Gambling involvement and increased risk of gambling problems.
The opportunity to gamble has undergone rapid expansion with technology allowing for access to gambling products 24 h a day. This increased online availability challenges governments' abilities to restrict access to gambling. Indeed, the ready access to multiple forms of gambling may potentially contribute to impaired control over urges for problem gamblers. The present study considered whether problem gamblers manifested a tendency to engage in multiple forms of gambling and identified forms of gambling which were more strongly related to problem gambling. In reanalyses of two surveys (Sample 1, N = 464, Sample 2, N = 1141), significant relationships accounting for between 11.3 and 13.5% of the variance were found between the numbers of forms of gambling accessed and degree of problem. Participation in online poker, playing cards and sports wagering were linked to problem gambling. Access to multiple forms of gambling may pose difficulties for the tracking and control of gambling.


A VP16-213- and cisplatin-containing regimen for treatment of refractory ovarian germ cell malignancies.
Chemotherapy with VP16-213 and cisplatin was administered to three patients with ovarian germ cell malignancies resistant to chemotherapy with methotrexate, actinomycin D, and chlorambucil and with vinblastine, bleomycin, and cisplatin. Remission was achieved in all patients and has been sustained for 9 to 50 months. Use of these agents in a salvage regimen for resistant germ cell malignancies is recommended.


Increased platelet surface expression of P-selectin and thrombospondin as markers of platelet activation in essential thrombocythaemia.
Essential thrombocythaemia (ET) is a clonal myeloproliferative disorder associated with an increased risk of both thromboembolic and bleeding complications. Platelet activation plays a crucial role in the pathogenesis of prethrombotic conditions. The platelet surface expression of p-selectin (CD62p) and thrombospondin (TSP) has been shown to correlate with platelet activation. In the present study, we used a flow cytometric assay to study whether the fraction of platelets expressing CD62p and TSP is increased in newly diagnosed ET. Thirty-four patients with newly diagnosed ET and 25 healthy control subjects were investigated. The proportion of platelets expressing the activation-dependent antigens CD62p and TSP was higher in patients with ET (CD62p: 14.7+/-15.0%; TSP: 12.4+/-9.9%) as compared with healthy control subjects (CD62p: 3.0+/-4.0%; TSP: 3.2+/-3.2%; p< 0.001). In ET, there was a linear correlation between platelet surface expression of CD62p and TSP (p<0.0001, r=0.83). At diagnosis of ET, 20 patients were symptomatic and 14 asymptomatic. Compared with asymptomatic ET patients there was no difference in the expression of CD62p (18.3+/-16.2% vs. 14.5+/-13.4%) and TSP (14.4+/-9.8% vs. 12.8+/-9.5%) in symptomatic ET patients. In conclusion, increased expression of platelet neoantigens is present at the diagnosis of ET. Both activation-dependent epitopes CD62p and TSP are increasingly expressed on the platelet surface in newly diagnosed ET patients.


The Hha protein facilitates incorporation of horizontally acquired DNA in enteric bacteria.
Hha-like proteins are an evolutive trait of members of the family Enterobacteriaceae. These proteins mimic the oligomerization domain of the nucleoid-associated protein H-NS and interact with this latter protein to modulate gene expression. In this report, we provide evidence that, as has been shown for H-NS, Hha-like proteins play an essential role facilitating acquisition of horizontally transferred DNA in both Escherichia coli and Salmonella. Incorporation of conjugative plasmids such as pHly152 or R27 results in a fitness cost in E. coli or Salmonella strains that lack Hha-like proteins. E. coli spontaneous derivatives from double hha ydgT mutants that showed an increased growth rate and a restored fitness overexpressed the H-NS protein. In addition to reinforcing the role of H-NS/Hha-modulating xenogeneic DNA, the results obtained demonstrate that the Enterobacteriaceae display regulatory features not found in other bacteria that facilitate incorporation of horizontally transferred DNA.


Spontaneous thrombosis of the abdominal aorta in two neonates.
Although relatively rare, thromboembolic events are a major complication of invasive procedures, mainly vascular catheterization, required for the survival of neonates admitted to the neonatal intensive care unit. Sometimes symptoms may be ambiguous and the diagnosis may not be immediate. The clinical relevance of polymorphism of methilene tetrahydrofolate reductase (MTHFR) gene heterozigosity and of omocystein level in the genesis of these thromboembolic events are poorly understood. We report two cases of thrombosis of the abdominal aorta, mimicking aortic coarctation, in two neonates, successfully treated at diagnosis with 170 UI/Kg of low molecular weight heparin (LMWH) twice daily, without side effects. Screening for prothrombotic defects revealed the heterozygosity for MTHFR C677T in both neonates and low omocystein level in one of them. We suggest that in newborns vascular thrombosis should be considered in the differential diagnosis of acute disorders of blood circulation at birth and familial thrombophilia should be investigated. LMWH therapy with a dose of 170 UI/Kg twice daily usually allows vascular recanalization, without side effects.


Additive perturbed molecular assembly in two-dimensional crystals: differentiating kinetic and thermodynamic pathways.
During attempts to produce novel two-dimensional cocrystals by coadsorbing components in a binary mixture, the formation of a metastable form was observed in analogy to the phenomenon of additive-induced polymorph formation reported in three-dimensional crystallization. Mechanistic insights into this phenomenon were gained through the use of scanning tunneling microscopy and several adsorbate/additive combinations. One additive plays a critical role in forming a disordered assembly through a process that is primarily kinetic whereas another additive thermodynamically stabilized an intermediate form, resulting in interrupting a phase transformation to a more stable form. These additive effects elucidate one of the potential pathways to kinetically isolate a metastable polymorph formed during cocrystallization in three-dimensional crystallization.


Subclinical peripheral neuropathy associated with chronic obstructive pulmonary disease.
Peripheral nervous system disorders in COPD (chronic obstructive pulmonary disease) have been found more frequently than usual neurologic practice. We planned this prospective clinical and electrophysiological study to determine the incidence and characteristics of neuropathy in patients with COPD. We studied 49 patients with COPD in whom other causes of polyneuropathy had been excluded. COPD patients were divided into two groups: 21 hypoxemic and 28 normoxemic. Age and sex matched, nonsmoker, 21 healthy subjects were included as the control group. We investigated the results of clinical (neurological symptom score-NSS, neurological disability score-NDS and vibration perception thresholds- VPT) and neurophysiological evaluations in COPD patients and the control group. A value over the mean +/- 2.5 SD of control group were accepted pathologic. NSS results were pathologic in 34% of COPD patients, NDS in 42% and VPT in 94%. Carpal tunnel syndrome was found in 24% of the patients, neuropathy in 55%, and polyneuropathy in 44.8%. In conclusion, the incidence of neuropathy was more than expected, the rate of axonal neuropathy was significantly higher in the hypoxemic group than normoxemic group and the severity of neuropathy was correlated with the degree of hypoxemia.


Ultracompact and broadband polarization beam splitter based on polarization-dependent critical guiding condition.
An ultracompact and broadband polarization beam splitter (PBS) based on the polarization-dependent critical guiding condition of an asymmetrical directional coupler is proposed. The device consists of a pair of silicon waveguides with different height and width. Due to the different cutoff conditions for the TE and TM polarization modes, it is possible to have the TM mode guided in one waveguide while the TE mode is supported in both. Therefore, only the phase-matching condition for the cross-coupling of the TE mode needs to be considered. This approach not only simplifies the design procedures but also significantly improves device performance with smaller total length and larger bandwidth. Finally, regardless of the contribution of S-bend waveguides, our proposed PBS has a coupling region as short as 0.2 μm, which is the shortest reported until now. The simulation result shows that the extinction ratios for the TE and TM polarization are 13.5 and 16.6 dB at their respective output ports, and their insertion losses are 0.29 and 0.13 dB, respectively. Numerical simulations also show that the device offers a very large bandwidth (∼140 nm) with large extinction ratio (>10 dB) and low insertion loss (<1 dB).


Radiative decay of nonstationary system.
When a finite quantum system, say a fluorescent molecule is attached to a bulk surface and excited by a short laser pulse, the decay dynamics of the system is modulated by the surface and the signal is enhanced due to the bulk surface. We have considered the decay dynamics of a model of displaced distorted molecule whose excited potential surface is coupled to a continuum and then this first continuum is in turn coupled to a second continuum. In the short time scale there is a coherent exchange of energy between the system molecule and the first continuum states. In the long time scale the energy of the whole system plus first continuum drains out to the final continuum states. A dendrimer nanocomposite with the gold surface shows an enhanced light emission. This can be qualitatively understood from the model we proposed here. We have numerically studied the various potential parameters of the molecule which can affect the signal. When the potential surfaces are flat, the band structure of the first continuum states along with its initial excitation has some nontrivial effect on the profile of the radiative decay.


Assessment of sedation levels in pediatric intensive care patients can be improved by using the COMFORT "behavior" scale.
The original COMFORT scale, including both observational and physiologic items, has been validated for measuring distress in children admitted to a pediatric intensive care unit. However, physiologic variables are influenced by drugs given in the pediatric intensive care unit setting. The objectives of this study were to assess the usefulness of physiologic variables in judgment of sedation and to determine new cutoff points for the COMFORT "behavioral" scale (COMFORT-B), using only observational items. Prospective observational study. Pediatric intensive care unit in a university hospital. Seventy-eight patients admitted to the pediatric intensive care unit. None. COMFORT scores were obtained in this patient group. Similar to the original COMFORT scale validation, the expert opinion of nurses (Nurse Interpretation Score of Sedation) served to determine optimal cutoff scores for the COMFORT-B scale. A total of 843 combined COMFORT and Nurse Interpretation Score of Sedation scores were obtained in 78 patients. Cronbach's alpha for the COMFORT scale was .78, increasing to .84 when the physiologic items, blood pressure and heart rate, were excluded. COMFORT scores were significantly different for the three Nurse Interpretation Score of Sedation categories (Kruskal-Wallis, p < .001). According to the pediatric intensive care unit nurses, undersedation was present in 11% and oversedation in 3% of all observations. Cutoff points for the COMFORT-B scale were </=10 for oversedation and >/=23 for undersedation. The area in the COMFORT-B score between 11 and 22 does not adequately predict under- or oversedation, pointing to a need for supplemental observation. The COMFORT-B scale is a reliable alternative to the original COMFORT scale. The cutoff points of the COMFORT-B scale in conjunction with the Nurse Interpretation Score of Sedation facilitate the use of sedation algorithms on the pediatric intensive care unit.


