Testing Jessor's problem behavior theory and syndrome: a nationally representative comparative sample of Latino and African American adolescents.
Based on Jessor's problem behavior theory (PBT; R. Jessor, 1987, Problem-behavior theory, psychosocial development, and adolescent problem drinking, British Journal of Addiction, Vol. 82, pp. 331-342), the comparability of a second-order problem behavior model (SPBM) was investigated employing structural equation modeling (SEM) and latent mean differences in problem behavior engagement were examined among racial/ethnic adolescents. Within a span of nearly 25 years, this study represents the first nationally representative sample of Latino and African American adolescents utilized in testing Jessor's PBT and problem behavior syndrome (PBS). Using a sample of 5,831 Latino, African American, and European American adolescents drawn from the National Longitudinal Study of Adolescent Health, a series of invariance tests evidenced support for Jessor's PBT and PBS. Latent mean difference test results evidenced significant differences in problem behaviors (e.g., academic failure [AF], aggression [AG], substance use [SU], and risky sexual activity[RSA]) across racial/ethnic adolescent groups, which could be explained partially by PBS. A discussion of findings, limitations, and recommendations for future research is presented.


Cytokinin action in response to abiotic and biotic stresses in plants.
The phytohormone cytokinin was originally discovered as a regulator of cell division. Later, it was described to be involved in regulating numerous processes in plant growth and development including meristem activity, tissue patterning, and organ size. More recently, diverse functions for cytokinin in the response to abiotic and biotic stresses have been reported. Cytokinin is required for the defence against high light stress and to protect plants from a novel type of abiotic stress caused by an altered photoperiod. Additionally, cytokinin has a role in the response to temperature, drought, osmotic, salt, and nutrient stress. Similarly, the full response to certain plant pathogens and herbivores requires a functional cytokinin signalling pathway. Conversely, different types of stress impact cytokinin homeostasis. The diverse functions of cytokinin in responses to stress and crosstalk with other hormones are described. Its emerging roles as a priming agent and as a regulator of growth-defence trade-offs are discussed.


Simultaneous management of congenital tracheal stenosis and cardiac anomalies in infants.
The present article aims to describe our experience with patients who underwent simultaneous repair of congenital tracheal stenosis and cardiac anomalies. Between January 2000 and December 2003, 9 infants underwent simultaneous surgical repair of a congenital tracheal stenosis and congenital heart disease. The intraoperative findings revealed localized tracheal stenosis in 3 patients. The funnel-type tracheal stenosis was present in 6 patients. Associated cardiac anomalies included ostium secundum atrial septal defect in 5 patients and ventricular septal defect in 2 patients, pulmonary artery sling in 4 patients, patent ductus arteriosus in 6 patients, atrioventricular septal defect in 1 patient, aortic arch hypoplasia in 1 patient, coarctation of the aorta in 1 patient, and partial anomalous pulmonary venous connection in 2 patients, one of them with "scimitar syndrome." Tracheal origin of the right upper lobe was diagnosed in 2 of the patients. A right aberrant subclavian artery (lusoria) was found in one patient. All patients were operated on through a median sternotomy and with cardiopulmonary bypass. Tracheal resection with direct end-to-end anastomosis was performed in all cases. There was no operative mortality. One patient died 6 weeks postoperatively. Eight patients were extubated between the 14th and 30th postoperative days under bronchoscopic monitoring. The extubation was performed after a stepwise respirator-weaning program. Postoperative endoscopic examination showed adequate airway dimensions and patency in every case. The midterm results after a mean follow-up of 37 months (range, 16-58 months) of the entire group demonstrate a stabile and complication-free clinical outcome. We advocate our current strategy for infants with congenital tracheal stenosis: resection with end-to-end anastomosis and simultaneous repair of associated intracardiac anomalies.


[Nephrotic syndrome and acute kidney injury associated with celiac disease: report of one case].
Celiac disease may be associated with other autoimmune diseases and exceptionally with glomerulopathies and nephrotic syndrome. Associations have been reported with IgA nephropathy, membranoproliferative glomerulonephritis, membranous glomerulopathy and minimal change disease. We report a 63-year-old woman who simultaneously presented with massive nephrotic syndrome (proteinuria 46 g/day) and cachexia due to a malabsorption syndrome secondary to celiac disease. The course of her diseases was complicated with cardiomyopathy due to severe malnutrition, septic shock, acute kidney injury that required dialysis for seven weeks and severe hypertension. A renal biopsy showed a membranoproliferative pattern of injury secondary to a thrombotic microangiopathy and diffuse podocyte damage. Four years later, the patient was in good general health, the glomerular filtration rate was 30 ml/min/1.73m² and there was non-nephrotic proteinuria.


The role of depression in the development of breast cancer: analysis of registry data from a single institute.
Although controversial, the belief that developing breast cancer may be associated with psychological distress is not uncommon. The present study examined the role of psychological variables in the development of breast cancer in women attending a breast clinic for medical examination in Tehran, Iran. During a three-year period (1997-1999) a trained female nurse interviewed all women attending the Iranian Center for Breast Cancer (ICBC) before a confirmed diagnosis was made (N = 3000). Data were collected on demographic variables (age, education and marital status), known risk factors (age at menarche, age at first time full term pregnancy, family history of breast cancer, menopausal status, and oral contraceptive use), psychological variables, including history of psychiatric medications, depression (depressed mood, hopelessness, and loss of interests and pleasures), anxiety (mental and somatic signs) and two single measures of overall health and quality of life. In all, 243 patients were diagnosed as having breast cancer. A total of 486 patients with benign disease were randomly selected from the original cohort as controls. Univariate and multivariate logistic regression analyses were performed to determine the predictive effect of each factor on the risk of breast cancer. There were no significant differences between cases and controls except for age at menarche (P = 0.007) and family history of breast cancer (P<0.001). With regard to psychological variables studied, the results showed that there were significant differences between cases and controls regarding depression (depressed mood P<0.0001, hopelessness P = 0.001, and loss of interest and pleasures P = 0.001), and anxiety (mental signs P = 0.006). Finally, after performing multiple logistic regression analysis in addition to family history and age at menarche, depressed mood and hopelessness showed significant results (odds ratios of 1.90, and 1.63 respectively). The findings of the present study suggest that in addition to the known risk factors, psychological determinants such as depressed mood may play an important role in etiology of breast cancer and deserve further investigation, especially in different populations.


Desferri-Exochelin, a lipid-soluble, hexadentate iron chelator, effectively removes tissue iron.
Chronic iron-overload is damaging to the heart, liver, and other organs. Better iron chelators are needed to treat this serious medical condition. The uptake and distribution of the lipid-soluble, hexadentate iron chelator desferri-Exochelin 772SM (D-Exo) is studied and its efficacy in removing iron from tissue in rodent models is evaluated. After an intravenous bolus of tritiated D-Exo to rats, counts rapidly disappeared from the blood and rapidly appeared in 15 organs studied, usually peaking within 15 min. There was considerable uptake in the heart and liver, 2 organs especially susceptible to damage from clinical iron overload. To assess actual decreases in cardiac and hepatic iron in response to D-Exo, mice loaded with 42 mg of iron dextran (2100 mg/kg) were studied. Untreated, iron-loaded mice sacrificed 9 weeks later had a 4-fold increase in cardiac iron and a 20-fold increase in hepatic iron compared with controls that were not iron-loaded. In iron-loaded mice treated with 7 mg of D-Exo intraperitoneally (i.p.) 4 days/week for 8 weeks (total 224 mg), tissue iron, measured by atomic absorption, was reduced by 20% in the liver and 25% in the heart (P < 0.01 for each organ). During the first 8 h after a D-Exo dose, iron was excreted in the urine. Mice treated with D-Exo gained weight normally and showed no evidence of toxicity. In conclusion, in this iron-overload mouse model, D-Exo administered intravenously or i.p. rapidly diffuses into multiple organs, including the heart and liver, and effectively removes iron without apparent toxicity.


Immunolocalization of collagen types I and III, tenascin, and fibronectin in intramembranous bone.
Structural components of the organic bone matrix were located by immunohistochemical techniques in fresh-frozen sections of normal and dysplastic bone. Fine and coarse birefringent fibers were identified as separate and distinctive features in the extracellular matrix by antibodies raised against human collagen Type III. The glycoprotein tenascin was located on a proportion of the fibers in a characteristic beaded pattern, which was absent in dysplastic bone. The fibers originated in the periosteum or in the fibrous stroma of the marrow cavity and were oriented with regard to both the spatial and the lamellar organization of the bone. The disposition and composition of the fibers suggests that they form a preliminary framework on which intramembranous bone modeling proceeds, and that the specific location of tenascin on the fibers in normal developing membrane bone may be important in determining the alignment of the bone tissue. Epitopes recognized by the collagen Type I and fibronectin antibodies were demonstrated throughout the mineralized matrix, but their incorporation into the collagen "Type III" fibers was evident only outside the mineralized matrix.


Iridium-catalyzed asymmetric hydrogenation of unfunctionalized, trialkyl-substituted olefins.
Chiral iridium complexes with bicyclic pyridine-based N,P ligands have emerged as efficient catalysts for the enantioselective hydrogenation of unfunctionalized trialkyl-substituted olefins. Optimization of the reaction conditions by variation of the solvent, pressure, and temperature led to enantiomeric excesses of up to 99%. Three pure alkenes, (E)-2-cyclohexyl-2-butene and (E)- and (Z)-3,4-dimethyl-2-pentene were converted into the corresponding chiral alkanes with 97%, 94%, and 93% ee, respectively. Hydrogenation of the three C=C bonds of both α- and γ-tocotrienyl acetate led to α- and γ-tocopheryl acetate with very high diastereoselectivity. The same catalysts were successfully applied in the hydrogenation of trisubstituted alkenes with a carboxylic ester or a keto group in the γ position. This reaction was used as a key step in a highly enantioselective synthesis of the pheromone of the caddisfly Hesperophylax occidentalis. The hydrogenation of a structurally analogous allylic alcohol also gave high enantioselectivities.


