.; p = 0.03) in VL. Shatavari supplementation did not alter plasma markers of bone turnover (P1NP, β-CTX) and stimulation of human osteoblasts with pooled sera (N = 8 per condition) from placebo and shatavari supplementation conditions did not alter cytokine or metabolic markers of osteoblast activity. Shatavari may improve muscle function and contractility via myosin conformational change and further investigation of its utility in conserving and enhancing musculoskeletal function, in larger and more diverse cohorts, is warranted.


The acoustic expression of stress in a songbird: does corticosterone drive isolation-induced modifications of zebra finch calls?
Animal vocalizations convey multiple pieces of information about the sender. Some of them are stable, such as identity or sex, but others are labile like the emotional or motivational state. Only a few studies have examined the acoustic expression of emotional state in non-human animals and related vocal cues to physiological parameters. In this paper, we examined the vocal expression of isolation-induced stress in a songbird, the zebra finch (Taeniopygia guttata). Although songbirds use acoustic communication extensively, nothing is known to date on how they might encode physiological states in their vocalizations. We tested the hypothesis that social isolation in zebra finches induces a rise of plasma corticosterone that modifies the vocal behavior. We monitored plasma corticosterone, as well as call rate and acoustic structure of calls of males in response to the playback of female calls of varied saliences (familiar versus stranger) in two situations: social isolation and social housing. Social isolation induced both a rise in plasma corticosterone, and a range of modifications in males' vocal behavior. Isolated birds showed a lower vocal activity, an abolition of the difference of response between the two stimuli, and evoked calls with longer duration and higher pitch. Because some of these effects were mimicked after oral administration of corticosterone in socially housed subjects, we conclude that corticosterone could be partly responsible for the isolation-related modifications of calls in male zebra finches. To our knowledge, this is the first demonstration of the direct implication of glucocorticoids in the modulation of the structure of vocal sounds.


Major clinical features of synostotic occipital plagiocephaly: mechanisms of cranial deformations.
The clinical diagnosis of most common single-suture craniosynostosis is easily set, based on the stereotype of deformities and knowledge of the mechanisms of cranial deformations. However, synostosis of unilateral lambdoid suture, probably due to its lower incidence and similarity with other non-synostotic deformities affecting the posterior portion of the skull, makes its clinical diagnosis more difficult and imprecise. The aim of this study is to evaluate the most easily and accurate clinical characteristics to be recognized in the synostotic occipital plagiocephaly. This study consisted of clinical evaluation of eight patients with synostotic occipital plagiocephaly, whose diagnosis was further corroborated by computed tomography. We identified the following: unilateral occipital flattening in eight out of eight patients (100 %), bulging of ipsilateral mastoid process in eight out of eight (100 %), "edge effect" of ipsilateral lambdoid suture in eight out of eight (100 %), inferior deviation of the ear in eight out of eight (100 %), "Dumbo" ears in eight out of eight (100 %), horizontal slant of the bimastoid line in seven out of eight (87.5 %), tilt of the head viewed from behind in seven out of eight (87.5 %), trapezoidal contour of the skull in top view in six out of eight (75 %), contralateral parietal bossing in six out of eight (75 %), and bossing of the contralateral forehead three out of eight (37.5 %). The most important clinical features specific to the clinical diagnosis of synostotic occipital plagiocephaly, not present in the positional posterior plagiocephaly, were bulging of the ipsilateral mastoid process, edge effect of the synostotic lambdoid suture, tilt of the head, and slant of the bimastoid line viewed from behind, inferior deviation of the ear, and contralateral parietal bossing.


[Strategies of coping with chronic illness in adolescents].
To develop a tool to evaluate coping strategies for chronic illness in adolescents. Based on a theoretical review and semi-structured interviews with adolescents, a questionnaire was prepared that was finally evaluated by judges experienced in in understanding, relevance and viability. A scale is proposed that consists of 60 items grouped into 12 coping families. The scale may be a useful clinical tool to provide key information about the experience and ways to cope with illness in adolescents.