Pain in the elderly: polymyalgia rheumatica.
Diagnosis of rheumatologic disorders in the elderly is often complicated by the primary care clinician's inability to differentiate among similar manifestations of rheumatologic disorders, the presence of comorbid conditions, and symptoms attributed simply to aging. A major consequence of the aches and pains associated with rheumatologic disorders, including polymyalgia rheumatica (PMR), is the impedance of activities of daily living, potentially leading to a loss of independence. PMR is common in the elderly. Often coexisting with PMR, temporal arteritis can lead to complications, including blindness, stroke, or cardiac sequelae. Timely detection and appropriate treatment of PMR in the elderly may improve quality of life, as well as deter irreversible problems. Patient education also has an important role.


Scinderin and chromaffin cell actin network dynamics during neurotransmitter release.
It has been demonstrated that filamentous actin (F-A) is mainly localized in the cortical surface of the chromaffin cell. This F-A network acts as a barrier to the chromaffin granules impeding their contact with the plasma membrane. Stimulation of chromaffin cells with either nicotine or a depolarizing concentration of K+ induces the disassembly of cortical F-A in focal areas underneath the plasma membrane. Sites of exocytosis are localised to these areas with low concentration of F-A. The cortical surface of the chromaffin cell also contains scinderin, a Ca(2+)-dependent actin filament-severing protein recently isolated in our laboratory. Nicotine and high K+ stimulation also induce redistribution of cortical scinderin. Both nicotine and high K(+)-induced scinderin redistribution and F-A disassembly are Ca(2+)-dependent events which seem to precede neurotransmitter secretion. A possible target for protein kinase C in the modulation of secretion is the cortical F-A network. Treatment of chromaffin cells with phorbol esters prior to secretion induced scinderin redistribution, F-A disassembly and enhanced the initial rate of subsequent nicotine-evoked catecholamine release. The present results strongly indicate the involvement of the cortical cytoskeleton in the regulation of neurotransmitter release.


Touch print cytology shows higher sensitivity than pleural lavage cytology for pleural micro-metastasis in lung cancer.
Many authors have used pleural lavage cytology for confirming pleural micro-metastasis in lung cancer, but the results showed relatively low sensitivity having positive range of 4-14%. So, if we have a method with higher sensitivity than lavage cytology, the significance of pleural micro-metastasis will be elucidated clearly. To detect micro-metastasis, we underwent touch print cytology using glass slides and lavage cytology. Just after thoracotomy, touch print was carried with 2 pieces of glass slide from the visceral pleural surface of tumor mass. Then, two lavage cytology were collected at the times of pre-resection and post-resection (after distilled water irrigation) using each 1 liter of saline. The glass slides and lavages were examined for confirming micro-metastasis of cancer cells. From June 1998 to May 2004, 146 tumor masses of lung cancer have been subjected. Among them, 127 sets of cytology slides were reviewed completely in the last one month. Touch print cytology was found to be positive in 81.9% (104/127), while lavage cytology in 4.7% (6/127) of pre-resection and in 0.8% (1/127) of post-resection. To detect pleural micro-metastasis, touch print cytology using a glass slide can be considered as an easy and effective method having higher sensitivity than lavage cytology.


Acute infectious purpura fulminans: a 15-year retrospective review of 28 consecutive cases.
Acute infectious purpura fulminans (AIPF) is a rare syndrome of hemorrhagic infarction of the skin, extremity loss, and intravascular thrombosis. It progresses rapidly and is accompanied by disseminated intravascular coagulation and vascular collapse. The victims often succumb to the disease. Our objective was to investigate the clinical manifestations, outline the clinical course, and delineate factors related to mortality among the patients with AIPF. Patients diagnosed with AIPF over a 15-year period were reviewed retrospectively for patient history, comorbid conditions, progression of clinical course, and medical and surgical management. The vast majority of the patients were under the age of 7; however, the disease process can be seen in adults. The overall mortality rate was 43 per cent. The major predisposing factors were history of recent upper respiratory infection, recent surgery or childbirth, young age, and absence of a spleen. The most common clinical manifestations were skin discoloration, disseminated intravascular coagulation, fever, and septic shock. The most common bacteria cultures were Neisseria meningitidis, Hemophilus influenzae, and Streptococcus pneumoniae. There appears to be a higher mortality in patients who did not undergo a surgical intervention. Compartment syndrome needs to be evaluated early on in the presentation. Rapid diagnosis, intensive care unit management, and prompt surgical consultation and debridement may decrease the mortality.


Physico-chemical properties and stabilities of the highly potent calcium antagonist benidipine hydrochloride.
(+/-)-(R*)-2,6-Dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3, 5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049), a highly potent calcium antagonist, was examined to clarify its physico-chemical properties, i.e. melting point, spectra (UV, IR, NMR, MS), X-ray diffraction pattern, thermal analysis, solubilities, pKá, partition coefficient and chromatography (TLC, HPLC). The stabilities of KW-3049 were studied under various conditions by HPLC. KW-3049 in solid state was very stable to heat and moisture, and fairly stable to light.


Obtaining lipases from byproducts of orange juice processing.
The presence of lipases was observed in three byproducts of orange juice processing: peel, core and frit. The enzymes were characterised biochemically over a wide pH range from neutral (6-7) to alkaline (8-9). The optimal temperature for the activity of these byproducts showed wide range at 20°C to 70°C, indicating fairly high thermostability. The activities were monitored on p-NP-butyrate, p-NP-laurate and p-NP-palmitate. For the first time, lipase activity was detected in these residues, reaching 68.5 lipase U/g for the crude extract from fractions called frit.


Professionals' views on the issues and challenges arising from providing a fertility preservation service through sperm banking to teenage males with cancer.
Interviews were undertaken with 22 health and social work professionals. Their analysis was completed using "selective transcription", noting understanding of process, issues and themes, and building a picture against which to consider the analysis of subsequent interviews with teenagers and parents. Professionals were also asked to identify areas for feedback from these participants. This work was part of a larger study of (i) the perceptions of adolescent males and their parents of fertility preservation services following a cancer diagnosis, and (ii) national postal surveys of common practices, areas of variance and issues experienced by professionals in UK regional paediatric oncology centres and licensed assisted conception centres. A large number of concerns were identified, which reflected professionals' difficulties in building and maintaining a relevant, adequate knowledge and skills base given the limited numbers of teenagers offered this service. The lack of appropriate training about the legal and consent frameworks, and the processes involved was also highlighted across all professional groups as was the confusion around professional and legal responsibilities for follow up. Thus, there was considerable professional uncertainty in a number of aspects of this sensitive area of service provision. Consideration needs to be given to the needs for national guidance, for training, support and updating, for liaison between the different health and social care sectors that may be involved, and for appropriate information systems. These need to be in place for each stage of the process, from diagnosis through to eventual discharge from the health system.


Toxic effects of zearalenone on gametogenesis and embryonic development: A molecular point of review.
Zearalenone is commonly generated from moldy cereal grain, which is toxic to the development of gametogenesis and embryo in human and animals. The zearalenone-induced reproductive damage is mainly attributed to four mechanisms. Firstly, zearalenone as an oestrogen-like compound binds to estrogen receptor and causes damage to germ cells and testicular structure. Secondly, zearalenone disrupts the blood-testis barrier, and causes the damage to germ cells. Thirdly, zearalenone elevates oxidative stress, which increases the production of lipid peroxides, and results in the damage to the antioxidant defense system. Fourth, zearalenone increases DNA damage and promotes cells apoptosis. In addition, Zearalenone induces inflammatory reactions and leads to the disorders of reproductive hormones. In this study, we systematically introduced the toxic effects of zearalenone on gametogenesis and embryonic development in animals, and focused on the molecular pathways, which providing a basis for further prevention of zearalenone-induced injury.


An analysis of functional communication training as an empirically supported treatment for problem behavior displayed by individuals with intellectual disabilities.
This paper examines the literature on the use of functional communication training (FCT) as a treatment for problem behavior displayed by individuals with intellectual disabilities (ID). Criteria for empirically supported treatments developed by Divisions 12 and 16 of the American Psychological Association (Kratochwill & Stoiber, 2002; Task Force, 1995) and adapted by Jennett and Hagopian (2008) for evaluation of single-case research studies were used to examine the support for FCT. Results indicated that FCT far exceeds criteria to be designated as a well-established treatment for problem behavior exhibited by children with ID and children with autism spectrum disorder, and can be characterized as probably efficacious with adults.


Proteasome activity limits the assembly of MHC class I molecules after IFN-gamma stimulation.
For an effective CD8+ cytotoxic T cell response to occur during infection, MHC class I molecules must be loaded with antigenic peptides in the endoplasmic reticulum. The cytosolic factor responsible for peptide generation is believed to be the proteasome, with the TAP heterodimer mediating peptide transport into the endoplasmic reticulum. However, the rate-determining step(s) in this intracellular pathway of Ag presentation is currently unresolved. The availability of a specific and irreversible proteasome inhibitor called lactacystin has enabled us to determine the amount of proteasomes required for the peptide loading of MHC class I molecules in four cell types. In the absence of the IFN-gamma-inducible proteasome subunits LMP2 and LMP7, the trypsin-like (but not the chymotrypsin-like) activity of the proteasome is directly related to MHC class I peptide loading. However, IFN-gamma stimulation or assimilation of catalytic LMP2 and LMP7 subunits into proteasomes causes both chymotrypsin- and trypsin-like activities of the proteasome to become limiting for the loading of class I molecules. Our data suggest that upon full IFN-gamma stimulation, peptide supply by the proteasome is the limiting step in the assembly of MHC class I polypeptides. This mechanism may enable the cell to prevent competition between novel Ags and the pool of endogenous proteins for binding to MHC class I molecules.


