Developmental changes in the topographical distribution of cells contributing to the lateral olfactory tract.
Developmental changes in the locations of cells in the olfactory bulb which contribute axons to the lateral olfactory tract (LOT) were investigated using retrograde transport of horseradish peroxidase (HRP). HRP was placed in the olfactory tubercle, LOT, and/or piriform cortex of golden hamsters aged 3,7,8 and 20 days. The numbers of labeled mitral and tufted cells were counted on equidistant sections through the olfactory bulb. In the younger animals (days 3 and 7), there was a distinct localization of labeled cells in the medial quadrant of the bulb. In the 3-day-old group 49% of all labeled cells were located in the medial quadrant, but by day 8 the per cent of cells in all 4 quadrants was equivalent. Between days 3 and 20, the average perimeter of the mitral cell layer doubled. There was a similar increase in the average relative total number of labeled cells per bulb. When pairs of brains from the different age groups with HRP placements of similar size and location were compared, the older brain always had more labeled cells. There was no relation of the number or distribution of labeled cells to the location of the injection. The number of labeled cells correlated positively with the size of the injection within each age group. We believe this is the first report of a developmental topographical gradient of the cells of origin of the LOT. This localization may be related to early topographical differences in functional activity which reflect a limited exposure to odors in the first week of life.


Glass Formation of a Coordination Polymer Crystal for Enhanced Proton Conductivity and Material Flexibility.
The glassy state of a two-dimensional (2D) Cd(2+) coordination polymer crystal was prepared by a solvent-free mechanical milling process. The glassy state retains the 2D structure of the crystalline material, albeit with significant distortion, as characterized by synchrotron X-ray analyses and solid-state multinuclear NMR spectroscopy. It transforms to its original crystal structure upon heating. Thus, reversible crystal-to-glass transformation is possible using our new processes. The glass state displays superior properties compared to the crystalline state; specifically, it shows anhydrous proton conductivity and a dielectric constant two orders of magnitude greater than the crystalline material. It also shows material flexibility and transparency.


Awareness and attitudes toward hepatitis B among Malaysian dentists.
A questionnaire was mailed to 1217 dentists whose names appear in the Dentist Register of 1987 in order to assess their awareness and acceptance of hepatitis B vaccine and their pattern of glove usage. Almost all the respondents (99.6%) were aware of the availability of the hepatitis B vaccine yet only 44.8% have received the vaccine. This is in spite of the fact that the majority (61.2%) of the vaccine non-acceptors have no reservations concerning the vaccine. About 71% and 63% of the vaccine-acceptors and non-acceptors respectively believed that the risk of their contracting hepatitis B was high or very high. About 22% of the vaccine non-acceptors never used gloves when treating patients as compared to 9% among vaccine acceptors. Overall, about 78% of the respondents have experienced needleprick injuries in the 3 years preceding the survey.


Differential peripheral nerve block by local anesthetics in the cat.
Controversy still surrounds the differential susceptibility of nerve fibers to local anesthetic conduction block. In order to help resolve this controversy, we developed an in vivo model of peripheral nerve blockade in the cat that closely reproduced the clinical state. Using this model, differential rate of nerve blockade of A-alpha, A-delta, and C fibers by 2-chloroprocaine, lidocaine, bupivacaine, and etidocaine was observed and quantitated. C fibers were blocked first by 2-chloroprocaine, lidocaine and bupivacaine. Etidocaine blocked A-delta fibers first. A-alpha fibers always were blocked last. Of the four local anesthetics tested, 2-chloroprocaine produced the greatest differential rate of block of the nerve fibers, and etidocaine produced the least.


An experimental and theoretical study of interactions between unlike surface anions and increases in the rate of electrochemical reactions.
Experimental and theoretical results are presented on increases in the rate of electrochemical reactions, which are achieved by replacing a small fraction of the original anions in solution with more inhibiting ones. The rate of the electrochemical oxidation of formic acid was substantially increased by replacing a small amount of the supporting electrolyte, perchloric acid, with either sulfuric acid or tetrafluoroboric acid. The largest increases were achieved by substituting mixtures of the last two acids. A theoretical analysis of an electrochemical reaction coupled to anion adsorption is presented. The analysis reveals that, if repulsive forces of appropriate strength form between unlike surface anions, replacing a fraction of the original anions in solution with one or two kinds of more inhibiting anions can increase the rate of reaction.


[Acute knee pain in pregnancy. Case report of Regional Transient Osteoporosis].
The article presents the case of a patient who after her first pregnacy, during the immediate postpartum period, suffered a femoral supracondylar fracture complicated by bone marrow edema syndrome (BMES), also known as regional temporary osteoporosis (RTO). The fracture of the distal femur was treated with an open reduction and internal fixation of the distal femur by means of a minimally invasive procedure.


Purification and some properties of Pseudomonas fluorescens lipase.
Lipase (triacylglycerol lipase, EC 3.1.1.3) has been purified from Pseudomonas fluorescens wild strain by chromatography on DEAE-cellulose and octyl-Sepharose CL-4B. The yield was 21% and the specific activity of the purified enzyme 4780 U/mg protein. It showed a Mr of about 45 x 10(4) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme is active over a wide pH range and at 50-55 degrees C.


Mode of action of an insecticidal peptide toxin from the venom of a weaving spider (Diguetia canities).
A recently discovered spider toxin (DTX9.2) induced a rapid paralysis when injected into insects. In neurophysiological experiments, DTX9.2 elevated spike discharges in sensory nerves and at the neuromuscular junction, and also caused a depolarization of the membrane potential in cockroach giant axons. All these effects were reversed by treatment with the specific sodium channel blocker, tetrodotoxin. These findings suggest that DTX9.2 acts upon the voltage-dependent sodium channels of insect nerve membrane.


Comparative economic analyses of patient safety improvement strategies in acute care: a systematic review.
The objective was to systematically review comparative economic analyses of patient safety improvements in the acute care setting. A systematic review of 15 patient safety target conditions and six improvement strategies was conducted. The authors searched the published literature through Medline (2000-November 2011) using the following search terms for costs: 'costs and cost analysis', 'cost-effectiveness', 'cost' and 'financial management, hospital'. The methodological quality of potentially relevant studies was appraised using Cochrane rules of evidence for clinical effectiveness in quality improvement, and standard economic methods. The authors screened 2151 abstracts, reviewed 212 potentially eligible studies, and identified five comparative economic analyses that reported a total of seven comparisons based on at least one clinical effectiveness study of adequate methodological quality. Pharmacist-led medication reconciliation to prevent potential adverse drug events dominated (lower costs, better safety) a strategy of no reconciliation. Chlorhexidine for vascular catheter site care to prevent catheter-related bloodstream infections dominated a strategy of povidone-iodine for catheter site care. The Keystone ICU initiative to prevent central line-associated bloodstream infections was economically dominant over usual care. Detecting surgical foreign bodies using standard counting compared with a strategy of no counting had an incremental cost of US$1500 (CAN$1676) for each surgical foreign body detected. Several safety improvement strategies were less economically attractive, such as bar-coded sponges for reducing retained surgical sponges compared with standard surgical counting, and giving erythropoietin to reduce transfusion requirements in critically ill patients to avoid one transfusion-related adverse event. Five comparative economic analyses were found that reported a total of seven comparisons based on at least one effectiveness study of adequate methodological quality. On the basis of these limited studies, pharmacist-led medication reconciliation, the Keystone ICU intervention for central line-associated bloodstream infections, chlorhexidine for vascular catheter site care, and standard surgical sponge counts were economically attractive strategies for improving patient safety. More comparative economic analyses of such strategies are needed.


Enhanced photo-catalytic activity of Sr and Ag co-doped TiO2 nanoparticles for the degradation of Direct Green-6 and Reactive Blue-160 under UV & visible light.
This work is focused on sol-gel synthesis of silver and strontium co-doped TiO2 nanoparticles and their utilization as photo-catalysts in degradation of two textile dyes. Effect of pH, intensity of light, amount of photo-catalyst, concentration of dye, sensitizers, etc., were studied to optimize conditions for obtaining enhanced photo-catalytic activity of synthesized nanoparticles. XRD, BET, HR-TEM, EDAX and UV-Vis (diffused reflectance mode) techniques were used to characterize the nanoparticles. Interestingly, band gap of Sr and Ag co-doped TiO2 nanoparticles showed considerable narrowing (2.6 eV) when compared to Ag doped TiO2 (2.7 eV) and undoped TiO2 (3.17 eV) nanoparticles. Incorporation of Ag and Sr in the lattice of TiO2 could bring isolated energy levels near conduction and valence bands thus narrowing band gap. The XRD analysis shows that both Ag and Sr nanoparticles are finely dispersed on the surface of titania framework, without disturbing its crystalline structure. TEM images indicate that representative grain sizes of Ag-doped TiO2 & Sr and Ag co-doped TiO2 nanoparticles are in the range of 8-20 nm and 11-25 nm, respectively. Effective degradation of Direct Green-6 (DG-6) and Reactive Blue-160 (RB-160) under UV and visible light has been achieved using the photo-catalysts. Sr and Ag co-doped TiO2 photo-catalysts showed higher catalytic activity during degradation process in visible region when compared to Ag-doped and undoped TiO2 nanoparticles which could be attributed to the interactive effect caused by band gap narrowing and enhancement in charge separation. For confirming degradation of the dyes, total organic carbon (TOC) content was monitored periodically.


High-resolution low-temperature scanning electron microscopy for observing intracellular structures of quick frozen biological specimens.
Intracellular structures of rapidly frozen biological tissues were observed in 3-D under a low-temperature scanning electron microscope using a newly developed side-entry type cryo-holder. The present low-temperature SEM is simple, easy to operate and effective for observing biological materials at high magnification. Biological tissues (the pancreas, small intestine, brown adipose tissue and Harderian gland) freshly removed from the mouse were immediately frozen in liquid propane cooled with liquid nitrogen, and their surfaces were manually fractured using a precooled razor blade in liquid nitrogen before introducing the cryo-holder into the SEM. When intracellular structures were revealed after appropriate sublimation, the specimens were coated with gold using a metal evaporator fitted to the side of the microscope column at one of the specimen chamber ports. The cryo-holder was connected to a copper braid coming from a liquid nitrogen reservoir to maintain a low temperature. Using this method, intracellular structures such as the mitochondria and endoplasmic reticulum were demonstrated at high magnifications. Ribosomal granules were discerned on the rough endoplasmic reticulum of the pancreatic acinar cells. Granular substances, presumably elementary particles, were also recognized on the mitochondrial cristae of the brown adipose tissue. The method was particularly effective for studying the 3-D configuration of lipid droplets which had been difficult to preserve by chemical fixation.


