Inductive effect of Porphyromonas gingivalis fimbriae on differentiation of human monocytic tumor cell line U937.
This study used the human monocytic tumor cell line U937 to examine whether Porphyromonas gingivalis fimbriae induce differentiation of monocyte/macrophage progenitors. When the progenitor cells were incubated with P. gingivalis fimbriae, the incubation resulted in increased Fc rosette formation and increased CD11b production by the cells. The presence of a protein kinase C inhibitor, H7 or calphostin C, in the medium eliminated the stimulatory effects of P. gingivalis fimbriae on Fc rosette formation. Furthermore, CD11b expression was inhibited by calphostin C. In contrast, HA1004 , an inhibitor of cyclic nucleotide-dependent protein kinase, had no effect on P. gingivalis fimbriae-induced Fc rosette formation or CD11b expression. These results demonstrate that P. gingivalis fimbriae are a potent inducer of the differentiation of the monocyte/macrophage tumor cell line U937, most probably via cyclic nucleotide-independent protein kinase C.


The Adolescence Scale (AS-ICSM): a tool for the retrospective assessment of puberty milestones.
Neurodevelopmental theories of psychosis, and schizophrenia in particular, have led to renewed interest in the relationships between brain maturation, adult personality and timing of puberty. Here we present a brief Adolescence Scale (AS-ICSM) for the retrospective assessment of puberty milestones. The recommended version comprises one item for females, three for males and one common to both. An original version of five items was administered to 318 young adults. We found good internal consistencies of Cronbach's alpha = 0.87 for females and 0.83 for males, having excluded an item assessing timing of growth spurt. These findings show that the AS-ICSM is a reliable and economic tool for research into the concomitants of early and late puberty.


The accordion gracilis muscle flap: a new design for coverage of recurrent and complicated ischeal pressure sores.
Management of patients with large or recurrent pressure ulcerations can be complicated by the lack of available local flap, whether already used or because adjacent lesions make such flap insufficient for complete coverage. In this article, the gracilis muscle was modified to cover large defects without help from its cutaneous territory. Twelve ischeal pressure sores were treated between August 2007 and 2009 with the modified gracilis muscle flap in a single-staged procedure. Five ulcers were recurrent and seven patients have associated pressure ulcers. All reconstructions were successful. Mean patient age was 35 years and nearly all patients had multiple significant comorbidities, including associated ulcers, diabetes and urethrocutaneous fistula. All flaps and donor sites healed uneventfully. There was one complication presented as cellulites at the donor site. Follow-up in some cases extend up to 1·5 years. No recurrence was observed. The accordion gracilis muscle flap is a handy, safe and fast flap for reconstruction of recurrent, difficult ischeal pressure sores.


Peroxisome proliferator-activated receptor-gamma (PPARgamma) modulates hypothalamic Trh regulation in vivo.
Thyroid hormone receptor (TR) and peroxisome proliferator-activated receptor gamma (PPARgamma) co-regulate numerous peripheral metabolic responses. To examine potential crosstalk between PPARgamma and TRbeta in the hypothalamus, thyrotropin-releasing hormone (Trh) regulation in the newborn mouse hypothalamus was followed. QPCR showed PPARgamma to be expressed in the hypothalamus at this developmental stage. Intracerebral injection of PPARgamma agonists modified transcription from a TRH-luc construct introduced into the hypothalamus and increased serum thyroxine levels. Furthermore, shRNA-based in vivo PPARgamma knockdown amplified T(3)-independent transcription and PPARgamma overexpression dose-dependently abrogated T(3)-dependent Trh repression. Overexpression of retinoid X receptor-alpha (RXRalpha), the common heterodimeric partner of PPARgamma and TRbeta, rescued PPARgamma abrogation of T(3)-dependent repression. Thus, competition for RXR could represent one mechanism underlying this hypothalamic crosstalk between PPARgamma and TRbeta. These demonstrations of PPARgamma effects on hypothalamic Trh transcription in vivo consolidate the role of the TRH neuron as a central integrator of energy homeostasis.


A case of esophageal stricture due to metastatic breast cancer diagnosed by endoscopic mucosal resection.
Metastasis of breast cancer to the esophagus has been reported but is rare. It is often difficult to diagnose metastases of breast cancer to the esophagus because they are often located in the submucosa and covered with normal mucosa. Although several methods have been reported in order to obtain specimens for pathological diagnosis, the adverse effects including bleeding and perforation were considerable problems. We report a case of a patient with esophageal stricture due to metastatic breast cancer to the esophagus. Pathological diagnosis was successfully obtained using endoscopic mucosal resection of the esophagus.


[Co-ordination of the resources on health information. A study of 4 sources].
During the 1979 Health Year a programme was undertaken in the Cape Province to co-ordinate the resources of two well-known national health information centres with the resources of two relatively unknown provincial health information resource centres. Evaluation of this scheme after 1 year indicated that co-ordination of the services of health information resource centres at provincial level can improve this service to remarkable extent.


Factors associated with home births in a selected ward in Mberengwa District, Zimbabwe.
Despite many efforts put by the Government to ensure that women give birth in health facilities under trained personnel supervision; statistics suggest that ward 2 in Mberengwa District in Zimbabwe has the highest home births. This study sought to assess factors that are associated with home births in ward 2 of Mberengwa District in Zimbabwe. Case- control. Ward 2 in Mberengwa District in Zimbabwe. 35 and 105 women who gave birth at home and facilities, respectively. A piloted researcher administered questionnaire was used to collect data from systematically selected respondents on factors leading to their choice of place to give birth. The home and facility births were geocoded using a Garmin etrex-30 Global Positioning System receiver and exported to Quantum Geographic Information System software for spatial analysis and mapping. Factors associated with home births were; being uneducated (2.90, CI 1.08-7.57), unemployed (2.56, CI 1.08-6.23), could not afford facility bills (20.92, 3.19-160.31), and lack of access to Ante Natal Care (23.8, 7.04-90). 69% (24) of cases and 30% (32) of resided within the 5 km radius of health facilities. There was significant difference in levels of knowledge between cases and controls about benefits of giving birth in facilities. It is acknowledged that costs are a huge barrier in accessing antenatal care services. These factors together with others need to be addressed so as to improve access by pregnant women to health facilities.


[Optical coherent tomography in diagnosis of peripheral retinal breaks].
The purpose of our study was to develop an optimal method of peripheral retinal breaks visualization and determine the presence of vitreoretinal traction using optical coherence tomography (OCT). A total of 152 patients (176 eyes) with peripheral retinal breaks were assessed, among them 57 men and 95 women, aged from 18 to 76. To visualize retinal periphery we used RTVue-100 optical coherent tomograph (USA). Photoregistration was done with Nikon NF-505 fundus camera (Japan). All patients were examined with Goldmann lens. OCT application enabled us to determine structural features and configuration of peripheral retinal breaks, the presence of vitreoretinal traction, and morphometric parameters of the defects: the average length and height, retinal thickness in three standard points (prior to the break, at its edge and at the bottom), and also the extent of vitreoretinal fusion and local detachment of retinal neuroepithelium (NE). Two groups of peripheral retinal tears were formed: group I (23 eyes)--retinal flap tears and group II (153 eyes)--perforated breaks. Optical coherence tomography is a highly informative method which enables in vivo evaluation of structural and morphometric characteristics of retinal defects and vitreoretinal fusion, as well as possible vitreoretinal traction and subclinical detachment of the retina. Its use will ensure proper documentation of study results and also provide the possibility to determine indications for laser and surgical treatment and perform a late follow-up.


[Epidemiology of pancreatic adenocarcinomas].
Pancreatic cancer, mostly represented by pancreatic ductal adenocarcinoma, is a major public health burden in developed countries. More than half a million people are expected to die from pancreatic cancer, worldwide, in 2030. Age and tobacco are the main identified risk factors in sporadic cases, when many genetic syndromes increase the risk significantly. History of pancreatic cancer is a significant risk factor for pancreatic cancer for any first-degree related individual, known as familial pancreatic cancer. The genetic signature of this syndrome is probably due to a still not identified autosomal dominantly inherited gene with reduced penetrance. The risk increases with the number of first-degree relatives involved. Precursor lesions are known to give rise to invasive pancreatic cancer. These particular lesions are either macroscopic (intraductal papillary mucinous neoplasia and mucinous cystic neoplasms), or microscopic (pancreatic intraepithelial neoplasia). It is possible to identify a orouo of hig h-risk individuals who could be candidate for screening.


[National Program on Pediatric Actualization (PRONAP): field works reports on the years 2003, 2005, and 2006].
PRONAP is a distance learning course from the Argentine Society of Paediatrics whose primary aim is contributing to improve the child/mother health. Annually, participants perform a field work. The subject in 2003 was "Deficiency, Disability, and Disablement". In the year 2005, a personal survey on tobacco use and knowledge on second-hand smoking was realized; another survey, to parents of ten 5-year-old children, was carried on regarding home exposition to ambience tobacco smoke. In 2006, the work deals with uremic-haemolytic syndrome and included survey implementations. The main results of these three works are presented.


A result on a 2 x 2 survival experiment.
Lifetime data classified according to categorical variables under the proportionality of the hazard functions of response variables for various treatment combinations is assumed. The proposed model is a combination of Cox's proportional hazards model and ANOVA model. The existence of a solution to the marginal likelihood function is examined for the case of 2 x 2 two-way classification. We provide an easily verifiable condition for the existence of a unique estimate.


Association between an interleukin-4 promoter polymorphism and the acquisition of CXCR4 using HIV-1 variants.
A polymorphism at position -589 in the interleukin 4 (IL-4) promoter region was recently described as being associated with the presence of syncytium-inducing CXCR4 using (X4) HIV-1 variants. To study the IL-4 promoter polymorphism -589T in relation to HIV-1 disease progression and acquisition of X4 HIV-1 variants. Retrospective longitudinal study among 342 HIV-1-infected homosexual men who participated in the Amsterdam Cohort study. Polymerase chain reaction was used in combination with restriction analysis to identify IL-4 promoter genotypes. Carriers of the -589T allele (either -589 C/T heterozygotes or -589 T/T homozygotes), showed comparable progression to AIDS [relative hazard (RH), 0.94; P = 0.71], and survival (RH IL-4 -589 C/T or T/T, 0.94; P = 0.69) as carriers of the -589 C/C genotype (the reference group). In contrast to a previous study, we found that the -589T polymorphism was associated with a delayed acquisition of X4 HIV-1 variants (RH, 0.56; P = 0.02 for IL-4 -589 C/T or T/T) and a reduced number of CCR5 expressing memory CD4 T cells. In the Amsterdam Cohort of homosexual men with HIV infection, the IL-4 -589T promoter polymorphism was associated with a delayed acquisition of X4 variants but did not affect overall disease progression.