Biomechanical comparison of fully and partially threaded screws for fixation of slipped capital femoral epiphysis.
Previous data have shown that an equal number of threads on each side of the physis maximizes stability for slipped capital femoral epiphysis (SCFE) fixation. The purpose of the current study was to determine if a fully threaded cancellous screw provides greater stability compared with a partially threaded screw in a porcine model. Twenty skeletally immature porcine femurs were sectioned, and a 30-degree angular wedge was resected from the femoral neck to simulate SCFE. Femora were randomly assigned to partially threaded (16 mm) or fully threaded screw groups (n = 10/group). Kirschner wires were inserted in a retrograde fashion to stabilize the proximal fragment. Each 7.3-mm-diameter screw was placed using fluoroscopic guidance to obtain 3 threads crossing the physis. Specimens were fixed in custom fixation rigs, and the epiphyseal fragment was loaded at 0.5 mm/s in a posterior-inferior direction to simulate slip progression. Data for displacement (in millimeters) and force (in newtons) were collected for the entire test. Forces at 2, 4, 6, and 8 mm of fragment displacement were compared between groups using a 1-way analysis of variance (p < 0.05). Increasing epiphyseal displacements were associated with incremental increases in loading. There were no significant differences between fully threaded or partially threaded screws for loads at each displacement. Each stepwise increase in displacement was associated with approximately 325 N of force. There was no biomechanical benefit when using a fully threaded screw for stabilization of an in vitro SCFE model. Although there were no differences between screw types in an in vitro model, bone healing around the fully threaded screw may eventually provide greater stability. The use of fully threaded screw remains a reasonable option in the treatment of SCFE, and implant removal may be easier with such a system. Further studies are warranted to verify these 2 points.


Perinatal intervention and neonatal outcomes near the limit of viability.
The purpose of this study was to evaluate trends in the level of obstetric and neonatal intervention near the limit of viability and perinatal morbidity and mortality rates over time. In this retrospective chart review, live-born infants who were delivered at 23 to 26 weeks of gestation and who weighed between 500 and 1500 g between 1990 and 2001 in an urban tertiary care center were identified. Maternal charts were reviewed for clinical characteristics and antenatal and intrapartum course. Neonatal charts were reviewed for short-term morbidities that included respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, retinopathy of prematurity, and survival. The study group was divided into 2 cohorts (group I:1990-95; group II:1996-2001); the obstetrician's willingness to intervene, neonatal resuscitation efforts, infant mortality (in gestational age subgroups) rate, and short-term morbidity rate were compared. Multivariate analyses, which controlled for obstetrician willingness to intervene, neonatal resuscitation, cohort, and gestational age, were performed to evaluate infant survival in the entire cohort and for morbidity in the survivors. Records for 260 mothers and 293 newborn infants were evaluated. Comparing the 2 cohorts (group I vs II), we found increases over time in intent to intervene for fetal indication (70% vs 89%; P = .0007), cesarean delivery for malpresentation (20% vs 42%; P = .0003), and survival (54% vs 70%; P = .003). Pregnancies in group 1 were less likely to have received antenatal steroids (7.7% vs 60%) or surfactant (39% vs 73%; P <.0001 for each). Survival increased with advancing delivery gestation (24%, 51%, 68%, and 85% at 23, 24, 25, and 26 weeks of gestation, respectively; P <.0001). However, among survivors, the incidences of necrotizing enterocolitis, retinopathy of prematurity, intraventricular hemorrhage, respiratory distress syndrome, sepsis, and bronchopulmonary dysplasia did not decline significantly with advancing gestational age, after controlling for other factors. Obstetric intervention and aggressive neonatal resuscitation have increased for pregnancies delivered between 23 and 26 weeks of gestation over the past decade. Although survival has increased over time and with advancing gestational age at delivery, short-term morbidity in survivors is similar, regardless of gestational age in this cohort. A brief delay in delivery of those pregnancies who are at risk for delivery between 23 and 26 weeks of gestation may improve survival, although short-term morbidity in survivors will not be affected substantially.


Fate of 137Cs, 90Sr and 239+240Pu in soil profiles at a water recharge site in Basel, Switzerland.
An important process in the production of drinking water is the recharge of the withdrawn ground water with river water at protected recharge fields. While it is well known that undisturbed soils are efficiently filtering and adsorbing radionuclides, the goal of this study was to investigate their behaviour in an artificial recharge site that may receive rapid and additional input of radionuclides by river water (particularly when draining a catchment including nuclear power plants (NPP)). Soil profiles of recharge sites were drilled and analysed for radionuclides, specifically radiocesium (137Cs), radiostrontium (90Sr) and plutonium (239+240Pu). The distribution of the analysed radionuclides were compared with an uncultivated reference soil outside the recharge site. The main activity of 137Cs was located in the top soil (4.5-7.5 cm) and reached down to a depth of 84 cm and 48 cm for the recharge and the reference site, respectively. The found activities of 239+240Pu originate from the global fallout after 1950. 239+240Pu appeared to be strongly adsorbed onto soil particles. The shape of the depth profile was similar to 137Cs, but also similar between the recharge and the reference site. In contrast, 90Sr showed a uniform distribution over the entire depth of the recharge and reference profiles indicating that 90Sr already entered the gravel zone and the ground water. Elevated inventories of the radionuclides were observed for the recharge site. The soil of the recharge field exhibited a threefold higher activity of 137Cs compared to the reference soil. Also for 239+240Pu higher inventories where observed for the recharge sites (40%). 90Sr behaved differently, showing similar inventories between reference and recharge site. We estimate that 75-89% of the total inventory of 137Cs in the soil at the recharge site (7.000 Bq/m2) originated from the fallout of the Chernobyl accident and from emissions of Swiss NPPs. This estimate is based on the actual activity ratio of 137Cs/239+240Pu of 22 for global fallout. The investigations identified radiostrontium as potential threat to the ground water.


Plant hemoglobins: a molecular fossil record for the evolution of oxygen transport.
The evolution of oxygen transport hemoglobins occurred on at least two independent occasions. The earliest event led to myoglobin and red blood cell hemoglobin in animals. In plants, oxygen transport "leghemoglobins" evolved much more recently. In both events, pentacoordinate heme sites capable of inert oxygen transfer evolved from hexacoordinate hemoglobins that have unrelated functions. High sequence homology between hexacoordinate and pentacoordinate hemoglobins in plants has poised them for potential structural analysis leading to a molecular understanding of this important evolutionary event. However, the lack of a plant hexacoordinate hemoglobin structure in the exogenously ligand-bound form has prevented such comparison. Here we report the crystal structure of the cyanide-bound hexacoordinate hemoglobin from barley. This presents the first opportunity to examine conformational changes in plant hexacoordinate hemoglobins upon exogenous ligand binding, and reveals structural mechanisms for stabilizing the high-energy pentacoordinate heme conformation critical to the evolution of reversible oxygen binding hemoglobins.


[Asymptomatic hematuria and/or proteinuria in children under 3 years of age: clinicopathological evaluation].
Six boys and six girls aged under 3 years with asymptomatic hematuria and/or proteinuria were found and renal biopsies were performed from 1 month to 10 years after the discovery. Light microscopy uncovered 4 cases of focal segmental glomerulosclerosis (FSGS), 3 cases of diffuse mild mesangial proliferation, and 5 cases of minor glomerular abnormalities. Immunofluorescent studies did not show any significant depositions. Electron microscopy revealed diffuse thinning of the glomerular basement membrane (GBM) in 2 cases, and segmental thinning of the GBM in 8 cases, including 2 cases of FSGS found in the light microscopy. Four cases, including 2 cases of FSGS, had irregular thickening of the GBM and splitting of the lamina densa. Two cases of FSGS did not have GBM abnormalities. The significance of GBM abnormalities in children with asymptomatic hematuria and/or proteinuria under 3 years of age needs to further evaluated.


Platelets and Platelet-Derived Microvesicles as Immune Effectors in Type 2 Diabetes.
The association between type 2 diabetes mellitus (T2DM) and systemic inflammation may increase platelet reactivity and the accelerated development of vascular disease. Platelets are able to modulate the function of immune cells via the direct release of growth factors and pro-inflammatory chemokines through the production of microvesicles. The microvesicles trigger a transcellular delivery system of bioactive molecules to other cells acting as vectors in the exchange of biological information. Here, we consider the influence of platelets and platelet-derived microvesicles on cells of the immune system and the implications in the pathogenesis of T2DM.


Pharmacological characterization and visualization of the glial serotonin transporter.
Astrocytes contain transport systems that are capable of removing various neurotransmitters from the synaptic cleft by transporters present in the plasma membrane. Glial serotonin transporter (SERT) plays an important role in the re-uptake of 5-hydroxytryptamine (5-HT). We examined the pharmacological characterization of 5-HT uptake into rat cortical synaptosomes and cultured rat astrocytes, and the immunodetection of glial SERT proteins using specific site-directed monoclonal antibodies (MoAb). Furthermore, using a reverse transcriptase-polymerase chain reaction (RT-PCR) method, we addressed the expression of SERT mRNA in cultured rat astrocytes. We investigated the inhibitory effects of various monoamine uptake inhibitors on the uptake of [3H]5-HT into cultured astrocytes and cortical synaptosomes. Tricyclic antidepressants (clomipramine and imipramine) as well as selective serotonin re-uptake inhibitors (fluvoxamine, fluoxetine and zimelidine) were very potent inhibitors of [3H]5-HT uptake in both preparations. In contrast, the inhibitory effects of NE uptake inhibitors (nisoxetine and desipramine) and cocaine were weaker than those of 5-HT uptake inhibitors. In addition, dopamine (DA) uptake inhibitors (nomifensine and GBR-12935) exhibited a Ki value in the low micromolar range. The inhibitory potencies were in the order 5-HT uptake inhibitors (clomipramine, fluvoxamine, fluoxetine, imipramine and zimelidine) > NE uptake inhibitors (nisoxetine and desipramine) = cocaine > DA uptake inhibitors (nomifensine and GBR-12935). There was no difference in the order of the inhibitory effects of various monoamine uptake inhibitors between the two preparations. A correlation analysis of the potencies of various monoamine uptake inhibitors in the inhibition of [3H]5-HT into cultured astrocytes and cortical synaptosomes produced a highly significant correlation coefficient of 0.9893 (P < 0.0001). Immunocytochemical staining using anti-SERT MoAb in cultured astrocytes revealed that the plasma membrane, as well as intracellular, perinuclear compartments, presumably endoplasmic reticulum or golgi membranes, showed a considerable level of immunoreactivity. Extracts of astrocytes and synaptosomes from the cortex were immunoblotted with anti-SERT MoAb. SDS-PAGE/Western blots indicate that anti-SERT MoAb recognized two bands of 120 and 73 kDa in both preparations. RT-PCR demonstrated that astrocytes in cultured expressed mRNA for the cloned SERT protein, which has been characterized as the neuronal SERT. These pharmacological experiments indicate that this uptake process takes place through glial SERT that is very similar to neuronal SERT. Furthermore, the present data also indicate that the presence of the mRNA and protein for the neuronal SERT were established in cultured rat astrocytes, and the polypeptide portion of SERT in astrocytes and frontal cortex could be the same gene product.


