The role of cadmium in the peroxidative response of kidney to stress.
Since the kidney is a main target for cadmium, its accumulation in the kidney tissue by increasing peroxidative damage make the kidney functions vulnerable to stress. For this reason, the effect of cadmium-induced peroxidative damage to kidney responses to stress was investigated in this study. Two-month-old albino rats receiving 15 micrograms/mL containing Cd drinking water for 30 d were exposed to restraint and cold stress for 6 h, and their responses were compared with those of unstressed counterparts. Lipid peroxidation was found to be significantly higher in the cortical portion of kidney in cadmium-exposed rats than that of unexposed animals. The mean thiobarbutyric acid reactive substance (TBARS) level rose from 211.6 +/- 64.2 to 303.4 +/- 46.4 nmol/g protein (p < 0.01). Six hours of cold and restraint stress caused an elevation in the cortical TBARS level in control animals without affecting its level in cadmium-exposed rats. Despite unaltered cortical TBARS, its medullar levels increased significantly in cadmium-exposed rats because of stress. These results suggested that cadmium accumulation in the kidney increases the susceptibility of medulla against peroxidative damage. However, further functional studies are necessary to explain the role of cadmium in the stress-induced deterioration of medullar functions.


[Electrophysiological study of the visual system in experimental pigment dystrophy].
Pigment retinal dystrophy induced by the administration of monoiodacetic acid was characterized by a unilateral inhibition of parameters of all components of not only electroretinography, but also evoked potentials of the visual cortex and superior colliculus: higher thresholds of their formation relatively to the controls, and displacement of saturation areas towards low intensities. Correlations of retinogeniculocortical and retinocolliculocortical pathways of visal information transmission were ascertained to be an important factor in the mechanism of visual analyzer functioning in certain abnormalities.


Good grief and not-so-good grief: countertransference in bereavement therapy.
This study examined the relationship between therapists' grief related to the death of a loved one and clients' perceptions of the process of bereavement therapy. Mail survey data were obtained from 69 client-therapist dyads. Results indicated that the extent to which therapists missed deceased loved ones was inversely related to client perceptions of therapist empathy, but not to client ratings of the alliance, session depth, or therapist credibility. Therapist acceptance of the death of a loved one was unrelated to any of the dependent measures. Results are discussed in terms of countertransference and its management.


Differential regulation of airway mucin gene expression and mucin secretion by extracellular nucleotide triphosphates.
The effects of extracellular nucleotide triphosphates on the stimulation of mucin production by airway epithelial cells were examined. The order of potency in stimulating mucin secretion in primary cultures of human tracheobronchial epithelial cells is: uridine 5'-triphosphate (UTP) approximately equal to adenosine 5'-triphosphate (ATP) approximately equal to ATP-gamma-S > uridine 5'-diphosphate approximately equal to adenosine 5'-diphosphate > alpha,beta-methylene ATP >> adenosine. However, only UTP can increase mucin gene (MUC5AC, MUC5B) expression; ATP and other analogues have no stimulatory effect. The stimulation of MUC5AC and MUC5B expression by UTP is time- and dose-dependent. A similar effect on the elevation of mucous cell population in mouse airway epithelium can be demonstrated in vivo by an intratracheal instillation of UTP-saline solution. The stimulatory effect of UTP or ATP on mucin secretion was inhibited by pertussis toxin, U73122, and Calphostin C, but not by PD98059, suggesting a G-protein/ phospholipase (PL) C/protein kinase (PK) C-dependent and mitogen-activated protein kinase (MAPK)-independent signaling pathway. However, the stimulatory effect of UTP on mucin gene expression was sensitive to pertussis toxin and PD98059, but not to Calphostin C and U73122, suggesting a G-protein/MAPK-dependent and PLC/PKC-independent signaling pathway. These findings are the first demonstration that UTP, a pyrimidine nucleotide triphosphate, can enhance both mucin secretion and mucin gene expression through different signaling pathways.


A cross-sectional study on vaccine coverage and seroprevalence in schoolchildren in Andorra.
A cross-sectional study on vaccine coverage and vaccine effectiveness was carried out on a randomized sample of the cohort of schoolchildren born in 1983 attending school in Andorra, prior to the introduction of a Systematic Immunisation Plan that included centralised import and delivery of vaccines to vaccinating clinics, surveillance of the cold-chain during vaccine delivery, and a clearly-defined immunization schedule against diphtheria, tetanus, -pertussis, polio, mumps, rubella and measles. Vaccine coverage was estimated from vaccination card records; history of disease and sociodemographic variables were obtained through a questionnaire to the children's parents and vaccine effectiveness was estimated through serum antibody testing. Vaccine coverage levels for DTP and OPV were 97.8% for both. Protective serum antibody prevalence was correspondingly high except for the polio viruses. The authors suggest that decreased vaccine effectiveness, probably due to poor preservation of the cold chain, might be the cause of this finding. In countries or regions with an otherwise developed organisation of health services, an important issue like this can still be overlooked.


Hypothalamic-pituitary-adrenocortical axis function in premenopausal women with rheumatoid arthritis not treated with glucocorticoids.
To assess hypothalamic-pituitary-adrenocortical axis function in patients with rheumatoid arthritis (RA) not previously treated with glucocorticoids in relation to their inflammatory condition and in comparison to healthy controls. We evaluated, in 10 premenopausal patients with RA and 7 age matched controls, plasma dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and cortisol concentrations, together with inflammatory cytokine levels [interleukin 6 (IL-6) and IL-12], both in basal conditions and after stimulation with ovine corticotropin releasing hormone (oCRH) and with low dose intravenous (5 microg) adrenocorticotropic hormone (ACTH). DHEA and DHEAS basal concentrations were found to be significantly lower (p<0.05) in premenopausal patients with RA than in controls. As expected, significantly higher basal levels of IL-6 and IL-12 (p<0.05) were found in patients with RA. After the low dose ACTH testing, the DHEA area under the curve value was found to be significantly lower (p<0.01) in patients than controls. Similar results, but without statistical significance, were observed after oCRH stimulation. DHEA levels at basal time showed a significant negative correlation with the erythrocyte sedimentation rate and platelet count, as well as with the Steinbrocker class of the disease (p<0.05). Normal plasma cortisol levels during oCRH and ACTH testing were found in patients with RA in spite of their inflammatory condition. After ACTH testing, IL-6 levels decreased significantly (p<0.05), whereas IL-12 levels were unchanged. No significant changes in IL-6 and IL-12 levels were found after oCRH testing. The abnormal androgen concentrations observed during testing in patients with RA might support the implication of adrenal androgens in the immune/inflammatory cytokine mediated mechanisms involved in the pathophysiology and clinical aspects of RA.


Gonadal dysfunction in uremic men. A study of the hypothalamo-pituitary-testicular axis before and after renal transplantation.
Evaluation of testicular function in 13 hemodialyzed patients revealed the following: plasma testosterone (ng/100 ml) was low (less than 300 ng/100 ml) in 6 and low normal in 7 patients; sperm counts ranged from 0 to 8 million/ml and motility from 0 to 8 per cent; testicular tissue from 2 patients showed an abnormal histologic picture ranging from hypospermatogenesis to germinal cell aplasia. Follicle-stimulating hormone (FSH, ng/ml) was normal in eight (10 to 217 ng/ml), and persistently eveated in five patients (265 to 760 ng/ml). Of the latter five patients, two were azzoospermic, one had germinal cell aplasia on postmortem examination, one had virtually no viable sperms, and the other was never able to furnish ejaculate for examination. Luteinizing hormone (LH, mg/ml) was high (more than 210 ng/ml) in five and normal in eight patients. Six patients when given clomiphene showed the normal response of increased FSH and LH release. Four of the 13 patients, when restudied 6 to 12 months later and while still on dialysis, showed further deterioration of plasma testosterone and sperm counts. Four of the patients subsequently underwent successful renal transplantation. All showed improvement in sperm counts (20 to 40 million/ml, motility 40 to 90 per cent) and plasma testosterone (440 to 850 ng/100 ml). These data suggest that both germinal cell and leydig cell functions were impaired among uremic men. These dysfunctions were not correctable by hemodialysis, but were completely reversed by renal transplantation. The high FSH among patients with azzospermia indicates a responsive pituitary. The positive response to clomiphene suggests that storage as well as release of both hypothalamic and pituitary hormones were normal. Attempts to localize a single defect at the testis failed to explain the post-transplant surge of FSH which invariably proceded improvement in spermatogenesis. It is therefore postulated that a defect in that portion of the hypothalamus involved in the receipt and/or interpretation of message might be at fault in uremia.


Lifelong learning, CPD and you.
The essence of clinical governance is continuing professional development (CPD) for all professional staff. A system is now in place to disseminate and support CPD throughout the NHS, from national to local level.


ALASCA proficiency testing scheme for occupational hygiene laboratories.
Nowadays, quality assurance is an important part in the environment of analytical laboratories, who need to prove their ability to perform analysis as well to handle routine control as research and development analysis. A proficiency testing scheme (PTS) is one of the possible and powerful tools to evaluate both bias and dispersion of the analysis. As far as industrial hygiene is concerned, since analytical uncertainty is insignificant with regard to sampling strategy uncertainty, laboratories could be tempted to neglect analytical uncertainty assessment as well. The department 'Métrologie des Polluants' (part of INRS) has been organising a proficiency testing scheme since 2002 with the intention of giving the most reliable performance assessment to the participant. The original features, which are also the strong points of the scheme, are: the determination of the assigned value by a method that is independent from the analytical method to be tested; the development of original tools for the fabrication of samples; the strength of the statistic model, which is based on the WASP HSL scheme model; a tool to visualize the results of participants in bias and dispersion contribution; communication with the participants; a completely computerized system to handle the participant database, the sample database, results treatment and report edition; and the use of internet facilities to allow the participant to submit the results via a secured website. All these technical and organisational points are detailed in this paper.


[Enzymatic detoxication of organophosphorus insecticides and nerve gases in primates].
The detoxication of organophosphorus compounds by phosphorylphosphatases was studied in primates. Taking into account the distribution of paraoxonase (EC 3.1.1.2) and DFPase (EC 3.8.2.1) in different tissues of the monkey (Macaca mulatta), the total detoxicating capacity for diethyl-p-nitrophenylphosphate (paraoxon, E 600) and diisopropylphosphorofluoridate (DFP) was determined. Acetylcholinesterase (AChE) (EC 3.1.1.7) of human brain was inhibited in vitro by paraoxon and DFP. Using the rate constants of AChE-inhibition and of AChE-synthesis those concentrations of organophosphorus inhibitors were calculated, which in vivo would reduce the steady-state AChE-activity to 20% of normal. This acute ineffective concentration is 7.6 X 10(-8) g/kg for DFP and 2.3 X 10(-8) g/kg for paraoxon. From substrate kinetics of the phosphorylphosphatases the time course of paraoxon and DFP detoxication in primates could be calculated. The time needed by phosphorylphosphatases to reduce a certain dose of an organophosphorus compound to the acute ineffective concentration is referred to as "effective detoxication time". The effective detoxication time (teff) was determined for different concentrations of paraoxon and DFP and was compared with the time needed by these organophosphate concentrations to inhibit AChE-activity to 12.5% of normal (t1/8). The significance of in vitro data for the evaluation of dose limits of organophosphate toxicity in vivo is discussed.


