A new specific inhibitor of monoamine oxidase A.
A new propynylamine has been tested as an inhibitor of MAO. Loosely based upon the structure of clorgyline, it is an irreversible inhibitor of MAO A but is apparently indifferent towards MAO B. This compound, N1-(2,4-dinitrophenyl)-N2-prop-2-ynyl 1,3-diaminopropane, may be useful as a model for the design of more potent but equally specific inhibitors of MAO A.


[Pseudoaneurysm of the uterine artery: apropos of 1 case].
Pseudoaneurism of the uterine artery is uncommon and is usually associated with pregnancy or surgical trauma. Diagnosis is based on both Doppler sonography and arteriography. We report a case of pseudoaneurysm of the uterine artery associated with a leiomyoma without prior surgery or pregnancy. Treatment, which consisted on laparotomy, allowed avoiding rupture and confirmed diagnosis.


Assessment of a Competency-Based Undergraduate Course on Genetics and Genomics.
In response to new demands in the nursing profession, an innovative undergraduate genetics course was designed based on the Essential Nursing Competencies and Curricula Guidelines for Genetics and Genomics. Reflective journaling and storytelling were used as major pedagogies, alongside more traditional approaches. Thematic content analysis of student reflections revealed transformational learning as the major theme emerging from genomic and genetic knowledge acquisition. Quantitative analyses of precourse/postcourse student self-assessments of competencies revealed significant findings.


Vascular responsiveness in adrenalectomized rats with corticosterone replacement.
To determine under resting, unstressed conditions the circulating glucocorticoid concentrations that best maintain sensitivity of the vascular smooth muscle and baroreceptor responses to vasoactive agents, rats with vascular cannulas were sham-adrenalectomized (sham) or adrenalectomized (ADRX) and provided with four levels of corticosterone replacement (approximately 100 mg fused pellets of corticosterone: cholesterol 0, 20, 40, and 80% implanted subcutaneously at the time of adrenal surgery). Changes in vascular and baroreflex responses were determined after intravenous injection of varying doses of phenylephrine and nitroglycerin with measurement of arterial blood pressure and heart rate in the conscious, chronically cannulated rats. Vascular sensitivity was decreased, and resting arterial blood pressure tended to be decreased in the adrenalectomized rats; both were restored to normal with levels of corticosterone (40%), which also maintained body weight gain, thymus weight, and plasma corticosteroid binding globulin concentrations at normal values. The baroreflex curve generated from the sham group was different from the curves generated from the ADRX+0, 20, and 40% groups, but not different from that of the ADRX+80% group, suggesting that the baroreflex is maintained by higher levels of corticosterone than are necessary for the maintenance of the other variables. These data demonstrate that physiological levels of corticosterone (40% pellet) restore vascular responsiveness, body weight, thymus weight, and transcortin levels to normal in ADRX rats, whereas higher levels (80% pellet) are necessary for restoration of the baroreflex.


[T(H1) and T(H2) cells in children with mycoplasma pneumonia].
To Study T lymphocyte subsets, including T(H1) and T(H2) cells in peripheral blood mononuclear cells (PBMC) of children with mycoplasma pneumonia, understand immunopathogenesis and explore the possibility of immunotherapy of patients with mycoplasma pneumonia. Fresh peripheral blood samples of patients from two groups, group 1, mycoplasma pneumonia (MP) group (35 cases, 15 males and 20 females, age range 3 - 13 years, mean 9 years), and control group consisted of 28 healthy children (14 males and 14 females, age range 3 - 12 years, mean 7 years) were treated and run through the flow cytometry. The data were obtained by using Simultest IMK-Lymphocyte software and the percentage of CD(3)(+), CD(3)(+)CD(4)(+), CD(3)(+)CD(8)(+), CD(3)(-)CD(19)(+) and CD(3)(-)CD(16 + 56)(+) cells were counted. The percentage of T(H1) and T(H2) cells were gained through determination of intracellular cytokines IFN-gamma or IL-4 in CD(4)(+) cells by flow cytometry. The 35 patients with MP were hospitalized at our hospital. In addition to fever and cough, all the patents had abnormal X-ray findings and/or moist rale on auscultation of the lungs. The IgM antibody to Mycoplasma pneumoniae was positive in each patient. Immunoglobulins were measured, and PPD skin tests were performed in 30 out of the 35 patients with MP. T test and rank sum test by SPSS FOR WINDOWS 10.0 was used for statistical analysis. The percentage of CD(3)(+) and CD(4)(+) T lymphocyte was 68.00 +/- 6.66 and 37.86 +/- 5.84, respectively, in MP group, and 63.71 +/- 7.92 and 34.54 +/- 6.23 in control group (P < 0.05). The percentage of T(H1) cells was 14.13 +/- 8.46 in patients and 20.77 +/- 6.89 in normal control group (P = 0.001). The percentage of NK cells was 15.57 +/- 12.16 and 20.39 +/- 9.64 in MP and control group (P < 0.01). The ratio of T(H1)/T(H2) in MP group was lower than that in control group (P < 0.05). However the percentage of CD(8), T(H2), B cells and CD(4)/CD(8) had no difference between the MP and control groups. The levels of IgG, IgA, and IgM in serum were normal in most of patients except for a few patients who had elevated IgA and IgM levels. The PPD skin tests were negative in 30 out of 35 patients. In this study a higher percentage of CD(3)(+), CD(4)(+) T lymphocyte and lower percentage of T(H1), NK cells in PBMC of patients with mycoplasma pneumonia were found. The ratio of T(H1) and T(H2) cells in patients was also lower. None of thirty patients had positive PPD skin tests. Unbalanced cell-mediated immunity with a tendency toward T(H2) existed in patients with MP. Therefore, immunomodulators may be useful in treatment of mycoplasma pneumonia.


Modified nucleosides in urine: selective removal and analysis.
Because excretion of certain nucleosides increases in all types of cancer, detection and treatment of the disease would be enhanced by rapid, simple quantitation of such nucleotides. To facilitate these analyses in urine, we have prepared a specific adsorbent for nucleosides. The affinity adsorbent gel contains an immobilized phenylboronic acid group that specifically binds cis-diols, as in ribonucleosides, which can then be quantititatively recovered by elution with acetic acid. The advantage of this boronate gel over other preparations lies in its high capacity in the swollen state (0.26 mmol/ml), so that only small volumes (less than 1 ml) of gel are required for assays. Nucelosides containing a free diol group on the ribosyl group are retained at pH 8.8 in 0.25 mol/liter salt solution with a retention volume of 15 or larger, as compared with values of 1 to 2 for the free bases. Negatively charged species (not including the boronate complex) are eluted earlier than neutral or cationic species. Added nucleosides (neutral, cationic, or anionic) are quantitatively recovered. Because pseudouridine is eluted in a unique position, this property has been used to measure it in urine. The procedures used are chemically mild. For example, we have confirmed the observation of Fink and Adams [Arch. Biochem. Biophys. 126, 27 (1968)] that urine contains N1-methyladenosine and not N6-methyladenosine, the alkaline rearranged product.


Red cell values on the first postnatal day during the last 16 weeks of gestation.
The hemoglobin concentration, red cell count, hematocrit, reticulocyte count, and red cell size distribution were determined on skin prick blood obtained on the first postnatal day from infants born at various stages of gestation, from week 24 to term. During this period the hemoglobin concentration and hematocrit remained constant, around 19 gm/100 ml and 60%, respectively. The mean corpuscular volume decreased progressively, with a corresponding rise in the red cell count. The reticulocyte count decreased progressively from 9.6% to 3.7% during the period of observation. The red cell size distribution (Price Jones) curve was markedly shifted to the macrocytic side at 24-25 weeks. Thereafter, cells larger than 102 mu3 decreased gradually, while the percentage of smaller cells increased. These observations are not consistent with the hypothesis of a progressive decrease in the supply of oxygen to the fetus during the later stages of gestation, to which the fetus adapts by increasing its hemoglobin concentration.


Reference method for detection of Pgp mediated multidrug resistance in human hematological malignancies: a method validated by the laboratories of the French Drug Resistance Network.
Multidrug resistance (MDR) associated with overexpression of the MDR1 gene and of its product, P-glycoprotein (Pgp), plays an important role in limiting cancer treatment efficacy. Many studies have investigated Pgp expression in clinical samples of hematological malignancies but failed to give definitive conclusion on its usefulness. One convenient method for fluorescent detection of Pgp in malignant cells is flow cytometry which however gives variable results from a laboratory to another one, partly due to the lack of a reference method rigorously tested. The purpose of this technical note is to describe each step of a reference flow cytometric method. The guidelines for sample handling, staining and analysis have been established both for Pgp detection with monoclonal antibodies directed against extracellular epitopes (MRK16, UIC2 and 4E3), and for Pgp functional activity measurement with Rhodamine 123 as a fluorescent probe. Both methods have been validated on cultured cell lines and clinical samples by 12 laboratories of the French Drug Resistance Network. This cross-validated multicentric study points out crucial steps for the accuracy and reproducibility of the results, like cell viability, data analysis and expression.


Extracorporeal shock wave therapy improves the walking ability of patients with peripheral artery disease and intermittent claudication.
Despite the recent advances in bypass surgery and catheter interventional therapy for peripheral artery disease (PAD), the long-term outcome of revascularization therapy for infrapopliteal lesions remains unsatisfactory. We have previously demonstrated that low-energy extracorporeal shock wave (SW) therapy effectively induces neovascularization through upregulation of angiogenic factors and improves myocardial ischemia in pigs and humans and in hindlimb ischemia in rabbits. In this study, we thus examined whether our SW therapy also improves the walking ability of patients with PAD and intermittent claudication. We treated 12 patients (19 limbs) in Fontaine II stage (males/females, 10/2; 60-86 years old) with low-energy SW therapy to their ischemic calf muscle 3 times/week for 3 consecutive weeks. After 24 weeks, the pain and distance subscale scores of the walking impairment questionnaire were significantly improved (33±25 vs. 64±26, 27±16 vs. 64±23, respectively, both P<0.01). Maximum walking distance was also significantly improved at 4 weeks (151±37% from baseline, P<0.01) and was maintained at 24 weeks (180±74% from baseline, P<0.01). Moreover, the recovery time of the tissue oxygenation index in the calf muscle during a treadmill test, which reflects local O<inf>2</inf> supply, was significantly shortened (295±222s vs. 146±137s, P<0.01). Importantly, no adverse effects were noted. Non-invasive SW therapy improves the walking ability of PAD patients.


