Incidence of gastrointestinal infections among U.S. active component service members stationed in the U.S. compared to U.S. civilians, 2012-2014.
Gastrointestinal (GI) infections in the U.S. Armed Forces have consistently been among the most frequent disease and non-battle injury diagnoses. A retrospective analysis of surveillance data categorized as GI infections among active component service members during 2012-2014 was performed. During the study period, 99% of inpatient and outpatient GI encounters were reported as nonspecific GI infection (13,331 cases per 100,000 people), leaving only a small percentage of cases attributed to specific causes. The five most common organisms associated with GI infections were Campylobacter (10.30 per 100,000 people), nontyphoidal Salmonella (7.43), Giardia (3.15), Shigella (2.11), and norovirus (1.25). The civilian population incidence rates of foodborne diseases during the same time period are significantly greater than incidence rates within the U.S. active component for all select bacterial and parasitic pathogens, except Campylobacter. Nonspecific gastroenteritis incidence increased during winter months, which is similar to the seasonal pattern for viruses such as norovirus. The preponderance of nonspecific infections highlights the need for increased testing and a more in-depth review of the impact of GI infections on operational effectiveness within the U.S.


The Hollow Fibre Assay as a model for in vivo pharmacodynamics of fluoropyrimidines in colon cancer cells.
The Hollow Fibre Assay (HFA) is usually applied as an early in vivo model for anti-cancer drug screening, but is potentially an excellent model for short-term in vivo pharmacodynamic studies. We used the model to study the in vivo role of thymidine phosphorylase/platelet-derived endothelial cell growth factor (TP/PD-ECGF) in the cytotoxicity and pharmacodynamics of TAS-102 in colon cancer cells. TAS-102 is a new oral drug formulation, which is composed of trifluorothymidine (TFT) and thymidine phosphorylase inhibitor (TPI), which prevents TFT degradation. We compared the activity with Xeloda (capecitabine), which is activated by TP into 5FU. Hollow fibres filled with human Colo320 or Colo320TP1 colorectal cancer cells with deficient or high TP expression, respectively, were implanted subcutaneously (s.c.) at both flanks of BALB/c mice. The mice were treated orally over 5 days with TAS-102, TFT alone, 5'DFUR+/-TPI or capecitabine at their maximum tolerated dose (MTD). The cells were retrieved from the fibres and assayed for growth (MTT assay), cell cycle distribution (flow cytometry) and apoptosis induction (FragEL method). TAS-102 induced considerable growth inhibition (50%, P<0.01) to both cell lines, which was completely abolished in the absence of TPI. Capecitabine and its metabolite 5'DFUR reduced proliferation of Colo320TP1 cells in the fibres significantly (down to 25-40%), but much less in Colo320 cells, whereas addition of TPI reduced the effect of 5'DFUR, although not completely. These differences in cytotoxic effects were reflected in the pharmacodynamic evaluation. TAS-102 induced a G2M-phase arrest (from 25 to 40%) and apoptosis (>8-fold), which was more pronounced in Colo320 than in Colo320TP1. Again, omission of TPI neutralised the effect of TAS-102. Similarly, 5'DFUR and capecitabine induced a significant G2M-phase arrest (up to 45%) in the Colo320TP1 cell line, but less pronounced in the parental Colo320. Addition of TPI to 5'DFUR reduced this effect to control levels. Also induction of apoptosis was reduced in the presence of TPI. The data demonstrated that the HFA is excellently suited for studying short-term pharmacodynamic effects of fluoropyrimidines in vivo. TAS-102 is only effective in inducing cytotoxicity when systemic TPI is present, but acts against both low and high TP expressing colon cancer cells, while 5'DFUR needs cellular TP to exert significant activity.


Cloning, expression and purification of arylsulfate sulfotransferase from Eubacterium A-44.
A gene (astA) encoding arylsulfate sulfotransferase (ASST), which transfers a sulfate group from phenolic sulfate esters to phenolic acceptors, was cloned from a Eubacterium A-44 genomic library. The probe (1.5 kb fragment) for the astA gene was prepared from the PCR product of the primers produced using two internal amino acid sequences of ASST, which had been purified from Eubacterium A-44. The astA gene was cloned into the pKF3 vector. Its sequence revealed a 1863 bp open reading frame (ORF) encoding a protein containing 620 amino acids with a secretary signal peptide, and showed 91% homology (identity) to Eubacterium rectale IIIH previously reported. The cloned astA gene was expressed under the T7 promoter of the expression vectors, pET-39b(+) and pET-26b(+), in Escherichia coli BL21 (DE3), and the expressed ASSTs were purified using His Bind column chromatography. The specific activities of the purified ASSTs were 25.6 micromol/min/mg and 37.1 micromol/min/mg, respectively.


[Novelties 2016 in pediatrics].
Nutrition is central in pediatric care : essential for growth and development, it plays also a role in the prevention of many diseases.Even if breastfeeding is highly recommended, its implementation may be difficult in particular for premature and ill newborns. The creation of a specific unit for breastfeeding support in neonatology allows to help mothers willing to nurse and to improve the rate of breastfeeding for these vulnerable infants.Eating disorders represent an important challenge for patient care. Early detection and rapid management of anorexia is essential for the prognosis. This article describes the challenges and the practical process underlying the development of a practical guideline to manage children and adolescents hospitalized for anorexia.


Duration of Tenofovir Use and Diabetes Mellitus Predict Microalbuminuria among Well-controlled Human Immunodeficiency Virus-infected Patients Attending a Tertiary Clinic in Gaborone, Botswana.
The study aimed to determine the prevalence and associated factors of microalbuminuria among patients infected with human immunodeficiency virus (HIV). A cross-sectional study was conducted at the Infectious Disease Control Center of Princess Marina Hospital, a Tertiary Clinic in Gaborone, Botswana. The risk factors of microalbuminuria were determined by comparing the sociodemographic and clinical characteristics of patients with the presence of microalbuminuria or normoalbuminuria. In total, 297 randomly selected HIV-infected patients were included in the analysis. The mean age of the study participants was 48.6 years, with the majority of patients (60.9%) being females. The study participants were largely well-controlled both immunologically and virologically, with 283/297 (95.3%) and 280/297 (94.3%), having CD4 counts of more than 200 cells/mm3 and undetected viral load (<400 copies/mL), respectively. The prevalence of microalbuminuria was found to be 46.5%. Microalbuminuria was associated with the duration of exposure to a regimen containing tenofovir [P <0.001, odds ratio = 1.137, 95% confidence interval (CI) = 1.073-1.205] and a history of diabetes mellitus (P = 0.044, odds ratio = 9.260, 95% CI = 1.058-81.06). Sociodemographic characteristics and other clinical factors were not associated with microalbuminuria. There is a need to carry out prospective studies among HIV- infected patients with microalbuminuria to determine the short- and long-term cardiovascular morbidity and mortality outcomes.


A functionalized polyoxometalate solid for selective oxidation of styrene to benzaldehyde.
The reaction of [Na(12)(H(2)O)(38)][WZn{M(H(2)O)}(2)(ZnW(9)O(34))(2)].3H(2)O (M = Mn, Co) and Co(NO(3))(2).6H(2)O in water at 80 degrees C afforded red crystals of [Co(H(2)O)(6)](2){[Co(H(2)O)(4)](2)[Co(H(2)O)(5)](2)WZn[Co(H(2)O)](2)(ZnW(9)O(34))(2)}.10H(2)O (1), which has been characterized by TGA, IR, PXRD, element analysis and single crystal X-ray diffraction. The polyanion [WZn{Co(H(2)O)}(2)(ZnW(9)O(34))(2)](12-) in is double-linked by cobalt(ii) cations to extend into a 1D anionic polymeric chain of {[Co(H(2)O)(4)](2)[Co(H(2)O)(5)](2)WZn[Co(H(2)O)](2)(ZnW(9)O(34))(2)}(4-) with partial free cobalt cations. The redox active cobalt(ii) sites made compound an excellent catalyst for the oxidation of styrene with high styrene conversion (up to 96%) and high benzaldehyde selectivity (up to 99%).


Patients harboring ALK rearrangement adenocarcinoma after acquired resistance to crizotinib and transformation to small-cell lung cancer: a case report.
Anaplastic lymphoma kinase (ALK) rearrangement responds to ALK tyrosine kinase inhibitors (TKIs) in lung cancer. Many cases ultimately acquire resistance to crizotinib. Resistance, including ALK-dominant or ALK non-dominant, mechanisms have been described. Transformation to small-cell lung cancer is rare. Herein, we report a 49-year-old man diagnosed with adenocarcinoma, who was negative for EGFR and ALK genes as detected by reverse transcription polymerase chain reaction, and was treated with crizotinib. A new biopsy showed a small-cell lung cancer after disease progression. Then, next-generation sequencing (NGS) was carried out and detected a TP53 gene mutation, an ALK rearrangement, and no loss of the retinoblastoma gene (RB). Although a regimen for small-cell lung cancer may be one treatment option, a heterogeneous tumor may exist at the time of diagnosis and manifest during the course of disease.


Identification of an anti-inflammatory principle from the stem bark of Millettia versicolor.
The dichloromethane-soluble fraction of the methanol extract of the stem bark of Millettia versicolor Welw. (Leguminosae) has been shown to possess anti-inflammatory activity. The chromatographic fractionation and subsequent analysis of the spectroscopic data of this extract led to the isolation and identification of 2-acetyl-7-methoxynaphtho[2,3- b]furan-4,9-quinone (1) along with two known quinones. Pharmacological data demonstrate that compound 1 has relevant anti-inflammatory properties whereas the other two isolated compounds do not.


Complete mitochondrial genomes confirm the generic placement of the plateau vole, Neodon fuscus.
The plateau vole, Neodon fuscus is endemic to China and is distributed mainly in Qinghai Province. It is of public health interest, as it is, a potential reservoir of Toxoplasma gondii and the intermediate host of Echinococcus multilocularis However, genetic data of this species are lacking, and its name and taxonomy are still a controversy. In the present study, we determined the nucleotide sequence of the entire mitochondrial (mt) genome of N. fuscus and analyzed its evolutionary relationship. The mitogenome was 16328 bp in length and contained 13 protein-coding genes, 22 genes for transfer RNAs (tRNA), two ribosomal RNA genes and two major noncoding regions (OL region and D-loop region). Most genes were located on the heavy strand. All tRNA genes had typical cloverleaf structures except for tRNASer (GCU) The mt genome of N. fuscus was rich in A+T (58.45%). Maximum likelihood (ML) and Bayesian methods yielded phylogenetic trees from 33 mt genomes of Arvicolinae, in which N. fuscus formed a sister group with Neodon irene and Neodon sikimensis to the exclusion of species of Microtus and other members of the Arvicolinae. Further phylogenetic analyses (ML only) based on the cytb gene sequences also demonstrated that N. fuscus had a close relationship with N. irene The complete mitochondrial genome was successfully assembled and annotated, providing the necessary information for the phylogenetic analyses. Although the name Lasiopodomys fuscus was used in the book 'Wilson & Reeder's Mammal Species of the World', we have confirmed here that its appropriate name is N. fuscus through an analysis of the evolutionary relationships.