A multiscale approach to the adsorption of core-shell nanoparticles at fluid interfaces.
Self-assembly of colloidal particles at liquid-liquid interfaces is a process with great potential for the creation of controlled structures, due to the trapping of the particles in the plane of the interface combined with their lateral mobility. Here we present a multiscale characterisation of the adsorption and interfacial behaviour of core-shell iron oxide-poly(ethylene glycol) nanoparticles at a water-n-decane interface using three complementary, in situ, methods, which span many different length scales. First, dynamic interfacial measurements are taken to follow the adsorption of particles from the bulk aqueous phase to the interface. The mechanical properties of the interface are then probed using micron-sized tracers in probe-particle tracking and nano-tracers in fluorescence correlation spectroscopy. The results show that the rate of particle adsorption to the interface scales with the square of bulk concentration, as predicted by a recent model. In addition, we show that despite full monolayers of nanoparticles forming, the interface remains unexpectedly fluid, with only a slowing of tracer particle mobility but no evidence of interface jamming as seen for hard nanoparticles. Our results illustrate that nanoparticles stabilised by soft, extended polymeric shells, display distinct features at fluid interfaces that can be harnessed for the fabrication of functional materials.


A nonspecific nucleoside hydrolase from Leishmania donovani: implications for purine salvage by the parasite.
In contrast to their mammalian hosts, protozoan parasites do not synthesize purines de novo, but depend on preformed nucleotides that they purportedly obtain by salvage pathways. Nucleoside hydrolases may play a crucial role in that salvage process. By screening Leishmania donovani libraries with polyclonal antibodies against promastigote soluble exo-antigens, we have identified a cDNA encoding a protein with significant homology to nonspecific and uridine-inosine-preferring nucleoside hydrolases. Sequence comparison demonstrated that all the residues involved in Ca(2+)-binding and substrate recognition in the active site are conserved among the characterized protozoan nucleoside hydrolases. Genomic analysis suggests that it is a single copy gene in L. donovani, and its homologues are present in members representing other Leishmania species complexes. Both Northern blot and immunoblot analyses indicate that it is constitutively expressed in L. donovani promastigotes. The recombinant enzyme overexpressed in and purified from bacteria showed significant activity with all naturally occurring purine and pyrimidine nucleosides, and efficient utilization of p-nitrophenyl-beta-D-ribofuranoside as a substrate. Altogether, the sequence comparison and substrate specificity data identify this L. donovani nucleoside hydrolase as a nonspecific nucleoside hydrolase. Further, the nucleoside hydrolase was localized to specific foci in L. donovani promastigotes by immunofluorescent assays. Although the conservation of the nucleoside hydrolases among protozoan parasites offers promise for the design of broad-spectrum anti-parasitic drugs, the existence of multiple and distinct nucleoside hydrolases in a single species demands special consideration.


Psychiatric advance directives and the right to refuse treatment in Canada.
To provide a Canadian perspective on psychiatric advance directives (PADs) and assess whether these documents can be implemented as an adjunct to mental health services to empower people with mental illness. We reviewed Canadian jurisprudence over the past 15 years related to people with mental illness and the right to refuse medical treatment. Provincial mental health legislation is explained to discern PADs' possible effect in Canada. Evidence is accumulating that legal and mental health professionals see PADs as useful documents to promote patient autonomy. Canadian jurisprudence, mental health legislation, and psychological research suggest that PADs could be implemented by legal and mental health professionals. Mental health legislation has the power to prohibit or facilitate choices regarding the right to refuse medical treatment. This review suggests the need for greater empirical research to be conducted in Canada to determine stakeholders' perceptions of whether PADs could successfully be implemented and their interaction with legislation.


Measurement of sialic acid in serum and urine: clinical applications and limitations.
Many recent studies have examined the sialic acid content of serum or urine in various pathological states. We have briefly reviewed the substances which contribute to the observed total sialic acid concentration, and given an overview of assay methods used. Three major areas of clinical interest in sialic acid metabolism are discussed. Serum total sialic acid, 'lipid-bound' and 'protein bound' sialic acid have all been proposed as tumour markers; but the usefulness of any of these tests is severely limited by changes due to accompanying inflammatory processes. Serum total sialic acid is not a valuable simple marker of an acute phase response. Urinary free and bound sialic acid measurements should be included in screening protocols for inherited disorders of lysosomal metabolism. Current developments in research and potential applications within the clinical biochemistry laboratory are briefly discussed.


Dietary patterns and metabolic phenotypes in Brazilian adults: a population-based cross-sectional study.
Dietary patterns have been pointed out as useful diet quality indicators, but evidence about their relationship to metabolic phenotypes is still scarce. Thus, the present study aimed to verify the relationship between dietary patterns and metabolic phenotypes in Brazilian adults. Cross-sectional study. A food consumption frequency questionnaire assessed food consumption profiles. Metabolic phenotypes were defined based on the criteria of the National Health and Nutrition Examination Survey: overweight or normal weight and metabolically healthy (MHOW and MHNW) or unhealthy (MUOW and MUNW). Dietary patterns were established through exploratory factor analysis and principal component analysis. The associations were tested using multinomial logistic regression. Viçosa, Minas Gerais, Brazil. Individuals (n 896) aged 20-59 years of both sexes, selected using probabilistic sampling. Three dietary patterns were identified: Unhealthy pattern (alcoholic beverages, oils and fats, condiments, soda and juice, sugars and sweets, snacks, and meat and derivatives), Traditional pattern (culinary preparations, beans, milk and dairy products, and coffee and tea) and Healthy pattern (vegetables and fruits, whole grains, chicken and fish, and skimmed milk). Unhealthy pattern was positively associated with the MHOW and MUOW phenotypes in the fourth quartile (OR = 1·84; 95 % CI 1·06, 3·22) and in the third (OR = 1·94; 95 % CI 1·11, 3·39) and fourth (OR = 2·56; 95 % CI 1·41, 4·64) quartiles of consumption, respectively. Healthy pattern was also associated with these phenotypes. Both the pattern comprising energy-dense foods and the healthier pattern were associated with overweight phenotypes among Brazilian adults.


Machine Learning as an Effective Method for Identifying True Single Nucleotide Polymorphisms in Polyploid Plants.
Single nucleotide polymorphisms (SNPs) have many advantages as molecular markers since they are ubiquitous and codominant. However, the discovery of true SNPs in polyploid species is difficult. Peanut ( L.) is an allopolyploid, which has a very low rate of true SNP calling. A large set of true and false SNPs identified from the Axiom_ 58k array was leveraged to train machine-learning models to enable identification of true SNPs directly from sequence data to reduce ascertainment bias. These models achieved accuracy rates above 80% using real peanut RNA sequencing (RNA-seq) and whole-genome shotgun (WGS) resequencing data, which is higher than previously reported for polyploids and at least a twofold improvement for peanut. A 48K SNP array, Axiom_2, was designed using this approach resulting in 75% accuracy of calling SNPs from different tetraploid peanut genotypes. Using the method to simulate SNP variation in several polyploids, models achieved >98% accuracy in selecting true SNPs. Additionally, models built with simulated genotypes were able to select true SNPs at >80% accuracy using real peanut data. This work accomplished the objective to create an effective approach for calling highly reliable SNPs from polyploids using machine learning. A novel tool was developed for predicting true SNPs from sequence data, designated as SNP machine learning (SNP-ML), using the described models. The SNP-ML additionally provides functionality to train new models not included in this study for customized use, designated SNP machine learner (SNP-MLer). The SNP-ML is publicly available.


Interaction between organophosphorous hydrolase and paraoxon studied by surface chemistry in situ at air-water interface.
Subphase conditions have been optimized to obtain stable organophosphorous hydrolase (OPH-EC 3.1.8.1) as Langmuir films. The Langmuir film was characterized by surface pressure and surface potential-area isotherms and UV-Vis spectroscopy in situ. The interaction of an organophosphorous compound, namely Paraoxon, with the OPH film was investigated for various surface pressures. The stability of the monolayer and the evidence of the enzyme activity at air-water interface support the use of enzyme LB films as biosensor.


Cucurbitane-type triterpenoids from the stems of Cucumis melo.
Phytochemical investigation of the stems of Cucumis melo led to the isolation and identification of 21 cucurbitane-type triterpenoids, including nine new compounds (1-9) and 12 known compounds. Their structures were determined on the basis of spectroscopic analyses, chemical methods, and comparison with spectroscopic data in the literature. Two known compounds, cucurbitacin B (10) and cucurbitacin A (11), showed significant cytotoxic activity against the proliferation of A549/ATCC and BEL7402 cells in vitro. Of the new compounds, only compound 7 was weakly cytotoxic. The inhibitory effects of all compounds on the Jak-Stat3 signaling pathway were evaluated, but only cucurbitacin B (10) showed significant inhibitory activity of phosphotyrosine STAT3.


[Angled micro-scissors for after-cataract surgery (author's transl)].
A report is given on new micro-scissors for after-cataract operations. Its shape permits a perfect direction of incision in the pupillary region not only form a temporally placed corneal incision but also from all other meridians without its handling being impeded by the orbital border or th nose of the patient. Especially in certain injury sequels and other postoperative conditions the scissors extend the operative possibilities.


Metal concentrations in surface sediments of Beyler reservoir (Turkey).
The accumulation of metals (Iron, Aluminium, Zinc, Copper, Manganese, Boron, Chromium, Nickel, Cadmium, Lead) was seasonally (November 2009 to July 2010) measured in sediment samples taken from different areas of Beyler reservoir which is an important water source for irrigation in West Black Sea region (Turkey). Metals in sediment samples were analyzed by ICP-OES. The difference between the stations except for Zn metal (p < 0.05) has not been considered as important and a statistical difference between seasons for Fe, Ni metals (p < 0.01) and Cu metal (p < 0.05) has been observed. The magnitude of metal concentrations in sediment was determined as Aluminium > Iron > Manganese > Zinc > Chromium > Copper > Boron > Nickel > Lead > Cadmium. Enrichment factor (EF) for all metals has been calculated (EF < 1). In the evaluation done by considering the EF values, it is seen that the metal concentrations found in the Beyler Dam Lake sediment stem from the natural composition of the sediment.


Changing essay writing in undergraduate nursing education through action research: a Swedish example.
This article describes the development of literature-based models for bachelor degree essays in Swedish undergraduate nursing education. Students' experiences in a course with literature-based models for bachelor degree essays are discussed. The ever-growing body of nursing research and specialized and complex health care practices make great demands on nursing education in terms of preparing students to be both skilled practitioners and users of research. Teaching to help students understand evidence-based practice is a challenge for nursing education. Action research was used to generate knowledge of and practical solutions to problems in everyday locations. Six models were developed: concept analysis, contributing to evidence-based nursing by means of quantitative research, contributing to evidence-based nursing by means of qualitative research, discourse analysis, analysis of narratives, and literature review. Action research was found to be a relevant procedure for changing ways of working with literature-based, bachelor degree essays. The models that were developed increased students' confidence in writing essays and preparedness for the nursing role.