Leukotriene B4 receptor BLT2 negatively regulates allergic airway eosinophilia.
Leukotriene B4 (LTB4) has been implicated in the pathogenesis of allergic diseases. BLT2, a low-affinity LTB4 receptor, is activated by LTB4 and 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT). Although the high-affinity LTB4 receptor BLT1 has been shown to exert proinflammatory roles, the role of BLT2 in allergic inflammation has not been clarified. To study the function of BLT2 in development of asthma, we used mice model of ovalbumin (OVA)-induced allergic airway disease. The 12-HHT levels were elevated in bronchoalveolar lavage (BAL) fluids of OVA-sensitized/challenged wild-type mice. BLT2-deficient mice exhibited enhanced eosinophilia in BAL fluids after OVA exposure. Interleukin (IL)-13 levels in BAL fluids and IL-13-producing CD4(+) T cells in the lungs were elevated in BLT2-deficient mice compared to wild-type mice, whereas the levels of IL-4, IL-5, and interferon (IFN)-γ in BAL fluids and serum OVA-specific IgE were comparable. Transfection of BLT2-specific small interfering RNA enhanced IL-13 production in CD4(+) T cells in vitro. Expression of BLT2 mRNA in CD4(+) T cells was significantly reduced in patients with asthma compared to healthy control subjects. These findings indicate that BLT2 has a protective role in allergic airway inflammation and that diminished BLT2 expression in CD4(+) T cells may contribute to the pathophysiology of asthma.


Length of Menstrual Cycle and Risk of Endometriosis: A Meta-Analysis of 11 Case-Control Studies.
Endometriosis is a complex disease that affects a large number of women worldwide and may cause pain and infertility. To systematically review published studies evaluating the relationship between menstrual cycle length and risk of endometriosis. We searched the Cochrane Library, PubMed, Web of Science, and EMBASE in databases in July 2014 using the keywords "case-control studies," "epidemiologic determinants," "risk factors," "menstrual cycle," "menstrual length," "menstrual character," and "endometriosis." We included case-control studies published in English that investigated cases of surgically confirmed endometriosis and examined the relationship between endometriosis risk and menstrual cycle. Eleven articles that met the inclusion criteria included data of 3392 women with endometriosis and 5006 controls. Fixed-effects and random-effects models were used for the evaluation. For the association of risk of endometriosis and menstrual cycle length shorter than or equal to 27 days (SEQ27) or length longer than or equal to 29 days (LEQ29), the odds ratio was 1.22 (95% confidence interval [CI]: 1.05-1.43) and 0.68 (95% CI: 0.48-0.96), respectively. In conclusion, this meta-analysis suggests that menstrual cycle length SEQ27 increase the risk of endometriosis and cycle length LEQ29 decrease the risk.


Severe sensorineural hearing loss associated with viral hepatitis.
A 41-year-old man who developed a sudden, profound, irreversible, unilateral hearing loss while acutely ill with viral hepatitis is described. Residual damage consisted of a nonfunctional left cochlea, right positional vertigo, and tinnitus. It is postulated that the pathophysiologic defect was due to direct invasion of the endolymphatic structures by type A hepatitis virus.


Extending donor source with bench coronary angiography: a case report.
This report proposes a safer, economical method to examine the marginal donor heart for a better chance of use, which also delivers comparable image quality of catheterization (CathLab) without creating potential damage to the kidney. Currently the examination of the coronary system mainly relies on the CathLab, which is not commonly accessible, and also results in nephrotoxic effects. Therefore, bench coronary angiography is hereby proposed because it is commonly available and economical as well as able to indicate coronary lesions for surgeons as well as the CathLab study. These benefits altogether provide a better chance to select usable hearts from older donors to help relieve the organ shortage.