Triacylglyceride metabolism by Fusarium graminearum during colonization and sexual development on wheat.
Fusarium graminearum, a devastating pathogen of small grains, overwinters on crop residues and produces ephemeral perithecia. Accumulation of lipids in overwintering hyphae would provide reserves for overwinter survival and perithecium development. Fatty acid composition of cultures during perithecium development indicated a drop in neutral lipid levels during development but little change in fatty acid composition across stages. Microscopic examination of cultures early in sexual development revealed hyphal cells engorged with lipid bodies. In comparison, vegetative hyphae contained few lipid bodies. Microarray analysis was performed on wheat stems at stages of colonization through perithecium development. Gene expression analysis during stages of perithecium development both in planta and in vitro (previously published) supports the view that lipid biosynthesis occurs during early stages of wheat colonization leading to sexual development and that lipid oxidation occurs as perithecia are developing. Analysis of gene expression during the stages of wheat stem colonization also revealed sets of genes unique to these stages. These results support the view that lipids accumulate in hyphae colonizing wheat stalks and are subsequently used in perithecium formation on stalk tissue. These results indicate that extensive colonization of plant tissue prior to harvest is essential for subsequent sporulation on crop residues and, thus, has important implications for inoculum reduction.


Characterization of pH-Dependent Poly(acrylic Acid) Complexation with Phospholipid Vesicles
The pH-dependent complexation of poly(acrylic acid) (PAA) with phospholipid (phosphatidylcholine) vesicles was characterized by fluorescence polarization, differential scanning calorimetry (DSC), and surface pressure measurements of phospholipid monolayers. The complexation was pronounced below pH 4, when the polymer carboxyl groups are protonated, as shown by the binding of PAA to vesicles and the decrease in polymer mobility. The complexation was strong at low polymer concentrations and was weaker at higher polymer concentrations. PAA complexation increased the gel to liquid crystalline (LC) phase transition temperature (Tm) and enthalpy (DeltaH) of the vesicles accompanied by a decrease in the transition cooperativity. This is most likely due to perturbations in the phospholipid headgroup upon PAA interaction. The effect of polymer adsorption on the phospholipid surface was investigated at the phospholipid/water interface. The ability of PAA to penetrate between the phospholipid molecules as a function of pH was determined by the lateral expansion of the monolayer at a constant surface pressure. The ability of the polymer to penetrate into the monolayer increased with decreasing pH. These results suggest that PAA complexation leads to expansion of the phospholipid packing of the vesicles by altering the phospholipid headgroup conformation.


The P300 component in sleep.
The present investigation utilized the P300 component of the auditory evoked potential as an index of information processing (discrimination) in sleep. Auditory evoked potentials were recorded to target and nontarget stimuli during sleep stages 3/4, 2 and REM under two probability conditions. Corresponding "nontone" waveforms were generated in each sleep stage, representing averaged EEG activity with no tones presented. Target P300 amplitude was higher than both corresponding "nontone" targets and tone nontargets. Probability did not affect the target-nontarget relationship. Latency of P300 increased and amplitude decreased from wakefulness through sleep; however, neither amplitude nor latency differed among sleep stages. Amplitude and latency of N200 increased during sleep. While N200 amplitude was highest in Stage 3-4, N200 latency did not differ among sleep stages. These findings suggest that the P300 recorded in sleep indexes similar cognitive processes as the P300 recorded in wakefulness. That P300 as well as N200 latency increased in sleep suggests that processes indexed by these components may slow during sleep.


Crystal structure of the yeast ribosomal protein rpS3 in complex with its chaperone Yar1.
Eukaryotic ribosome assembly involves a plethora of factors, which ensure that a correctly folded ribosome contains all ribosomal protein components. Among these assembly factors, Yar1 has recently emerged as a molecular chaperone for ribosomal protein rpS3 of the small ribosomal subunit (40S) in yeast. In complex with its chaperone, rpS3 is imported into the nucleus and protected from aggregation. How rpS3 and other ribosomal proteins are initially sequestered and subsequently integrated into pre-ribosomal particles is currently poorly understood. Here, we present the crystal structure of yeast rpS3 in complex with its chaperone Yar1 at 2.8Å resolution. The crystal structure rationalizes how Yar1 can protect rpS3 from aggregation while facilitating nuclear import and suggests a mechanism for a stepwise exchange of molecular partners that ribosomal proteins interact with during ribosome assembly.


Acute dysarthria induced by low dose methotrexate therapy in a patient with erythrodermic cutaneous T-cell lymphoma: an unusual manifestation of neurotoxicity.
Neurotoxicity has been associated on rare occasions with methotrexate therapy. We now report the case of a 71-year-old man with erythrodermic cutaneous T-cell lymphoma who developed symptoms of dysarthria and inco-ordination within 1 month of the initiation of oral methotrexate; discontinuation of the therapy then resulted in a gradual resolution of the problems.


Quinapril. A reappraisal of its pharmacology and therapeutic efficacy in cardiovascular disorders.
Following systemic absorption, quinapril is converted by de-esterification to quinaprilat (the active diacid metabolite), an inhibitor of angiotensin converting enzyme (ACE). Pharmacodynamic studies in animals indicate inhibition of ACE both in plasma and at tissue sites, such as the arterial wall and heart, following administration of quinapril. Tissue ACE inhibition may be an important component of the mechanism of action of quinapril (and other ACE inhibitors) in achieving favourable effects in cardiovascular disorders. Quinaprilat has a short elimination half-life (approximately 2 hours), but binds potently to and dissociates slowly from ACE, thus allowing once or twice daily administration of quinapril in the treatment of patients with hypertension or congestive heart failure. Quinapril 10 to 40 mg/day has achieved adequate control of blood pressure in most patients with essential hypertension in clinical trials. Some patients required quinapril dosages up to 80 mg/day and/or concomitant diuretic therapy. Titrating quinapril dosages from 10 to 40 mg/day increased response rates without increasing the incidence or severity of adverse events. Addition of hydrochlorothiazide to quinapril therapy improved response rates by approximately 10 to 20% in patients with hypertension. In general, blood pressure control with quinapril monotherapy was similar to that achieved with enalapril or other standard antihypertensive agents in comparative trials. Quinapril < or = 40 mg/day improved exercise tolerance, reduced the severity and frequency of symptoms, and improved functional (New York Heart Association) class in most clinical studies of patients with congestive heart failure. In addition, beneficial haemodynamic and echocardiographic changes achieved with quinapril were maintained for up to 1 year with continued administration to such patients, but its effect on survival in patients with congestive heart failure has not been reported. The tolerability profile of quinapril is broadly similar to that of other ACE inhibitors; pooled data from clinical trials indicated that 12% of patients with hypertension or congestive heart failure receiving quinapril experienced a treatment-related adverse effects compared with 15% of enalapril recipients and 16% of captopril recipients. Thus, quinapril has clearly established a role as an effective and well tolerated alternative to other ACE inhibitors for the treatment of hypertension and congestive heart failure. While effects of quinapril on survival of patients with congestive heart failure have not been determined, large intervention studies have demonstrated improved mortality rates with other ACE inhibitors. Further studies, including a large ongoing trial of normotensive patients with coronary artery disease but normal left ventricular function, may also establish a role for quinapril in treating patients with ischaemic heart disease.


Chylomicron catabolism differs between Hooded and albino laboratory rats.
To extend previous reports that some aspects of lipid metabolism are different between Hooded and albino strains of laboratory rats, thoracic duct lymph chylomicrons were collected and their composition and metabolism were compared in this study. Chylomicrons from Hooded rats had more core components and fewer surface components than albino rats. After adding 1% cholesterol to the diet the ratio of cholesterol:phospholipid was higher in Hooded rat chylomicrons. Nascent lymph chylomicrons from Hooded rats contained less apolipoprotein A-IV, but after incubation with serum there was a gain of apolipoprotein A-IV and a loss of A-I from both types of chylomicron. The ratio of apoC to apoE was higher in Hooded than in albino rats. The metabolism of injected chylomicrons was slower in Hooded rats. Twenty minutes after a single injection, only 1-3% of chylomicron triacylglycerol and 8-13% of chylomicron cholesteryl ester remained in the plasma of albino rats, compared with 6-12% of triacylglycerol and 30-33% of cholesteryl ester in Hooded rats. At 30 min in the Hooded rats, the uptake of injected chylomicron cholesterol into the liver was decreased whereas uptake into other tissues, notably adipose tissue and muscle, was increased. During the steady intravenous injection of chylomicrons from the same strain, the fractional clearance rate of chylomicron triaclyglycerol was about three-fold faster in albino rats than in Hooded rats, and the fractional clearance rate of chylomicron cholesteryl ester was 70% faster in albino rats. When chylomicrons were allowed to circulate for 30 min after injection into functionally hepatectomized rats, with or without heparin, the remnant formation and chemical composition were similar in Hooded and albino rats. Hence the deficiency in chylomicron metabolism in Hooded rats was not due to an absolute impairment in the formation of remnants by the action of lipoprotein lipase in peripheral tissues, although our findings were most likely accounted for by some relative impairment of remnant formation in the Hooded strain. The deficiency in chylomicron metabolism correlated with an increased cholesterolemic response in Hooded rats compared with albino rats when 1% cholesterol was added to the diet.-Jeffery, F., and T. G. Redgrave. Chylomicron catabolism differs between Hooded and albino laboratory rats.


A formate based precursor for the preparation of technetium complexes.
Tc-formate complexes have been prepared by electrolytic, stannous, and borohydride reduction of pertechnetate in formate buffer. Individual Tc-formate complexes were isolated from reaction mixtures with silica bonded phase anion-exchange HPLC. The predominate air stable red Tc-formate complex has a negative charge, an absorption maximum at 536 nm, and a molecular weight between 100 and 300 dalton. The isolated major Tc-formate complex was found to react with isocyanide, diphosphonate, and various nitrogenous ligands. The relevant use of Tc-formate complexes as synthetic precursors to other technetium complexes is seen as being beneficial to the understanding of technetium ligand substitution.