Pyloric stenosis associated with malrotation.
Three cases of pyloric stenosis associated with malrotation are presented. In one case, the diagnosis was made synchronously, and in two cases, pyloric stenosis was noted following correction of malrotation. All three patients underwent pyloromyotomy and Ladd's procedure. These cases differ from the few reported hereditary cases of pyloric stenosis associated with malrotation, which have congenitally shortened bowel, functional obstruction, and poor prognosis. The unusual finding of pyloric stenosis and malrotation occurring together in the first patient was diagnosed with upper gastrointestinal series, obtained because of a high index of suspicion despite a palpable pyloric tumor and positive ultrasound examination. The second and third cases illustrate that vomiting following Ladd's procedure may be due to pyloric stenosis. When clinical findings do not support the presumed diagnosis, further investigation prior to operation is recommended so that rare concommitant pathology can be corrected.


Nucleotide sequence of the traD region in the Escherichia coli F sex factor.
The complete nucleotide sequence has been determined of a 3635-bp region, extending from the HpaI site in traT, at F coordinate 90.3 kb, to beyond the end of traD, of the F sex factor plasmid of Escherichia coli K-12. This region contains the C-terminal coding part of traT and the entire traD gene. An open reading frame (ORF) of 2148 bp within the sequence confirms that traD encodes an 81.4-kDa cytoplasmic membrane protein. The TraD protein has several regions with an unusually high pI (greater than 10), suggesting that they may correspond to the DNA-binding domains. Several other ORFs were detected within the region including the gene (ORF1) for a 26.3-kDa protein and ORF2, probably corresponding to traI, which continues to the end of the sequence. An ORF for an 8.5-kDa protein preceded by an excellent promoter and ribosome-binding site is present in the region following traD but on the opposite strand. This promoter is thought to correspond to the major RNA polymerase binding site in this region, implying that traI does not have its own promoter. The lack of a typical terminator following traD and ORF1 and the translational coupling provided by overlapping stop and start codons is consistent with this conclusion.


[Tetany as a difficult diagnostic problem in the neurological outpatient department].
The paper presents a model of diagnostic and therapeutic management of tetany, with special attention paid the role of magnesium and to psychotherapy or psychiatric treatment. Two types of tetany are distinguished: manifest and latent (spasmophilia). The former, due to hypocalcemia, is relatively rare and usually postoperative (parathyroid tetany), while the mechanism of the much more common latent tetany or spasmophilia involves hyperventilation and magnesium deficiency. Latent tetany affects particularly young women. There are many signs of spasmophilia, but none is specific, so this pathology is difficult to diagnose.


Sensitive and selective electrochemical determination of quinoxaline-2-carboxylic acid based on bilayer of novel poly(pyrrole) functional composite using one-step electro-polymerization and molecularly imprinted poly(o-phenylenediamine).
A facile and efficient molecularly imprinted polymer (MIP) recognition element of electrochemical sensor was fabricated by directly electro-polymerizing monomer o-phenylenediamine (oPD) in the presence of template quinoxaline-2-carboxylic acid (QCA), based on one-step controllable electrochemical modification of poly(pyrrole)-graphene oxide-binuclear phthalocyanine cobalt (II) sulphonate (PPY-GO-BiCoPc) functional composite on glassy carbon electrode (GCE). The MIP film coated on PPY-GO-BiCoPc functional composite decorated GCE (MIP/PPY-GO-BiCoPc/GCE) was presented for the first time. The synergistic effect and electro-catalytic activity toward QCA redox of PPY-GO-BiCoPc functional composite were discussed using various contrast tests. Also, the effect of experimental variables on the current response such as, electro-polymerization cycles, template/monomer ratio, elution condition for template removal, pH of the supporting electrolyte and accumulation time, were investigated in detail. Under the optimized conditions, the proposed MIP sensor possessed a fast rebinding dynamics and an excellent recognition capacity to QCA, while the anodic current response of square wave voltammetry (SWV) was well-proportional to the concentration of QCA in the range of 1.0×10(-8)-1.0×10(-4) and 1.0×10(-4)-5.0×10(-4) mol L(-1) with a low detection limit of 2.1 nmol L(-1). The established sensor was applied successfully to determine QCA in commercial pork and chicken muscle samples with acceptable recoveries (91.6-98.2%) and satisfactory precision (1.9-3.5% of SD), demonstrating a promising feature for applying the MIP sensor to the measurement of QCA in real samples.


Kuru with incubation periods exceeding two decades.
The clinical characteristics of kuru in 15 patients are described. All the patients had a history of joint pains preceding difficulty walking. The severity of the neurological dysfunction varied from mild truncal and limb ataxia necessitating the use of a stick for walking to terminal illness accompanied by marked ataxia, rigidity, spasticity, and dementia. All the patients with kuru in this study had a apprehensive, frightened facial expression. Most of the patients examined showed diminished or absent optokinetic nystagmus bilaterally. Apprehensive facies and diminished optokinetic nystagmus have not previously been described in kuru. The other clinical features of the current patients with kuru are similar to those recorded twenty years ago. Epidemiological surveillance, anamnesis, and missionary reports strongly suggest that all the patients described in this study were exposed to the kuru agent more than two decades ago through ritualistic cannibalism. Thus the incubation period or time interval from exposure to the onset of clinical illness exceeds two decades, while the duration of illness is two years or less. The cause of these extraordinarily long incubation periods is unknown but may result in part from exposure to small doses of the kuru agent through an inefficient oral route.


Antifungal coatings by caspofungin immobilization onto biomaterials surfaces via a plasma polymer interlayer.
Not only bacteria but also fungal pathogens, particularly Candida species, can lead to biofilm infections on biomedical devices. By covalent grafting of the antifungal drug caspofungin, which targets the fungal cell wall, onto solid biomaterials, a surface layer can be created that might be able to provide long-term protection against fungal biofilm formation. Plasma polymerization of propionaldehyde (propanal) was used to deposit a thin (∼20 nm) interfacial bonding layer bearing aldehyde surface groups that can react with amine groups of caspofungin to form covalent interfacial bonds for immobilization. Surface analyses by x-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry confirmed the intended grafting and uniformity of the coatings, and durability upon extended washing. Testing for fungal cell attachment and ensuing biofilm formation showed that caspofungin retained activity when covalently bound onto surfaces, disrupting colonizing Candida cells. Mammalian cytotoxicity studies using human primary fibroblasts indicated that the caspofungin-grafted surfaces were selective in eliminating fungal cells while allowing attachment and spreading of mammalian cells. These in vitro data suggest promise for use as antifungal coatings, for example, on catheters, and the use of a plasma polymer interlayer enables facile transfer of the coating method onto a wide variety of biomaterials and biomedical devices.


Dosimetry of extremely-low-frequency magnetic fields.
Extrapolation of quantitative measurements across biological systems requires knowledge of field-organism interaction mechanisms. In the absence of such knowledge, one can only indicate which parameters would be important under some plausible assumptions that still lack experimental proof. In the first part of the paper it is assumed that biological effects of low intensity, extremely low frequency magnetic fields are caused by the electric fields which they induce. It is shown that detailed knowledge of electrical properties on a microscale is important to predict effects that may be due to local current density, electric field strength, surface charge distribution, and mechanical forces. In the second part of the paper, it is shown that all proposed mechanisms for direct interaction between alternating magnetic fields and cells involve also the magnitude and direction of a simultaneously present static magnetic field. Reviewed are "cyclotron resonance," quantum mechanical effects on ions weakly bound to proteins, nuclear magnetic resonance, and recent progress in magneto chemistry dealing with effects of magnetic fields of a few hundred microtesla on chemical reactions that involve free radicals.


Inhibition of K/HCO(3) cotransport in squid axons by quaternary ammonium ions.
Previous squid-axon studies identified a novel K/HCO3 cotransporter that is insensitive to disulfonic stilbene derivatives. This cotransporter presumably responds to intracellular alkali loads by moving K(+) and HCO(3)(-) out of the cell, tending to lower intracellular pH (pH(i)). With an inwardly directed K/HCO(3) gradient, the cotransporter mediates a net uptake of alkali (i.e., K(+) and HCO(3)(-) influx). Here we test the hypothesis that intracellular quaternary ammonium ions (QA(+)) inhibit the inwardly directed cotransporter by interacting at the intracellular K(+) site. We computed the equivalent HCO(3)(-) influx (J(HCO3)) mediated by the cotransporter from the rate of pH(i) increase, as measured with pH-sensitive microelectrodes. We dialyzed axons to pH(i) 8.0, using a dialysis fluid (DF) free of K(+), Na(+) and Cl(-). Our standard artificial seawater (ASW) also lacked Na(+), K(+) and Cl(-). After halting dialysis, we introduced an ASW containing 437 mm K(+) and 0.5% CO(2)/12 mm HCO(3)(-), which (i) caused membrane potential to become transiently very positive, and (ii) caused a rapid pHi decrease, due to CO(2) influx, followed by a slower plateau-phase pH(i) increase, due to inward cotransport of K(+) and HCO(3)(-). With no QA(+) in the DF, J(HCO3) was approximately 58 pmole cm(-2) sec(-1). With 400 mm tetraethylammonium (TEA(+)) in the DF, J(HCO3) was virtually zero. The apparent K(i) for intracellular TEA(+) was approximately 78 mm, more than two orders of magnitude greater than that obtained by others for inhibition of K(+) channels. Introducing 100 mm inhibitor into the DF reduced J(HCO3) to approximately 20 pmole cm(-2) sec(-1) for tetramethylammonium (TMA(+)), approximately 24 for TEA(+), approximately 10 for tetrapropylammonium (TPA(+)), and virtually zero for tetrabutylammonium (TBA(+)). The apparent K(i) value for TBA(+) is approximately 0.86 mm. The most potent inhibitor was phenyl-propyltetraethylammonium (PPTEA(+)), with an apparent K(i) of approximately 91 microm. Thus, trans-side quaternary ammonium ions inhibit K/HCO(3) influx in the potency sequence PPTEA(+) > TBA(+) > TPA(+) > TEA(+) congruent with TMA(+). The identification of inhibitors of the K/HCO(3) cotransporter, for which no inhibitors previously existed, will facilitate the study of this transporter.