[Post-mastectomy radiotherapy with different fractionated dose schemes in early breast cancer].
To study the effect of post-mastectomy radiotherapy with different fractionated dose schemes for early breast cancer. From January 1987 to January 1993, 367 patients with early breast cancer were given post-mastectomy radiotherapy with three different fractionated dose schemes. 149 patients received conventional radiotherapy with 50 Gy/25 fractions/5 weeks (Group A). 177 patients received 45 Gy/15 fractions/5 weeks (Group B). Forty-one patients were treated with 23 Gy/4 fractions/17 days (Group C). 257 patients received systemic therapy (chemotherapy and/or endocrine therapy). The overall 5-year survival and 5-year disease-free survival rates were 87.4% and 89.6%. The 5-year disease-free survival rate were 90.8%, 86.5% and 84.6% for A, B and C groups (P = 0.16). The corresponding loco-regional failure rates were 2.7%, 2.8% and 2.4%, respectively. There was no statistically significant difference in the local control and efficacy of the three groups. With similar 5-year tumor-free survival rates by the conventional fractionation and hypofractionation, the scheme with 45 Gy/15 fractions/5 weeks has the advantage of giving less factions, which is suitable for a unit with limited radiation resources. The course of hypofractionation with 23 Gy/4 fractions/17 days is much shorter than conventional radiotherapy, which may benefit patients with higher risk of metastasis who need to undergo chemotherapy earlier. This study warrants further investigations.


[Suppressive effect of Notch signal activation on apoptosis of multiple myeloma cells].
The proliferation and apoptosis of multiple myeloma (MM) cells were regulated by bone marrow microenvironments in which Notch signal plays important role in mediating cell-cell communication. However, the regulatory effect of Notch signal on the proliferation and apoptosis of multiple myeloma cells remains unclear. In this study, regulatory effect of Notch signal on the apoptosis of MM cells induced by DMS (N, N-dimethylsphingosine) was investigated. RT-PCR was used to identify the expression of Notch receptor and related molecules such as Dll-1, Jagged-1, Deltex-1 in MM cell lines. The intracellular domain of Notch (ICN), active form of Notch, was transferred into MM cells by retrovirus. The apoptosis of MM cells was determined by trypan blue exclusion tests and TdT-mediated dUTP nick end labeling (TUNEL) assay. The results showed that multiple myeloma cells expressed the Notch-1 and its related molecules. Notch activated multiple myeloma cell lines were obtained. Activation of Notch protected the multiple myeloma cells from the apoptosis induced by DMS,which was determined by cell viability and TUNEL assay. In conclusion, Notch signal suppressed the apoptosis of multiple myeloma cells and would possibly be a novel therapeutic target.


[Reliability of self-reported maternal smoking during early lactation period].
Smoking cigarettes is very common among lactating women. The objective evaluation of an exposure to cigarette smoke is needed, as cotinine concentration. On many research a questionnaire is the only determinant of fact and intensification of smoking. The aim of this research was to establish a reliability of the questionnaire concerning cigarette smoking among lactating mothers by analyzing cotinine/creatinine ratio. In 51 lactating mothers (participants of the research on oxidative stress in Obstetrics Departments on 3rd day post partum) during check-up visit, on 30th day post partum a questionnaire concerning smoking cigarettes before, during pregnancy and after childbirth, and amount of cigarettes smoked was made. Samples of matutinal urine were deep freezed in - 700 till cotinine was evaluated immunoenzymatically. Women were divided into groups: I of non-smokers (32 women), II of smokers (19 women). Statistical analysis was made by means of unparametric test U Mann-Whitney. Average cotinine/creatinine ratio was 33,8 ng/mg in group I; 1275.9 ng/mg in group II. Specificity and sensitivity of data earned by virtue of statement of correspondents was 81% and 89%. Test of cotinine concentration in urine demonstrated 100% sensitivity and 94% specificity compared to the cotinine/creatinine ratio. Directly proportional relationship was stated between amount of cigarette smoked and concentration of cotinine in urine (55.9 ng/ ml cotinine/cigarette). A questionnaire should not be the only method evaluating smoking among lactating women. The concentration of cotinine shows slightly lower specificity than cotinine/creatinine ratio. Both tests can be dealt equivalent.


Delayed gadolinium-enhanced magnetic resonance imaging (dGEMRIC) of hip joint cartilage: better cartilage delineation after intra-articular than intravenous gadolinium injection.
To investigate and compare delayed gadolinium (Gd-DTPA)-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) in the hip joint using intravenous (i.v.) or ultrasound-guided intra-articular (i.a.) Gd-DTPA injection. In 10 patients (50% males, mean age 58 years) with clinical and radiographic hip osteoarthritis (OA; Kellgren score II-III), MRI of the hip was performed twice on a clinical 1.5T MR scanner: On day 1, before and 90-180 min after 0.3 mmol/kg body weight i.v. Gd-DTPA and, on day 8, 90-180 min after ultrasound-guided i.a. injection of a 4 mmol/l Gd-DTPA solution. Coronal STIR, coronal T1 fat-saturated spin-echo, and a cartilage-sensitive gradient-echo sequence (3D T1 SPGR) in the sagittal plane were applied. RESULTS Both the post-i.v. and post-i.a. Gd-DTPA images showed significantly higher signal-to-noise (SNR) and contrast-to-noise (CNR) in the joint cartilage compared to the non-enhanced images (P < 0.002). I.a. Gd-DTPA provided significantly higher SNR and CNR compared to i.v. Gd-DTPA (P < 0.01). Furthermore, a better delineation of the cartilage in the synovial/cartilage zone and of the chondral/subchondral border was observed. The dGEMRIC MRI method markedly improved delineation of hip joint cartilage compared to non-enhanced MRI. The i.a. Gd-DTPA provided the best cartilage delineation. dGEMRIC is a clinically applicable MRI method that may improve identification of early subtle cartilage damage and the accuracy of volume measurements of hip joint cartilage.


Synergistic anti-proliferative effects of vitamin D derivatives and 9-cis retinoic acid in SH-SY5Y human neuroblastoma cells.
This study examines the effect of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], 24,25-dihydroxyvitamin D(3) [24,25(OH)(2)D(3)], two vitamin D analogues (KH 1060 and EB 1089, which are 20-epi-22-oxa and 22,24-diene-analogues, respectively), 9-cis retinoic acid and all-trans retinoic acid on proliferation of SH-SY5Y human neuroblastoma cells, after treatment for 7 days. Cell number did not change when the cells were incubated with 1, 10 or 100 nM 1,25(OH)(2)D(3) or its derivatives, but significantly decreased in the presence of the two retinoids (0.001--10 microM final concentration). A synergistic inhibition was observed, when SH-SY5Y cells were treated combining 0.1 microM 9-cis retinoic acid and 10 nM 1,25(OH)(2)D(3) or 10 nM KH 1060, and 1 microM 9-cis retinoic acid and 10 nM 1,25(OH)(2)D(3) or 10 nM EB 1089. Acetylcholinesterase activity showed a significant increase, in comparison with controls, after treatment of the cells for 7 days with 0.1 or 1 microM 9-cis retinoic acid, alone or combined with 10 nM 1,25(OH)(2)D(3) or 10 nM KH 1060 or 10 nM EB 1089. This increase was synergistic, combining 1 microM 9-cis retinoic acid and 10 nM 1,25(OH)(2)D(3) or EB 1089. The levels of the c-myc encoded protein remarkably decreased after treatment of SH-SY5Y cells for 1, 3, 7 days with 0.1 and 1 microM 9-cis retinoic acid, alone or combined with 10 nM 1,25(OH)(2)D(3) or 10 nM KH 1060 or 10 nM EB 1089. In particular, the association of 1 microM 9-cis retinoic acid and 10 nM 1,25(OH)(2)D(3) or 10 nM EB 1089 resulted in a synergistic c-myc inhibition, in comparison with that obtained in the presence of the retinoid alone. These findings may have therapeutic implications in human neuroblastoma.


Transportation to clinic: findings from a pilot clinic-based survey of low-income suburbanites.
Health care policymakers have cited transportation barriers as key obstacles to providing health care to low-income suburbanites, particularly because suburbs have become home to a growing number of recent immigrants who are less likely to own cars than their neighbors. In a suburb of New York City, we conducted a pilot survey of low income, largely immigrant clients in four public clinics, to find out how much transportation difficulties limit their access to primary care. Clients were receptive to the opportunity to participate in the survey (response rate = 94%). Nearly one-quarter reported having transportation problems that had caused them to miss or reschedule a clinic appointment in the past. Difficulties included limited and unreliable local bus service, and a tenuous connection to a car. Our pilot work suggests that this population is willing to participate in a survey on this topic. Further, since even among those attending clinic there was significant evidence of past transportation problems, it suggests that a population based survey would yield information about substantial transportation barriers to health care.


Photothermal-Responsive Single-Walled Carbon Nanotube-Based Ultrathin Membranes for On/Off Switchable Separation of Oil-in-Water Nanoemulsions.
Oil-contaminated wastewater threatens our environment and health, especially that stabilized by surfactants. Conventional separation protocols become invalid for those surfactant-stabilized nanoemulsions due to their nanometer-sized droplets and extremely high stability. In this paper, photothermal-responsive ultrathin Au nanorods/poly(N-isopropylacrylamide-co-acrylamide) cohybrid single-walled carbon nanotube (SWCNT) nanoporous membranes are constructed. Such membranes are capable of separating oil-in-water nanoemulsions with a maximum flux up to 35 890 m(2)·h(-1)·bar(-1) because they feature hydrophilicity, underwater oleophobicity, and nanometer pore sizes. It is remarkable that the permeation flux can be simply modulated by light illumination during the process of separation, due to the incorporation of thermal-responsive copolymers and Au nanorods. Meanwhile, it shows ultrahigh separation efficiency (>99.99%) and desired antifouling and recyclability properties. We anticipate that our ultrathin photothermal-responsive SWCNT-based membranes provide potential for the generation of point-of-use water treatment devices.


[Radiologic staging of renal cell carcinoma].
The routine staging work-up for renal cancer includes a contrast-enhanced multiphasic spiral CT and a chest radiograph. If there is doubt regarding the presence and extent of (supradiaphragmatic) IVC thrombus, MR imaging should be performed. Dynamic contrast-enhanced MR imaging should be used in place of CT in any patient with severe renal dysfunction, symptomatic polycystic kidney disease, or a history of allergy to iodinated contrast media. Cavography is no longer needed in the era of (adaptive array detector) spiral CT and MR venography.


