Syndecan-1 facilitates breast cancer metastasis to the brain.
Although survival rates for patients with localized breast cancer have increased, patients with metastatic breast cancer still have poor prognosis. Understanding key factors involved in promoting breast cancer metastasis is imperative for better treatments. In this study, we investigated the role of syndecan-1 (Sdc1) in breast cancer metastasis. To assess the role of Sdc1 in breast cancer metastasis, we silenced Sdc1 expression in the triple-negative breast cancer human MDA-MB-231 cell line and overexpressed it in the mouse mammary carcinoma 4T1 cell line. Intracardiac injections were performed in an experimental mouse metastasis model using both cell lines. In vitro transwell blood-brain barrier (BBB) and brain section adhesion assays were utilized to specifically investigate how Sdc1 facilitates brain metastasis. A cytokine array was performed to evaluate differences in the breast cancer cell secretome when Sdc1 is silenced. Silencing expression of Sdc1 in breast cancer cells significantly reduced metastasis to the brain. Conversely, overexpression of Sdc1 increased metastasis to the brain. We found that silencing of Sdc1 expression had no effect on attachment of breast cancer cells to brain endothelial cells or astrocytes, but migration across the BBB was reduced as well as adhesion to the perivascular regions of the brain. Loss of Sdc1 also led to changes in breast cancer cell-secreted cytokines/chemokines, which may influence the BBB. Taken together, our study demonstrates a role for Sdc1 in promoting breast cancer metastasis to the brain. These findings suggest that Sdc1 supports breast cancer cell migration across the BBB through regulation of cytokines, which may modulate the BBB. Further elucidating this mechanism will allow for the development of therapeutic strategies to combat brain metastasis.


Study of Enteromorpha polysaccharides as a new-style coagulant aid in dye wastewater treatment.
Enteromorpha is one of the common fouling green algae, which has brought serious environmental problems in past years. This study was aimed to apply it in water treatment process. Enteromorpha polysaccharides (Ep) were used as a new-style coagulant aid to assess its effect on coagulation behavior and floc characteristics. Color removal was used to evaluate coagulation effects and floc properties were investigated by Photometric Dispersion Analyzer (PDA). Results showed that when Ep was used in combination with aluminum chloride (AC), color removal could be apparently improved, and the optimal solution pH ranged 6.0-8.0. The growth rate and average size of flocs formed by AC-Ep were larger than those by AC in steady-state after floc growth phase, and meanwhile the distribution of floc size had a wider range. Besides, floc recoverability could be significantly improved when Ep was used as coagulant aid.


Microsomal metabolism of N,N-diethyl-m-toluamide (DEET, DET): the extended network of metabolites.
1. The aim was to set out to establish the complete network of metabolites arising from the phenobarbital-treated rat liver microsomal oxidation of N,N-diethyl-m-toluamide (DEET). The products formed from DEET and all its subsequent metabolites were identified by HPLC retention times, UV spectroscopy, mass spectrometry and by comparison with authentic standards. 2. DEET (1a) produces three major metabolites, N-ethyl-m-toluamide (1b), N,N-diethyl-m-(hydroxymethyl)benzamide (2a) and N-ethyl-m-(hydroxymethyl)benzamide (2b), and, at low substrate concentrations or extended reaction times, two minor metabolites, toluamide (1c) and N,N-diethyl-m-formylbenzamide (3a). 1b and 2a are primary metabolites and their formation follows Michaelis-Menten-type kinetics. At low DEET concentrations, ring methyl group oxidation is favoured; at saturation concentrations, methyl group oxidation and N-deethylation proceed at similar rates. The rate of formation of 2b decreases with increasing DEET concentration; 2b is therefore a secondary metabolite of DEET and DEET acts as a competitive inhibitor of the metabolism of 1b and 2a. 3. Except for the primary amides, where N-dealkylation is impossible, metabolism of all subsequent compounds, 1b,c, 2a-c, 3a-c and 4a,b, involves an N-deethylation (NEt2 --> NHEt or NHEt --> NH2) competitive with a ring substituent oxidation (CH3 --> CH2OH, CH2OH --> CHO or CHO --> CO2H). Surprisingly, the aldehydes 3a-c are also reduced to the corresponding alcohols 2a-c (CHO --> CH2OH); CO inhibits the oxidative metabolism of 3a-c, but reduction to 2a-c continues uninhibited. 4. The outcomes of this work are that (1) previously unreported aldehydes 3b and 3c form part of the DEET network of metabolites, (2) the reduction of the aldehydes 3a-c has the potential to inhibit the formation of the more highly oxidized DEET metabolites, (3) amide hydrolysis was not observed for any substrate and (4) no evidence was obtained for N-(1-hydroxyethyl)amide intermediates.


Anion-stimulated phosphohydrolase activity of intestinal alkaline phosphatase.
Phosphohydrolase activity of a highly enriched commercial preparation of calf intestinal alkaline phosphatase was stimulated in the presence of HCO3. SO4, Cl, SCN, and acetate did not stimulate hydrolysis, whereas SO3 exhibited a bimodal effect, stimulating at low (25mM) concentration but inhibiting at high (100 mM) concentration. The pH optimum of this stimulation by HCO3 or SO3 was 8.5--9.0 and was maximal at a Mg concentration of 0.5 mM. HCO3 increased the Vmax of the reaction without changing the Km for ATP. ATP, GTP, UTP, and xanthosine triphosphate were equally effective as substrates, whereas AMP and p-nitrophenyl phosphate were much less effective. Alkaline phosphatase activity was inhibited by L-cysteine and L-phenylalanine, compounds that also inhibited the HCO3-ATPase activity of the preparation. Passage of the commercial preparation through an anion-exchange column yielded a fraction with enriched alkaline phosphatase and HCO3-ATPase activities; this fraction proved to be a single protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, on isoelectric focusing, and by immunologic techniques. These studies strongly suggest that alkaline phosphatase and anion-stimulated phosphohydrolase activities are properties of the same protein in small intestine. It is possible that alkaline phosphatase may function as a HCO3-ATPase involved in intestinal absorption and secretion.


Signals involved in T cell activation. I. Phorbol esters enhance responsiveness but cannot replace intact accessory cells in the induction of mitogen-stimulated T cell proliferation.
The role of accessory cells (AC) in the initiation of mitogen-induced T cell proliferation was examined by comparing the effect of intact macrophages (M phi) with that of 4-beta-phorbol 12-myristate 13-acetate (PMA). In high-density cultures, purified guinea pig T cells failed to proliferate in response to stimulation with phytohemagglutinin (PHA), concanavalin A (Con A), or PMA alone. The addition of M phi to PHA or Con A but not PMA-stimulated cultures restored T cell proliferation. The addition of PMA to high-density T cell cultures stimulated with PHA or Con A also permitted [3H]thymidine incorporation, but was less effective than intact M phi in this regard. This action of PMA was dependent on the small number of AC contaminating the T cell cultures as evidenced by the finding that PMA could not support mitogen responsiveness of T cells that had been depleted of Ia-bearing cells by planning, even when these cells were cultured at high density. When PMA was added to T cell cultures supported by optimal numbers of M phi, catalase-reversible suppression of responses was noted. Even in cultures containing catalase, PMA failed to enhance responsiveness above that supported by optimal numbers of M phi. A low-density culture system was used to examine in greater detail the possibility that PMA could completely substitute for M phi in promoting T cells activation. In low-density cultures, mitogen-induced T cell proliferation required intact M phi. PMA could not support responses even in cultures supplemented with interleukin 1-containing M phi supernatants or purified interleukin 2 alone or in combination. Similar results were found in high-density cultures of T cells depleted of Ia-bearing cells. These results support a model of T cell activation in which AC play at least two distinct roles. The initiation of the response requires a signal conveyed by an intact M phi, which cannot be provided by either a M phi supernatant factor or PMA. The response can be amplified by additional M phi or M phi supernatant factors. PMA can substitute for M phi in this regard and can provide the signal necessary for amplification of T cell proliferation supported by small numbers of intact AC.


Extracorporeal circulation in the management of massive propranolol overdose.
A case of refractory hypotension following propranolol overdose is reported. Management included isoprenaline, glucagon and extracorporeal circulatory support using femoral vein-femoral artery bypass. The unreliability of neurological observations, especially unreactive pupils, in the presence of drug overdose is reiterated.


Localization of sites in periventricular forebrain mediating cardiovascular effects of gamma-aminobutyric acid agonists and antagonists in anesthetized cats.
Previous studies have shown that injection of gamma-aminobutyric acid (GABA) antagonists such as bicuculline methiodide (BMI) into the forebrain (i.e., lateral and third) ventricular system elicits neurally mediated increases in blood pressure and heart rate and inhibits baroreflex bradycardia in anesthetized cats. Similar administration of muscimol, a GABA agonist, blocks or reverses the effects of BMI but has no effect on blood pressure or heart rate in untreated animals. These findings suggest that GABAergic inhibition may tonically suppress a forebrain mechanism capable of modifying autonomic outflow to the cardiovascular system. In the present study, we used a technique designed to restrict the distribution of intraventricularly administered drugs to varying degrees in order to better localize the relevant sites of drug action. Our findings show that BMI increases heart rate and blood pressure and that muscimol counters these changes by acting at a site that is accessible from the intermediate (as opposed to the rostral or caudal) region of the third ventricle. In contrast, these agents influence baroreflex bradycardia by acting at more rostral periventricular sites. These findings are consistent with the notion that the GABAergic mechanisms involved in the cardiovascular effects resulting from intraventricular administration of BMI and muscimol are located in the periventricular hypothalamus.


Injecting Hope--A Review of Breast Cancer Vaccines.
There is significant interest in investigating immunotherapeutic strategies to be used for the treatment of breast cancer patients. One form of immunotherapy under active investigation is the cancer vaccine. Vaccines are a form of active immune therapy designed to stimulate the immune system to recognize tumor cells as foreign. Vaccines include an antigen that serves as the target for the immune response, and an immunoadjuvant, which is a nonspecific stimulator of the immune response that promotes an environment conducive to immune stimulation. Vaccines are an appealing therapeutic strategy because they are specific and are associated with minimal toxicity. In addition, they stimulate the adaptive immune system, thereby producing a memory response allowing for sustained effect without repeated therapy. Currently, there are no US Food and Drug Administration-approved breast cancer vaccines; however, there are multiple vaccines and treatment strategies employing these vaccines that are being actively investigated in clinical trials.