Simultaneous quantification of dopamine, serotonin, their metabolites and amino acids by LC-MS/MS in mouse brain following repetitive transcranial magnetic stimulation.
Repetitive Transcranial Magnetic Stimulation (rTMS) is a form of non-invasive brain stimulation that has shown therapeutic potential for various nervous system disorders. In addition to its modulatory effects on neuronal excitability, rTMS is capable of altering neurotransmitter (e.g., glutamate, GABA, dopamine and serotonin) concentrations in cortical and subcortical brain regions. Here we used a modified liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) to quantify changes in 27 free amino acids and the monoamines: dopamine (DA), serotonin (5HT) and their metabolites (DOPAC, HVA; 5HIAA) in the mouse brain. Awake C57BL/6 J mice (either sex, 8-12 weeks old) received 10 Hz rTMS using two devices that can deliver low (LI-; 12 mT; custom built) or high (Fo8-; 1.2 T; MagVenture) intensity rTMS. Sham (unstimulated) mice were used as controls. Samples were collected immediately following a single session of rTMS or sham and processed for LC-MS/MS. The modified LC-MS/MS method used to detect DA, 5-HT and their metabolites showed good accuracy and precision with regression coefficients greater than 0.999, and an intra- and inter-day reproducibility with values < 13%. Fo8-rTMS induced a significant reduction in cortical 5-HT turnover rates, hippocampal DOPAC and an increase in striatal DOPAC concentrations. Fo8-rTMS also reduced concentrations of hippocampal α-aminoadipic acid, and striatal serine, threonine, sarcosine, aspartate and glutamate. There were no changes in the level of any compounds following LI-rTMS as compared to sham. The rapid change in monoamine turnover and amino acid concentrations following Fo8-rTMS but not LI-rTMS suggests that different stimulation parameters recruit different cellular mechanisms related to rTMS-induced plasticity. The described method can be used for the characterisation of trace levels of neurotransmitters and amino acids in brain tissue homogenates, providing a useful and precise tool to investigate localised neurotransmitter changes in animal models of health and disease.


["There is no room for more"--case report of a Kurdish adolescent with an eating disorder in relation to family background of political persecution].
Migrant families make up almost 10% of the population of the German state of Schleswig-Holstein and a significant number of patients in the clinics for paediatrics. A casuistry shall show the specific problems and needs in the psychosomatic treatment of foreign children and adolescents, especially the problems of children of political refugees. In the Clinic for Paediatrics at the University of Lübeck a task group for migration and health has been formed which deals with the special needs of these patients. A better and more specific treatment of these patients shall prevent unnecessary long stays at the clinics, false diagnoses, wrong treatments, and the chronification of illnesses in the future.


A randomized trial comparing holmium laser enucleation of the prostate with transurethral resection of the prostate for the treatment of bladder outlet obstruction secondary to benign prostatic hyperplasia in large glands (40 to 200 grams).
Holmium laser enucleation of the prostate (HoLEP) is a surgical treatment for bladder outlet obstruction secondary to benign prostatic hyperplasia. HoLEP is a transurethral procedure that uses the holmium laser fiber (wavelength 2,140 nm) to dissect whole prostatic lobes off of the surgical capsule in retrograde fashion, while maintaining excellent hemostasis. The lobes are removed from the bladder by a purpose built transurethral morcellator, which means that large volume prostates can be enucleated endoscopically. We compared this procedure with transurethral prostate resection (TURP) in a randomized trial by evaluating outcomes in patients with a prostate volume of 40 to 200 ml on transrectal ultrasound. A total of 61 patients with urodynamically proved bladder outlet obstruction secondary to benign prostatic hyperplasia were randomized to TURP or HoLEP. Perioperative parameters recorded included resectoscope, laser, electrocautery, morcellation and catheter time, hospital stay, bladder irrigation, volume blood transfusion the rate and resected tissue weight. Patients were followed 1, 3, 6 and 12 months postoperatively with peak urinary flow rate measurement and quality of life and American Urological Association symptom scores. Patients also underwent urodynamic assessment at 6 months with measurement of peak detrusor pressure at maximal flow, post-void residual volume and prostate volume by transrectal ultrasound. Continence, potency and all adverse events were recorded at each visit. HoLEP was superior to TURP in terms of mean catheter time (17.7 +/- 0.7 vs 44.9 +/- 10 hours) and hospital stay (27.6 +/- 2.7 vs 49.9 +/- 5.6 hours) but it required more time to perform (62.1 +/- 5.9 vs 33.1 +/- 3.7 minutes). More prostate tissue was removed in the HoLEP group (40.4 +/- 5.7 vs 24.7 +/- 3.4 gm). HoLEP was also superior to TURP in terms of relieving urodynamic obstruction at 6 months of followup (postoperative detrusor pressure at maximum flow 20.8 +/- 2.8 vs 40.7 +/- 2.7 cm H2O). HoLEP and TURP led to significant improvements in peak flow rates, symptom scores and quality of life scores compared with baseline and there was no significant difference between the 2 procedures with respect to these parameters at 12 months. Fewer adverse events were recorded in the HoLEP group. HoLEP is superior to TURP for relieving bladder outlet obstruction in men with benign prostatic hyperplasia. It allows more rapid catheter removal and hospital discharge. It requires more time to perform than TURP but more prostate tissue is removed, resulting in similar efficiency in tissue retrieval. HoLEP is equivalent to TURP in relieving men of lower urinary tract symptoms and in improving peak urinary flow rates at 12 months of followup.


Calorimetric studies on the phenolic glycoside D(-)-salicin.
A pure orthorhombic phase sample of D(-)-salicin was purified and characterized for calorimetric measurements. From differential scanning calorimetry (DSC) measurements it was found that the onset and maximum temperatures of the fusion peak were T(on) = (473.30 +/- 0.05) K and T(max) = (474.74 +/- 0.05) K, respectively, and that the corresponding standard enthalpy of fusion was Delta(cr)(l) H(m)(o) = (55.5 +/- 0.4) kJ mol(-1). From the last two values the standard entropy of fusion is calculated as Delta(cr)(l) S(m)(o) = (116.9 +/- 0.4) J mol(-1) K(-1). The standard molar enthalpy of formation of orthorhombic D(-)-salicin at T = 298.15 K, was determined as Delta(f) H(m)(o) (C(13)H(18)O(7), cr, orthorhombic) = -(1366.9 +/- 3.2) kJ mol(-1), by combustion calorimetry. From the results of solution calorimetry obtained in this work and some auxiliary values taken from the literature the enthalpy of reaction of hydrolysis of D(-)-salicin to produce beta-glucose and o-hydroxybenzyl alcohol was found marginally thermoneutral, if the uncertainty interval was considered. Additionally, specific heat capacity measurements on the orthorhombic phase, glass and liquid-quenched glass obtained by DSC was reported.


Febrile temperature reprograms by redox-mediated signaling the mitochondrial metabolic phenotype in monocyte-derived dendritic cells.
Fever-like hyperthermia is known to stimulate innate and adaptive immune responses. Hyperthermia-induced immune stimulation is also accompanied with, and likely conditioned by, changes in the cell metabolism and, in particular, mitochondrial metabolism is now recognized to play a pivotal role in this context, both as energy supplier and as signaling platform. In this study we asked if challenging human monocyte-derived dendritic cells with a relatively short-time thermal shock in the fever-range, typically observed in humans, caused alterations in the mitochondrial oxidative metabolism. We found that following hyperthermic stress (3h exposure at 39°C) TNF-α-releasing dendritic cells undergo rewiring of the oxidative metabolism hallmarked by decrease of the mitochondrial respiratory activity and of the oxidative phosphorylation and increase of lactate production. Moreover, enhanced production of reactive oxygen and nitrogen species and accumulation of mitochondrial Ca2+ was consistently observed in hyperthermia-conditioned dendritic cells and exhibited a reciprocal interplay. The hyperthermia-induced impairment of the mitochondrial respiratory activity was (i) irreversible following re-conditioning of cells to normothermia, (ii) mimicked by exposing normothermic cells to the conditioned medium of the hyperthermia-challenged cells, (iii) largely prevented by antioxidant and inhibitors of the nitric oxide synthase and of the mitochondrial calcium porter, which also inhibited release of TNF-α. These observations combined with gene expression analysis support a model based on a thermally induced autocrine signaling, which rewires and sets a metabolism checkpoint linked to immune activation of dendritic cells.


Indirect estimation of pediatric between-individual biological variation data for 22 common serum biochemistries.
Derivation of between-individual biological variation (CVg) data requires repeat sampling of the same subject, which is undesirable and challenging in children. We describe an indirect sampling (data mining) approach to obtain these data in children. Twenty-two serum biochemistry results from 6,989 children, who visited their primary care physician in Queensland, Australia, and were tested only twice within a year were included. The CVg and index of individuality of the boys and girls were estimated by year of age, according to the procedures recommended by Fraser and Harris. The CVg was generally higher during the first year of life and declined to reach a constant level by age 4 to 6 years, except for aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, and phosphate. The CVg for these tended to increase after age 10 years. Most of the serum biochemistries examined in this study had indices of individuality 0.6 or less, except sodium, anion gap, bicarbonate, and chloride, which ranged from 0.6 to 1.4. The indices of individuality were very stable across all ages. These data are comparable to those reported by the Canadian Laboratory Initiative on Pediatric Reference Intervals study and the Ricos database for adults. This study reports the CVg trends and data for boys and girls by year of age, which have not been described previously.


The therapeutic effect of natriuretic peptides in heart failure; differential regulation of endothelial and inducible nitric oxide synthases.
The abnormal regulation of nitric oxide synthase activity represents an underlying feature of heart failure. Increased peripheral vascular resistance, and decreased renal function may be in part related to impaired endothelium-dependent nitric oxide (NO) synthesis. Paradoxically, the chronic production of NO by inducible nitric oxide synthase (iNOS) in heart failure exerts deleterious effects on ventricular contractility, and circulatory function. Consequently, pharmacologically improving endothelium-dependent NO synthesis and the concomitant inhibition of iNOS activity would be therapeutically advantageous. Interestingly, natriuretic peptides have been shown to differentially regulate endothelial NOS (eNOS) and iNOS activity. Moreover, in both patients and animal models of heart failure, pharmacologically increasing plasma natriuretic peptide levels ameliorated vascular tone, renal function, and ventricular contractility. Based on these observations, the following review will explore whether the therapeutic benefit of the natriuretic peptide system in heart failure may occur in part via the amelioration of endothelium-dependent NO synthesis, and the concomitant inhibition of cytokine-mediated iNOS expression.


α-Melt Structure of 1,3-Dipalmitoyl-2-oleoyl-sn-glycerol (POP) under a Thermal Thawing Process Studied by Infrared Spectroscopy.
The temperature thawing, as called tempering, of triacylglycerols (TAGs) is an important processing method in food productions, such as chocolates, cream, confections, and spreads. Especially, melt-mediation by temperature thawing is famous in chocolate production for controlling the polymorphic crystalline forms and accelerating crystallization. In the present study, we investigated the α-melt structure of 1,3-dipalmitoyl-2-oleoyl-sn-glycerol (POP), one of the major continuants of cacao butter, under a phase transition from its melt to γ-crystal with in-situ attenuated total reflection-infrared (ATR-IR) spectroscopy. The differential IR spectrum between α-melt via temperature thawing (α-melt mediation) and melt via simple cooling revealed that crystal-like local ordered structures remained in part in the α-melt, and that they acted as nuclei for a rapid phase transition to the γ-crystal. The changes to the γ-crystal occur in the local ordered structures at first from the glycerol moiety to the acyl chains in the crystallization, providing an important suggestion concerning the mechanism for the acceleration of crystallization to the γ-form via α-melt mediation.


