The nature of intermolecular interactions between aromatic amino acid residues.
The nature of intermolecular interactions between aromatic amino acid residues has been investigated by a combination of molecular dynamics and ab initio methods. The potential energy surface of various interacting pairs, including tryptophan, phenilalanine, and tyrosine, was scanned for determining all the relevant local minima by a combined molecular dynamics and conjugate gradient methodology with the AMBER force field. For each of these minima, single-point correlated ab initio calculations of the binding energy were performed. The agreement between empirical force field and ab initio binding energies of the minimum energy structures is excellent. Aromatic-aromatic interactions can be rationalized on the basis of electrostatic and van der Waals interactions, whereas charge transfer or polarization phenomena are small for all intermolecular complexes and, particularly, for stacked structures. Proteins 2002;48:117-125.


Glycoprotein isolated from Rhus verniciflua Stokes inhibits inflammation-related protein and nitric oxide production in LPS-stimulated RAW 264.7 cells.
Rhus verniciflua Stokes (RVS) has traditionally been used for medical purpose, such as healing of inflammatory diseases in South Korea. Glycoprotein (36 kDa) was isolated from RVS fruit, purified and used to evaluate the inhibitory effect on inflammatory-related proteins and nitric oxide (NO) production in lipopolysaccharide (LPS, 200 ng/ml)-stimulated RAW 264.7 (murine macrophage cell line). Our results were showed that RVS glycoprotein has a strong antioxidative activity against lipid peroxyl radicals in cell-free system, and inhibits NO production in LPS-stimulated RAW 264.7 cells. To elucidate the inhibitory effect of RVS glycoprotein on activities of inflammatory-related proteins, we firstly evaluated the amount of intracellular reactive oxygen species (ROS), and expression of intracellular protein kinase C (PKC), nuclear factor (NF)-kappaB, and activator protein-1 (AP-1). The results in the present study showed that RVS glycoprotein (200 microg/ml) inhibits ROS production and PKCalpha translocation, and down-regulates the expression of NF-kappaB and AP-1. Such upstream signals consequently inhibited the levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 expression. Therefore, we speculate that RVS glycoprotein inhibits the inflammatory-related protein and can act as an anti-inflammatory agent.


[Soil organic carbon mineralization and priming effects in the topsoil and subsoil under no-tillage black soil.]
Priming effect is one of the important mechanisms regulating soil organic matter decomposition. However, the variation of priming effects in different soil layers remains unclear. In this study, we conducted a 30-day incubation experiment using no-tillage black soil from northeastern China. 13C-glucose and dynamic CO2 trapping methods were employed to investigate soil organic carbon (SOC) mineralization rates and the priming effect of the added 13C-glucose in the upper soil layer (0-10 cm) and the lower soil layer (30-40 cm). Our results showed that the cumulative SOC-specific mineralization rate in the upper layer was similar to that in the lower layer soil without glucose addition. Glucose addition significantly altered the mineralization rates in both layers, resulting in a positive priming effect (36.7%) in the upper layer but a negative priming effect (-12.4%) in the lower layer. The cumulative priming effect during the 30-day incubation was 3.24 mg C·g-1 SOC for the upper layer soil and -1.24 mg C·g-1 SOC for the lower layer soil. There was still a net SOC increase, even with positive priming effects in the upper layer soil. This was due to considerable amount of added glucose-C remained un-mineralized in the soil which would compensate the carbon loss from priming effects. Overall, our results demonstrated that the magnitude and direction of priming effects might differ between soil layers. Our findings contribute to a better understanding of the effects of conservation tillage practices (no-tillage and straw incorporation) on soil organic matter dynamics in agroecosystems.


Inter-rater reliability for noninvasive measurement of cardiac function in children.
A transcutaneous ultrasound monitor has recently been developed which noninvasively and quickly measures cardiac output. Validity and reliability testing has been reported in adults. No reliability testing has been undertaken in the pediatric population. Our objective was to evaluate the inter-rater reliability of a transcutaneous Doppler ultrasound technique to measure cardiac index (CI) and stroke volume index (SVI) in pediatric emergency department patients. An 8-month prospective observational study was conducted on a convenience sample of emergency department patients younger than 18 years old. Five raters were trained to use an ultrasound cardiac output monitoring device. Two raters, blinded to each other's results, obtained independent measurements from the same patient within 15 minutes of each other. Inter-rater agreement was measured with the Pearson product correlation coefficient. Bland-Altman analysis demonstrated the extent of deviation from a line of agreement between raters. Ninety-seven patients were enrolled. Major diagnostic categories included infection, trauma, and gastrointestinal disorders. There was significant inter-rater correlation for CI (r = 0.76; 95% confidence interval, 0.66Y0.83; P G 0.0001) and SVI (r = 0.79; 95% confidence interval, 0.70Y0.86; P G 0.0001). Bland-Altman analysis of CI measurements between 2 raters showed bias of 0.06, SD of bias 1.00, and 95% limits of agreement j1.91 to 2.02 L/min/m2. Stroke volume index showed bias of j0.5, SD of bias 11.01, and 95% limits of agreement j22.08 to 21.08 mL/m2. Transcutaneous Doppler ultrasound technique demonstrates acceptable inter-rater agreement for measuring CI and SVI in children.


Elevated plasma cfDNA may be associated with active lupus nephritis and partially attributed to abnormal regulation of neutrophil extracellular traps (NETs) in patients with systemic lupus erythematosus.
The abnormal formation and insufficient clearance of neutrophil extracellular traps (NETs) has been reported to be involved in the pathogenesis of lupus nephritis (LN). The abnormal regulation of NETs may contribute to increases in the levels of circulating cell-free DNA (cfDNA). The present study tested the hypothesis that elevated plasma cfDNA levels are related to LN. Fifty-four systemic lupus erythematosus (SLE) patients and 43 control subjects were included in this study. The cfDNA concentrations were measured using the Picogreen Kit, the low-density granulocyte (LDG) percentage in peripheral blood mononuclear cells (PBMCs) was tested using a flow cytometer and the DNase I activity was measured according to the radial enzyme-diffusion method. The mean cfDNA concentration in the SLE group was 236.66±40.09 ng/mL, which was significantly higher than that observed in the healthy control group (187.96±40.55 ng/mL, p<0.0001). Meanwhile, the mean cfDNA concentration in the patients with LN was significantly higher than that observed in the patients without LN (247.27±46.79 ng/mL vs. 213.56±31.34 ng/mL, p=0.0094), and the mean cfDNA concentration in the patients with active LN was significantly higher than that observed in the patients with inactive LN (254.22±50.16 ng/mL vs. 215.93±29.10 ng/mL, p=0.0349). In the SLE group, the cfDNA concentration was to positively correlate with the quantitative 24-hour urinary protein (r=0.350, p=0.013), LDG (r=0.6361, p=0.0019) and neutrophil (r=0.5990, p<0.0001) levels and inversely correlate with the albumin level (r=-0.500, p<0.0001) and endogenous creatinine clearance rate (r=-0.354, p=0.044). Compared to that observed in the control group, the SLE group exhibited a significantly increased percentage of LDGs in PBMCs and a significantly decreased DNase I activity. Our data indicate that elevated plasma cfDNA concentrations may be associated with active LN and partially attributed to the abnormal regulation of NETs in SLE patients, thus suggesting that NETs constitute an intrinsic link between cfDNA and active LN.


[Czech bariatry in 2010].
It is only during the past two decades, when obesity has become to be considered a pandemic disorder. However, in 1953 Varco performed jejunoileal bypass as the world's first bariatric surgical procedure. 30 years later, Pesková performed the first bariatric surgery--a gastroplasty--in Czechoslovakia. From 1984 she started to perform fixed gastric bandages, through laparotomic app- roach at that time. The first laparoscopic fixed bandage in Czechoslovakia was performed in 1993. Over the years, the number of surgical procedures to treat morbid obesity, as well as the number of bariatric surgeons, continued to increase. In 2004, Czech Bariatric Section of the Czech Surgical Society and the Czech Society of Obesitology of the Czech Medical Association of J. E. Purkyne, were established. 170 bariatric surgeries were performed in the Czech Republic in 1999. The majority of procedures included fixed gastric bandage, rarely, adjustable bandage was performed. At that time, bariatric procedures were performed at five sites only. However, over the past 10 years, bariatric surgery has largely developed in the Czech Republic. The exact number of bariatric procedures completed per year was unknown, therefore, 21 surgical clinics, at which bariatric procedures are performed, were contacted from January to June 2010. Heads of the clinics were asked to provide basic data on surgical treatment of obesity. The aim of the study was to analyze the situation in bariatric surgery in the Czech Republic at the end of 2009. A total of 18 clinics (85.8%) joined the study and provided their own statistical data. 14 of them perform over 20 bariatric procedures a year. The analysis data showed that, in 2009, a total of 1558 bariatric procedures were completed at 18 surgical clinics and approximately 1600 procedures were performed in the whole Czech Republic. However, out of the total, over 230 patients were foreigners. In 99% of bariatric procedures in morbid obese subjects, laparoscopic approach was used. Over the ten year period, the number of clinics performing over 20 bariatric procedures a year increased from five to 14 clinics and the number of bariatric procedures increased from 170 to 1600 procedures a year. It is 900% increase, compared to the year 1999! Nevertheless, compared to other countries, e.g. Austria, the number of bariatric procedures does not correspond with prevalence rates of obesity in the Czech Republic.


Cystoid macular edema associated with the use of latanoprost.
Cystoid macular edema is a common clinical finding following intraocular surgery. Certain medications have been associated with an increased incidence of cystoid macular edema. This article describes the clinical findings in two eyes of two patients in whom cystoid macular edema developed directly following treatment with the anti-glaucoma medication latanoprost, and assesses the possible causal relationship. Clinical correlative and angiographic studies of two patients in a referral practice are presented. The main outcome measurement was visual acuity and fundus examination on discontinuation of latanoprost. Cystoid macular edema developed in two pseudophakic patients after the use of latanoprost. Latanoprost should be used with caution in pseudophakic and aphakic patients--especially those with retinal vascular fragility, any inflammatory uveal disease, or other factors that may predispose to the breakdown of the blood-retinal barrier.


