Adsorption mechanism of lead ions on porous ceramsite prepared by co-combustion ash of sewage sludge and biomass.
This study attempted to synthesize a novel ceramsite with excellent adsorption property compositing through the co-combustion of biomass and sewage sludge ash (CBSA), gasification of coal fly ash (GCFA) and sewage sludge (SS) to dispose wastewater contaminated by Pb (II). The optimum preparation conditions included a CBSA/SS/GCFA ratio of 70:18:12, preheating at 480 °C, and sintering at 1060 °C for 15 min. The basic and environmental characteristics of the novel ceramsite meet specific standards requirements. The removal rate could reach 99.9% under optimum conditions in a high-concentration solution, and the novel ceramsite could be reused 6 times and maintain in high remove rate. The adsorption mechanism was determined to be as follows: (1) Ceramsite features a mesoporous structure with an abundance of pores on which cationic exchange could occur. (2) Pb (II) enters the pores of the adsorbent and are attracted by anionic groups to deposit on the surface of ceramsite. (3) A large amount of Pb (II) bonds with SiO or AlOSiO to embed in the matrix frame of the adsorbent; the rest of the metal forms precipitates on the frame layer or [PO4].


Solid-state 17O NMR study of benzoic acid adsorption on metal oxide surfaces.
Solid-state (17)O NMR spectra of (17)O-labeled benzoic and anisic acids are reported and benzoic acid is used to probe the surface of metal oxides. Complexes formed when benzoic acid is dry mixed with mesoporous silica, and nonporous titania and alumina are characterized. Chemical reactions with silica are not observed. The nature of benzoic acid on silica is a function of the water content of the oxide. The acid disperses in the pores of the silica if the silica is in equilibrium with ambient laboratory humidity. The acid displays high mobility as evidenced by a liquid-like, Lorentzian resonance. Excess benzoic acid remains as the crystalline hydrogen-bonded dimer. Benzoic acid reacts with titania and alumina surfaces in equilibrium with laboratory air to form the corresponding titanium and aluminum benzoates. In both materials the oxygen of the (17)O-labeled acid is bound to the metal, showing the reaction proceeds by bond formation between oxygen deficient metal sites and the oxygen of the carboxylic acid. (27)Al MAS NMR confirms this mechanism for the reaction on alumina. Dry mixing of benzoic acid with alumina rapidly quenches pentacoordinate aluminum sites, excellent evidence that these sites are confined to the surface of the alumina particles.


Role of Cardiac MRI Imaging of Focal and Diffuse Inflammation and Fibrosis in Cardiomyopathy Patients Who Have Pacemakers/ICD Devices.
This focused report aims to discuss and summarize the use of conventional and emerging methods using cardiovascular magnetic resonance (CMR) imaging in cardiomyopathy patients with implanted cardiac devices to identify diffuse and focal inflammation and fibrosis. Many cardiomyopathy patients with diffuse and focal myocardial fibrosis have a unique need for cardiac imaging that is complicated by cardiovascular implantable electronic devices (CIEDs). CMR imaging can accurately image myocardial fibrosis and inflammation using T1 mapping and late gadolinium enhancement (LGE) imaging. CMR imaging in CIED patients, however, has been limited due to severe imaging artifacts associated with the devices. The emergence of wideband imaging variants of LGE and T1 mapping techniques can successfully reduce or eliminate CIED artifacts for the evaluation of myocardial substrate in cardiomyopathy patients. Wideband imaging variants of LGE and T1 mapping techniques provide new tools for imaging focal and diffuse fibrosis and imaging in cardiomyopathy patients with implanted cardiac devices. These emerging techniques have the potential for great impact in clinical care of such patients as well as clinical research where imaging endpoints are desired.


[Study on the quality standard of danmo capsule].
To establish the quality standard for Danmo capsule. TLC was used for the qualitative identification of Salviae Miltiorrhizae Radix Et Rhizoma and Lonicerae Japonicae Flos. HPLC was used to determine the content of Salvianolic acid B. TLC spots were clear and well-separated without negative interference. The linear range of Salvianolic acid B was 0.120042 - 2.40084 microg (r = 0.9999) with an average recovery of 103.63%, RSD was 0.6% (n = 6). The method is simple, accurate and reliable. It can be used for the quality control of Danmo capsule.


Post-infarct left ventricular thrombosis is mechanistically related to ventricular wall rupture.
Left ventricular thrombus (LVT) after acute myocardial infarction (AMI) remains to be a common complication bearing adverse prognostic implication. Majority of LVT occurs within the first week after AMI. Over decades, the regional stasis of blood flow is regarded as the main reason for LVT formation. Here we hypothesize that LVT developed within the first week after AMI is the consequence of an incomplete wall rupture. Endocardial rupture with exposure of infarcted tissues triggers platelet thrombosis within the rupture site and then the thrombus grows towards the ventricular chamber forming LVT. This hypothesis is implicated by the comparable clinical features of patients with LVT or with cardiac rupture, and supported by experimental findings in murine model of AMI revealing the mechanistic link between rupture and LVT. This hypothesis, if confirmed, would improve our understanding on the pathophysiology of both rupture and LVT as two pivotal mechanical complications after AMI, and the role of platelets in the setting of AMI and hence the use of anti-platelet therapies. Future studies are warranted to test this hypothesis by serial cardiac imaging on AMI patients with high risk of LVT.


Dimaprit -(S-[3-(N,N-dimethylamino)prophyl]isothiourea) - a highly specific histamine H2 -receptor agonist. Part 1. Pharmacology.
S-[3-(N,N-Dimethylamino)propyl]isothiourea (dimaprit), has been shown to be a highly specific histamine H2-receptor agonist. Parallel line assays showed that in vitro at H2-receptors it had approximately 17.5% the activity of histamine on the rat uterus and 71% on the guinea-pig right atrium, with similar maximal responses; it had less than 0.0001% the activity of histamine on H1-receptors. Dimaprit stimulated gastric acid secretion in the rat, dog and cat in which it had, respectively, approximately 19,58 and 400-500% the activity of histamine. In the dog and cat the maximum secretory response to dimaprit was significantly greater than that obtained to histamine. The H2-receptor specificity of dimaprit in causing depressor and vasodilator effects was also demonstrated in the cat, in which it had 18-20% of the H2-receptor activity of histamine. Dimaprit should prove to be a very useful tool in studies examining the role of histamine in physiology and pathology. The absence of marked cardiovascular effects at doses maximal for the stimulation of gastric acid secretion, as seen in the cat studies, could lead to this compound being of value as a diagnostic agent in the measurement of maximal acid secretory capacity.


Expressional alterations of fibrillin-1 during wound healing of human dental pulp.
The degradation of fibrillins, the major constituents of microfibrils, is known to facilitate the release of active transforming growth factor-β (TGF-β), a signaling molecule contributing to mineralized tissue barrier formation in exposed dental pulps. To examine the involvement of fibrillins in the barrier formation, we examined the temporospatial expression of (1) genes and proteins of fibrillins and (2) factors possibly associated with fibrillin degradation and cytodifferentiation in exposed human pulps. Human pulp slice cultures were also examined for the role of fibrillins in mineralization. Clinically healthy pulps were mechanically exposed and capped with mineral trioxide aggregate. After 7 to 42 days, the teeth were processed for immunohistochemical and cytochemical staining of fibrillin-1, fibrillin-2, latent TGF-β-binding protein (LTBP)-1, matrix metalloproteinase-3 (MMP-3), alkaline phosphatase (ALP), and in situ hybridization of fibrillin-1. Pulp tissue slices cultured with β-glycerophosphate were analyzed for fibrillin-1, fibrillin-2, and ALP with the immunohistochemical/cytochemical staining and quantitative reverse-transcriptase polymerase chain reaction. Fibrillin-1-immunoreactivity was seen until 7 days but turned into undetectable since 14 days in the pulpal area just beneath the exposure site. MMP-3-immunoreaction was transiently detected at 14 days. At 42 days when the mineralized barrier was evident, fibrillin-1-immunoreactivity and fibrillin-1 expression remained down-regulated. Fibrillin-2, LTBP-1, and ALP were constantly detected in the fibrillin-1-undetectable area. Pulp slices cultured with β-glycerophosphate showed mineralization with up-regulation of ALP and down-regulation of fibrillin-1. Degradation and down-regulation of fibrillin-1 expression took place during the mineralized tissue barrier formation in exposed pulps in vivo and β-glycerophosphate-induced pulpal mineralization in vitro.


A comparison of the effects of aspirin and histamine of fluid balance in the recruited lung.
Salicylate administration has been reported to increase the flow of protein-rich lymph from the lungs of animals, however, the mechanism of this response is unclear. In the present study we measured pulmonary hemodynamics and lung fluid and protein flux in anesthetized sheep, surgically prepared for the collection of lung lymph, in order to examine the possible effect of aspirin (ASP) on lung vascular permeability. ASP was given during recruitment of pulmonary microvascular surface area induced by sustained elevation of left atrial pressure (Pla) (Group 1) or continuous infusion of adenosine triphosphate (ATP) (Group 2). We compared the results of ASP administration to those found in similarly prepared animals given histamine (H) during like periods of increased Pla (Group 3) or ATP infusion (Group 4). ASP administration resulted in increased lymphatic protein clearance (Cp) in both Groups 1 and 2. In Group 1, following the characteristic increase in lung lymph flow (Q1) and fall in the ratio of lung lymph to plasma protein concentration (L/P) produced by Pla elevation, ASP administration resulted in a further increase in Q1 and a significant increase in L/P. The results found in ASP animals are qualitatively similar to those observed in Groups 3 and 4 after H. While we cannot specifically rule out a hemodynamic effect of the drug, our results suggest the increased protein flux observed following ASP administration was mediated at least in part through an increase in lung microvascular permeability.


Communication skills training to address disruptive physician behavior.
Disruptive behavior among health care providers has been linked to negative patient outcomes. High-stress areas, including the perioperative setting, are especially prone to this behavior. The purpose of this study was to develop, implement, and evaluate an educational communication skills intervention aimed at increasing the perceived self-efficacy of perioperative nurses to address disruptive physician behavior. Seventeen perioperative nurses participated in a two-day communication skills program presented by a certified Crucial Conversations trainer. By using paired t test analysis, I found that there was a statistically significant increase in total mean self-efficacy scores immediately after the intervention and four weeks after the intervention. In addition, four weeks after the intervention, participants reported the ability to address disruptive physician behavior 71% of the time. The results of this study suggest that one intervention strategy to address the serious threat of disruptive physician behavior to patient safety is to educate nurses in communication skills.