New species for Virgilia Stål, 1870 (Hemiptera, Lophopidae), genus review and key to species.
Two new species of the lophopid genus Virgilia Stål 1866, are described and illustrated, V. cocovora Soulier-Perkins sp. nov. and V. imuganensis Soulier-Perkins sp. nov. A key to the species of the genus is provided. Photos for the four Virgilia species are presented and the male terminalia illustrations are given. A comment on the potential pest status of one of the described species, V. cocovora, is given.


Single payer health insurance in pediatric surgery: US impressions and Canadian experience.
Some advocate single payer national health insurance, present in Canada, as a solution to problems in US health care. Pediatric surgeons in the US and Canada were surveyed regarding their attitudes (US) and experience (Canada) under a single payer by electronic mail regarding features of a single payer using a Likert scale (1-strongly disagree to 5-strongly agree) on quality, administration, organization, and economics. Overall response rate of 22% (175/835), 153 US, 22 Canadian. US and Canadian respondents predicted a higher quality of care for both emergency (66 and 36%, respectively) and elective conditions (47 and 9%) under a single payer. Both groups recognized delays for elective surgery. Better access to surgical care under a single payer, seen by most Canadians (81%), was not predicted among Americans (44%, p = 0.00012). Americans (68%) did not believe a single payer would address workforce shortages, while Canadians (68%) disagreed (p = 0.00001). Both groups agree (p = 0.7) that personal income is decreased. US surgeons anticipate benefits and problems that Canadian surgeons with direct experience with a single payer do not experience. This discrepancy must be recognized during the ongoing debate over the future of US health care.


Effect of combined mutations in the enhancer II and basal core promoter of hepatitis B virus on development of hepatocellular carcinoma in Qidong, China.
To investigate the roles of mutations in enhancer II (Enh II), basal core promoter (BCP) and precore (PC) regions of hepatitis B virus (HBV) in the progression of hepatocellular carcinoma (HCC) in Qidong, China. We conducted a case-control study within a cohort of 2387 male HBV carriers who were recruited between August and September 1996. The HBV DNA sequence was determined in 152 HCC and 131 chronic hepatitis patients. Mutation exchanges during follow up in 115 cases were compared with 108 controls with serum samples taken during a similar length of follow up. In addition, a longitudinal study was conducted in 22 cases in which serial serum samples were available before HCC. After adjustment for age, history of cigarette smoking and alcohol consumption, hepatitis B e-antigen positivity, T1653, V1753 and T1762/A1764 double mutations were associated with risk of HCC. Multivariate analysis showed that T1653, V1753 and T1762/A1764 double mutations were independent risk factors of HCC. Moreover, a significant biological gradient of HCC risk by number of mutations in Enh II/BCP regions was observed. Paired samples analysis indicated that the increased HCC risk for at-risk sequence mutations were attributable to the persistence of these mutations, but not a single time point mutation. The longitudinal observation demonstrated a gradual combination of mutations in Enh II/BCP regions accumulated during the development of HCC. T1653, V1753 and T1762/A1764 double mutations were independent risk factors of HCC. The effect of combined mutations in Enh II/BCP regions increased the risk and persistence of at-risk sequence mutations and was critical for HCC development.


Translocation pathways in the petioles and stem between source and sink leaves of Populus deltoides Bartr. ex Marsh.
Microautoradiography was used to follow the translocation pathways of (14)C-labeled photosynthate from mature source leaves, through the stem, to immature sink leaves three nodes above. Translocation occurred in specific bundles of the midveins and petioles of both the source and sink leaves and in the interjacent internodes. When each of six major veins in the lamina of an exporting leaf was independently spot-fed (14)CO2, label was exported through specific bundles in the petiole associated with that vein. When the whole lamina of a mature source leaf was fed (14)CO2, export occurred through all bundles of the lamina, but acropetal export in the stem was confined to bundles serving certain immature sink leaves. Cross-transfer occurred within the stem via phloem bridges. Leaves approaching maturity translocated photosynthate bidirectionally in adjacent subsidiary bundles of the petiole. That is, petiolar bundles serving the lamina apex were exporting unlabeled photosynthate while those serving the lamina base were simultaneously importing labeled photosynthate. The petioles and midveins of maturing leaves were strong sinks for photosynthate, which was diverted from the export front to differentiating structural tissues. The data support the idea of bidirectional transport in adjacent bundles of the petiole and possibly in adjacent sieve tubes within an individual bundle.


Multi-colored homologs of the green fluorescent protein from hydromedusa Obelia sp.
The presence of green fluorescent protein (GFP) within the bioluminescent system of Obelia (Cnidaria, Hydrozoa, Campanulariidae) was inferred shortly after the discovery of GFP in Aequorea. Despite the enormous success of Aequorea GFP as a genetically encoded fluorescent label, Obelia GFP thus far has been defeating attempts to clone it from the hydroid life cycle stage. Here, we report cloning of three GFP-like fluorescent proteins (FPs) from Obelia medusa, representing cyan, green, and yellow spectral types. Such color diversity has never been detected outside class Anthozoa, suggesting a more general function for multi-colored fluorescence in cnidarians than has been previously hypothesized. An unusual property of the new FPs is the formation of large soluble complexes of well-defined sizes and molecular weights, corresponding to up to 128 individual polypeptides. This aligns well with the earlier observation that luminescence in Obelia, unlike in Aequorea, is localized within subcellular granules, which prompts further inquiry into the self-assembly properties of the new FPs and their interactions with the photoprotein. The discovery of Obelia FPs fills the four-decade-old gap in the knowledge of cnidarian bioluminescence and provides experimental material to further investigate the details of its molecular mechanism.


Hydrogen sulfide ameliorates learning memory impairment in APP/PS1 transgenic mice: A novel mechanism mediated by the activation of Nrf2.
Beta-amyloid (Aβ) plaques and oxidative stress are associated with the pathogenesis of Alzheimer's disease (AD). Hydrogen sulfide (H2S) has been recognized as a cytoprotectant, which improves learning memory impairment and exerts antioxidant effects in neurodegenerative disorders, including AD. The experiment was projected to explore the effects of H2S on cognitive deficits, Aβ levels and possible antioxidant mechanisms. Here, APP/PS1 transgenic mice were injected sodium hydrosulfide (NaHS, a H2S donor, 2.8mg/kg) once a day for three months. It was found that APP/PS1 transgenic mice exhibited cognitive deficits and a large number of senile plaques, along with neurons decrease and Aβ increase. However, intraperitoneal (i.p.) injection of NaHS improved learning memory deficits, decreased the number of senile plaques, Aβ1-40 and Aβ1-42 levels, suppressed neurons loss, together with up-regulated the levels of cystathionine-β-synthase (CBS) and 3-mercaptopyruvate-sulfurtransferase (3MST). Furthermore, the protein levels of beta-amyloid precursor (APP) and beta-secretase 1 (BACE1) were dramatically restrained after administration of H2S. In addition, H2S exerted antioxidant effects via up-regulation nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1(HO-1) and glutathione S-transferase (GST). Taken together, these findings suggest that H2S ameliorates learning memory impairment, decreases the number of senile plaques in APP/PS1 mice possibly through inhibition of Aβ production and activation of Nrf2/antioxidant response element (ARE) pathway.


The role of serum calcium on carbohydrate metabolism in severely uraemic patients.
In 25 severely uraemic patients, the relation of serum calcium levels and oral glucose tolerance test (GTT) was studied. Seventeen of the 25 patients, who had a creatinine clearance of 6.16 +/- 1.24 ml . l-1 and a low serum calcium (6.53 +/- 0.35 mg%), had abnormal oral GTT, while from the other 8 patients, who had a creatinine clearance of 6.73 +/- 1.05 ml . l-1 and a normal serum calcium (8.75 +/- 0.60 mg%), only 4 had abnormal oral GTT. In 6 out of 17 patients, the low serum calcium (6.50 +/- 0.34 mg%) was normalized (8.85 +/- 0.54 mg%) by giving calcium gluconate in normal saline intravenously for two days. Subsequently to the calcium treatment, in four of these six patients the oral GTT changed to normal. The insulinogenic index showed increased secretion of insulin in the four patients whose oral GTT was normalized. These findings led us to the conclusion that low serum calcium is one of the contributing factors in the development of abnormal GTT in severely uraemic patients.


Therapy of human carcinoma xenografts with antibodies to EGFr and HER-2 conjugated to radionuclides emitting low-energy electrons.
Low-energy electrons (10-50 keV) can be effective and specific cytotoxic agents when delivered to the cell surface by antibodies, because their path length in tissue is comparable to a cell diameter. In this study, we have begun to evaluate the therapeutic potential of antibodies (Abs) conjugated to (111)In against carcinoma xenografts in nude mice. Abs to EGFr or HER-2 were labeled with (111)In to a high specific activity of approximately 1.48 GBq/mg (40 mCi/mg). They were injected into nude mice 5-6 days after inoculation of human carcinoma cells, either A431 or SK-OV-3, and tumor growth was monitored. In preliminary in vitro experiments, we calculated the cumulative decays per cell, estimated the centigray dose delivered to the nucleus, and related this to the fraction surviving. Abs to both antigens provided significant protection in nude mouse xenograft models (p values ranging from <0.05 to <0.001). Some mice appeared to be cured, but most had delayed tumor growth. The specificity of the effect was demonstrated by testing non-reactive Abs labeled in the same way. The radioactivity was required, because unconjugated Abs had no therapeutic effect. The maximum tolerated dose was required in order for therapy to be effective, but most of the treated mice had no significant weight loss or other overt signs of toxicity. Abs labeled with nuclides emitting low-energy electrons, such as (111)In, can be effective therapeutic agents against microscopic s.c. tumors. This strategy should be considered for clinical applications.


Neurotrophin regulation of gene expression.
The neurotrophins comprise a family of secreted proteins that elicit profound responses in cells of the developing and mature vertebrate nervous system including the regulation of neuronal survival and differentiation. The molecular mechanisms by which the neurotrophins exert their effects have been the subject of intense investigation. The neurotrophins elicit responses in neurons via members of the Trk family of receptors and the p75 neurotrophin receptor. Once activated, neurotrophin receptors trigger a large number of biochemical events that propagate the neurotrophin signal from the plasma membrane to the interior of the cell. An important target of the neurotrophin-induced signaling pathways is the nucleus, where neurotrophin-induced signals are coupled to alterations in gene expression. These neurotrophin-induced changes in gene expression are critical for many of the phenotypic effects of neurotrophins including the regulation of neuronal survival and differentiation.


