Effective solidification/stabilisation of mercury-contaminated wastes using zeolites and chemically bonded phosphate ceramics.
In this study, two kinds of zeolites materials (natural zeolite and thiol-functionalised zeolite) were added to the chemically bonded phosphate ceramic processes to treat mercury-contaminated wastes. Strong promotion effects of zeolites (natural zeolite and thiol-functionalised zeolite) on the stability of mercury in the wastes were obtained and these technologies showed promising advantages toward the traditional Portland cement process, i.e. using Portland cement as a solidification agent and natural or thiol-functionalised zeolite as a stabilisation agent. Not only is a high stabilisation efficiency (lowered the Toxicity Characteristic Leaching Procedure Hg by above 10%) obtained, but also a lower dosage of solidification (for thiol-functionalised zeolite as stabilisation agent, 0.5 g g(-1) and 0.7 g g(-1) for chemically bonded phosphate ceramic and Portland cement, respectively) and stabilisation agents (for natural zeolite as stabilisation agent, 0.35 g g(-1) and 0.4 g g(-1) for chemically bonded phosphate ceramic and Portland cement, respectively) were used compared with the Portland cement process. Treated by thiol-functionalised zeolite and chemically bonded phosphate ceramic under optimum parameters, the waste containing 1500 mg Hg kg(-1) passed the Toxicity Characteristic Leaching Procedure test. Moreover, stabilisation/solidification technology using natural zeolite and chemically bonded phosphate ceramic also passed the Toxicity Characteristic Leaching Procedure test (the mercury waste containing 625 mg Hg kg(-1)). Moreover, the presence of chloride and phosphate did not have a negative effect on the chemically bonded phosphate ceramic/thiol-functionalised zeolite treatment process; thus, showing potential for future application in treatment of 'difficult-to-manage' mercury-contaminated wastes or landfill disposal with high phosphate and chloride content.


Global structure search and physical properties of Os2C.
The crystal structures of Os2C were extensively investigated using the structure search method from the first-principles calculations. In contrast to the P6 3 /mmc phase previously proposed as the ground state at ambient pressure, an energetically favorable structure with space group P-6m2 was found more stable at ambient condition. The structural stabilities of the new phase are confirmed by the phonon dispersion and elastic constants. Further calculations indicate that the newly predicted P-6m2 phase is ultra-incompressible with a high bulk modulus of 387 GPa and has a larger ideal shear strength than the P6 3 /mmc phase.


Connexin31 cannot functionally replace connexin43 during cardiac morphogenesis in mice.
In the gastrulating mouse embryo, the gap junction protein connexin43 is expressed exclusively in cells derived from the inner cell mass, whereas connexin31 is expressed in cells of the trophoblast lineage. Since connexin43 and connexin31 do not form heterotypic gap junction channels in exogenous expression systems, such as HeLa cells and Xenopus oocytes, previous studies have suggested that the incompatibility of these two connexins could contribute to the separation of connexin43-expressing and connexin31-expressing compartments between embryo and extraembryonic tissues at gastrulation, respectively. Thus, we have generated connexin43 knock-in connexin31 mice, in which the coding region of the connexin43 gene was replaced by that of connexin31. Interbreeding of heterozygous connexin43 knock-in connexin31 mice resulted in homozygous connexin43 knock-in connexin31 mice, but none of them survived to adulthood. As these mice were born at the expected Mendelian frequency, we conclude that the reported incompatibility of connexin43 and connexin31 to form heterotypic gap junction channels does not interfere with normal embryonic development. Neonatal homozygous connexin43 knock-in connexin31 hearts showed malformation in the subpulmonary outlet of the right ventricle, similar to general connexin43-deficient mice. Electrocardiograms of neonatal hearts in homozygous connexin43 knock-in connexin31 mice revealed significantly low voltage of the QRS complex. This is in contrast to previous results from our laboratory which showed that replacement of connexin43 by connexin40 resulted in morphologically and functionally normal hearts. We conclude that connexin31 cannot functionally replace connexin43 during cardiac morphogenesis.


Flavonoids with anti-Helicobacter pylori activity from Cistus laurifolius leaves.
Cistus laurifolius flower buds are used traditionally in folk medicine against gastric ailments. In a prior study we showed that the chloroform extract of Cistus laurifolius had a potent anti-ulcer activity. It has been known that there is a causal relationship between peptic ulcer and Helicobacter pylori infection. Then in a previous study, we demonstrated that chloroform extract of Cistus laurifolius possessed a significant anti-Helicobacter pylori activity. We designed this study to isolate and define the active component(s) involved in the anti-Helicobacter pylori activity of the extract through activity-guided fractionation procedures. The chloroform extract was fractionated by using various chromatography techniques, i.e., Sephadex LH-20 column chromatography and preparative thin layer chromatography and six compounds were isolated (1-6). Each of these six compounds' anti-Helicobacter pylori activity was tested in vitro and was measured as minimum inhibition concentration (MIC) values by using agar dilution method. The compound 2 had the highest activity against Helicobacter pylori (MIC 3.9 microg/mL). Its chemical structure was elucidated as quercetin 3-methyl ether (isorhamnetin) by various spectroscopic techniques. We believe that the therapeutic effect of Cistus laurifolius in ulcer is at least partially related to its effect on Helicobacter pylori. We hope that the isolated flavonoid having anti-Helicobacter pylori activity ultimately can be utilized as an alternative or additive agent to the current therapy.


The effects of the M40 protective mask on sleep.
There are very few data available on the effects of respiratory protective masks on sleep. This study was to undertaken to investigate the effects of the M-40 protective mask on sleep architecture. We asked 21 healthy volunteers (18-35 yr) to participate in a two-night study. During the first night, subjects underwent standard polysomnography without the M40 mask. The second night entailed sleeping while wearing the mask, without the hood. Specific variables measured on each night included sleep stage distribution, time awake, number of awakenings, oxygen saturation, number of apneas and hypopneas, and time to sleep onset. Statistical analysis was performed using a two-tailed, paired t-test for all variables except REM sleep, for which a one-tailed, paired t-test was used. There was a significant difference between mask and non-mask nights when measuring total sleep time, total awake time, percentage of time in REM, and number of awakenings. It is concluded that sleep in the M40 mask is disrupted compared to sleep without the mask, with significant decreases in total sleep time and REM sleep.


Travelling Scientist, Circulating Images and the Making of the Modern Scientific Journal.
The early astrophysicist Norman Lockyer was both editor of the journal Nature from its creation in 1869 and for the following five decades, and an early practioner of the new astronomy. He frequently used the journal to expound his scientific theories, report on his work and send news home while on expeditions. I look into the particular visual culture of astrophysics developed by Lockyer in Nature, its evolution at a time of rapid development both of the techniques of astrophysical observation and visualization and of the techniques of image reproduction in print. A study of the use and reuse of visual materials in different settings also makes it possible to sketch the circulating economy of Lockyer's images and the ways in which he put himself forward as a scientist, at a time when he was advocating the State support of research and scientists and helping create the modern scientific journal.


Postvagotomy changes in neurogenic plasma extravasation in rat bronchi.
The present study was carried out to test if plasma extravasation induced by capsaicin (90 micrograms/kg) in the bronchi of Sprague-Dawley rats could be reduced 10-30 min (0 day), 20-24 h (1 day), 3, 7 or 14 days after unilateral midcervical vagotomy. The second aim of this study was to demonstrate if substance P (3 micrograms/kg) could intensify neurogenic plasma extravasation in the bronchi in which sensory innervation was partially deprived by vagotomy. In the rats 0 days after vagotomy (0 days postvagotomy) that received capsaicin, plasma extravasation in the mainstem and secondary bronchi ipsilateral to vagotomy did not decrease. Capsaicin-evoked plasma extravasation in the secondary bronchi ipsilateral to vagotomy decreased significantly 1, 3, 7 and 14 days after vagotomy as compared with that of 0 days postvagotomy. Differences in extravasation between the secondary bronchi of the two sides were usually significant in animals 3, 7 or 14 days postvagotomy. The effect of unilateral vagotomy on plasma extravasation in the mainstem bronchi was variable. Plasma extravasation produced by substance P in the mainstem and secondary bronchi of rats 0 days postvagotomy was similar to that of unoperated rats receiving either capsaicin or substance P. Unilateral vagotomy did not decrease the amount of substance-P-induced plasma extravasation in the mainstem or secondary bronchi ipsilateral to vagotomy in rat groups 1, 3, 7 or 14 days postvagotomy as compared with that of their contralateral bronchi. This study suggests that the secondary bronchi were the chief location of the bronchial tree that could be desensitized after unilateral cervical vagotomy to stimulation by the irritant capsaicin. This desensitization developed within 1 day after vagotomy, therefore the capsaicin-evoked neurogenic inflammation in the bronchi of the vagotomized side was reduced. Exogenous substance P resulted in mucosal edema and degranulation of goblet cells in the bronchi of both vagotomized and opposite sides. The number of mediator-sensitive blood venules did not decrease following vagotomy operation. It is suggested that substance P was insufficient after vagal denervation, but substance-P receptors on the endothelial cells and goblet cells in the denervated regions were still operative.


Pharmacokinetics of antivirals in neonate.
About 1000 neonates with HIV infection are born every day worldwide. The antiviral therapy for newborn infants is a real necessity. Pharmacokinetics is an important contribution to therapy and no review has been published on the pharmacokinetics of antivirals in neonates up to now. This article provides a review on the pharmacokinetics of antivirals in the neonate. The pharmacokinetic parameters in the neonate are compared with those of the adult, and when possible, the pharmacokinetic parameters were compared in neonates of different ages. Zidovudine is the antiviral with the largest amount of information on its pharmacokinetics. The clearance (Cl; l/h/kg) of zidovudine is 0.15 (premature), 0.34 (1 day), 0.69 (7 days), 0.65 (< or =14 days), 1.14 (>14 days) and 1.56 (adult). t(1/2) (h) of zidovudine is 7.2 (premature), 4.2 (1 day), 4.0 (7 days), 3.1 (< or =14 days), 1.9 (>14 days) and 1.1 (adult). Zidovudine is mainly eliminated by conjugation with glucuronic acid and glucuronosyl transferase develops postnatally. Cl of lamivudine is 0.19 (1 day), 0.32 (7 days) and 0.30 (adult) and the Cl (l/h/m2) of didanosine is 65 (1 day) and 271 (7 days). A greater volume of distribution (Vd) has been observed in the neonate compared with the adult for nelfinavir, nevirapine and pleconaril. The pharmacokinetic parameters of antivirals differ in the neonate and in the adult. The Cl is reduced and t(1/2) is increased in the neonate compared with the adult for zidovudine, lamivudine and ganciclovir. t(max) is generally greater in the neonate than in the adult due to reduced absorption rate in the neonate. The Vd of nelfinavir, nevirapine and pleconaril is greater in the newborn than in the adult. The neonate is a developing organism and the pharmacokinetic parameters of antivirals vary during the first weeks of life.