Milk and dairy product consumption in patients with inflammatory bowel disease: Helpful or harmful to bone mineral density?
Limiting the consumption of milk and dairy products (DPs) constitutes a risk factor for osteoporosis in patients with inflammatory bowel disease (IBD). The aim of this study was to evaluate bone mineral density (BMD) and the frequency of osteopenia and osteoporosis in patients with IBD. We also investigated the correlation between BMD and consumption of milk and DPs, as well as with calcium, phosphate, and parathyroid hormone (PTH) and 25-hydroxyvitamin D [25(OH)D] serum concentration levels. The study comprised 208 patients with IBD. Densitometric measurements were performed using the dual-energy x-ray absorpiometry. Before (IBD-I) and after the diagnosis (IBD-II) of IBD, we used a questionnaire to assess the consumption of milk and DPs. Serum concentrations of PTH, 25(OH)D, calcium, and phosphate were determined. The prevalence of osteopenia and osteoporosis in the IBD patient group was 48.1%. At the same time, 87% of patients with IBD reported milk consumption. Patients from this group with proper bone mass amounted to 91.7%, whereas patients with osteopenia and osteoporosis comprised 82% (P = 0.0382) of patients. In patients with IBD who consumed milk, femoral neck BMD (0.97 ± 0.17 g/cm2) was higher than in those not drinking milk (0.897 ± 0.154 g/cm2; P = 0.0587). The percentage of patients with IBD consuming DPs was 96.2%; however, this number decreased after diagnosis and was equal to IBD-II: 83% (P < 0.0001). Additionally, concentration levels of 25(OH)D decreased in the IBD group (21.82 ± 10.82 ng/dL). Not only does IBD entail a high prevalence of osteoporosis, but BMD values are also indirectly affected by the fact that patient consumption of milk and other DPs decreases after diagnosis.


Atrial flutter in the newborn resulting from maternal lithium ingestion.
We report a case of isolated atrial flutter in a neonate, attributable to maternal lithium treatment, and suggest that the assessment of all infants born to mothers on lithium treatment during pregnancy should include an electrocardiogram.


Cojedes: a leprosy hyperendemic state.
Leprosy is a chronic infectious disease produced by Mycobacterium leprae. In 1997 Venezuela reached the goal of elimination of leprosy as a public health problem (according to the World Health Organization a prevalence rate of ≤ 1/10,000 inhabitants), but five states still had prevalence rates over that goal. For this study we selected Cojedes State, where prevalence rates remain over the elimination goal. Evaluate the real leprosy situation in high-prevalence areas of Cojedes State. Seven communities of Cojedes State were selected because they had the highest historic prevalence, as well as the highest prevalence in the year to be studied (1997). A rank correlation using Spearman's test comparing historical prevalence rates (1946-1996) and detection rates (1998-2004) gave a statistically significant P < 0.05 value. Diagnosed leprosy cases were as follows: age: 3.2% under 15 years old; sex: male/female rates between 60% and 91.66% males. The highest number of cases were paucibacillary forms: indeterminate leprosy (33.07%) and borderline tuberculoid leprosy (32.28%); tuberculoid leprosy (7.00%); and multibacillary cases (lepromatous leprosy, LL) were only 2.36%. Bacteriologically, 18.52 patients were M. leprae positive. At the moment of diagnosis, 96.6% showed no disabilities, 3.4% showed grade I disabilities, and there were no grade II or III disabilities. This study confirms that several communities in Cojedes State have extremely high leprosy rates.


Analysis of cytotoxicities of platinum compounds.
Extent of DNA platination, loss of cell viability, DNA fragmentation, and impairment of cellular mitochondrial oxygen consumption are measures of drug cytotoxicity. We measured and compared these effects for cisplatin, oxaliplatin and carboplatin. Because reaction with intracellular thiols may be responsible for drug resistance, we also determined the rates of Pt drug reactions with metallothionein. Jurkat cells were exposed at 37 degrees C to 25 microM Pt drugs for 3 h. Pt-DNA adducts were determined at the end of the incubation period by atomic absorption spectroscopy. Viability, DNA fragmentation, and cellular respiration (microM O2/min/10(6) cells) were determined 24 h post drug exposure. The average amount of Pt-DNA adducts (Pt atoms/10(6) nucleotides) produced by cisplatin was 43.4, by oxaliplatin 4.8 and by carboplatin 1.5. Cisplatin decreased the rate of respiration by approximately 63% and oxaliplatin by approximately 37%. DNA fragmentation by cisplatin and oxaliplatin was very similar. Carboplatin produced an unnoticeable effect on cellular respiration, and only approximately 10% of the DNA fragmentation was produced by cisplatin or oxaliplatin. Although, for a given drug, all four measures of cytotoxicity were proportional, this did not hold for comparisons between the drugs. The rate constants (M-1 s-1) for reaction of cisplatin, oxaliplatin and carboplatin with Cd/Zn thionein were 0.75, 0.44 and 0.012, respectively. For comparison, the rate constants (M-1 s-1) for reaction of cisplatin, oxaliplatin and carboplatin with glutathione were 0.027, 0.038 and 0.0012, respectively. The low reactivity of carboplatin with metallothionein and glutathione suggests that its low cytotoxic activities are not due to reaction of Pt2+ with cellular thiols. Despite a tenfold difference in Pt-DNA adducts between cisplatin and oxaliplatin, the cytotoxicities of these compounds are very similar, suggesting that oxaliplatin lesions are more potent than cisplatin lesions. The results demonstrate a large influence of the ligands occupying Pt coordination spheres on the chemical and biologic activities of Pt drugs.


A morphometric study of the cortex of the human femur from early childhood to advanced old age.
One hundred and ninety-five mid-shaft femoral bone samples were collected at the Victorian Institute of Forensic Pathology, Melbourne, Australia. These samples came from individuals aged 1-97 years, who had dies unexpectedly and were considered healthy immediately before death. From the samples, transverse sections 100-200 micronM thick were cut on a sawing microtome. Three groups of sections [from persons aged 19-21 (n = 9), 39-41 (n = 9), and 59-61 years (n = 9) at death] were adjusted to a thickness of 100 +/- 5 microns by hand-lapping and microradiographs were taken of these sections. Automatic image analysis methods were used to measure the area and perimeter of the femoral cortex for all 195 sections. Additionally, the number and areas of all holes within the cortex were measured for those sections that were microradiographed. The results show that, even though the number of Haversian canals measured from the entire bone cortex changes with age, the spread of values at any given age makes these measurements of limited value for age determination. From this it may be inferred that all methods that rely, to any extent, upon measurements of this parameter are likely to be flawed.


A new strategy for the fluorescence discrimination of Cys/Hcy and GSH/H2S simultaneously colorimetric detection for H2S.
The development of fluorescent probes enabling distinguishable detection Cys, Hcy, GSH and H2S is still a considerable challenge owing to their similar functional group with comparable reactivity. In this work, a novel fluorescent probe FHC-O-NBD has been synthesized, and a practicable strategy for the fluorescence discrimination of Cys/Hcy and GSH/H2S, especially the colorimetric detection for H2S have been presented. FHC-O-NBD reacted with Cys/Hcy to produce two fluorescent emissions at 486 nm and 550 nm, while for GSH/H2S, only one fluorescent signal at 486 nm appeared. And, only upon addition of H2S, the color of the system changed from colorless to pink. So it can serve as a colorimetric probe for H2S by "naked eye". Furthermore, FHC-O-NBD can selectively distinguish Cys/Hcy and GSH/H2S in living cells, meaning it has great potential in biological applications.


Legumain-cleavable 4-arm poly(ethylene glycol)-doxorubicin conjugate for tumor specific delivery and release.
Traditional chemotherapy strategy exists undesirable toxic side-effects to normal tissues due to the low selectively to cancer cells of micromolecule cytotoxic drugs. One considered method to realizing the targeted delivery and increasing the specificity to tumor tissues of the cytotoxic drug is to transporting and discharging it through an environment-sensitive mechanism. In this study, a novel enzyme-sensitive polymer-doxorubicin conjugate was designed to delivery chemotherapeutic drug in a tumor-specific behavior and selectively activated in tumor tissue. Briefly, doxorubicin (DOX) was conjugated to carboxyl-terminated 4-arm poly(ethylene glycol) through a tetrapeptide linker, alanine-alanine-asparagine-leucine (AANL), which was one of the substrates of legumain, an asparaginyl endopeptidase that was found presented in plants, mammals and also highly expressed in human tumor tissues. Hereinafter, the polymer-DOX conjugate was termed as 4-arm PEG-AANL-DOX. Dynamic laser scattering (DLS) and transmission electron microscopy (TEM) measurements indicated that the 4-arm PEG-AANL-DOX could self-assemble into micelles in aqueous solution. Drug release and in vitro cytotoxicity studies revealed that the 4-arm PEG-AANL-DOX could be cleaved by legumain. Ex vivo DOX fluorescence imaging measurements demonstrated that the 4-arm PEG-AANL-DOX had an improved tumor-targeting delivery as compared with the free DOX·HCl. In vivo studies on nude mice bearing MDA-MB-435 tumors revealed that the 4-arm PEG-AANL-DOX had a comparable anticancer efficacy with the free DOX·HCl but without DOX-related toxicities to normal tissues as measured by body weight change and histological assessments, indicating that the 4-arm PEG-AANL-DOX had an improved therapeutic index for cancer therapy. Herein we describe the construction of a novel tumor environment-sensitive delivery system through the instruction of a legumain-cleavable linkage to a polymer-DOX conjugate (4-arm PEG-AANL-DOX). This particular design strategy allows for polymer-DOX conjugates to be delivered in a tumor-specific manner and selectively activable in tumor microenvironment so that it can combine the advantages of tumor-specific delivery and tumor intracellular microenvironment-triggered release systems.


Hepatocellular Carcinoma: Molecular Pathogenesis and Therapeutic Advances.
Hepatocellular carcinoma (HCC), the most common form of liver cancer, continues to be a serious medical problem with poor prognosis, without major therapeutic improvement for years and increasing incidence. Fortunately, advances in systemic treatment options are finally arriving for HCC patients. After a decade of sorafenib as a standard therapy for advanced HCC, several tyrosine kinase inhibitors (TKIs), antiangiogenic antibodies, and immune checkpoint inhibitors have reached the clinic. Although infections by hepatitis B virus and hepatitis C virus remain principal factors for HCC development, the rise of non- alcoholic steatohepatitis from diabetes mellitus or metabolic syndrome is impeding HCC decline. Knowledge of specific molecular mechanisms, based on the etiology and the HCC microenvironment that influence tumor growth and immune control, will be crucial for physician decision-making among a variety of drugs to prescribe. In addition, markers of treatment efficacy are needed to speed the movement of patients towards other potentially effective treatments. Consequently, research to provide scientific data for the evidence-based management of liver cancer is guaranteed in the coming years and discussed here.


