Turbulence Statistics of Arbitrary Moments of Wall-Bounded Shear Flows: A Symmetry Approach.
The calculation of turbulence statistics is considered the key unsolved problem of fluid mechanics, i.e., precisely the computation of arbitrary statistical velocity moments from first principles alone. Using symmetry theory, we derive turbulent scaling laws for moments of arbitrary order in two regions of a turbulent channel flow. Besides the classical scaling symmetries of space and time, the key symmetries for the present work reflect the two well-known characteristics of turbulent flows: non-Gaussianity and intermittency. To validate the new scaling laws we made a new simulation at an unprecedented friction Reynolds number of 10 000, large enough to test the new scaling laws. Two key results appear as an application of symmetry theory, which allowed us to generate symmetry invariant solutions for arbitrary orders of moments for the underlying infinite set of moment equations. First, we show that in the sense of the generalization of the deficit law all moments of the streamwise velocity in the channel center follow a power-law scaling, with exponents depending on the first and second moments alone. Second, we show that the logarithmic law of the mean streamwise velocity in wall-bounded flows is indeed a valid solution of the moment equations, and further, all higher moments in this region follow a power law, where the scaling exponent of the second moment determines all higher moments. With this we give a first complete mathematical framework for all moments in the log region, which was first discovered about 100 years ago.


HLA-B*27 allele associated to Behçet's disease and to anterior uveitis in Moroccan patients.
Human leukocyte antigen HLA-B51 is the most strongly associated gene with Behçet disease (BD) in different ethnic populations. We analyze the influence of HLA-B alleles in BD predisposition in Moroccan population and its association with clinical manifestations. The HLA-B phenotype frequencies were analyzed by serologic HLA class I typing and by polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) reverse dot blot hybridization in 120 unrelated Moroccan patients: all of whom fulfilled the international study group criteria for Behçet's disease, and in 112 ethnically matched healthy controls. Besides HLA-B*51 allele (20%), a significant increased frequency of the HLA-B*27 allele was found in Moroccans patients with Behçet's disease when compared to controls (13.3% of patients versus 2.7% of controls, chi square = 8.75, OR = 5.59, 95% IC [1.58-19.75] and particularly in the patients who presented an anterior uveitis (25% vs. 5.5%, p < 0.005).


Biased Spin-State Energetics of Fe(II) Molecular Complexes within Density-Functional Theory and the Linear-Response Hubbard U Correction.
The spin-state energetics of six Fe(II) molecular complexes are computed using the linear-response Hubbard U approach within DFT. The adiabatic energy differences, ΔEH-L, between the high-spin (S = 2) and the low-spin (S = 0) states are computed and compared with accurate-coupled cluster-corrected CASPT2 results. We show that DFT+U fails in correctly capturing the ground state for strong-field ligands yielding ΔEH-L that are almost constant throughout the molecular series. This bias toward high spin together with the metal/ligand charge transfer upon U correction are here quantified and explained using molecular orbital diagrams involving both σ- and π-bonding interactions. With increasing ligand-field strengths this bias also increases owing to the stronger molecular character of the metal/ligand Kohn-Sham orbitals thus resulting in large deviations from the reference larger than 4 eV. Smaller values of U can be employed to mitigate this effect and recover the right energetics.


Distribution of NADPH-diaphorase activity in the pineal gland of the Turkey.
NADPH-diaphorase activity was histochemically demonstrated in the nerve fibers, neuronal-like cell bodies and in the endothelial cells of the vasculature in the pineal gland of the turkey. The nerve fibers were localized in the choroid plexus, connecting the pineal gland with the diencephalon as well as inside the pineal gland, where they formed basket-like structures around the pineal follicles. A group of neuronal-like cell bodies was observed in the proximal part of the gland. The positive staining was not observed in the pinealocytes of rudimentary-photoreceptor type and in the supporting cells.


miR-100-5p Promotes Epidermal Stem Cell Proliferation through Targeting MTMR3 to Activate PIP3/AKT and ERK Signaling Pathways.
Skin epidermal stem cells (EpSCs) play a critical role in wound healing and are ideal seed cells for skin tissue engineering. Exosomes from human adipose-derived stem cells (ADSC-Exos) promote human EpSC proliferation, but the underlying mechanism remains unclear. Here, we investigated the effect of miR-100-5p, one of the most abundant miRNAs in ADSC-Exos, on the proliferation of human EpSCs and explored the mechanisms involved. MTT and BrdU incorporation assays showed that miR-100-5p mimic transfection promoted EpSC proliferation in a time-dependent manner. Cell cycle analysis showed that miR-100-5p mimic transfection significantly decreased the percentage of cells in the G1 phase and increased the percentage of cells in the G2/M phase. Myotubularin-related protein 3 (MTMR3), a lipid phosphatase, was identified as a direct target of miR-100-5p. Knockdown of MTMR3 in EpSCs by RNA interference significantly enhanced cell proliferation, decreased the percentage of cells in the G1 phase and increased the percentage of cells in the S phase. Overexpression of MTMR3 reversed the proproliferative effect of miR-100-5p on EpSCs, indicating that miR-100-5p promoted EpSC proliferation by downregulating MTMR3. Mechanistic studies showed that transfection of EpSCs with miR-100-5p mimics elevated the intracellular PIP3 level, induced AKT and ERK phosphorylation, and upregulated cyclin D1, E1, and A2 expression, which could be attenuated by MTMR3 overexpression. Consistently, intradermal injection of ADSC-Exos or miR-100-5p-enriched ADSC-Exos into cultured human skin tissues significantly reduced MTMR3 expression and increased the thickness of the epidermis and the number of EpSCs in the basal layer of the epidermis. The aforementioned effect of miR-100-5p-enriched ADSC-Exos was stronger than that of ADSC-Exos and was reversed by MTMR3 overexpression. Collectively, our findings indicate that miR-100-5p promotes EpSC proliferation through MTMR3-mediated elevation of PIP3 and activation of AKT and ERK. miR-100-5p-enriched ADSC-Exos can be used to treat skin wound and expand EpSCs for generating epidermal autografts and engineered skin equivalents.


Language abilities of neurologically normal and suspect preterm children now in preschool.
Multiple aspects of speech and language performance of 29 four- to five-year-old preterm children (10 neurologically suspect) were assessed. Data were collected using a variety of measures including standardized tests and analysis of language samples. Each child's performance was compared with reference data on the various outcomes which yielded an over-all pass score and individual profiles of performance. Neurologically normal children had significantly higher passing scores than suspect children but appeared to be at risk for mild language delays, particularly in morphosyntactic development. Neurologically suspect children appeared to be at risk for moderate and more generalized language delays, including morphosyntactic and phonological development.