Dual luminescence in solid CuI(piperazine): hypothesis of an emissive 1-D delocalized excited state.
Solid [CuI(piperazine)0.5]∞, characterized by a structure with an infinite double chain of CuI, presents an unexpected dual luminescence. The short copper-copper distances allow the existence of both cluster-centered and 1-D delocalized electronic transitions, as emerged from theoretical calculations. Beyond the more common cluster-centered emission a higher energy band, which differs in lifetime and in temperature dependence, is observed.


Headspace solid-phase microextraction analysis of 3-alkyl-2-methoxypyrazines in wines.
A procedure to determine 3-alkyl-2-methoxypyrazines in wines is described. It is based on the headspace solid-phase microextraction (HS-SPME) technique after a clean-up of the sample by distillation (previously acidified to pH 0.5) to remove ethanol and other volatile compounds that can interfere in the SPME. Determination is performed by means of capillary gas chromatography using a nitrogen-phosphorus detector. The method allows quantification of 3-isobutyl-2-methoxypyrazine, 3-sec-butyl-2-methoxypyrazine and 3-isopropyl-2-methoxypyrazine at their natural concentration levels and below their sensory thresholds in Cabernet Sauvignon and Merlot wines. The method was successfully applied to experimental red wines and the evolution of their pyrazine contents during the winemaking process was monitored. Pyrazine content increased during the first maceration day but did not change significantly during alcoholic and malolactic fermentation. Final contents in wines were 12-27 ng/l of 3-isobutyl-2-methoxypyrazine and 5-10 ng/l of 3-sec-butyl-2-methoxypyrazine.


Maxillary versus mandibular arch form differences in human permanent dentition assessed by Euclidean-distance matrix analysis.
Euclidean-distance matrix analysis (EDMA) was used to analyse the dental arch form in 50 men and 45 women aged 20-27 yr with sound dentitions. Fourteen landmarks, corresponding to the centres of gravity (centroids) of the occlusal surfaces of all permanent teeth (right second molar to left second molar), were identified on the dental casts of subjects. All the possible linear distances between pairs of teeth were computed and maxillary/mandibular arch differences within sex were tested by EDMA. In both sexes, the maxillary arch was larger than the mandibular arch; arch shape was also significantly different. All teeth contributed to the shape difference between arches regardless of gender. EDMA also separated the influence of anterior and posterior teeth in the determination of upper/lower arch characteristics.


Restoration of visual cortical plasticity by local microperfusion of norepinephrine.
Using a newly developed technique of continuous microperfusion, we obtained further evidence in support of our hypothesis that the neocortical catecholamines (CAs), particularly norepinephrine (NE), are responsible for a high level of cortical plasticity. We used the visual cortical changes in ocular dominance which follow a brief monocular deprivation as a simple and reliable index of cortical plasticity. Local perfusion of kitten visual cortex with 1 mg/ml (4.0 mM) 6-hydroxydopamine (6-OHDA) prevented the effects of monocular deprivation in kittens, thus replicating the results we had obtained using intraventricular injections (Kasamatsu and Pettigrew, '76b, '79). Locally perfused NE at a concentration of of 10(-2) mg/ml (48.6 micron) restored visual cortical plasticity in animals which were no longer susceptible to brief monocular lid-suture. These numbers refer to the concentration of solutions in the cannula/minipump system. The effective concentrations at the site of recording (about 2 mm away) are probably much lower than these. This effect of NE perfusion was seen both in kittens which had received prior 6-OHDA treatment as well as in older animals which had outgrown the susceptible period. In the kittens we obtained as a nearly complete shift in ocular dominance toward the open eye and in the older animals a decrease in binocularity was obtained. The changes were found only in the local region of visual cortex perfused with either NE or 6-OHDA, while nearby cortical regions in the same animals were unaffected. There were no obvious changes in receptive field properties of individual neurons other than ocularity, and externally perfused NE did not itself reduce binocularity in normal animals: the effects of NE described about only occurred when the animal's visual experience was simultaneously altered. These results support the view that NE plays an important role in cortical plasticity.


Immunohistochemical analysis and comparison of napsin A, TTF1, SPA and CK7 expression in primary lung adenocarcinoma.
We investigated the expression of napsin A, TTF1, SPA and CK7 in primary lung adenocarcinoma (ADC) and compared antibody specificity and sensitivity. We used immunohistochemistry (IHC) using antibodies directed against napsin A, TTF1, SPA, and CK7 on cancer tissue from 454 patients diagnosed with lung cancer. In primary lung ADC, napsin A exhibited a sensitivity of 87.25% and specificity of 95.02%, TTF1 exhibited a sensitivity of 80.72% and specificity of 90.48%, SPA exhibited a sensitivity of 60.46% and specificity of 94.87% and CK7 exhibited a sensitivity of 100% and specificity of 80.31%. The order of sensitivity of the four indicators was CK7 > napsin A > TTF1 > SPA, and the order of specificity was napsin A > SPA > TTF1 > CK7. We can select effective indicators for diagnostic and differential diagnostic purposes based on differences in sensitivity and specificity.


Activation of the endoplasmic reticulum Ca2+ pump of pancreatic acini by Ca2+ mobilizing hormones.
Stimulation of the pancreatic acinar cells with Ca2+ mobilizing hormones increased the ATP-dependent Ca2+ uptake into the ER of permeabilized cells. Activation of the ER Ca2+ pump resulted in increased apparent affinity for Ca2+ from 0.26 to 0.09 uM and Vmax from 2.68 to 5.74 nmoles/mg prot./min. The apparent affinity of the pump for VO4 = was dependent on [Ca2+]. Activation of the pump also decreased apparent affinity for VO4 = from 12 to 32 uM at [Ca2+] of 0.138 uM. These findings suggest that pump activation is due to acceleration of the rate of the conformational transition between the VO4 = (E2) and Ca2+ (E1) sensitive forms of the pump.


Trisomy 21 as a sole acquired abnormality in an adult Omani patient with CD7- and CD9-positive acute myeloid leukemia.
We describe a case of acute myeloid leukemia (AML) in which trisomy 21 was the sole acquired cytogenetic abnormality. The immunophenotype showed positivity for CD7 and CD9 along with CD13, CD33, and CD34. The chromosomal analysis of bone marrow showed 47,XY +21 in all the metaphases analyzed. The constitutional karyotype was normal. The patient was an adult and did not have any features of Down's syndrome. The bone marrow morphology was AML-M2 as per the French-American-British (FAB) criteria. A final diagnosis of CD7- and CD9-positive AML-M2 was established with trisomy 21 as a sole cytogenetic abnormality. The patient responded remarkably well to chemotherapy and achieved complete clinical remission. This is the first case of CD7- and CD9-positive AML with trisomy 21 as a sole abnormality. A putative role for the co-expression of abnormal lymphoid markers in achieving quick remission is discussed.


Erythrocyte sodium-hydrogen antiport activity is not a predictor of diabetic nephropathy.
Erythrocyte sodium-hydrogen antiport activity was measured by Orlov's method in 36 healthy volunteers (18 with negative, 18 with positive family history of hypertension) and 52 subjects with type 1 insulin-dependent diabetes mellitus: 29 patients were without known diabetic complications, 23 patients with microangiopathy (10 with diabetic retinopathy, 13 with 'incipient' diabetic nephropathy). Normotensive healthy adults had similar antiport activities independently of a positive or negative family history of hypertension (6.45 +/- 2.61 vs. 5.80 +/- 3.07 mmol/l of cells per h, respectively). Sodium-hydrogen antiport resulted 8.38 +/- 3.91 mmol/l of cells per h in the 29 uncomplicated diabetic patients, significantly higher (p < 0.05) compared to healthy subjects, both without and with family hypertension. Complicated diabetics confirmed to have an exchange rate higher than healthy controls (8.18 +/- 2.50 mmol/l of cells per h, p < 0.01): patients with retinopathy showed the highest antiport activity (8.96 +/- 2.95 mmol/l of cells per h, p < 0.01), while patients with nephropathy had milder antiport overactivity (7.58 +/- 2.02 mmol/l of cells per h), not significantly different from either uncomplicated diabetics or healthy controls. Thus, an increased sodium-hydrogen exchange rate in peripheral erythrocytes does not seem to be an early indicator of diabetic nephropathy.


Urban air pollution, and asthma and COPD hospital emergency room visits.
There is little previous information of the effects of size fractioned particulate air pollution and source specific fine particles (PM(2.5); <2.5 microm) on asthma and chronic obstructive pulmonary disease (COPD) among children, adults and the elderly. To determine the effects of daily variation in levels of different particle size fractions and gaseous pollutants on asthma and COPD by age group. Levels of particulate air pollution, NO(2) and CO were measured from 1998 to 2004 at central outdoor monitoring sites in Helsinki, Finland. Associations between daily pollution levels and hospital emergency room visits were evaluated for asthma (ICD10: J45+J46) in children <15 years old, and for asthma and COPD (ICD10: J41+J44) in adults (15-64 years) and the elderly (>or=65 years). Three to 5 day lagged increases in asthma visits were found among children in association with nucleation (<0.03 microm), Aitken (0.03-0.1 microm) and accumulation (0.1-0.29 microm) mode particles, gaseous pollutants and traffic related PM(2.5) (7.8% (95% CI 3.5 to 12.3) for 1.1 microg/m(3) increase in traffic related PM(2.5) at lag 4). Pooled asthma-COPD visits among the elderly were associated with lag 0 of PM(2.5), coarse particles, gaseous pollutants and long range transported and traffic related PM(2.5) (3.9% (95% CI 0.28 to 7.7) at lag 0). Only accumulation mode and coarse particles were associated with asthma and COPD among adults. Among children, traffic related PM(2.5) had delayed effects, whereas among the elderly, several types of particles had effects that were more immediate. These findings suggest that the mechanisms of the respiratory effects of air pollution, and responsible pollutants, differ by age group.


