Biaxial crystal α-BaTeMo(2)O(9): theory study of large birefringence and wide-band polarized prisms design.
α-BaTeMo(2)O(9) is a novel biaxial crystal with wide-band transmittance spectrum. The refractive index dispersion curves and birefringence of the α-BaTeMo(2)O(9) crystal were obtained in spectral range of 0.4~5 μm. The origin of the birefringence for the crystal has been calculated and interpreted on the basis of the crystal structure combined with theoretical studies. The polarized directions and formulations of refractive index of optical waves in biaxial α-BaTeMo(2)O(9) were investigated by solving the refractive index ellipsoid equations. Furthermore, polarized prisms based on the α-BaTeMo(2)O(9) crystal used in spectral ranges of 0.4~2.7 μm and 0.48~4.5 μm were designed and characterized. The extinction ratios of both prisms were determined to be larger than 10000:1, which would satisfy the practical requirements. The impacts on extinction ratio for biaxial and uniaxial crystals were also discussed. To our knowledge, it is the first report about biaxial crystals for the polarized prisms, and the results show that the α-BaTeMo(2)O(9) crystal is a promising material for polarized optical components, especially in the range of 3~5 μm.


A phase II window trial of procarbazine and topotecan in children with high-grade glioma: a report from the children's oncology group.
The role of chemotherapy in the treatment of high-grade gliomas in children is unclear. Early reports were suggestive of improved outcome in children with high-grade glioma with the addition of chemotherapy after surgery and radiation therapy. Subsequent studies did not show similar favorable contribution of chemotherapy to the outcome of these children. Further efforts to identify active chemotherapy agents in children include use of agents that have shown efficacy in adult patients with high-grade glioma and agents that have shown promise in mice bearing human xenografts of brain tumors. A Pediatric Oncology Group (POG 9431) trial tested the activity of two such agents, procarbazine and topotecan in newly diagnosed patients with high-grade glioma who had measurable disease after diagnostic surgery. Neither agent showed efficacy within the confines of the statistical design of the study. This study showed that children with high-grade glioma have an innate resistance to alkylating agents based on mismatch repair deficiency and high levels of alkyguanine transferase (AGT). Future trials should consider strategies to overcome the resistance mechanisms in children with high-grade glioma.


Delay in Diagnosis of Congenital Linear Scleroderma until Adulthood.
Scleroderma encompasses a spectrum of disorders characterized by thickening of the skin and subcutaneous tissue with increased collagen deposition. Linear scleroderma is subdivided into progressive hemifacial atrophy and en coup de sabre subtype. We report a case of congenital linear scleroderma identified in an adult, misdiagnosed since birth as birth trauma. We completed a review of the literature for similar cases using PubMed and Medline. This is the first report of congenital linear scleroderma en coup de sabre diagnosed in an adult following an initial misdiagnosis of birth trauma. The sequelae of linear scleroderma can be significant as it can result in growth retardation, muscle atrophy, contractures, limb length discrepancy, and disfigurement. This report emphasizes the importance of educating practitioners about linear scleroderma. Early recognition is key as a delay in diagnosis can result in potentially preventable, irreversible growth defects and disfigurements.


Characterization of the human histone H2A.X gene. Comparison of its promoter with other H2A gene promoters.
The human gene for the replication-unlinked histone protein H2A.X is a naturally occurring chimera that contains a replication-unlinked promoter yet produces a stemloop mRNA characteristic of replication-linked histone genes. Consistent with the latter attribute, the H2A.X gene was found to lack introns. The promoter of the H2A.X gene was localized to a 120-base pair region upstream of the transcription start site, a region which included a TATA and two CCAAT sequence elements. The proximal of the two CCAAT elements was shown to be an important determinant of H2A.X gene promoter activity. In a comparative study with the CCAAT elements from the replication-linked H2A.1a gene and the replication-unlinked H2A.Z gene, the proximal CCAAT element of the H2A.X gene was found to bind nuclear factors also bound by CCAAT elements in the latter but not in the former. The specificity of the replication-unlinked H2A.X and H2A.Z gene promoters for CCAAT-binding transcription factors appeared to also reside in short homologous sequences about 10 base pairs away on either side of the CCAAT sequence.


Interaction of single-chain urokinase-type plasminogen activator with human endothelial cells.
The interaction of urokinase-type plasminogen activators with receptors on the surface of endothelial cells may play an important role in the regulation of fibrinolysis and cell migration. Therefore, we investigated whether human umbilical vein endothelial cells (HUVEC) express receptors for single-chain urokinase (scu-PA) on the cell surface and examined the effect of such binding on plasminogen activator activity. Binding of 125I-labeled scu-PA to HUVEC, performed at 4 degrees C, was saturable, reversible, and specific (k+1 4 +/- 1 X 10(6) min-1 M-1, k-1 6.2 +/- 1.4 X 10(-3) min-1, Kd 2.8 +/- 0.1 nM; Bmax 2.2 +/- 0.1 X 10(5) sites/cell; mean +/- S.E.). Binding of radiolabeled scu-PA was inhibited by both natural and recombinant wild-type scu-PA, high molecular weight two-chain u-PA (tcu-PA), catalytic site-inactivated tcu-PA, an amino-terminal fragment of u-PA (amino acids 1-143), and a smaller peptide (amino acids 4-42) corresponding primarily to the epidermal growth factor-like domain. Binding was not inhibited by low molecular weight urokinase or by a recombinant scu-PA missing amino acids 9-45. Cell-bound scu-PA migrated at its native molecular mass on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the presence of plasminogen, scu-PA bound to endothelial cells generated greater plasmin activity than did scu-PA in the absence of cells. In contrast, when tcu-PA was added directly to HUVEC, sodium dodecyl sulfate-stable complexes formed with cell or matrix-associated plasminogen activator inhibitors with a loss of plasminogen activator activity. These studies suggest that endothelial cells in culture express high affinity binding sites for the epidermal growth factor domain of scu-PA. Interaction of scu-PA with these receptors may permit plasminogen activator activity to be expressed at discrete sites on the endothelial cell membrane.


[Cerebrolysin in the treatment of partial optic atrophy in children].
The purpose of the trial was to investigate efficacy of cerebrolysin in children with partial optic atrophy and to compare different ways of injections of the drug. Cerebrolysin was injected in retrobulbar space and in Tenon's space. The drug was given separately and in combination with trental. Favorable effect has been achieved in all the patients treated with cerebrolysin injections in Tenon's space. In patients treated with retrobulbar injections of cerebrolysin and with injections of cerebrolysin and trental improvement occurred in 50% of cases. In control group, who did not receive cerebrolysin favorable results were achieved in 25% of patients. A 12-month follow-up study stated stability of the effect of cerebrolysin.


The importance of analysis of long-range rearrangement of BRCA1 and BRCA2 in genetic diagnosis of familial breast cancer.
Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers. Identification of BRCA mutations greatly improves the preventive strategies and management of breast cancer. Sanger sequencing has been the gold standard in identifying these mutations. However, 4-28% of inherited BRCA mutations may be due to large genomic rearrangements (LGRs), which could be missed by using Sanger sequencing alone. Our aim is to evaluate the pick-up rate of LGRs in our cohort. A total of 1,236 clinically high-risk patients with breast and/or ovarian cancers were recruited through The Hong Kong Hereditary Breast Cancer Family Registry from 2007 to 2014. Full gene sequencing (either Sanger or next generation sequencing) and multiplex ligation-dependent probe amplification (MLPA) were performed. We identified 120 deleterious BRCA mutations: 57 (4.61%) were in BRCA1 and 63 (5.10%) were in BRCA2. LGRs accounted for 6.67% (8 of 120) of all BRCA mutations, whereas 8.77 % (5 of 57) were BRCA1 mutations and 4.76% (3 of 63) were BRCA2 mutations. Through this integrated approach, both small nucleotide variations and LGRs could be detected. We suggest that MLPA should be incorporated into the standard practice for genetic testing to avoid false-negative results, which would greatly affect the management of these high-risk families.


Electrogenic events upon photolysis of CO from fully reduced cytochrome c oxidase.
CO photolysis from fully reduced Paracoccus denitrificans aa(3)-type cytochrome c oxidase in the absence of O(2) was studied by time-resolved potential electrometry. Surprisingly, photo dissociation of the uncharged carbon monoxide results in generation of a small-amplitude electric potential with the same sign as the physiological charge separation during activity. The number of electrogenic events after CO photolysis depends on the state of the enzyme. CO photolysis following immediately after activation by an enzymatic turnover, showed a two-component potential development. A fast (~1.5μs) phase was followed by slower potential generation with a time constant varying from 8μs at pH 7 to 250μs at pH 10. The amplitude of the fast phase was independent of the time of incubation after enzyme activation, whereas the slower phase vanished with a time constant of ~25min. CO photolysis from enzyme that had not undergone a prior single turnover showed the fast phase, but the amplitude of the slow phase was reduced to 10-30%. The amplitude of the fast phase corresponds to charge movement of 0.83Å perpendicular to the membrane dielectric, and is independent of the time after enzyme activation. Thus it can be used as an internal ruler for normalization of the electrogenic responses of CcO. The slow phase was absent in the K354M mutant with a blocked proton-conducting K channel. We propose that CO photolysis increases the pK of the K354 residue, which results in its partial protonation, and generation of electric potential.


PCDD/Fs levels in indoor environments and blood of workers of three municipal waste incinerators in Taiwan.
This study monitored ambient air concentrations of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in three municipal waste incineration plants. Blood PCDD/Fs levels of 133 workers randomly selected from these plants were also measured. The associations between workers' blood PCDD/Fs concentrations and occupational exposures to PCDD/Fs were assessed. Means of air PCDD/Fs levels ranged from 0.08 to 3.01 pg/m3 in international toxic equivalents (I-TEQ). The geometric means of blood PCDD/Fs concentrations were 14.6, 15.8, 19.1 pg/g lipid in World Health Organization (WHO) TEQ, respectively, for workers from three plants. Air levels of total I-TEQ and all congeners, except 2,3,7,8-tetrachlorinated dibenzo-p-dioxin (TeCDD) and 1,2,3,4,7,8,9-heptachlorinated dibenzofuran (HpCDF), were significantly higher in plant B. However, blood concentrations of 2,3,7,8-TeCDD, 1,2,3,7,8-PeCDD, 2,3,7,8-TeCDF, 1,2,3,7,8-PeCDF and 1,2,3,4,7,8,9-HpCDF were significantly elevated in plant C workers. Although job contents, duration of employment and time spent in certain location were significantly different among incineration plants, they were not significantly associated with blood concentrations of any congener. Furthermore, results of the multiple regression analysis that assessed important occupational factors simultaneously and adjusted for potential confounders, showed significant associations between four congeners and incineration plant or job contents. However, the results were limited by small R-squares of the regression models. In conclusion, blood concentrations of several PCDD/Fs congeners were significantly different among three incineration plants. The differences were not explained by the discrepancy in job contents, duration of employment, and time activity in these plants.


