Immobilization of selenite via two parallel pathways during in situ bioremediation.
It is widely understood that selenite can be biologically reduced to elemental selenium. Limited studies have shown that selenite can also be immobilized through abiotic precipitation with sulfide, a product of biological sulfate reduction. We demonstrate that both pathways significantly contribute to selenite immobilization in a microfluidic flow cell having a transverse mixing zone between propionate and selenite that mimics the reaction zone along the margins of a selenite plume undergoing bioremediation in the presence of background sulfate. The experiment showed that red particles of amorphous elemental selenium precipitate on the selenite-rich side of the mixing zone, while long crystals of selenium sulfides precipitate on the propionate-rich side of the mixing zone. We developed a continuum-scale reactive transport model that includes both pathways. The simulated results are consistent with the experimental results, and indicate that spatial segregation of the two selenium precipitates is due to the segregation of the more thermodynamic favorable selenite reduction and the less thermodynamically favorable sulfate reduction. The improved understanding of selenite immobilization and the improved model can help to better design in situ bioremediation processes for groundwater contaminated by selenite or other contaminants (e.g., uranium(IV)) that can be immobilized via similar pathways.


Iliac osteomyelitis in a newborn: a case report.
Pelvis is a rare location of the hematogeneous osteomyelitis during the newborn period. Successful cure of osteomyelitis during the newborn period is dependent on a fast and true diagnosis and on sufficient treatment. In this case report, iliac osteomyelitis of a newborn that was clinically suspected on the fifth day, was diagnosed radiologically and was found to be caused by methicillin-sensitive Staphylococcus aureus, is presented. According to our knowledge, this is the youngest osteomyelitis case in the literature and the third presented iliac osteomyelitis case of the newborn period.


PPARdelta activation inhibits angiotensin II induced cardiomyocyte hypertrophy by suppressing intracellular Ca2+ signaling pathway.
Peroxisome proliferator-activated receptors delta (PPARdelta) is known to be expressed ubiquitously, and the predominant PPAR subtype of cardiac cells. However, relatively less is known regarding the role of PPARdelta in cardiac cells except that PPARdelta ligand treatment protects cardiac hypertrophy by inhibiting NF-kappaB activation. Thus, in the present study, we examined the effect of selective PPARdelta ligand L-165041 on angiotensin II (AngII) induced cardiac hypertrophy and its underlying mechanism using cardiomyocyte. According to our data, L-165041 (10 microM) inhibited AngII-induced [(3)H] leucine incorporation, induction of the fetal gene atrial natriuretic factor (ANF) and increase of cardiomyocyte size. Previous studies have implicated the activation of focal adhesion kinase (FAK) in the progress of cardiomyocyte hypertrophy. L-165041 pretreatment significantly inhibited AngII-induced intracellular Ca(2+) increase and subsequent phosphorylation of FAK. Further experiment using Ca(2+) ionophore A23187 confirmed that Ca(2+) induced FAK phosphorylation, and this was also blocked by L-165041 pretreatment. In addition, overexpression of PPARdelta using adenovirus significantly inhibited AngII-induced intracellular Ca(2+) increase and FAK expression, while PPARdelta siRNA treatment abolished the effect of L-165041. These data indicate that PPARdelta ligand L-165041 inhibits AngII induced cardiac hypertrophy by suppressing intracellular Ca(2+)/FAK/ERK signaling pathway in a PPARdelta dependent mechanism.


Graphene microtubings: controlled fabrication and site-specific functionalization.
Manipulating graphene through engineering for macroscopic assemblies of practical importance is a big challenge. We develop a dually geometric confinement approach for the scalable preparation of meter-long graphene microtubings (μGTs) with a tunable diameter. They have strength comparable to graphene fiber and can be shaped to hierarchical multichannel μGT systems in a straightforward way. Of particular importance, μGTs can be selectively functionalized in a site-specific outer-wall, inner-wall, outer/inner-wall, and within-wall fashion, which endows the μGTs with unique properties for desirable applications. Apart from the magnetically and photoelectronically responsive μGTs developed here, a self-powered micromotor made of Pt inner-wall modified μGT showing agile motion in aqueous medium has been also achieved. Beyond the applications demonstrated in this study, the well-defined μGT systems can also play essential role in other important fields such as fluidics, catalysis, purification, separation, and sensing.


Computer-controlled cardiopulmonary bypass increases jugular venous oxygen saturation during rewarming.
Conventional roller pump apulsatile cardiopulmonary bypass (CPB) was compared with computer-controlled pulsatile bypass, which was designed to recreate biological variability (return of beat-to-beat variability in rate and pressure with superimposed respiratory rhythms). The degree of jugular venous oxygen saturation (SjvO2) less than 50% during rewarming from hypothermic CPB was compared for the two bypass techniques. An SjvO2 less than 50% during rewarming from hypothermic CPB is correlated with cognitive dysfunction in humans. Pigs were placed on CPB for 3 hours using a membrane oxygenator with alpha-stat acid-base management and arterial filtration. After baseline measurements and normothermic CPB, the animals were randomized to apulsatile CPB (n = 12) or computer-controlled pulsatile CPB (roller pump speed adjusted by an average of 2.9 voltage output modulations/s; n = 12). The animals were then cooled to a nasopharyngeal temperature of 28 degrees C. During rewarming to stable normothermic temperatures, SjvO2 was measured at 5-minute intervals. The mean and cumulative areas for an SjvO2 less than 50% were determined for all animals. No between-group differences in temperature were noted during hypothermic CPB or during rewarming. The rate of rewarming was not different between groups. Mean arterial pressure, partial pressure of oxygen in arterial blood, and partial pressure of carbon dioxide in arterial blood also did not differ between groups. The hemoglobin concentration was within 0.4 g/dL between groups at all time periods. Mean pulse pressure was 10.0 +/- 4.8 mm Hg in the apulsatile CPB group and 20.7 +/- 5.2 mm Hg in the pulsatile CPB group (p = 0.0002; unpaired t test). Markedly greater mean and cumulative areas under the curve for SjvO2 less than 50% were seen with apulsatile CPB (164 +/- 209 versus 1.9 +/- 3.6% x min, p = 0.021; and 1,796 +/- 2,263 versus 23 +/- 45% x min, p = 0.020, respectively). Computer-controlled pulsatile CPB was associated with significantly greater SjvO2 during rewarming from hypothermic CPB. Both the mean and cumulative areas under the curve for SjvO2 less than 50% exceeded a ratio of 75:1 for apulsatile versus computer-controlled pulsatile CPB. These experiments suggest that cerebral oxygenation was better preserved during rewarming from moderate hypothermia with computer-controlled pulsatile CPB, which returned biologic variability to the flow pattern.


[Phenotypic and genotypic characteristics of non fermenting atypical strains recovered from cystic fibrosis patients].
We used partial 16S rRNA gene (16S DNA) sequencing for the prospective identification of nonfermenting Gram-negative bacilli recovered from patients attending our cystic fibrosis center (hôpital Necker-Enfants malades), which gave problematic results with conventional phenotypic tests. During 1999, we recovered 1093 isolates of nonfermenting Gram-negative bacilli from 702 sputum sampled from 148 patients. Forty-six of these isolates (27 patients) were not identified satisfactorily in routine laboratory tests. These isolates were identified by 16S DNA sequencing as Pseudomonas aeruginosa (19 isolates, 12 patients), Achromobacter xylosoxidans (10 isolates, 8 patients), Stenotrophomonas maltophilia (9 isolates, 9 patients), Burkholderia cepacia genomovar I/III (3 isolates, 3 patients), Burkholderia vietnamiensis (1 isolate), Burkholderia gladioli (1 isolate) and Ralstonia mannitolilytica (3 isolates, 2 patients). Fifteen isolates (33%) were resistant to all antibiotics in routine testing. Sixteen isolates (39%) resistant to colistin were recovered on B. cepacia-selective medium: 2 P. aeruginosa, 3 A. xylosoxidans, 3 S. maltophilia and the 8 Burkholderia--Ralstonia isolates. The API 20NE system gave no identification for 35 isolates and misidentified 11 isolates (2 P. aeruginosa, 2 A. xylosoxidans and 1 S. maltophilia classified as B. cepacia ). Control measures and/or treatment were clearly improved as a result of 16S DNA sequencing in three of these cases. This study confirms the weakness of phenotypic methods for identification of atypical nonfermenting Gram-negative bacilli recovered from cystic fibrosis patients. The genotypic methods, such as 16S DNA sequencing which allows identification of strains in routine practice, appears to have a small, but significant impact on the clinical management of CF patients.


Breast cancer screening among low-income or uninsured women: results from the National Breast and Cervical Cancer Early Detection Program, July 1995 to March 2002 (United States).
To describe the results of breast cancer screening among low-income and uninsured women in the only national organized screening program in the US, the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). We analyzed mammography and diagnostic follow-up data for 789,647 women who received their first mammogram in the NBCCEDP and 454,754 subsequent mammograms among these women. We calculated the rate of mammograms with abnormal findings, diagnostic follow-up, biopsy, and cancers detected per 1000 mammograms by age and racial or ethnic groups. Positive Predictive Values (PPVs) were estimated for abnormal mammograms and biopsy. Nearly 64% of the women screened in the program were from 50 to 64 years of age and about 46% were members of racial or ethnic minority groups. Women aged 40 to 49 years had the highest rates of abnormal mammograms and of diagnostic follow-up. However, cancer detection rates were highest in women aged 60 to 64 years. In addition, the PPVs for both abnormal mammograms and biopsy were highest in the oldest age group. Cancer detection rates and PPVs for both abnormal mammograms and biopsy were highest in women aged 50 years or more. These results support the programs focus on screening women aged 50 and older for breast cancer.