Quantitative proteomics by 2-DE, 16O/18O labelling and linear ion trap mass spectrometry analysis of lymph nodes from piglets inoculated by porcine circovirus type 2.
Porcine circovirus type 2 (PCV2) has been identified as the essential causal agent of postweaning multisystemic wasting syndrome. However, little is known regarding the mechanism(s) underlying the pathogenesis of PCV2-induced disease and the interaction of the virus with the host immune system. Here, we present a proteomics study on inguinal lymph nodes of piglets inoculated with PCV2, in order to better understand the pathogenesis of postweaning multisystemic wasting syndrome and the pathways might be affected after infection. We used two proteomics strategies, 2-DE and 1-DE followed by (16)O/(18)O peptide labelling and peptide identification and quantification by MS. More than 100 proteins were found to be differentially regulated and the results obtained by the two strategies were fairly concordant but also complementary, the (18)O labelling approach being a more robust alternative. Analysis of these proteins by systems biology tools revealed the implication of acute phase response and NrF2-mediated oxidative stress, suggesting a putative role for these pathways in the pig immune response. Besides, CD81 was found to be up-regulated, suggesting a possible role in the internalization of the virus. The use of proteomics technologies together with biology analysis systems opens up the way to gain more exhaustive and systematic knowledge of virus-pathogen interactions.


[Dissection of cervical arteries].
INDICENCE: Cervical artery dissection (CAD) is one of the major cause of cerebral infarction before 45 years of age. The average annual incidencerate is between 2.5 and 3 per 100,000, but the reported incidence of CAD is probably underestimated because of frequent asymptomatic forms, or producing only minor and local symptoms. Dissection of the internal carotid artery (ICA) is more frequent than dissection of the vertebral artery (VA) and intracranial dissection is less frequent than extracranial dissection. Traumas and primary diseases of the arterial wall are the main predisposing factors, but the pathogenesis of spontaneous DAC remains unknown in most cases, although the possibility of an underlying arteriopathy is suspected. The clinical presentation of ICA dissections includes isolated local signs (Homer's sign, headaches) followed by a few hours or days later by signs of cerebral or retinal ischemia. Brainstem infarcts and occipital or cervical pain are the most strinking clinical feature of VA dissection. Recent progress in neuroradiology (i.e. CT-scan, MRI, magnetic resonance ongiography) and neurosonology (i.e. transcranial Doppler) allows a non invasive approach in the diagnosis and follow-up of CAD. The prognosis is highly variable, but remains usually good. Heparin in the acute stage, followed by an oral anticoagulant or aspirin treatment for 3 to 6 months is most commonly used, although it has never been proved by a randomized trial.


Contradictory effects of mitochondria- and non-mitochondria-targeted antioxidants on hepatocarcinogenesis by altering DNA repair in mice.
Conflicting effects of antioxidant supplementation on cancer prevention or promotion is of great concern to healthy people and cancer patients. Despite recent studies about antioxidants accelerating the progression of lung cancer and melanoma, antioxidants may still play a role in cancer prevention. Both tumor and antioxidants types influence the actual efficacy. However, little is known about the impact of different types of antioxidants on primary hepatocellular carcinoma (HCC), including non-mitochondrial- and mitochondrial-targeted antioxidants. Utilizing mouse models of chemical hepatocarcinogenesis, we showed that administration of non-mitochondria-targeted antioxidants N-acetylcysteine (NAC) and the soluble vitamin E analog, Trolox, prevented tumorigenesis, whereas administration of mitochondria-targeted antioxidants SS-31 (the mitochondria-targeted peptide) and Mito-Q (a derivative of ubiquinone) facilitated tumorigenesis. RNA sequencing revealed that NAC and SS-31 caused very different changes in the oxidation-reduction state and DNA damage response. In diethylnitrosamine (DEN)-treated primary hepatocytes, NAC and Trolox alleviated DNA damage by activating ataxia-telangiectasia mutated (ATM)/ATM and Rad3-related (ATR) for DNA repair whereas SS-31 and Mito-Q aggravated damage by inactivating them. Interestingly, partial recovery of SS-31-scavengened mitochondrial reactive oxygen species (mtROS) could alleviate SS-31-aggravated DNA damage. Localization of ATM between mitochondria and nuclei was altered after NAC and SS-31 treatment. Furthermore, blockage of phospho-ATR (p-ATR) led to the recurrence of NAC-ameliorated DEN HCC. In contrast, reactivation of p-ATR blocked SS-31-promoted DEN HCC. Conclusion: These results demonstrate that the type of antioxidants plays a previously unappreciated role in hepatocarcinogenesis, and provide a mechanistic rationale for exploring the therapeutic use of antioxidants for liver cancer. (Hepatology 2018;67:623-635).


Expression of the bcl-2 homologue bax in normal human skin, psoriasis vulgaris and non-melanoma skin cancers.
Bax (bcl-2-associated X protein) is a recently identified member of the bcl-2 family and one of the principal inducers of apoptosis. We examined the distribution of bax protein in normal human skin and several skin diseases by immunohistochemistry. Bax immunoreactivity was present in normal epidermis and its appendages, with the suprabasal compartment being stained more strongly than basal keratinocytes. Bax immunostaining was also detected in the epidermis of psoriasis vulgaris and 5 keratoacanthomas examined. We could observe only weak bax immunoreactivity in 15 squamous cell carcinomas examined, with the exception of well-differentiated tumour islands in two tumours, which expressed immunostaining for bax comparable to that of normal suprabasal epidermis. Immunostaining for bax was negative in 12 out of 17 basal cell carcinomas and the remaining five tumours showed weak bax reactivity in tumour cells scattered within tumour masses and in palisading layers of some tumour formations. Western blot analysis confirmed the expression of bax protein in normal skin, psoriasis vulgaris and squamous cell carcinoma as well as the absence of bax in basal cell carcinoma. Our findings suggest that the loss of pro-apoptotic bax protein in basal cell carcinoma and its reduced expression in squamous cell carcinoma might be an important step in the development of these two skin cancers.


Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson's disease models.
Aggregation of α-synuclein (α-syn) is neuropathologically and genetically linked to Parkinson's disease (PD). Since stereotypic cell-to-cell spreading of α-syn pathology is believed to contribute to disease progression, immunotherapy with antibodies directed against α-syn is considered a promising therapeutic approach for slowing disease progression. Here we report the identification, binding characteristics, and efficacy in PD mouse models of the human-derived α-syn antibody BIIB054, which is currently under investigation in a Phase 2 clinical trial for PD. BIIB054 was generated by screening human memory B-cell libraries from healthy elderly individuals. Epitope mapping studies conducted using peptide scanning, X-ray crystallography, and mutagenesis show that BIIB054 binds to α-syn residues 1-10. BIIB054 is highly selective for aggregated forms of α-syn with at least an 800-fold higher apparent affinity for fibrillar versus monomeric recombinant α-syn and a strong preference for human PD brain tissue. BIIB054 discriminates between monomers and oligomeric/fibrillar forms of α-syn based on high avidity for aggregates, driven by weak monovalent affinity and fast binding kinetics. In efficacy studies in three different mouse models with intracerebrally inoculated preformed α-syn fibrils, BIIB054 treatment attenuated the spreading of α-syn pathology, rescued motor impairments, and reduced the loss of dopamine transporter density in dopaminergic terminals in striatum. The preclinical data reported here provide a compelling rationale for clinical development of BIIB054 for the treatment and prevention of PD.


An overview of the integration of ozone systems in biological treatment steps.
Despite the well-known potential and performance of combined biological and ozonation processes for wastewater treatment, only few full-scale applications are published. Beside the synergistic effects of such process combination, which lead to oxidation of recalcitrant and inhibitory compounds or intermediates by enhancement of their biodegradability, the key for raising applicability is the improvement of the ozonation efficiency. An overview about the history and progress of full-scale applications, which deals with combined ozonation and biological treatment is given. Recently more than 40 applications exist, but many of them are not published. Therefore, a couple of selected not yet published applications have been mentioned in this paper. Landfill leachate and industrial wastewater treatment were mostly applicated, while treatment of municial wastewater treatment plant (WWTP) effluents are of increasing interest due to several advantages such as disinfection, decolourisation and removal of persistent dissolved organic carbon (DOC) for water re-use and groundwater recharge.


Identification of core-attachment complexes based on maximal frequent patterns in protein-protein interaction networks.
In this paper, we present a method for core-attachment complexes identification based on maximal frequent patterns (CCiMFP) in yeast protein-protein interaction (PPI) networks. First, we detect subgraphs with high degree as candidate protein cores by mining maximal frequent patterns. Then using topological and functional similarities, we combine highly similar protein cores and filter insignificant ones. Finally, the core-attachment complexes are formed by adding attachment proteins to each significant core. We experimentally evaluate the performance of our method CCiMFP on yeast PPI networks. Using gold standard sets of protein complexes, Gene Ontology (GO), and localization annotations, we show that our method gains an improvement over the previous algorithms in terms of precision, recall, and biological significance of the predicted complexes. The colocalization scores of our predicted complex sets are higher than those of two known complex sets. Moreover, our method can detect GO-enriched complexes with disconnected cores compared with other methods based on the subgraph connectivity.


Brucellosis in children in Iraq.
We studied 50 children with brucellosis. Diagnoses were made from clinical pictures and agglutination titres. Fevers, sweating and chills were common complaints. Hepatosplenomegaly and arthritis were usual findings. Tetracycline is an effective drug for management of childhood brucellosis. Seven patients with relapse were treated successfully with combination of tetracycline and co-trimoxazole.


Bioconjugation of barium titanate nanocrystals with immunoglobulin G antibody for second harmonic radiation imaging probes.
The second harmonic generation (SHG) active nanocrystals have been demonstrated as attractive imaging probes in nonlinear microscopy due to their coherent, non-bleaching and non-blinking signals with a broad flexibility in the choice of excitation wavelength. For the use of these nanocrystals as biomarkers, it is essential to prepare a chemical interface for specific labeling. We developed a specific labeling scheme for barium titanate (BaTiO3) nanocrystals which we use as second harmonic radiation imaging probes. The specificity was achieved by covalently coupling antibodies onto the nanocrystals. We demonstrate highly specific labeling of the nanocrystal conjugates in an antibody microarray and also the membrane proteins of live biological cells in vitro. The development of surface functionalization and bioconjugation of SHG active nanocrystals provides the opportunities of applying them to biological studies.


Author Correction: Climatic controls of decomposition drive the global biogeography of forest-tree symbioses.
In this Letter, a middle initial and additional affiliation have been added for author G. J. Nabuurs; two statements have been added to the Supplementary Acknowledgements; and a citation to the French National Institute has been added to the Methods; see accompanying Author Correction for further details.