[Effect of different nutritional routes on the intestinal mucus barrier in scalded rats].
To observe the effect of different nutritional routes of giving nutrition on the intestinal mucus barrier in severely scalded rats. Wistar rats inflicted with 30% TBSA III degree scalding on the back were employed as the model and were randomly divided into 3 groups, i.e. control (C), parenteral nutrition (PN) and enteral nutrition (EN) groups. The rats in PN and EN groups were supplied with equal amount of nitrogen and calories and with equal volume of nutrition solution. The dynamic changes in the thickness of intestinal mucus layer and the contents of protein, hexose and acetylneuraminate in the mucus were examined. When compared with those in C group, the intestinal mucus layer became thinner and the contents of protein, hexose and acetylneuraminate in the mucus in both PN and EN groups decreased evidently after scalding. When compared between two nutritional groups, the thickness of intestinal mucus layer and the contents of the hexose and acetylneuraminate in the mucus in EN were much thicker and higher than those in PN group, while the mucus protein content exhibited no obvious difference between PN and EN groups. It was suggested that intestinal goblet cell synthesized and secreted less mucus after scalding in rats resulting in thinning of intestinal mucus layer and the change in mucus components. When compared with those in PN group, less injury to the intestinal goblet cells occurred and the intestinal mucus synthesis was less affected in EN group, and the components of intestinal mucus were maintained stable.


A preliminary report of the collaborative study of maternal phenylketonuria in the United States and Canada.
The Maternal Phenylketonuria Collaborative Study (MPKUCS), encompassing all the United States and provinces of Canada, is a prospective, longitudinal investigation designed to ascertain the efficacy of phenylalanine-restricted therapy in protecting the fetus from high maternal phenylalanine concentrations in women with hyperphenylalaninaemia. Preliminary findings are reported for 147 pregnancies for whom the recommended therapeutic range of blood phenylalanine was 120-360 mumols/L. Sixty-three pregnancies had complete data for analysis. Dietary control was attempted prior to conception in 10 out of 63 women. Significant negative correlations were noted in length, weight and head circumference and blood phenylalanine concentrations during pregnancy. Average reported phenylalanine levels by trimester for 63 hyperphenylalaninaemic pregnancies resulting in live births revealed that no group requiring treatment achieved levels below 360 mumols/L until the third trimester. Median birth measurement percentiles revealed that all groups studied generally had smaller head size compared with birth length and weight. Those started on diet after the first trimester achieved a head circumference below the 10th percentile. The implication of small head circumference for subsequent intellectual development is unclear at this time. Furthermore, the study must evaluate more offspring of women having optimal preconception and pregnancy restriction of phenylalanine.


Ab initio multiple spawning dynamics using multi-state second-order perturbation theory.
We have implemented multi-state second-order perturbation theory (MS-CASPT2) in the ab initio multiple spawning (AIMS) method for first-principles molecular dynamics including nonadiabatic effects. The nonadiabatic couplings between states are calculated numerically using an efficient method which requires only two extra energy calculations per time step. As a representative example, we carry out AIMS-MSPT2 calculations of the excited state dynamics of ethylene. Two distinct types of conical intersections, previously denoted as the twisted-pyramidalized and ethylidene intersections, are responsible for ultrafast population transfer from the excited state to the ground state. Although these two pathways have been observed in prior dynamics simulations, we show here that the branching ratio is affected by dynamic correlation with the twisted-pyramidalized intersection overweighting the ethylidene-like intersection during the decay process at the AIMS-MSPT2 level of description.


Crystallization as a means for the switching of nanoscale containers.
Melting and crystallization are reported as a means for reversible switching of nanoscale containers. Aqueous dispersions of 10 nm particles of polyethylene with variable branching and crystallinity were prepared by catalytic polymerization with water-soluble Ni(II) complexes. Fluorescence studies of lipophilic probe molecules show that in the low-crystallinity particles they experience a more apolar environment. In crystalline particles, the amorphous portions which can accommodate guest molecules are at the periphery of the particle, such that the probe experiences the water-particle interface to some extent. The polarity experienced by the probe molecules can be switched reversibly by melting and crystallization of the individual dispersed particles. The temperature at which this occurs can be adjusted via the microstructure, that is, degree of branching, of the polymer.


Therapeutic approaches targeting the prion receptor LRP/LR.
Transmissible spongiform encephalopathies known as prion diseases are a group of fatal neurodegenerative disorders that affect both humans and animals. The generally accepted principle of the disease is that the conversion of the cellular prion protein (PrP(c)) into the disease associated isoform PrP(Sc) leads to spongiform degeneration of the brain and amyloid plaque formation. Until now no therapy leading to potential alleviation or even cure of the disease exists. It is therefore important to develop therapeutic approaches for the treatment of TSEs since these infections are inevitably fatal and, especially in the case of vCJD, they affect youngsters. Besides current conventional therapeutic strategies, this review summarizes new therapeutic tools targeting the prion receptor LRP/LR.


Efficacy and safety of a polyester leukocyte removal filter for whole blood and red cell concentrate filtration.
Patients receiving multiple whole blood transfusions often experience adverse clinical symptoms caused by leukocytes. In the present study, the efficacy and safety of a polyester filter for leukocytes (Sepacell R-500) was evaluated. Donor units of whole blood and red cell concentrate stored for varying lengths of time were filtered. Emphasis was placed on humoral parameters indicative of release and/or activation reactions of granulocytes (neutral proteinase elastase, lysozyme, aggregation, chemiluminescence) and erythrocytes (lactate dehydrogenase, plasma haemoglobin). Nonspecific adsorption effects were investigated by plasma protein determinations (albumin, alpha 2-macroglobulin). A complete blood cell count as well as values of haemoglobin and haematocrit were determined. Sepacell R-500 proved to be a highly efficient filter to the leukocyte depletion of blood. Our results of erythrocyte and granulocyte related humoral parameters provided no significant evidence of filtration mediated activation or releasing reactions of clinical consequence.


[Hepatic intra-arterial infusion chemotherapy using polymer-coated 2.9 Fr implantable catheter-port system--initial experience].
We developed a new 2.9 Fr implantable catheter-port system (reservoir) to perform arterial infusion chemotherapy in patients with unresectable liver tumors. This study was undertaken to evaluate the feasibility of placing this new reservoir system in patients in whom placement of a 5 Fr-reservoir system would seem to be difficult because of severe stricture, tortuosity or angulation of the hepatic artery. A new reservoir system was successfully implanted in 25 patients during 27 sessions. After a side hole was opened, a 2.9 Fr catheter was inserted in the distal hepatic artery or in the gastroduodenal artery in 24 sessions. The catheter tip was then fixed with coils to prevent catheter dislocation. In the other 3 sessions, a 2.9 Fr catheter was inserted without catheter fixation in the replaced right hepatic artery and a small sized collateral artery towards the liver. Arterial infusion chemotherapy was done without any trouble after 20 sessions. Catheter dislocation was found after 2 sessions in which the catheter tip was not fixed or inadequately fixed. Early arterial occlusion was found after placing a 2.9 Fr catheter in the replaced hepatic artery and the small sized-collateral artery after 4 sessions. In conclusion, although sequellae should be evaluated over a long-term period, implantation of a new 2.9 Fr reservoir system is technically feasible and useful in performing arterial infusion chemotherapy.


Use of the Core Bereavement Items in Adults Aged 50 and Older: A Psychometric Evaluation.
The Core Bereavement Items (CBI) is a commonly used measure that assesses core grief and bereavement experiences. Although previous psychometric testing has been conducted, no studies have assessed its use specifically aimed at adults aged 50 and older or for those who lost a loved one who was hospice care. This is critical, as losses and additional obstacles in bereavement compound throughout the aging process. The present study investigated reliability, content validity, and internal structure of the CBI in bereaved adults aged 50 and older whose loved one died while in hospice care (N = 205). Associations based on age, marital status, and relationship with the died patients were consistent with preexisting research. Results of a Cronbach α reliability test found that the CBI has excellent reliability in this population. Further, content validity was established based on the judgment of subject matter experts. Exploratory factor analysis supported a 1-factor structure, with all items loading as General Grief Experiences. Based on this analysis, the CBI is a valid and reliable tool when used with adults aged 50 and older.


[M.BstF5I-4, the forth DNA methyltransferase of BstF5I restriction-modification system from Bacillus stearothermophilus F5].
The fourth DNA-methyltransferase of the BstF5I restriction-modification (RM) system from Bacillus stearothermophilus F5 (M.BstF5I-4) was discovered, which modifies the adenine residue within the upper strand of the recognition site 5'-GGATG-3'/5'-CATCC-3'. Thus, unlike other known RM systems, the BstF5I RM system comprises four genes encoding DNA-methyltransferases, three of which possess the same substrate specificity and methylate adenine within the 5'-GGATG sequence. The English version of the paper.


[A case of cutaneous pseudallescheriosis resembling sporotrichosis].
An 83-year-old man with aplastic anemia and steroid induced diabetes mellitus developed multiple nodules with pus on the back of his right hand and forearm. He had been treated with a daily dose of 30mg prednisolone for 2 months. These lesions had appeared a month before his visit. The histopathological findings revealed dermal abscesses containing hyphal structures, lymphocytes, histiocytes and giant cells. Grocott-Methenamine stain demonstrated abundant fungal elements. In culture, colonies grow rapidly and produce a white, cottony mycelium which later becomes gray in color. Microscopically, ovoid and pyriform conidia are produced at the ends of long slender conidiophores. On PCA agar, synnemata with small conidal heads developed at 37 degrees C but cleistothecia did not appear. The patient did not respond to itraconazole therapy, however, with hyperthermic treatment, the eruptions gradually healed. Based on these findings, this fungal infection was diagnosed as pseudallescheriosis.


Tourette syndrome: impact on Canadian family functioning.
An evaluation of the impact of Tourette Syndrome on the family. Self-report data were gathered from a Canadian sample of over two hundred Tourette Syndrome patients and/or their families regarding the effects of TS on family life. Patients rated the extent to which having TS interfered with the family's day-to-day activities. Also indicated was whether marital difficulties or difficulties with alcohol or drugs arose since the Tourette diagnosis was made. Data were also gathered on the number of TS patients or other family members who sought professional counselling and the extent to which counselling was found helpful.