In Situ Transmission Electron Microscopy Study of Bubble Behavior Near the Surface of Ice Crystals by Using a Liquid Cell With a Peltier Cooling Holder.
Liquid cell transmission electron microscopy (LC-TEM) is a unique technique that permits in situ observations of various phenomena in liquids with high spatial and temporal resolutions. One difficulty with this technique is the control of the environmental conditions in the observation area. Control of the temperature ranging from room temperature to minus several tens of degrees Celsius, is desirable for controlling the supersaturation in various materials and for observing crystallization more easily. We have developed a cooling transmission electron microscopy specimen holder that uses Peltier devices, and we have combined it with a liquid cell to realize accurate temperature control in LC-TEM. We evaluated this system by using water as a specimen. Motionless bubbles, shown to be voids containing pressurized gas, formed in the specimen sometime after the temperature had reached -12°C. An electron diffraction pattern showed that the specimen turned into ice Ih after the formation of these bubbles, confirming that our system works properly and can induce crystallization. In addition, we analyzed the behavior of bubbles formed in the ice Ih, and we discussed the formation of these bubbles and their internal pressure.


Evaluation of Death Cases Connected to Electric Current in Aydin Province, Western Turkey.
In this article, the authors discuss electric shock fatalities in Aydın province and compare these findings with the findings of other studies conducted in Turkey and worldwide. Data were gathered from 2001-2013 autopsy reports retrospectively. A total of 34 cases were reviewed in terms of age and gender, scene and time of event, number of lesions and their locations, organ injuries, origin of electricity, and degree of burns. In all cases, electrical death was accidental. Electrical shock fatalities were most common in the 30 to 39 age group. Fourteen cases (41.2%) involved workers: 7 cases (2.6%) were agricultural workers, 4 cases (11.8%) were housewives, 2 (5.9%) were electrical workers, and 7 (20.6%) were unemployed or in other occupations. The authors are addressing this public health problem to minimize the number of electrical deaths.


Stability Analysis of Shear Deformable Inhomogeneous Nanocomposite Cylindrical Shells under Hydrostatic Pressure in Thermal Environment.
In this study, the stability of inhomogeneous nanocomposite cylindrical shells (INCCSs) under hydrostatic pressure in a thermal environment is presented. The effective material properties of the inhomogeneous nanocomposite cylindrical shell are modeled on the basis of the extended mixture rule. Based on the effective material properties, the fundamental relations and stability equations are derived for thermal environments. In this process, the first-order shear deformation theory (FSDT) for the homogeneous orthotropic shell is generalized to the inhomogeneous shell theory. This is accomplished using the modified Donnell-type shell theory. The analytical expressions are obtained for hydrostatic buckling pressure of INCCSs in the framework of FSDT and classical shell theory (CST) by obtaining a solution based on Galerkin's procedure. The numerical examples presented include both comparisons and original results. The last section shows the influences of carbon nanotube (CNT) models, volume fraction, and shell characteristics on the hydrostatic buckling pressure in the thermal environment.


Factors influencing tolerance to the effects of delta9-THC on a conditioned avoidance response.
Male, Fischer strain rats were resistant to the impairing effects of delta9--THC (15-60 mg/kg, IG) on performance of a conditioned pole-climb avoidance response (CAR) after daily subacute pretreatment for 4 or 6 days. A single administration of 20 mg/kg delta9--THC independent of the performance test did not attenuate the subsequent impairment caused by delta9--THC when tested 1-6 days later; however, administration 2 hr before each test attenuated the effect on subsequent tests given at intervals of 1-5 weeks. Similarly, subacute treatment with 20 mg/kg delta9--THC for 4 days independent of the performance test attenuated the impairment caused by delta9--THC during tests given to separate groups of rats 1 or 6, but not 14 days later. However, when the tests for tolerance were conducted repeatedly in the same rats, the attenuation appeared to persist for intervals up to 5 weeks. The results are discussed in terms of metabolic, functional and compensatory (behavioral) tolerance.


Synthetic receptors for chemical sensors--subnano- and micrometre patterning by imprinting techniques.
Antibody-like selectivities are introduced into man-made polymeric systems by means of molecular imprinting. On the molecular scale, organic contaminants in water were analysed by 10 MHz QCM sensors coated both with affinity layers and with selective imprinted polymers. Affinity layers, polystyrene/silicone, yield sensor effects for aromatic hydrocarbons according to, e.g., molecular weight and solubilities, a prediction by molecular modelling is proposed. Imprinted layers, however, recognise molecular shapes: the lean toluene is favoured by factor of six to the more bulky o-xylene; even the three xylenes can be distinguished from each other. On the micrometre scale, erythrocytes of different blood groups are differentiated, although their geometrical shape is identical. In this case, the recognition is accomplished by a predefined hydrogen bonding network between excess OH groups of the polyurethane layer and the sugar molecules on the cell surface defining the blood group.


A follow-up study of Sydenham's chorea.
Twenty-five patients convalescing from Sydenham's chorea were contrasted by clinical examination, electroencephalograms, and psychometric and psychologic tests to 15 siblings and 20 matched rheumatic fever controls. A group of 10 postchoreic patients who had two or more signs could be identified. Patients in this group had all the signs classified as moderate or severe, performed less well than other choreic subjects on the Bender gestalt test, and had a higher percentage of abnormal electroencephalograms but not a higher incidence of behavioral disorders. This subgroup could not be predicted from a review of neurologic history or from analysis of the acute episode of chorea. Our data would suggest that uncomplicated Sydenham's chorea is not necessarily a benign self-limited affliction of the central nervous system and that some patients are left with definite, albeit minimal, neurologic residua.


Proteomic Modulation in TGF-β-Treated Cholangiocytes Induced by Curcumin Nanoparticles.
Curcumin is a natural polyphenol that exhibits a variety of beneficial effects on health, including anti-inflammatory, antioxidant, and hepato-protective properties. Due to its poor water solubility and membrane permeability, in the present study, we prepared and characterized a water-stable, freely dispersible nanoformulation of curcumin. Although the potential of curcumin nanoformulations in the hepatic field has been studied, there are no investigations on their effect in fibrotic pathological conditions involving cholangiocytes. Exploiting an in vitro model of transforming growth factor-β (TGF-β)-stimulated cholangiocytes, we applied the Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS)-based quantitative proteomic approaches to study the proteome modulation induced by curcumin nanoformulation. Our results confirmed the well-documented anti-inflammatory properties of this nutraceutic, highlighting the induction of programmed cell death as a mechanism to counteract the cellular damages induced by TGF-β. Moreover, curcumin nanoformulation positively influenced the expression of several proteins involved in TGF-β-mediated fibrosis. Given the crucial importance of deregulated cholangiocyte functions during cholangiopathies, our results provide the basis for a better understanding of the mechanisms associated with this pathology and could represent a rationale for the development of more targeted therapies.


Endovascular treatment of late thoracic aortic aneurysms after surgical repair of congenital aortic coarctation in childhood.
In some patients, local surgery-related complications are diagnosed many years after surgery for aortic coarctation. The purposes of this study were: (1) to systematically evaluate asymptomatic adults after Dacron patch repair in childhood, (2) to estimate the formation rate of secondary thoracic aortic aneurysms (TAAs) and (3) to assess outcomes after intravascular treatment for TAAs. This study involved 37 asymptomatic patients (26 female and 11 male) who underwent surgical repair of aortic coarctation in the childhood. After they had reached adolescence, patients with secondary TAAs were referred to endovascular repair. Follow-up studies revealed TAA in seven cases (19%) (including six with the gothic type of the aortic arch) and mild recoarctation in other six (16%). Six of the TAA patients were treated with stentgrafts, but one refused to undergo an endovascular procedure. In three cases, stengrafts covered the left subclavian artery (LSA), in another the graft was implanted distally to the LSA. In two individuals, elective hybrid procedures were performed with surgical bypass to the supraaortic arteries followed by stengraft implantation. All subjects survived the secondary procedures. One patient developed type Ia endoleak after stentgraft implantation that was eventually treated with a debranching procedure. The long-term course of clinically asymptomatic patients after coarctation patch repair is not uncommonly complicated by formation of TAAs (particularly in individuals with the gothic pattern of the aortic arch) that can be treated effectively with stentgrafts. However, in some patients hybrid procedures may be necessary.


[Primary central nervous system lymphoma: pathogenesis and histomorphology].
Lymphoproliferative diseases of the central nervous system are rare, diagnostics and treatment are accordingly challenging. Since the introduction of the 2008 WHO lymphoma classification, primary CNS DLBCL - also covering the associated primary ocular (vitreoretinal) lymphoma - is a separate entity. The special localization is related with a series of newly recognized genetic, genomic and immunologic features directing to the strong interaction between transformed lymphoma cells, neural tissue components and the local immune response. Histological differentiation is frequently disabled by the limited sampling opportunities and requires the application of all available hematopathologic technologies including immunohistochemistry, cytology, liquor serology, flow cytometry, fluorescence in situ hybridization and polymerase chain reaction with sequencing.


Field testing of an enzymatic quorum quencher coating additive to reduce biocorrosion of steel.
Microbial colonization can be detrimental to the integrity of metal surfaces and lead to microbiologically influenced corrosion. Biocorrosion is a serious problem for aquatic and marine industries in the world and severely affects the maritime transportation industry by destroying port infrastructure and increasing fuel usage and the time and cost required for maintenance of transport vessels. Here, we evaluate the potential of a stable quorum quenching lactonase enzyme to reduce biocorrosion in the field. Over the course of 21 months, steel samples coated with lactonase-containing acrylic paint were submerged at two different sites and depths in the Duluth-Superior Harbor (Lake Superior, MN, USA) and benchmarked against controls, including the biological biocide surfactin. In this experiment, the lactonase treatment outperformed the surfactin biocide treatment and significantly reduced the number of corrosion tubercles (37%; P < 0.01) and the corroded surface area (39%; P < 0.01) as compared to the acrylic-coated control coupons. In an attempt to evaluate the effects of signal disruption of surface microbial communities and the reasons for lower corrosion levels, 16S rRNA sequencing was performed and community populations were analyzed. Interestingly, surface communities were similar between all treatments, and only minor changes could be observed. Among these changes, several groups, including sulfate-reducing bacteria (SRB), appeared to correlate with corrosion levels, and more specifically, SRB abundance levels were lower on lactonase-treated steel coupons. We surmise that these minute community changes may have large impacts on corrosion rates. Overall, these results highlight the potential use of stable quorum quenching lactonases as an eco-friendly antifouling coating additive. IMPORTANCE Biocorrosion severely affects the maritime transportation industry by destroying port infrastructure and increasing fuel usage and the time and cost required to maintain transport vessels. Current solutions are partly satisfactory, and the antifouling coating still largely depends on biocide-containing products that are harmful to the environment. The importance of microbial signaling in biofouling and biocorrosion is not elucidated. We here take advantage of a highly stable lactonase that can interfere with N-acyl homoserine lactone-based quorum sensing and remain active in a coating base. The observed results show that an enzyme-containing coating can reduce biocorrosion over 21 months in the field. It also reveals subtle changes in the abundance of surface microbes, including sulfate-reducing bacteria. This work may contribute to pave the way for strategies pertaining to surface microbiome changes to reduce biocorrosion.