Novel insights into epithelial polarity proteins in Drosophila.
Apical-basal polarity is a basic organizing principle of epithelial cells. Consequently, defects in polarity are associated with numerous human pathologies, including many forms of cancer. Recent work in Drosophila has identified novel roles for, or has greatly enhanced our understanding of, functional modules within the epithelial polarity network. A series of recent papers have highlighted the key function of the scaffolding protein Bazooka/Par3 as an early polarity landmark, and its crucial role in dynamic segregation of the apical membrane from the adherens junction. Moreover, novel polarity modules have recently been discovered; the Yurt/Coracle group supports the basolateral membrane during a defined time window of development, while a second module, including the kinases LKB1 and AMP-activated protein kinase, is required for polarity when epithelial cells experience metabolic stress. These new findings emphasize unforeseen complexities in the regulation of epithelial polarity, and raise new questions about the mechanisms of epithelial tissue organization and function.


Leucobacter corticis sp. nov., isolated from symptomatic bark of Populus × euramericana canker.
A Gram-stain-positive, aerobic, non-motile, rod-shaped bacterial strain, designated 2C-7T, was isolated from symptomatic bark of a Populus × euramericana canker. Growth occurred between 10 and 37 °C and between pH 6 and 10, with optimal growth at 30 °C and pH 7.0-8.0. Growth was present under 0-8 % (w/v) salinity conditions (optimum 1-2 %). Growth occurred in the presence of 10 mM chromium (Cr6+). The major fatty acids (≥10 %) of the novel strain were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phospholipid, glycolipid and two unknown lipids. The major respiratory quinone was menaquinone MK-11. The cell wall amino acids were 2,4-diaminobutyric acid, alanine, glutamic acid and glycine. Strain 2C-7T was most similar to Leucobacter celer subsp. celer NAL101T (97.2 % 16S rRNA gene sequence similarity), 'Leucobacter kyeonggiensis' F3-P9T (97.1 %) and Leucobacter chromiireducens L-1T (97.1 %). In the phylogenetic tree, the isolate formed a single distinct branch separate from those of L. celer subsp. celer NAL101T, 'L. kyeonggiensis' F3-P9T and Leucobacter chironomi DSM 19883T. The DNA-DNA hybridization values between the novel strain and the reference strains were lower than the accepted bacterial threshold level of 70 % for species delineation. The DNA G+C content of strain 2C-7T was 70.0 mol%. Based on the data, strain 2C-7T represents a novel species in the genus Leucobacter, for which the name Leucobacter corticis sp. nov. is proposed. The type strain is 2C-7T (=CFCC 11901T=KCTC 39643T).


Environmental safety to decomposer invertebrates of azadirachtin (neem) as a systemic insecticide in trees to control emerald ash borer.
The non-target effects of an azadirachtin-based systemic insecticide used for control of wood-boring insect pests in trees were assessed on litter-dwelling earthworms, leaf-shredding aquatic insects, and microbial communities in terrestrial and aquatic microcosms. The insecticide was injected into the trunks of ash trees at a rate of 0.2 gazadirachtin cm(-1) tree diameter in early summer. At the time of senescence, foliar concentrations in most (65%) leaves where at or below detection (<0.01 mg kg(-1) total azadirachtin) and the average concentration among leaves overall at senescence was 0.19 mg kg(-1). Leaves from the azadirachtin-treated trees at senescence were added to microcosms and responses by test organisms were compared to those in microcosms containing leaves from non-treated ash trees (controls). No significant reductions were detected among earthworm survival, leaf consumption rates, growth rates, or cocoon production, aquatic insect survival and leaf consumption rates, and among terrestrial and aquatic microbial decomposition of leaf material in comparison to controls. In a further set of microcosm tests containing leaves from intentional high-dose trees, the only significant, adverse effect detected was a reduction in microbial decomposition of leaf material, and only at the highest test concentration (∼6 mg kg(-1)). Results indicated no significant adverse effects on litter-dwelling earthworms or leaf-shredding aquatic insects at concentrations up to at least 30 × the expected field concentrations at operational rates, and at 6 × expected field concentrations for adverse effects on microbial decomposition. We conclude that when azadirachtin is used as a systemic insecticide in trees for control of insect pests such as the invasive wood-boring beetle, emerald ash borer, resultant foliar concentrations in senescent leaf material are likely to pose little risk of harm to decomposer invertebrates.


Development of the stapedius muscle canal and its possible clinical consequences.
To study the development of the stapedius muscle canal in human embryos and foetuses. 46 temporal bones with ages between 9mm and new-borns were studied. The preparations were dyed using Martins' trichrome technique. Two areas of different embryological origin form the stapedius muscle canal, which contains this muscle and the facial nerve. On the otic capsule, at 11 weeks an extension starts to grow from its caudal part, which moves outwards and near to Reichert's cartilage, forming the footplate and internal wall. The pyramidal eminence comes from the mesenchyme that surrounds the muscle, forming a partition to separate it from the laterohyale portion of Reichert's cartilage. Extensive connections are observed in its development between bone marrow and mesenchyme. At 35 weeks the muscle and nerve start to separate by means of a bony partition. If this partition does not form, there is going to be a dehiscence that could cause peripheral nerve pathology due to the repeated contraction of the muscle, or the dissemination of infections from middle ear. During the development of the stapedius muscle canal the presence of dehiscences between the facial nerve and the muscle may have clinical repercussions.


Acute Breast Implant Periprosthetic Cerebrospinal Fluid Collection After Ventriculoperitoneal Shunt Migration: A Case Report and Review of Literature.
Ventriculoperitoneal shunt (VPS) placement is a common neurosurgical procedure with a high rate of distal catheter malfunction. Rarely, the catheter may migrate to other tissues in the body including the breast pockets. There are increasing odds that a patient may undergo both breast augmentation and VPS placement, because breast augmentation is the most common aesthetic surgical procedure. Complications are possible with both surgical procedures. Proximal migration of the distal aspect of a VPS into the breast pocket containing an implant is a rare complication. We hereby present a successful management of VPS migration with implant salvage and culture-directed antibiotics using a careful no touch technique by avoiding breast incision and washout, or percutaneous drainage, and using the existing VPS as an in situ drainage access point for CSF fluid aspiration and culture.


Individual and combined effects of heat stress and aqueous or dietary copper exposure in fathead minnows (Pimephales promelas).
Despite its role as an essential micronutrient, copper (Cu) can be present in aquatic ecosystems at concentrations able to cause adverse health effects on aquatic organisms. Although Cu is acquired by fish by either water or diet, studies that have investigated Cu impacts in fish have mainly focused on the toxicity of waterborne Cu. Moreover, as the majority of experiments were carried out under simplified conditions, little is known about the effects of natural factors other than competitive ions on Cu toxicity in fish. As temperature is a primary factor that affects the physiological state of poikilotherm organisms, we investigated the individual and combined effects of temperature and waterborne or dietary Cu on fathead minnows (Pimephales promelas). Fish were exposed to environmentally realistic concentrations of waterborne or dietary Cu at 20 °C and 32 °C. Transcriptional and enzymatic responses of various indicators of metabolic capacities as well as indicators of heat, oxidative and metal stresses were measured in fish muscle. Under our experimental conditions, temperature was the most important factor affecting the general condition of fish. Although no significant Cu accumulation was observed in the muscle of Cu-exposed fish, at 20 °C, waterborne and dietary Cu triggered significant changes in the transcription level of genes encoding for proteins involved in energy metabolism, metal detoxification and protein protection. Moreover, the response was quantitatively more important for dietary Cu than for waterborne Cu. Combined exposure to heat and Cu triggered the most significant changes in gene transcription levels and enzyme activities. During combined exposure to heat and Cu, in addition to synergistic effects of the two factors, both waterborne and dietary Cu impaired the adaptive response developed by fish to curb heat stress. Reciprocally, temperature impaired the adaptive response developed by fish to combat Cu toxicity. These results suggest that wild fish populations subjected to elevated temperatures due to seasonal warming or global climate change may become more susceptible to Cu pollution, and vice versa.


A study of basal movement with rapid maxillary expansion.
This investigation was undertaken to examine the effect of rapid maxillary expansion horizontally and posterior to the dental arch, there being some doubt that the expansion would be carried in this dimension and whether dilation of the non-tooth-bearing bones (palatines and sphenoidal pterygoid processes) was possible. The increases in the intermolar arch widths and the interpterygoid hamular widths were recorded in a group of thirty-two orthodontic patients. (twelve male and twenty female, aged 8 to 24 years), before and after rapid maxillary expansion. The mean percentage increase in interhamular widths to intermolar widths was 58 percent (range, 35 percent to 89 percent). The correlation between the relative increases was weak (r = +0.55). A slight reduction in the percentage increases in interhamular widths to intermolar widths as age advanced suggested an age factor, but the correlation was very weak (r = -0.33). From this evidence, it would seem that rapid maxillary expansion will separate the palatine bones and splay outward the pterygoid processes of the sphenoid bone.


Pancreatic beta-cell dysfunction as the primary genetic lesion in NIDDM. Evidence from studies in normal glucose-tolerant individuals with a first-degree NIDDM relative.
To test the hypothesis that insulin resistance precedes impaired insulin secretion in individuals genetically predisposed to non-insulin-dependent diabetes mellitus (NIDDM). Case-control study. Outpatient facility of clinical research center. One hundred volunteers of European ancestry having normal glucose tolerance, 50 with and 50 without a first-degree NIDDM relative, matched for age, sex, and degree of obesity. Insulin secretion and insulin sensitivity assessed by hyperglycemic (N = 100) and euglycemic-hyperinsulinemic (N = 62) clamp experiments. The individuals with a first-degree NIDDM relative had reduced first- and second-phase insulin responses (mean +/- SEM, 939 +/- 68 vs 1209 +/- 82 pmol/L, and 322 +/- 19 vs 407 +/- 24 pmol/L, respectively, P = .001 and .01), but their insulin sensitivity (148 +/- 6 and 92 +/- 6 nmol.kg-1.min-1/pmol.L-1 in hyperglycemic and euglycemic clamp studies) did not differ from that of the control group (126 +/- 5 and 81 +/- 7 nmol.kg-1.min-1/pmol.L-1, in hyperglycemic and euglycemic clamp studies, P = .07 and .24, respectively). In some individuals only first- or only second-phase insulin responses were reduced. In this study population, heterogeneous defects in insulin secretion were demonstrated, while defects in insulin sensitivity were not evident. We therefore conclude that since the earliest defects identified in a group genetically at high risk to develop NIDDM are those related to insulin secretion, defects in insulin secretion rather than insulin sensitivity are likely the major genetic factor predisposing to development of NIDDM.