Suicide by poisoning.
An epidemiological evaluation was conducted on 270 patients who died at the General Hospital, Port-of-Spain after presenting with deliberate self-poisoning between January, 1986 and June, 1990. The cause of death was confirmed by autopsy and toxicological analysis. Epidemiological variables of age, sex, race, precipitating factors and types of poison used were assessed. It was found that the male to female ratio was 2.7:1. East Indians accounted for 54.4%, Africans 42.0%, people of mixed ethnic origin 3% and Caucasians 0.6%. The majority of cases (52.6%) were seen in the age group 11-34 years. "Lovers' quarrels" (35.4% of cases), psychiatric illness (27.8% of cases) and family disputes (27% of cases) were reported as the most frequent precipitating events in suicide. East Indians predominated in those suicides precipitated by "lovers' quarrels" and family disputes, accounting for 63.2% and 58.9% of these cases, respectively; while for those suicides in which psychiatric illnesses were the main precipitating event. Africans were represented by 53.3% and East Indians 45.3%. Depression was the most common psychiatric illness diagnosed. Paraquat was the most popular poison used in 63.7% of the suicidal cases, and other agrochemicals were used in 20% of cases.


Anterior osteophytectomy for cervical spondylotic myelopathy in developmentally narrow canal.
The authors present 19 cases of cervical spondylotic myelopathy in patients with developmentally narrow canal treated by microsurgical anterior osteophytectomy with interbody fusion, with follow-up periods of 1 to 8 years (mean 38 months). Postoperatively, the lower limb function, evaluated by Nurick's six-grade classification, improved two or three grades in 16 cases, one grade in two cases, and remained unchanged in one case. The upper limb function, evaluated by the authors' own four-grade classification, improved two or three grades in 11 cases, one grade in seven cases, and remained unchanged in one case. No deterioration caused by the osteophytectomy was seen. During the follow-up period, spondylolisthesis appeared 31 months postoperatively in one patient and soft disc hernia occurred 66 months postoperatively in another; these two patients were treated by a second operation and cervical traction, respectively. The authors conclude that anterior osteophytectomy with interbody fusion is applicable as a surgical treatment of cervical spondylotic myelopathy even where developmental canal stenosis is present.


Acute subdural haematoma without subarachnoid haemorrhage caused by rupture of an internal carotid artery bifurcation aneurysm: case report and review of literature.
Spontaneous pure acute subdural haematoma (ASDH) without intraparenchymal or subarachnoid haemorrhage caused by a ruptured cerebral aneurysm is extremely rare. To our knowledge, the present case is the first report of an internal carotid artery bifurcation aneurysm presenting as pure ASDH. Suitable diagnostic investigations and therapeutic strategies are discussed. Arterial origin of bleeding should be considered in all cases of non-traumatic ASDH and a vascular anomaly has to be excluded. The neurological status on admission dictates the appropriate timing and methodology of the neuroradiological investigations.


Catalytically active nanoparticles stabilized by host-guest inclusion complexes in water.
Hydrogenation of arene derivatives can be successfully performed in water by using ruthenium(0) nanoparticles stabilized by 1 : 1 inclusion complexes formed between methylated cyclodextrins and an ammonium salt bearing a long alkyl chain.


Primary and predicted secondary structures of the caseins in relation to their biological functions.
In free solution, the caseins behave as non-compact and largely flexible molecules with a high proportion of residues accessible to solvent. Historically, they have been described as random coil-type proteins with only a nutritional function. Nevertheless, secondary structure prediction algorithms indicate that many parts of the (unphosphorylated, unglycosylated) polypeptide chains can form regular structures. In particular, a recurrent motif of the Ca2+-sensitive caseins in man, rat, mouse, guinea pig and ruminant species is an alpha-helix--loop--alpha-helix conformation in which the loop region typically contains a cluster of sites of phosphorylation. The biological function of the caseins is considered and it is suggested that the potential or actual conformations of the group of Ca2+-sensitive caseins are suited to the function of modulating the precipitation of calcium phosphate from solution. Either they can act as sites for nucleation or they can bind rapidly to calcium phosphate nuclei as they form spontaneously from supersaturated solution.


Optimization of the separation of salbutamol and its decomposition products by liquid chromatography with diode-array detection.
A high-performance liquid chromatographic (HPLC) method based on diode-array detection is developed and optimized for stability studies on salbutamol. In establishing the method, the effects of mobile phase constituents (buffers, buffer concentration, pH, modifiers, organic solvents, ion-pair reagents) upon the resolution of salbutamol and its degradation products are studied. The optimum method involves the use of a LiChrosorb RP-18 column with a one-step gradient elution with acetonitrile-sodium dihydrogen phosphate (40 mM)-triethylamine (5.74 mM) (pH 3.0). The acetonitrile content is increased from 4 to 9% after 6 min.


Time-resolved microspectrofluorimetry and fluorescence lifetime imaging of hypericin in human retinal pigment epithelial cells.
Hypericin is the active ingredient of the off-the-shelf antidepressant St. John's Wort. It is an effective phototoxic agent and its systemic administration at therapeutic doses could induce particular damage in the eye due to continuous light exposure. Hypercin is strongly fluorescent and its fluorescence properties can be monitored to investigate noninvasively its localization and interactions. To this aim, time-resolved microspectrofluorimetry and fluorescence lifetime imaging were used to assess the spectral and temporal properties as well as the spatial distribution of the fluorescence emitted by retinal pigment epithelium (RPE) cells treated with Hyp at concentrations in the micromolar range (0.5-10 microM). In the presence of hypericin, the emission peaks at 600-605 nm and the fluorescence decay is best fitted with three lifetimes (5.5-7 ns, 1.9-2.5 ns and <0.8 ns). Spectral and temporal differences were observed between high (> or =5 microM) and low hypericin concentrations. In particular, upon increasing concentration, the emission spectrum of the slow component broadens and its lifetime shortens. The latter change is observed also when high concentrations are reached locally, due to more efficient localization within the cell.


A luminescent cationic metal-organic framework featuring [Cu-pyrazolate]3 units for volatile organic compound sensing.
A new metal-organic framework (1) constructed from 4-(4-(3,5-dimethyl-1H-pyrazol-4-yl)phenyl)pyridine (HL) and CuBr shows potential as a luminescent sensor for volatile organic compounds.


Case of direct insertion within a chromosome 3 leading to a chromosome 3p duplication in an offspring.
An infant with developmental delay and multiple minor congenital anomalies had a duplication of bands p11.1----p14.2 in 3p. Maternal chromosome studies demonstrated a direct intrachromosomal insertion within chromosome 3p.


Dietary fish oil and flaxseed oil suppress inflammation and immunity in cats.
The modulatory activity of dietary n-3 fatty acids on inflammation and immune response in domestic cats is unknown. Mature female cats (n=14/treatment) were fed control, fish oil or flaxseed oil diets with n-6:n-3 fatty acid ratios of 20:1, 5:1 and 5:1, respectively, for 12 wk. Immune response was assessed on wk 0, 6 and 12, and skin hypersensitivity response on wk 6 and 12. Fish oil increased (P<0.01) eicosapentaenoic and docosahexaenoic acids in plasma and skin, whereas flaxseed oil increased α-linolenic acid. Fish and flaxseed oils decreased (P<0.01) skin inflammatory response to histamine. Cats fed fish but not flaxseed oil had higher (P<0.05) skin leukotriene LTB(5), but not LTB(4). Fish and flaxseed oils lowered B, total T and T(h) subset populations, and leukocyte proliferative response to PWM (P<0.05). In contrast, there was no change in ConA- or PHA-induced lymphocyte proliferation, Tc and MHC II cell populations, DTH response, NK cytotoxicity, IL-2 production, or plasma IgG concentrations. Therefore, fish and flaxseed oil can reduce skin inflammatory responses in cats, however, flaxseed oil appears less immunosuppressive than fish oil.


Performance of Geno2Pheno[coreceptor] to infer coreceptor use in human immunodeficiency virus type 1 (HIV-1) subtype A.
Assessment of human immunodeficiency virus type 1 (HIV-1) coreceptor usage is required prior to treatment with the CCR5 antagonist maraviroc to exclude the presence of CXCR4-using (X4) strains. Genotype-based interpretation systems are mostly designed on subtype B and have been reported to be less accurate for subtype A/CRF02_AG. To evaluate the performance of the widely used Geno2Pheno[coreceptor] (G2P[c]) algorithm for prediction of coreceptor usage with subtype A/CRF02_AG vs. subtype B. Co-receptor tropism of 24 subtype A/CRF02_AG and 24 subtype B viruses was measured phenotypically by a homebrew single-cycle assay and genotypically by using G2P[c]. Samples with discrepant genotype-phenotype results were analyzed by next generation sequencing (NGS) and interpreted by the NGS Geno2Pheno algorithm (G2P[454]). At 10% false positive rate (FPR), the G2P[c]/phenotype discordance rate was 12.5% (n = 3) for subtype A/CRF02_AG and 8.3% (n = 2) for subtype B. Minority X4 species escaping detection by bulk sequencing but documented by NGS explained the two subtype B and possibly one subtype A/CRF02_AG discordant case. The other two subtype A/CRF02_AG miscalled by G2P[c] could be explained by X4 overcalling at borderline FPR and/or by algorithm failure. Our study did not demonstrate relevantly higher G2P[c] inaccuracy with subtype A/CRF02_AG with respect to subtype B. Genotype/phenotype discordances can be due to different reasons, including but not limited to, algorithm inaccuracy. Very large genotype/phenotype correlation panels are required to detect and explain the reason for any consistent difference in genotypic tropism prediction for subtype A/CRF02_AG vs. subtype B.