Pro-apoptotic effect of epigallo-catechin-3-gallate on B lymphocytes through regulating BAFF/PI3K/Akt/mTOR signaling in rats with collagen-induced arthritis.
To investigate the role of PI3K/Akt/mTOR signaling mediated by B cell-activating factor belonging to the TNF family (BAFF) involved in anti-apoptosis of B lymphocytes in rats with collagen-induced arthritis (CIA) and the regulation of epigallo-catechin-3-gallate (EGCG). Sprague-Dawley rats were immunized to induce CIA. CIA rats were randomly separated into different groups and treated with EGCG (40, 80 mg/kg), Paeoniflorin (100mg/kg) from day 18 to day 38 after immunization. The effects of EGCG on B lymphocytes were evaluated by the levels of BAFF, anti-CII antibody, IgA, IgG and IgM, and the expressions of BAFF receptor, P110δ, p-Akt, mTORC1, Bcl-xL and Bim. B lymphocyte proliferations were analyzed by MTT assay. Apoptosis of B lymphocyte were assayed by flow cytometry. Results showed that, in CIA rats, the levels of BAFF, anti-CII antibody, IgA, IgG and IgM enhanced. BAFF receptor, P110δ, p-AKT, mTORC1 and Bcl-xL were expressed highly, while Bim expression decreased. EGCG (40, 80 mg/kg) and Paeoniflorin decreased the levels of BAFF, anti-CII antibody, IgA, IgG, IgM and the expressions of BAFF receptor, P110δ, p-AKT, mTORC1, Bcl-xL in CIA rats, and increased Bim expression. Further studies showed that EGCG could reduce the expression of P110δ and mTORC1 in vitro. EGCG inhibited B lymphocyte proliferation and induced B lymphocyte apoptosis. In conclusion, BAFF/BAFF receptor might regulate B cell anti-apoptosis through PI3K/Akt/mTOR pathway. EGCG had therapeutic effects on CIA rats, which might be relative to the inhibition effects of EGCG on BAFF and PI3K/Akt/mTOR signaling, and then the apoptosis of B lymphocytes was promoted further.


Are Callous-Unemotional Traits Associated with Conflict Adaptation in Childhood?
This study examined associations between childhood callous-unemotional (CU) traits and cognitive control using a conflict adaptation paradigm. Participants were (N = 158) children aged 9 to 12 years (M = 10.42, SD = 1.05; 57 % boys), who completed a modified color-word Stroop task. CU traits and conduct problems were indexed via self-reports on the Strengths and Difficulties Questionnaire and the Inventory of Callous-Unemotional Traits. CU traits were found to be uniquely associated with reduced conflict adaptation, however, this significant association was specific to boys. Conversely, conduct problems were associated with increased conflict adaptation, but among girls only. These findings contribute to evidence of atypical goal directed behavior in boys with CU traits by providing preliminary evidence that the specific impairments in cognitive control that characterize these boys include those concerning dynamic adjustments in cognitive control. Findings are discussed in relation to accounts of childhood CU traits based on the Response Modulation hypothesis.


Drug therapy persistence and stroke recurrence.
To assess the effect of persistence of use of warfarin sodium, aspirin, or clopidogrel bisulfate on stroke recurrence in a Medicaid high-risk, largely female, African American population. Prospective non-concurrent cohort, longitudinal data analysis of medical and pharmacy claims of stroke patients from Medicaid managed care organizations between January 1, 2001, and December 31, 2003. Cox proportional hazards models were used to predict the likelihood of avoiding a recurrence as a function of persistence of use of the initial medication (warfarin, aspirin, or clopidogrel) after stroke, adjusting for age, race, sex, hypertension and other comorbidities, and the pharmacotherapies prescribed. We used propensity scores to adjust for confounding by indication. Among 925 stroke patients (64.6% female, 75.1% > or =50 years, and 57.8% African American), hypertension and heart disease were the most prevalent comorbidities (66.1% and 65.1%, respectively); most initial strokes were nonhemorrhagic. Persistence of use of warfarin, aspirin, or clopidogrel after stroke increased the likelihood of avoiding a recurrence (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.22-2.01). Having a hemorrhagic stroke initially (HR, 0.37; 95% CI, 0.18-0.74) or having heart disease (HR, 0.82; 95% CI, 0.67-1.01), hypertension (HR, 0.63; 95% CI, 0.51-0.79), or diabetes mellitus (HR, 0.74; 95% CI, 0.60-0.91) after an initial stroke significantly decreased the likelihood of avoiding a recurrence. Patient's age, race, sex, and urban residence did not significantly predict the likelihood of avoiding a recurrence. Persistence of use of the initial stroke preventive medication after stroke is effective in avoiding a recurrence. Hemorrhagic stroke, heart disease, hypertension, and diabetes increase the likelihood of a recurrence.


Algal virus: isolation.
Freshwater blue-green algae of the genera Lyngbya, Plectonema, and Phormidium are susceptible to a virus recently isolated from a waste-stabilization pond. Electron micrographs of a partially purified preparation show that the viral particle has an icosahedral structure about 66 mmicro in diameter.


RB-mediated tumor suppression of a lung cancer cell line is abrogated by an extract enriched in extracellular matrix.
To examine whether the expression of retinoblastoma (RB) protein could mediate tumor suppression in a lung carcinoma cell line carrying multiple genetic defects, we transfected the Rb gene into a non-small cell lung cancer cell line with absent RB protein. We observed that the stable expression of a functional RB product was associated with a decreased efficiency of soft agar cloning and partial suppression of tumorigenicity in nude mice. The suppression of tumorigenicity was marked when 10(6) cells were injected into the flanks of nude mice but was less prominent when 10(7) cells were injected. RB-mediated tumor suppression, however, was consistently blocked by preincubation of the transfected cells with an extract enriched with an extracellular matrix (Matrigel). Analysis of tumors harvested from nude mice showed that they continued to express detectable levels of human RB protein which retained functional E1A binding activity and nuclear localization. RB-mediated inhibition of soft agar cloning was also blocked in a dose-dependent manner by the addition of Matrigel. These observations demonstrate that the expression of wild-type RB may suppress certain parameters of tumorigenicity in lung carcinoma cells that contain multiple genetic alterations. In addition, the reversal of tumor suppression by an extract enriched in basement membrane components may offer clues for further investigations into the mechanism of RB-mediated tumor suppression.


Responses of hematological parameters, beta-endorphin, cortisol, reactive oxygen metabolites, and biological antioxidant potential in horses participating in a traditional tournament.
Several concerns have been raised over the health of animals used in equestrian games that have their origins in historical or religious events and are currently held in many countries. This study investigated physiological stress response and health status of horses participating in the Sartiglia, a historical horse tournament held in the city of Oristano, Italy, which is principally based on the attempts of masked horsemen at a gallop to run a sword through a hole in a suspended silver star. Blood samples were collected from 21 horses the day before the tournament (D0), during the tournament (D1), and the day after the tournament (D2). Samples were analyzed for complete blood count and biochemical, hormonal, and oxidative stress assays. Data were analyzed using the mixed effect model with sampling session as one of the fixed effects. On the whole, blood parameters evidenced an optimal health status of horses at D0. Significant dehydration and increase of circulating glucose, enzymes, cortisol, and β-endorphin were registered at D1 (P < 0.001) with a complete recovery of physiological values just at D2. The reactive oxygen metabolites (d-ROM), from which the prooxidant activity can be evaluated, showed an increase from D0 to D1 and D2. Concentration of biological antioxidant potential, which measured the antioxidant capacity, was characterized by the maximum level registered during the tournament and counteracted the simultaneous increase of d-ROM. It can be hypothesized that the tournament played an important role in causing high levels of oxidant markers not only because of the physical exercise represented by the gallop but also because the emotional stressors. In conclusion, the tournament caused significant changes of most parameters, which rapidly recovered to baseline values within the day after. These data will certainly be useful for a future implementation of tests in equine medicine and for the improvements of knowledge of changes of blood parameters and health of horses in similar tournaments.


Magnetization transfer in MRI: a review.
This review describes magnetization transfer (MT) contrast in magnetic resonance imaging. A qualitative description of how MT works is provided along with experimental evidence that leads to a quantitative model for MT in tissues. The implementation of MT saturation in imaging sequences and the interpretation of the MT-induced signal change in terms of exchange processes and direct effects are presented. Finally, highlights of clinical uses of MT are outlined and future directions for investigation proposed.


Circadian component influences the photoperiodic induction of diapause in a drosophilid fly, Chymomyza costata.
The last-instar larvae of a drosophilid fly, Chymomyza costata enter diapause in response to the dark-phases longer than 9 h (Yoshida, T., Kimura, M.T., 1995. The photoperiodic clock in Chymomyza costata. Journal of Insect Physiology 41, 217-222). In order to switch the developmental programming of the sensitive larvae from continuous development to diapause, after they were transferred from the short (8 h) to the long (14 h) dark-phase, significantly less time (1-2 days) was required when the dark-phase was abruptly and asymmetrically extended into the evening, than when it was extended symmetrically into both morning and evening (2-3 days), or asymmetrically into the morning hours (4-6 days). Diapause was also induced in 40-70% of sensitive larvae that were reared under the gradually shortening light-phase (from 16 h to 2 h, by 1 h in each cycle), despite that the dark-phase remained constant and short (8 h). Larvae developed continuously, however, when reared under the gradually extending light-phase (from 16 h to 24 h) and a constantly short dark-phase. We interpret such results, with the help of the two-oscillator model of circadian rhythmicity (Pittendrigh, C.S., Daan, S., 1976. A functional analysis of circadian pacemakers in nocturnal rodents. V. Pacemaker structure: A clock for all seasons. Journal of Comparative Physiology A 106, 333-355), as indicating that two mutually coupled oscillators (evening and morning) differing in their entrainability may participate in measuring of the dark-phase duration. The levels of dopamine (DA) and serotonin (5-HT) in the larval CNS transiently increased (by up to 20%) after the dusk, while no apparent change was observed during the dawn. The dusk-related increase was observed also after the asymmetric extension of the dark-phase into evening, while the asymmetric extension into morning had no effect on the levels of the DA and 5-HT.


New insights into roles of tubulobulbar complexes in sperm release and turnover of blood-testis barrier.
Tubulobulbar complexes are actin-filament-related structures that form at intercellular junctions in the seminiferous epithelium of mammalian testis. The structures occur both at adhesion junctions between Sertoli cells and the maturing spermatids in apical regions of the epithelium, and at junction complexes between neighboring Sertoli cells near the base of the epithelium. Here, we review the general morphology and molecular composition of tubulobulbar complexes, and also include a description of tubulobulbar complex structure in the human seminiferous epithelium. Although tubulobulbar complexes are unique to the seminiferous epithelium, they have the molecular signature of clathrin-based endocytosis machinery present generally in cells. We review the evidence that tubulobulbar complexes internalize intact intercellular junctions and are significant components of the sperm-release mechanism and the process by which spermatocytes translocate from basal to adluminal compartments of the epithelium.