D-dimer, C-reactive protein and matrix metalloproteinase 9 for prediction of type A aortic dissection patient survival.
Acute type A aortic dissection (ATAAD) is a life-threatening condition requiring prompt diagnosis and treatment. Surgery is an effective treatment for ATAAD, but the in-hospital mortality rate in the 30 day perioperative period is still as high as 9-30%. It is critical to identify biological factors for preoperative assessment of post-operative survival in patients with ATAAD. This is a retrospective study, investigating the association of combined measurements of d-dimer, C-reactive protein (CRP), and matrix metalloproteinase 9 (MMP9) for 1 year of survival in patients with ATAAD. Data from 247 patients who underwent surgery were analysed, including 89 patients who did not survive and 158 patients who survived within 1 year after surgery. Pearson's correlation analysis was carried out to determine the correlations between CRP in whole blood, d-dimer in plasma, and CRP in whole blood. Receiver operating characteristic (ROC) analysis was used to analyse the value of preoperative whole blood CRP, plasma d-dimer, and serum MMP9 concentration and the combined detection model in predicting death of patients with ATAAD. Deceased patients with ATAAD exhibited higher age, hypertension prevalence, systolic blood pressure, white blood cell count, whole blood CRP, plasma d-dimer, and serum MMP9 levels compared with survivors. Preoperative CRP, d-dimer, and MMP9 levels were significantly higher in patients with ATAAD compared with healthy controls. Positive correlations were observed between CRP and d-dimer, CRP and MMP9, and d-dimer and MMP9 in patients with ATAAD. ROC analysis showed that the combined detection model of CRP, d-dimer, and MMP9 had the highest predictive value for 1 year of survival (area under the curve = 0.88). Combined measurement of CRP, d-dimer, and MMP9 is associated with 1 year of survival in patients with ATAAD.


The rational phase of therapeutic angiogenesis.
Largely disappointing results from early clinical trials have settled down the initial unrealistic hope that fueled therapeutic angiogenesis. Now that this research has reached a rational phase, every concept in the theory of neo-vascularization needs to be re-evaluated. Neo-vascularization in adult tissues has been described as the result of either arteriogenesis, angiogenesis or vasculogenesis. The contribution of these mechanisms to neo-vascularization in vivo can likely not be separated experimentally. All currently known growth factors are pleiotropic and induce the secondary release of other growth factors. A complete analysis of the efficacy of growth factors therefore should include parameters of arteriogenesis, angiogenesis and vasculogenesis. Current clinical studies have likely suffered from drug regimens with short exposure of a single growth factor. Although combinations of growth factors may be theoretically appealing to create robust sustained neo-vessels, preclinical and clinical study designs may become too complex. Instead, there is some evidence that prolonged exposure to a single growth factor might result in vessels that are resistant to regression. With the vast and rapidly growing body of data that is being obtained on growth factors and pro-angiogenic strategies, approaches will emerge that are more effective than the ones presently tested in the clinic. It remains imperative however, that these approaches are rationally based on fundamental and preclinical data.


[Bond durability of self-adhesive resin cement to glass ceramic].
To evaluate the bond durability of glass ceramic to self-adhesive and conventional resin cements. Maximum water sorption and solubility of two resin cements (A: self-adhesive type, G-CEM; B: conventional type, Linkmax HV) were measured during 6 week water storage. And their surface Knoop hardness number was measured at 0.5, 24 h and 6 week after irradiation. Sixty-four glass ceramic samples were or were not silanized with one of the three silane coupling agents (A: Monobond S; B: Clearfil Ceramic Primer; C: GC Ceramic Primer), and then cemented with two resin cements. The micro-bond strength between the two cements and glass ceramic were measured at baseline and after 30 000 thermal cycle. Cement A had higher water sorption [(79.62 +/- 5.63) microg/mm³] and solubility [(4.78 +/- 3.33) microg/mm³] than cement B[(35.03 +/- 3.33) microg/mm³, (0.00 +/- 0.00) microg/mm³]. Cement A and B could achieve maximal surface hardness at 24 h after irradiation, and this was maintained during 6 week water storage. After 30 000 thermal cycle, the micro-bond strength between unsilanized glass ceramic and cement A or B was (0.00 +/- 0.00) MPa, and those between cement A and silanized glass ceramic with silane coupling agent A, B and C, were (2.86 +/- 3.25), (12.75 +/- 1.55) and (11.98 +/- 2.35) MPa respectively [for cement B, the data was (5.15 +/- 5.20), (10.94 +/- 3.30) and (14.18 +/- 3.13) MPa]. No significant diffrence was found between the micro-bond strength of cement A and that of cement B with glass ceramic. Self-adhesive resin cement can achieve similar bond durability to glass ceramic as conventional resin cement does.


Reductive defluorination of perfluorooctanoic acid by titanium(III) citrate with vitamin B12 and copper nanoparticles.
Perfluorooctanoic acid (PFOA) is widespread in the environment, which causes serious health and safety concerns. A mechanistic study on reductive defluorination of PFOA by titanium(III) citrate in the presence of catalysts was conducted. Vitamin B12 was used to catalyze reduction reactions by shuttling electrons from a reducing agent (electron donor) to PFOA to produce a Co-carbon bond intermediates. In the presence of copper nanoparticles, a precursor complex, B12-C7F14COOH, adsorbed on the metal surface, followed by a hydrogenolytic reaction to form less-fluorinated products. The synergistic effect between vitamin B12 and copper nanoparticles enhances the reductive activities by electron-transfer reactions and hydrogenolysis. The efficient reduction of PFOA to less-noxious compounds was demonstrated with a copper dose of 2gL-1, titanium(III) citrate (45mM), and vitamin B12 (0.2mM) with an initial pH of 9.0 and 70°C. In this anoxic aqueous solution, the biomimetic reductive system effectively removed 65% of PFOA. The mass balance on fluoride matched the observed degradation of PFOA, while no short-chain intermediates were detected.


The best-worst scaling approach: an alternative to Schwartz's Values Survey.
Traditional self-report ratings have some measurement problems that a relatively new method, best-worst scaling (BWS; Finn & Louviere, 1992), may overcome. This alternative method, based on Louviere's BWS, can be used to measure the relative importance or perceived trade-offs among choice alternatives. The method is illustrated as an alternative to the Schwartz Value Survey (SVS; Schwartz, 1992). In a series of samples, it was found that Schwartz values best-worst survey (SVBWS) reproduced Schwartz's (1992) theoretical value structure and supported hypothesized relationships between values and value-expressive behaviors, ethnocentrism, and environmental-related tourism activities. In addition, the SVBWS approach took significantly less respondent time than the traditional SVS approach.


Electrostatic layer-by-layer nanoassembly on biological microtemplates: platelets.
Platelets were coated with 78-nm silica nanoparticles, 45-nm fluorescent nanospheres, or bovine immunoglobulin G (IgG) through layer-by-layer assembly by alternate adsorption with oppositely charged linear polyions. Sequential deposition on platelet surfaces of cationic poly(dimethyldiallylammonium chloride) and anionic poly(styrene sulfonate) was followed by adsorption of nanoparticles or immunoglobulins. Nano-organized shells of platelets were demonstrated by transmission electron microscopy and fluorescence microscope images. Bovine IgG was assembled on platelets, as verified with anti-bovine IgG-FITC labeling. Localized targeting of anti-IgG shelled platelets was also demonstrated. An ability to coat blood cells with nano-organized shells can have applications in cardiovascular research and targeted drug delivery.


Computational function assignment for potential drug targets: from single genes to cellular systems.
Biomedical science is currently undergoing an epoch-marking transition from its classical phase to the post-genome era. The outstanding success of world-wide genome sequencing efforts, evidenced by the recent publication of the draft of the human genome, together with the completion of several genomes of eukaryotic model organisms and the availability of microbial genome sequences, is opening up data sources of unprecedented scale for drug discovery. Furthermore, the elucidation of genome expression states through transcriptomic and proteomic techniques is playing a crucial role in the characterisation of disease at the molecular level. At the same time, our still very limited knowledge of the biological functions of genes and proteins at different levels of cellular organisation is preventing full exploitation of the available data. This review will discuss current computational techniques for function prediction based on the sequence-structure-function paradigm. Newly emerging approaches aimed at gaining an expanded understanding of function through integration of data from various sources and modelling of complex cellular systems will also be highlighted.


Childhood exposure to Libby amphibole asbestos and respiratory health in young adults.
Vermiculite ore containing Libby amphibole asbestos (LAA) was mined in Libby, MT, from the 1920s-1990. Recreational and residential areas in Libby were contaminated with LAA. This objective of this study was to characterize childhood exposure to LAA and investigate its association with respiratory health during young adulthood. Young adults who resided in Libby prior to age 18 completed a health and activity questionnaire, pulmonary function testing, chest x-ray and HRCT scan. LAA exposure was estimated based on participant report of engaging in activities with potential LAA exposure. Quantitative LAA estimates for activities were derived from sampling data and literature reports. A total of 312 participants (mean age 25.1 years) were enrolled and reported respiratory symptoms in the past 12 months including pleuritic chest pain (23%), regular cough (17%), shortness of breath (18%), and wheezing or whistling in the chest (18%). Cumulative LAA exposure was significantly associated with shortness of breath (aOR = 1.12, 95% CI 1.01-1.25 per doubling of exposure). Engaging in recreational activities near Rainy Creek Road (near the former mine site) and the number of instances heating vermiculite ore to make it expand or pop were also significantly associated with respiratory symptoms. LAA exposure was not associated with pulmonary function or pleural or interstitial changes on either chest x-ray or HRCT. Pleural or interstitial changes on x-ray or HRCT were not observed among this cohort of young adults. However, childhood exposure to LAA was significantly associated with respiratory symptoms during young adulthood. Pleuritic chest pain, in particular, has been identified as an early symptom associated with LAA exposure and therefore warrants continued follow-up given findings of progressive disease in other LAA exposed populations.


Acute Coronary Syndrome: Inpatient Management.
The first step in inpatient management of acute coronary syndrome (ACS) is determining whether the patient has ST-segment elevation myocardial infarction (STEMI). For STEMI, the initial approach to management is cardiac catheterization with percutaneous coronary intervention (PCI) to reperfuse the blocked artery; PCI should take place within 120 minutes of first medical contact. However, if no contraindications are present, fibrinolytic therapy is preferred if PCI will take more than 120 minutes. In ACS without STEMI, cardiac catheterization with PCI is the recommended approach for patients who are unstable, and for stable patients with high risk assessment scores, diabetes or renal insufficiency, stent placement within the past 6 months, or prior bypass surgery. Treatment of patients with ACS who do not meet the previously discussed criteria can be noninvasive when troponin levels are not elevated, no ST-segment elevations or depressions are present on electrocardiogram, and risk assessment scores are low. Assuming no contraindications exist, all patients with or without STEMI should receive medical therapy that includes nitroglycerin, antiplatelet agents, anticoagulants, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, aldosterone blockade if left ventricular function is impaired, beta blockers, and statins.