Skeletonization of internal thoracic artery affects its innervation and reactivity.
The studies showing the superior characteristics of ITA graft and its impact on the clinical results of coronary artery surgery were performed with ITA harvested almost exclusively as a pedicle. This study assesses the impact of ITA skeletonization on its innervation and reactivity. Segments of skeletonized and non-skeletonized ITA were stained with antibodies against protein S-100 to look for the presence of sympathetic nerve fibers. The functional studies were performed on segments of discarded human pedicled ITA that were divided into two 3mm rings, one skeletonized and another non-skeletonized. We compared concentration-effect relationships for the contraction to norepinephrine and endothelium-dependent relaxation to acetylcholine and bradykinin, as well as endothelium-independent relaxation to sodium nitroprusside in skeletonized and non-skeletonized segments of the same ITA. Skeletonized ITA was devoid of protein S-100 positive nerve fibers. It contracted stronger (maximal response 37.0+/-2.04 vs. 25.4+/-1.83mN (P<0.001)) and was twice as sensitive to norepinephrine: pD(2) 6.03+/-0.10 vs. 5.70+/-0.12 (P=0.035). The endothelium-dependent relaxation responses did not differ between skeletonized and non-skeletonized ITA rings. The skeletonized ITA rings appeared over 10 times more sensitive to sodium nitroprusside: pD(2) 6.66+/-0.20 vs. 5.59+/-0.37 (P=0.012)-potency ratio 11.61. The maximal responses did not differ significantly: 112.0+/-6.71 vs. 129.4+/-16.4% (P=0.33). Skeletonization results in sympathectomy of ITA. It has no effect on endothelium-dependent relaxation but increases reactivity of ITA to norepinephrine. This augmented response to alpha-agonist is small, in comparison with over a ten-fold increase in sensitivity to sodium nitroprusside. Pedicled and skeletonized ITA are functionally significantly different vessels when studied in vitro.


[Peak oxygen consumption, NT-proBNP and echocardiographic changes in patients with chronic heart failure].
To assess peak oxygen consumption (peak VO₂) derived from cardiopulmonary exercise testing (CPET), concentrations of NT-proBNP and echocardiographic changes in patients with chronic heart failure (CHF) and reduced left ventricular ejection fraction (LVEF, <40%). Seventy patients were included and divided into two groups according to the New York Heart Association (NYHA) classification: NYHA II group (17 cases) and NYHA III-IV group (53 cases). The basic clinical information, plasma concentration of NT-proBNP at rest, echocardiographic parameters and peak VO₂from CPET were compared between two groups. Correlation among peak VO₂, NT-proBNP and echocardiographic parameters in this patient cohort was assessed and their abilities to discriminate the NYHA III-IV grade were analyzed through c-Statistic. Left atrial diameter ((51.3 ± 7.2) mm vs. (44.0±7.4) mm, P<0.001) was larger, plasma concentration of NT-proBNP (1 379-4 399 pmol/L vs. 1 109-2 356 pmol/L, P<0.01) was higher and peak VO₂((13.4 ± 3.5) ml·kg⁻¹·min⁻¹ vs. (18.2 ± 3.7) ml·kg⁻¹·min⁻¹, P<0.001) were significantly lower in NYHA III-IV group than those in NYHA II group. However, left ventricular end-diastolic diameter (LVEDD) and LVEF were similar between two groups. Peak VO₂correlated significantly with NT-proBNP (r=-0.311, P<0.01), but neither peak VO₂nor NT-proBNP correlated with echocardiographic parameters (LA, LVEDD and LVEF). ROC analysis showed that peak VO₂had the strongest discriminatory power for detecting NYHA III-IV grade patients (AUC=0.835, P<0.001), followed by the NT-proBNP (AUC=0.723, P<0.01). Peak VO₂is a more sensitive parameter to detect the disease aggravation (NYHA III-IV grade) of the CHF patients with reduced LVEF compared to plasma NT-proBNP and echocardiographic parameters (LA, LVEDD, LVEF).


The LC/MS analysis of glycation of IgG molecules in sucrose containing formulations.
Glycation of a recombinant monoclonal IgG2 molecule, in sucrose containing liquid formulations, was studied using reversed-phase LC/MS analysis of the intact IgG, the F(ab')2 fragments and after complete tryptic digestion. The extent of glycation in sucrose containing formulations was monitored at different temperatures over a period of 21 months using the Hexose index (Hex(I)). Hex(I) represents the average number of hexose molecules per molecule of IgG and was calculated by using the intensity values of peaks corresponding to hexose isoforms in the deconvoluted mass spectra. The rate of glycation in mildly acidic sucrose containing formulations was proportional to the incubation temperature. No glycation was observed in sucrose containing formulations incubated at 4 degrees C even after 18 months. However, when the same formulations were incubated at 37 degrees C glycation was observed after just 1 month. The glycation sites were mapped to 10 lysine residues distributed throughout the molecule. The amino terminal end of the light chain was also shown to contain glycation. The surface accessibility of the lysine side chain could influence its susceptibility to glycation.


Innovative way to dispense pheromones for off-host control of Rhipicephalus sanguineus sensu lato ticks.
Vapour patches dispensing pheromones were evaluated as lures to increase the attractiveness of sticky tick traps for Rhipicephalus sanguineus sensu lato (s.l.). Sex pheromone (SP), assembly pheromone (AP) and a combination of SP + AP at optimal concentrations were impregnated in vapour patches. The responses of the different stages of R. sanguineus s.l. (i.e. larvae, nymphs and adults) to the pheromones were evaluated using a Petri dish bioassay. The impregnated vapour patches were retained as such for a period of two mo and their efficacy was reassessed. In a subsequent field trial, pheromone impregnated vapour patches were placed as lures in bamboo (Bambusa vulgaris) sticky traps designed for the control of ticks in dog kennels. In vitro AP impregnated vapour patches were effective in attracting the different life stages of R. sanguineus s.l. whereas SP was effective in attracting the unfed and fed male stages of R. sanguineus s.l. The field trial revealed that questing and engorged larvae, nymphs and females of R. sanguineus s.l. were attracted more towards AP impregnated vapour patches than SP and AP + SP impregnated vapour patches. Fed and unfed male ticks were lured effectively by SP alone. The combination of SP + AP revealed no potent additive or synergistic effect.


Preparation and Evaluation of Chitosan Submicroparticles Containing Pilocarpine for Glaucoma Therapy.
The objective of the present study was to optimize the preparation of chitosan submicroparticles and to assess whether they enhanced ocular permeation of pilocarpine. Submicroparticles were produced by spray drying and characterized to determine process yield, encapsulation efficiency, morphology, size distribution, drug-polymeric matrix interaction, porcine sclera permeation as well as ocular irritancy and drug retention. Quantification of pilocarpine using High Performance Liquid Chromatography was found to be selective, linear, precise, accurate and robust. The spray drying method proved to be simple and reproducibly produced particles with satisfactory yields, thus showing potential for industrial scale applications. The pilocarpine-loaded chitosan particles exhibited adequate morphological characteristics as well as high encapsulation efficiency. The particles produced were on a submicrometric scale and compatible with intraocular administration. In pilocarpine-loaded particles, the interaction between pilocarpine and chitosan polymeric matrix resulted in delayed release of the drug, attributed to formation of a reservoir system. The best fit for drug release was obtained using the Higuchi equation. The chitosan submicroparticles enhanced the permeation effect and increased the passage of pilocarpine through porcine sclera and also demonstrated low irritancy potential. Therefore, the particles produced can be considered a promising system for the ocular delivery of pilocarpine.


Hydroxychloroquine, dosage parameters and retinopathy.
In a study designed to determine the presence of retinopathy in patients taking hydroxychloroquine we compared 82 patients attending a rheumatology clinic who had taken hydroxychloroquine for over 1 year with controls. Outcome measurements included fundoscopy, fundus photography and automated computerized visual fields of the macular area. No patient was found to have retinopathy. No correlation could be found between indices of visual field function and total drug usage, average daily dose, dosage in mg/kg body weight or duration of treatment. Retinopathy is unlikely to occur at dosages of hydroxychloroquine of less than 6.5 mg/kg body weight with under 10 years of treatment. Present guidelines for ophthalmic screening of patients on antimalarial therapy are too rigorous and visual field testing if not of benefit. Further recommendations are made for ophthalmic supervision.


Human umbilical cord blood mononuclear cells decrease fibrosis and increase cardiac function in cardiomyopathy.
We investigated whether human umbilical cord blood mononuclear cells (HUCBC) can limit progressive cardiomyopathy in TO2 hamsters. A total of 22 TO2 1-month-old hamsters were treated with intramyocardial HUCBC, 4 x 10(6) in Isolyte, and 23 TO2 1-month-old hamsters were treated with intramyocardial Isolyte. A total of 16 1-month-old F1B hamsters served as controls and received intramyocardial Isolyte. Echocardiograms were performed on all hamsters prior to and monthly after treatment for 6 months. Heart tissues were then stained with hematoxylin and eosin, Masson's Trichrome and human leukocyte antibody. In F1B hamsters, left ventricular fractional shortening (FS) and ejection fractions (EF) did not significantly decrease over 6 months. By contrast, in Isolyte-treated TO2 hamsters, FS decreased from 56.2 +/- 1.0% to 19.7 +/- 3.2% and EF decreased from 89.5 +/- 1.4% to 44.9 +/- 5.9% at 6 months (both p < 0.0001). The FS and EF in HUCBC-treated TO2 hamsters also progressively decreased over 6 months but the changes were more gradual, especially during the first month after HUCBC treatment when FS was 52.0 +/- 1.5% and EF was 89.5 +/- 1.4%, which was not significantly different from the FS and EF in the F1B hamsters. Moreover, in the HUCBC-treated hamsters, the FS and EF were 20-30% greater than FS and EF in Isolyte TO2 hamsters at 3 and 5 months (p < 0.01). In Isolyte-treated TO2 hamsters at 6-7 months, fibrosis involved 30.0 +/- 5.0% of left ventricle and 35.0 +/- 5.0% of septum. By contrast, in HUCBC-treated hamsters, fibrosis involved only 6.5 +/- 2.3% of the left ventricle and 6.3 +/- 1.8% of septum (p < 0.05). The average number of blood vessels per myocardial microscopic field in HUCBC-treated hearts was 53.5 +/- 0.8 versus 46.2 +/- 3.0 in Isolyte-treated TO2 hearts (p < 0.05). HUCBC, when given as a single intramyocardial injection, can limit fibrosis and increase heart function over the short term in TO2 hamsters with cardiomyopathy.


Reversibility of lumbar epidural lipomatosis in obese patients after weight-reduction diet.
We present three obese patients with symptomatic lumbar epidural lipomatosis. All three were treated with a calorie-controlled diet and considerable weight reduction was achieved. MRI demonstrated a reduction in the epidural fat and relief of thecal sac compression in all three; two also improved clinically.