In vitro and in silico characterization of alkaline serine protease from Bacillus subtilis D9 recovered from Saudi Arabia.
In this study, we have isolated and characterized proteolytic soil bacteria and their alkaline protease. Based on 16S rRNA sequence analysis, 12 isolates with the highest protease activity were classified as B. subtilis and B. cereus groups. B. subtilis D9 isolate showing the highest protease activity was selected for in vitro and in silico analysis for its ِِAKD9 protease. The enzyme has a molecular mass of 48 kDa, exhibiting optimal activity at 50 °C pH 9.5, and showed high stability till 65 °C and pH 8-11 for 1 h. Fe3+ stimulated, but Zn2+ and Hg2+ strongly inhibited the protease activity. Also, the maximum inhibition with PMSF indicated serine protease-type of AKD9 protease. AkD9 alkaline serine protease gene showed high sequence similarity and close phylogenetic relationship with AprX serine protease of B. subtilis isolates. Functional prediction of AKD9 resulted in the detection of subtilase domain, peptidase_S8 family, and subtilase active sites. Moreover, prediction of physicochemical properties indicated that AKD9 serine protease is hydrophilic, thermostable, and alkali-halo stable. Secondary structure prediction revealed the dominance of the coils enhances AKD9 activity and stability under saline and alkaline conditions. Based on molecular docking, AKD9 showed very promising binding affinities towards casein substrate with expected intrinsic proteolytic activities matching our obtained in vitro results. In conclusion, AKD9 alkaline serine protease seems to be a significant candidate for industrial applications because of its stability, hydrophilicity, enhanced thermostability, and alkali-halo stability.


Peptide YY: a key mediator of orexigenic behavior.
Peptide YY (PYY) is the most potent orexigenic peptide or substance known. However, neither the underlying physiology of this hyperphagia nor PYY's natural role in brain are well understood. Thus, this review details the neuroanatomical sites, the neurochemical and systemic interactions, the food-related properties and the motivational factors that characterize hyperphagia elicited by central PYY. Emphasis also is given to evidence that central PYY has properties functionally distinct from neuropeptide Y. Finally, future research directions are outlined that aim at accelerating our understanding of the roles that brain PYY and PYY-preferring receptors occupy in normal and abnormal feeding behavior.


Presynaptic inhibitory effects of catecholamines on cholinergic transmission in the smooth muscle of the chick stomach.
In the vagus nerve--smooth muscle preparation isolated from the chick proventriculus, adrenaline, clonidine (10(-8) - 2.5 x 10(-7) M), noradrenaline (10(-7) - 2.5 x 10(-6) M) and dopamine (10(-5) - 10(-4) M) inhibited the contraction induced by low frequency (0.5 Hz) stimulation of the vagus nerve, but they did not inhibit the contraction elicited by acetylcholine (5 x 10(-8) - 5 x 10(-7) M). The concentration producing 50% inhibition was 10(-7) M for adrenaline and clonidine, 10(-6) M for noradrenaline, and 5 x 10(-5) M for dopamine. Isoproterenol (5 x 10(-8) - 5 x 10(-7) M) inhibited the responses induced by both stimulation of the vagus nerve and acetylcholine. The inhibitory effects of the catecholamine and clonidine were blocked by phentolamine (2.7 x 10(-6) M) but not by 5-(3-tert-Butylamino-2-hydroxy)-propoxy-3, 4-dihydrocarbostyril hydrochloride (OPC 1085) which blocked the effect of isoproterenol. It is suggested that presynaptic alpha-receptors are present in the myenteric plexus of the chick proventriculus, and that the catecholamines and clonidine exert their inhibitory effects on cholinergic transmission via these receptors.


Separation and characterization of microplastic and nanoplastic particles in marine environment.
Microplastics (<5 mm) are divided into primary and secondary microplastics, which are further degraded into nanoplastics. The microplastic particles are widely distributed in marine environment, terrestrial ecosystem and biological organism, leading to damages to whole environmental system. Microplastics are not only difficult to degrade, but also able to adsorb pollutants. Due to the tiny size and various properties, the separation and characterization of microplastic particles has become more and more challenging. This review introduces the sources and destinations of the microplastic particles and summarizes the general methods for the sorting and characterization of microplastics, especially the manipulation of microplastic particles on microfluidic chip, showing possibility to deal with smaller nanoplastic particles over traditional methods. This review focuses on studies of the size-based separation and property-dependent characterization of microplastics in marine environment by utilizing the microfluidic chip device.


Hormonal phenotype and HLA-genotype in families of patients with congenital adrenal hyperplasia (21-hydroxylase deficiency).
The response of 17-hydroxyprogesterone (17-OHP) and cortisol (F) to a 6-hr ACTH stimulation in families of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency was studied. These studies demonstrated that siblings who should be heterozygous carriers of the 21-hydroxylase deficiency gene based on HLA genotyping are hormonally different from the general population. In pre- and early pubertal children predicted to be heterozygous carriers of the gene based on HLA genotyping, the 17-OHP level (13.1 +/- 4.5 ng/ml), the rate of increase of 17-OHP (0.03 +/- 0.01), and the ratio of 17-OHP/F at 6 hr (0.27 +/- 0.07) were significantly higher (P less than 0.001) than in the control population, (3.9 +/- 1.9, 0.009 +/- 0.005, and 0.08 +/- 0.04 ng/ml, respectively). In late and postpubertal males, these hormonal parameters in the heterozygotes (17 +/- 9.7, 0.04 +/- 0.026, 0.42 +/- 0.33 ng/ml, respectively) were significantly higher (P less than 0.001) than in the general population (5.3 +/- 1.6, 0.009 +/- 0.004, and 0.1 +/- 0.03 ng/ml, respectively). In postmenarchal females, the mean hormone responses in the heterozygotes (12.1 +/- 9.7, 0.03 +/- 0.02, and 0.27 +/- 0.24 ng/ml, respectively) were significantly higher (P less than 0.005, less than 0.01, less than 0.005, respectively) than in the general population (5.2 +/- 2.5, 0.01 +/- 0.007, and 0.1 +/- 0.04 ng/ml, respectively). However, the overlapping values did not permit a clear differentiation of the hormonal responses in these two groups. Another (ACTH) stimulation in one family demonstrated that a father of a patient probably is a previously unrecognized homozygous affected patient and,thus, revision of the congenital adrenal hyperplasia (CAH) genotype for this family was required.


Practices among General Practitioners in Rheumatoid Arthritis (GEPRA-I): results of a region-wide online survey.
To assess current practice regarding the management of rheumatoid arthritis patients among general practitioners of a French region, and their perception about the deployment of a multidisciplinary collaboration. A cross-sectional online survey was sent to the general practitioners of a French region. The questionnaire comprised of 3 sections to collect data regarding 1/demographics, 2/practice and knowledge in rheumatoid arthritis, and 3/perception about the deployment of a multidisciplinary collaboration. 1/A total of 247 general practitioners (M/F ratio: 1.4; mean age: 46.7 years) completed the survey. 2/More than half of general practitioners believed that their role was very or extremely important in disease diagnosis (72.5%), and management of comorbidities (67.2%). Among respondents, 6.1% considered that they did not face any difficulty concerning the patient management and 61.5% had already identified causes of non-adherence. 3/A total of 151 (61.1%) general practitioners were willing to participate in a multidisciplinary programme to improve medication adherence in rheumatoid arthritis. General practitioners are motivated to contribute to an overall management of rheumatoid arthritis patients. Nevertheless, they need professional education about rheumatoid arthritis treatment and training in motivational interviews before getting involved in a multidisciplinary collaboration.


Morphometric and cytomorphologic characterization of EGFR-mutated cancer cells-comparison between cultured lung cancer cell lines and lung adenocarcinoma clinical samples.
Recently molecular targeting therapies such as inhibition of enzyme activities associated with gene mutations responsible for lung carcinogenesis have been demonstrating promising outcomes, increasing the importance of gene analysis using clinical samples. Cytomorphologic findings with predictive value toward specific gene mutation such as EGFR mutation could be a useful tool to select appropriate gene analyses using limited clinical samples. Morphometrical and cytomorphological evaluations were performed in 7 cultured lung cancer cell lines and 51 lung adenocarcinoma clinical samples to identify specific cytomorphologic characterization of EGFR-mutated cancer cells compared to the wild type. Morphometry demonstrated that the EGFR mutated cell lines had significantly smaller nuclear area and perimeter and more circular nuclei compared to the wild type. In contrast, EGFR-mutated clinical samples had significantly greater nuclear area and perimeter compared to the wild type EGFR samples. There were no clear differences in cytomorphologic parameters assessing nuclear atypicality between EGFR mutated cells and wild type EGFR cells in either cultured cell lines or clinical samples. Although our study suggested that EGFR mutation may have specific effects on nuclear morphology, no consistent characteristics of EGFR-mutated cells were identified in the clinical samples, probably due to various factors such as different pathologic stages and various incidences of lepidic growth. Further assessment of morphological characterization of EGFR-mutated cells in lung adenocarcinoma is warranted, increasing the number of samples and considering the effects of polyploidy, other gene mutations, pathology stage and tumor subtypes such as lepidic growth. Diagn. Cytopathol. 2016;44:717-724. © 2016 Wiley Periodicals, Inc.


The orthopaedic aspect of spastic cerebral palsy.
Spastic Cerebral Palsy (CP) is the most common form of CP, comprising of 80% of all cases. Spasticity is a type of hypertonia that clinically manifests as dynamic contractures. The dynamic contracture along with the reduced level of physical activity in a child with CP leads to secondary structural and morphological changes in spastic muscle, causing real musculotendinous shortening, known as fixed contractures. When fixed muscle contractures are not treated early, progressive musculoskeletal deformities develop. As a consequence, spastic CP from a static neurological pathology becomes a progressive orthopaedic pathology which needs to be managed surgically. Orthopaedic surgical management of CP has evolved from previous "multi-event single level" procedures to a "single event multilevel" procedures, with changes in selection and execution of treatment modalities. There is increasing evidence that multilevel surgery is an integral and essential part of therapeutic management of spastic CP, but more research is needed to ensure effectiveness of this intervention on all domains of physical disability in CP.


Molecular characterization and functional analysis of MyD88 in Chinese soft-shelled turtle Trionyx sinensis.
Myeloid differentiation factor 88 (MyD88) is one of the key adaptor proteins to signal transduction that triggers downstream cascades involved in innate immunity. In this study, the MyD88 gene from Chinese soft-shelled turtle (Trionyx sinensis) (tMyD88) was identified, representing the fist example from reptile species. The tMyD88 has a 894-bp ORF and encodes a polypeptide of 297 amino acids including a typical death domain (DD) at the N-terminus and a conservative Toll/IL-1R (TIR) domain at the C-terminus. It was expressed at high levels in spleen, blood, lungs and liver, but marginal in kidneys and intestines of turtles challenged with live cells of Aeromonas hydrophila, as determined by real-time PCR. RAW 264.7 cells transfected with pcDNA-tMyD88 showed higher NF-κB activity than the vector control (673.78 vs 410.72, P < 0.05). Expression of proinflammatory cytokines IL-1β and TNF-α was also significantly higher in RAW 264.7 cells transfected with pcDNA-tMyD88 than those having pcDNA3.1 control vector (P < 0.01). These results indicate that tMyD88 might possess an important role in defense against microbial infection in Chinese soft-shelled turtles similar to that in mammals.