Hereditary of the three enzyme systems EsD, Gt and GLO in the Polish population. The family studies and mother/child combinations.
Hereditary of the three enzyme systems EsD, Gt and GLO was studied in families and mother/child combinations. EsD types were determined in 88 families with 197 children and 1813 mother/child combinations. Gt types were studied in 78 families with 174 children and 114 mothers with one child. GLO types were determined in 82 families with 180 children and 298 mother/child pairs. The segregation in the different family combinations is in accordance with the simple formal model of two alleles at the autosomal loci.


Cutaneous gnathostomiasis in a woman from Bangladesh.
A woman from Bangladesh who had lived in Germany for more than 2 years presented with migratory, painful swellings on her left hand and arm of 5 months duration. Laboratory examinations yielded a marked eosinophilia and a grossly elevated IgE level in combination with an inflammatory reaction restricted to the subcutaneous tissues. A preliminary diagnosis of gnathostomiasis was established and confirmed by a positive gnathostoma serology by enzyme immunoassay (EIA). Treatment was initiated with albendazole, leading to the outward migration of a larva and complete resolution of clinical disease. Currently, there is no definitive therapy that has been proved to be both safe and highly effective. A wide range of potential agents has been used in clinical studies, but only albendazole has proved to be reliably effective to date, stimulating the outward migration of larvae in a proportion of cases of cutaneous disease, as observed in the present case.


A computer model study of the ventricular fibrillation vulnerable window: sensitivity to regional conduction depressions.
The cardiac vulnerable window is typically defined to be that portion of the cardiac cycle during which ectopic stimuli can induce ventricular fibrillation (VF). We have used cardiac electrophysiological computer modeling to investigate how the size and shape of the cardiac vulnerable window is affected by regional conduction velocity depressions (RCVDs), as might be found in ischemia. Computer simulations were performed on a three-dimensional finite-state, discrete-element model of the ventricles of a dog heart, with simulated RCVDs of 0% (normal) to 100% (infarcted) isolated to the apical region of this heart. Using a programmed electrical stimulation protocol, vulnerability was quantified as the number of ectopic stimuli necessary to induce VF. We observed a nonlinear and nonmonotonic relation between increases in RCVD and the vulnerability of the heart to ectopic stimuli. The size and shape of the vulnerable window remained stable through RCVDs of 30%, expanded rapidly thereafter through RCVDs of 90%, and then contracted significantly at the RCVD of 100%. These increases in vulnerability were manifest as both a lowering of the overall stimulus thresholds necessary for fibrillation (window "deepening"), and an increase in the fraction of the cardiac cycle susceptible to these ectopic stimuli (window "widening"). In all cases of induced VF, the mechanism of induction was through reentry facilitated by temporary functional block. Moreover, the ability to form such a block--and thus the likelihood of subsequent VF--was enhanced as the RCVD increased. Taken together, these results demonstrate the complex relation between vulnerability and RCVD and, at the very least, suggest that the entire shape of the vulnerable window, rather than just its minimum threshold, is important when determining a heart's electrical stability. These conclusions are supported by results obtained from an experimental study--which utilized a similar programmed stimulation protocol--of normal and ischemic canine hearts.


Absence of phosphorylation of retinoid-binding proteins by protein kinase C in vitro.
Cellular retinol-binding protein, cellular retinoic acid-binding protein, and fetal cellular retinol-binding protein were purified to homogeneity and each polypeptide had a molecular weight of 16,000. Their apoproteins were not phosphorylated under the same conditions. Their holoproteins did not inhibit the phosphorylation of histone III-S by protein kinase C. Each of these observations is contrary to the results reported by Cope et al. (Biochem. Biophys. Res. Commun., 120, 593-601, 1984).


Emotional effects of hypospadias surgery on Turkish boys.
The aim of this study is to investigate in Turkish boys the emotional effects of hypospadias repair before and after the optimal age for repair. Forty hypospadias patients treated in our department were included in this study. Group 1 consisted of 13 patients operated on at less than 30 months of age. Group 2 consisted of 27 patients operated on at over 30 months of age. Age at time of study, severity of hypospadias, age at repair and number of operations were evaluated for both groups retrospectively. Socio-economic and socio-demographic characteristics of these patients including place of residence, educational level of their parents and parental occupations were determined. The Turkish versions of the Children's Depression Inventory and the State-Trait Anxiety Inventory for Children A-State scale were used to evaluate the emotional effects of hypospadias surgery. For statistical analysis, the Mann-Whitney U test, Student's t test and Chi-squared test were used. There was a significant difference in the age at repair between Groups 1 and 2. No significant differences existed in severity of hypospadias and number of operations between the two groups. All 40 patients had the same socio-economic and socio-demographic characteristics. Group 1 did not significantly differ from Group 2 in regard to the educational level of their parents and parental occupations. Age at repair, which was the only difference between the two groups, did not affect the level of depression and anxiety-state symptoms. There is a close relationship between emotional effect of hypospadias surgery and age at repair. Possibility of depression and anxiety, which were dominating emotional symptoms among boys operated on for hypospadias, was found not to be high after the recommended age. It is concluded that, as hypospadias surgery creates a circumcised penis, the degree of emotional trauma is lower in Turkish boys than in other nationalities.


Physics of SrTiO3-based heterostructures and nanostructures: a review.
1 Overview 1
 1.1 Introduction 1
 1.1.1 Oxide growth techniques are rooted in search for high-Tc superconductors 2
 1.1.2 First reports of interface conductivity 2
 1.2 2D physics 2
 1.3 Emergent properties of oxide heterostructures and nanostructures 3
 1.4 Outline 3
 2 Relevant properties of SrTiO3 3
 2.1 Structural properties and transitions 3
 2.2 Ferroelectricity, Paraelectricity and Quantum Paraelectricity 4
 2.3 Electronic structure 5
 2.4 Defects 6
 2.4.1 Oxygen vacancies 6
 2.4.2 Terraces 7
 2.5 Superconductivity 7
 3 SrTiO3-based heterostructures and nanostructures 8
 3.1 Varieties of heterostructures 8
 3.1.1 SrTiO3 only 9
 3.1.2 LaAlO3/SrTiO3 9
 3.1.3 Other heterostructures formed with SrTiO3 10
 3.2 Thin-film growth 10
 3.2.1 Substrates 10
 3.2.2 SrTiO3 surface treatment 11
 3.2.3 Pulsed Laser Deposition 11
 3.2.4 Atomic Layer Deposition 13
 3.2.5 Molecular Beam Epitaxy 14
 3.2.6 Sputtering 15
 3.3 Device Fabrication 15
 3.3.1 "Conventional" photolithography - Thickness Modulation, hard masks, etc. 15
 3.3.2 Ion beam irradiation 16
 3.3.3 Conductive-AFM lithography 16
 4 Properties and phase diagram of LaAlO3/SrTiO3 16
 4.1 Insulating state 16
 4.2 Conducting state 17
 4.2.1 Confinement thickness (the depth profile of the 2DEG) 17
 4.3 Metal-insulator transition and critical thickness 18
 4.3.1 Polar catastrophe ( electronic reconstruction) 18
 4.3.2 Oxygen Vacancies 19
 4.3.3 Interdiffusion 20
 4.3.4 Polar Interdiffusion + oxygen vacancies + antisite pairs 20
 4.3.5 Role of surface adsorbates 21
 4.3.6 Hidden FE like distortion - Strain induced instability 21
 4.4 Structural properties and transitions 21
 4.5 Electronic band structure 22
 4.5.1 Theory 22
 4.5.2 Experiment 23
 4.5.3 Lifshitz transition 24
 4.6 Defects, doping, and compensation 25
 4.7 Magnetism 25
 4.7.1 Experimental evidence 25
 4.7.2 Two types of magnetism 27
 4.7.3 Ferromagnetism 27
 4.7.4 Metamagnetism 28
 4.8 Superconductivity 28
 4.9 Optical properties 29
 4.9.1 Photoluminesce experiments 29
 4.9.2 Second Harmonic Generation 29
 4.10 Coexistence of superconductivity and magnetism 30
 4.11 Magnetic and conducting phases 30
 5 Quantum transport in LaAlO3/SrTiO3 heterostructures and microstructures 31
 5.1 2D transport 31
 5.2 Inhomogeneous Transport 31
 5.3 Anisotropic Magnetoresistance 32
 5.4 Spin-orbit coupling 32
 5.5 Anomalous Hall Effect 34
 5.6 Shubnikov-de Haas (SdH) Oscillation 35
 5.7 Quantum Hall Effect 37
 5.8 Spintronic Effects 38
 6 Quantum transport in LaAlO3/SrTiO3 nanostructures 39
 6.1 Quasi-1D Superconductivity 39
 6.2 Universal conductance fluctuations 40
 6.3 Dissipationless Electronic Waveguides 40
 6.4 Superconducting Quantum Interference Devices (SQUID) 41
 6.5 Electron pairing without superconductivity 41
 6.6 Tunable Electron-Electron Interaction 42
 7 Outlook 43
 7.1 Outstanding physics questions 43
 7.1.1 Polar catastrophe (not) 43
 7.1.2 Coexistence of phases 43
 7.1.3 Novel superconducting states (e.g., FFLO, other pairing symmetries) 43
 7.1.4 Magnetism mechanism 43
 7.1.5 Exotic phases (eg. Majorana physics) 43
 7.1.6 Luttinger liquids 44
 7.2 Future applications 44
 7.2.1 Spintronics 44
 7.2.2 Quantum simulation 44
 7.2.3 Qubits/quantum computing 44
 7.2.4 Sensing 44
 8 Figures 45
 9 Reference 6.


Spectroelectrochemistry study on the electrochemical reduction of ethidium bromide.
The electrochemical reduction mechanism of ethidium bromide was first studied by spectroelectrochemistry. This reduction was proved to be a two-step process by cyclic voltammetry, differential pulse voltammetry and spectroelectrochemistry, in which each step was proved to be a one-electron transfer process by a spectropotentiostatic fluorescence technique. Hydroethidine was confirmed to be the final product by comparing the spectrum of the product of the electrochemical reduction to that of the product of the chemical reduction of ethidium bromide, and a carbon-centered radical was concluded to be a reasonable intermediate product during the electrochemical reduction of ethidium bromide.


