Relationship between specialized cells, capillaries and intermediary cytofibrillary elements. XIth note. Biological evolution of the emunctory subsystem and stereotype in vertebrates.
This note completes in vertebrates the study of the emunctory subsystem and stereotype in invertebrates (Xth note). The theory of systems (and of open biological systems) of Bertalanffy, the theory of internal laws and limits of each organizational level (Needham) and the theory of biological stereotypes and of their morphofunctional expression (Mârza, Repciuc and Eskenasy) are also corroborated. In this light there were studied: the characters of the emunctory stereotype in vertebrates, its similar formation mode by three links (extracting, conveying and excretory links) as in the coelomatous invertebrates, and the passage of the emunctory stereotype from invertebrates to vertebrates. The present-day Acraniata and their offsprings, the Protocraniata, Agnatha and aquatic Gnathostoma, have an emunctory stereotype identical in its essential characters, without discrepancies between its links. The passage does not occur, however, from the metanephridia to the pronephros, but to the mesonephros. This latter reaches its highest functional limits in Dipnoi and Amphibia. The author indicates the mechanisms which, in its opinion, play a role in the activation of organo-genetic capacities of the metanephros in the caudal nephrogenic area. The importance of the three nephrogenic areas of the vertebrates, their succession and interdependence are also discussed. The problem of the archi(holo)nephros is critically reviewed, and the author's hypothesis that the glomerular ultrafiltrate and the coelomic liquid of invertebrates with metanephridia had the same composition and underwent the same processes of reabsorption-secretion is dwelt upon. A conclusion is drawn from these two notes, according to which stability--directed by the stabilizing selection--plays a directional role in the evolution of the new organizational levels, in the maintenance and development of the characters of the emunctory stereotype within the emunctory subsystem (EMSS). Between variability and stability strong relations are established and hereditarily transmitted.


Unenhanced computed tomography in acute renal colic reduces cost outside radiology department.
Unenhanced multidetector computed tomography (UMDCT) is well established as the procedure of choice for radiologic evaluation of patients with renal colic. The procedure has both clinical and financial consequences for departments of surgery and radiology. However, the financial effect outside the radiology department is poorly elucidated. To evaluate the financial consequences outside of the radiology department, a retrospective study comparing the ward occupation of patients examined with UMDCT to that of intravenous urography (IVU) was performed. A total of 594 consecutive patients were admitted for renal colic during two 6-month periods. One hundred seventy-three consecutive patients were examined with IVU in 2000 and 421 with UMDCT in 2005. The only difference between the two groups was the imaging procedure. The duration of hospital stay and pathology findings were registered. In 50% of the patients undergoing UMDCT, a stone was found; a stone was found or suspected in 40% of patients undergoing IVU. Patients undergoing IVU stayed significantly longer in the ward than patients examined by UMDCT (P<0.0001). The new procedure (UMDCT) saved the hospital USD 265,000 every 6 months compared to the use of IVU. Use of UMDCT compared to IVU in patients with renal colic leads to cost savings outside the radiology department.


Analysis of Amaryllidaceae alkaloids from Narcissus by GC-MS and capillary electrophoresis.
Amaryllidaceae are known as ornamental plants, furthermore some species of this family contain galanthamine, an acetylcholinesterase inhibitor approved for the treatment of Alzheimer's disease, and other alkaloids with interesting pharmacological activity. In the present work, the quali- and quantitative analysis of Amaryllidaceae-type alkaloids in the bulbs of Narcissus species is presented using different analytical approaches. Extracts of Narcissus pseudonarcissus cv. Carlton and Narcissus jonquilla Quail, were first examined by GC-MS using a Rtx-5 MS (programmed temperature) and the major alkaloids were identified. Together with galanthamine, high contents of haemanthamine, were found. Galanthamine was reliably quantified by GC-MS, whereas haemanthamine partly decomposed under the GC conditions, thus alternative analytical methods were investigated. Firstly, reversed-phase HPLC-ESI-MS was applied to identify and isolate at semipreparative levels haemanthamine. The compound was fully characterized by MS/MS and (1)H NMR and then used as a reference substance. The quantitation of both galanthamine and haemanthamine was then accomplished by capillary electrophoresis with spectrophotometric detection. A non-aqueous (NACE) approach was selected in order to use a running buffer fully compatible with samples in organic solvent. In particular, a mixture methanol-acetonitrile (75:25, v/v) containing ammonium acetate (90 mM) was used as a background electrolyte. The same analytical sample was subjected to GC-MS and NACE analysis; the different selectivity displayed by these techniques allowed different separation profiles that can be useful in phytochemical characterization of the extracts. The GC-MS and NACE methods were validated and applied to the quantitation of galanthamine (GC-MS and NACE) and haemanthamine (NACE) in bulbs of N. jonquilla.


An eigenspace projection clustering method for inexact graph matching.
In this paper, we show how inexact graph matching (that is, the correspondence between sets of vertices of pairs of graphs) can be solved using the renormalization of projections of the vertices (as defined in this case by their connectivities) into the joint eigenspace of a pair of graphs and a form of relational clustering. An important feature of this eigenspace renormalization projection clustering (EPC) method is its ability to match graphs with different number of vertices. Shock graph-based shape matching is used to illustrate the model and a more objective method for evaluating the approach using random graphs is explored with encouraging results.


Renal Denervation: A Novel Therapy at the Crossroads of Imaging, Intervention, and Innovation.
Hypertension (HTN) is one of the most significant medical problems affecting society today. The estimated 76 million Americans with hypertension represent a significant public health problem, contributing to cardiac, vascular, renal, and neurovascular morbidity and mortality. HTN is the most common indication for lifelong pharmacologic treatment, mainly because of the incontrovertible reductions in cardiovascular events with blood pressure (BP) reduction and control. However, despite the availability and potency of multiple different antihypertensive drugs, up to half of American patients have BPs above the recommended target. Given the overwhelming evidence of both the cost to society of HTN and the benefits that are accrued from improved BP control, alternatives or adjuncts to current management options have been sought to aid in treatment of these patients. Over the past few years, a device-based approach involving modulation of the autonomic nervous system, termed renal denervation, has evolved to meet this challenge. With early trials showing startlingly good results, with few side effects, multiple devices were fast-tracked to clinical trials and hence to the market. However, larger trials have shone an unfavorable light on the field, with concerns about the short- and long-term effectiveness, diverting attention back to operational and procedural details. Despite this, image-guided manipulation of the sympathetic nervous system to treat HTN remains a fertile area of laboratory and clinical research.


Investigation of the regiospecificity and stereospecificity of proton transfer in the yeast inorganic pyrophosphatase catalyzed reaction.
The regiospecificity and stereospecificity of proton transfer in the yeast inorganic pyrophosphatase (PPase) catalyzed hydrolysis of P1,P2-bidentate Mg(H2O)4(PPi)2- were probed with exchange-inert metal complexes of imidodiphosphate (PNP) and thiopyrophosphate (PPS). PPase was unable to catalyze the hydrolysis of Mg(H2O)4PNP and P1,P2-bidentate Co(NH3)4PNP under conditions that resulted in rapid hydrolysis of the corresponding metal-PPi complexes. PPase was found to catalyze the hydrolysis of Mg(H2O)4PPS at 17% the rate of Mg(H2O)4PPi hydrolysis. The Km of Mg(H2O)4PPS was determined to be 300 microM, which is a value 10-fold greater than that observed for Mg(H2O)4PPi. P1,P2-Bidentate Cr(H2O)4PPS and Co(NH3)4PPS (prepared from PPS) were both found to be substrates for PPase. The enzyme specifically catalyzed the hydrolysis of the Rp enantiomers of these complexes and not the Sp enantiomers. These results are accommodated by a reaction mechanism involving enzyme-mediated proton transfer to the pro-R oxygen atom of the incipient phosphoryl leaving group of the bound P1,P2-bidentate Mg(H2O)4PPi2- complex.


[Long-term efficacy of anticholinergic and alpha-blockader drugs on the detrusor muscle in children with myelomeningocele].
Pharmacological agents, essentially anticholinergic and alpha-blocking drugs, occupy an important place in the stabilization of congenital neurogenic bladders. In actual fact, the functional characteristics of the detrusor, contractility, compliance and functional capacity, are important factors in the prognosis of these neurogenic bladders, both for the future of the upper urinary tract and for the possibilities of continence. This behaviour of the detrusor may be pharmacologically modified not only by anticholinergic drugs, but also by alpha-blockers due to the adrenergic innervation of foetal bladders by short neurones. This study compared the activity of these 2 drugs prescribed separately over a minimal period of 2 years to 54 children with congenital neurogenic bladder. The amplitude of vesical contraction was reduced in about 75% of cases with both drugs, but this result was obtained more rapidly with anticholinergic drugs than with alpha-blockers. No escape phenomenon over time was observed. Anticholinergic drugs were more effective on phasic contractions while alpha-blockers were more effective on rhythmic contractions. In contrast, they had an insignificant action on hypertonia. The increase in functional vesical capacity was 4 times greater with anticholinergic drugs than with alpha-blockers, possibly because of a simultaneous reduction in peripheral resistance with alpha-blockers.


Measurement of Lung Phosphatidylcholines in Exhaled Breath Particles by a Convenient Collection Procedure.
An analytical method based on high-performance liquid chromatography coupled to quadrupole tandem mass spectrometry was developed for the quantitative determination of four phosphatidylcholines (PCs) in human exhaled breath particles. Analytes were conveniently collected on an electrostatic polymer filter and extracted with methanol prior to analysis. Chromatographic separation was performed on an ultraperformance liquid chromatographic ethylene bridged hybrid phenyl column using a mobile phase consisting of water and methanol containing 4 mM ammonium formate and 0.1% ammonia. The mass spectrometer operated in positive electrospray ionization and selected reaction monitoring mode. Detection limits for PC 16:0/16:0 (dipalmitoylphosphatidylcholine, DPPC), PC 16:0/18:1, PC 16:0/18:2, and PC 18:0/18:2 were <0.01 ng/filter. Method recoveries at concentration levels of 0.1 and 10 ng/filter were 100-110% and 101-121%, respectively. Acceptable precision with coefficients of variation <20% and accuracies of 100% ± 20% were achieved. Identification of the individual PCs was performed on the basis of two product ions with correct ion ratios and chromatographic retention times. The highest amount in exhaled breath was found for DPPC with median concentration 1.14 ng/filter (range 0.6-21 ng/filter), and median molar ratios of DPPC/PC (16:0/18:1) of 1.98 (range 0.48-2.75). A different pattern with lower molar ratio (∼0.15) was found for oral fluid. The most significant element of this study was to use a precolumn in the LC system and to collecting exhaled particles in an electret polymer filter. Due to chromatographic interference by background contamination, an isolator column (PFC kit) was installed in between eluent mixer and injector to reduce contamination. This is the first LC/MS study where the method was successfully applied to analyze PCs in human exhaled breath by using a simple and convenient collection procedure.