Surgical resident bedside rescue successes.
Attempts at improvements in emergent bedside care of hospitalized patients is an ongoing process in many institutions. Recently, the development and role of rapid response teams has been well described in the literature. However, the role of surgical residents, who are typically not part of these "medical" teams, in emergent bedside care of patients, has not been well described in the literature. Surgical residents have been responsible for many bedside emergent "rescue successes," in teaching hospitals. We present 11 instances of surgical resident bedside rescues over a 1-year period at Monmouth Medical Center as a means of emphasizing their critical role in reducing adverse events and even mortalities. These cases were presented at our Morbidity and Mortality conferences and involved only surgical residents performing various technical maneuvers. Monmouth Medical Center. The 11 cases are representative and do not include multiple central lines and do include 2 of many chest tube-related cases. There was no "failure to rescue case" that involved only the surgical residents. Surgical bedside rescues included: an emergent reintubation, 2 openings of neck incisions for expanding hematomas, replacement of a dislodged tracheostomy tube, rigid sigmoidoscopy for rectal bleeding, bronchoscopy for hemoptysis, control of a permacatheter bleed, control of a ruptured femoral-femoral crossover bypass, control of a bleeding tracheoinominate fistula, and emergent placement of chest tubes. Surgical residents possess bedside procedural skills beyond those of nonsurgical health care workers and rapid response members. These lifesaving skills are needed to reduce adverse events and even prevent mortalities in hospitalized patients. Bleeding complications and invasive procedures such as chest tube placement, venous cutdowns, and emergency endoscopy are situations where a surgical resident should be called first, in a teaching hospital.


Modeling of an optically side-pumped alkali vapor amplifier with consideration of amplified spontaneous emission.
Diode pumped alkali vapor amplifier (DPAA) is a potential candidate in high power laser field. In this paper, we set up a model for the diode double-side-pumped alkali vapor amplifier. For the three-dimensional volumetric gain medium, both the longitudinal and transverse amplified spontaneous emission (ASE) effects are considered and coupled into the rate equations. An iterative numerical approach is proposed to solve the model. Some important influencing factors are simulated and discussed. The results show that in the case of saturated amplification, the ASE effect can be well suppressed rather than a limitation in power scaling of a DPAA.


Cerebral amobarbital sodium distribution during Wada testing: utility of digital subtraction angiography and single-photon emission tomography.
We aimed to determine if the cerebral distribution of anesthetic during Wada testing is reflected by findings on digital subtraction angiography (DSA) and single-photon emission computed tomography (SPECT) and if the findings on these studies are relevant to the outcome of the Wada test. We carried out selective internal carotid artery (ICA) DSA on 29 patients underwent studies prior to a Wada test. In patients without angiographic cross-filling, amobarbital and a radiotracer were injected into each ICA, beginning with the epileptogenic side. In patients with cross-filling, the ICA ipsilateral to the epileptogenic focus was injected with amobarbital and radiotracer while other was injected with amobarbital alone. We analyzed the DSA studies for cross-filling and filling of the posterior cerebral arteries (PCA). We reviewed the SPECT for activity in the territories of the anterior, middle cerebral, and posterior cerebral arteries. We compared the results of both studies with the success or failure of the neuropsychological portion of the Wada test. In 20 patients without cross-filling, the results of DSA and SPECT were comparable: symmetrical hemisphere activity was seen. In nine patients with cross-filling, SPECT showed bilateral, almost symmetrical activity. Filling or nonfilling of the PCA correlated with activity (or lack of it) in the medial temporal and occipital regions in all patients. The Wada test was considered successful in all patients. The findings on SPECT did not alter interpretation of the Wada test and we suggest that it may not be needed in all patients undergoing Wada testing.


Surgical treatment of colonic ganglioneuromatosis in neurofibromatosis.
Gastrointestinal involvement in neurofibromatosis occurs in three forms: neurofibromatous tumours, visceral vasculopathy and ganglioneuromatosis. A case of colonic ganglioneuromatosis is reported and six similar cases from the literature are reviewed. The clinical and pathological features of this condition are summarized and guidelines for surgical therapy formulated. Subtotal colectomy is recommended for pseudo-obstructive symptoms refractory to medical management.


3D imaging and stealth navigation instead of CT guidance for radiofrequency ablation of osteoid osteomas: a series of 52 patients.
Osteoid osteomas are benign bone neoplasms that may cause severe pain and limit function. They are commonly treated by radiofrequency ablation (RFA) through a needle inserted into the nidus of the lesion under CT guidance, which is associated with exposure of young patients to relatively high dose of radiation. The objective of this study was to investigate the amount of radiation, effectiveness and safety of an alternative imaging approach, the 3D image-guided (O-arm) technology and the Stealth navigation. We retrospectively reviewed 52 electronic medical files of patients (mean age 24.7 years, range 8-59 years) who were treated with thermal ablation of benign osteoid osteomas guided by the navigated O-arm-assisted technique in our institution between 2015 and 2017. Data were extracted on the associated complications, the reduction in pain at 3 months and one year postoperatively, and the amount of radiation administered during the procedure. The level of pain on a visual analogue scale decreased from the preoperative average of 7.73 to 0 at the 3-month follow-up. The mean dose-length product was 544.7 mGycm2 compared to the reported radiation exposure of 1971-7946 mGycm2 of CT-guided radio ablations. The one intra-operative complication was a superficial burn in the subcutaneous lesion in a tibia that was treated locally with no major influence on recovery. RFA ablation guided by 3D O-arm stealth navigation is as effective as the traditional CT-guided technique with the advantage of lower radiation exposure. Retrospective study number 0388-17-TLV at Tel Aviv Sourasky Medical Center IRB, approved at 25.10.17.


The methionine synthase reductase (MTRR) A66G polymorphism is a novel genetic determinant of plasma homocysteine concentrations.
Epidemiological evidence has revealed that an elevated plasma homocysteine level (hyperhomocysteinemia) confers an increased risk of cardiovascular disease and neural tube defects. Hyperhomocysteinemia is caused by both nutritional (e.g. folate, vitamins B(6) and B(12)) and genetic factors, including functional polymorphisms of key enzymes involved in homocysteine metabolism. One such enzyme, methionine synthase reductase (MTRR), maintains adequate levels of methylcob(III)alamin, the activated cofactor for methionine synthase, which catalyzes the remethylation of homocysteine to methionine. A common MTRR polymorphism, i.e. a 66 A-->G substitution specifying an isoleucine to methionine substitution (I22M), was recently identified. To assess the influence of this polymorphism on total plasma homocysteine (tHcy), we undertook a genotype/phenotype analysis in a study population of 601 Northern-Irish men, aged 30--49, for which biochemical and genetic data relevant to folate/homocysteine metabolism had already been acquired. The 66AA genotype has a frequency of 29% in this population. We established that there was a significant influence of MTRR genotype on tHcy ranking (P=0.004) and that the 66AA genotype contributes to a moderate increase in tHcy levels across the distribution [OR 1.59 (95% CI: 1.10--2.25) for the 66AA genotype to be in the upper half of the tHcy distribution, P=0.03]. The homocysteine-elevating effect of the 66AA genotype is independent of serum folate, vitamin B(12) and vitamin B(6) levels. Based on published estimates of the enhanced cardiovascular disease risk conferred by defined increments of plasma tHcy, we estimate that 66AA homozygotes have, on average, an approximately 4% increase in cardiovascular disease risk compared to 66GG homozygotes. This study provides the first evidence that the MTRR A66G polymorphism significantly influences the circulating tHcy concentration.


The availability of original data and statistics: an improvement in good publication practice.
The purpose of this paper is to highlight the aspects of good publication practices, with particular reference to data analysis, and to propose an innovative initiative for improving the quality of scientific information in this field. Several committees within the scientific community provide information and publish guidelines in order to support scientists in the application of good publication practices and to improve quality in medical research. Those guidelines suggest that the possibility of verifying the original data warrants the reliability of the published results by reducing the occurrence of misconduct related to data analysis. The initiative proposed in this article is aimed at making the original data and the statistical reports available to the scientific community together with the actual paper. Such a practice is undoubtedly an improvement in the quality of publication permitting verification of the results as well as allowing for further elaboration of the same data.


Inhibiting tumor growth of colorectal cancer by blocking the expression of vascular endothelial growth factor receptor 3 using interference vector-based RNA interference.
Many reports show that vascular endothelial growth factor receptor 3 (VEGFR3) plays an essential role in tumor metastasis and is a promising target for cancer therapy. The present study was designed to determine the role of VEGFR3 in tumor growth using RNA interference (RNAi) technology. Three small interfering RNA (siRNA) sequences for the VEGFR3 gene were cloned into expression plasmids (pSUPER) and transfected into human colorectal carcinoma (CRC) LoVo cells. Stable transfection of these plasmids decreased VEGFR3 protein expression, leading to the potent suppression of tumor cell proliferation and lymphangiogenesis in vitro. Furthermore, we selected the most effective silenced expressor vector and injected it and pSUPER vector into a tumor xenograft model in nude mice. The tumor growth of LoVo cells expressing VEGFR3 siRNA were significantly inhibited compared with cells transfected with control vector alone. Immunohistochemical analyses of tumor sections revealed a decreased vessel density and decreased VEGFR3 expression in animals when siRNA against VEGFR3 was expressed. These results showed that RNAi of VEGFR3 is an effective tool to reduce lymphangiogenesis in CRC.


Pseudoxanthoma elasticum: a rare cause of gastrointestinal bleeding.
Pseudoxanthoma elasticum (PXE) is a rare connective tissue disorder. The main clinical features of this condition are characteristic skin lesions, angioid streaks of the fundus oculi, and occlusive vascular disease. Gastric hemorrhage is a rare complication. A gastroscopic examination was performed on two patients with PXE who presented with upper gastrointestinal tract bleeding. The two patients had submucosal yellowish nodular lesions similar to the xanthoma-like skin lesions seen in the disease. We suggest that a diagnosis of PXE be considered for any patient with gastrointestinal hemorrhage, especially if routine clinical and endoscopic examination fail to reveal the cause, and if raised yellow plaque-like lesions are seen in the stomach by endoscopy.