Correlation between miR-1207-5p expression with steroid-induced necrosis of femoral head and VEGF expression.
The aim of this study was to investigate the expression level of micro-ribonucleic acid-1207-5p (miR-1207-5p) in steroid-induced necrosis of femoral head (SNFH) and its correlation with SNFH. Meanwhile, we also aimed to analyze the relationship between miR-1207-5p expression and vascular endothelial growth factor (VEGF) in the femoral head. From May 2016 to December 2017, 60 patients aged (55.4±8.7) were selected in our hospital. All patients were diagnosed and confirmed as SNFH. Total RNA was extracted from the necrotic femoral head tissues and peripheral blood. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was used to detect the expression level of miR-1207-5p in tissues. At the same time, immunohistochemistry and Western blotting were adopted to detect VEGF expression in the bone tissue of patients with high or low expression of miR-1207-5p. 7 patients with femoral neck fracture aged (45.6±4.51) were enrolled in the control group. In the animal experiment, the rat SNFH model was established by intraperitoneal injection of lipopolysaccharide and methylprednisolone. Subsequently, the expression levels of miR-1207-5p and VEGF in necrotic femoral tissues were detected. Meanwhile, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was applied to detect cell apoptosis in bone lacunae of miR-1207-5p high expression group and miR-1207-5p low expression group, respectively. The expression level of miR-1207-5p in the necrotic bone tissue of the SNFH group was significantly higher than that of the control group. The expression level of miR-1207-5p was inversely proportional to Harris Hip score (p<0.05). A higher expression of miR-1207-5p indicated a lower expression level of VEGF (p<0.05). The animal experimental results revealed that miR-1207-5p expression in the necrotic femoral head tissue of SNFH group was significantly higher than that of the control group. Furthermore, the number of apoptotic cells in bone lacunae was remarkably higher in miR-1207-5p high expression group (p<0.05). MiR-1207-5p is significantly up-regulated in necrotic femoral head tissue and serum of SNFH patients. Meanwhile, its expression level is inversely proportional to Harris Hip score of patients. The possible underlying mechanism may be related to the inhibitory effect of miR-1207-5p on VEGF.


Neonatal screening for citrullinaemia.
In a period of 40 months (1st March 1999 to 30th June 2002) 610,000 blood samples were analysed in one screening centre for citrulline as a pilot study for neonatal screening using tandem mass spectrometry. Persistent hypercitrullinaemia (Cit >1.5 mg/dl or 85.5 micro mol/l, not corrected for recovery) was identified in 15 newborns. Four children were diagnosed with classical neonatal onset citrullinaemia and eight with persisting asymptomatic hypercitrullinaemia. In two asymptomatic newborns and in one symptomatic preterm patient, argininosuccinate lyase deficiency was identified as the cause of moderately elevated levels of citrulline (cases not described in this paper). Citrulline concentrations were only temporarily mildly elevated in two newborns and in these the results of the original neonatal screening were therefore regarded as false-positive; we did not find any other false-positives. The screening result allowed the introduction of immediate specific treatment in two cases of citrullinaemia and may have prevented metabolic decompensation in those with presumed mild citrullinaemia. In one child who developed severe hyperammonaemia on the 2nd day of life, sequelae could not be avoided. neonatal screening for citrullinaemia is more complex than expected and, with the actual logistics, results may be obtained too late in severe forms.


Nailing Down Metaphors in CBT: Definition, Identification and Frequency.
Metaphors are common in psychotherapy and have potential to enhance therapy in numerous ways. However, the empirical study of metaphors in cognitive behaviour therapy (CBT) has tended to be put in the "too hard basket", confined to being part of the art rather than the science of therapy. The lack of research is largely due to problems with definition, lack of a consistent, reliable approach to metaphor identification and the challenges of finding appropriate methodology to study this language-based activity. This study aimed to assess the frequency of metaphors in CBT in a large sample of therapy sessions and to evaluate the reliability and utility of the discourse dynamics approach to metaphor identification. The discourse dynamics approach, recently developed by linguists, was used to identify metaphors in 48 CBT session transcripts (from 12 clients and 3 therapists) and the reliability of this approach was evaluated, using an independent rater. The total frequency of metaphors was 31.5 (range 17-49) per 1000 words of therapy conversation. Therapists produced metaphors twice as often (21.2, range 7-36) as clients (10.3, range 3-24). Reliability of the Discourse Dynamics approach was adequate. Metaphors clearly occur in CBT sessions, with therapists using them at a higher rate than clients. While Discourse Dynamics is currently the most detailed identification approach available for investigating metaphor in CBT sessions, it is challenging to acquire skill in it and we found only adequate reliability. Ways to improve reliability and future research possibilities are discussed.


Myc protein expression correlates with MYC amplification in small-cell lung carcinoma.
Myc family members are important contributors to oncogenesis in a variety of tumours. Identification of therapeutic targets is needed in small-cell lung carcinoma (SCLC), an aggressive disease with limited treatment options. Sequencing studies have identified MYC amplification in 2-7% of SCLCs. This study aims to determine the rate of MYC gene amplification and its correlation with Myc protein overexpression in SCLC. One hundred and three cases of formalin-fixed, paraffin-embedded SCLC were examined. Myc protein expression was scored according to the extent of immunohistochemical staining. MYC copy number (CN) was evaluated with dual-colour chromogenic in-situ hybridization (CISH) for the MYC locus and a chromosome 8 (Chr8) centromeric control. Amplification was defined as a MYC/Chr8 ratio of ≥2. Thirty-eight per cent of SCLCs had some degree of Myc protein expression, and 9% of cases were MYC-amplified. MYC CN was significantly correlated with the extent of Myc protein expression (Spearman's ρ = 0.57, P < 0.01). There was no significant association between Myc expression or CN and clinicopathological features. MYC amplification by CISH was identified in 9% of SCLCs, and correlated with protein expression. As novel Myc-targeted therapies are developed, CISH and IHC should be considered as biomarkers of Myc pathway dysregulation in SCLC.


Imaging of acute appendicitis in children: EU versus U.S. ... or US versus CT? A North American perspective.
The timing, type, and technique of imaging evaluation of suspected appendicitis in children are all debated. This debate is both local and international. The fact is that choices in imaging evaluation will depend on both local and national influences, which are reasonable and to be expected. There still is a responsibility, though, for those involved with evaluation of patients with possible appendicitis to come to agreement about an appropriate diagnostic pathway that considers standards of care and available resources.


Gender, gender roles and completion of nursing education: a longitudinal study.
The current worldwide nursing shortage and high attrition of nursing students remain a challenge for the nursing profession. The aim of this paper was to investigate how key psychological attributes and constructions differentiate between completers and non-completers of nursing education. A questionnaire including measures of gender role identity and perceived gender appropriateness of careers was administered to 384 students early in the first year of the course. At the end of the programme attrition rates were obtained. The findings indicate that males were more likely to leave the course than females. Furthermore, those who completed the course tended to view nursing as more appropriate for women, in contrast to the non-completers who had less gender typed views. The female-dominated nature of nursing, prevalent stereotypes and gender bias inherent in nursing education seem to make this an uncomfortable place for males and those with less gendered typed views. Whilst it is acknowledged that attrition is undoubtedly a complex issue with many contributing factors, the nursing profession need to take steps to address this bias to ensure their profession is open equally to both female and male recruits.


[Non-fatal rupture of a cocaine packet in a man with the 'bodypacker' syndrome].
A 24-year-old patient was admitted to the intensive care unit because he had swallowed about 20 cocaine packets 48 hours before admission; he also complained of abdominal cramps, perspiration and dizziness. The patient reported that he had not defecated since swallowing the packets. Abdominal X-ray revealed only coprotasis. On conservative therapy with bowel irrigation, two packets were eliminated, after which a second abdominal X-ray revealed several cocaine packets in the colon. Four days afterwards, the cocaine packets in the colon had not progressed despite adequate bowel irrigation. The patient now showed signs of mild cocaine intoxication (hallucinations and tachycardia). It was therefore decided to perform a laparotomy. Via a sigmoidotomy, 7 intact packets were removed; another 3 had already ruptured and were empty. The rupture of 3 cocaine packets in this patient was probably not fatal because of the sedation with midazolam and because the patient had diarrhoea as a result of the extensive irrigation, so that a large proportion of the cocaine was probably not absorbed. This case also shows that the presence of foreign bodies cannot be established adequately by an abdominal X-ray if there is coprostasis.


Penile horn.
A case of penile horn is reported. Its occurrence is uncommon, and treatment consists of excision.


Translational control by the La antigen. Structure requirements for rescue of the double-stranded RNA-mediated inhibition of protein synthesis.
The La antigen is a protein which can bind both single-stranded and double-stranded forms of RNA and has regulatory effects on gene expression at the levels of transcription and translation. It was previously shown to inhibit the activation of the dsRNA-dependent protein kinase PKR by sequestering and/or unwinding double-stranded RNA. Here, we demonstrate that, as predicted by these properties, the La antigen can rescue protein synthesis in the reticulocyte lysate system from inhibition by low concentrations of dsRNA. This effect is reversed by higher concentrations of dsRNA. Using a series of deletion mutants we have investigated the structural features of the La antigen that are required for these effects. The ability to bind dsRNA is influenced by regions within both the previously characterized N-terminal RNP motif and the C-terminal half of the protein. La mutants with either N-terminal or C-terminal deletions retain the ability to inhibit the protein kinase activity of PKR and to rescue protein synthesis from inhibition by dsRNA. It is notable that sequences in the C-terminal half of the La antigen, including a phosphorylation site at Ser366, which are needed for other regulatory effects of the protein on gene expression are dispensable for the effects of La on PKR. We suggest that La regulates PKR activity solely as a result of its ability to act as an RNA-binding protein that can compete with PKR for limiting amounts of dsRNA.


Blocking effect of serotonin on inhibitory dopamine receptor activity of Aplysia ganglion cells.
The abdominal ganglion of Aplysia includes neurons with a characteristic dopamine (DA) receptor, the activation of which induces a marked hyperpolarization with a specific increase in the permeability of the membrane to K+. The DA receptor of this type is called the "HK-type." A 2-min exposure to 1 microM serotonin (5-HT) had little effect on the resting membranes with the receptor of HK-type, but significantly depressed the responses to 10 microM DA. The depressing effect of 5-HT on this type of response was completely reversible after a 15-min washing with normal artificial Aplysia blood. Lineweaver-Burke type plotting of the DA-induced responses showed a systematic shift of the straight lines when the concentration of 5-HT was increased; the slope of the line became steeper but the intercept on the ordinate remained unchanged. The dose-inhibition curves, in which relative responses to a given [DA] were plotted against log [5-HT], showed a parallel shift toward the right when the concentration of DA increased. These findings suggest that 5-HT competes with DA for common binding sites at the DA receptor of HK-type, and that the blockade is not due to the interaction of 5-HT with K+-channels in the receptor membrane. The effect of other indole derivatives suggests that the DA receptor of HK-type includes anionic and cationic sites to which the NH2 group and 5-HO group of 5-HT could specifically bind, thus exhibiting competitive blockade.