The development of a computer controlled system to simulate in rats, the rapid, frequent changes in oxygen experienced by preterm infants developing retinopathy of prematurity.
Preterm infants that develop severe ROP have significantly more fluctuations in their transcutaneous oxygen compared to mild or no ROP, despite the fact that all these infants are kept within clinically 'safe' limits. Current animal models do not accurately reflect this oxygen environment. Our aim was to custom build equipment capable of reproducing the transcutaneous oxygen (TcPO2) levels recorded by infant cotside monitoring equipment in a rat model and assess the equipment's precision. Using previously published data for the rat that translates TcPO2 into the equivalent inspired FiO2, a profile was derived from a datalog of TcPO2 values recorded every minute for 14 days in an infant that had developed severe ROP. This profile was controlled in the animal chamber by software algorithms which calculated the amount and type of gas to be injected to move oxygen to each new set-point. CO2 regulation within the chamber was also possible. Absolute differences between the datalog set-points (n = 17,465) and the oxygen sensor were median 0.3% oxygen, IQR 0.2-0.7% oxygen, with 95% of the differences < +/- 2% oxygen. The equipment is capable of reproducing the oxygen environment experienced by a preterm ventilated infant, giving a satisfactory level of precision.


[Validation of the choice of antibacterial agents for treating periodontitis].
Sensitivity of microflora sampled from the dental root channels of periodontitis patients to chlorhexidine, dioxidine, quinosol, Metrodgile was investigated. Chlorhexidine and dioxidine were shown to act predominantly on gram-positive and gram-negative bacteria, Metrodgile most active against anaerobic flora. High antibacterial activity of quinosol and chlorhexidine was combined with their pronounced cytotoxic effects. Metrodgile could be successfully used for preventing purulent odontogenic inflammations caused by anaerobic flora.


Operative management of rectal injuries during laparoscopic radical prostatectomy.
To present our experience in the management of rectal injuries during laparoscopic radical prostatectomy. All patients underwent bowel preparation and received perioperative antibiotics. If rectal injury was suspected, digital rectal examination was performed, aided by bubbling air into the rectum if required. When the diagnosis was confirmed, the hole was closed in two layers of absorbable sutures. A fat flap was developed from the omentum (in the transperitoneal approach) or the perirectal fat (in the extraperitoneal approach) and placed on the suture line. Anal dilation was performed. After surgery, broad-spectrum antibiotics and a low-residue diet were prescribed. Of 300 patients who underwent surgery between May 1998 and June 2002, 6 (2%) had a rectal injury. The first patient had received neoadjuvant hormonal therapy. Five cases were in the transperitoneal approach and were closed using omental fat and 1 was in the extraperitoneal approach with a perirectal fat flap. The first patient presented with a rectourethral fistula and was treated with catheterization for 1 month and a diverting colostomy. The others were detected intraoperatively and were treated laparoscopically. In the second patient, a diverting colostomy was performed at the end of surgery using a separate incision. Patients resumed oral intake within 2 to 7 days and were discharged from the hospital between 6 and 18 days postoperatively. No wound infection was noted. Rectal injuries during laparoscopic radical prostatectomy can be identified and managed intraoperatively without requiring conversion. Double-layered closure reinforced by a fat flap resulted in an uneventful recovery.


Relationship between hair, serum and bone aluminium in hemodialyzed patients.
To establish the predictive value in osteodystrophy of hair aluminium content in patients on hemodialysis, we compared the aluminium levels in serum, cortical and trabecular bone and hair of 40 such patients with the levels in 23 healthy controls. In the patients, mean hair aluminium content was significantly higher than the controls (0.226 mumol/g, range: 0.09-0.500 mumol/g, n = 39 versus 0.126 mumol/g, range: 0.020-0.330 mumol/g, n = 49) but there was a large overlap between the two groups. The patients exhibited a significant correlation between serum and cortical bone aluminium measured by atomic absorption spectrometry (rs = 0.67, n = 37, p less than 0.05), but no correlation between aluminium in hair and in serum or bone, whether cortical or trabecular. Bone histomorphometric studies also indicated that unlike aluminium levels in cortical or trabecular bone, its levels in hair are not predictive of aluminium-induced osteomalacia. Consequently, hair aluminium cannot suitably replace bone and serum aluminium as a criterion of osteodystrophy in hemodialyzed patients.