PET/CTA detection of muscle inflammation related to cholesterol crystal emboli without arterial obstruction.
PET/CTA was used to evaluate the effect of cholesterol crystal emboli (CCE) on muscle injury. Cholesterol crystals (CCs) released during plaque rupture travel downstream and lodge in muscle triggering inflammation and tissue injury. Thigh muscles in three groups of rabbits (n = 22) were studied after intra-arterial injection of CCs, Group I (n = 10); polystyrene microspheres, Group II (n = 5); or normal saline, Group III (n = 7). After 48 hours, muscle inflammation and injury were measured by fluorodeoxy-glucose uptake using PET/CTA, serum tissue factor (TF), and creatinine phosphokinase (CPK). Macrophages were stained with RAM11 and CCs with Bodipy. SUVmax of thigh muscles was greater for Group I vs Group II and III (0.40 ± 0.16 vs 0.21 ± 0.11, P = .038 and 0.23 ± 0.06, P = .036). CPK levels rose significantly in Group I vs Group II and III (6.7 ± 6.0 vs 0.6 ± 0.4, P = .007 and 0.9 ± 0.4 mg·dL-1, P = .023). No arterial thrombosis was detected by CTA or histology of embolized arteries and TF did not rise significantly. There were extensive macrophage infiltrates surrounding muscle necrosis in Group I only. Cholesterol crystal emboli triggered muscle inflammation and necrosis with an intact circulation. PET/CTA may help in the early detection of inflammation caused by CCs.


Magnetic Resonance Imaging of Rheumatoid Arthritis: Peripheral Joints and Spine.
Both the fields of rheumatology and radiology are changing rapidly. Effective medication has become available for rheumatoid arthritis (RA) and transformed it from a progressive disabling disease into a chronic disease. Indications for magnetic resonance imaging (MRI) have changed accordingly, shifting toward early detection. There is also an overall increased clinical demand for high-end imaging. Together with improvement of MRI units and sequences, MRI protocols are adapted based on clinical indications. This article addresses (1) the clinical background and present role of MRI in early disease detection, (2) RA involvement of peripheral joints, (3) RA involvement of the spine, and (4) state-of-the-art RA MRI protocols. The key toward cost-effective MRI examination in RA is communication between radiologist and rheumatologist as well as awareness and knowledge of the basics and advancements in both fields.


FDG uptake in axillary lymph nodes after vaccination against pandemic (H1N1).
To alert the imaging community to potential false positive findings related to current immunization programmes against H1N1 influenza virus. We reviewed 10 patients referred for positron emission tomography/computed tomography (PET/CT) who had undergone recent vaccination. All studies showed( 18)F-fluorodeoxyglucose (FDG) uptake in the draining axillary lymph nodes close to the vaccination site, while low-dose CT revealed lymph nodes ranged between 0.5 cm and 1.2 cm at the same site. This potential pitfall in PET/CT should be borne in mind during current vaccination programmes.


Guidelines for establishing a technical support group for the radiation therapy clinic.
During the last decade, radiation therapy has grown to become an important medical treatment in the treatment of cancer. The growth of this field has created a need for an electronic and mechanical support group to service the needs of the treatment centers (clinics). Because of the uniqueness of equipment, the maintenance criteria are somewhat different than that for other types of equipment. The information for this paper was derived from five years of experience that the Mallinckrodt Institute has accumulated through its own technical group plus information gained through discussions with other groups in the therapy field. The technical support group at Mallinckrodt Institute of Radiology (MIR) presently maintains six high-energy therapy machines, two simulators, and a superficial X-ray unit. Topics discussed include the technical personnel required, the duties of the group, working hours, suggested electronic/mechanical equipment, and other pertinent aspects.


Inadequate Glycaemic Control and Therapeutic Management of Adults over 65 Years Old with Type 2 Diabetes Mellitus in Spain.
The glycaemic goals for older patients with type 2 diabetes mellitus (DM) are recommended to avoid an HbA1c levels <7%. The purpose of this study was to analyse the glycaemic control and therapeutic management of older adults (≥65 years) with type 2 DM. Pooled analysis of patients enrolled in three Spanish cross-sectional epidemiological studies. The study was conducted between 2009 and 2011 by primary care or specialist physicians. A total of 7,269 patients aged ≥65 years with type 2 DM. Sociodemographic, medical history, lifestyle habits, biochemical laboratory parameters, comorbidities, type 2 DM complications, and pharmacological treatment data collected from medical records. In total, data from 7,269 patients were analysed (mean age 73.4 years old; 48.4% male). A total of 10.9% of patients had HbA1c levels ≥8.5% and 43.2% <7%. The most common comorbidities were hypertension (82.0%) and dyslipidaemia (76.6%). The microvascular complications were mainly diabetic nephropathy (23.6%) and retinopathy (19.3%). Oral antidiabetic drugs (OADs) were taken by 70.5% of patients (sulphonylureas 65.3%), 4.1% were taking insulin alone and 25.4% took both insulin and an OAD. Half of the patients (51.0%) were taking a combination of OADs. In conclusion, more than half of older patients with type 2 DM had unsatisfactory management: approximately one in ten had inadequate glycaemic control (HbA1c ≥8.5%) despite hypoglycaemic drugs and four in ten were potentially overtreated (HbA1c <7%).


Partial structure of the human alpha 2(IV) collagen chain and chromosomal localization of the gene (COL4A2).
We have isolated a 2.1-kb cDNA clone from a human placental library encoding part of the alpha 2 chain of collagen IV, a major structural protein of basement membranes. The DNA sequence encodes 446 amino acids in the triple-helical domain plus the 227 amino acids of the carboxy-terminal globular domain. The latter structure is composed of two homologous subdomains and is highly conserved between the alpha 1 and alpha 2 chains. The triple-helical domain contained seven interruptions of the Gly-X-Y repeat and these interruptions were in general larger than their counterparts in the alpha 1 chain. DNA from human rodent hybrid cell lines was analyzed under conditions in which there was no cross-hybridization of the alpha 2(IV) cDNA probe with the gene for the alpha 1(IV) collagen chain. An EcoRI fragment characteristic of the alpha 2 chain had a concordance of 0.97 with chromosome 13. This result was confirmed and extended with in situ localization of the gene at 13q34. Since the alpha 1(IV) gene has previously been localized to 13q34, the two type IV collagen genes reside in the same chromosome region (13q34), possibly in a gene cluster. The presence of the genes for type IV collagen chains on chromosome 13 excludes a primary role for these genes in adult polycystic kidney disease and X-linked forms of hereditary nephritis.


Compound Metaoptics for Amplitude and Phase Control of Wave Fronts.
Metasurfaces allow tailored control of electromagnetic wave fronts. However, due to local conservation of power flow, passive, lossless, and reflectionless metasurfaces have been limited to imparting phase discontinuities-and not power density discontinuities-onto a wave front. Here, we show how the phase and amplitude profiles of a wave front can be independently controlled using two closely spaced phase-discontinuous metasurfaces. The two metasurfaces, each designed to exhibit spatially varying refractive properties, are separated by a wavelength-scale distance and together form a compound metaoptic. A method of designing the compound metaoptic is presented, which enables transformation between arbitrary complex-valued field distributions without reflection, absorption, polarization loss, or active components. Such compound metaoptics may find applications in the optical trapping of particles, displaying three-dimensional holographic images, shrinking the size of optical systems, or producing custom (shaped and steered) far-field radiation patterns.


Comparison of macrophage scavenger receptor-A knockout mice with wild type ones in the immune response against repeated infestation with Haemaphysalis longicornis.
Using macrophage scavenger receptor-A knockout (SRKO) mice, we examined the role of macrophage class A scavenger receptors (MRS-A) on the immune response and acquisition of host resistance against repeated infestation with Haemaphysalis longicornis. Except for one batch of nymphs that infested one of the SRKO (SR-/-) mice and showed no appreciable reduction in body weight, all the other groups of nymphs manifested significant decrease in body weight. Both SR-/- and wild type (SR+/+) mice showed a sustained increase in anti-tick antibody titers, but SR+/+ mice showed significantly higher titers. The IFN-gamma assayed in SR-/- mouse immune sera was substantially less compared with that in SR+/+ mice. Immune sera from SR-/- and SR+/+ mice recognized the 51 and 44 kDa, and 44 kDa proteins, respectively, of the salivary gland antigen. The difference in the level of anti-tick resistance manifested by both groups of mice may be influenced by less efficient trapping and processing of tick antigens by macrophages in mice lacking for the macrophage scavenger receptors, and consequently affected the cascade of Th1 and Th2 responses. We have thus obtained valuable data that strongly infer the role of MSR-A in enhancing host defense against repeated infestation with H. longicornis.


Haemolytic-uraemic syndrome in childhood: surveillance and case-control studies in Italy. Italian HUS Study Group.
Seventy-six cases of haemolytic-uraemic syndrome (HUS) were collected over a 4-year period during a surveillance and case-control study. The annual incidence of 0.2 per 100,000 children aged 0-14 years is lower than in other countries; 34% had no prodromal diarrhoea. Evidence for verocytotoxin-producing Escherichia coli (VTEC) infection was found in 72% of patients and 3% of controls; 88% of patients with bloody diarrhoea, 67% with non-bloody diarrhoea and 55% without diarrhoea were VTEC positive. Seventy-three percent of patients had creatinine clearance > or = 80 ml/min per 1.73 m2, normal blood pressure, no proteinuria and haematuria < 2+ after 1 year of follow-up. One patient died and none had non-renal sequelae. VTEC positivity was significantly correlated with a good outcome, while the absence of diarrhoea and a high total white blood cell count at onset were not predictors of a bad outcome. Household contacts of HUS patients had diarrhoea more frequently than those of the control group, supporting the hypothesis of person-to-person transmission of VTEC infection.


Biodegradation of toluene using Candida tropicalis immobilized on polymer matrices in fluidized bed bioreactors.
A yeast strain, Candida tropicalis, was whole-cell-immobilized on polymer matrices of polyethylene glycol (PEG) and polyethylene glycol/activated carbon/alginate (PACA). The polymer matrices were used as fluidized materials in bubble-column bioreactors for the biodegradation of toluene. Simultaneously, another bubble-column bioreactor using granular activated carbon (GAC) and a conventional compost biofilter were operated for comparison. In the compost biofilter, the toluene removal efficiency gradually deteriorated due to the limitation of microbial activity. The toluene removal in the GAC bioreactor was relatively high because of an increase of toluene mass transfer. However, low toluene removal efficiencies were observed in the PEG bioreactor, presumably because the synthetic polymer alone was not suitable for yeast cell immobilization. In the PACA bioreactor, toluene removal was found to be greater than 95% overall. The CO(2) yield coefficient calculated at the highest toluene loading condition for the PACA bioreactor was found to be higher than those observed in the other bioreactors. Furthermore, almost complete elimination capacities were observed in the PACA bioreactor at short-term toluene loading up to 180 g/m(3)/h. In conclusion, the immobilization of C. tropicalis in the PACA matrix resulted in enhanced toluene biodegradation because of the increases of both mass transfer and microbial activity.