Treating autoimmune disorders with venom-derived peptides.
The effective treatment of autoimmune diseases remains a challenge. Voltage-gated potassium Kv1.3 channels, which are expressed in lymphocytes, are a new therapeutic target for treating autoimmune disease. Consequently, Kv1.3 channel-inhibiting venom-derived peptides are a prospective resource for new drug discovery and clinical application. Area covered: Preclinical and clinical studies have produced a wealth of information on Kv1.3 channel-inhibiting venom-derived peptides, especially from venomous scorpions and sea anemones. This review highlights the advances in screening and design of these peptides with diverse structures and potencies. It focuses on representative strategies for improving peptide selectivity and discusses the preclinical research on those venom-derived peptides as well as their clinical developmental status. Expert opinion: Encouraging results indicate that peptides isolated from the venom of venomous animals are a large resource for discovering immunomodulators that act on Kv1.3 channels. Since the structural diversity of venom-derived peptides determines the variety of their pharmacological activities, the design and optimization of venom-peptides for improved Kv1.3 channel-specificity has been advanced through some representative strategies, such as peptide chemical modification, amino acid residue truncation and binding interface modulation. These advances should further accelerate research, development and the future clinical application of venom-derived peptides selectively targeting Kv1.3 channels.


Glutamic acid decarboxylase-containing axons synapse on LHRH neurons in the rat medial preoptic area.
A double-label electron microscopic immunostaining procedure was employed to examine the interconnections of glutamic acid decarboxylase(GAD)- and LHRH-immunoreactive neurons in the medial preoptic area of the rat. The results provide ultrastructural evidence that GABA-ergic neurons establish symmetric (Gray II) synapses on LHRH neurons.


An isomer-specific high-energy collision-induced dissociation MS/MS database for forensic applications: a proof-of-concept on chemical warfare agent markers.
Spectra database search has become the most popular technique for the identification of unknown chemicals, minimizing the need for authentic reference chemicals. In the present study, an isomer-specific high-energy collision-induced dissociation (CID) MS/MS spectra database of 12 isomeric O-hexyl methylphosphonic acids (degradation markers of nerve agents) was created. Phosphonate anions were produced by the electrospray ionization of phosphonic acids or negative-ion chemical ionization of their fluorinated derivatives and were analysed in a hybrid magnetic-sector-time-of-flight tandem mass spectrometer. A centre-of-mass energy (E(com)) of 65 eV led to an optimal sequential carbon-carbon bond breakage, which was interpreted in terms of charge remote fragmentation. The proposed mechanism is discussed in comparison with the routinely used low-energy CID MS/MS. Even-mass (odd-electron) charge remote fragmentation ion series were diagnostic of the O-alkyl chain structure and can be used to interpret unknown spectra. Together with the odd-mass ion series, they formed highly reproducible, isomer-specific spectra that gave significantly higher database matches and probability factors (by 1.5 times) than did the EI MS spectra of the trimethylsilyl derivatives of the same isomers. In addition, ionization by negative-ion chemical ionization and electrospray ionization resulted in similar spectra, which further highlights the general potential of the high-energy CID MS/MS technique.


Hemodynamics in sleep-induced apnea. Studies during wakefulness and sleep.
Twelve patients with predominantly obstructive type sleep apnea underwent cardiac catheterization, hemodynamic monitoring, and arterial blood gas analysis during wakefulness and sleep. Abnormalities during wakefulness included systemic hypertension in four of 12, exercise-induced mild pulmonary hypertension in five of 12, and alveolar hypoventilation in one. During sleep nine patients had cyclic elevations of arterial pressure with each apneic episode, exceeding 200 mm Hg systolic in three of 12. Pulmonary artery pressures increased in 10 of 12, exceeding 60 mm Hg systolic in five. Marked degrees of hypoxemia (arterial P02, less than 50 mm Hg in eight of 12) and moderate hypercapnia with respiratory acidosis were associated with these hemodynamic changes. Cyclic upper airway obstruction during sleep may result in hypercapnia, acidosis, and pronounced hypoxemia, which can lead to hemodynamic abnormalities during sleep. Sustained pulmonary hypertension and possibly systemic hypertension may follow. Tracheostomy is an effective therapy and is recommended to symptomatic patients who have predominantly obstructive apnea but no relievable anatomic cause of upper airway obstruction.


Dry mouth with conventional and controlled-release oxybutynin in urinary incontinence. The Ditropan XL Study Group.
To compare the efficacy and safety of controlled-release oxybutynin with conventional, immediate-release oxybutynin and determine rates of dry mouth. Patients (n = 226) who were known to be responsive to anticholinergic therapy and who had seven or more urge incontinence episodes per week were randomized to receive controlled-release oxybutynin or immediate-release oxybutynin. After an initial placebo run-in period, dosing in each began at 5 mg per day and increased weekly by 5 mg per day to a maximum of 20 mg per day or when a balance between improvement of incontinence symptoms and tolerability of side effects was achieved. Rates of urge incontinence and dry mouth were compared. Post hoc Kaplan-Meier survival analysis was used to describe elimination of incontinence episodes by dose and to analyze dry mouth risk by dose. Reductions in urge urinary incontinence episodes from baseline to the end of treatment were 18.6 to 2.9 per week (83% mean decrease) and 19.8 to 4.4 per week (76% mean decrease) in the controlled- and immediate-release oxybutynin groups (P =.36), respectively. At equal doses, comparable proportions of patients in both groups reported the absence of urge incontinence (P =.85). The incidence of dry mouth increased with dose in both groups, but there was no difference in dry mouth rates between the groups: 47.7% and 59.1% for the controlled- and immediate-release oxybutynin (P =.09), respectively. However, Kaplan-Meier analysis to examine first report of dry mouth at a given dose revealed that a significantly lower proportion of patients taking controlled-release oxybutynin had moderate to severe dry mouth (P =.007) or any dry mouth (P =.003) compared with those taking immediate-release oxybutynin. At the same daily dose, controlled- and immediate-release oxybutynin demonstrated comparable efficacy in reduction of urge incontinence episodes. The incidence of dry mouth was dose dependent but equal in both groups; first report of moderate to severe dry mouth was significantly lower in the controlled-release group.


Characterization of rat embryo cells transformed by ts mutants and sheared DNA of herpes simplex virus types 1 and 2 and a derived tumor cell line.
Four independent isolated lines transformed by ts mutant or sheared DNA of herpes simplex virus types 1 and 2 and one tumor cell line were characterized according to their behavior in assays of aggregation, growth in low serum, doubling times, saturation density, agglutination by lectins, uptake of metabolites, and production of plasminogen activator. The criteria used to select the transformed cells used in this study were the formation of altered foci of cells followed by the formation of a continuous cell line, the continuing expression of herpes simplex virus-specific antigens, and the tumorigenicity of the transformed cell lines. The results indicate that, whereas the one herpes simplex virus type 2-transformed cell line investigated showed many of the transformation parameters accepted as typical of cells transformed by the papovaviruses, the three herpes simplex virus type 1-transformed cell lines do not share or express many of these transformation parameters.


[Severe diarrhea after the original well-functioning percutaneous endoscopic gastrostomy tube was replaced by a Mic-Key button].
We report two cases of colocutaneous fistula as a complication of percutaneous endoscopic gastrostomy (PEG) in small children. Both children developed severe osmotic diarrhoea immediately after the original PEG tube was replaced by a Mic-Key button which subsequently migrated to the colon.


Primary Oral Presentation of Sarcoidosis in a Pediatric Patient.
Sarcoidosis is a multisystem granulomatous disease of unknown etiology that commonly affects the lungs, lymph nodes, and skin. The disease often presents in patients between the third and sixth decade and its pathology is defined by the presence of noncaseating granulomas within organs throughout the body. Oral and neurologic involvement of sarcoid is extremely rare and occurs in approximately 1% and 5% of patients with the disease, respectively. A case of sarcoidosis involving the gingiva and submandibular lymph nodes is described in a 14-year-old girl. Further neural involvement of the disease was recognized after initial biopsy examinations and systemic evaluation. This presentation is especially rare given the patient's lack of symptoms, age at diagnosis, and initial oral manifestations.


Species effects on nitrogen cycling: a test with perennial grasses.
To test for differing effects of plant species on nitrogen dynamics, we planted monocultures of five perennial grasses (Agropyron repens, Agrostis scabra, Poa pratensis, Schizachyrium scoparium, and Andropogon gerardi) on a series of soils ranging from sand to black soil. In situ net N mineralization was measured in the monocultures for three years. By the third year, initially identical soils under different species had diverged up to 10-fold in annual net mineralization. This divergence corresponded to differences in the tissue N concentrations, belowground lignin concentrations, and belowground biomasses of the species. These results demonstrate the potential for strong feedbacks between the species composition of vegetation and N cycling. If individual plant species can affect N mineralization and N availability, then competition for N may lead to positive or negative feedbacks between the processes controlling species composition and ecosystem processes such as N and C cycling. These feedbacks create the potential for alternative stable states for the vegetation-soil system given the same initial abiotic conditions.


Caffeic acid phenethyl ester to inhibit posterior capsule opacification in rabbits.
To assess whether caffeic acid phenethyl ester (CAPE) prevents posterior capsule opacification (PCO) by suppressing the transformation of the lens epithelial cells. Departments of Ophthalmology, Chemistry, and Pathology, Turgut Ozal Medical Center, University of Inonu, Malatya, Turkey. Twenty pigmented island rabbits having phacoemulsification in their right eyes were randomized into two groups. In group 1, 10 micrograms/ml of CAPE was added to the anterior chamber irrigating solution and a 1% solution of CAPE was injected subconjunctivally for 3 weeks postoperatively. The irrigating solution in Group 2 (control) did not include CAPE. The development of PCO was assessed weekly and its density was graded by slitlamp biomicroscopy. Histologic analysis was performed 3 months after surgery. Group 1 had clear capsules or minor PCO. Group 2 developed more severe PCO or complete opacification. The difference between the two groups was statistically significant (P = .04). These preliminary results indicate that CAPE is effective in suppressing PCO in pigmented rabbits and may be beneficial in clinical use in humans because it has no documented harmful effects on normal cells.