[Dysembryoplastic neuroepithelial tumor (DNT)--case report and literature review].
Neuroepithelial dysembryoplastic tumour was first described by Daumas-Duport in 1988 and in WHO classification was included into the group of neuronal and mixed neuroglial tumours. This is a benign and very rare tumor with a good prognosis occurring in children and young adults. The tumour caused characteristic clinical symptoms: epileptic fits, supratentorial, intracortical localisation, most often in temporal lobe and specific nodular architecture with heterogenic cell composition. Oligodendrocyte-like cells, glial and neuronal elements are usually found. The authors present a case of a 24-years old female with partial epileptic sensorial symptomatology. CT examination revealed a tumour in the left parietal lobe. Histological findings showed a typical texture of DNT. The tumour has no tendency for recurrence even in case of incomplete removal and does not require chemotherapy nor radiotherapy which is significantly important for accurate diagnosis, in order to avoid an aggressive therapy in young patients.


Frequency range extension of spectral analysis of pulse rate variability based on Hilbert-Huang transform.
Heart rate variability (HRV) is a well-accepted indicator for neural regulatory mechanisms in cardiovascular circulation. Its spectrum analysis provides the powerful means of observing the modulation between sympathetic and parasympathetic nervous system. The timescale of HRV is limited by discrete beat-to-beat time intervals; therefore, the exploration region of frequency band of HRV spectrum is relatively narrow. It had been proved that pulse rate variability (PRV) is a surrogate measurement of HRV in most of the circumstances. Moreover, arterial pulse wave contains small oscillations resulting from complex regulation of cardiac pumping function and vascular tone at higher frequency range. This study proposed a novel instantaneous PRV (iPRV) measurement based on Hilbert-Huang transform. Fifteen healthy subjects participated in this study and received continuous blood pressure wave recording in supine and passive head-up tilt. The result showed that the very-high-frequency band (0.4-0.9 Hz) varied during head-up tilt and had strong correlation (r = 0.77) with high-frequency band and medium correlation (r = 0.643) with baroreflex sensitivity. The very-high-frequency band of iPRV helps for the exploration of non-stationary autoregulation and provides the non-stationary spectral evaluation of HRV without distortion or information loss.


Genetic hypertension accelerates nephropathy in the streptozotocin diabetic rat.
To evaluate whether hypertension is a cause or just an association with diabetic renal disease, diabetes was induced in both normotensive Wistar-Kyoto and spontaneously hypertensive rats (WKY and SHR). Animals were assessed monthly for 8 months before sacrifice. When compared to normotensive diabetic rats (WKY-STZ), hypertensive diabetic rats (SHR-STZ) had an earlier and more rapid rise in urinary albumin excretion. In addition, SHR-STZ had increased glomerular basement membrane thickness when compared to WKY-STZ or SHR. In a separate experiment, Enalapril therapy (35 mg/L) was administered in drinking water to WKY-STZ and SHR-STZ. Enalapril significantly reduced blood pressure in both animal groups, and this was associated with a decrease in urinary albumin excretion. The SHR-STZ model has accelerated nephropathy as determined by both functional and structural parameters. Angiotensin-converting enzyme inhibition is associated with a reduction in albuminuria in both hypertensive and normotensive models of diabetic nephropathy.


Low-angle vascular access for neurovascular procedures using the Arstasis AXERA access device.
To evaluate the safety and efficacy of the Arstasis AXERA access device in patients undergoing neuroendovascular procedures. A single-center retrospective study of 94 patients undergoing neurovascular procedures with the use of an AXERA arterial access device was performed. The procedures were performed with 5-6-F vascular sheaths, and hemostasis was obtained with manual compression. A total of 104 neurovascular procedures (81 diagnostic, 23 interventional) were performed in 94 subjects. Eighty-seven procedures (83%) were performed with a 5-F sheath, and 17 procedures (16%) used a 6-F sheath. Intravenous heparin was administered in 64 procedures (61%), and 32 patients (30%) were taking antiplatelet medications at the time of the procedure. Median time to hemostasis was 4 minutes with manual compression, and outpatients undergoing diagnostic angiography were permitted to ambulate at 1 hour. Complications occurred in a total of 3% of cases; these included one local hematoma (1%) and two failed procedures (2%). The new AXERA arterial access device modifies the arterial puncture angle in an attempt to reduce manual compression and ambulation times.


A new angiographic method to assess coronary flow reserve-validation in humans.
Coronary flow reserve (CFR) is defined as the ratio between coronary artery flow during maximal hyperemia and rest. It is considered as a marker for the integrity of the epicardial coronary circulation and the microcirculation. CFR measurement typically requires the introduction of a guide wire into a diseased coronary artery. We tested a new algorithm, which allows to estimate CFR by analysis of coronary angiograms without the need for direct intracoronary measurements. Twenty seven patients (10 female, mean age 64 +/- 11 years) underwent diagnostic cardiac catheterization for the evaluation of chest pain. A Doppler wire was introduced into the diseased coronary artery and CFR(doppler) was calculated by the flow velocity ratio between rest and maximal hyperemia, induced by intravenous administration of 140 microg of adenosine per kg bodyweight. This was compared to the angiographically determined CFR (CFR(angio)) under the same conditions (rest and induced maximal hyperemia) by densitometry. CFR(angio) was based on the creation of two time density curves representing the disappearance of contrast over time. CFR(angio) was the resulting ratio between the density values during hyperemia and rest. An excellent correlation was found between CFR(doppler) and CFR(angio): CFR(angio) = 1 x CFR(doppler) (r = 0.87; P < 0.0001). The average absolute difference between both indeces was 0.36 +/- 0.31. Measurement of CFR(angio) by densitometry is feasible and provides results, which are comparable to Doppler-derived intracoronary flow velocity measurements.


Smooth muscle relaxing activity of gentiopicroside isolated from Gentiana spathacea.
Bioassay directed fractionation of the (1:1) chloroform-methanol extract of Gentiana spathacea H.B.K (Gentianaceae) led to the isolation of gentiopicroside (gentiopricrin) (1), the major spasmolytic component of the plant. Gentiopicroside inhibited, in a concentration-dependent manner, the spontaneous contractions of isolated guinea pig ileum. Contractions induced by histamine, acetylcholine, BaCl2 and KCl on the ileum were also significantly blocked by this monoterpene glucoside, which suggests that this compound might be interfering with calcium influx into the smooth muscle cells.


Initial evaluation of Advanced Collapsed cone Engine dose calculations in water medium for I-125 seeds and COMS eye plaques.
To investigate the dose calculation accuracy in water medium of the Advanced Collapsed cone Engine (ACE) for three sizes of COMS eye plaques loaded with low-energy I-125 seeds. A model of the Oncura 6711 I-125 seed was created for use with ACE in Oncentra® Brachy (OcB) using primary-scatter separated (PSS) point dose kernel and Task Group (TG) 43 datasets. COMS eye plaque models of diameters 12, 16, and 20 mm were introduced into the OcB applicator library based on 3D CAD drawings of the plaques and Silastic inserts. To perform TG-186 level 1 commissioning, treatment plans were created in OcB for a single source in water and for each COMS plaque in water for two scenarios: with only one centrally loaded seed, or with all seed positions loaded. ACE dose calculations were performed in high accuracy mode with a 0.5 × 0.5 × 0.5 mm3 calculation grid. The resulting dose data were evaluated against Monte Carlo (MC) calculated doses obtained with MCNP6, using both local and global percent differences. ACE doses around the source for the single seed in water agreed with MC doses on average within < 5% inside a 6 × 6 × 6 cm3 region, and within < 1.5% inside a 2 × 2 × 2 cm3 region. The PSS data were generated at a higher resolution within 2 cm from the source, resulting in this improved agreement closer to the source due to fewer approximations in the ACE dose calculation. Average differences in both investigated plaque loading patterns in front of the plaques and on the plaque central axes were ≤ 2.5%, though larger differences (up to 12%) were found near the plaque lip. Overall, good agreement was found between ACE and MC dose calculations for a single I-125 seed and in front of the COMS plaques in water. More complex scenarios need to be investigated to determine how well ACE handles heterogeneous patient materials.


[Abdominal myomectomy and subsequent fertility].
45 cases of myomectomy in infertile patients were analyzed. The study of the couples problem did not report another cause of the infertility. The number and localization of the tumors did not alter the prognostic of the fertility. We had 23 pregnancies (51%), all this surgeries must be made by strictly microchirurgical technique, so the rates of success will be improved.


Collateral projections from vestibular nuclear and inferior olivary neurons to lobules I/II and IX/X of the rat cerebellar vermis: a double retrograde labeling study.
Axon collateral projections to various lobules of the cerebellar cortex are thought to contribute to the coordination of neuronal activities among different parts of the cerebellum. Even though lobules I/II and IX/X of the cerebellar vermis are located at the opposite poles in the anterior-posterior axis, they have been shown to receive dense vestibular mossy fiber projections. For climbing fibers, there is also a mirror-image-like organisation in their axonal collaterals between the anterior and posterior cerebellar cortex. However, the detailed organisation of mossy and climbing fiber collateral afferents to lobules I/II and IX/X is still unclear. Here, we carried out a double-labeling study with two retrograde tracers (FluoroGold and MicroRuby) in lobules I/II and IX/X. We examined labeled cells in the vestibular nuclei and inferior olive. We found a low percentage of double-labeled neurons in the vestibular nuclei (2.1 ± 0.9% of tracer-labeled neurons in this brain region), and a higher percentage of double-labeled neurons in the inferior olive (6.5 ± 1.9%), especially in its four small nuclei (18.5 ± 8.0%; including the β nucleus, dorsal cap of Kooy, ventrolateral outgrowth, and dorsomedial cell column), which are relevant for vestibular function. These results provide strong anatomical evidence for coordinated information processing in lobules I/II and IX/X for vestibular control.


Anatomical and radiological evaluation of the triangular fibrocartilage complex of the wrist.
109 wrists from 69 cadavers (mean age 74 years) have been studied to clarify the pathology and morphology of the triangular fibrocartilage complex (TFCC) and to correlate pathological and radiological findings. Perforation of the TFCC was observed in 65% of the specimens and was considered to be secondary to a degenerative process, because it was often accompanied by degenerative changes in the ulnar carpal bones and perforation of the lunotriquetral ligament. To detect TFCC perforations on plain postero-anterior radiographs, it is important to evaluate ulnar plus variance and degenerative changes in the ulnar carpus. Existence of ulnar plus variance alone is more sensitive but less specific in detection of TFCC perforation than the existence of degenerative changes in the ulnar carpus.