An androgen receptor-microrna-29a regulatory circuitry in mouse epididymis.
MicroRNAs are involved in a number of cellular processes; thus, their deregulation is usually apt to the occurrence of diverse diseases. Previous studies indicate that abnormally up-regulated miR-29a is associated with several diseases, such as human acute myeloid leukemia and diabetes; therefore, the proper level of miR-29a is critical for homeostasis. Herein, we observed that miR-29a was repressed by androgen/androgen receptor signaling in mouse epididymis by targeting a conserved androgen response element located 8 kb upstream of miR-29b1a loci. It is well known that multiple regulatory programs often form a complicated network. Here, we found that miR-29a reversibly suppressed androgen receptor and its target genes by targeting IGF1 and p53 pathways. miR-29b1a-overexpressing transgenic mice displayed epididymis hypoplasia partially similar to the phenotype of those mice with an impaired androgen-androgen receptor signal system. Taken together, the results demonstrated that there is a regulatory circuitry between the androgen signaling pathway and miR-29a in mouse epididymis that may be vital for epididymal development and functions.


Symptomatic mesentery Castleman disease mimicking a pancreatic tumor.
Castleman disease (CD) is an uncommon lymphoproliferative disorder of unknown etiology. It can be localized or multicentric. There are two major histological variants. The hyaline-vascular type predominates in the thorax and the mesenteric disease is usually of the plasma cell type. Hyaline-vascular CD of the mesentery is very rare. We report such a neoplasm of mesenteric root in a 38-year-old woman who presented with abdominal discomfort. Dynamic magnetic resonance imaging (MRI) of CD has rarely been reported previously. The imaging findings of CD on computed tomograms, MR images and angiograms were described.


Neuroendocrine tumor targeting: study of novel gallium-labeled somatostatin radiopeptides in a rat pancreatic tumor model.
Somatostatin analogs labeled with radionuclides are of considerable interest in the diagnosis and therapy of SSTR-expressing tumors, such as gastroenteropancreatic, small cell lung, breast and frequently nervous system tumors. In view of the favorable physical characteristics of the Ga isotopes (67)Ga and (68)Ga, enabling conventional tumor scintigraphy, PET and possibly internal radiotherapy, we focused on the development of a Ga-labeled somatostatin analog suitable for targeting SSTR-expressing tumors. For this purpose, 3 somatostatin analogs, OC, TOC and TATE were conjugated to the metal chelator DOTA and labeled with the radiometals (111)In, (90)Y and (67)Ga. They were then evaluated for their performance in the AR4-2J pancreatic tumor model by testing SSTR2-binding affinity, internalization/externalization in isolated cells and biodistribution in tumor-bearing nude mice. Surprisingly, we found that, compared to (111)In or (90)Y, labeling with (67)Ga considerably improved the biologic performance of the tested somatostatin analogs with respect to SSTR2 affinity and tissue distribution. (67)Ga-labeled DOTA-somatostatin analogs were rapidly excreted from nontarget tissues, leading to excellent tumor-to-nontarget tissue uptake ratios. Of interest for radiotherapeutic application, [(67)Ga]DOTATOC was strongly internalized by AR4-2J cells. Furthermore, our results suggest a link between the radioligand charge and its kidney retention. The excellent tumor selectivity of Ga-DOTA somatostatin analogs together with the different applications of Ga in nuclear oncology suggests that Ga-DOTA somatostatin analogs will become an important tool in the management of SSTR-positive tumors.


Bioresponsive nano-antibacterials for H2S-sensitized hyperthermia and immunomodulation against refractory implant-related infections.
There is an increasingly growing demand for nonantibiotic strategies to overcome drug resistance in bacterial biofilm infections. Here, a novel "gas-sensitized hyperthermia" strategy is proposed for appreciable bacteria killing by the smart design of a metal-organic framework (MOF)-sealed Prussian blue-based nanocarrier (MSDG). Once the biofilm microenvironment (BME) is reached, the acidity-activated MOF degradation allows the release of diallyl trisulfide and subsequent glutathione-responsive generation of hydrogen sulfide (H2S) gas. Upon near-infrared irradiation, H2S-sensitized hyperthermia arising from MSDG can efficiently eliminate biofilms through H2S-induced extracellular DNA damage and heat-induced bacterial death. The generated H2S in the biofilm can stimulate the polarization of macrophages toward M2 phenotype for reshaping immune microenvironment. Subsequently, the secretion of abundant regeneration-related cytokines from M2 macrophages accelerates tissue regeneration by reversing the infection-induced pro-inflammatory environment in an implant-related infection model. Collectively, such BME-responsive nano-antibacterials can achieve biofilm-specific H2S-sensitized thermal eradiation and immunomodulatory tissue remodeling, thus realizing the renaissance of precision treatment of refractory implant-related infections.


The estrogen receptor from a tamoxifen stimulated MCF-7 tumor variant contains a point mutation in the ligand binding domain.
The nonsteroidal antiestrogen tamoxifen (TAM) is the most commonly used endocrine treatment for all stages of breast cancer in both pre- and postmenopausal women. However, the development of resistance to the drug is common, as most patients treated with TAM eventually experience a recurrence of tumor growth. One of the potential mechanisms of treatment failure is the acquisition by the tumor of the ability to respond to TAM as a stimulatory rather than inhibitory ligand. We (Gottardis and Jordan, Cancer Res 48:5183-5187, 1988; Wolf et al., J Natl Cancer Inst 85:806-812, 1993) and others (Osborne et al., Eur J Cancer Clin Oncol 23: 1189-1196, 1987; Osborne et al., J Natl Cancer Inst 83: 1477-1482, 1991) have extensively described the reproducible development of TAM stimulated growth in a laboratory model system using MCF-7 human breast cancer cells grown as solid tumors in athymic mice. In this paper we report on the isolation of an estrogen receptor (ER) from a TAM stimulated tumor (MCF-7/MT2) which contains a point mutation that causes a tyrosine for aspartate substitution at amino acid 351 in the ligand binding domain. The mutant appears to the major form of ER expressed by this tumor. We also report that only wild type ER was detected in three other TAM stimulated MCF-7 tumor variants, suggesting that multiple mechanisms are possible for the development of TAM stimulated growth. The implications of these findings are discussed.


Effects of Age and Parkinson's Disease on the Relationship between Vocal Fold Abductory Kinematics and Relative Fundamental Frequency.
This study reports on two experiments to examine vocal fold abduction and its relationship with relative fundamental frequency (RFF), considering two attributes that have been shown to elicit group differences in RFF: age (Experiment 1) and Parkinson's disease (PD; Experiment 2). For both experiments, simultaneous acoustic and nasendoscopic recordings were collected as participants produced the utterance, /ifi/. RFF values were computed from the acoustic signal, whereas abduction duration and glottic angle at voicing offset were identified from the laryngoscopic images. In Experiment 1, 50 speakers with typical voices (18-83 years) were analyzed to examine (1A) the effects of speaker age on individual outcome measures (RFF, abduction duration, glottic angle) via Pearson's correlation coefficients, and (1B) the effects of abductory measures and age on RFF via an analysis of covariance. In Experiment 2, 20 speakers with PD and 20 matched controls were analyzed to examine (2A) the effects of group (with/without PD) on outcome measures via an analysis of variance, and (2B) the relationship of RFF with abduction duration, glottic angle, and age when considering group via an analysis of covariance. Age demonstrated a significant, negative relationship with glottic angle (1A) but was not a significant factor when examining the relationship of vocal fold abduction and RFF (1B). Speaker group (with/without PD) demonstrated a significant effect on measures of RFF and abduction duration (2A) but was not a significant factor when examining the relationship of vocal fold abduction and RFF (2B). RFF is sensitive to changes in vocal fold abductory patterns during devoicing, irrespective of speaker age or PD status.


The Collection 6 MODIS burned area mapping algorithm and product.
The two Moderate Resolution Imaging Spectroradiometer (MODIS) instruments on-board NASA's Terra and Aqua satellites have provided nearly two decades of global fire data. Here, we describe refinements made to the 500-m global burned area mapping algorithm that were implemented in late 2016 as part of the MODIS Collection 6 (C6) land-product reprocessing. The updated algorithm improves upon the heritage Collection 5.1 (C5.1) MCD64A1 and MCD45A1 algorithms by offering significantly better detection of small burns, a modest reduction in burn-date temporal uncertainty, and a large reduction in the extent of unmapped areas. Comparison of the C6 and C5.1 MCD64A1 products for fifteen years (2002-2016) on a regional basis shows that the C6 product detects considerably more burned area globally (26%) and in almost every region considered. The sole exception was in Boreal North America, where the mean annual area burned was 6% lower for C6, primarily as a result of a large increase in the number of small lakes mapped (and subsequently masked) at high latitudes in the upstream C6 input data. With respect to temporal reporting accuracy, 44% of the C6 MCD64A1 burned grid cells were de-tected on the same day as an active fire, and 68% within 2 days, which represents a substantial reduction in temporal uncertainty compared to the C5.1 MCD64A1 and MCD45A1 products. In addition, an areal accuracy assessment of the C6 burned area product undertaken using high resolution burned area reference maps derived from 108 Landsat image pairs is reported.


[Blindness due to head injury in an adolescent patient].
We describe the case of a 15 year old male adolescent with blindness of the right eye secondary to frontal head injury and blindness as the sole complication. Computed tomography and magnetic resonance imaging studies were both normal. We postulate a non anatomical severing of the optic nerve as the etiological cause for blindness. Clinical management included intraocular steroids. The patient was discharged with unilateral blindness and followed-up in outpatient care.


Decadal epidemiology of malaria in KwaZulu-Natal, a province in South Africa targeting elimination.
Although malaria remains a noteworthy disease in South Africa, the provinces are at differing stages of the malaria elimination continuum. KwaZulu-Natal has consistently reported the lowest number of cases over the past 5 years and it is expected that the goal of elimination will be achieved in this province over the next few years. The study reports on few key indicators that realistically represents the provinces progress over the past decade. Local and imported morbidity and mortality is seen as the key indicator as is malaria in children under the age of five and pregnant women. The only vector control intervention in the province is indoor residual spraying (IRS) and this gives an estimate of the population protected by this intervention. Trend analysis was used to examine the changing epidemiology in KwaZulu-Natal over the past decade from 2008 to 2018. The data used in this decadal analysis was obtained from the provincial Department of Health. Since malaria is a medically notifiable disease, all malaria cases diagnosed in the province are reported from health facilities and are captured in the malaria information system in the province. The results have shown that imported cases are on the increase whilst local cases are decreasing, in keeping with an elimination objective. Preventing secondary cases is the key to reaching elimination. Only 10% of the cases reported occur in children under 5 years whereas the cases in pregnant women account for about 1% of the reported cases. Over 85% of the houses receive IRS and this is also the same proportion of the population protected by the intervention. Several challenges to elimination have been identified but these are not insurmountable. Although there are major impediments to achieving elimination, the changing epidemiology suggests that major strides have been made in the past 10 years and KwaZulu-Natal is on track to achieving this milestone in the next few years.