Iatrogenic cortical aneurysm post-craniotomy.
Taking into account the number of craniotomies performed every day around the world, iatrogenic aneurysm post-craniotomy is extremely rare with only anecdotal cases reported in literature. We report an iatrogenic aneurysm affecting a cortical vessel which probably developed during dural closure of a conventional craniotomy. The aneurysm was discovered 6 months after surgery on a routine control angiography. The patient was successfully treated by trapping the parent vessel and excising the aneurysm. Histopathological findings were compatible with a true type of traumatic aneurysm. The possibility of this rare condition occurring highlights the risk of arterial injury during craniotomy.


Bi-organ paired exchange-Sentinel case of a liver-kidney swap.
Organ transplantation is the optimal treatment for patients with end stage liver disease and end stage renal disease. However, due to the imbalance in the demand and supply of deceased organs, most transplant centers worldwide have consciously pursued a strategy for living donation. Paired exchanges were introduced as a means to bypass various biologic incompatibilities (blood- and tissue-typing), while expanding the living donor pool. This shift in paradigm has introduced new ethical concerns that have hitherto been unaddressed, especially with nondirected, altruistic living donors. So far, transplant communities have focused efforts on separate liver- and kidney-paired exchanges, whereas the concept of a transorgan paired exchange has been theorized and could potentially facilitate a greater number of transplants. We describe the performance of the first successful liver-kidney swap.


Angular-dependent polarization-insensitive filter fashioned with zero-contrast grating.
We report here an angular-dependent polarization-insensitive filter fashioned with a free-standing zero-contrast grating (ZCG), which is implemented on an HfO(2)/Silicon platform. The spectral characteristics are investigated by rigorous coupled-wave analysis method and measured on angular-resolved micro-reflectance system. The proposed ZCG structure experimentally shows that the polarization-insensitive resonances occur at 595nm for the incidence angle θ of 12.8° and 500nm for the incidence angle θ of 14.2°. When the incident light is normal to the grating surface, the ZCG device generates yellow and red colors for p- and s-polarization, respectively. The experimental results are in good agreement with the simulations, which indicate that the free-standing ZCG device is promising for polarization-insensitive filter and polarization-controlled tunable color filter.


Crystal orientation mapping of NiO grown on cube textured Ni tapes.
Samples of cube textured Ni tapes were oxidized in flowing oxygen at different temperatures. Crystal orientation maps (COMs) of the resulting oxide layers were produced by electron backscatter diffraction. The oxide layers were also analysed by X-ray diffraction (XRD), scanning electron microscopy and atomic force microscopy (AFM). The oxide grain size of a sample oxidized at 600 degrees C was similar to that of the substrate and the oxide was highly textured, both indicating epitaxial growth. The orientation relationship between the substrate and the oxide was directly observed from XRD to be (111)NiO//(001)Ni, [101]NiO//[110]Ni with four, equivalent, in-plane variants. In each variant, the oxide has both <110>- and <211>-type directions parallel to the Ni <110> directions. Differences in oxide thickness and surface roughness on neighbouring grains were revealed by AFM and these were attributed to the existence of a range of oxide growth conditions resulting from small differences in the orientation of each substrate grain. Similar macrotexture and microstructure were observed on a sample oxidized at 1300 degrees C, but additional, facetted oxide crystals had formed at the oxide grain boundaries. COMs showed that these crystals were either cube or 45 degrees rotated cube orientated, a texture different to that of the large oxide grains. The grain boundary crystals were thought to form by inward diffusion of oxygen at defects in the growing oxide scale.


Menometrorrhagia in an oral contraceptive user.
Endometrial carcinoma is the most frequent malignancy of the female reproductive tract, and irregular vaginal bleeding is the most common presenting symptom. Endometrial carcinoma is found most commonly among postmenopausal women and is associated with obesity, nulliparity, and anovulation. Oral contraceptive (OC) use and tobacco smoking have been reported to protect against endometrial carcinoma. Irregular vaginal bleeding is a common side effect of OC therapy. We report the case of an obese, premenopausal nulliparous woman with normal menses who developed menometrorrhagia and was then found to have endometrial carcinoma despite her youth and her use of both tobacco and combination OC.


Xenopus Cds1 is regulated by DNA-dependent protein kinase and ATR during the cell cycle checkpoint response to double-stranded DNA ends.
The checkpoint kinase Cds1 (Chk2) plays a key role in cell cycle checkpoint responses with functions in cell cycle arrest, DNA repair, and induction of apoptosis. Proper regulation of Cds1 is essential for appropriate cellular responses to checkpoint-inducing insults. While the kinase ATM has been shown to be important in the regulation of human Cds1 (hCds1), here we report that the kinases ATR and DNA-dependent protein kinase (DNA-PK) play more significant roles in the regulation of Xenopus Cds1 (XCds1). Under normal cell cycle conditions, nonactivated XCds1 constitutively associates with a Xenopus ATR complex. The association of XCds1 with this complex does not require a functional forkhead activation domain but does require a putative SH3 binding region that is found in XCds1. In response to double-stranded DNA ends, the amino terminus of XCds1 is rapidly phosphorylated in a sequential pattern. First DNA-PK phosphorylates serine 39, a site not previously recognized as important in Cds1 regulation. Xenopus ATM, ATR, and/or DNA-PK then phosphorylate three consensus serine/glutamine sites. Together, these phosphorylations have the dual function of inducing dissociation from the ATR complex and independently promoting the full activation of XCds1. Thus, the checkpoint-mediated activation of XCds1 requires phosphorylation by multiple phosphoinositide 3-kinase-related kinases, protein-protein dissociation, and autophosphorylation.


P2 purinoceptor-mediated intracellular Ca2+ transients in human sural nerve.
Segments of biopsied human sural nerve were stained with the Ca(2+)-sensitive fluorescent dyes Calcium Green-1 and Fura Red. The emission ratio was used to follow changes in the intracellular free Ca2+ concentration ([Ca2+]i). Application of ATP and analogues in concentrations between 0.3 and 300 microM via the bathing solution resulted in a transient rise in [Ca2+]i. The rank order of agonist potency, 2-methylthioATP > ATP > UTP, and the failure of adenosine, alpha,beta-MeATP and beta,gamma-MeATP to evoke rises in [Ca2+]i indicate the presence of P2Y/U subtypes of purinoceptors in this preparation. ATP-induced Ca2+ transients in biopsied human nerve preparations might serve as a diagnostic tool in neuropathies.