Inter-observer agreement of the Wagner, University of Texas and PEDIS classification systems for the diabetic foot syndrome.
The aim of this cohort study was to assess the inter-observer agreement of three diabetic foot classification systems: the Wagner, the University of Texas and the PEDIS. We included 250 consecutive patients diagnosed of diabetic foot syndrome in 2009-2013. Wound scores were recorded at admission and a reevaluation was performed simultaneously or 24h later by a different evaluator. Demographical, laboratory data and associated risk factors were obtained from the patients' medical records. The Kappa coefficient showed a moderate inter-observer agreement between the first evaluation and the reevaluation for Wagner scale (Kappa=0.55; 95% CI: 0.507-0.593), University of Texas scale (Kappa=0.513; 95% CI: 0.463-0.563) and for PEDIS scale (Kappa=0.574; 95% CI: 0.522-0.626). This moderate agreement shows that these scales should not be used alone for management decisions regarding diabetic foot syndrome and should, therefore, be integrated with other clinical data to ensure an adequate handover.


Selective oestrogen receptor modulators.
Selective oestrogen receptor modulators (SERMs) are compounds which act like oestrogens in some target tissues but which antagonise their effects in others. The first example of a SERM (referred to as a first-generation compound) was tamoxifen, for which oestrogen-like agonist activity on bone was seen to occur simultaneously with oestrogen antagonist activity on the breast. An unwanted effect of tamoxifen was its oestrogen-like action on the endometrium. Second-generation compounds have since been developed, most notably raloxifene, which has oestrogen-like actions on bone, lipids and the coagulation system, and oestrogen antagonist effects on the breast and uterus. Raloxifene has undergone very extensive, prospective, placebo-controlled, randomised trial evaluation, in which anti-fracture efficacy (to date only for vertebral fracture) has been accompanied by a major reduction in the incidence of new breast cancer. The compound is similar to placebo in its uterine effects, and similar to oestrogen in causing a two- to threefold increase in the risk of venous thromboembolism. Its lipid effects are similar to those of oestrogen, except for a relatively small effect on high-density lipoprotein cholesterol, and no significant effect on triglycerides. Data on cardiovascular event rates are not yet available; data on cognitive function are preliminary and, to date, reassuring. The mechanisms by which the same compound can exert oestrogen agonist effects on one target and antagonist effects on another are still being clarified. Important aspects include the fact that the oestrogen receptor undergoes different conformational changes according to the ligand. Thus the crystal structure of oestradiol bound to the oestrogen receptor differs from that of raloxifene bound to the same receptor. The existence of two oestrogen receptor subtypes may also be relevant. Mechanisms include differing interactions with various domains of the oestrogen receptor, and tissue-specific recruitment of steroid receptor co-activators and co-repressors may underlie some of the tissue-specific effects. The SERMs may be the prototype for other selective steroid receptor modulators, for example the androgen and progesterone receptors. The development of tissue target-specific agents is an exciting advance in endocrine pharmacology and can be extended to agents, such as tibolone, which exert some of their tissue specificity through their metabolites.


Osteoclasts are capable of particle phagocytosis and bone resorption.
Osteoclasts are multinucleated cells specialized for the function of lacunar bone resorption. Although they are known to be capable of phagocytosis of inert particles, it is not known whether this abolishes their ability to respond to hormones or to form resorption lacunae. Human and rat osteoclasts were isolated from giant cell tumours of bone and rat long bones, respectively, and cultured on coverslips and cortical bone slices, both in the presence and in the absence of particles of latex (1 micron diameter) and polymethylmethacrylate (PMMA) (< 50 microns). By light microscopy, it was evident that osteoclasts which had phagocytosed both latex and PMMA particles remained responsive to calcitonin. Osteoclast phagocytosis of particles was also evident on scanning electron microscopy, where it could also be seen that these cells were associated with the formation of resorption lacunae. These findings underline the fact that the osteoclast is a true member of the mononuclear phagocyte system and that phagocytosis does not abrogate either its hormonal response to calcitonin or its highly specialized function of bone resorption. That osteoclasts which have phagocytosed biomaterial particles such as PMMA are still able to carry out lacunar bone resorption is of interest in clinical conditions such as aseptic loosening, where a heavy foreign body particle load is often associated with extensive bone resorption.


Benzodiazepines impair a behavioral effect induced by stimulation of 5-HT1B receptors.
Seven days of isolation induce in mice a social behavioral deficit (decrease in escape attempts) reversed by TFMPP acting through activation of 5-HT1B receptors. The present experiments were performed to investigate the interaction between tranquillizing drugs and one aspect of the serotonergic functioning through the TFMPP-induced increase in escape attempts. The benzodiazepines diazepam, alprazolam, triazolam and chlordiazepoxide impaired significantly TFMPP-induced increase in escape attempts at behaviorally inactive doses. Buspirone opposed TFMPP effect, but the active doses 4 and 16 mg/kg alone decreased the number of escape attempts. ICS 205-930 in a large dose range (0.001-1 mg/kg) modified neither the number of escape attempts nor the increase induced by TFMPP. Chronic (11 days) treatment with buspirone (16 mg/kg) or ICS 205-930 (1 mg/kg) modified neither the number of escape attempts of isolated mice nor the increase induced by TFMPP. These results suggest that tranquillizing drugs of the benzodiazepines group, but not of other groups, interact with the 5-HT1B receptors; they add to the knowledge of relations between benzodiazepines and serotonin by specifying the involvement of 5-HT1B receptors.


Therapeutic options in the management of incidental carcinoma of the prostate.
Incidental carcinoma of the prostate is a protean disease with a natural course which may be indolent or aggressive, with prognosis correlated with histologic grade and extent of disease. Treatment of this pathologic entity has varied over time and has been governed by institutional policy rather than randomized comparison of therapies. This report reviews the literature on incidental prostate cancer focusing on outcomes of patients as related to different therapeutic maneuvers. Observation alone with careful follow-up is appropriate therapy only for those patients with well differentiated disease of limited extent. Patients with diffuse or less differentiated disease required definitive therapy to prevent symptomatic progression. Hormonal manipulation alone has not been demonstrated to be of benefit. Radioactive implants have yielded poor disease-free survival. Radical prostatectomy by an experienced surgeon for patients with adequate health to tolerate the procedure has been associated with acceptable morbidity and excellent local control and survival. Radiation therapy has yielded similar excellent local control and survival and appears to be appropriate for a broader range of patients regardless of health or age.


Poloxamer thermogel systems as medium for crystallization.
To prepare a thermoreversible gel system able to work as a medium for crystallization at around 20°C, allowing easy retrieval of crystals by simply decreasing the gel temperature. Lactose was selected has model substance for crystallization. Water solutions with different% of poloxamer 407, α-Lactose monohydrate, and ethanol were prepared and analysed by rheology to understand how the different components alter the gelling temperature. The systems with the required characteristics for lactose crystallization were prepared and the crystals recovered by cooling and then filtering the dispersion. Rheological analysis showed interaction between the poloxamer and lactose. Increasing the quantity of poloxamer or lactose lowered the gelation temperature while the addition of small amounts of ethanol had a modest effect on the same property. These data were used to identify the ideal concentration of the components in order to prepare a system matching the features of our purpose. Such system yielded high quality crystals, with well-defined geometry and narrow particle size distribution. Poloxamer is a very interesting polymer in that it is able to generate a reversible gelling medium from which crystals can be harvested by filtering, without the addition of any chemicals to promote the sol-gel transition.


DNA conformational variations in the in vitro torsionally strained Ig kappa light chain gene localize on consensus sequences.
We have analyzed the localization and the dependence upon superhelical density of the DNA sites which modify their conformation under torsional strain in a mouse Ig L kappa gene. The conformational variations occur on DNA sites which have been defined as protein interaction sites and consensus sequence motifs: the 5'-upstream regulatory decanucleotides, the TATA sequence, the consensus heptanucleotides of the J recombinational sequences.


A single-section model for enamel de- and remineralization studies. 1. The effects of different Ca/P ratios in remineralization solutions.
A prerequisite for the accurate measurement of differences between pre- and post-experimental mineral profiles in single sections by quantitative microradiography is a high degree of reproducibility of the analytical procedures. We have determined the reproducibility of both the production and analyses of microradiographs. Lesions were made in seven single bovine enamel sections and radiographed three times. Each microradiograph was then analyzed on three different occasions by use of an image analysis system. This resulted in only small standard deviations in the lesion parameters. The method was used to determine the sites of mineral deposition in lesions in single sections during remineralization in three different solutions, one of which contained 1.5 mmol/L Ca and 0.9 mmol/L PO4 (standard solution); the other two solutions were low in either Ca or PO4, but all three had the same degree of supersaturation. The mineral profiles and lesion parameters were determined after lesion formation and after remineralization for 4 days, 1, 2, and 3 weeks. The decrease in IML (integrated mineral loss) in the lesions remineralized in the standard solution was greatest during the first week. Lesion profiles revealed that, under non-standard conditions, mineral deposition was retarded in the deeper part of the lesion, in contrast to the even distribution of mineral deposition from the standard solution. Differences in IML changes and lesion profiles between these bovine enamel experimental groups diminished when remineralization continued for 2 and 3 weeks. Possibly, the reactivity of mineral surfaces in newly made lesions affected the diffusion of remineralizing ions from low concentration solutions to the lesion front.


Derivation and validation of an early diagnostic score for mediastinitis after cardiothoracic surgery.
The aim of this study was to elaborate on and validate a score for the early diagnosis of mediastinitis after cardiothoracic surgery. Between 2007 and 2017, patients who experienced thoracic surgical-site infection after cardiothoracic surgery were enrolled. Laboratory, clinical, and chest CT findings were retrospectively analyzed. Patients were followed up until hospital discharge or intra-hospital death. Univariate and multivariate regression analyses were performed. 950 surgical-site infections were found and analyzed (131 mediastinitis, 819 superficial/deep infections). Of the 131 mediastinitis episodes, 88% required surgical thoracic debridement,Staphylococcus aureus was identified in 43%, and overall mortality was 42%. The following variables were related to mediastinitis diagnosis: sternal diastasis (OR=2.5; 95% confidence interval [95%CI]: 1.2-5.3; P=0.012), bilateral pleural effusion (OR=1.9; 95%CI: 1.0-3.6; P=0.04), leukocyte count ≥14,000cells/mm3 (OR=2.5; 95%CI: 1.3-4.7; P=0.006), male sex (OR=2; 95%CI: 1.11-4; P=0.022), and positive blood culture (OR=3.0; 95%CI: 1.6-5.6; P=0.001). The score predicted with reasonable accuracy mediastinitis in the derivation cohort (AUC-ROC, 0.7476) and the validation cohort (AUC-ROC, 0.7149). Groups with high (31%) and low (5%) risk of mediastinitis were identified. An early diagnostic score in patients with surgical-site infection after cardiothoracic surgery identified groups with a low and high risk for mediastinitis.