Recent topics on single-molecule fluctuation analysis using blinking in surface-enhanced resonance Raman scattering: clarification by the electromagnetic mechanism.
Surface-enhanced Raman scattering (SERS) spectroscopy has become an ultrasensitive tool for clarifying molecular functions on plasmonic metal nanoparticles (NPs). SERS has been used for in situ probing of detailed behaviors of few or single molecules (SMs) at plasmonic NP junctions. SM SERS signals are commonly observed with temporal and spectral changes known as "blinking", which are related to various physical and chemical interactions between molecules and NP junctions. These temporal and spectral changes simultaneously take place, therefore resulting in serious complexities in interpretations of the SM SERS results. Dual contributions of Raman enhancement mechanisms in SERS (i.e., electromagnetic (EM) and chemical enhancements) also make interpretations more difficult. To resolve these issues and reduce the degree of complexities in SM SERS analyses, the present review is focused on the recent studies of probing SM behaviors using SERS exclusively within the framework of the EM mechanism. The EM mechanism is briefly introduced, and several recent topics on SM SERS blinking analysis are discussed in light of the EM mechanism. This review will provide a basis for clarification of complex SERS fluctuations of various molecules.


International study on Sagliker syndrome and uglifying human face appearance in severe and late secondary hyperparathyroidism in chronic kidney disease patients.
It is known that skeletal changes due to secondary hyperparathyroidism (SH) can be severe in chronic kidney disease (CKD). Recently described Sagliker syndrome (SS) is a very striking and prominent feature of SH in CKD, including an uglifying appearance to the face, short stature, extremely severe maxillary and mandibulary changes, soft tissue in the mouth, teeth/dental abnormalities, fingertip changes, knee and scapula deformities, hearing abnormalities, and neurological and, more important, severe psychological problems. In the past 8 years, we have encountered 40 cases of SS in SH and CKD by performing an international study in Turkey, India, Romania, Egypt, Maleysia, Tunis, and China. The medical history of these patients showed that they did not receive proper therapy. Changes, particularly in children and teenagers, become irreversible, which was disastrous for the patients both aesthetically and psychologically. Treatment must begin early and be the appropriate treatment given in centers with sophisticated skills. Otherwise, the inability to correct all the changes in the skull and face, to remodel a new face, to extending the height, and, most important, to convince the patients to face the dramatic psychological problems can be catastrophic for those patients.


Dosimetric characteristics of Novalis shaped beam surgery unit.
The dosimetric characteristics of a new dedicated radiosurgical treatment unit are systematically measured in terms of its percent depth dose, beam profile, and relative scatter factor. High-resolution diode detector, mini-ion-chamber detector, and conventional Kodak XV films are used to measure dosimetric data for a range of field sizes from 6x6 mm to 100x100 mm. The effects of collimator size, micro-multileaf collimator shape, and detector type on the dosimetric data are investigated. Results indicate that, with careful design, accurate dosimetric data could be acquired using either a dedicated diode detector or a mini-ion-chamber detector, and film detector. Special attention is required when measuring dosimetric data for small field sizes such as 6x6 mm.


Personalised fish intake recommendations: the effect of background exposure on optimisation.
National dietary guidelines are directed at the general population. However, these guidelines may be perceived as unrealistic by a substantial part of the population, as they differ considerably from individual consumption patterns and preferences. Personalised dietary recommendations will probably improve adherence, and it has been shown that these recommendations can be derived by mathematical optimisation methods. However, to better account for risks and benefits of specific foods, the background exposure to nutrients and contaminants needs to be considered as well. This background exposure may come from other foods and supplements, and also from environmental sources like the air and the sun. The objective of this study was therefore to analyse the effect of including individual variation in background exposure when modelling personalised dietary recommendations for fish. We used a quadratic programming model to generate recommended fish intake accounting for personal preference by deviating as little as possible from observed individual intake. Model constraints ensure that the modelled intake meets recommendations for EPA, DHA and vitamin D without violating tolerable exposure to methyl mercury, dioxins and dioxin-like polychlorinated biphenyls. Several background exposures were analysed for 3016 Danish adults, whose food intakes and body weights were reported in a national dietary survey. We found that the lower nutrient constraints were critical for the largest part of the study population, and that a total of 55% should be advised to increase their fish intake. The modelled fish intake recommendations were particularly sensitive to the vitamin D background exposure.


Regression of IgA nephropathy: a repeat biopsy study.
Histological cure of immunoglobulin A (IgA) nephropathy has been reported only rarely in adults. To elucidate the reversibility of established IgA nephropathy, we performed a repeat biopsy study. A second biopsy was performed in 35 patients with IgA nephropathy in whom hematuria, an essential finding of IgA nephropathy, had disappeared (proteinuria also had disappeared in 23 patients) after a treatment protocol involving high doses of methylprednisolone and tonsillectomy. The interval between the first and second biopsy was 18 to 138 months (mean, 77.1 months). Mean serum creatinine level was 1.11 +/- 0.35 (SD) mg/dL (range, 0.6 to 1.9 mg/dL) at the time of the first biopsy and 0.96 +/- 0.24 mg/dL at the time of the second biopsy. Mesangial proliferation was significantly reduced in second-biopsy specimens (mesangial proliferation score: first-biopsy specimens, 2.49 +/- 0.74; second-biopsy specimens, 0.91 +/- 0.89; P < 0.001). Acute inflammatory glomerular lesions, such as endocapillary proliferations, glomerular tuft necrosis, and cellular crescents, were present in 32 patients in first-biopsy specimens, whereas these were no longer present in any of the second-biopsy specimens. Although no significant difference in percentage of globally sclerotic glomeruli was observed between the first and second biopsy specimens, the percentage of segmentally sclerotic glomeruli was significantly lower in second-biopsy specimens (P < 0.001). Interstitial mononuclear cell infiltration was markedly reduced in second-biopsy specimens (P < 0.001). The area of renal cortex affected by interstitial fibrosis and/or edema was significantly reduced in second-biopsy specimens (first-biopsy specimens, 21.4% +/- 20.3%; second-biopsy specimens, 9.6% +/- 11.7%; P < 0.01). The distribution of IgA mesangial deposits had diminished in most patients, and no IgA deposits were seen in second-biopsy specimens from 8 patients. These findings indicate that mesangial proliferation and interstitial changes in IgA nephropathy are reversible to a considerable extent. A histological cure may be obtainable in a considerable proportion of patients, especially if treatment is initiated at a relatively early stage.


The amino acid sequence of the enterotoxin from Clostridium perfringens type A.
The amino acid sequence of the enterotoxin from Clostridium perfringens type A was determined by analysis of peptides derived from the protein by digestion with trypsin chymotrypsin, thermolysin, pepsin, a lysine-specific protease. S. aureus V8 protease and a proline-specific protease, and fragments generated by cleavage with cyanogen bromide or by dilute acetic acid in 7 M guanidine HCl. The sequence which is complete except for the definite order of 3 small peptides between residues 88 and 103 consists of 309 amino acids and contains a correction to our preliminary announcement [(1984) FEMS Symp. 24, 329-330].


Temporal changes in treatments and outcomes after acute myocardial infarction among cancer survivors and patients without cancer, 1995 to 2013.
There is a paucity of information about treatment and mortality trends after acute myocardial infarction (AMI) for cancer survivors (CS). In this population-based study, the authors compared temporal trends of treatments and outcomes (mortality, nonfatal cardiovascular outcomes), among CS and patients without cancer (the noncancer patient [NCP] group) with AMI in Ontario (Canada) using inverse probability treatment weight (IPTW)-adjusted modeling. Of 270,089 patients with AMI (22,907 CS, 247,182 NCP, 1995-2013; median follow-up, 10.1 and 11.0 years, respectively), the use of invasive coronary strategies and pharmacotherapies increased and mortality declined for CS and NCP (all Ptrend < .001). At 30 days after AMI, there was no difference between CS and NCP in the receipt of coronary angiography (incidence risk ratio [IRR], 0.98; 95% confidence interval [CI], 0.96-1.01; P = .23), percutaneous coronary intervention (IRR, 0.98; 95% CI, 0.94-1.02; P = .29), or bypass (IRR, 0.93; 95% CI, 0.85-1.02; P = .11). At 90 days after AMI, there was no difference in the receipt of β-blockers, clopidogrel, or nitrates; but CS were less often prescribed angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and statins. CS had higher all-cause mortality at 30 days (adjusted hazard ratio [HR] 1.12; 95% CI, 1.07-1.17; P < .001), at 1 year (1.16; 95% CI, 1.12-1.20; P < .001), and long term (HR, 1.21; 95% CI, 1.17-1.25; P < .001) and had a greater risk of heart failure (HR, 1.08; 95% CI, 1.03-1.14; P = .001), but not myocardial re-infarction (HR, 0.98; 95% CI, 0.95-1.01; P = .22) or stroke (HR, 1.06; 95% CI, 0.97-1.16; P = .18). Among CS and NCP with AMI in Ontario, similar improvements in mortality and receipt of treatments were observed between 1995 and 2013. However, compared with NCP, CS had a higher risk of mortality and heart failure. Cancer 2018;124:1269-78. © 2017 American Cancer Society.


[Microbiological studies of small hot-bath-pools and hot-whirl-pools (author's transl)].
Hot small bathing pools and hot whirl-pools have the following characteristics: small watervolume, thick squeeze of swimmers, high water temperature (37-40 degrees C) and small dimension of filters. By this, the quality of bathing-water is influenced detrimentally. To elaborate the hygienic problems, bathing-water samples were taken before, during and after the visiting-hours and were tested for facultative-pathogenic microorganisms. During this investigation E. coli was isolated in 25 degrees, Coliforms and Proteus species in 37.3%, P. aeruginosa in 36%, S. aureus in 26.3%, Enterococci in 42.3 %, Candida albicans in 3.6% and yeast totally in 8.3%.


Neuroadaptations to antipsychotic drugs: Insights from pre-clinical and human post-mortem studies.
Antipsychotic drugs, all of which block the dopamine D2 receptor to a greater or lesser extent, are the mainstay for the pharmacological treatment of schizophrenia. Engaging in a deeper understanding of how antipsychotics act on the brain and body, at the cellular, molecular and physiological level is vital to comprehend both the beneficial and potentially harmful actions of these medications and stimulate development of novel therapeutics. To address this, we review recent advances in our understanding of neuroadaptations to antipsychotics, focusing on (1) treatment efficacy, (2) impact on brain volume and (3) evidence from human post-mortem studies that attempt to dissect neuropathological effects of antipsychotic drugs from organic schizophrenia neurobiology and (4) cardio-metabolic side effects. Our aim is to stimulate discussion on these highly clinically relevant topics and consider how we might use current and evolving knowledge and new methodologies in the fields of neuropharmacology and neuroscience, to advance our understanding of the long-term impact of antipsychotic treatment. Ultimately, this may inform the clinical use of these drugs.