Adatom Doping of Transition Metals in ReSe2 Nanosheets for Enhanced Electrocatalytic Hydrogen Evolution Reaction.
Two-dimensional Re dichalcogenide nanostructures are promising electrocatalysts for the hydrogen evolution reaction (HER). Herein, we report the adatom doping of various transition metals (TM = Mn, Fe, Co, Ni, and Cu) in ReSe2 nanosheets synthesized using a solvothermal reaction. As the atomic number of TM increases from Mn to Cu, the adatoms on Re sites become more favored over the substitution. In the case of Ni, the fraction of adatoms reaches 90%. Ni doping resulted in the most effective enhancement in the HER catalytic performance, which was characterized by overpotentials of 82 and 109 mV at 10 mA cm-2 in 0.5 M H2SO4 and 1 M KOH, respectively, and the Tafel slopes of 54 and 81 mV dec-1. First-principles calculations predicted that the adatom doping structures (TMs on Re sites) have higher catalytic activity compared with the substitution ones. The adsorbed H atoms formed a midgap hybridized state via direct bonding with the orbitals of TM adatom. The present work provides a deeper understanding into how TM doping can provide the catalytically active sites in these ReSe2 nanosheets.


Effect of Incisal Porcelain Veneering Thickness on the Fracture Resistance of CAD/CAM Zirconia All-Ceramic Anterior Crowns.
In some clinical situations, the vertical length of either a prepared tooth or an implant abutment is short, while the occlusal clearance to be restored by a porcelain crown is large. Incisal thickness of the veneering porcelain should be considered to prevent mechanical failure of the crown. The aim of this study is to evaluate the effect of two different incisal veneering porcelain thickness on the fracture resistance of the anterior all-ceramic CAD/CAM zirconia crown system as compared with the conventionally used metal ceramic crown system. CAD/CAM zirconia all-ceramic and metal ceramic crowns were fabricated on the prepared dies with standardized dimensions and designs using standardized methods according to the manufacturer's instructions. All crowns were then adhesively luted with resin-based cement (Multilink cement system), subjected to thermal cycling and cyclic loading, and were loaded until fracture using the universal testing machine to indicate the fracture resistance for each crown material in each veneering thickness. Statistical analysis was carried out, and the results showed that the fracture resistance of the nickel-chromium metal ceramic group was significantly higher than that of the CAD/CAM zirconia all-ceramic group. Also, the fracture resistance of crowns with 1.5 mm incisal veneering thickness was significantly higher than those with 3 mm incisal veneering thickness in both groups. Furthermore, there was no significant difference in the fracture mode of the two groups where 50% of the total specimens demonstrated Mode II (veneer chipping), while 35% demonstrated Mode I (visible crack) and only 15% demonstrated Mode III (bulk fracture). High failure load values were demonstrated by the specimens in this study, which suggest sufficient strength of both incisal veneering thickness in both crown systems to withstand clinical applications; however, the fracture patterns still underline the requirement of a core design that support a consistent thickness of the veneering ceramic, and it is recommended to conduct long-term prospective clinical studies to confirm findings reported in the present study.


Development of a core set from a large rice collection using a modified heuristic algorithm to retain maximum diversity.
A new heuristic approach was undertaken for the establishment of a core set for the diversity research of rice. As a result, 107 entries were selected from the 10 368 characterized accessions. The core set derived using this new approach provided a good representation of the characterized accessions present in the entire collection. No significant differences for the mean, range, standard deviation and coefficient of variation of each trait were observed between the core and existing collections. We also compared the diversity of core sets established using this Heuristic Core Collection (HCC) approach with those of core sets established using the conventional clustering methods. This modified heuristic algorithm can also be used to select genotype data with allelic richness and reduced redundancy, and to facilitate management and use of large collections of plant genetic resources in a more efficient way.


Presentation and outcome of surgically managed liver trauma: experience at a tertiary care teaching hospital.
To document and analyse the presentation and outcome of surgical management of liver trauma. The study was a retrospective review of records of all surgeries carried out at the Department of General Surgery, Pakistan Institute of Medical Sciences (PIMS), Islamabad, from January 2003 to December 2010. The study included all adult patients of either gender who presented with liver trauma and underwent operative management. Convenience sampling technique was employed. The study excluded patients who were managed conservatively. The data were collected through a proforma and analysed through SPSS 10. Out of 113 cases of liver trauma, 91 (80.5%) were males and 22 (19.4%) were females. The mean age was 34.8 +/- 9.7 years. Road traffic accidents were the leading cause (n = 75; 66.3%) of injuries. There were 37 (32.7%) patients with grade I injury; 41 (36.2%) with grade II injury; 29 (25.6%) with grade III injury; and 7 (6.1%) patients with grade IV injury. Besides, 62 (54.8%) patients had associated extra-hepatic injuries. Majority of the patients presented with haemodynamic compromise (n = 97; 85.8%). Perihepatic packing was the commonest operative procedure instituted (n = 43;38%). The in-hospital mortality was 9.7% (n = 11). Liver trauma constitutes an important cause of emergency hospitalisation, morbidity and in-hospital mortality in our population. It predominantly affects the younger males and road traffic accidents are the leading cause. Majority of the patients are successfully managed with perihepatic packing.


Mom empowerment, too! (ME2): a program for young mothers involved in substance abuse.
Substance abuse among young people is of critical concern to public health nurses. When substance abusers are young mothers without the skills, experience, guidance, or resources to become adequate parents, this problem is compounded This study examined a community-based intervention program for young mothers from the perspective of 42 participants. A qualitative, descriptive design was used within a process of participatory action research. Two major domains emerged from the data: risk perceptions and behaviors, and health promoting perceptions and behaviors. The study demonstrated the value of obtaining data from the participants and offers implications for practice and research.