Sarcoidosis and reactive pulmonary hypertension.
Despite diffuse disease of the lungs (often with widespread inflammation or obliteration of blood vessels) in sarcoidosis, pulmonary hypertension is uncommon, occurring in 1% to 4% of cases. We report a case of sarcoidosis and severe pulmonary hypertension that, in striking contrast to other reports, occurred in the absence of obliterative pulmonary vascular disease. We therefore examined the possibility of whether an abnormality in pulmonary vascular tone might be a cause of the pulmonary hypertension. In pharmacologic studies, we demonstrated pulmonary vasodilatation and, in response to increased pulmonary blood flow, the elaboration of the pulmonary vasoconstricting eicosanoid, thromboxane.


Immunohistochemical findings in primary fallopian tube cancer. Case report.
Primary fallopian tube carcinoma is a rare malignancy, representing about 1% of female genital tract malignancies. We present a case report and compare the medical performance with accessible data from the literature as well as present immunohistochemical analysis of estrogen, progesterone, and proliferative together with basic cytokeratin reactions. We found that immunohistochemical expression of ER-beta was dominant over ER-alpha which encourages further evaluations to be performed on a larger number of samples, especially taking into account the very scant progesterone receptor expression we noted. On the basis of the course of disease under study, etiological problems and the possibility of clinical misdiagnosis have been discussed. The low prevalence rate and lack of clear symptoms of this type of carcinoma makes the final clinical diagnosis almost impossible without an intraoperative histopathological study. Multicenter studies are needed to improve the understanding of possible risk factors.


An analysis of first-order release kinetics from albumin microspheres.
Release rates from BSA microspheres prepared from various conditions are analysed using a previously reported equation expressing the first-order release rate constant. The permeability constants calculated applying the equation on experimental release rates are in good agreement with the constants measured from permeation studies using planar membrane, for various preparation conditions. It is shown that the equation expressing the first-order release rate constant is valid more extensively. The permeability constant varies depending on the preparation conditions, and the reason for variation is shown clearly to be the difference in degree of swelling of the polymer. It was found from regression analysis that there is relatively simple correlation between unknown parameters of the equation and the preparation conditions. Release rate constants can be calculated applying the equation on the known parameters and the estimated values of the unknown parameters from the correlation. Good agreement was found between the calculated values and experimental ones; therefore, at least as far as we examined here, the release rate constant of the microsphere can be estimated from the preparation conditions.


Control of molecular energy redistribution pathways via surface plasmon gating.
Strong coupling of molecular electronic states with tunable surface plasmon resonances is used to control electronic energy redistribution pathways in molecules adsorbed on a silver film. Ultrafast excitation of porphyrinic molecular J aggregates into the S2 state is followed by a second pulse of varying incident wave vector to produce a tunable plasmon in the film. When the plasmon overlaps the S1 state, energy flows from S2 to S1 at high efficiency. If the plasmon hybridizes with the S2 state, the excitation remains in the S2 vibrational manifold during quenching to the ground state. These results could have significant impact on the design of active molecular devices.


The use of HPLC-MS in T-cell epitope identification.
The hunt for T-cell epitopes is going on because hopes are set on such peptide sequences for diagnosis and vaccine development in the fight against infectious and tumor diseases. In addition to a variety of other techniques used in T-cell epitope identification, mass spectrometers coupled to microcapillary liquid chromatography have now become an important and sensitive tool in separation, detection, and sequence analysis of highly complex natural major histocompatibility complex (MHC) ligand mixtures. In this article, we review the basics of mass spectrometric techniques and their on-line coupling to microcapillary liquid chromatography (microcap-LC). Furthermore, we introduce current strategies for the identification of new T-cell epitopes using microcapillary liquid chromatography-mass spectrometry (microcap-LC-MS).


Effects of consecutive high-dose alcohol administration on the utilization of sulfur-containing amino acids by rats.
In this study, we attempted to evaluate changes in sulfur-containing amino acid (SCAA) metabolism after short-term high-dose alcohol ingestion. At the beginning of the study, six animals were sacrificed as the baseline group and then other animals in the experiment were consecutively gavaged with alcohol (30%, 3 g/kg) for 7 days. Animals (n=6 each) were subsequently sacrificed at the time points of Days 1 (Group E1), 3 (Group E3) and 7 (Group E7). Blood samples and selected tissues were collected at each time interval. SCAA, pyridoxal phosphate (PLP) and glutathione (GSH) levels were analyzed. Results showed that taurine levels of tissues (brain, liver, heart and kidneys) all declined after the ethanol intervention and continued to decrease in selected tissues except the brain during the experiment. Furthermore, the trends of plasma taurine and PLP contents were highly correlated (r=.98, P=.045). A similar utilization pattern of plasma taurine and PLP indicated that transsulfuration preferred taurine production to GSH synthesis. The trend of plasma taurine levels being positively correlated with PLP levels reveals that dramatic transsulfuration occurred to meet the urgent demand for taurine by brain cells. In conclusion, we reported that continual alcohol ingestion alters SCAA utilization, especially by depletion of taurine and hypotaurine and by elevation of S-adenosyl homocysteine in the selected organs.


Solution phase gold nanorings on a viral protein template.
Current studies on materials that exhibit metamaterial properties are mainly focused on lithography-generated 2D substrates. Here we report the successful fabrication of 22 nm gold nanoparticle rings with and without a central nanoparticle assembled on Tobacco Mosaic Virus coat protein disks. These structures are one of the first examples of nanorings produced independently of a substrate and represent the first steps toward the realization of a solution-phase or coatings-based metamaterial.


Bradykinin-induced airway contraction in two lines of guinea pigs with congenitally different airway sensitivity.
The airway responsiveness to bradykinin (0.1, 1 and 10 microg/kg, i.v.) was examined in two lines of guinea pigs, BHS (bronchial hypersensitive) and BHR (bronchial hyposensitive) lines, with different airway sensitivity to inhalation of acetylcholine (ACh)-aerosol. Normal Hartley strain guinea pigs were used as a control group. The airway contraction was measured by recording intratracheal pressure (P[IT]) and respiratory airflow (V) under the condition of artificial ventilation in anesthetized guinea pigs. The results show airway responsiveness to bradykinin in BHS guinea pigs to be significantly greater than in BHR and normal Hartley strain guinea pigs.


Ginger polyphenols attenuate cyclosporine-induced disturbances in kidney function: Potential application in adjuvant transplant therapy.
Cyclosporine (CYA), a common immuno-suppressant drug that is used in organ transplants, is associated with nephrotoxic effects. Scientific exploration of natural products of plant origin should be considered; especially, in a world with increasing prevalence of kidney diseases. Effects of ginger polyphenols (GP) in Wistar rats with CYA-induced perturbations in electrolyte balance and kidney function was determined. Fifty Wistar rats were recruited for this study such that graded doses of GP were administered following CYA-induced kidney injury and comparisons were made against control and toxic groups at p < 0.05. Distilled water, CYA (50 mg/kg p.o. for 10 days) and GP (100, 200 and 400 mg/kg p.o. for 21 days) were administered to the rats at 0.2 ml/100 g. CYA administration induced kidney injury as characterized by significant deleterious alterations in plasma and urine levels of creatinine, urea, Na+ and K+ electrolyte balance as well as creatinine clearance. Also, there was a significant derangement in feeding pattern and relative kidney weight. Using GSH and SOD as antioxidant indicators, there was significant disturbance of the anti-oxidant system while histopathological results showed evidence of interstitial vacuolations with atrophic glomeruli. These conditions were significantly attenuated (p < 0.05) following administration of graded doses of GP. It was, therefore, concluded that GP could potentially be a therapeutic choice for patients with CYA-induced kidney injury.


Competition of chemically related antigens for presentation by accessory cells to T cells requires expenditure of metabolic energy by the accessory cells.
The immune responsiveness of guinea pigs both to dinitrophenyl-poly-L-lysine (DNP-PLL) and to the lysine-rich random copolymer of L-glutamic acid and L-lysine (GL) is controlled by the 'poly-L-lysine gene'. We have previously demonstrated that accessory cells of responder strains can be made incapable of presenting DNP-PLL to responsive T cells in assays for proliferation, by in vitro exposure of the cells to GL before and during their exposure to DNP-PLL. We demonstrate here that the presence of anti-Ia antibody in the cultures does not interfere with the apparent competition of the two antigens for presentation by accessory cells. Furthermore, the two antigens do not compete for presentation when the accessory cells are exposed to them at 1 degree C, suggesting that endocytosis and/or other energy-requiring cellular events are necessary for the competition.


Postinfarction left ventricular pseudoaneurysm--echocardiographic diagnosis and surgical repair.
Left ventricular wall perforation after acute myocardial infarction, without immediate rupture to fatal haemopericardium, is a rare complication that may result in a pseudoaneurysm. Transoesophageal echocardiography demonstrated a posterior wall perforation and the unique blood flow pattern at the neck of a pseudoaneurysm 6 days after acute myocardial infarction. In a second patient with angina and congestive heart failure 7 years after an acute myocardial infarction echocardiography demonstrated a huge pseudoaneurysm. Surgical repair was successful in both patients. Turbulence of blood at the neck of a pseudoaneurysm generates a murmur, and systolic regurgitation into a large aneurysm may cause symptoms of heart failure. Exact diagnosis, anatomical relations and size can be assessed with echocardiography. Angiography is required before surgery only to rule out coronary artery pathology. Occasionally a pseudoaneurysm may persist for many years but because of a high risk of rupture, prophylactic repair is indicated soon after diagnosis.


The interaction of domain-specific knowledge and domain-general discovery strategies: a study with sinking objects.
Recent work on scientific reasoning has largely focused on either domain-specific content knowledge or domain-general reasoning knowledge. This study investigated the interaction between the 2 types of knowledge in a real-world domain in which strict control of variables was not possible. We used a context, sinking objects, in which 10-, 12-, and, 14-year-old children's strong a priori beliefs could be revealed by participant-designed experiments. The results showed that most children initially believed weight alone determined an object's sinking rate. Older, but not younger, participants typically viewed experimentation as a means of exploring the effects of attributes other than weight. However, experimentation did help all children to understand the effects of object shape and material on sinking rates. The results suggests a number of questions for further research, including how children come to understand experimentation as a matter of evaluation rather than demonstration, and the role of unexpected experimental results in driving conceptual understanding.