Effects of administration of cholecystokinin into the VTA on DA overflow in nucleus accumbens and amygdala of freely moving rats.
The carboxyterminal octapeptide of cholecystokinin (CCK-8) coexists with dopamine (DA) in mesolimbic neurons of the ventral tegmental area (VTA). In the present study, in vivo microdialysis in freely moving rats was used to assess the relative effects of sulfated CCK-8 (CCK-8S), unsulfated CCK-8 (CCK-8US) and CCK tetrapeptide (CCK-4), focally injected into the VTA, on DA overflow in two mesolimbic DA/CCK-8S terminal regions, the nucleus accumbens and the amygdala. Consistent with electrophysiological findings, microinjection of CCK-8S, but not CCK-8US or CCK-4, elicited increases in DA overflow in both terminal regions. In the absence of anatomical evidence of CCK-containing fibers in the VTA region, it seems reasonable to conclude that the modulation of terminal DA overflow by CCK-8S through actions at the somatodendritic region represents a form of autoregulation of these cells. Whereas CCK-8US and CCK-4 are preferential CCK-B receptor agonists, CCK-8S binds non-selectively to CCK-A and CCK-B receptors. Thus, these results implicate CCK-A receptors in the stimulatory effects of CCK-8S on VTA DA neurons.


Effects of a novel calcium aluminate cement on the early events of the progression of osteogenic cell cultures.
The present study evaluated the progression of osteogenic cell cultures exposed to a novel calcium aluminate cement (CAC+) in comparison with the gold standard mineral trioxide aggregate (MTA). Cells were enzimatically isolated from newborn rat calvarial bone, plated on glass coverslips containing either CAC+ or a control MTA samples in the center, and grown under standard osteogenic conditions. Over the 10-day culture period, roundening of sample edges was clearly noticed only for MTA group. Although both cements supported osteogenic cell adhesion, spreading, and proliferation, CAC+-exposed cultures showed significantly higher values in terms of total cell number at days 3 and 7, and total protein content and alkaline phosphatase activity at day 10. The present in vitro results indicate that the exposure to CAC+ supports a higher differentiation of osteogenic cells compared with the ones exposed to MTA. Further experimental studies should consider CAC+ as a potential alternative to MTA when the repair of mineralized tissues is one of the desired outcomes in endodontic therapy.


DNA recombination as a possible mechanism in declarative memory: a hypothesis.
The durability of declarative memory suggests that it has either a chemical or a structural basis. Current models of long-term memory are based on the general assumption that traces of memory are stored by structural modifications of synaptic connections, resulting in alterations in the patterns of neural activity. Changes in gene expression, regulated at both the transcriptional and the translational levels, are considered essential for structural synaptic modifications. Here we present an alternative hypothesis stating that permanent memory has a chemical rather than a structural basis. We suggest that the mechanism of memory coding in the brain is similar to that in the immune system so that the permanence of memories in the nervous system is ensured at the genomic level by a somatic recombination mechanism. Thus, we hypothesize that traces of permanent declarative memory might present within cerebral neurons in the form of novel proteins coded by the modified genes. This discussion is intended to provide evidence in support of a DNA recombination mechanism for memory storage in the brain and to stimulate further research working toward the evaluation of this hypothesis.


[Rapid virus diagnosis by electrosyneresis (author's transl)].
Electrosyneresis (counter-current immunoelectrophoresis) detected the presence of 7 coxsackieviruses and 1 poliovirus in 70 specimens of stools. Identical results were obtained by inoculation of mice and tissue cultures. First screening of specimens was undertaken with a human "standard" gammaglobulin; only specimens precipitating with this reagent contained viral antigens. Hence, especially in children, all negative stools could be excluded from subsequent tests with antiserum pools and monospecific antisera. In our experience, electrosyneresis is a specific method: every type of coxsackievirus and poliovirus types react only with the corresponding monospecific antisera. Electrosyneresis appears to be a sensitive procedure: viral antigens corresponding to 10(4) TCID50/ml can be dtected.


Renal cell carcinomas with t(6;11)(p21;q12): A clinicopathologic study emphasizing unusual morphology, novel alpha-TFEB gene fusion point, immunobiomarkers, and ultrastructural features, as well as detection of the gene fusion by fluorescence in situ hybridization.
Renal cell carcinomas (RCCs) with t(6;11)(p21;q12) are extremely rare and characterized by specific chromosome translocation, involving the transcription factor EB (TFEB). Fewer than 30 cases have been described in the literature. We examined 7 additional cases of this rare tumor by clinicopathologic, immunohistochemical, molecular, and ultrastructural analyses. Four tumors had the typical morphologic features of TFEB RCCs, whereas 3 cases demonstrated uncommon morphologic features, mimicking epithelioid angiomyolipoma, chromophobe cell RCC, and clear cell RCC, respectively. Immunohistochemically, aside from TFEB and cathepsin K, kidney-specific cadherin was another sensitive and relatively specific marker for TFEB RCCs, supporting a distal nephron origin for these renal tumors. We also observed different ultrastructures including mitochondrion with areas of lipofuscin pigment in the smaller cells in these cases. An identical Alpha-TFEB fusion gene, 486 bp, was identified in 2 cases. In addition to the polymerase chain reaction method, we also developed a fluorescence in situ hybridization assay to serve as a cost-effective and time-efficient diagnostic tool. We detected a TFEB gene rearrangement in all 7 cases using the fluorescence in situ hybridization method. TFEB RCC seemed to be an indolent tumor. During a mean follow-up of 31 months, none of the cases developed tumor recurrence, progression, or metastasis.


The intermediate-conductance Ca2+ -activated K+ channel (KCa3.1) in vascular disease.
The intermediate-conductance Ca(2+)-activated K(+) channel (K(Ca)3.1) was first described by Gardos in erythrocytes and later confirmed to play a significant role in T-cell activation and the immune response. More recently, K(Ca)3.1 has been characterized in numerous cell types which contribute to the development of vascular disease, such as T-cells, B-cells, endothelial cells, fibroblasts, macrophages, and dedifferentiated smooth muscle cells (SMCs). Physiologically, K(Ca)3.1 has been demonstrated to play a role in acetylcholine and endothelium-derived hyperpolarizing factor (EDHF) induced hyperpolarization, and thus control of blood pressure. Pathophysiologically, K(Ca)3.1 contributes to proliferation of T-cells, B-cells, fibroblasts, and vascular SMCs, as well as the migration of SMCs and macrophages and platelet coagulation. Recent studies have indicated that blockade of K(Ca)3.1, by specific blockers such as TRAM-34, could prove to be an effective treatment for vascular disease by inhibiting T-cell activation as well as preventing proliferation and migration of macrophages, endothelial cells, and SMCs. This vasculoprotective potential of K(Ca)3.1 inhibition has been confirmed in both rodent and swine models of restenosis. In this review, we will discuss the physiological and pathophysiological role of K(Ca)3.1 in cells closely associated with vascular biology, and the effect of K(Ca)3.1 blockers on the initiation and progression of vascular disease.


Combined HQSAR method and molecular docking study on genotoxicity mechanism of quinolones with higher genotoxicity.
Using the hologram quantitative structure-activity relationship (HQSAR) method, a quantitative model of the structure-activity relationship between the genotoxicity of quinolones towards gram-negative bacteria and structure of quinolones is constructed. A series of novel quinolones are designed, and 4 environmentally friendly quinolone derivatives are finally selected, because of their enhanced genotoxicity towards gram-negative/positive bacteria, decreased bioconcentration and increased photodegradability and biodegradability. The mechanisms underlying the genotoxicity of quinolones and its derivatives are analysed based on amino acid residues and molecular interactions. Three hydrophilic amino acids [arginine (ARG), asparagine (ASN) and aspartic acid (ASP)] play important roles in the antibacterial effects of quinolones. The introduction of highly hydrophilic groups into the C-7 position of amifloxacin (AMI) not only improved the stability of the AMI derivative-topoisomerase IV-DNA complex but also improved the antibacterial activities of AMI derivatives.


Confocal fluorescence lifetime imaging of free calcium in single cells.
Ca(2+) concentrations in biological cells are widely studied with fluorescent probes. The probes have a high selectivity for free calcium and exhibit marked changes in their photophysical properties upon binding. The differences in the fluorescent lifetime of the probes can now be used as a contrast mechanism for imaging purposes. This technique can be further exploited for the quantitative determination of ion concentrations within the cells. We describe the use of a fast fluorescence lifetime imaging method in combination with a standard confocal laser scanning microscope for the determination of Ca(2+) concentrations in single rat cardiac myocytes using the intensity probe Calcium Green.


Age-related differentiation in newly generated DCX immunoreactive neurons in the subgranular zone of the gerbil dentate gyrus.
In the present study, we investigated age-related changes of newborn neurons in the gerbil dentate gyrus using doublecortin (DCX), a marker of neuronal progenitors which differentiate into neurons in the brain. In the postnatal month 1 (PM 1) group, DCX immunoreactivity was detected in the subgranular zone of the dentate gyrus, but DCX immunoreactive neurons did not have fully developed processes. Thereafter, DCX immunoreactivity and its protein levels in the dentate gyrus were found to decrease with age. Between PM 3 and PM 18, DCX immunoreactive neuronal progenitors showed well-developed processes which projected to the granular layer of the dentate gyrus, but at PM 24, a few DCX immunoreactive neuronal progenitors were detected in the subgranular zone of the dentate gyrus. DCX protein level in the dentate gyrus at PM 1 was high, thereafter levels of DCX were decreased with time. The authors suggest that a decrease of DCX immunoreactivity and its protein level with age may be associated with aging processes in the hippocampal dentate gyrus.


Transmembrane 6 superfamily 1 (Tm6sf1) is a novel lysosomal transmembrane protein.
The lysosome is a membrane-bound organelle involved in the turnover of various intracellular and extracellular macromolecules. These are degraded by acidic hydrolases in the lumen of lysosome. The lysosomal membrane is important not only in retaining the acidic hydrolases to protect cells against cytosolic proteolysis, but it also facilitates protein trafficking though organelle fusion. In this study, we report on a novel lysosomal membrane protein transmembrane 6 superfamily 1 (Tm6sf1). Expression of Tm6sf1-DsRed fusion proteins in HEK293A cells displayed punctate or ringlike vesicles, which colocalized with conventional lysosome markers including LAMP1/2, RAB7, and Rnf167. Using fluorescence time-lapse live cell imaging, we demonstrated the fusion of Tm6sf1 vesicles with lysosomes and the integration of Tm6sf1 into the lysosomal membrane. We also examined the expression of Tm6sf1 in mouse tissues and found immunopositive signals in major organs such as the cerebellum, kidney, and intestine. These data suggest that Tm6sf1 is a widely expressed lysosomal transmembrane protein and can be used as a novel marker of lysosome.