SCD5-induced oleic acid production reduces melanoma malignancy by intracellular retention of SPARC and cathepsin B.
A proper balance between saturated and unsaturated fatty acids (FAs) is required for maintaining cell homeostasis. The increased demand of FAs to assemble the plasma membranes of continuously dividing cancer cells might unbalance this ratio and critically affect tumour outgrowth. We unveiled the role of the stearoyl-CoA desaturase SCD5 in converting saturated FAs into mono-unsaturated FAs during melanoma progression. SCD5 is down-regulated in advanced melanoma and its restored expression significantly reduced melanoma malignancy, both in vitro and in vivo, through a mechanism governing the secretion of extracellular matrix proteins, such as secreted protein acidic and rich in cysteine (SPARC) and collagen IV and of their proteases, such as cathepsin B. Enforced expression of SCD5 or supplementation of its enzymatic product, oleic acid, reduced the intracellular pH (pHe > pHi) and, in turn, vesicular trafficking across plasma membranes as well as melanoma dissemination. This intracellular acidification appears also to depend on SCD5-induced reduction of the C2 subunit of the vacuolar H(+) -ATPase, a proton pump whose inhibition changes the secretion profile of cancer cells. Our data support a role for SCD5 and its enzymatic product, oleic acid, in protection against malignancy, offering an explanation for the beneficial Mediterranean diet. Furthermore, SCD5 appears to functionally connect tumour cells and the surrounding stroma toward modification of the tumour microenvironment, with consequences on tumour spread and resistance to treatment.


Chromatin tethering and retroviral integration: recent discoveries and parallels with DNA viruses.
Permanent integration of the viral genome into a host chromosome is an essential step in the life cycles of lentiviruses and other retroviruses. By archiving the viral genetic information in the genome of the host target cell and its progeny, integrated proviruses prevent curative therapy of HIV-1 and make the development of antiretroviral drug resistance irreversible. Although the integration reaction is known to be catalyzed by the viral integrase (IN), the manner in which retroviruses engage and attach to the chromatin target is only now becoming clear. Lens epithelium-derived growth factor (LEDGF/p75) is a ubiquitously expressed nuclear protein that binds to lentiviral IN protein dimers at its carboxyl terminus and to host chromatin at its amino terminus. LEDGF/p75 thus tethers ectopically expressed IN to chromatin. It also protects IN from proteosomal degradation and can stimulate IN catalysis in vitro. HIV-1 infection is inhibited at the integration step in LEDGF/p75-deficient cells, and the characteristic lentiviral preference for integration into active genes is also reduced. A model in which LEDGF/p75 acts to tether the viral preintegration complex to chromatin has emerged. Intriguingly, similar chromatin tethering mechanisms have been described for other retroelements and for large DNA viruses. Here we review the evidence supporting the LEDGF/p75 tethering model and consider parallels with these other viruses.


[Synthesis of new nitrosoureas].
Two chemical pathways were used for the synthesis of three new N'-(2-chloroethyl)-N-[2-(4-alkoxyphenylthio)ethyl]-N'-nitrosoureas and two new N'-(2-chloroethyl)-N)[2-(4-alkoxyphenyl-thio)ethyl]-N-nitrosoureas . The study of the cytotoxicity of the three N'-nitrosoureas, was carried out in two experimental models (P 388 and NSCLCN6).


Effect of a controlled-release urea supplement on rumen fermentation in sheep fed a diet of sugar cane tops (Saccharum officinarum), corn stubble (Zea mays) and King grass (Pennisetum purpureum).
Four cannulated sheep were used to study ruminal fermentation of a diet consisting of 60% sugar cane tops (Saccharum officinarum), 30% corn stubble (Zea mays), 10% King grass (Pennisetum purpureum) and 0% (control), 10, 20 or 30% controlled-release urea supplement (CRUS) (diets 1, 2, 3 and 4, respectively). Average ruminal pH did not differ among diets (P>0.05), but during the first 6h of sampling tended to be higher for CRUS diets. Ammonia concentrations were higher (P<0.01) in all treatments over controls, indicating microbial protein generation. Acetic acid production (mM/1) decreased (P<0.05), propionic acid increased (P<0.05), while butyric acid production did not differ among CRUS diets and controls (P>0.05). Total amounts of ruminal VFA were lowest (P<0.01) in controls, while CRUS diets produced more of these energy sources. Supplementation of the high fiber diets with 10, 20 or 30% CRUS increasingly improved rumen fermentation, ammonia supply and VFA production. The results show that low quality forages (up to 70% DMI) can be used efficiently by sheep when conditions for ruminal microorganism are improved with a controlled-release urea supplement.


PLGA nanoparticles of different surface properties: preparation and evaluation of their body distribution.
The opsonization or removal of nanoparticulate drug carriers from the body by the reticuloendothelial system (RES) is a major obstacle that hinders the efficiency of the nanoparticulate drug delivery systems. Therefore, several methods of camouflaging or masking nanoparticles (NPs) have been developed to increase their blood circulation half-life. In this study, rhodamine B isothiocyanate (RBITC) loaded NPs were fabricated by an emulsification/solvent diffusion method. The surface of NPs was then modified using either poly ethylene glycol (PEG) or block copolymer of ethylene oxide and propylene oxide, Poloxamer 407 (POL). The surface treatment was carried out using two different methods: (a) co-incorporation of the surface modifying agents (SMAs) into NPs and (b) the external surface adsorptions method and both of these methods were done only by physical incorporation of the SMAs into the NPs, without the need of special chemical reagents. The biodistribution properties of the NPs were then measured. The results confirmed that the surface treatment of the NPs using co-incorporation of the SMAs into NPs is more efficient in increasing the blood circulation half-life of the NPs when compared with the external surface adsorptions method.


Dexfenfluramine in psychotic patients.
Dexfenfluramine (DF) is contraindicated in severe psychiatric disorders and in depression. We used DF in 3 patients with chronic psychosis and severe overeating without changes in psychiatric pharmacotherapy. Two patients had paranoid schizophrenic psychosis with hallucinations, one patient mixed psychosis, beginning with lactation psychosis, and several attacks of hallucinations and depression later. Overeating was removed in all 3 patients without any negative effect on the psychotic state. All patients were able to maintain their body weight. Two patients with poorly controlled diabetes improved markedly their metabolic status. Doses up to 75 mg per day of DF were necessary during binge eating episodes in one patient. We conclude that DF can be used with care under close psychiatric supervision in psychotic patients with severe overeating.


IVIG for the treatment of toxic epidermal necrolysis.
Intravenous immunoglobulin (IVIG) has been proposed as a treatment for toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome (SJS). A number of retrospective and prospective studies have been conducted, with varying levels of evidence for the efficacy of IVIG. Recent publications provide opposing conclusions. A multi-center, comparative, long-term analysis needs to be conducted to determine the role of IVIG in the management of patients with SJS/TEN.


Fetal hemoglobin in sickle cell disease: relationship to erythrocyte phosphatidylserine exposure and coagulation activation.
In sickle cell disease (SCD), loss of erythrocyte membrane phospholipid asymmetry occurs with the exposure of phosphatidylserine (PS), which provides a docking site for coagulation proteins. In vivo sickling/desickling, with resulting red cell membrane changes and microvesicle formation, appears to be one of the factors responsible for PS exposure. We evaluated children with SCD homozygous for sickle hemoglobin (SS disease) and controls (n = 65) and demonstrate that high levels of fetal hemoglobin (assessed as F cells) are associated with decreased microvesicle formation, PS exposure, and thrombin generation. F cells correlated inversely with both microvesicles and PS positivity (P <.000001) in SS disease. Multiple regression analyses using various hematologic parameters as independent variables, and either microvesicles or PS positivity as the dependent variable, showed a strong relationship only with F cells. Additionally, plasma prothrombin fragment F1.2 levels (a marker for thrombin generation) correlated with both PS positivity (P <.001) and F cells (P <.01). An F-cell level of approximately 70% was associated with normal levels of prothrombin fragment F1.2 and with microvesicle formation indistinguishable from control values. We suggest that the use of such surrogate biologic markers in conjunction with F-cell numbers may provide valuable insights into the biology and consequences of in vivo sickling.


Decolorization of azo dyes with Enterobacter agglomerans immobilized in different supports by using fluidized bed bioreactor.
Immobilized cells of Enterobacter agglomerans, able to reduce azo dyes enzymatically, were used as a biocatalyst for the decolorization of synthetic medium containing the toxic azo dye methyl red (MR). This bacterial strain exhibits high ability to completely decolorize 100 mg/L of MR after only 6 h of incubation under aerobic conditions. Cells of E. agglomerans were immobilized in calcium alginate, polyacylamide, cooper beech, and vermiculite, and were used for the decolorization of MR from synthetic water by using a fluidized bed bioreactor. The highest specific decolorization rate was obtained when E. agglomerans was entrapped in calcium alginate beads and was of about 3.04 mg MR/g cell/h with a 50% conversion time ( t(1/2)) of about 1.6 h. Moreover, immobilized cells in calcium alginate continuously decolorized MR even after seven repeated experiments without significant loss of activity, while polyacrylamide-, cooper beech-, and vermiculite-immobilized cells retained only 62, 15, and 13% of their original activity, respectively.


Specific social influences on the acceptance of novel foods in 2-5-year-old children.
Social influences have been shown to be very important to overcome food neophobia in young children. However, there is no experimental evidence about whether social influences on food acceptance are specific, that is if models eating the same food as the child are more effective in promoting food acceptance than models eating a different food. We assessed children's behavior towards novel foods when an adult model (a) was not eating (Presence condition), (b) was eating a food of a Different color (Different color condition), and (c) was eating a food of the Same color (Same color condition). We tested 27 children (ages 2- to 5-years-old) recruited from The Pennsylvania State University day-care facilities. Results show that children accepted and ate their novel food more in the Same color condition than in the Different color and in the Presence conditions. Therefore, in young children food acceptance is promoted by specific social influences. These data indicate that children are more likely to eat new food if others are eating the same type of food than when others are merely present or eating another kind of food.