Engineering E. coli to synthesize butanol.
Biobutanol is gaining much attention as a potential biofuel due to its superior properties over ethanol. Butanol has been naturally produced via acetone-butanol-ethanol (ABE) fermentation by many Clostridium species, which are not very user-friendly bacteria. Therefore, to improve butanol titers and yield, various butanol synthesis pathways have been engineered in Escherichia coli, a much more robust and convenient host than Clostridium species. This review mainly focuses on the biosynthesis of n-butanol in engineered E. coli with an emphasis on efficient enzymes for butanol production in E. coli, butanol competing pathways, and genome engineering of E. coli for butanol production. In addition, the use of alternate strategies for butanol biosynthesis/enhancement, alternate substrates for the low cost of butanol production, and genetic improvement for butanol tolerance in E. coli have also been discussed.


Necrotizing enterocolitis in an infant with Omenn syndrome.
Omenn syndrome (OS) is a rare disorder within the combined immunodeficiency family that is characterized by a diffuse exudative, erythematous rash, lymphadenopathy, hepatosplenomegaly, alopecia, and failure to thrive. Specific lab findings unique to OS include hypereosinophilia, elevated IgE, excess production of oligoclonal T-cells and near-to-absent B-cells. Much remains elucidated about the underlying genetic cause of OS. Until recently, it was felt that the disease was primarily caused by mutations of the RAG1 or RAG2 genes. The type of mutation of the RAG1 and RAG2 genes in patients with OS affects the degree of functioning variable (diversity) joining [V(D)J] recombination activity, which is critical to the development of lymphoid cell receptor diversity. New work has also shown that thymic tissue in OS patients demonstrates a severe defect in the expression of the autoimmune regulator element. This may contribute to the development of autoreactive T-cells that are felt to be the causative agent of a number of the clinical hallmarks unique to OS. The genetic spectrum of OS was further expanded when a patient with clinical and immunologic features consistent with OS, without RAG mutation, was found to have mutations in both alleles coding for ARTEMIS, a key V(D)J recombination/DNA repair factor. Regardless of the underlying cause, early recognition is critical because patients die at a very young age without bone marrow transplantation. We describe an infant diagnosed with OS post-mortem in which death was directly related to the development of necrotizing enterocolitis.


Simultaneous determination of glipizide and its four hydroxylated metabolites in human urine using LC-MS/MS and its application in urinary phenotype study.
Cytochrome P450 (CYP) 2C9 and CYP2C19 genetic mutant could influence the plasma concentration of glipizide in human subjects, which refers to glipizide safety and adverse effects in clinic practice. A further study to investigate the relationship of the concentrations between glipizide and its metabolites in human with different CYP mutants was valuable. We firstly develop a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of glipizide and its hydroxylated metabolites in human urine. After simple protein precipitation with methanol including 4'-OH-tolbutamide and gliclazide (both are internal standards), the analytes were chromatographed on a reversed-phased column with a mobile phase of 0.1% formic acid in acetonitrile and 0.1% formic acid in water by a gradient elution. The ion transitions of the precursor to the product ion were principally protonated ions [M+H]+ at m/z 446.4→m/z 321.1 for glipizide, m/z 462.2→m/z 321.1 for the four hydroxylated forms of glipizide, m/z 287.2→m/z 188.0 for 4'-OH-tolbutamide, and m/z 324.1→m/z 127.1 for gliclazide. The method was linear over a concentration range of 0.02-20.0ng/mL. The intraday and inter-day variances were less than 9.9%, and accuracy was within ±6.8%. The method was successfully applied to the urinary phenotyping study in volunteers after a single oral administration of 5-mg glipizide tablet, and two new hydroxycyclohexyl metabolites of glipizide (OH-gp), 4-cis-OH-gp and 3-trans-OH-gp, were found in this study.


Functional rehabilitation and brain tumour patients. A review of outcome.
The increasing prevalence of brain tumours and longer duration of survival achieved by recent advances in treatment prompt a critical analysis of the impact of functional rehabilitation on patients with brain tumours. In this review brain tumours and outcome of brain tumour patients are discussed from a rehabilitation perspective, taking into account not only life expectancy but also the direct and indirect causes of functional impairment. Results of functional rehabilitation and factors involved in its effectiveness are presented and analysed to serve as a basis to neurologists involved in the management of patients with brain tumours.


Determination of the monomer-dimer equilibrium of interleukin-8 reveals it is a monomer at physiological concentrations.
Interleukin-8 has been shown by X-ray crystallography and NMR to be a homodimer, suggesting that this is the form which binds to its receptor. Here we measure, for the first time, the monomer-dimer equilibrium of interleukin-8 using analytical ultracentrifugation and titration microcalorimetry and find that it dissociates readily to monomers with an equilibrium dissociation constant of 18 +/- 6 microM at 37 degrees C. The present findings suggest that the monomer is the form which binds to the receptor. Comparison of experimental and structure-based calculated thermodynamics of interleukin-8 dimerization argues for limited subunit conformational changes upon dissociation to monomer.


Identification of key biomarkers based on the proliferation of secondary hyperparathyroidism by bioinformatics analysis and machine learning.
Secondary hyperparathyroidism (SHPT) is a frequent complication of chronic kidney disease (CKD) associated with morbidity and mortality. This study aims to identify potential biomarkers that may be used to predict the progression of SHPT and to elucidate the molecular mechanisms of SHPT pathogenesis at the transcriptome level. We analyzed differentially expressed genes (DEGs) between diffuse and nodular parathyroid hyperplasia of SHPT patients from the GSE75886 dataset, and then verified DEG levels with the GSE83421 data file of primary hyperparathyroidism (PHPT) patients. Candidate gene sets were selected by machine learning screens of differential genes and immune cell infiltration was explored with the CIBERSORT algorithm. RcisTarget was used to predict transcription factors, and Cytoscape was used to construct a lncRNA-miRNA-mRNA network to identify possible molecular mechanisms. Immunohistochemistry (IHC) staining and quantitative real-time polymerase chain reaction (qRT-PCR) were used to verify the expression of screened genes in parathyroid tissues of SHPT patients and animal models. A total of 614 DEGs in GSE75886 were obtained as candidate gene sets for further analysis. Five key genes (USP12, CIDEA, PCOLCE2, CAPZA1, and ACCN2) had significant expression differences between groups and were screened with the best ranking in the machine learning process. These genes were shown to be closely related to immune cell infiltration levels and play important roles in the immune microenvironment. Transcription factor ZBTB6 was identified as the master regulator, alongside multiple other transcription factors. Combined with qPCR and IHC assay of hyperplastic parathyroid tissues from SHPT patients and rats confirm differential expression of USP12, CIDEA, PCOLCE2, CAPZA1, and ACCN2, suggesting that they may play important roles in the proliferation and progression of SHPT. USP12, CIDEA, PCOLCE2, CAPZA1, and ACCN2 have great potential both as biomarkers and as therapeutic targets in the proliferation of SHPT. These findings suggest novel potential targets and future directions for SHPT research.


Body packing and its radiologic manifestations: a review article.
Body packing is described as using the abdominal or pelvic cavity for concealing illegal drugs. Leakage from the packets may cause catastrophic effects on smugglers and medical history is not reliable in these patients. Moreover, new sophisticated smuggling techniques make it imperative that radiologists and emergency physicians understand and familiarize themselves with the different radiological manifestations of ingested drug packets. Currently, there is no gold standard for imaging patients suspected of body packing; nevertheless, computed tomography (CT) seems to be the best modality for packet detection and unenhanced CT without bowel preparation is a reliable technique for detection of ingested packets. On abdominal radiography, packets may be visualized as oval or round radiopaque foreign bodies surrounded by a gas halo. In the literature, sensitivity of abdominal radiography is reported from 74% to 100%. Visualization of the drug packets may be strikingly hampered by administration of oral or intravenous contrast medium in abdomino-pelvic CT; hence, contrast-enhanced CT does not seem to be a suitable modality for searching the ingested packets in suspicious smugglers.


Prevalence of functional haplotypes of the peptidylarginine deiminase citrullinating enzyme gene in patients with rheumatoid arthritis: no influence of the presence of anti-citrullinated peptide antibodies.
Citrullinated peptides produced by enzymatic deimination of arginine residues in proteins by peptidylarginine deiminases are of particular interest in the pathogenesis of rheumatoid arthritis (RA). One type of citrullinated protein - the cyclic citrullinated peptide - is the target of the anti-cyclic citrullinated peptide antibody, the most sensitive and specific autoantibody in RA. The peptidylarginine deiminase type 4 (PADI4) gene, which codes one of the PADI enzyme isotypes, has genetic variants that confer susceptibility to RA in Asian, but not in European populations. Genetic associations were examined in 214 Hungarian RA patients characterized for the presence of anti-CCP and rheumatoid factor. The patients were characterized for the existing haplotypes of the PADI4 gene (defined by the combinations of 4 exonic padi4_89: 163G/A, padi4_90: 245T/C, padi4_92: 335C/G, padi4_104: 349T/C and 2 intronic padi4_94: 17535226C/T and padi4_102: 17546809C/T variants) by the PCR-RFLP method. None of the PADI4 haplotypes was accumulated in RA patients. One new finding was that we also did not detect the accumulation of any haplotypes either in the anti-CCP or in the RF-positive subgroups of patients. The data presented here show that none of the naturally occurring haplotypes of the PADI4 gene conferred susceptibility to RA in an average group of Hungarian patients; this is in agreement with findings for other European populations. In addition, none of the functional PADI4 haplotypes were associated with the pathologic immune response, which was evidenced by the absence of accumulation of anti-CCP-positive subjects in the specific PADI4 haplotypes.