A basic study on quantitative evaluation of 3-dimensional foot contact with an inertial sensor for FES foot drop correction.
In these days, FES is used to control ankle dorsiflexion of hemiplegic gait. Since not only dorsiflexion but also 3-dimensional foot contact isimportant for gait stability in hemiplegic gait, evaluation and control system of 3-dimensional foot contact with FES is needed to correct foot movement. In this study, the timing of initial contact and the timing when foot movement became stationary in the sagittal plane were detected, and the inclination angles in the sagittal and the frontal planes at these timings were used for evaluation. Using the inclination angles, 10 m walking of a hemiplegic subject under the 4 different gait conditions were quantitatively evaluated. The gait conditions were without FES, stimulation to the tibialis anterior, stimulation to the common peroneal nerve, and stimulation to both the tibialis anterior and the common peroneal nerve. Result of evaluation with the inclination angles showed that stimulation to the tibialis anterior could control foot contact appropriately in the sagittal plane, and stimulation to the common peroneal nerve was better to control foot inclination angle in the frontal plane. Inclination angle at the beginning of the stance phase indicated that FES system which used in clinical site commonly is not appropriate to control 3-dimensional foot contact. It was shown that inclination angle at the beginning of the stance phase was useful to evaluate 3-dimensional foot movements for FES foot drop correction.


Misrepresentations of evolutionary psychology in sex and gender textbooks.
Evolutionary psychology has provoked controversy, especially when applied to human sex differences. We hypothesize that this is partly due to misunderstandings of evolutionary psychology that are perpetuated by undergraduate sex and gender textbooks. As an initial test of this hypothesis, we develop a catalog of eight types of errors and document their occurrence in 15 widely used sex and gender textbooks. Consistent with our hypothesis, of the 12 textbooks that discussed evolutionary psychology, all contained at least one error, and the median number of errors was five. The most common types of errors were "Straw Man," "Biological Determinism," and "Species Selection." We conclude by suggesting improvements to undergraduate sex and gender textbooks.


The expression of transforming growth factor-beta and interleukin-1beta mRNA and the response to 1,25(OH)2D3' 17 beta-estradiol, and testosterone is age dependent in primary cultures of mouse-derived osteoblasts in vitro.
The aim of the present study was to examine the hypothesis that primary cultures of osteoblasts obtained from bones of young animals respond to hormones better than cell cultures obtained from old animals. We studied in cultured osteoblastic cells the effects of 1,25(OH)2D3 and sex steroid hormones on several mouse osteoblastic phenotypic expressions including transforming growth factor-beta (TGF-beta) and interleukin-1beta (IL-1beta) mRNAs. Second passages of long bone-derived osteoblastic cells from young donors (5-12 wk) and old donors (10-12 mo old) were used for this study. The cells obtained from old animals had decreased ALP activity and cAMP compared with cells obtained from young animals with no change in collagen production and mineralization. The addition of 17beta-estradiol and testosterone increased ALP activity and mineralization in the cultured cells from both age groups and collagen production in cells obtained from old mice. Using in situ hybridization IL-1beta and TGF-beta mRNA expression was observed to be higher in the osteoblasts from young than from old donors. 1,25(OH)2D3 increased IL-1beta mRNA expression in the cells derived from young mice. Testosterone and 17beta-estradiol inhibited IL-1beta mRNA expression only in cells derived from young mice. Sex steroid hormones did not change TGF-beta mRNA expression in any of the cell lines, but 1,25(OH)2D3 increased its expression in cells derived from old donors. The results of the present study indicate that cells obtained from old mice are generally less active than those obtained from young animals.


A fe/male transsexual patient in psychoanalysis.
The author describes the analysis of a transsexual who had undergone a vaginoplasty as a young man and had since been living as a woman. The complexity of the psychic reality is epitomised by the analyst's difficulty in deciding whether to use masculine or feminine grammatical forms to refer to this patient. The author tells how she assumed the fantasy role of parents expecting a baby whose sex they did not yet know. She discusses at length her hesitation about accepting a transsexual patient into analysis and reports how she overcame her misgivings after analysing her own countertransference and consulting the literature. Noting that this borderline analysand resorted to both psychotic and neurotic mechanisms, the analyst decided to rely on the capacity for symbolisation and mental representation evinced in the latter. On the psychotic level, the delusional neo-reality of the appearance of a woman sought to replace the unbearable reality of being a man, whereas the neurotic part was aware that s/he could never really be a woman. The author observes that in this analysand sexualisation served to conceal a fundamental narcissistic fault. She also describes how she worked with her own madness to help the patient emerge from a situation of paradoxical fusion with the mother in madness.


The monocyte locomotion inhibitory factor produced by Entamoeba histolytica inhibits induced nitric oxide production in human leukocytes.
The monocyte locomotion inhibitory factor, an anti-inflammatory pentapeptide produced by Entamoeba histolytica, inhibits the in vitro production of nitric oxide induced by cytokines (INF-gamma, TNF-alpha) or PMA in human leukocytes. This can be added to the other previously reported functional effects of this factor, such as the inhibition of monocyte locomotion and the synthesis of reactive oxygen intermediates in both monocytes and neutrophils. The decreased nitric oxide production may interfere with the killing of amebas by neutrophils in the early invasive stages of amebiasis, when oxidative mechanisms are used [reactive oxygen and nitrogen intermediates either individually or synergistically via peroxynitrite (ONOO(-))], and in the advanced stages, when both non-oxidative and oxidative (including nitric oxide) mechanisms are employed by macrophages. Diminished nitric oxide production by leukocytes may also contribute to the paucity of late inflammatory components in amebic abscess of the liver and other amebic lesions.


The role of sirtuins in the regulation of metabolic homeostasis in skeletal muscle.
To discuss recent findings regarding the role of the histone deacetylase sirtuin SirT1 in anabolic and catabolic signaling pathways in skeletal muscle. Since its discovery as a regulator of peroxisome proliferator-activated receptor γ-coactivator 1α transcriptional activity, SirT1 has received much attention for its role in the regulation of tissue-specific and whole body regulation of metabolic processes. Although these early seminal discoveries identified SirT1 as a central player in metabolism, it is only more recently that we have begun to understand the complexities of SirT1 signaling. In addition to peroxisome proliferator-activated receptorgamma-coactivator 1α, SirT1 has been found to regulate the activity and/or transcription of protein kinase B, mammalian target of rapamycin, forkhead box O 1 and 3a and myogenic determination factor, all of which are central players in the regulation of energy status in skeletal muscle, via actions on catabolic and anabolic signaling. SirT1-mediated regulation of skeletal muscle metabolism (and indeed, whole body metabolism) likely occurs at numerous levels, from cell membrane receptors to transcription factors and histones. The end result of these regulatory actions of SirT1 is to maintain cellular homeostasis.


Alternative transcripts of presenilin-1 associated with frontotemporal dementia.
We have analyzed the expression of Alzheimer's disease-associated presenilin 1 (PS1) in various neurodegenerative disorders. Western blotting identified PS1 N- and C-terminal fragments similarly in the cortex of controls, Parkinson, Huntington and schizophrenia subjects. Additional PS1 immunoreactive species of 42 and 46 kDa were present in six out of seven cases of sporadic frontotemporal dementia (FTD) and these were particularly prominent in two cases. RT-PCR analysis using nested primers showed the presence of PS1 gene products with deletions within the exon 4-8 region. Our results suggest that alternative transcription of PS1 may be associated with FTD.


The "subjective" pupil old/new effect: is the truth plain to see?
Human memory is an imperfect process, prone to distortion and errors that range from minor disturbances to major errors that can have serious consequences on everyday life. In this study, we investigated false remembering of manipulatory verbs using an explicit recognition task and pupillometry. Our results replicated the "classical" pupil old/new effect as well as data in false remembering literature that show how items must be recognize as old in order for the pupil size to increase (e.g., "subjective" pupil old/new effect), even though these items do not necessarily have to be truly old. These findings support the strength-of-memory trace account that affirms that pupil dilation is related to experience rather than to the accuracy of recognition. Moreover, behavioral results showed higher rates of true and false recognitions for manipulatory verbs and a consequent larger pupil diameter, supporting the embodied view of language.


Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response.
Physical exercise induces cell proliferation in the adult hippocampus in rodents. Serotonin (5-HT) and angiotensin (Ang) II are important mediators of the pro-mitotic effect of physical activity. Here, we examine precursor cells in the adult brain of mice lacking angiotensin-converting enzyme (ACE) 2, and explore the effect of an acute running stimulus on neurogenesis. ACE2 metabolizes Ang II to Ang-(1-7) and is essential for the intestinal uptake of tryptophan (Trp), the 5-HT precursor. In ACE2-deficient mice, we observed a decrease in brain 5-HT levels and no increase in the number of BrdU-positive cells following exercise. Targeting the Ang II/AT1 axis by blocking the receptor, or experimentally increasing Trp/5-HT levels in the brain of ACE2-deficient mice, did not rescue the running-induced effect. Furthermore, mice lacking the Ang-(1-7) receptor, Mas, presented a normal neurogenic response to exercise. Our results identify ACE2 as a novel factor required for exercise-dependent modulation of adult neurogenesis and essential for 5-HT metabolism.


[Making Patient-focused Information Provision a Reality: One Company's Approach].
In recent years, as the market has seen the appearance of innovative medical products with novel mechanisms of action, adverse reactions that cannot be expected from the approved product label are being detected in the postmarketing phase. It is increasingly important to undertake timely product label updates and other drug safety measures through the monitoring, early detection, and reporting of adverse reactions. In 2013, the risk management plan (RMP) system was introduced in Japan. An RMP documents efforts to ensure the safety of a medical product, and sharing the RMP with stakeholders results in enhanced postmarketing safety measures. Healthcare providers have already started to utilize RMPs, but issues with perception and utilization remain. The industry, regulators, and academia are also working together to facilitate the use of RMPs. With the implementation of the RMP requirement, pharmaceutical companies are seeking to improve safety assurance by enhancing their drug safety functions, including the collection, assessment, and dissemination of drug safety information. Chugai Pharmaceutical is starting a completely new approach to patient-focused information provision, exemplified by the "PMS & SAFETY DB Tools," designed to give healthcare providers quick access to its extensive database of real-world drug safety information. This paper introduces Chugai Pharmaceutical's new efforts to manage adverse reactions and raises issues for future consideration.