Synthetic miR-143 Inhibits Growth of HER2-Positive Gastric Cancer Cells by Suppressing KRAS Networks Including DDX6 RNA Helicase.
Gastric cancer (GC) is one of the most common cancers worldwide. In the clinical setting, the identification of HER2 overexpression in GC was a significant finding, as trastuzumab, an anti-HER2 drug, provides a survival advantage to HER2-positive GC patients. In HER2-postive GC, the dysregulation of PI3K/AKT and MAPK/ERK signaling pathways has been reported, and inhibition of these pathways is an important therapeutic strategy. MiR-143 is known to act as a tumor suppressor in several cancers, such as bladder cancer, breast cancer, colorectal cancer, and gastric cancer. In the current study, we developed a novel chemically-modified miR-143 and explored the functions of this synthetic miR-143 (syn-miR-143) in HER2-positive gastric cancer. The expression level of miR-143 was down-regulated in GC cell lines, including HER2-positive GC cell lines, MKN7, and KATO-III. The ectopic expression of miR-143 in those cell lines suppressed cell growth through systemic silencing of KRAS and its effector signaling molecules, AKT and ERK. Furthermore, syn-miR-143 indirectly down-regulated the expression of HER2, an upstream molecule of KRAS, through silencing DEAD/H-box RNA helicase 6 (DDX6), RNA helicase, which enhanced HER2 protein expression at the translational step in HER2-positive GC cells. These findings suggested that syn-miR-143 acted as a tumor suppressor through the impairment of KRAS networks including the DDX6.


Dystonia: a disorder of motor programming or motor execution?
For some time, dystonia has been seen as purely a motor disorder. Relatively novel concepts published approximately 10 years ago also presumed that in the development of dystonic dyskinesias, only motor behaviour was abnormal. Neurophysiological observations of various types of dystonic disorders, which were performed using sophisticated electromyography, polymyography, H-reflex examination, long-latency reflex, etc., as well as new insights into the behaviour of dystonia, have urged the inclusion of sensory (particularly somatosensory) mechanisms into the pathophysiological background of dystonia. The major role has been considered to be played by abnormal proprioceptive input by means of the Ia proprioceptive afferents, with the source of this abnormality found in the abnormal processing of muscle spindle afferent information. However, neurophysiological investigations have also provided evidence that the abnormality in the central nervous system is located not only at the spinal and subcortical level, but also at the cortical level; specifically, the cortical excitability and intracortical inhibition have been revealed as abnormal. This evidence was revealed by SEP recordings, paired transcranial magnetic stimulation recordings, and BP and CNV recordings. The current concept of dystonic movement connects the abnormal function of somatosensory pathways and somatosensory analysers with the dystonic performance of motor action, which is based on the abnormality of sensorimotor integration.


Diastereoselective Methylation at the Congested β-Position of a Butenolide Ring: Studies toward the Synthesis of seco-Prezizaane-Type Sesquiterpenes.
We established a method for installing a methyl group at the β-position of a butenolide ring. The methylated position is located at the congested ring juncture of a 5,6,5-tricyclic lactone, which is common to neurotrophic seco-prezizaane-type sesquiterpenes. The samarium(II)-mediated conjugate addition of the halomethylsilyl ethers tethered to the proximal hydroxy groups efficiently formed the desired C-C bond. Subsequent fluoride-free Tamao oxidation and Barton-McCombie deoxygenation converted the resultant cyclic silyl ether into the corresponding methyl group.


Trials of antivirals in the treatment of multiple sclerosis.
There is increasing evidence that human herpes viruses and human endogenous retroviruses (HERV) are involved in the aetiology and pathogenesis of multiple sclerosis (MS). In order to acquire the ultimate evidence to confirm such a relationship, it is probably required to use specific antiviral drugs in clinical trials of MS. The results of published antiviral clinical trials in patients with MS are summarized in this review. None of them showed statistically significant effects on primary outcomes of disease activity or on disability development. However, given their small sample sizes, the strong trends and effects observed in subgroup analysis of antiherpes virus treatment in patients with MS warrant further studies. The possible involvement of HERV in MS is intriguing, and drugs have been developed that could reduce the impact of HERV in MS. However, larger studies are needed as the phase I and II trials were not designed to show clinical efficacy in MS.


Comparison of lateralized and binasal olfactory thresholds.
We investigated whether dirhinal olfactory thresholds differ from monorhinal ones. Experiments 1 and 2 investigated butanol, Experiment 3 phenylethylalcohol. In Experiments 2 and 3 pen-like odor dispensing devices were used, in Experiment 1 odors were presented in glass bottles. Participants were in excellent health (Experiment 1: 14 female [f], 15 m [m], mean age [ma] 24 years; Experiment 2: 12 f, 19 m, ma 24 years; Experiment 3: 19 f, 19 m, ma 32 years). Thresholds were assessed for left, right, and both nostrils. No significant difference was found between dirhinal results and results for the best of two nostrils. Apart from this, thresholds were found to improve with repeated testing. In conclusion, using two odorants with different techniques of administration in studies performed at different sites, the present results indicated that there is no major difference between odor detection thresholds obtained for the best and both nostrils.


Analysis of T cell receptor V beta gene expression in B cell deficient mice after experimental herpes simplex virus keratitis.
To examine the importance of B cells in the regulation of the T cell response to herpes simplex virus (HSV) infection, we have analyzed the selection of the T cell receptor (TCR) repertoire in C.B-17 mice that lack B cells (B. mice) compared with age-matched immunocompetent C.B-17 mice, usually resistant to herpes simplex keratitis (HSK). TCR V beta transcripts used by these mice were analyzed by polymerase chain reaction (PCR) with variable gene-specific primers. Clinical examination showed that the incidence of HSK was significantly different between untreated (control) and anti-mu antibody (Ab)-treated mice (p < 0.0001). Passive transfer of anti-HSV Ab into B. mice, before infection, prevented HSK; transfer of naive B cells allowed HSK to evolve in 50% of these mice. AT the level of gene expression, we demonstrated that the anti-mu Ab treatment altered TCR V beta gene expression in eyes, spleen, thymus and lymph nodes (LN) of C.B-17 mice. Preferential utilization of a single TCR Tb gene was not detected in the course of the disease except in LN, although in resistant mice there were different patterns of mRNA induction in T cells expressing specific TCR Vb elements that were not seen in susceptible mice, namely the lack of expression of V beta 8.1, V beta 8.2 and V beta 8.3 in eyes, the expression of V beta 7 in spleen, and the lack expression of V beta 6 and V beta 13 in thymus. These observations together with previous findings suggest that at the level of protein production, anti-HSV Ab not only can provide protection against HSK but is also a critical component for protection against HSV in normally resistant C.B17 mice, and that a dysregulation of the immune system in B. mice is manifested by dramatic changes in TCR V beta usage at the molecular level.


Probucol prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbit, an animal model for familial hypercholesterolemia.
In this study, we questioned whether in vivo probucol could prevent the progression of atherosclerosis in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model for familial hypercholesterolemia. At 2 months of age, eight WHHL rabbits were divided into two groups. Group A (n = 4) was fed standard rabbit chow for 6 months. Group B (n = 4) was fed standard rabbit chow containing 1% probucol for 6 months. At the end of the experiments, average plasma concentrations of cholesterol were 704 +/- 121 mg/dl in group A and 584 +/- 61 mg/dl in group B, respectively. The percentage of surface area of total thoracic aorta with visible plaques in group A versus group B was 54.2% +/- 18.8% versus 7.0% +/- 6.3%, respectively. What was noteworthy was that the percentage of plaque in the descending thoracic aorta was almost negligible (0.2% +/- 0.2%) in group B rabbits compared to that in group A rabbits (41.1% +/- 20.2%). Low density lipoproteins (LDL) isolated from WHHL rabbits under treatment with probucol (group B) were shown to be highly resistant to oxidative modification by cupric ion and to be minimally recognized by macrophages. On the contrary, LDL from group A rabbits incubated with cupric ion showed a 7.4-fold increase in peroxides (thiobarbituric acid-reactive substances) and a 4.3-fold increase in the synthesis of cholesteryl ester in macrophages compared to those of LDL from group B rabbits. Thus, probucol could definitely prevent the progression of atherosclerosis in homozygous WHHL rabbits in vivo by limiting oxidative LDL modification and foam cell transformation of macrophages.


[Obsessive-compulsive behaviour in two patients with right temporal variant frontotemporal dementia].
There is often a long delay before right temporal variant of frontotemporal dementia (rtlv) is correctly diagnosed. The late diagnosis is usually due to the occurrence of psychiatric symptoms as the first signs of disease and to the relatively young age of the patient. We report two patients who were initially treated for obsessive-compulsive disorder but were later diagnosed as having rtlv.


Mitochondrial transport in processes of cortical neurons is independent of intracellular calcium.
Mitochondria show extensive movement along neuronal processes, but the mechanisms and function of this movement are not clearly understood. We have used high-resolution confocal microscopy to simultaneously monitor movement of mitochondria and changes in intracellular [Ca(2+)] ([Ca(2+)](i)) in rat cortical neurons. A significant percentage (27%) of the total mitochondria in cortical neuronal processes showed movement over distances of >2 microM. The average velocity was 0.52 microm/s. The velocity, direction, and pattern of mitochondrial movement were not affected by transient increases in [Ca(2+)](i) associated with spontaneous firing of action potentials. Stimulation of Ca(2+) transients with forskolin (10 microM) or bicuculline (10 microM), or sustained elevations of [Ca(2+)](i) evoked by glutamate (10 microM) also had no effect on mitochondrial transit. Neither removal of extracellular Ca(2+), depletion of intracellular Ca(2+) stores with thapsigargin, or inhibition of synaptic activity with TTX (1 microM) or a cocktail of CNQX (10 microM) and MK801 (10 microM) affected mitochondrial movement. These results indicate that movement of mitochondria along processes is a fundamental activity in neurons that occurs independently of physiological changes in [Ca(2+)](i) associated with action potential firing, synaptic activity, or release of Ca(2+) from intracellular stores.


Ionic mechanisms underlying depolarizing responses of an identified insect motor neuron to short periods of hypoxia.
Hypoxia can dramatically disrupt neural processing because energy-dependent homeostatic mechanisms are necessary to support normal neuronal function. In a human context, the long-term effects of such disruption may become all too apparent after a "stroke," in which blood-flow to part of the brain is compromised. We used an insect preparation to investigate the effects of hypoxia on neuron membrane properties. The preparation is particularly suitable for such studies because insects respond rapidly to hypoxia, but can recover when they are restored to normoxic conditions, whereas many of their neurons are large, identifiable, and robust. Experiments were performed on the "fast" coxal depressor motoneuron (Df) of cockroach (Periplaneta americana). Five-minute periods of hypoxia caused reversible multiphasic depolarizations (10-25 mV; n = 88), consisting of an initial transient depolarization followed by a partial repolarization and then a slower phase of further depolarization. During the initial depolarizing phase, spontaneous plateau potentials normally occurred, and inhibitory postsynaptic potential frequency increased considerably; 2-3 min after the onset of hypoxia all electrical activity ceased and membrane resistance was depressed. On reoxygenation, the membrane potential began to repolarize almost immediately, becoming briefly more negative than the normal resting potential. All phases of the hypoxia response declined with repeated periods of hypoxia. Blockade of ATP-dependent Na/K pump by 30 microM ouabain suppressed only the initial transient depolarization and the reoxygenation-induced hyperpolarization. Reduction of aerobic metabolism between hypoxic periods (produced by bubbling air through the chamber instead of oxygen) had a similar effect to that of ouabain. Although the depolarization seen during hypoxia was not reduced by tetrodotoxin (TTX; 2 microM), lowering extracellular Na+ concentration or addition of 500 microM Cd2+ greatly reduced all phases of the hypoxia-induced response, suggesting that Na influx occurs through a TTX-insensitive Cd2+-sensitive channel. Exposure to 20 mM tetraethylammonium and 1 mM 3,4-diaminopyridine increased the amplitude of the hypoxia-induced depolarization, suggesting that activation of K channels may normally limit the amplitude of the hypoxia response. In conclusion we suggest that the slow hypoxia-induced depolarization on motoneuron Df is mainly carried by a TTX-resistant, Cd2+-sensitive sodium influx. Ca2+ entry may also make a direct or indirect contribution to the hypoxia response. The fast transient depolarization appears to result from block of the Na/K pump, whereas the reoxygenation-induced hyperpolarization is largely caused by its subsequent reactivation.