Determination of oxymatrine in human plasma by LC-MS and study on its pharmacokinetics.
A sensitive and selective liquid chromatographic-mass spectrometric method is built to determine oxymatrine in human plasma. After a liquid-liquid extraction for samples, samples are analyzed on a C18 column interfaced with a mass spectrometer. Positive electrospray ionization is employed as the ionization source. The mobile phase is methanol-water containing 10 mmol/L ammonium acetate (60:40) at the flow rate of 0.8 mL/min. The method is linear in the concentration range of 10-1000 ng/mL. The lower limit of quantitation is 10 ng/mL. The intra- and inter-day relative standard deviation across three validation runs over the entire concentration range is less than 14.27%. The accuracy determined at three concentrations (20, 100, and 500 ng/mL for oxymatrine) is within +/- 10.0% in terms of relative error. The method herein described is successfully applied to the evaluation of pharmacokinetic profiles of oxymatrine tablets pills in 18 healthy volunteers. The results show AUC, Tmax, Cmax, and T1/2 between the testing formulation and reference formulation have no significant difference (P > 0.05). Relative bioavailability is 104.2 +/- 13.8%.


Role of beta112 Cys (G14) in homo- (beta4) and hetero- (alpha2 beta2) tetramer hemoglobin formation.
In order to assess the role of beta112 Cys in homo- and hetero-tetrameric hemoglobin formation, we expressed four beta112 variants (beta112Cys-->Asp, beta112Cys-->Ser, beta112Cys-->Thr, and beta112Cys-->Val) and studied assembly with alpha chains in vitro. beta112 Cys is normally present at beta1 beta2 and alpha1 beta1 interaction sites in homo- (beta4) and hetero-tetramers (alpha2 beta2). beta4 formation in vitro was influenced by the amino acid at beta112. beta112 Asp completely inhibited formation of homo-tetramers, whereas beta112 Ser showed only slight inhibition. In contrast, beta112 Thr or Val enhanced homo-tetramer formation compared with betaA chains. Association constants for homo-tetramer formation increased in the order of beta112Cys-->Ser, betaA, beta112Cys-->Thr, and beta112Cys-->Val, whereas the value for beta112Cys-->Asp was zero under the same conditions. These beta112 changes also affected in vitro alpha2 beta2 hetero-tetramer formation. Order of alpha2 beta2 formation under limiting alpha-globin chain conditions showed Hb betaC112S > Hb A > Hb S = Hb betaC112T = Hb betaC112V >>> Hb betaC112D. Hb beta112D can form tetrameric hemoglobin, but this beta112 change promotes dissociation into alpha and beta chains instead of alpha beta dimer formation upon dilution. These results indicate that amino acids at alpha1 beta1 interaction sites such as beta112 on the G helix play a key role in stable alpha beta dimer formation. Our findings suggest, in addition to electrostatic interaction between alpha and beta chains, that dissociation of beta4 homo-tetramers to monomers and hydrophobic interactions of the beta112 amino acid with alpha chains governs stable alpha1 beta1 interactions, which then results in formation of functional hemoglobin tetramers. Information gained from these studies should increase our understanding of the mechanism of assembly of multi-subunit proteins.


Measurement of renal function in a kidney donor: a comparison of creatinine-based and volume-based GFRs.
We aimed to evaluate the performance of various GFR estimates compared with direct measurement of GFR (dGFR). We also sought to create a new formula for volume-based GFR (new-vGFR) using kidney volume determined by CT. GFR was measured using creatinine-based methods (MDRD, the Cockcroft-Gault equation, CKD-EPI formula, and the Mayo clinic formula) and the Herts method, which is volume-based (vGFR). We compared performance between GFR estimates and created a new vGFR model by multiple linear regression analysis. Among the creatinine-based GFR estimates, the MDRD and C-G equations were similarly associated with dGFR (correlation and concordance coefficients of 0.359 and 0.369 and 0.354 and 0.318, respectively). We developed the following new kidney volume-based GFR formula: 217.48-0.39XA + 0.25XW-0.46XH-54.01XsCr + 0.02XV-19.89 (if female) (A = age, W = weight, H = height, sCr = serum creatinine level, V = total kidney volume). The MDRD and CKD-EPI had relatively better accuracy than the other creatinine-based methods (30.7% vs. 32.3% within 10% and 78.0% vs. 73.0% within 30%, respectively). However, the new-vGFR formula had the most accurate results among all of the analyzed methods (37.4% within 10% and 84.6% within 30%). The new-vGFR can replace dGFR or creatinine-based GFR for assessing kidney function in donors and healthy individuals. • Accurate prediction of GFR is crucial in kidney donors. • DTPA is accurate but costly, invasive, and clinically difficult to apply. • Volume-based GFR estimation performs as well as the Cr-based method. • New volume-based GFR estimation performs better among GFR estimation formulas.


Melatonin protects against chronic intermittent hypoxia-induced cardiac hypertrophy by modulating autophagy through the 5' adenosine monophosphate-activated protein kinase pathway.
Obstructive sleep apnea syndrome (OSAS) is usually associated with multiple cardiovascular disorders, including myocardial hypertrophy. Melatonin protects the heart from damaging conditions. However, whether melatonin alleviates heart damage induced by chronic intermittent hypoxia (CIH) is unknown. We investigated the melatonin-induced protective role of AMPK-regulated autophagy in the myocardium by exposing rats to CIH and treating them with melatonin or saline daily for six weeks. In vivo, CIH induced significant myocardial hypertrophy; this trend was strikingly reversed by melatonin. Moreover, AMPK activation and autophagy was enhanced, and the number of autophagosomes increased. CIH induced apoptosis of cardiomyocytes; this was significantly mitigated by melatonin. In vitro, CIH induced hypertrophic changes in cardiomyocytes; this effect was significantly reversed by melatonin. Autophagy decreased after AMPK inhibition, and we found that autophagy was required for the protective function of melatonin. Our results suggest that melatonin ameliorates cardiac hypertrophy caused by CIH by inducing autophagy via the AMPK pathway and by autophagy-regulated apoptosis.


The impact of conventional and high-dose therapy for lymphoma on fertility.
The impact of chemotherapy on gonadal function is an important issue for younger patients surviving lymphoma. This article reviews the effects on fertility of conventional and intensive-dose chemotherapy regimens with or without radiation therapy. In general, conventional dose regimens such as ABVD (doxorubicin/bleomycin/vinblastine/decarbazine) and CHOP21 (cyclophosphamide/doxorubicin/vincristine/prednisone) are not sterilizing, but data are limited on the effects of newer aggressive regimens such as BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone), CHOP14, and CHOP/etoposide. Infertility after myeloablative transplant conditioning is common but not invariable. The role of prechemotherapy gonadotrophin-releasing hormone agonists and antagonists for the prevention of gonadal damage is under evaluation. In addition, new techniques for sperm and oocyte retrieval offer the prospect of improved fertility after sterilizing treatment. Management guidelines for patients undergoing nonmyeloblative and myeloablative therapy are presented, addressing additional issues such as contraception during and after the administration of cytotoxics and the importance of gynecologic and endocrine follow-up in determining the need for short- and long-term hormone replacement therapy.


[Effects of electrical stimulation at acupoints in the distribution area of auricular vagus nerve combined with sound masking method on auditory brainstem response and neurotransmitters of inferior colliculus in rats of tinnitus].
To explore the effects of electrical stimulation at acupoints in the distribution area of auricular vagus nerve combined with sound masking on auditory brainstem response (ABR) and contents of neurotransmitters of γ-aminobutyric acid (γ-GABA), 5-hydroxytryptamine (5-HT) and acetyl choline (Ach) in inferior colliculus of tinnitus rats. Twenty-four male adult SD rats were randomized into a control group, a model group, a 7-d treatment group and a 15-d treatment group. Except the control group, rats in the remaining groups were treated with intraperitoneal injection of 10% salicylate sodium at a dose of 350 mg/kg to establish tinnitus model. Rats in the control group were treated with injection of 0.9% NaCl. Rats in the 7-d treatment group and 15-d treatment group were treated with electrical stimulation at "Shenmen (TF₄)" and "Yidan (CO₁₁)" in the distribution area of auricular vagus nerve combined with sound masking, once a day, for 7 days and 15 days. The SigGenRP software of TDT system was applied to provide voice for single ear and collect the signal, and the voice threshold of ABR was tested. The levels of γ-GABA, 5-HT and Ach in inferior colliculus of rats were detected by enzyme linked immunosorbent assay (ELISA) and compared. Compared with the model group, the threshold values of ABR in 12 kHz and 16 kHz voice stimulation in the 7-d treatment group were significantly lower all P < 0.05); the threshold values of ABR from 4 kHz to 28 kHz voice stimulation in the 15-d treatment group were signally reduced (P < 0.05, P < 0.01), which was more significant than those in the 7-d treatment group. The level of γ-GABA in the model group was significantly lower than that in the control group (P < 0.05), and that in the 15-d treatment group was apparently higher than that in the model group (P < 0.05). The level of 5-HT in the model group was markedly higher than that in the control group (P < 0.05), and that in the 7-d treatment group was lower than that in the model group (P < 0.05), while that in the 15-d treatment group was apparently higher than that in the model group (P < 0.05). The level of Ach in the model group was obviously; lower than that in the control group (P < 0.05), and that in the 7-d treatment group was higher than that in the model group (P < 0.05). Electrical stimulation at auricular vagus nerve combined with sound masking) could regulate the threshold of ABR, especially in the 15-d treatment group. This may be ascribed to modulating the levels of neurotransmitter of γ-GABA, 5-HT and Ach in inferior colliculus.


Characterization of optical resonators with an incoherent light.
A new and simple technique is proposed and demonstrated for measuring the free spectral range (FSR) and bandwidth of optical resonators. For a broadband light input the resonator output forms an incoherent frequency comb with the spacing and linewidth corresponding to the FSR and bandwidth of the resonator, respectively. Photodetection of the resonator output produces heterodyne beat signals between the comb lines, from which the above two parameters can be estimated by spectrum analysis. The proposed technique overcomes the difficulties of conventional methods base on frequency-swept lasers. As demonstrations, fiber-optic Fabry-Perot and ring resonators are successfully characterized with the bandwidths as small as 10 kHz.