Fasting for 21days leads to changes in adipose tissue and liver physiology in juvenile checkered garter snakes (Thamnophis marcianus).
Snakes often undergo periods of prolonged fasting and, under certain conditions, can survive years without food. Despite this unique phenomenon, there are relatively few reports of the physiological adaptations to fasting in snakes. At post-prandial day 1 (fed) or 21 (fasting), brain, liver, and adipose tissues were collected from juvenile checkered garter snakes (Thamnophis marcianus). There was greater glycerol-3-phosphate dehydrogenase (G3PDH)-specific activity in the liver of fasted than fed snakes (P=0.01). The mRNA abundance of various fat metabolism-associated factors was measured in brain, liver, and adipose tissue. Lipoprotein lipase (LPL) mRNA was greater in fasted than fed snakes in the brain (P=0.04). Adipose triglyceride lipase (ATGL; P=0.006) mRNA was greater in the liver of fasted than fed snakes. In adipose tissue, expression of peroxisome proliferator-activated receptor (PPAR)γ (P=0.01), and fatty acid binding protein 4 (P=0.03) was greater in fed than fasted snakes. Analysis of adipocyte morphology revealed that cross-sectional area (P=0.095) and diameter (P=0.27) were not significantly different between fed and fasted snakes. Results suggest that mean adipocyte area can be preserved during fasting by dampening lipid biosynthesis while not changing rates of lipid hydrolysis. In the liver, however, extensive lipid remodeling may provide energy and lipoproteins to maintain lipid structural integrity during energy restriction. Because the duration of fasting was not sufficient to change adipocyte size, results suggest that the liver is important as a short-term provider of energy in the snake.


Signal amplification strategy for sensitive immunoassay of prostate specific antigen (PSA) based on ferrocene incorporated polystyrene spheres.
A new kind of signal amplification strategy based on ferrocene (Fc) incorporated polystyrene spheres (PS-Fc) was proposed. The synthesized PS-Fc displayed narrow size distribution and good stability. PS-Fc was applied as label to develop immunosensors for prostate specific antigen (PSA) after the typical sandwich immunoreaction by linking anti-PSA antibody (Ab2) onto PS-Fc. After the fabrication of the immunosensor, tetrahydrofuran (THF) was dropped to dissolve PS and release the contained Fc for the following stripping voltammetric detection. PS-Fc as a new electrochemical label prevented the leakage of Fc and greatly amplified the immunosensor signal. In addition, the good biocompatibility of PS could maintain the bioactivity of the antibodies. The response current was linear to the logarithm of PSA concentration in the range from 0.01 ng mL(-1) to 20 ng mL(-1) with a detection limit of 1 pg mL(-1). The immunosensor results were validated through the detection of PSA in serum samples with satisfactory results.


Cumulative impacts of human activities on urban garden soils: origin and accumulation of metals.
The concentration of heavy metals and soil properties in fifty urban garden soils of Szeged (SE Hungary) were determined to evaluate the cumulative impacts of urbanization and cultivation on these soils. Using two enrichment factors (EFs) (based on reference horizon; Ti as reference element) and multivariate statistical analysis (PCA), the origin of the studied elements was defined. According to statistical coincidence of EFs confirmed by t-test, anthropogenic enrichment of Cu (EF = 4), Zn (EF = 2.7) and Pb (EF = 2.5) was significant in topsoils. Moreover, PCA also revealed the geogenic origin of Ni, Co, Cr and As and differentiated two groups of the anthropogenic metals [Pb, Zn] [Cu]. Spatial distribution of the metals visualized by GIS reflected the traffic origin of Pb; while based on ANOVA, the anthropogenic source of Cu is relevant (mainly pesticides) and there is a statistically significant difference in its concentration depending on land use.


Integrated metasurfaces for re-envisioning a near-future disruptive optical platform.
Metasurfaces have been continuously garnering attention in both scientific and industrial fields, owing to their unprecedented wavefront manipulation capabilities using arranged subwavelength artificial structures. To date, research has mainly focused on the full control of electromagnetic characteristics, including polarization, phase, amplitude, and even frequencies. Consequently, versatile possibilities of electromagnetic wave control have been achieved, yielding practical optical components such as metalenses, beam-steerers, metaholograms, and sensors. Current research is now focused on integrating the aforementioned metasurfaces with other standard optical components (e.g., light-emitting diodes, charged-coupled devices, micro-electro-mechanical systems, liquid crystals, heaters, refractive optical elements, planar waveguides, optical fibers, etc.) for commercialization with miniaturization trends of optical devices. Herein, this review describes and classifies metasurface-integrated optical components, and subsequently discusses their promising applications with metasurface-integrated optical platforms including those of augmented/virtual reality, light detection and ranging, and sensors. In conclusion, this review presents several challenges and prospects that are prevalent in the field in order to accelerate the commercialization of metasurfaces-integrated optical platforms.