Real-world analysis of treatment patterns and clinical outcomes in patients with newly diagnosed chronic lymphocytic leukemia from seven Latin American countries.
To describe chronic lymphocytic leukemia (CLL) treatment patterns and patient outcomes in Latin America. This chart review study (NCT02559583; 2008-2015)evaluated time to progression (TTP) and overall survival (OS) outcomes among patients with CLL who initiate done (n = 261) to two (n = 96) lines of therapy (LOT) since diagnosis. Differences in TTP and OS were assessed by Kaplan-Meier analysis, with a log-rank test for statistical significance. Association between therapeutic regimen and risk for disease progression or death was estimated using Cox proportional hazard regression. The most commonly prescribed therapies in both LOTs were chlorambucil-, followed by fludarabine- and cyclophosphamide (C)/CHOP-based therapies. Chlorambucil- and C/CHOP-based therapies were largely prescribed to elderly patients (≥65 years) while fludarabine-based therapy was predominantly used by younger patients (≤65 years). In LOT1, relative to chlorambucil-administered patients, those prescribed fludarabine-based therapies had lower risk of disease progression (hazard ratio [HR] and 95% confidence interval [CI] 0.32 [0.19-0.54]), whereas C/CHOP-prescribed patients had higher risk (HR 95%CI 1.88 [1.17-3.04]). Similar results were observed in LOT2. There was no difference in OS between treatments in both LOTs. Novel therapies such as kinase inhibitors were rarely prescribed in LOT1 or LOT2in Latin America. The greater TTP observed forfludarabine-based therapies could be attributed to the fact that fludarabine-based therapies are predominantly administered to young and healthy patients. Chlorambucil-based therapy, which has limited benefits, is frequently prescribed in Latin America. Prescribing novel agents for fludarabine-based therapy-ineligible patients with CLL is the need of the hour. Trial registration: ClinicalTrials.gov identifier: NCT02559583.


Detection of unidentified chromosome abnormalities in human neuroblastoma by spectral karyotyping (SKY).
Spectral karyotyping (SKY) is a novel technique based on the simultaneous hybridization of 24 fluorescently labeled chromosome painting probes. It provides a valuable addition to the investigation of many tumors that can be difficult to define by conventional banding techniques. One such tumor is neuroblastoma, which is often characterized by poor chromosome morphology and complex karyotypes. Ten primary neuroblastoma tumor samples initially analyzed by G-banding were analyzed by SKY. In 8/10 tumors, we were able to obtain additional cytogenetic information. This included the identification of complex rearrangements and material of previously unknown origin. Structurally rearranged chromosomes can be identified even in highly condensed metaphase chromosomes. Following the SKY results, the G-banding findings were reevaluated, and the combination of the two techniques resulted in a more accurate karyotype. This combination allows identification not only of material gained and lost, but also of breakpoints and chromosomal associations. The use of SKY is therefore a powerful tool in the genetic characterization of neuroblastoma and can contribute to a better understanding of the molecular events associated with this tumor.


Regulation of pyrimidine and arginine biosynthesis investigated by the use of phaseolotoxin and 5-Fluorouracil.
Purified phaseolotoxin inhibits the growth of carrot cells. Such inhibitions can be reversed completely by citrulline but not by arginine. This toxin inhibits ornithine transcarbamylase activity in vitro, which leads to an accumulation of ornithine and a decrease in arginine levels intracellularly. In carrot cells, 5-fluorouracil (5-FU) toxicity can be reduced by the addition of purified toxin and citrulline, or ornithine. The toxin also decreases the incorporation of [(14)C]uracil and [(14)C]5-FU into trichloroacetic acid precipitable material by 50%. Finally, a 5-FU-resistant line, F5 (Sung ZR, Jacques S 1980 Planta 148: 389-396), was found to be more sensitive to the toxin than were 5-FU-sensitive cells. One millimolar 5-FU roughly doubled the ability of F5 to tolerate phaseolotoxin. These results demonstrate a close regulation between the pyrimidine and arginine path-ways in carrots.


A study of speech fractal dimensions.
The fractal dimension (D) of a signal gives an estimate of its degree of freedom, which allows estimation of its fluctuations. Using 16 kHz time sampling and the box counting method we studied the Ds of some of the main stationary parts of French speech, the phonemes [a], [e], [i], [o], [y], pronounced 4 times by 10 males and 10 females. Our study demonstrated that the stationary signal of vowels is not fractal, but may, at the smallest scale, provide a kind of signature for each vowel, though the present categorization is not totally significant. Since the box counting method objectifies and quantifies the roughness of the signal, this procedure may be useful for clinical applications. In case of dysphonia, moreover, these signatures could be perhaps be included in the speech signal processing of cochlear implants.


[Reconstruction of right ventricular outflow tract using transannular patch in 52 children with tetralogy of Fallot].
52 children with tetralogy of Fallot received reconstruction of right ventricular outflow tract (RVOT) by using transannular patch. The indications for using transannular patch to reconstruct RVOT, patch materials, and the standard of enlargement pulmonary annulus were studied. The indications were held correctly for reconstruction of RVOT with transannular patch. The autologous pericardium was the most acceptable material for patch. All patients showed no obstruction of RVOT during early and late postoperative follow-up, althought most of them had certain degree of pulmonary regurgitation (PR) in first postoperative year, whicli was gradually attenuated as their life time long-drawn, with better exertion tolerance.


Regulatory T cells and IL-10 in allergic inflammation.
Recent studies suggest that human regulatory T (T reg) cells protect against the development of allergic and asthmatic disease and that their function is impaired during active disease. Two new studies contribute to our understanding of the role that T reg cells play in the control of allergic airway disease in mice. However, these studies also highlight several outstanding questions in the field.


[Clinical effects of combination chemotherapy with irinotecan hydrochloride and cisplatin on cervical cancer: study of 46 patients].
To evaluate the efficacy and toxicity of the combination chemotherapy of irinotecan hydrochloride plus cisplatin on cervical cancer. Forty-six patients with cervical cancer, 43 with squamous cell carcinoma, 2 adenocarcinoma, and 1 small cell carcinoma, 41 being treated initially and 5 being recurrent cases of which 2 had undergone radiotherapy plus chemotherapy, 2 radical hysterectomy plus pelvic radiotherapy after operation, and 1 radical hysterectomy plus chemotherapy, aged 38 (22-61), were treated with irinotecan hydrochloride, 60 mg/m(2) in 250 ml normal saline administered on days 1, 8, and 15 by intravenous infusion over 60 min, plus cisplatin, 60 mg/m(2) in 500 ml 5% glucose given on day 1. This regimen was repeated every 28 days. Effectiveness evaluation was conducted after 1-2 courses for the initially treated patients and after 2-6 courses for the recurrent patients. Totally 79 courses of treatment were given to the 41 patients. After 1-2 courses 4 (9.8%) of the 41 stage Ib2-IIIb initially treated patients achieved complete remission, 30 (73.2%) achieved partial remission, and 7 (17.1%) remained at stationary phase with a overall effective rate of 82.9%. Of the 29 IIb and IIIb stage advanced patients who failed to receive operation originally 20 patients (69%) succeeded to be treated by radical hysterectomy after 1 to 2 courses when the tumorless space between the uterine and the pelvic wall > or = 3 cm with an operatibility rate of 69%. Of the 5 recurrent patients 1 case achieved complete remission, 2 partial remission, and 2 remained stable; none progression of disease was observed after 4-6 courses. The main toxic response and side effect included myelosuppression and diarrhea. Effective neoadjuvant chemotherapy on cervical cancer, combination therapy of irinotecan hydrochloride and cisplatin win opportunity for treatment and improves their life quality with tolerable side effects.


Combining [13C6]-phenylisothiocyanate and the Edman degradation reaction: a possible breakthrough for absolute quantitative proteomics together with protein identification.
This manuscript describes the results of a preliminary experiment performed as 'proof of concept' of a novel approach to absolute quantitation of proteins without the use of standard proteins. Absolute quantitation remains a challenging issue in the proteomics field. Therefore, we propose a combination of [(13)C(6)]-phenylisothiocyanate (PITC) and the Edman degradation reaction as a possible breakthrough. [(13)C(6)]-PITC was synthesized from [(13)C(6)]-aniline with O,O'-di-2-pyridyl thiocarbonate to prepare [(13)C(6)]-phenylthiohydantoin (PTH)-amino acids as internal standards. Upon the Edman degradation reaction, it has been confirmed that a model protein, bovine serum albumin (BSA), releases the N-terminal amino acid quantitatively as PTH-Asp. The standard curve of PTH-Asp against [(13)C(6)]-PTH-Asp showed good linearity (r(2) = 0.9977). BSA could be quantified as PTH-Asp using the standard curve. In addition, the residual des-Asp(1)-BSA provided sufficient information for further protein identification.


[Problems of surgical treatment for multiple intracranial aneurysms].
A series of 105 patients presenting with multiple aneurysms and subarachnoid hemorrhage (SAH) were operated on for ruptured and unruptured aneurysms between 1976 and 1984. Clinical factors other than the severity of SAH affecting the outcomes included: 1) Misdiagnosis of the location of a ruptured aneurysm among multiple aneurysms resulted in poor outcomes because of multiple surgical approaches or rebleeding during the acute period. 2) Combinations of aneurysmal locations requiring multiple surgical approaches, such as interhemispheric and transsylvian, during the acute stage caused worse outcomes than with multi-stage surgeries. If an unruptured aneurysm could not be reached during the initial exposure, multi-stage surgery was safe if the ruptured aneurysm had been clipped during the acute period. 3) Complications occurring during unruptured aneurysm surgery. The patient's age, the location and size of the unruptured aneurysms were significant factors in the clinical prognosis. Surgery for unruptured aneurysm caused 1.8% morbidity in patients between 28 and 55 years, but 18.0% morbidity in patients over 56 years of age. Surgery for internal carotid artery aneurysms resulted in 14.8% overall morbidity. Surgery for middle cerebral and anterior cerebral artery aneurysms caused below 5% morbidity. Postoperative morbidity in patients with aneurysms less than 5 mm in diameter was 1.3%, and with aneurysms measuring 10 mm or more, 20%. The optimum treatment for multiple aneurysms with SAH should be based on all factors of the patient's condition, including the unruptured aneurysms.