Exploring gas-phase ion-ionophore interactions: infrared spectroscopy of argon-tagged alkali ion-crown ether complexes.
Argon-tagged alkali metal ion-crown ether complexes were generated in the gas phase and investigated using a combination of infrared predissociation (IRPD) spectroscopy, density functional, and symmetry-adapted perturbation theory (SAPT). The IRPD spectra of M(+)(12-crown-4 ether)Ar and M(+)(18-crown-6 ether)Ar, where M = Li, Na, K, Rb, and Cs, were collected in the CH stretching region, using the argon-messenger technique. The gas-phase neutral vibrations for each crown ether shift to higher frequency when complexed to an alkali metal ion. Similarities in the experimental IRPD spectra of Li(+)(12-crown-4 ether)Ar and Li(+)(18-crown-6 ether)Ar indicate that the binding of Li(+) is similar for both crown ethers. In the 12-crown-4 ether systems, there are trackable changes with ion size in the IRPD spectra until the point is reached where the ion is too large to bind to the interior of the macrocycle. Starting with Na(+), the 18-crown-6 spectra vary only slightly as the ion size is increased. The overall profiles of the IRPD spectra indicate that a similar configuration of the complexes is adopted for the ions larger than Na(+). The calculated SAPT interaction energies mirror the trends exhibited by the IRPD spectra and provide interesting insights on the roles of the different interaction energy components in binding the cation to the crown-ether.


Developing techniques in blood transfusion.
Expansion of transfusion medicine has led to an increasing awareness of the importance of its practice. Specialists in this branch of haematology whose main aim is to provide adequate and safe supplies of blood (and blood products) and to ensure these are used appropriately, are increasingly aware that to do this efficiently requires the development and utilization of new laboratory and technical procedures. Review of cross-matching techniques has led to the introduction of more rapid methods using low ionic strength saline. Use of monoclonal antibodies for blood grouping has made use of new technology, whilst allowing scarce human plasma to be used more appropriately for therapeutic purposes. Similarly, the implementation of a more rational approach to blood ordering, as in a maximum surgical blood-order schedule, allows for the more efficient use of donor blood. The use of microtitre plates for grouping and cross-matching techniques allows for speed and economy in the transfusion laboratory. Their use is also associated with increased automation and computer use. The possibility of using solid-phase techniques, monocyte-macrophage assays and antibody-dependent cellular cytotoxicity assays introduces new techniques differing markedly from time-honoured liquid-phase serology methods. The application of flow cytometry, which has already been shown to be useful in many aspects of haematology, is also of benefit in the field of blood transfusion science. Safety of blood transfusion is an important aspect of its practice and has led to the introduction and development of screening tests for donor blood to exclude infection risks from such organisms as HIV-1, hepatitis B and non-A, non-B hepatitis. Another approach to ensure the safety of transfused blood has been increased usage of autologous transfusion by means of both predeposit donation and intraoperative cell salvage.


Dynamics of the interventricular septum and ventricular free walls during regional ischaemia in open-chest dogs.
The significance of ischaemia of the left ventricular (LV) and right ventricular (RV) free walls for the dynamics of the interventricular septum (IVS) and the right ventricle was examined in open-chest dogs. Left ventricular and RV ischaemia reduced stroke volume similarly, by 11.2 +/- 1.4% and 11.2 +/- 2.4%, respectively. The dynamics of myocardial segment lengths (SL), recorded in the LV and RV free walls and the IVS, differed. During LV ischaemia, end-diastolic SL (EDSL) and systolic shortening (SS) increased in the IVS, whereas SL remained unchanged in the RV free wall. During RV ischaemia, LV EDSL, and SS decreased. Interventricular septum EDSL also decreased, but this reduction was not statistically significant. During blood volume expansion, LV and RV function curves were shifted right, and/or downwards by LV ischaemia, whereas only the RV function curve was shifted downwards and to the right by RV ischaemia. Thus, ischaemia of the LV free wall induces activation of the Frank-Starling mechanism in the interventricular septum and a deterioration of right ventricular performance.


Early diagnosis of cardiac sarcoidosis using magnetic resonance imaging.
Cardiac sarcoidosis can be a challenging diagnosis to make. The introduction of newer technologies, such as cardiac magnetic resonance imaging and positron emission tomography, have meant earlier diagnosis is possible. This is crucial as early treatment improves symptoms and prognosis.


Symptom cluster: Depression and pain.
Pain and depression are two frequently associated aspects in oncology. The reciprocal influence of both pathologies is discussed under both the point of view of the underlying biological mechanisms as well as its emotional and cognitive aspects. Mood depression somatic symptoms include pain, just as chronic pain emotional aspects are strictly related to anxiety and depressed mood. Pharmacological treatment for pain with antidepressant drugs (ADs) is discussed, since such drugs offer a direct and an indirect mitigating action on pain perception, and also allow positive changes in the cognitive attitude toward pain. The social and emotional aspects of pain are also discussed bringing evidences of how combined antalgic therapies (analgesics, antidepressants, psychotherapies among others), especially on elderly oncological patients, are more effective than each treatment alone.


[The usefulness of MRI for the diagnosis of abnormal pregnancies].
The clinical usefulness of MRI for the diagnosis of abnormal pregnancies was evaluated. Pelvic MRI was carried out on 29 cases suspected of abnormal pregnancy by ultrasonography and clinical examinations. The abnormal pregnancies were classified into three categories: (1) maternal abnormalities, (2) fetal abnormalities and (3) placental abnormalities. (1) MRI was of great value for the diagnosis of maternal abnormalities, particularly in cases of coexistent pelvic tumors. MRI allowed diagnosis of uterine leiomyomas and dermoid cyst through its excellent tissue characterization and broad range of vision. (2) MRI was useful in making diagnoses of fetal central nervous anomalies and fetal death, since the lack of fetal movement and the lesions were clear enough to be detected by MRI. However, anomalies in the fetal trunk or extremities could only be demonstrated, but not diagnosed, by MRI owing to its inferior spatial and time resolution. (3) MRI showed placenta accreta and placental hematoma. Although accurate diagnosis was difficult because of their rarity, MRI revealed the hemorrhagic component of the lesions, which was not shown by ultrasonography. The author believes MRI has potential usefulness in making diagnoses of placental abnormalities through its tissue characterization. MRI was superior to ultrasonography in the soft tissue characterization, field of view, while MRI was inferior in time and spatial resolution. In summary MRI should be used in case of abnormal pregnancies such as pelvic tumors, fetal nervous anomalies and placental hemorrhagic lesions. MRI will become useful for the diagnosis of other abnormalities as its spatial resolution and fast scan technology advances.


Inhibition of rat testicular 17 alpha-hydroxylase and 17,20-lyase activities by anti-androgens (flutamide, hydroxyflutamide, RU23908, cyproterone acetate) in vitro.
Flutamide, hydroxyflutamide, RU23908 and cyproterone acetate (CPA) inhibited rat testicular microsomal 17 alpha-hydroxylase and 17,20-lyase activities in vitro. The Km of [3H] progesterone for 17 alpha-hydroxylase was 45 +/- 0.62 nmol/l (+/- SEM, n = 12) and the Km of [3H] 17 alpha-hydroxyprogesterone for 17,20-lyase was 192 +/- 0.42 nmol/l (+/- SEM, n = 12). The Ki values for 17 alpha-hydroxylase, determined from Lineweaver-Burk plots were 102 +/- 3.2 mumol/l (+/- SEM, n = 6), 363 +/- 3.8 mumol/l (+/- SEM, n = 6), 118 +/- 1.4 mumol/l (+/- SEM, n = 6) and 123 +/- 2.1 mumol/l (+/- SEM, n = 6) for flutamide, hydroxyflutamide, RU23908 and CPA respectively. Flutamide and CPA were mixed-type inhibitors, whereas hydroxyflutamide and RU23908 were competitive inhibitors of 17 alpha-hydroxylase activity. Ki values for 17,20-lyase were 33 +/- 3.1 mumol/l (+/- SEM, n = 6), 112 +/- 3.1 mumol/l (+/- SEM, n = 6), 69 +/- 4.4 mumol/l (+/- SEM, n = 6) and 71 +/- 3.2 mumol/l (+/- SEM, n = 6) for flutamide, hydroxyflutamide, RU23908 and CPA, respectively. Inhibition was found to be competitive in each case. Although the characteristic action of anti-androgens is at the receptor level, these results demonstrate that anti-androgens may also have inhibitory effects on androgen biosynthesis which could prove to be of clinical significance.


Growth and vibrational spectral investigation of nonlinear optical crystal L-Argininum Perchlorate-DFT study.
Nonlinear optical active L-Argininum Perchlorate single crystals are grown by slow evaporation technique. The second-order NLO properties of the molecule are studied by Kurtz-Perry powder technique. FT-IR, FT-Raman spectra have been recorded and analyzed. The equilibrium geometry, vibrational wavenumbers and the first order hyperpolarizability have been calculated with the aid of density functional theoretical method. The NBO analysis explains the intramolecular interactions, electron densities within the molecule. It also confirms the presence of weak intermolecular C-H···O hydrogen bonding in the molecule. The blue-shift in CH stretching wavenumbers is due to the C-H···O hydrogen bonding. The Mulliken population analysis on atomic charges and the HOMO, LUMO energies were also calculated.


Metabolic rates associated with distress and begging calls in birds.
Rates of oxygen consumption during begging behaviour in nestlings of seven species and distress call behaviour in adults of eight species of Australian birds were measured. A transparent mask coupled to an open-flow respirometry system was used, and calling was elicited by the presentation of food or by the perceived threat of a predator. Distress calling significantly increased oxygen consumption above the measured resting levels in six of the species of birds tested. The factorial increase in oxygen consumption during distress calling was independent of body mass. In most cases, begging behaviour in juvenile birds caused a significant increase in metabolic rate, with some individuals showing factorial increases over fourfold. There was a significant negative correlation between body mass and the factorial cost of begging behaviour.


Thalamotomy, DBS-Vim, and DBS-GPi for generalized dystonia: a case report.
Generalized dystonia is a disabling disorder that can severely affect quality of life. Pharmacological treatment is unsatisfactory, and surgical therapy has been the focus for symptom improvement. We present the first case report of a patient with disabling generalized dystonia treated with a thalamotomy and deep brain stimulation of the thalamus and globus pallidus (DBS-Vim, DBS-GPi). His tremor and dystonic symptoms have dramatically improved through combining these surgical interventions.


A federalist approach to health reform: the worst way, except for all the others.
Support for state action should be part of any strategy to expand health insurance coverage. Decades-long political deadlock in Washington has frustrated national efforts to expand coverage. Some states have already undertaken to do this; others show a determination to do so. Regulatory and legislative flexibility would trigger widespread state action. Whether one thinks that ensuring coverage requires a unified national approach or that diverse conditions require different methods in different states, the likelihood of progress will be advanced if states test out various ways to expand coverage. We describe a practical way by which the federal government can promote state action to expand health insurance coverage.


Subacute cystic expansion of intracranial juvenile psammomatoid ossifying fibroma.
Juvenile psammomatoid ossifying fibroma (JPOF) is a benign fibro-osseous lesion typically associated with the jaw, paranasal region, or orbit. However, JPOF may also originate from the skull base and locally invade the cranium. In published reports, intracranial JPOFs constitute only a small percentage of cases, and therefore it is not known whether more aggressive behavior typifies this distinct population of JPOFs compared with those in other locations. Nevertheless, JPOF histopathology is characterized by a number of active processes, including cystic transformation, that may precipitate violation of skull base boundaries. In the following article, the authors present a case of skull base JPOF that underwent cystic expansion in a young girl, produced a focal neurological deficit, and was resolved using a staged surgical approach.