Investigation of the effects of 50 Hz magnetic fields on platelet aggregation using a modified aggregometer.
Electromagnetic fields have various effects on intracellular calcium levels, free oxygen radicals and various enzymes. The platelet activation pathway involves an increase in intracellular calcium levels and protein kinase C activation; and free oxygen radicals play a mediating role in this pathway. This study investigated whether 1 mT and 6 mT, 50 Hz magnetic fields had any effects on platelet aggregation. Blood from healthy volunteers was anticoagulated with either citrate or heparin. Each sample was divided in half and assigned to exposure and control groups. Platelet rich plasma samples in the exposure group were exposed to a 1 mT or a 6 mT, 50 Hz magnetic field for 1.5 or 1 h, respectively. The samples from both exposure and control groups were simultaneously evaluated using a modified optical aggregometer. Adenosine-diphosphate, collagen, and epinephrine were used as inducing agents. The slopes of the aggregation curve, the maximum values and the areas under the curves were recorded and compared. A significant effect was observed only in the 1 mT-citrate group. It was found that magnetic field exposure significantly increased the maximum values and slopes of the collagen-induced aggregations. It was found that magnetic field exposure has an activating effect on platelet aggregation.


Up-regulation of muscle uncoupling protein 3 gene expression by calcium channel blocker, benidipine hydrochloride in rats.
To examine whether benidipine hydrochloride, one of the calcium channel blockers, up-regulate uncoupling protein 3 (UCP3) expression in two skeletal muscles (gastrocnemius and soleus) in rats. Wistar rats were treated orally with benidipine hydrochloride at 4 mg/kg for 7 days. Blood pressure was measured after 4 days. At the end of experiments, the rats were weighed, and brown adipose tissue (BAT) and skeletal muscles (gastrocnemius and soleus muscles) were removed. The mRNA levels of uncoupling protein 1 (UCP1) and UCP3 were measured using the real-time quantitative reverse transcription-polymerase chain reaction method. Benidipine reduced body weight and also had a hypotensive effect. In rats treated with benidipine, UCP1 mRNA levels were significantly increased 1.4-fold in BAT, and UCP3 mRNA levels in BAT and gastrocnemius muscle were significantly increased 1.7 and 3.0-fold, respectively, compared with the control rats. There was no difference in UCP3 mRNA levels in soleus muscle between the two groups. We concluded that benidipine up-regulates not only UCP1 gene expression in BAT but also UCP3 gene expression in BAT and gastrocnemius muscle, which may contribute to thermogenesis in rats.


Patient-specific blood pressure correction technique for arterial stiffness: evaluation in a cohort on anti-angiogenic medication.
Arterial pulse wave velocity (PWV) depends on blood pressure (BP). Correction of PWV for BP is commonly performed using a statistical approach, requiring a patient cohort. We recently developed a mechanistic, model-predictive approach to assess BP-independent changes in carotid PWV (cPWV) at the level of the individual. The goal of the present study is to compare our novel technique to conventional statistical correction, in the context of anti-cancer therapy using anti-angiogenic drugs (AADs). AADs frequently lead to a PWV increase, but also to hypertension, underlining the need for BP correction of PWV measurements. We obtained carotid artery systolic and diastolic cross-sectional areas (echotracking) and corresponding BPs (tonometry) in 48 patients before starting AAD treatment (sorafenib/sunitinib), and at four follow-up visits spaced 2 weeks apart. For each patient, we derived cPWV and a baseline single-exponential BP cross-sectional area curve. Based on these baseline curves and follow-up BPs, we predicted cPWV at follow-up due to BP. By comparing predicted and measured cPWVs at follow-up, we assessed the BP-independent cPWV increase. In the same way, we assessed whether diastolic cross-sectional area (Ad) changed beyond the BP-induced amount. The AAD-induced BP-independent increase in cPWV was 0.43(0.09,0.77) m s-1 (mean (95%CI), P=0.014, mechanistic approach) and 0.48(0.14,0.82) m s-1 (P=0.006, statistical approach). Ad increased with 1.92(0.93,2.92) mm2 (P<0.001) and 2.14(1.06,3.23) mm2 (P<0.001), respectively. In conclusion, the present study demonstrates the feasibility and potential of our mechanistic, model-predictive approach to quantify BP-independent effects on arterial stiffness at the level of the individual, in a clinically relevant setting of AAD therapy.


[Comparison between clinical information capability of increased alpha-fetoprotein values in amniotic fluid and in maternal serum (author's transl)].
Tests were applied to 118 out of 1,534 patients in a programme for alpha-fetoprotein analysis to compare values recorded from amniotic fluid with those obtained from maternal serum. The tests were part of a prenatal diagnosis scheme by which to rule genetic defects. Six clearly increased alpha-fetoprotein values which were indicators to malformations and admixture of fetal blood were recorded from amniotic fluid by means of Mancini's technique. No falsely negative findings were recordable. Only two values were increased in maternal serum, among them one falsely positive result with no malformation at all. The conclusion drawn from the above findings is that in the context of prenatal diagnosis of malformation the most reliable values are obtainable from determination of alpha-fetoprotein in amniotic fluid. Maternal serum tests may be recommended for screening for neural tube defects, with due reference to be made to upper limit values.


Psychological distress among students from five universities in Sri Lanka.
To determine the proportion of university students that are psychologically distressed when compared to an age and sex matched population sample and to describe the factors that may contribute to their distress. A cross-sectional comparison study. The general health questionnaire (GHQ 30), previously validated in Sinhala, was administered as a screening test to random samples of undergraduates in 5 universities. Age and sex matched controls from the respective communities were also administered the screening test. The undergraduates also filled in a pre-tested questionnaire with personal details. Chi-square tests were used to determine statistical significance between groups. Among the undergraduates, 104 (39.8%) had scores for psychological distress whereas only 67 (25.7%) from the community sample had scores for similar distress. This difference was significant (p = 0.0007). A significantly greater proportion (p = 0.009) of those entering from rural schools were psychologically distressed than those from suburban and urban schools, and a greater proportion living in rented rooms and hostels were (p = 0.001) distressed than those travelling from their homes. The psychological distress among undergraduates was significantly greater than among the general population. More students who enter from rural schools seem to be distressed than those who enter from suburban and urban schools.


[The interactive lecture. A simple form of student-activating learning].
Activation of students in lectures to enhance learning by means of questions to be answered in buzz groups has been described in pedagogic handbooks and articles. We tried the concept in three lectures in biochemistry in order to evaluate use of time, training requirements of the lecturer, and method acceptance by students. The experiment was carried out with a group of 87 medical students from a 4th semester course in biochemistry. Evaluation was made by direct observation and analysis of quantitative and qualitative data from a student questionnaire. Buzz groups and questions took less time than anticipated and not more than ten minutes of the lecture time. The lecturer needed supervision from a colleague to function well. Acceptance of the procedure was high among the students. Qualitative data indicate that students used more time for self-studies and moved towards deep learning. We conclude that interactive lecture could be implemented without major problems in lecture based educational programmes and that it is useful for the learning of the students.


Robotic surgery in Gynecology: the present and the future.
Since its introduction, laparoscopic surgery has been often preferred over open surgery in obstetrics and gynecology due to its advantages, such as less bleeding, lower incidence of adhesions, reduced postoperative pain, short hospital stay, and quick return to daily life. However, in the case of complex surgeries, laparoscopy presented some limitations. Nonetheless, since the 1980s, medical robots have been introduced to overcome the technical limitations of laparoscopy and start a new age for minimally invasive surgery. In this review, we explore the indications and advantages and disadvantages of robotic surgery in the field of gynecology, and try to assess the recent trend of robotic surgery.


Low-level laser effects on simulated orthodontic tension side periodontal ligament cells.
The purpose of this study was to analyze proliferation, inflammation, and osteogenic effects on periodontal ligament (PDL) cells after low-level laser therapy (LLLT) under simulated orthodontic tension conditions. Low-level lasers affect fibroblast proliferation and collagen synthesis and reduce inflammation. Few studies have focused on the LLLT changes in the PDL caused by moving teeth. A human PDL cell line was cultured in a -100 kPa tension incubator. The PDL cells were treated with a 670 nm low-level diode laser, output power of 500 mW (continuous wave modus) for 2.5 or 5 sec, spot area 0.25 cm(2), corresponding to 1.25 and 2.5 J at an energy density of 5 or 10 J/cm(2), respectively. PDL cell viability was assayed by detecting the ability of the cells to cleave tetrazolium salt to formazan dye. Inflammation and osteogenic markers were analyzed by Western blot analysis. PDL cell viablity increased in the experimental group, based on the ability of the cells to cleave tetrazolium salt at day 7 (p<0.05). The experimental group showed no difference in PDL cellular morphology compared with the control group. The inflammation markers inducible NO synthase (iNOS), cyclooxygenase (COX)-2 and interleukin (IL)-1 showed stronger expression in 5 and 10 J/cm(2) therapy at days 1 and 5, but decreased in expression at day 7. The osteogenic marker osteocalcin (OC) expression level was significantly higher at day 7 (p<0.05) than in the control cells. LLLT significantly increased PDL cell proliferation, decreased PDL cell inflammation, and increased PDL OC activity under the tension conditions used in this study.


Note: Design and test of a compact flexure z-stage for atomic force microscopy.
We describe the design and test of a flexure z-stage with 12.5 mm height and 4 microm travel to be coupled with a commercial xy stage. The geometrical model was simulated by means of finite element calculations which have provided an accurate description of the stage dynamics also taking into account the effect of a load to get a resonance frequency of 8 kHz with a 10 g load. The tests of the complete xyz stage were performed in intermittent-contact mode on a sample having periodic features (1.6 microm period, 100 nm height) and with additional loads to increase the mass up to 20 g. The results show that for a 10 g load the surface profiles are well reproduced up to 60 microm/s while with a 20 g sample the speed is reduced to 40 microm/s.


Development of nanostructure in resistant starch type III during thermal treatments and cycling.
The effect of recrystallization temperature on the lamellar structure of RSIII samples was studied using XRD and SAXS. The polymorph type could be manipulated in a controlled manner, independently of the plant source. In RSIII from corn starch and from high-amylose corn starch, retrogradation at a low temperature led to the formation of polymorph B with lamellas arranged in long-range periodicity, whereas retrogradation at a high temperature led to the formation of polymorphs A and V with no defined periodicity. The retrogradation temperature of wheat starch did not have a major effect on its nanostructure. For both polymorphs, the enzymatic degradation decreased as the degree of order within the crystal increased.


Oxindole-3-spiropyrrolidines and -piperidines. Synthesis and local anesthetic activity.
The synthesis and local anesthetic properties of five 1-dealkyloxindole-3-spiropyrrolidines and six 1-dealkyloxindole-3-spiropiperidines are described. The compounds studied include members of all five possible positional isomers of the two classes of spirooxindoles; all showed local anesthetic activity by the rat sciatic nerve block method. The coincidence of the least variability in the relative positions of basic nitrogen, amide carbonyl, and aromatic ring (compounds 1 and 6) with lowest normalized toxicity is noteworthy.