Pseudophaeochromocytoma associated with clozapine treatment.
We describe a 44 year old man with treatment resistant schizophrenia who developed pseudophaeochromocytoma on clozapine with high blood pressure, tachycardia and elevated 24 hour urinary catecholamines. All resolved on discontinuing clozapine. We reviewed the literature and found five other cases. We suggest that this is a common side effect, transient in some patients. Elevated plasma noradrenaline does not appear to be relevant to the unique benefits of clozapine.


Autonomous application of quantitative PCR in the deep sea: in situ surveys of aerobic methanotrophs using the deep-sea environmental sample processor.
Recent advances in ocean observing systems and genomic technologies have led to the development of the deep-sea environmental sample processor (D-ESP). The D-ESP filters particulates from seawater at depths up to 4000 m and applies a variety of molecular assays to the particulates, including quantitative PCR (qPCR), to identify particular organisms and genes in situ. Preserved samples enable laboratory-based validation of in situ results and expanded studies of genomic diversity and gene expression. Tests of the D-ESP at a methane-rich mound in the Santa Monica Basin centered on detection of 16S rRNA and particulate methane monooxygenase (pmoA) genes for two putative aerobic methanotrophs. Comparison of in situ qPCR results with laboratory-based assays of preserved samples demonstrates the D-ESP generated high-quality qPCR data while operating autonomously on the seafloor. Levels of 16S rRNA and pmoA cDNA detected in preserved samples are consistent with an active community of aerobic methanotrophs near the methane-rich mound. These findings are substantiated at low methane sites off Point Conception and in Monterey Bay where target genes are at or below detection limits. Successful deployment of the D-ESP is a major step toward developing autonomous systems to facilitate a wide range of marine microbiological investigations.


Comparison between Hummelsheim and Jensen procedures in the management of chronic sixth nerve palsy.
To compare the postoperative alignment, degree of improvement of abduction, and complications of the Hummelsheim procedure to the Jensen procedure in chronic sixth nerve palsy, and to calculate the dose-response of both procedures. A retrospective study was done on patients who either had Hummelsheim or Jensen procedure for chronic sixth nerve palsy. Demographic characteristics, details of surgical procedure, ductions, versions, and angles of misalignment before and after surgery were analyzed. A total of 79 patients were identified: 38 Jensen and 41 Hummelsheim. There were no statistically significant differences in baseline characteristics of both groups. Medial rectus recession was performed in 35 patients in the Jensen group and in 30 patients in the Hummelsheim group. Success defined as orthotropia within 8 PD was achieved in 25 (66%) patients in the Jensen group and in 24 (59%) patients in the Hummelsheim group (P = 0.51). The mean improvement in the angle of deviation in the primary position was 42 ± 12 PD in the Jensen group and 42 ± 16 PD in the Hummelsheim group (P = 0.89). The mean improvement in abduction was slightly better in the Hummelsheim group (1.8 vs 1.5, P = 0.32). A new vertical deviation occurred in three patients in the Jensen group and in 4 patients in the Hummelsheim group. Anterior segment ischemia occurred in one patient in the Jensen group. There was no difference in the success rate between the Hummelsheim and Jensen procedures in cases of chronic sixth nerve palsy. Strabismus surgeons can choose between the two procedures according to their preference.


Brain-gut axis in pancreatic secretion and appetite control.
The stimulation of exocrine pancreatic secretion that has been attributed by Pavlov exclusively to various reflexes (nervism), was then found that it depend also on numerous enterohormones, especially cholecystokinin (CCK) and secretin, released by duodeno-jejunal mucosa and originally believed to act via an endocrine pathway. Recently, CCK and other enterohormones were found to stimulate the pancreas by excitation of sensory nerves and triggering vago-vagal and entero-pancreatic reflexes. Numerous neurotransmitters and neuropeptides released by enteric nervous system (ENS) of gut and pancreas have been also implicated in the regulation of exocrine pancreas. This article was designed to review the contribution of vagal nerves and entero-hormones, especially CCK and other enterohormones, involved in the control of appetitive behavior such as leptin and ghrelin and pancreatic polypeptide family (peptide YY and neuropeptide Y). Basal secretion shows periodic fluctuations with peals controlled by ENS and by motilin and Ach. Plasma ghrelin, that is considered as hunger hormone, increases under basal conditions, while plasma leptin falls to the lowest level. Postprandial pancreatic secretion, classically divided into cephalic, gastric and intestinal phases, involves predominantly CCK, which under physiological conditions acts almost entirely by activation of vago-vagal reflexes to stimulate the exocrine pancreas, being accompanied by the fall in plasma ghrelin and increase of plasma leptin, reflecting feeding behavior. We conclude that the major role in postprandial pancreatic secretion is played by vagus and gastrin in cephalic and gastric phases and by vagus in conjunction with CCK and secretin in intestinal phase. PP, PYY somatostatin, leptin and ghrelin that affect food intake appear to participate in the feedback control of postprandial pancreatic secretion via hypothalamic centers.


Feature Extraction of a Non-Stationary Seismic-Acoustic Signal Using a High-Resolution Dyadic Spectrogram.
Using a novel mathematical tool called the Te-gram, researchers analyzed the energy distribution of frequency components in the scale-frequency plane. Through this analysis, a frequency band of approximately 12 Hz is identified, which can be isolated without distorting its constituent frequencies. This band, along with others, remained inseparable through conventional time-frequency analysis methods. The Te-gram successfully addresses this knowledge gap, providing multi-sensitivity in the frequency domain and effectively attenuating cross-term energy. The Daubechies 45 wavelet function was employed due to its exceptional 150 dB attenuation in the rejection band. The validation process encompassed three stages: pre-, during-, and post-seismic activity. The utilized signal corresponds to the 19 September 2017 earthquake, occurring between the states of Morelos and Puebla, Mexico. The results showcased the impressive ability of the Te-gram to surpass expectations in terms of sensitivity and energy distribution within the frequency domain. The Te-gram outperformed the procedures documented in the existing literature. On the other hand, the results show a frequency band between 0.7 Hz and 1.75 Hz, which is named the planet Earth noise.


Tumor mutational burden standardization initiatives: Recommendations for consistent tumor mutational burden assessment in clinical samples to guide immunotherapy treatment decisions.
Characterization of tumors utilizing next-generation sequencing methods, including assessment of the number of somatic mutations (tumor mutational burden [TMB]), is currently at the forefront of the field of personalized medicine. Recent clinical studies have associated high TMB with improved patient response rates and survival benefit from immune checkpoint inhibitors; hence, TMB is emerging as a biomarker of response for these immunotherapy agents. However, variability in current methods for TMB estimation and reporting is evident, demonstrating a need for standardization and harmonization of TMB assessment methodology across assays and centers. Two uniquely placed organizations, Friends of Cancer Research (Friends) and the Quality Assurance Initiative Pathology (QuIP), have collaborated to coordinate efforts for international multistakeholder initiatives to address this need. Friends and QuIP, who have partnered with several academic centers, pharmaceutical organizations, and diagnostic companies, have adopted complementary, multidisciplinary approaches toward the goal of proposing evidence-based recommendations for achieving consistent TMB estimation and reporting in clinical samples across assays and centers. Many factors influence TMB assessment, including preanalytical factors, choice of assay, and methods of reporting. Preliminary analyses highlight the importance of targeted gene panel size and composition, and bioinformatic parameters for reliable TMB estimation. Herein, Friends and QuIP propose recommendations toward consistent TMB estimation and reporting methods in clinical samples across assays and centers. These recommendations should be followed to minimize variability in TMB estimation and reporting, which will ensure reliable and reproducible identification of patients who are likely to benefit from immune checkpoint inhibitors.


Down-regulation of microRNA-203-3p initiates type 2 pathology during schistosome infection via elevation of interleukin-33.
The type 2 immune response is the central mechanism of disease progression in schistosomiasis, but the signals that induce it after infection remain elusive. Aberrant microRNA (miRNA) expression is a hallmark of human diseases including schistosomiasis, and targeting the deregulated miRNA can mitigate disease outcomes. Here, we demonstrate that efficient and sustained elevation of miR-203-3p in liver tissues, using the highly hepatotropic recombinant adeno-associated virus serotype 8 (rAAV8), protects mice against lethal schistosome infection by alleviating hepatic fibrosis. We show that miR-203-3p targets interleukin-33 (IL-33), an inducer of type 2 immunity, in hepatic stellate cells to regulate the expansion and IL-13 production of hepatic group 2 innate lymphoid cells during infection. Our study highlights the potential of rAAV8-mediated miR-203-3p elevation as a therapeutic intervention for fibrotic diseases.


Comparison of objective and subjective factors in the adherence to antimuscarinics when treating overactive bladder in employed persons.
This study examines subjective reasons for the refusal of treatment and the state of objective status markers of various factors influencing the resistance of patients when treating overactive bladder by antimuscarinic drugs (AMs). The socioeconomic and medical parameters were studied in 2465 patients aged 18-60 years (1446 women (58.7%), 1019 men (41.3%); mean age was 52.1) taking AMs during the year. The study control was carried out by studying passport data, employers' income certificates, patients' ambulatory medical records, the use of OABq-SF and MOS SF-36 questionnaires, voiding diaries and uroflowmetry. The average time to reach the 30-day break in the AM administration was 177 days. During the 12-month follow up, 74.7% of patients discontinued their participation. In total, 35.9% of patients stated medical reasons for the refusal of AM treatment; in 31.9% of individuals in the group the deviation of objective health status markers from average sample values was established. Economic reasons for the refusal were given by 20.4% of patients; in 18.5% of individuals economic status markers were different from average sample values. In 24.1% of cases of refusal of treatment, patients indicated social and psychological reasons; objective social and psychological status markers were altered in 35.9%. The percentage of patients indicating economic and medical reasons for the refusal of AM treatment is statistically uniform with respect to the percentage of patients with objective disturbances of health and economic statuses. The percentage of patients indicating social and psychological factors as a reason for the refusal of treatment was significantly lower than the percentage of patients with altered social and psychological status markers. These results can be used in practical healthcare when predicting adherence to AM use.