CdSe/V2O5 core/shell quantum dots decorated reduced graphene oxide nanocomposite for high-performance electromagnetic interference shielding application.
The present work reports nanocomposite of CdSe/V2O5 core-shell quantum dots with reduced graphene oxide (rGO-V-CdSe), as an efficient lightweight electromagnetic wave shielding material, synthesized by a simplistic solvothermal approach. The as-synthesized nanocomposite was analyzed for its structural, compositional and morphological features by x-ray diffraction (XRD), transmission electron microscopy (TEM), Raman spectroscopy and x-ray photoelectron spectroscopy (XPS). The measurement of complex permittivity/permeability and total shielding efficiency of the as-synthesized samples has been done in a wide frequency range of 8-12 GHz (X-band). Compared to rGO and rGO-CdSe, rGO-V-CdSe nanocomposite exhibits significantly enhanced EMI shielding properties in terms of both dielectric loss and total shielding SE T . The high value of real permittivity (average ε'∼70) and the overall shielding effectiveness up to ∼38 dB have been recorded for rGO-V-CdSe nanocomposite. The studies also infer that the absorption contributes more in total shielding than reflection. The high value of dielectric loss and shielding effectiveness could also be attributed to the presence of various defects leading to dipolar and interfacial polarizations. The excellent EMI shielding properties of the nanocomposite in GHz frequency range (X-band) pave an intuitive way for fabricating a versatile EMI shielding nanocomposite material for applications.


Analysis on Forensic Expertise of 49 Medical Disputes in Prenatal Examination.
To analyze the cases of medical disputes involving prenatal examination from a point of view of forensic expertise, and to discuss the risk of medical disputes and the preventive measures. A retrospective analysis was conducted on 49 forensic expertise cases of medical disputes in prenatal examination which were identified in Academy of Forensic Science and Shanghai Di'an Forensic Science Limited Company from 2010 to 2017. In recent years, the number of medical disputes involving prenatal examination showed an increasing trend year by year. The common causes of medical disputes were: uninformed or insufficiently informed disclosure （20 cases）; the propaganda and application of three-dimensional, four-dimensional ultrasound were not standardized （14 cases）; ultrasound examination and serological screening process were not standardized （12 cases）; no antenatal counseling （2 cases）, etc. In order to minimize the occurrence of such medical disputes, hospitals or related associations should avoid the risk of prenatal examination through the standardization of management and operation.


Erectile dysfunction in men with obstructive sleep apnea: an early sign of nerve involvement.
Erectile dysfunction (ED) is common in men with obstructive sleep apnea (OSAS) but no completely convincing hypotheses about the underlying pathogenic mechanisms have been published in the literature. The aims of the present study were to assess the presence of ED in a group of OSAS patients without daytime respiratory failure and to determine whether this dysfunction was related to peripheral nerve involvement. Evaluation of the bulbocavernosus reflex (BCR) and the somato-sensory evoked potentials of pudendal nerve (PSEPs), the most widely established method of documenting pudendal neuropathies as being the cause of impotence, was performed in 25 patients. Data on BCR were compared with those of 25 healthy males volunteers matched for age. BCR was altered in 17 patients: in 6 it was elicited while in 11 it had a prolonged latency and reduced amplitude. Patients with altered BCR presented an higher AHI, an higher percentage of sleep time spent with SaO2 <90% (TST90) and a lower daytime PaO2. Six patient had clinically silent neurophysiological signs of mild polyneuropathy. The degree of OSAS and gas exchange alteration was more severe in patients with polyneuropathy than in those with isolated BCR alteration. ED is a common finding in OSAS patients and this alteration seems to be related to a nerve dysfunction. The development of nerve dysfunction is associated with a more severe degree of OSAS and nocturnal hypoxia.


Detection of pathogenic Streptococcus suis bacteria using magnetic glycoparticles.
Detection of the zoonotic bacterial pathogen Streptococcus suis was achieved using magnetic glycoparticles. The bacteria contain an adhesion protein for the carbohydrate sequence Galalpha1,4Gal. After incubation with various amounts of the pathogen, magnetic concentration and ATP detection, bacterial levels down to 10(5) cfu could be detected. Submicrometer particles were needed, since with the larger microparticles the method did not succeed.


Chromatid association in acrocentric chromosomes of abnormal sexual development (ASD) cases.
Concordant/discordant associations at chromatid level were compared and found significant (P less than 0.05) in females with primary amenorrhea. This probably suggested that the acrocentric association pattern in this group of ASD and infertility did not follow a random segregation in subsequent cell divisions and that the concordant acrocentric chromosomes have regularly established physical connections with one another, held together for several cell cycles. It could only be speculated that the association of acrocentric chromosome anomalies in some females with abnormal sex chromosomes are due to this reason. In the event that chromosome association has a bearing on chromosome aberrations, the non-random pattern of acrocentric association probably would increase the choice for translocation and non disjunction in the somatic cells in females with primary amenorrhea during ontogenesis.


Migrant health: the Apulian model.
Since the 1990s Puglia has been totally involved in the reception and assistance of refugees. The prevention of infectious diseases among migrants, especially those residing in communities, is an important concern for public health authorities, since infectious diseases eliminated in Europe may still be widespread in the migrants' countries of origin, and other diseases may have a higher incidence than in European countries. Thus immigrants may contribute to the burden and spread of infectious diseases. We describe the Apulian model of management and prevention of infectious disease among the population of Asylum Seeker Centres (CARA). It consists of a number of activities: surveillance of Poliovirus circulation, tuberculosis screening, seroprevalence studies of viral hepatitis and HIV, an immunization program for children, and syndromic surveillance. All the activities are organized and carried out by the Regional Observatory for Epidemiology among refugees hosted in the Bari Palese CARA. Surveillance of Poliovirus circulation has been carried out periodically since 2008 by assessing the presence of wild poliovirus or Sabin-like poliovirus in stool samples and seroprevalence studies. Data did not show circulation of poliovirus and indicated a good level of immunization against polio among refugees. Seroprevalence studies of viral hepatitis and HIV were carried out in 2008 and involved 529 refugees; 44 individuals (8.3%) were HBsAg positive, 24 (4.5%) were anti-HCV positive, 8 (1.5%) were HIV positive. Tuberculosis screening started in 2009 after a refugee's death due to tuberculosis and has been ongoing since then. The Mantoux tuberculin skin test is used and cutipositive migrants are examined by chest X-ray. Around 50% of migrants have been found to be cutipositive and 10% showed TB sequelae. Syndromic surveillance and an immunization program began in 2011 because of the significant increase in migration flow following civil unrest in North Africa; respiratory tract infection and diarrhoea were the most frequent notified syndromes. The immunization program involved 129 children coming from 23 countries: all received the appropriate vaccinations. The program also includes an annual special session to vaccinate all refugees against flu. The results confirmed some traditional concerns about migrant health and especially about the control of infectious diseases among these populations and the need, from our point of view, to strengthen screening to aid the development of trust between migrants and resident population.


Development of human liver UDP-glucuronosyltransferases.
The development of multiple UDPGT activities towards eight substrates has been studied in fetal term and adult post-mortem (less than 5 h after death) liver samples. Most fetal and term liver activities were less than 14% of adult values, except that towards 5-hydroxytryptamine which was present in fetal and term liver at adult levels. The majority of UDPGT activities develop to adult levels within 10-20 weeks postnatally, and even premature (30 weeks) which survive for up to 10 weeks will develop these enzyme activities. Immunoblot analysis of human liver microsomes and cDNA cloning of human UDPGT shows the existence of the family of isoenzymes in man, and it is important to determine the developmental pattern of individual drug glucuronidating enzymes in liver. Immunoblot analysis of developing liver shows the presence of two major UDPGT polypeptides in fetal liver, whereas more than five are observed in adult liver. The investigation of substrate specificity of individual UDPGTs by expression of cloned genes in COS-7 cells and the use of antibodies will facilitate the identification of enzymes present in perinatal liver.


Effect of growth factors on the activation of human Tenon's capsule fibroblasts.
To investigate stimulatory effects of PDGF-AA, PDGF-AB, PDGF-BB, bFGF, IL-1beta, TGF-beta1 and TGF-beta2 on the proliferation and myofibroblast transformation of cultured human Tenon's capsule fibroblasts and to characterize expression of PDGF- and TGF-beta-receptors in these cells. To determine cell proliferation, cell number of 2nd passage cultured human Tenon's capsule fibroblasts was measured before and after addition of growth factors using a computer-based cell counter system. Immunoblotting was used to detect and quantitate alpha-smooth-muscle actin (alpha-SMA) expression. Expression of PDGF- and TGF-beta-receptor mRNA was detected by RT-PCR, expression of the corresponding protein was demonstrated using Western blot. A significant increase in proliferation (p < or = 0.05) was detected after exogenous stimulation with PDGF-AA (10 ng/ml and 100 ng/ml), PDGF-AB (10 ng/ml and 100 ng/ml), PDGF-BB (10 ng/ml and 100 ng/ml), bFGF (100 ng/ml), IL-1beta (1 ng/ml and 10 ng/ml), TGF-beta1 (0.5 ng/ml) and TGF-beta2 (0.5 ng/ml). Both TGF-beta1 and TGF-beta2 stimulated expression of alpha-SMA in a dose dependent manner with peak activity at a concentration of 50 ng/ml (TGF-beta1) and 500 ng/ml (TGF-beta2). Protein and mRNA of PDGF-receptor type alpha and type beta and TGF-beta-receptors type I, II and III are expressed in cultured human Tenon's capsule fibroblasts. The present investigation strongly supports the hypothesis that PDGF-isoforms are major stimulators of proliferation of Tenon's capsule fibroblasts after glaucoma filtering surgery while TGF-beta-isoforms are essential for the transformation of Tenon's capsule fibroblasts into myofibroblasts.


Next-generation sequencing of PTEN mutations for monitoring minimal residual disease in T-cell acute lymphoblastic leukemia.
Minimal residual disease (MRD) analysis has become a powerful indicator to refine therapy in acute lymphoblastic leukemia (ALL). Here, we present an MRD detection based on the next-generation sequencing of PTEN exon 7 mutations (NGS-PTEN) in 30 pediatric T-cell ALL patients. By comparing the NGS-PTEN results with current quantitative PCR of antigen receptor gene rearrangements (qPCR-Ig/TR), an overall concordance of 80% was found between the two methods. However, the NGS-PTEN qualified a lower number of high-risk patients than qPCR-Ig/TR. These findings suggest that NGS-PTEN is a promising tool that could potentially be used to support current MRD methodologies for T-ALL patients.