[Plasma endothelin levels in patients with multiple organ dysfunction syndrome caused by fish gall bladder poisoning].
To investigate the correlation between the change of plasma endothelin (ET) and the occurrence and progress of multiple organ dysfunction syndrome (MODS) caused by fish gall bladder poisoning. Plasma ET was measured in 85 patients with fish gall bladder poisoning and 30 healthy controls and comparison of the levels of plasma ET was carried out between patients groups with different severity of fish gall bladder poisoning. The relationship between plasma ET levels and enzymology as well as some biochemistry indexes in patients with fish gall bladder poisoning was then analyzed. Plasma ET in patients with fish gall bladder poisoning (150.5 +/- 90.5) ng/L was much higher than that in controls (52.8 +/- 9.3) ng/L. The concentration of plasma ET in slight poisoning group (61.2 +/- 13.6) ng/L increased a little, but it was not significantly different with that in controls (P > 0.05). The concentration of plasma ET was significantly higher in moderate poisoning group and severe poisoning group (162.3 +/- 82.3) ng/L and (232.6 +/- 92.7) ng/L as compared with that in the controls (P < 0.01), with the severe poisoning group much higher than the moderate poisoning group and the latter much higher than the normal. At the same time, plasma ET in MODS group and non-MODS group (210.2 +/- 98.7) ng/L and (126.3 +/- 68.3) ng/L were both notably higher than that in the controls. Furthermore plasma ET in the MODS group was much higher than that in the non-MODS (P < 0.01). It was also found that a positive correlation existed between plasma ET and creatine kinase-MB, cardiac troponin I, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen and serum creatinine (P < 0.01) and a negative correlation between plasma ET and endogenous creatinine clearance rate (P < 0.01). Plasma ET may be involved in the process of fish gall ladder poisoning and later in the progress of MODS. It was shown that the higher the level of plasma ET, the severer the degree of poisoning and the higher the fatality rate. So monitoring plasma ET level dynamically may be an important clinical index in judging the patients condition and their prognosis in fish gall bladder poisoning. Simultaneously it is useful for earlier diagnosis of fish gall bladder poisoning and alertness of MODS caused by it as well as for proper management with antagonist and inhibitor against plasma ET for prevention and cure of fish gall bladder poisoning.


The role of circulating mevalonate in nephrotic hypercholesterolemia in the rat.
The cause of the hypercholesterolemia that characterizes the nephrotic syndrome has never been adequately explained. The present study examines the possibility that enhanced availability of the cholesterol precursor, mevalonic acid, to the liver in the nephrotic state may result in increased hepatic cholesterogenesis. In normal animals, the kidneys are known to be the major site of the metabolism of circulating mevalonate to both cholesterol and CO2. Previous studies, using perfusion of isolated, intact kidneys, have shown that the excretion and metabolism of mevalonate are both impaired in nephrosis. The present investigation has demonstrated in vivo that puromycin aminonucleoside nephrosis results in a 25% reduction in the oxidation of mevalonate to CO2. In the same nephrotic animals, cholesterogenesis from circulating mevalonate was significantly increased in both liver and carcass. In addition, liver slices from nephrotic animals incorporated increased amounts of [5-14C]mevalonate into cholesterol when calculated per whole liver, but not per gram of liver. Oxidation of mevalonic acid by kidney slices was significantly reduced, whether expressed as per gram of tissue or per whole organ. HMG-CoA (3-hydroxy-3-methylglutaryl) reductase activity in liver of nephrotic animals was significantly increased. We conclude that, in the nephrotic state, impaired mevalonate metabolism by the kidney may contribute to enhanced cholesterogenesis by increasing delivery of mevalonate to liver and carcass; in addition, nephrosis appears to provide an undefined stimulus for HMG-CoA reductase activity in the liver, thereby providing an additional enhancement of hepatic cholesterogenesis.


Cloning and molecular characterization of two complement Bf/C2 genes in large yellow croaker (Pseudosciaena crocea).
Complement components factor B and C2 are two crucial proteases in the alternative pathway (AP) and classical pathway (CP). Two Bf/C2 cDNAs, LycBf/C2A and LycBf/C2B were isolated from the large yellow croaker (Pseudosciaena crocea) by suppression subtractive hybridization (SSH) and rapid amplification of cDNA ends (RACE). Through sequence alignment and computer 3D modeling analysis, we found that both of the deduced proteins contain three complement control protein (CCP) modules, a von Willebrand factor A (vWFA) domain, and one serine protease (SP) domain. Both structural analysis and phylogenetic analyses suggested that LycBf/C2A is more like human factor B than human C2 while LycBf/C2B is more human C2-like. After that, RT-PCR assay showed that LycBf/C2A and LycBf/C2B were mostly expressed in liver, albeit detectable in other tissues. Finally, after being infected with attenuated live Vibrio anguillarum strain, the expression level of LycBf/C2A and LycBf/C2B were found remarkably up-regulated in liver, spleen and kidney, indicating that the two complement factors play a pivotal role in the immune response to bacterial challenge in large yellow croaker.


[Voiding disorders in childhood: from diagnosis to treatment].
In voiding disorders in childhood, after a precise diagnosis, treatment can be provided. Aspecific hygienic and dietetic measures are the basis of care in all micturating disorders and frequently must be established to allow a precise diagnosis. In case of enuresis, restriction of beverage and diuretic foods is recommended in the evening. Other treatments for enuresis should be proposed to motivated children. In the polyuric form of enuresis, the treatment is desmopressin (DDAVP) and in the form with low bladder capacity, alarms or a combination of these 2 treatments. In dysfunctional voiding, after caring for the secondary causes, and depending on the characteristics of the disorder, the first-step treatment is pelvic floor rehabilitation with or without anticholinergic therapy. Other medical treatments are used in a second step. Isolated urethral instability remains controversial.


Metabolism of styrene oxide to styrene glycol in enriched mouse clara-cell preparations.
Styrene is a widely used chemical that has been shown to cause lung tumors in mice but not in rats. Styrene toxicity appears to be related to its bioactivation to styrene oxide, and this occurs almost exclusively in Clara cells. An important pathway in the detoxification of styrene oxide is via epoxide hydrolase to yield styrene glycol. When mouse Clara cells were incubated with racemic styrene oxide, R-styrene glycol was the predominant metabolite, giving an R/S ratio of 3.6. When the pure styrene oxide enantiomers were used as substrates, the corresponding styrene glycols were the predominant but not exclusive metabolites. Activity was slightly higher with the S-styrene oxide than with the R-styrene oxide. Addition of reduced glutathione to the incubation medium resulted in an increase in epoxide hydrolase activity, perhaps by decreasing oxidative stress. Mouse Clara cells thus show the capacity for detoxifying styrene oxide.


Assessing personal process learning in a health promotion module for medical students.
This paper describes the development and evaluation of an assessment method for personal process learning in a student-centred health promotion module. Personal process learning refers to students' awareness and understanding of their learning about personal values and attitudes, their skills for planning change, and their communication skills. The assessment forms part of the professional examination in public health. The paper documents and critically reviews the assessment method in the light of student feedback. The problem of student acceptability is highlighted and we describe the adjustments that have been made in response to this and how they have been received. It is concluded that medical students are open to innovative forms of assessment as long as they perceive them to be valid, fair and equitable.


Inhibition of translation and progesterone-induced maturation of Xenopus oocytes by expressing the amino-terminal portion of the eukaryotic translation initiation factor 4G.
The eukaryotic translation initiation factor 4G (eIF4G) plays a pivotal role in translation. EIF4G interacts with several other factors including eIF4E, which is a cap-binding protein, and the poly(A)-binding protein (PABP). In this work, we demonstrate that the expression of the amino-terminal one-third of eIF4G, which interacts with eIF4E and PABP, in Xenopus oocyte inhibits translation and progesterone-induced maturation.


Development and characterization of silver-based antimicrobial ethylene-vinyl alcohol copolymer (EVOH) films for food-packaging applications.
The use of silver as an antimicrobial in the food area has raised wide interest in recent years. In the present work, 0.001-10 wt % silver ions was satisfactorily incorporated into an ethylene-vinyl alcohol (EVOH) copolymer matrix by a solvent casting technique. The antibacterial efficacy of the composite was evaluated under laboratory conditions and in contact with some foods. The ionic compound did not affect the crystallinity or the water-induced plasticization of the materials and was homogeneously distributed across the surface and thickness of the films. When immersed in water, sorption-induced release of 50-100% of the silver ions took place in <30 min. In the bacterial minimal growth medium M9, the minimal inhibitory concentration (MIC) of the film was in the range of 0.01-0.1 ppm. High protein content food samples displayed low susceptibility to the films (<1 log reduction in any case), whereas low protein content food samples exhibited no detectable bacterial counts for films with 1 and 10 wt % silver and about 2 log reduction for films with 0.1 wt % silver. These results represent a step forward in the understanding of silver antimicrobial efficacy and its possible application in the food-packaging industry, most likely as food coatings.


The role of terminal-link stimuli in concurrent-chain schedules: revisited using a behavioral-history procedure.
A behavioral-history procedure was used to study the function of terminal-link stimuli as conditioned reinforcers in multiple concurrent-chain schedules of reinforcement. First, three pigeons were exposed to multiple concurrent-chain schedules in which the two multiple-schedule components were correlated with a blue and a white stimulus, respectively. In each component the initial links were equal independent variable-interval (VI) 15 s schedules. A fixed-interval (FI) 10 s schedule operated on the red key in one terminal link while extinction operated on the green key in the alternative terminal link. When large preferences for the red stimulus had been established, two tests were conducted. In the terminal-link test, under new initial-link stimuli--purple and brown--an FI 10 s schedule operated for both the red and green terminal-link stimuli. In the subsequent initial-link test, the blue and white initial-link stimuli were reintroduced, and, as in the terminal-link test, FI 10s operated for both the red and the green terminal-link stimuli. In the terminal-link test, the three pigeons showed no preference for the terminal links with the red stimulus, but showed clear and consistent preferences for the red stimulus when blue and white stimuli were reintroduced as initial-link stimuli in the initial-link test. This suggests that there are multiple sources of control over initial-link response allocation in concurrent-chains, including control by both terminal- and initial-link stimuli.


The regenerative medicine laboratory: facilitating stem cell therapy for equine disease.
This article focuses on the emerging field of equine regenerative medicine with an emphasis on the use of mesenchymal stem cells (MSCs) for orthopedic diseases. We detail laboratory procedures and protocols for tissue handling and MSC isolation, characterization, expansion, and cryopreservation from bone marrow, fat, and placental tissues. We provide an overview of current clinical uses for equine MSCs and how MSCs function to heal tissues. Current laboratory practices in equine regenerative medicine mirror those in the human field. However, the translational use of autologous and allogeneic MSCs for patient therapy far exceeds what is currently permitted in human medicine.