The Association Between Air Pollution and Onset of Depression Among Middle-Aged and Older Women.
Despite recently reported associations between air pollution and acute psychiatric outcomes, the association with depression onset has not, to our knowledge, been previously examined. We conducted a prospective cohort study among 41,844 women in the Nurses' Health Study, in the United States. The women had an average age of 66.6 (standard deviation, 7.6) years, were depression-free in 1996, and were followed through 2008. May-September ozone exposures were predicted by interpolating concentrations from the 5 nearest monitors. One-, 2-, and 5-year average concentrations of particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM2.5) were predicted at each participant's residence using a spatiotemporal model. We defined depression as report of doctor's diagnosis or use of antidepressant medication. We estimated adjusted hazard ratios with time-varying Cox models. Hazard ratios for both pollutants were elevated (per 10-parts-per-billion increase in ozone, hazard ratio (HR) = 1.06; 95% confidence interval (CI): 1.00, 1.12; per 10-μg/m3 increase in 1-year PM2.5, HR = 1.08; 95% CI: 0.97, 1.20). Associations were stronger when only antidepressant use was used to define cases (for ozone, HR = 1.08; 95% CI: 1.02, 1.14; for PM2.5, HR = 1.12; 95% CI: 1.00, 1.25). To our knowledge, these results represent the first identification of a possible association between both long-term ozone and PM2.5 exposure and depression onset. Although the stronger association specifically with antidepressant use may reflect that this endpoint better captures the onset time and milder cases, our findings should be interpreted with caution.


Borel Summability of Perturbative Series in 4D N=2 and 5D N=1 Supersymmetric Theories.
We study weak coupling perturbative series in 4D N=2 and 5D N=1 supersymmetric gauge theories with Lagrangians. We prove that the perturbative series of these theories in the zero-instanton sector are Borel summable for various observables. Our result for the 4D N=2 case supports an expectation from a recent proposal on a semiclassical realization of infrared renormalons in QCD-like theories, where the semiclassical solution does not exist in N=2 theories and the perturbative series are unambiguous, namely, Borel summable. We also prove that the perturbative series in an arbitrary number of instanton sectors are Borel summable for a wide class of theories. It turns out that exact results can be obtained by summing over the Borel resummations with every instanton number.


Enhancement of ribosomal ribonucleic acid synthesis by deoxyribonucleic acid gyrase activity in Escherichia coli.
The effect of the deoxyribonucleic acid (DNA) gyrase inhibitors coumermycin A1, novobiocin, and oxolinic acid on ribonucleic acid (RNA) synthesis in Escherichia coli was studied in vivo and in vitro. Preferential inhibition of ribosomal RNA (rRNA) synthesis was observed. No effect of oxolinic acid and coumermycin on rRNA synthesis was seen in mutants having a DNA gyrase which is resistant to these inhibitors. In a temperature-sensitive DNA gyrase mutant rRNA synthesis was decreased at nonpermissive temperatures. Thus, a functional DNA gyrase is required for rRNA synthesis. Purified DNA gyrase had no effect on rRNA synthesis in a purified system. However, DNA gyrase does show preferential stimulation of rRNA synthesis in a system supplemented with other proteins. Apparently, DNA gyrase stimulation of rRNA synthesis requires another protein.


Behavioural and emotional disturbance in fragile X syndrome.
A range of behaviours has been postulated as specific manifestations of the Fragile X (fra(X)) syndrome. This study examines a broad range of behaviours in subjects with fra(X) syndrome and in control individuals. It was designed to take account of methodological factors which may account for differing findings in previous studies. Subjects were 48 children, adolescents, and young adults with fra(X) syndrome. They were compared with a large community epidemiological sample (N = 454) of persons with mental retardation (M.R.), matched for age, sex, and IQ. Behavioural problems were studied using the Developmental Behaviour Checklist, an instrument of established reliability and validity in the evaluation of behavioural and emotional disturbance in children and adolescents with mental retardation. Fragile X subjects had more shyness and avoidance of eye contact and less antisocial behaviour. Further methodological issues pertaining to studies of behaviour phenotype in general are discussed.


Glaucomas.
Canine and feline glaucomas are commonly presented as ocular emergencies. Glaucoma is a common cause of vision loss and a frustrating disorder in terms of medical and surgical treatment. Increased intraocular pressure (IOP) is a significant risk factor in the disease, leading to damage of the retina and optic nerve head. IOP measurement and gonioscopic and fundic examinations provide the instruments for diagnosis of glaucoma. The primary goal in glaucoma therapy is aimed at vision preservation. Medical treatment provides temporary relief, but alone it fails to control IOP in the long term, and surgical intervention is recommended. Surgical patient selection depends on several factors, from type and stage of glaucoma to the presence of or potential for vision. Available surgical procedures to decrease IOP consist of cyclodestructive techniques to decrease aqueous humor production and filtering techniques to increase its drainage. Even with recent surgical and medical advances, pain and blindness are still common occurrences in the disease: end-stage procedures such as enucleation, evisceration with intrascleral prosthesis, and pharmacologic ablation of ciliary bodies are then recommended to address chronic discomfort for buphthalmic and blind globes.


Cleft Palate and Aglossia Result From Perturbations in Wnt and Hedgehog Signaling.
The objective of this study was to explore the molecular basis for cleft secondary palate and arrested tongue development caused by the loss of the intraflagellar transport protein, Kif3a. Kif3a mutant embryos and their littermate controls were analyzed for defects in facial development at multiple stages of embryonic development. Histology was employed to understand the effects of Kif3a deletion on palate and tongue development. Various transgenic reporter strains were used to understand how deletion of Kif3a affected Hedgehog and Wnt signaling. Immunostaining for structural elements of the tongue and for components of the Wnt pathway were performed. BrdU activity analyses were carried out to examine how the loss of Kif3a affected cell proliferation and led to palate and tongue malformations. Kif3a deletion causes cranial neural crest cells to become unresponsive to Hedgehog signals and hyper-responsive to Wnt signals. This aberrant molecular signaling causes abnormally high cell proliferation, but paradoxically outgrowths of the tongue and the palatal processes are reduced. The basis for this enigmatic effect can be traced back to a disruption in epithelial/mesenchymal signaling that governs facial development. The primary cilium is a cell surface organelle that integrates Hh and Wnt signaling, and disruptions in the function of the primary cilium cause one of the most common-of the rarest-craniofacial birth defects observed in humans. The shared molecular basis for these dysmorphologies is an abnormally high Wnt signal simultaneous with an abnormally low Hedgehog signal. These pathways are integrated in the primary cilium.


Dietary (n-3)-fatty acids, prostaglandins, and prolonged gestation in humans.
Prostaglandins, especially prostaglandin F2 alpha, are important regulators in the onset and maintenance of parturition in humans. Inhibition of prostaglandin formation by drugs can prolong gestation in humans. High dietary intake of long chain (n-3)-fatty acids can inhibit formation of many arachidonic acid-derived prostaglandins as well as stimulate formation of eicosapentaenoic acid-derived prostaglandins. The latter ones often have lower biological activity than the former ones. The effect of (n-3)-fatty acids on prostaglandin formation has been shown by analysis of prostaglandin metabolites in human urine. Very little is known about the tissue origin as well as the physiologicalfunctions of those prostaglandins, the metabolites of which are quantitated in urine from non-pregnant humans. In pregnant women the increased amount of prostaglandin F2 alpha-metabolites in urine, plasma and amniotic fluid probably is of uterine origin. Women in the Faroe Islands have longer gestation and are giving birth to infants with higher birth weight than women in Denmark. The Faroe Islands is a fishing community with an old cultural tradition for eating pilot whales. Fish and marine mammals are rich in long chain (n-3)-fatty acids. We have hypothesized that a high intake of long chain (n-3)-fatty acids prolongs gestation in humans by interfering with uterine prostaglandin formation, possibly by inhibiting formation of prostaglandin F2 alpha and prostaglandin E2. Preliminary results of an epidemiological observational study have shown a positive correlation between (n-3)-fatty acids in maternal erythrocytes and length of gestation. These results are in accordance with our hypothesis, but a causal relationship remains to be shown.


Betaine Lipid Is Crucial for Adapting to Low Temperature and Phosphate Deficiency in Nannochloropsis.
Diacylglyceryl-N,N,N-trimethylhomo-Ser (DGTS) is a nonphosphorous, polar glycerolipid that is regarded as analogous to the phosphatidylcholine in bacteria, fungi, algae, and basal land plants. In some species of algae, including the stramenopile microalga Nannochloropsis oceanica, DGTS contains an abundance of eicosapentaenoic acid (EPA), which is relatively scarce in phosphatidylcholine, implying that DGTS has a unique physiological role. In this study, we addressed the role of DGTS in N. oceanica We identified two DGTS biosynthetic enzymes that have distinct domain configurations compared to previously identified DGTS synthases. Mutants lacking DGTS showed growth retardation under phosphate starvation, demonstrating a pivotal role for DGTS in the adaptation to this condition. Under normal conditions, DGTS deficiency led to an increase in the relative amount of monogalactosyldiacylglycerol, a major plastid membrane lipid with high EPA content, whereas excessive production of DGTS induced by gene overexpression led to a decrease in monogalactosyldiacylglycerol. Meanwhile, lipid analysis of partial phospholipid-deficient mutants revealed a role for phosphatidylcholine and phosphatidylethanolamine in EPA biosynthesis. These results suggest that DGTS and monogalactosyldiacylglycerol may constitute the two major pools of EPA in extraplastidic and plastidic membranes, partially competing to acquire EPA or its precursors derived from phospholipids. The mutant lacking DGTS also displayed impaired growth and a lower proportion of EPA in extraplastidic compartments at low temperatures. Our results indicate that DGTS is involved in the adaptation to low temperatures through a mechanism that is distinct from the DGTS-dependent adaptation to phosphate starvation in N. oceanica.