Neuropsychological functioning in children with Tourette syndrome with and without attention-deficit/hyperactivity disorder.
Neuropsychological functioning in children with Tourette syndrome (TS) has been characterized by subtle deficits in response inhibition, visual-motor integration, and fine-motor coordination. The association of these deficits with the tics of the TS versus co-occurring attention-deficit/hyperactivity disorder (ADHD) has not been well understood because of small sample sizes and lack of adequate control conditions. We examined neuropsychological functioning in relatively large and well-characterized samples of children categorized as TS, TS-plus-ADHD, ADHD, and unaffected controls. A total of 56 children with TS-only, 45 with TS-plus-ADHD, 64 with ADHD, and 71 healthy community control subjects were assessed on a battery of neuropsychological measures including the Connors' Continuous Performance Test (CPT), the Stroop Color-Word Interference Test (Stroop), the Beery Visual-Motor Integration Test (VMI), and the Purdue Pegboard Test. There were no differences between children with TS-only and unaffected controls on the measures of response inhibition and visual-motor integration. Boys with TS-only but not girls with TS-only were impaired in the dominant hand Purdue performance. Children with ADHD were impaired on all study measures. Children with TS-plus-ADHD revealed no deficits on the Stroop, VMI, and Purdue tests but were impaired on the sustained attention portion of the CPT. These results indicate that co-occurring ADHD may be responsible for the neuropsychological deficits, or at least those assessed in the present study, in children with TS. Explanations in terms of neurobiological mechanisms of co-occurring TS and ADHD, as well as possible compensatory mechanisms in children with TS, are discussed.


Association of Osteoprotegerin with Obesity, Insulin Resistance and Non-Alcoholic Fatty Liver Disease in Children.
Osteoprotegerin (OPG) is a member of the tumor necrosis factor superfamily. Reduced OPG levels are related to obesity, insulin resistance, and non-alcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the relationship between OPG levels, obesity, insulin resistance, and NAFLD in pediatric patients. This was a prospective, cross-sectional, controlled study that was conducted in the department of pediatrics at Bagcilar training and research hospital in Istanbul, Turkey, between April and August 2015. The study was performed on 107 children with obesity and 37 controls aged 5 - 17 years. In the obese subset, 62 patients had NAFLD. Homeostatic model assessment-insulin resistance (HOMA-IR) was used to calculate insulin resistance. Insulin resistance was defined as a HOMA-IR value greater than 2.5. Plasma OPG levels were measured using enzyme-linked immunosorbent assays. NAFLD was diagnosed by hepatic ultrasound. The mean age was 11.25 ± 3.38 years in the patient group and 10.41 ± 3.15 years in the control group. The OPG level in the obese group with the mean of 55.20 ± 24.55 pg/mL (median = 48.81 pg/mL) was significantly lower than that in the control group with the mean of 70.78 ± 33.41 pg/mL (median = 64.57 pg/mL) (P = 0.0001). The optimal cut-off point (sensitivity, specificity) of the OPG level for the diagnosis of obesity was ≤ 46, 19 pg/mL. According to logistic regression analysis, fasting insulin (P = 0.036) and OPG (P = 0.01) levels were most affected by obesity. In the obese patients, who had HOMA-IR < 2.5, the mean level of OPG was 58.91 ± 6.88729 pg/mL (median = 49.55). In the obese patients, who had HOMA-IR ≥ 2.5, the mean level of OPG was 54.19 ± 22.21 pg/mL (median = 48.47). No significant correlations were found between OPG and HOMA-IR (P = 0.791). No statistically significant difference was observed in the mean OPG between patients with hepatosteatosis (mean = 54.55 ± 25.01 pg/mL) (median = 49.46) and those without the disease (56.30 ± 24.02 pg/mL) (mean = 48.34) (P = 0.089). We confirmed that serum OPG concentrations reduce in obese children. However, no correlation was identified between OPG and insulin resistance. OPG levels are not meaningful in the diagnosis of NAFLD in children with obesity.


Multiple osteoid osteoma in the 7th dorsal vertebra.
The authors report a case of osteoid osteoma localised in both laminae of D7. No bilateral case of this type has previously been reported in the literature.


[Administration of a single dose of 100,000 U.I. of vitamin D3 in the pregnant woman in winter. The effect on blood calcium level of the newborn infant].
Serum levels of 25-hydroxyvitamin D [25-(OH)D], calcium, phosphate and alkaline phosphatase activity were measured between December and July in 110 pregnant women during the last trimester of pregnancy, and in their infants on the fifth day of life. This study showed a fall, during spring, below 6 ng/ml, of the maternal 25-(OH)D concentration at the time of delivery, and a fall of the 25-(OH)D and calcium concentrations in newborns. The existence of a positive correlation between calcium and 25-(OH)D levels in the newborns suggests that the low calcium concentrations found in the infants born in spring is related to a vitamin D deficiency of the infant and therefore of the mother. The administration of a single low dose of vitamin D3 (100,000 I.U.) on the sixth or seventh month of pregnancy allowed to prevent the seasonal fall in serum calcium and 25-(OH)D concentrations. This dosage appears therefore to be sufficient to reduce the risk of vitamin D deficiency of the newborn and the occurrence of neonatal hypocalcemia.


Real-Time Cellular Thermal Shift Assay to Monitor Target Engagement.
Determining a molecule's mechanism of action is paramount during chemical probe development and drug discovery. The cellular thermal shift assay (CETSA) is a valuable tool to confirm target engagement in cells for a small molecule that demonstrates a pharmacological effect. CETSA directly detects biophysical interactions between ligands and protein targets, which can alter a protein's unfolding and aggregation properties in response to thermal challenge. In traditional CETSA experiments, each temperature requires an individual sample, which restricts throughput and requires substantial optimization. To capture the full aggregation profile of a protein from a single sample, we developed a prototype real-time CETSA (RT-CETSA) platform by coupling a real-time PCR instrument with a CCD camera to detect luminescence. A thermally stable Nanoluciferase variant (ThermLuc) was bioengineered to withstand unfolding at temperatures greater than 90 °C and was compatible with monitoring target engagement events when fused to diverse targets. Utilizing well-characterized inhibitors of lactate dehydrogenase alpha, RT-CETSA showed significant correlation with enzymatic, biophysical, and other cell-based assays. A data analysis pipeline was developed to enhance the sensitivity of RT-CETSA to detect on-target binding. RT-CETSA technology advances capabilities of the CETSA method and facilitates the identification of ligand-target engagement in cells, a critical step in assessing the mechanism of action of a small molecule.