Comparison of current staging systems for advanced hepatocellular carcinoma not amendable to locoregional therapy as inclusion criteria for clinical trials.
The prognosis of patients with advanced hepatocellular carcinoma (HCC) is poor and testing drug efficacy in clinical trials is hazardous. This study was aimed to evaluate different prognostic scoring systems for HCC in estimating prognosis (3-month survival and overall survival (OS)). From November 2008 to April 2010, 208 patients with advanced HCC who were not amendable to locoregional therapy were included in this study. Data were collected to classify patients according to the following: the Japanese integrated staging scoring system, TNM stage by the Liver Cancer Study Group of Japan criteria, TNM 6th edn, the cancer of the liver Italian program scoring system (CLIP), the advanced liver cancer prognostic system (ALCPS), the model of end-stage liver disease, the Groupe d'étude et de Traitement du Carcinome Hepatocellulaire (GETCH) scoring system, the Chinese University prognostic index staging system (CUPI), the Okuda scoring system, the Child-Pugh score, the Tokyo scoring system and the Barcelona Clinic liver cancer staging. Survival analysis and relative operating characteristic (ROC) were utilized to access the prognostic value of each scoring system. ALCPS performed best, with the largest area under the ROC curve in predicting 3-month OS (sensitivity 76.32%, specificity 78.72%). CLIP and CUPI were similar to ALCPS in prognostic discrimination but with relatively lower power. ALCPS, CLIP and CUPI are the preferred scoring systems in the prediction of OS and 3-month survival among the 12 systems analyzed, and should be used as inclusion criteria in clinical trials for advanced HCC patients.


The risk factors for the development of complications during the recovery phase following blunt chest wall trauma: a retrospective study.
The difficulties in the management of the blunt chest wall trauma patient in the Emergency Department (ED) due to the development of late complications are well recognised in the literature. The aim of this study was to investigate the risk factors for the development of complications in the recovery phase following blunt chest wall trauma. A retrospective study was completed in which the medical notes were analysed of all blunt chest wall trauma patients presenting to a large trauma centre in South Wales in 2009 and 2010. Using univariate and multivariable logistic regression analysis, the risk factors for development of complications during the recovery phase following blunt chest wall trauma were investigated. Risk factors for development of complications in the recovery phase following blunt chest wall trauma in the univariate analysis were a patient age of 65 years or more, three or more rib fractures, presence of chronic lung disease or cardiovascular disease, pre-injury anticoagulant use and blood oxygen saturation levels of less than 90%. On multivariable analysis, the risk factors were three or more rib fractures, chronic lung disease, pre-injury anticoagulant use and oxygen saturations of less than 90%. A number of risk factors have been presented in this study which should be considered in the management of the blunt chest wall trauma patient. This is the first study in which a number of the risk factors have been investigated and this may provide the basis for further prospective studies.


[Zinc protoporphyrin (ZPP) in diagnosis of anemia].
In iron deficiency, zinc protoporphyrin (ZPP) is produced instead of heme, and the ZPP concentration in erythrocytes increased (normal value < 2.3 micrograms ZPP/g Hb). The ZPP level and comparison with the other normally used tests in iron deficiency in the group of the patients with iron deficiency, ACD, MDS, AML, plasmocytoma was investigated. The ZPP level was determined by hematofluorometry in samples from 96 patients. Thirty five patients with iron depletion showed decreased both serum ferritin (median 5.9 ng/ml), and hemoglobin level (median 9.8 g/dl) with significantly increased ZPP level (median 8.5 micrograms/gHb). An increased level of ZPP (median 3.95 micrograms/gHb) with normal level of ferritin (median 24 ng/ml) and iron (median 50 (g/dl) in the serum of patients with ACD was determined. Measurement of ZPP level in the combination with ferritin and peripheral blood morphology allows to classify the degree of iron deficiency. The ZPP levels higher than 4.55 micrograms/gHb confirms iron deficiency in the group of anaemic patients.


[Clinico-pathologic analysis of 26 cases of leiomyoma of the vagina].
To study the clinicopathological features, the histogenesis, and the correlation between the expressions of estrogen receptor(ER) and epidermal growth factor receptor(EGFR) in leiomyoma of the vagina. The data of 26 patients with leiomyoma of the vagina were analyzed retrospectively, and S-P immunohistochemistry was used to detect smooth muscle actin(SMA), S-100 protein, CD34, ER and EGFR in the tumor tissues. All patients with leiomyoma of the vagina in this group were married women, with age ranging from 30 to 52 years (mean, 44.5 years). Leiomyoma of the vagina was slow in growth and occasionally recurred with borderline and malignant transformation. Immunohistochemical staining demonstrated to be strongly positive for SMA, and negative for S-100 protein and CD34 in all cases. Positive expression rates for ER and EGFR were 38.5 (10/26) and 34.6 (9/26) respectively. There was a significant positive correlation between the expressions of ER and EGFR (Fisher exact, P = 0.0023, r = 0.75). Resection of the tumor mass was an effective method to cure the disease. Leiomyoma of the vagina is a rare condition, which may be derived from stem cells of mesenchyma of the vagina differentiating towards smooth muscle. The estrogen hormone and EGF may play an important role in the development and growth of leiomyoma of the vagina. Follow-up is needed after operation for the patient with borderline tumor.


A real-time inspection system using a terahertz technique to detect microleak defects in the seal of flexible plastic packages.
A method to detect production faults in flexible plastic packages with the use of terahertz radiation is presented. Relying on the large difference between the absorption coefficients of plastic and water (for water-filled channel defects) and on the refraction index difference between plastic and air (for air-filled channel defects), our technique consists of focusing and scanning a terahertz beam on the sealed area of the package, followed by detection of the transmitted signal. Compared with previous methods, such as visual and ultrasound inspection, our technique can be applied to optically opaque packages and does not require immersion in a matching liquid. We tested our system on defects that we fabricated as water-filled and air-filled channels imbedded in polyethylene films, with diameters in the range of 10 to 100 microm. The detection limit (the minimum size of a detectable defect) depends on the conveying speed; this relationship was determined and analyzed. The results show that our system has the potential for application in an actual production line for real-time inspection.


The three R's of writing: reading, "riting," and risking.
The mere thought of writing an article can be intimidating. But, even if you have the desire, despite the fear, to write an article, how do you get started? How can you produce satisfying work? Is there a way to begin writing, get your ideas down, and save judgments and editing for alter? Here are some steps--Reading, "Riting," and Risking--to help you write that article you've been thinking about. By separating the process into two stages, creativity or freewriting, and then criticism or editing, you'll find writing much easier.


Bright thermal (blackbody) emission of visible light from LnO2 (Ln = Pr, Tb), photoinduced by a NIR 980 nm laser.
The increasing demand for renewable energy has been promoting a rapid development of photovoltaic technologies. Given this, photoinduced thermal emission is being explored with the aim of improving solar cell performance by converting low-energy IR photons into visible light. Here, we report the light-induced blackbody emission from LnO2 (Ln = Pr and Tb) as a potential emitter for thermophotovoltaic applications. Lanthanide dioxides display broad IR absorption and a direct optical band gap of 1.49 (PrO2) and 1.51 eV (TbO2). These materials achieve a maximum temperature of ∼1500 K under a power density excitation of 160 W cm-2 and display a stable bright light emission. Thermal emission can be tuned from laser power density modulation.


Efficacy of conservative treatment, without necrosectomy, for infected pancreatic necrosis: a systematic review and meta-analysis.
Conservative treatment (intensive care, a combination of antimicrobial agents, and nutritional support, with or without drainage of the infected fluid) has recently been shown to be effective for patients with infected pancreatic necrosis (IPN), but the data from individual studies are not robust enough to recommend it as the standard of care. We performed a systematic review and meta-analysis of studies related to primary conservative management for IPN. We performed a literature search of MEDLINE/PubMed from January 1990 to March 2012 for studies of a priori protocols for primary conservative treatment, without necrosectomy, for consecutive patients with IPN. We analyzed data from 8 studies, comprising 324 patients with IPN who received primary conservative management. We then analyzed an additional 4 studies (comprising 157 patients) that reported the efficacy of percutaneous drainage in nonconsecutive patients with IPN. Outcome measures were the success of conservative management strategy, need for necrosectomy, and mortality. There was significant heterogeneity in results among the studies. Based on a random effects model, conservative management was successful for 64% of patients (95% confidence interval [CI], 51%-78%); mortality was 12% (95% CI, 6%-18%), and 26% of patients required necrosectomy or additional surgery for complications (95% CI, 15%-37%). A separate analysis of 4 studies that reported outcomes of nonconsecutive patients with IPN following percutaneous drainage had comparable results; 50% had successful outcomes (95% CI, 43%-58%), mortality was 18% (95% CI, 6%-30%), and 38% of patients required surgery (95% CI, 20%-56%). Conservative management without necrosectomy is a successful approach for 64% of patients with IPN. This approach has low mortality and prevents surgical necrosectomy.


Identification of a chemokine receptor encoded by human cytomegalovirus as a cofactor for HIV-1 entry.
The human cytomegalovirus encodes a beta-chemokine receptor (US28) that is distantly related to the human chemokine receptors CCR5 and CXCR4, which also serve as cofactors for the entry into cells of human immunodeficiency virus-type 1 (HIV-1). Like CCR5, US28 allowed infection of CD4-positive human cell lines by primary isolates of HIV-1 and HIV-2, as well as fusion of these cell lines with cells expressing the viral envelope proteins. In addition, US28 mediated infection by cell line-adapted HIV-1 for which CXCR4 was an entry cofactor.


Risk of preterm birth, low birthweight and small-for-gestational-age infants in pregnancies with adenomyosis: A cohort study of the Japan Environment and Children's Study.
This study evaluated the risk of preterm birth, low birthweight and small-for-gestational-age neonates born to mothers with adenomyosis during pregnancy. We used the results of a Japanese nationwide prospective birth cohort study, identifying 93 668 singleton deliveries from 2011 to 2014. We identified 314 pregnancies with adenomyosis using self-reported questionnaires. Multiple logistic regression analyses were conducted to examine whether adenomyosis was associated with adverse pregnancy outcome. Maternal age, smoking status, method of conception, history of parity, fibroids, endometriosis and body mass index before pregnancy were analyzed as confounding factors. Multiple logistic regression analysis showed that pregnancy with adenomyosis was a risk factor for preterm birth at less than 37 weeks (adjusted odds ratio [aOR: 2.49, 95% confidence interval [CI] 1.89-3.41), preterm birth at less than 34 weeks (aOR 1.91, 95% CI 1.02-3.55), low birthweight <2500 g (aOR 1.83, 95% CI 1.36-2.45), low birthweight <1500 g (aOR 2.39, 95% CI 1.20-4.77) and small-for-gestational-age neonates (aOR 1.68, 95% CI 1.13-2.51). This study found that pregnancy with adenomyosis was associated with preterm birth, low birthweight and small-for-gestational-age neonates.