[Inhibition of 1,2-dimethylhydrazine-induced carcinogenesis in rat gut by the antidiabetic drug Diabenol].
Diabenol, a new Russian antidiabetic drug, was used to investigate its effect on 1,2-dimethylhydrazine (DMH)-induced carcinogenesis in rat large gut. Five doses of 21 mg/kg DMH were injected at an interval of one week. Administration of 10 mg/kg diabenol with drinking water had no effect on either body mass or feed and water consumption. Yet, it was followed by a significant decrease in tumor incidence (4.22 vs. 5.77 tumors per tumor-bearers), frequency of neoplasms in the ascending colon (40.0% vs. 89.5%) and in their number (0.60% vs. 1.63 tumors per rat in a group). In the other groups, those indices tended to be still lower. Another tendency characteristic of the experimental group was a significantly high percentage of exophytic tumors (76.3% as compared with 50% in control) consisting of well-differentiated cells (47.4% and 14.7%, respectively) and with predominantly shallow invasion into the gut wall. Our results suggest the ability of the drug to inhibit DMH-induced carcinogenesis in the rat large gut.


[Clinical reasoning and decision-making in practice. An older man with prostate carcinoma and a painless paraparesis of the legs].
A 78-year-old man with metastasised prostate carcinoma presented with a painless paraparesis. His cerebrospinal fluid showed elevated protein and a mononuclear pleiocytosis, but cytology investigations of 5 separate samples revealed no malignant cells in the cerebrospinal fluid. Extensive viral and bacterial tests (including ELISA for Borrelia burgdorferi) of serum and cerebrospinal fluid were negative. On the day radiation therapy for presumed leptomeningeal metastases was due to start the IgG and IgM Western blot for Borrelia were found to be positive, indicating neuroborreliosis. Soon after the start of antibiotic therapy the paraparesis began to improve and after four weeks the patient had made a complete recovery. In patients with a progressive paraparesis, neuroborreliosis should be considered even in the absence of pain.


Deterministic escape dynamics of two-dimensional coupled nonlinear oscillator chains.
We consider the deterministic escape dynamics of a chain of coupled oscillators under microcanonical conditions from a metastable state over a cubic potential barrier. The underlying dynamics is conservative and noise free. We introduce a two-dimensional chain model and assume that neighboring units are coupled by Morse springs. It is found that, starting from a homogeneous lattice state, due to the nonlinearity of the external potential the system self-promotes an instability of its initial preparation and initiates complex lattice dynamics leading to the formation of localized large amplitude breathers, evolving in the direction of barrier crossing, accompanied by global oscillations of the chain transverse to the barrier. A few chain units accumulate locally sufficient energy to cross the barrier. Eventually the metastable state is left and either these particles dissociate or pull the remaining chain over the barrier. We show this escape for both linear rodlike and coil-like configurations of the chain in two dimensions.


Selective bladder-sparing protocol consisting of induction low-dose chemoradiotherapy plus partial cystectomy with pelvic lymph node dissection against muscle-invasive bladder cancer: oncological outcomes of the initial 46 patients.
To evaluate oncological outcomes of muscle-invasive bladder cancer (MIBC) patients who were treated with a selective bladder-sparing protocol consisting of induction low-dose chemoradiotherapy (LCRT) plus partial cystectomy (PC) with pelvic lymph node dissection. From 1997-2010, 183 consecutive patients with cT2-4aN0M0 bladder cancer (median age 70 years, women/men = 46/137, T2/3/4a = 100/69/14) underwent debulking transurethral resection followed by LCRT (radiation at 40 Gy to the small pelvis concurrently with two cycles of i.v. cisplatin at 20mg/day for 5 days). Criteria for PC include: (i) essentially solitary MIBC or intravesically circumscribed tumours (≈25% or less of the bladder in area, excluding the bladder neck and trigone); (ii) no involvement of bladder neck or trigone; and (iii) clinically, no residual disease or minimal amounts of non-invasive disease in the original MIBC site after LCRT; otherwise, radical cystectomy (RC) is recommended. Primary and secondary endpoints were cancer-specific survival (CSS) and intravesical MIBC recurrence-free survival (MRFS) for bladder-preserved patients, respectively. Of the 183 patients, 87 (48%) achieved a clinical complete response after LCRT and 65 (36%) met the PC criteria; 46 (25%) patients actually underwent PC, 86 (47%) had RC, and the remaining 51 (28%) had neither PC, nor RC. Histological examination of the 46 PC specimens showed residual muscle-invasive disease in three (7%). Overall, 5-year overall survival and CSS rates were 64% and 71%, respectively (median follow-up for survivors of 45 months). In the 46 PC patients, neither MIBC, nor pelvic recurrence was observed; 5-year CSS and MRFS rates were both 100%. In 13 non-PC patients who achieved a complete response after LCRT and who met PC criteria but declined PC, 5-year CSS and MRFS rates were 74% and 81%, respectively; CSS and MRFS were significantly better in the PC group than in the non-PC group (P= 0.025 and 0.002, respectively). In the current selective bladder-sparing protocol, one-third of MIBC patients met the PC criteria; when patients from this group underwent PC with pelvic lymph node dissection, their oncological outcomes were excellent. Consolidative PC potentially reduces MIBC recurrence in the preserved bladder, eventually improving survival in properly selected MIBC patients.


Spirosoma sordidisoli sp. nov., a propanil-degrading bacterium isolated from a herbicide-contaminated soil.
A novel Gram-stain negative, aerobic, rod-shaped, asporogenous, propanil-degrading bacterial strain, TY50T, was isolated from a herbicide-contaminated soil in Nanjing, China. Strain TY50T was found to grow optimally at pH 9.0, 30 °C and in the absence of NaCl. The G + C content of the total DNA was determined to be 55.5 mol%. The 16S rRNA gene sequence of strain TY50T shows high identity to that of Spirosoma lacussanchae CPCC 100624T (99.3%), Spirosoma metallicum PR1014kT (94.8%) and Spirosoma soli MIMBbqt12T (94.6%). DNA-DNA hybridization indicated that the isolate had relatively low levels of DNA-DNA relatedness with S. lacussanchae CPCC 100624T (48.3%). Average nucleotide identity and the digital DNA-DNA hybridizations for draft genomes between strain TY50T and S. lacussanchae CPCC 100624T were 93.2% and 51.0%, respectively. The major cellular fatty acids of strain TY50T were identified as C16:1ω5c (24.5%) and summed feature 3 (C16:1ω6c/C16:1ω7c, 40.7%). MK-7 was found to be the predominant respiratory quinone. The major polar lipid profile includes phosphatidylethanolamine, an unidentified lipid and an unidentified aminolipid. These chemotaxonomic data support the affiliation of strain TY50T with the members of the genus Spirosoma. Strain TY50T can be distinguished from its close phylogenetic neighbours based on its phenotypic, genotypic, and chemotaxonomic features. Therefore, strain TY50T represents a novel member of the genus Spirosoma, for which the name Spirosoma sordidisoli sp. nov. is proposed. The type strain is TY50T (= KCTC 62494T = CCTCC AB 2018041T).


Effect of subcutaneous desferrioxamine on iron balance in young thalassemia major patients.
In this study we evaluated the effect of 1-year, subcutaneous desferrioxamine daily infusion on iron balance in 23 thalassemia major children, aged 8-74 months, with transfusional iron accumulation less than 3.8 g at the outset of the trial. Statistical analysis showed a significant correlation between transfusional iron accumulation and percentage of transfusional iron eliminated. Confidence limits analysis of these data indicated that over 3.5 g of transfusional iron load, 95% of the patients may achieve balance. The appropriate time to begin desferrioxamine infusion, therefore, seems to be after about 30 transfusions of packed red blood cells when iron accumulation of approximately 3 g is reached. As we found a statistically significant correlation between transfusional iron eliminated and serum ferritin levels, the evaluation of serum ferritin alone can also predict when balance can be obtained.


Bone healing in drill hole defects in spontaneously hypertensive male and female rats' femurs. A histological and histometric study.
The aim of this study was to evaluate the bone healing in spontaneously hypertensive rats (SHR) and compare the results with normotensive rats, evaluating male and female animals. A bone drill defect was created in the left femur of 24 SHR (12 males and 12 females) and 24 normotensive rats (12 males and 12 females). The animals were divided into two groups and sacrificed 7 and 21 days after the surgical procedure. After the routine laboratory processing, histological and histometric analysis were carried out and data were submitted to ANOVA and Tukeys test (5%). Males and females from the same group had similar histological characteristics. After seven days, all animals presented irregular bone trabeculae. The periosteal osteoblasts were flattened in SHR, and presented a cuboid shape in normotensive animals. After 21 days, the bone defects of all specimens showed a linear closure in all the superficial extension. In addition, SHR presented flattened osteoblasts surrounding the bone trabeculae, while normotensive ones showed cuboidal cells. Statistical analysis of the histometric data indicated similar means between the male and female groups, except for normotensive rats on day 7. In addition, a larger amount of new bone formation was observed in hypertensive when compared to normotensive rats on day 21, in males as well as females. We conclude that bone healing in SHR was more significant than in normotensive ones, as shown by the histological and histometric evaluation 21 days after surgery.


[Diarrhea cause by parasites].
Parasites, once an exclusively tropical problem, are rare causes of diarrhea in our countries. Increasing tourism and immune deficiencies due to treatment or to Aids lead to an increase of intestinal parasites in western countries. The most frequent pathogenic parasites are Giardia lamblia and Entamoeba histolytica but other organisms like Cryptosporidia seem to be of increasing importance and have to be considered in diarrhea of unknown origin.


Egas Moniz and internal carotid occlusion.
Egas Moniz discovered cerebral angiography in 1927 and introduced leukotomy as a form of treatment of mental illness, for which he received the Nobel Prize in 1949. His work on occlusive cerebrovascular disease is less known. In 1937 he originally described internal carotid occlusion as documented by angiography. His observations and comments on the clinical, pathogenic, and therapeutic aspects of internal carotid thrombosis are reviewed.