Assessing climate change impacts on fresh water resources of the Athabasca River Basin, Canada.
Proper management of blue and green water resources is important for the sustainability of ecosystems and for the socio-economic development of river basins such as the Athabasca River Basin (ARB) in Canada. For this reason, quantifying climate change impacts on these water resources at a finer temporal and spatial scale is often necessary. In this study, we used a Soil and Water Assessment Tool (SWAT) to assess climate change impacts on fresh water resources, focusing explicitly on the impacts to both blue and green water. We used future climate data generated by the Canadian Center for Climate Modelling and Analysis Regional Climate Model (CanRCM4) with a spatial resolution of 0.22°×0.22° (~25km) for two emission scenarios (RCP 4.5 and 8.5). Results projected the climate of the ARB to be wetter by 21-34% and warmer by 2-5.4°C on an annual time scale. Consequently, the annual average blue and green water flow was projected to increase by 16-54% and 11-34%, respectively, depending on the region, future period, and emission scenario. Furthermore, the annual average green water storage at the boreal region was expected to increase by 30%, while the storage was projected to remain fairly stable or decrease in other regions, especially during the summer season. On average, the fresh water resources in the ARB are likely to increase in the future. However, evidence of temporal and spatial heterogeneity could pose many future challenges to water resource planners and managers.


Joint analysis of individual-level and summary-level GWAS data by leveraging pleiotropy.
A large number of recent genome-wide association studies (GWASs) for complex phenotypes confirm the early conjecture for polygenicity, suggesting the presence of large number of variants with only tiny or moderate effects. However, due to the limited sample size of a single GWAS, many associated genetic variants are too weak to achieve the genome-wide significance. These undiscovered variants further limit the prediction capability of GWAS. Restricted access to the individual-level data and the increasing availability of the published GWAS results motivate the development of methods integrating both the individual-level and summary-level data. How to build the connection between the individual-level and summary-level data determines the efficiency of using the existing abundant summary-level resources with limited individual-level data, and this issue inspires more efforts in the existing area. In this study, we propose a novel statistical approach, LEP, which provides a novel way of modeling the connection between the individual-level data and summary-level data. LEP integrates both types of data by LEveraging Pleiotropy to increase the statistical power of risk variants identification and the accuracy of risk prediction. The algorithm for parameter estimation is developed to handle genome-wide-scale data. Through comprehensive simulation studies, we demonstrated the advantages of LEP over the existing methods. We further applied LEP to perform integrative analysis of Crohn's disease from WTCCC and summary statistics from GWAS of some other diseases, such as Type 1 diabetes, Ulcerative colitis and Primary biliary cirrhosis. LEP was able to significantly increase the statistical power of identifying risk variants and improve the risk prediction accuracy from 63.39% (±0.58%) to 68.33% (±0.32%) using about 195 000 variants. The LEP software is available at https://github.com/daviddaigithub/LEP. Supplementary data are available at Bioinformatics online.


New applications and developments in the use of multiplex ligation-dependent probe amplification.
Multiplex ligation-dependent probe amplification (MLPA) is a commonly used technique for determining relative DNA sequence dosage (or copy number) in a complex DNA sample. Originally MLPA was designed as a copy number analysis tool for detecting disease-causing genomic mutations and has been successfully applied in the testing and identification of hundreds of genomic mutations in numerous genes including DMD, BRCA1, NF1, and TSC2. More recently, several modifications of the original technique have been implemented. Arguably the most important enhancement of MLPA has been probe generation by chemical synthesis, enabling the facile creation of novel probe sets for any desired application. Other newer applications of MLPA include methylation status determination, copy number analysis in segmentally duplicated regions, expression profiling, and transgene genotyping. MLPA has a potential major role in the analysis of common copy number variation in genome-wide association analyses, which may be enhanced by future improvements to increase throughput and lower costs, such as array-MLPA.


Effect of fuel to oxidizer ratio on the structure, micro structure and EPR of combustion synthesized NiO nanoparticles.
In this work we describe the synthesis, micro structure (XRD, SEM) and EPR of NiO nanoparticles synthesized by urea-based combustion method using Ni nitrate as the source of Ni. We used fuel-to-oxidizer ratio (psi) as a control parameter to investigate how lattice parameter, particle size and EPR susceptibility vary with psi = 0.25 to 2. Earlier we have studied NiO as a substitutional solute in MgO. The average particle size of NiO was estimated from the full width half maximum (gaussian and lorentzian fits) of the X-ray diffraction peaks of powders using Sherrer's formula and Williamson-Hall plot. The particle size varies from 7 nm to 38 nm as psi is varied systematically. The surface areas were measured using BET method. FT-IR confirms the Ni-O crystalline bond formation. We also calculated porosity and strain in the NiO nanoparticles with varying psi. EPR spectra have yielded the susceptibility of the NiO nanoparticles. Band gap of NiO was determined by UV-visible absorption edge.


Cadmium-induced Sertoli Cell Injury Through p38-MAPK and Related Signaling Proteins-A Study by RNA Sequencing.
Environmental toxicants, such as cadmium, found in foods, water, and consumer products are known to induce male reproductive dysfunction. However, the underlying molecular mechanism(s) by which cadmium-induced Sertoli cell injury as manifested by a disruption of the blood-testis barrier (BTB) remains unknown. Interestingly, one of the primary targets of cadmium toxicity in the testis is the cytoskeletons of the Sertoli cells, which, in turn, impedes cell junctions in the seminiferous epithelium. In order to expand these earlier observations and to provide a roadmap for future studies, we embarked a study using RNA sequencing to identify the pertinent genes involved in cadmium-induced Sertoli cell injury. Using bioinformatics analyses, multiple gene sets that regulated actin and microtubule (MT) cytoskeletons were identified along with components of the mitogen-activated protein kinase (MAPK) signaling protein and several signaling pathways. More important, we have also discovered that while the gene expression of p38-MAPK (also JNK or c-Jun) was considerably up- or downregulated during cadmium-induced Sertoli cell injury, the activated (phosphorylated) form was upregulated. Importantly, doramapimod (also known as BIRB 796), a specific p38-MARK inhibitor, that was shown to selectively block cadmium-induced p-p38 MAPK activation via phosphorylation in Sertoli cells, was indeed capable of blocking cadmium-induced Sertoli cell injury including disruption of the Sertoli cell-permeability barrier function, disruptive distribution of BTB-associated proteins, and disruptive organization of the actin and MT cytoskeletons. These data provide a helpful source of information for investigators to probe the role of signaling proteins and/or their signaling cascades, besides MAPKs, that likely utilized by cadmium to induce reproductive dysfunction.


[Variations in blood cholinesterase activity and exposure to chlorpyrifos in termite-control workers].
Chlorpyrifos, an organophosphate insecticide, has often been used as a termite-control agent since the advent of regulatory measures against the use of chlordanes in September 1986. A current concern is hazards such as organophosphorus poisoning among termite-control workers. In this study, the blood cholinesterase activity, the number of hours engaged in termite-control work, general conditions, and various test values were examined regularly in eight workers at a termite-control office. The results are summarized as follows. 1. The plasma cholinesterase level was within the normal range from October 1986 until April 1987 in all workers, but started decreasing after May following the initiation of the full-scale termite-control season. It remained lower than the normal range (0.6 pH) from June until August in five of the six termite-control workers. The lowest level observed during this period was less than 50% of the mean value for each worker prior to the busy season in the six termite-control workers and was less than 10% of the pre-season values in three of them. In two workers, engaged mainly in sales, the plasma cholinesterase activity remained higher than in termite-control workers throughout the season. The lowest level in this minimally-exposed group during this period was not less than 50% of the mean value for each worker before the busy season. With the arrival of the off season, the level began to recover and returned to normal in all workers in January 1988. 2. The red cell cholinesterase activity remained within the normal range throughout the observation period, but it was generally low during the busy season from June to September and relatively high during the off season from December 1987 to January 1988. On the average, the red cell cholinesterase activity during the season was about 30% lower than that in the off season. 3. No marked subjective or objective abnormalities were seen in the workers. The results of other tests were generally normal, although a slight decrease in the red cell and white cell counts as well as abnormalities in serum lipid and lipase were noted in some workers. Further observations are necessary. 4. A significant negative correlation was noted between the number of hours engaged in termite-control work and variations in the plasma cholinesterase activity.(ABSTRACT TRUNCATED AT 400 WORDS)


How much does household food insecurity explain income inequalities in untreated dental caries?
The pathway by which socioeconomic disadvantages are manifested in the occurrence of dental caries remains unclear. To explore how much the association between untreated dental caries and income inequalities is related to household food insecurity (HFI). A population-based study was conducted with a sample of 466 12-year-old students. Dental caries was evaluated by an examiner who had undergone calibration exercises. HFI was assessed using the Food Insecurity Scale validated for Brazilian Portuguese. Poisson regression models were created to determine associations between dental caries and both household income and HFI. The proportion of the income effect on dental caries explained by HFI was determined by the variation in percentages between the crude prevalence ratio (PRc ) for dental caries and this measure adjusted by HFI (PRa ). The prevalence of dental caries was higher among children from families with a per capita household income lower than US$ 71 (PR: 1.69; 95%CI: 1.15-2.49) or from US$ 71 to US$ 142 (PR: 1.50; 95%CI: 1.04-2.17). Moreover, 14% of the association between a low income and dental caries was explained by HFI. Differences in the prevalence of dental caries in schoolchildren related to socioeconomic inequalities could partially be attributed to HFI in low-income families.


Multiple two-step oscillation regimes produced by the alto saxophone.
A saxophone mouthpiece fitted with sensors is used to observe the oscillation of a saxophone reed, as well as the internal acoustic pressure, allowing to identify qualitatively different oscillating regimes. In addition to the standard two-step regime, where the reed channel successively opens and closes once during an oscillation cycle, the experimental results show regimes featuring two closures of the reed channel per cycle, as well as inverted regimes, where the reed closure episode is longer than the open episode. These regimes are well-known on bowed string instruments and some were already described on the Uilleann pipes. A simple saxophone model using measured input impedance is studied with the harmonic balance method, and is shown to reproduce the same two-step regimes. The experiment shows qualitative agreement with the simulation: in both cases, the various regimes appear in the same order as the blowing pressure is increased. Similar results are obtained with other values of the reed opening control parameter, as well as another fingering.