Dielectric properties of conductively loaded polyimides in the far infrared.
The dielectric properties of selected conductively-loaded polyimide samples are characterized in the microwave through far-infrared wavebands. These materials, belonging to the Vespel family, are more readily formed by direct machining than their ceramic-loaded epoxy counterparts and present an interesting solution for realizing absorptive optical control structures. Measurements spanning a spectral range from 1 to 600 cm-1 (0.03-18 THz) were performed and used in parametrization of the media's dielectric function at frequencies below ≈3 THz.


Prevalence and clinical characteristics of body dysmorphic disorder in adolescent inpatient psychiatric patients-a pilot study.
Background: Body dysmorphic disorder (BDD) is preoccupation with perceived body defects leading to distress and impairment in social functioning. Most of adolescent BDD literature has been done on patients within the outpatient setting with prior versions of DSM with dearth of information about BDD and comorbid psychiatric conditions among adolescents within the inpatient setting. Aims: This pilot study evaluated the prevalence rate, clinical characteristics in adolescent BDD compared to non-BDD adolescents in a psychiatric in patient setting in addition to their comorbid issues like anxiety, OCD, ADHD and substance abuse. Methods: Forty-five consecutively admitted adolescent patients participated with 17 meeting the DSM 5 criteria for BDD while 28 did not. Patients were asked four questions designed around the DSM-5 criteria for BDD after which they were asked to complete questionnaires like BDDQ child and adolescent version, BDDM, Multiaxial Anxiety Scale for Children, Children's Depression Inventory, Y-BOCS and Vanderbilt ADHD rating scales. Results: Seventeen participants had BDD. Mean age of BDD patients was 13.1 while non-BDD was 12.4. Male patients with BDD were seven (41%) while female BDD patients were 10 (58.8%). Anxiety, depression, OCD and substance use disorders were common comorbid diagnoses. Majority of patients in the BDD group classified their BDD as a severe problem with more BDD, patient's considering suicide because of their BDD. Discussion: BDD is present in adolescents admitted in inpatient psychiatric hospital with more female patients endorsing BDD versus their male counterparts. Patients with BDD are more likely to endorse more comorbid psychiatric issues such as anxiety, OCD, ADHD and substance abuse.


Induction of cyclooxygenase-2 by staurosporine through the activation of nuclear factor for IL-6 (NF-IL6) and activator protein 2 (AP2) in an osteoblast-like cell line.
The induction of cyclooxygenase-2 (COX-2) plays a crucial role in many physiological and pathological processes. The expression of the COX-2 gene is regulated by many extracellular stimuli, including growth factors, cytokines, and tumor promoters. Staurosporine, a potential anti-tumor drug, was found recently to up-regulate the expression of the COX-2 gene in the mouse osteoblast-like cell line MC3T3-E1. The ability of staurosporine to induce the expression of the COX-2 gene was investigated using luciferase reporters controlled by various COX-2 core promoter regions. Two cis-acting sites for activator protein 2 (AP2) and nuclear factor for IL-6 (NF-IL6), respectively, were identified as responsible for the staurosporine-mediated COX-2 up-regulation. Mutational analysis further verified that both NF-IL6 and AP2 are involved in this process. Further studies showed the stimulatory effect of staurosporine on luciferase activity to be both time- and concentration-dependent. Luciferase activity could be induced at as low as 5 nM staurosporine and reached a maximum at around 20 nM. At 50 nM, the stimulatory effect of staurosporine on luciferase activity reached a maximum at about 8 hr and fell rapidly following 10 hr of incubation. Interestingly, a selective protein kinase C inhibitor, 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl) maleimide (GF109203X), failed to stimulate luciferase activity under the same conditions. This finding implies that staurosporine-mediated COX-2 gene expression is specific and independent of protein kinase C activity.


Maternal obesity leads to long-term altered levels of plasma ceramides in the offspring as revealed by a longitudinal lipidomic study in children.
Maternal obesity is associated with increased risk of obesity and other symptoms of the metabolic syndrome in the offspring. Nevertheless, the molecular mechanisms and cellular factors underlying this enhanced disease susceptibility remain to be determined. Here, we aimed at identifying changes in plasma lipids in offspring of obese mothers that might underpin, and serve as early biomarkers of, their enhanced metabolic disease risk. We performed a longitudinal lipidomic profiling in plasma samples from normal weight, overweight, and obese pregnant women and their children that participated in the Prenatal Omega-3 Fatty Acid Supplementation, Growth, and Development trial conducted in Mexico. At recruitment women were aged between 18 and 35 years and in week 18-22 of pregnancy. Blood samples were collected at term delivery by venipuncture from mothers and from the umbilical cord of their newborns and from the same infants at 4 years old under non-fasting conditions. Lipidomic profiling was done using ultra-performance liquid chromatography high-resolution mass spectrometry. Analysis of the lipidomic data showed that overweight and obese mothers exhibited a significant reduction in the total abundance of ceramides (Cer) in plasma, mainly of Cer (d18:1/20:0), Cer (d18:1/22:0), Cer (d18:1/23:0), and Cer (d18:1/24:0), compared with mothers of normal body weight. This reduction was confirmed by the direct quantification of these and other ceramide species. Similar quantitative differences in the plasma concentration of Cer (d18:1/22:0), Cer (d18:1/23:0), and Cer (d18:1/24:0), were also found between 4-year-old children of overweight and obese mothers compared with children of mothers of normal body weight. Noteworthy, children exhibited equal daily amounts of energy and food intake independently of the BMI of their mothers. Maternal obesity results in long-lasting changes in plasma ceramides in the offspring suggesting that these lipids might be used as early predictors of metabolic disease risk due to maternal obesity.


Surfactant alterations following donation after cardiac death donor lungs.
The use of lungs from donation after cardiac death (DCD) donors is one of the strategies to increase the donor pool. The aim of this study was to assess the surfactant alterations in DCD donor lungs. Pigs were sacrificed and left untouched for 1 (DCD1), 2 (DCD2) and 3 (DCD3) h. Lungs were then topically cooled with saline for 1, 2 or 3 h to reach a total ischemic time of 4 h. Heart-beating donors (HBD) served as control group. Bronchoalveolar lavage (BAL) samples were assessed for protein levels and surfactant function. Left lungs were prepared for ex-vivo evaluation. Pulmonary vascular resistance (PVR), oxygenation, airway pressure (AWP) and wet-to-dry weight ratio were significantly different between HBD and DCD3 groups (P < 0.05). BAL protein levels were statistically higher in DCD3 compared with HBD group (P < 0.05). Surface tension and surface tension measured at minimal bubble diameter (adsorption) were lower in HBD compared with DCD groups (P < 0.05). Adsorption was also lower in DCD1 compared with DCD2 (P < 0.05). Adsorption and surface tension were correlated with oxygenation and AWP (P < 0.05). This study has shown that lung function deteriorates with increasing warm ischemic time intervals. BAL protein, surface tension, adsorption, peak AWP and PVR increase significantly after 2 h of warm ischemia together with a significant reduction of the ratio PaO(2)/FiO(2).


The need for feasible compromises on conscientious objection: response to Card.
Robert Card criticises our proposal for managing some conscientious objections in medicine. Unfortunately, he severely mischaracterises the nature of our proposal, its scope and its implications. He also overlooks the fact that our proposal is a compromise designed for a particular political context. We correct Card's mischaracterisations, explain why we believe compromise is necessary and explain how we think proposed compromises should be evaluated.


Temporal recalibration of motor and visual potentials in lag adaptation in voluntary movement.
Adaptively recalibrating motor-sensory asynchrony is critical for animals to perceive self-produced action consequences. It is controversial whether motor- or sensory-related neural circuits recalibrate this asynchrony. By combining magnetoencephalography (MEG) and functional MRI (fMRI), we investigate the temporal changes in brain activities caused by repeated exposure to a 150-ms delay inserted between a button-press action and a subsequent flash. We found that readiness potentials significantly shift later in the motor system, especially in parietal regions (average: 219.9 ms), while visually evoked potentials significantly shift earlier in occipital regions (average: 49.7 ms) in the delay condition compared to the no-delay condition. Moreover, the shift in readiness potentials, but not in visually evoked potentials, was significantly correlated with the psychophysical measure of motor-sensory adaptation. These results suggest that although both motor and sensory processes contribute to the recalibration, the motor process plays the major role, given the magnitudes of shift and the correlation with the psychophysical measure.


Surface cleanser.
A disinfectant supplier has claimed a new breakthrough with the first: 'Single means available for safe, effective disinfection and cleansing of hard surfaces in one operation.'


[SENTIERI-ReNaM: Integration of incidence, mortality, and hospitalization: general remarks and a focus on mesothelioma].
The integration of current data sources is now a practice widely used in epidemiology, especially in the environmental field. To better describe the health profile of populations residing in proximity to areas characterized by a "strong environmental pressure", the combined use of multiple indicators (i.e., mortality, hospitalization, cancer incidence) is recommended. To choose an indicator is complex, as indicators should be contextualized and they need to be related to the several issues involved in the studied pathology. This chapter explores the general considerations that are to be addressed both at the time of the study design, during the selection of outcomes and of the proper data sources, and at the time of the discussion of the results, when different and complementary data are compared. A special focus is devoted to the case of mesothelioma.


Catalyst-free regioselective hydroxyfluorination and aminofluorination of α,β-unsaturated ketones.
The catalyst-free direct regioselective α-fluoro-β-hydroxylation and α-fluoro-β-amidation of α,β-unsaturated ketones has been developed. Various α,β-unsaturated ketones react with Selectfluor in water and acetonitrile to give α-fluorohydrins and α-fluoroamides respectively with moderate to good yields. The mechanistic studies revealed the possibility of a radical based pathway.


Glomerular epithelial cells transform to myofibroblasts: early but not late removal of TGF-beta1 reverses transformation.
Studies were carried out to determine whether epithelial-mesenchymal transformation (EMT), well described in renal tubular epithelial cells, also occurs in glomerular epithelial cells and whether it is reversible. To this effect, cultured glomerular epithelial cells were incubated with TGF-beta(1) and their transformation into myofibroblasts was studied. At 4 days, the cells altered their phenotype, as shown by a change in shape, an increase in intracellular staining for alpha-smooth muscle actin (alpha-SMA), a decrease in membrane staining for cytokeratin, and an increase in matrix deposition. Changing the medium after 4 days by excluding TGF-beta(1) and adding fetal bovine serum (FBS) [as a source of epidermal growth factor (EGF) and other growth factors] caused the cells to revert to their original epithelial phenotype. By contrast, when the medium was changed in the same manner after 8 days of exposure to TGF-beta(1), the cells did not revert but remained myofibroblastic. Staining the cells for expression of EGF receptor before and after exposure to TGF-beta(1) caused this receptor, originally present on the plasma membrane, to become partly intracellular after 4 days of TGF-beta(1) exposure and completely intracellular after 8 days of TGF-beta(1) exposure. Kidney sections from 2 models of renal mass reduction were stained. Loss of the epithelial marker (podocalyxin) staining and the acquisition of alpha-SMA staining was observed in the glomeruli. It is concluded that EMT takes place in glomerular epithelial cells in vivo and in vitro. In cultured glomerular epithelial cells, the process can be reversed by early, but not late intervention. It seems that TGF-beta(1) exposure progressively downregulates the EGF receptor on the membrane, rendering the cell refractory to EGF signals critical for maintaining the epithelial phenotype.