Inhibition of telomerase by G-quartet DNA structures.
The ends or telomeres of the linear chromosomes of eukaryotes are composed of tandem repeats of short DNA sequences, one strand being rich in guanine (G strand) and the complementary strand in cytosine. Telomere synthesis involves the addition of telomeric repeats to the G strand by telomere terminal transferase (telomerase). Telomeric G-strand DNAs from a variety of organisms adopt compact structures, the most stable of which is explained by the formation of G-quartets. Here we investigate the capacity of the different folded forms of telomeric DNA to serve as primers for the Oxytricha nova telomerase in vitro. Formation of the K(+)-stabilized G-quartet structure in a primer inhibits its use by telomerase. Furthermore, the octanucleotide T4G4, which does not fold, is a better primer than (T4G4)2, which can form a foldback structure. We conclude that telomerase does not require any folding of its DNA primer. Folding of telomeric DNA into G-quartet structures seems to influence the extent of telomere elongation in vitro and might therefore act as a negative regulator of elongation in vivo.


Longer survival of rat limb allograft. Combined immunosuppression of FK-506 and 15-deoxyspergualin.
We studied the individual and synergistic effect of 3 immunosuppressive drugs, FK-506 (1 mg/kg/day), 15-deoxyspergualin (2.5 mg/kg/day) and cyclosporine (15 mg/kg/day) in a DA/Lewis rat limb allotransplantation model. 74 right hindlimb transplantations were performed. The median time for onset of rejection was 4 days in animals without immunosuppression, 37 days in animals receiving cyclosporine immunosuppression for 30 days, 61 days in animals receiving FK-506 for 30 days, 36 days in animals receiving a 30-day course of cyclosporine and, in the first 15 days, a course of 15-deoxyspergualin, and 76 days in animals receiving a 30-day course of FK-506 and 15-deoxyspergualin in the first 15 days. The combination of cyclosporine with 15-deoxyspergualin did not prolong graft survival and no synergistic effect was evident. In contrast, survival time in rat limb allografts receiving FK-506 and 15-deoxyspergualin was longer than in those receiving single FK-506 therapy. Our findings suggest a positive synergistic immunosuppressive effect with FK-506 and 15-deoxyspergualin in limb allotransplantation.


[Mortality and possible lost years of life due to tobacco consumption in Mexico].
An analysis was performed to estimate mortality and YPLL attributable to 20 smoking related diseases, based on the prevalence rates of current and former smokers obtained from a national survey; mortality data from vital statistics, and their relative risks and attributable mortality fractions due to tobacco consumption of the 20 diagnoses set for 1986. Numerical estimates of national mortality and YPLL attributable to cigarette consumption for the diagnosis set were made. Among the population of 20 years of age and older on 1986, a total of 17,405 deaths where attributable to smoking cases (47.0/100,000 individuals of 20 to 74 years of age), and takes the 9th place of grouped general mortality. Cardiovascular disease rated first place with 33 per cent of total cases; respiratory disease came second with 31.6 per cent. All 20 diagnoses someans 146.299 YPLL between 20 to 65 years (1.4 per cent from total ypll 0-70 years).


Evaluation of two experimental infection models for Avibacterium paragallinarum.
The clinical symptoms of infectious coryza are multiple and include nasal discharge, facial swelling, lacrimation, and anorexia. In general, the disease is not fatal to chicken; so, in experiments where animals are infected with Avibacterium paragallinarum, there have been debates about conducting the challenge model and evaluating the clinical signs. In this experiment, 150 chickens, aged 30 days, were randomly divided into different groups. Some groups were infected with the 'in-contact' challenge model and others with the artificial intrasinus-injection-route model. The bacterial isolates used were three field isolates of different serogroups of A. paragallinarum, including Hpg-8 (Page serovar A), CCM6075 (Page serovar B) and Hpg-668 (Page serovar C). During this study, a scoring system was used to record the clinical signs of the infected birds and evaluate the pathogenic diversity of the two models. The final results indicated that the 'in-contact' challenge model of the three isolates showed a more reliable representation of the natural infection under field conditions than the artificial intrasinus-injection-route model. Thus, on carrying out animal experiments, the effect of 'in-contact' challenge model is more accurate than the artificial intrasinus-injection-route model.


Morphometric analysis of human oocytes using time lapse: does it predict embryo developmental outcomes?
The aim of this prospective study was to evaluate the relationship between morphometric parameters of metaphase II (MII) oocytes and the morphokinetic behaviour of subsequent embryos derived by intra-cytoplasmic sperm injection (ICSI). The association between oocyte morphometry: (whole oocyte), ooplasm, width of zona pellucida (ZP) and perivitelline space (PVS) and first polar body (PB) with embryo morphokinetic variables, including time of second PB extrusion (tPB2), pronuclei appearance (tPN), pronuclei fading (tPNf), formation of two to eight cells (t2 to t8) and irregular cleavage events [uneven at two cells stage, cell fusion (Fu) and trichomonas mitoses (TM)] were assessed. tPB2, t5 and t8 timings were related to the ooplasm diameter (p = 0.003, r = -0.12; p = 0.001, r = -0.16; p < 0.001 r = -0.36, respectively); otherwise, there were no significant relationships apart from an association between the oocyte morphometry and other morphokinetic parameters, irregular cleavage embryos as well as embryo arrest which approached significance (p > 0.05). Overall, the data showed that morphometric parameters of oocytes did not provide a tool for the prediction of embryo morphokinetic or embryo selection in ICSI cycles. However, ooplasm diameter might be useful as a marker for predicting the timing of embryo cleavage.


CNS drug delivery systems: novel approaches.
The brain is a delicate organ, and nature has very efficiently protected it. The brain is shielded against potentially toxic substances by the presence of two barrier systems: the blood brain barrier (BBB) and the blood cerebrospinal fluid barrier (BCSFB). Unfortunately, the same mechanisms that protect it against intrusive chemicals can also frustrate therapeutic interventions. Despite aggressive research, patients suffering from fatal and/or debilitating central nervous system (CNS) diseases, such as brain tumours, HIV encephalopathy, epilepsy, cerebrovascular diseases and neurodegenerative disorders, far outnumber those dying of all types of systemic cancers or heart diseases. The abysmally low number of potential therapeutics reaching commercial success is primarily due to the complexity of the CNS drug development. The clinical failure of many probable candidates is often, ascribable to poor delivery methods which do not pervade the unyielding BBB. It restricts the passive diffusion of many drugs into the brain and constitutes a significant obstacle in the pharmacological treatment of central nervous system (CNS) disorders. General methods that can enhance drug delivery to the brain are, therefore, of great pharmaceutical interest. Various strategies like non-invasive methods, including drug manipulation encompassing transformation into lipophilic analogues, prodrugs, chemical drug delivery, carrier-mediated drug delivery, receptor/vector mediated drug delivery and intranasal drug delivery, which exploits the olfactory and trigeminal neuronal pathways to deliver drugs to the brain, are widely used. On the other hand the invasive methods which primarily rely on disruption of the BBB integrity by osmotic or biochemical means, or direct intracranial drug delivery by intracerebroventricular, intracerebral or intrathecal administration after creating reversible openings in the head, are recognised. Extensive review pertaining specifically, to the patents relating to drug delivery across the CNS is currently available. However, many patents e.g. US63722506, US2002183683 etc., have been mentioned in a few articles. It is the objective of this article to expansively review drug delivery systems for CNS by discussing the recent patents available.


Admission to Intensive Care for a trauma related to alcohol or drugs, a 'teachable moment' for the beginning of a change.
To estimate how many of the trauma patients admitted to ICU would be candidates for a secondary prevention programme for trauma related to alcohol or drug use by brief motivational intervention and to define what factors prevent that intervention being performed. All 16-70year old trauma patients (n=242) admitted to ICU in 32 non-consecutive months (November 2011 to March 2015) were included in the study, coinciding with the implementation of a screening and brief motivational intervention programme for trauma patients related to substance consumption. The programme includes screening for exposure to substances at admission. Sociodemographic and clinical variables were collected prospectively. The screening for substances was not performed in 38 (15.7%) of all admitted patients. Of the patients screened, 101 (49.5%) were negative. The variables that in greater proportion impeded intervention between screening positive patients were neurological damage due to the trauma with 23 patients (37.1%) and prior psychiatric disorder with 18 (29%). Both variables were associated with substance consumption: negatives 9.9% vs positive 22.3% (P=.001) and negatives 3% vs positive 17.5% (P=.016) respectively. The number of candidates for motivational intervention was 41, 16.9% of all admitted patients. Almost 2 out of 10 patients were potential candidates. The factors that in a greater proportion precluded the intervention were the same as those associated with consumption. Mortality in ICU was associated with non-compliance with the screening protocol.


Validating the ATLS Shock Classification for Predicting Death, Transfusion, or Urgent Intervention.
The Advanced Trauma Life Support (ATLS) shock classification has been accepted as the conceptual framework for clinicians caring for trauma patients. We sought to validate its ability to predict mortality, blood transfusion, and urgent intervention. We performed a retrospective review of trauma patients using the 2014 National Trauma Data Bank. Using initial vital signs data, patients were categorized into shock class based on the ATLS program. Rates for urgent blood transfusion, urgent operative intervention, and mortality were compared between classes. 630,635 subjects were included for analysis. Classes 1, 2, 3, and 4 included 312,404, 17,133, 31, and 43 patients, respectively. 300,754 patients did not meet criteria for any ATLS shock class. Of the patients in class 1 shock, 2653 died (0.9%), 3123 (1.0%) were transfused blood products, and 7115 (2.3%) underwent an urgent procedure. In class 2, 219 (1.3%) died, 387 (2.3%) were transfused, and 1575 (9.2%) underwent intervention. In class 3, 7 (22.6%) died, 10 (32.3%) were transfused, and 13 (41.9%) underwent intervention. In class 4, 15 (34.9%) died, 19 (44.2%) were transfused, and 23 (53.5%) underwent intervention. For uncategorized patients, 21,356 (7.1%) died, 15,168 (5.0%) were transfused, and 23,844 (7.9%) underwent intervention. Almost half of trauma patients do not meet criteria for any ATLS shock class. Uncategorized patients had a higher mortality (7.1%) than patients in classes 1 and 2 (0.9% and 1.3%, respectively). Classes 3 and 4 only accounted for 0.005% and 0.007%, respectively, of patients. The ATLS classification system does not help identify many patients in severe shock.