An epizootic of adenovirus-induced hemorrhagic disease in captive black-tailed deer (Odocoileus hemionus).
Ten fawns and four adult black-tailed deer (Odocoileus hemionus) in a captive herd died as a result of adenovirus-induced hemorrhagic disease. Acute, systemic infections were characterized by hemorrhagic enteropathy, pulmonary edema, and occasional ulceration of the upper alimentary tract. Localized infections were limited to the upper alimentary tract and included stomatitis, pharyngitis, mandibular osteomyelitis, and rumenitis. In deer with acute, systemic infections, a diagnosis was made by histopathology and immunohistochemistry. The serum neutralization test was useful for confirming a diagnosis in animals with prolonged, localized infections. Deer originating from herds with a history of adenovirus infection should not be transferred to other captive herds or released into free-ranging populations because they may serve as carriers of adenovirus.


Structural properties of the microsomal triglyceride-transfer protein complex.
The microsomal triglyceride-transfer protein (MTP), which catalyzes the transport of triglyceride and cholesteryl ester between membranes, is a complex composed of two proteins having apparent molecular weights of 58,000 and 88,000. The 58,000 molecular weight component of MTP has been identified as the multifunctional protein, protein disulfide isomerase (PDI). The multisubunit nature of MTP as well as the presence of PDI as one of the subunits distinguishes this protein from previously characterized lipid-transfer proteins. In this study, we have more clearly defined structural elements of MTP that may play important functional roles. The molecular weight of the transfer protein complex was determined to be 150,000 by sedimentation equilibrium experiments performed at three different speeds, suggesting that MTP is a complex of one PDI and one 88,000 molecular weight polypeptide (88K). Following SDS-polyacrylamide gel electrophoresis, the Coomassie Blue staining intensity of PDI in a known amount of MTP was compared to that of known amounts of a PDI standard. A 1 to 0.98-1.30 ratio of PDI to 88K was determined, confirming the 1:1 stoichiometry of MTP. The sedimentation coefficient (5.85) determined by analytical ultracentrifugation and the Stokes radius (47 A) determined by polyacrylamide gradient gel electrophoresis indicate that the 150,000 molecular weight MTP complex is asymmetric and/or has an unusually high water of hydration. PDI and 88K form a stable protein complex; there was no evidence of a dissociation-reassociation reaction occurring between the two components. Analysis of far-ultraviolet circular dichroism spectra revealed MTP has about 28% alpha-helical and 28% beta-structural content.(ABSTRACT TRUNCATED AT 250 WORDS)


Deferoxamine preconditioning to restore impaired HIF-1α-mediated angiogenic mechanisms in adipose-derived stem cells from STZ-induced type 1 diabetic rats.
Both excessive and insufficient angiogenesis are associated with progression of diabetic complications, of which poor angiogenesis is an important feature. Currently, adipose-derived stem cells (ADSCs) are considered to be a promising source to aid therapeutic neovascularization. However, functionality of these cells is impaired by diabetes which can result from a defect in hypoxia-inducible factor-1 (HIF-1), a key mediator involved in neovascularization. In the current study, we sought to explore effectiveness of pharmacological priming with deferoxamine (DFO) as a hypoxia mimetic agent, to restore the compromised angiogenic pathway, with the aid of ADSCs derived from streptozotocin (STZ)-induced type 1 diabetic rats ('diabetic ADSCs'). Diabetic ADSCs were treated with DFO and compared to normal and non-treated diabetic ADSCs for expression of HIF-1α, VEGF, FGF-2 and SDF-1, at mRNA and protein levels, using qRT-PCR, western blotting and ELISA assay. Activity of matrix metalloproteinases -2 and -9 were measured using a gelatin zymography assay. Angiogenic potential of conditioned media derived from normal, DFO-treated and non-treated diabetic ADSCs were determined by in vitro (in HUVECs) and in vivo experiments including scratch assay, three-dimensional tube formation testing and surgical wound healing models. DFO remarkably enhanced expression of noted genes by mRNA and protein levels and restored activity of matrix metalloproteinases -2 and -9. Compromised angiogenic potential of conditioned medium derived from diabetic ADSCs was restored by DFO both in vitro and in vivo experiments. DFO preconditioning restored neovascularization potential of ADSCs derived from diabetic rats by affecting the HIF-1α pathway.


Nonionic contrast media. Procoagulants or clotting innocents?
Compared with ionic contrast media, nonionic contrast media cause fewer adverse reactions, including hemodynamic and electrophysiologic complications, and are better tolerated by patients. However, concern as to whether nonionic agents are associated with more thromboembolic complications has been raised in recent years. This article reviews in-vitro and in-vivo coagulation studies with nonionic contrast media, including the authors' current study using blood samples from percutaneous transluminal coronary angioplasty (PTCA) patients. Articles for this review were selected on the basis of providing viewpoints representative of both sides of the clotting controversy involving nonionic contrast media. In addition, articles were selected that, in toto, include the several relevant aspects of thrombosis during PTCA: whole blood clotting, angiography catheters, angiography syringes, rheology, and vascular endothelium. The preliminary work described used platelet adhesion/aggregation to a collagen-coated surface under controlled conditions of heparinized, whole blood flow. Adhesion/aggregation was quantified by digital analysis of real-time images obtained by epifluorescence videomicroscopy. In parallel studies, changes in markers (membrane glycoproteins) of platelet activation were measured using whole blood flow cytometry. Although nonionic contrast media are weaker anticoagulants than ionic contrast media, no convincing evidence demonstrates that they are procoagulant. On the contrary, in-vitro studies suggest that ionic media may weaken the antithrombotic properties of vascular endothelium by direct endothelial injury. Certain clinical trials of PTCA patients substantially challenge the use of nonionics. Yet, Grabowski et al found no evidence of platelet activation by ioxaglate or iohexol in preliminary work. This result was obtained with two of the most sensitive platelet assays available: flowing whole blood aggregometry and whole blood flow cytometry. Attention should be given to the adequacy of heparinization in future clinical studies. Nonionic contrast media are not procoagulant in vitro in the hands of most research groups. The focus of current controversy, therefore, is whether there is a clinical and in-vivo difference in thrombotic events seen with nonionic versus ionic media during PTCA. Elements in this controversy include platelet activation, blood-foreign surface (catheter and syringe) interaction, rheology, vascular endothelium, and adequacy of heparinization.


Upper gastrointestinal swallow study following bariatric surgery: institutional review and review of the literature.
The aim of this study was to determine the efficacy of routine upper gastrointestinal imaging following the three forms of laparoscopic bariatric surgery completed at our institution (laparoscopic Roux en Y gastric bypass (LRYGB), laparoscopic sleeve gastrectomy (LS), and laparoscopic adjustable gastric banding (LAGB)). Radiograph reports were reviewed from the period of January 2005 to July 2010. During that time, 129 patients underwent LRYGB, 209 underwent LS, and 12 patients underwent LAGB. Of those patients, 120 LRYGB patients, 188 LS patients, and 11 LAGB patients underwent upper gastrointestinal studies on postoperative days (POD) 1 or 2. Of the 319 total patients who underwent UGI, no contrast leaks were found. One LRYGB patient was found to have stenosis of the jejunojejunal anastomosis and was taken to the operating room for revision. A total of ten patients went on to develop leaks: four LRYGB patients, six LS patients, and zero LAGB patients. The results of our study show that a positive UGI study for stricture has a specificity of 100 %. In terms of leak, which offers a much higher risk of significant morbidity and mortality, UGI was unable to find any on postoperative days 1 or 2. Based on the results of this study, our institution has stopped completing routine UGI on POD 1 following bariatric surgery.


Mercury concentrations in tropical resident and migrant songbirds on Hispaniola.
Despite growing concerns over mercury (Hg) exposure to humans and wildlife on a global scale, little is known about Hg bioaccumulation in the New World tropics. From 2005 to 2011, we monitored Hg concentrations in blood of nine avian species occupying a geographic range of tropical wet broadleaf sites on the island of Hispaniola, including eight passerines (two Nearctic-Neotropical migrant and six resident species) and one top order predatory accipiter. Invertivorous songbirds were further differentiated by foraging guild, with six species of ground-foragers and two species of foliage-gleaners. Blood Hg concentrations were orders of magnitude higher in birds sampled in central and southern cloud forest sites (1,000-1,800 m elevation) than in northern and northeastern rainforest sites (50-500 m elevation), with migratory and resident species both showing 2-20× greater blood Hg concentrations in cloud forests than in rainforests. Within cloud forest sites, ground-foraging species had higher Hg concentrations than foliage-gleaning species. Top order predatory sharp-shinned hawks (Accipiter striatus) had the highest blood Hg concentrations among all species, suggesting that Hg biomagnification is occurring in terrestrial forests of Hispaniola. Two migrant songbird species overwintering on the island had higher blood Hg concentrations than have been recorded on their North American breeding grounds. Future studies should seek to elucidate sources of variation in atmospheric Hg deposition on Hispaniola and to quantify the dynamics of Hg cycling in tropical forest ecosystems, which may differ in important ways from patterns documented in temperate forest ecosystems.


On femtosecond micromachining of HPHT single-crystal diamond with direct laser writing using tight focusing.
We investigate the formation of diversiform micro-/nano-structures in High-Pressure High-Temperature (HPHT) synthetic single-crystal diamond by tight-focusing 200 fs regeneratively amplified Ti: Sapphire laser pulses centered at lambda = 800 nm. Ablated samples of synthetic single crystal nanodiamond and their acetate replicas are analyzed using scanning electron microscopy (SEM). Using pulse energies that are significantly above the threshold for permanent change, it is shown from this work that amplified femtosecond pulses are capable of producing controlled modification of HPHT single-crystal diamond at size scales below the diffraction limit and provided negligible collateral heating and shock-wave damage. This is attributed to the low thermal losses and negligible hydrodynamic expansion of the ablated material during the femtosecond laser pulse. It is shown that low pulse energy is a key factor for the accurate and precise machining of micropattems.