Prolactin-Elevating Antipsychotics and the Risk of Endometrial Cancer.
The use of antipsychotics may increase the risk of endometrial cancer through elevation of prolactin levels. We investigated the association between antipsychotics that are known to cause prolactin elevation and the risk of endometrial cancer. In data from the United Kingdom Clinical Practice Research Datalink, all women who were newly treated with antipsychotics from 1990-2013 were identified and followed until 2014. Within this cohort of antipsychotic users, a nested case-control analysis was conducted. Main exposure was nonsporadic use of prolactin-elevating antipsychotics, and the active comparator was prolactin-sparing antipsychotics. Cases were women newly diagnosed with endometrial cancer (ICD-10) matched with up to 20 controls on age, calendar year of cohort entry, linkability to the Hospital Episode Statistics repository, and duration of follow-up. Conditional logistic regression models were used to determine the association of prolactin-elevating antipsychotics and endometrial cancer compared with prolactin-sparing antipsychotics. All analyses were adjusted for relevant potential confounders, including smoking, obesity, and diabetes mellitus. The cohort included 65,930 women. During 366,112 person-years of follow-up, there were 139 cases of endometrial cancer (incidence rate: 38/100,000 person-years), which were matched to 1,603 controls. Compared with the use of prolactin-sparing antipsychotics, the use of prolactin-elevating antipsychotics was not associated with an increased risk of endometrial cancer (adjusted odds ratio [aOR] = 1.00; 95% CI, 0.68-1.48). These findings remained similar with different durations of use (≤ 1 year, aOR = 1.07; 95% CI, 0.64-1.78, and > 1 year, aOR = 0.95; 95% CI, 0.58-1.54) and were robust to various sensitivity analyses. Prolactin-elevating antipsychotics were not associated with an increased risk of endometrial cancer.


Oxidation of pentachlorophenol in manganese oxide suspensions under controlled Eh and pH environments.
Abiotic oxidation of pentachlorophenol (PCP) by manganese(IV) oxide (MnO2) was examined in orderto understand the physiochemical environment(s) where PCP oxidation occurs. An Eh-pH potentiostat was used to simulate natural groundwater environments where MnO2 (0.025 g L(-1)) and PCP (0.020 g L(-1)) suspensions were incubated from Eh -300 to 300 mV and pH 4.5 to 7.0. The pH-Eh region where maximum PCP sorption occurred corresponded to the same region where the greatest concentrations of soluble Mn(II) where measured (Eh > -100 mV and pH <5.0). Reduced Mn species [Mn(II,III)] released by reductive dissolution were readsorbed and restricted further abiotic oxidation of PCP by the MnO2 surface. A greater transformation of PCP to primarily tetrachloro-1,4-benzoquinone (p-chloranil) and smaller amounts of lesser chlorinated phenols occurred under increasing pH and Eh conditions.


Low-dose paclitaxel synergizes with oncolytic adenoviruses via mitotic slippage and apoptosis in ovarian cancer.
The microtubule-stabilizing drug paclitaxel has activity in relapsed ovarian cancer. dl922-947, an oncolytic adenovirus with a 24-bp deletion in E1A CR2, replicates selectively within and lyses cells with a dysregulated Rb pathway and has efficacy in ovarian cancer. In the aggressive A2780CP xenograft, combination treatment with weekly dl922-947 and paclitaxel has significantly greater efficacy than either treatment alone and can produce complete tumor eradication in some animals. We investigated the mechanisms of paclitaxel's synergy with dl922-947 in ovarian cancer. The host-cell microtubule network is grossly rearranged and stabilized following adenovirus infection, but paclitaxel does not increase this significantly. Paclitaxel does not synergize by increasing infectivity, viral protein expression or virus release. However, destabilizing the microtubule network with nocodazole reduces viral exit, revealing a novel microtubule-dependent pathway for non-lytic adenoviral exit. dl922-947 can override multiple cell cycle checkpoints but induces cell death by a non-apoptotic mechanism. In combination, dl922-947 and low-dose paclitaxel induces aberrant, multipolar mitoses, mitotic slippage and multinucleation, triggering an apoptotic cell death.


IgG antibodies to human cytomegalovirus late protein UL94 in patients with systemic sclerosis.
Human cytomegalovirus (HCMV) has been proposed as an amplifying agent for at least some of the spectrum of systemic sclerosis (SSc; scleroderma). In support of this hypothesis, antibodies to the HCMV late protein UL94 have been detected in the majority of SSc patients in a study involving Caucasian subjects from Italy. The aim of this investigation was to determine whether elevated levels of anti-UL94 antibodies are present in African American and Caucasian SSc patients from the U.S. We further wished to determine whether there was a significant difference in the levels of anti-UL94 antibodies between the diffuse and the limited forms of the disease. IgG antibodies to a UL94 peptide were measured in 254 Caucasian and 90 African American subjects by an enzyme-linked immunosorbent assay (ELISA). In both Caucasian and African American subjects, the mean antibody level in the diffuse form of SSc was significantly higher than that in the respective control subjects (714 vs. 466 ng/ml, p = 0.005; 1226 vs. 512 ng/ml, p < 0.0001). Also, among Caucasian SSc patients, the mean antibody level in the diffuse form of SSc was significantly higher than that in the limited form of the disease (714 vs. 465 ng/ml, p = 0.02). These results show that increased levels of antibodies to the HCMV late protein UL94 are associated with SSc and they may be a marker for the severity of the disease.


Effect of active application of self-etching ceramic primer on the long-term bond strength of different dental CAD/CAM materials.
The objective of this in vitro study was to evaluate the effect of the active application of self-etching ceramic primer (ME&P) on the bond strength of different dental CAD/CAM materials (Lithium Disilicate ceramic (LD), Leucite ceramic (LE), Zirconia reinforced lithium silicate ceramic (ZLS), and Hybrid ceramic (HC)) with thermocycling aging. The samples were randomly divided into 16 groups (n = 20). Dual resin cement cylinders were made and light cured for 10 s (1.200 mW/cm2) for the shear bond strength test. 3-way ANOVA revealed that the factors were statistically significant (P< 0.05). The aging process had a negative impact on the bond strength for all groups except for Lithium Disilicate, with active application. ZLS and LE showed promising results with high bond strength values for the ME&P active application; however, after aging the bond strength value was significantly reduced. HC showed reduced bond strength values regardless the ME&P application. In order to obtain a durable bond strength, the recommended protocol of 20 s of active application followed by 40 s of sitting time in the self-etching ceramic primer should be followed when using reinforced-glass ceramics as restorative materials. Key words:Dentistry, dental materials, silane, shear strength, computer-aided design.