A novel system for intracoronary beta-irradiation: description and dosimetric results.
A dosimetric evaluation of a new device dedicated to intravascular irradiation, associating a beta source and a centering device, was carried out before initiation of a clinical pilot study. A 29-mm-long 90Y coil, coated with titanium and fixed to the end of a thrust wire, was introduced into the inner lumen of purpose-built centering balloons of different diameters (2.5, 3, 3.5, and 4 mm). Dose homogeneity was evaluated by studying both axial and circumferential dose variations, based on readings from thermoluminescent dosimeters (TLDs) placed on the balloon surface. Axial homogeneity was determined by comparing the readout values of dosimeters located on peripheral balloon segments with those located on segments adjacent to the midpoint of the source. The centering ability of the device was studied by comparing measurements on opposing surfaces of the balloon. The dose attenuation by water and contrast medium was evaluated and compared with that in air. The balloon contamination was studied using a contamination counter. The total 90Y coil activity was measured by liquid scintillation to relate activity to surface dose. Activity-surface dose correlation showed that for a linear coil activity of 1 mCi/mm, the mean dose rate at the surface of a 2.5-mm balloon filled with contrast medium was 8.29 Gy/min. The doses at the surface of larger balloons (3, 3.5, and 4 mm) filled with contrast were 78%, 59%, and 47%, respectively, of the dose measured at the surface of the 2.5-mm balloon. The coefficient of variation (CV) in surface dose for 2.5-, 3-, 3.5-, and 4-mm centering devices filled with contrast medium were 9%, 8%, 9%, and 12%, respectively. There was no statistically significant difference between readouts from central and peripheral balloon segments or among rows of dosimeters facing each other. For a 2.5-mm balloon, compared with air the dose attenuation by water and contrast medium was similar (0.70 and 0.69, respectively), but a significant difference was seen between the readouts of water- and contrast-filled balloons when the diameter was larger than 3 mm (p < 0.001). No contamination was found in the balloon shaft after source retrieval. The dosimetric tests showed very good surface dose homogeneity, demonstrating satisfactory centering of the source within the centering balloons. The achievable dose rates will permit intravascular irradiation within a short time interval. The absence of residual balloon contamination after source retrieval meets the requirements for a sealed source used in a clinical setting.


The development of memory for location: what role do spatial prototypes play?
Two experiments investigated the role of spatial prototypes in estimates of location. In Experiment 1 (N = 144), children and adults learned the locations of 20 objects in an open, square box designed to look like a model house. In two conditions, opaque lines or walls divided the house into four regions, and in the other condition, no boundaries were present. Following learning, the dots marking the locations were removed, and participants attempted to replace the objects. Children and adults overestimated distances between target locations in different regions. Contrary to Huttenlocher, Hedges, and Duncan's hierarchical theory of spatial memory, none of the groups displaced the objects toward the region centers. In Experiment 2 (N = 96), boundaries were removed during testing to determine whether children and adults were more likely to displace objects toward region centers when uncertainty about location increased. Again, all age groups overestimated distances between target objects in different regions. In addition, adults and 11-year-olds in the most salient boundary condition displaced objects toward the region centers. Discussion focuses on the implications of these results for understanding how children and adults estimate location.


[Meconium ileus equivalent].
Meconium ileus equivalent (MIE) can be defined as a clinical manifestation in cystic fibrosis (CF) patients caused by acute intestinal obstruction by putty-like faecal material in the cecum or terminal ileum. A broader definition includes a more chronic condition in CF patients with abdominal pain and a coecal mass which may eventually pass spontaneously. The condition occurs only in CF patients with exocrine pancreatic insufficiency (EPI). It has not been seen in other CF patients nor in non-CF patients with EPI. The frequency of these symptoms has been reported as 2.4%-25%. Pathophysiologically, MIE is probably caused by a combination of EPI, increased intestinal transit time, and abnormal intestinal mucus. The treatment should primarily be non-operative. Specific treatment with N-acetylcysteine, administrated orally and/or as an enema is recommended. Enemas with the water soluble contrast medium, meglucamine diatrizoate (Gastrografin), provide an alternative form for treatment and can also serve diagnostic purposes. It is important that the physician is familiar with this disease entity and the appropriate treatment with the above mentioned drugs. Non-operative treatment is often effective, and dangerous complications following surgery can thus be avoided.


[Cytologic characteristics of bronchitis in patients with acute lung abscesses].
Results of cytological examination of smears obtained after brush-biopsy from mucosa of ostium of bronchus which drains cavity of acute abscess were analyzed in 96 patients. Correlation between number of neutrophils, eosinophils, monocytes and fibroblasts was demonstrated. Criteria of inflammation intensity evaluation in endobronchitis were developed. It is necessary to combine endoscopic examination with cytological examination of smear.


[A case of ceftriaxone-associated pseudolithiasis in an adult patient that disappeared after the discontinuation of ceftriaxone].
We report a case of a 47-year-old female patient with ceftriaxone (CTRX)-associated pseudolithiasis. CTRX was administered at a dosage of 2g/day for 8 days because of colonic diverticulitis. A routine abdominal computed tomography (CT) scan was performed to investigate the diverticulitis. However, the CT scan demonstrated stones and sludge in the gallbladder, which had not been present before CTRX administration. Therefore, we diagnosed the patient with pseudolithiasis caused by CTRX and stopped CTRX administration. The stones and sludge disappeared 6 days after stopping CTRX administration. This underreported adverse effect of CTRX should be considered when treating both children and adult patients.


Inducible CO-stimulator molecule, a candidate gene for defective isotype switching, is normal in patients with hyper-IgM syndrome of unknown molecular diagnosis.
Inducible CO-stimulatory molecule (ICOS), the third member of the CD28/CTLA4 family, is expressed by activated T cells and interacts with its ligand (ICOSL, B7-related protein-1 [B7RP-1]) that is constitutively expressed by B cells. The interaction of ICOS with its ligand leads to terminal differentiation of B cells to plasma cells. ICOS-deficient mice fail to undergo immunoglobulin-class switch recombination (CSR) and germinal center formation, suggesting that ICOS could be a candidate gene for phenotypic hyper-IgM (HIGM) syndromes characterized by recurrent infections, low serum IgG and IgA, and normal or elevated IgM. Genetically, at least 4 distinct molecular defects have been identified that result in defective CSR and present as HIGM syndromes: defects of the CD40 ligand gene (CD40L; HIGM1, X-linked), the activation-induced cytidine deaminase gene (AID; HIGM2, autosomal recessive), the CD40 gene (HIGM3, autosomal recessive), and the nuclear factor-kappaB (NF-kappaB) essential modulator gene (NEMO, or IKK-gamma, X-linked). In a substantial subgroup of HIGM patients, these 4 genes are normal, and the genetic defect is unknown. We sought to investigate the possibility that mutations of ICOS could account for some patients' belonging to this HIGM subgroup. The expression of ICOS protein by activated peripheral blood mononuclear cells and/or interleukin-2-dependent T cell lines derived from these patients was estimated by flow cytometery after incubation of the cells with the ICOS ligand fusion protein B7RP-1 Fc. The coding region and exon-intron boundaries of ICOS were assessed by sequence analysis. We studied 33 HIGM patients from 30 families, selected from an original cohort of 136 patients from 113 families, by excluding mutations of CD40L, AID, CD40, and NEMO. Activated T cells from all 33 patients expressed ICOS normally, and sequence analysis of the coding region and exon-intron boundaries revealed only wild-type ICOS, predicting that the protein structure is normal in this patient population. These findings strongly suggest that ICOS does not belong to the group of genes that, if mutated, present clinically as the HIGM syndrome.


Morphometric analysis of fetal rat lung development.
Applying the zone concept described previously, we quantitatively analyzed fetal rat lung development. The zone concept allowed us to coherently define reference spaces in the developing lung, a prerequisite for morphometric analysis. The peripheral zone I corresponds to a zone of growth of yet undifferentiated tissues; zone II arises from zone I and represents a region of structural and cellular differentiation; zones III and IV comprise the conducting airways and vessels. Lungs of fetal rats aged 17-23 days and 20 hours postnatal were fixed with OsO4 and glutaraldehyde and processed for light and electron microscopic morphometry implemented by point and intersection counting. Fetal lung volume grew in proportion to body weight. Zone II being the largest compartment, its volume changes largely determined lung growth rates. Zone II increased in mass owing to differentiation processes at the interface to zone I where the proximal portions of zone I were continuously shifted into zone II by differentiation. New tissue was generated within zone I. Due to these combined processes zone I changed little in volume until it disappeared at the end of the canalicular stage. The presence in the pseudoglandular stage of half of the parenchymal epithelial mass available around birth indicated that parenchymal development started earlier than assumed so far. While the endothelial surface increased most at birth, the epithelial surface grew by more than 600% at day 21, reflecting the onset of canalisation. The study confirmed the usefulness of the zone concept for morphometry and provided some new insights into lung development.


Electrophysiological follow-up of acute and chronic experimental allergic encephalomyelitis in the Lewis rat.
Cortical somatosensory evoked potentials (c-SEP) and flash visual evoked potentials (f-VEP) were serially recorded in acute monophasic and chronic relapsing experimental allergic encephalomyelitis (EAE) in the Lewis rat. In acute EAE, a significantly delayed latency and broadened peak of the c-SEP were observed corresponding to the clinical onset, and then returned to normal with the disappearance of clinical signs. In chronic EAE, the c-SEP showed the same changes as in acute EAE, also reflecting the first attack, remission and relapsing phase. However, chronic EAE, when paralysis had recovered in the relapsing phase, showed c-SEP abnormalities suggestive of subclinical active lesions. In contrast, the f-VEP showed no obvious abnormalities in acute or chronic EAE. These findings suggest that the c-SEP is an objective and sensitive index for detecting clinical and pathological changes in acute and chronic EAE in the Lewis rat.


Repeated dosing of piperine induced gene expression of P-glycoprotein via stimulated pregnane-X-receptor activity and altered pharmacokinetics of diltiazem in rats.
This study investigated the effect of piperine on the gene expression of P-glycoprotein (P-gp) as well as pregnane-X-receptor (PXR) activity and also its implication on the bioavailability of diltiazem, a P-gp substrate. The effect of piperine on the systemic exposure of diltiazem was examined in rats after the intravenous and oral administration of diltiazem with/without 2 week pretreatment with piperine. Compared with the control group given diltiazem (20 mg/kg) alone, the pretreatment with piperine (10 or 20 mg/kg, once daily for 2 weeks) decreased the oral exposure of diltiazem by 36-48% in rats. Consequently, the bioavailability of oral diltiazem was significantly lower (p < 0.05) after the 2 week pretreatment with piperine. The pretreatment with piperine for 2 weeks also reduced the systemic exposure of desacetyldiltiazem, a major active metabolite of diltiazem by approximately 73%, accompanied by a significant decrease in the metabolite-parent ratio. In contrast to the oral pharmacokinetics, piperine did not affect the intravenous pharmacokinetics of diltiazem in rats. Immunoblot analysis indicated that the protein expression level of intestinal P-gp was significantly enhanced after the 2 week pretreatment with piperine in rats. In addition, piperine increased the PXR reporter activity in human hepatoma cells. Taken together, the 2 week pretreatment with piperine significantly induced intestinal P-gp expression in conjunction with stimulated PXR activity and decreased the oral exposure of diltiazem and desacetyldiltiazem in rats.