Three new species of Eimeria Schneider 1875 in the montane grass mouse, Akodon montensis (Rodentia: Cricetidae: Sigmodontinae), and redescription of Eimeria zygodontomyis Lainson and Shaw 1990 from southeastern Brazil.
We describe three new coccidian species of the genus Eimeria Schneider 1875 (Apicomplexa: Eimeriidae) and redescribe and report Eimeria zygodontomyis Lainson and Shaw, 1990 in the montane grass mouse, Akodon montensis Thomas, 1913 from the Serra dos Órgãos National Park in southeastern Brazil. Sporulated oocysts of Eimeria zygodontomyis are ellipsoidal to cylindrical with a 0.6 (0.5-0.8) μm thick very delicate bi-layered wall; length × width (n = 49) 18.3 × 12.5 (16-20 × 11-13) μm; length/width ratio of 1.4 (1.2-1.6); 1 polar granule occasionally present; micropyle, residuum both absent. Sporocysts are ellipsoidal; length × width 8.5 × 5.2 (8-11 × 5-6) μm; length/width ratio of 1.5 (1.3-1.7) μm; Stieda body is prominent; sub-Stieda body is absent; sporocyst residuum is compact. Sporulated oocysts of Eimeria montensis n. sp. are spheroidal to subspheroidal with a 1.2 (1.0-1.4) μm thick bi-layered wall; outer layer lightly pitted; length × width (n = 30) 16.3 × 12.5 (15-17 × 13-15) μm; length/width ratio of 1.3 (1.0-1.4); 1 polar granule present; micropyle, residuum both absent. Sporocysts are ellipsoidal; length × width 7.2 × 5.1 (6-8 × 4-6) μm; length/width ratio of 1.4 (1.2-1.6); Stieda body is present, sub-Stieda body is absent; sporocyst residuum consists of small, scattered granules. Sporulated oocysts of Eimeria uricanensis n. sp. are ovoidal to pyriform with a 1.4 ( 1.3-1.6) μm thick bi-layered wall; outer layer lightly pitted; length × width (n = 40) 26.6 × 18.6 (23-30 × 17-20) μm; length/width ratio of 1.4 (1.3-1.6); 1 polar granule present; micropyle, residuum both absent. Sporocysts are ellipsoidal, length × width 13.3 × 8.0 (10-16 × 7-9) μm; length/width ratio of 1.7 (1.5-1.9); Stieda body, sub-Stieda body both absent; sporocyst residuum consists of a cluster of granules, forming a spheroid mass. Sporulated oocysts of Eimeria parnasiensis n. sp. are subspheroidal to ellipsoidal with a 1.8 ( 1.3-2.4) μm thick bi-layered wall; outer layer lightly pitted; length × width (n = 54) 28.2 × 21.9 (26-32 × 19-28) μm; length/width ratio of 1.3 (1.2-1.4); 1 polar granule present; micropyle is absent; oocyst residuum is present and consists of a cluster of granules of varying thickness. Sporocysts are ovoidal, tapering towards the Stieda body; length × width 12.2 × 7.6 (10-13 × 6-9) μm; length/width ratio of 1.6 (1.4-1.9); Stieda body is present; sub-Stieda body is absent; sporocyst residuum is present and consists of an aggregate of thin granules.


The most important risk factors affecting mental health during pregnancy: a systematic review.
Pregnant women comprise a vulnerable population owing to the changes they experience in various stages that affect their mental health. Mental health problems affects nearly one-fifth of pregnant women during the prenatal and postpartum periods. Millennium Development Goals 4 and 5 focus on maternal and child health and specify that overall health cannot be reached without mental health. The aim of this comprehensive systematic review was to evaluate research evidence on the determinants of antenatal mental health disorders among Iranian women. Using a systematic literature review of observational studies in English and Farsi we focused on Iranian women being evaluated for the determinants of antenatal mental health problems. PubMed, Scopus, ISI Web of Science, Scientific Information Databases (SID), Global Medical Article Limberly, Iranian Biomedical Journal and the Iranian Journal Database were independently searched to identify articles published during 2000-2016. Thirty-one studies met the inclusion criteria and the results showed a significant relationship between antenatal mental health risks and variables such as lack of social support, marital status, domestic violence, unintended pregnancy and socioeconomic status. The paucity of high quality research evidence limited proper evidenced-based planning and generating results deemed essential to address antenatal mental health issues for Iranian pregnant women. Our results showed that socioeconomic status and marital quality are the most important risk factors for disturbing mental health among Iranian pregnant women.


Sports clubs as settings for health promotion: fundamentals and an overview to research.
This paper explores the efficacy and value of sports clubs as a setting for health promotion. Sports clubs for children and adolescents are the primary focus of the paper, and the aims are two-fold. Firstly, the paper aims to review the basis for and elements of the health promoting sports club (HPSC) concept. Secondly, the aim is to overview the international evolution of the HPSC concept and its usefulness in the research. The settings-based health promotion approach forms the basis for the HPSC concept and it is introduced first. Thereafter, both obligating and prospecting factors, to justify the importance for sports clubs to address health promotion, are expressed. Major prospecting factors relate to the facts that sports club activities reach a lot of children and adolescents, and that its educational nature is informal due to voluntary participation. The paper also presents multilevel structure of sports clubs, as well as the determinants affecting the settings-based work. The research concerning health promotion in sports-related settings is evolving worldwide, and Nordic countries are in the front line of this new-wave of settings-based health promotion. Indeed, it has been claimed that, for the settings approach to assimilate to current societal challenges, there is a need to widen the reach of the approach to non-traditional, non-institutional settings, like sports clubs.


Role of neoadjuvant chemotherapy in the management of advanced ovarian yolk sac tumor.
The aim of the study was to identify the role of neoadjuvant chemotherapy (NACT) in the treatment of the patients with advanced stage ovarian yolk sac tumor (OYST). The comparative study was based on 53 cases with advanced stage OYST registered at Peking Union Medical College Hospital from 1995 to 2010. Twenty one cases were treated with NACT followed by interval debulking surgery (IDS). Thirty two cases were treated with primary debulking surgery (PDS). Data on patient characteristics, treatment and survival were analyzed and compared between two groups to assess the outcome of NACT. After NACT, the overall status of the patients was improved significantly. Patients in NACT had better optimal cytoreduction rate and less peri-operative morbidities. Seven patients (13.2%) suffered from relapse. There was a significantly better PFS for patients with ovarian tumor size >20cm in the NACT than those underwent PDS. Residual disease >2cm was the independent risk factor of relapse. NACT is the better treatment option for some patients with advanced stage OYST, especially for those with unresectable tumors and poor general condition.


The diagnostic accuracy of myocardial perfusion scintigraphy in athletes with abnormal exercise test results.
Background Previous studies revealed a relatively high prevalence of electrocardiographic findings indicative for myocardial ischemia in asymptomatic athletes undergoing pre-participation screening. Myocardial perfusion scintigraphy is generally considered a valuable diagnostic and prognostic modality and often used for further diagnostic evaluation in these subjects. However, data on the diagnostic accuracy of myocardial perfusion scintigraphy in athletes are scarce. Objectives The main purpose of this study was to investigate the positive predictive value of myocardial perfusion scintigraphy for detection of coronary artery disease in asymptomatic athletes with abnormal exercise testing results during pre-participation screening. The secondary aim was to evaluate the prognostic value of myocardial perfusion scintigraphy. Methods Electronic charts of asymptomatic athletes who underwent myocardial perfusion scintigraphy following an abnormal exercise testing were retrospectively reviewed. Myocardial perfusion scintigraphy and exercise testing studies were revised. Athlete characteristics and cardiovascular risk factors were evaluated. Results One hundred and forty-three athletes were included. 29 athletes (20%) showed concordant abnormal exercise testing and myocardial perfusion scintigraphy results. Coronary imaging was performed in 20 of these 29 athletes. Four athletes showed significant coronary artery disease (positive predictive value = 20%). The positive predictive value increased to 33% when athletes were selected who should have undergone exercise testing according to the guideline recommendations. During a mean follow-up interval of 4.7 ± 2.2 years, eight cardiac events occurred. Athletes with an abnormal myocardial perfusion scintigraphy result had a fourfold increased risk at a future cardiac event (2.9%/year versus 0.75%/year, p = 0.031). Conclusions The positive predictive value of myocardial perfusion scintigraphy for the detection of significant coronary artery disease in asymptomatic athletes with a positive exercise testing result is low, even in a selection of athletes with a relatively high cardiovascular risk. Although an abnormal myocardial perfusion scintigraphy result was associated with a fourfold higher annual event rate, the absolute annual event rate in this group was still low. Efforts should be made to develop better diagnostic strategies to evaluate asymptomatic athletes with abnormal exercise testing results during pre-participation screening.


Determination of reduced biopterins by high pressure liquid chromatography and subsequent electrochemical detection.
L-erythro-Tetrahydrobiopterin plays an important role as the cofactor of various hydroxylation reactions. We report here the separation of biopterin and its reduced forms by reversed-phase high pressure liquid chromatography. Subsequent electrochemical detection yields a sensitivity at the picomole level for dihydrobiopterin and tetrahydrobiopterin.


The effect of substituted sydnonimines on coronary smooth muscle relaxation and cyclic guanosine monophosphate levels.
In vitro experiments on precontracted canine coronary arteries were performed to study the direct relaxant effects of molsidomine (MOLS) and its active metabolite, SIN-1, and to determine if there is a relationship between effect and cGMP level elevations. The effects of MOLS and SIN-1 were compared with those of a classic vasodilator, nitroglycerin (NTG). At equimolar doses (10(-6)M) SIN-1 exerted greater relaxant effect than NTG (80 +/- 2% and 60 +/- 5%, respectively) in spite of the fact that it produced less of an increase in cyclic guanosine monophosphate (cGMP) levels. cGMP levels fell rapidly after they peaked, but relaxation was maintained. cGMP elevation preceded the induction of relaxation by NTG but not that induced by SIN-1. Relaxation occurred faster after NTG than after SIN-1. Since SIN-1 has a greater relaxant effect than NTG in spite of the fact that SIN-1 induces less of an increase in cGMP levels and the fact that the peak elevation does not precede the onset of relaxation, the causal nexus between GMP level elevation and relaxation effect after sydnonimines should be challenged.