Dietary adequacy among rural Yup'ik women in western Alaska.
To assess (1) energy and nutrient intake; (2) dietary adequacy; (3) traditional and nontraditional foods consumed; and (4) main foods contributing to energy and selected nutrient intake among Yup'ik women in Western Alaska. Up to 3 24-hour dietary recalls were collected to assess the dietary intake. Dietary adequacy was determined by comparing women's daily nutrient intakes to corresponding dietary reference intakes (DRIs). Mean daily energy intake for the women was 2172 kcal, exceeding the DRI for energy. The majority of women (90-100%) fell below the recommendations for dietary fiber, calcium, and vitamins D and E. More than 50% of women fell below the recommendations for vitamin A, and more than one third were below the DRI for zinc and vitamins C and B6. Juices/pop (including Tang, Kool-Aid, soda/pop, fruit juice, and energy drink), coffee, and traditional fish were the most frequently reported food items. Sweetened beverages and pop were the main contributors to energy, carbohydrate, and sugar intake. Traditional foods provided 34% of protein, 27% of iron, 23% of vitamin A, and 21% of zinc. Among Yup'ik women, juices/pop were the most frequently consumed foods contributing to the high energy intake. However, traditional food still contributes substantially to certain nutrients. These data contribute to an understanding of dietary adequacy in this population and will aid in the development of a nutritional intervention program.


Management of unsuccessful LASIK surgery.
Refractive procedures enjoy very high success rates and are among the most commonly performed elective surgeries in medicine. With better insights into preoperative screening, the overwhelming majority of cases have successful outcomes. Unfortunately, however, all refractive surgeons must appropriately manage unsuccessful cases. Unsuccessful refractive surgery procedures may relate to each step of the refractive surgery process: preoperative screening, surgical planning, intraoperative events, and postoperative biomechanical or healing anomalies. This paper reviews the management of unsuccessful laser-assisted in situ keratomileusis (LASIK) procedures, focusing on significant advances related to wavefront-guided therapeutic ablations.


Sciatic neurosteatosis: Relationship with age, gender, obesity and height.
To evaluate inter-reader performance for cross-sectional area and fat quantification of bilateral sciatic nerves on MRI and assess correlations with anthropometrics. In this IRB-approved, HIPPA-compliant study, three readers performed a cross-sectional analysis of 3T lumbosacral plexus MRIs over an 18-month period. Image slices were evaluated at two levels (A and B). The sciatic nerve was outlined using a free hand region of interest tool on PACS. Proton-density fat fraction (FF) and cross-sectional areas were recorded. Inter-reader agreement was assessed using intra-class correlation coefficient (ICC). Spearman correlation coefficients were used for correlations with age, BMI and height and Wilcoxon rank sum test was used to assess gender differences. A total of 67 patients were included in this study with male to female ratio of 1:1. Inter-reader agreement was good to excellent for FF measurements at both levels (ICC=0.71-0.90) and poor for sciatic nerve areas (ICC=0.08-0.27). Positive correlations of sciatic FF and area were seen with age (p value<0.05). Males had significantly higher sciatic intraneural fat than females (p<0.05). Fat quantification MRI is highly reproducible with significant positive correlations of sciatic FF and area with age, which may have implications for MRI diagnosis of sciatic neuropathy. • MR proton density fat fraction is highly reproducible at multiple levels. • Sciatic intraneural fat is positively correlated with increasing age (p < 0.05). • Positive correlations exist between bilateral sciatic nerve areas and age (p < 0.05). • Males had significantly higher sciatic intraneural fat than females (p < 0.05).


High stress hormone levels accelerate the onset of memory deficits in male Huntington's disease mice.
Huntington's disease (HD) is a neurodegenerative disorder caused by a tandem repeat mutation in the huntingtin gene. Lifestyle factors, such as lack of activity may contribute to the variability in the age of disease onset. Therefore, better understanding of environmental modifiers may uncover potential therapeutic approaches to delay disease onset and progression. Recent data suggest that HD patients and transgenic mouse models show a dysregulated stress response. In this present study, we elevated stress hormone levels through oral corticosterone (CORT) treatment and assessed its impact on the development of motor impairment and cognitive deficits using the R6/1 transgenic mouse model of HD. We found that CORT consumption did not alter rotarod performance of R6/1 HD or wild-type (WT) littermates. However, the onset of hippocampal-dependent Y-maze deficits was accelerated in male R6/1 mice by 5days of CORT treatment, whereas short term memory of WT and female R6/1 mice was unaffected. We then further investigated the male HD susceptibility to CORT by measuring TrkB activation, BDNF and glucocorticoid receptor expression as well as the level of cell proliferation in the hippocampus. CORT treatment increased the levels of phosphorylated TrkB in male R6/1 mice only. There were no effects of CORT on hippocampal BDNF protein or mRNA levels; nor on expression of the glucocorticoid receptors in any group. Hippocampal cell proliferation was decreased in male R6/1 mice and this was further reduced in CORT-drinking male R6/1 mice. Female mice (WT and R6/1) appeared to be protected from the impacts of CORT treatment in all our hippocampal measures. Overall, our data demonstrate that treatment with corticosterone is able to modulate the onset of HD symptomatology. We present the first evidence of a male-specific vulnerability to stress impacting on the development of short-term memory deficits in HD. More generally, we found that female mice were protected from the detrimental effects of CORT treatment on a variety of hippocampus-based measures. Hippocampal plasticity and memory in HD may be more susceptible to the impacts of stress in a sex-dependent manner. We propose clinical investigations of stress as a key environmental modifier of HD symptom onset.


Metabolic constraints on voluntary intake in ruminants.
The weak point in all current methods or models of diet formulation is the prediction of intake. The major uncertainty is not in the cases in which physical constraints apply, but in those in which voluntary intake is limited by feedback from metabolic factors. Voluntary intake is, ultimately, a psychological phenomenon, involving the integration of many signals, and reflects the flexibility of biological systems evolved to cope with variability in food supply, composition and animal state. Conditions giving rise to regulatory signals may provide a framework for modeling metabolic constraints on intake. The empirical evidence for metabolic feedback shows that the animal's productive potential, which affects its ability to utilize nutrients, interacts with the balance of absorbed nutrients to regulate intake. The relative importance of the sites where nutrient imbalance occurs (microbial or host animal metabolism) is unclear, as is the relevant time scale (minutes or days) of response. A model of the effects of asynchrony of nutrient supply to ruminal microbes suggests that ammonia and microbial recycling and the contribution of hind-gut fermentation reduce the asynchrony in the balance of nutrients absorbed into the bloodstream. Hitherto, rather little progress has been made in mathematical modeling of the metabolic processes controlling intake. Models that describe the phenomenon in terms of global variables, such as total energy intake, protein supply, and protein synthetic capacity, can simulate the way constraints may operate without requiring or providing a deeper understanding of the metabolic processes involved. Models describing the flux of energy and materials down established metabolic pathways have the potential to explore constraints on intake, but until the problem of parameterizing such models can be overcome, that potential will remain untapped.


Fabrication and evaluation of a biodegradable proanthocyanidin-crosslinked gelatin conduit in peripheral nerve repair.
This study proposed a novel and biodegradable nerve guide conduit in its applicability to peripheral nerve regeneration. A naturally occurring proanthocyanidin (PA) was selected as a cross-linking reagent in preparing the PA-crosslinked gelatin (PCG) conduit. Experimental results indicate that 5 wt % of PA was optimal in the complete cross-linking reaction in the PCG conduit. The PCG conduit was brownish and round with a rough outer surface whereas its inner lumen was smooth. The cross-linked networks of the PCG conduit resisted enzymatic hydrolysis under in vitro degradation studies. PA and gelatin were released from the soaked PCG conduit. During the release phase, the concentrations of PA, gelatin, and PCG-soaking solutions were not only nontoxic but also promoted the viability and growth of Schwann cells. The PCG conduit more effectively supported cell attachment and growth. The effectiveness of the PCG conduit as a guidance channel was studied when it was used to repair a 10 mm gap in the rat sciatic nerve. Throughout the 8-week experimental period, the peak amplitude and area under the muscle action potential curve both increased with the recovery period. Histological observations revealed that various regenerated nerve fibers crossed through and beyond the gap region. These results suggest that the PCG conduit can be a candidate for peripheral nerve repair.


Properties of star-branched polymer brushes.
A simple model of a polymer brush was constructed. The star polymers with three arms were terminally attached with one arm (the stem) to an impenetrable surface with the other two arms (branches) free. The excluded volume effect was included into the model as the only interaction. Therefore, the system was studied in good solvent conditions. The simulations were carried out by means of the dynamic Monte Carlo method using the local changes of chain conformations to sample efficiently the conformational space. The influence of both the number of chains (the grafting density) and the length of chains on the static properties of the polymer brush was studied. The internal and local structure of a formed polymer layer was determined. It was shown that the size of the stems increased rapidly with the increase of the grafting density, while the size of the branches diminished. The changes of the spatial orientations of the stems and the branches for different grafting densities were shown and discussed.


Chromogranin A assay in clinical practice.
Chromogranins belong to the family of secretory chromogranin and secretogranin proteins. They are found in secretory vesicles throughout the neuroendocrine system. Chromogranin A (CgA) is the main component. CgA acts as a prohormone submitted to processes of degradation through which active peptides are generated. CgA has auto, para and endocrine functions. It is widely used as an immunohistochemical marker. Despite the lack of international standardization, and the lack of an accurate definition of the diagnostic cut-off levels, some CgA assays are reliable. Numerous studies have suggested that CgA determination may be of interest for the diagnosis and the follow-up of various endocrine tumors. Plasma levels of this general marker are proportional to tumor mass. The localization of the primitive tumor, the presence of associated hormonal secretions and possible renal failure and/or hypergastrinemia must be taken into consideration for proper interpretation of CgA levels. New clinical indications are emerging for the evaluation of stress in intensive care units and the assessment of cardiovascular risk. New assays estimating the concentration of active peptides are under development.


Eyelash reconstruction with strip composite eyebrow graft.
Eyelash hairs have certain unique properties such as parallel direction, limited length, and tapering, which makes eyelash reconstruction considerably difficult. Several methods for eyelash reconstruction have been reported. Among them, strip composite eyebrow graft is the most suitable because the properties of eyebrow hairs are very similar to those of the original eyelash hairs. A rich blood supply in the eyelid ensures a good survival of the graft. Careful selection of the donor strip harvesting site is critical for preserving a good direction of hairs. The thickness of the graft strip should be determined considering the optimal thickness of hairs being obtained. When suturing the graft strip to the recipient bed, the burying method is suitable for preventing the protrusion of the graft. A well-performed surgical procedure results in a postoperative outcome that closely resembles the natural eyelashes.