Immunohistochemical expression of excision repair cross-complementing 1 (ERCC1) in non-small-cell lung cancer: implications for patient outcome.
INTRODUCTION The identification of novel prognostic markers may help to better assess survival probability in different subgroups of patients with non-small-cell lung cancer (NSCLC) and to tailor treatment according to the molecular profile of the tumour. AIM We sought to examine whether the immunohistochemical expression of excision repair cross-complementing 1 (ERCC1), an essential component of the nucleotide excision repair pathway, may predict prognosis in NSCLC. MATERIAL AND METHOD Formalin-fixed paraffin-embedded tumour samples from 44 Turkish patients with NSCLC treated by adjuvant platinum-based chemotherapy were included in the study. Immunohistochemical expression levels of ERCC1 were correlated with clinical outcomes by Kaplan-Meier curves and multivariable Cox proportional hazards regression analysis. RESULTS A total of 29 patients had ERCC1-negative tumours while 15 had ERCC1-positive tumours. The mean progression- free survival (PFS) was significantly lower in patients with ERCC1-positive tumours (13±2 months) than in those with ERCC1-negative tumours (27±5 months, p<0.05). Similarly, the mean overall survival (OS) was significantly lower in patients with ERCC1-positive tumours (20±3 months) than in those with ERCC1-negative tumours (33±5 months, p<0.05). After allowance for potential confounders, Cox regression analysis demonstrated that ERCC1 expression was significantly associated with both PFS and OS (both p<0.05). CONCLUSION This study provides support for the prognostic value of ERCC1 immunohistochemical expression in patients with NSCLC treated by adjuvant platinum-based chemotherapy. If independently confirmed, these findings may improve prognostic stratification in this group of patients.


Chemometrical classification of pumpkin seed oils using UV-Vis, NIR and FTIR spectra.
The main outcome of this work is elaboration of classification models for edible oil samples representing the most widespread brands of Austrian pumpkin seed oil. A complete spectral characterisation of the pumpkin seed oil samples by UV-Vis, NIR and FTIR spectra was obtained together with their basic sensorial classification. Chemometrical processing of the measured data enabled the detection of the most important spectral features, which are crucial for categorising the oils into two or three classes according to their sensory quality evaluated by a panel of experts. The elaborated models thus make it possible to predict the category into which a hitherto unclassified oil sample belongs--considering classification into either two categories, containing oils with overall acceptable scores or oils that were not accepted, or three categories, involving oils fulfilling all quality criteria, oils with good scores and not accepted oils. This will perspectively facilitate the determination of chemical substances responsible for bad taste, odour and colour of the respective oil brands, as well as finding substances contributing to the excellent sensorial perception of some tested products.


Distances between the antigen-binding sites of three murine antibody subclasses measured using neutron and X-ray scattering.
For three different murine immunoglobulins (IgG subclasses 1, 2a, and 2b), the distances between their antigen-binding sites have been measured using neutron scattering from deuterated antigens complexed with proteated IgG. Neutron-scattering data were measured for each antibody-antigen complex in a 41% D2O solvent. Unlike the proteated antibody molecule, the deuterated antigens are strongly contrasted against the 41% D2O solvent and give rise to a scattering profile that contains an interference term related to the distance between the deuterated antigens. For all three subclasses, the damping of this interference term, which gives information on the relative flexibility of the antigen-binding sites, indicates that a single distance is inadequate to describe the observed scattering and a distribution of distances is needed. The scattering profile has been modeled for each subclass to give the mean distance between the antigens and the variance of this distance. For all three IgG subclasses, the mean distance is between 117 and 134 A, and the variance is large (approximately 40 A), indicating a high degree of flexibility of the Fab arms. Small-angle X-ray scattering measurements on the same samples are consistent with the neutron-scattering results.


Hepatitis B virus DNA in blood specimens of anti HBc IgM positive patients.
This study compares the presence of hepatitis B virus (HBV) DNA and HBV e antigen in sera positive for IgM antibody to HBV core antigen. Of the 31 sera included in the study, 14 were HBV DNA positive. Eight sera were positive for HBV DNA but negative for HBeAg and 3 sera were negative for HBV DNA but positive for HBeAg. The HBV DNA positive specimens included also 3 HBsAg negative sera. The importance of the level of the anti HBc IgM antibody is discussed.


Brain changes following four weeks of unimanual motor training: Evidence from fMRI-guided diffusion MRI tractography.
We have reported reliable changes in behavior, brain structure, and function in 24 healthy right-handed adults who practiced a finger-thumb opposition sequence task with their left hand for 10 min daily, over 4 weeks. Here, we extend these findings by using diffusion MRI to investigate white-matter changes in the corticospinal tract, basal-ganglia, and connections of the dorsolateral prefrontal cortex. Twenty-three participant datasets were available with pre-training and post-training scans. Task performance improved in all participants (mean: 52.8%, SD: 20.0%; group P < 0.01 FWE) and widespread microstructural changes were detected across the motor system of the "trained" hemisphere. Specifically, region-of-interest-based analyses of diffusion MRI (n = 22) revealed significantly increased fractional anisotropy (FA) in the right caudate nucleus (4.9%; P < 0.05 FWE), and decreased mean diffusivity in the left nucleus accumbens (-1.3%; P < 0.05 FWE). Diffusion MRI tractography (n = 22), seeded by sensorimotor cortex fMRI activation, also revealed increased FA in the right corticospinal tract (mean 3.28%; P < 0.05 FWE) predominantly reflecting decreased radial diffusivity. These changes were consistent throughout the entire length of the tract. The left corticospinal tract did not show any changes. FA also increased in white matter connections between the right middle frontal gyrus and both right caudate nucleus (17/22 participants; P < 0.05 FWE) and right supplementary motor area (18/22 participants; P < 0.05 FWE). Equivalent changes in FA were not seen in the left (non-trained) hemisphere. In combination with our functional and structural findings, this study provides detailed, multifocal evidence for widespread neuroplastic changes in the human brain resulting from motor training. Hum Brain Mapp 38:4302-4312, 2017. © 2017 Wiley Periodicals, Inc.


Emergency medicine training in Canada.
Canada is the only country with two colleges governing emergency medicine (EM) certification. Does this serve us well or does it divide us and our resources? If most CCFP(EM) graduates practise strictly EM, with no family or rural practice, then reform in the certification process may be necessary. At the same time, FRCPC residencies seem excessively long and lack the numbers to develop "critical mass." Shortening the length of training would allow more residency positions to be created, thus advancing the goal of optimum emergency care for the Canadian public. Canadians deserve one standardized, certified, accredited EM training program that produces the highest quality emergency physicians.


[How do Sick People and Their Caregivers Live Non-Invasive Ventilation? Systematic Literature Review of Qualitative Research].
W know that non-invasive ventilation (NIV) is a basic ventilator support, but sometimes it fails, because of intolerance, lack of adherence, breach, etc. How can we anticipate that failure? We intend to explore the qualitative evidence on the experiences of people with this treatment and their formal and informal caregivers. Systematic literature review of original articles indexed from 2005 to 2015, which study the NIV in adult population with qualitative methodology in six databases. Peer review of scientific quality with tool of the CASPe Program. Qualitative metasynthesis of the findings. 15 articles met selection criteria, based on Grounded Theory and Phenomenology, which use interviews, observation and focus group, directed both patients, and families and health professionals. Its studies emphasize the feeling of anxiety and loss of control, although the NIV relieves them dyspnea (ambivalence). Search daily well-being through routines and active participation. Interaction dependence/autonomy, especially in decision-making, finding differences that make complex the process information and advance directives. Practical wisdom of nursing care 24 hours with patients id described basic, and difficulties being narrated: lack of time, overload of work, technocentrism, inexperience. The qualitative evidence of treatment with VNI is varied although scarce; different plots (acute situations, chronic, terminals) are explored, from different points of view. The integration of these findings in our practice will help us to increase adherence and become the treatment successful, but especially to improve the quality of life of ventilated patients and their families.


The use of health care services and psychotropic medication in a community sample of 9-year-old schoolchildren with ADHD.
To examine the prevalence of the use of health care services and psychotropic medication within a community sample (N = 283) of 9-year-old school children and, more specifically, to evaluate the use of prescribed stimulants. Data from the second follow-up phase of the "Study of Attention Deficit Maastricht" (SAM) were analysed. Assessments at age 9 included a structured psychiatric interview with parents, behaviour and family situation questionnaire, IQ estimate and global assessment scale. Use of health care services and medication was obtained by the DICA-R and from the Youth Health Care records. About 190 children of the selected sample had at least one child psychiatric diagnosis, 26 (14%) of them were clinically referred and 12 (6%) received stimulants. Of the children with ADHD (N = 45), 10/45 (22%) received stimulants. Conversely, 2 out of 12 children who were treated with stimulants did not meet full DSM-IV diagnostic criteria, but were subthreshold ADHD cases. The treatment status was highly dependent on being clinically referred. The major finding of our survey is a lack of referral to child mental health services, and associated underdiagnosis and undertreatment, particularly in children with ADHD. There is a critical need to translate and implement the diagnostic and treatment guidelines to clinical practice.


The new revolution in toxicology: the good, the bad, and the ugly.
In 2007, the United States National Academy of Sciences issued a report entitled Toxicity Testing in the 21(st) Century: A Vision and a Strategy. The report reviewed the state of the science and outlined a strategy for the future of toxicity testing. One of the more significant components of the vision established by the report was an emphasis on toxicity testing in human rather than animal systems. In the context of drug development, it is critical that the tools used to accomplish this strategy are maximally capable of evaluating human risk. Since 2007, many advances toward implementation of this vision have been achieved, particularly with regard to safety assessment of new chemical entities intended for pharmaceutical use.


Quality driven wireless video transmission for medical applications.
Wireless telemedicine is currently a reality, requiring also the transmission of medical video sequences over often unreliable links. The contrasting requirements of almost lossless compression and low available bandwidth have to be tackled in this case. On one side compression techniques need to be conservative, in order to avoid removing perceptively important information; on the other side error resilience and correction should be provided, with the constraint of a limited bandwidth. An approach based on quality driven, network aware, joint source and channel coding is described in this paper. The approach has been developed in the framework of the IST PHOENIX project (www.ist phoenix.org), focusing on wireless multimedia transmission over IP networks. After a description of the considered cross-layer approach and of the information to be exchanged among the system component blocks, the techniques considered for this information exchange and the concept of "JSCC/D controllers" are introduced. The implementation of the demonstrator realized is then described.


