The relationships between heart rate deceleration capacity and spectral indices of heart rate variability during different breathing frequencies.
The frequency of breathing influences the spectral powers of heart rate variability (HRV) as well as the magnitudes of heart rate deceleration capacity (DC) and acceleration capacity (AC). We compared the strength of their relationships under different breathing frequencies. We studied 14 healthy young adults who breathed spontaneously and controlled their breathing rates to 0.1, 0.2, 0.3 and 0.4 Hz in a supine position. A 5-min R-R interval time series without movement artefacts or ectopic beats was obtained for each study period. Spectral indices were defined as the square roots of spectral powers in the very low frequency (0.01-0.04 Hz), low frequency (0.04-0.15 Hz), high frequency (0.15-0.4 Hz) and respiratory frequency bands. We also combined these frequency bands into LHF (0.04-0.4 Hz) and VLHF (0.01-0.4 Hz). DC and AC were obtained using phase rectified signal averaging. DC and AC were significantly correlated with all indices of HRV. The within-subject correlation coefficients for the LHF index had the greatest absolute values (0.953 and -0.919, respectively). DC and AC had different strength of relationships with the LHF index, but became comparable (0.954 vs. -0.943) when the data obtained under 0.1-Hz breathing were excluded. DC is strongly correlated with the spectral index of the LHF band, indicating that they are controlled by similar influences under the conditions used in this study. AC is less related to the LHF index due to the fact that its magnitude deceases during 0.1-Hz breathing.


Finite element modeling and simulations in orthopedics: a bibliography 1998-2005.
The paper gives a bibliographical review of the finite element modeling and simulations in orthopedics from the theoretical as well as practical points of view. The bibliography lists references to papers, conference proceedings and theses/dissertations that were published between 1998 and 2005. At the end of this paper 1264 references are given dealing with subjects as: bones and their parts, special tissues; spine mechanics; movable joints and computational modeling.


The socioeconomic gradient in all-cause mortality for women with breast cancer: findings from the 1998 to 2006 National Cancer Data Base with follow-up through 2011.
To analyze the association between socioeconomic status (SES) and all-cause mortality among women diagnosed with breast cancer before and after controlling for insurance status, race and ethnicity, stage, treatment modalities, and other demographic and hospital characteristics. Data analyzed included follow-up through 2011 for 582,396 patients diagnosed between 1998 and 2006 with ductal carcinoma in situ or invasive (stage I-IV) breast cancer from the National Cancer Data Base. SES was measured by grouping patients into six income and education-level ZIP code categories. Hierarchical Cox regression models were used to analyze SES survival differences. Five- and 10-year survival probabilities for the highest SES group were 87.8% and 71.5%, versus 79.5% and 61.5% for the lowest SES group. Controlling for all covariates reduced the highest-to-lowest SES hazard ratio from 1.69 (95% confidence interval: 1.64-1.74) to 1.27 (95% confidence interval: 1.24-1.31). Results were virtually identical in models that included comorbidity and invasive cancer patients only. Differences in insurance status, race, and stage at diagnosis are important components of SES disparities and explain about two-thirds of the initial SES survival disparity. The residual SES effect likely mirrors underlying social determinants of health for all American women.


Micro-Raman spectroscopy as a routine tool for garnet analysis.
A rapid system to obtain molar compositions of minerals belonging to the garnet group by means of Raman spectroscopy is illustrated here. A series of standard garnets, whose composition was determined by means of Wavelength Dispersive System (WDS) electron microprobe measurements, was used to correlate the wavenumbers of the different Raman peaks with chemical composition. A simple software routine was then developed in order to obtain garnet molar composition starting from the Raman spectrum, based on the assumption that in a solid solution belonging to the garnet family the Raman wavenumbers are linear combinations of end member wavenumbers, weighted by their molar fraction. The choice of the Raman bands used for the calculations and their behaviour are also discussed. The method, called MIRAGEM (Micro-Raman Garnets Evaluation Method), was then tested on a second series of garnets with satisfactory results.


Permissive effect of insulin on the adenosine 3',5'-monophosphate-dependent up-regulation of low density lipoprotein receptors and the stimulation of steroid release in bovine adrenal cortical cells.
Bovine adrenal cortical cells growth on extracellular matrix-coated dishes in the presence of F-12 medium supplemented with high density lipoprotein (30 micrograms protein/ml), insulin (50 ng/ml), transferrin (1 microgram/ml), and fibroblast growth factor (100 ng/ml) expressed high affinity low density lipoprotein (LDL) receptors (Kd = 2.0 X 10(-8) M) present at a density of 3 X 10(4) receptors/cell. The density of LDL receptors per cell could be increased 3-fold (9 X 10(4) receptors/cell) by incubating the cells for 24 h with cholera toxin (CT; 10 ng/ml), but not with insulin (100 ng/ml). This correlated with increased LDL internalization (10-fold) and degradation (5-fold). 11-Deoxycortisol (11 DOC) release was increased by 2.7-fold. The addition of insulin (100 ng/ml) together with CT (10 ng/ml) markedly potentiated the effects of CT on LDL binding, internalization, and degradation as well as on steroid release. Preincubation (24 h) of the cells with insulin (100 ng/ml) together with CT resulted in a 12.7-fold increase in high affinity LDL receptor density (3.6 X 10(5) receptors/cell), while LDL internalization and degradation were increased by 45- and 22-fold, respectively. This correlated with a 9.6-fold increase in the 11 DOC released into the medium. The effects of insulin on the induction of high affinity LDL receptors as well as increased internalization and degradation of [125I]LDL were both time and concentration dependent in cultures exposed to CT. Secretion of 11 DOC paralleled in a time-dependent manner the amount of internalized [125I]LDL. Exposure of the cells to chloroquine (100 microM) resulted in a 95% inhibition of [125I]LDL degradation correlating with an 80% decrease in 11 DOC released in cells preexposed to CT and insulin. The results of these studies suggest that in bovine adrenal cortex cells grown in chemically defined medium, insulin modulates steroidogenic cAMP-induced response by increasing both the LDL receptor pathway activity and 11 DOC release.


Antibodies to islet 37k antigen, but not to glutamate decarboxylase, discriminate rapid progression to IDDM in endocrine autoimmunity.
Apart from islet cell antibodies (ICAs), antibodies to glutamate decarboxylase (GAD), insulin autoantibodies (IAAs), and a novel islet antigen (37k antigen) are potential markers for insulin-dependent diabetes mellitus (IDDM). GAD is also an antigen in stiff-man syndrome (SMS), and both SMS and IDDM are associated with ICAs and autoimmunity to other endocrine organs. We investigated possible links between antibody responses to islet antigens with autoimmunity to other endocrine organs and determined which specific antibodies can identify individuals who progress to IDDM. Antibodies to GAD were detected in > or = 90% of both diabetic and nondiabetic patients with ICAs and other endocrine autoimmunity, in 59% of ICA-positive IDDM patients without endocrine autoimmunity, in all patients with SMS, but in only 1-3% of healthy (nondiabetic) and autoimmune disease control subjects. GAD antibody levels were increased in ICA-positive IDDM patients with polyendocrine autoimmunity compared with those without. In contrast, antibodies to 37k antigen were only detected in patients who developed acute-onset IDDM. IAAs were also associated with IDDM. Thus, certain factors enhance antibody responses to GAD in polyendocrine autoimmunity, but this does not necessarily lead to development of IDDM or SMS. Antibodies to 37k antigen are strongly associated with acute-onset IDDM and are useful serological markers for disease.


Functional and phenotypical alterations of polymorphonuclear cells in Sézary syndrome patients.
Sézary syndrome (SS), the leukemic variant of cutaneous T-cell lymphoma (CTCL), has a poor prognosis and infections represent the most frequent cause of death. Polymorphonucleate granulocytes (PMNs) constitute an essential part of the innate immune system: their phagocytic and killing activity against pathogens is mediated by the interactions between Toll-like receptors (TLRs) and the Pathogen-associated molecular patterns (PAMPs). The aim of this study was to investigate PMN functional activity and phenotype in SS patients and their correlation with the onset of infectious complications. This prospective study enrolled 18 consecutive SS patients; PMN functional activity was evaluated by phagocytosis and intracellular killing tests towards Klebsiella pneumoniae. Flow-cytometry was applied to analyze PMN phenotype. PMNs from SS patients displayed a reduced phagocytic activity and intracellular killing against K. pneumoniae at 30 min and 60 min, more pronounced in SS patients with recurrent infections. CD11b and CD66b median fluorescence intensity (MFI) was significantly higher in SS than in healthy subjects, whereas CD62L MFI was decreased. No significant differences in TLR2, 4, 8 and 9 percentage expression or MFI were found. An increased TLR5 percentage expression was documented. The impairment in PMN functional activities in SS could favour the immune-suppression and raise infection risk.


Impaired function of bipolar cells in the Royal College of Surgeons rat.
The retina of the Royal College of Surgeons (RCS) strain of rat, which is being used as an animal model for human retinal degenerations, has been employed in the study of the function of second order neurons. By about the 33rd postnatal day the dendritic branching of isolated bipolar cells is more sparse than in bipolar cells of the normal rat retina, but their GABA channels are as in the normal rat retina. The normally occurring light-induced distal potassium increase has been used as the indicator of the functional competence of second order neurons in the isolated RCS rat retina. These are dependent upon the integrity of ionotropic and metabotropic synapses. At about the 22nd postnatal day MgCl2 enlarges the light-induced distal potassium increase in the young RCS rat retina as in the normal rat retina. It seems that MgCl2 does not block the metabotropic synapses of on-bipolar cells. At about postnatal day 33, at which time the photoreceptors of the RCS rat retina had become severely damaged, the size of this light-induced distal potassium increase was not changed, but it was abolished by MgCl2. This indicates that bipolar cells are still active but that the synaptic function of on-bipolar cells has become vulnerable to MgCl2. The conclusion is that at a time when photoreceptor degeneration is already severe bipolar cells are still active, but that on-bipolars, mainly rod bipolar cells, have some functional deficit.