An Overview of Angle Deviations of Fiber-Reinforced Polymer Composite Angular Laminates.
After manufacturing, fiber-reinforced polymer composite laminates may have residual stresses, resulting in warpage in flat structures and angle changes in angular sections. These shape distortions may cause fitting mismatch problems under high-level assembly, and extra efforts to fix these problems may be needed. The present paper only makes an overview of the angle deviation of angular composite laminates made of either thermoset matrix with autoclave curing or thermoplastic matrix with thermoforming. Depending on the positive or negative angle deviation, spring-back or spring-in behavior is observed. There are many parameters, including intrinsic and extrinsic parameters, that could affect the angle deviation. In the first part of this review paper, experimental results concerning the effects of the part angle, part thickness, lay-up sequence, corner angle, flange size, tool material, tool surface, and cure cycle are summarized. Spring-in angles are generally obtained in this part. In the second part, several prediction methods, such as simple equations and finite element methods, are compared to indicate the considered parameters. Some have good agreement and some have larger errors. The crucial differences may be dependent on the micromechanical theories and the input properties of the composite and the constituents.


Fluorescent Poly(glycerol-co-sebacate) Acrylate Nanoparticles for Stem Cell Labeling and Longitudinal Tracking.
The stable presence of fluorophores within the biocompatible and biodegradable elastomer poly(glycerol-co-sebacate) acrylate (PGSA) is critical for monitoring the transplantation, performance, and degradation of the polymers in vivo. However, current methods such as physically entrapping the fluorophores in the polymer matrix or providing a fluorescent coating suffer from rapid leakage of fluorophores. Covalent conjugation of fluorophores with the polymers and the subsequent core-cross-linking are proposed here to address this challenge. Taking rhodamine as the model dye and PGSA nanoparticles (NPs) as the model platform, we successfully showed that the synthesized rhodamine-conjugated PGSA (PGSAR) NPs only released less than 30% rhodamine at day 28, whereas complete release of dye occurred for rhodamine-encapsulated PGSA (PGSA-p-R) NPs at day 7 and 57.49% rhodamine was released out for the un-cross-linked PGSAR NPs at day 28. More excitingly, PGSAR NPs showed a strong quantum yield enhancement (26.24-fold) of the fluorophores, which was due to the hydrophobic environment within PGSAR NPs and the restricted rotation of (6-diethylamino-3H-xanthen-3-ylidene) diethyl group in rhodamine after the conjugation and core-cross-linking. The stable presence of dye in the NPs and enhanced fluorescence allowed a longitudinal tracking of stem cells both in vitro and in vivo for at least 28 days.


Social determinants of health and dental caries in Brazil: a systematic review of the literature between 1999 and 2010.
To review epidemiological studies conducted in Brazil that investigated the distribution of dental caries according to socioeconomic status and demographic characteristics. The systematic review included articles published between 1999 and 2010 available in six bibliographic sources, without any other restriction. We analyzed the bibliometric and methodological characteristics of the studies, and the direction and statistical significance of associations tested. Of the 1,128 references identified, 67 were incorporated into this study. There was a higher percentage of publications in the last two years and most of the studies were conducted in the South and Southeast of the country with a young population. The cross-sectional design, using a complex sampling procedure, was the most commonly adopted. The DMFT and dmft indexes were the most commonly used to measure dental caries, while sex/gender, income, education, race/skin color and type of school were the most common socioeconomic exposures. Most studies identified a high rates of dental caries among the poorest, least educated, black and brown and female individuals. A more detailed methodological and theoretically sound study of the relationship between dental caries and socioeconomic conditions is needed.


Urinary excretion of benzo[a]pyrene metabolites following intravenous, oral, and cutaneous benzo[a]pyrene administration.
The effect of the administration route, dose, and sampling time on the total urinary excretion of four major benzo[a]pyrene (BaP) metabolites, 3-hydroxyBaP (3-OHBaP), 9-hydroxyBaP 9-hydroxyBaP (9-OHBaP), trans-4,5-dihydrodiolBaP (4,5-diolBaP), and trans-9,10-dihydrodiolBaP (9,10-diolBaP), was studied in male Sprague-Dawley rats exposed to a single intravenous, oral, and cutaneous dose of 2, 6, 20, and 60 mumol BaP/kg. Urine samples were collected at 24-h intervals following treatment. Over the 0-72 h period and for a given dose, amounts of BaP metabolites were 3-OHBaP > 4,5-diolBaP > > 9-OHBaP following intravenous and oral dosing, and 3-OHBaP > > 9-OHBaP > or = 4,5-diolBaP after cutaneous treatment. 9,10-diolBaP was barely detected. On the other hand, amounts of 3-OHBaP and 4,5-diolBaP excreted in urine over the 0-72 h period and for a given dose appeared in the following order: intravenous approximately oral > or = cutaneous. Amounts of 9-OHBaP excreted varied as follows: oral > or = cutaneous > intravenous. For all routes of administration, excretion of 4,5-diolBaP was almost complete over the 0-24 h period in contrast with 3-OHBaP and 9-OHBaP. Peak excretion of 3-OHBaP and 9-OHBaP was reached in the 0-24 h period following intravenous and oral treatment and in the 24-48 h period following cutaneous application. Overall, for a given administration route and dose, there were variations in the time profiles between metabolites. In general, there was nonetheless a good correlation between the BaP dose and urinary excretion of 3-OHBaP, 9-OHBaP, and 4,5-diolBaP. Furthermore, total urinary excretion of a specific metabolite, its time profile, and the relative proportion of the metabolites studied depended on the administration route. Data also suggest that a measure of the concentration ratio of the different metabolites could reflect the time and main route of exposure.


Enterolactone induces apoptosis in human prostate carcinoma LNCaP cells via a mitochondrial-mediated, caspase-dependent pathway.
The mammalian lignan enterolactone is a major metabolite of plant-based lignans that has been shown to inhibit the growth and development of prostate cancer. However, little is known about the mechanistic basis for its anticancer activity. In this study, we report that enterolactone selectively suppresses the growth of LNCaP prostate cancer cells by triggering apoptosis. Mechanistic studies showed that enterolactone-induced apoptosis was characterized by a dose-dependent loss of mitochondrial membrane potential, release of cytochrome c and cleavage of procaspase-3 and poly(ADP-ribose)-polymerase (PARP). Caspase dependence was indicated by the ability of the pan-caspase inhibitor z-VAD-fmk to attenuate enterolactone-mediated apoptosis. Mechanistic studies suggested roles for Akt, GSK-3beta, MDM2, and p53 in enterolactone-dependent apoptosis. Our findings encourage further studies of enterolactone as a promising chemopreventive agent against prostate cancer.


Efficient Removal of Organic Pollutants by Metal-organic Framework Derived Co/C Yolk-Shell Nanoreactors: Size-Exclusion and Confinement Effect.
Selective removal of organic pollutants from surface water with high efficiency is crucial in water purification. Here, yolk-shell Co/C nanoreactors (YSCCNs) are facilely synthesized via pyrolysis of controllably etched ZIF-67 by tannic acid, and their degradation performance on multiple pollutants is demonstrated. To present the structure-performance relationship between the designed nanocatalyst and the selective removal of organic pollutants, bisphenol A (BPA) was selected as the targeted pollutant with coexistence of humus acid (HA). For comparison, solid and hollow ZIF-67 derived Co/C nanoparticles denoted as SCCNs and HCCNs, were also tested. The results show that YSCCNs exhibit enhanced BPA degradation rate of 0.32 min-1, which is 23.1% and 45.4% higher than that of HCCNs and SCCNs in HA (10 ppm) system. The essential improvement can be ascribed to the synergetic effects from shell layer (size-exclusion) and core/shell (confinement effect). The degradation mechanism and pathway are further confirmed by radical quenching experiments and liquid chromatography-mass spectrograph (LC-MS), respectively. In addition, some influential factors, including reaction temperature, pH value, and peroxymonosulfate (PMS) dosage are investigated in detail. This work provides a possible way to selectively remove target contaminant from multiple pollutants in complex water system.


[Current views on diagnostic standards and treatments with L-thyroxine of single non-toxic thyroid nodules or multinodular non-toxic goiter].
The present opinions on the therapy with L-thyroxine (L-T4) of single non-toxic thyroid nodules, as well as of multinodular non-toxic goitre are rather divergent. This treatment is based on the suppression of TSH secretion from the pituitary. There are no doubts that FNAB performance is the first and--at the same time--the most significant diagnostic procedure in the case of thyroid structural lesions (nodules, goitre, thyroiditis). FNAB performance should--by all means--precede the beginning of L-T4 application for the treatment of thyroid nodules. The simplicity, clearness and high efficacy, with comparable results in each case, are the core of good diagnostic algorithm. Unfortunately, non all diagnostic algorithms concerning thyroid nodules and multinodular goiter, fulfill these important criteria.


[Indirect articular lymphography using Tc 99m-labeled Dextran in animals].
Looking for a standardization of the articular lymphoscintigraphy, an experimental research was conducted on 14 dogs injected in the ankle, with 2.5 mCi of 99m Tc-labeled dextran (P.M. = 70,000). Good scintigraphic images of the lymphatic system have been obtained. After having collected blood samples during the experimentation as well as aliquots of organs and of tissues, after the necropsy of the animal, it was verified that the 99m Tc-labeled dextran was useful for quantitative studies of the articular lymphatic drainage. The activities attained, in the drainage lymph nodes of injected articulation, are 152 times superior to those obtained in the kidney and one gramma of popliteal ganglion was 8929 times more active than one gramma of blood. The dextran 70,000, widely used in our clinical routine, can be injected to the human being, without any risk, and it may be the tracer which permits studies of the articular lymphatic drainage and the usage of the lymphoscintigraphy, already in expansion in many other Medicine branches, in the articular studies, nowadays.


Angiotensin II and long-term arterial pressure regulation: the overriding dominance of the kidney.
The renin-angiotensin system (RAS) is one of the body's most powerful regulators of arterial pressure and body fluid volumes. Although the acute effects of angiotensin II (AngII), the primary active component of the RAS, on arterial pressure are mediated primarily by peripheral vasoconstriction, its chronic BP effects are closely intertwined with volume homeostasis, particularly with intrarenal actions that influence pressure natriuresis. AngII shifts pressure natriuresis toward higher BP primarily by increasing tubular reabsorption rather than decreasing GFR. In fact, activation of the RAS can serve as an important means of preventing decreases in GFR during volume depletion or circulatory depression. However, with prolonged excess AngII formation, particularly in association with hypertension or overperfusion of the kidney, AngII can contribute to glomerular injury and a gradual loss of nephron function through its hemodynamic actions. The multiple effects of AngII to increase tubular reabsorption provide a powerful mechanism to protect against volume depletion and low BP. However, when AngII levels are inappropriately elevated, this necessitates increased arterial pressure to maintain sodium and water balance. Blockade of the RAS has proved to be a powerful therapeutic tool for lowering BP and improving kidney function in disorders such as hypertension, congestive heart failure, and chronic renal disease.