Ultrasonic surgical aspiration with endoscopic confirmation for osmidrosis.
Ultrasonic surgical aspiration of axillary apocrine glands with endoscopic confirmation was used for treating osmidrosis in 87 patients. Ultrasound energy liquefies fat and sweat glands via cavitation, but minimally affects blood vessels and nerves at the same energy level. We hypothesised that since the apocrine glands were located within the subcutaneous fat layer, ultrasound liposuction would be effective in its removal and also preserve vasculature of the axillary skin for optimal wound healing. The endoscope was used to visually confirm adequate removal of fat and sweat glands. Our method was effective in 84 patients (96.5%) and recurrence of odour occurred in three patients (3.5%). There were no cases of haematoma, seroma, or skin necrosis. Our method leaves a small inconspicuous scar, maintains normal axillary hair pattern and avoids contracture of the axillary skin after a short and comfortable recovery period.


[Membrane proteins and phospholipids as effectors of reverse cholesterol transport].
The review highlights the membrane aspect of cholesterol efflux from cell membranes to high density lipoproteins (HDL), an initial stage of reverse cholesterol transport to liver. Special attention is paid to ABC-A1 transporter and membrane SR-B1 receptor, their properties, putative mechanisms of action and their role in reverse cholesterol transport. Interaction of ABC-AI with plasma free apoA1 is suggested to facilitate the efflux of membrane phospholipids and formation of their complex with apoAI. Then this complex accepts the membrane cholesterol, with lipidation till the full HDL particle is formed. For a number of cells the correlation of cholesterol efflux into HDL with SR-BI expression was shown. The reversible binding of receptor SR-BI with HDL is supposed to influence molecular organization of membrane lipids, that promotes the efflux of cholesterol molecules out of the membrane.


From energy efficiency under stress to rapid development and a long life in natural populations.
Simplistically, high fitness depends upon high energy efficiency in the stressful habitats of organisms in the wild. Rapid development and high survival to adulthood should be followed by long-lived stress-resistant genotypes under this reductionist model. Empirical evidence is very limited because of the common use of benign laboratory environments, which remains a major difficulty in understanding relationships between life-history traits under more natural settings. Heterozygotes tend to show greater energy efficiency than do corresponding homozygotes especially in stressful environments, which leads the above connections among fitness traits. In particular rapid development and increased longevity should be correlated, and underwritten by the availability of metabolic energy. Empirical work is needed based upon severe stresses where a small environmental perturbation cases lethality; drought, heat and nutritional inadequacy are suitable candidate stresses. The importance of viewing fitness in energy terms is emphasized throughout. A byproduct is the potential to fuse functional and evolutionary biology under stressful environments.


Layer-by-layer buildup of poly(L-glutamic acid)/chitosan film for biologically active coating.
A new biocompatible film based on chitosan and poly(L-glutamic acid) (CS/PGA), created by alternate deposition of CS and PGA, was investigated. FT-IR spectroscopy, UV-vis spectroscopy and QCM were used to analyze the build-up process. The growth of CS and PGA deposition are both exponential to the deposition steps at first. After about 9 (CS/PGA) depositions, the exponential to linear transition takes place. QCM measurements combined with UV-vis spectra revealed the increase in the multilayer film growth at different pH (4.4, 5.0 and 5.5). The build-up of the multilayer stops after a few depositions at pH = 6.5. A muscle myoblast cell (C2C12) assay showed that (CS/PGA)(n) multilayer films obviously promote C2C12 attachment and growth.


Fluticasone propionate and budesonide do not influence bone metabolism in the long term treatment of asthma.
Inhaled corticosteroids (ICS) are recommended in the treatment of asthmatic patients. They have been said to be efficacious in the treatment of asthma in respect to cortisol and bone metabolism. The effects of the two inhaled corticosteroid, budesonide (BUD) and fluticasone propionate (FP) on bone metabolism, morning cortisol and their effects on the clinical parameters (FEV1, diurnal variation of peak expiratory flow rate = PEFR and log PC20) were examined in a group of 16 asthmatic patients. Eight patients used 800 micrograms/daily BUD and 8,400 micrograms/daily FP during 6 months period. Both BUD and FP improved clinical parameters as determined by FEV1 (p < 0.05) and PEFR (p < 0.01). There was no difference in respect to log PC20 values in either group (p > 0.05). Both treatments didn't change morning cortisol (p < 0.05). Both FP and BUD didn't change any indices of bone formation as determined by serum alkaline phosphatase, bone alkaline phosphatase, osteocalcin and carboxyterminal propeptide of type 1 procollagen and bone resorption as determined by urinary calcium and deoxypyridinoline (p > 0.05). In addition there was no significant effect on calcium and phosphate metabolism (serum calcium, phosphate and parathyroid hormone). As a result, having no adverse effect on bone metabolism and adrenal function, in the regard to clinical efficacy, FP is as effective as the double dose of BUD on PEFR and FEV1.


Abdominal wound dehiscence: a review of 60 cases at the University College Hospital, Ibadan.
A total of 212 cases of abdominal wound dehiscence requiring secondary closure occurred in 8632 surgical obstetric and gynaecological laparotomies over a 7-year period ending in December 1981. The incidence of abdominal wound dehiscence at Ibadan was 2.5%. Contaminated wounds were the most susceptible with an incidence of 19%. A detailed review of 60 cases revealed a mean age of 29 years. Wound infection was the most prominent contributory factor. Tension sutures appeared to be ineffective in preventing wound dehiscence. Following secondary closure, 53% of the patients developed further wound complications, mainly wound infection, incisional hernia and repeat dehiscence. The average duration of hospitalization was 35 days and 7% of the patients died post-operatively.


Experience with the chin tuck maneuver in postesophagectomy aspirators.
Aspiration is a common finding in the postesophagectomy barium swallow that often necessitates premature termination of the study prior to complete evaluation of the gastric conduit. More importantly, aspiration may play a significant role in the high incidence of postoperative pulmonary complications in this population. The chin tuck maneuver is a postural technique that reduces and often eliminates aspiration in swallowing-impaired patients. To evaluate the ability of the chin tuck maneuver to prevent aspiration during radiographic examination of the gastric conduit, the technique was used in 21 esophagectomy patients who aspirated during a swallowing evaluation combining the barium swallow and videofluoroscopy. Aspiration was eliminated in 81% of aspirators using the chin tuck maneuver. The results of this study demonstrate that the chin tuck maneuver is a simple technique that should be attempted in patients who aspirate postesophagectomy during radiographic imaging studies that require multiple swallows of contrast materials. Combining the barium swallow with the videofluoroscopic evaluation of swallowing provides objective documentation of both the structural integrity of the gastric conduit and swallowing function in patients after esophagectomies who are at high risk for postoperative morbidity.


Acute and chronic cadmium telluride quantum dots-exposed human bronchial epithelial cells: The effects of particle sizes on their cytotoxicity and carcinogenicity.
Quantum dots (QDs) are semiconducting nanocrystals with unique optical properties. When coated with shell/capping, QDs are not deleterious to cells and organisms. However, when QDs are retained in the cellular environment for a certain period of time, their coatings may be degraded, yielding "naked" QDs. Although some studies have documented the acute effects of cadmium telluride (CdTe) QDs in various cell lines, however, to our knowledge, there are no published studies on the chronic effects of CdTe QDs in normal lung cells. In this study, we therefore sought to study the effects of CdTe QDs of various particle sizes on their cytotoxicity and carcinogenicity in normal human bronchial epithelial cells (BEAS-2B). A total of three particle sizes of CdTe QD with emission maximum at 520, 580, and 730 nm were employed (abbreviated as 520Q, 580Q, and 730Q, respectively). Our results indicated that acute exposure to 520Q (∼2.04 nm in diameter) and 580Q (∼3.24 nm in diameter) elicited dose-dependent cytotoxicity; while acute exposure to 730Q (∼5.40 nm in diameter) elicited negligible cytotoxicity in BEAS-2B cells. Notably, chronic exposure to CdTe QD of all three tested particle sizes induced BEAS-2B cell transformation as evidenced by enhanced cell migration and anchorage-independent growth on soft agar. Taken together, our findings suggest that CdTe QDs are potent human lung carcinogens.


Pyrimidine nucleoside analogues as inducers of pyrimidine nucleoside catabolizing enzymes in Salmonella typhimurium.
Various structural analogues of cytosine and uracil nucleosides were tested as potential inducers of the nucleoside catabolizing (cyt) enzymes in Salmonella typhimurium. Some analogues, e.g. 5'-O-alkyl cytidines and uridines, resistant to catabolic enzymes, were as effective as the natural inducers cytidine and uridine; but etherification of one of the cis 2' or 3'hydroxyls fully abolished activity, pointing to a requirement of an intact ribose cis-glycol system for activity. A uridine analogue in the syn conformation, 6-methyluridine, a good substrate for uridine phosphorylase, was inactive as an inducer. The behavior of various other analogues, in relation to their structure, conformation and substrate properties, indicated the absence of any correlation between inducing activity and substrate susceptibility. The overall findings are consistent with conclusions derived from genetic experiments. The active analogues apparently act via similar pathways, and probably affect the same regulatory mechanism(s) as the natural inducers.


Views of UK melanoma patients on routine follow-up care.
Although the need for melanoma follow-up is universally accepted, there is still much debate on the duration and frequency of appointments. The UK guidelines were revised in June 2002 to streamline melanoma follow-up. Following the change in protocol, some of our patients expressed concern at the shorter duration of follow-up. We therefore polled all our active melanoma patients to obtain their views on the outpatient clinics. In particular we asked whether they would be happy to have routine follow-up in a primary care setting. In conjunction with the department of psychology, a short questionnaire was devised assessing patient satisfaction and concerns about follow-up. This was sent to all active melanoma patients in our trust. Out of 304 eligible patients currently attending outpatients, 231 (76%) completed replies were received. Ninety-eight percent of respondents found the clinics to be useful. Twenty two and a half percent felt it was difficult to attend the clinic and this was mainly due to logistical problems, i.e. hospital car parking. The majority were reassured by the clinic visits and felt it was a chance to ask questions and check for new disease. Of the 12% of respondents who had a recurrence, 52% indicated that they had detected it themselves. Sixty percent of patients would be happy to consider routine follow-up with their GP, provided they were suitably experienced and trained. A survey of 50 local GP's found that 70% would be unhappy to monitor their patients. Patients want and benefit from follow-up. However, they are an increasing burden on outpatient clinics, given the increasing incidence of melanoma. GP follow-up may be appropriate for a small subgroup of patients. This combined with shared care and practice based clinical nurse specialists may be the way forward in melanoma follow-up.