Impaired counterregulatory hormonal and metabolic response to exhaustive exercise in obese subjects.
A reduction of postprandial thermogenesis has been described in obesity; insulin resistance and/or decreased sympathetic nervous system activity seem to play the major role in its pathogenesis. On the other hand, a normal energy expenditure during exercise has been reported. At present, the response and the role of catecholamines in energy metabolism during exercise in obesity have not been well clarified yet. The aim of this work was to study the metabolic and hormonal changes caused by intense exercise in obesity. Nine obese subjects and ten normal weight controls were submitted to exhaustive exercise on a cycloergometer. Blood glucose, free fatty acids (FFA), glycerol, lactate, beta-OH-butyrate, insulin, glucagon, plasma growth hormone (HGH), catecholamine plasma levels were assayed before and at the end of exercise, and after a recovery period. The energy cost of exercise was evaluated by indirect calorimetry. In our experiment muscular exercise did not provoke any change in blood glucose and FFA plasma levels in either of our groups. In the obese subjects the insulin plasma levels were higher than in the controls. Glucagon plasma levels did not change. The exercise responses of norepinephrine (NE) (4.28 +/- 0.74 vs 8.81 +/- 1.35 nmol/l; P < 0.01), epinephrine (E) (234.21 +/- 64.18 vs 560.51 +/- 83.38 pmol/l; P < 0.01) and plasma growth hormone (HGH) (134.84 +/- 58.97 vs 825.92 +/- 195.25 pmol/l; P < 0.01) were significantly lower in obese subjects. At the end of exercise, the thermic effect of exercise did not differ between obese and control subjects (0.335 +/- 0.038 vs 0.425 +/- 0.040 kJ/min x kg fat-free mass. Our findings indicate that an impaired counterregulatory hormone response to exercise exists in obese subjects. The thermic effect of exercise does not seem to be affected by either the reduced catecholamine response nor insulin resistance.


Efficiency of liming in controlling the mobility of lead in shooting range soils as assessed by different experimental approaches.
Shooting range soils contaminated by lead (Pb) are a great environmental risk. Reducing mobility and leaching of Pb by liming, for example, has produced contradictory results. This laboratory study compares the efficiency of two liming agents differing in their reactivity, CaCO(3) and blast furnace slag (BFS), in diminishing the mobility of Pb. In a batch test, contaminated humic soil samples were incubated in closed vessels without and with liming materials added in quantities to correspond additions of 5 t ha(-1). Water soluble Pb (Pb(w)), dissolved organic carbon (DOC), pH and substrate induced respiration (SIR) in soils were monitored for 21 days. In the experiment carried out with freely drained vessels, contaminated humic soil treated without and with liming agents was leached five times during the experimental period of 141 days. Leachates were analyzed for pH, DOC and Pb. At the end of the experiment, soil samples were analyzed for pH, DOC, Pb(w), and SIR. In both systems, CaCO(3) raised pH and DOC more than BFS. The liming agents did not significantly differ in their effect on Pb chemistry. Neither had any effect on SIR: however, liming agents markedly reduced the leaching of Pb in the open system, while in the closed system they increased rather than reduced the extractability of Pb. Incubation in a closed vessel proved not to be a suitable experimental system for Pb mobility estimation, since the ionic strength may be raised to abnormal levels, resulting from accumulated reaction products of liming agents.


Benefits and risks of maintaining normothermia during cardiopulmonary bypass in adult cardiac surgery: a systematic review.
Cardiopulmonary bypass is associated with significant morbidities, and the ideal temperature management during cardiopulmonary bypass remains uncertain. This review assessed the benefits and risks of maintaining normothermia during cardiopulmonary bypass in adult cardiac surgery. A total of 6,731 patients from 44 randomized controlled trials in 14 countries, comparing normothermic (> 34°C) and hypothermic (≤34°C) cardiopulmonary bypass in cardiac surgery (>18 years of age), were identified from MEDLINE (1966 to August 10, 2009), EMBASE (1988 to August 10, 2009), and Cochrane controlled trials register and subject to meta-analysis. Two investigators examined all studies and extracted the data independently. Mortality after normothermic and hypothermic bypass was not significantly different (1.4% vs. 1.9% respectively, relative risk [RR] 1.38, 95% confidence interval [CI] 0.94-2.04, I(2) = 0%, P = 0.10). Hypothermic bypass was, however, associated with an increased risk of allogeneic red blood cells (RR 1.19, 95% CI 1.07-1.34, I(2) = 0%, P = 0.002), fresh frozen plasma (RR 1.54, 95% CI 1.06-2.24, I(2) = 7.7%, P = 0.02), and platelet transfusion (RR 2.53, 95% CI 1.26-5.06, I(2) = 44%, P = 0.009). The risk of stroke, cognitive decline, atrial fibrillation, use of inotropic support or intra-aortic balloon pump, myocardial infarction, all-cause infections, and acute kidney injury after cardiac surgery was not significantly different between the two groups. The differences in the bypass time and targeted perfusion temperature were not significantly related to the risk of mortality and stroke. The current evidence suggests that maintaining normothermia during cardiopulmonary bypass in adult cardiac surgery is as safe as that of hypothermic surgery, and associated with a reduced risk of allogeneic blood transfusion.


BARHL1 homeogene, the human ortholog of the mouse Barhl1 involved in cerebellum development, shows regional and cellular specificities in restricted domains of developing human central nervous system.
The mouse homeobox gene Barhl1 plays a central role in cerebellum development and its expression is activated by the transcription factor Math1 which is involved in bone morphogenetic protein response pathways. We studied the human ortholog BARHL1 and we found that human, mouse, monkey, rat, and zebrafish orthologs were highly conserved and are members of the BarH homeogene family, containing Drosophila BarH1 and BarH2. The N-terminus of BARHL1 protein presents two FIL domains and an acidic domain rich in serine/threonine and proline, while the C-terminus contains a canonical proline-rich domain. Secondary structure analysis showed that outside the three helixes of the homeodomain, BARHL1 protein has essentially random coil structure. We isolated BARHL1 and defined its expression pattern in human embryonic and fetal central nervous system (CNS) and compared it to the mouse Barhl1 transcription. BARHL1 mRNA was found exclusively in the CNS restricted to p1-p4 prosomeres of the diencephalon, to the dorsal cells of the mesencephalon, to the dorsal dl1 sensory neurons of the spinal cord, and to the rhombic lips yielding the cerebellar anlage. Detailed analysis of BARHL1 expression in fetal cerebellar cell layers using our new optic microscopy technology showed BARHL1 expression in external and internal granular cells and also in mouse adult granular cells, in agreement to Barhl1 null mouse phenotype affecting the differentiation and migration of granular cells. These findings indicate that the regional and cellular specificities of BARHL1 transcriptional control well correspond to the mouse Barhl1 transcription and suggest a potential role of this gene in the differentiation of BARHL1-expressing neuronal progenitors involved in the pattern formation of human cerebral and cerebellar structures.


Vascular endothelial growth factor-stimulated actin reorganization and migration of endothelial cells is regulated via the serine/threonine kinase Akt.
Vascular endothelial growth factor (VEGF) induces endothelial cell proliferation, migration, and actin reorganization, all necessary components of an angiogenic response. However, the distinct signal transduction mechanisms leading to each angiogenic phenotype are not known. In this study, we examined the ability of VEGF to stimulate cell migration and actin rearrangement in microvascular endothelial cells infected with adenoviruses encoding beta-galactosidase (beta-gal), activation-deficient Akt (AA-Akt), or constitutively active Akt (myr-Akt). VEGF increased cell migration in cells transduced with beta-gal, whereas AA-Akt blocked VEGF-induced cell locomotion. Interestingly, myr-Akt transduction of bovine lung microvascular endothelial cells stimulated cytokinesis in the absence of VEGF, suggesting that constitutively active Akt, per se, can initiate the process of cell migration. Treatment of beta-gal-infected endothelial cells with an inhibitor of NO synthesis blocked VEGF-induced migration but did not influence migration initiated by myr-Akt. In addition, VEGF stimulated remodeling of the actin cytoskeleton into stress fibers, a response abrogated by infection with dominant-negative Akt, whereas transduction with myr-Akt alone caused profound reorganization of F-actin. Collectively, these data demonstrate that Akt is critically involved in endothelial cell signal transduction mechanisms leading to migration and that the Akt/endothelial NO synthase pathway is necessary for VEGF-stimulated cell migration.


[Secondary traumatic stress, the side effect of clinical empathy].
There is growing clinical evidence that a second category of trauma victims can result from working with traumatized populations. This article introduces the concept of secondary traumatic stress (STS) and analysis its impact and relevance in the particular situation of medical staff. In the second part we discuss medical workers' empathy as an important factor associated with clinical competence and patient outcomes on one side, and as a recognized risk factor for STS on the other side. Finally, we conclude that the paradox of the clinical relationship needs further attention and study, to find a mutual beneficial solution. Assessment has to be connected to prevention and intervention efforts to ensure effective management of STS among medical workers.


Isolation and developmental expression of Mitf in Xenopus laevis.
Mitf (gene for microphthalmia-associated transcription factor) encodes a transcription factor of the basic/helix-loop-helix/leucine-zipper family and is a key regulator during the development of two different types of melanin-producing cell lineages, namely neural crest-derived melanocytes/melanophores, and the retinal pigment epithelium (RPE) differentiated from the outer layer of the eye cup. Mitf-deficient mice show a lack of melanocytes and small eyes caused by abnormal RPE development. An interesting feature of Mitf is the existence of multiple isoforms with different amino termini and their functions in the development of these melanin-producing pigment cells. In this study, we isolated two Mitf homologues (XlMitfalpha and XlMitfbeta) and their isoforms from Xenopus laevis. Alignment analysis of the amino acid sequences of the N-termini suggests that these isoforms are homologues of mouse Mitf-M (expressed specifically in the melanocyte lineage) and Mitf-A (strongly expressed in the RPE, although this expression is ubiquitous). In Xenopus, XlMitfalpha is strongly expressed in the melanophore lineage (especially in premigratory melanoblasts) and the presumptive RPE and the epiphysis, in which melanin-producing cells differentiate in some vertebrates. Conservation of the Mitf isoforms expected to possess specific functions in the development of melanin-producing cells and of the expressions in such cell types in Xenopus suggest that XlMitf plays a central role in the development of melanin-producing cell lineages, and that, as in mice and humans, most of the signaling molecules or transcription factors implicated genetically in the development of melanin-producing cell lineages affect either Mitf expression or its function (Goding [2000] Genes Dev. 14:1712-1728).