Hyperkalemic Emergency: When You Have Taken a Few Too Many KCl Tablets.
Hyperkalemia is a common clinical problem that varies significantly in severity and indications for treatment. Hyperkalemic emergency exists when there are clinical signs or symptoms, including cardiac conduction abnormalities. The combination of nebulized albuterol and insulin with glucose is most effective for managing clinically significant hyperkalemia. Prompt recognition of hyperkalemic emergency, immediate interventions to lower extracellular potassium, and involvement of multiple disciplines (including critical care and nephrology) are essential to addressing this life-threatening presentation.


Influence of Lithium Vacancy Defects on Tritium Diffusion in β-Li2TiO3.
Lithium metatitanate, Li2TiO3, is a leading candidate for application as a tritium breeding material in a future fusion reactor. Following transmutation of lithium, the tritium must escape the crystal in order to be extracted for use in the fusion plasma. The rate-limiting step to release tritium from the Li2TiO3 pebbles is diffusion through the crystal grains. In this work, the activation barriers for tritium diffusion have been calculated using density functional theory. The results show that tritium can diffuse as an interstitial with a barrier of 0.52 eV. However, when a tritium ion becomes bound to a lithium vacancy defect, the energy required to either detrap the tritium from the vacancy or for the cluster to diffuse increases to >1 eV. Overall, these results suggest that the introduction of lithium vacancies due to Li burn-up may lead to an increase in tritium retention in the pebbles.


Pinpoint modification strategy for stabilization of single guide RNA.
The clustered regularly interspaced short palindromic repeats-CRISPR associated protein9 (CRISPR-Cas9) system, which includes a single guide RNA (sgRNA) and a Cas9 protein, is an emerging and promising gene editing technology that produces specific changes, including insertions, deletions, or substitutions, in desired targets. This approach can be applied in novel therapeutic areas for multiple cancers and genetic diseases, including Parkinson's disease, sickle cell disease, and muscular dystrophy. However, there are many limitations to its potential application to therapeutics. CRISPR-Cas9 activity without side effects, delivery of CRISPR-Cas9 to the target cell within the desired tissue including liver, lungs, brain and muscle and the expression of Cas9 endonuclease in the target cell are key factors in achieving therapeutic efficacy. Generally, single-stranded RNA is immediately degraded in cells and biological fluids such as serum, as chemically unmodified single-stranded RNA shows extremely poor stability against nuclease degradation. To overcome this limitation, sgRNA is chemically modified to obtain a highly stable sgRNA for efficient gene editing in cells and in vivo. Here, we identified the cleavage site of sgRNA for pinpoint modification in biological tissues using mass spectrometry and improved stability of pinpoint modified sgRNA in these fluids. Although improved efficiency provided by modified sgRNA has already been reported, we identified the cleavage site by mass spectrometry and revealed that the stability increased with the pinpoint modification strategy for the first time in this study. In future studies, the efficiency of pinpoint modification strategy for the potential application of sgRNA by systematic routes, including intravenous and subcutaneous administration will be assessed.


Knockout of HDAC9 Gene Enhances Foot-and-Mouth Disease Virus Replication.
Foot-and-mouth disease virus (FMDV) is a highly contagious viral disease that mainly infects cloven-hoofed animals. Propagation of FMDV by cell culture is an important method to preserve viral biological and antigenic characteristics, which is crucial in FMD monitoring and vaccine production. However, only a few cell lines are sensitive to FMDV, and there is still a lot of room for improvement. Acetylation is an important post-translational modification, which is dynamically regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). However, the study of the relationship between FMDV and HDACs is still unclear. HDAC9 belongs to the class II of HDACs family; in this study, HDAC9 knockout (KO) BHK-21 cells were successfully established using CRISPR/cas9 technology. The results of karyotype analysis, growth curve analysis, and morphological observation showed that the HDAC9 knockout cell line was stable in growth and morphological characteristics. After infection with FMDV, the expression of viral RNA and protein, viral titers, and the copies of viral RNA in HDAC9-KO cells were significantly higher than those in NC cells. Meanwhile, RNA-seq technology was used to sequence HDAC9-KO cells and NC cells infected and uninfected with FMDV. It was found that the differentially expressed innate immune factors containing NFKBIA, SOD2, IL2RG, BCL2L1, CXCL1/2/3, and IL1RAP have significantly enriched in the Jak-STAT, NOD-like receptor, Toll-like receptor, NF-κB, and MAPK signaling pathway. RT-qPCR was performed to detect the expression level of differentially expressed genes and showed consistency with the RNA-seq data. These results preliminarily reveal the role of HDAC9 in host antiviral innate immune response, and the HDAC9-KO cell line could also serve as a useful tool for FMDV research.


The coalescent in a continuous, finite, linear population.
In this article we present a model for analyzing patterns of genetic diversity in a continuous, finite, linear habitat with restricted gene flow. The distribution of coalescent times and locations is derived for a pair of sequences sampled from arbitrary locations along the habitat. The results for mean time to coalescence are compared to simulated data. As expected, mean time to common ancestry increases with the distance separating the two sequences. Additionally, this mean time is greater near the center of the habitat than near the ends. In the distant past, lineages that have not undergone coalescence are more likely to have been at opposite ends of the population range, whereas coalescent events in the distant past are biased toward the center. All of these effects are more pronounced when gene flow is more limited. The pattern of pairwise nucleotide differences predicted by the model is compared to data collected from sardine populations. The sardine data are used to illustrate how demographic parameters can be estimated using the model.


Reversions of QuantiFERON-TB Gold Plus in tuberculosis contact investigation: A prospective multicentre cohort study.
Interferon-y Release Assays (IGRA) reversions have been reported in different clinical scenarios for the diagnosis of tuberculosis (TB) infection. This study aimed to determine the rate of QuantiFERON-TB Gold Plus (QFT-Plus) reversions during contact investigation as a potential strategy to reduce the number of preventive treatments. Prospective, multicentre cohort study of immunocompetent adult contacts of patients with pulmonary TB tested with QFT-Plus. Contacts with an initial positive QFT-Plus (QFT-i) underwent a second test within 4 weeks (QFT-1), and if negative, underwent a repeat test 4 weeks later (QFT-2). Based on the QFT-2 result, we classified cases as sustained reversion if they remained negative and as temporary reversion if they turned positive. We included 415 contacts, of whom 96 (23.1%) had an initial positive test (QFT-i). Following this, 10 had negative QFT-1 results and 4 (4.2%) of these persisted with a negative result in the QFT-2 (sustained reversions). All four sustained reversions occurred in contacts with IFN-γ concentrations between ≥0.35 and ≤0.99 IU•mL-1 in one or both QFT-i tubes. In this study, TB contact investigations rarely reveal QFT-Plus reversion. These results do not support retesting cases with an initial positive result to reduce the number of preventive treatments.


Tacrines as Therapeutic Agents for Alzheimer's Disease. IV. The Tacripyrines and Related Annulated Tacrines.
Notwithstanding the clinical use of tacrine was hampered by severe hepatotoxicity, tacrine still remains a reference scaffold in the search for new efficient drugs for Alzheimer's disease therapy. In this account we summarize the efforts toward the development and characterization of non-hepatotoxic tacripyrines and related tacrine analogues resulting from the substitution of the benzene ring by a 1,4-dihydropyridine, a 1,2,3,4-tetrahydropyrimidine or a pyridone nucleus. These efforts have successfully led to the identification of a number of promising hits endowed with interesting multifunctional profiles. These include the 4'-metoxytacripyrine (S)-ITH122, able to target cholinesterases (ChEs), beta-amyloid (Aβ) and Ca2+ channels, the racemic 3'-methoxytacripyrimidine EB65F2, the first fully balanced micromolar inhibitor of ChEs and Ca2+ channels, and tacripyrine (-)-SCR1693 a GSK-3β (enzyme involved in tau phosphorylation) inhibitor able to also lower Aβ production in N2a cells.


Elicitor-Induced l-Tyrosine Decarboxylase from Plant Cell Suspension Cultures : II. Partial Characterization.
Properties of purified l-tyrosine decarboxylase (EC 18.104.22.168) from elicitor-induced cell suspension cultures of Eschscholtzia californica Cham. and Thalictrum rugosum Ait. are described. l-Tyrosine decarboxylase is a dimeric enzyme with a molecular weight of 112,600 +/- 600 daltons. The isoelectric point was estimated to be at pH 5.2 and pH 5.4 for the enzyme from E. californica and T. rugosum, respectively. The purified enzymes were stabilized in the presence of pyridoxal-5-phosphate. Optimum pH for the enzyme from both plants was found to be 8.4. Enzyme activity was dependent on exogeneously supplied pyridoxal-5-phosphate. The enzyme decarboxylated l-tyrosine and l-beta-3,4-dihydroxyphenylalanine but was inactive toward l-phenylalanine and l-tryptophan. Apparent K(m) values of Eschscholtzia- and Thalictrum-decarboxylase for l-tyrosine were 0.25 +/- 0.03 and 0.27 +/- 0.04 millimolar, respectively. Similar affinities were found for l-3,4-dihydroxyphenylalanine. Eschscholtzial-tyrosine decarboxylase was strongly inhibited by the phenylalanine analogue l-alpha-aminooxy-beta-phenylpropionate and largely unaffected by d,l-alpha-monofluoromethyl-3,4-dihydroxyphenylalanine and alpha-difluoromethyltyrosine.


Community structure and its dynamics of pest, predatory and neutral insects in a jujube ecosystem.
An investigation on the insects in the jujube ecosystem in Taigu District of Shanxi Province, Northern China showed that more species and individual numbers of pest, predatory and neutral insects were found on the tree than on the ground. The ratio of the species and individual numbers of predatory and neutral insects to those of pest insects fluctuated from year to year. Homoptera, Coleoptera and Lepidoptera were the dominant groups of pest insects, while those of predatory insects were Coleopteran, Hemiptera, Diptera and Hymenoptera. The vertical distribution of the community structure of the same or different subcommunity was different in different seasons, as was the case of the same or different subcommunity in the same season. The diversity indexes of pest, predatory and neutral insects fluctuated with seasons, and the populations of predatory and neutral insects had a significant correlation (r = 0.9833, P <0.05) with the fluctuation of pest insects. There was also a significant correlation between the pest, predatory and neutral insects in different stratums of tree canopy, especially in the middle stratum of tree canopy (r = 0.9887, P <0.01).