Oral contraception does not alter typical post-exercise interleukin-6 and hepcidin levels in females.
The post-exercise interleukin-6 (IL-6) and hepcidin response was investigated during the hormone-deplete and hormone-replete phases of an estradiol and progestogen regulated oral contraceptive cycle (OCC). Counterbalanced, repeated measures cross-over study. Ten active female monophasic oral contraceptive pill (OCP) users completed two 40 min treadmill running trials at 75% of their pre-determined peak oxygen uptake velocity (vVO2peak). These trials were randomly performed in two specific phases of the OCC: (a) Day 2-4, representing a hormone-free withdrawal period (D-0); (b) Day 12-14, representing the end of the first week of active hormone therapy (D+7). Venous blood samples were drawn pre-, post- and 3h post-exercise. In both trials, serum IL-6 was significantly elevated (p<0.05) immediately post-exercise, while serum hepcidin was significantly elevated (p<0.05) 3h post-exercise, with no significant differences recorded between trials. These findings suggest that exercise performed during the different phases (D-0 vs. D+7) of a monophasic OCP regulated cycle does not alter exercise induced IL-6 or hepcidin production. As such, future studies looking to investigate similar variables post-exercise, may not need to 'control' for different phases of the OCC, provided participants are current monophasic OCP users.


Merkel cell tumour: report of a case.
We report the case of a 75-year-old lady with recurrent primary cutaneous Merkel cell tumours. The condition can be misdiagnosed as lymphoma or anaplastic carcinoma, and the definitive diagnosis can be made only by electron microscopy of fresh tissue. This is the first reported case in the British literature.


Children and managed care: what research can, can't, and should tell us about impact.
The speed and ubiquity of the move from fee-for-service to managed care raises questions about how these changes affect children. This article examines (1) the pace and context of the move to managed care for children, (2) potential opportunities and challenges emerging from these changes, (3) research findings on how managed care affects children, and (4) next steps for learning more. The research review provides a consistent answer to whether managed care is good for children: it depends on what kind of managed care, which children, and under what circumstances. This finding suggests lessons for future research: (1) focus on particular features of managed care, (2) get inside the "black box" of managed care and examine providers, (3) expand the portfolio of research on children: research on adults cannot "trickle down" to children, (4) foster research partnerships and networks, and (5) focus on poor and chronically ill children.


[Acute pancreatitis. Our experience].
Between the years 1975 and 1984, 228 patients with acute pancreatitis (A.P.) have been studied at the "A. Posadas Hospital". The diagnosis was confirmed in 212 patients by surgery, in the remaining 16 by clinical evaluation, increase in the activity of serum or peritoneal fluid amylase, ultra-sonography and computed tomography. The sex distribution was: female 151 (66.2%) male 77 (33.8%), the mean age in each group was 42.9 and 45 years respectively. The etiologic factors were: biliary tract disease 178 (78%) alcohol 24 (10.5%) idiopathic 16 (7%) others factors 10 (4.4%). We found mild and moderate forms of the illness in 179 (78.5%) and severe form in 49 (21.5%) patients. The mortality rate of the whole group was 29 (12.7%) and according to the etiology it was, in the biliary group 20 (11.2%) alcoholic 4 (16.6%) idiopathic 3 (18.7%). The mortality in the mild and moderate forms was 5% and 40.8% in the severe forms. The patients who underwent surgery were classified in three groups according to the opportunity of surgical treatment: elective surgery, early surgery, surgery for complications. There was no mortality in the elective surgery group. The patients operated on early period had a mortality of 18.75% (21 pts.) whereas those operated due to complications had a mortality of 42.1% (8 pts.). According to the above mentioned experience we consider that a patient with an A.P. must be classified with the known indexes in mild or severe forms, at the same time one should study the actual etiologic factor.(ABSTRACT TRUNCATED AT 250 WORDS)


Statistical examination of AOAC use-dilution method for testing disinfectant efficacy.
The AOAC use-dilution method is examined from a statistical viewpoint by using the fundamental concept of operating characteristic curves to focus attention on the inadequately defined aspects of the acceptance/rejection criteria used for disinfectant registration and enforcement purposes.


Age-specific reference interval of serum TSH levels is high in adolescence in an iodine excess area: Korea national health and nutrition examination survey data.
Serum thyroid-stimulating hormone level was influenced by several factors, including age, gender, thyroid auto-antibodies, race, and intake of dietary iodine. We evaluated age-specific reference interval of serum thyroid-stimulating hormone levels in Korea, an iodine excess area. This nationwide population-based cross-sectional study included representative civilian, non-institutional population (n = 6564) who underwent thyroid function tests from Korea National Health and Nutrition Examination Survey VI (2013-2015). The reference interval of serum thyroid-stimulating hormone levels was defined between the 2.5th and 97.5th percentiles in the reference population. The geometric mean of serum thyroid-stimulating hormone levels in the reference population was 2.17 mIU/L with a reference interval of 0.62-6.84 mIU/L. In the reference population, the geometric mean of serum TSH levels in each age group of 10-18, 19-29, 30-39, 40-49, 50-59, 60-69, and equal or older than 70 years was 2.47, 2.20, 2.07, 2.04, 2.23, 2.12, and 2.27 mIU/L, with a reference interval of 0.74-7.35, 0.67-6.42, 0.63-6.04, 0.62-6.20, 0.56-7.37, 0.57-6.90, and 0.42-6.58 mIU/L, respectively. In the reference population, the urinary iodine concentrations were consistently high in all age groups (median 298.5 μg/L). Subjects aged 10-18 years had the highest urinary iodine concentrations. There was no shift toward higher levels with age in the distribution of serum thyroid-stimulating hormone levels. The reference interval of serum thyroid-stimulating hormone levels was consistently high in all age group, especially from adolescence 10-18 years in a Korean population who had excessive intake of dietary iodine.


Trends in covalency for d- and f-element metallocene dichlorides identified using chlorine K-edge X-ray absorption spectroscopy and time-dependent density functional theory.
We describe the use of Cl K-edge X-ray absorption spectroscopy (XAS) and both ground-state and time-dependent hybrid density functional theory (DFT) to probe the electronic structure and determine the degree of orbital mixing in M-Cl bonds for (C(5)Me(5))(2)MCl(2) (M = Ti, 1; Zr, 2; Hf, 3; Th, 4; U, 5), where we can directly compare a class of structurally similar compounds for d- and f-elements. Pre-edge features in the Cl K-edge XAS data for the group IV transition-metals 1-3 provide direct evidence of covalent M-Cl orbital mixing. The amount of Cl 3p character was experimentally determined to be 25%, 23%, and 22% per M-Cl bond for 1-3, respectively. For actinides, we find a pre-edge shoulder for 4 (Th) and distinct and weak pre-edge features for U, 5. The amount of Cl 3p character was determined to be 9% for 5, and we were unable to make an experimental determination for 4. Using hybrid DFT calculations with relativistic effective core potentials, the electronic structures of 1-5 were calculated and used as a guide to interpret the experimental Cl K-edge XAS data. For transition-metal compounds 1-3, the pre-edge features arise due to transitions from Cl 1s electrons into the 3d-, 4d-, and 5d-orbitals, with assignments provided in the text. For Th, 4, we find that 5f- and 6d-orbitals are nearly degenerate and give rise to a single pre-edge shoulder in the XAS. For U, 5, we find the 5f- and 6d-orbitals fall into two distinct energy groupings, and Cl K-edge XAS data are interpreted in terms of Cl 1s transitions into both 5f- and 6d-orbitals. Time-dependent DFT was used to calculate the energies and intensities of Cl 1s transitions into empty metal-based orbitals containing Cl 3p character and provide simulated Cl K-edge XAS spectra for 1-4. For 5, which has two unpaired 5f electrons, simulated spectra were obtained from transition dipole calculations using ground-state Kohn-Sham orbitals. To the best of our knowledge, this represents the first application of Cl K-edge XAS to actinide systems. Overall, this study allows trends in orbital mixing within a well-characterized structural motif to be identified and compared between transition-metals and actinide elements. These results show that the orbital mixing for the d-block compounds slightly decreases in covalency with increasing principal quantum number, in the order Ti > Zr approximately = Hf, and that uranium displays approximately half the covalent orbital mixing of transition elements.


Preclinical investigations into the antipsychotic potential of the novel histamine H3 receptor antagonist GSK207040.
To test the novel nonimidazole histamine H3 receptor antagonist 5-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazapin-7-yl)oxy]-N-methyl-2-pyrazinecarboxamide (GSK207040) in a series of behavioral and neurochemical paradigms designed to evaluate its antipsychotic potential. Acute orally administered GSK207040 was investigated for its capacity to reverse a 24-h-induced deficit in novel object recognition memory, deficits in prepulse inhibition (PPI) induced by isolation rearing, and hyperlocomotor activity induced by amphetamine. The acute neurochemical effects of GSK207040 were explored by analyzing rat anterior cingulate cortex microdialysates for levels of dopamine, noradrenaline, and acetylcholine and by c-fos immunohistochemistry. The potential for interaction with the antipsychotic dopamine D2 receptor antagonist haloperidol was explored behaviorally (spontaneous locomotor activity and catalepsy), biochemically (plasma prolactin), and via ex vivo receptor occupancy determinations. GSK207040 significantly enhanced object recognition memory (3 mg/kg) and attenuated isolation rearing-induced deficits in PPI (1.0 and 3.2 mg/kg) but did not reverse amphetamine-induced increases in locomotor activity. There was no evidence of an interaction of GSK207040 with haloperidol. GSK207040 (3.2 mg/kg) raised extracellular concentrations of dopamine, noradrenaline, and acetylcholine in the anterior cingulate cortex and c-fos expression in the core of the nucleus accumbens was increased at doses of 3.2 and 10.0 mg/kg. The behavioral and neurochemical profile of GSK207040 supports the potential of histamine H3 receptor antagonism to treat the cognitive and sensory gating deficits of schizophrenia. However, the failure of GSK207040 to reverse amphetamine-induced locomotor hyperactivity suggests that the therapeutic utility of histamine H(3) receptor antagonism versus positive symptoms is less likely, at least following acute administration.


Non-penicillinase producing Neisseria gonnorhoeae: are they still in existence in Ibadan, Nigeria?
In an attempt to evaluate the current prevalence rate of penicillinase producing Neisseria gonorrhoeae (PPNG) and whether non-PPNG strains are still in existence in Ibadan, Nigeria, all isolates of Neisseria gonorrhoeae from patients that attended our clinic between January and December 1997 were studied. Of the 155 patients that had gonococcal infections, 118 were male (76.1%) and 37 (23.9%) were female with 31 (83.8%) being the partners of infected men. Sixty-four (54.2%) of the male and 19 (51.4%) of the female were aged between 20 and29 years while 21.2% of the male and 16.2% of the female were in the age of 40 and above. The sex difference is not statistically significant (chi2=1.47,P=-0.69). The present study revealed that non-PPNG strains have reduced considerably to 5.4% from 100% in 1977. This has posed a great threat to the usefulness of penicillin and ampicillin as the drugs of choice in gonococcal therapy in Nigeria.