Close proximity to busy roads increases the prevalence and onset of cardiac disease--Results from RHINE Tartu.
To analyze whether living close to a busy road would increase the risk of having cardiac disease and hypertension. Longitudinal cross-sectional study. We used cross-sectional longitudinal questionnaire data from the RHINE study for Tartu in 2000/2001 and 2011/2012. Home addresses of the respondents were geocoded and traffic data obtained from annually conducted traffic counts in Tartu. Relationships between proximity to a busy road and self-reported cardiac disease and hypertension were analyzed with multiple logistic regression. In terms of total traffic (≥10,000 vehicles per day) within a 150-m zone of a busy road, the odds ratio (OR) for prevalence of cardiac disease was significant in 2000/2001 (1.91, 95% CI 1.15-3.16) and 2011/2012 (1.58, 95% CI 1.01-2.47). Prevalence of hypertension was significant only in 2011/2012 (1.61, 95% CI 1.08-2.39). In terms of heavy duty vehicle traffic (≥500 vehicles per day) within a 150-m zone in 2000/2001, the OR was 1.52 (95% CI 1.04-2.24) and 1.49 (95% CI 1.02-2.17) respectively for the prevalence of cardiac disease and hypertension. In 2011/2012 no significant relationship between heavy duty vehicle traffic and cardiac disease or hypertension was found. We also saw a significant relationship between total traffic and the onset of cardiac disease (OR = 2.04, 95% CI 1.07-3.87). This study showed that living closer than 150 m to a busy road can increase the odds of having cardiac disease and hypertension, which should be taken into account in city planning.


Determination of a structural ensemble representing the dynamics of a G-quadruplex DNA.
It is increasingly recognised that the structure and dynamics of G-quadruplex DNA are dictated by its sequence and greatly affected by environmental factors. The core guanine tetrads (G-tetrads) coordinate cations and display a strong conformational rigidity compared with the connecting loops. Although long loops linking the G-tetrads are typically disfavoured, when present, they provide a striking view of the dynamics of short, single-stranded DNA regions. In addition to their role in determining the stability of the G-quadruplex state, these loops are potential drug targets. In order to characterise accurately the dynamics of this DNA state, we apply the principles of structural ensemble determination developed in the last two decades for protein molecules to DNA molecules. We thus performed extensive molecular dynamics simulations restrained with NMR residual dipolar couplings to determine a structural ensemble of the human CEB25 minisatellite G-quadruplex, which contains a connecting loop of 9 nucleotides. This structural ensemble displays a wide set of arrangements for the loop and a compact, well-defined G-quadruplex core. Our results show that stacking interactions dominate over intra-residue contacts in the loop and strengthen the ability of the closing base pairs to confer a large thermodynamic stability to the structure.


Analysis of glutathione and glutathione disulfide in human saliva using hydrophilic interaction chromatography with mass spectrometry.
A sensitive method for the determination of glutathione (GSH) and glutathione disulfide (GSSG) in human saliva was developed and validated. GSH was captured and stabilized by the addition of N-ethylmaleimide (NEM). Solid-phase extraction (SPE) using an Oasis MAX extraction cartridge was employed for sample preparation and analysis was performed on a Shimadzu LCMS-2010 A that was operated in the single ion monitoring mode using positive ion electrospray ionization (ESI) as the interface. The monitored ion for GSH-NEM was m/z 433 and that for GSSG was m/z 613. Chromatography was carried out on an Atlantis HILIC silica column (150 mm x 2.1 mm, 5 microm) with acetonitrile and formate buffer as the mobile phase at the flow rate of 0.2 ml/min. The calibration curve was linear over the range of 0.1-100 microM for GSH-NEM. The extraction recoveries of GSH-NEM spiked at concentrations of 25 and 50 microM were 97.1 and 104.4%, respectively. Similar results were obtained for GSSG. The newly developed hydrophilic interaction chromatography with mass spectrometry (HILIC/MS) method showed superior sensitivity for the determination of GSH and GSSG in human saliva samples.


Defining the need for radiotherapy for lung cancer in the general population: a criterion-based, benchmarking approach.
We have previously used an evidence-based, epidemiologic approach to estimate the proportion of incident cases that should be treated with radiotherapy (RT) for lung cancer. The first objective of the present study was to compare this evidence-based estimate of the appropriate rate of use of RT with the rates observed in selected "benchmark" communities where there are no barriers to the appropriate use of RT and no incentives to the unnecessary use of RT. The second objective of the study was to compare the rates of use of RT in the general populations in the United States and Canada with the estimated appropriate rate. We established benchmark rates for the use of RT for lung cancer in Ontario, Canada, where: 1) residents make no direct payments for RT; 2) all RT is provided by site-specialized radiation oncologists in multidisciplinary cancer centers, and 3) radiation oncologists receive a salary in lieu of technical fees. Communities located close to cancer centers without long waiting lists for RT were selected to serve as benchmarks. Prospectively gathered electronic treatment records from all RT cancer centers were linked to the provincial cancer registry to describe the rate of use of RT in Ontario. The public use file of Surveillance, Epidemiology and End Results Registries (SEER) was used to describe the use of RT in the United States. Overall, 41.3% (95% confidence interval [CI], 39.9%, 42.7%) of incident cases of lung cancer received RT as part of their initial management in the benchmark communities compared with the evidence-based estimate of 41.6% (95% CI, 39.2%, 44.1%). The rate of use of RT in the initial management of nonsmall cell lung cancer (NSCLC) in the benchmark communities was 49.3% (95% CI, 47.5%, 51.1%) compared with the evidence-based estimate of 45.9% (95% CI, 41.6%, 50.2%). The use of RT in the initial management of small-cell lung cancer (SCLC) in the benchmark communities was 47.0% (95% CI, 43.3%, 50.7%) compared with the evidence-based estimate of 45.4% (95% CI, 42.4%, 48.4%). In many counties of Ontario, the observed rates of RT use in the initial management of lung cancer were significantly lower than either the benchmark rate or the evidence-based estimate of the appropriate rate. In contrast, rates of use of RT in most counties in the SEER regions of the United States were close to, or higher than, the estimated appropriate rate. The observed benchmark rate converged on the evidence-based estimate of the appropriate rate of use of RT for lung cancer, suggesting that either measure might reasonably be used as a "standard" against which to compare rates observed in similar populations elsewhere.


Effectiveness of culturally focused interventions in increasing the satisfaction of hospitalized Asian patients: a systematic review.
Patient satisfaction is a driving force for healthcare organizations to enhance patient services. As the Asian population in the United States is increasing at a significant rate, it is important to understand the needs of this population to implement culturally focused services that will lead to increased Asian in-patient satisfaction. The objective of the systematic review was to identify the best available evidence on the effectiveness of culturally focused interventions in increasing satisfaction of hospitalized adult Asian patients. This review considered studies that included Asian adults, 18 years of age and older, who were admitted to acute-care hospitals in countries where Asians are a minority culture. This review considered studies that included any intervention or sets of interventions implemented by hospitals for the purpose of making the hospital experience consistent with the cultural preferences of adult Asian in-patients. Satisfaction of adult Asian hospitalized patients as measured by self-report satisfaction scales or tools considered by accrediting and/or governing bodies to be acceptable sources of evidence of patients' perceptions of their care. This review first considered randomized controlled trials (RCTs), non-RCTs and quasi-experimental studies. As no RCTs or quasi-experimental studies were found, the reviewers also considered before and after studies, cohort studies and case-control studies for inclusion. This review also considered for inclusion descriptive study designs including case series, individual case reports and descriptive cross-sectional studies related to the adult Asian population in acute-care hospital settings. Three descriptive studies were selected in the review. The search strategy aimed to find both published and unpublished studies in English and Chinese (Mandarin and Cantonese) languages. A search of MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Educational Research Information Clearinghouse (ERIC), the Cochrane Library, the Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports, Scopus, Excerpta Medical Databases (Embase) and Academic Search Premier was conducted, followed by a reference search of relevant studies and a gray literature search of the Virginia Henderson Library, Google Scholar, Mednar, conference proceedings and websites. The initial key words searched were patient satisfaction, culturally focused, hospitals, Asian-American and adult. Data were extracted using a standardized critical appraisal checklist and data extraction instrument from the Joanna Briggs Institute. Due to the statistical and methodological heterogeneity between included studies, statistical meta-analysis was not possible. Results are presented in a narrative summary. Three descriptive studies were reviewed with sample sizes ranging from 107 to 19,583 and a total of 386 Asian participants. Two of the studies reported on nine measures of patient satisfaction, whereas the third provided data on four measures. The interventions identified were: communication between physician/registered nurse and patient, cultural services, Asian social workers, interpreters, and cultural food. The first study included intervention groups that were exposed to inpatient information on hospitalized Chinese cultural services compared to the "usual care" control. The percentage of patients' satisfaction in the group who knew about the services (95%) was significantly higher (p < 0.01). In the same study, patients' satisfaction with nurses was higher (95%) in patients with nurses who were aware of Chinese cultural services, compared to patients with nurses who were unaware (83%) (p < 0.01). The second study developed a survey measuring 'Level of Top Box' satisfaction of Chinese patients in Chinese unit ('Informed of Chinese Culture Service') and non-Chinese unit ('Usual Care') with the outcome measure for patient satisfaction without p value. The two studies showed an increase in Asian inpatient satisfaction with communication between the physician/registered nurse and patient, as well as with pain control and quietness of the room. Also, two studies used the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) questions as patient satisfaction surveys. The third study was a descriptive/comparative secondary analysis of HCAHPS and Cultural Competency Assessment Tool for Hospitals (CCATH) surveys. There was also no p value for patient satisfaction measurement. The design and analysis of this study was more complex, using hospital wide-cultural competency and addressing factors such as race and language ability (English and non-English speakers). The surveys completed in Chinese were less than 0.1% of the sample size and the Asian data were eliminated. This study also showed that a greater degree of cultural competence in hospitals was positively associated with patient satisfaction with doctors' communication (P < 0.05). Evidence was insufficient to demonstrate cause and effect. Results suggest that culturally competent communication with patients by physicians and registered nurses, quietness of the room, information about treatments and procedures, and cultural foods are associated with increased satisfaction among hospitalized adult Asian patients.