AdimFlu-S(®) influenza A (H1N1) vaccine during pregnancy: the Taiwanese Pharmacovigilance Survey.
This study evaluated the incidence, nature, and seriousness of adverse drug reactions (ADRs) occurring after AdimFlu-S(®) influenza A (H1N1) vaccination in pregnant women was administered. This is a retrospective cohort study. Between October 2009 and February 2010, 198 pregnant women who had received the AdimFlu-S(®) influenza A (H1N1) vaccine during pregnancy and 198 age-matched pregnant women who had not received influenza vaccine were included and recorded. The pregnancy outcome and maternal adverse effects were extracted from chart reviews. Infant health status data were followed up until 8 weeks post-partum. During the observation period of each cohort, four subjects (2.0%) in the exposed group experienced vaccine-related adverse events that were mild in severity. A total of 17 women (8.6%) in the vaccine exposed group and 40 women (20.2%) in the unexposed group underwent at least one adverse effect during their pregnancy. A total of 72 infants (35.6%) in the exposed group and 101 infants (49%) in the unexposed group had at least one adverse event within 8 weeks after they were born (p<0.05). The adverse events experienced by the women and their infants were not increased when the vaccine was administered during the first trimester. There were no significant differences between these two groups with regard to preterm delivery rate and stillbirth rate. AdimFlu-S (®) influenza A (H1N1) vaccine is safe for pregnant women and their infants.


Co-expression of a prophage system and a plasmid system in Bacillus subtilis.
A dual expression system for overexpressing two proteins by a single cell strain has been developed in Bacillus subtilis. This dual expression system combines the phi105MU331 prophage system and a plasmid system within a single cell. Protein expression by the prophage system is heat inducible, while that of the plasmid system is constitutive. Three candidate genes, BPN, BT, and amyE, all of Bacillus origin, were used as test models. Seven strains (BPN, BT, AMY, BS168K, MU331K, BPNK, and BTK) were constructed to investigate the influences of the prophage system and the plasmid system on each other, and to compare the efficiency of the individual expression systems with that of the dual expression system. Individually, the yield of the plasmid system is higher than that of the prophage system, which could be attributed to the constitutive nature of the expression of the plasmid system. Nonetheless, for the dual expression strains, the expression of two enzymes in a single fermentation run can reduce costs in facilities, manpower, and utilities. Fed-batch fermentation of BPNK strains confirmed the feasibility of applying this dual expression system in industrial-scale production.


The effect of phencyclidine on the turnover rate of acetylcholine in various regions of rat brain.
Although the mechanism of action of phencyclidine is poorly understood, an interaction of phencyclidine with central cholinergic systems has been proposed. To test this hypothesis directly, we investigated the effects of this compound on the turnover rate of acetylcholine (TRACh) in various areas of the rat brain. In doses of 14.3 to 114.4 mumol/kg (i.p.), phencyclidine increased the TRACh in the frontal cortex, parietal cortex and diencephalon when rats were sacrificed 30 min after drug treatment. In contrast, these doses of phencyclidine had no effect on the TRACh in the hippocampus or striatum. The increases in cortical and diencephalic TRACh were temporally correlated with the behavioral activity elicited by phencyclidine. A 7 day chronic treatment regimen (28.6 mumol/kd/day) provided no further evidence for tolerance development to the effects of phencyclidine on the TRACh in the frontal cortex or diencephalon. These results demonstrate that phencyclidine differentially affects cholinergic dynamics in various areas of the rat brain. The neurochemical profile of phencyclidine reported herein is similar to those previously described for central stimulants such as d-amphetamine, nomifensine and cocaine.


11p15.5-specific libraries for identification of potential gene sequences involved in Beckwith-Wiedemann syndrome and tumorigenesis.
Constitutional and somatic chromosomal abnormalities of the chromosome 11p15 region are involved in an overgrowth malformation syndrome, the Beckwith-Wiedemann syndrome (BWS), and in several types of associated tumors. The bias in parental origin for the different etiologic forms of this syndrome and for loss of heterozygosity in the tumors suggests that a gene (or genes) mapping to this region undergoes genomic imprinting. However, the precise localization of the locus (or loci) for the BWS and associated tumors is still unknown and more markers are required. We therefore isolated 11p15 markers from two libraries: the first one obtained by microdissection of the chromosome 11p15.5 region and the second one, a phage library, constructed from a hybrid cell line containing this region as its sole human DNA. Of 19 microclones isolated from the microdissection library, 11 were evolutionarily conserved. Four phage clones were isolated; one (D11S774) detected a highly informative variable number of tandem repeats (VNTR) and another (D11S773) a biallelic polymorphism. These clones were sublocalized using a panel of somatic cell hybrids that defines eight physical intervals in 11p15.5. Twenty-one clones map to the distal interval that harbors the BWS locus.


Cytochrome oxidase activity in the rat retina following unilateral thalamic lesion.
The present study has investigated the cytochrome oxidase (CO) activity in retinas of normal rats and rats which received central lesions at birth or young adult stage. The results show that a thalamic lesion which injured the retinal ganglion cell axons in young adult rats led to severe loss of CO activity in the ganglion, inner and outer plexiform layers in the retina contralateral to the lesion as compared to those of normal rats. In contrast, distinct CO-reactive bands and cells were clearly observed in corresponding laminae in retinas in which almost the entire population of retinal ganglion cells was eliminated by a neonatal thalamic lesion. These results indicate that retinal ganglion cells contribute significantly to the CO activity observed in the inner retinal laminae under normal but not under abnormal conditions, and suggest that considerable changes in the activity of the remaining neurons and possibly reorganization of neural circuitry within the retina in rats which received neonatal lesions has taken place, as revealed by CO histochemistry.


Clinical evaluation of a resorbable wrap-around implant as an alternative to nerve repair: a prospective, assessor-blinded, randomised clinical study of sensory, motor and functional recovery after peripheral nerve repair.
Peripheral nerve injures are common and often result in impaired functional recovery. The majority of injuries involve the arm and/or the hand. The traditional treatment for peripheral nerve injuries is repair by using microsurgical techniques, either by primary nerve suture or nerve graft, but research to find more successful methods that could improve recovery is ongoing. Tubulisation has been investigated by several authors and is suggested as an alternative to microsurgical techniques. The resorbable poly[(R)-3-hydroxybutyrate] (PHB) is one of the materials that has been previously tested experimentally. In this prospective, randomised, assessor-blinded clinical study, PHB was investigated as an alternative to epineural suturing in the treatment of peripheral nerve injuries at the wrist/forearm level of the arm. Twelve patients, with a complete, common, sharp injury of the median and/or ulnar nerve at the wrist/forearm level, were treated by either using PHB or microsurgical epineural end-to-end suturing. All patients were assessed using a battery of tests, including evaluation of functional, sensory and motor recovery by means of clinical, neurophysiological, morphological and physiological evaluations at 2 weeks and 3, 6, 9, 12 and 18 months after surgery. No adverse events or complications considered as product related were reported, and thus PHB can be regarded as a safe alternative for microsurgical epineural suturing. The majority of the methods in the test battery showed no significant differences between the treatment groups, but one should consider that the study involved a limited number of patients and a high variability was reported for the evaluating techniques. However, sensory recovery, according to the British Medical Research Council score and parts of the manual muscle test, suggested that treating with PHB may be advantageous as compared to epineural suturing. This, however, should be confirmed by large-scale efficacy studies.


Risk and protective factors associated with speech and language impairment in a nationally representative sample of 4- to 5-year-old children.
To determine risk and protective factors for speech and language impairment in early childhood. Data are presented for a nationally representative sample of 4,983 children participating in the Longitudinal Study of Australian Children (described in McLeod & Harrison, 2009). Thirty-one child, parent, family, and community factors previously reported as being predictors of speech and language impairment were tested as predictors of (a) parent-rated expressive speech/language concern and (b) receptive language concern, (c) use of speech-language pathology services, and (d) low receptive vocabulary. Bivariate logistic regression analyses confirmed 29 of the identified factors. However, when tested concurrently with other predictors in multivariate analyses, only 19 remained significant: 9 for 2-4 outcomes and 10 for 1 outcome. Consistent risk factors were being male, having ongoing hearing problems, and having a more reactive temperament. Protective factors were having a more persistent and sociable temperament and higher levels of maternal well-being. Results differed by outcome for having an older sibling, parents speaking a language other than English, and parental support for children's learning at home. Identification of children requiring speech and language assessment requires consideration of the context of family life as well as biological and psychosocial factors intrinsic to the child.


[Cochleovestibular manifestations in hypothyroidism].
An study of cochleo-vestibular disturbances in different kinds of hypothyroidism is carried out. The majority of the patients suffered from sensorineural deafness of the flat type, lacking Recruitment. The evoked potentials of the brainstem were normal, where as myogenic ones showed a decrease in their amplitude. Evident central disturbances appeared on vestibular examination and a saccadic pursuit was frequently observed in the tracking test. The topography of the lesions is discussed.


Effects of galectin-9 on apoptosis, cell cycle and autophagy in human esophageal adenocarcinoma cells.
The incidence of esophageal adenocarcinoma (EAC) is rapidly increasing in western countries. The overall mortality of this disease remains high with a 5-year survival rate of less than 20%, despite remarkable advances in the care of patients with EAC. Galectin-9 (Gal-9) is a tandem-repeat type galectin that exerts anti-proliferative effects on various cancer cell types. The aim of the present study was to evaluate the effects of Gal-9 on human EAC cells and to assess the expression of microRNAs (miRNAs) associated with the antitumor effects of Gal-9 in vitro. Gal-9 suppressed the proliferation of the EAC cell lines OE19, OE33, SK-GT4, and OACM 5.1C. Additionally, Gal-9 treatment induced apoptosis and increased the expression levels of caspase-cleaved cytokeratin 18, activated caspase-3 and activated caspase-9. However, it did not promote cell cycle arrest by reducing cell cycle-related protein levels. Furthermore, Gal-9 increased the level of the angiogenesis-related protein interleukin-8 (IL-8) and markedly altered miRNA expression. Based on these findings, Gal-9 may be of clinical use for the treatment of EAC.