The resistance of the trabecular meshwork to aqueous humor outflow.
A theoretical model is presented that is able to explain for the first time the pressure drop across the trabecular meshwork. The ramified flow paths in the subendothelial region of the trabecular meshwork can be interpreted as a filter bed. Data from transmission electron microscope (TEM) photographs are the starting point of the theoretical consideration. Taking shrinkage of the sections into account, the pressure gradient across the subendothelial region amounts to 0.05 mm Hg. As these canaliculi are coated by a film of glycosaminoglycans (GAGs), the pressure drop is presumably a function of the film thickness. Only film thicknesses of 0.35 micron led to pressure gradients in the experimentally verified magnitude. As the whole filter bed probably does not contribute to the filtration but only about 10%, the pressure drop specified is reached when the GAG coating is 0.25 micron. As these values seem to be fairly realistic, it can be concluded that the subendothelial region of the juxtacanalicular meshwork (about 2 micron thickness) can be regarded as the "locus generis" of aqueous humor outflow resistance.


Significance of complete 1p/19q co-deletion, IDH1 mutation and MGMT promoter methylation in gliomas: use with caution.
The histopathological diagnosis of diffuse gliomas often lacks the precision that is needed for tailored treatment of individual patients. Assessment of the molecular aberrations will probably allow more robust and prognostically relevant classification of these tumors. Markers that have gained a lot of interest in this respect are co-deletion of complete chromosome arms 1p and 19q, (hyper)methylation of the MGMT promoter and IDH1 mutations. The aim of this study was to assess the prognostic significance of complete 1p/19q co-deletion, MGMT promoter methylation and IDH1 mutations in patients suffering from diffuse gliomas. The presence of these molecular aberrations was investigated in a series of 561 diffuse astrocytic and oligodendroglial tumors (low grade n=110, anaplastic n=118 and glioblastoma n=333) and correlated with age at diagnosis and overall survival. Complete 1p/19q co-deletion, MGMT promoter methylation and/or IDH1 mutation generally signified a better prognosis for patients with a diffuse glioma including glioblastoma. However, in all 10 patients with a histopathological diagnosis of glioblastoma included in this study complete 1p/19q co-deletion was not associated with improved survival. Furthermore, in glioblastoma patients >50 years of age the favorable prognostic significance of IDH1 mutation and MGMT promoter methylation was absent. In conclusion, molecular diagnostics is a powerful tool to obtain prognostically relevant information for glioma patients. However, for individual patients the molecular information should be interpreted with caution and weighed in the context of parameters such as age and histopathological diagnosis.


Providing intraosseous anesthesia with minimal invasion.
A new variation of intraosseous anesthesia--crestal anesthesia--that is rapid, site-specific and minimally invasive is presented. The technique uses alveolar crest nutrient canals for anesthetic delivery without penetrating either bone or periodontal ligament.


Proximity of jupiter-like planets to low-mass stars.
The sensitivities of astrometric and radial velocity searches for extrasolar planets are strongly dependent on planetary masses and orbits. Because most nearby stars are less massive than the sun, the first detection is likely to be of a Jupiter-mass planet orbiting a low-mass star, with a possible theoretical expectation being that Jupiter-like planets will be found much closer [inside the Earth-sun separation of 1 astronomical unit (AU)] to these low-luminosity stars than Jupiter is to the sun (5.2 AU). However, radiative hydrodynamic models of protoplanetary disks around low-mass stars (of 0.1 to 1 solar mass) show that Jupiter-like planets should form at distances (approximately 4 to 5 AU) that are only weakly dependent on the stellar mass.


[Toxic effects of cooking oil fumes on testis of rats].
To investigate the toxic effects of inhaling cooking oil fumes (COF), 30 male SD rats were submitted to inhaling COF at a constant concentration and duration (35-53 mg/m3, 30 min/d) for different length of time (20, 40 and 60 days), and examined for change in body weight, spermtogenesis and content of trace elements in their testes. The results indicated that the body weight and the ratio of gonad to body weight in rats inhaling COF for 40 and 60 days were lower than those in the controls (P < 0.05). Fewer alive sperms and more malformed or dead sperms were fond in the epididymis of rats exposed to COF for 40 and 60 days. Among the four trace elements(Zn, Mn, Cu, Fe) studied, the content of Zn in the testis was found to be significantly decreased and that of Mn significantly increased in the rats exposed to COF for longer periods. There existed a time-effect relationship in all of the above findings. The results suggested that inhaling COF was significantly toxic to male gonads, and the imbalance of Zn, Mn might be contributive to the damage of testis.


Effect of ligustrazine on pulmonary vascular changes induced by chronic hypoxia in rats.
1. Acute and chronic effects on the pulmonary circulation of ligustrazine, a chemically identified and synthesized principle of a Chinese herb, were studied in rats. It dilated lung vessels and reversed hypoxic pulmonary vasoconstriction. 2. In rats kept 2 weeks in 10% O2 in a normobaric chamber and simultaneously treated with ligustrazine, right ventricular hypertrophy and muscularization of pulmonary arterioles were attenuated compared with saline-treated rats. Pulmonary artery pressure, measured in isolated lungs perfused at a constant flow rate, was also less in ligustrazine-treated rats. 3. In isolated blood-perfused lungs of chronically hypoxic and control rats, the relation between pressure and flow was measured during normoxia (ventilation with air plus 5% CO2), hypoxia (2% O2 plus 5% CO2) and after ligustrazine during continued hypoxia. Alveolar pressure was always greater than left atrial pressure; thus flow was determined by the pulmonary artery minus alveolar pressure difference. 4. Pressure/flow lines were measured during normoxia in four groups of rats: (1) control, saline-treated; (2) control, ligustrazine-treated; (3) chronically hypoxic, saline-treated; (4) chronically hypoxic, ligustrazine-treated. Both chronically hypoxic groups had steeper lines (higher resistance) than the control groups, which were similar in all respects. However, in chronically hypoxic rats, the extrapolated intercept of the line on the pressure axis, probably attributable to small newly muscularized arterioles in a state of tone, was much increased in the saline-treated group but did not differ from controls in the ligustrazine-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)


[Approach to the pterygomaxillary region by the Lefort I osteotomy].
Approach to the pterygomaxillary fossa under the base of skull, a difficult operation, has been facilitated by the use of a technique derived from the Lefort I osteotomy. Satisfactory access to the fossa and to the posterior-base region is obtained and esthetic or functional sequelae avoided.


Intensive care unit admitting patterns in the Veterans Affairs health care system.
Critical care resource use accounts for almost 1% of US gross domestic product and varies widely among hospitals. However, we know little about the initial decision to admit a patient to the intensive care unit (ICU). To describe hospital ICU admitting patterns for medical patients after accounting for severity of illness on admission, we performed a retrospective cohort study of the first nonsurgical admission of 289,310 patients admitted from the emergency department or the outpatient clinic to 118 Veterans Affairs acute care hospitals between July 1, 2009, and June 30, 2010. Severity (30-day predicted mortality rate) was measured using a modified Veterans Affairs ICU score based on laboratory data and comorbidities around admission. The main outcome measure was direct admission to an ICU. Of the 31,555 patients (10.9%) directly admitted to the ICU, 53.2% had 30-day predicted mortality at admission of 2% or less. The rate of ICU admission for this low-risk group varied from 1.2% to 38.9%. For high-risk patients (predicted mortality >30%), ICU admission rates also varied widely. For a 1-SD increase in predicted mortality, the adjusted odds of ICU admission varied substantially across hospitals (odds ratio = 0.85-2.22). As a result, 66.1% of hospitals were in different quartiles of ICU use for low- vs high-risk patients (weighted κ = 0.50). The proportion of low- and high-risk patients admitted to the ICU, variation in ICU admitting patterns among hospitals, and the sensitivity of hospital rankings to patient risk all likely reflect a lack of consensus about which patients most benefit from ICU admission.


The effect of phospholipids and fatty acids on tight-junction permeability and bacterial translocation.
The activity of phospholipase A2 (PLA2) is elevated in the intestinal epithelia of patients with inflammatory bowel disease (IBD). We recently reported that PLA2 mediates hydrolysis of phosphatidylcholine (PC) to lysophosphatidylcholine (L-PC) when both are applied to the apical surface of cultured EC monolayers, resulting in increased bacterial translocation (BT) and decreased transepithelial electrical resistance (TEER). Free fatty acids (FFA) are the other products of this reaction, however, their effect on Caco-2 cell permeability has not been reported. In addition to PC, other luminal phospholipids are present at the surface of the enterocyte. PLA2 may also mediate the hydrolysis of luminal phospholipids other than PC. The aim of this study was to examine the effects of phospholipids other than PC and common FFA on intestinal epithelial permeability and BT. Human Caco-2 enterocytes were grown to confluence on porous filters in the apical chamber of a two-chamber cell-culture system. Monolayer integrity and tight-junction permeability were measured as TEER. First, common FFA released by PC hydrolysis were determined using thin-layer chromatography (TLC). In separate experiments, monolayers were treated with phosphatidylethanolamine (PE), lysophosphatidylethanolamine (L-PE), or palmitoleic acid, oleic acids, linoleic acids, and arachidonic acid solubilized in solution with PC. The magnitude of BT was determined 2 h after treatment by adding Escherichia coli C25 to the apical chamber followed by quantitatively culturing basal-chamber samples. Statistical analysis was by the Kurosaki-Wallis test. TLC of PC samples incubated with PLA2 on the apical surface of Caco-2 monolayers demonstrated the production of palmitoleic acid, oleic acids, linoleic acids, and arachidonic acid. L-PE significantly decreased TEER compared to controls, but to a lesser degree than L-PC alone. L-PE had no effects on BT. Palmitoleic acid and oleic acid likewise significantly decreased TEER compared to controls, however, less than L-PC. All FFA tested had no effect on BT. Phospholipids applied to the apical surface of enterocytes, such as those found in vivo in mucus, can be hydrolyzed by the enzyme PLA2 resulting in lysophospholipid and FFA species that can alter enterocyte monolayer permeability. However, FFA and L-PL, other than L-PC, appear to have no effect to stimulate BT. This observation may have clinical implications in the pathogenesis and treatment strategies for IBD patients in whom enterocyte PLA2 activity has been shown to be elevated.