Neovascular expression of VE-cadherin in human atherosclerotic arteries and its relation to intimal inflammation.
The present work aimed to investigate how the Ca(2+)-dependent cell adhesion molecule vascular endothelial (VE)-cadherin might be involved in atherogenesis. Specimens of human carotid artery and aorta were obtained at operation. An immunohistochemical approach using cell-type specific antibodies examined how VE-cadherin expression in areas of neovascularisation related to the accumulation of immunocompetent and inflammatory cells within atherosclerotic plaque. Electron microscopy was used to examine the structural characteristics of neovessels and the cell composition in the surrounding intimal matrix. In all the non-atherosclerotic aortic segments, VE-cadherin expression was observed only in the adventitia and the outer third of the media. Within the atherosclerotic arterial segments, VE-cadherin was expressed in all layers of the arterial wall including the intima where VE-cadherin was expressed by endothelial cells in areas of neovascularization. In some neovessels, loss of VE-cadherin expression was associated with increased focal accumulation of T-cells, macrophages and dendritic cells. Electron-microscopic examination demonstrated varying degrees of endothelial continuity in the intimal neovessels. Within those neovessels which were surrounded by a large number of immunocompetent and inflammatory cells, some inter-endothelial cell contacts were open allowing the penetration of blood cells through patent intercellular zones. VE-cadherin is expressed in atherosclerotic lesions by endothelial cells associated with neovascularisation. Downregulation of VE-cadherin expression within some intimal neovessels is accompanied by increased entry of immunocompetent cells into the intimal matrix surrounding areas of neovascularization which suggests that disorganizing endothelial cell-to-cell interactions within neovessels is significant in atherogenesis.


Suggested standards for reporting on arterial aneurysms. Subcommittee on Reporting Standards for Arterial Aneurysms, Ad Hoc Committee on Reporting Standards, Society for Vascular Surgery and North American Chapter, International Society for Cardiovascular Surgery.
The literature on arterial aneurysms is subject to potential misinterpretation because of inconsistencies in reporting standards. The joint councils of the Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery appointed an ad hoc committee to address this issue. This communication, prepared in response to the need for standardized reporting, defines and classifies arterial aneurysms and recommends standards for describing the causes, manifestations, treatment, and outcome criteria that are important when publishing data on aneurysmal disease.


Surfactant-induced friction reduction for hydrogels in the boundary lubrication regime.
We studied the ability of surfactants to reduce friction by boundary lubrication for a bulk hydrogel sliding on a solid surface in an aqueous solution. A piece of negatively charged polyelectrolyte hydrogel was slid across solid surfaces with various levels of hydrophobicity, using a strain-controlled parallel-plate rheometer in water. A dramatic reduction in the sliding friction, especially in the low velocity region, was detected by the addition of a surfactant to the water medium. This friction reduction was only observed in gel-solid friction but not in solid-solid friction, indicating that the soft and wet nature of the gel surface was crucial for this surfactant-induced friction reduction. This phenomenon reveals that surfactants can remain at the gel-mated interface, thus preventing direct interfacial interaction between the sliding surfaces, and significantly decreasing the frictional stress. The reported dramatic reduction in friction highlights the frictional characteristics of soft and wet hydrogel materials.


Temperature dependence of fluctuations in HIV1-protease.
Revealing the structure and the intrinsic dynamics of a protein is paramount to understand its function and other properties of evolutionary importance. Several schemes to obtain such insight in silico were developed over the decades. A computationally efficient protocol approximates the molecular dynamics around its native state by a harmonic potential. In this paper, we introduce a new methodology to combine the various harmonic approaches to understand the folding/unfolding dynamics and the dynamics around the native structure of the protein in a temperature dependent way. We apply this new protocol to the HIV1-protease and discuss the results in the light of events in the adaptive evolution towards drug resistance, which is a major problem in HIV infection.


Pathology of the placenta and cord in ascending and in haematogenous infection.
The two main patterns of inflammatory response in the placenta and its adnexae are: (1) amniotic infection, usually bacterial ascending, with acute chorioamnionitis and funisitis; (2) haematogenous villitis, usually viral, with early necrotizing lesions and vasculitis and, later, chronic infiltrates and obliterative vasculitis. In amniotic infection most cells in the exudate are maternal. These leucocytes participate in antibacterial defence of the amniotic cavity in conjunction with substances such as zinc polypeptide and lysozyme and may contribute directly to fetal defence. Immunoglobulins may be produced in the cord of placenta only in protracted lesions such as 'healed' funisitis. Individual variations in the resistance of the membranes to bacterial penetration are possible. In viral infections a massive multifocal production by plasmacytes of immunoglobulins M, G and A is seen in affected villi. The secretion of non-specific antiviral substances in the infected placenta is possible. In all affected villi there is an activation of fixed macrophages (Hofbauer cells) that remain partly 'immature', i.e. are lysozyme-negative. Multifocal lymphoplasmacytic villitis is uncommon and has helped to focus the diagnosis on prenatal infection. In contrast, non-specific lymphocytic villitis is common; since there is no morphological difference between cases known to be associated with an infection, e.g. varicella, and the others, many cases may well be due to silent infection, although a graft-versus-host reactions remains a distinct possibility.


Structure and function of restriction endonucleases.
Structures of two restriction endonucleases, BamHI and PvuII, were reported in the past year. This doubles the number of restriction endonuclease structures now known from two to four, and enables a comparative analysis of their structures and modes of DNA recognition. Despite a lack of sequence homology between the enzymes, BamHI turns out to resemble EcoRI, and PvuII turns out to resemble EcoRV. The active-site regions are structurally similar in all four enzymes, but their mechanisms of cleavage may differ.


Mid-life adiposity factors relate to blood-brain barrier integrity in late life.
We explored the relationship between adiposity factors measured during mid-life and blood-brain barrier (BBB) integrity measured via the cerebrospinal fluid/serum (CSF/S) albumin ratio in late life. Adiposity factors included body mass index and blood levels of sex hormone binding globulin (SHBG) and leptin. Design. Retrospective analyses over 24 years within a longitudinal study. Population-based sample. Subjects. Eighty-one women. CSF/S albumin ratio. The CSF/S albumin ratio measured at age 70-84 years was higher amongst women who were overweight or obese (6.50 +/- 2.79 vs. 5.23 +/- 1.61, age-adjusted P = 0.012), and was inversely correlated with SHBG (age-adjusted r = -0.321, P < 0.005) at age 46-60 years. In stepwise regression models, SHBG predicted the CSF/S albumin ratio (beta = -0.017, R2 = 0.107, P = 0.007). The best model (R2 = 0.187) predicting CSF/S albumin ratio included SHBG, age group (age 46 years versus >46), overweight or obesity, and an age group by SHBG interaction. Lower levels of SHBG in mid-life were related to worse BBB integrity in women after 24 years in late life, even considering other adiposity factors. SHBG may be important for understanding sex hormone-mediated mechanisms in brain health or as an independent marker of adipose tissue, the largest endocrine organ.


Methylmalonic aciduria in pregnancy: a case report.
Methylmalonic aciduria is a rare metabolic disorder of amino acid metabolism that is characterized by accumulation of large amounts of methylmalonic acid in the blood and urine. To our knowledge this is the first case report of a patient with methylmalonic aciduria who carried a pregnancy to term; the outcome was favorable despite high levels of methylmalonic acid in the serum and urine.


Enhancing nursing practice potential: breast free flap reconstruction following mastectomy.
Breast cancer is the most common cancer for women in both the developed and the developing world, comprising nearly one quarter of all female cancers. The most advanced forms of treatment, including mastectomy, may produce a five-year survival rate of 75% or more for certain types of cancer. For women experiencing breast cancer, breast reconstruction is often a positive option that can enhance quality of life and plays a significant role in a woman's recovery from breast cancer. The aim of this article is to present some different cases of women who have undergone autologous breast reconstruction free flaps and discuss advanced and intensive nursing care practice. Nurses need to not only be proficient in the postoperative physical care of patients who undergo mastectomy but also demonstrate advanced skills related to the educational needs of patients and their families and to ensure care is delivered in a manner that is patient centred and individualised. Nurses require advanced skills to meet the social and psychological care needs of the patient and their family during this major life event.


Retrovesical migration of malpositioned double-j ureteral stent.
A case of extraperitoneal migration of a double-J ureteral stent in the retrovesical space as a result of malposition is being described. The management of this very rare complication of stent placement, which has never been reported in the international literature, is presented in detail.


Dysmenorrhea and use of oral contraceptives in adolescent women attending a family planning clinic.
This study examined the prevalance of dysmenorrhea in female adolescents and the effect of experiencing a reduction in dysmenorrhea on oral contraceptive use. This was a prospective panel study in which 308 adolescent women at an inner-city family planning clinic were interviewed about their experiences with dysmenorrhea and their oral contraceptive use at three points in time over a 6-month period. A chi 2 test and multiple logistic regression analysis were done. The overall prevalence of dysmenorrhea in this population was 79.6%; 18.2% reported severe dysmenorrhea. Those who had severe dysmenorrhea and also experienced the reduction of dysmenorrhea as a result of oral contraceptives were eight times more likely to be consistent oral contraceptive users (p less than or equal to 0.02). It is important to screen female adolescents for dysmenorrhea, provide them with information about the beneficial side effects of oral contraceptives, and follow up these young women to make sure they are experiencing the alleviation of their symptoms.


A high proportion of bovine blastocysts produced in vitro are mixoploid.
Fluorescence in situ hybridization with chromosome 6- and chromosome 7-specific probes was used to assess the extent of chromosome abnormalities in developing bovine blastocysts at 7-8 days after insemination in vivo or in vitro. Interphase nuclei (N = 10 946) were analyzed from 151 blastocysts produced in vitro and from 28 blastocysts recovered from superovulated animals. This revealed that 72% (109 of 151) of the in vitro-produced blastocysts were mixoploid, i.e., were a mixture of normal, diploid, and polyploid cells. However, only a small fraction of the total number of cells were chromosomally abnormal. Of the mixoploid blastocysts, 83% (91 of 109) contained less than 10% polyploid cells, 13% (14 of 109) contained 11-25% polyploid cells, and only 4% (4 of 109) of the blastocysts had more than 25% polyploid cells per blastocyst. In contrast, a significantly lower proportion (25%) of mixoploidy was found in 28 bovine blastocysts developed in vivo (p < 0.0001). All of the mixoploid blastocysts that had developed in vivo contained less than 10% polyploid cells. No entirely aneuploid blastocysts, i. e., blastocysts in which all cells had the same type of chromosome abnormality, were found in either of the groups. Taken together, the most common chromosome abnormalities observed were diploid-triploid mixoploidies and diploid-tetraploid mixoploidies. Thus, our results confirm earlier reports that morphologically normal bovine blastocysts developed in vivo are often mixoploids. We further show that in vitro-produced bovine blastocysts have a high rate of mixoploidy. Although the difference in mixoploidy rate detected in this study may not be general, it is an interesting phenomenon for further studies.


Recent advances in scleroderma-associated pulmonary hypertension.
This review summarizes recent advances in pulmonary hypertension, a leading cause of morbidity and mortality in scleroderma (SSc). Although WHO Group I pulmonary arterial hypertension (PAH) is the most common cause of pulmonary hypertension, all WHO Groups can occur. PAH is now a criterion for the diagnosis of SSc. Results of recent research have resulted in greater insight into the epidemiology of SSc-pulmonary hypertension with regard to prevalence, incidence and clinical risk factors. There is also greater understanding of the role of inflammation in the pathogenesis of SSc-PAH. Advances have also been made in the evaluation and screening of patients with SSc-PAH, and early detection has been shown to improve survival in a disease that typically has worse outcomes than other forms of PAH. Finally, recommendations have been made with regard to goal-directed therapy. Although there have been many recent advances in SSc-pulmonary hypertension, further research is needed in order to prevent/cure this deadly complication.