Incontinence, Incontinence-Associated Dermatitis, and Pressure Injuries in a Health District in Australia: A Mixed-Methods Study.
This purpose of this study was to measure the prevalence of incontinence, incontinence-associated dermatitis (IAD), and pressure injuries (PIs) in a local health district in Australia. We also aimed to determine associated evidence-into-practice gaps. Multisite mixed-methods study. The sample comprised 250 adult patients in 12 units across 4 hospitals; their mean age was 73 years. Nurses caring for the patient at the time of the audit were questioned on nursing practice for patients with incontinence. A 2-page audit tool was developed and used to capture demographic data, continence and mobility status, IAD and PI, incontinence products, nursing practice observations, and nurses' comments. Each patient was assessed by 2 senior nurses. Quantitative analysis included descriptive statistics and bivariate analysis using a χ test to examine the association between mobility and incontinence and a Fisher exact test to examine the association between IAD and PI. Content analysis was used to analyze qualitative data and develop themes. Almost half of patients had incontinence (n = 111/250), 20.7% of patients with incontinence (n = 23/111) had IAD, and 6.3% (n = 7/111) had hospital-acquired PI. There was a significant association between incontinence and mobility, and between IAD and PIs. In addition, 22.3% of patients who were continent (31/139) were wearing an incontinence product. Analysis of qualitative data found that both incontinence management and language used to refer to incontinence pads were incompatible with current best practices. The prevalence of incontinence among patients observed in this study was similar to rates reported internationally, but the prevalence of IAD was slightly lower. The association between IAD and PIs, as well as incontinence and mobility, was statistically and clinically significant. Nurses commonly used interventions with little or no evidence. Hospitals should put measures in place to improve nurses' knowledge of incontinence, IAD, and PI practices.


[Loss of metastatic deposits in breast sentinel lymph nodes during intra-operative frozen section analysis].
The intraoperative evaluation of sentinel lymph nodes is an ongoing debated issue. In this review we discuss different approaches to sentinel lymph node processing in an intra operative setting and in the consecutive embedding in paraffin. We propose a method, which uses routine intra operative examination of lymph nodes with stereo microscopy with selected frozen section analysis. We demonstrate preliminary data on a larger patient collective along with data on a control group. We could show in our study that a higher rate of metastates can be achieved avoiding intra operative frozen sections on grossly inconspicuous sentinel lymph nodes.


Relationship between serum CA 125 levels, endometrial thickness and corpus luteum function in different stages of ovarian activity.
CA 125 is a cell surface antigen expressed in some derivatives of celomic epithelium, predominantly in ovarian cancer cells. However, it has also been detected in serum of healthy women and in patients with benign gynecologic diseases. The exact source or sources of the circulating levels of CA 125 and their elevations are not known. In the present study, the relationship between serum CA 125 levels, ovarian steroidogenesis and endometrial thickness is investigated at different periods: 1) mid-follicular, 2) midcycle, and 3) midluteal phases in normal cycles of fertile women, in patients stimulated for intrauterine insemination (IUI) and in patients stimulated for in vitro fertilization (IVF). Only in patients with mild and moderate ovarian hyperstimulation (OHSS) of the IVF group were luteal phase CA 125 levels (149.7 +/- 24.4 U/ml) significantly higher than midfollicular (21.2 +/- 1.9 U/ml) and midcycle phase levels (24.4 +/- 2.5 U/ml) (p < 0.001). The mean midcycle estradiol and midluteal progesterone concentrations in patients stimulated for IUI and IVF were significantly higher than those of normally cycling women (p < 0.001). Mean endometrial thickness in patients stimulated for IVF was significantly higher than in patients stimulated for IUI and normally cycling women (p < 0.001). Midluteal CA 125 levels correlated with midcycle endometrial thickness (r = 0.585, p < 0.05) and midluteal P levels (r = 0.497, p < 0.05) in patients with OHSS of IVF group. This correlation was not observed in patients who had no signs and symptoms of OHSS during stimulation for IVF and in patient stimulated for IUI and the controls.(ABSTRACT TRUNCATED AT 250 WORDS)


Eating behavior in humans, characterized by cumulative food intake curves--a review.
Cumulative food intake curves have been obtained by monitoring eating from a plate, placed on a scale built into a table, and connected to a digital computer. They describe and integrate parameters of consumption of an ad lib single course meal, i.e. meal size, meal duration, eating rate, change in eating rate, bite size and bite frequency. It is concluded that they are an adequate tool for analyzing dietary and clinical interventions on meal size, because the cumulative food intake curve parameters: are stable and consistent within subjects; show a clear relationship with the subject characteristics dietary restraint and obesity; show a clear relationship with the physiological parameters satiation, diet-induced thermogenesis and body-temperature near the liver, and with the cognitive parameter: estimating forthcoming ingestion; are sensitive to instructions, clinical and dietary interventions (preloads, palatability, energy density, macronutrient composition), and to a state of negative energy balance. Because of possible compensatory post-prandial effects, it is suggested that assessment of meal size should be part of a 24 h appetite profile and food intake observation.


Site-specific methionine sulfoxide formation is the structural basis of chromatographic heterogeneity of apolipoproteins A-I, C-II, and C-III.
ApoA-I and apoC-II are eluted in two isoforms and apoC-III2 is eluted in three isoforms by reversed phase high performance liquid chromatography (HPLC). The structural basis of these nongenetic heterogeneities was unravelled using HPLC of proteolytic peptides and time-of-flight secondary ion mass spectrometry (TOF-SIMS). In apoA-I, the chromatographic microheterogeneity was caused by the formation of methionine sulfoxides (MetSO). However, only residues Met112 and Met148 were found oxidized, whereas Met86 was unaffected and also resistant towards artificial oxidation. To assess whether and to what extent amino acid substitutions in apoA-I might affect methionine sulfoxidation, the tryptic peptides of 13 different mutant apoA-I proteins from 24 heterozygous apoA-I variant carriers were analyzed by HPLC. In normal apoA-I, the ratios MetSO112/Met112 and MetSO148/Met148 were highly variable. By contrast, the relative ratio of oxidation of methionine residues 112 and 148 was constant. The amino acid changes Lys107----Met, Lys107----O, Glu139----Gly, Glu147----Val, and Pro165----Arg resulted in the preferential oxidation of Met112, and Asp103----Asn resulted in a preferential oxidation of Met148; whereas Pro3----Arg, Pro3----His, Pro4----Arg, Asp89----Glu, Ala158----Asp, Glu198----Lys, and Asp213----Gly had no impact. ApoC-II and apoC-III isoforms differed by the oxidation of the two methionine residues in these proteins. Whereas in apoC-II both methionine residues were oxidized in parallel, in apoC-III the two methionine residues differed in their susceptibility towards oxidation. We conclude that the formation of MetSO depends on the molecular microenvironment within a protein.


A Critical Review of Miniaturised Percutaneous Nephrolithotomy: Is Smaller Better?
In an effort to reduce morbidity related to percutaneous nephrolithotomy (PCNL), some investigators have progressively introduced miniaturised approaches. The development of miniaturised nephroscopes facilitated widespread dissemination of these techniques and a significant expansion of the role of PCNL in endourology. To discuss the different techniques comprising modern PCNL and identify the pros and cons of each of them. Data for this review were identified through a search of PubMed, including studies published in the last 20 yr in core clinical journals in English. The search terms included "urolithiasis", "nephrolithiasis", or "urinary stones" in combination with "miniaturised PCNL", "mini-PCNL", "micro-PCNL", "minimally invasive PCNL", and "ultra-mini PCNL". Publications relevant to the subject were retrieved and critically appraised. The indications for miniaturised PCNL have not been standardised yet. Even though data in the literature reveal limitations and conflicting results, these techniques seem promising in terms of effectiveness and safety for the treatment of renal stones. The development of miniaturised scopes facilitated knowledge of the physics behind the vacuum cleaner effect generated during procedures, and greater efficacy of holmium laser generators and surgeon skill have led to progressive expansion of the indications for miniaturised techniques. Well-designed, randomised, multi-institutional studies are needed to better understand the indications for these miniaturised techniques before considering them a standard procedure for potential replacement of conventional PCNL. Miniaturised PCNL represents a valuable new tool in the armamentarium of modern endourologists, capable of offering good outcomes with lower complications rates compared to the standard technique and higher cost effectiveness compared to flexible ureteroscopy. Miniaturised percutaneous nephrolithotomy represents a safe and effective alternative to standard techniques for the treatment of renal stones. Each patient needs to be considered individually and tailored surgical treatment has to be offered.


Presence of substance P and angiotensin II in corticotropic cells of the lizard Gallotia galloti: immunochemical study in the adult and during ontogenesis.
The hypophysis of the lizard Gallotia galloti showed substance-P-like immunoreactivity in both the adenohypophysis (pars distalis, PD; pars intermedia, PI) and the neurohypophysis (median eminence and pars nervosa), whereas angiotensin-II-like immunoreactivity appeared only in PD and PI. The elution-restaining procedure has allowed us to demonstrate the colocalization of both peptides with adrenocorticotropic hormone (ACTH) in PD and PI cells. Electron microscopic study revealed the presence of substance P immunoreactivity on ACTH secretory granules. The ontogeny of both peptides in corticotropic cells has been studied, revealing that the presence of substance P in ACTH-containing cells of the PI occurs from the embryonic stage 33 (S 33), whereas in the PD it occurs from S 34, coinciding with the appearance of ACTH within the same cells. In both median eminence and pars nervosa of the neurohypophysis, substance P appeared later in development, at S 38. Angiotensin II immunoreactivity in PI cells first appeared at S 38, while in PD it appeared from S 40.


Vitamin D receptor gene polymorphisms, bone mass, bone loss and prevalence of vertebral fracture: differences in postmenopausal women and men.
Bone mineral density (BMD), the major determinant of fracture risk, is under strong genetic control. Although polymorphisms of the vitamin D receptor (VDR) gene have been suggested to account for some of the genetic variation in bone mass, the influence of VDR genotypes on osteoporosis remains controversial. Previous published studies have focused mainly on women, but the pattern of response in men has not been determined. Using the BsmI restriction enzyme, we studied the influence of the different VDR genotypes on bone mass, bone loss and the prevalence of vertebral fractures in a population-based sample of both sexes (n = 326). BMD was measured at the lumbar spine and femoral neck, with a 4-year interval, using dual-energy X-ray absorptiometry. Vertebral fractures were assessed by two lateral radiographs at the beginning and end of the study. The prevalence of the three possible VDR genotypes was similar to those in other Caucasian populations and no differences were found between men and women. Women with the favorable bb genotype showed significantly higher BMD values at the lumbar spine and femoral neck, and a positive rate of BMD change at the femoral neck compared with women with the BB and Bb genotypes. Moreover, women with the bb genotype showed a trend toward a lower prevalence and incidence of vertebral fractures (p = 0.07). We have not found any differences between VDR genotypes in men. In conclusion, VDR gene polymorphisms are related to bone mass and bone loss in women; also a trend in the prevalence of vertebral fractures was observed in postmenopausal women but not in men.