Antibacterial, cyto and genotoxic activities of A22 compound ((S-3, 4 -dichlorobenzyl) isothiourea hydrochloride).
The A22 is a chemical compound that acts as a reversible inhibitor of a bacterial cell wall protein MreB leading the rods to the coccoid form. Thus, by changing the bacterial form, many properties can be affected, as the acquisition of nutrients, cell division, the clamping surfaces, motility and pathogenesis. Infections caused by strains of Pseudomonas aeruginosa have great clinical importance because these microorganisms can include more than one resistance mechanism acting together, limiting treatment options. Thus, it is important to investigate the action of A22 against P. aeruginosa, once there are urgent needs for new antimicrobial compounds for increase the arsenal therapeutic to treat diseases caused by this microrganism. Therefore, this study investigated for the first time the antimicrobial activity of A22 against seve standards strains of Gram negative microorganisms and twenty-eight clinical isolates of P. aeruginosa. This study performed an additional investigation to analyze the cyto and genotoxic potential effects from A22 on human peripheral blood mononuclear cells (PBMCs). The antibacterial activity of A22 was studied by broth microdilution method and time-kill assay. The cytotoxicity was evaluated by MTT assay at 24, 48 and 72 h of exposure to A22 and the genotoxicity was evaluated by the Comet assay. The susceptibility tests showed A22 has a relevant antibacterial activity against P. aeruginosa, including multidrug-resistant (MDR) clinical isolates. The A22 treatment not showed genotoxic effects against PBMCs in almost all concentrations tested at 24 and 48 h of exposure. Only for concentration of 32 μg/mL (highest tested) the damage index was significantly higher in all moments. The MTT assay demonstrated that A22 was able to maintain cell viability in all exposure times. In summary, the A22 demonstrated important anti-Pseudomonas activity and showed no cyto and genotoxic significant effect. These results need to be considered in future in vitro and in vivo studies in order to introduce the A22 as a possible therapeutic option.


Semi-quantitative analysis of tramadol, dextromethorphan, and metabolites in decomposed skeletal tissues by ultra performance liquid chromatography quadrupole time of flight mass spectrometry.
The use of filtration/pass-through extraction (FPTE) and ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) to detect tramadol (TRAM), dextromethorphan (DXM), and metabolites from skeletal remains is described. Rats (n=5) received 50 mg/kg tramadol and were euthanized by CO2 asphyxiation approximately 30 minutes post-dose. Rats (n=4) received 75 mg/kg dextromethorphan and were euthanized by CO2 asphyxiation approximately 45 minutes post-dose. Remains decomposed to skeleton outdoors and vertebral bones were collected. Bones were cleaned, dried, and pulverized to a fine powder. Bones underwent dynamic methanolic extraction followed by FPTE before analysis using UPLC-qTOF-MS. Recovery was at least 90% of maximal value within the first 10 minutes of methanolic extraction for all samples assayed. Analytical response was measured over the concentration range of 1-500 ng/mL, with precision and bias <20% in triplicate analyses of all calibrators, and a limit of detection of 1 ng/mL for TRAM, DXM, and all metabolites. The vertebral bone analyzed using this method detected TRAM, DXM, and their respective metabolites in all samples analyzed.


Probing the Heterogeneous Ozonolysis of Squalene Nanoparticles by Photoemission.
The heterogeneous reaction of ozone (O3) with 200 nm squalene nanoparticles is studied using near-edge X-ray absorption fine structure (NEXAFS) and ultraviolet (UPS) and X-ray photoelectron spectroscopy (XPS). Photoelectrons are detected from free nanoparticle beams using a velocity map imaging (VMI) spectrometer capable of detecting photoelectrons with up to 40 eV of kinetic energy. Heterogeneous kinetics are quantified using changes in the UPS, XPS, and NEXAFS spectrum, yielding uptake coefficients for the decay of the double bonds in squalene of (3.1 ± 0.7) × 10-4, (2.6 ± 0.6) × 10-4, and (2.9 ± 0.7) × 10-4, respectively. When comparing these values with the uptake coefficient, (1.0 ± 0.2) × 10-3, determined by the molecular decay of squalene measured with aerosol mass spectrometry, it is found that on average 1.6 ± 0.2 double bonds are removed for each ozone-squalene reactive collision, suggesting the importance of evaporation of small molecular weight reaction products from the aerosol. From further analysis of the nanoparticle XPS spectrum, it is found that ozonolysis increases the oxygen-to-carbon (O:C) ratio of the aerosol to 0.43 ± 0.03 and produces 16 ± 4% and 84 ± 4% secondary ozonides and carbonyls, respectively. The methods developed here show how aerosol photoemission can be used to quantify heterogeneous reaction on free nanoparticles.


Nine new species of Phoridae (Insecta: Diptera) from Spain.
One new species of Triphleba Rondani and eight new species of Megaselia Rondani are described from Montseny Natural Park (mainland Spain). The new species are Megaselia arbuciensis García-Romera sp.nov., Megaselia barrientosi García-Romera sp. nov., Megaselia callunae García-Romera sp. nov., Megaselia carminis García-Romera sp. nov., Megaselia ivanis García-Romera sp. nov., Megaselia longianalis García-Romera sp. nov., Megaselia montseniensis García-Romera sp. nov., Megaselia sarae García-Romera sp. nov., Triphleba beatricis García-Romera sp. nov.


Combined effect of environmental pollutants (nickel, chlorpyrifos) and temperature on the ground beetle, Pterostichus oblongopunctatus (Coleoptera: Carabidae).
Terrestrial organisms in the field often are exposed to a combination of stress factors of various origins, but little is known about interactions between different types of stressors. In the present study, we demonstrate the results of a study on interactions between Ni, chlorpyrifos (CPF), and temperature in the ground beetle, Pterostichus oblongopunctatus. The results revealed that all factors, and their interactions, influenced life-cycle parameters of the beetles (survival and reproduction). Significant three-factor interactions were found for effects on beetle survival, indicating that the combined negative effect of Ni and CPF was temperature dependent. In addition, significant effects of body mass were found: The survival of beetles treated with CPF and the reproduction of beetles exposed to Ni were positively correlated with body mass. All studied endpoints were affected by temperature. The results indicate that understanding interactions between temperature and toxicants, as well as among chemicals themselves, is essential for proper ecological risk assessment.


Regulation of proopiomelanocortin gene expression in rat brain and pituitary as studied by in situ hybridization.
The major sites of POMC gene expression are the intermediate and anterior lobes of the pituitary and the arcuate nucleus of the hypothalamus. We have investigated the regulation of POMC mRNA levels in the pituitary and hypothalamus by quantitative in situ hybridization using a 35S-labeled cDNA probe encoding or POMC. In the arcuate nucleus, where the POMC-producing neurons are concentrated, adrenalectomy induced a marked decrease in POMC mRNA levels, an effect that was completely reversed by dexamethasone administration. The stimulating effect of dexamethasone was much more striking in the most caudal regions of the nucleus. Since in the anterior pituitary, glucocorticoids exert an inhibitory action on POMC gene expression, it might be suggested that POMC is differentially regulated by glucocorticoids in the anterior pituitary and the hypothalamus. Ovariectomy induced an increase in mRNA levels in the most rostral region of the arcuate nucleus, an effect that was prevented by the concurrent administration of estradiol or dihydrotestosterone. The role of dopamine was investigated following the administration of the dopaminergic antagonist haloperidol and the D2 dopaminergic receptor agonist bromocriptine. In the arcuate nucleus, bromocriptine increased and haloperidol decreased the hybridization signal. Conversely, in the intermediate lobe of the pituitary, bromocriptine markedly depressed and haloperidol increased the levels of mRNA. These results indicate that the population of POMC neurons in the arcuate nucleus is heterogeneous. They also demonstrate that POMC gene expression is regulated by central and peripheral factors and that this regulation is different in the brain and the pituitary.


Anomalous portal venous connection to the suprahepatic vena cava: sonographic demonstration.
The authors report a congenital portosystemic shunt which was detected with ultrasound in an infant with a fatal congenital hypertrophic cardiomyopathy. An aberration in primitive vitelline venous development may have contributed to the formation of this unusual vessel.


The traditional medical uses and cytotoxic activities of sixty-one Egyptian plants: discovery of an active cardiac glycoside from Urginea maritima.
Medicinal plants from the Sinai desert are widely used in traditional Bedouin medicine to treat a range of conditions including, cancers, and may thus be useful sources of novel anti-tumor compounds. Information on plants used in this way was obtained through collaboration with Bedouin herbalists. To document the traditional uses of 61 species from 29 families of Egyptian medicinal plants and to investigate their biological activity using a cytotoxicity assay. MeOH extracts of the 61 plant species investigated were dissolved in 10% DMSO and their cytotoxic activity was evaluated. The extracts were tested in duplicate on three separate occasions at three different concentrations (1, 10 and 100μg/ml) against human lymphoma U-937 GTB. The most active extract was subjected to bioassay-guided fractionation using HPLC and LC/ESI-MS to isolate and identify its active components. The most potent extracts were those from Asclepias sinaica, Urginea maritima, Nerium oleander and Catharanthus roseus, followed by those from Cichorium endivia, Pulicaria undulate and Melia azedarach. Literature reports indicate that several of these plants produce cardiac glycosides. Bioassay-guided fractionation of alcoholic U. maritima extracts led to the isolation of a bioactive bufadienolide that was subsequently shown to be proscillaridin A, as determined by 1D and 2D NMR spectroscopy. This result demonstrates the value of plants used in traditional medicine as sources of medicinally interesting cytotoxic compounds.


Two stable levels of diastolic potential at physiological K+ concentrations in human ventricular myocardial cells.
Cells in many specimens of human ventricle can exhibit either of two stable levels of diastolic potential (DP) when exposed to 4 mM K+ in vitro (i.e., -78 +/- 4 mV or -45 +/- 5 mV, mean +/- SEM). In this report we show that the DP of some partially depolarized human ventricular cells developed a sustained 25-35 mV hyperpolarization (n = 28) when bath K+ concentration (K+b) was raised from 4 to 7 mM. On return of K+b to 4 mM, the DP of most, but not all, of these cells returned to the original depolarized levels. In other cells, the transition between the two levels of DP occurred at variable K+b ranging from 1 to 20 mM. We investigated the ionic mechanism(s) underlying the shifts between the two levels of potential by studying the K+ dependence of the DP in partially depolarized cells in 22 specimens of human ventricle. DP hyperpolarized an average of 25.6 mV (from -44.4 +/- 1.3 to -70.0 +/- 1.3 mV; n = 25) when K+b was increased from 4 to 7 mM. Intracellular K+ activity, determined by K+-selective microelectrodes, was within the range of normal reported for other mammalian species (106.7 +/- 4.4 mM in 4 mM K+; n = 22) and was unaffected by increasing K+b to 7 mM (111.7 +/- 6.6 mM; n = 6). Ba2+ (0.05 mM), a blocker of the inward rectifying K+ current, reversibly prevented the hyperpolarization, whereas acetylstrophanthidin (9 microM) failed to inhibit it. These results suggest that the hyperpolarization was due to a K+-dependent increase in K+ permeability and that electrogenic sodium pumping did not contribute significantly to the process. The ionic basis of the depolarization from a hyperpolarized level of DP also was investigated. Decreasing bath Na+ concentration and exposure to 30 microM tetrodotoxin did not prevent the depolarization. However, the depolarization could be inhibited by 2 mM Mn2+. These findings suggest that the depolarization may have been due to a Mn2+-sensitive inward current.