Laser-induced ultrafast demagnetization in the presence of a nanoscale magnetic domain network.
Femtosecond magnetization phenomena have been challenging our understanding for over a decade. Most experiments have relied on infrared femtosecond lasers, limiting the spatial resolution to a few micrometres. With the advent of femtosecond X-ray sources, nanometric resolution can now be reached, which matches key length scales in femtomagnetism such as the travelling length of excited 'hot' electrons on a femtosecond timescale. Here we study laser-induced ultrafast demagnetization in [Co/Pd](30) multilayer films, which, for the first time, achieves a spatial resolution better than 100 nm by using femtosecond soft X-ray pulses. This allows us to follow the femtosecond demagnetization process in a magnetic system consisting of alternating nanometric domains of opposite magnetization. No modification of the magnetic structure is observed, but, in comparison with uniformly magnetized systems of similar composition, we find a significantly faster demagnetization time. We argue that this may be caused by direct transfer of spin angular momentum between neighbouring domains.


Natural killer cell cytolytic function in Korean patients with adult-onset Still's disease.
To investigate natural killer (NK) cell proportions, NK cell cytotoxicity, and interleukin 18 (IL-18) expression, in patients with adult-onset Still's disease (AOSD). Forty-five patients with AOSD (active = 22, inactive = 23) and 32 healthy controls were included. The proportions of NK cells among peripheral blood mononuclear cells were assessed by flow cytometry. IL-18 and IL-18-binding protein (IL-18BP) concentrations were measured by ELISA. Twenty-four patients with AOSD and 18 controls were examined for cytotoxic activity of NK cells by co-incubating NK cells with NK-sensitive K562 cells. The association of NK cell function with clinical and laboratory measures was investigated. The proportions of NK cells were significantly lower in patients with active AOSD than in patients with inactive disease and controls. NK cell cytotoxic function was significantly lower in patients with AOSD than in controls. NK cell proportions and cytotoxic functions were reexamined in 11 and 6 patients, respectively, after treatment. Low NK cell proportion and cytotoxic dysfunction were improved with clinical improvements of the patients. IL-18 and IL-18BP levels were much higher in patients with active AOSD than in controls. NK cell cytotoxic functions were consistently low and IL-18 and IL-18BP levels were constantly high in patients with AOSD, regardless of disease activity. Low NK cell proportion, defective cytotoxic function, and elevated IL-18 levels may be significant features of AOSD. After resolution of the acute phase, low NK cell proportion was recovered and NK cell cytolytic function was restored along with clinical improvement. These findings possibly contribute to immunologic abnormalities in AOSD.


Maximizing the benefit--minimizing the risk: the developing role of radiographers in performing intravenous injections.
Performance of intravenous (iv) injections as part of radiographer role development has become fundamental to the operational management of diagnostic imaging departments in the UK. Through discussion of appropriate areas, this review aims to highlight current issues pertaining to iv injection. More importantly, the framework described could be transposed to other existing or future areas of role development. Within a validated system of delegation, utilization of radiographers' skills in an expanded role improves allocation of resources and may increase radiographer motivation and provide career enhancement. Professional body accreditation as well as civil and employment law provide clear guidelines on medicolegal implications, valid consent and accountability. Implementation of an iv administration policy, based on Royal College of Radiologists guidelines, includes proper delegation of duties and safe administration of substances. This should help ensure acceptance of vicarious liability by an employer. Failure to adhere to these established guidelines could leave employers and radiographers vulnerable to medicolegal action. Furthermore, evaluation of radiographer performance, facilitated by clinical governance and departmental audits, should ensure effective and safe practice whilst minimizing associated risks. Evidence-based radiography will provide the necessary drive for future changes in practice as well as further expansion of the radiographer's role.


Measurement of Force-Dependent Release Rates of Cytoskeletal Motors.
Optical tweezers permit measuring motor-filament rupture forces with piconewton sensitivity. For deeper structural and mechanistic understanding of motors, different structural constraints can be induced by pulling motor proteins at various positions and manipulating the direction of the exerted force. Here, we present an optical-trapping approach to investigate the effect of the magnitude and direction of tension applied to the linker element of cytoskeletal motors on motor-filament interactions. Using this approach, force-dependent microtubule release rates of monomeric kinesins can be directly measured by pulling on kinesin's "neck linker" with a constant force.


Ultrasonic demonstration of renal vein thrombosis.
The sonographic findings of renal vein thrombosis are described in a patient examined for pain in the upper right abdomen. Since sonographic findings of the kidney itself are nonspecific, as are clinical appearance, laboratory data, and excretory urography, direct sonographic visualization of thrombus within the lumen of the renal vein and the inferior vena cava is of major importance in the diagnosis of renal vein thrombosis.


Is the Patellar Pubic Percussion Test useful to diagnose only femur fractures or something else? Two case reports.
In the literature, the utility of the Patellar Pubic Percussion Test (PPPT) to diagnose occult fractures of the femur is well described. However, up to now there are no studies demonstrating the efficacy of this test in recognizing fractures of the pelvis. In this two case report a positive PPPT allowed the therapist to recognize clinical conditions requiring caution, protecting patients from a potentially unsuitable treatment. Both patients had a negative pelvis and femur x-ray after a fall, but the clinical findings and a positive PPPT lead the physiotherapist to suggest further examinations. In these two cases the PPPT seemed to be a useful diagnostic tool to identify periacetabular, ileo-pubic and ischio-pubic ramus fractures. These findings suggest that PPPT could be positive even for a bone lesion in any of the transit points of the vibration, from the patella to the pubic symphysis.


DNA copy number changes in malignant ovarian germ cell tumors.
Malignant ovarian germ cell tumors (OGCTs) include immature teratomas (ITs), dysgerminomas (DGs), endodermal sinus tumors (ESTs), choriocarcinomas, and embryonal carcinomas. Knowledge about the genetic changes associated with malignant OGCT development is sparse. We therefore analyzed 25 OGCTs (12 DGs, 4 ESTs, and 9 ITs) for gains and losses by comparative genomic hybridization. In total, more gains than losses were observed, and the number of alterations ranged from 0-20 per tumor. The average number of changes among DGs, ESTs, and ITs was 10, 6, and 1.4, respectively. The most common changes in DGs were gains from chromosome arms 1p (33%), 6p (33%), 12p (67%), 12q (75%), 15q (42%), 20q (50%), 21q (67%), and 22q (58%); gains of the whole of chromosomes 7 (42%), 8 (42%), 17 (42%), and 19 (50%); and losses from 13q (58%). Two of three DGs with a gonadoblastoma component showed gains of 3p21 and loss of 5p, whereas none of the nine pure DGs had these changes, suggesting that they might be characteristic either of gonadoblastoma or of DG developing from a gonadoblastoma. Gain of 12p and gain from 1q were seen in three of four ESTs, whereas gains from 3p, 11q, and Xp and loss from 18q were each found in two tumors. Five of the ITs revealed changes (range, 1-4 changes/tumor), with gains from 1p, 16p, 19, and 22q each being found in two tumors. We conclude that ovarian DGs and ESTs seem to develop via the same genetic pathways that are already known for testicular germ cell tumors. On the other hand, ITs do not exhibit gain of 12p and also typically show fewer changes than other malignant OGCTs, indicating that they arise via different pathogenetic mechanisms.


Mitochondrial glutaminase enhances extracellular glutamate production in HIV-1-infected macrophages: linkage to HIV-1 associated dementia.
Dysfunction in mononuclear phagocyte (MP, macrophages and microglia) immunity is thought to play a significant role in the pathogenesis of HIV-1 associated dementia (HAD). In particular, elevated extracellular concentrations of the excitatory neurotransmitter glutamate, produced by MP as a consequence of viral infection and immune activation, can induce neuronal injury. To determine the mechanism by which MP-mediated neuronal injury occurs, the concentration and rates of production of extracellular glutamate were measured in human monocyte-derived macrophage (MDM) supernatants by reverse phase high-performance liquid chromatography (RP-HPLC). Measurements were taken of supernatants from MDM infected with multiple HIV-1 strains including ADA and DJV (macrophage tropic, M-tropic), and 89.6 (dual tropic). High levels of glutamate were produced by MDM infected with M-tropic viruses. AZT, an inhibitor of HIV-1 replication, inhibited glutamate generation, demonstrating a linkage between HIV-1 infection and enhanced glutamate production. In our culture system, glutamate production was dependent upon the presence of glutamine and was inhibited by 6-diazo-5-oxo-L-norleucine, a glutaminase inhibitor. Supernatants collected from HIV-1-infected MP generated more glutamate following glutamine addition than supernatants isolated from uninfected MP. These findings implicate the involvement of a glutamate-generating enzyme, such as phosphate-activated mitochondrial glutaminase (PMG) in MP-mediated glutamate production.


[Effect of the male sex hormone and its 5 alpha-reduced metabolites on the function of the thyroid in vivo and in vitro].
The administration of testosterone propionate, dihydrotestosterone and androstandiol to male rats was followed by different changes in thyroid function. Testosterone propionate exerted a stimulating effect, whereas its metabolites induced marked depression of thyroid functional activity in the experiments in vivo. In vitro both sex hormones and 5-alpha-reduced metabolites inhibited radioactive iodine absorption by rat thyroid slices and human thyrotoxic struma. The data demonstrate that testosterone may produce a direct effect on the thyroid without the hypophysis.


Cranberry phytochemicals inhibit glycation of human hemoglobin and serum albumin by scavenging reactive carbonyls.
Protein glycation caused by sugars and reactive carbonyls is a contributing factor to diabetic complications, aging, and other chronic diseases. The objective of this study was to investigate the inhibitory effects of cranberry phytochemicals on protein glycation. Cranberries, purified to yield sugar-free phytochemical powder, were fractionated into ethyl acetate and water fractions. Water fraction was further separated into water fraction I, II, and III on a Sephadex LH-20 column. Cranberry phytochemical powder and its fractions significantly inhibited the formation of glycated hemoglobin. The concentrations of cranberry phytochemicals required to inhibit 50% of albumin glycation (EC(50)) in albumin-glucose assay were lower than that of aminoguanidine except for water fraction I. Cranberry phytochemicals inhibited glycation of human serum albumin mediated by methylglyoxal, but the EC(50) were higher than that of aminoguanidine. Carbonyl scavenging assay showed that water fraction II scavenged 89.3% of methylglyoxal at 6 h of reaction. Fractions enriched with procyanidins showed higher antiglycation activities, suggesting procyanidins were the major active components. The hypothesis whether cranberry procyanidins scavenged reactive carbonyls by forming adducts was tested. Epicatechin was used as a model compound to react with methylglyoxal and glyoxal at pH 7.4. Five adducts were detected and their structures were tentatively identified using HPLC-ESI-MS/MS.