Label-free discrimination and quantitative analysis of oxidative stress induced cytotoxicity and potential protection of antioxidants using Raman micro-spectroscopy and machine learning.
Diesel exhaust particles (DEPs) are major constituents of air pollution and associated with numerous oxidative stress-induced human diseases. In vitro toxicity studies are useful for developing a better understanding of species-specific in vivo conditions. Conventional in vitro assessments based on oxidative biomarkers are destructive and inefficient. In this study, Raman spectroscopy, as a non-invasive imaging tool, was used to capture the molecular fingerprints of overall cellular component responses (nucleic acid, lipids, proteins, carbohydrates) to DEP damage and antioxidant protection. We apply a novel data visualization algorithm called PHATE, which preserves both global and local structure, to display the progression of cell damage over DEP exposure time. Meanwhile, a mutual information (MI) estimator was used to identify the most informative Raman peaks associated with cytotoxicity. A health index was defined to quantitatively assess the protective effects of two antioxidants (resveratrol and mesobiliverdin IXα) against DEP induced cytotoxicity. In addition, a number of machine learning classifiers were applied to successfully discriminate different treatment groups with high accuracy. Correlations between Raman spectra and immunomodulatory cytokine and chemokine levels were evaluated. In conclusion, the combination of label-free, non-disruptive Raman micro-spectroscopy and machine learning analysis is demonstrated as a useful tool in quantitative analysis of oxidative stress induced cytotoxicity and for effectively assessing various antioxidant treatments, suggesting that this framework can serve as a high throughput platform for screening various potential antioxidants based on their effectiveness at battling the effects of air pollution on human health.


Niemann-Pick Type C disease and Alzheimer's disease: the APP-endosome connection fattens up.
Niemann-Pick Type C (NPC) is an inherited neurodegenerative disease of childhood and adolescence that develops from a failure of cholesterol trafficking within the endosomal-lysosomal pathway. Although NPC differs in major respects from Alzheimer's disease (AD), intriguing parallels exist in the cellular pathology of these two diseases, including neurofibrillary tangle formation, prominent lysosome system dysfunction, and influences of apolipoprotein E epsilon4 genotype. Added to these similarities are new findings that some neuronal populations develop abnormalities of endosomes resembling those seen at the earliest stages of AD and also accumulate beta-cleaved amyloid precursor protein (APP) and Abeta peptides within endosomes. In this commentary, the common features of endosome dysfunction are reviewed. Emerging evidence that endosome dysfunction may lead to beta-amyloidogenic APP processing or neurodegeneration by several different means is discussed.


Phase 2, Randomized, Open-Label Parallel-Group Study of Two Dosing Regimens of Netarsudil for the Treatment of Corneal Edema Due to Fuchs Corneal Dystrophy.
Background: This phase 2 study evaluated the therapeutic potential of netarsudil to reduce corneal edema and to improve vision in patients with Fuchs corneal dystrophy (FCD). Methods: Patients (N = 40) with baseline central corneal thickness (CCT) of ≥600 μm and best-corrected visual acuity (BCVA) of 70-20 letters (20/40-20/400 Snellen equivalent) were randomized 1:1 to receive netarsudil once a day (QD) or twice a day (BID) for 8 weeks. Primary endpoint was mean CCT change from baseline at week 4. Results: Netarsudil QD and BID significantly reduced CCT at week 4 [mean change (standard error of mean), 28.4 (7.99) μm, P = 0.0021; and 20.1 (8.75) μm, P = 0.0335, respectively]. Five (12.5%) patients achieved complete resolution of corneal edema at week 4. BCVA improved by 3.2 (2.76) letters with QD and 1.5 (2.84) letters with BID, and 10 (25%) patients [5 with QD (P = 0.0078) and 5 with BID (P = 0.0096)] gained ≥10 letters at week 4. Improvements in CCT and vision were observed at week 2 and persisted at week 8, without significant differences between the 2 doses at any time point. Netarsudil QD significantly improved visual acuity and glare factor scores on the Visual Function and Corneal Health Status (V-FUCHS) questionnaire at weeks 4 and 8 (mean change, -0.4 to -0.3; P ≤ 0.0200). Netarsudil was well tolerated. Reticular edema developed in one (2.5%) patient with BID, which resolved with treatment discontinuation. Conclusions: Netarsudil QD led to significant reductions in corneal edema as well as improvements in vision and patient-reported symptoms of glare and visual impairment in patients with FCD. Clinical Trial Registration Number: NCT04498169.


Postoperative pain control with a new transdermal fentanyl delivery system. A multicenter trial.
A new transdermal delivery system for fentanyl is available in two strengths: 70-80 and 90-100 micrograms.kg-1.h-1 (40- and 60-cm2 patches, respectively). Their short onset and 24-h drug delivery make them attractive for postoperative pain control. Both doses of the new transdermal fentanyl patches were evaluated for the relief of postoperative pain in 143 patients after gynecologic exploratory laparotomy. The study was conducted at four centers using a prospective, randomized, placebo-controlled, double-blind format. Patients were randomly assigned to one of three study groups: group 1 patients received two placebo patches: group 2 patients received a 40-cm2 fentanyl patch and a 60-cm2 placebo patch; and group 3 patients received a 60-cm2 fentanyl patch and a 40-cm2 placebo patch. Patient-controlled morphine use and pain, sedation, and comfort scores were assessed postoperatively every 4 h for 36 h after patch placement. Patients' assessment of their analgesia was significantly (P < or = 0.05) better in group 2 at 16 and 24 h and in group 3 at 8, 12, 16, 20, and 24 h postoperatively, compared with the patients in group 1. Patients in groups 2 and 3 required less supplemental morphine to maintain satisfactory analgesia than did the patients in group 1. Patients in groups 2 and 3 had greater incidences of pruritus, erythema, and respiratory depression than did those receiving placebo. Concern exists regarding the side effects of this this new transdermal fentanyl patch. Therefore, this new patch will need further research before it can be recommended as an adjunct in controlling postoperative pain.


High-dose pamidronate in the management of resistant Paget's disease.
Current recommendations for the total dose of intravenous pamidronate to be used in the treatment of Paget's disease range up to 400 mg per course, although up to 980 mg has been suggested for resistant cases. However, in a proportion of Paget's disease patients remission is difficult to induce and maintain. In five patients with resistant symptomatic Paget's disease, in whom a variety of antipagetic therapies had failed to induce remission, we have examined the effects of high dose pamidronate (1.44-2.52 g intravenously over 12-42 weeks). All five subjects had a marked symptomatic improvement, and disease activity was suppressed to a greater extent than had been achieved previously, but in only one did alkaline phosphatase activity suppress into the normal range. A plateau in the biochemical response was evident, with successive pamidronate doses of 120 mg producing smaller decrements in alkaline phosphatase. The plateau was reproducible on repeated courses. Bone biopsies in two patients showed continued pagetic activity with an increased mineralization rate and no osteomalacia. Worthwhile clinical and biochemical improvements can be obtained in patients with resistant Paget's disease by the use of high-dose pamidronate. Though this approach does not seem to cause defective mineralization, it may be difficult to suppress disease activity completely.


Clinical outcomes following a strategy of optimized medical management and selective "downstream" procedures following coronary computed tomography angiography.
Prior studies have shown a consistent relationship between coronary artery calcium (CAC) scores or the degree of coronary stenoses on coronary computed tomography angiography (CCTA) and all-cause mortality. Whether CCTA-targeted therapy, including intensive medical management, stress testing and/or invasive coronary angiography (ICA), can lead to a substantial reduction in adverse outcomes is not yet known. We retrospectively analyzed 691 patients (55±13 years, male=63%) from a single medical practice who underwent a CAC scan and CCTA and were followed for a mean of 2.9±1.0 years. Of these, 416 (60%) patients were asymptomatic. All changes in medications, coronary risk factors (including lipids profiles), downstream testing, revascularization procedures, and clinical events (myocardial infarction and death) were recorded. Among our patients cohort 279 (40%) had no coronary artery disease. The most severe stenosis was <50% in 314 (46%) patients, 50-70% in 76 (11%) patients, and >70% in 22 (3%) patients. A high frequency of medical therapy was employed for those patients with any degree of stenosis, while stress testing was primarily applied for patients with >50% stenosis and ICA was primarily performed in those with >70% stenosis. Only two non-cardiovascular deaths and no cardiovascular deaths occurred during the follow-up period. Our findings support the hypotheses that among patients undergoing CCTA, comprehensive medical management, including targeted percutaneous coronary interventions and increasingly intensive medical therapy with progressively worse CCTA findings, can reduce event rates among patients with abnormal CCTA studies.


Nonstationary frequency analysis and uncertainty quantification for extreme low lake levels in a large river-lake-catchment system.
Extreme hydrological events have become increasingly frequent on a global scale. The middle Yangtze River also faces a substantial challenge in dealing with extreme flooding and drought. However, the long-term characteristics of the extreme hydrological regime have not yet been adequately recognized. Moreover, there is uncertainty in the extreme value estimation, and this uncertainty needs to be distinguished and quantified. In this study, we investigated the nonstationary frequency characteristics of extreme low lake levels (ELLLs), taking the Poyang Lake as an example. Daily lake levels from 1960 to 2022 were utilized to estimate the return level using the generalized Pareto distribution (GPD). The uncertainty from three sources, i.e., the parameter estimator, threshold selection, and covariate, was quantified via variance decomposition. The results indicate that (1) the parameter estimator is the predominant source of uncertainty, with a contribution rate of approximately 87 %. The total uncertainty of the covariate, threshold, and interaction term is only 13 %. (2) Two indexes, namely the annual minimum water level (WLmin) and the days with peak over the 90 % threshold per year (DPOT90), decreased (0.01-0.03 m/year) and increased (0.17-1.39 days/year), respectively, indicating a progressively severe drought trend for Poyang Lake. (3) The return level with return period of 5 to 100 years significantly decreased after the early 21st century. A large spatial heterogeneity was identified for the variation in the return level, and the change rate of the return level with a 100-year return period ranged from 5 % to 40 % for the whole lake. (4) The ELLLs had a stronger correlation with the catchment discharge than with the Yangtze River discharge and the large-scale atmospheric circulation indices. This study provides a methodology with reduced uncertainty for nonstationary frequency analysis (NFA) of ELLLs exemplified in large river-lake systems.