Structural, geometric and genetic factors predict interregional brain connectivity patterns probed by electrocorticography.
Electrocorticography (ECoG) data can be used to estimate brain-wide connectivity patterns. Yet, the invasiveness of ECoG, incomplete cortical coverage, and variability in electrode placement across individuals make the network analysis of ECoG data challenging. Here, we show that the architecture of whole-brain ECoG networks and the factors that shape it can be studied by analysing whole-brain, interregional and band-limited ECoG networks from a large cohort-in this case, of individuals with medication-resistant epilepsy. Using tools from network science, we characterized the basic organization of ECoG networks, including frequency-specific architecture, segregated modules and the dependence of connection weights on interregional Euclidean distance. We then used linear models to explain variabilities in the connection strengths between pairs of brain regions, and to highlight the joint role, in shaping the brain-wide organization of ECoG networks, of communication along white matter pathways, interregional Euclidean distance and correlated gene expression. Moreover, we extended these models to predict out-of-sample, single-subject data. Our predictive models may have future clinical utility; for example, by anticipating the effect of cortical resection on interregional communication.


Anticipating deep autumn: a widening lens.
Medicine has become one of the most powerful influences of the twentieth century, and currently dominates how we approach and think about another powerful phenomenon: the aging of the world's population. Our reliance on the medical model, with its focus on pathology, physiology, and biomedical interventions, makes it difficult for aging men and women and those in the health care field who care for them to seek alternative ways to attach meaning to the process of growing old. This article explores the role of the humanities as an alternative to the biomedical model which can enlarge our abilities to see the multidimensional aspects of aging. Age related writings and visual images by Kenyon, Neel, Olds, Valadon, and Hemingway are discussed to illustrate how fictive representations can and do serve as a moral impetus or stimulus for meaningful reflection about life stages that have not yet been experienced.


Borges in my office: the analysis of a man dwelling outside of time.
This article weaves together two threads: the intricacies of the analysis of a difficult-to-reach yet extraordinary patient and the literary works of Jorge Luis Borges, which played a significant role in the analysis as a source of inspiration, enriching the analyst's reverie and opening up new psychic spaces. The authors demonstrate the analyst's recourse to several of Borges's stories in order to enrich his own inner world and to better understand the analysand. Some of these stories are briefly presented through the analyst's dialogue with them, and there is a discussion of their function in facilitating the process of working through issues of time, memory, mortality, and identity, contributing to the enhancement of the patient's ability to come face to face with the unwanted, split-off parts of his self and of reality.


Childhood cancer: incidence and early deaths in Argentina, 2000-2008.
Knowledge on the epidemiology of childhood cancer in Latin America is limited. The Argentinean Oncopaediatric Registry (ROHA) has been active since 2000. Data for 2000-2008 are described in the present work. ROHA is fed from a network of paediatric units and population-based cancer registries. Cases are coded by the International Classification of Childhood Cancer. A total of 11447 children aged 0-14 diagnosed with cancer were reported. Histologically verified cases and cases identified only through death certificates were respectively 91% and 6%. The annual age of standardised incidence rate of all cancers was 128.5 per million. Proportions of leukaemia's, lymphoma's and Central Nervous System tumours were 37%, 13% and 18%. The distribution of rates of acute lymphatic leukaemia by the year of age showed a peak around age 3. Eighty percent of the patients are treated in public hospital and around 35% migrate for some of the treatment. Deaths within a month of diagnosis were 5% in 2000 and 3% in 2008. Childhood cancer incidence in Argentina is somewhat lower than in North American and in Western European countries: the deficit is mainly due to tumours of the Central Nervous system and other solid tumours. Childhood cancer incidence did not show any tendency to increase. The possible excess of Hodgkin lymphoma in the Northeast region requires additional studies. Early deaths after diagnosis indicate an unsatisfactory state of the overall organisation of childhood cancer care. Data from ROHA are used for decision making at local and national levels.


New scalarane-based sesterterpenes from the sponge Phyllospongia madagascarensis.
Two new natural scalaranes, 16beta-acetoxy-20,24-dimethyl-12,24-dioxo-25-norscalarane and 12beta-hydroxy-20,24-dimethyl-13,18-oxa-25-norscalarane, were isolated from the Madagascaran sponge Phyllospongiamadagascarensis, together with three previously decribed tetracyclic sesterterpenoids, phyllofolactones F, G, and B, and a new artifactual ethyl ether of scalaradisin B. Structure determinations were based on NMR and other spectral data. Compounds 1 and 2 represent new examples of 20,24-dimethyl-25-norscalarane sesterterpenes, and compound 2 has a seven-membered oxacycle that makes its skeletal system unique.


Intramedullary neurofibroma of the cervical spinal cord: case report with review of the literature.
A case of cervical intramedullary neurofibroma diagnosed and surgically treated is reported. This patient, a 27-year-old man, had no evidence of von Recklinghausen's disease. The case is discussed, and a review of literature is presented.


Simultaneous analysis of cyclophosphamide, doxorubicin and doxorubicinol by liquid chromatography coupled to tandem mass spectrometry.
A method for the simultaneous determination of cyclophosphamide (CP), doxorubicin (dox), and doxorubicinol (dol) was developed and validated to analyze 400 microL of plasma from patients receiving chemotherapeutic treatment with CP and dox. Final calibration ranges for the analytes were 0.440-60.0 microg/mL for cyclophosphamide, 7.20-984 ng/mL for dox and 3.04-104 ng/mL for dol. The samples were prepared using solid phase extraction and analyzed using a gradient separation over a Waters Symmetry C18, 2.1 by 30 mm (Milford, MA) column. Detection was achieved in positive mixed reaction monitoring mode on a triple quadrupole mass spectrometer.


The Burden of Macular Diseases in Central and Eastern Europe-Implications for Healthcare Systems.
Despite the significant impact of retinal diseases such as wet age-related macular degeneration (wAMD) and diabetic macular edema (DME), there is a limited understanding of how these conditions are managed in Central and Eastern Europe (CEE). To provide a comprehensive overview of the clinical and economic burden of wAMD and DME in CEE and the status quo associated with their management. A narrative literature review was undertaken to identify existing data on wAMD and DME, including epidemiology, economic burden, clinical guidelines, and available and reimbursed treatments. Data were collected from relevant sources such as PubMed, ophthalmology associations, national statistical offices, and government agency websites; practical viewpoints were provided by local ophthalmologists and healthcare economics experts in CEE. Epidemiological data on wAMD and DME are limited in CEE, and intercountry comparison is difficult because of differences in data collection methodologies. There are effective treatment options for wAMD and DME, and international guidelines advocate the use of intravitreal anti-vascular endothelial growth factor injections as first-line therapy. Local expert organizations broadly support these recommendations; nevertheless, no clinical practice guidelines exist on the treatment of wAMD and DME in CEE. Access to and reimbursement of anti-vascular endothelial growth factor agents vary significantly in the region and, as a result, many patients remain untreated or inadequately treated. There is an urgent need for the creation of a wAMD/DME treatment program in CEE to ensure that patients have timely access to the most appropriate treatments.


Pilot trial to compare tolerance of chlorhexidine gluconate to povidone-iodine antisepsis for central venous catheter placement in neonates.
The purpose of this pilot trial was to determine whether rates of contact dermatitis following cutaneous antisepsis for central catheter placement were similar among neonates treated with chlorhexidine gluconate and povidone-iodine. Chlorhexidine gluconate absorption was also evaluated. Infants weighing > or =1500 g and > or =7 days of age were randomized to a 10% povidone-iodine or 2% chlorhexidine gluconate site scrub before catheter placement. Primary outcomes evaluated included dermatitis, catheter colonization and chlorhexidine gluconate absorption. A total of 48 neonates were enrolled. Colonization rates were similar among treatment groups (P<0.6). Dermatitis did not occur at chlorhexidine gluconate (central catheters, n=24; peripheral catheters, n=29) sites. Seven neonates had measurable chlorhexidine gluconate concentrations (range 13 to 100 ng ml(-1)) during catheterization. In this small trial chlorhexidine gluconate antisepsis was tolerated by study neonates. Chlorhexidine gluconate was cutaneously absorbed. Larger trials are needed to determine efficacy and tolerance of chlorhexidine gluconate in neonates.


Glutamate release from guinea-pig synaptosomes: stimulation by reuptake-induced depolarization.
Glutamate (10-100 microM) reversibly depolarizes guinea-pig cerebral cortical synaptosomes. This does not appear to be because of a conventional autoreceptor. Neither kainate at 1 mM, 100 microM N-methyl-D-aspartate (NMDA), 100 microM L-2-amino-4-phosphonobutanoate (APB), nor 100 microM quisqualate affects the Ca2+-dependent release of glutamate from suboptimally depolarized synaptosomes. However, kainate, quisqualate, and the quisqualate agonists beta-N-oxalylamino-L-alanine and alpha-amino-3-hydroxy-5-methylisoxazole propionate cause a slow Ca2+-independent release of glutamate from polarized synaptosomes. However, unlike kainate, quisqualate does not inhibit the acidic amino acid carrier. APB, NMDA, and the NMDA receptor-mediated neurotoxin beta-N-methylamino-L-alanine do not influence Ca2+-independent release at 100 microM. The depolarization of the plasma membrane by glutamate can be mimicked by D-aspartate, can be blocked by the transport inhibitor dihydrokainate, and is accompanied by the net uptake of acidic amino acids. L-Glutamate or D-aspartate at 100 microM increases the cytoplasmic free Ca2+ concentration. D-aspartate at 100 microM causes a Ca2+-dependent release of endogenous glutamate, superimposed on the Ca2+-independent heteroexchange with glutamate through the acidic amino acid carrier. The results suggest that the glutamatergic subpopulation of synaptosomes can be depolarized by exogenous glutamate.


Highly efficient protein separations in high-performance capillary electrophoresis, using hydrophilic coatings on polysiloxane-bonded columns.
Three methods for preparing hydrophilic coatings on polysiloxane bonded CElect H-type capillary electrophoresis columns have been shown. The polyalkylsiloxane-bonded phase is the first coating layer on the capillary surface, and nonionic surfactant, hydrophilic polymer, or polymer surfactant, adsorbed onto this first later through hydrophobic interactions, forms the second coating layer. The resultant capillary surfaces are inert, hydrophilic, and suitable for highly efficient protein separations. The effectiveness and applicability of these capillary surface modification methods were tested for the separations of a variety of proteins over a wide range of buffer pH values under different capillary electrophoretic operations modes.


Ranitidine-enhanced 99mtechnetium pertechnetate imaging in children improves the sensitivity of identifying heterotopic gastric mucosa in Meckel's diverticulum.
Meckel's diverticulum is the most common congenital gastrointestinal anomaly. (99m )Technetium pertechnetate imaging (Meckel's scan) is the best noninvasive method used to diagnose this condition when heterotopic gastric mucosa (HGM) is present. Although cimetidine enhancement has been shown to improve sensitivity of the Meckel's scan, ranitidine enhancement has also been advocated; however, this recommendation is based on unpublished data. Thirty-seven children with confirmed Meckel's diverticulum were reviewed retrospectively. Of eight children with HGM in the Meckel's diverticulum who presented with profuse rectal bleeding and underwent the conventional Meckel's scan, three of them (37.5%) had a false negative study. Ranitidine, when administered either intravenously or orally for 24 h prior to the Meckel's scan, enhanced the sensitivity of this test to 87.5% in our patient cohort.