[Anaphylactic accidents due to glaphenine. 5 cases].
The authors report 5 cases of shock type anaphylactic reactions after the ingestion of glafenine. Up to the present, acute tubulo-interstitial nephritis had chiefly been reported. The existence of allergy to this medication remains to be proved by the wider application of allergological studies.


Characterization of lymphocyte function-associated antigen 1 (LFA-1)-deficient T cell lines: the alphaL and beta2 subunits are interdependent for cell surface expression.
The leukocyte, or beta2, integrins are heterodimeric cell surface molecules that share a common beta subunit, and have unique alpha subunits. LFA-1 is the predominant beta2 integrin on lymphocytes, and plays an important role in many lymphocyte functions; however, most studies of the cytoplasmic regions of LFA-1 have been performed in transfected epithelial cells, such as COS, in part because no lymphoid cell lines deficient in the LFA-1 alpha subunit have been described. To address structure-function studies of beta2 integrins in relevant cell types, two T lymphoblastoid cell clones that completely lack cell surface LFA-1, J-(beta2).7 and SK-(beta2).7, derived from Jurkat and SKW3, respectively, were prepared by chemical mutagenesis and selection. Biosynthetic labeling and immunoprecipitation showed that the J-(beta2).7 clone did not translate any LFA-1 alpha subunit protein, while the SK-(beta2).7 cells did not synthesize any beta2 subunit protein. Northern blot analysis of poly(A+) RNA from these cells revealed an absence of the corresponding mRNA in each case. By transfection analysis, only the alpha subunit reconstituted LFA-1 expression in the J-(beta2).7 cells, while only the beta subunit restored cell surface LFA-1 expression in the SK-(beta2).7 cells. Functional studies with the parental cell lines, the J-(beta2).7 and SK-(beta2).7 cells, and the transfectants showed that all binding of Jurkat and SKW3 cells to purified ICAM-1 is mediated by LFA-1, and the reconstituted LFA-1 expressed by the J-(beta2).7 and SK-(beta2).7 transfected cells is regulated normally.


Endosome to trans-Golgi network transport of Proprotein Convertase 7 is mediated by a cluster of basic amino acids and palmitoylated cysteines.
Proprotein Convertase 7 (PC7) is a Furin-like endoprotease that cleaves precursor proteins at basic amino acids. PC7 is concentrated in the trans-Golgi network (TGN) but it shuttles between the plasma membrane and the TGN depending on sequences in the cytoplasmic tail. A short region containing a three amino acids motif, P724-L725-C726, is essential and sufficient for internalization of PC7 but not for TGN localization, which requires the additional presence of the juxtamembrane region. In this study we have investigated the contribution of a cluster of basic amino acids and two reversibly palmitoylated cysteine residues to endocytic trafficking. Stable cell lines overexpressing chimeric proteins (CD25 and CD46) containing the cytoplasmic domain of PC7 in which the basic cluster alone or together with both palmitoylated cysteines are mutated showed enhanced surface expression as demonstrated by immunofluorescence experiments and surface biotinylation. The mutant proteins no longer recycled to the TGN in antibody uptake experiments and accumulated in an endosomal compartment. Recycling of wild type PC7 to the TGN is blocked by nocodazole, suggesting that PC7 shuttles to the TGN via late endosomes, similar to Furin. Unlike furin, however, PC7 was found to recycle to a region within the TGN, which is deficient in sialyltransferase, as shown by resialylation experiments. In conclusion, a novel motif, composed of a basic amino acid cluster and two palmitoylated cysteines are essential for TGN localization and endocytic trafficking.


NosP Signaling Modulates the NO/H-NOX-Mediated Multicomponent c-Di-GMP Network and Biofilm Formation in Shewanella oneidensis.
Biofilms form when bacteria aggregate in a self-secreted exopolysaccharide matrix; they are resistant to antibiotics and implicated in disease. Nitric oxide (NO) is known to mediate biofilm formation in many bacteria via ligation to H-NOX (heme-NO/oxygen binding) domains. Most NO-responsive bacteria, however, lack H-NOX domain-containing proteins. We have identified another NO-sensing protein (NosP), which is predicted to be involved in two-component signaling and biofilm regulation in many species. Here, we demonstrate that NosP participates in the previously described H-NOX/NO-responsive multicomponent c-di-GMP signaling network in Shewanella oneidensis. Strains lacking either nosP or its co-cistronic kinase nahK (previously hnoS) produce immature biofilms, while hnoX and hnoK (kinase responsive to NO/H-NOX) mutants result in wild-type biofilm architecture. We demonstrate that NosP regulates the autophosphorylation activity of NahK as well as HnoK. HnoK and NahK have been shown to regulate three response regulators (HnoB, HnoC, and HnoD) that together comprise a NO-responsive multicomponent c-di-GMP signaling network. Here, we propose that NosP/NahK adds regulation on top of H-NOX/HnoK to modulate this c-di-GMP signaling network, and ultimately biofilm formation, by governing the flux of phosphate through both HnoK and NahK. In addition, it appears that NosP and H-NOX act to counter each other in a push-pull mechanism; NosP/NahK promotes biofilm formation through inhibition of H-NOX/HnoK signaling, which itself reduces the extent of biofilm formation. Addition of NO results in a reduction of c-di-GMP and biofilm formation, primarily through disinhibition of HnoK activity.


Dolutegravir and elvitegravir plasma concentrations following cessation of drug intake.
To evaluate dolutegravir and elvitegravir/cobicistat pharmacokinetics in HIV-negative volunteers up to 10 days after drug cessation. Healthy volunteers received 50 mg of dolutegravir once-daily for 10 days, then underwent a 9 day wash-out period, and then received elvitegravir/cobicistat as part of Stribild(®) (245 mg of tenofovir, 200 mg of emtricitabine, 150 mg of elvitegravir and 150 mg of cobicistat) for 10 days. Serial pharmacokinetic (PK) sampling occurred prior to the final dose of each course and at regular intervals for up to 216 h (10 days) after drug cessation. Concentrations were determined by LC-MS/MS, and PK parameters were illustrated as geometric mean and 90% CI. Seventeen volunteers completed the study. For dolutegravir, plasma terminal elimination t1/2 to the last measurable concentration (within 216 h) was longer than its t1/2 within the dosing interval (0-24 h): 14.3 h (12.9-15.7 h) versus 23.1 h (19.7-26.6 h); conversely, the terminal elimination t1/2 for elvitegravir was lower than its t1/2 within the dosing interval (0-24 h): 10.8 h (9.7-13.0 h) versus 5.2 h (4.7-6.1 h). Dolutegravir concentrations were above the protein-adjusted (PA) IC90 (64 ng/mL) in 100% of subjects after 36 and 48 h and in 94% after 60 and 72 h. All subjects had detectable dolutegravir concentrations at 96 h, a mean of 23.5% above the IC90. Elvitegravir concentrations were above the PA IC95 (45 ng/mL) in 100% of subjects at 24 h, 65% at 36 h but 0% after 48 h. Our data show marked differences in the elimination rates of dolutegravir and elvitegravir following treatment interruption, which is likely to impact the extent to which drug doses can be delayed or missed. They suggest that clinical differences may emerge in patients who have suboptimal adherence.


[Effects of physical activity on women's morphology].
Objective To analyze the effect of 12 weeks of physical activity on the morphology of the women enrolled in the Family Health Program in the city of Patos, Paraíba, Brazil. During these weeks, different physical activity programs were applied. Methods A quasi-experimental study, in which 28 women were analyzed. All were volunteers, aged between 42 and 56 years and divided into groups: G1 (n=15, recreational activities) and G2 (n=13, dance activities). For data analysis, the Student t-test for independent samples was used with a significance level of p<0.05. Results The comparison of body composition variables showed no difference between the two groups. However, when the pre- and post-exercise moments are compared, it is seen that the two different physical activity programs produce significant changes in the morphology of women. Conclusion The results indicate that the applied physical activity programs produce significant changes in the morphology of women. On the other hand, we consider that the comparison between a physical exercise program and recreational physical activity program and their effects on the morphology of women could be good.


Clinical trials in multiple sclerosis: a critical review (1970-1990).
The present study is a critical review of 100 papers concerning clinical trials in Multiple Sclerosis (MS), published between 1970-1990. We analyzed 20 validity criteria (internal 12, and external 8) and codified each item as "adequate" or "not adequate", so that the validity of each report was quantified. In addition, we used a statistical method of automatic classification (cluster analysis) to subdivide all the papers in 4 groups with growing validity. Only 52 reports had a fairly good or good validity, therefore more efforts are suggested to correctly plan clinical trials in MS and lead to reliable results.


Unraveling the photoelectrochemical properties of ionic liquids: cognizance of partially reversible redox activity.
Ionic liquid based electrolytes are gaining great interest in the field of photoenergy conversion. We have found that the ionic liquids namely BMIm Cl, BMIm PF6 and BMIm Tf2N inherently offer redox activity. The device performance of the photoelectrochemical (PEC) cells of the configuration PbOx (0.25 cm(2))|blank ionic liquids|platinum (2 cm(2)) was analyzed in detail to get insights into the working principle of such systems. It was found that partially reversible redox ion pairs diminish the performance of such cells as power generating devices. The partial redox activity of the ionic liquids was confirmed by a number of observations derived from the PEC spectra. The important parameter, Vredox, which determines the performance of any PEC cell was also calculated for all the ionic liquids. The difficulties that arise in high frequency C-V measurements for ionic liquid systems were overcome by choosing the appropriate probing frequency. The evaluated Vredox of BMIm Cl, BMIm PF6 and BMIm Tf2N ionic liquids was found to be -0.30, -0.20 and -0.78 V (vs. NHE), respectively. This study will be beneficial to understand the role of ionic liquids as redox active electrolyte media in several applications.