A simplified and highly sensitive detection of Trypanosoma evansi by DNA amplification.
In Southeast Asia Trypanosoma evansi infection is a disease of economic importance since it affects the health of buffalo, cattle and swine. The acute stage symptoms include abortion, central nervous system disorder and even death, and in the chronic condition working capacity and productivity of the animals are affected. A polymerase chain reaction (PCR)-based detection technique has been developed with a sensitivity of 0.5 pg of parasite DNA or one single parasite in 10 microliters of blood samples which were allowed to clot and then boiled before DNA amplification. This permitted storage of blood collection at ambient temperature for at least one month. Phosphate-saline-glucose solution, normally used as trypanosome maintenance buffer, inhibited PCR. Although DNA primers used were derived from T. evansi specific sequence, amplification of the genome of T. brucei and T. equiperdum generated the same 227 bp fragment. This method should now make it possible to detect infections in livestock in the very early stages where microscope examination is equivocal and to monitor groups of animals after trypanocidal treatment.


Increased diagnosis of thin superficial spreading melanomas: A 20-year study.
Diagnostic practice by dermatopathologists evaluating pigmented lesions may have evolved over time. We sought to investigate diagnostic drift among a group of dermatopathologists asked to re-evaluate cases initially diagnosed 20 years ago. Twenty nine cases of dysplastic nevi with severe atypia and 11 cases of thin radial growth-phase melanoma from 1988 through 1990 were retrieved from the pathology files of the Massachusetts General Hospital. All dermatopathologists who had rendered an original diagnosis for any of the 40 slides and the current faculty in the Massachusetts General Hospital Dermatopathology Unit were invited to evaluate the slide set in 2008 through 2009. The mean number of melanoma diagnoses by the 9 study participants was 18, an increase from the original 11 melanoma diagnoses. A majority agreed with the original diagnosis of melanoma in all 11 cases. In contrast, a majority of current raters diagnosed melanoma in 4 of the 29 cases originally reported as dysplastic nevus with severe atypia. Interrater agreement over time was excellent (kappa 0.88) and fair (kappa 0.47) for cases originally diagnosed as melanoma and severely atypical dysplastic nevus, respectively. The unbalanced composition of the slide set, lack of access to clinical or demographic information, access to only one diagnostic slide, and imposed dichotomous categorization of tumors were limitations. A selected cohort of dermatopathologists demonstrated a general trend toward the reclassification of prior nonmalignant diagnoses of severely atypical dysplastic nevi as malignant but did not tend to revise prior diagnoses of cutaneous melanoma as benign.


Effect of conversion from ciclosporin to tacrolimus on endothelial progenitor cells in stable long-term kidney transplant recipients.
Endothelial progenitor cell (EPC) counts are proposed surrogate markers for vascular function and cardiovascular risk. The effect of tacrolimus (TAC) on EPC is unknown. In this randomized controlled trial, we assigned 148 stable long-term kidney transplant recipients (KTR) to maintaining ciclosporin (CSA) or to commencing TAC-based immunosuppression at a 2:1 ratio. EPC counts (CD34/KDR) after 24 months were defined as primary endpoint. The intent-to-treat analysis included 141 KTR (estimated glomerular filtration rate, 46.7 [40.1-61.8] mL/min per 1.73 m). Median (interquartile range [IQR]) EPC counts at baseline and month 24 were 6 (2-9) and 3 (1-9) cells and 4 (2-8) and 2 (0-5) cells per 5×10 mononuclear cells in CSA and TAC, respectively. Median (IQR) circulating angiogenic cells at baseline and month 24 were 28 (10.7-57) and 44.33 (14.6-59.8) cells and 22 (10.8-41) and 21 (9.7-49.5) cells per high-power field in CSA and TAC, respectively. Median (IQR) endothelial cell colony-forming units count per well at baseline and month 24 were 10.5 (3.3-34.3) and 4.38 (1.7-26.5) in CSA and significantly declined from 9.31 (1.8-29.3) to 4.13 (1.1-9.5) in TAC (P=0.003). There were no cardiovascular events in either group. Although late conversion from CSA to TAC appears safe in KTR, conversion to TAC has no favorable effect on EPC. Low EPC levels are associated with a higher risk of subsequent cardiovascular events and are therefore of prognostic value. Their trend to decline over time deserves further examination.


[Application of auxiliary manipulation channel during performance of cholecystectomy using minimal access].
The conduction of the supportive manipulation channel (SMCH) during the cholecystectomy and the oblique-changing gall bladder puncture performance was proposed to improve the conditions for doing the operation, rational application of minimal oblique subcostal access (MOSA) and postoperative complications prophylaxis. There were operated 17 patients using MOSA, in 15 SMCH was conducted, including 2 with intervention on extrahepatic biliary ducts: choledocholithotomy with external draining of common biliary ducts. In 12 patients intradermal suture was done.


Eicosapentaenoic acid inhibits prostaglandin D2 generation by inhibiting cyclo-oxygenase-2 in cultured human mast cells.
Eicosapentaenoic acid (EPA) is catalysed by cyclo-oxygenase (COX), as is arachidonic acid, and is a competitive inhibitor of arachidonate metabolism. We examined the effect of EPA on prostaglandin (PG) D2 generation in the cultured human mast cells with IgE-anti-IgE challenge incubation. Cultured human mast cells were incubated with EPA (1 micromol/L) for 20 h, then challenged with anti-IgE incubation after treatment with IgE. At the same time, COX inhibitors were tested to identify COX-1 and COX-2 activity. PGD2 synthetic activity was also assayed in a cell-free homogenate of cultured mast cells with COX inhibitors and EPA. Histamine in the culture medium and in cells was assayed with the HPLC-fluorescent method. PGD2 and PGD3 were assayed with gas chromatography-mass spectrometry and the stable isotope dilution method. Although EPA incubation did not affect histamine release by cultured human mast cells in response to IgE-anti-IgE challenge incubation, it did decrease PGD2 generation by inhibiting the COX-2 pathway. In contrast, in the cell-free homogenate of cultured human mast cells, EPA inhibited both COX-1 and COX-2 activities. Pre-incubation with EPA primarily affects the COX-2 pathway in cultured human mast cells and reduces PGD2 generation in response to IgE-anti-IgE challenge incubation. These findings suggest that COX-1 and COX-2 have different substrate flow systems in mast cells. They also suggest that endogenous EPA diet supplementation would reduce PGD2 production and could serve as an anti-inflammatory substrate in human mast cells.


Reproductive mode and population genetic structure of the cereal aphid Sitobion avenae studied using phenotypic and microsatellite markers.
As French populations of the aphid Sitobion avenae exhibit a range of reproductive modes, this species provides a good opportunity for studying the evolution of breeding system variation. The present analysis combined ecological and genetic investigations into the spatial distribution of variation in reproductive mode. Reproductive mode was characterized in 277 lineages of S. avenae from France, and these aphids were scored for five microsatellite loci. The analyses revealed strong geographical partitioning of breeding systems, with obligate asexuals mostly restricted to the south of France, while lineages producing sexual forms were more common in the north. Contrary to what might be anticipated for organisms with frequent parthenogenesis, there was substantial genic and genotypic diversity, even in the obligately asexual lineages. More than 120 different genotypes were detected among the 277 aphid lineages, with an average of 5.9 alleles per locus (range four to 16) and heterozygosity of 56.7%. As with previous studies of allozyme variation in aphids, most loci showed heterozygote deficits, and disequilibrium was common among allelic variants at different loci, even after removal of replicate copies of genotypes that might have been derived through clonal reproduction. Our results suggest that selection is important in structuring reproductive systems and genetic variation in French S. avenae. Canonical correspondence analysis was employed to examine the associations between genotypic and phenotypic variables, enabling the identification of alleles correlated with life-history traits.


Participation of NK1 receptors in nociceptin-induced modulation of rat knee joint mechanosensitivity.
Nociceptin is known to act peripherally in the rat knee joint to modulate articular mechanosensitivity and it has been postulated that neurokinin-1 (NK1) receptors may be involved in this process. To test this hypothesis, single unit extracellular recordings were made from knee joint primary afferents in response to normal and extreme rotation of the joint. Afferent firing rate was assessed following close intraarterial injection of the NK1 antagonist RP67580 followed by administration of 20 nmol nociceptin. With both normal and hyper-rotation of the knee, nociceptin was unable to elicit its usual mechanomodulatory effect such that afferent activity was not significantly different from control (P = 0.7572 and P = 0.9182 for normal and hyper-rotation of the joint, respectively). These data indicate that nociceptin-induced mechanosensitivity changes in the rat knee depend upon NK1 receptor activation possibly through secondary release of substance P.


[Studies on biological actions of sperm immobilizing antibody on human fertilization in vitro].
Effects of sperm immobilizing antibodies on sperm penetration through human zonae pellucidae have been studied. Exposure of human spermatozoa obtained from fertile donors to seven serum samples with sperm immobilizing antibody impaired sperm penetration completely in six cases and incompletely in one case. During the course of treatment of a patient with circulating sperm immobilizing antibody by means of an in vitro fertilization and embryo transfer program, it was found that fertilization was completely blocked in the presence of the patient's serum, but three matured ova fertilized successfully when umbilical cord serum was used instead of autoserum from the patient. Furthermore, when spermatozoa were exposed to an IgG fraction of sera containing sperm immobilizing antibody, sperm binding and penetration were markedly inhibited. The spermatozoa, preincubated with sperm immobilizing antibody, showed penetrability across the zona pellucida. However, exposure of possibly capacitated sperm to the antibody completely blocked sperm binding to and penetration through the zona pellucida. These results suggest that sperm immobilizing antibodies cause infertility by preventina sperm binding to and penetration through the zona pellucida, possibly by interfering with the step of fertilization beyond sperm capacitation.


Pain and Surgical Outcomes Reporting After Laparoscopic Ventral Hernia Repair in Relation to Mesh Fixation Technique: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
The aim of this meta-analysis was to examine postoperative pain and surgical outcomes (operative time, hospital stay, the incidence of seroma and recurrence) with different mesh fixation methods following laparoscopic ventral hernia repair (LVHR). Randomized clinical trials compared different methods of mesh fixation in LVHR and reported on pain outcome measures analyzed. The results were expressed as odds ratio (OR) for combined dichotomous and mean difference (MD) for continuous data. Five randomized controlled trials (RCTs) with a total of 466 patients comparing tack mesh fixation to suture mesh fixation technique in LVHR were identified, all were published after 2005. A meta-analysis gave statistically similar odds of postoperative chronic pain (OR, 1.24; 95% CI, 0.65-2.38; z = 0.65; P = .51). No difference in pain intensity (PI) scores was found at 4-6 weeks (MD, 0.18;% CI, -0.48 to 0.85; z = 0.54; P = .59) and at 3-6 months postoperatively (MD, 0.10; 95% CI, -0.21 to 0.42; z = 0.64; P = .52). There was no difference in the pooled analysis of seroma/hematoma formation (OR, 0.60; 95% CI, 0.29-1.26; z = 1.35; P = .18), recurrence (OR, 1.11; 95% CI, 0.34-3.62; z = 0.18; P = .86), and hospital stay (MD, -0.06; 95% CI, -0.19 to 0.08; z = 0.83; P = .40). Operative time was significantly lower with tack fixation (MD, -19.25; 95% CI, -27.98 to -10.51; z = 4.32; P < .05). Meta-analysis of RCTs comparing tacks to suture fixation in LVHR showed comparable results with regard to postoperative chronic pain incidence and PI, and hernia recurrence. However, the operative time is shorter with tacks compared to suture fixation technique.