Biochemical analyses in osteoarthritis of the hip: a correlative study between glycosaminoglycan loss, enzyme activity and radiologic signs.
This article describes a correlative study between biochemical analyses and radiologic signs in 90 hips with osteoarthritis (OA) removed at operation. On the basis of possible etiologic considerations, the hips are separated into three groups: mechanically induced OA; OA with mainly inflammatory signs; OA in which neither of the two above factors are clearly present. Respective findings of glycosaminoglycan loss, and enzyme activity in cartilage and synovia demonstrate that in mechanically induced OA the glycosaminoglycan loss is less than in inflammatory OA. In the latter, the enzyme activity level is higher than in the former group, suggesting that two important factors in cartilage degradation are represented differently in osteoarthritis. In individual patients, X-ray examination alone may be sufficient to identify the etiologic group. Body weight is an important etiologic factor; heavy individuals show a greater loss of ground substance, with less enzyme activity compared with individuals weighing 70 kg or less.


Polyphenol protection and treatment of hypertension.
High blood pressure is the major risk factor for cardiovascular diseases and the rising prevalence of human hypertension precedes the trend toward a global epidemic of unhealthy ageing. A focus on lifestyle and dietary interventions minimizes dependency on pharmacological antihypertensive therapies. Observational studies indicate that the intake of dietary flavonoids is associated with a decreased risk of cardiovascular disease (CVD). The evidence suggests that the dietary intakes of polyphenol-rich foods, herbs and beverages including flavonols, anthocyanidins, proanthocyanidins, flavones, flavanones, isoflavones and flavan-3-ols, improves vascular health, thereby significantly reducing the risk of hypertension and CVD. Consumption is associated with an improvement in endothelial function via vascular eNOS and Akt activation. Increased NO bioavailability improves vasodilation and blood circulation, effects protein kinases, ion channels and phosphodiesterases, counteracting vascular inflammation and LDL oxidative stress. Importantly, some polyphenols also inhibit the activity of matrix metalloproteinases, inhibit angiotensin converting enzyme activity and thereby improving SBP and DSB. We review the improvement of polyphenol intake on blood pressure and endothelial function for the treatment of hypertension, including not only observational but also RCTs and pre-clinical studies. The antihypertensive phytotherapy of polyphenol-rich foods for protection and improving endothelial function with vascular relaxation occurs via the NO-cGMP pathway and ACE inhibition. OPCs stimulate endothelium-dependent vasodilation, suppress vasoconstrictor ET-1 synthesis, activate a laminar shear stress response in endothelial cells and also inhibit the activity of metalloproteinases including ACE lowering blood pressure.


Preparation and pharmacokinetics of ceftiofur sodium liposomes in cows.
The objective of this study was to prepare ceftiofur sodium liposomes and assess their physical properties, stability, antibacterial effects, and pharmacokinetics. These liposomes appeared as a milky, light yellow suspension with encapsulation efficiency at 57.2 ± 1.17%, and there were no significant changes in all estimated indexes at 4 °C for 90 days. The minimum inhibitory concentrations of liposomes were all 1/4th that of ceftiofur sodium against Streptococcus suis, Staphylococcus aureus, Escherichia coli, and Salmonella enteritidis. Six healthy, adult cows in two treatment groups were dosed intravenously with ceftiofur sodium liposomes and ceftiofur sodium, serial blood samples collected, and plasma concentrations determined by high performance liquid chromatography. Intravenous plasma concentration profiles of liposomes best fit a two-compartment model and the elimination half-life was 2.11 times that of ceftiofur sodium. Thus, this liposome preparation provided therapeutically effective plasma concentrations for a longer duration than with the drug alone, making it more effective and convenient for use in treating bovine mastitis that requires long duration maintenance of therapeutic plasma concentrations.


Ultraviolet-laser ablation of skin.
We report on the use of pulsed ultraviolet-laser irradiation at 193 nm from an argon-fluoride laser and at 248 nm from a krypton-fluoride laser to ablate skin. In vitro, both wavelengths performed comparably, removing tissue precisely and cleanly, and leaving minimal thermal damage to the surrounding tissue. In vivo, the 193-nm laser radiation failed to remove tissue after bleeding began. The 248-nm radiation, however, continued to remove tissue despite bleeding and left a clean incision with only minimal thermal damage. The krypton-fluoride excimer laser beam at 248 nm, which should be deliverable through a quartz optical fiber, has great potential as a surgical instrument.


Design, synthesis and evaluation of a series of 5-methoxy-2,3-naphthalimide derivatives as AcrB inhibitors for the reversal of bacterial resistance.
A series of novel 5-methoxy-2,3-naphthalimide derivatives were designed, synthesized and evaluated for their biological activities. In particular, the ability of the compounds to synergize with antimicrobials, to inhibit Nile Red efflux, and to target AcrB was assayed. The results showed that the most of the tested compounds more sensitized the Escherichia coli BW25113 to the antibiotics than the parent compounds 7c and 15, which were able to inhibit Nile Red efflux. Significantly, compound A5 possessed the most potent antibacterial synergizing activity in combination with levofloxacin by 4 times and 16 times at the concentration of 8 and 16 µg/mL, respectively, whilst A5 could effectively abolish Nile Red efflux at 100 μM. Additionally, target effect of A5 was confirmed in the outer- or inner membrane permeabilization assays. Therefore, A5 is an excellent lead compound for further structural optimization.


Developmental regulation of CYP3A4 and CYP3A7 in Chinese Han population.
CYP3A4 and CYP3A7 are generally served as the major adult and fetal liver forms, respectively, and exhibited a developmental switch during liver maturation. The objective of this study was to explore the potential mechanisms associated with the developmental switch of CYP3A4 and CYP3A7 in the Chinese Han population. We analyzed CYP3A4/7, nuclear receptors, and epigenetic modifications in human liver samples. We found that the expression levels of CYP3A4 mRNA in adults were significantly higher than the levels in fetus. In contrast, CYP3A7 mRNA expression reached a maximal level at an estimated gestational age of 25 weeks and then substantially decreased during the first year after birth. We also found that the expression level of hepatocyte nuclear factor 4 alpha (HNF4A) was most associated with CYP3A4 expression in adult liver; whereas the expression level of glucocorticoid receptor (GR) was intensively correlated with CYP3A7 expression in fetal liver. Furthermore, we illustrated the dynamic changes of H3K4me2 and H3K27me3 in the developmental switch of CYP3A7 and CYP3A4. In summary, our data suggested that HNF4A and GR, and epigenetic changes of H3K4me2 and H3K27me3 are associated with the ontogenic expressions of CYP3A4/3A7 in the livers of the Chinese Han population.


Thymidine analogues to assess microperfusion in human tumors.
To validate the use of the thymidine analogues as local perfusion markers in human tumors (no labeling indicates no perfusion) by comparison with the well-characterized perfusion marker Hoechst 33342. Human tumor xenografts from gliomas and head-and-neck cancers were injected with iododeoxyuridine (IdUrd) or bromodeoxyuridine (BrdUrd) and the fluorescent dye Hoechst 33342. In frozen sections, each blood vessel was scored for the presence of IdUrd/BrdUrd labeling and Hoechst in surrounding cells. The percentage of analogue-negative vessels was compared with the fraction of Hoechst-negative vessels. Collocalization of the two markers was also scored. We found considerable intertumor variation in the fraction of perfused vessels, measured by analogue labeling, both in the human tumor xenografts and in a series of tumor biopsies from head-and-neck cancer patients. There was a significant correlation between the Hoechst-negative and IdUrd/BrdUrd-negative vessels in the xenografts (r = 85, p = 0.0004), despite some mismatches on a per-vessel basis. Thymidine analogues can be successfully used to rank tumors according to their fraction of perfused vessels. Whether this fraction correlates with the extent of acute hypoxia needs further confirmation.


Ophthalmic Complications Following Acoustic Neuroma Resection.
Past studies have shown high rates of ocular complications with the need for ophthalmic surgery following acoustic neuroma resection (ANR). To determine the rates of ophthalmic complications, referrals, and surgery following ANR, and the factors associated with poor outcomes. A retrospective study of ophthalmic outcomes in patients who underwent ANR was conducted, following institutional review board approval. Surgical approach, tumor size, tumor characteristics, completeness of resection, postoperative House-Brackmann grades, ocular complications, referrals to ophthalmology, and ophthalmic treatments were recorded. Between 2007 and 2012, 174 patients underwent ANR. There were 3 surgical groups: retrosigmoid (n = 97), translabyrinthine (n = 59), and combined retrosigmoid and translabyrinthine (n = 18). Median tumor size was 2.2 cm. Postoperatively, 30% of patients had facial nerve dysfunction (House-Brackmann ≥3), which recovered to 19% by 1 mo and 8.6% by 1 yr following ANR. Fifty-six (32.9%) patients experienced ocular complications postoperatively, with lagophthalmos, dry eye, and blurry vision as the most common complications. Thirty-six (67.9%) of the patients who required ophthalmic treatment were managed nonsurgically, with just 13 (7.6%) patients requiring referral to an ophthalmologist. In total, only 9 (5.3%) patients received an ophthalmic procedure. Patients with tumors >2 cm, those undergoing combined retrosigmoid and translabyrinthine resection, and those with severe facial nerve dysfunction which did not improve in the first month following surgery were more likely to have poor ophthalmic outcomes. We present lower rates of ophthalmic complications following ANR than previously reported. Improved surgical technique, better postoperative eye care, and facial nerve monitoring most likely accounted for the improved ocular outcomes.


Reconstructing dynamical networks via feature ranking.
Empirical data on real complex systems are becoming increasingly available. Parallel to this is the need for new methods of reconstructing (inferring) the structure of networks from time-resolved observations of their node-dynamics. The methods based on physical insights often rely on strong assumptions about the properties and dynamics of the scrutinized network. Here, we use the insights from machine learning to design a new method of network reconstruction that essentially makes no such assumptions. Specifically, we interpret the available trajectories (data) as "features" and use two independent feature ranking approaches-Random Forest and RReliefF-to rank the importance of each node for predicting the value of each other node, which yields the reconstructed adjacency matrix. We show that our method is fairly robust to coupling strength, system size, trajectory length, and noise. We also find that the reconstruction quality strongly depends on the dynamical regime.