Caffeic acid phenethyl ester protects rabbit brains against permanent focal ischemia by antioxidant action: a biochemical and planimetric study.
The present study was conducted to investigate whether caffeic acid phenethyl ester (CAPE), an active component of propolis extract, has a protective effect on brain injury after focal permanent cerebral ischemia, and to determine the possible antioxidant mechanisms. Cerebral infarction in adult male New Zealand rabbits was induced by microsurgical procedures producing right focal permanent middle cerebral artery occlusion (pMCAO). CAPE was administered to the treatment group after pMCAO at a dose of 10 micromol kg(-1) once a day intraperitoneally for 7 days. Neurological deficits were evaluated, using a modified six-point scale. Spectrophotometric assay was used to determine the contents of malondialdehyde (MDA), glutathione (GSH), catalase (CAT), nitric oxide (NO) and xanthine oxidase (XO). In the ipsilateral hemisphere, the infarct volume of the brain was assessed in brain slices stained with heamatoxylen and eosin. The results showed that treatment with CAPE significantly reduced the percentage of infarction in the ipsilateral hemisphere compared with the ischemia group. CAPE treatment significantly attenuated the elevation of plasma MDA, CAT and XO content (p<0.05), whereas it significantly increased the levels of plasma GSH and NO (p<0.05). Therefore, subacute CAPE administration plays a protective role in focal pMCAO due to attenuation of lipid peroxidation and its antioxidant activity. All of these findings suggest that CAPE provides neuroprotection against cerebral ischemia injury through its antioxidant action.


Essential dynamics of lipase binding sites: the effect of inhibitors of different chain length.
The biochemical activity of enzymes, such as lipases, is often associated with structural changes in the enzyme resulting in selective and stereospecific reactions with the substrate. To investigate the effect of a substrate and its chain length on the dynamics of the enzyme, we have performed molecular dynamics simulations of the native Rhizomucor miehei lipase (Rml) and lipase-dialkylphosophate complexes, where the length of the alkyl chain ranges from two to 10 carbon atoms. Simulations were performed in water and trajectories of 400 ps were used to analyse the essential motions in these systems. Our results indicate that the internal motions of the Rml and Rml complexes occur in a subspace of only a few degrees of freedom. A high flexibility is observed in solvent-exposed segments, which connect beta-sheets and helices. In particular, loop regions Gly35-Lys50 and Thr57-Asn63 fluctuate extensively in the native enzyme. Upon activation and binding of the inhibitor, involving the displacement of the active site loop, these motions are considerably suppressed. With increasing chain length of the inhibitor, the fluctuations in the essential subspace increase, levelling off at a chain length of 10, which corresponds to the size of the active-site groove.


The development of plasmid-free strains of Agrobacterium tumefaciens by using incompatibility with a Rhizobium meliloti plasmid to eliminate pAtC58.
Agrobacterium tumefaciens strains LBA275 and LBA290 were cured of their cryptic plasmid pAtC58 by the introduction of the Rhizobium meliloti plasmid pRme41a, which is incompatible with pAtC58. pRme41a and pTiC58, the resident Ti plasmid of LBA275, were subsequently eliminated by growth at supraoptimal temperature (40 degrees C). The resulting plasmid-free Agrobacterium strains, UBAPF1 and UBAPF2, have proved extremely useful for the study of Rhizobium plasmids. The loss of the cryptic plasmid pAtC58 has no effect on the tumor-forming ability of the Agrobacterium strains; when the Ti plasmid is present, normal tumors are formed on Kalanchoe daigremontiana.


Low-dose bupivacaine-fentanyl spinal anaesthesia for transurethral prostatectomy.
We evaluated the effect of low-dose bupivacaine plus fentanyl administered intrathecally in elderly patients undergoing transurethral prostatectomy. Patients were randomly assigned to one of two groups. Group F received plain bupivacaine 4 mg with 25 micro g of fentanyl and sterile water to a total of 1.5 ml, and Group B received only 0.5% plain bupivacaine 7.5 mg for spinal anaesthesia. Sensory block was adequate for surgery in all patients. The mean level of motor block was higher and the duration of motor block was longer in Group B (p < 0.0001). Hypotension and shivering were significantly more common in Group B (p < 0.05). The addition of fentanyl 25 micro g to plain bupivacaine 4 mg provides adequate analgesia for transurethral prostatectomy with fewer side-effects in elderly patients when compared with the conventional dose of bupivacaine.


nanoDSF as screening tool for enzyme libraries and biotechnology development.
Enzymes are attractive tools for synthetic applications. To be viable for industrial use, enzymes need sufficient stability towards the desired reaction conditions such as high substrate and cosolvent concentration, non-neutral pH and elevated temperatures. Thermal stability is an attractive feature not only because it allows for protein purification by thermal treatment and higher process temperatures but also due to the associated higher stability against other destabilising factors. Therefore, high-throughput screening (HTS) methods are desirable for the identification of thermostable biocatalysts by discovery from nature or by protein engineering but current methods have low throughput and require time-demanding purification of protein samples. We found that nanoscale differential scanning fluorimetry (nanoDSF) is a valuable tool to rapidly and reliably determine melting points of native proteins. To avoid intrinsic problems posed by crude protein extracts, hypotonic extraction of overexpressed protein from bacterial host cells resulted in higher sample quality and accurate manual determination of several hundred melting temperatures per day. We have probed the use of nanoDSF for HTS of a phylogenetically diverse aldolase library to identify novel thermostable enzymes from metagenomic sources and for the rapid measurements of variants from saturation mutagenesis. The feasibility of nanoDSF for the screening of synthetic reaction conditions was proved by studies of cosolvent tolerance, which showed protein melting temperature to decrease linearly with increasing cosolvent concentration for all combinations of six enzymes and eight water-miscible cosolvents investigated, and of substrate affinity, which showed stabilisation of hexokinase by sugars in the absence of ATP cofactor. ENZYMES: Alcohol dehydrogenase (NADP+ ) (EC 1.1.1.2), transketolase (EC 2.2.1.1), hexokinase (EC 2.7.1.1), 2-deoxyribose-5-phosphate aldolase (EC 4.1.2.4), fructose-6-phosphate aldolase (EC 4.1.2.n).


Flower-, wire-, and sheet-like MnO2-deposited diatomites: Highly efficient absorbents for the removal of Cr(VI).
Flower-, wire-, and sheet-like MnO2-deposited diatomites have been prepared using a hydrothermal method with Mn(Ac)2, KMnO4 and/or MnSO4 as Mn source and diatomite as support. Physical properties of the materials were characterized by means of numerous analytical techniques, and their behaviors in the adsorption of chromium(VI) were evaluated. It is shown that the MnO2-deposited diatomite samples with different morphologies possessed high surface areas and abundant surface hydroxyl groups (especially the wire-like MnO2/diatomite sample). The wire-like MnO2/diatomite sample showed the best performance in the removal of Cr(VI), giving the maximum Cr(VI) adsorption capacity of 101 mg/g.


Premature surgical menopause and Factor V Leiden heterozygosity: case report and literature review.
Premature surgical menopause is becoming increasingly common in the setting of both benign and malignant disease. These women are at an increased risk of all-cause and cardiovascular mortality, cognitive dysfunction and metabolic bone disease. We present the case of a 28-year-old woman with premature surgical menopause due to bilateral oophorectomy, following ovarian torsion occurring on two separate occasions, one episode during her second trimester of pregnancy. The decision regarding hormone replacement therapy in this lady was complicated due to the presence of Factor V Leiden heterozygosity. A brief discussion and review of the literature follow.


Detoxification of pentachlorophenol and creosote contaminated groundwater by physical extraction: chemical and biological assessment.
Chemical analyses revealed that polycyclic aromatic hydrocarbons (PAHs) and other organic compounds were present in a perennial freshwater stream that flowed through the abandoned American Creosote Works and into Pensacola Bay, Florida. Moreover, groundwater pumped from a well depth of 21 m at a location adjacent to the site was heavily contaminated with PAHs and other organics. A study was conducted to determine the efficacy of ultrafiltration for removal of organics from groundwater at this U.S. Environmental Protection Agency, Super Fund site. Ultrafiltration reduced the concentration of total identified organics from 210.0 mg/L in groundwater to 1.5 mg/L in the post-filtration permeate. Tests for toxicity/teratogenicity in embryonic inland silversides, Menidia beryllina; and Microtox 15 min EC50's were conducted with: 1) streamwater, 2) untreated groundwater, 3) feedwater used in the ultrafiltration system and 4) permeate water that passed through the ultrafiltration system. A concentration of 100% streamwater caused significant (alpha less than or equal to 0.05) teratogenic responses in fish embryos and larvae; the Microtox EC50 was 3.7% streamwater. Groundwater and feedwater caused significant embryo toxic or teratogenic responses at concentrations of 100, 10, and 1%; the Microtox EC50's were 0.85 and 0.48%, respectively. In contrast, only 100% permeate water caused significant increases in terata, compared to the control response; at 10 and 1% concentrations greater than 90% of hatched larvae appeared normal. The Microtox EC50 was 30% permeate water.


Aureobasidium pullulans as a source of liamocins (heavy oils) with anticancer activity.
Liamocins are structurally unique, heavier-than-water “oils” produced by certain strains of Aureobasidium pullulans. The aim of the current study is to identify new sources of liamocins and evaluate their potential as anticancer agents. Nine strains of A. pullulans from phylogenetic clades 8, 9, and 11 were examined for the first time for production of liamocins. Strains in these clades have only been isolated from tropical environments, and all strains tested here were from various locations in Thailand. Strains RSU 9, RSU 21, and RSU 29, all from clade 11, produced from 7.0 to 8.6 g liamocins/l from medium containing 5 % sucrose. These are the highest yields of liamocins that we have found thus far. These strains also produced from 9.4 to 17 g pullulan/l. The structural identity of liamocins was confirmed by matrix-assisted laser desorption/ionization mass spectrometry; differential spectra were obtained in which the dominant ion was either at about m/z 805.5 or m/z 949.6, consistent with the structure of liamocins. Liamocins from A. pullulans strains RSU 9 and RSU 21 inhibited two human breast cancer cell lines and a human cervical cancer cell line (IC50 values of 32.2 ± 1.4 to 63.1 ± 2.4 μg liamocins/ml) but were not toxic to a normal cell line. Liamocins weakly inhibited a strain of Enterococcus faecalis, but did not inhibit strains of Lactobacillus fermentum, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Thus, A. pullulans phylogenetic clade 11 is a promising source of liamocins, and these compounds merit further examination as potential anticancer agents.


Retinal vascular caliber and migraine: the Blue Mountains Eye Study.
To assess whether migraine is associated with retinal microvascular caliber. Migraine is believed to be associated with vascular disease, but few studies have investigated the relationship between structural microvascular changes and migraine. Population-based cross-sectional study. Participants in the Blue Mountains Eye Study follow-up (1997 to 1999, n = 2,335, aged 54+) had retinal photographs taken. A computer-assisted method was used to measure average retinal arteriolar and venular diameters and calculate the arteriole-to-venule ratio. History of migraine was recorded by interview using International Headache Society criteria (1988). Subjects giving a history of migraine without aura (n = 128) had narrower retinal arterioles than subjects giving a history of migraine with aura (n = 182) or subjects with no migraine history (n = 1619). After multivariate adjustment, mean retinal arteriolar diameter was 4.3 microm (95% confidence interval 0.5, 8.1) narrower in subjects reporting migraine without aura as compared to subjects with no migraine. Individuals with a history of migraine without aura were more likely to have slightly narrower retinal arteriolar caliber than individuals without migraine. This relationship was not present for migraine with aura. These data support the hypothesis that microvascular disease may be associated with certain types of migraine.