LR11, an LDL receptor gene family member, is a novel regulator of smooth muscle cell migration.
LR11, a member of the LDL receptor family, is highly expressed in vascular smooth muscle cells (SMCs) of the hyperplastic intima, and induces enhanced migration of SMCs in vitro via its upregulation of urokinase-type plasminogen activator receptor (uPAR) expression. In this study, we have delineated the mechanism by which LR11 elevates the expression levels of uPAR in SMCs. Secretion of soluble LR11 is induced in SMCs during the rapidly proliferating phase, and the secreted LR11 induces the migration activities of SMCs. Both the cell-anchored and secreted forms of LR11 have the capacity to bind to and form complexes with uPAR. LR11-overexpressing cells show significantly enhanced uPAR binding, but decreased uPAR internalization. LR11 colocalizes with uPAR on the cell surface and inhibits the LDL receptor-related protein (LRP)-mediated binding and internalization of uPAR. Thus, LR11 mediates the uPAR localization to the plasma membrane. LR11 is highly expressed in the atheromatous plaque areas of apoE knockout mice, particularly in the intimal SMCs at the border between intima and media. The neutralization of LR11 function with anti-LR11 antibody reduced cuff-induced intimal thickness in mice. The novel mechanism of regulation of uPAR localization in SMCs accompanied with enhanced migration activity possibly constitutes an important factor in the process of atherosclerosis and arterial remodeling.


The changing landscape of scholarly publishing: will radiation research survive?
As a society published journal, Radiation Research has been a successful and enduring project of the Radiation Research Society (RRS). In 59 years of publication, the journal has produced 732 issues and 10,712 articles. As a nonprofit organization, RRS, like most societies, has used revenues from subscriptions to support, in part, the life of the organization (meetings, conferences and grants to new scholars). The model for scientific publishing, however, continues to evolve. Radiation Research has weathered the rise of electronic publishing, consolidation in the commercial publishing industry, the aggregation of library subscriptions and library subscription cuts. Recent years have seen dramatic changes in how scholarly publishing is financed and new funder and institution policies will accelerate these changes. The growth of open access to journal articles reflects the information habits of readers and facilitates the dissemination of new knowledge. The Radiation Research Society, however, will need to account for and adapt to changes in the publishing market if it intends to support the communication of peer reviewed scholarship in the future.


High-performance liquid chromatography analysis of ten dyes for control of safety of commercial articles.
Two high-performance liquid chromatographic methods, with ultraviolet-visible spectrophotometry detection (HPLC-UV/Vis) and with tandem mass spectrometry triple quadrupole interfaced with positive ion mode electrospray ionization detection (HPLC-ESI+-QqQ-MS/MS), for determination and quantification of ten commercial dyes are proposed for control in commercial products. Multiple peaks observed for some of the studied dyes in HPLC-UV/Vis chromatograms forced to obtain structural information by HPLC-ESI-MS/MS method with scan mode. The quality parameters of the two proposed chromatographic methods were evaluated for different requirements of normative, showing detection (LODs) and quantification (LOQs) limits around 60-890 and 200-2990 microg L(-1) for HPLC-UV/Vis, and 4.54-14.3 and 15.0-47.6 microg L(-1) for HPLC-ESI+-QqQ-MS/MS.


External whole-body image of EGFP gene expression.
Whole-body optical imaging is an external and noninvasive procedure that enables the continuous visual monitoring of malignant growth and spread within intact animals. The human colon adenocarcinoma cell-line HCT-15 was transfected with a pIRES 2-EGFP vector, and stable enhanced green fluorescence protein (EGFP) expression was established (Fig.1). Approximately 10(6) HCT-15 EGFP stable transfectant cells were subcutaneously injected into the left flank of six-week-old male Balb/c-nu/nu mice. On post-injection day 78, the size of the subcutaneous tumor was 13.1 mm x 15.4 mm in diameter, as observed using an ORCA-C 7780-20 three-chip cooled color charge-coupled-device camera (Hamamatsu Photonics Systems, Hamamatsu City, Japan). An external fluorescent image of the tumor was acquired through the skin (Fig.2B). The tumor could be seen more clearly once the skin was removed (Fig.2D). Furthermore, in the peritoneal metastasis (Fig.3B) and liver metastasis models (Fig.3D), metastasis could also be seen through the skin. This new technology is a useful method for investigating tumor growth in vivo. In the future, this method could be applied to the detection of peritoneal, liver and lung metastasis in living animals.


Tumor cell apoptosis present at diagnosis may predict treatment outcome for patients with medulloblastoma.
To determine if the degree of tumor cell apoptosis at diagnosis predicts outcome, tissue sections of medulloblastoma were examined and the amount of apoptosis and progression-free survival were correlated. The study cohort consisted of 43 children in whom medulloblastoma was diagnosed between 1984 and 1995: 29 patients at high risk (HR) treated with radiation and chemotherapy, and 14 children at low risk (LR) treated with radiation alone. A terminal deoxynucleotidyl transferase (TdT) end-labeling assay was used to detect apoptosis in paraffin-embedded tissue sections prepared at diagnosis. Progression-free survival was examined in cohorts of children whose tumors were divided into quartiles based on the apoptotic index (AI) of their pretreatment tumor specimens. A comparison of these four groups of children revealed an association between AI and outcome (p = 0.03); patients with tumors in the highest AI quartile had substantially improved outcome compared to all other patients combined (p = 0.02). In this cohort of patients treated with different therapies, assignment at the time of diagnosis to LR and HR groups based on widely-accepted clinical criteria was not closely associated with outcome (p = 0.47). AI is a strong indicator of treatment outcome for children with medulloblastoma after treatment with cytotoxic therapy, independent of risk group. Because HR and LR patients included in this study received different modalities of cytotoxic therapy, it is possible that AI predicts outcome independent of the precise antineoplastic therapy a patient receives.


Imaging Radiation-Induced Normal Tissue Injury to Quantify Regional Dose Response.
Noninvasive imaging has and will continue to play a pivotal role in the assessment of radiation-induced normal tissue toxicity. In this review, we will examine key literature regarding the use of anatomic and physiological imaging in relation to radiation-induced normal tissue toxicity. Additionally, this review contains a novel methodology for potentially incorporating dose-response data into treatment planning and normal tissue toxicity modeling.


Flexible, layered biofuel cells.
Similar to conventional electrolyte batteries, biofuel cells often need to be stacked in order to boost their single cell voltage (<1 V) up to a practical level. Here, we report a laminated stack of biofuel cells that is composed of bioanode fabrics for fructose oxidation, hydrogel sheets containing electrolyte and fuel (fructose), and O(2)-diffusion biocathode fabrics. The anode and cathode fabrics were prepared by modifying fructose dehydrogenase and bilirubin oxidase, respectively, on carbon nanotubes-decorated carbon fiber fabrics. The total thickness of the single set of anode/gel/cathode sheets is just 1.1mm. The laminated triple-layer stack produces an open-circuit voltage of 2.09 V, which is a 2.8-fold increase over that of a single set cell (0.74 V). The present layered cell (5 mm × 5 mm) produces a maximum power of 0.64 mW at 1.21 V, a level that is sufficient to drive light-emitting diodes.


Dissociative experience in a group of adolescents with history of abuse.
57 successive admissions of adolescents with a history of abuse were examined to assess the extent of dissociative experience and possible differences in amount of dissociation related to types of abuse (physical, sexual, and both). The subjects showed a trend towards increased dissociation with inclusion of sexual abuse in their histories, and over-all significant dissociation when compared with a general inpatient psychiatric sample.


[Primary and initial bacterial resistances in tuberculosis patients at a general hospital, 1983-1987].
From july 1982 to december 1987 we prospectively evaluated the primary resistance (PR) of 248 strains of M. tuberculosis isolated from patients with several clinical forms of tuberculosis. The results were compared with those of a similar study carried out between 1978-1982. PR persisted relatively stable with time, although it showed a trend towards reduction. Isoniazide resistance (4.8%) still has a leading epidemiological interest. The 89% of strains showed isolated resistance to a single drug. Only two strains had associated resistance to INH and SM. Strains with PR to RIF, ETB or PZA were not detected. Of the 248 evaluated strains, 32 were isolated from intravenous drug abusers with AIDS. Only one of these strains had a low level (0.2 mg/l) PR to INH. At last two of these drug abusers developed acquired resistance to INH and ETB-RIF, respectively. Considering the difficulty to control chemotherapy in this group of patients, our finding has a considerable epidemiological interest.


Long-term trends in first hospitalization for heart failure and subsequent survival between 1986 and 2003: a population study of 5.1 million people.
We examined whether population-level hospitalization rates for heart failure (HF) and subsequent survival have continued to improve since the turn of the century. We also examined trends in the prescribing of evidence-based pharmacological treatment for HF. All patients in Scotland hospitalized with a first episode of HF between 1986 and 2003 were followed up until death or the end of 2004. Prescriptions of evidence-based treatments issued from 1997 to 2003 by a sample of primary care practices were also examined. A total of 116 556 individuals (52.6% women) had a first hospital discharge for HF. Age-adjusted first hospitalization rates for HF (per 100 000; 95% CI in parentheses) rose from 124 (119 to 129) in 1986 to 162 (157 to 168) in 1994 and then fell to 105 (101 to 109) in 2003 in men; in women, they rose from 128 (123 to 132) in 1986 to 160 (155 to 165) in 1993, falling to 101 (97 to 105) in 2003. Case-fatality rates fell steadily over the period. Adjusted 30-day case-fatality rates fell after discharge (adjusted odds [2003 versus 1986] 0.59 [95% CI 0.45 to 0.63] in men and 0.77 [95% CI 0.67 to 0.88] in women). Adjusted 1- and 5-year survival improved similarly. Median survival increased from 1.33 to 2.34 years in men and from 1.32 to 1.79 years in women. Age-adjusted prescribing rates for angiotensin-converting enzyme inhibitors, beta-blockers, and spironolactone increased from 1997 to 2003 (all P<0.0001 for trend). After rising between 1986 and 1994, rates of first hospitalization for HF declined. Case-fatality rates also fell. Prescribing rates for HF therapies increased from 1997 to 2003. These findings suggest that improvements in the prevention and treatment of HF may have had progressive, sustained effects on outcomes at the population level; however, prognosis remains poor in HF.