GC determination of acetone, acetaldehyde, ethanol, and methanol in biological matrices and cell culture.
A gas chromatography with flame ionization detection method (GC-FID) with direct injection, using a capillary column, was validated to determine ethanol, acetaldehyde, methanol, and acetone in different human matrices, such as whole blood, vitreous humour, and urine, with clinical and forensic interest. This method was also employed to quantify these compounds in cell culture medium, thus being useful in basic research. A good peak resolution was achieved, with linear correlation between concentration and peak areas for all the compounds in all the matrices. The inter- and intra-day precisions of the method were always under 15% and 10%, respectively. The accuracy of the method, calculated as the percentage of the target concentration, was within the acceptable limits. The obtained limits of detection were below 0.85 mg/L for acetaldehyde and below 0.75 mg/L for the other considered compounds. The small injection volume and the high split ratios applied, allied to the high performance of the GC column, resulted in very good peak resolution and high sensitivities. This method is easy to perform, making it suitable for the routine of clinical biochemistry and forensic laboratories.


Integrated chemical--physical processes kinetic modelling of multiple mineral precipitation problems.
A three-phase (aqueous/gas/solid) mixed weak acid/base chemistry kinetic model is applied to evaluate the processes operative in the aeration treatment of swine wastewater (SWW) and sewage sludge anaerobic digester liquor (ADL). In both applications, with a single set of constants (except for the aeration rates which are situation specific), close correlation could be obtained between predicted and measured data, except for the Ca concentration-time profile in the SWW. For this wastewater, the model application highlighted an inconsistency in the measured Ca data which could not be resolved; this illustrates the value of a mass balance-based model in evaluating experimental data. From the model applications, in both wastewaters the dominant minerals precipitating are struvite and amorphous calcium phosphate (ACP), which precipitate simultaneously competing for the same species, P. The absolute and relative masses of the two precipitants are governed by the initial solution state (e.g. total inorganic C (C(T)), Mg, Ca and P concentrations), their relative precipitation rates (struvite > ACP) and the system conditions imposed (aeration rates and time applied). It is concluded that the kinetic model is able to predict correctly the time-dependent weak acid/base chemistry reactions and final equilibrium state for situations where multiple minerals competing for the same species precipitate simultaneously or sequentially, a deficiency in traditional equilibrium chemistry-based algebraic models.


Localization of sequences within the latency-related gene of bovine herpesvirus 1 that inhibit mammalian cell growth.
The latency-related (LR) RNA of bovine herpes virus 1 (BHV-1) is abundantly expressed in sensory neurons of latently infected cattle. Wild-type expression of LR gene products is required for the latency-reactivation cycle. LR gene products inhibit apoptosis, bICP0 expression, and mammalian cell growth. The cell growth inhibitory function of the LR gene maps to a 463-bp XbaI-PstI fragment. Introduction of stop codons into the XbaI-PstI fragment had no effect on inhibiting growth. Expression of a LR strand-specific transcript correlates with growth inhibition in bovine fibroblasts and mouse neuroblastoma cells.


A New Perspective on Fault Geometry and Slip Distribution of the 2009 Dachaidan Mw 6.3 Earthquake from InSAR Observations.
On 28 August 2009, the northern margin of the Qaidam basin in the Tibet Plateau was ruptured by an Mw 6.3 earthquake. This study utilizes the Envisat ASAR images from descending Track 319 and ascending Track 455 for capturing the coseismic deformation resulting from this event, indicating that the earthquake fault rupture does not reach to the earth's surface. We then propose a four-segmented fault model to investigate the coseismic deformation by determining the fault parameters, followed by inverting slip distribution. The preferred fault model shows that the rupture depths for all four fault planes mainly range from 2.0 km to 7.5 km, comparatively shallower than previous results up to ~13 km, and that the slip distribution on the fault plane is complex, exhibiting three slip peaks with a maximum of 2.44 m at a depth between 4.1 km and 4.9 km. The inverted geodetic moment is 3.85 × 10(18) Nm (Mw 6.36). The 2009 event may rupture from the northwest to the southeast unilaterally, reaching the maximum at the central segment.


Magnetic MAX phases from theory and experiments; a review.
This review presents MAX phases (M is a transition metal, A an A-group element, X is C or N), known for their unique combination of ceramic/metallic properties, as a recently uncovered family of novel magnetic nanolaminates. The first created magnetic MAX phases were predicted through evaluation of phase stability using density functional theory, and subsequently synthesized as heteroepitaxial thin films. All magnetic MAX phases reported to date, in bulk or thin film form, are based on Cr and/or Mn, and they include (Cr,Mn)2AlC, (Cr,Mn)2GeC, (Cr,Mn)2GaC, (Mo,Mn)2GaC, (V,Mn)3GaC2, Cr2AlC, Cr2GeC and Mn2GaC. A variety of magnetic properties have been found, such as ferromagnetic response well above room temperature and structural changes linked to magnetic anisotropy. In this paper, theoretical as well as experimental work performed on these materials to date is critically reviewed, in terms of methods used, results acquired, and conclusions drawn. Open questions concerning magnetic characteristics are discussed, and an outlook focused on new materials, superstructures, property tailoring and further synthesis and characterization is presented.


[St. John's wort as antidepressive therapy].
St. John's Wort (Hypericum perforatum) has been used to treat a variety of complaints since ancient times. Recent studies have shown that it is clinically effective for the treatment of the symptoms of depression. It has proved superior to placebo, equally as effective as standard medication and has a clear advantage over the latter in terms of side-effects. It follows that, on the basis of our present knowledge, St. John's Wort can be recommended for use as an anti-depressant.


Natural course of chronic hepatitis C.
We studied 333 chronic hepatitis C patients to evaluate the natural course of this disease. Among 57 patients undergoing serial biopsies, 20 had chronic persistent hepatitis (CPH) at the first biopsy, and 10 of them progressed to chronic active hepatitis (CAH) or liver cirrhosis (LC) after 11 yr. Sixteen patients had CAH 2A, and this progressed to CAH 2B or LC in 10 cases over 9 yr. Among the 21 patients with CAH 2B, progression to LC was noted in 15 after 7 yr. Among the 100 patients observed for over 5 yr, the normalization of liver function for at least 3 yr was seen in only four patients. In two of these four patients, serum HCV-RNA was tested serially. Despite the sustained normalization of alanine aminotransferase levels, HCV-RNA continued to be detectable in one patient. We conclude that many patients with chronic hepatitis C eventually show progression of their disease after a long and symptomless course.


Early and long-term results of hypothermic circulatory arrest in aortic surgery: a 20-year single-centre experience.
The aim of this study was to document the postoperative outcomes of patients who underwent hypothermic circulatory arrest (HCA), the evolution of HCA management over time and to identify the risks factor for early mortality and postoperative stroke. Four hundred and twenty-four patients who underwent aortic surgery with HCA at our institution between January 1995 and June 2016 were consecutively included. The main indications were degenerative aneurysm (254; 59.9%) and acute type A aortic dissection (146; 34.4%). Interventions were performed under deep (18.4 ± 0.9°C; n = 350; 82.5%) or moderate (23.9 ± 1.9°C; n = 74; 17.5%) hypothermia. Antegrade cerebral perfusion (ACP) was employed in 86 (20.3%) cases. The use of moderate hypothermia significantly increased from 2011, to become the preferred strategy in 2016. The in-hospital mortality was 12.5% and the postoperative stroke rate was 7.1%. Kaplan--Meier 5-year survival was 65.7%. Nonelective timing [odds ratio (OR) 4.05; P < 0.001], stroke (OR 3.77' P = 0.032), renal failure (OR 2.49; P = 0.023), redo surgery (2.42; P = 0.049) and CPB time (OR 1.05; P = 0.03) were independent risk factors for in-hospital mortality in multivariate analysis. Femoral cannulation was the only independent risk factor for stroke (OR 3.97; P = 0.002). The level of hypothermia and the use of ACP were not associated with either in-hospital mortality or postoperative stroke. HCA might be widely considered to achieve a radical treatment of the aortic disease, provided that hypothermia is maintained below the 24°C safety threshold and ACP is used for HCA exceeding 30 min, to ensure optimal brain, spinal cord and visceral organs protection.


Mucocele of the appendix presenting as a sigmoid mass.
Mural tumours of the colon are rare and may be difficult to distinguish from extrinsic lesions. We report a case of an apparent intramural sigmoid tumour due to a mucocele of the appendix and discuss the radiological diagnosis of mural tumours of the large bowel.


Secondary amyloidosis associated with giant cell arteritis/polymyalgia rheumatica.
Although giant cell arteritis (GCA) is characterized by chronic inflammation, secondary (AA) amyloidosis appears to be an exceptionally rare complication of this disorder. We describe an 84-year-old man with biopsy proven GCA and polymyalgia rheumatica (PMR) who was found at autopsy to have AA amyloid deposition in numerous organs, 9 years after his diagnosis of GCA. Persistent musculoskeletal symptoms, attributed to refractory PMR during the patient's life, were likely due to AA amyloidosis. This unrecognized complication of GCA/PMR confounded his therapy, leading to excessive treatment with corticosteroids and methotrexate. This case shows that the occurrence of AA amyloidosis should be considered in patients with "refractory PMR" developing after a period of treatment, and that autopsies play a vital role in enigmatic cases.


Expression of HOXD9 in fibroblast-like synoviocytes from rheumatoid arthritis patients.
The proteins of homeobox (HOX) genes are transcription regulators involved in cell type-specific differentiation and patterning of the body plan in vertebrates. Particularly, the HOXD family is involved in limb formation in mice and chicks. There is also some evidence that the HOXD9 gene, a member of the HOXD family, is involved in the pathology of rheumatoid arthritis (RA). The purpose of the present study was to determine if the HOXD9 protein was expressed in RA synovium and then to characterize the HOXD9-expressing cell. Western blotting and immunohistochemical analysis showed that the HOXD9 protein was expressed in the synovium from patients with RA, but not in those from patients with osteoarthritis or healthy individuals. The HOXD9-positive cells were localized in both the lining and sublining areas of the synovium. Furthermore, fluorescent double-staining showed that the HOXD9 protein was expressed in fibroblast-like synoviocytes (FLS). These findings not only indicate that the HOXD9 gene is exclusively expressed in the RA synovium but also suggest that the HOXD9 gene contributes to the pathology of rheumatoid arthritis through the FLS.