Land use greenhouse gas emissions from conventional oil production and oil sands.
Debates surrounding the greenhouse gas (GHG) emissions from land use of biofuels production have created a need to quantify the relative land use GHG intensity of fossil fuels. When contrasting land use GHG intensity of fossil fuel and biofuel production, it is the energy yield that greatly distinguishes the two. Although emissions released from land disturbed by fossil fuels can be comparable or higher than biofuels, the energy yield of oil production is typically 2-3 orders of magnitude higher, (0.33-2.6, 0.61-1.2, and 2.2 5.1 PJ/ha) for conventional oil production, oil sands surface mining, and in situ production, respectively). We found that land use contributes small portions of GHGs to life cycle emissions of California crude and in situ oil sands production ( <0.4% or < 0.4 gCO₂e/MJ crude refinery feedstock) and small to modest portions for Alberta conventional oil (0.1-4% or 0.1-3.4 gCO₂e/MJ) and surface mining of oil sands (0.9-11% or 0.8-10.2 gCO₂e/MJ).Our estimates are based on assumptions aggregated over large spatial and temporal scales and assuming 100% reclamation. Values on finer spatial and temporal scales that are relevant to policy targets need to account for site-specific information, the baseline natural and anthropogenic disturbance.


Intracranial tuberculoma -- a diagnostic dilemma.
The characteristics of intracranial tuberculoma on computed tomography (CT) and magnetic resonance imaging (MRI) are not well known. The authors present a patient with an intracranial tuberculoma in whom the diagnosis was confirmed only after surgical excision.


Physical activity of young overweight and obese children: parent reports of child activity level compared with objective measures.
The purpose of this study was to compare objectively measured physical activity (PA) and parent-reported assessments of the children's PA in an overweight/obese child sample. A total of 67 child-parent dyads were recruited for study participation. Child anthropometric measures and parent-reported questionnaires were completed, and then PA was measured by accelerometers for 48 consecutive hours. These children demonstrated moderate-to-vigorous PA for 17.32 min per day on average. The children spent 86.7% of their time in sedentary activities. Parents' reports of hyperactivity were significantly related to the objectively measured PA; however, the parents significantly overestimated the average amount of time children spent in each activity level. These findings suggest that although parents may be able to generally characterize their child's PA, they may not be able to accurately report specific information and thus may struggle to identify clear activity goals for their child and/or be unable to assess intervention effects.


Effect of thiamine deficiency and its reversal on cerebral blood flow in the rat. Observations on the phenomena of hyperperfusion, "no reflow," and delayed hypoperfusion.
Local CBF (LCBF) was determined in the same rat model and at the same intervals of thiamine deficiency and reversal as in previous studies of local cerebral glucose utilization (LCGU) and pH (LCpH). The results showed that prior to the appearance of the clinical sequelae of thiamine deficiency (opisthotonus, which usually occurs on day 18 of deficiency) cerebral structures such as the mammillary body, vestibular nucleus, inferior colliculus, and thalamus showed significant hyperperfusion, reaching greater than 200% of control values. At opisthotonus, there was a general decline in LCBF, but, in addition, the larger of these structures developed inhomogeneous perfusion with patches of hyperperfusion adjacent to others of low flow. Seven days of thiamine replenishment at opisthotonus resulted in delayed hypoperfusion notably in the mammillary body, inferior colliculus, and thalamic nuclei. Superimposition of the LCBF, LCGU, and LCpH data reveals that structures known to be vulnerable to the development of histological lesions in this model showed an early phase of hyperperfusion uncoupled from declining LCGU and normal LCpH. Then, following a significant but only focal rise in LCGU between days 11 and 14 of deficiency, hyperperfusion persisted while the pH was dropping and LCGU was rapidly declining. The phase of patchy perfusion occurred only in the histologically vulnerable structures when LCGU was very low and acidosis was at its peak, suggesting that it may have resulted from these opposing influences on LCBF. Following replenishment with thiamine, the vulnerable structures showed delayed hypoperfusion coupled to LCGU.(ABSTRACT TRUNCATED AT 250 WORDS)


Optimised conditions for the synthesis of (17)O and (18)O labelled cholesterol.
Conditions are described for the preparation of cholesterol with (17)O and (18)O labels from i-cholesteryl methyl ether using minimal amounts of isotopically enriched water. Optimum yields employed trifluoromethanesulfonic acid as catalyst in 1,4-dioxane at room temperature with 5 equivalents of water. An isotopic enrichment >90% of that of the water used for the reaction could be attained. Tetrafluoroboric acid could also be used as catalyst, at the expense of a lower overall reaction yield. Byproducts from the reaction included dicholesteryl ether, methyl cholesteryl ether, compounds formed by ether hydrolysis, and olefins arising from elimination reactions. Reactions in tetrahydrofuran yielded significant amounts of cholesteryl ethers formed by reaction with alcohols arising from hydrolysis of the solvent.


Nitrogen-Doped Carbon Vesicles with Dual Iron-Based Sites for Efficient Oxygen Reduction.
A nitrogen-doped vesicle-like porous carbon with well-integrated dual iron-based catalytic sites was developed through direct pyrolysis of inexpensive and abundant precursors. Benefiting from the mesoporous structures with synchronous construction of Fe-Nx and Fe/Fe3 C@NC sites, the optimized catalyst exhibited outstanding performance for the oxygen reduction reaction (ORR) in alkaline media, even superior to the commercial Pt/C catalyst. Detailed characterizations revealed that Fe/Fe3 C@NC sites can make major catalytic contributions in basic media, whereas the Fe-Nx sites were found to play an indispensable role for ORR in acidic media.


Effect of waiting time on substance abuse treatment completion in pregnant women.
Although substance abuse treatment is associated with improved maternal and neonatal outcomes, pregnant women may be at increased risk of attrition. To explore the hypothesis that shorter waiting time for treatment is associated with increased completion, we analyzed all pregnant treatment admissions and discharges in the Treatment Episode Data Set-Discharges. There were 10,661 pregnant admissions in 2006. The effect of waiting time on treatment completion was modified by treatment setting. Immediate entry into ambulatory treatment, where most pregnant women are treated, was significantly associated with completion (odds ratio = 1.27, 95% confidence interval = 1.14-1.41). Criminal justice referral and a high school education were identified as completion predictors in all treatment settings. Waiting time impacts treatment completion in pregnant women. Resources need to be directed to ensure immediate access to treatment, particularly in the ambulatory setting.


Biochemical features of dietary chloride deficiency syndrome: a comparative study of 30 cases.
The diagnosis in one infant of a severe state of chloride deficiency after ingesting a diet consisting exclusively of a modified cow milk formula containing only 0.5 mEq/100 kcal chloride ion led to the identification of 30 additional infants (age 2.6 +/- 0.7 months) fed the same commercial formula. The total absence of chloride in the urine was used as a biochemical index of subclinical dietary chloride deficiency. Serum and urine values were studied at diagnosis and 10 to 12 days after chloride replenishment, and compared statistically with the values obtained in a control group of 40 infants (age 2.8 +/- 1.2 months) fed exclusively a different modified formula containing an adequate chloride concentration. The outstanding laboratory abnormalities noted in the infants ingesting a low chloride formula were hypochloremia and metabolic alkalosis. Mean serum concentrations of potassium, urea, creatinine, and uric acid were in the normal range, but group values were statistically different from normal. A previously unreported finding was the demonstration of a significant elevation in the serum concentrations of calcium and phosphate and in the urinary excretions of calcium and magnesium, which persisted after almost complete recovery of the remaining biochemical disturbances. These results indicate the potential risk of nephrocalcinosis after dietary chloride deficiency.


Auditory postauricular responses in patients with peripheral facial nerve palsy.
Auditory postauricular response (PAR) was determined in 52 subjects with normal hearing and 83 patients with unilateral peripheral facial nerve palsy. PAR was induced bilaterally by bilateral aural stimulation in 50 (96%) of the 52 subjects. Determination of PAR in the 83 patients disclosed that the prognosis was significantly (p less than 0.01) better for those in whom PAR occurred within 4 weeks of onset, in comparison with those without PAR. PAR determination was thus considered to be a useful procedure for determining the prognosis of peripheral facial nerve palsy.


Lip cancer: Reconsidering the at-risk patients with pathological assessment.
This study was aimed to overview the treatment protocols of lip cancer and find out a cutoff point of tumor diameter and depth of invasion (DOI) for the survival parameters. One hundred and ninety-one patients with lip SCC were studied. The average age of the patients was 62 years. Among 191 patients, 82.7% of the patients were men, 96.4% of them had lower lip cancer, and 84% were staged as early (pT1, pT2 ). Primary tumor excision with neck dissection was applied to 62.3% of the patients. Lymph node metastases rate was found to be 11%, and recurrence rate was 6.3%. There was statistically significant difference in between the tumor diameters and DOI values of patients with and without metastasis, and recurrence (p < 0.01, p < 0.05, respectively). Regarding to the lymph node metastasis, the optimal cutoff point was found to be 7.5 mm for DOI and 21.5 mm for tumor diameter. Regarding to the recurrence, the optimal cutoff point was found to be 7.5 mm for DOI and 24.5 mm for tumor diameter. T2 lip cancer patients also seem to be in at-risk group for metastasis and recurrence. As a conclusion, elective neck dissection and frequent follow-up are recommended for these early-stage lip cancer patients.


The abuse potential of the synthetic cannabinoid nabilone.
Nabilone is a synthetic cannabinoid prescription drug approved in Canada since 1981 to treat chemotherapy-induced nausea and vomiting. In recent years, off-label use of nabilone for chronic pain management has increased, and physicians have begun to express concerns about nabilone becoming a drug of abuse. This study evaluates the evidence for abuse of nabilone, which is currently ill-defined. Scientific literature, popular press and internet databases were searched extensively for evidence of nabilone abuse. Focused interviews with medical professionals and law enforcement agencies across Canada were also conducted. The scientific literature and popular press reviews found very little reference to nabilone abuse. Nabilone is perceived to produce more undesirable side effects, to have a longer onset of action and to be more expensive than smoked cannabis. The internet review revealed rare and isolated instances of recreational use of nabilone. The database review yielded little evidence of nabilone abuse, although nabilone seizures and thefts have occurred in Canada in the past few years, especially in Ontario. Most law enforcement officers reported no instances of nabilone abuse or diversion, and the drug has no known street value. Medical professionals reported that nabilone is not perceived to be a matter of concern with respect to its abuse potential. Reports of nabilone abuse are extremely rare. However, follow-up of patients using nabilone for therapeutic purposes is prudent and should include assessment of tolerance and dependence. Prospective studies are also needed to definitively address the issue of nabilone abuse.