Inhibition by 5-hydroxytryptamine and noradrenaline in substantia gelatinosa of guinea-pig spinal trigeminal nucleus.
1. Whole-cell and intracellular recordings were made from neurons in slices of guinea-pig spinal trigeminal nucleus pars caudalis. 2. 5-Hydroxytryptamine (5-HT) hyperpolarized 70% of neurons by activating 5-HT1A receptors. The effect was mimicked by 5-carboxamidotryptamine (5-CT) and (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronapthalene hydrobromide (8-OH-DPAT) and antagonized by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)-butyl]-piperazine hydrobromide (NAN 190) and pindobind-5-HT1A. Nine per cent of the neurons were depolarized by 5-HT. 3. In about 20% of recordings, 5-HT also evoked repetitive inhibitory postsynaptic potentials that were mediated by glycine. 4. Noradrenaline (NA) hyperpolarized 71% of neurons. This effect was mediated by activation of alpha 2-adrenoceptors, since 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK14304) also caused a hyperpolarization and idazoxan (1 microM) blocked the hyperpolarization to both NA and UK14304. Phenylephrine depolarized a subset of neurons and this depolarization was blocked by prazosin, suggesting an action mediated by activation of alpha 1-adrenoceptors. 5. NA also evoked repetitive GABAA-mediated inhibitory postsynaptic potentials in about 20% of recordings. The increase in synaptic activity was mimicked by phenylephrine and blocked by prazosin. 6. These results indicate that there are at least two mechanisms through which 5-HT and NA inhibit neurons: (i) in many cells both 5-HT and NA mediate a hyperpolarization through an increase of a potassium conductance; (ii) 5-HT and NA also activated GABA- and glycine-containing interneurons to cause IPSPs in separate groups of cells.


Muscle fascia and force transmission.
This paper reviews the major intramuscular extracellular matrix (IM-ECM) structures (endomysium, perimysium and epimysium) and their possible mechanical contributions to muscle functions. The endomysium appears to provide an efficient mechanism for transmission of contractile forces from adjacent muscle fibres within fascicles. This coordinates forces and deformations within the fascicle, protects damaged areas of fibres against over-extension, and provides a mechanism whereby myofibrils can be interrupted to add new sarcomeres during muscle growth without loss of contractile functionality of the whole column. Good experimental evidence shows that perimysium and epimysium are capable in some circumstances to act as pathways for myofascial force transmission. However, an alternative role for perimysium is reviewed, which involves the definition of slip planes between muscle fascicles which can slide past each other to allow large shear displacements due to shape changes in the whole muscle during contraction. As IM-ECM is continually remodelled so as to be mechanically adapted for its roles in developing and growing muscles, control of the processes governing IM-ECM turnover and repair may be an important avenue to explore in the reduction of fibrosis following muscle injury.


Computer-assisted modeling of osseous impingement and resection in femoroacetabular impingement.
The purpose of this study was to evaluate the utility of computer-assisted 3-dimensional modeling in diagnosing and treating symptomatic hip impingement. Eight patients with symptomatic, focal cam and/or pincer impingement lesions underwent high-resolution computed tomography scans and computer-assisted, 3-dimensional modeling of the involved hip. Cam location, alpha angle, neck-shaft angle, femoral version, and acetabular version at the 12-o'clock through 3-o'clock positions were measured. The model was subsequently dynamized to define the preoperative range of motion and location of impingement with hip flexion, internal rotation, and internal rotation at 90° of hip flexion. Virtual cam and pincer osteoplasty was performed to establish normal head-neck offset and head sphericity and to eliminate focal rim impingement lesions. Range of motion and location of impingement were reassessed after resection in the defined area of impingement. The cam lesion was located between the 12-o'clock and 4-o'clock positions in all cases. The mean alpha angle was 66.4° (range, 53° to 80°). Mean femoral version was 14.6° (range, 5° to 23°). Mean preoperative hip flexion was 109.7° (range, 87.5° to 125.5°), and mean internal rotation at 90° of hip flexion was 16.2° (range, 1.7° to 25.5°). The location of impingement was unique in each case and not predictable based on radiographic measures alone. Virtual osteoplasty in the defined regions of impingement resulted in significant improvements in both hip flexion and internal rotation (P < .05). Computed tomography-based computer modeling can localize regions of anticipated mechanical impingement in symptomatic patients with hip pain. Computer-assisted navigation may be a valuable surgical tool to more accurately and reliably eliminate offending impingement lesions. Level IV, diagnostic study.


Comparison of bacteria with and without plasmid-encoded proteins as antigens for measurement of immunoglobulin M, G, and A antibodies to Yersinia enterocolitica by enzyme-linked immunosorbent assay.
Yersinia enterocolitica serovar O:3 bacteria with and without plasmid-encoded proteins were compared as antigens in an enzyme-linked immunosorbent assay. Good correlations between the two antigen preparations were obtained for immunoglobulin M (IgM), IgG, and IgA antibodies of patients with yersiniosis. For routine diagnostic purposes, these antigens are considered equal.


IPSC Models of Chromosome 15Q Imprinting Disorders: From Disease Modeling to Therapeutic Strategies.
The chromosome 15q11-q13 region of the human genome is regulated by genomic imprinting, an epigenetic phenomenon in which genes are expressed exclusively from one parental allele. Several genes within the 15q11-q13 region are expressed exclusively from the paternally inherited chromosome 15. At least one gene UBE3A, shows exclusive expression of the maternal allele, but this allele-specific expression is restricted to neurons. The appropriate regulation of imprinted gene expression across chromosome 15q11-q13 has important implications for human disease. Three different neurodevelopmental disorders result from aberrant expression of imprinted genes in this region: Prader-Willi syndrome (PWS), Angelman syndrome (AS), and 15q duplication syndrome.


Antinociceptive effects of flower extracts and the active fraction from Styrax japonicus.
Flowers from Styrax japonicus sieb. et Zucc. have been used as a Chinese folk medicine to alleviate pain such as toothache and sore throat. To testify the analgesic effect of flowers from Styrax japonicus, analyze components of the active fraction, and investigate the mechanism of analgesia. Flower extracts were obtained by ethanol, petroleum ether and hydrodistillation extraction. Different fractions of ethanol extracts (EE) were isolated by silica gel column chromatography and preparative liquid chromatography. Analgesic effects of EE, petroleum ether extracts (PEE), hydrodistillation extracts (HDE), and fractions of EE were evaluated using hot plate, acetic acid-induced writhing and formalin tests on mice. Components of the active fraction 1 (F1) were determined by the ultrahigh-performance liquid chromatography Q extractive mass spectrometry (UHPLC-QE-MS). Anti-inflammatory and sedative effects involving analgesic mechanisms were evaluated by carrageenan induced hind paw oedema and pentobarbital sodium sleep tests, respectively. In addition, antagonists including naloxone hydrochloride (NXH), flumazenil (FM), SCH23390 (SCH) and WAY100635 (WAY) were used to investigate the possible mechanism of analgesia. Contents of neurotransmitters and relevant metabolites in different brain regions of mice were also quantified by the ultraperformance liquid chromatography with a fluorescence detector (UPLC-FLD). EE rather than PEE and HDE at medium and high doses (150 mg/kg and 300 mg/kg) significantly prolonged the latency time of the response of mice to the thermal stimulation in the hot plate test. Moreover, EE significantly decreased number of writhes in the acetic acid-induced writhing test, and reduced licking time in both two phases of the formalin test in a dose-dependent manner. The F1 (50 mg/kg) showed effective antinociceptive responses in all mice models. However, fraction 2 (F2) and fraction 3 (F3) at 50 mg/kg performed no analgesic action. Kaempferol-3-O-rutinoside, isorhamnetin-3-O-rutinoside, pinoresinol-4-O-glucoside, forsythin and arctiin were identified from components of the F1. Furthermore, F1 (50 mg/kg) did not significantly affect hind paw oedema of mice induced by carrageenan but significantly shortened sleep latency and increased sleep duration in the pentobarbital sodium sleep test. In addition, the antinociceptive response of F1 was not affected by NXH in two mice models, but significantly blocked by FM and WAY in the hot plate test. In the formalin test, FM avoided the effect of F1 only in the first phase, while the analgesic activity of F1 was totally suppressed by WAY in both two phases. Otherwise, contents of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) increased significantly in hippocampus and striatum of mice in the F1 group. EE from flowers of Styrax japonicus, and F1, the active part isolated from EE, showed significant antinociceptive activities. The analgesic effect of F1 appeared to be related to the sedative effect, partially mediated by the GABAergic system, and highly involved in the serotonergic system. This was the first study confirming the analgesic effect of Styrax japonicus flower, which provided a candidate for the development of non-opioid analgesics.


Predictive ability of creatinine clearance versus estimated glomerular filtration rate for outcomes in patients with non-valvular atrial fibrillation: Subanalysis of the J-RHYTHM Registry.
Renal impairment is a risk factor for various adverse events, especially for death. In general, creatinine clearance (CrCl) is used for dose-adjustments of many drugs including oral anticoagulants, and estimated glomerular filtration rate (eGFR) is adopted for the diagnosis of chronic kidney disease. Predictive ability of CrCl versus eGFR for outcomes in patients with non-valvular atrial fibrillation (NVAF) remains controversial; therefore, this was compared using data from the J-RHYTHM Registry. Out of 7406 outpatients with NVAF from 158 institutions, 6004 (age, 69.7 ± 9.9 years; men, 71.2%) having data of CrCl (mL/min, by the Cockcroft-Gault formula), eGFR (mL/min/1.73 m2, by the equations of the Japanese Society of Nephrology), and body surface area (BSA) were analyzed. C-statistics (area under the receiver-operating characteristic curve) of CrCl and eGFR for events were compared by DeLong's test. Thromboembolism, major hemorrhage, and all-cause death occurred in 107 (1.8%), 117 (1.9%), and 154 (2.6%) patients during the 2-year follow-up period. C-statistics of CrCl for each event were 0.609 (95% confidence interval, 0.559-0.658), 0.599 (0.548-0.657), and 0.746 (0.706-0.786); and those of eGFR were 0.542 (0.487-0.597), 0.573 (0.519-0.626), and 0.677 (0.631-0.723), respectively. C-statistics of CrCl for thromboembolism and all-cause death were significantly higher than those of eGFR (P < 0.001 for both). These results were consistent when BSA-unadjusted eGFR was used instead of eGFR (P = 0.002 for thromboembolism and P < 0.001 for all-cause death). CrCl was superior to eGFR in the prediction of adverse outcomes, i.e., thromboembolism and all-cause death in Japanese patients with NVAF.