An integrative review of promoting trust in the patient-primary care provider relationship.
An integrative review of empirical studies on factors promoting trust in the patient-primary care provider relationship. Trust is essential to the patient-provider relationship. Patients with high trust in their healthcare providers have been found to have improved outcomes, including improved chronic disease management, increased use of preventative services and satisfaction with care. Breaches of trust in the healthcare system threaten trust. Exploring factors that promote trust in the patient-provider relationship is warranted. Integrative literature review. Electronic databases searched included CINAHL, MEDLINE and PsycARTICLES, using combinations of the key term 'trust' with: concept, practitioner, provider, physician, developing, creating, engendering, promoting and establishing. The results were limited to original publications in English, published between 1998-2013. A review of the literature was conducted by two independent reviewers based on the criteria established by Cooper; Whittemore and Knafl; and Polit and Beck. Methodological assessment tools were used to organize, evaluate the quality of and synthesize the data. A new conceptual definition of promoting trust is proposed that includes three core qualities: interpersonal and technical competence, moral comportment and vigilance. Gaps in the literature still exist related to rural, young adult, older adult and well patient populations. The core qualities could serve as target areas for the development of interventions aimed at modifying provider behaviours so that trust can be established, maintained or improved. Future prospective longitudinal research studies are needed that enhance understanding of trust with multiple primary care provider types.


Improvement of Fast Model-Based Acceleration of Parameter Look-Locker T1 Mapping.
Quantitative mapping is desirable in many scientific and clinical magneric resonance imaging (MRI) applications. Recent inverse recovery-look locker sequence enables single-shot T1 mapping with a time of a few seconds but the main computational load is directed into offline reconstruction, which can take from several minutes up to few hours. In this study we proposed improvement of model-based approach for T1-mapping by introduction of two steps fitting procedure. We provided analysis of further reduction of k-space data, which lead us to decrease of computational time and perform simulation of multi-slice development. The region of interest (ROI) analysis of human brain measurements with two different initial models shows that the differences between mean values with respect to a reference approach are in white matter-0.3% and 1.1%, grey matter-0.4% and 1.78% and cerebrospinal fluid-2.8% and 11.1% respectively. With further improvements we were able to decrease the time of computational of single slice to 6.5 min and 23.5 min for different initial models, which has been already not achieved by any other algorithm. In result we obtained an accelerated novel method of model-based image reconstruction in which single iteration can be performed within few seconds on home computer.


Teen compliance with contraception. Analysis Of the ohio medicaid claims data
Background: Teen pregnancy is an important and costly issue for society and often commits the mother to a life of poverty. Physicians play an important role in preventing teen pregnancy by identifying teens at risk for pregnancy and prescribing contraception. This study examines for the first time, whether pharmacy data can be used to evaluate teens' compliance with contraception. Such a method may be useful to physician groups, health plans or state agencies to identify teens at risk for unwanted pregnancy and target interventions.Methods: Secondary analysis of the Ohio Medicaid Claims Data from 1998 was done identifying continuously enrolled young women ages 12-19 years, at high risk for pregnancy defined by ICD 9 codes for an STD, an abnormal pap smear, contraception, or a CPT code for a pregnancy test.Results: Between 1/1/98-3/31/98 we identified 4009 females, ages 12-19 years at high risk for pregnancy. During the study interval, 1084 (27%) became pregnant. 1732 (43%) used no prescription contraception and 1190 (30%) used a method at some time. Depo only (551) and OCP only (552) use was equal. Eighty-three combined the use of Depo and OCP. Compliance was poor. Only 20% of the contracepting group had coverage for the full year and approximately 30% used a method for 3 months or less. There was little difference in age or concurrent chronic physical or mental illness between the contracepting and non-contracepting groups. General practice physicians provided 40% of the OCP prescriptions to teens compared with 36% Ob/Gyn, 10% Pediatrics, and 6% Internal Medicine.Conclusions: Analysis of pharmacy data to evaluate the contraceptive compliance of teens at high risk for pregnancy demonstrated poor compliance. This may be a useful tool for identifying teens at risk for unwanted pregnancy and targeting interventions.


Salmonella enterica serovar Kentucky recovered from human clinical cases in Maryland, USA (2011-2015).
Salmonella Kentucky is among the most frequently isolated S. enterica serovars from food animals in the United States. Recent research on isolates recovered from these animals suggests there may be geographic and host specificity signatures associated with S. Kentucky strains. However, the sources and genomic features of human clinical S. Kentucky isolated in the United States remain poorly described. To investigate the characteristics of clinical S. Kentucky and the possible sources of these infections, the genomes of all S. Kentucky isolates recovered from human clinical cases in the State of Maryland between 2011 and 2015 (n = 12) were sequenced and compared to a database of 525 previously sequenced S. Kentucky genomes representing 12 sequence types (ST) collected from multiple sources on several continents. Of the 12 human clinical S. Kentucky isolates from Maryland, nine were ST198, two were ST152, and one was ST314. Forty-one per cent of isolates were recovered from patients reporting recent international travel and 58% of isolates encoded genomic characteristics similar to those originating outside of the United States. Of the five isolates not associated with international travel, three encoded antibiotic resistance genes conferring resistance to tetracycline or aminoglycosides, while two others only encoded the cryptic aac(6')-Iaa gene. Five isolates recovered from individuals with international travel histories (ST198) and two for which travel was not recorded (ST198) encoded genes conferring resistance to between 4 and 7 classes of antibiotics. Seven ST198 genomes encoded the Salmonella Genomic Island 1 and substitutions in the gyrA and parC genes known to confer resistance to ciprofloxacin. Case report data on food consumption and travel were, for the most part, consistent with the inferred S. Kentucky phylogeny. Results of this study indicate that the majority of S. Kentucky infections in Maryland are caused by ST198 which may originate outside of North America.


Induction of Hyphal Growth in Schizosaccharomyces japonicus.
Schizosaccharomyces japonicus is a dimorphic yeast. Depending on the nutrient conditions, the transition between growth as yeast cells and growth as hyphal cells can be reversibly induced. In addition to nutrient stress, induced DNA lesions, such as those produced by camptothecin, also induce hyphal growth regardless of the nutrient status. This protocol describes both methods of induction.


Effects of angiotensin II type 1 receptor blockade in ApoE-deficient mice with post-ischemic heart failure.
We investigated in mice whether atherosclerosis exacerbates the development of post-ischemic heart failure and alters the beneficial effects of long-term angiotensin II type 1 receptor blockade in this model. ApoE-deficient (ApoE(-/-)) and C57BL/6J (C57) mice with myocardial infarction (coronary ligation) received vehicle (C57 and ApoE(-/-)) or irbesartan (Ir, 50mg/kg/d orally, C57-Ir and ApoE(-/-)-Ir). Ten months post myocardial infarction, survival rates were similar in C57 (58%) and ApoE(62%). Atherosclerosis induced no significant alteration in blood pressure, cardiac output (fluospheres), total peripheral resistance, or shortening fraction (echocardiography) but increased renal resistance (+50%, P<0.05). Chronic Ir treatment significantly improved survival to a similar extent in both C57-Ir (85%) and ApoE(-/-)-Ir (86%). It also decreased blood pressure to a similar extent in both strains (-16% and -18%, both P<0.05). In C57-Ir mice, Ir did not modify cardiac output or total peripheral resistance, but it decreased renal resistance (-28%, P<0.001) and left-ventricular weight (-28%, P<0.05). In ApoE(-/-)-Ir mice, Ir limited atherosclerotic lesions (-13%, P<0.05), increased cardiac output (+28%, P<0.05) and shortening fraction (+24%, P<0.05), and decreased total peripheral resistance (-33%, P<0.01), renal resistance (-61%, P<0.001), and left-ventricular weight (-27%, P<0.001). In conclusion, atherosclerosis does not worsen heart failure development in mice and, although the beneficial cardiovascular effects of AT1 receptor blockade are greater in ApoE(-/-) than in C57, reduction in mortality is similar in both strains.


Comparison of tobramycin pharmacokinetics after administration by CRIS and a traditional intravenous piggyback infusion.
To compare the administration pharmacokinetics of a 30-minute intravenous piggyback (ivpb) infusion of tobramycin with those of controlled-release infusion system (CRIS) using a 20-mL vial at rates of 60 and 120 mL/h. Randomized, controlled, crossover, prospective, open-label trial. Medical college-affiliated hospital. Eight healthy volunteer men between the ages of 22 and 24 years weighing between 60 and 90 kg. Volunteers received, in random order, tobramycin sulfate 2 mg/kg i.v. on 3 occasions separated by 1 week. The drug was administered using a 50-mL ivpb infusion at 100 mL/h for 30 minutes, and with the CRIS using a 20-mL vial with flow rates of 60 mL/h for 1 hour (slow) and 120 mL/h for 1 hour (fast). Primary endpoints were area under the time-concentration curve (AUC), time to reach maximum concentration (tmax), and maximum concentration (Cmax). Secondary endpoints were elimination rate constant (ke), clearance (Cl), and half-life (t1/2). Six volunteers successfully completed the trial. The tmax values observed following fast CRIS and ivpb were 28 +/- 8 and 32 +/- 4 minutes, respectively, and not significantly different from each other. Both occurred significantly earlier than the tmax associated with slow CRIS (44 +/- 7 min). The Cmax values observed following ivpb (11.2 +/- 1.5 mg/L) and slow CRIS (10.9 +/- 0.9 mg/L) administration were not significantly different from each other, but both were significantly lower than that of fast CRIS (13.4 +/- 1.5 mg/L). The AUCs of slow and fast CRIS were 29.8 +/- 4.8 and 31.2 +/- 3.8 mg/L.h, respectively, and were not significantly different from each other. The AUC of fast CRIS was significantly greater than that observed with ivpb (27.4 +/- 4.3 mg/L.h). No significant difference in ke (fast CRIS 0.32 +/- 0.03 h-1; slow CRIS 0.33 +/- 0.04 h-1; ivpb 0.34 +/- 0.0 h-1) was observed among any of the methods. CRIS administration of tobramycin resulted in higher AUCs than did ivpb administration. Compared with ivpb, fast CRIS resulted in a higher Cmax, but the tmax values of fast CRIS and ivpb administration were not statistically different. Compared with ivpb, slow CRIS resulted in a more delayed tmax, but the Cmax values of slow CRIS and ivpb were not statistically different.