Modulation transfer function measurement of scanning reflectance microscopes.
Real-time medical imaging systems such as reflectance confocal microscopes and optical coherence microscopes are being tested in multiple-patient and multiple-center clinical trials. The modulation transfer function (MTF) of these systems at any given time influences the image information content and can affect the interpretation of the images. MTF is difficult to measure in real-time scanning systems when imaging at the Nyquist limit. We describe a measurement technique similar to the electronic imaging resolution standards ISO-12233 (electronic cameras) that can be applied to scanned spot imaging systems with asynchronous pixel clocks. This technique requires the acquisition of a single image of a reflective stripe object. An asynchronous pixel clock induces subpixel jitter in the edge location. The jitter is removed using a Fourier method, and an oversampled edge response function is calculated using algorithms developed in MATLAB. This technique provides fast, simple to use, and repeatable full-width at half maximum lateral resolution and MTF measurements based on only one test image. We present the results for reflectance confocal microscopes operating at 0.9 numerical aperture.


[Usefulness of the neuroandrologic profile study in patients with erectile dysfunction: review of a series of 180 cases].
To determine the usefulness of a complete neuroandrologic evaluation and SPACE (Single Potential Analysis Cavernous Electromyography) in the study of impotence. We performed a clinical study, erection test with papaverine-phentolamine and neuroandrologic evaluation (bulbocavernous EMG, S2-S4 evoked potentials, evoked somatosensorial potentials, SPACE, D10-L2 skin sympathetic potentials, cystometrogram, and filling videocystography) in 180 patients consulting for impotence. We observed a relationship between the clinical diagnosis of impotence and the data from the neuroandrogenic study. The results of the study were classified as normal [in the clinical diagnosis of psychogenic impotence (100%), hormonal (80%) and vascular (60%)], abnormal [prevalent in the clinical diagnosis of structural impotence (87%)]. The erection test was mainly negative in all clinical diagnoses of impotence, except in psychogenic and vascular impotence (60% positive tests). The clinical data are useful in the diagnosis of impotence. The pharmacological erection test was not found to be very reliable. Complete neuroandrologic evaluation is indicated in non typified and mixed impotence, and can be performed in neurogenic impotence to identify the level of the lesion. Alone, SPACE does not appear to be useful as a screening test for neurologic lesions, but can be useful as a screening test for neuromuscular cavernous lesions. SPACE is indicated in structural, vascular and hormonal impotence. If SPACE is abnormal, the differential diagnosis between neurogenic and myogenic lesion can be made through a complete neuroandrologic evaluation.


HPLC-MS method for the quantification of nine anti-HIV drugs from dry plasma spot on glass filter and their long term stability in different conditions.
A bioanalytical method for the determination of most commonly prescribed protease inhibitors (saquinavir, atazanavir, amprenavir, darunavir, lopinavir and ritonavir) and non-nucleoside reverse transcriptase inhibitors (etravirine, efavirenz and nevirapine) was developed, modifying our previous HPLC-MS chromatographic run, validated and a complete short and long term stability evaluation was carried out. One hundred microlitres of plasma were distributed on a collection glass paper filter (Glass-Microfibre from Sartorius), then the filter underwent thermal treatment, both for drying and for HIV inactivation, and stored at room temperature, 4 degrees C and -20 degrees C. The analytes were extracted from the filter disc using tert-butylmethylether with basic pH, after the addition of the internal standards quinoxaline. The extract was dried, reconstituted and the chromatographic separation was performed on a reversed-phase C-18 column (150 mm x 2.0 mm) and the analytes were quantified using a single quadrupole mass spectrometer. The method was validated considering the concentration ranges encountered in clinical trials and the routine clinical practice. The assay was linear over the concentration ranges tested. Accuracies ranged from 92.1% to 111.9% and intra-day and inter-day relative standard deviation for all quality control levels ranged from 0.2 to 12.9 and 3.1 to 14.4, respectively. Analytes in dried plasma spots were stable for longer time when dried/inactivation step was carried out before storage compared to samples not dried/inactivated before the analysis. The dried/inactivation step allows shipment of samples at room temperature without any risks, therefore the developed and validated method enables an easy and cheap sample shipment for therapeutic drug monitoring and pharmacokinetic studies.


[Dynamic change of soluble saccharides and amino acids during the growing period of Coptis chinensis].
To study the changes of soluble saccharides and amino acids during the growing period of Coptis chinensis. Amino acid contents were estimated by Indene tri-ketone colorimetric method; saccharide contents were determined by anthracene ketone method. The contents of soluble saccharides and amino acids in different organs were low in plants of 1-2 years old. And they were increased in plants of 3-4 years old. At maturation (5 years), the contents of amino acids kept on increasing in rhizome and flower stalk, while decreased in fibre and leaves, and the contents of soluble saccharides showed the downtrend in rhizome, leaves and fibre, except the uptrend in flower stalk.


Need satisfaction of older persons living in the community and in institutions, part 1. The environment.
A descriptive study was conducted that compared the need satisfaction of older persons living in institutions. In the first article of a two-part series, the impact of environment on the satisfaction of needs was examined. Subjects included 20 community and 21 institutionalized older persons. Using Maslow's need hierarchy as the theoretical framework, it was found that the community environment satisfied belongingness/love and esteem needs to a greater degree than the institutional environment. No difference was found in the satisfaction of physiological, safety, and self-actualization needs between the two environments. Race, mental status, and whether a community resident lived alone or with others were variables that influenced the results. The findings emphasized the complexity of need satisfaction and supported the formulation that environment is a crucial factor in need satisfaction. In the second article, the relationship between engagement in activity and need satisfaction will be explored.


[Epilepsy and its impact in northwest region of the Central African Republic].
In African countries, epilepsy is an important public health problem with major medical, socio-cultural, and economic implications. This study was carried out to evaluate attitudes towards epilepsy in the Central African Republic. A total of 187 epileptic patients were included. Only 20.9% of the study population were married. School attendance never exceeded the elementary level. Epilepsy was active in 98.4% of patients who continued to present attacks despite extensive treatment which was either poorly complied with or inadequate. Attitudes towards epilepsy remain rooted in belief in supernatural phenomenon and evil spirits with use of traditional therapies involving abstinence from certain foods and use of laxative agents to drive out evil forces. Epileptics are excluded from their families and not allowed to attend school but, in our study, they were not prevented from the work place since 70% held jobs. In this study, 54% of epileptics believed that the disease was contagious, 55.6% that it was incurable, and 20.9% that it was due occult or supernatural causes. While precise quantification is impossible, our experience based on interviews with patients and frequent observation of burn wounds suggests that moral and physical suffering is immense among epileptics in the Central African Republic. Epilepsy in Black Africa is a major public health problem requiring serious attention from government officials, health care specialists, and the families of patients. Better information to promote awareness of the non-contagious nature of the disease, greater support for families of patients, and improvement in treatment compliance are essential.


[Upper airway obstruction and anesthesia--on warning signals illustrated by some cases reported to the Swedish Medical Responsibility Board].
Upper airway obstruction (e.g., epiglottitis, Ludwig's angina, or laryngeal tumour) can be a serious and life-threatening condition. The patient is asphyxiated, tired and prone to sudden apnoea and/or cardiovascular collapse. In using i.v. anaesthesia and muscle relaxation (e.g., by means of succinylcholine), the anaesthetist is taking a chance, and relying on being able to intubate the patient. Such an approach may lead to the patient's death, however, should the anaesthetist be unable to secure a free airway for artificial ventilation or to intubate the patient. Clinical symptoms are described as is the pathophysiology of upper airway obstruction. Preparatory intubation, while the patient is conscious, would seem to be the safest procedure to use in such cases.


[Effect of macrolides on biofilm of mucoid Pseudomonas aeruginosa].
To observe the effect of macrolides with different structures on biofilm of mucoid Pseudomonas aeruginosa so as to provide a theoretical basis for treatment of bacterial biofilm diseases. Modified plate culture method was used to establish in vitro bacterial biofilm model, which was identified by silver nitrate staining. After the biofilm was treated by gatifloxacin and/or macrolides with different structures and of different concentrations, the number of viable bacteria was measured by MTT method and bacterial adherence was measured by crystal violet staining. Clarithromycin and azithromycin of 1/4 and 1/16 MIC combined with gatifloxacin significantly inhibited the adherence of mucoid Pseudomonas aeruginosa (P < 0.05) and reduced the number of viable mucoid Pseudomonas aeruginosa compared with gatifloxacin alone (P < 0.05), while such effects could not be seen for rovamycin. Inhibiting the adherence of mucoid Pseudomonas aeruginosa may be one of the mechanisms by which macrolides such as clarithromycin and azithromycin enhance the antibacterial activity of gatifloxacin against mucoid Pseudomonas aeruginosa.


Evidence for multiple bone resorption-stimulating factors produced by normal human keratinocytes in culture.
Conditioned medium from cultured normal human foreskin keratinocytes enhanced the release of calcium from neonatal mouse calvaria in organ culture. Unfractionated keratinocyte-conditioned medium (KCM) stimulated bone resorption in a dose-dependent manner, but it did not increase the concentration of prostaglandin E2 (PGE2) in the bone culture medium until a maximal dose of KCM for resorption was used. Furthermore, inhibitors of PGE2 synthesis, indomethacin, ibuprofen, and piroxicam, did not inhibit KCM-induced calcium release. High concentrations of KCM increased cAMP production by calvaria in the presence of isobutylmethylxanthine, but the increase was small compared with that produced by a dose of bovine PTH that caused a similar level of bone resorption. The bone resorption-stimulating activity of KCM was not lost after incubation at 56 C for 60 min, but it was lost after heating at 100 C for 10 min. Fractionation of KCM by gel filtration chromatography revealed two distinct peaks of bone resorption-stimulating activity. One peak, KCMI, caused a significant increase in bone resorption at 2 micrograms protein/ml. KCMI did not increase medium PGE2, and inhibition of PGE2 synthesis in bone had no effect on KCMI-induced bone resorption. KCMI failed to increase cAMP production by human osteosarcoma SaOS-2 cells. Another peak, KCMII, caused a dose-dependent increase in bone resorption, and a significant increase in medium calcium was noted at a 20-fold lower concentration (0.1 microgram protein/ml) than with KCMI. In contrast to KCMI, the increase in bone resorption stimulated by KCMII was accompanied by a parallel increase in the production of PGE2, and inhibition of PGE2 synthesis completely inhibited the bone resorption-stimulating activity of KCMII. KCMII also caused an increase in cAMP production by SaOS-2 cells. We conclude that KCM contains at least two distinct bone resorption-stimulating factors, one of which acts via a PG-mediated mechanism and the other by a PG-independent pathway.