Chromatographic estimation of p-coumaric acid and triacontanol in an Ayurvedic root drug patala (Stereospermum suaveolens Roxb.).
A high-performance thin layer chromatographic method has been established for the identification and standardization of Stereospermum suaveolens extracts using two active biomarkers viz. triacontanol and p-coumaric acid in root samples collected from different geographical locations of India. These marker components have different therapeutic activities: p-coumaric acid is a good antioxidant and also has anti-diabetic properties; triacontanol has anti-inflammatory and anti-ulcer properties. Studies on root as well as stem samples showed characteristic bands of triacontanol and p-coumaric acid at R(f) 0.51 and 0.42, respectively. The amount of triacontanol varied from 0.035-8.472 mg/g in the root samples while the amount of p-coumaric acid was in the range 0.081-0.203 mg/g. The limit of detection for triacontanol was 100 ng/spot whereas that for p-coumaric acid was 10 ng/spot.


Everlasting initial memory threshold for rare events in equilibration processes.
Conventional wisdom indicates that initial memory should decay away exponentially in time for general (noncritial) equilibration processes. In particular, time-integrated quantities such as heat are presumed to lose initial memory in a sufficiently long-time limit. However, we show that the large deviation function of time-integrated quantities may exhibit initial memory effect even in the infinite-time limit, if the system is initially prepared sufficiently far away from equilibrium. For a Brownian particle dynamics, as an example, we found a sharp finite threshold rigorously, beyond which the corresponding large deviation function contains everlasting initial memory. The physical origin for this phenomenon is explored with an intuitive argument and also from a toy model analysis. Our results can be applied to general nonequilibrium relaxation processes reaching (non)equilibrium steady states.


Absence of cystatin C involvement in ventricular remodelling and heart failure.
Cystatin C (CysC) is a protease encoded by housekeeping genes. Although its prognostic value in heart failure (HF) is well known, it is debatable whether this value is due to the greater accuracy of CysC in calculating the glomerular filtration rate or to its involvement in pathological ventricular remodelling. The aim of this study was to determine whether CysC expression changes in the myocardium of foetuses of different ages and in the myocardium of adults with various cardiovascular diseases, as well as to analyse the correlation between its serum concentrations and cardiac structure and morphology in a patient group with HF. We analysed the correlations (Pearson's r and Spearman's test) between the serum CysC levels and echocardiographic parameters of 351 patients with HF. We also performed immunohistochemical staining for CysC, metalloproteinase-9 (MMP-9) and desmin in 9 cardiac tissue samples from autopsies of 4 foetuses of different gestational ages and 5 healthy adults or adults with cardiovascular disease. For the patients with HF, there was no correlation between the CysC concentrations and the cardiac parameters measured by 2D echocardiography. The immunohistochemistry showed a weak background staining for CysC in all samples, regardless of age and the presence or absence of cardiovascular diseases. Our results suggest that CysC does not have a significant role in the pathological remodelling of the left ventricle in HF.


Decrease of ZEB1 expression inhibits the B16F10 cancer stem-like properties.
Increasing evidence supports that cancer stem cells (CSCs) are responsible for driving tumor initiation and maintenance. Zinc-finger E-box binding homeobox 1 (ZEB1) is a transcription factor for regulating tumor progression, and contributes to maintenance of CSC-like properties. The goal of the present study is to investigate the effect of decreasing ZEB1 expression on the B16F10 CSC-like properties. The recombinant shRNA targeting ZEB1 were transfected into melanoma B16F10 cells, and shZEB1-CD133(+)CD44(+) CSCs were isolated from the stable transfected cells using the magnetic-associated cell sorting method. The shZEB1-CD133(+)CD44(+) CSC-like properties were systematically analyzed. The results show the B16F10 shZEB1-CD133(+)CD44(+) CSCs significantly decreased the ability of clonogenicity, cellular proliferation, migration, and invasion. Importantly, tumorigenicity and tumor lung metastasis was significantly inhibited in B16F10 shZEB1-CD133(+)CD44(+) CSCs compared with B16F10 scramble-CD133(+)CD44(+) CSCs. The decrease of ZEB1 expression markedly resulted in down-regulation of vimentin and N-cadherin expression as well as up-regulation of E-cadherin expression in tumor tissues from the mice injected with B16F10 shZEB1-CD44(+)CD133(+) CSCs. These findings contribute to understanding the maintenance of B16F10 CD133(+)CD44(+) CSC-like properties that was closely associated with ZEB1 expression. ZEB1 may serve as a new therapeutic target for treatment of malignant melanoma.


Duplex ultrasonography of the fetal aorta, umbilical artery, and placental arcuate artery throughout normal human pregnancy.
A cross-sectional duplex study of blood flow in the fetal aorta, umbilical artery, and arcuate arteries of 111 normal subjects was performed once at between 20 and 42 weeks gestation. Peak systolic velocity, end-diastolic velocity, mean velocity, and volume flow were measured in the fetal aorta, and systolic to diastolic (S/D) ratios were measured in all three vessels. Velocities show an inverse exponential (Y = Exp [1/X x B + C]) increase with gestational age, reaching a plateau just before term, while S/D ratios in the aorta and umbilical arteries show a linear decrease. Such findings are at variance with some published data. Our results suggest a reduction in fetal placental resistance at term and provide useful data concerning normal fetal and placental circulations.


Effects of ionophores X537a and A23187 and calcium-free medium on corneal endothelial morphology.
Past studies have shown that apical junctional complexes (AJCs) of corneal endothelial cells break down in the presence of a Ca++-free medium. The purpose of this study was to examine the ability of Ca++ ionophores to maintain the AJCs in the Ca++-free media in both isolated perfused corneas and cultured endothelial cells. In addition, the ability of disintegrated AJCs to re-form when the endothelium is returned to a medium containing calcium ws also examined. Rabbit corneas were mounted in an in vitro specular microscope and perfused with a Ca++-free medium, or a Ca++-free medium containing 10(-5)M X537A or A23187 calcium ionophore. Also, confluent monolayer cultures of bovine corneal endothelial cells were placed in a Ca++-free medium or a Ca++-free medium containing 10(-5)M X537A or A23187 Ca++ ionophore and incubated for selected time periods. When junctional breakdown occurred, one cornea or culture plate was fixed for scanning and transmission electron microscopy (SEM and TEM), and the other was returned to a medium containing Ca++ and subsequently fixed for SEM and TEM. Both isolated perfused and cultured corneal endothelial cell AJCs exhibited marked disintegration in the presence of Ca++-free medium. The presence of an ionophore in the medium cultured cells. When returned to a medium containing Ca++, the corneas that had been perfused with Ca++-free medium containing an ionophore re-formed the junctions sooner than did those that had been perfused with a Ca++-free medium alone. These results suggests that the ionophores may be capable of mobilizing intracellular calcium to protect the AJCs.


A research-based use of Tai Chi/movement therapy as a nursing intervention.
Tai Chi has been widely practiced in China for centuries as an art form, religious ritual, relaxation technique, exercise, and a method of self-defense for people of all ages. It has been used to improve balance; promote postural stability; decrease falls; enhance cardiovascular and ventilatory functions; rehabilitate persons with acute myocardial infarction and rheumatoid arthritis; and reduce pain, stress, and nightmares. The purpose of this article is to summarize, synthesize, and critically evaluate the research-based use of Tai Chi presented in the current literature and give implications and directions for future research. Additional studies about the effects of Tai Chi from a nursing perspective are needed to make clear when it is beneficial as a nursing intervention.


Quantification of Plasmodium falciparum gametocytes in differential stages of development by quantitative nucleic acid sequence-based amplification.
Two quantitative nucleic acid sequence-based amplification assays (QT-NASBA) based on Pfs16 and Pfs25, have been developed to quantify sexual stage commitment and mature gametocytes of Plasmodium falciparum. Pfs16 mRNA is expressed in all sexual forms including sexually committed ring stages while expression of Pfs25 mRNA is restricted to late stage gametocytes. Both assays showed a sensitivity of one sexual stage parasite/microl of blood. Blood samples from experimentally infected non-immune human volunteers were tested for Plasmodium falciparum by standard microscopy, a previously developed asexual 18S rRNA QT-NASBA, Pfs16 and Pfs25 mRNA QT-NASBA. Pfs16 QT-NASBA was positive in 9 out of 10 volunteers within 48 h after first detection of 18S rRNA, mostly before or at the day of positive microscopy. In contrast, the Pfs25 mRNA QT-NASBA was negative during the 28 days of follow-up, but consistently positive in gametocyte samples from naturally infected Kenyan patients. These data suggest that sexual stage commitment can occur early in the blood-stage infection without successful maturation into infectious gametocytes. In conclusion, Pfs16 and Pfs25 QT-NASBA assays in combination with a previously developed asexual stage QT-NASBA allow for the separate quantification of all developmental stages present in the circulation. The application of sexual stage QT-NASBA assays may contribute to a better understanding of the biology and epidemiology of malaria transmission.


Profound LH suppression after GnRH antagonist administration is associated with a significantly higher ongoing pregnancy rate in IVF.
The significance of suppressed LH levels in GnRH antagonist cycles for IVF outcome is currently unknown. The purpose of this study was to evaluate prospectively the association between LH levels and ongoing pregnancy achievement after GnRH antagonist initiation in IVF cycles. Ovarian stimulation with a fixed dose of 200 IU recombinant FSH and daily GnRH antagonist (ganirelix) 0.25 mg from day 6 of stimulation was initiated in 116 women. Patients were not pretreated with an oral contraceptive. Induction of final oocyte maturation was performed with HCG 10,000 IU as soon as three follicles of > or =17 mm were present in ultrasound, and was followed by oocyte pick-up, conventional IVF or ICSI, and embryo transfer. The luteal phase was supplemented with vaginal progesterone. A significant decrease of both ongoing pregnancy rate and implantation rate was present across groups of patients with increasing LH levels. The highest implantation rate and ongoing pregnancy rate was present in those patients with LH levels on day 8 of stimulation < or =0.5 IU/l. Profound suppression of LH on day 8 of stimulation is associated with a significantly higher chance of achieving an ongoing pregnancy. More studies are necessary to evaluate this phenomenon further.