Action of hyperbaric oxygenation in the rat skin flap.
To evaluate the morphology, necrotic area and collagen content in skin flaps of rats subjected to hyperbaric oxygenation (HBO). Forty adult rats were divided into four groups: GEC - epilated; GE/HBO - epilated subjected to HBO; GER - epilated submitted to skin flap (2 cm in width /8 cm length in the dorsal area) and GER/HBO - epilated, subjected to skin flap and HBO. HBO (2.4 ATA) was performed for two hours during seven consecutive days. In the eighth day, the rats were anesthetized and the skin flaps were removed and separated into three portions, relative to pedicle fixation. The material fixed in 10% formalin was processed for paraffin embedding; sections were stained by H.E and subjected to picrosirius-red method. The slides examined under light microscopy for evaluation of the collagen content in polarized light microscope and ImageLab(r) software (Bio-Rad). The data showed larger area of necrosis and lower levels of collagen in the three regions of the GER group, whereas in the GER/HBO group the collagen content was similar to the GEC and GE/HBO groups. Hyperbaric oxygenation reduced the area of necrosis and preserved the morphology and collagen content in skin flaps of rats.


Brainstem evoked potentials in adult sleep apnea.
Brainstem evoked potentials (BSEP) were recorded in 23 patients with adult sleep apnea (ASA). Three patients were studied with all-night polysomnography prior to our testing. They were categorized as having obstructive, central, or mixed sleep apnea depending on the predominant sleep findings. All patients with central sleep apnea had abnormal BSEP with prolongation of wave V. A majority of the remaining patients with obstructive sleep apnea and mixed sleep apnea had abnormal BSEP, but without specific configurations. These findings substantiate our hypothesis that brainstem dysfunction may play a role in ASA.


Treatment of Liver Cancer by C/EBPA saRNA.
The prognosis for hepatocellular carcinoma (HCC) remains poor and has not improved in over two decades. Most patients with advanced HCC who are not eligible for surgery have limited treatment options due to poor liver function or large, unresectable tumors. Although sorafenib is the standard-of-care treatment for these patients, only a small number respond. For the remaining, the outlook remains bleak. A better approach to target "undruggable" molecular pathways that reverse HCC is therefore urgently needed. Small activating RNAs (saRNAs) may provide a novel strategy to activate expression of genes that become dysregulated in chronic disease. The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα), a critical regulator of hepatocyte function, is suppressed in many advanced liver diseases. By using an saRNA to activate C/EBPα, we can exploit the cell's own transcription machinery to enhance gene expression without relying on exogenous vectors that have been the backbone of gene therapy. saRNAs do not integrate into the host genome and can be modified to avoid immune stimulation. In preclinical models of liver disease, treatment with C/EBPα saRNA has shown reduction in tumor volume and improvement in serum markers of essential liver function such as albumin, bilirubin, aspartate aminotransferase (AST), and alanine transaminase (ALT). This saRNA that activates C/EBPα for advanced HCC is the first saRNA therapy to have entered a human clinical trial. The hope is that this new tool will help break the dismal 20-year trend and provide a more positive prognosis for patients with severe liver disease.


Segmental pancreatic autotransplantation for chronic pancreatitis.
Three patients who underwent 95 percent removal of the pancreas for chronic pancreatitis with autotransplantation of the body and tail of the gland to the femoral area are described. The follow-up periods are 18, 6, and 2 months. Pain lessened in all patients and none required exogenous insulin. Patency of the graft was documented in all patients by angiography, technetium scan, and Doppler studies. Percutaneous selective venous assays of both external iliac veins showed a high insulin concentration in the transplanted side, both early and late in the postoperative period. In one patient the operative insulin levels obtained at the completion of autotransplantation proved to be highest in the external iliac vein on the transplanted side, lowest in the iliac vein on the nontransplanted side, and intermediate in the portal vein. Subsequent biopsies of the autografts showed fibrosis of the gland and atrophy of the acinar tissue with preservation of islet tissue. This technique appears to offer a means of preserving endocrine function in selected patients who require extensive resection for chronic pancreatitis.


Cognitive skills in mathematical problem solving in Grade 3.
Research on the relationship between cognitive skills and mathematical problem solving is usually conducted on adults or on participants with acquired deficits associated with brain injury (e.g.Cipolotti, 1995; Cohen, Dehaene, & Verstichel, 1994; McCloskey, 1992). In these studies we wanted to make a contribution to the field of children's mathematical problem solving. The first aim of this study was to investigate whether mathematical problem solving in children is merely determined by semantic elaboration, as hypothesized in some of the models of adult processing (semantic hypothesis). In addition, we aimed to investigate whether there is a continuum from very good to very poor mathematical problem solving among children with mathematical learning disabilities showing immature cognitive skills (maturational lag hypothesis). The participants were 376 third graders and 107 second graders. The internal structure of the data was analysed with a principal components analysis. In addition, two MANOVA were conducted to compare children with learning disabilities or problems with age-matched and performance-matched subjects. Two components, a semantic and a non-semantic one, were needed to account for an adequate fit of the dataset. In addition, children with mathematical learning disabilities had less-developed cognitive skills compared with peers without learning disabilities, but they did not differ from younger children on seven of the nine cognitive skills. This study highlighted that children's mathematical problem solving is not determined by one general component. The picture is more complex, since two mathematics components were found. In addition, although our findings point in the direction of the maturational lag hypothesis it may be important to assess the different cognitive skills and especially assess the number system knowledge, since it seems below average in children with mathematical learning disabilities, compared with the knowledge of younger children with comparable skills in mathematics.


Taenia infestation in the appendix: a case report.
Taenia saginata is a zoonotic cestode causing taeniasis. Taeniasis refers to the intestinal infection with the adult stage of this tapeworm. An association between teaniasis and acute appendicitis is uncommon. We present the case of a 37 year old male who presented with abdominal pain for one day. He was diagnosed with having appendicitis and an appendectomy was performed. Pathology of the appendix showed Taenia saginata with eggs in the lumen. Histological analysis showed acute inflammation consistent with acute appendicitis caused by T. saginata.


The growth cycle of influenza viruses as studied in touch preparations of the allantoic layer of chick embryos. 2. The morphology of allantoic cells infected by influenza A virus.
The morphology of allantoic cells infected by influenza A virus was studied in touch preparations of the allantoic layer from 11-day embryos inoculated by the intra-allantoic route. Two comparative doses were used: 10(9) ID50 or large inocula (multiplicity: 100 ID50 to 3 cells) and 200 ID50 (multiplicity: 1 ID50 to 150,000 cells) or small inocula. The allantoic layer from 11-day eggs is an epithelium consisting of at least two strats: a superficial stratum and a deep one. Both with the large and the small inocula, a total and irreversible destruction of the superfifial stratum (cells having free facets in ocntact wit- allantoic fluid) was produced, while the profound one (a layer underlying the surface stratum, with cells normally not having any contact with the allantoic fluid) remained essentially intact. Three successive stages were observed. 1. Incubation period: The cells of both strata exhibited a normal appearance during the first 10 hours with the higher multiplicity, and for the first 15-17 hours with the lower multiplicity. 2. Necrotic period: The cells of the superficial stratum exhibited degenerative changes (the chromatin breaks up into numerous irregular and deeply stained fragments) followed by desquamation into the allantoic fluid within the next 10 hours (from 10th to 20-22th hour after inoculation) with the large, and the next 17 hours (from 15th-17th to 32nd-34th h.) with the small inocula. No morphological changes were observed with the profound cells. 3. Post-necrotic period: The profound stratum with cells of sound appearance, some of whoch showed giant nuclei (polyploid cells?) REMAINED UNTIL THE DEATH OF THE EMBRYos which occurred within a maximum of 6-7 days after inoculation. Occasionally, throughout this period, degenerated deep cells were found (about 1-5% in quantity) which, with the aid of immunofluorescence procedure, are believed to be related to a minor cycle of virus multiplication.


Interaction between tetraplex structure of yeast telomeric DNA and tetraplex-binding ligand.
Fission yeast telomeric DNA sequence, SP4G4: 5'-(GGGGTTAC)(4)-3' has been reported to form the antiparallel tetraplex in the presence of K(+). We examined the structural properties of budding yeast telomeric DNA sequences, SCTELG4: 5'-(TGGGTGT G)(4)-3' and SCTELGG4: 5'-(TGGGTGTGG)(4)-3', in the presence of K(+). The major conformation of SCTELG4 and SCTELGG4 was a parallel tetraplex DNA. We also examined the interaction between tetraplex-binding ligand, TMPyP4, and each of the antiparallel tetraplex of SP4G4 and the parallel tetraplex of SCTELG4 and SCTELGG4. The ability of TMPyP4 to bind with all of the tetraplexes was observed. We conclude that TMPyP4 has the ability to bind with both the parallel and antiparallel tetraplex of the telomeric DNA sequences from budding and fission yeasts.


Review article: Environmental heatstroke and long-term clinical neurological outcomes: A literature review of case reports and case series 2000-2016.
Global temperatures are rising; extreme environmental heat can result in adverse health effects including heatstroke. Acute effects of heat are well recognised, but there is less understanding of potential long-term adverse outcomes. Our aim was to review recent medical literature for clinical cases of environmental heatstroke with a focus on neurological outcome. Structured search strategies were designed to retrieve publications of heatstroke case reports using Ovid Medline and Embase (2000-2016). One thousand and forty-nine abstracts were identified, and after application of exclusion criteria 71 articles deemed relevant. Ninety cases were identified from 71 articles. 100% presented with acute neurological symptoms; 87.8% presented with non-neurological symptoms. 44.4% patients recovered fully, 23.3% died, 23.3% suffered convalescent or long-term neurological sequelae, and in 8.9% no long-term follow up was available. 57.1% of the patients who died or had a neurological deficit had no documented co-morbidity. Patterns of neurological deficits included 66.7% patients with motor dysfunction, 9.5% cognitive impairment, 19% both motor and cognitive impairment and 4.7% other. In total 71.4% of the impaired patients had long-term cerebellar dysfunction. Adverse long-term neurological outcomes were common in surviving patients presenting with environmental heatstroke. Permanent neurological deficits were present in 34.4% of survivors where outcome was known; many were young, healthy individuals. Cerebellar injury was common suggesting cerebellar structures are vulnerable to heat. These findings highlight that people of all ages and pre-morbid states are at risk of severe heat-related illness. In the face of climate change, effective interventions for heat-related illness, including both treatment and prevention are necessary.


Genetic algorithm-based efficient feature selection for classification of pre-miRNAs.
In order to classify the real/pseudo human precursor microRNA (pre-miRNAs) hairpins with ab initio methods, numerous features are extracted from the primary sequence and second structure of pre-miRNAs. However, they include some redundant and useless features. It is essential to select the most representative feature subset; this contributes to improving the classification accuracy. We propose a novel feature selection method based on a genetic algorithm, according to the characteristics of human pre-miRNAs. The information gain of a feature, the feature conservation relative to stem parts of pre-miRNA, and the redundancy among features are all considered. Feature conservation was introduced for the first time. Experimental results were validated by cross-validation using datasets composed of human real/pseudo pre-miRNAs. Compared with microPred, our classifier miPredGA, achieved more reliable sensitivity and specificity. The accuracy was improved nearly 12%. The feature selection algorithm is useful for constructing more efficient classifiers for identification of real human pre-miRNAs from pseudo hairpins.