Removing selenite from groundwater with an in situ biobarrier: laboratory studies.
Laboratory biobarriers were evaluated for their ability to remove selenite from flowing groundwater. Microbial activity in aquifers is usually limited by substrate availability, and biobarriers stimulate microbial activity by providing a substrate; for these studies soybean oil was used. Water containing 10 mg L(-1) selenite-Se was pumped through the biobarriers for 74 days and the amount present in the effluent monitored. The amounts remained high for the first 2 weeks of the study but then declined. From day 28 until the end of the study the amount of selenite-Se in the column effluents averaged 0.20 +/- 0.04 mg L(-1), a decrease of approximately 98%. At the end of the study about half of the selenite-Se applied to the columns was recovered as immobilized selenium trapped by the biobarrier. This study suggests that biobarriers containing vegetable oil might be used as a process for removing selenite from contaminated groundwater.


Implant positioning (IMPO) in undisplaced femoral neck fractures: Association to reoperation and development of an IMPO scoring system.
This study aims to investigate whether implant positioning is associated to risk of reoperation following internal fixation of undisplaced femoral neck fractures (FNF) with a posterior tilt < 20° in patients > 65 years. Patients were retrieved from the Danish Multidisciplinary Hip Fracture Register in the period 2009-2013. The patients' health records and x-rays were reviewed for age, sex, implant, Charlson Comorbidity Index, mortality, reoperation, fracture classification and implant positioning. X-rays were measured for implant positioning using a pre-existing scoring system (the Schep score) as well as some additional measurements. Primary outcome was reoperation within 2 years. The study included 406 patients, 75% females and the median (range) age was 82 (65-99) years. Odds ratios (OR) are shown with 95% confidence interval. There were 45 (11%) reoperations. Six measurements were individually associated to risk of reoperation: 1) Distance to inferior calcar < 1 or ≥ 6 mm, OR 2 (1.1-4), 2) Distance to superior cortex 10 mm, OR 2(1.1-5), 3) Tip-head distance < 3 or ≥ 20 mm, OR 2 (1.1-4), 4) Placement in the superior or inferior 15 mm, OR 2 (1.1-5), 5) Placement in the anterior 25 %, OR 6 (1.8-20), 6) Inter-implant angle ≥ 5°, OR 3 (1.4-8). The Schep score had no associated to reoperation, and therefore a new implant positioning (IMPO) score was developed. The IMPO score consists of 6 items; 1 point given for each acceptable implant placement. An IMPO score less than 5 had an increased risk of reoperation; 0-2 points OR 22 (7-71) and OR 5 (2-11) for 3-4 points, compared to a score of 5-6. Among the 207 patients with a score of 5-6, the reoperation frequency was 4%. This study identified implant positioning as a predictor to an increased risk of reoperation in undisplaced FNF. The newly developed IMPO score seems promising for identifying risk of reoperation.


Corneal endothelial changes after laser in situ keratomileusis.
To ascertain whether 193 nm excimer laser in situ keratomileusis (LASIK) to correct high myopia causes in vivo changes in the human corneal endothelium 3 and 6 months after surgery. Alicante Institute of Ophthalmology, University of Alicante, Spain. Preoperative and serial postoperative specular microscopy of the central corneal endothelium was done in 33 eyes of 19 patients (Group 1) with a mean age of 34.3 years +/- 10.6 (SD) (range 20 to 60 years) who had LASIK to correct myopia of between 8.25 and 18.50 diopters (D) (mean 11.90 +/- 2.20 D). Twelve patients (20 eyes) were contact lens wearers (Group 2), and 7 (13 eyes) had never worn contact lenses (Group 3). The central endothelium was analyzed for several parameters including cell density, coefficient of variation in cell size, and hexagonality. The data obtained before surgery were compared with those obtained after surgery in all groups. There was no significant difference in age, sex, and preoperative myopia between Groups 2 and 3. In Group 1, mean cell density was significantly higher (3.5%) 6 months after surgery (P = .017) and the coefficient of variation decreased 3 and 6 months after surgery (P < .001); no significant changes were noted in the percentage of hexagonal cells. In Group 2, there was a significant increase in cell density (4.8%) 6 months after surgery (P = .010) and the coefficient of variation decreased at 3 and 6 months after surgery (P < .001); the hexagonality did not change postoperatively. In Group 3, there were no significant differences between preoperative and postoperative mean cell density, coefficient of variation, or hexagonality. Laser in situ keratomileusis caused no damage to the central corneal endothelium. Postoperative improvements in the endothelial cell density and the coefficient of variation in cell size values were related to the discontinuance of contact lens use after surgery.


3-Deoxyclocinnamox: the first high-affinity, nonpeptide mu-opioid antagonist lacking a phenolic hydroxyl group.
The C(3)-substituent in morphinan opioids is of critical importance; the 3-OH group is usually associated with very much higher affinity for mu-receptors than H or -OMe. However in this series of 14beta-cinnamoylamino derivatives the codeinones (e.g. methoclocinnamox, MC-CAM) had unexpectedly high mu-opioid receptor affinity, similar to that of the morphinone (clocinnamox, C-CAM). The current report relates to the synthesis and in vitro evaluation of deoxyclocinnamox (DOC-CAM) which acted as a high-affinity opioid antagonist similar to C-CAM but with greater mu selectivity. Thus it appears that the C(3)-substituent does not play a major role in the binding of the 14beta-cinnamoyl series and that the cinnamoyl group itself may in fact be the dominant binding feature.


Fetal growth sustained by parenteral nutrition in pregnancy.
Severe maternal nutritional deprivation has been associated with intrauterine growth retardation, premature labor, and increased perinatal mortality and morbidity. The authors present four cases in which total parenteral nutrition was used successfully to support fetal growth in such diverse complications as twin pregnancy with maternal jejunoileal bypass, regional enteritis, and acute pancreatitis. Maintenance of fetal growth as evidenced by serial sonographic examination allows achievement of fetal lung maturation before delivery. In all the cases presented there was no perinatal mortality or morbidity. The main clinical implication of the report is the possible application of total parenteral nutrition to maintain adequate growth in fetuses small for gestational age because of maternal nutritional deprivation.


Volvulus of the sigmoid colon in paediatric patients: report of two cases.
Two cases of volvulus of the sigmoid colon in paediatric patients are presented. The condition is rare in childhood. The diagnosis was established at laparotomy in the first case while the second case was diagnosed because of heightened awareness. The clinical features of the disease are essentially as in adults.


Increasing the number of biopsies increases the concordance of Gleason scores of needle biopsies and prostatectomy specimens.
To determine the importance of increasing the number of biopsy cores to decrease the discrepancy of Gleason scores of needle biopsy and radical prostatectomy specimens. Between May 1998 and July 2005, 392 patients with clinically localized prostate cancer diagnosed by 18-gauge transrectal needle biopsy underwent radical prostatectomy. We categorized the cohort into 2 groups according to the number of the cores. Group 1 consisted of 206 patients diagnosed by extended biopsies (> or =10 cores, range 10-14, median 11). The remaining 186 patients who were diagnosed by sextant biopsies were categorized as being in group 2. Preoperative clinical variables, including patient age, digital rectal examination findings, serum prostate-specific antigen, and the number of cores positive for cancer the parameters, were assessed in both groups. The concordance of Gleason scores in both groups were analyzed by both individual Gleason scores and clinical subgroups of Gleason scores: 2-4 (well differentiated), 5-6 (moderately differentiated), 7 (intermediate), and 8-10 (poorly differentiated). Needle biopsies revealed moderately differentiated tumors (Gleason 5-6) for the 2 groups (55.3% and 60.2%). Gleason scores of the needle biopsies were identical to that of the prostatectomy specimen in 116 (56.31%) and 76 cases (40.86%) for each group (kappa: 0.432 and 0.216 for each group, respectively). Gleason score of the needle biopsy differed by 1 grade in 56 (27.18%) and 84 cases (45.16%), and by > or =2 units in 34 (16.50%) and 26 cases (15.05%) for each group, respectively. Of the specimens, 34% were undergraded, and 10% were overgraded in group 1. These rates were 38% and 22% in group 2, respectively. A total of 70% in group 1 and 56% in group 2 remained in the same categorical group, 28% and 32% of the specimens were undergraded, and 4% and 12% were overgraded in groups 1 and 2, respectively. In group 1, the number of patients with Gleason scores of 2-4, 5-6, 7, and 8 were 9.7%, 55.3%, 21.4%, 13.6%, and 1.9%, 47.6%, 32%, 18.4%, graded by needle biopsies and radical prostatectomy specimens, respectively. However, in the sextant group, the change was the number of patients with Gleason scores of 2-4, 5-6, 7, and 8-10 was 5.4% 60.2%, 24.7%, and 9.7%, detected by needle biopsies, respectively. Radical prostatectomy specimens revealed the same Gleason categories in 4.3%, 41.9%, 38.7%, and 15.1%, respectively. There was no correlation between categorized prostate-specific antigen levels and concordance of the Gleason grade. Age and digital rectal examination results did not affect Gleason correlation. We have shown that an extended biopsy scheme beyond its superior diagnostic capability also improves the concordance of Gleason scores of needle biopsies and radical prostatectomy specimens.


An updated genetic map of Peromyscus with chromosomal assignment of linkage groups.
Species across the rodent genus Peromyscus have become prominent models for studying diverse mechanistic and evolutionary processes, including chromosome evolution, infectious disease transmission and human health, ecological adaptation, coat color variation, and parental care. Supporting such diverse research programs has been the development of genetic and genomic resources for species within this genus, including genome data, interspecific chromosome homologies, and a recently developed genetic map. Based on interspecific hybrids between the deer mouse (Peromyscus maniculatus bairdii) and the old-field, or beach, mouse (Peromyscus polionotus) and backcross progeny to Peromyscus maniculatus, a linkage map was developed based on 190 genes and 141 microsatellite loci. However, resolution of several linkage groups with respect to chromosome assignment was lacking and four chromosomes (8, 16, 20, and 21) were not clearly delineated with linkage data alone. The recent development of a high-density map for Peromyscus proved ineffective in resolving chromosome linkage for these four chromosomes. Herein we present an updated linkage map for Peromyscus maniculatus, including linkage group-chromosome assignments, using fluorescence in situ hybridization mapping of BACs and whole chromosome paints. We resolve the previously conflicting chromosome assignment of linkage groups to Chromosomes 8, 16, 20, and 21, and confirm the assignment of linkage groups to Chromosomes 18 and 22. This updated linkage map with validated chromosome assignment provides a solid foundation for chromosome nomenclature for this species.