Mean arterial blood pressure values of complaint-free pregnant women in the first and second trimesters
Introduction: The cardiovascular system of women adapts to pregnancy to maintain the growth of the fetus. Objective: The aim of this prospective study is to measure the mean arterial pressure of each gestational week. Hemo-dynamical changes in pregnancy are different in every trimester. Normally the mean arterial pressure decreases at the beginning of the pregnancy, and starts to increase in the third trimester. Method: We have examined 185 pregnant women between May 2020 and July 2020. We used a validated device, TensioMed Arteriograph 2020, which can monitor blood pressure parameters non-invasively. We measured the following parameters: mean arterial pressure, central systolic blood pressure, pulse wave velocity, ankle-brachial index. Results: We found that the mean arterial pressure and the central systolic blood pressure decrease from the 12th to the 15th week, and then start to rise. We did not find significant difference considering the ankle-brachial index and pulse wave velocity. Discussion: The change at the 15th gestational week is the result of circulatory redistribution, histological change when the placenta replaces the chorion. Thus, a high-flow and low-resistance blood flow is created. Compared to the reference values in non-pregnant women, we can say that the values vary significantly within the normal range. Conclusion: Hereafter, we would like to extend our studies to the third trimester as well as to include not only healthy pregnant women, but also pregnant women at risk of developing hypertension. This would create a Hungarian database, which could become a useful pillar in national prenatal care in screening for gestational hypertension.


[Standard prescriptions for the formulation of medicinal preparations in pharmacies. I. Suspensions for dermal administration].
The paper summarizes the present state of standard prescriptions for the formulation of suspensions for dermal administration in the Czech Republic and compares it with the NRF (Neues Rezeptur-Formularium in Deuscher Arzneimittel-Codex) standard prescriptions. The analysis of medical prescriptions for suspensions for dermal administration dispensed in the pharmacies of the Czech Republic has revealed that 18.8 % of the prescriptions were for 50% suspension of zinc(II) oxide in sunflower oil. This preparation should therefore become a candidate for standardization as a monograph in the national part of the Czech Pharmacopoeia.


Sesquiterpenes and cyclopeptides from the endophytic fungus Trichoderma asperellum SAMUELS, LIECKF. & NIRENBERG.
Trichodones A-C (1-3, resp.), three new sesquiterpenes, together with the two known cyclopeptides PF1022F and halobacillin (4 and 5, resp.), have been isolated from the crude extract of the endophytic fungus Trichoderma asperellum SAMUELS, LIECKF. & NIRENBERG residing in the traditional Chinese medicinal plant Panax notoginseng (BURKILL) F.H.CHEN. The structures and configurations of compounds 1-3 were determined by NMR spectroscopy and mass spectrometry. The relative configuration for 1 was determined by analysis of its pertinent coupling constants and NOESY correlations, whereas the absolute configuration of 1 was established by CD spectroscopy. Compounds 4 and 5 displayed antibacterial activities against Enterococcus faecium (CGMCC 1.2025) with IC₅₀ values of 7.30 and 5.24 μM, and against Staphylococcus aureus COL (CGMCC 1.2465) with IC₅₀ values of 19.02 and 14.00 μM, respectively.


Paediatric cancer in low-income and middle-income countries.
Patterns of cancer incidence across the world have undergone substantial changes as a result of industrialisation and economic development. However, the economies of most countries remain at an early or intermediate stage of development-these stages are characterised by poverty, too few health-care providers, weak health systems, and poor access to education, modern technology, and health care because of scattered rural populations. Low-income and middle-income countries also have younger populations and therefore a larger proportion of children with cancer than high-income countries. Most of these children die from the disease. Chronic infections, which remain the most common causes of disease-related death in all except high-income countries, can also be major risk factors for childhood cancer in poorer regions. We discuss childhood cancer in relation to global development and propose strategies that could result in improved survival. Education of the public, more and better-trained health professionals, strengthened cancer services, locally relevant research, regional hospital networks, international collaboration, and health insurance are all essential components of an enhanced model of care.


Ultra-Wide-Field Fundus Autofluorescence and Spectral-Domain Optical Coherence Tomography Findings in Syphilitic Outer Retinitis.
To determine the ultra-wide-field fundus autofluorescence (UWFFAF) and optical coherence tomography (OCT) features of syphilitic outer retinopathy (SOR). Retrospective chart review. Three patients with SOR were investigated. Treatment with parenteral penicillin led to improvement of outer retinopathy, visual acuity, and symptoms. UWFFAF showed speckled hyperautofluorescence, hypoautofluorescence, and normal autofluorescence, similar to what has been described as a trizonal pattern in acute zonal occult outer retinopathy (AZOOR) in the chronic case of SOR, but with hyperautofluorescent areas in the two acute cases. OCT showed disruption of the photoreceptor outer segment ellipsoid zone and external limiting membrane, which improved after penicillin treatment, and corresponded to normalization of the hyperautofluorescent areas on UWFFAF. There was irregularity and nodular thickening of retinal pigment epithelium on OCT in areas of mottled hyperautofluorescence. SOR can present similarly to AZOOR on UWFFAF and should be highly suspected in cases presenting like AZOOR. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:208-215. ].


Citrate-induced aggregation of conjugated polyelectrolytes for Al(3+)-ion-sensing assays.
This work shows the sodium citrate induced efficient interpolymer π-stacking aggregation of the planar cationic conjugated polyelectrolyte poly[{9,9-bis[6'-(N,N-trimethylamino)hexyl]-2,7-fluorenyleneethynylene}-alt-co-(1,4-phenylene)] dibromide (PFE) in aqueous solution, which results in the self-quenching of fluorescence. Using the citrate-induced aggregation properties of PFE and the strong chelation ability of citrate with aluminum ions (Al(3+)), a sensitive and selective Al(3+)-ion detection assay in aqueous solution was developed through monitoring of the fluorescence recovery of PFE. The fluorescence intensity recovery of PFE depends on the concentration of Al(3+) ions, and linear fluorescence recovery was observed in the range of 0.5-9 μM. The limit of detection of this assay is 0.37 μM. Its simplicity and rapidity mean this assay shows promise for the real-time detection of Al(3+).


Three-dimensional investigation and scoring of extracellular matrix remodeling during lung fibrosis using multiphoton microscopy.
The organization of collagen during fibrotic processes is poorly characterized because of the lack of appropriate methodologies. Here we show that multimodal multiphoton microscopy provides novel insights into lung fibrosis. We characterize normal and fibrotic pulmonary tissue in the bleomycin model, and show that second-harmonic generation by fibrillar collagen reveals the micrometer-scale three-dimensional spatial distribution of the fibrosis. We find that combined two-photon excited fluorescence and second-harmonic imaging of unstained lung tissue allows separating the inflammatory and fibrotic steps in this pathology, underlining characteristic features of fibroblastic foci in human Idiopathic Pulmonary Fibrosis samples. Finally, we propose phenomenological scores of lung fibrosis and we show that they unambiguously sort out control and treated mice, with a better sensitivity and reproducibility in the subpleural region. These results should be readily generalized to other organs, as an accurate method to assess extracellular matrix remodeling during fibrosis.


Simultaneous Phase Transfer and Surface Modification of TiO₂ Nanoparticles Using Alkylphosphonic Acids: Optimization and Structure of the Organosols.
An original protocol of simultaneous surface modification and transfer from aqueous to organic phases of anatase TiO2 nanoparticles (NPs) using alkylphosphonic acids (PAs) is studied. The influence of the solvent, the nature and concentration of the PA, and the size, concentration, and aggregation state of the TiO2 NPs was investigated. Complete transfer was observed for linear alkyl chains (5, 8, 12, and 18 C atoms), even at very high sol concentrations. After transfer, the grafted NPs were characterized by (31)P solid-state MAS NMR. The dispersion state of NPs before and after phase transfer was monitored by dynamic light scattering (DLS). Small-angle neutron scattering (SANS) was used to characterize the structure of PA-grafted NPs in the organic solvent. Using a quantitative core-shell model cross-checked under different contrast conditions, it is found that the primary particles making up the NPs are homogeneously grafted with a solvated PA-layer. The nanometric thickness of the latter is shown to increase with the length of the linear carbon chain of the PA, independent of the size of the primary TiO2 NP. Interestingly, a reversible temperature-dependent aggregation was evidenced visually for C18PA, and confirmed by DLS and SANS: heating the sample induces the breakup of aggregates, which reassemble upon cooling. Finally, in the case of NPs agglomerated by playing with the pH or the salt concentration of the sols, the phase transfer with PA is capable of redispersing the agglomerates. This new and highly versatile method of NP surface modification with PAs and simultaneous transfer is thus well suited for obtaining well-dispersed grafted NPs.


Cross-Sectional Analysis of the Distal Fibular Intramedullary Canal: A Cadaveric Evaluation.
Fractures of the distal fibula secondary to rotational ankle injuries are one of the most common injuries requiring surgical intervention. The aim of this study was to describe the anatomy of the distal fibular medullary canal as a means of aiding in surgical management with an intramedullary device. Twenty fresh cadaveric below-knee specimens (group 1, 10 in 2015, group 2, 10 in 2016) were dissected to expose the distal fibular. Fifteen (10 mm each) segments were sectioned with a sagittal saw from the distal tip proximally and measured with a digital caliper. In group I, the widest and narrowest fibular diameter was at the 20-mm interval (mean 15.02 mm) and 90-mm interval (mean 3.51 mm), respectively. From 70 to 120 mm, the mean diameter was less than 4.0 mm. In group 2, the widest and narrowest diameter was at the 20-mm interval (mean 15.05 mm) and 100-mm interval (mean 4.33 mm), respectively. From 70 to 140 mm, the mean diameter was less than 5.0 mm. The combined mean diameter at the 60- to 80-mm intervals were 4.99 ± 1.70, 4.35 ± 1.63, and 4.02 ± 1.35 mm, respectively. Based on our investigation, we propose an intramedullary device diameter of 4.5 to 5.0 mm in diameter with a length of 60 to 80 mm may provide most appropriate bony purchase to achieve acceptable cortical contact for expected osseous compression. Level IV: Cadaveric case series.


Maximizing flap survival in a prefabrication model using exogenous and endogenous bFGF: a new approach.
Flap prefabrication is dependent on the neovascular response that occurs between the implanted arteriovenous pedicle and the recipient tissue. Augmentation of this neovascular response with angiogenic growth factors would maximize flap survival and minimize the interval between pedicle implantation and flap rotation. Maximizing the biologic activity of endogenous growth factors would likewise positively impact upon flap survival. This study examined the role of basic fibroblast growth factor, a known potent angiogenic growth factor, on flap survival in a rabbit ear prefabrication model. Sucrose octasulfate, a substance that binds basic fibroblast growth factor, stabilizes it, and protects it from degradation, was also studied to determine its impact on flap survival. Flap survival was increased using basic fibroblast growth factor, sucrose octasulfate, and the two substances combined together. The use of substrates designed to maximize the biologic activity of endogenous growth factors, rather than relying on the artificial addition of exogenous growth factors, represents a new approach in the search for methods that will improve flap survival.