Study of respirable suspended particulates and polycyclic aromatic hydrocarbons in indoor and outdoor air.
To study the concentration change of respirable suspended particulate (RSP) in indoor and outdoor air environment, a new portable sampler (AND-sampler) was made. The sampler could collect particles above 10 microns, 2 to 10 microns, and below 2 microns in aerodynamic diameter separately. The relationship between the airborne particulate concentration in indoor and outdoor air environment varied with the aerodynamic diameter of the particles. The concentration of RSP in indoor air environment increased in proportion to that in outdoor environment. Polycyclic aromatic hydrocarbons (PAH) concentration in airborne particulate also varies with the aerodynamic diameter of the particles. Fine particles below 2 microns in aerodynamic diameter contains high concentration of PAH. The PAH concentration in indoor air environment increases in proportion to that in outdoor air.


Unsaturated Alcohols as Chain-Transfer Agents in Olefin Polymerization: Synthesis of Aldehyde End-Capped Oligomers and Polymers.
Palladium diimine-catalyzed polymerization of olefins using unsaturated alcohols as chain-transfer agents has been demonstrated. The reaction affords aldehyde end-capped polymers whose molecular weight can be tuned by varying the ratio of olefin/chain-transfer agent. Notably, >95% efficient end capping with aldehyde can be achieved under optimized conditions. This end-capping procedure is a rare example of introducing a highly reactive and versatile terminal functionality in polyolefin chains using a functional group-tolerant late metal catalyst. The reactivity of these end-capped polymers is illustrated here via functionalization with dyes to yield colored, hydrocarbon-soluble polyolefin derivatives.


Magnetic resonance imaging manifestations of idiopathic haemochromatosis in the wrist.
The magnetic resonance imaging features of the wrist of a patient suffering from the arthropathy of haemochromatosis are presented. It is apparent that the deposition of iron within the bone marrow is focal in origin and may be associated with cyst formation. In addition, changes in serum ferritin levels with treatment suggest that the deposition is irreversible. Studies of two other patients with haemochromatosis without cyst formation in the wrists did not yield similar artefacts, in spite of having high ferritin levels and arthritis.


Microarray expression profile analysis of long non-coding RNAs in optineurin E50K mutant transgenic mice.
The biological role of long non-coding RNAs (lncRNAs) involves various cellular processes and leads to human diseases. Mutations in the optineurin (OPTN) gene, including E50K, which encodes an amino acid substitution, have been associated with primary open angle glaucoma (POAG). The present study was designed to identify lncRNAs associated with OPTN (E50K) transgenic mice and investigate its functions in the pathogenesis of POAG. The retinas from six OPTN (E50K) transgenic and wild-type mice were collected separately, and lncRNA expression profiling was performed using microarray analysis. Based on Pearson's correlation analysis, an lncRNA and mRNA co‑expression network was constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the lncRNAs and coexpressed mRNAs was used to identify the associated biological modules and pathological pathways. The GO biological processes (BPs) of the differentially expressed lncRNAs were predicted using a computational method of gene set enrichment analysis. A total of 69 lncRNAs showed differential expression between the OPTN (E50K) transgenic mice and wild‑type mice, which included 37 downregulated and 32 upregulated lncRNAs. The pathway analysis revealed that the lncRNAs coexpressed with mRNAs were enriched in mRNA surveillance and RNA transport pathways. In addition, eight lncRNAs were annotated in the GO BPs, and two of these eight lncRNAs, ASMM10P055228 and ASMM10P040128, were annotated with the negative regulation of oxidative stress-induced cell death and regulation of execution phase of apoptosis. These results showed that lncRNAs were differentially expressed in the retinas between OPTN (E50K) transgenic and wild‑type mice, and this may be important in the pathogenesis of POAG caused by the OPTN (E50K) mutation.


Exploring the Effect of Cation Vacancies in TiO2: Lithiation Behavior of n-Type and p-Type TiO2.
TiO2 offers several advantages over graphite as an anode material for Li-ion batteries (LIBs) but suffers from low electrical conductivity and Li-diffusion issues. Control over defect chemistry has proven to be an effective strategy to overcome these issues. However, defect engineering has primarily been focused on oxygen vacancies (VO). The role of another intrinsic TiO2 vacancy [i.e., titanium vacancies (VTi)] with regard to the Li+ storage behavior of TiO2 has largely evaded attention. Hence, a comparison of VO- and VTi-defective TiO2 can provide valuable insight into how these two types of defects affect Li+ storage behavior. To eliminate other factors that may also affect the Li+ storage behavior of TiO2, we carefully devised synthesis protocols to prepare TiO2 with either VO (n-TiO2) or VTi (p-TiO2). Both TiO2 materials were verified to have a very similar morphology, surface area, and crystal structure. Although VO provided additional sites that improved the capacity at low C-rates, the benefit obtained from over-lithiation turned out to be detrimental to cycling stability. Unlike VO, VTi could not serve as an additional lithium reservoir but could significantly improve the rate performance of TiO2. More importantly, the presence of VTi prevented over-lithiation, significantly improving the cycling stability of TiO2. We believe that these new insights could help guide the development of high-performance TiO2 for LIB applications.


Conformational fluctuations of a protein-DNA complex and the structure and ordering of water around it.
Protein-DNA binding is an important process responsible for the regulation of genetic activities in living organisms. The most crucial issue in this problem is how the protein recognizes the DNA and identifies its target base sequences. Water molecules present around the protein and DNA are also expected to play an important role in mediating the recognition process and controlling the structure of the complex. We have performed atomistic molecular dynamics simulations of an aqueous solution of the protein-DNA complex formed between the DNA binding domain of human TRF1 protein and a telomeric DNA. The conformational fluctuations of the protein and DNA and the microscopic structure and ordering of water around them in the complex have been explored. In agreement with experimental studies, the calculations reveal conformational immobilization of the terminal segments of the protein on complexation. Importantly, it is discovered that both structural adaptations of the protein and DNA, and the subsequent correlation between them to bind, contribute to the net entropy loss associated with the complex formation. Further, it is found that water molecules around the DNA are more structured with significantly higher density and ordering than that around the protein in the complex.