Beneficial effect of pretreatment and treatment continuation with risedronate and vitamin K2 on cancellous bone loss after ovariectomy in rats: a bone histomorphometry study.
The purpose of the present study was to examine the effect of pretreatment with risedronate and/or vitamin K2 and treatment continuation with reduced dosing frequency of the drugs on the early cancellous bone loss induced by ovariectomy (OVX) in rats. Eighty female Sprague-Dawley rats, 4 mo of age, were randomized by the stratified weight method into eight groups (n= 10 in each group); rats subjected to OVX, but not sham-operated rats, were treated with vehicle, risedronate, vitamin K2 (menatetrenone), or risedronate+vitamin K2 for 4 wk before the surgery, and the treatment was either discontinued (pretreatment groups) or continued after the surgery (treatment continuation groups) for 2 wk. Sham-operated rats (controls) were treated with the vehicle throughout the experimental period. During the 4 wk prior to the surgery (pretreatment), risedronate and vitamin K2 were administered five times a week either subcutaneously at a dose of 2.5 microg/kg body weight (risedronate) or orally at the dose of 30 mg/kg body weight (vitamin K2). During the 2 wk after the surgery (treatment continuation), the dosing frequency of the drugs was reduced to twice a week. Risedronate and vitamin K2 had an anti-resorptive effect on the bone. Pretreatment with risedronate alone, but not vitamin K2 alone, prevented the loss of the cancellous bone volume/total volume (BV/TV) of the proximal tibial metaphysis after OVX. Treatment continuation with vitamin K2 alone prevented the loss of the cancellous BV/TV after OVX, while treatment continuation with risedronate alone increased the cancellous BV/TV to beyond the values in controls. Pretreatment with risedronate+vitamin K2 had a more beneficial effect in increasing the cancellous bone mass than pretreatment with risedronate alone. Treatment continuation with risedronate and/or vitamin K_ appeared to have a more beneficial effect in increasing the cancellous bone mass than the respective pretreatment. Neither the total tissue area nor the cortical area of the tibial diaphysis was affected by any treatment. The present study demonstrated that pretreatment with risedronate had a beneficial effect on the early cancellous bone loss after OVX in rats, with a more beneficial effect when combined with vitamin K2. Moreover, even though the dosing frequency of the drugs was reduced after OVX, treatment continuation appeared to be more beneficial than pretreatment for increasing the cancellous bone mass.


Bioimpedance spectroscopy for the detection of fluid overload in Chinese peritoneal dialysis patients.
Fluid overload probably contributes to the cardiovascular risk of peritoneal dialysis (PD) patients. We studied the relationship between over-hydration as determined by bioimpedance spectroscopy and dialysis adequacy, nutritional status, and arterial stiffness in Chinese PD patients. We studied 122 asymptomatic prevalent PD patients: bioimpedance spectroscopy, arterial pulse wave velocity, dialysis adequacy and nutritional status were determined. Of the 122 patients, 88 (72.1%) had over-hydration of ≥ 1 L, while 25 (20.5%) were ≥ 5 L. Over-hydration significantly correlated with total body water (r = 0.474, p < 0.001) and extracellular water (r = 0.755, p < 0.001). Over-hydration was more severe in male and diabetic patients, and significantly correlated with Charlson's comorbidity score, blood pressure, body mass index, body weight, peritoneal transport characteristics, and carotid-femoral pulse wave velocity. Over-hydration significantly correlated with Kt/V (r = -0.287, p = 0.016), serum albumin level (r = -0.465, p < 0.001) and malnutrition inflammation score (r = 0.410, p = 0.006), but not residual renal function. Over-hydration is common in asymptomatic Chinese PD patients. The degree of over-hydration is particularly pronounced in patients who are inadequately dialyzed, have multiple comorbid conditions and low serum albumin levels. Over-hydration is associated with high blood pressure and arterial stiffness, and may contribute to the excessive risk of cardiovascular disease in this group of patients.


Shedding of oocysts in piglets experimentally infected with Isospora suis.
Forty-seven piglets were inoculated with doses of 100 to 50,000 sporulated oocysts of Isospora suis. After 5-7 days oocysts were found in faeces. The patent period extended from 8 to 16 days. The shedding of oocysts showed a cyclic pattern with 2-3 peaks separated by intervals of approximately 5 days. Subpatent periods were often seen between the peaks. The level of oocyst shedding during the initial days of the patent period reflected, to some extent, the inoculation dose. However, a maximum of OPG at the 100,000 level was observed among one or more piglets from all groups, regardless of the inoculation dose. Among the majority of piglets inoculated with more than 100 oocysts, the highest OPG-figures were observed in the first peak of the cyclic pattern. Unlike this, the maximum of OPG was observed in the second peak of the cycle among 6 of the 7 piglets inoculated with 100 oocytes only. The triphasic pattern was most pronounced in the low dose group. The marked upscaling of oocyst production, as particularly registered in the low dosed groups, seams to explain at least part of the problems met under practical conditions, when trying to eliminate the transmission of oocytes between successive litters in the farrowing boxes. The cyclic excretion pattern and an apparent absence of autoinfection may indicate that the development of I. suis in the host includes several oocyte producing generations descending from the same initial infection. The presence of subpatent periods can probably explain the marked variation in OPG, as they are often recorded when examining faecal samples from piglets, even when the samples are originating from the same litter.


Congenital Syphilis in Honiara, Solomon Islands.
Congenital syphilis remains a significant cause of newborn mortality and long-term neurodevelopmental problems in some low- and middle-income countries. This study was done in Honiara, Solomon Islands to determine the incidence of babies born to mothers with a positive venereal disease research laboratory (VDRL) test and a positive Treponema pallidum haemagglutination assay (TPHA); to determine the VDRL status of newborns and features of congenital syphilis; and to estimate the proportion of stillbirths associated with syphilis. All neonates born to VDRL-positive mothers, including stillbirths were included between April and July 2019. Neonates were examined, investigated and treated. Among 1534 consecutive births, 1469 were live births and 65 (4.2%) were stillbirths. One hundred and forty-three neonates were born to VDRL-positive mothers: 130 (90.1%) were live infants and 13 (8.9%) stillbirths. Of the 130 VDRL-exposed live-born infants, 72 (55%) had reactive VDRL and a positive TPHA and 7 (9.7%) had clinical signs of congenital syphilis. Five of the infants with clinical signs of syphilis infection had a 4-fold higher VDRL titre than their mother. Four infants of VDRL-positive mothers died during admission, all of whom had clinical signs of syphilis. Ninety percent of affected infants were born to mothers who were not treated or only partially treated during pregnancy. In this study, 1:210 live-born babies had clinical and serological evidence of congenital syphilis, and evidence of Treponema infection was found disproportionately in stillbirths. In a setting where Treponema infections are common, an empirical approach to prevention may be needed.


Preferential susceptibility of limbic cortices to microstructural damage in temporal lobe epilepsy: A quantitative T1 mapping study.
The majority of MRI studies in temporal lobe epilepsy (TLE) have utilized morphometry to map widespread cortical alterations. Morphological markers, such as cortical thickness or grey matter density, reflect combinations of biological events largely driven by overall cortical geometry rather than intracortical tissue properties. Because of its sensitivity to intracortical myelin, quantitative measurement of longitudinal relaxation time (qT1) provides and an in vivo proxy for cortical microstructure. Here, we mapped the regional distribution of qT1 in a consecutive cohort of 24 TLE patients and 20 healthy controls. Compared to controls, patients presented with a strictly ipsilateral distribution of qT1 increases in temporopolar, parahippocampal and orbitofrontal cortices. Supervised statistical learning applied to qT1 maps could lateralize the seizure focus in 92% of patients. Intracortical profiling of qT1 along streamlines perpendicular to the cortical mantle revealed marked effects in upper levels that tapered off at the white matter interface. Findings remained robust after correction for cortical thickness and interface blurring, suggesting independence from previously reported morphological anomalies in this disorder. Mapping of qT1 along hippocampal subfield surfaces revealed marked increases in anterior portions of the ipsilateral CA1-3 and DG that were also robust against correction for atrophy. Notably, in operated patients, qualitative histopathological analysis of myelin stains in resected hippocampal specimens confirmed disrupted internal architecture and fiber organization. Both hippocampal and neocortical qT1 anomalies were more severe in patients with early disease onset. Finally, analysis of resting-state connectivity from regions of qT1 increases revealed altered intrinsic functional network embedding in patients, particularly to prefrontal networks. Analysis of qT1 suggests a preferential susceptibility of ipsilateral limbic cortices to microstructural damage, possibly related to disrupted myeloarchitecture. These alterations may reflect atypical neurodevelopment and affect the integrity of fronto-limbic functional networks.


Constraining Gluonic Quartic Gauge Coupling Operators with gg→γγ.
Gluon-gluon to photon-photon scattering gg→γγ offers to the LHC experiments a uniquely powerful probe of dimension-8 operators in the standard model effective field theory that are quadratic in both the electromagnetic and gluonic field-strength tensors, such as would appear in the Born-Infeld extension of the standard model. We use 13-TeV ATLAS data on the production of isolated photon pairs to set lower limits on the scales of dimension-8 operators M≳1 TeV and discuss the prospective sensitivities of possible future hadron colliders.


Insect repellent [correction of repellant] interactions: sunscreens enhance DEET (N,N-diethyl-m-toluamide) absorption.
Toxicology studies are typically performed on single compounds, which we hypothesized would miss adverse synergies from chemical mixtures. This hypothesis was tested using an insect repellant and sunscreens because both groups include known permeation enhancers, with prior pediatric reports of toxicity from highly concentrated DEET (N,N-diethyl-m-toluamide). Using real-time mass spectroscopy in a hairless mouse skin model, we confirmed substantial penetration of a 20% DEET standard. Despite a lower (10%) DEET content, a commercially marketed sunscreen formulation had a 6-fold more rapid detection (5 versus 30 min) and 3.4-fold greater penetration at steady state. We also tested the efficacy of DEET microemulsion products and confirmed that one successfully slowed the onset of absorption, but not the steady-state permeation. Risks from mixtures of potential toxins are worthy of routine testing, which can be accomplished by simple assays, and are of utmost importance for pediatric applications.