Isolation and characterization of stem cells from the placenta and the umbilical cord.
In addition to its essential role in the development, nutrition and immunological tolerance of the product of conception, human placenta is an important source of stem cells. Over the past years, scientific research has been aimed at isolating and characterizing mesenchymal cells and amniocytes, which show a high plasticity and are found in the chorionic villi and the membranes. At the level of the umbilical cord, two types of stem cells can be found: hematopoietic and mesenchymal. The blood of the umbilical cord is already in the focus of attention of researchers, as an important source of hematopoietic stem cells that can be used for transplantation.


Dual-wavelength interferometry based on the spatial carrier-frequency phase-shifting method.
From a single-frame dual-wavelength spatial carrier-frequency interferogram (SCFI), we propose a novel phase retrieval method of dual-wavelength interferometry (DWI). First, by continuously moving the intercepted area pixel-by-pixel in a single-frame SCFI along the horizontal and vertical directions, we construct a sequence of phase-shifting sub-interferograms. Second, the wrapped phases of each single wavelength can be retrieved from those phase-shifting sub-interferograms via the least-squares iteration algorithm. Third, the phase of synthetic wavelength can be obtained by subtraction between the wrapped phases of single wavelengths. Both the numerical simulation and the experimental result demonstrate that the proposed method reveals greater accuracy and convenience. Furthermore, because only single-frame SCFI can perform the phase retrieval of DWI, the proposed method offers better ability in resisting external vibration and disturbance, which will greatly facilitate the application of DWI in the dynamic phase measurement.


Effect of delmopinol on the viscosity of extracellular glucans produced by Streptococcus mutans.
The surfactant delmopinol, which is a new antiplaque agent with a low anti-microbial profile, was tested for its effects on the viscosity of bacterial extracellular glucans. Glucans were isolated from Streptococcus mutans broth supernatants incubated with 0.15 M sucrose in 50 mM sodium phosphate buffer at pH 6. The viscosity was measured in a shear rate range from 15 to 230 reciprocal seconds. The viscosity of the water-soluble glucan was found to be independent of shear rate whereas the water-insoluble glucan showed a strong shear thinning. The addition of delmopinol to preformed glucans did not affect the viscosity nor the shear rate dependence of the glucans. However, when present during synthesis of the polysaccharides, delmopinol was found to reduce the viscosity of both water-soluble and water-insoluble glucans by approximately 50% at the shear rates investigated. The reduction in viscosity for the water-soluble glucans was obtained at a delmopinol concentration of 0.32 mM (0.01%) and for the water-insoluble glucans at 3.2 mM delmopinol. The observed reduction of viscosity of glucans indicates that the in vivo stability of plaque matrix after delmopinol treatment would be lowered, which may lead to a reduction of plaque cohesion and thus facilitate mechanical plaque removal.


Functional significance of the copper transporter ATP7 in peptidergic neurons and endocrine cells in Drosophila melanogaster.
The Drosophila ATP7 copper transporter has sequence homology to the human copper transporters ATP7A and ATP7B, which are defective in Menkes and Wilson disease, respectively. We show here that in Drosophila ATP7 is expressed by many peptidergic neurons. As C-terminal amidation of neuropeptides depends on the copper-containing enzyme PHM, it seemed likely that in the absence of ATP7 the activity of PHM might be compromised. Indeed, inhibition of ATP7 expression by RNAi led to a decrease in mature amidated neuropeptides and the appearance of C-terminally Gly-extended neuropeptides. The strength of this effect differed from one cell type to another; it was very pronounced for AKH and corazonin, but much less so for SIFamide and myosuppressin. Nevertheless, down-regulation of ATP7 specifically in the SIFamide-expressing neurons resulted in male-male courtship behavior.


[Prospective evaluation of modalities of ceftazidime prescription].
Between November 1987 and October 1988, we have prospectively studied 101 hospital prescriptions of ceftazidime, a third generation cephalosporine, including all the health care departements of St Joseph hospital. A standard questionnaire was used to collect the date: dosage, length, and conditions of prescriptions. We observed that this antibiotic is correctly prescribed concerning dosage, length of prescription, and is adapted to bacteriological findings. The striking results were a high proportion of empirical prescriptions (48%) comparing to less than 10% 6 months before the beninning of this study. 75% of these empirical prescriptions being later on confirmed by bacteriological exams.


[Correlation of mercury, selenium and other elements in the tissues of fishes from the regions at different mercury exposure level].
The contents of selenium and other elements in fish liver and muscle tissues collected from mercury polluted area of Wanshan, Guizhou province of China and non-known mercury polluted one of Beijing were determined with instrumental neutron activation analysis, and that of mercury was determined with atomic fluorescence spectrometry. The correlation among the determined elements, especially between mercury and selenium, in the fish tissues were studied. For most of the elements significant difference of elemental content was found between tissues of liver and muscle, and mostly the content in liver was higher than that in muscle. It was interesting to note that the average content of mercury in Guizhou fish liver was 25-fold higher than that in Beijing one, and 5-fold higher in Guizhou fish muscle than that in Beijing one. For most of the elements no significant difference on the average content was found between the same tissues of the two areas. The molar ratio of Hg/Se increased with the increasing of Hg content at the low Hg level, but the alteration trend became gently and reached to a higher constant value (about 0.2) at the higher Hg level. Only the element of bromine and rubidium was found to have strong linear correlation between the two different tissues of liver and muscle. Though certain correlation existed among the different elements of fish tissues from the two areas, the most significant and the closest one existed between the mercury and selenium of muscle tissue of Guizhou fishes. A closer correlation was also found between them of liver tissue of Guizhou fishes. As for Beijing fish tissues, the correlation of mercury and selenium only existed in liver but no correlation of them was found in muscle. Our results confirm the fact that a certain interaction exists between mercury and selenium in organisms including fish, and it is more evident as the mercury-exposed level is higher. Some significant correlation was also observed between other elements, such as potassium and sodium, cesium and rubidium, iron and zinc, in fish tissues and it could be well explained by their similar chemical and physical properties or their different biological functions.


The diagnosis and treatment of depression in Parkinson's disease.
Depression is common in Parkinson's disease (PD) and associated with considerable morbidity, including a worsening of motor symptoms and measures of quality of life. Therefore, patients with PD should be routinely screened for depressive symptoms with rating scales such as the Geriatric Depression Scale. Patients meeting criteria should be treated using established algorithms for the management of depression and associated symptoms such as insomnia, anxiety, psychosis, and mania. The algorithm outlined in this paper describes the importance of maintaining an adequate dose of medication over a medication trial that can last up to 12 weeks. To optimally monitor patients' progress, clinicians should also consider using rating scales that measure depression severity, such as the Montgomery-Asberg Depression Rating Scale and Beck Depression Inventory.


Intraoperative Doppler sonogram in pediatric liver transplants: a pictorial review of intraoperative and early postoperative complications.
A spectrum of vascular complications can be seen in pediatric liver transplant patients, including occlusion and hemodynamically significant narrowing of the vessels that provide inflow to or outflow from the graft. Intraoperative Doppler ultrasound (US) has the potential benefit of identifying vascular complications in pediatric liver transplant patients prior to abdominal closure. Importantly, intraoperative Doppler US can be used as a problem-solving tool in situations such as position-dependent kinking of the portal or hepatic veins, or in suspected vasospasm of the hepatic artery. Furthermore, this technique can be used for real-time reassessment after surgical correction of vascular complications. This pictorial review of intraoperative Doppler US in pediatric liver transplant patients illustrates normal findings and common vascular complications, including examples after surgical correction, in the perioperative period.


Is p16(INK4A) expression more useful than human papillomavirus test to determine the outcome of atypical squamous cells of undetermined significance-categorized Pap smear? A comparative analysis using abnormal cervical smears with follow-up biopsies.
To correlate high-risk human papillomavirus (HR-HPV) viral load to p16(INK4A) expression in atypical squamous cells of undetermined significance (ASCUS)-categorized Pap smears with follow-up biopsies in order to elucidate their relationships in gynecological pathology. We studied 66 ASCUS-categorized Pap smears with subsequent follow-up biopsies. HR-HPV viral load was determined by Hybrid Capture II assay from the cervical swab in each ASCUS-diagnosed Pap smear. Both smears and biopsies were immunostained with a primary anti-p16 antibody, clone E6H4, and we analyzed the correlations between HR-HPV viral load in each ASCUS-diagnosed Pap smear and p16 expression of smears with follow-up biopsies. Correlation analyses of the corresponding histological diagnoses from 66 ASCUS-diagnosed Pap smears revealed that 21 (32%) cases had only reactive changes and 45 cases showed cervical intraepithelial neoplasia including LSIL (24 cases, 36%) and HSIL or higher (21 cases, 32%). Tests for HR-HPV viral load revealed 17 (26%) negative cases and 49 (74%) positive cases. Immunostaining showed that 26 cases (39%) were negative and 40 (61%) were positive for p16 expression. Comparative analysis of these two tests indicated consistencies as well as discrepancies. They showed significant differences (P < 0.001) between negative p16 expressions of Pap smears with the presence of reactive lesions in follow-up biopsies and HR-HPV viral load. However, no significant difference (P = 0.739 and 0.606) between p16 expression of Pap smears with the presence of LSIL, HSIL or higher in follow-up biopsies and high HR-HPV viral load was found. In addition, there were significant differences (P < 0.001) in specificity and positive predictive value, but no significant differences were found in sensitivity (P = 0.606) and negative predictive value (P = 0.062) between p16 immunostaining and HR-HPV viral load. The results indicate that there is a close association between weak or strong p16 expressions in ASCUS-categorized smears with the presence of SILs in follow-up biopsies and positive HR-HPV viral loads. Conversely, there is also a clear association between the lack of p16 expression and the absence of significant lesions in follow-up biopsies, but this is not consistent with a negative HR-HPV viral load. It is concluded that p16 expression is an indicator of pathogenic activity of HR-HPV, which is an objective biomarker for clarification of ASCUS-categorized Pap smears in gynecological cytopathology. Furthermore, through comparative analysis, directly visualized p16 immunostaining on smears appears to be a more effective method than HR-HPV viral load for the detection of reactive changes and LSILs from ASCUS-categorized Pap smears.