Mental Accounting in Portfolio Choice: Evidence from a Flypaper Effect.
Consistent with mental accounting, we document that investors sometimes choose the asset allocation for one account without considering the asset allocation of their other accounts. The setting is a firm that changed its 401(k) matching rules. Initially, 401(k) enrollees chose the allocation of their own contributions, but the firm chose the match allocation. These enrollees ignored the match allocation when choosing their own-contribution allocation. In the second regime, enrollees simultaneously selected both accounts' allocations, leading them to mentally integrate the two. Own-contribution allocations before the rule change equal the combined own- and match-contribution allocations afterwards, whereas combined allocations differ sharply across regimes.


Multidisciplinary approach to chronic back pain: prognostic elements of the outcome.
This study presents an evaluation of a multidisciplinary approach to patients with chronic back pain. Sixty-seven patients with back pain of more than three months duration participated in a comprehensive 4 week program which included back schooling, psychological intervention, and treatment by acupuncture, chiropractic, the Alexander technique and a pain specialist. At admission to the study, patients were asked to complete a questionnaire concerning their socio-demographic background and disease history. Patients also underwent a psychological evaluation based on a questionnaire and an interview. On the basis of this evaluation, patients were graded on three criteria: (i) predominance of psychological factors; (ii) secondary gain; (iii) personality features. At the end of the treatment, patients were divided into three groups according to their degree of improvement. Patients were evaluated at the end of the four week program and after 6 months of follow up. Significant improvement in the pain rating, pain frequency and analgesic drug consumption was observed in the treatment group, and was maintained for a period of 6 months. Satisfactory outcome was correlated to a moderate predominance of psychological factors, good functioning, a high level of motivation, and family support. Poor outcome was associated with a divorced marital status and unemployment, diffuse complaints, post surgery status, a high predominance of psychological factors, and the presence of secondary gain and personality disorders. Patients with chronic back pain seem to benefit from this proposed multidisciplinary approach. The improvement was maintained for a period of 6 months. Outcome was clearly related to psychosocial factors.


Colonic movements in healthy subjects as monitored by a Magnet Tracking System.
The Magnet Tracking System (MTS) is a minimally-invasive technique of continuous evaluation of gastrointestinal motility. In this study, MTS was used to analyse colonic propulsive dynamics and compare the transit of a magnetic pill with that of standard radio-opaque markers. MTS monitors the progress in real time of a magnetic pill through the gut. Ten men and 10 women with regular daily bowel movements swallowed this pill and 10 radio-opaque markers at 8 pm. Five hours of recordings were conducted during 2 following mornings. Origin, direction, amplitude and velocity of movements were analysed relative to space-time plots of the pill trajectory. Abdominal radiographs were taken to compare the progress of both pill and markers. The magnetic pill lay idle for 90% of its sojourn in the colon; its total retrograde displacement accounted for only 20% of its overall movement. Analysis of these movements showed a bimodal distribution of velocities: around 1.5 and 50 cm min(-1), the latter being responsible for 2/3 of distance traversed. There were more movements overall and more mass movements in males. Net hourly forward progress was greater in the left than right colon, and greater in males. The position of the magnetic pill correlated well with the advancement of markers. MTS showed patterns and propulsion dynamics of colonic segments with as yet unmet precision. Detailed analysis of slow and fast patterns of colonic progress makes it possible to specify the motility of colonic segments, and any variability in gender. Such analysis opens up promising avenues in studies of motility disorders.


Hemolysis in a Patient during Hemodialysis.
We report a case of hemolysis during a hemodialysis (HD) session in a 71-year-old man. His end-stage kidney disease is secondary to light-chain amyloidosis with renal involvement. Despite immunosuppressive treatment, his renal function continued to decline, and dialysis had to be initiated. Peritoneal dialysis (PD) was started but that had to be converted to HD because of pleural effusion due to PD fluid leakage. On the event day, the patient presented a respiratory distress 2 h after the initiation of HD. He developed a sudden onset of dyspnea with hypoxemia, associated with abdominal pain, nausea, and vomiting. He also presented chest pain with arterial hypertension. The pre-pump arterial and post-pump pressures were, respectively, 40 and 100 mm Hg, with no machine alarm. The blood color in the circuit changed and became darker, so HD was stopped immediately without blood restitution, and then a blood workup was obtained, and the patient was treated with oxygen therapy, IV methylprednisolone 40 mg, and IV furosemide 100 mg. Tubing checkup performed after the incident showed a kinked arterial tube which led to the suspicion of acute hemolysis. Blood transfusion was therefore urgently ordered, and the patient was immediately transferred to the intensive care unit (ICU). Artificial ventilation was required for 4 days, with initial massive blood transfusion. A 24-h treatment with extracorporeal cytokine adsorber CytoSorb® was also performed, followed by the regular HD sessions thrice weekly. Evolution was favorable, and the patient was discharged from the ICU 18 days later.


Epidemiological investigation on hepatitis A virus infection outbreak in the area of Rzeszow city during the years 2017/18.
To define the threats and epidemiological differences between outbreaks of hepatitis A (HA) in adults and children, and to assess the efficiency of implemented prophylaxis. We also present a summary of treatment and sick leave costs as compared to the predicted money-load in the case of properly initiated prophylaxis in hepatitis A virus (HAV)-exposed persons. The cause of two outbreaks was contamination related to food mishandling by a person infected with HAV. Especially health-threatening was exposure to the infection of 137 pre-school children. A second outbreak caused by the same source was observed among 25 exposed adults. On the basis of medical documentation we determined costs related to hospitalization and sickness leave absence at work, comparing it with money load related to implementation of required prophylaxis in both groups of people exposed to risk of HAV infection. As a consequence of exposure in the kindergarten area, an infection was confirmed in 32 patients from the first and subsequent generations and 7 cases were observed in the second outbreak. Costs of hospitalization and related to the sick leave were estimated to double the predicted costs of prophylaxis. In the case of lack of proper hand hygiene of a food handler with HA or in the case of food-borne exposure of children to HAV it is necessary to apply post-exposure prophylaxis. Costs of the prophylaxis are significantly lower than costs of HA. Both outbreaks underwent self-limitation with longer course of morbidity and larger number in the case of the kindergarten focus.