Physicochemical assessment of dextran-g-poly (ɛ-caprolactone) micellar nanoaggregates as drug nanocarriers.
Self-assembling polymers in aqueous solution have attracted significant attention with recent research efforts focused on the development of new strategies to design devices useful in the field of controlled drug delivery. In this context, amphiphilic copolymers having specific structural features and self-assembling behaviors in aqueous media that would enable controlled drug release over longer time periods. In this work, we report on the synthesis and characterization of a Poly (ɛ-caprolactone)-grafted Dextran copolymer and its use in the preparation of micellar nanoaggregates. The characterization and study of the morphology, topography, size distribution and stability of micellar nanoaggregates by Transmission Electron Microscopy (TEM), Atomic Force Microscopy (AFM), Dynamic Light Scattering (DLS) and Zeta Potential (ζ), respectively, were carried out. Spherical-shaped morphologies and an average size of approximately 83 nm, for drug-free nanoaggregates, were observed. In addition, Zeta Potential studies showed that drug-free nanoaggregates are more stable than drug-loaded structures measured in a phosphate buffer (pH 7.2) medium. UV-vis spectrophotometry of both the drug entrapment efficiency (EE%) and in vitro drug release behavior were assessed. The EE% was determined to be 78% (w/w), and a combination of diffusion and eroding polymer matrix mechanisms for drug release were established. Finally, these results indicate that Dx-g-PCL micellar nanoaggregates are suitable for use as a potential nanocarrier having both biodegradable and biocompatible properties.


Does subthalamic nucleus stimulation affect the frontal limbic areas? A single-photon emission computed tomography study using a manual anatomical segmentation method.
Among the basal ganglia nuclei, the subthalamic nucleus (STN) is considered to play a major role in output modulation. The STN represents a relay of the motor cortico-basal ganglia-thalamo-cortical circuit and has become the standard surgical target for treating Parkinson's patients with long-term motor fluctuations and dyskinesia. But chronic bilateral stimulation of the STN produces cognitive effects. According to animal and clinical studies, the STN also appears to have direct or indirect connections with the frontal associative and limbic areas. This prospective study was conducted to analyse regional cerebral blood flow changes in single-photon emission computed tomography imaging of six Parkinson's patients before and after STN stimulation. We particularly focused on the dorsolateral prefrontal cortex and the frontal limbic areas using a manual anatomical MRI segmentation method. We defined nine regions of interest, segmenting each MR slice to quantify the regional cerebral blood flow on pre- and postoperative SPECT images. We normalised the region-of-interest-based measurements to the entire brain volume. The patients showed increased activation during STN stimulation in the dorsolateral prefrontal cortex bilaterally and no change in the anterior cingulate and orbito-frontal cortices. In our study, STN stimulation induced activation of premotor and associative frontal areas. Further studies are needed to underline involvement of the STN with the so-called limbic system.


PPAR alpha inhibits vascular smooth muscle cell proliferation underlying intimal hyperplasia by inducing the tumor suppressor p16INK4a.
Vascular SMC proliferation is a crucial event in occlusive cardiovascular diseases. PPARalpha is a nuclear receptor controlling lipid metabolism and inflammation, but its role in the regulation of SMC growth remains to be established. Here, we show that PPARalpha controls SMC cell-cycle progression at the G1/S transition by targeting the cyclin-dependent kinase inhibitor and tumor suppressor p16(INK4a) (p16), resulting in an inhibition of retinoblastoma protein phosphorylation. PPARalpha activates p16 gene transcription by both binding to a canonical PPAR-response element and interacting with the transcription factor Sp1 at specific proximal Sp1-binding sites of the p16 promoter. In a carotid arterial-injury mouse model, p16 deficiency results in an enhanced SMC proliferation underlying intimal hyperplasia. Moreover, PPARalpha activation inhibits SMC growth in vivo, and this effect requires p16 expression. These results identify an unexpected role for p16 in SMC cell-cycle control and demonstrate that PPARalpha inhibits SMC proliferation through p16. Thus, the PPARalpha/p16 pathway may be a potential pharmacological target for the prevention of cardiovascular occlusive complications of atherosclerosis.


Familial distal renal tubular acidosis.
We report the case of a family in which two sisters have distal renal tubular acidosis (dRTA). Familial dRTA is a rare disorder, with both autosomal dominant and recessive transmission. This is a report of familial dRTA from China.


Resveratrol is rapidly metabolized in athymic (nu/nu) mice and does not inhibit human melanoma xenograft tumor growth.
Resveratrol has been shown to have anticarcinogenic activity. We previously found that resveratrol inhibited growth and induced apoptosis in 2 human melanoma cell lines. In this study we determined whether resveratrol would inhibit human melanoma xenograft growth. Athymic mice received control diets or diets containing 110 micromol/L or 263 micromol/L resveratrol, 2 wk prior to subcutaneous injection of the tumor cells. Tumor growth was measured during a 3-wk period. Metabolism of resveratrol was assayed by bolus gavage of 75 mg/kg resveratrol in tumor-bearing and nontumor-bearing mice. Pellets containing 10-100 mg resveratrol were implanted into the mice, next to newly palpated tumors, and tumor growth determined. We also determined the effect of a major resveratrol metabolite, piceatannol, on experimental lung metastasis. Resveratrol, at any concentration tested, did not have a statistically significant effect on tumor growth. The higher levels of resveratrol tested (0.006% in food or 100 mg in slow-release pellets) tended to stimulate tumor growth (P = 0.08-0.09). Resveratrol and its major metabolites, resveratrol glucuronide and piceatannol, were found in serum, liver, skin, and tumor tissue. Piceatannol did not affect the in vitro growth of a murine melanoma cell line, but significantly stimulated the number of lung metastases when these melanoma cells were directly injected into the tail vein of the mouse. These results suggest that resveratrol is not likely to be useful in the treatment of melanoma and that the effects of phytochemicals on cell cultures may not translate to the whole animal system.


Parathyroid hormone degradation by chymotrypsin-like endopeptidase in the opossum kidney cell.
Cathepsin-D has been previously reported to cleave intact PTH into PTH-(1-34) and -(35-84) in membranous fractions of rat and bovine kidney. Whether PTH degradation occurs by intact kidney cells, however, has not been examined in detail. We have, therefore, examined this possibility using an opossum kidney (OK) cell line which possesses the characteristics of proximal renal tubules and responds to PTH. PTH radioimmunoreactivity recovered in trichloroacetic acid-soluble products and in fractions eluted from reverse phase HPLC was measured using an antibody directed to the midregion and C-terminus of PTH. In this study, intact OK cells, but not extracellular enzymes, cleaved human (h) PTH-(1-84) into three discrete fragments which were released into the medium in a time- and temperature-dependent fashion. Half-maximal velocity of PTH-degrading activity (PTHDA) was observed at 9 nM hPTH-(1-84). A 1000-fold molar excess of PTH antagonists [hPTH-(3-34) and [Tyr34]hPTH-(7-34)amide] markedly inhibited PTHDA, whereas ACTH, glucagon, or big gastrin did not suppress it, suggesting an involvement of the PTH receptor in PTHDA. This PTHDA was strongly inhibited by phenylmethylsulfonylfluoride and chymostatin, but not by trypsin inhibitor, elastatinal, or inhibitors of aspartic, cysteine, or metalloproteinases, suggesting that it is due to a seryl chymotrypsin-like endopeptidase. Analysis of chymotrypsin-digested products of hPTH-(1-84) eluted from HPLC exhibited five fragments detected by UV absorbance (210 nm), three of which were measurable by PTH RIA, and each corresponded to the three PTH fragments produced by OK cells. All three fragments were predominantly suppressed in the presence of chymostatin, suggesting that chymotrypsin-like activity is solely responsible for PTHDA in intact OK cells. To further explore the cleavage sites of PTH by chymotrypsin, amino acid analysis of chymotrypsin-cleaved products was performed. The results strongly support the conclusion that a chymotrypsin-like enzyme in OK cells cleaved the hormone between residues 23-24, and 34-35 to produce, at least, hPTH-(24-84) and -(35-84). Lysosomal blockers (chloroquine, ammonium chloride, or monensin) did not affect this PTHDA. Our present study indicates that chymotrypsin-like endopeptidase, but not other endopeptidase or lysosomal enzymes, is responsible for the limited hydrolysis of PTH by intact OK cells.


Propranolol and serotonin removal in lung injury.
Indicator dilution technique was used to study effects of reduced vascular volume or acute injury on removal of low doses of [3H]propranolol and [14C]serotonin (5-hydroxytryptamine, 5-HT) by perfused rabbit lung. Glass-bead (500 micron) embolization doubled pulmonary arterial pressure (Ppa) at flow rates of 20, 50, and 100 ml/min, decreased volume of distribution by approximately 50%, and increased pulmonary vascular resistance by at least 60%. Before embolization, (flow rate 20 ml/min) removal of [3H]propranolol and [14C] 5-HT was 89 +/- 2 and 75 +/- 5%, respectively, and was unaltered by changes in flow rate. However, after embolization, [3H]propranolol and [14C]5-HT removal decreased in a flow-dependent manner, reaching 28 +/- 4 and 1 +/- 3% (P less than 0.05), respectively, at a flow rate of 100 ml/min. When phorbol myristate acetate (PMA, 200 nM) was perfused (50 ml/min) through the lungs for 15 min, Ppa increased from 13 +/- 1 to 25 +/- 2 cmH2O (P less than 0.05), whereas [3H]propranolol removal decreased from 92 +/- 1 to 75 +/- 5% (P less than 0.05) and [14C]5-HT removal decreased from 73 +/- 3 to 46 +/- 8% (P less than 0.05). The PMA also caused vasoconstriction, which could be partially blocked by adding papaverine (500 microM) to the perfusion medium. Under the latter conditions, Ppa increased to 19 +/- 1 cmH2O and [3H]propranolol removal was unaffected. However, the combination of PMA and papaverine reduced [14C]5-HT removal from 64 +/- 4 to 19 +/- 3%.(ABSTRACT TRUNCATED AT 250 WORDS)


B cell abnormality and autoimmune disorders.
Various abnormalities have been described in B cells from patients with systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and lupus-prone mice. Many of the abnormalities do not appear to be connected with the pathogenesis of the disease. However, various animal models developing lupus-like disease including both spontaneous mutans such as (NZB x NZW)F1 and MRL/lpr and mice generated by transgenic or knockout technology such as Bim-deficient and CD40L-transgenic mice show defect in apoptosis of mature B cells induced by ligation of the B cell antigen receptor (BCR). BCR-mediated apoptosis appears to be involved in deletion of self-reactive B cells. Thus, defect in BCR-mediated apoptosis is a widely observed B cell abnormality in lupus-prone mice and may play a role in the pathogenesis of systemic autoimmune diseases by abrogating deletion of self-reactive B cells.