Palladium-Catalyzed Domino Addition and Cyclization of Arylboronic Acids with 3-Hydroxyprop-1-yn-1-yl Phosphonates Leading to 1,2-Oxaphospholenes.
A novel and efficient palladium-catalyzed domino addition-cyclization of a wide range of arylboronic acids with various 3-hydroxyprop-1-yn-1-yl phosphonates has been developed, affording a convenient and powerful tool for the preparation of valuable 1,2-oxaphospholenes with mild reaction conditions, broad substrate applicability, and good to excellent yields. Mechanistic studies revealed that the reaction might involve Michael addition and nucleophilic substitution.


Antitubercular activity and inhibitory effect on Epstein-Barr virus activation of sterols and polyisoprenepolyols from an edible mushroom, Hypsizigus marmoreus.
Seven sterols (1-7) and eight polyisoprenepolyols (8-15), isolated from the non-saponifiable lipid fraction of the dichloromethane extract of an edible mushroom, Hypsizigus marmoreus (Buna-shimeji), were tested for their antitubercular activity against Mycobacterium tuberculosis strain H37Rv using the Microplate Alamar Blue Assay (MABA). Six sterols (2-7) and two polyisoprenepolyols (8, 12) showed a minimum inhibitory concentration (MIC) in the range of 1-51 microg/ml, while the others (1, 9-11, 13-15) were inactive (MIC>128 microg/ml). The seven sterols (1-7) and three polyisoprenepolyols (8, 10, 12) were further evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Sterols 6 and 7 showed potent inhibitory effects while preserving the high viability of Raji cells.


Normative contrast sensitivity values for the back-lit Melbourne Edge Test and the effect of visual impairment.
The Melbourne Edge Test (MET) is a portable forced-choice edge detection contrast sensitivity (CS) test. The original externally illuminated paper test has been superseded by a backlit version. The aim of this study was to establish normative values for age and to assess change with visual impairment. The MET was administered to 168 people with normal vision (18-93 years old) and 93 patients with visual impairment (39-97 years old). Distance visual acuity (VA) was measured with a log MAR chart. In those eyes without disease, MET CS was stable until the age of 50 years (23.8 +/- 0.7 dB) after which it decreased at a rate of approximately 1.5 dB per decade. Compared with normative values, people with low vision were found to have significantly reduced CS, which could not be totally accounted for by reduced VA. The MET provides a quick and easy measure of CS, which highlights a reduction in visual function that may not be detectable using VA measurements.


Localization of ictal onset zones in Lennox-Gastaut syndrome (LGS) based on information theoretical time delay analysis of intracranial electroencephalography (iEEG).
Precise localization of ictal onset zones is of great clinical importance for successful surgery in patients with intractable drug-resistant epilepsy. Time delay analysis has been one of the most reliable and most widely used computational electroencephalogram (EEG) analysis methods for localizing ictal onset zones. However, the majority of previous studies have only been applied to the localization of ictal onset zones in focal epilepsy. In the present study, we analyzed intracranial EEG (iEEG) recordings acquired from patients with Lennox-Gaustaut syndrome (LGS), which is a type of intractable, pediatric, secondary generalized epilepsies with bilaterally synchronous ictal epileptiform discharges. To estimate the ictal onset zones from ictal iEEG recordings, we estimated time delays among iEEG signals based on the information theoretical approach. The results of the time delay analysis applied to the iEEG data of four successfully treated LGS patients corresponded well with the surgical resection areas identified by experienced epileptologists and multiple neuroimaging modalities, suggesting that the time delay analysis may provide useful information on the precise locations of ictal onset zones prior to epilepsy surgery in LGS patients.


Palladium-Catalyzed Synthesis of Δ(2)-Isoxazoline from Toluene Derivatives Enabled by the Triple Role of Silver Nitrate.
A palladium-catalyzed direct synthesis of Δ(2)-isoxazoline from toluene derivatives has been established. The present reaction proceeds through nondirected Csp(3)-H activation, benzylic nitration, dehydration, and cycloaddition. This protocol also features the unusual triple role of silver nitrate in a one-pot reaction.


Risk factors of psychosis: identifying vulnerable populations premorbidly.
This article reviews premorbid indicators of psychosis that may be relevant to primary intervention. These risk markers are divided into two categories: (1) precursors related to early etiological factors (family psychiatric history, perinatal and obstetric complications, neurobehavior deficits, early parental separation, institutionalization, and poor family function) and (2) precursors signaling latent mental illness (personality measurements indicating proneness to psychosis, and teacher ratings indicating emotional lability, social anxiety, social withdrawal, passivity, poor peer relations, and disruptive and aggressive behavior). Because teacher ratings have been shown to be powerful predictors of adult mental breakdown, part of this article focuses on a specific study that assesses such ratings as predictors of psychosis in a high-risk population. Risk indicators may also provide clues about protective factors relevant for primary prevention.


[Quality standards for resection of non-small cell lung cancer].
Surgical resection remains the only curative treatment option for non small cell lung cancer. In contrast to other modalities (chemotherapy, radiation therapy) where the benefit is modest, there are no universally accepted guide-lines for quality. Several studies have demonstrated that the best results in terms of operative mortality and long term survival are achieved by specialized surgeons working in high volume institutions. The basic principle of operative treatment is a combination of anatomic resection and radical ipsilateral lymph node dissection. Lymph node dissection ascertains adequate nodal staging and recent research has found that it is associated with an increased in the medium term. The usual mortality rate is about 2% after lobectomy and 6-10% following pneumonectomy. Given the high operative risk of pneumonectomy, extended lobectomies with bronchoplasty or angioplasty are valuable alternatives, provided that a complete resection is achieved. Anatomic segmentectomy may be an alternative to lobectomy in selected patients with peripheral tumors of less than 2 cm in diameter. There is no evidence that neo-adjuvant chemotherapy increases the risk of pneumonectomy.


Sleep-disordered breathing in children with congenital muscular dystrophies.
Most types of neuromuscular diseases are known to be associated with a high risk of sleep-disordered breathing. We performed a prospective study in a well individualized group of muscular disorders, congenital muscular dystrophies (CMD), to characterize the frequency of sleep-disordered breathing and thereby to determine the potential usefulness of sleep studies in such patients. Twenty CMD children (12 F, 8 M, aged 4-17 years) were included. Using overnight polysomnography, we determined the following parameters: sleep stages, sleep latency, sleep efficiency index, wake time duration, total sleep time (TST), apnea/hypopnea index (AHI), arterial blood oxygen saturation, and nocturnal paroxysmal EEG activity. As compared to healthy controls, we detected in our study group frequent awakenings, a decreased TST (mean 448 ± 44.4 min) and a decreased REM duration (mean 11.5 ± 3.5% of TST). Significant increase in wake time duration (28-90 min) and decrease in REM duration were observed in 12 patients. An apnea/hypopnea syndrome was detected in 13 patients (65%) with central apneas in 8, obstructive apneas in 2 and 3 mixed apneas in 3 patients. AHI was >10 in 3 cases, <10> 5 in 4 cases and were concomitant with blood oxygen de-saturation in four cases. NPA were detected in 10 patients ranging from 10 to 40% of TST. Our results confirm the high incidence of sleep disordered breathing in children with CMD, and thereby, the usefulness of overnight polysomnography recordings in such patients.


Do mobile phone base stations affect sleep of residents? Results from an experimental double-blind sham-controlled field study.
The aim of the present double-blind, sham-controlled, balanced randomized cross-over study was to disentangle effects of electromagnetic fields (EMF) and non-EMF effects of mobile phone base stations on objective and subjective sleep quality. In total 397 residents aged 18-81 years (50.9% female) from 10 German sites, where no mobile phone service was available, were exposed to sham and GSM (Global System for Mobile Communications, 900 MHz and 1,800 MHz) base station signals by an experimental base station while their sleep was monitored at their homes during 12 nights. Participants were randomly exposed to real (GSM) or sham exposure for five nights each. Individual measurement of EMF exposure, questionnaires on sleep disorders, overall sleep quality, attitude towards mobile communication, and on subjective sleep quality (morning and evening protocols) as well as objective sleep data (frontal EEG and EOG recordings) were gathered. Analysis of the subjective and objective sleep data did not reveal any significant differences between the real and sham condition. During sham exposure nights, objective and subjective sleep efficiency, wake after sleep onset, and subjective sleep latency were significantly worse in participants with concerns about possible health risks resulting from base stations than in participants who were not concerned. The study did not provide any evidence for short-term physiological effects of EMF emitted by mobile phone base stations on objective and subjective sleep quality. However, the results indicate that mobile phone base stations as such (not the electromagnetic fields) may have a significant negative impact on sleep quality.


[Fractures of the proximal femur in patients over 70 years--choice of procedure and results].
From 1978 till oct. 1981 110 patients between 70 and 99 years old were operated upon fractures of the proximal femur. Out of those 43 presented with fractures of the femoral neck, 46 with pertrochanteric, and 17 with subtrochanteric. In fractures of the femoral neck we generally perform alloplastic replacement of the femoral head or total hip arthroplasty. By means of a 24 hour preparing period (volume and electrolyte replacement, digitalis) and intraoperative administration of dopamine the systemic reaction to bone cement could be avoided. Pertrochanteric fractures are treated by Ender- rods immediately. Subtrochanteric fractures are the greatest technical problem. We now use long-stem-prosthesis as compound-osteosynthesis. Physiotherapy is applied aggressively. The patients are trained to walk from the second day p.op. on. Perioperative lethality rated 17%. Within the group of age 70 till age 80 only four died (7,5%), over 80 years 15 (30% of this group). Following hip-replacement there were 13 deaths, after Ender-rods only 4 lethalities. 83% of all patients could be discharged after a mean of 19 days, 86% of those ambulatory.


Impacts of Family Rewards on Adolescents' Mental Health and Problem Behavior: Understanding the Full Range of Effects of a Conditional Cash Transfer Program.
This paper examines the effects of Opportunity New York City-Family Rewards, the first holistic conditional cash transfer (CCT) program evaluated in the USA, on adolescents' mental health and problem behavior (key outcomes outside of the direct targets of the program) as well as on key potential mechanisms of these effects. The Family Rewards program, launched by the Center for Economic Opportunity in the Mayor's Office of the City of New York in 2007 and co-designed and evaluated by MDRC, offered cash assistance to low-income families to reduce economic hardship. The cash rewards were offered to families in three key areas: children's education, family preventive health care, and parents' employment. Results that rely on the random assignment design of the study find that Family Rewards resulted in statistically significant reductions in adolescent aggression and rates of substance use by program group adolescents as well as their friends, relative to adolescents in the control condition, but no statistically significant impacts on adolescent mental health. One possible mechanism for the benefits to adolescent behavior appears to be time spent with peers, as fewer adolescents in the program group spent time with friends and more adolescents in the program group spent time with family. Findings are discussed with regard to their implication for conditional cash transfer programs as well as for interventions targeting high-risk youth.