Estrogen modulation of retinol-binding protein in immature chicks: comparison with riboflavin carrier protein.
The kinetics of estrogen (E) modulation of retinol-binding protein (RBP) production in the liver of immature chicks were compared with those governing de novo induction of riboflavin carrier protein (RCP) in the same tissue. A single dose of E markedly enhanced the plasma levels of RBP without any detectable lag period to reach peak value by 24 h and this was followed by a decline to attain the baseline by 4 days. There was no amplification of the response during secondary stimulation unlike the case with RCP induction. With multiple E administration, the 4-fold increased plasma RBP concentrations were sustained at a steady state during both primary and secondary stimulations, whereas concomitant RCP concentration progressively increased with each hormone administration and this response was further amplified during secondary stimulation. Unlike RCP induction, enhanced RBP accumulation was not strictly E dose dependent although a minimal threshold level of the steroid was required to elicit measurable response. Progesterone (P) could neither modulate nor substitute for E in enhancing plasma levels of either of the 2 proteins while the anti-estrogens, en- and zuclomifene citrate severely suppressed the production of both the proteins. RCP induction was completely inhibited by both alpha-amanitin and cycloheximide for prolonged periods while E-stimulated RBP production was affected only partially by alpha-amanitin. Likewise, cycloheximide inhibition of RBP accumulation followed a pattern similar to that of hepatic general protein synthesis.


Staging of Hodgkin disease in children: comparison of CT and lymphography with laparotomy.
Proper therapy for Hodgkin disease requires accurate staging of the disease. We compared the value of CT and lymphography with that of laparotomy for staging newly diagnosed Hodgkin disease in 46 children. The laparotomy revealed disease in one or more subdiaphragmatic sites in 46%. Correlation of the imaging studies with the laparotomy findings showed that lymphography has a greater sensitivity (80%) than does CT (40%) in detecting retroperitoneal lymph nodes. The sensitivity of CT in detecting splenic involvement was only 19%, presumably because of the small size of tumor deposits in involved spleens. Staging laparotomy altered the clinical stage in 37% of children, which resulted in a significant change of therapy in those patients. Although lymphography and, to a lesser degree, CT are useful for staging of Hodgkin disease, laparotomy continues to be the most important tool in choosing appropriate therapy for children with Hodgkin disease.


Conversation analysis can help to distinguish between epilepsy and non-epileptic seizure disorders: a case comparison.
Factual items in patients' histories are of limited discriminating value in the differential diagnosis of epilepsy and non-epileptic seizures (NES). A number of studies using a transcript-based sociolinguistic research method inspired by Conversation Analysis (CA) suggest that it is helpful to focus on how patients talk. Previous reports communicated these findings by using particularly clear examples of diagnostically relevant interactional, linguistic and topical features from different patients. They did not discuss the sequential display of different features although this is crucially important from a conversation analytic point of view. This case comparison aims to show clinicians how the discriminating features are displayed by individual patients over the course of a clinical encounter. CA-inspired brief sequential analysis of two first 30-min doctor-patient encounters by a linguist blinded to all medical information. A gold standard diagnosis was made by the recording of a typical seizure with video-EEG. The patient with epilepsy volunteered detailed first person accounts of seizures. The NES patient exhibited resistance to focusing on individual seizure episodes and only provided a detailed seizure description after repeated prompting towards the end of the interview. Although both patients also displayed some linguistic features favouring the alternative diagnosis, the linguist's final diagnostic hypothesis matched the diagnosis made by video-EEG in both cases. This study illustrates the importance of the time point at which patients share information with the doctor. It supports the notion that close attention to how patients communicate can help in the differential diagnosis of seizures.


Pre-trained convolutional neural networks as feature extractors for tuberculosis detection.
It is estimated that in 2015, approximately 1.8 million people infected by tuberculosis died, most of them in developing countries. Many of those deaths could have been prevented if the disease had been detected at an earlier stage, but the most advanced diagnosis methods are still cost prohibitive for mass adoption. One of the most popular tuberculosis diagnosis methods is the analysis of frontal thoracic radiographs; however, the impact of this method is diminished by the need for individual analysis of each radiography by properly trained radiologists. Significant research can be found on automating diagnosis by applying computational techniques to medical images, thereby eliminating the need for individual image analysis and greatly diminishing overall costs. In addition, recent improvements on deep learning accomplished excellent results classifying images on diverse domains, but its application for tuberculosis diagnosis remains limited. Thus, the focus of this work is to produce an investigation that will advance the research in the area, presenting three proposals to the application of pre-trained convolutional neural networks as feature extractors to detect the disease. The proposals presented in this work are implemented and compared to the current literature. The obtained results are competitive with published works demonstrating the potential of pre-trained convolutional networks as medical image feature extractors.


Common mechanisms of promoter recognition by RNA polymerases II and III.
Recent results indicate that RNA polymerase III can use upstream promoters that are structurally and functionally very similar to those recognized by RNA polymerase II. The demonstration that RNA polymerases II and III can use the same transcription factors emphasizes the fundamental similarities between these distinct activities. It is also clear now that transcription factors can be functionally interchanged between distantly related species, indicating that the basic structures involved in promoter recognition are highly conserved throughout evolution.


Mobilization of an ERV9 human endogenous retroviral element during primate evolution.
ERV9 is a low repeated family of human endogenous retroviral elements, which has close to 50 members, in addition to at least 4000 solitary LTRs. Previous work has shown that randomly selected LTRs can promote transcription of reporter genes, raising the possibility that these sequences may affect the expression of adjacent cellular genes. We report here the structural organization in different primate species of a zinc-finger coding gene whose expression is driven in humans by a solitary ERV9-LTR promoter. Using a PCR strategy and library screening, we were able to trace the origin of the insertion event in the primate lineage and to evaluate the impact of this event on gene structure. Our findings indicate that the integration of the ERV9 element occurred after the split of orangutang from the great apes, but before the divergence of the gorilla lineage. These results suggest that ERV9 elements have been mobile within the primate lineages and may still be active in humans.


Effects of endothelin and vasopressin on portal pressure of rats.
Endothelin is a vasoconstrictor peptide which has recently been isolated and sequenced from the vascular endothelial cells. It was reported to increase blood pressure in vivo and produce a prolonged contraction with a slow onset in vitro. The purpose of this study was to investigate whether endothelin can lower the portal pressure as another endogenous vasoconstriction peptidevasopressin (AVP) can. Heart rate, systemic blood pressure, portal pressure, and portal vein blood flow were measured. Effects of endothelin on these parameters were compared with those of AVP. Endothelin 10(-10) mol/Kg significantly decreased all of the parameters mentioned. At the higher dose (5 x 10(-10) mol/Kg), however, the portal pressure and blood pressure were increased and portal vein blood flow was unchanged. On the other hand, AVP decreased the portal pressure and portal vein blood flow but elevated the systemic blood pressure. In vitro experiments revealed that endothelin contracted both tail artery and portal vein of rat and vasopressin contracted only tail artery. We concluded that although both are endogenous vasoconstricting peptides, endothelin and AVP affect differently on arterial and venous vascular beds as well as on portal pressure.


Iodinated hyaluronic acid oligomer-based nanoassemblies for tumor-targeted drug delivery and cancer imaging.
Nano-sized self-assemblies based on amphiphilic iodinated hyaluronic acid (HA) were developed for use in cancer diagnosis and therapy. 2,3,5-Triiodobenzoic acid (TIBA) was conjugated to an HA oligomer as a computed tomography (CT) imaging modality and a hydrophobic residue. Nanoassembly based on HA-TIBA was fabricated for tumor-targeted delivery of doxorubicin (DOX). Cellular uptake of DOX from nanoassembly, compared to a DOX solution group, was enhanced via an HA-CD44 receptor interaction, and subsequently, the in vitro antitumor efficacy of DOX-loaded nanoassembly was improved in SCC7 (CD44 receptor positive squamous cell carcinoma) cells. Cy5.5, a near-infrared fluorescence (NIRF) dye, was attached to the HA-TIBA conjugate and the in vivo tumor targetability of HA-TIBA nanoassembly, which is based on the interaction between HA and CD44 receptor, was demonstrated in a NIRF imaging study using an SCC7 tumor-xenografted mouse model. Tumor targeting and cancer diagnosis with HA-TIBA nanoassembly were verified in a CT imaging study using the SCC7 tumor-xenografted mouse model. In addition to efficient cancer diagnosis using NIRF and CT imaging modalities, improved antitumor efficacies were shown. HA and TIBA can be used to produce HA-TIBA nanoassembly that may be a promising theranostic nanosystem for cancers that express the CD44 receptor.


A comparison of hyperthermia cisplatin sensitization in human ovarian carcinoma and glioma cell lines sensitive and resistant to cisplatin treatment.
Two pairs of human tumor cell lines (glioma and ovarian carcinoma (OvCa) each having a parental cell line and cisplatin-resistant variant, were evaluated for (a) cisplatin response, (b) hyperthermia response, and (c) combined hyperthermia and cisplatin response. The two resistant lines had comparable resistant responses while for the parental lines, the OvCa was more sensitive than the glioma to cisplatin doses up to 14 microgram/ml. For the hyperthermia response, the OvCa parental line was more resistant than the variant line at low-temperature hyperthermia (41 degrees C or 42 degrees C) but became more sensitive at high temperature (45 degree C). For the glioma, the parental line was more sensitive to hyperthermia at all temperatures tested. Hyperthermia caused sensitization to cisplatin in all cell lines but was generally greater in the glioma cell lines. In the OvCa system, hyperthermia had a slightly greater sensitizing effect on the resistant cell lines, while in the glioma the opposite was true. The degree of sensitization increased with hyperthermia temperature. In summary, the results showed that there is no cross- resistance for hyperthermia and cisplatin, that the degree of thermal sensitization is not reduced in cisplatin- resistant cell lines, and that cisplatin thermal sensitization is cell-line and temperature dependent. Thus, hyperthermia can effectively improve tumor cell response to cisplatin and may be useful in overcoming resistance to cisplatin.