The clinical significance of median occlusal position.
The harmony of the occlusal components of the teeth, mandibular joint and muscles, were investigated in 180 human subjects by clinical, dental articulator, radiographic and electrodiagnostic methods. Significant correlations were found between disharmony of these components at median occlusal position (MOP), and with pain-dysfunction of the masticatory system. Using the standardized stimuli of opening the jaw wide and snapping it shut automatically into MOP, temporalis and masseter muscle co-ordination and somesthetic reflex effects were quantified. The interval from tooth contact (s) to reinstitution of EMG activity (x), and the EMG silent-period duration (SP), were prolonged in the patients but returned to within the control range with elimination of the pain-dysfunction. Muscle incoordination with mandibular dysfunction was prevalent in the patients, and the incidence of osteoarthritis was greatest in those with persistent symptoms. The hypothesis was supported that disharmony of MOP exists in pain-dysfunction patients--while successful occlusal therapy leads to the restoration of the harmony within the biologic range. This implies physiological significance to this hitherto clinically neglected occlusal position.


Safety and efficacy of physiologist-led dobutamine stress echocardiography
Dr Porter in his editorial comment (1) on a physiologist-led stress echo service (2) acknowledges that the service was safe in terms of adverse effects but is concerned that 'the interpretation of the study was also done by the cardiac physiologist'. He reminds us 'that the biggest danger associated with dobutamine stress echocardiography is in misinterpreting the data obtained…'.


Purification, characterization and antioxidant activity of dextran produced by Leuconostoc pseudomesenteroides from homemade wine.
An exopolysaccharide (EPS) was produced by Leuconostoc pseudomesenteroides DRP-5 isolated from homemade wine. The EPS was obtained with ethanol extraction, which was further purified by chromatography of Sephadex G-100 to get a purified fraction. The monosaccharide composition of the EPS was glucose, and its molecular weight (Mw) was 6.23 × 106 Da, as determined by gas chromatography (GC) and high-performance size-exclusion chromatography (HPSEC). Fourier transform infrared spectra (FT-IR) and nuclear magnetic resonance spectra (NMR) showed that the EPS was a linear glucan with α-(1→6)-linked glucosidic bonds. The water holding capacity (WHC), water solubility index (WSI) and emulsifying activity (EA) of DRP-5 EPS were 296.76 ± 18.93%, 98.62 ± 3.57% and 87.22 ± 2.18%, respectively. DRP-5 EPS have a higher degradation temperature of 278.36 °C, suggesting high thermal stability of the EPS. Also, DRP-5 EPS was found to have moderate 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, hydroxyl radical, superoxide anion radical, 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical, Fe2+ scavenging activities and reducing power. All these characteristics suggest that DRP-5 EPS might have potential applications in the pharmaceutical, cosmetic and food industries.


3D Ta/TaO x /TiO2/Ti synaptic array and linearity tuning of weight update for hardware neural network applications.
The implementation of highly anticipated hardware neural networks (HNNs) hinges largely on the successful development of a low-power, high-density, and reliable analog electronic synaptic array. In this study, we demonstrate a two-layer Ta/TaO x /TiO2/Ti cross-point synaptic array that emulates the high-density three-dimensional network architecture of human brains. Excellent uniformity and reproducibility among intralayer and interlayer cells were realized. Moreover, at least 50 analog synaptic weight states could be precisely controlled with minimal drifting during a cycling endurance test of 5000 training pulses at an operating voltage of 3 V. We also propose a new state-independent bipolar-pulse-training scheme to improve the linearity of weight updates. The improved linearity considerably enhances the fault tolerance of HNNs, thus improving the training accuracy.


Nanostructured Silica-Titania Hybrid using Dendritic Fibrous Nanosilica as a Photocatalyst.
A new method has been developed to fabricate active TiO2 photocatalysts by tuning the morphology of the catalyst support. A sustainable solution-phase TiO2 deposition on dendritic fibrous nanosilica (DFNS) protocol is developed, which is better than the complex and expensive atomic layer deposition technique. In general, catalytic activity decreases with an increased TiO2 loading on conventional mesoporous silica because of the loss of the surface area caused by the blocking of pores. Notably, in the case of the dendritic fibrous nanosilica KCC-1 as a support, because of its open fibrous morphology, even at the highest TiO2 loading, a relatively large amount of surface area remained intact. This improved the accessibility of active sites, which increased the catalytic performance of the KCC-1/TiO2 photocatalyst. KCC-1-supported TiO2 is a superior photocatalyst in terms of H2 generation (26.4 mmol gTiO2 -1 h-1 ) under UV light. This study may provide a new direction for photocatalyst development through the morphology control of the support.


[Current methods of ulcer therapy and their efficacy and cost].
The purpose of this study is to assess the efficiency of the anti-ulcer therapy taking into account the economic aspects of treatment. We have examined 708 HP-positive(+) patients with stomach ulcers (SU) and duodenal ulcers (DU). Various schemes of anti-helicobacter and anti-secretory therapy were administered to them. Positive dynamics of some clinical data (local palpatory tenderness and abdominal wall resistance) and gastritis (gastroduodenitis) activity was discovered in all groups of patients. The cost of the treatment was determined with the help of marketing studies by taking the lowest price of drugs. There were no statistically reliable differences found groups of traditional treatment regimens by both results of HP eradication and the cost of eradicative and anti-secretory therapy. All drugs under study are highly effective for rapid relief of symptoms at an exacerbation of stomach ulcer associated with HP as well as the decrease of gastritis (gastroduodenitis) activity. It is possible to recommend them for both eradicative therapy and prolonged treatment.


Views of persons with schizophrenia on their own disorder: an Italian participatory study.
This study explored the views of 241 patients with schizophrenia about their own disorder. Patients' knowledge of their diagnosis, confidence that they will be well again, and perception of limitations in their own life as a result of the disorder were explored in relation to patients' opinions about the social consequences of schizophrenia. Study results were presented to participants, and suggestions were collected regarding how these study results should be used. Seventy-two respondents (30%) reported that a psychiatrist told them that they have schizophrenia. Respondents who were confident that they would be well again had a lower duration of contact with psychiatric services and a less pronounced perception of affective and social difficulties related to schizophrenia. Respondents who did not feel limited in their life by the disorder reported less social distance and more optimism about the usefulness of treatments. Participatory studies may provide ideas for a more constructive interaction between patients and professionals.


Epilepsy awareness among parents of school children--a municipal survey.
A pilot study was undertaken to assess the knowledge, attitude and practice of parents of school-going children in a semi-urban municipal area of Bengal. An open-ended questionnaire with 14 questions were put in local language. A total of 1068 parents were interviewed with 76.9% males and 23.1% females. Most of them (60.7%) having an educational level above primary but below higher secondary school level; 41.4% surveyed believe epilepsy is caused by an infection and 40.8% have the idea that it is contagious too; 80.3% have the idea that epilepsy can be treated but 7.3% interviewed carry the idea that it cannot be treated at all. Only 35.9% responders are ready to allow an epileptic child to attend school and sit together with other children. In terms of first-aid management only 36.6% mentioned some useful first-aid measure. The general public attitude is reflected in this study. False belief and negative attitude leads to barrier in children education. Larger and comprehensive community-based educational programme is very much essential to bring about a change in negative attitude towards epilepsy.


Hip and Groin Pain in Soccer Players.
Purpose The aim of this article is to illustrate the recent framework necessary to standardize studies on groin pain and review the existing literature on groin pain in football. Methods The common pathological processes underlying groin pain such as muscle, tendon or ligament strain, bone injury or fracture, sport hernia, bursitis, osteitis pubis, and hip-related diseases have been reviewed and current management options have been considered. Results Groin pain is considered a pain in pubic or lower abdominal or adductors region which can be monolateral or bilateral. It is common in high-intensity team sports and can negatively affect an athlete's professional carrier, causing serious disruption in the performance. Despite a high prevalence of groin pain in athletes, diagnosis and management of the underlying pathological processes remain a challenge for surgeons, radiologists, and physiotherapists alike. Conclusion A multidisciplinary approach is essential for patients with groin pain allowing prompt diagnosis and initiation of treatment thus facilitating more rapid return to play and preventing potential long-term sequelae of chronic groin pathology.


Asymmetric organocatalytic Michael addition of ketones to vinyl sulfone.
Highly enantioselective organocatalytic Michael addition of ketones to vinyl sulfone catalyzed by a cinchona alkaloid-derived primary amine is reported for the first time; the described synthetic methodology was applied to the synthesis of sodium cyclamate.


Batch and continuous 2-heptanone production by Ca-alginate/Eudragit RL entrapped spores of Penicillium roquefortii.
The synthesis of 2-heptanone from octanoic acid by Caalginate/Eudragit RL entrapped spores of Penicillium roquefortii is performed in batch and continuous reactions. The measurement of the HCI solution needed to overcome the pH increase during the course of a reaction allows continuous monitoring of the reaction progress of batch as well as continuous processes without any aliquot sampling. The hydration of the biocatalyst prior to a bioconversion performance is of major importance to achieve reproducible results. A continuous reaction carried out at pH 6.5 for one month demonstrates the feasibility of such a process and shows that the reaction occurs with a Michaelian behavior, with K(M) = 1.82 mmol/L and r(sm) = 0.82 mmol/L h, and no intraparticle diffusion limitation is found. The complex behavior of the spores during batch reactions makes this kind of operation unsuitable for kinetic studies.


Stimulation of P2 receptors causes release of IL-1beta-loaded microvesicles from human dendritic cells.
Dendritic cells (DCs) are professional antigen-presenting cells that initiate the immune response by activating T lymphocytes. DCs express plasma membrane receptors for extracellular nucleotides named P2 receptors (P2Rs). Stimulation of P2Rs in these cells is known to cause chemotaxis, cytokine release, and cell death and to modulate LPS-dependent differentiation. Here we show that stimulation of the P2X(7) receptor subtype (P2X(7)R) causes fast microvesicle shedding from DC plasma membrane. Vesicle release occurs from both immature and mature DCs; however, only vesicles from mature DCs, due to their previous exposure to LPS, contain IL-1beta. Microvesicles, whether from immature or mature DCs, also contain caspase-1 and -3 and cathepsin D. They also express the P2X(7)R in addition to other P2Rs and known markers of immune cells such as major histocompatibility complex II (MHC II) and CD39. Activation of the P2X(7)R by extracellular ATP causes IL-1beta release from the vesicle lumen. Previous studies demonstrated that high extracellular K(+) inhibits IL-1beta processing and release; here we show that high ionic strength reduces microvesicle shedding when compared with a low ionic strength medium but strongly increases microvesicle IL-1beta loading.