Elevated glucose levels influence in vitro hatching, attachment, trophoblast outgrowth and differentiation of the mouse blastocyst.
A glucose concentration of 3.5 mg/ml is optimal for in vitro embryo attachment and trophoblastic cell outgrowth. Raising the concentration above 3.5 mg/ml does not improve embryo culture and can at certain concentrations be detrimental to embryo development.


The role of an aromatic group in remote chiral induction during conjugate addition of alpha-sulfonylallylic carbanions to ethyl crotonate.
The impact of a remote aromatic nucleus on the stereochemical outcome of the conjugate addition of alpha-sulfonylallylic carbanions to an alpha,beta-unsaturated ester was investigated. alpha-Regioselectivity coupled with anti-diastereoselectivity is accompanied by a prominent preference for relative configuration 3 over 4. The 9-anthryl moiety has shown itself greatly superior over all other groups in this bias. A lithium ion-aromatic pi interaction has been postulated as decisive for the remote transmission of chirality.


Stenting for vertebrobasilar artery stenosis.
We report our experience with stenting for symptomatic vertebrobasilar artery stenosis. One hundred and sixteen patients with vertebrobasilar artery stenosis (101 vertebral ostial stenosis, 15 intracranial vertebrobasilar artery stenosis) were treated with stenting. Indication criteria of treatment were 1) symptomatic lesion, 2) angiographical stenosis more than 60%. Under local anesthesia, pre-dilatation was first performed, then stents were placed to the lesion. Successful dilatation was obtained in 115 cases. The stenosis rate reduced to 2% post-stenting in ostial lesions and 16% in intracranial lesions. Transient neurological complications developed in 2 patients. Follow-up angiographies more than 6 months after stenting were performed in 94 patients with ostial lesions and all patients with intracranial lesions. Of these, 8 patients (9.5%) with ostial lesions and 4 patients (27%) with intracranial lesions developed restenosis. All patients with restenosis were treated successfully with PTA (percutaneous transluminal angioplasty). During the follow-up period, 3 patients developed recurrence of VBI (vertebro-basilar insufficiency) symptoms due to restenosis. One patient developed brain stem infarction due to in-stent occlusion 8 months after stenting. Conclusion. Stenting for vertebrobasilar artery stenoses is feasible and safe. Prevention of restenosis, especially in intracranial arteries, is the next problem to be solved.


Iterative control approach to high-speed force-distance curve measurement using AFM: time-dependent response of PDMS example.
Force-distance curve measurements using atomic force microscope (AFM) has been widely used in a broad range of areas. However, currently force-curve measurements are hampered the its low speed of AFM. In this article, a novel inversion-based iterative control technique is proposed to dramatically increase the speed of force-curve measurements. Experimental results are presented to show that by using the proposed control technique, the speed of force-curve measurements can be increased by over 80 times--with no loss of spatial resolution--on a commercial AFM platform and with a standard cantilever. High-speed force curve measurements using this control technique are utilized to quantitatively study the time-dependent elastic modulus of poly(dimethylsiloxane) (PDMS). The force-curves employ a broad spectrum of push-in (load) rates, spanning two-order differences. The elastic modulus measured at low-speed compares well with the value obtained from dynamic mechanical analysis (DMA) test, and the value of the elastic modulus increases as the push-in rate increases, signifying that a faster external deformation rate transitions the viscoelastic response of PDMS from that of a rubbery material toward a glassy one.


Inhibitory effect of calcium antagonists on histamine release from human leukocytes. In vivo and in vitro experiments.
A study was made of the influence of calcium antagonists on human basophil histamine release induced in vitro by specific antigen, anti-IgE or the calcium ionophore A23187. Both verapamil, nifedipine, and nimodipine were found to inhibit the release, and a similar effect was also observed after peroral administration of verapamil and nifedipine. The inhibitory effect of the drugs on histamine release seems to depend on interaction with calcium at different sites. The anti-allergic effect might explain the improvement found with calcium antagonists in exercise-induced asthma.


Identification of plasmid-encoded extended spectrum beta-lactamases produced by a clinical strain of Proteus mirabilis.
Emergence and dissemination of multiresistant strain of Proteus mirabilis have made infections treatment more difficult that this bacterium is responsible. The aim of this study is to determine the implication of the enzymatic mechanism and to describe the properties of ESBLs (extended spectrum beta-lactamases). A clinical strain of Proteus mirabilis SM514 isolated in the intensive care unit at the Military hospital in Tunisia during the period 2004 was found to be highly resistant to cephalosporins and penicilins. Cells sonicate of the isolate hydrolysed cefotaxime more efficiently than ceftriaxone and ceftazidime and had three beta-lactamases bands of approximate of isoelectric points (pI) of 5.4; 5.6 and superior to 7.6. The specific activities (AS) vary from 5.26 to 7.77U/mg of protein respectively for cefotaxime and the benzylpenicillin. These activities are inhibited by the clavulanic acid and the sulbactam. The values of the IC(50) are respectively 3.7 and 11.7muM. Only the beta-lactamases of pI 5.4 and superior to 7.6 hydrolyze the cefotaxime. Transformant produces the ESBLs of pI 5.4; 7.45 and greater than 7.6. The genes coding for this enzymes are carried by a transferable plasmids.


Insulin regulates the expression of the GLUT5 transporter in L6 skeletal muscle cells.
Skeletal muscle, a primary insulin target tissue, expresses the GLUT5 fructose transporter. Although insulin has no acute effect on GLUT5 expression and function in muscle, we show here that long-term (24 h) insulin treatment of L6 muscle cells induces a dose-dependent increase in GLUT5 protein (by up to two-fold), leading to a concomitant increase in fructose uptake. The increase in GLUT5 expression and function was suppressed by inhibitors of gene transcription and protein synthesis, suggesting that insulin promotes de novo carrier synthesis. Transfection of the GLUT5 gene promoter fused to luciferase into L6 cells revealed that insulin induced a 1.8-fold increase in GLUT5 promoter activity. Our findings indicate that insulin is capable of increasing the abundance and functional activity of GLUT5 in skeletal muscle cells and that this is most likely mediated via activation of the GLUT5 promoter.


Functional Fas-ligand expression on T cells from HIV-1-infected patients is unrelated to CD4+ lymphopenia.
Recent studies have demonstrated that the expression of Fas by peripheral T cells from HIV-1+ patients is deregulated and increases the susceptibility of these cells to undergo apoptosis. Here, we show that secretion of Fas-ligand (L), the complementary agonist of Fas, is abnormally upregulated in CD4+ cells from HIV-1-infected individuals, particularly during the non-lymphopenic stages of the disease. An increase of soluble Fas-L occurred in T cell cultures from 26 patients with a number of CD4+ cells higher than 400/microliter, whereas it was almost undetectable in cultures from 21 severely lymphopenic patients (CD4+ < 200/microliter). The MTT test, cytofluorimetric analysis of cellular DNA, cytotoxicity, and proliferative assays using the Fas-transfected WC8 mouse lymphoma confirmed the cytocidal capability of T cell supernatants from non-lymphopenic patients. Double-fluorescence analysis revealed that the majority of CD4+ cells (approximately 90%) in these cultures secreted Fas-L in the presence of high intracellular gamma-interferon and low Bcl-2. In contrast, the CD8+/Fas-L+ population was comparably decreased (approximately 55%). Molecular cloning of Fas-L revealed a substantial expression of Fas-L mRNA in cells from non-lymphopenic patients compared with patients with advanced disease and healthy controls. Since CD4+ cells of Th1 phenotype are impaired during HIV-1 infection and show high cellular expression of Fas-L, it is conceivable that excess Fas-L during the early or non-lymphopenic phase of the disease increases the extent of apoptosis in these cells by the Fas/Fas-L pathway. The defective expression of the ligand in severely lymphopenic stages could be explained by exhaustion of this mechanism as the disease progresses.


Minimally invasive valve surgery with antegrade perfusion strategy is not associated with increased neurologic complications.
A Society of Thoracic Surgeons' publication recently associated "minimally invasive" approaches with increased neurologic complications; this proposed association was questionable due to imprecise definitions. To critically reevaluate this issue, we reviewed a large minimally invasive valve experience with robust definitions. From November 1995 to January 2007, 3,180 isolated, non-reoperative valve operations were performed; 1,452 (45.7%) were aortic replacements and 1,728 (54.3%) were mitral valve procedures. Surgical approach was standard sternotomy (28%) or minimally invasive technique (72%). Antegrade arterial perfusion was used in 2,646 (83.2%) patients and retrograde perfusion in 534 (16.8%). Aortic clamping was direct in 83.4%, with endoclamp in 16.4% and no clamp in 0.2%. Patients were prospectively followed in a proprietary database and the New York State Cardiac Surgery Reporting System (mandatory, government audited). A neurologic event was defined as a permanent deficit, a transient deficit greater than 24 hours, or a new lesion on cerebral imaging. Hospital mortality for aortic valve replacement was 4.0% (sternotomy [5.1%] versus minimally invasive [3.4%] p = 0.13); for mitral procedures it was 2.4% (sternotomy [4.8%] versus minimally invasive [1.8%] p = 0.001). Multivariate analysis revealed that age, female gender, renal disease, ejection fraction less than 0.30, chronic obstructive pulmonary disease, and emergent operation were risk factors for mortality. Stroke occurred in 71 patients (2.2%) (sternotomy [2.1%] versus minimally invasive [2.3%] p = 0.82). Multivariate analysis of neurologic events revealed that cerebrovascular disease, emergency procedure, no-clamp, and retrograde perfusion were risk factors. In patients 50 years old or younger (n = 662), retrograde perfusion had no significant impact on neurologic events (1.6% vs 1.1%, p = 0.57). A minimally invasive approach with antegrade perfusion does not result in increased neurologic complications. Retrograde perfusion, however, is associated with increased neurologic risk in older patients.


Trends in smoking-related diseases by socioeconomic position following a national smoking ban in 2007: a nationwide study in the Danish population.
National comprehensive smoke-free legislation has been found to decrease the incidence of several smoking-related diseases. In 2007, Denmark introduced a national smoking ban, which banned smoking indoor in workplaces and public places, although only partial restrictions were applied in certain settings. We examined the impact of the smoking ban on smoking-related diseases and whether this differed across socioeconomic groups. Interrupted time series analyses of nationwide register data were performed using Poisson regression models to examine the differential impact of the smoking ban on monthly incidence rates of acute myocardial infarction, chronic obstructive pulmonary disease, and smoking-related cancers from 2002 to 2015. Immediate changes in incidence rates after the smoking ban and long-term changes in disease trends were estimated by comparing data from the pre- and post-ban period. Models were stratified by socioeconomic position. Overall, we found neither immediate changes in rates of acute myocardial infarction, chronic obstructive pulmonary disease, and smoking-related cancers following the smoking ban nor long-term post-ban changes in disease trends as compared to before the ban. Results did not differ across socioeconomic groups. A pronounced socioeconomic gradient in incidence rates was observed for all outcomes both before and after the smoking ban. The national smoking ban was not associated with a lower incidence of smoking-related diseases in the post-ban period compared to pre-ban levels and no differences between socioeconomic groups were observed. Future tobacco control in Denmark should consider which measures most effectively target the low socioeconomic groups to decrease the current strong socioeconomic inequality in health.