[Use of x-ray scanning densitometry and computerized tomography in the evaluation of the effect of tumor treatment].
The paper considers the ways of quantitative assessment of changes occurring in the density and size of a tumorous focus during its treatment (radiation, chemical and hormonal therapies). They are based on scanning densitometric techniques by identifying quantitative integral and differential parameters. The parameters are used to assess tissue alterations by applying computerized tomography. The investigations into the impact of radiation and chemotherapy on tumor tissue in breast and lung cancers have indicated that scanning densitometry and computerized tomography may be used to evaluate therapeutical effects.


Review of microarray experimental design strategies for genetical genomics studies.
Genetical genomics approaches provide a powerful tool for studying the genetic mechanisms governing variation in complex traits. By combining information on phenotypic traits, pedigree structure, molecular markers, and gene expression, such studies can be used for estimating heritability of mRNA transcript abundances, for mapping expression quantitative trait loci (eQTL), and for inferring regulatory gene networks. Microarray experiments, however, can be extremely costly and time consuming, which may limit sample sizes and statistical power. Thus it is crucial to optimize experimental designs by carefully choosing the subjects to be assayed, within a selective profiling approach, and by cautiously controlling systematic factors affecting the system. Also, a rigorous strategy should be used for allocating mRNA samples across assay batches, slides, and dye labeling, so that effects of interest are not confounded with nuisance factors. In this presentation, we review some selective profiling strategies for genetical genomics studies, including the selection of individuals for increased genetic dissimilarity and for a higher number of recombination events. Efficient designs for studying epistasis are also discussed, as well as experiments for inferring heritability of transcriptional levels. It is shown that solving an optimal design problem generally requires a numerical implementation and that the optimality criteria should be intimately related to the goals of the experiment, such as the estimation of additive, dominance, and interacting effects, localizing putative eQTL, or inferring genetic and environmental variance components associated with transcriptional abundances.


Balneotherapy and quality assessment: interobserver reliability of the Maastricht criteria list and the need for blinded quality assessment.
This study investigates aspects of the reliability of the Maastricht criteria list for quality assessment in systematic reviews, and whether blinded reviewing is necessary to prevent review bias. We used the data set of 12 articles from a systematic review concerning the efficacy of balneotherapy in patients with arthritis. Twenty reviewers participated of which two reviewers, who have been involved in developing the Maastricht criteria list, acted as reference standard. Half of all assessments were performed blindly. A high level of agreement was found between the reviewers and a high level of correlation with the reference standard. The quality scores between the blinded and unblinded assessment did not differ much. Based on the results we conclude that the Maastricht criteria list is a reliable instrument in quality assessment of clinical trials. Within the limits of this study we found no evidence that blinding is necessary to prevent review bias.


Fluconazole dosing in renal impairment: a drug usage evaluation.
Fluconazole is an antifungal agent available for oral and parenteral use. Drug dosage is based on the type and severity of infection, identity of the causative organism, the patient's renal function as determined by creatinine clearance, and response to therapy. To determine whether or not IV fluconazole was being dosed appropriately based on the above parameters, the pharmacy department at St. Joseph Hospital in Flint, Michigan, decided to perform a 3-month drug usage evaluation. As had been speculated, many fluconazole-treated patients were receiving inappropriate dosages. Specifically, renal function was not being taken into consideration in 30% of the cases. Additionally, 33% of patients received higher than necessary doses based on site and severity of infection. With the help of the P & T Committee, an educational program was implemented to assist physicians in the appropriate dosing of fluconazole.


Meniscal regeneration in the long-term after total meniscectomy?
A cohort of 39 patients (28 male, 11 female) that had undergone total meniscectomy as adolescents (mean age 16 years) underwent FISP 3D Magnetic Resonance Imaging at a mean follow up of 30 years. The presence of meniscal tissue was assessed by two independent observers blinded to the operation details. The volume of any meniscal tissue present was calculated. A posterior horn remnant was seen in 57% of medial and 45% of lateral meniscectomy cases. The mean volume of an operated medial meniscal remnant was 0.29 mL compared with a mean volume of 1.15 mL for an intact medial meniscus. The mean volume of an operated lateral meniscal remnant was 0.30 mL compared with 1.07 mL for an intact lateral meniscus. We have shown that the incidence of incomplete excision of the posterior horn is more common after total medial meniscectomy, and that at a mean follow up of 30 years there is no convincing in vivo MRI evidence of long-term meniscal regeneration.


A randomised trial comparing the effect of exercise training and weight loss on microvascular function in coronary artery disease.
Coronary microvascular function is associated with outcome and is reduced in coronary artery disease (CAD) and obesity. We compared the effect of aerobic interval training (AIT) and weight loss on coronary flow reserve (CFR) and peripheral vascular function in revascularised obese CAD patients. Seventy non-diabetic patients (BMI 28-40 kg × m(-2), age 45-75 years) were randomised to 12 weeks' AIT (three weekly sessions lasting 38 min with ≈ 16 min at 85-90% of VO2peak) or low energy diet (LED, 800-1000 kcal/day). Per protocol adherence was defined by training-attendance ≥ 60% and weight loss ≥ 5%, respectively. CFR was assessed by Doppler echocardiography of the LAD. Peripheral vascular function was assessed by arterial tonometry as reactive hyperaemia index (RHI) and augmentation index. Most participants had impaired CFR with a mean CFR of 2.38 (SD 0.59). Twenty-six AIT and 24 LED participants completed the study per protocol with valid CFR measurements. AIT resulted in a 10.4% improvement in VO2peak and LED in a 10.6% weight loss (between group differences both P<0.001). CFR increased by 0.26 (95%CI 0.04;0.48) after AIT and by 0.39 (95%CI 0.13;0.65) after LED without significant between-group difference (-0.13 (95%CI -0.45;0.20)). RHI and augmentation index remained unchanged after both interventions (P>0.50). Intention-to-treat analyses showed similar results. 12 weeks' AIT and LED increased CFR by comparable magnitude; thus both interventions might impact prognosis of CAD through improvement of coronary microvascular function. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01724567.


Central action of adrenaline.
Adrenaline (A) administered in doses of 10, 50 and 100 micrograms/rat into the right lateral ventricle of the brain (i.v.c.) in rats reduced the spontaneous and exploratory locomotor activity, decreased the body temperature, and increased the effects of narcotics. The reduction of the locomotor activity after A was antagonized by nialamide, alpha-MT, and yohimbine. Total chemical destruction of catecholaminergic neurons and selective destruction of dopaminergic neurons caused increase in A-induced locomotor activity. A had no effect on the locomotor activity in rats subjected to the action of reserpine, reserpine with 6-OHDA, and phenoxybenzamine or propranolol. In rats treated with phenoxybenzamine, propranolol, spiroperidol or subjected to selective destruction of noradrenalinergic neurons adrenaline decreased significantly the locomotor activity. A (10 micrograms) increased and in higher doses inhibited amphetamine-induced hyperactivity. It potentiated amphetamine and apomorphine stereotypy and antagonized catalepsy induced with haloperidol or fluphenazine. In the despair test adrenaline reduced the duration of akinesia. In doses of 0.1, 1.0 and 10 micrograms/kg i.v. A increased slightly the flexor reflex of the hind paw of spinal rats. This action was antagonized by phentolamine as well as by propranolol. In biochemical investigations it was demonstrated that A decreased the level of dopamine in rat brain but had no effect on its utilization. The obtained results indicate that A i.v.c. stimulated catecholaminergic receptors.


Structural and functional heterogeneity of naturally occurring hepatitis B virus variants.
Most organisms have developed sophisticated machineries to preserve their genomic integrity. On the contrary hepatitis B virus (HBV), like a lot of other viruses can undergo rapid and drastic sequence changes, especially if the virus has to cope with natural or therapy induced antiviral mechanisms in the host. Here, we try to summarize possible implications for the molecular pathogenesis of HBV based on the extensive research on the genetic variants of HBV.


[Formation of focus of West Nile fever on the territory of Saratov Region].
Detection of circulation of West Nile virus (WNV) on the territory of Saratov Region and prerequisites for formation of natural focus of West Nile fever (WNF), determination of the role of WNV in infectious pathology on the territory of the region. of organs of small mammals, birds, blood-sucking arthropods for the presence of WNV markers (antigens and/or RNA) were studied. Clinical material from patients with symptoms not excluding WNF was studied. Donor blood sera samples were analyzed with the aim of detection of immune layer against WNV in population of Saratov Region. In 2010 WNV antigens were detected by EIA in 12 samples (7.1%) of mammal organ suspensions. In 2012 by using RT-PCR and EIA, markers of WNV were detected in 6 samples of bird brain suspensions (6.3%) and 1 sample of mammal organ suspension. Immune layer of population against WNV was 4% in 2011, 2.8% in 2012. In 2012 in 11 of 27 examined patients IgM against WNV in diagnostic titers and/or serconversion of IgG in paired sera were detected. In addition in 5 individuals virus RNA was detected in blood. Based on clinical, laboratory data and epidemiologic anamnesis 11 patients were diagnosed with WNF. The results obtained give evidence on the circulation of WNV on the territory of Saratov Region in 2010 - 2012. With the development of complications of WNF epidemiologic situation in 2012 an expansion of WNV areal onto the territory of the region took place and the process of formation of WNF natural foci is ongoing.


Prevalence of germline truncating mutations in ATM in women with a second breast cancer after radiation therapy for a contralateral tumor.
Patients treated with conservative surgery and radiation therapy for early-stage breast cancer develop a contralateral breast cancer at a rate of approximately 0.75% per year. Ataxia-telangiectasia (AT) is an autosomal recessive disease that is characterized by increased sensitivity to ionizing radiation (IR) and cancer susceptibility. Epidemiologic studies have suggested that AT carriers, who comprise 1% of the population, may be at an increased risk for developing breast cancer, particularly after exposure to IR. To test this hypothesis, we analyzed blood samples from 57 patients who developed a contralateral breast cancer at least 6 months after completion of radiation therapy for an initial breast tumor. A cDNA-based truncation assay in yeast was used to test for heterozygous mutations in the ATM gene, which is responsible for AT. No mutations were detected. Our findings fail to support the hypothesis that AT carriers account for a significant fraction of breast cancer cases arising in women after exposure to radiation. Genes Chromosomes Cancer 27:124-129, 2000.