NaF-loaded core-shell PAN-PMMA nanofibers as reinforcements for Bis-GMA/TEGDMA restorative resins.
A kind of core-shell nanofibers containing sodium fluoride (NaF) was produced and used as reinforcing materials for dimethacrylate-based dental restorative resins in this study. The core-shell nanofibers were prepared by coaxial-electrospinning with polyacrylonitrile (PAN) and poly(methyl methacrylate) (PMMA) solutions as core and shell fluids, respectively. The produced PAN-PMMA nanofibers varied in fiber diameter and the thickness of PMMA shell depending on electrospinning parameters. NaF-loaded nanofibers were obtained by incorporating NaF nanocrystals into the core fluid at two loadings (0.8 or 1.0wt.%). Embedment of NaF nanocrystals into the PAN core did not damage the core-shell structure. The addition of PAN-PMMA nanofibers into Bis-GMA/TEGDMA clearly showed the reinforcement due to the good interfacial adhesion between fibers and resin. The flexural strength (Fs) and flexural modulus (Ey) of the composites decreased slightly as the thickness of PMMA shell increasing. Sustained fluoride releases with minor initial burst release were achieved from NaF-loaded core-shell nanofibers and the corresponding composites, which was quite different from the case of embedding NaF nanocrystals into the dental resin directly. The study demonstrated that NaF-loaded PAN-PMMA core-shell nanofibers were not only able to improve the mechanical properties of restorative resin, but also able to provide sustained fluoride release to help in preventing secondary caries.


[Tissue typing and donor-recipient selection in dogs for experimental organ transplants].
About first results of a tissue typing for donor recipient selection in dog is reported on obtaining an optimum degree of histocompatibility. The modified NIH-test according to Brand and coworker was carried out. The sera for typing were prepared by means of artificial or natural immunisation. Serologic and genetic problems are discussed. Possibilities on perfection are shown for donor recipient selection in dogs.


The impact of early palatal obturation on consonant development in babies with unrepaired cleft palate.
The purpose of this investigation was to determine whether palatal obturators enhance consonant development during babbling for babies with unrepaired cleft palate. Fourteen babies with cleft palate who had worn anterior palatal obturators prior to palatal surgery were matched to 14 unobturated babies according to cleft type, sex, and age at time of presurgical evaluation. Spontaneous vocalizations of the obturated and unobturated groups were compared to determine whether differences were evident in size of consonant inventory as well as place and manner of consonant production. Paired t tests revealed no significant differences between the groups in size of consonant inventory or place and manner of consonant production. There was a trend for babies in the obturated group to produce more glottal consonants. In general, the findings of this study suggested that palatal obturators do not appear to facilitate production of anterior palatal consonants during babbling.


Highly conserved DNA sequence present in small plasmids from Selenomonas ruminantium.
Plasmid pJW1 from Selenomonas ruminantium subsp. lactilytica strain JW13 has been cloned in Escherichia coli vector pBluescriptSK(-) and completely sequenced. The plasmid is only 1410 bp with an overall GC content of 42.2%. Computer analysis of sequence data revealed a single open reading frame (ORF1, 146 amino acids, MW 16,525.5 Da) encoding a putative replication protein which is similar to the Rep protein of Ruminobacter amylophilus plasmid pRAO1. ORF1 is followed by a long AT-rich (75%) region and a region abundant in direct and inverted repeats. Comparison of DNA sequences revealed the presence of a short (<250 bp) DNA segment which is highly conserved between several small S. ruminantium plasmids including pJDB21.


[Frequency and significance of inflammatory pancreatic duct changes in patients with upper abdominal pain of unknown origin].
In 104 patients with longstanding abdominal pain of unknown origin endoscopic pancreatography was carried through after a thorough noninvasive exploration (Secretin-CCK-test included). Pancreatography revealed in 18% slight but distinct-pathological changes at the pancreatic duct system compatible with chronic pancreatitis. As the frequency of the pathological pancreatographic findings showed no correlation with duration of pain history but a significant correlation with age it is suggested that the duct changes encountered represent rather age-dependent irrelevant fibrosis of the pancreas tan clinically relevant chronic pancreatitis. Slight pathological duct changes are by themselves no proof of chronic pancreatitis because there is no possibility to discriminate between chronic pancreatitis and age-dependent fibrosis on the ground of pancreatography. ERP therefore is of little or no value in patients with otherwise insubstantial suspicion of chronic pancreatitis.


Neoadjuvant treatment followed by surgery versus definitive chemoradiation in stage IIIA-N2 non-small-cell lung cancer: A multi-institutional study by the oncologic group for the study of lung cancer (Spanish Radiation Oncology Society).
The role of surgery in stage IIIA-N2 non-small cell lung cancer (NSCLC) is an actively debated in oncology. To evaluate the value of surgery in this patient population, we conducted a multi-institutional retrospective study comparing neoadjuvant chemoradiotherapy or chemotherapy plus surgery (CRTS) to definitive chemoradiotherapy (dCRT). A total of 247 patients with potentially resectable stage T1-T3N2M0 NSCLC treated with either CRTS or dCRT between January 2005 and December 2014 at 15 hospitals in Spain were identified. A centralized review was performed to ensure resectability. A propensity score matched analysis was carried out to balance patient and tumor characteristics (n = 78 per group). Of the 247 patients, 118 were treated with CRTS and 129 with dCRT. In the CRTS group, 62 patients (52.5%) received neoadjuvant CRT and 56 (47.4%) neoadjuvant chemotherapy. Surgery consisted of either lobectomy (97 patients; 82.2%) or pneumonectomy (21 patients; 17.8%). In the matched samples, median overall survival (OS; 56 vs 29 months, log-rank p = .002) and progression-free survival (PFS; 46 vs 15 months, log-rank p < 0.001) were significantly higher in the CRTS group. This survival advantage for CRTS was maintained in the subset comparison between the lobectomy subgroup versus dCRT (OS: 57 vs 29 months, p < 0.001; PFS: 46 vs 15 months, p < 0.001), but not in the comparison between the pneumonectomy subgroup and dCRT. The findings reported here indicate that neoadjuvant chemotherapy or chemoradiotherapy followed by surgery (preferably lobectomy) yields better OS and PFS than definitive chemoradiotherapy in patients with resectable stage IIIA-N2 NSCLC.


Peroxidase activity in Malpighian tubules of Triatoma infestans Klug.
Benzidine and diamino benzidine (DAB) oxidation, typically performed by peroxidases, was demonstrated by light and electron microscopy in peroxisomes, mitochondria and membranous structures which occurred in close contact with urate crystals in Malpighian tubules of nymphs and adults of Triatoma infestans. Peroxisomes were predominantly identified in cells of the distal region of the tubules, which is engaged in excretory mechanisms. DAB oxidation in mitochondria, even in the absence of hydrogen peroxide, may indicate the existence of a mitochondrial peroxidase and possibly a cytochrome c peroxidase. The localization of the extracellular membranous structures appeared restricted to the lumen of the proximal region of the tubules and they were assumed to be remnants of endoplasmic reticulum containing peroxidases.


Expression profile of HIN200 in leukocytes and renal biopsy of SLE patients by real-time RT-PCR.
HIN200 is a human IFN-inducible gene and homologous to murine IFI202 gene, which was identified as a candidate gene for SLE susceptibility in lupus mouse model. We determined these gene expressions in leukocytes from 20 SLE patients and 10 healthy controls and in renal biopsies from 29 SLE patients and 15 kidney donors using sensitive real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The expressions of MNDA, IFIX, IFI16 and AIM2 genes significantly increased in leukocytes but not in kidney biopsies from SLE patients as compared to the control individuals, with P = 0.0003, P = 0.0056, P = 0.0002 and P < 0.0001, respectively. We also assessed the expression profiles of IFIX and IFI16 isoforms using semi-quantitative RT-PCR. We found up-regulation of B isoform (short product) of IFI16 in SLE patients. In addition, the expression levels were analyzed in correlation with disease activity and clinical characteristics. Interestingly, higher expression of MNDA was observed in patients who were positive for anti-dsDNA antibodies than in patients who were negative (P = 0.0276). In conclusion, it is suggested that the HIN200 genes have a role in SLE pathogenesis. Our study also observed a possible important role of a specific short isoform of IFI16 as well as a link between MNDA and anti-dsDNA antibody production.


Long term response to therapy of chronic anti-HBe-positive hepatitis B is poor independent of type and schedule of interferon.
The response rate to alpha interferon (IFN) of chronic anti-HBe-positive hepatitis B is variable. We studied whether type, dose, and schedule of IFN, and type and frequency of posttreatment monitoring, influence the response rate. Seventy-two consecutive anti-HBe-positive chronic hepatitis B patients (59 male and 13 female, median age 41 yr) stratified by sex and histology were randomly allocated to three treatment arms. Twenty-seven patients (A) received 10 million units alpha-N1 IFN i.m. t.w. for 24 wk (total dose: 720 million units); 21 (B) received 9 million units alpha-2a IFN i.m. t.w. for 4 wk, followed by 18 million units for 12 wk and 9 million units for 8 wk (972 million units); 24 (C) received 2 alpha-2a IFN courses (9 million units i.m. t.w. for 16 and 12 wk separated by a 6-month interval [756 million units]). Primary response was defined by normal ALT and serum HBV-DNA levels below 10 pg/ml at the end of therapy and sustained response by normal ALT (tested monthly), undetectable HBV-DNA and IgM anti-HBc (<7 I.U. Paul Ehrlich Institute) (tested every 3 months) during the posttreatment follow-up. At the end of treatment, 12, 8, and 13 patients from groups A, B, and C, respectively, were responders. At the 18-month follow-up, two patients in group A and only one in groups B and C maintained the response. Overall, after 34 months (median posttreatment follow-up), three patients were long term responders, whereas three showed a sustained remission after relapse. The rate of long term response to interferon of anti-HBe-positive chronic hepatitis B is poor, independent of IFN type, dose, or schedule; the more stringent the monitoring, the higher the relapse rate.


Combustion of brominated flame retardants and behavior of its byproducts.
The substance flow rate of PBDDs/DFs into flue gas and incineration residues from incineration of three types of waste samples containing brominated flame retardants were examined. The samples used consisted of PBDEs (a typical retardant), used TV casing materials (actual waste materials), and waste printed circuit boards. PBDDs/DFs concentrations in the experimental samples of PBDEs/PE, waste TV casing materials and printed circuit boards ranged between 3000 and 130,000 ng/g. These values are very high when compared to other investigations. The increase of chlorine concentration in input sample reduced the ratio of PBDDs/DFs in flue gas and raised the ratio of PCDDs/DFs. With adequate combustion control and flue gas treatment, the amount of PBDDs/DFs released from the incineration of resin containing brominated flame retardants was lower than the input amount. The presence of PBDDs/DFs in incineration residues dominated the total amount of dioxins released. When PBDDs/DFs, PCDDs/DFs and PXDDs/DFs were considered as a total, the total amount released was lower than the total amount input.