Increasing public support for supervised injection facilities in Ontario, Canada.
To determine the level and changes in public opinion between 2003 and 2009 among adult Canadians about implementation of supervised injection facilities (SIFs) in Canada. Population-based, telephone survey data collected in 2003 and 2009 were analysed to identify strong, weak, and intermediate support for SIFs. Ontario, Canada Representative samples of adults aged 18 years and over. Analyses of the agreement with implementation of SIFs in relation to four individual SIF goals and a composite measure. The final sample sizes for 2003 and 2009 were 1212 and 968, respectively. Between 2003 and 2009, there were increases in the proportion of participants who strongly agreed with implementing SIFs to: reduce neighbourhood problems (0.309 versus 0.556, respectively); increase contact of people who use drugs with health and social workers (0.257 versus 0.479, respectively); reduce overdose deaths or infectious disease among people who use drugs (0.269 versus 0.482, respectively); and encourage safer drug injection (0.213 versus 0.310, respectively). Analyses using a composite measure of agreement across goals showed that 0.776 of participants had mixed opinions about SIFs in 2003, compared with only 0.616 in 2009. There was little change among those who strongly disagreed with all SIF goals (0.091 versus 0.113 in 2003 and 2009, respectively). Support for implementation of supervised injection facilities in Ontario, Canada increased between 2003 and 2009, but at both time-points a majority still held mixed opinions.


Colloidal soft matter as drug delivery system.
Growing interest is being dedicated to soft matter because of its potential in delivering any type of drugs. Since hydrophilic, lipophilic, small and big molecules can be loaded into these colloidal systems and administered through the parenteral or nonparenteral route, soft matter systems have been used to solve many biomedical and pharmaceutical problems. In fact, they make possible to overcome difficulties in the formulation and delivery of poorly water-soluble drug molecules, settle some stability issues typical of biological drug molecules, design parenteral sustained release forms and provide functionalized soft particles that are very effective in drug targeting. This review deals with the important role that colloids play in the drug delivery and targeting, with particular attention to the more currently used systems such as microemulsions, organogels, liposomes, micelles, and dendrimers. Though significant progress has been made in drug targeting, some challenges still remain. Further efforts will be required to better understand the characteristics of targets and to discover new ones. In-depth knowledge of the physico-chemical structure and properties of the systems used for targeting is fundamental for understanding the mechanism of interaction with the biological substrate and the consequent drug release.


Clinical features and pattern of indeterminate colitis: Crohn's disease with ulcerative colitis-like clinical presentation.
Although an accurate diagnosis of inflammatory bowel disease (IBD) and differentiation between ulcerative colitis (UC) and Crohn's disease (CD) can be made in most patients, it is sometimes impossible to distinguish UC from CD even after thorough pathological study. Recently, clinicians have used the term indeterminate colitis (IC) for patients with features of both diseases that overlap temporarily or persistently. The frequency, reasons, and outcome of patients with a clinical diagnosis of IC based on radiological, endoscopic, and histopathological findings were investigated retrospectively. Based on records of 735 patients with IBD, IC was defined as having features of both UC and CD, with differentiation from each other impossible at least once during the observation period (average 6.8 years) based on diagnostic criteria using endoscopic, radiological, and histological findings. Twenty-three patients were identified as having IC. They were classified into three patterns according to the clinical course and the final diagnosis: (1) UC changing to CD (n = 8); (2) CD changing to UC (n = 5); and (3) UC or CD (n = 10). The frequency of IC was 24.5%-43.4% of colitis-type CD (n = 53), 2.3%-6.5% of all CD (n = 352), and 3.1% of IBD (n = 735). The reasons for the indetermination were temporary (56.5%) or persistent (43.5%) overlapping of UC-like and CD-like presentations. Treatment of IC was inappropriate in only two patients, and the prognoses of all patients except one were fairly good. Overlapping of UC-like presentations (persistent bloody stool and diffuse colitis) was frequently observed with Crohn's colitis but less so in CD patients during their clinical course. The basis of differentiation and treatment of IC needs more attention.


Autonomic nervous system arousal and cognitive functioning in bipolar disorder.
Previous theories about the etiology of cognitive dysfunction in bipolar disorder (BD) emphasized trait factors such as neurological impairment. State factors, other than mood symptoms, that may exacerbate functional deficits have not yet been considered. The purpose of this study was to examine autonomic nervous system (ANS) arousal following cognitive challenge. The study compared patients with BD and healthy controls (HC) in physiological measures and neuropsychological test scores. Thirty euthymic patients with BD and 22 HC completed the study. Participants completed mood [Beck Depression Inventory-II (BDI-II) and Young Mania Rating Scale (YMRS)], anxiety (State-Trait Anxiety Inventory), and substance abuse (Drug Abuse Screening Test-20 item and Alcohol Use Disorders Identification Test) measures. They were connected to an electrogram, a sensitive thermometer for measuring finger temperature, and electrodes that measure galvanic skin response. After a five-min baseline measurement in a restful state, participants completed a computerized neuropsychological battery (CNS Vital Signs). The group with BD reported significantly more mood symptoms (BDI-II, t = 3.71, p < 0.001; YMRS, t = 6.73, p < 0.001) and scored higher on a measure of trait-anxiety (State-Trait Anxiety Inventory, t = 2.91, p < 0.001) than HC. A multivariate analysis of variance revealed higher arousal on all physiological measures in the BD group relative to HC at baseline [F(3,48) = 13.1, p < 0.001] and during cognitive testing [F(3,48) = 11.3, p < 0.001]. The increase in physiological arousal from a restful state to the time of testing was higher for the BD group [F(3,37) = 8.06, p < 0.001]. With respect to cognitive data, HC scored higher than patients with BD across the measures of memory (F = 8.5, p < 0.001), sustained (F = 9.5, p < 0.001) and complex (F = 2.7, p < 0.04) attention, processing speed (F = 10.0, p < 0.001), reaction time (F = 7.8, p < 0.001), cognitive flexibility (F = 19.7, p < 0.001), working memory (F = 10.8, p < 0.001), and social acuity (F = 5.7, p < 0.01), with partial eta-squared from 0.18 to 0.62. Correlational analysis revealed significant associations between various cognitive test scores and changes in physiological arousal from baseline to testing (-0.59 ≤ r ≤ 0.22). Relative to HC, patients with BD experience larger changes in ANS arousal between a restful baseline and cognitive testing, and achieve lower cognitive test scores. Further research is needed to determine whether acute physiological symptoms of anxiety directly compromise cognitive functioning in BD.


Airborne laser Doppler velocimeter.
A CO(2) laser Doppler detection system has been developed to measure remotely the true airspeed of an aircraft. The system uses a 50-W sealed-off CO(2) laser in a homodyne detection system employing a collinear optical telescope, a HgCdTe detector, and a frequency tracking loop. The system was successfully flight tested on a NASA Convair 990 research aircraft during December 1971 and June 1972. The results indicate that an airspeed measurement under clear weather conditions is feasible up to an altitude of 3000 m with an error of less than 0.5%.


Genomic localization of the human gene for KCNA10, a cGMP-activated K channel.
Potassium (K) channels are important components of virtually all cells, and they play critical roles in many cellular functions. KCNA10 represents a new class of K channel specifically regulated by cGMP and postulated to mediate the effects of substances that increase intracellular cGMP. Since KCNA10 has the potential to be useful in candidate gene analysis of inherited diseases, the human gene for KCNA10 was characterized. Fluorescence in situ hybridization indicates that human KCNA10 maps to chromosome 1 at p13.1-->p22.1. Finer mapping of the gene was achieved by PCR of a set of CEPH YAC clones that spanned the region of interest. We found that YAC 818b9 contains human KCNA10. These data indicate human KCNA10 maps to 1p13.1 and resides within the genetic interval defined by microsatellite loci D1S2809 and D1S2726. That region of chromosome 1 contains another K channel gene, KCNA3.


Total knee arthroplasty with rotating-hinge Endo-Model prosthesis: clinical results in complex primary and revision surgery.
Rotating-hinge knee implants are highly constrained devices able to provide the stability needed for arthroplasty in case of severe bone loss and complex instability. Notable doubts still exist in using rotating-hinge devices, mainly due to risk of mechanical failure and risk of infection. We retrospectively evaluated the functional and clinical outcomes in a series of patients treated with the rotating-hinge Endo-Model prosthesis either for primary or revision total knee arthroplasty. Between 1997 and 2009 we implanted 123 Endo-Model prosthesis (118 patients) at our institution. At the time of this study we could evaluate 45 prosthesis (25 primary and 20 revision TKAs) from the clinical and radiological site, with average follow-up of 42.2 months. During the follow-up period, three patients reported complications, which in two cases finally led to revision with explantation. Mean survival of the implants attested at 93.3 %. The average post-operative clinical Knee Society score in the evaluated series was 94.2, the functional one 78.7. The average range of motion was 0°-108°. No signs of joint instability or misalignment were noted. Pain was present in a minority of patients, but always at a mild/occasional extent. No evidences of loosening or implant failure have been reported. No substantial divergences in the outcomes have been found across different patient categories after stratification in agreement with the Knee Society. Coherent with previously published works, we confirm the Endo-Model prosthesis to provide excellent pain relief, restoration of walking capacity and intrinsic knee stability both in complex primary and in revision knee arthroplasty, with good or excellent results in the majority of patients and acceptable complication rate.


[Reconstructive surgery with polypropylene mesh associated with kidney transplant].
There is very little literature on hernial complications of the abdominal wall in association to renal transplantation. The present report aims to evaluate their incidence and type, as well as the intervention carried out and its results. A retrospective analysis of a series of 650 renal transplantations has been carried out between 1978-1996 in our centre. A braided polypropylene mesh (Prolene) was used to repair abdominal wall defects and/or diagnosed hernias in 8 (1.2%) cases: 5 eventrations, 1 inguinal hernia and one combination of both: the last case required extensive debridement of the abdominal wall due to necrotizing fascitis. Mean time to eventration was 47.3 months (range 1-106). In all cases, the mesh was placed in the pre-peritoneal space. Two patients developed complications (one haematoma and one wound infection), though graft removal was not necessary in any case. Follow-up was 33.1 months (range 6-78) with no findings of hernial relapse. One patient started successful chronic ambulatory peritoneal dialysis (CAPD) 30 days after the intervention. The polypropylene mesh is a sound alternative in the treatment of hernial complications associated to renal transplantation, with acceptable morbidity, and efficacy rates that in our series reached 100%.


Subjective and objective changes noted by patients with bronchial asthma taking slow-release aminophylline.
The authors describe a placebo controlled trial of a slow-release form of aminophylline in a total of twenty asthmatic patients. The data resulting from this work confirmed the fact that the aminophylline is a bronchodilator which improves mean peak flow rate and reduces the intake of beta-agonist drugs in the majority of asthmatic patients.