Surrogate strains of human pathogens for field release.
Surrogate microorganisms, in short surrogates, are an essential part of pathogen research. Compared to surrogates used in controlled laboratory environments, surrogates for field release are restricted by concerns about human and environmental safety. For field research of food-borne pathogens, strains of an attenuated pathogen or strains of genetically close non-pathogenic species have been used as surrogates. Genetic modification is usually performed to attenuate virulence, through for examples deletion of genes of virulence and transcriptional regulators and removal of virulence plasmids, and to facilitate detection and monitoring through observing antibiotic resistance, fluorescence, and bioluminescence. For field research of a biological warfare agent Bacillus anthracis, strains of genetically close non-pathogenic species or strains of genetically distant non-pathogenic species have been used, mostly without any genetic modification. Recently, we constructed strains of Bacillus thuringiensis as surrogates for B. anthracis, demonstrating that strain engineering could significantly enhance the utility of surrogates, and that the application of a simple genetic circuit could significantly impact surrogate safety. Thus far, enormous potential of biotechnology has not been exploited enough due to safety concerns regarding the field release of genetically engineered microorganisms. However, synthetic biology is rapidly developing, providing new concepts for biocontainment as well as ingenious genetic circuits and devices, which should be applied in future research of field-use surrogates.


Suicidal intent disclosure among adult suicide decedents: Four age group comparisons.
Research on who does/does not disclose suicidal intent (SI) and related factors has important implications for suicide risk management. In this paper based on the 2017-2019 National Violent Death Reporting System, we compared four age groups (18-24, 25-44, 45-64, and 65+ years) of suicide decedents with respect to associations between SI disclosure and (1) suicide contributing/precipitating factors, and (2) suicide means. The results shows that those age 18-44 were more likely to disclose SI than those age> =45, especially among those with relationship problems. Physical health problems and death/suicide of family/friend increased the likelihood of SI disclosure in the 65+ age group.


Self-Organization of Binary Colloidal Mixtures via Diffusiophoresis.
Catalytic activity of the colloids and chemotactic response to gradients of the chemicals in the solution leads to effective interaction between catalytic colloids. In this paper, we simulate mixtures of active and passive colloids via a Brownian dynamics algorithm. These particles interact via phoretic interactions, which are determined by two independent parameters, surface activity and surface mobility. We find rich dynamic structures by tuning passive colloids' surface mobility, size, and area fractions, which include schools of active colloids with exclusion zone, yolk/shell cluster, and stable active-passive alloys to motile clusters. Dynamical cluster can also be formed due to the nonreciprocity of the phoretic interaction. Increasing the size ratio of passive colloids to active colloids favors the phase separation of active and passive colloids, resulting in yolk/shell structure. Increasing the area fraction of active colloids tends to transfer from dynamical clusters into stable alloys. The simulated binary active colloid systems exhibit intriguing nonequilibrium phenomena that mimic the dynamic organizations of active/passive systems.


Portosystemic collaterals in portal hypertension: visualization by using blood-pool SPECT imaging.
Single-photon emission CT (SPECT) was performed with technetium-99m autologous RBCs in 11 patients with chronic hepatitis and in 46 cirrhotic patients with portal hypertension to determine the value of the procedure for identifying portosystemic collateral blood flow. Twenty millicuries (740 MBq) of 99mTc-RBCs, labeled by an in vivo technique, were given IV, and tomographic imaging of the intraabdominal vascular blood pool was performed. Fourteen patients with cirrhosis also had arterial portography, and 37 had scintiphotosplenoportography. In 38 of 46 patients with cirrhosis, SPECT images showed portosystemic collaterals. The coronary vein was seen in 52% of the patients, the short gastric vein in 11%, the gastrorenal or splenorenal shunt in 24%, the umbilical vein in 11%, and the anterior abdominal wall vein in 17%. Portosystemic collaterals were not shown in any of the patients with chronic hepatitis. Collaterals were identified on SPECT images in 10 of 11 patients in whom collaterals were documented by arterial portography and in all 28 patients in whom collaterals were shown by scintiphotosplenoportography. Furthermore, SPECT clearly showed a patent portal vein in three patients and the coronary vein in two patients, when these veins were not identified by means of scintiphotosplenoportography. This experience suggests that SPECT is useful for the noninvasive identification of portosystemic collaterals in patients with portal hypertension.


Physicochemical, sensory properties and starch in vitro digestion of gluten-free breads.
The physicochemical (volume, crumb grain and color), sensory and starch in vitro digestion properties were investigated in four gluten-free breads, produced using gluten-free commercial mixes. Different mixes' formulations and processing parameters led to the production of breads with different crumb grain, specific volume, crust and crumb color, which affected product's sensory acceptability. Generally, more heterogeneous and coarser crumb grain and darker color were more appreciated by the judges. Nutritional composition of gluten-free breads differed mainly for starch and lipids contents, due to a wide variety of ingredients used in breads formulations. Starch availability to hydrolytic enzymes in the gluten-free breads was not influenced by variation in ingredients and nutritional composition, but it was related to the physical structure in terms of specific volume. The higher was the specific volume, the higher was the starch-digested fraction.


From Sound to Significance: Exploring the Mechanisms Underlying Emotional Reactions to Music.
A common approach to studying emotional reactions to music is to attempt to obtain direct links between musical surface features such as tempo and a listener's responses. However, such an analysis ultimately fails to explain why emotions are aroused in the listener. In this article we explore an alternative approach, which aims to account for musical emotions in terms of a set of psychological mechanisms that are activated by different types of information in a musical event. This approach was tested in 4 experiments that manipulated 4 mechanisms (brain stem reflex, contagion, episodic memory, musical expectancy) by selecting existing musical pieces that featured information relevant for each mechanism. The excerpts were played to 60 listeners, who were asked to rate their felt emotions on 15 scales. Skin conductance levels and facial expressions were measured, and listeners reported subjective impressions of relevance to specific mechanisms. Results indicated that the target mechanism conditions evoked emotions largely as predicted by a multimechanism framework and that mostly similar effects occurred across the experiments that included different pieces of music. We conclude that a satisfactory account of musical emotions requires consideration of how musical features and responses are mediated by a range of underlying mechanisms.


Adrenoceptors of the human internal thoracic artery.
Adrenoceptor function in the human internal thoracic artery (ITA) was characterized in vitro using segments of the artery obtained during coronary bypass operations. Specimens were prepared as isolated arterial rings mounted in a tissue bath, and mechanical activity (isometric tension) was measured in response to drugs. The ITA responded to phenylephrine (PE), epinephrine, and norepinephrine with concentration-dependent contractions. The PE-induced contractions were antagonized by phenoxybenzamine, prazosin, and high concentrations of yohimbine. The ITA was not effectively contracted by clonidine in the concentration range normally associated with alpha 2-adrenoceptor stimulation. The beta-adrenoceptor agonist, isoproterenol, had a weak and variable effect on the ITA; samples from 9 out of 12 subjects did not respond to isoproterenol, whereas samples from 3 subjects responded with relaxations of between 33 and 42%. These in vitro studies indicate that the most important adrenoceptors of the human ITA are alpha-adrenoceptors; this may be relevant for the pharmacologic management of patients undergoing coronary bypass surgery using the ITA.


Microporous cellulosic scaffold as a spheroid culture system modulates chemotherapeutic responses and stemness in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) treatments are evaluated by two-dimensional (2D) in vitro culture systems, despite their limited ability to predict drug efficacy. The three-dimensional (3D) microporous scaffold provides the possibility of generating more reliable preclinical models to increase the efficacy of cancer treatments. The physical properties of a microporous cellulosic scaffold were evaluated. The cellulosic scaffold was biocompatible and had a highly porous network with appropriate pore size, swelling rate, and stiffness of cancer cell cultures. Cellulosic scaffolds were compared with 2D polystyrene for the culture of HepG2 and Huh7 human HCC cells. Cellulosic scaffolds promoted tumor spheroid formation. Cells cultured on scaffolds were more resistant to chemotherapy drugs and showed upregulation of EpCAM and Oct4. The migration ability of HCC cells cultured on scaffolds was significantly greater than that of cells grown in 2D cultures as evidenced by the downregulation of E-cadherin. In addition, the proportion of CD44+/CD133+ HCC cancer stem cells (CSCs) was significantly greater in cells cultured on scaffolds than in those grown in 2D cultures. These findings suggest that cellulosic scaffolds effectively mimic the in vivo tumor behavior and may serve as a platform for the study of anticancer therapeutics and liver CSCs.


Anticarcinogenic effect of a flavonoid antioxidant, silymarin, in human breast cancer cells MDA-MB 468: induction of G1 arrest through an increase in Cip1/p21 concomitant with a decrease in kinase activity of cyclin-dependent kinases and associated cyclins.
There is an increasing interest in identifying potent cancer preventive and therapeutic agents against breast cancer. Silymarin, a flavonoid antioxidant isolated from milk thistle, exerts exceptionally high to complete anticarcinogenic effects in tumorigenesis models of epithelial origin. In this study, we investigated the anticarcinogenic effect of silymarin and associated molecular mechanisms, using human breast carcinoma cells MDA-MB 468. Silymarin treatment resulted in a significantly high to complete inhibition of both anchorage-dependent and anchorage-independent cell growth in a dose- and time-dependent manner. The inhibitory effects of silymarin on cell growth and proliferation were associated with a G1 arrest in cell cycle progression concomitant with an induction of up to 19-fold in the protein expression of cyclin-dependent kinase (CDK) inhibitor Cip1/p21. Following silymarin treatment of cells, an incremental binding of Cip1/p21 with CDK2 and CDK6 paralleled a significant decrease in CDK2-, CDK6-, cyclin D1-, and cyclin E-associated kinase activity with no change in CDK2 and CDK6 expression but a decrease in G1 cyclins D1 and E. Taken together, these results suggest that silymarin may exert a strong anticarcinogenic effect against breast cancer and that this effect possibly involves an induction of Cip1/p21 by silymarin, which inhibits the threshold kinase activities of CDKs and associated cyclins, leading to a G1 arrest in cell cycle progression.