Evaluation of the sedative and cardiovascular effects of intramuscular administration of dexmedetomidine with and without concurrent atropine administration in dogs.
To evaluate degree of sedation and cardiovascular, respiratory, acid-base excess, and electrolyte variables in response to IM administration of dexmedetomidine or dexmedetomidine with atropine. Randomized crossover study. Animals-5 healthy 1- to 2-year-old sexually intact male Treeing Walker Coonhounds. Dogs were instrumented with catheters placed in the dorsal pedal artery and lateral saphenous vein. All dogs received dexmedetomidine (10 μg/kg [4.5 μg/lb], IM) or dexmedetomidine with atropine (0.02 mg/kg [0.009 mg/lb], IM). Variables were measured at baseline (time 0) and 5, 15, 30, and 60 minutes after drug administration. In all dogs, lithium dilution cardiac output decreased from a mean ± SD baseline value of 5.07 ± 1.0 L/min to 2.1 ± 0.9 L/min. Cardiac output was not different between dexmedetomidine group dogs and dexmedetomidine-atropine group dogs. Mean arterial pressure increased from baseline in both groups but was significantly higher in dexmedetomidine-atropine group dogs, compared with dexmedetomidine group dogs. Heart rate in dexmedetomidine group dogs decreased from 110 ± 14.2 beats/min to 49.4 ± 10.4 beats/min by 15 minutes. No differences were seen in blood gas values, electrolyte concentration, or hemoglobin values over time or between groups. Arrhythmias were detected in dexmedetomidine-atropine group dogs and included atrioventricular block, ventricular premature contractions, and ventricular bigeminy. Administration of atropine at 0.02 mg/kg, IM, with dexmedetomidine at 10 μg/kg, IM, resulted in an increase in mean arterial blood pressure and heart rate; deleterious cardiac arrhythmias were also observed. Use of atropine with dexmedetomidine is not recommended in dogs.


Unresolved problems concerning optimal therapy of puberty in children with chronic renal diseases.
Many children with chronic renal insufficiency (CRI) show growth retardation and severely delayed pubertal development. Successful renal transplantation (RTx) also rarely results in full growth rehabilitation. Pubertal height gain in CRI patients is only 58% and 48% of that observed in late-maturing boys and girls, respectively. Growth retardation in both CRI and RTx patients is not the result of abnormal GH secretion or decreased levels of IGF-I, but rather of elevated levels of IGFBPs inhibiting the bioavailability of the IGFs. In RTx patients prednisone may also inhibit growth directly via inhibition of bone matrix formation. Several studies have convincingly shown that GH therapy at a dose of 4 IU/m2/day results in a sustained improvement of growth in prepubertal and pubertal children with CRI and in growth-retarded prepubertal and pubertal post-transplant patients. The following consensus was reached concerning optimal therapy of puberty in children with chronic renal disease. GH therapy does not lead to an earlier start of puberty. It is safe to give GH to RTx patients if transplant function is stable. GH therapy will not accelerate bone maturation and can improve the final height of children with CRI and after RTx. Increasing the GH dose above 4 IU/m2/day in pubertal RTx patients does not increase height gain or final height and is not advised as it may increase insulin resistance. GH should best be started before the start of the pubertal growth spurt but will still be effective in RTx patients with advanced bone age. GH testing should not be a prerequisite for starting GH therapy. It is important to optimise other therapies during puberty. During GH therapy of RTx patients use minimum daily, not alternate-day, steroid dosing. Further research is still required on the possible long-term effects of GH therapy in children with chronic diseases. Two studies demonstrated improved long-term growth and final height within the target height range, without significant side effects. Renal graft function did not deteriorate more than in matched controls. A GH dose of 4 IU/m2/day proved adequate.


Preoperative shaving: patient and surgeon preferences and complications for the Gillies incision.
A modified technique for the Gillies temporal approach without previous hair removal is described. A randomized prospective study of two groups of patients requiring elevation of fractures of the zygomaticomalar complex via this approach with and without hair removal was performed with respect to patients' attitudes and surgeons' assessment.


Mogul skier's palm: traumatic hypothenar ecchymosis.
A unique purpuric--golden lesion on the hypothenar eminence of each palm is described in a mogul skier. These painful lesions, resulting from vigorous repetitive pole planting in the "bumps" at a ski area, are postulated to represent a form of localized soft tissue injury.


Environmental contaminants and low-level cancer risks: perceptions and scientific strategies.
Scientific and public perceptions concerning low-level lung cancer risks may vary. Recently the public has been more convinced of causal links between low-level risk agents and cancer, and more interested in prevention of environmental exposures, especially those induced by others. Thus, scientific strategy is partly driven by the public need to resolve issues concerning the importance of low-level exposures and risks. Further, investigators have been challenged intellectually to create methodologies in order to study some of these relationships further, and scientific curiosity has been stimulated by the difficulties of pursuing such investigations. The importance of host characteristics, including the genetic bases of susceptibility, has become a major theme. Likewise, host behaviour has become a potential positive factor (e.g. diet) as well as a negative factor in the risk model for low-level agents. This paper discusses some of the information available on low-level agents and some of the methodological issues involved in studying them. The importance of measuring exposure as well as response is stressed, especially multi-pollutant exposures and interactions with host behaviour.


A study of event related potential frequency domain coherency using multichannel electroencephalogram subspace analysis.
Event related potentials (ERP) are time-locked electrical activities of the brain in direct response to a specific sensory, cognitive, or motor stimulus. ERP components, such as the P300 wave, which are involved in the process of decision-making, help scientists diagnose specific cognitive disabilities. In this study, we utilize the angles between multichannel electroencephalogram (EEG) subspaces in different frequency bands, as a similarity factor for studying the spatial coherency between ERP frequency responses. A matched filter is used to enhance the ERP from background EEG. While previous researches have focused on frequencies below 10 Hz, as the major frequency band of ERP, it is shown that by using the proposed method, significant ERP-related information can also be found in the 25-40 Hz band. These frequency bands are selected by calculating the correlation coefficient between P300 response segments and synthetic EEG, and ERP segments without P300 waves, and by rejecting the bands having the most association with background EEG and non-P300 components. The significance of the results is assessed by real EEG acquired in brain computer interface experiments versus synthetic EEG produced by existing methods in the literature, to assure that the results are not systematic side effects of the proposed framework. The overall results show that the equivalent dipoles corresponding to narrow-band events in the brain are spatially coherent within different (not necessarily adjacent) frequency bands. The results of this study can lead into novel perspectives in ERP studies.


Dracunculiasis in Burkina Faso: results of a national survey.
National surveys using active reporting are essential steps in the global dracunculiasis eradication programme. All the known villages of Burkina Faso were visited at the end of 1990 by teams of field-workers who organized meetings with local informants in order to enquire about all cases of the emergence of Guinea worms during the past twelve months. The annual incidence for 1990 was then calculated using recent demographic data. Data collected were validated by a second survey of a random sample of 221 villages. The national coverage rate was 99.3% of villages; 42,227 cases were reported. The annual incidence for 1990 was 46.4 cases per 10,000. There was a pronounced heterogeneity in the spatial distribution of endemic foci, with a concentration of cases in the north and centre of the country. In Burkina Faso, dracunculiasis has a heterogeneous distribution with a pronounced concentration of cases in the North and Centre that reach mesoendemic incidence rates.


Dissatisfaction with traditional birth attendants in rural Tanzania.
To assess women's satisfaction with traditional birth attendants (TBAs) in rural Tanzania. A population-representative sample of households in Kasulu district was used to collect data on demographics, childbirth history, and perception of TBAs and doctors/nurses from women who had recently had a child and from their partners. Two-thirds of women who gave birth in a health facility reported being very satisfied with the experience, compared with 21.2% of women who delivered at home with TBAs. A sizeable proportion of women felt that TBAs had poor medical skills (23.1%), while only 0.3% of women felt the same about doctors' and nurses' skills. Of women who delivered with a TBA, 16.0% reported that TBAs had poor medical skills whereas 0.5% stated the same for doctors and nurses. Although many women delivered at home in this rural study district, women and their partners reported higher confidence in doctors and nurses than in TBAs. Policymakers and program managers should not assume that women prefer TBAs to trained professionals for delivery but should consider system barriers to facility delivery in interventions aimed at reducing maternal mortality.


Binary VOCs absorption in a rotating packed bed with blade packings.
This investigation addressed the mass transfer of rotating packed beds with blade packings in removing methanol and 1-butanol from binary mixtures by absorption using water as the absorbent. The dependences of the overall volumetric gas-phase mass transfer coefficient (K(G)a) on the inlet methanol concentration, the inlet 1-butanol concentration, the rotational speed, the gas flow rate, and the liquid flow rate, were explored. The results demonstrated that the inlet methanol and 1-butanol concentrations had a negligible effect on the K(G)a values of methanol and 1-butanol. The K(G)a values of methanol and 1-butanol increased with the rotational speed, the gas flow rate, and the liquid flow rate. The dependence of K(G)a on the gas flow rate was higher than that on the liquid flow rate, revealing that the mass transfer in binary VOCs absorption may be controlled considerably by the mass transfer in gas phase.


Magnetic resonance imaging of guinea pig cochlea after vasopressin-induced or surgically induced endolymphatic hydrops.
To investigate the ability to detect the in vivo cochlear changes associated with vasopressin-induced and surgically induced endolymphatic hydrops using MRI at 3 tesla (T). Prospective, animal model. Animal laboratory. In group 1, five guinea pigs underwent post-gadolinium temporal bone MRI before and after seven and 14 days of chronic systemic administration of vasopressin by osmotic pump. In group 2, five guinea pigs underwent temporal bone MRI eight weeks after unilateral surgical ablation of the endolymphatic sac. Three-tesla high-resolution T1-weighted sequences were acquired pre- and postcontrast administration. Region of interest signal intensities of the perilymph and endolymph were analyzed manually. Quantitative evaluation of hydrops was measured histologically. Gadolinium preferentially concentrated in the perilymph, allowing for distinction of cochlear compartments on 3.0-T MRI. The T1-weighted contrast MRI of vasopressin-induced hydropic cochlea showed significant increases in signal intensity of the endolymph and perilymph. Surgically induced unilateral hydropic cochlea also showed increased signal intensity, compared with the control cochlea of the same animal, but less of an increase than the vasopressin group. The histological degree of hydrops induced in the vasopressin group was comparable to previous studies. In vivo postcontrast MRI of the inner ear demonstrated cochlear changes associated with chronic systemic administration of vasopressin and surgical ablation of the endolymphatic sac. Understanding the MRI appearance of endolymphatic hydrops induced by various methods contributes to the future use of MRI as a possible tool in the diagnosis and treatment of Ménière's disease.