Surgery and Resource Utilization Trends for Pediatric Intussusception From 2005 Through 2014.
Air or barium enema reduction is becoming increasingly common and safer for pediatric intussusception. However, little is known about trends of pediatric intussusception requiring surgical intervention in the United States. Methods: National Inpatient Sample database was analyzed from 2005-2014 to identify pediatric (≤18 years) intussusceptions along with procedures such as enema and/or surgical intervention. Trends in the rates of surgical intervention were examined according to encounter-level (age, gender, race, comorbidities) and hospital-level (hospital census region, teaching status) characteristics. Outcomes of pediatric intussusception requiring surgical intervention were analyzed in terms of length of stay and cost of hospitalization. Factors associated with surgical intervention were also analyzed. P value of < 0.05 was considered significant. Results: Out of 21,835 intussusception hospitalizations requiring enema or surgical intervention, 14,415 (66%) had surgical intervention; 90% of which (12,978) had no preceding enema. Surgical intervention rates among intussusception hospitalizations varied by age (highest < 1 year), gender (male > females) and race (Hispanics > Whites and Blacks). During the study period, overall surgical intervention rate remained stable (2.2 to 1.7, P=0.07) although it declined in those under 1 year of age. Children with severe disease, gastrointestinal comorbidities over the age of 4 years had increased odds of surgical intervention, whereas hospitalization in large and urban teaching hospitals had decreased odds of surgical intervention. Length of stay and hospital cost remained stable from 2005-2014. The rates of surgical intervention and resource utilization for pediatric intussusception remained stable from 2005-2014, however they declined significantly in infants. The proportion of intussusception hospitalization requiring surgery remains high and further studies are needed to explore the possible factors.


Stem cells of the respiratory tract.
Childhood respiratory diseases are accompanied by various forms of epithelial repair and remodelling. Respiratory stem cells are likely to be of great importance in these processes but their identification remains uncertain. By contrast, an enormous effort has been made to identify specific markers of stem cells of other organs; this has given rise to the new concept of plasticity. This proposes that stem cell differentiation is influenced by the niches in which the cells reside rather than their site of origin. Many studies provide evidence in support of this concept, including one demonstrating that respiratory epithelium can arise from bone marrow stem cells. Recent findings from human and animal studies suggest that Clara cell-specific protein-expressing cells with pre-Clara cell phenotypes may be candidate stem cells for the entire respiratory tract.


Identification of Flap Endonuclease 1 With Diagnostic and Prognostic Value in Breast Cancer.
This study aims to identify the potential value of flap endonuclease 1 (FEN1) as a diagnostic and prognostic marker for breast cancer (BC). ELISA was used to measure serum FEN1 levels and ECLIA for CA153 and CEA levels. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value. Oncomine and UALCAN databases were used to analyze the differences in FEN1 mRNA and protein expressions. Kaplan-Meier Plotter database was then used to assess the prognostic value. Bioinformatics analysis showed that the FEN1 mRNA and protein levels were significantly higher in BC tissues than in normal tissues. FEN1 was detected in culture medium of BC cell lines and serum FEN1 concentrations were significantly increased in BC patients than in cancer-free individuals. Besides, FEN1 exhibited higher diagnostic accuracy (AUC values>0.800) than CA153 and CEA for distinguishing BC patients, especially early BC, from the healthy and benign groups, or individually. Additionally, serum FEN1 levels were significantly associated with the stage (P=0.001) and lymph invasion (P=0.016), and serum FEN1 levels were increased with the development of BC. Furthermore, serum FEN1 levels were significantly decreased in post-operative patients than in pre-operative patients (P=0.016). Based on the Kaplan-Meier Plotter database, the survival analysis indicated that FEN1 overexpression was associated with poor prognoses for overall survival (OS), relapse-free survival (RFS), and distant metastasis-free survival (DMFS) in BC patients. FEN1 might be a novel diagnostic and prognostic marker for BC.


Effect of enalapril on urinary glycosaminoglycan, heparan sulphate and microalbuminuria in type II diabetic patients.
Recent studies in diabetic humans have shown that angiotensin converting enzyme (ACE) inhibitors may provide additional renal benefit above and beyond conventional antihypertensive agents. We investigated the effect of enalapril on urinary glycosaminoglycans (GAG), heparan sulphate (HS) and microalbuminuria (MAU) in diabetic patients. Urinary GAG and HS levels were determined in controls (n=16, 41.3 +/- 12.9 years old) and in type II diabetics (n=18, 53 +/- 9.6 years old) who were not using ACE inhibitors. Four of these patients had also hypertension. The duration of diabetes was 5.5 +/- 3 years (mean +/- SD). Microalbuminuria was detected in seven patients. The subjects were treated with enalapril (5-10 mg day-1) for 6 weeks. The median values of GAG (n=18, 2.8 mg uronic acid g-1 crea. day-1) and HS (n=18, 1.36 mg glycosamine g-1 crea. day-1) in the pre-treatment group were significantly (p < 0.01) higher than the control group (n=16, 1.98 mg uronic acid g-1crea. day-1 and 0.87 mg glycosamine g-1crea. day-1, respectively. Before treatment, GAG and HS levels seemed to be not different between microalbuminuric and normoalbuminuric as well as hypertensive and normotensive patients. Following enalapril treatment, the median values of GAG (n=18, 1.35 mg uronic acid g-1 crea. day-1) and HS (n= 18, 0.99 mg glycosamine g-1 crea. day-1) tended to decrease to the levels which were not significantly different from the control group. Following treatment, significant reduction in urinary albumin excretion (from 15.45 to 11.1 mg day-1) (p < 0.0005) was also observed. When considering the pre- and post-treatment concentrations, there were positive correlations between urinary GAG and HS values (p < 0.05, r=0.6541 and p < 0.01, r=0.5984). These results suggest that measurement of urinary heparan sulphate may be another useful predictor of clinical diabetic nephropathy; and enalapril causes marked reduction in HS and GAG values in all patients independently by the presence of hypertension.


Multi-generational effects of polybrominated diphenylethers exposure: embryonic exposure of male American kestrels (Falco sparverius) to DE-71 alters reproductive success and behaviors.
Polybrominated diphenylethers (PBDEs) are additive flame-retardants that are environmentally persistent and bioaccumulative compounds of particular concern to species at high trophic levels, including predatory birds. The developmental effects of in ovo exposure to male birds at environmentally relevant levels of the PBDE technical mixture, DE-71, on reproductive success and behaviors using captive American kestrels (Falco sparverius) were determined. Males were exposed in ovo by direct maternal transfer to DE-71 and unintentionally to low concentrations of hexabromocyclododecane (HBCD) at three mean +/- standard error DE-71 concentrations of 288.60 +/- 33.35 ng/g wet weight (low-exposure), 1130.59 +/- 95.34 ng/g wet weight (high-exposure), or background levels of 3.01 +/- 0.46 ng/g wet weight (control). One year following exposure, males were paired with unexposed females. Reproductive success was lower in the high exposure pairs: 43% failed to lay eggs while all other pairs laid complete clutches; they also laid smaller clutches and produced smaller eggs with reduced fertility, parameters that were negatively correlated with paternal in ovo concentrations of all PBDEs, as well as individual congeners and HBCD. Throughout courtship, there were fewer copulations by all in ovo exposed males, fewer mate-calls made by high-exposure males, and decreasing trends in pair-bonding and nest-box behaviors across treatments that continued during brood rearing. The reductions in clutch size and fertility were associated with the reduced frequencies of male courtship behaviors, and were associated with increasing concentrations of the PBDE congeners BDE-47, -99, -100, -53, -138, and HBCD. The results of the present study confirm effects noted in the F(0) generation and demonstrate that exposure to DE-71 affects multiple generations of this predatory avian species at environmentally relevant levels of exposure.


Modulation of Ia-like antigen expression and antigen-presenting activity of human monocytes by endotoxin and zymosan A.
The environmental agents E. coli endotoxin and zymosan A modulated antigen-specific T cell proliferation in vitro, assessed by 3H-TdR uptake. In the continual presence of these agents, human mononuclear leukocyte responses to the antigens tuberculin PPD, Candida albicans, and mumps were significantly reduced. Treatment of adherent cell-depleted T cells with the agents did not affect their subsequent reactivity to soluble antigens in the presence of normal M phi. However, cultures consisting of pretreated M phi, normal T cells, and soluble antigen gave responses that were only 7 to 38% of control values, indicating that the function of the antigen-presenting cell, not the T cell, was inhibited. This effect was observed only when treatment with endotoxin or zymosan A preceded antigen stimulation by at least 24 hr, suggesting that a gradual inhibition of antigen presentation had occurred. When various ratios of normal antigen-pulsed and agent-treated M phi were cultured with normal T cells, antigen-specific responses were not significantly different from control cultures; this indicated that M phi-mediated suppression was not involved. It did not appear that the inhibition was due to enhanced antigen degradation by the treated M phi because responses were not reconstituted in the presence of excess antigen. After endotoxin or zymosan A treatment of the M phi population the proportion of Ia+ cells was reduced significantly, and surface expression of Ia antigen correlated with the ability of the cell population to present antigens to immune T cells. This suggested that endotoxin and zymosan A induce a loss of surface Ia antigen on antigen-presenting cells that inhibits immune T cell activation.


Lumbar intravertebral disc herniation secondary to idiopathic calcific discitis.
Calcific discitis is a well recognized entity in the paediatric population but more recently has been increasingly reported in adults. It typically involves the lower thoracic vertebrae and is of unknown aetiology. Herniation of the calcified fragment is rare but typically occurs out through the annulus fibrosus into the canal space. Herein we describe the first reported case of calcific discitis involving the lumbar vertebrae with subsequent herniation of the calcified disc into and through the anterior aspect of the L5 vertebra. The patient first presented with a history of right back pain and leg sciatica. Radiographic imaging demonstrated calcification within the L4/5 interspace, which was managed with simple analgesia. She subsequently re-presented 24-months later with worsening sciatica, right leg weakness and faecal incontinence. No evidence of cord or root compression was noted on MRI. However, an abnormality was noted at the anterior body of L5 with evidence of superior endplate depression and marrow signal change. Subsequent radionucleide bone studies confirmed a solitary focus of increased linear activity extending across the width of the L4-L5 interspace. Her symptoms were managed medically. Serial radiographic imaging demonstrated regression of the disc space calcification and healing of the L5 fracture. Despite its sinister presentation this condition was self-limiting. We describe the radiographic evolution of this pathology and postulate a putative hypothesis through which it may have arisen.