Almanac 2014: aortic valve disease.
The past few years have seen major advances in the diagnosis of aortic valve disease and in our understanding of the pathophysiology of disease. In addition, transcatheter aortic valve implantation has transformed our clinical management options. This article summarises new aortic valve disease research published in Heart in 2013 and 2014, within the context of other major studies published in general medical journals, including a discussion of the potential impact of these new research findings on the clinical approach to management of adults with aortic valve disease.


Estrogen receptor-α drives adiponectin effects on cyclin D1 expression in breast cancer cells.
Obesity is a risk factor for breast cancer, largely due to altered expression of various adipocytokines. As it concerns adiponectin, there are not univocal results regarding its role in breast cancer occurrence and progression. Here, we demonstrate that in animals injected with human estrogen receptor (ER)-α-negative MDA-MB-231 cells pretreated with adiponectin (1 and 5 µg/ml), a significant reduction (60 and 40%, respectively) in tumor volume is observed, whereas an increased tumor growth (54 and 109%, respectively) is evidenced in the animals receiving human ER-α-positive MCF-7 cells. Moreover, cyclin D1 (CD1) mRNA and protein levels are decreased in MDA-MB-231 cells, whereas they are up-regulated in ER-α-positive cells by adiponectin. These findings fit with the opposite effects of adiponectin on CD1 promoter: 0.44- and 0.34-fold decrease in MDA-MB-231 cells and 0.63- and 0.95-fold increase in MCF-7 cells, treated with 1 and 5 µg/ml, respectively. Functional studies indicate that these effects are mediated by the specific protein 1 motif located in the CD1 promoter. In the absence of ER-α, the adiponectin-mediated down-regulation of CD1 involves the recruitment of corepressors. In the presence of ER-α, the adiponectin-induced expression of CD1 requires the involvement of an activator complex. In conclusion, we propose that a possible mechanism through which adiponectin differently affects breast cancer growth is the opposite modulation of CD1 levels accordingly to ER-α expression.


Descending frequency swept tones have lower thresholds than ascending frequency swept tones for a harbor seal (Phoca vitulina) and human listeners.
Many seal vocalizations consist of frequency swept tones. The signal detection thresholds of a harbor seal (Phoca vitulina) and of human listeners were measured using ascending and descending frequency swept tones at 1/3- and 1-oct bandwidths. The swept tones increased or decreased exponentially and traversed the same frequency range. The sweeps were centered on 2, 4, and 8 kHz for the seal study and 0.5, 1, and 2 kHz for the human listeners. The bandwidth of the sweep did not affect signal detection abilities of either the seal or human listeners. The seal had lower signal detection thresholds (1-5 dB) when presented with the descending frequency swept tones (F = 32.04, df = (1,31), p < 0.000001). Human listeners also had lower detection thresholds for descending frequency swept tones (t = -4.78, df = 52, p < 0.0001). Pinniped ascending frequency swept calls may not function as well as descending frequency sweeps for long-distance communicative signals.


Assessment of the acuteness of heroin deaths from the analysis of multiple blood specimens.
Data was compiled from 126 morphine-involved cases investigated by the Office of the Chief Medical Examiner, State of Maryland, USA. An investigation was conducted into whether comparison of morphine concentrations from a central and peripheral site could be used to determine whether a morphine death was acute or delayed. Fifty cases were identified as 'acute' because the urine free morphine concentration by radioimmunoassay (RIA) was less than 25 ng/mL; 76 cases were classified as 'random' because they had a urine morphine concentration greater than 25 ng/mL by RIA. The average heart blood to peripheral blood morphine concentration ratio in the acute deaths was 1.40. The average heart blood to peripheral blood morphine concentration ratio in the random deaths was 1.18. Because there was considerable overlap between the two groups of data, the authors conclude that it was not possible to predict 'acute' opiate intoxication deaths versus 'delayed' deaths when the only information available is heart and peripheral blood free morphine concentrations.


Local recurrence after conservative surgery and radiation therapy for ductal carcinoma in situ: Possible importance of family history.
The optimal treatment of ductal carcinoma in situ is controversial. Traditionally, women with this disease have been treated with mastectomy with excellent results, but recently the need for such extensive surgery has been questioned. Long-term data on the use of conservative surgery and radiation therapy for treatment are limited. A retrospective analysis was performed to assess treatment outcome and prognostic factors for patients with ductal carcinoma in situ treated with conservative surgery and radiotherapy. From 1976 to 1990, 76 women with ductal carcinoma in situ were treated with conservative surgery followed by radiation therapy. The median age at diagnosis was 48 years. Seventeen patients had a positive family history of breast cancer in a first-degree (n=8) or second-degree (n=9) relative. Median follow-up interval was 74 months for the 71 survivors. In 54 patients, the carcinoma was detected by mammography alone; in 13 patients, by mammography and physical examination; and in 4 patients, by physical examination with a normal mammogram; and in 5 patients, by physical examination alone without mammography. Fifty patients had re-excision after initial biopsy. Final margins were positive in 11, close in 11, negative in 34, and unknown in 20. The median volume of excised tissue was 60 cm3. The axilla was surgically staged in 30 patients (39%) and all were negative. The whole breast was irradiated to a dose of 45 to 50 Gy in all patients. Seventy-two patients also received a boost to the primary site. The median total radiation dose to the primary site was 61 Gy (range, 46 to 71). Seven patients had a recurrence in the treated breast at 16, 18, 41, 63, 72, 83, and 104 months after treatment. The 5- and 10-year actuarial rates of local recurrence were 4% and 15%, respectively. Six of seven recurrences occurred in the vicinity of the original lesion. Four local recurrences were invasive, and three were ductal carcinoma in situ. Two patients developed a contralateral invasive carcinoma. The 5- and 10-year cause-specific survival rates were 100% and 96%, respectively. The 10-year actuarial rate of local recurrence was 25% in the group with a total excision volume less than 60 cm3, as compared with 0% in those with 60 cm3 or more excised (P=0.04). In patients with a positive family history, the 10-year actuarial rate of local recurrence was 37%, as compared with 9% in patients with a negative family history (P=0.008). Of the 17 patients with a positive family history, four developed either an ipsilateral or contralateral invasive breast cancer, whereas 1 of the 58 patients without a family history developed a subsequent invasive breast cancer (P=0.008). These results suggest that patients with ductal carcinoma in situ treated with conservative surgery and radiotherapy (including a boost to the primary site) appear to benefit from wide, rather than limited, resection. These results also suggest that family history may be an important prognostic factor for progression of disease.


Sarcomas of the uterus: a clinicopathologic study of 119 patients.
This series consists of 119 uterine sarcoma patients treated at the University of Helsinki Central Hospital during the 20-year period of 1958 to 1977. It comprises the three main histologic varieties: leiomyosarcomas, 51 patients; mixed müllerian sarcomas, 45 patients; and endometrial stromal sarcomas, 23 patients. The clinicopathological features that could have had a bearing on prognosis were examined retrospectively. The clinical stage at the time of primary treatment was the main prognostic factor. Other important factors were the degree of histologic differentiation and the mitotic activity. The overall five-year survival rate for patients with leiomyosarcomas was 39%; for mixed müllerian sarcomas, 33%; and for endometrial stromal sarcomas, 61%. The ten-year survival figures were 27, 14, and 37%, respectively. Some features of the diagnosis, the natural history, and the different methods of treatment of these diseases are discussed.


Isolation and characterization of IgG2a-reactive autoantibodies from influenza virus-infected BALB/c mice.
Repeated influenza virus infection induces the production of dominantly IgG2a-type virus-specific antibodies as well as the appearance of IgG2a-reactive autoantibodies in BALB/c mice characterized by low spontaneous rheumatoid factor-type autoantibody production. IgG2a-reactive autoantibody-producing hybridomas could be isolated from the spleen of influenza virus-infected BALB/c mice. The mAb produced by these clones represent not only IgM but also IgG and IgA isotypes and show strong isotype or isoallotype specificity. The common functional property of these autoantibodies is their preferential- and high-affinity binding to complexed, solid-phase-bound or heat-aggregated IgG2a when compared to native soluble or cell-bound IgG2a. The mechanism of induction and the possible biological function of these autoantibodies are discussed in the light of their fine specificity and functional properties.


Predictive validity of the Motivation To Stop Scale (MTSS): a single-item measure of motivation to stop smoking.
Many different measures of motivation to stop smoking exist but it would be desirable to have a brief version that is standard for use in population surveys and for evaluations of interventions to promote cessation. The aim of this study was to assess the predictive validity and accuracy of the single-item Motivation To Stop Scale (MTSS). This study is part of the "Smoking Toolkit Study;" a monthly survey of representative samples of the English population. We used data from 2483 respondents to the surveys from November 2008 to January 2011, who were smokers, used the MTSS, and were followed up 6 months later to provide information on quit attempts since baseline. The MTSS consists of one item with seven response categories ranging from 1 (lowest) to level 7 (highest level of motivation to stop smoking). A total of 692 smokers (27.9% (95% CI=26.1-29.6)) made an attempt to quit smoking between baseline and 6-month follow-up. The odds of quit attempts increased linearly with increasing level of motivation at baseline (p<0.001) and were 6.8 (95% CI=4.7-9.9) times higher for the highest level of motivation compared with the lowest. The accuracy of the MTSS for discriminating between smokers who did and did not attempt to quit was ROC(AUC)=0.67 (95% CI=0.65-0.70). The MTSS provides strong and accurate prediction of quit attempts and is a candidate for a standard single-item measure of motivation to stop smoking. Further research should assess the external validity of this measure in different smoking populations.


Isolation and characterization of glycosaminoglycans from human atheromatous vessels.
The complex cascade of events leading to the formation of atheromatous plaques depends on the interaction between several cell types, growth factors, cytokines, and molecules of the extracellular matrix (ECM) (1). Among different molecules of the ECM involved in atherogenesis, the glycosaminoglycan(GAGs) have been reported to contribute to key events leading to the formation of atherosclerotic lesions (2). GAGs are linear acidic polysaccharides of variable length and composition, which occur either in free form or attached to a protein core to form proteoglycans (3). On the basis of their composition, GAGs are grouped into four major categories: hyaluronic acid, heparin and heparan sulfate, chondroitin and dermatan sulfates, and keratan sulfate. ECM GAGs provide structural links between fibrous and cellular elements, contribute to viscoelastic properties, regulate permeability and retention of plasma components within the matrix (2,4), inhibit vascular cell growth (5), affect hemostasis and platelet aggregation (6), and interact with lipoproteins (7) and various growth factors (8,9).