Alopecia Risk and the Thickness, Number, and Frequency of Scalp Skin Harvests.
The aim of this study was to elucidate the relationships between the thickness, number, and frequency of scalp skin harvests and alopecia risk.In a PubMed search, the search terms (scalp AND graft AND alopecia) were used, resulting in 148 papers. Among 21 abstracts, 11 full papers were reviewed, and 3 papers were ultimately analyzed.The donor-site alopecia rate was significantly higher in patients who experienced hair growth on their grafts than in those who did not (odds ratio = 10.875, 95% confidence interval, 2.677-44.178; P < 0.001). The depth of the infundibulum can be estimated to be 451.8 μm at 5 years of age, 528.8 μm at 10 years, 605.8 μm at 15 years, and 682.8 μm at 20 years. Therefore, the limits of safe thickness for graft harvesting from the scalp are <18/1000 inches for 5-year olds, 21/1000 inches for 10-year olds, 24/1000 inches for 15-year olds, and 27/1000 inches for 20-year olds. The safe number of harvests (intersection of the alopecia and nonalopecia groups) was 2.7, and the safer number of harvests (limits of 2 standard deviations of the alopecia group) was 1.0. The safe time interval between harvests was 14.0 days, and the safer time interval between harvests was 15.6 days. The safe single minimal interval (SMI) between harvests was 12.7 days, and the safer SMI was 13.7 days.Since the safe thickness for graft harvesting from scalps exceeds the thickness in usual practice, following the safer SMI between harvests (13.7 days) is expected to be more important for minimizing alopecia risk.


Lipoxins: potential anti-inflammatory, proresolution, and antifibrotic mediators in renal disease.
Lipoxins are lipoxygenase-derived lipid mediators with both anti-inflammatory and proresolution properties that have been demonstrated in vivo and in vitro. The bioactivity profile of lipoxins in vitro suggests that they have therapeutic potential in acute renal failure and glomerulonephritis; predictions that have been borne out to date in experimental models of renal disease. We review recent developments on the molecular basis of lipoxin bioactions mediated through receptor crosstalk and the accumulating evidence that lipoxins may have potential as novel anti-inflammatory agents.


Salt resistance and synergistic effect with vancomycin of alpha-helical antimicrobial peptide P18.
P18 (KWKLFKKIPKFLHLAKKF-NH(2)) is an alpha-helical antimicrobial peptide designed from a cecropin A-magainin 2 hybrid. In this study, P18 was found to show strong antimicrobial activity against several antibiotic-resistant bacterial and fungal strains. Both the salt resistance on antimicrobial activity and the synergistic effect with clinically used antibiotic agents are critical factors in developing effective peptide antibiotic drugs. For this reason, we investigated the salt resistance of P18 to antagonism by NaCl, CaCl(2), and MgCl(2) on antimicrobial activity and the synergistic effect of P18 with vancomycin against vancomycin-resistant Enterococcus faecium (VREF). Compared to magainin 2, P18 showed strong resistance on antimicrobial activity against bacterial strains and C. albicans under high NaCl concentrations of 100-200 mM. In addition, P18 displayed much greater salt resistance on antibacterial activity against Gram-negative bacteria at the physiological or elevated concentrations of CaCl(2) and MgCl(2) than magainin 2. Furthermore, the combination study revealed that P18 has a relatively effective synergistic effect with vancomycin against VREF. Thus, these results support that P18 may prove to be a salt-resistant antibiotic peptide potentially useful in the treatment of cystic fibrosis patients as well as a valuable adjuvant for antimicrobial chemotherapy.


Vaginal delivery compared with elective caesarean section: the views of pregnant women and clinicians.
To quantify the risk of morbidity from vaginal delivery (VD) that pregnant women would be prepared to accept before requesting an elective caesarean section and to compare these views with those of clinicians. Cross-sectional survey. Major teaching hospital (nulliparas and midwives) and national samples of medical specialists. Nulliparas (n = 122), midwives (n = 84), obstetricians (n = 166), urogynaecologists (n = 12) and colorectal surgeons (n = 79). Face-to-face interviews (nulliparas) and mailed questionnaire (clinicians). Maximum level of risk participants would be prepared to accept before opting for an elective caesarean section for each of 17 potential complications of VD. Utility scores for each complication were calculated with higher scores (closer to 1) indicating a greater acceptance of risk. Pregnant women were willing to accept higher risks than clinicians for all 17 potential complications. They were least accepting of the risks of severe anal incontinence (mean utility score 0.32), emergency caesarean section (0.51), moderate anal incontinence (0.56), severe urinary incontinence (0.56), fourth-degree tears (0.59) and third-degree tears (0.72). The views of midwives were closest to those of pregnant women. Urogynaecologists and colorectal surgeons were the most risk averse, with 42 and 41%, respectively, stating that they would request an elective caesarean for themselves or their partners. Pregnant women were willing to accept significantly higher risks of potential complications of VD than clinicians involved in their care. Pregnant women's views were more closely aligned to midwives than to medical specialists.


Temporomandibular joint response to mandibular deviation in rabbits detected by 3D micro-CT imaging.
Micro-computed tomography enables continuous and dynamic observation of the three-dimensional morphology of small structures. We observed morphological changes of the temporomandibular joint condyle under mandibular deviation continuously in an animal model by micro-computed tomography. Twelve Dutch rabbits were used (9 as experimental and 3 as control). In the experimental rabbits, the mandible was deviated posteriorly on the left side using an elastic band. Bilateral temporomandibular joints were scanned by micro-computed tomography preoperatively and at 3, 6, and 12 weeks after the operation. Histopathological examination was also carried out to confirm the changes. It was shown that mandibular deviation induces condyle resorption in either ipsilateral or contralateral temporomandibular joint, which consequently makes the condyle smaller. Bone resorption settled down earlier in the contralateral joint and the quantity of bone resorption on the contralateral side was smaller than on the experimental side. Histopathological examination also showed destructive bone changes in the condyle, although they could not completely reflect the morphological changes. These results suggested that reduction of the condylar size occurred as an adaptive change to mandibular deviation.


[The echocardiogram in the first attack of rheumatic fever in childhood].
In order to evaluate the contribution of echocardiography (echo) in the first episode of rheumatic fever, 18 children (mean age: 8.5 +/- 2.9 years) observed between 1987 and 1992 have been retrospectively studied. In 11 of them the echo has been done in the first month after the initial episode. By M-Mode echo the most constant finding was a high left atrium: aorta ratio in all cases with clinical carditis. By 2D-echo, hyperechogenicity of mitral valve leaflets and subvalvular apparatus was a common finding, three patients having mitral valve prolapse, one with dilatation of the mitral ring and the other with leaflets not able to coapt. Doppler-echo displayed in 17 patients mitral valve regurgitation, and in three aortic regurgitation. In three children the diagnosis of carditis was made by echo in the absence of murmur. During follow-up mitral valve regurgitation disappeared in four children. The authors conclude that early echo is very important in all children suspected to have rheumatic fever, specially because mitral valve regurgitation can be demonstrated by color flow mapping even in the absence of cardiac murmur.


Randomized trial of postpartum care after hospital discharge.
Harmful effects of short postpartum hospital stays include dehydration and malnutrition of breastfed infants. These may be prevented by adequate breastfeeding frequency; however, rigorous research to determine the relative effectiveness of various follow-up strategies in supporting breastfeeding frequency is absent. This study addressed the question, "Is there a difference in breastfeeding frequency or infant weight gain for singleton infants discharged within 36 hours' postpartum who received either community nurse (home visit) or hospital nurse (clinic) follow-up?" A randomized, controlled trial was conducted at a university teaching hospital (3700 births/y) and affiliated community health centers. A consecutive sample of 586 healthy mother-infant pairs were recruited from January 1997 to September 1998 before discharge; 513 (87.5%) contributed data on 1 or more outcomes. Forty-eight-hour postpartum telephone contact and day 3 nurse contact in the home (experimental) or at the hospital (control) were provided. The main outcomes measured were breastfeeding frequency and infant weight gain assessed at 2 weeks' postpartum by maternal diary and weight at home by research assistants, masked to group allocation. No clinically important or statistically significant group differences were found in daily breastfeeding frequency (mean difference experimental minus control = 0.1 feeds [95% confidence interval: -0.1-0.3]) or daily rate of infant weight gain (-1.1 g [-2.5-0.3]) based on intention-to-treat analyses. Follow-up by nurses after short postpartum hospital stays, in either the home or a hospital-based clinic, of healthy infants discharged at <36 hours seems associated with satisfactory infant breastfeeding outcomes.


Remogliflozin etabonate : a novel SGLT2 inhibitor for treatment of diabetes mellitus.
Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) represent a new class of anti-hyperglycemic agents with a unique mechanism of action. These drugs lower blood glucose by increasing urinary glucose excretion. Remogliflozin etabonate (RE) is a prodrug of remogliflozin, an SGLT2 inhibitor under development. Areas covered: The following article reviews all of the clinical studies published regarding metabolism, drug interaction, safety and efficacy of RE in healthy subjects, patients with type 1 and type 2 diabetes. Expert opinion: Available data suggest low potential for RE to interact with other drugs affecting the P450 system. Compared with placebo, RE reduces hemoglobin A1c (HbA1c) levels by an average of 0.5 - 1.0% after 12 weeks of therapy in drug-naive patients with type 2 diabetes. Because of its relatively short half-life, RE may be slightly more effective when used twice daily than once daily. One preliminary study also showed that RE decreased plasma glucose levels in type 1 diabetes. Advantages of RE include modest weight loss of ∼ 2 kg, low risk of hypoglycemia, and a trend toward decrease in blood pressure. The commonest adverse effects of RE are genital mycotic infections, urinary tract infections, and dizziness. However, further studies are needed to establish its long-term safety and efficacy, and to determine whether it has specific advantages over currently approved SGLT2 inhibitors.