Prevalence of drug resistance mutations among ART-naive and -experienced HIV-infected patients in Sierra Leone.
The aim of this study was to assess the prevalence of HIV drug resistance (HIVDR) in HIV-infected ART-naive and -experienced patients in Sierra Leone. We conducted a cross-sectional study of HIV-positive adults aged ≥18 years at Connaught Hospital in Freetown, Sierra Leone in November 2017. Sequencing was performed in the reverse transcriptase, protease and integrase regions, and interpreted using the Stanford HIVDR database and WHO 2009 mutation list. Two hundred and fifteen HIV-infected patients were included (64 ART naive and 151 ART experienced). The majority (66%) were female, the median age was 36 years and the median ART exposure was 48 months. The majority (83%) were infected with HIV-1 subtype CRF02_AG. In the ART-naive group, the pretreatment drug resistance (PDR) prevalence was 36.7% (14.2% to NRTIs and 22.4% to NNRTIs). The most prevalent PDR mutations were K103N (14.3%), M184V (8.2%) and Y181C (4.1%). In the ART-experienced group, 64.4% harboured resistance-associated mutations (RAMs) and the overall prevalence of RAMs to NRTIs and NNRTIs was 85.2% (52/61) and 96.7% (59/61), respectively. The most prevalent RAMs were K103N (40.7%), M184V (28.8%), D67N (15.3%) and T215I/F/Y (15.3%). Based on the genotypic susceptibility score estimates, 22.4% of ART-naive patients and 56% of ART-experienced patients were not susceptible to first-line ART used in Sierra Leone. A high prevalence of circulating NRTI- and NNRTI-resistant variants was observed in ART-naive and -experienced HIV-1-infected patients in Sierra Leone. This necessitates the implementation of HIVDR surveillance programmes to inform national ART guidelines for the treatment and monitoring of HIV-infected patients in Sierra Leone.


The involvement of gRNA-binding protein gBP21 in RNA editing-an in vitro and in vivo analysis.
RNA editing in the parasitic organism Trypanosoma brucei is characterised by the insertion and deletion of uridylate residues into otherwise incomplete primary transcripts. The processing reaction is a required pathway for the expression of most mitochondrial genes and proceeds by a cascade of enzyme-catalysed steps. RNA editing involves one or more macromolecular ribonucleoprotein complexes which are likely to interact with additional components as the reaction proceeds. Here we examined the involvement of the gRNA-binding polypeptide gBP21, a protein which has been demonstrated to be associated with active RNA editing complexes. We show that in vitro RNA editing can be suppressed by the addition of a gBP21-specific antibody or by immunodepletion of the protein. By creating a gBP21 knockout mutant we analysed the requirement for the protein in vivo. gBP21(-) trypanosomes are viable as bloodstream stage cells and contain edited mRNAs. However, the knockout mutant is not capable of differentiating from the bloodstream to the insect life cycle stage in vitro. Moreover, mutant cells are characterised by a low mitochondrial transcript abundance. Together, these data establish that gBP21 contributes a non-essential function to the RNA editing reaction and further suggest that the protein is involved in additional mitochondrial processes which impact a larger pool of mitochondrial transcripts.


Analysis of expansion of myeloid progenitors in mice to identify leukemic susceptibility genes.
The myeloid progenitor cell compartment (MPC) exhibits pronounced expansion in human myeloid leukemias. It is becoming more apparent that progression of myelodysplastic syndromes and myeloproliferative diseases to acute myelogenous leukemia is the result of defects in progenitor cell maturation. The MPC of bone marrow was analyzed in mice using a cell culture assay for measuring the relative frequency of proliferative myeloid progenitors. Response to the cytokines SCF, IL-3, and GM-CSF was determined by this assay for the leukemic mouse strain BXH-2 and ten other inbred mouse strains. Significant differences were found to exist among ten inbred mouse strains in the nature of their MPC in bone marrow, indicating the presence of genetic polymorphisms responsible for the divergence. The SWR/J and FVB/J strains show consistently low frequencies of myeloid progenitors, while the DBA/2J and SJL/J inbred strains show consistently high frequencies of myeloid progenitors within the bone marrow compartment. In addition, in silico linkage disequilibrium analysis was conducted to identify possible chromosomal regions responsible for the phenotypic variation. Given the importance of this cell compartment in leukemia progression and the soon to be released genomic sequence of 15 mouse strains, these differences may provide a valuable tool for research into leukemia.


Asymmetrical ocular pursuit with posterior fossa tumors.
We report two patients with posterior fossa neoplasms who demonstrated asymmetrically impaired horizontal ocular pursuit documented with electrooculography. One patient had impaired pursuit contralateral to a pontomedullary lesion, whereas the second patient had impaired pursuit ipsilateral to a pontocerebellar lesion. These patients demonstrate that posterior fossa lesions may impair ocular pursuit either contralaterally or ipsilaterally unlike cerebral hemispheric lesions, which impair ocular pursuit ipsilaterally or bilaterally.


Photothermal Therapy as Adjuvant to Surgery in an Orthotopic Mouse Model of Human Fibrosarcoma.
Surgery is still the first-line treatment for multiple solid cancers. However, recurrence is a common issue, especially when dealing with aggressive tumors or tumors that are difficult to completely remove due to their location. Getting clear surgical margins can be challenging, but treatment strategies combining surgery with other anti-cancer therapies can potentially improve the outcome. Photothermal therapy (PTT) is a technique that relies on photoabsorbing agents, such as gold nanoparticles, to transform light into local hyperthermia. This technique can be used to ablate tumor tissue where the photoabsorbing agent accumulates, sparing healthy surrounding tissue. In this study, we examined the potential of gold nanoparticle-based PTT as an adjuvant treatment to surgery in a mouse model of human fibrosarcoma. For this we performed subtotal tumor resection to mimic a clinical situation where total tumor removal is not achieved, and subsequent PTT was applied on the surgical field. Our results showed that animals undergoing adjuvant PTT after surgery presented sustained delayed tumor growth and improved survival when compared to animals that only underwent surgery. We believe that these findings show the potential of PTT as an adjuvant method to traditional tumor surgery and could pave way to more personalized treatment options.


Mixing at the external boundary of a submerged turbulent jet.
We study experimentally and theoretically mixing at the external boundary of a submerged turbulent jet. In the experimental study we use particle image velocimetry and an image processing technique based on the analysis of the intensity of the Mie scattering to determine the spatial distribution of tracer particles. An air jet is seeded with the incense smoke particles, which are characterized by a large Schmidt number and a small Stokes number. We determine the spatial distributions of the jet fluid characterized by a high concentration of the particles and of the ambient fluid characterized by a low concentration of the tracer particles. In the data analysis we use two approaches, whereby one approach is based on the measured phase function for the study of the mixed state of two fluids. The other approach is based on the analysis of the two-point second-order correlation function of the particle number density fluctuations generated by tangling of the gradient of the mean particle number density by the turbulent velocity field. This gradient is formed at the external boundary of a submerged turbulent jet. We demonstrate that probability density function of the phase function of a jet fluid penetrating into an external flow and the two-point second-order correlation function of the particle number density do not have universal scaling and cannot be described by a power-law function. The theoretical predictions made in this study are in qualitative agreement with the obtained experimental results.


[Involvement of miR-200a in chemosensitivity regulation of ovarian cancer].
To explore the role of miR-200a in chemosensitivity regulation of ovarian cancer. Firstly miR-200a was up-regulated in ovarian cancer cell lines (SKOV-3 and ES-2) by lentiviral vector. Then the effects of miR-200a on cytotoxicity of paclitaxel and cisplatin were investigated by methyl thiazolyl tetrazolium (MTT). Furthermore miR-200a regulation of chemoresistance associated with ATP-binding cassette (ABC) family genes expression was detected by quantitative real-time polymerase chain reaction (PCR) and Western blot. Finally the interaction between miR-200a and ABCG2 mRNA 3'untranslated region (3'-UTR) was verified by dual-luciferase reporter assay. An over-expression of miR-200a were successfully achieved in SKOV-3 and ES-2 cells. MiR-200a enhanced the chemosensitivity of SKOV-3 and ES-2 to paclitaxel, but not to cisplatin. Chemoresistance associated ABC family (ABCB3, ABCC1, ABCC2, ABCC3, ABCG2) were down-regulated by miR-200a at several levels. However, the direct interaction between miR-200a and the 3'-UTR of ABCG2 mRNA was not found. An over-expression of miR-200a may increase chemosensitivity to paclitaxel in ovarian cancer cells through negatively regulated chemoresistance associated ABC family. However, no direct action on 3'-UTR of ABCG2 was not found after its down-regulation by miR-200a.


A Polarization-Switching, Charge-Trapping, Modulated Arithmetic Logic Unit for In-Memory Computing Based on Ferroelectric Fin Field-Effect Transistors.
Nonvolatile logic devices are crucial for the development of logic-in-memory (LiM) technology to build the next-generation non-von Neumann computing architecture. Ferroelectric field-effect transistors (Fe FET) are one of the most promising candidates for LiMs because of high compatibility with mainstream silicon-based complementary metal-oxide semiconductor processes, nonvolatile memory, and low power consumption. However, because of the unipolar characteristics of a Fe FET, a nonlinear XOR or XNOR logic gate function is difficult to realize with a single device. In addition, because single Fe polarization switch modulation is available in the devices, a reconfigurable logic gate usually needs multiple devices to construct and realize fewer logic functions. Here, we introduced polarization-switching (PS) and charge-trapping (CT) effects in a single Fe FET and fabricated a multi-field-effect transistor with bipolar-like characteristics based on advanced 10 nm node fin field-effect transistors (PS-CT FinFET) with 9 nm thick Hf0.5Zr0.5O2 films. The special hybrid effects of charge-trapping and polarization-switching enabled eight Boolean logic functions with a single PS-CT FinFET and 16 Boolean logic functions with two complementary PS-CT FinFETs were obtained with three operations. Furthermore, reconfigurable full 1 bit adder and subtractor functions were demonstrated by connecting only two n-type and two p-type PS-CT FinFET devices, indicating that the technology was promising for LiM applications.


Complete nucleotide sequence of the gene for human interleukin 1 alpha.
The chromosomal gene for human interleukin 1 alpha (IL-1 alpha) was isolated from a human genomic DNA library by using as a probe cloned human IL-1 alpha cDNA. Complete nucleotide sequence of about 12 kilobase pairs (kbp) long was determined and the structure and organization of this gene were elucidated. This gene contains seven exons and six introns. The first exon encodes the 5'-untranslated region. Most of the prepeptide portion of the precursor polypeptide is encoded by the next three exons, and the mature form of IL-1 alpha is encoded by the remaining three exons. The last exon also encodes the intronless 3'-untranslated region. The fourth intron as well as both 5'- and 3'-flanking regions contains the sequence of an Alu family member. In the middle part of the last intron, a 46-bp sequence with a unique structure is repeated five times in a head to tail manner. These repeats are flanked by the regions containing alternative purine and pyrimidine tracts. In the 5'-flanking region, immediately upstream of the putative TATA box, the 16-bp sequence highly homologous to the binding site of the adenovirus 2 major late promoter transcription factor is identified. The nucleotide sequence reported here showed only one nucleotide substitution in the 3'-untranslated exon in comparison with the nucleotide sequence of the cDNA from HL-60, a promyelocytic leukemia cell line, previously cloned and sequenced in our laboratories.