Prostate cancer: the role of hormonal therapy.
Prostate cancer is the cause of more than 1% of all deaths in men. Its incidence is increasing by 2-3% per year. The general prognosis for diagnosed prostate cancer remains poor, with 70% survival at 10 years compared to the general population. About 50% of the cases are diagnosed at a locally advanced stage, and about 30% have bone metastases at the time of diagnosis. Adjuvant systemic treatments (hormones or chemotherapy), which are effective for advanced-stage disease, might have a greater role in early-stage disease. Advanced prostate cancer is an incurable disease. Treatment objective is palliation only. Here, we review the major controversies concerning hormonal therapy, and provide a general approach to management of patients with early-stage and advanced prostate cancer.


Multiple-Level Porous Polymer Monoliths with Interconnected Cellular Topology Prepared by Combining Hard Sphere and Emulsion Templating for Use in Bone Tissue Engineering.
A combination of hard sphere and high internal phase emulsion templating gives a platform for synthesizing hierarchically porous polymers with a unique topology exhibiting interconnected spherical features on multiple levels. Polymeric spheres are fused by thermal sintering to create a 3D monolithic structure while an emulsion with a high proportion of internal phase and monomers in the continuous phase is added to the voids of the previously constructed monolith. Following polymerization of the emulsion and dissolution of the templating structure, a down-replicating topology is created with a primary level of pores as a result of fused spheres of the 3D monolithic structure, a secondary level of pores resulting from the emulsion's internal phase, and a tertiary level of interconnecting channels. Thiol-ene chemistry with divinyladipate and pentaerythritol tetrakis(3-mercaptopropionate) is used to demonstrate the preparation of a crosslinked polyester with overall porosity close to 90%. Due to multilevel porosity, such materials are interesting for applications in bone tissue engineering, possibly simulating the native sponge like bone structure. Their potential to promote ossteointegration is tested using human bone derived osteoblasts. Material-cell interactions are evaluated and they reveal growth and proliferation of osteoblasts both on surface and in the bulk of the scaffold.


Uptake studies for evaluating activity of efflux transporters in a cell line representative of the blood-brain barrier.
In this unit, protocols are presented for performing uptake studies with bovine brain microvessel endothelial cells (BBMECs) using either radiolabeled compounds, or rhodamine 123 as a marker for a P-glycoprotein substrate. The protocols can easily be modified for the investigation of substrate uptake in other cell lines.


Precision Analysis of the ^{136}Xe Two-Neutrino ββ Spectrum in KamLAND-Zen and Its Impact on the Quenching of Nuclear Matrix Elements.
We present a precision analysis of the ^{136}Xe two-neutrino ββ electron spectrum above 0.8 MeV, based on high-statistics data obtained with the KamLAND-Zen experiment. An improved formalism for the two-neutrino ββ rate allows us to measure the ratio of the leading and subleading 2νββ nuclear matrix elements (NMEs), ξ_{31}^{2ν}=-0.26_{-0.25}^{+0.31}. Theoretical predictions from the nuclear shell model and the majority of the quasiparticle random-phase approximation (QRPA) calculations are consistent with the experimental limit. However, part of the ξ_{31}^{2ν} range allowed by the QRPA is excluded by the present measurement at the 90% confidence level. Our analysis reveals that predicted ξ_{31}^{2ν} values are sensitive to the quenching of NMEs and the competing contributions from low- and high-energy states in the intermediate nucleus. Because these aspects are also at play in neutrinoless ββ decay, ξ_{31}^{2ν} provides new insights toward reliable neutrinoless ββ NMEs.


Construction, expression, and characterization of AG11-843 and AG11-1581.
AG1, a member of the DUF1220 protein family, exhibits the most extreme human lineage-specific copy number expansion of any protein-coding sequence in the genome. These variations in copy number have been linked to both brain evolution among primates and brain size in humans. Unfortunately, our current understanding of the structure and function of these proteins is limited because current cloning and expression techniques fail to consistently produce recombinant protein for in vitro studies. The present work describes a method for amino acid and DNA sequence optimization and synthesis, recombinant protein expression and analysis of two AG1 fragments, AG11-843 and AG11-1581. It was first necessary to modify the nucleotide sequence, while holding the GC content at 52.9%. The genes were then sectionally synthesized by overlap PCR. The resulting segments were cloned into the pET-15 b-sumo expression vector and subsequently transformed into BL21 (DE3) cells. After inducing their expression, the AG11-843 and AG11-1581 proteins were isolated and purified. Furthermore, using dynamic light scattering and gel filtration analysis, AG11-843 and AG11-1581 were shown to be present in tetrameric and dimeric forms in solution. To our knowledge, this is the first study to synthesize and express fragments of the DUF1220 protein family for in vitro analysis. Taken together, the proven utility and versatility of this method indicate that it can be used as an effective technique to construct and express other proteins with complicated sequences, thus providing the means to study their function and structure in vitro.


Adrenaline stimulates thromboxane and inhibits leukotriene synthesis in man.
Catecholamines and other catecholic compounds have opposite effects on the cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism in human polymorphonuclear leukocytes and whole blood in vitro. The hypothesis that high levels of adrenaline, found e.g. in myocardial infarction, are involved in the regulation of arachidonic acid metabolism was tested. Adrenaline (0.1 micrograms/kg per min for 45 min and thereafter 0.2 micrograms/kg per min for 15 min) was infused to healthy male volunteers to mimic relationships between high levels of adrenaline and arachidonic acid metabolism in myocardial infarction. Adrenaline infusion increased Ca ionophore A23187-induced TXB2 formation in whole blood. The effect was smaller when spontaneous clotting was used as a stimulus. Urinary 11-dehydro-TXB2 excretion, an indicator of total in vivo thromboxane synthesis, increased twofold. Adrenaline infusion decreased both LTB4 and LTE4 synthesis in A23187-stimulated whole blood. These results demonstrate that high levels of adrenaline influence the cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism differentially in man.


Piezo-Phototronic Matrix via a Nanowire Array.
Piezoelectric semiconductors, such as ZnO and GaN, demonstrate multiproperty coupling effects toward various aspects of mechanical, electrical, and optical excitation. In particular, the three-way coupling among semiconducting, photoexcitation, and piezoelectric characteristics in wurtzite-structured semiconductors is established as a new field, which was first coined as piezo-phototronics by Wang in 2010. The piezo-phototronic effect can controllably modulate the charge-carrier generation, separation, transport, and/or recombination in optical-electronic processes by modifying the band structure at the metal-semiconductor or semiconductor-semiconductor heterojunction/interface. Here, the progress made in using the piezo-phototronic effect for enhancing photodetectors, pressure sensors, light-emitting diodes, and solar cells is reviewed. In comparison with previous works on a single piezoelectric semiconducting nanowire, piezo-phototronic nanodevices built using nanowire arrays provide a promising platform for fabricating integrated optoelectronics with the realization of high-spatial-resolution imaging and fast responsivity.


Squamous cell carcinoma masquerading as a thoracic intramural hematoma.
Transesophageal echocardiography (TEE) is an excellent tool for the diagnosis of thoracic aortic pathology. However, not all lesions of the aortic wall represent primary pathology of the aorta. This case presents an elderly, hypertensive patient with back pain and crescentic thickening of the aortic wall that proved to represent external aortic infiltration by lung cancer. Invasion of the aortic wall mimicking intramural hematoma should be considered the differential diagnosis of patients with dissection-like symptoms and crescentic aortic lesions.


A simple method for the preparation of cell cultures for ultrastructural investigation.
A method is described that allows investigation of cultured cells at the light or electron microscopical level without changing the culturing conditions or the in situ situation during dehydration or embedding. Fixed and dehydrated cell culture layers were cut into small pieces and separated from the plastic dish by adding propylene oxide. With this simple method we could obtain orientated sections of selected cell groups.


Prenatal exposure to benzodiazepine--I. Prenatal exposure to lorazepam in mice alters open-field activity and GABAA receptor function.
Prenatal exposure to benzodiazepines may lead to developmental abnormalities in humans and animals. To assess the behavioral and neurochemical effects of such exposure, pregnant mice were treated with lorazepam, 2 mg/kg/day, from days 13-20 of gestation, and open-field activity was assessed in offspring at 3 and 6 weeks of age and the function of GABAA receptors at 6 weeks of age. Activity was increased in mice exposed to lorazepam, compared to untreated or vehicle-treated controls at 3 weeks, but was unchanged at 6 weeks. Muscimol-stimulated uptake of chloride was decreased in lorazepam-treated mice, compared to controls, with a decrease in maximum uptake but no change in the EC50 for muscimol. Concentrations of lorazepam in maternal plasma and brain showed a similar brain:plasma ratio as previously reported and concentrations in fetal brain were about 50% of maternal levels. Lorazepam persisted for 48 hours after birth in dams but not in the offspring. These results indicate persistent behavioral and neurochemical alterations after prenatal exposure to lorazepam. This model may be useful in assessing other effects of prenatal exposure to benzodiazepine.


A nanobody-based method for tracking factor XII activation in plasma.
The physiological role of the plasma protein factor XII (FXII), as well as its involvement in human pathology, is poorly understood. While FXII is implicated in thrombotic pathology as a coagulation factor, it can contribute to inflammatory conditions without triggering coagulation. We recently generated nanobodies against the catalytic domain of activated FXII (FXIIa). Here, we describe two of these nanobodies, A10 and B7, both of which do not recognise FXII. Nanobody A10 recognises the catalytic domain of purified α-FXIIa (80 kDa), but not that of purified β-FXIIa (28 kDa), whereas nanobody B7 recognises both. This suggests minute differences in the catalytic domain between these isoforms of FXIIa. The detection of FXIIa by these nanobodies in plasma can become compromised through inactivation by serine protease inhibitors. This effect can be efficiently countered through the addition of the small-molecular protease inhibitor PPACK. Finally, we show that our nanobody-based assays in vitro distinguish various activation products of FXII that differ with the type of activator present: whereas procoagulant activators solely trigger the formation of a species that is captured by B7, proinflammatory activators first generate a species that is recognised by B7, which is later converted into a species that is recognised by A10. These findings suggest that a progressive proteolysis of FXIIa results in the generation a non-procoagulant form of FXIIa, whereas retention of intermediate forms triggers coagulation. Moreover, our findings indicate the development of nanobodies against activated enzymes offers improved opportunities to investigate their contribution to health and disease.