Prevalence of and attitudes towards complementary therapy use for weight after breast cancer in Australia: a national survey.
Weight gain is common after breast cancer (BC) treatment and may increase the risk of disease recurrence. Complementary medicine (CM) use is high amongst BC patients. This paper describes the use of CM from a cross-sectional self-administered survey on prevalence and management of weight after BC. Use of CM was assessed using a question modified from the I-CAM Questionnaire. Participants were asked to rate perceived effectiveness, advantages and disadvantages, and which CM they were willing to use for weight management if there was evidence for effectiveness. The survey was emailed to members of the Breast Cancer Network Australia Survey and Review Group, the largest consumer advocacy group in Australia for people with breast cancer. There were a total of 309 responses. Three quarters had used CM in the past 12 months. One third had tried CM for weight loss. Yoga, meditation and pilates were perceived to be effective for weight loss. Perceived advantages of CMs for weight loss were the ability to improve general wellbeing, relaxation, and being non-pharmacological while disadvantages were financial cost, finding a reliable practitioner, and lack of research for effectiveness. Three quarters would be willing to try CM for weight loss if there was evidence for effectiveness, with the most popular CMs being acupuncture, relaxation, yoga, supplements, and meditation. The high use of CM in this group is consistent with previous research. Our research suggests that BC survivors would use acupuncture, meditation, supplements and yoga for weight loss if supported by scientifically-credible evidence. Research into the effectiveness of these treatments on weight loss after BC is warranted.


Inhibitory effects of astilbin, neoastilbin and isoastilbin on human cytochrome CYP3A4 and 2D6 activities.
Astilbin, neoastilbin and isoastilbin are three flavonoid isomers from Smilacis glabrae Roxb. (S. glabrae). Several studies have shown that consumption of flavonoids can increase the risk of food/drug-drug interaction by affecting the activities of human cytochrome CYP3A4 and 2D6. In the present study, an ultrahigh-performance liquid chromatography and triple quadrupole mass spectrometry method was developed for the determination of the interaction between three flavonoid isomers and two CYPs. Under the optimized reaction conditions, the Km values were 18.9 and 36.4 μM and the Vmax values were 0.02 and 0.20 μM/min for CYP3A4 and 2D6 in vitro, respectively. Astilbin showed the strongest inhibition on CYP3A4, followed by isoastilbin and neoastilbin with IC50 values of 2.63, 3.03 and 6.51 μM. Neoastilbin showed the strongest inhibition on CYP2D6, followed by isoastilbin and astilbin, with IC50 values of 1.48, 11.87 and 14.16 μM, respectively. The three isomers showed reversible inhibition on both enzymes. Neoastilbin and astilbin were noncompetitive type for CYP3A4 and 2D6, isoastilbin was a mixture and noncompetitive type for CYP3A4 and 2D6, respectively. Our study suggests that the three isomers may increase the risk of food/drug-drug interactions by affecting the activities of CYP3A4 and 2D6.


Reliability of estimating ductions in thyroid eye disease: an International Thyroid Eye Disease Society multicenter study.
To determine intraobserver and interobserver reliability of 3 clinical techniques for measuring ocular ductions in patients with thyroid eye disease and to compare these with an established method using a Goldmann perimeter. Our secondary goals were to compare the clinical methods for test duration, ease of learning and performance, and whether these differed between novices and experts. Multicenter, prospective, comparative trial. We recruited 38 patients with thyroid orbitopathy and reduced ocular motility from 7 academic centers. At each center, 2 novices and 2 experts measured the ocular ductions of each eye of each patient in 4 directions (0°, 90°, 180°, and 270°) using 3 techniques (best guess [BG], light reflex [LR], and a ruler measuring [RU] technique). Test duration and clinicians' feedback were recorded. A subjective and objective measurement for ocular ductions using a Goldmann perimeter was performed for each subject by a trained technician. The 3 clinical measurements and the perimetry measurements were performed twice, separated by ≥1 hour. We measured the intraobserver and interobserver reliability of the 3 clinical techniques and intraobserver reliability of Goldmann perimeter. Clinical testing reliability was compared between experts and novices. We also examined test duration and clinician feedback. The LR technique had significantly better intraobserver and interobserver repeatability compared with the BG or RU clinical measurements and statistically was equivalent to the gold-standard perimetric technique. Reliability was constant regardless of the amount of restriction in ocular movement. There was no difference between reliability values for experts and novices. The LR and BG techniques were significantly faster than the RU or perimetry techniques and were considered easiest to learn and perform, but clinicians had most confidence in the LR technique results. The LR technique for measuring ocular ductions in thyroid orbitopathy is more reliable than other clinical techniques and as reliable as the established technique using the perimeter. However, unlike the latter method, it is easier to learn and perform by both novices and experts, is significantly faster, and can be performed by the clinician without machinery or a trained technician.


IKs, a slow and intriguing cardiac K+ channel and its associated long QT diseases.
Shaping of cardiac action potentials depends on a finely tuned orchestra of ion channels. Among them, K(+) channels probably form the most diverse family. They are responsible for inwardly rectifying (I(K1), I(KAch), I(KATP)), transient (I(to)), and sustained outward rectifying (I(Kur), I(Kr), I(Ks)) K(+) currents. The properties of these cardiac K(+) channels have recently been extensively reviewed. This article focuses on recent progress made toward understanding the molecular structure of the particular channel responsible for the slow outward K(+) current I(Ks) and its implication in the delayed ventricular repolarization that characterizes the congenital long QT syndrome.


Estrogen's Effects on Excitatory Synaptic Transmission Entail Integrin and TrkB Transactivation and Depend Upon β1-integrin function.
Estradiol (E2) perfusion rapidly increases the strength of fast excitatory transmission and facilitates long-term potentiation in the hippocampus, two effects likely related to its memory-enhancing properties. Past studies showed that E2's facilitation of transmission involves activation of RhoA signaling leading to actin polymerization in dendritic spines. Here we report that brief exposure of adult male hippocampal slices to 1 nM E2 increases the percentage of postsynaptic densities associated with high levels of immunoreactivity for activated forms of the BDNF receptor TrkB and β1-integrins, two synaptic receptors that engage actin regulatory RhoA signaling. The effects of E2 on baseline synaptic responses were unaffected by pretreatment with the TrkB-Fc scavenger for extracellular BDNF or TrkB antagonism, but were eliminated by neutralizing antisera for β1-integrins. E2 effects on synaptic responses were also absent in conditional β1-integrin knockouts, and with inhibition of matrix metalloproteinases, extracellular enzymes that generate integrin ligands. We propose that E2, acting through estrogen receptor-β, transactivates synaptic TrkB and β1-integrin, and via mechanisms dependent on integrin activation and signaling, reversibly reorganizes the spine cytoskeleton and thereby enhances synaptic responses in adult hippocampus.


Thoracic Syndesmophytes Commonly Occur in the Absence of Lumbar Syndesmophytes in Ankylosing Spondylitis: A Computed Tomography Study.
To determine the extent of thoracic involvement with syndesmophytes in ankylosing spondylitis (AS) relative to lumbar involvement. We performed thoracolumbar spine computed tomography (CT) and lumbar radiography on 18 patients. We quantitated syndesmophytes in 11 intervertebral disc spaces and related these to the presence of syndesmophytes on lumbar radiographs. Syndesmophytes were slightly more common in the thoracic than in the lumbar spine and bridging was significantly more common. Thoracic syndesmophytes were universally present in patients without visible lumbar syndesmophytes on either radiographs or CT. Syndesmophytes predominate in the thoracic spine. Lumbar radiographs underestimate the degree of thoracic involvement.


Environmental, social, and governance (ESG) and market efficiency of China's commercial banks under market competition.
As the leading financial institutions in China, it is crucial for commercial banks to pay attention to environmental protection (E), social responsibility (S), and corporate governance (G) in order to enhance operational efficiency and to advance the high-quality development of the country's social economy. This research explores the market share of banks as exogenous variables in the profit stage and the market and sustainability stage to investigate the efficiency of 20 listed banks in China over 2016-2020 and innovatively incorporates indicators such as green credit, social giving, executive compensation, and ESG score into the meta-dynamic two-stage SBM under the exogenous variable DEA model. The results demonstrate the following. (1) By integrating market share as an exogenous variable in the model, the efficiency estimate is more precise. (2) In overall, UCBs are the most efficient type of banks, JSCBs are the second, SOCBs are the least efficient. All three types of banks are more efficient in profit stage versus the market and sustainability stage, JSCBs perform best in the profit stage, where SOCBs perform best in the market and sustainability stage. The three different bank types' TGR performance is comparable to their efficiency value performance. (3) SOCBs lead in ESG investment and have the best ESG performance due to their distinct state-owned background. With their ongoing dedication to profit maximization and disregard for social responsibility and sustainable development, JSCBs have the worst ESG performance. (4) Policy recommendations are made based on the study's findings for commercial banks, stakeholders, and regulators to support ESG investment and to bring about long-term sustainable development. Finally, as ESG develops in China, future research can consider longer time scales and larger perspectives to investigate the sustainability efficiency of commercial banks themselves, as well as their role in the local economy and industrial transformation.


The effect of dispersed Petrobaltic oil droplet size on photosynthetically active radiation in marine environment.
Oil pollution in seawater, primarily visible on sea surface, becomes dispersed as an effect of wave mixing as well as chemical dispersant treatment, and forms spherical oil droplets. In this study, we examined the influence of oil droplet size of highly dispersed Petrobaltic crude on the underwater visible light flux and the inherent optical properties (IOPs) of seawater, including absorption, scattering, backscattering and attenuation coefficients. On the basis of measured data and Mie theory, we calculated the IOPs of dispersed Petrobaltic crude oil in constant concentration, but different log-normal size distributions. We also performed a radiative transfer analysis, in order to evaluate the influence on the downwelling irradiance Ed, remote sensing reflectance Rrs and diffuse reflectance R, using in situ data from the Baltic Sea. We found that during dispersion, there occurs a boundary size distribution characterized by a peak diameter d0 = 0.3 μm causing a maximum E d increase of 40% within 0.5-m depth, and the maximum Ed decrease of 100% at depths below 5 m. Moreover, we showed that the impact of size distribution on the "blue to green" ratios of Rrs and R varies from 24% increase to 27% decrease at the same crude oil concentration.