Cloning of the newt Pleurodeles waltlii chromosomal DNA.
Pleurodeles waltlii genomic DNA has been cloned using several phage lambda vectors. We have isolated approx. 600 000 clones, which correspond to about 20% of the total DNA sequences of this organism. This constitutes the first large gene library of a Urodele. The low yield of cloning was attributable to the abundance of highly repetitive sequences, since recombinations in the bacterial host could lead to the loss of clones. Indeed, the existence of highly repetitive sequences was directly demonstrated by hybridization between recombinants and the total genome, and some of the cloned DNA was found to be unstable. We suggest new methods for cloning the highly repetitive sequences.


EPIDERMAL PATTERNING FACTOR LIKE5 peptide represses stomatal development by inhibiting meristemoid maintenance in Arabidopsis thaliana.
Stomatal development in Arabidopsis epidermis is both positively and negatively regulated by a family of Cys-rich peptides, EPIDERMAL PATTERNING FACTOR LIKEs (EPFLs). We synthesized biologically active synthetic EPFL5 (sEPFL5) peptide, which reduced the number of stoma in leaves and cotyledons. The sEPFL5 possesses three disulfide bonds at positions identical to those of a positive development factor, stomagen. Application of sEPFL5 had little inhibitory effect on protodermal cells entering the stomatal lineage, but did inhibit the maintenance of meristemoid activity, resulting in the differentiation of arrested meristemoids into pavement cells. This phenotype was enhanced in the too many mouths (tmm) mutant background. RNA analysis revealed that sEPFL5 application halved SPEECHLESS expression and abolished MUTE expression in tmm mutants, explaining the phenotype observed. The action of sEPFL5 was mediated by ERECTA family receptors. We propose that EPFL5 functions to establish the differentiation of stomatal lineage cells to pavement cells.


Effects of furosemide and acute salt loading on vasopressin and renin secretion in the fetal lamb.
Circulating arginine vasopressin (AVP) and plasma renin activity responses to furosemide (2 mg/kg) and acute hypertonic saline (10 mEq/kg) were studied in the fetal lamb from 100 days gestation to term. The baseline to peak plasma AVP response (delta 3.7 +/- 1.2 uU/ml) and area under the response curve (209 +/- 57 uU/ml/65 min) in the fetal lambs > 123 days were greater than in those < 106 days gestation (delta 1.8 +/0 1.1 and (171 +/- 61, respectively), P < 0.02. The plasma renin activity/AVP ratio after furosemide was similar in the two gestational groups. The log plasma AVP responses corrected for rise in plasma osmolality (0.090 +/- .01 uU/ml) 30 min after infusion, and the area under the response curve (253 +/- 49 uU/ml/30 min) was greater (P < 0.02) in the fetal lambs > 120 days than in those under 115 days gestation (.035 +/0 0.01 and 88 +/0 29, respectively), P < 0.02. These results confirm that the fetal lamb responds to an osmotic stimulus with increased plasma AVP levels and documents that this response significantly matures during the last trimester of gestation. The fetal lamb also manifests a hypothalamus-posterior pituitary AVP response to furosemide that is proportional to the maturing renal renin response.


Extraskeletal versus Skeletal Ewing Sarcoma in the adult population: Controversies in care.
A lack of consensus exists on the prognosis of extraskeletal Ewing sarcoma (EES) relative to its skeletal (ES) counterpart in adults. This study sought to characterize outcome differences between the two diagnoses. From 2004 to 2014, the NCDB identified 2,660 Ewing Sarcoma patients. Cox proportional hazards regression analysis was used to identify risk factors for overall survival (OS). EES patients were older, more likely to be female, and have smaller tumors. Among patients with ES, 4.0% received no treatment, 2.5% received local therapy only (surgery and/or radiation), 16.8% received chemotherapy only, while 52.2% received combination therapy (local and chemotherapy), and 17.0% recieived triple therapy (surgery, radiation and chemotherapy). Among patients with EES, 4.3% recived no treatment, 5.6% received local therapy only, 15.6% received chemotherapy only, while 47.0% received combination therapy, and 21.6% received triple therapy. No difference in OS was observed between the two groups (P = 0.816). Factors independently associated with OS for ES included age (HR = 1.26, P = 0.01), Charlson-Deyo Score (CDS) ≥2 (HR = 3.66, P < 0.001), combination therapy (HR = 0.39, P < 0.001) and triple therapy (HR = 0.34, P < 0.001). For EES, factors for OS were age (HR = 1.52, P < 0.001), CDS ≥2 (HR = 1.90, P = 0.02), combination therapy (HR = 0.44, P < 0.001), triple therapy (HR = 0.34, P < 0.001) and PNET histology (HR = 1.33, P = 0.02). Demographic, histological, and treatment characteristics differ between adult patients diagnosed with ES and ESS. However, survival and independent predictors of survival are consistent between the two diagnoses.


VopA inhibits ATP binding by acetylating the catalytic loop of MAPK kinases.
The bacterial pathogen Vibrio parahemeolyticus manipulates host signaling pathways during infections by injecting type III effectors. One of these effectors, Vibrio outer protein A (VopA), inhibits MAPK signaling via a novel mechanism, distinct from those described for other bacterial toxins, that disrupts this signaling pathway. VopA is an acetyltransferase that potently inhibits MAPK signaling pathways not only by preventing the activation of MAPK kinases (MKKs) but also by inhibiting the activity of activated MKKs. VopA acetylates a conserved lysine found in the catalytic loop of all kinases and blocks the binding of ATP, but not ADP, on the MKKs, resulting in an inactive phosphorylated kinase. Acetylation of this conserved lysine inhibits kinase activity by a new mechanism of regulation that has not been observed previously. Identifying the target of VopA reveals a way that the reversible post-translational modification of lysine acetylation can be used to regulate the activity of an enzyme.


Self-Assembly Behaviors of a Penta-Phenylene Maltoside and Its Application for Membrane Protein Study.
We prepared an amphiphile with a penta-phenylene lipophilic group and a branched trimaltoside head group. This new agent, designated penta-phenylene maltoside (PPM), showed a marked tendency to self-assembly into micelles via strong aromatic-aromatic interactions in aqueous media, as evidenced by 1 H NMR spectroscopy and fluorescence studies. When utilized for membrane protein studies, this new agent was superior to DDM, a gold standard conventional detergent, in stabilizing multiple proteins long term. The ability of this agent to form aromatic-aromatic interactions is likely responsible for enhanced protein stabilization when associated with a target membrane protein.


Nanoscale chemical mapping using three-dimensional adiabatic compression of surface plasmon polaritons.
The fields of plasmonics, Raman spectroscopy and atomic force microscopy have recently undergone considerable development, but independently of one another. By combining these techniques, a range of complementary information could be simultaneously obtained at a single molecule level. Here, we report the design, fabrication and application of a photonic-plasmonic device that is fully compatible with atomic force microscopy and Raman spectroscopy. Our approach relies on the generation and localization of surface plasmon polaritons by means of adiabatic compression through a metallic tapered waveguide to create strongly enhanced Raman excitation in a region just a few nanometres across. The tapered waveguide can also be used as an atomic force microscope tip. Using the device, topographic, chemical and structural information about silicon nanocrystals may be obtained with a spatial resolution of 7 nm.


Assessing the intellectural consequences of early intervention with high-risk infants.
Infants at-risk for mental retardation were divided into a group that received early day-care intervention and a matched control group that did not. The purpose of the intervention was to prevent sociocultural retardation. Children were tested at 7 and 18 months on a simple two-choice visual-discrimination task and on the Bayley Scales of Infant Development to assess the impact of the intervention program on their development. Analyses revealed that the experimental group's performance was reliably superior to that of the control group on both measures and that experimental subjects scoring high on the Bayley Scales reached criterion on the discrimination task on fewer trials than low Bayley scorers. The relationship was particularly strong at 18 months.


Comparison of body composition assessments by bioelectrical impedance and by anthropometry in premenopausal Chinese women.
Fat-free mass (FFM) was estimated in forty-seven premenopausal Chinese women, aged 18-43 years, from anthropometric data (skinfolds, body mass index (weight/height2; BMI)) or bioelectrical impedance, using several prediction formulas for body composition from the literature, and values compared with the mean of these three individual methods used as a frame of reference. In thirty-six women these values could be compared with FFM calculated from total body water (TBW) determined by D2O dilution. The prediction formulas used were developed from studies on Caucasian adults and their validity will have to be shown in populations with different ethnic backgrounds. The mean difference between FFM predicted from BMI and the frame of reference was 0.1 kg (95% confidence interval (CI) -0.1, 0.4), from bioelectrical impedance it was 0.5 kg (95% CI 0.3, 0.7), and from skinfolds it was -0.6 kg (95% CI -0.9, -0.4). The mean difference between FFM calculated from TBW and the frame of reference was higher (2.2 kg, 95% CI 1.2, 3.3). The results of the present study indicate that the three methods may be valid for predicting body composition in adult Chinese females, but further research is needed on development and cross-validation of prediction equations for body composition for Chinese.


Autonomic effects of cognitive reappraisal and acceptance in social anxiety: evidence for common and distinct pathways for parasympathetic reactivity.
Few studies investigated the effects of emotion regulation strategies on autonomic parameters in socially anxious individuals. We asked 99 socially anxious participants to give an impromptu speech in front of an audience in a virtual reality environment. In the anticipation phase, they practiced an emotion regulation strategy: negative functional reappraisal, acceptance, negative dysfunctional reappraisal. All strategies led to decreases in parasympathetic activity and increases in heart rate during anticipation. Parasympathetic activity remained low in the recovery phase, while heart rate increased, indicating a possible rebound effect of social performance. Exploratory moderation analysis revealed that for subjects with higher social anxiety, acceptance led to increased parasympathetic activity in the anticipation and recovery phases than negative functional reappraisal. Our results indicate that although globally parasympathetic reactivity seems to be a more general marker of simply attempting to regulate emotions, it could help distinguish between emotion regulation strategies for some participant subgroups.


Persistent staining of lattice lines after intraoperative trypan blue use in patients with lattice corneal dystrophy.
The aim of this study was to report the persistent staining of corneal lattice lines resulting from the intraoperative use of trypan blue. This is a case series. Four patients with lattice corneal dystrophy (LCD) who underwent either deep anterior lamellar keratoplasty or cataract extraction with intraoperative trypan blue use demonstrated persistent, postoperative trypan staining of lattice lines on slit-lamp examination out to final follow-up (range, 176 to 541 days postoperatively). This case series demonstrates the previously unreported finding that intraoperative trypan blue stains corneal lattice lines in LCD. Trypan blue staining, localized in previous laboratory studies to amyloid deposits, seems to persist for months or longer and may be permanent in human tissue. Although the staining was not visually significant, animal models suggest a stimulatory effect on progression of amyloidosis. Clinicians should be aware of the potential for permanent corneal staining and possible disease progression with the use of intraoperative trypan blue in patients with LCD.