Laparoscopic parastomal hernia repair using a nonslit mesh technique.
The management of parastomal hernia is associated with high morbidity and recurrence rates (20-70%). This study investigated a novel laparoscopic approach and evaluated its outcomes. A consecutive multi-institutional series of patients undergoing parastomal hernia repair between 2001 and 2005 were analyzed retrospectively. Laparoscopy was used with modification of the open Sugarbaker technique. A nonslit expanded polytetrafluoroethylene (ePTFE) mesh was placed to provide 5-cm overlay coverage of the stoma and defect. Transfascial sutures secured the mesh, allowing the stoma to exit from the lateral edge. Five advanced laparoscopic surgeons performed all the procedures. The primary outcome measure was hernia recurrence. A total of 25 patients with a mean age of 60 years and a body mass index of 29 kg/m2 underwent surgery. Six of these patients had undergone previous mesh stoma revisions. The mean size of the hernia defect was 64 cm2, and the mean size of the mesh was 365 cm2. There were no conversions to open surgery. The overall postoperative morbidity was 23%, and the mean hospital length of stay was 3.3 days. One patient died of pulmonary complications; one patient had a trocar-site infection; and one patient had a mesh infection requiring mesh removal. During a median follow-up period of 19 months (range, 2-38 months), 4% (1/25) of the patients experienced recurrence. On the basis of this large case series, the laparoscopic nonslit mesh technique for the repair of parastomal hernias seems to be a promising approach for the reduction of hernia recurrence in experienced hands.


Induction of fertile oestrus in cats by administration of hCG and calcium-naloxone.
The aim of this study was to evaluate the possibility of inducing fertile oestrus in queens by administering hCG in combination with Ca(2+)-naloxone. It is well established that an increase in endogenous opioids leads to a decrease in LH. The administration of naloxone, an opioid antagonist, inhibits endogenous opioidergic tone and induces the onset of pro-oestrus. The opioidergic block is related to the increase in binding of beta-endorphins to specific receptors, which determines calcium channel blockage. Pretreatment with hCG results in a rapid increase in the number of LH receptors and Ca(2+)-naloxone induces G protein activity. Twenty-one anoestrous queens were divided into four groups: (i) group 1, nine queens were treated with a single s.c. injection of hCG (1000 iu) and daily for 4 days with 0.1 ml kg-1 body weight i.m. of a solution containing 0.4 mg naloxone ml-1 dissolved in 20% calcium gluconate; (ii) group 2, four animals were treated with a single s.c. injection of hCG (1000 iu); (iii) group 3, four queens were treated with Ca(2+)-naloxone (0.1 ml body weight kg-1 i.m.) daily for 4 days; and (iv) group 4, four queens received no treatment (controls). Queens were monitored using vaginal cytology and blood progesterone concentrations, and pregnancy was detected using ultrasonography. In groups 2, 3 and 4 clinical signs of oestrus were not observed. In group 1, 88.8% of treated queens were mated (8 of 9) and ovulated on the basis of an increase in progesterone, and 75% (6 of 8) of these queens became pregnant. In conclusion, pretreatment with hCG increased the number of LH receptors and Ca(2+)-naloxone antagonized the hypothalamic GnRH opioid block thus inducing the pulsatility of LH leading to fertile oestrus in queens.


Development of the endothelium.
Our understanding of the regulation of vascular development has exploded over the past decade. Prior to this time, our knowledge of vascular development was primarily based on classic descriptive studies. The identification of stem cells, lineage markers, specific growth factors and their receptors, and signalling pathways has facilitated a rapid expansion in information regarding details of the mechanisms that govern development of the vascular system.


[How to reduce the incidence of traumatic phlebitis].
The authors carried out an analytic study on 2572 patients to reduce the occurrence of phlebitis having a traumatic cause. The authors conclude that the use of extensions after three way valves, or infusion systems and a venous catheter, considerably reduces the risk of traumatic phlebitis occurring. Furthermore, their use reduces 1. the bother patients incur, 2. the amount of work nursing professionals have derived by the appearance of traumatic phlebitis and 3. the cost of health care.


A low-temperature-responsive translation elongation factor 1 alpha from barley (Hordeum vulgare L.).
A cDNA clone (pBLT63) encoding a protein synthesis elongation factor 1 alpha (EF-1 alpha) was isolated from a low-temperature winter barley shoot meristem library by differential screening. The nucleotide sequence of the coding region of the low-temperature-induced barley gene shows very high homology with two EF-1 alpha plant genes from tomato and Arabidopsis. The barley genome contains an EF-1 alpha gene family situated on the short arm of chromosome 2 and the long arm of chromosome 5.


[Effect of pelvic inflammatory disease grades on in vitro fertilization-embryo transfer outcome].
To evaluate the effect of different grades of pelvic inflammatory disease (PID) and of salpingectomy on outcomes of in vitro fertilization-embryo transfer (IVF-ET). Two hundred and twenty three cycles of IVF-ET were divided into three groups, including mild group, moderate group and severe group, according to different grades of sequelae of PID finding in exploratory operations before IVF. Patients in each group were divided into two subgroups according to receiving salpingectomy or not. The data of total dose of gonadotrophin (Gn), oocyte number, low response rate, fertilization rate, good embryo number and pregnancy rate were analysed between three groups and the two subgroups of each group, respectively. All parameters were related to PID grades except fertilization rate. The total dose of Gn, oocyte number, good embryo number, low response rate and pregnancy rate were (2057 +/- 503) IU/L, (16 +/- 6), (6.0 +/- 4.3), 4.2%, 63.9% in mild group; (2204 +/- 603) IU/L, (12 +/- 6), (4.5 +/- 3.5), 13.9%, 46.8% in moderate group; and (2372 +/- 1018) IU/L, (9 +/- 6), (3.1 +/- 2.9), 33.8%, 41.2% in severe group. The total dose of Gn and low response rate increased with the aggravation of the grades of PID (P < 0.05). The oocyte number, good embryo number and pregnancy rate also had significant differences between three groups (P < 0.01, P < 0.01, P < 0.05, respectively). In mild and severe groups, the salpingectomy had no contribution to the outcome of IVF-ET treatment. In moderate group, patients receiving salpingectomy had more oocytes and good embryos and higher pregnancy rate than the others who retained oviducts (P < 0.05). Grades of PID have an adverse effect on IVF-ET outcomes. Receiving salpingectomy or not should be based on different grades of PID, but operations of ovary-free should be performed in all patients.


Why Do Migratory Birds Sing on Their Tropical Wintering Grounds?
Many long-distance migratory birds sing extensively on their tropical African wintering grounds, but the function of this costly behavior remains unknown. In this study, we carry out a first empirical test of three competing hypotheses, combining a field study of great reed warblers (Acrocephalus arundinaceus) wintering in Africa with a comparative analysis across Palearctic-African migratory songbird species. We asked whether winter song (i) functions to defend nonbreeding territories, (ii) functions as practice to improve complex songs for subsequent breeding, or (iii) is a nonadaptive consequence of elevated testosterone carryover. We found support for neither the long-assumed territory-defense hypothesis (great reed warblers had widely overlapping home ranges and showed no conspecific aggression) nor the testosterone-carryover hypothesis (winter singing in great reed warblers was unrelated to plasma testosterone concentration). Instead, we found strongest support for the song-improvement hypothesis, since great reed warblers sang a mate attraction song type rather than a territorial song type in Africa, and species that sing most intensely in Africa were those in which sexual selection acts most strongly on song characteristics; they had more complex songs and were more likely to be sexually monochromatic. This study underlines how sexual selection can have far-reaching effects on animal ecology throughout the annual cycle.


Microwave induced synthesis of novel 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor agents.
A series of new racemic 4-amino-6-aryl-8-(1,3-benzodioxol-5-yl)-8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines 4a-f and 4-amino-8-aryl-6-(1,3-benzodioxol-5-yl)-8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines 5a-f were obtained regioselectively from the reaction of 4,5,6-triaminopyrimidine 1 with 1equiv of methylenedioxychalcones 2a-f and 3a-f, under microwave irradiation. Detailed NMR measurements confirm the high regioselectivity of this reaction. These compounds have been evaluated in the US National Cancer Institute (NCI) for their ability to inhibit approximately 60 different human tumor cell lines, where 4e, 5a and 5b presented remarkable activity against 47, 11 and 37 cancer cell lines, respectively, with the most important GI50 values ranging from 0.068 to 0.35 microM, in vitro assay.


Short stature, microcephaly, characteristic face, syndactyly and mental retardation: the Filippi syndrome. Report on a second family.
Report on a second family. The patients, an 18-year-old boy and his 15-year-old sister, have pre and postnatal short stature, microcephaly, moderate to severe mental retardation, and cutaneous syndactylies of hands and feet. In addition, they show a mildly dysmorphic but apparently characteristic face. Radiologically, hands and feet demonstrate brachydactyly, metacarpals and metatarsals being the most severely affected. This observation confirms that this multiple congenital anomalies/mental retardation pattern is a distinct, probably autosomal recessively inherited entity.


Lateralization of headache: possible role of an upper cervical trigger point.
An ipsilateral upper neck trigger point was found in 21 of 24 patients with unilateral headache. During the prodromic period this trigger point was detected as a tender protrusion on neck palpation. In 18 out of 24 patients it was also found during the headache-free period. On standard roentgenogram, this protrusion seemed to be a laterally developed C2 spinous process. The EMG study showed latent trapezius hypertonicity on the side of the headache, even during the headache-free period. The association of the painful protrusion and trapezius hypertonicity could create an autoreinforcing nociceptive loop, which in turn could be the cause of lateralization of the pain.


Some factors influencing the proportion of periplasmic hepatitis B virus pre-S2 antigen in the recombinant yeast Hansenula polymorpha.
A central composite design (CCD) was used to evaluate, for the purpose of future process optimization, the influence of pH, yeast extract and ammonium chloride concentrations on the proportion of periplasmic hepatitis B pre-S2 antigen in the recombinant yeast Hansenula polymorpha. Each factor was tested at five levels, and a second order polynomial model for the proportion of periplasmic antigen was fitted to the treatment combinations. pH showed the greatest effect: the proportion of periplasmic antigen was greatly increased at the higher pH levels. At the higher pH levels used, the proportion of periplasmic antigen was enhanced by a high concentration of ammonium chloride. Additional experiments have confirmed both the validity of the selected model and the optimal conditions found. A significant correlation was found between the proportion of periplasmic antigen and the total yield of antigen. These results indicated that it should be possible to modulate the distribution of the pre-S2 antigen between the periplasm and the cytoplasm of the yeast.