Dinitrophenol-Hyaluronan Conjugates as Multivalent Antibody-Recruiting Glycopolymers for Targeted Cancer Immunotherapy.
Multivalent antibody-recruiting glycopolymers (MARGs) composed of hyaluronic acid (HA) grafted with multiple copies of dinitrophenol (DNP) were developed for targeted cancer immunotherapy. Structure-activity studies demonstrated that the MARGs were able to specifically recognize CD44-positive cancer cells and displayed remarkable antibody-recruiting capacities and tumor cell killing activities dependent on the introduced multivalent effect and the length of PEG linker. One of the MARGs, HA-[PEG3 -DNP]8 , showed the best capacity for clustering anti-DNP antibodies onto CD44-positive cancer cells and displayed potent in vitro anti-cancer activity by triggering complement dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Moreover, we found that HA-[PEG3 -DNP]8 significantly inhibited the xenograft tumor growth of Babl/c nude mice bearing triple negative breast cancer cells, while it did not cause detectable histological cytotoxicity. Given the easy access of this type of natural glycopolymer and the practical synthesis approach, these MARGs provide promising immunotherapeutics for cancer immunotherapy.


Bimodal Nanocomposite Platform with Antibiofilm and Self-Powering Functionalities for Biomedical Applications.
Advances in microelectronics and nanofabrication have led to the development of various implantable biomaterials. However, biofilm-associated infection on medical devices still remains a major hurdle that substantially undermines the clinical applicability and advancement of biomaterial systems. Given their attractive piezoelectric behavior, barium titanate (BTO)-based materials have also been used in biological applications. Despite its versatility, the feasibility of BTO-embedded biomaterials as anti-infectious implantable medical devices in the human body has not been explored yet. Here, the first demonstration of clinically viable BTO-nanocomposites is presented. It demonstrates potent antibiofilm properties against Streptococcus mutans without bactericidal effect while retaining their piezoelectric and mechanical behaviors. This antiadhesive effect led to ∼10-fold reduction in colony-forming units in vitro. To elucidate the underlying mechanism for this effect, data depicting unfavorable interaction energy profiles between BTO-nanocomposites and S. mutans using the classical and extended Derjaguin, Landau, Verwey, and Overbeek theories is presented. Direct cell-to-surface binding force data using atomic force microscopy also corroborate reduced adhesion between BTO-nanocomposites and S. mutans. Interestingly, the poling process on BTO-nanocomposites resulted in asymmetrical surface charge density on each side, which may help tackle two major issues in prosthetics-bacterial contamination and tissue integration. Finally, BTO-nanocomposites exhibit superior biocompatibility toward human gingival fibroblasts and keratinocytes. Overall, BTO-embedded composites exhibit broad-scale potential to be used in biological settings as energy-harvestable antibiofilm surfaces.


Correlation of Systemic Inflammatory Status and Cardiac Myonecrosis in Patients Undergoing Percutaneoues Coronary Intervention.
Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Pre-Percutaneoues coronary intervention (PCI) plasma hs-CRP concentration has been reported to influence both short and long term outcome after percutaneoues coronary intervention (PCI). Studies have reported association between pre-PCI CRP and PCI induced cardiac myonecrosis evaluated by sensitive marker of myocardial injury. The present study attempts to evaluate the influence of pre-PCI CRP levels, factors related to the procedure and ongoing medications on the event of post-PCI cardiac myonecrosis. This prospective observational study was done in a Tertiary referral hospital (St. James's Hospital, Dublin, Ireland) involving 38 patients with normal pre-procedural serum troponin T (<0.03μg/litre) undergoing elective PCI. Significantly high basal levels of hs-CRP was detectable in >60% patients undergoing elective PCI. This was further increased to >65% after PCI. Median value of hs-CRP before PCI was 3.61 (range 0.21-47.2mg/L). This value increased to 4.58 (range 0.44-39.2mg/L) after PCI (p<0.05). Though there was significant increase in the post-PCI median value (compared to the pre-PCI value) of TnT (0.015 vs. 0.01μg/L; p<0.001) and CKMBM (4.54 vs. 2.40μg/L; p<0.001), no significant correlation was found between pre-PCI hsCRP and post-PCI TnT (spearman correlation coefficient - 0.074; p=NS) as well as post-PCI CKMBM (spearman correlation coefficient - 0.036; p=NS). The changes in the values of TnT & CKMBM showed moderate positive correlation (spearman correlation coefficient - 0.52; p<0.001). Procedural parameters (of balloon dilatation and stent implantation) did not have significant correlation either. No significant influence of age and ongoing medications was found. Increased hs-CRP levels in serum before PCI was not correlated with significant cardiac myonecrosis detected after PCI.


[Development of a new noninvasive blood sugar detector].
The level of blood sugar is an improtant indicator used in the diagnosis and management of diabetes mellitus. In this respect, polarimeter and blood sugar detector were conventionally and generally used in hospitals; However, the former one is already obsolete; the latter one is invasive. In this paper, the development of a novel noninvasive blood-sugar detector is described. The experiment indicate that this detector is nonivasive, safe, fast, and easy to operate, and it can be of wide application.


Concomitant Lumbosacral Perimedullary Arteriovenous Fistula and Spinal Dural Arteriovenous Fistula.
Although multifocal spinal arteriovenous malformations (AVMs) have been reported before, the present case is the first case of 2 different types, including 1 perimedullary arteriovenous fistula and 2 spinal dural arteriovenous fistulas of lumbosacral AVMs, coexisting in 1 patient. We also report the use of hybrid techniques in treatment of concomitant lumbosacral spinal AVMs. A 65-year-old man presented with a 4-year history of progressive sensory, motor, and sphincter dysfunction. Spinal magnetic resonance imaging and digital subtraction angiography showed 2 spinal dural arteriovenous fistulas (fed by the right L2 lumbar artery and the right lateral sacral artery, respectively) and 1 perimedullary arteriovenous fistula (fed by the filum terminale artery from the left L2 lumbar artery [i.e., filum terminale arteriovenous fistulas]. A hybrid technique was used to perform embolization of the right L2 spinal dural arteriovenous fistula and microsurgery of the L5 level filum terminale vein. The patient was asymptomatic 1 year later. Multifocal spinal vascular malformations may coexist in 1 case, and standardized spinal digital subtraction angiography, including the bilateral internal iliac arteries and median sacral artery, should be performed to avoid a missed diagnosis. The concomitant phenomenon indicates that venous hypertension may be a risk factor for the development of arteriovenous fistulas. Hybrid techniques are effective in treatment of multifocal and complex spinal AVMs.


Photolytic Aging of Secondary Organic Aerosol: Evidence for a Substantial Photo-Recalcitrant Fraction.
Photolytic aging has been proposed as a major mass loss mechanism for atmospheric secondary organic aerosol (SOA). However, estimated mass loss rates vary by orders of magnitude, and their impacts on modeled SOA loadings and properties are highly uncertain. In this study, photolysis rates and composition changes of α-pinene SOA are analyzed in situ over multiple days in an environmental chamber. After an initial exponential decay (τ ∼ 22 h), the mass loss rate slows dramatically, with more than ∼70-90% of the SOA particulate mass undergoing an essentially negligible photolytic degradation. Scaled to ambient conditions, SOA undergoes rapid photolysis over only its first day in the atmosphere; beyond this, the remaining SOA is photo-recalcitrant, and photolysis ceases to be a major sink compared to wet deposition time scales. Thus, extrapolation of the initial photolysis loss rate to the entire aerosol mass may significantly overestimate the role of photolysis in the removal of atmospheric SOA.


Two cases of renal hypouricemia with nephrolithiasis.
We treated two cases of renal hypouricemia with nephrolithiasis. The serum uric acid level of the first patient was 1.5 mg/dl, and the ratio of uric acid clearance to creatinine clearance (CUA/Ccr) was 75.7%. In the benzbromarone (BZB) suppression test, CUA/Ccr was increased from 60.4% to 130.0%, but was not decreased in response to the pyrazinamide (PZA) suppression test. This patient was considered to have a presecretory reabsorptive urate transportation defect. His condition was also associated with IgA nephropathy. The serum uric acid level in the second patient was 1.0 mg/dl and CUA/Ccr was 56.0%. Neither PZA nor BZB had a significant effect on CUA/Ccr. He was considered to have a subtotal uric acid transportation defect. Both patients were incidentally found to have nephrolithiasis. The second patient had abnormal maximum tubular secretory capacity for para-aminohippurate (PAH) (TmPAH), and was found to have two kinds of proximal tubular abnormalities related to uric acid and PAH.


Two Pests Overlap: Drosophila suzukii (Diptera: Drosophilidae) Use of Fruit Exposed to Halyomorpha halys (Hemiptera: Pentatomidae).
Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) and brown marmorated stink bug, Halyomorpha halys (Stål) (Hemiptera: Pentatomidae), are global economic pests that may co-occur on small fruits. We investigated whether fruit recently exposed to H. halys affected subsequent host use by D. suzukii. Laboratory no-choice and choice tests presented D. suzukii with H. halys-fed and unfed raspberries and blueberries immediately or 3 d after H. halys feeding. Resulting D. suzukii eggs, or larvae and pupae, were counted. The number of D. suzukii immatures among fed and unfed fruit was not significantly different in lab studies. There was no relationship between the intensity of H. halys feeding, as estimated by the number of stylet sheaths, and D. suzukii oviposition on blueberry. Lastly, field studies compared D. suzukii infestation between H. halys-fed and unfed raspberries. Raspberries were previously exposed to H. halys for 3 d or simultaneously exposed to both pests for 7 d. Natural infestation by D. suzukii in the field was similar among raspberries previously or simultaneously exposed to H. halys compared to control fruit.


The impact of antithrombotic therapy on neurosurgical emergency referral load.
The authors sought to determine the impact of antithrombotic therapy on emergency referrals at one neurosurgical centre. All emergency telephone referrals over a 90 day period were carefully documented with particular attention paid to current antithrombotic medications and their indication. Details regarding age, gender, diagnosis, radiological findings and treatment were also recorded. 713 emergency referrals were documented in the data collection period. 174 (24.4%) patients presented with intracranial or spinal haemorrhage and 75 (43.1%) of these were on antithrombotic therapy, ranging in age from 46-94 years (mean 71.1 years) with 29 (31.8%) on warfarin, 43 (47.2%) on aspirin and 15 (16.4%) on clopidogrel alone or in combination with another antithrombotic agent. 17 (22.6%) had no documented indication for antithrombotic therapy (all of these were on aspirin therapy) and 9 (31%) of those on warfarin had an INR in excess of 3.5 on presentation. Almost one quarter of those on antithrombotic therapy who presented with a haemorrhagic complication had no obvious indication for such therapy. One third of those on warfarin were over anticoagulated.