Stable C and N isotope natural abundances of intraradical hyphae of arbuscular mycorrhizal fungi.
Data for stable C and N isotope natural abundances of arbuscular mycorrhizal (AM) fungi are currently sparse, as fungal material is difficult to access for analysis. So far, isotope analyses have been limited to lipid compounds associated with fungal membranes or storage structures (biomarkers), fungal spores and soil hyphae. However, it remains unclear whether any of these components are an ideal substitute for intraradical AM hyphae as the functional nutrient trading organ. Thus, we isolated intraradical hyphae of the AM fungus Rhizophagus irregularis from roots of the grass Festuca ovina and the legume Medicago sativa via an enzymatic and a mechanical approach. In addition, extraradical hyphae were isolated from a sand-soil mix associated with each plant. All three approaches revealed comparable isotope signatures of R. irregularis hyphae. The hyphae were 13C- and 15N-enriched relative to leaves and roots irrespective of the plant partner, while they were enriched only in 15N compared with soil. The 13C enrichment of AM hyphae implies a plant carbohydrate source, whereby the enrichment was likely reduced by an additional plant lipid source. The 15N enrichment indicates the potential of AM fungi to gain nitrogen from an organic source. Our isotope signatures of the investigated AM fungus support recent findings for mycoheterotrophic plants which are suggested to mirror the associated AM fungi isotope composition. Stable isotope natural abundances of intraradical AM hyphae as the functional trading organ for bi-directional carbon-for-mineral nutrient exchanges complement data on spores and membrane biomarkers.


Somatostatin receptor scintigraphy in gastrinomas.
Recent studies report that the radiolabelled synthetic somatostatin analogue, [111In-DTPA-DPhe1]octreotide, is useful for imaging carcinoid tumours and pancreatic endocrine tumours. At present, it is unclear whether this method is superior to conventional imaging studies (computed tomography, magnetic resonance imaging, ultrasound, angiography) and what its role should be, if any, in the management of these patients. The aim of this paper is to review five recent studies performed at the National Institutes of Health in patients with Zollinger-Ellison syndrome to define the role of somatostatin receptor scintigraphy. Patients were from a tertiary referral centre, all had Zollinger-Ellison syndrome. In Study n. 1: the sensitivity of somatostatin receptor scintigraphy was assessed compared to conventional studies in 80 patients. Study n. 2: the effect of somatostatin receptor scintigraphy on management was determined in 122 patients. Study n. 3: ability of somatostatin receptor scintigraphy and other conventional methods to distinguish small hepatic metastases (< 2 cm) from hepatic haemangiomas was assessed in 29 patients. Study n. 4: somatostatin receptor scintigraphy, magnetic resonance imaging and bone scanning were compared in 115 consecutive patients to detect bone metastases. Study n. 5: ability of somatostatin receptor scintigraphy to detect gastrinomas found at surgery in 35 patients and its effect on cure rate and determinants of detection of gastrinomas by somatostatin receptor scintigraphy were analysed. Briefly, results showed: Study n. 1: somatostatin receptor scintigraphy is the most sensitive modality for detection of primary or metastatic gastrinomas; Study n. 2: somatostatin receptor scintigraphy changes management in 47% of cases; Study n. 3: somatostatin receptor scintigraphy is the only method to distinguish small liver metastases from small haemangiomas; Study n. 4: somatostatin receptor scintigraphy and magnetic resonance imaging have higher sensitivity and predictive values for bone metastases than bone scanning; Study n. 5: somatostatin receptor scintigraphy misses 33% of gastrinomas found at surgery, primarily small duodenal tumours. Size is the important factor. The use of somatostatin receptor scintigraphy does not increase cure rate. In conclusion, Somatostatin receptor scintigraphy is now the imaging method of choice in patients with Zollinger-Ellison syndrome for preoperative primary tumour localization, detection of bone or liver metastases, and to distinguish small liver metastases from small hepatic haemangiomas. Its specificity appears to be high but has been poorly studied as has the use of it in combination with endoscopic ultrasound. Studies by others suggest these recommendations will apply to carcinoid tumours and other pancreatic endocrine tumours except insulinomas.


Part 2, Responding to PPS. Development and interpretation of the diagnosis-related groups (DRGs).
As they are now, defined, the DRGs form a manageable, clinically coherent set of patient classes that relate a hospital's case mix to the resource demands and associated costs experienced by the hospital. DRGs are defined based on the principal diagnosis, secondary diagnoses, surgical procedures, age and discharge status of the patients treated. Through DRGs, hospitals can gain an understanding of the patients being treated, the costs incurred and within reasonable limits, the services expected to be required. The classification of patients into DRGs is a constantly evolving process. As coding schemes change, as more comprehensive data is collected or as medical technology or practice changes, the DRG definitions will need to be reviewed and revised.


A 15-year-old with chest pain: An unexpected etiology.
A 15-year-old female with no significant past medical history presented to the emergency department with 1 day of substernal and pleuritic chest pain, chills, cough, and hematuria. She also had swelling of the face and ankles that resolved by presentation. She was found to have elevated troponin and brain natriuretic peptide during initial workup. Electrocardiogram was normal, but there were significant pleural effusions on chest x-ray. She was strep positive and had blood pressure up to 150/90, prompting admission for cardiac monitoring and cardiology consultation. Blood pressure decreased down to 125/72 without intervention. She was afebrile with unlabored breathing and normal saturations. She was clear to auscultation bilaterally, with no abdominal distension or hepatosplenomegaly, and edema was not evident on exam. There was mild erythema to the bilateral tonsillar pillars. Initial considerations included viral myocarditis, pericarditis, and atypical nephritic syndrome. Workup revealed elevated antistreptolysin antibodies, low C3 complement, negative antineutrophil cytoplasmic antibodies, and negative flu testing. Renal sonography was unremarkable. Cardiology recommended echocardiography, which confirmed pleural effusions but revealed no cardiac abnormalities. Urinalysis revealed hematuria and mild proteinuria. Diagnosis was found to be post-streptococcal glomerulonephritis complicated by fluid overload and left ventricular strain secondary to hypertensive emergency. Post-streptococcal glomerulonephritis is the most common cause of acute glomerulonephritis in children. The mechanism of disease is a proliferation and inflammation of the renal glomeruli secondary to immunologic injury, with deposition of immune complexes, neutrophils, macrophages, and C3 after complement activation. This leads to hematuria, proteinuria, and fluid overload. Edema is present in 65%-90% of patients, progressing to pulmonary involvement in severe cases. Cardiac dysfunction secondary to fluid overload is a potentially fatal outcome in the acute setting. Physicians should consider post-streptococcal glomerulonephritis for patients presenting with hypertension, cardiac/pulmonary pathology, or symptoms of acute heart failure in the context of strep infection.


Coexpression of human alpha- and circularly permuted beta-globins yields a hemoglobin with normal R state but modified T state properties.
For the first time, a circularly permuted human beta-globin (cpbeta) has been coexpressed with human alpha-globin in bacterial cells and shown to associate to form alpha-cpbeta hemoglobin in solution. Flash photolysis studies of alpha-cpbeta show markedly biphasic CO and O(2) kinetics with the amplitudes for the fast association phases being dominant due the presence of large amounts of high-affinity liganded hemoglobin dimers. Extensive dimerization of liganded but not deoxygenated alpha-cpbeta was observed by gel chromatography. The rate constants for O(2) and CO binding to the R state forms of alpha-cpbeta are almost identical to those of native HbA (k'(R(CO)) approximately 5.0 microM(-1) s(-1); k'(R(O(2))) approximately 50 microM(-1) s(-1)), and the rate of O(2) dissociation from fully oxygenated alpha-cpbeta is also very similar to that observed for HbA (k(R(O(2))) approximately 21-28 s(-1)). When the equilibrium deoxyHb form of alpha-cpbeta is reacted with CO in rapid mixing experiments, the observed time courses are monophasic and the observed bimolecular association rate constant is approximately 1.0 microM(-1) s(-1), which is intermediate between the R state rate measured in partial photolysis experiments (approximately 5 microM(-1) s(-1)) and that observed for T state deoxyHbA (k'(T(CO)) approximately 0.1 to 0.2 microM(-1) s(-1)). Thus the deoxygenated permutated beta subunits generate an intermediate, higher affinity, deoxyHb quaternary state. This conclusion is supported by equilibrium oxygen binding measurements in which alpha-cpbeta exhibits a P(50) of approximately 1.5 mmHg and a low n-value (approximately 1.3) at pH 7, 20 degrees C, compared to 8.5 mmHg and n approximately 2.8 for native HbA under identical, dilute conditions.


Powassan virus: vernal spread during 1965.
Powassan virus was isolated from seven pools of Ixodes cookei ticks removed from groundhogs (Marmota monax) collected near North Bay, Ontario, between May and August 1965, including five pools obtained during spring. Tick pools, each comprising one to nine ticks, contained 2.0 to 5.5 log(10) TCD(50) of virus upon titration in monolayer cultures of primary swine kidney cells. Powassan virus neutralizing antibody prevalence in sera of the current season's groundhogs increased steadily from zero during May to 25% during August but remained relatively unchanged (42% to 58%) in the previous season's groundhogs, thereby confirming that active infection had occurred particularly amongst juvenile groundhogs mainly during spring 1965. Isolation of one strain of Silverwater virus from Haemaphysalis leporis-palustris ticks and detection of neutralizing antibody in three of nine snowshoe hares (Lepus americanus) confirmed the active spread of this agent during 1965.


Effect of thymosin and irradiation on immune modulation in head and neck and esophageal cancer patients.
Fifty-five patients with squamous cell carcinoma of the head and neck and esophagus were evaluated prior to irradiation and thymosin fraction 5 therapy. Immunity prior to treatment, as measured by total lymphocyte count, E and EAC rosettes, lymphocyte stimulation with phytohemagglutinin (PHA) and in mixed leukocyte culture (MLC) with allogeneic cells, delayed hypersensitivity skin tests, and quantitative serum immunoglobulins, was comparable and normal in the 40 control patients and in the 15 thymosin-treated patients. After irradiation, significant depression (P less than 0.01) was demonstrated in cellular immunity in both groups of patients with decreased T- and B-cell numbers and depressed phytohemagglutinin and MLC stimulation. Six months after irradiation, our preliminary results suggest that the thymosin-treated patients may be reversing their immunosuppression by a return of MLC function and positivity of delayed hypersensitivity skin tests. The ultimate effect of thymosin on disease control and survival remains uncertain.