The efficacy of intrauterine devices for emergency contraception and beyond: a systematic review update.
The copper intrauterine device (IUD) is a very effective form of emergency contraception. The failure rate is about 0.1%. IUDs are also very cost-effective when used as long acting-reversible contraception (LARC). The purpose of this review is to attempt to confirm these findings. The references for this study were generated by entering the terms "intrauterine device" and "emergency contraception" in Medline, PubMed, Popline, Global Health and ClinicalTrials.gov. Chinese references were obtained from the Wanfang database. For the emergency contraception study, articles with a defined population who were followed up until outcome were eligible. Women who were adequately followed for at least 6 months were included in the long term arm of the study. There were 18 (of 228) studies which met our selection criteria and were conducted in five countries, between August 2011 and January 2018. There were 1720 insertions of seven types of copper IUD with a failure rate of 0.12%. The maximum time from intercourse to IUD insertion was 14 days. The discontinuation rate at 12 months was over 20% in the long term studies. There are now a combined total of 8550 reported insertions from two reviews with 8 pregnancies and a failure rate of 0.093%. Copper IUDs remain an effective form of emergency contraception, for which they are under-promoted. The major limitation of the studies is the lack of data relating unprotected intercourse to the day of the cycle.


Community pharmacists' adoption of medicines reclassified from prescription-only status: a systematic review of factors associated with decision making.
Subsequent to reclassification of legal status, more than 90 prescription-only medicines have become available in the UK alone without a prescription. Similar changes are taking place internationally. The aim was to systematically review studies reporting factors associated with community pharmacists' decision making around adoption of these reclassified medicines into practice. A systematic review of English language peer-reviewed published literature from 1990 to 2010 was conducted. Literature was identified through MEDLINE, EMBASE, IPA, CINAHL, BSP, Cochrane Library and PsychINFO databases and other sources including key conference abstracts. A total of 38 studies were included. Twenty-eight factors associated with pharmacists' decision making were identified. Medicine safety was consistently shown to be one of the key factors; however, the importance of evidence base and financial benefits of reclassification were less obvious. A paucity of high-quality studies limits generalisation of findings. Patient safety appears to be the key to pharmacists' decision making. However, the study quality limitations indicate the need for further robust research. The 28 factors identified in this systematic review from international literature can aid rigorous research instrument development for future evaluations.


Attack and defense in rodents as ethoexperimental models for the study of emotion.
1. In wild and laboratory rats, offense and defense constitute nonoverlapping behavior patterns seen in response to resource or dominance challenge, or, to predatory, conspecific or environmental threat, respectively. 2. Defensive behaviors are determined by both the threat stimulus and the situation. Defense patterns to discrete, approaching, predators or conspecifics and to nondiscrete, potential, threat have several behaviors in common. However, the latter also includes an important risk assessment complex not seen to discrete, present, threat. Behaviorally and functionally, risk assessment shows considerable similarity to the apprehensive expectation and vigilance and scanning components of generalized anxiety reactions. 3. There are parallels between lower mammal offense and human angry aggression in terms of eliciting stimuli, and a variety of experiential factors including inhibition by fear/pain, and reinforcement effects. 4. A variety of neuroanatomical or pharmacological manipulations have different, often opposite, effects on offense and defense. Differentiation of the two and attention to the specific behaviors involved provide a more precise basis for the use of these patterns as animal models of emotion states.