Sealing of gastrointestinal anastomoses with fibrin glue coated collagen patch.
Colorectal cancer (CRC) is the most common cancer of the gastrointestinal tract. In Denmark is CRC the 3. most frequent form of cancer and the 3. leading cause of cancer-related death. Anastomoses: Surgical resection is the only curative treatment of CRC and in Denmark about 85% of patients with CRC are therefore operated. An anastomosis will be established in most cases. Colorectal anastomoses are established in the treatment of benign diseases too, i.e. as part of the surgical treatment of inflammatory bowel disease and in acute surgery. Furthermore anastomoses are conducted in other parts of the gastrointestinal tract i.e. esophagus, stomach, small bowel and bile system. Anastomotic leakage (AL): AL is the most serious complication of gastrointestinal surgery with a 30-day mortality of 13-27%. The reported AL rate ranges from 1 to 39%. In addition to immediate clinical consequences AL is an independent predictor of reduced general and cancer-specific survival. Leakage can manifest as generalized peritonitis, requiring acute resurgery or as a more localized accumulation/abscess or as a subclinical leakage. Sealing of anastomoses: Numerous studies on anastomotic sealing have been conducted with the aim of reducing the number of AL's. The results of these are conflicting and predominantly disappointing. The drug Tacho-Sil (TS) consists of a collagen patch, which on the one side is coated with fibrin glue (FG), which gives it an adhesive property. TS is registered for use in surgical hemostasis. Animal models: Spontaneous AL in animals is infrequent. It is therefore necessary to use a model of AL. No such model exists and must be developed. To clarify if the sealing of anastomoses with TS is feasible and safe in an experimental design. To develop a standardized model of AL in pigs. To clarify if sealing of colon-anastomoses with TS can reduce the number of clinical ALs in an experimental design. To clarify whether there is evidence that FG influences healing of gastrointestinal anastomosis. Safety study, that examines whether it is safe to seal anastomoses with a TS. Experimental study on pigs. Two anastomoses on each pig, one sealed with TS. After 1-6 weeks of observation the anastomosis were examined for AL, stenoses, strength and compared microscopic. No difference between sealed and unsealed anastomosis. This study is completed and published. Model study, to develop model of AL on pigs. A total of 22 pigs had an anastomosis of colon. All anastomoses were left with a standardized defect on 5-21 mm. The pigs were observed in order to assess how big the defect should be before the pigs developed visible leakage and/or fecal peritonitis. Model developed. 21 mm defect significant. This study is completed and published. Efficacy study, testing if TachoSil can seal an AL and thus prevent that this becomes clinically significant. A total of 20 pigs had a colon-anastomoses with a standardized defect of 21 mm. The pigs were randomized to sealing with TS or no sealing. Re-laparotomy after 7 days examining for visible leakage and/or fecal peritonitis. TachoSil® able to seal the defect (p=0.0055). This study is completed and published. Systematic review, with the purpose to study whether there is evidence that FG influence the healing of gastrointestinal anastomosis. Conflicting. FG does not seem to have an effect. This study completed and published. Sealing of GI-anastomosis with TachoSil is safe and feasible. A defect of at least 21mm must be left in colon anastomosis to induce clinical peritonitis. Sealing of defect colon-anastomosis in pigs with TachoSil can prevent clinical leakage and peritonitis. FG has no positive effect on microscopically healing of GI-anastomosis.


Molecular cloning and sequence determination of a novel aspartic proteinase from Antarctic fish.
In the present report, we describe a novel aspartic proteinase from the liver of two Antarctic fish species. The nucleotide sequences of the cDNA obtained from the two fishes show 90% identity with each other but only 58% identity with aspartic proteinases from other sources. Sequence analysis shows features for the Antarctic enzymes which are not present in related enzymes of other organisms.


The role of depression in verbal memory following traumatic brain injury.
The purpose of this study was to characterize the relationship between verbal memory and depression scores on the Personality Assessment Inventory following traumatic brain injury. Depression was associated with diminished delayed recall and recognition on the California Verbal Learning Test-II (CVLT-II), even after controlling for a neuropsychological composite score and/or a measure of motivation (i.e., the TOMM). There was no relationship between depression and recall on Verbal Paired Associates or Logical Memory when controlling for the same covariates. The findings were most consistent with depressed subjects failing to utilize the semantic organization of the CVLT-II list to enhance their learning.


Manic-depressive psychosis in children younger than 15 years: a register-based investigation of 39 cases in Denmark.
Using a nationwide psychiatric case register covering a background population of 5.1 million inhabitants, 39 children (23 boys, 16 girls) were identified who got the diagnosis of manic-depressive psychosis between 1970 and 1986 before the age of 15. The frequency of manic-depressive psychosis in this child psychiatric population was 1.2%. The mean age for first-time admission with this diagnosis was 12.7 years. There was no sex difference. Twenty-six of the children got the diagnosis of manic-depressive psychosis during their first admission. Survival analysis was used to describe the prognosis and the diagnostic development of the group. As a whole, the group had a poor prognosis with many readmissions. The most common differential diagnoses were other types of psychosis in boys and oppositional and emotional disorders in girls.


Fitness study of the RDRio lineage and Latin American-Mediterranean family of Mycobacterium tuberculosis in the city of Rio Grande, Brazil.
RD(Rio) is a novel Mycobacterium tuberculosis lineage of the Latin American-Mediterranean (LAM) family. LAM has been found worldwide but is more predominant in South America. The aim of this study was to assess the presence of the RD(Rio) lineage and LAM family in the city of Rio Grande, Brazil, and to investigate the fitness of these strains based on determination of their growth rate. Fifty clinical isolates of M. tuberculosis were genotyped and 43 different patterns were found by spoligotyping and mycobacterial interspersed repetitive units-variable number of tandem repeats. The predominant genotypes belonged to the LAM family (54% of the strains) followed by clade T (22%) and Haarlem (16%). The RD(Rio) lineage represented 38% of the total strains and 70.4% of the LAM strains found in this study. Strains belonging to the LAM family showed a fitness advantage when comparing their rate of growth with that of non-LAM strains, but a significant difference between RD(Rio) and non-RD(Rio) strains was not confirmed.


Divergence of virulence factors of Helicobacter pylori among clinical isolates does not correlate with disease specificity.
The aim of this study was to examine the relation between disease specificity and the virulence factors of Helicobacter pylori isolated from patients with gastric cancer (GC), duodenal ulcer (DU), and gastritis (GS). Altogether 18 isolates obtained from patients with GC, 28 isolates from DU patients, and 13 isolates from GS patients were analyzed. All isolates were tested for the presence of the cagA gene, and genotyping of the vacA gene was done by the polymerase chain reaction. Production of VacA protein and expression of vacuolating cytotoxic activity in the H. pylori culture supernatant were examined. The serum antibody titers against purified VacA and CagA proteins were determined by enzyme-linked immunosorbent assay (ELISA). Interleukin-8 (IL-8) production by AGS cells in response to H. pylori isolates was measured by an hIL-8 ELISA kit. Genetic analysis of vacA revealed that most of the clinical isolates were classified into the S1a type by signal sequence typing. There were no differences in cagA detection rates, vacuolating cytotoxin activity, or mean antibody titers against VacA and CagA protein among the three groups. The mean IL-8 concentrations in the supernatants of AGS cells were similar in the three groups. In this study, there was no difference in virulence factors of H. pylori among isolates from GC, DU, and GS.


Does prey preference change as a result of prey species being presented together? Analysis of prey selection by the predatory mite Typhlodromus pyri (Acarina: Phytoseiidae).
Prey-selection behaviour of the phytoseiid mite Typhlodromus pyri Scheuten was analysed with a Markovtype model of feeding-state dynamics and feeding-state dependent searching behaviour (Sabelis 1981, 1986, 1989; Metz and Van Batenburg 1985a, b). All behavioural characteristics of the predator which are independent of the feeding state were represented by one parameter. The remaining feeding-state dependent characteristics were represented by a function of the feeding state, with one parameter. The best parameter values to describe a predator-prey interaction were determined by fitting the model to the predation rates in monocultures. Under the assumption that the parameter values are not dependent on the composition of prey species supply, the diet of the predators in mixed cultures was predicted from parameters estimated in monoculture experiments.Two prey types, apple rust mite (Aculus schlechtendali (Nalepa)) adults and European red spider mite (Panonychus ulmi (Koch)) larvae were studied. A large discrepancy was observed between calculated and experimentally determined predation rates of T. pyri in mixed cultures: the predators actually killed 3-7 times more P. ulmi larvae than was predicted by the model.The large difference between observed and predicted predation rates in mixed cultures cannot be explained by changes in the behaviour of the prey species as a result of being together. Therefore, it seems likely that the prey selection behaviour of the predator was different when prey species were presented together than when presented singly. Apparently the predatory mite T. pyri prefers P. ulmi to S. schlechtendali.


[A study on genetic polymorphism of rRNA gene pattern of Vibrio cholerae O139 in China].
To investigated the genetic polymorphism of the isolated strains using ribotyping method. One hundred twenty-two strains of V. cholerae O139 isolated from different areas of China from 1993 to 1999 were selected and characterized with ribotyping, including 16s rDNA and 23s rDNA probes. One hundred twenty-two strains were differentiated into 10 different ribotypes (RT1-RT10) on the basis of rRNA gene probes hybridization (with Bgl I digestion), which consisted of 7 - 9 bands between 12 and 1.5 kb in size. RT1 and RT3, as two predominant ribotypes, comprised most number of the strains which spread to the extensive range. Nine strains, which are negative to ctxAB, zot and RS individually, belong to 4 special ribotypes. The dendrogram revealing genetic relationship among different clones of V. cholerae O139 showed that the clones belonging to RT1 and RT2 had genetic similarity on high degree, although they were isolated from different regions. The two predominant ribotypes (RT1 and RT3) were distant in genetic relationship. Results showed the clonal diversity and the wide area distribution of V. cholerae O139 strains in China, suggesting the multiple origins of O139 epidemics.


Chlorogenic acid-enriched green coffee bean extract affects arterial stiffness assessed by the cardio-ankle vascular index in healthy men: a pilot study.
The effect of chlorogenic acid-enriched green coffee bean extract (cGCE) intake on arterial stiffness was investigated using the cardio-ankle vascular index (CAVI) as a novel surrogate marker for predicting arteriosclerosis. A placebo-controlled double-blind pilot study was conducted with 16 healthy Japanese men. Subjects were divided into two groups and consumed beverages containing either cGCE or placebo daily for 2 weeks. The CAVI, the primary endpoint of the study, was evaluated at the beginning of the study and 2 weeks later. Endothelium-dependent flow-mediated dilation (FMD) and sympathetic nervous activity (SNA), which are thought to be related to the CAVI, were also measured. The CAVI change was significantly greater in the cGCE group than in the placebo group. In addition, FMD increased and SNA decreased in the cGCE group. These findings suggest that 2-week ingestion of cGCE may improve arterial stiffness as assessed by the CAVI.