Non-radioactive in situ hybridization of DNA probes to chromosomes and nuclei. A comparison of techniques.
We have used a moderate repeat probe and a number of single copy DNA probes of varying sizes to compare different approaches to non-radioactive in situ hybridization. We have compared the ease and speed of the methods, the sensitivity, resolution, reproducibility, the availability and costs of reagents, and the potential for clinical application. Following biotinylation or mercuration, the probes were hybridized to human metaphases and nuclei and detected by different affinity systems. Visualization of signals was by brightfield, phase contrast, fluorescence or reflection contrast microscopy. As a result of our study, we recommend two simple and reliable methods using the biotinylation approach with either the avidin-peroxidase conjugate and diaminobenzidine detection and reflection contrast microscopy, or the streptavidin-alkaline phosphatase conjugate and bromochlorodinolyl phosphate nitroblue tetrazolium chloride detection using phase contrast microscopy.


Regional distribution of the AMPA glutamate receptor subunits GluR2(4) in human hippocampus.
In order to characterize the regional and cellular distribution patterns of individual ionotropic excitatory amino acid receptor subunits in the human hippocampus we performed an immunohistochemical analysis using the monoclonal antibody 3A11 to the AMPA GluR2(4) subunit. The study was based on paraffin embedded hippocampal specimens of five human brains obtained at autopsy. GluR2(4) immunoreactivity was consistently higher in hippocampus as compared to the adjacent areas of the mesial temporal lobe. Virtually all neurons showed intracytoplasmic staining of the perikarya and dendritic profiles with well defined laminar patterns. The most intense GluR2(4) immunoreactivity was observed in the target structures of mossy fibers, thus indicating that GluR2(4) AMPA subunits may be involved in NMDA-independent synaptic transmission pathways and long-term potentiation. Glial cells were not immunoreactive. These findings may provide basic information for studies of the GluR2(4) subunit in human hippocampus during various neuropathological conditions, such as temporal lobe epilepsy, ischemia and Alzheimer's disease.


Peripheral neurons: Master regulators of skin and mucosal immune response.
The body is innervated by a meshwork of heterogeneous peripheral neurons (including sensory neurons) which project virtually to all the organs. Peripheral neurons have been studied extensively in the context of their primary function of initiation of voluntary and involuntary movement, transmission of sensations and induction of appropriate behavioral response such as withdrawal to avoid tissue injury or scratching to remove irritating molecules. More recently, breakthrough articles have shown that, on top of their primary function of signal transmission to the spinal cord and brain, peripheral neurons (including afferent neurons) could directly sense environmental alarms and consequently regulate the development of various type of immune responses through the release of neuropeptides or growth factors. In this review, we discuss recent advances in the neural regulation of the immune response, both in physiological and pathological contexts by taking into account the type of organs (lungs, skin and gut), subtypes of peripheral neurons (sympathetic, nociceptive and intrinsic gut neurons) or immune cells and strains of pathogens studied. We also highlight future challenges in the field and potential therapeutic innovations targeting neuro-immune interactions.


Matrix metalloproteinase-sensitive size-shrinkable nanoparticles for deep tumor penetration and pH triggered doxorubicin release.
Nanocarriers are widely used for delivering drugs to tumors and are progressing in a stable trend. The enhanced permeability and retention (EPR) effect has been a key rationale for the development of stimulus-responsive nanocarriers to solid tumor. In this study, we developed a kind of novel nanocarrier, G-AuNPs-DOX-PEG, which was constructed with shrinkable gelatin nanoparticles coated, doxorubicin (DOX) tethered gold nanoparticles and long chain polyethylene glycol (PEG). The particle size of G-AuNPs-DOX-PEG was 186.5 nm with a zeta potential of -4.21 mV and the DOX loading capacity was 9.22%. In vitro, the G-AuNPs-DOX-PEG could be degraded by MMP-2 proteins with a size shrink from 186.5 nm to 59.3 nm. The release of DOX from G-AuNPs-DOX-PEG was in a pH- and time-dependent manner. At pH 5.0, the release of DOX was much quicker than that at high pH value and the cumulative release rate of DOX from G-AuNPs-DOX-PEG was approach 90.9%. Cellular uptake demonstrated that G-AuNPs-DOX-PEG could be internalized via the endosome-mediated pathway. Tumor spheroid penetration and collagen gel diffusion showed G-AuNPs-DOX-PEG with pre-incubation with MMP-2 could significantly enhance its penetrating efficiency. In vivo and ex vivo imaging exhibit that G-AuNPs-DOX-PEG could distribute into 4T1 and B16F10 tumor at a highest intensity. Correspondingly, 4T1 and B16F10 tumor bearing mice treated with G-AuNPs-DOX-PEG displayed the lowest tumor growth rate. In summary, the tumor microenvironment sensitive size-shrinkable G-AuNPs-DOX-PEG could deliver into deep tumor region and then release DOX, resulting in a best anti-tumor effect.


Evaluation of the effect of Cassia surattensis Burm. f., flower methanolic extract on the growth and morphology of Aspergillus niger.
Cassia (C.) surattensis Burm. f. (Leguminosae), a medicinal herb native to tropical equatorial Asia, was commonly used in folk medicine to treat various diseases. The aim of the present study is to investigate the effects of methanolic flower extract of C. surattensis against Aspergillus (A.) niger. Antifungal activity of C. surattensis flower extract was studied by using agar disc diffusion method, broth dilution method, percentage of hyphal growth inhibition and scanning electron microscopy (SEM) observation. The extract exhibited good antifungal activity with zone of inhibition 15 mm and minimum inhibitory concentration (MIC) 6.25 mg/ml. The flower extract exhibited considerable antifungal activity against A. niger with a IC50 of 2.49 mg/ml on the hyphal growth. In scanning electron microscopy (SEM) squashed, collapsed, empty and deformation of hyphae were the major changes observed. Shrunken conidiophores were the obvious alteration on the spores. Morphological alterations observed on A. niger caused by the flower extract could be the contribution of chemical compounds present in the Cassia flower. Phytochemical screening reveals the presence of carbohydrate, tannins, saponins and phenols in the extract. The amount of tannin, total phenolics and flavonoids were estimated to be 55.14 ± 3.11 mg/g, 349.87 ± 5.41 mg/g gallic acid equivalent and 89.64 ± 3.21 mg/g catechin equivalent respectively. C. surattensis flower extract potently inhibited the growth of A. niger and are, therefore, excellent candidates for use as the lead compounds for the development of novel antifungal agents.


Icosahedron oligomerization and condensation in intermetallic compounds. Bonding and electronic requirements.
Icosahedron-based clustering has been found to be very common in intermetallics, particularly for group 13 and early p-block icosogen elements. Linking of the icosahedral building blocks depends on the valence electron concentrations. Vertex-, edge-, or face-sharing icosahedra occur as the structure compensates for electron deficiency. Some examples of icosahedron-based clusters have been selected for an analysis of the relationships between the structural features (icosahedron oligomerization, atomic defects, etc.) and the bonding and electronic requirements. The extended Hückel method has been used with either a molecular approach or an electronic band structure calculation to rationalize bonding in the intermetallic framework.


Expression of Sox transcription factors in the developing mouse pancreas.
Previous work has identified members of the homeodomain and basic helix-loop-helix families of transcription factors as critical determinants of mammalian pancreatic development. Here, we describe the identification of HMG-box transcription factors of the Sox gene family in the mouse pancreas. We detected transcripts for Sox11, Sox4, Sox13, Sox5, Sox9, Sox8, Sox10, Sox7, Sox17, Sox18, Sox15, and Sox30 in embryonic pancreas and found Sox4, Sox9, and Sox13 in adult pancreatic islets. Expression of seven of these Sox factors was studied in more detail by in situ hybridization from the stage of early pancreatic outgrowth to birth. Expression of Sox11 was found in the mesenchyme surrounding the pancreatic buds, whereas Sox4 and Sox9 were confined to the pancreatic epithelium and later to islets. Sox13 and L-Sox5 showed expression in most of the pancreatic epithelial cells between embryonic days 12.5 and 14.5. Sox8 and Sox10 were detected in a thin layer of cells surrounding the islets. The expression patterns of Sox genes in the embryonic pancreas suggest that they could have important and possibly redundant functions in pancreas development.


Upregulation of RAGE and its ligands in proliferative retinal disease.
We sought to study the presence of the receptor for advanced glycation endproducts (RAGE) and its ligands, advanced glycation endproducts (AGEs), S100/calgranulins and amphoterin (high mobility group box 1 protein; HMGB1), in the vitreous cavity and epiretinal membranes (ERMs) of eyes of patients with proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). Undiluted vitreous specimens were collected from 30 eyes of 30 patients undergoing pars plana vitrectomy for repair of retinal detachment (RD) secondary to PDR (n = 15) or PVR (n = 15). The vitreous samples obtained from 10 eyes undergoing macular hole repair were used as controls. Epiretinal membranes were obtained from eight eyes with PDR and from 10 eyes with PVR. The levels of AGEs in the vitreous were measured using ELISA. The vitreous levels of soluble RAGE (sRAGE), S100/calgranulins and amphoterin were measured using Western blot analyses. The localization of RAGE and its ligands in ERMs was determined with immunohistochemistry. The vitreous levels of sRAGE were significantly increased in both PDR and PVR (p < or = 0.05) compared to control vitreous. In both PDR and PVR, the vitreous levels of AGEs (p < or = 0.01), S100/calgranulins (p < or = 0.05), and amphoterin (p < or = 0.01) were also elevated compared to control eyes. Expression of RAGE was detected in six of eight ERMs from eyes with PDR and eight of 10 ERMs from eyes with PVR. Many cells expressing RAGE also expressed vimentin, suggesting a glial cell origin. Ligands for RAGE were also detected in ERMs, with AGEs detected in five eyes with PDR and eight eyes with PVR. Similarly, S100 and amphoterin ERM expression was observed in six eyes with PDR; these ligands were also expressed in ERMs from eyes with PVR (8 and 7 cases, respectively). We conclude that RAGE and its ligands are increased in the vitreous cavity of eyes with PDR and PVR and are present in ERMs of eyes with these proliferative retinal disorders. These findings suggest a role for the proinflammatory RAGE axis in the pathogenesis of proliferative retinal diseases.


[Congenital nasal cysts and fistulae].
Congenital nasal cysts and fistulae are relatively rare. Their localization is usually medial, sometimes lateral at sites of facial junctions during the embryonic period, either above or below the nasal bones. In a group of 16 children operated in the course of 25 years on account of a congenital nasal fistula or cyst the authors encountered in two instances junction of the fistula with the dura mater. According to the histological examination dermoids or epidermoids were involved. As the pressure of the cyst may cause usuration of bone and distension of the osseous nasal skeleton, it is recommended to operate as soon as possible.