Time-dependent regulation of neuregulin-1β/ErbB/ERK pathways in cardiac differentiation of mouse embryonic stem cells.
Neuregulin-1β (NRG-1β)/ErbB signaling plays crucial roles in the cardiac differentiation of mouse embryonic stem cells (ESCs), but its roles and the underlying mechanisms in cardiac differentiation are incompletely understood. This study showed that NRG-1β significantly increased the percentage of beating embryoid bodies (EBs) and up-regulated the gene expressions of Nkx2.5, GATA4, α-actin, MLC-2v, and ANF in a time-dependent manner, with no effect on the gene expressions of HCN4 and Tbx3. Inhibition of ErbB receptors with AG1478 significantly decreased the percentage of beating EBs; down-regulated the gene expressions of Nkx2.5, GATA4, MLC-2v, ANF, and α-actin; and concomitantly up-regulated the gene expressions of HCN4 and Tbx3 in a time-dependent manner. Moreover, the up-regulation of transcripts for Nkx2.5 and GATA4 by NRG-1β was blocked by the extracellular signal-related kinases (ERK) 1/2 inhibitor, U0126. However, U0126 could not inhibit the transcript up-regulations of MLC-2v and ANF by NRG-1β. The protein quantitation results were consistent with those of gene quantitation. Our results suggest that NRG-1β/ErbB signaling plays critical roles in the cardiac differentiation of mouse ESCs and in the subtype specification of cardiomyocytes in a time-dependent manner. The ERK1/2 pathway may be involved in the early cardiogenesis, but not in the subtype specification of cardiomyocytes.


The Nrde Pathway Mediates Small-RNA-Directed Histone H3 Lysine 27 Trimethylation in Caenorhabditis elegans.
Small-RNA-mediated chromatin modifications have been widely studied in plants and S. pombe. However, direct evidence of small-RNA-guided sequence-specific chromatin alterations is scarce in animals. In C. elegans, the nuclear RNAi defective (Nrde) pathway functions to transport siRNA from the cytoplasm to the nucleus, modulate transcription elongation, induce histone H3 lysine 9 (H3K9) trimethylation, and mediate transgenerational inheritance of RNAi. Here, we show that both exogenous RNAi and NRDE-bound endogenous 22G RNAs can direct sequence-specific histone H3 lysine 27 (H3K27) trimethylation at targeted loci through the Nrde pathway. The resulting H3K27me3 status can be inherited by progeny for multiple generations. piRNAs and WAGO-1-associated siRNAs induce H3K27 methylation as well. Interestingly, CSR-1-associated endogenous siRNAs fail to trigger H3K27 methylation, whereas exogenous provision of dsRNAs can induce H3K27 methylation at the CSR-1-targeted loci via the Nrde pathway. We further observed distinct genetic requirements of H3K9 and H3K27 trimethylation. Whereas set-25 and met-2 are required for K9 methylation, mes-2 is required for K27 methylation. The depletion of mes-2 leads to a nuclear RNAi defective phenotype. These results indicate that dsRNA-triggered chromatin modification is a sequence-specific response that engages the Nrde pathway in C. elegans.


Antidepressant pharmaceuticals in aquatic systems, individual-level ecotoxicological effects: growth, survival and behavior.
The growing consumption of antidepressant pharmaceuticals has resulted in their widespread occurrence in the environment, particularly in waterways with a typical concentration range from ng L-1 to μg L-1. An increasing number of studies have confirmed the ecotoxic potency of antidepressants, not only at high concentrations but also at environmentally relevant levels. The present review covers literature from the last decade on the individual-level ecotoxicological effects of the most commonly used antidepressants, including their impact on behavior, growth, and survival. We focus on the relationship between antidepressants physico-chemical properties and dynamics in the environment. Furthermore, we discuss the advantages of considering behavioral changes as sensitive endpoints in ecotoxicology, as well as some current methodological shortcomings in the field, including low standardization, reproducibility and context-dependency.


Toward understanding molecular mechanisms of light harvesting and charge separation in photosystem II.
Conversion of light energy in photosynthesis is extremely fast and efficient, and understanding the nature of this complex photophysical process is challenging. This review describes current progress in understanding molecular mechanisms of light harvesting and charge separation in photosystem II (PSII). Breakthroughs in X-ray crystallography have allowed the development and testing of more detailed kinetic models than have previously been possible. However, due to the complexity of the light conversion processes, satisfactory descriptions remain elusive. Recent advances point out the importance of variations in the photochemical properties of PSII in situ in different thylakoid membrane regions as well as the advantages of combining sophisticated time-resolved spectroscopic experiments with atomic level computational modeling which includes the effects of molecular dynamics.