Adult Alexander disease with autosomal dominant transmission: a distinct entity caused by mutation in the glial fibrillary acid protein gene.
Infantile and juvenile forms of Alexander disease are well characterized and are caused by de novo mutations in the glial fibrillary acid protein (GFAP) gene. In contrast, the adult form of the disease has been rarely described, and the etiology of this variant remains unknown. To characterize the clinical phenotype and identify the gene causing an autosomal dominant form of adult Alexander disease. We identified a large kindred segregating clinical features compatible with adult Alexander disease in an autosomal dominant fashion. A neurological examination was performed on all affected members of this family. Most of these patients also underwent magnetic resonance imaging of the brain and a polysomnographic study. The diagnosis was confirmed pathologically in 2 individuals. We screened all coding regions of the GFAP gene in affected individuals by means of direct sequencing and single-stranded conformational polymorphisms analysis. We found a novel D78E mutation in GFAP in all affected individuals. This mutation was not detected in more than 100 control subjects. Clinical and radiological features of affected individuals were clearly different from those of patients with the infantile and juvenile forms of the disease. The most consistent finding was the presence of bulbar signs. In addition, sleep disturbance (mainly sleep apnea), symptoms of dysautonomia, and dysmorphism were found in all affected individuals. In younger patients, magnetic resonance imaging showed T2 signal abnormalities in the medulla compatible with an area of demyelination. In contrast, in older patients, we found marked atrophy of the medulla without signal abnormalities. None of the affected individuals exhibit signs of demyelination of the cerebral white matter. The present study is the first demonstration of a mutation in GFAP that causes an autosomal dominant form of Alexander disease and establishes the existence of the adult variant. Clinical evaluation in individuals carrying mutation in the GFAP gene allowed a better definition of this heterogeneous clinical syndrome and will help increase its recognition in neurological practice.


Dysregulated DNA Methyltransferase 3A Upregulates IGFBP5 to Suppress Trophoblast Cell Migration and Invasion in Preeclampsia.
Preeclampsia is a unique multiple system disorder during human pregnancy, which affects ≈5% to 8% of pregnancies. Its risks and complications have become the major causes of maternal and fetal morbidity and mortality. Although abnormal placentation to which DNA methylation dysregulation is always linked is speculated to be one of the reasons causing preeclampsia, the underlying mechanisms still remain elusive to date. Here we revealed that aberrant DNA methyltransferase 3A (DNMT3A) plays a critical role in preeclampsia. Our results show that the expression and localization of DNMT3A are dysregulated in preeclamptic placenta. Moreover, knockdown of DNMT3A obviously inhibits trophoblast cell migration and invasion. Mechanistically, IGFBP5 (insulin-like growth factor-binding protein 5), known as a suppressor, is upregulated by decreased DNMT3A because of promoter hypomethylation. Importantly, IGFBP5 downregulation can rescue the defects caused by DNMT3A knockdown, thereby, consolidating the significance of IGFBP5 in the downstream of DNMT3A in trophoblast. Furthermore, we detected low promoter methylation and high protein expression of IGFBP5 in the clinical samples of preeclamptic placenta. Collectively, our study suggests that dysregulation of DNMT3A and IGFBP5 is relevant to preeclampsia. Thus, we propose that DNMT3A and IGFBP5 can serve as potential markers and targets for the clinical diagnosis and therapy of preeclampsia.


Parasitological and serological diagnosis of Strongyloides stercoralis in domesticated dogs from southeastern Brazil.
Canine strongyloidiasis is a parasitic infection caused by the nematode Strongyloides stercoralis and presents a great zoonotic potential. Its confirmation, using coproparasitological methods, is difficult. The detection of serum specific antibodies, however, may facilitate the diagnosis. The aims of this study were to determine the presence of S. stercoralis through the use of parasitological methods and to detect specific antibodies to the parasite in serum samples from domestic dogs by using the indirect fluorescent antibody test (IFAT) on slides and the enzyme-linked immunosorbent assay (ELISA). A total of 215 dogs of various breeds, from the cities of Uberlândia, Araxá and Campo Belo in the State of Minas Gerais, were examined and distributed according to age into the following groups: (I) 19 males and 20 females of 1-2 months old; (II) 11 males and 20 females of 2-month- to 1-year-old and (III) 41 males and 104 females, from 1 to 7 years old. Coproparasitological results showed that 63/215 (29.3%) of the dogs presented some kind of parasite, with two (0.9%) dogs (one from Araxá and the other from Uberlândia) passing S. stercoralis larvae in the feces. Serological results revealed antibodies to S. stercoralis in 45/215 (20.9%) of the dogs, with seropositivity rates of 0% (0/39) in Group I, 22.6% (7/31) in Group II, and 26.2% (38/145) in Group III. No serological cross-reactivity between S. stercoralis and hookworms or Ascaridae was found. Hookworm infections were seen in 31 dogs, but only one of these dogs (infected with both hookworm and Cystoisospora spp.) was S. stercoralis seropositive by IFAT. The present study demonstrated, for the first time, natural S. stercoralis infections in dogs diagnosed by coproparasitological and serological methods. It was concluded that the detection of specific antibodies to S. stercoralis by IFAT and ELISA may contribute to the diagnosis of canine strongyloidiasis.


The role of host lymphoid populations in the response of mouse EMT6 tumor to photodynamic therapy.
Photodynamic therapy (PDT) treatment of murine EMT6 mammary sarcoma using Photofrin (10 mg/kg) and light (110 J/cm2) cured all these lesions growing in syngeneic BALB/c mice. In contrast, the same treatment produced initial ablation but no long-term cures of EMT6 tumors growing in either scid or nude mice, the immunodeficient strains sharing the same genetic background with BALB/c mice. No difference was detected in either the level of Photofrin accumulated per g of tumor tissue or the extent of tumor cell killing during the first 24 h after PDT of EMT6 tumors growing in BALB/c or scid mice. The assumption that the difference in tumor cures could be ascribed to the absence of functional lymphoid cells in scid and nude mice was supported by the results of experiments involving the adoptive T-cell transfer into scid mice or bone marrow transfer between BALB/c and scid mice. The adoptive transfer of splenic virgin T lymphocytes from BALB/c mice into scid mice performed 9 days before PDT of EMT6 tumors growing in the recipients was successful in delaying the recurrence of treated tumors. Adoptive transfer done immediately after PDT or 7 days after PDT had no obvious benefit. Even better improvement and a high cure rate of PDT-treated tumors was obtained with scid mice reconstituted with BALB/c bone marrow. In contrast, a marked drop in tumor cure rate was observed with BALB/c mice reconstituted with scid bone marrow. These results suggest that the activity of host lymphoid populations was essential for preventing the recurrence of EMT6 tumors following the PDT treatment used in this study. The contribution of PDT-induced immune reaction may, therefore, be of critical importance for the cure with at least some tumors.


mRNA regions where 80S ribosomes pause during translation elongation in vivo interact with protein uS19, a component of the decoding site.
In eukaryotic ribosomes, the conserved protein uS19, formerly known as S15, extends with its C-terminal tail to the decoding site. The cross-linking of uS19 to the A site codon has been detected using synthetic mRNAs bearing 4-thiouridine (s4U) residues. Here, we showed that the A-site tRNA prevents this cross-linking and that the P site codon does not contact uS19. Next, we focused on determining uS19-mRNA interactions in vivo by applying the photoactivatable-ribonucleoside enhancing cross-linking and immunoprecipitation method to a stable HEK293 cell line producing FLAG-tagged uS19 and grown in a medium containing s4U. We found that when translation was stopped by cycloheximide, uS19 was efficiently cross-linked to mRNA regions with a high frequency of Glu, Lys and, more rarely, Arg codons. The results indicate that the complexes, in which the A site codon is not involved in the formation of the mRNA-tRNA duplex, are present among the cycloheximide-arrested 80S complexes, which implies pausing of elongating ribosomes at the above mRNA regions. Thus, our findings demonstrate that the human ribosomal protein uS19 interacts with mRNAs during translation elongation and highlight the regions of mRNAs where ribosome pausing occurs, bringing new structural and functional insights into eukaryotic translation in vivo.


Being a team leader: newly registered nurses relate their experiences.
This paper presents a study that explores how newly qualified registered nurses experience their leadership role in the ward-based nursing care team. A nurse's clinical leadership affects the quality of care provided. Newly qualified nurses experience difficulties during the transition period from student to qualified professional and find it challenging to lead nursing care. Twelve nurses were interviewed and the transcribed texts analysed using qualitative content analysis to assess both manifest and latent content. Five themes were identified: feeling stranded; forming well-functioning teams; learning to lead; having the courage, strength, and desire to lead; and ensuring appropriate care. The findings indicate that many factors limit nurses' leadership but some circumstances are supportive. The leadership prerequisites for newly registered nurses need to improve, emphasizing different ways to create a supportive atmosphere that promotes professional development and job satisfaction. To increase nurse retention and promote quality of care, nurse managers need to clarify expectations and guide and support newly qualified nurses in a planned way.


Does pregnancy increase graft loss in female renal allograft recipients?
Although many transplanted women who were previously infertile can conceive during the posttransplant period, maternal and fetal complications are likely. We evaluated the effect of pregnancy after renal transplantation in this study. We retrospectively evaluated female renal transplant recipients who became pregnant. Age- and transplantation time-matched nonpregnant patients were used as a control group. We analyzed data regarding the demographic features of the pregnant patients, their serum creatinine levels before pregnancy, during pregnancy and during the postpartum period until now, immunosuppressive drugs, complications during pregnancy and fetal complications. In total 57 patients were included in this study. We divided the transplanted patients into two groups: 22 deliveries in 19 patients (delivery group) and 38 nonpregnant patients (control group). The mean follow-up durations and ages of transplantation were similar in the two groups. There was no significant difference in the mean serum creatinine values of the two groups (p = 0.42). Regarding immunosuppressive drugs, there was no significant difference between the two groups (p = 0.23). The frequencies of chronic hypertension, proteinuria, use of erythropoietin, and urinary tract infection were not statistically significantly different between the two groups (p = 0.31, 0.59, 0.36, 0.28, respectively). There were also no significant differences noted in graft and patient survival between the groups (p = 0.577). Female transplant recipients who have stable creatinine levels, insignificant proteinuria, and normal blood pressure or controlled hypertension may become pregnant, and they can have successful pregnancies. Their graft functions and survivals are not affected by gestation.