Generating new mixtures of food additives with antimicrobial and cytotoxic potency against Bacillus cereus and Staphylococcus aureus.
Food additives have been shown to help regulate or prevent the spread of microbes during food manufacturing. Phloxine B, nisin, and sorbic acid were tested to see whether they had a synergistic impact on the inactivation of Bacillus cereus and Staphylococcus aureus, respectively. The combination of phloxine B and nisin had a synergistic interaction (FICI: 0.25-0.50) against B. cereus, where it demonstrated an additive effect among the three combinations examined (FICI: 0.91). A time-kill test was used in both cases to verify that a food additive combination has synergistic antibacterial action against B. cereus and S. aureus. B. cereus had a 50% reduction in bacterial colony count after 10 h, whereas S. aureus had a 60% reduction after 6 h of their independent impacts after 48 h. Phloxine B, nisin, and sorbic acid demonstrated synergistic antibacterial action and might be used as a source of safe and potent antibacterial agents in the pharmaceutical and food industries.


Ventilation-perfusion inhomogeneity increases gas uptake: theoretical modeling of gas exchange.
Ventilation-perfusion (VA/Q) inhomogeneity was modeled to measure its effect on gas exchange in the presence of inspired mixtures of two soluble gases using a two-compartment computer model. Theoretical studies involving a mixture of hypothetical gases with equal solubility in blood showed that the effect of increasing inhomogeneity of distributions of either ventilation or blood flow is to paradoxically increase uptake of the gas with the lowest overall uptake in relation to its inspired concentration. This phenomenon is explained by the concentrating effects that uptake of soluble gases exert on each other in low VA/Q compartments. Repeating this analysis for inspired mixtures of 30% O(2) and 70% nitrous oxide (N(2)O) confirmed that, during "steady-state" N(2)O anesthesia, uptake of N(2)O is predicted to paradoxically increase in the presence of worsening VA/Q inhomogeneity.


Yeast sugar transporters.
Transport of sugars is a fundamental property of all eukaryotic cells. Of particular importance is the uptake of glucose, a preferred carbon and energy source. The rate of glucose utilization in yeast is often dictated by the activity and concentration of glucose transporters in the plasma membrane. Given the importance of transport as a site of control of glycolytic flux, the regulation of glucose transporters is necessarily complex. The molecular analysis of these transporters in Saccharomyces has revealed the existence of a multigene family of sugar carriers. Recent data have raised the question of the actual role of all of these proteins in sugar catabolism, as some appear to be lowly expressed, and point mutations of these genes may confer pleiotropic phenotypes, inconsistent with a simple role as catabolic transporters. The transporters themselves appear to be intimately involved in the process of sensing glucose, a model for which there is growing support.


From AVATAR Mice to Patients: RC48-ADC Exerted Promising Efficacy in Advanced Gastric Cancer With HER2 Expression.
RC48-ADC is a novel humanized antibody specific for human epidermal growth factor receptor 2 (HER2)in conjugation with a microtubule inhibitor via a cleavable linker. This study was to evaluate the antitumor activity and mechanism of RC48-ADC in gastric cancer (GC) and explore the population that may benefit from RC48-ADC treatment. Four human GC cell lines and nine patient-derived xenograft (PDX) models were exploited to evaluate the antitumor effect of RC48-ADC or trastuzumab treatment in vitro and in vivo. The expression and phosphorylation of HER2 were assessed by immunohistochemistry (IHC) staining. Critical molecules of downstream PI3K/AKT and cell cycle and apoptosis signaling pathways were detected and quantified by immunoblotting. Combined with preliminary results of preclinical research, three patients with IHC3+, IHC2+/FISH+, and IHC2+/FISH- of HER2 were enrolled to verify the efficacy of RC48-ADC treatment in advanced GC. In vitro, RC48-ADC had superior antiproliferative effects in a dose-dependent manner on GC cells, especially on HER2-positive cells. In vivo, RC48-ADC exceeded trastuzumab in GC PDX models with HER2 expression, even in models with moderate to low expression of HER2. Further exploration of mechanism showed that RC48-ADC exerted the antitumor effect by inhibiting phosphorylation of HER2, inducing G2/M phase arrest and cell apoptosis in HER2-expressed PDX models. In clinical practice, RC48-ADC had satisfactory efficacy in HER2-positive and HER2 moderately expressed GC patients and demonstrated promising efficacy in HER2-positive patients who have progressed after anti-HER2 therapy. In conclusion, RC48-ADC exerted promising antitumor activity in HER2-positive as well as score of 2+ in IHC and ISH-negative AGC patients after progression of systematic treatment.


Stroma formation in Ehrlich carcinoma. I. Oedema phase. A mitosis burst as an index of physiological reoxygenation?
Tumor stroma induction has been shown closely to resemble wound repair process, both involving the replacement of a fibrin gel by vascularized connective tissue. In such a process the initial phase of hyperpermeability of blood vessels leads to diffuse oedema. It is here reported that cell loosening and a remarkably high mitotic burst were observed in Ehrlich carcinoma in regions in contact with the exudate, particularly at the perinecrotic (hypoxic) region. This suggests both an enhanced cell detachment from the tumour parenchyma and an improvement of the microenvironment, the exudate thus appearing as beneficial to the malignant cells contributing to the reoxygenation of formerly hypoxic regions. The temporary and well-localized concentration of mitoses in inner tumour areas has perhaps been disregarded by the pathologists engaged in mitosis counting for tumour grading. Peripheric and intraparenchymal concentrations of mast cells, lipid pools and platelets were seen in apparently key geometric disposition for controlling fibrin deposition and angiogenesis. Hypoxia is known to cause resistance to oxygen-dependent treatments and to facilitate cell detachment; normal fibroblasts respond and survive under hypoxic conditions by exhibiting features of the malignant phenotype. During reoxygenation, gene instability, cellular heterogeneity and increased drug resistance and metastatic spread have been reported. A reoxygenation process can also be deduced from several other histochemical and morphological patterns observed in this study. The findings here reported thus suggest that the oedema phase is a crucial phase regulating growth, invasion and dissemination of tumour cell populations, that should be specifically addressed therapeutically.


Clinical Comparison of Three Esthetic Full-Coverage Restorations in Primary Maxillary Incisors at 12 Months.
Purpose: The purpose of this study was to compare the 12-month clinical outcomes of primary maxillary incisors restored with composite strip crowns (CSCs), NuSmile preveneered stainless steel crowns (PVSSCs), and NuSmile zirconia crowns (ZCs). Methods: A total of 135 teeth in 49 two- to four-year-olds with early childhood caries were randomly assigned to crown groups. Demographic and tooth-related variables at baseline and 12 months were assessed by calibrated examiners. Fisher's exact or chi-square tests were used to test associations (P<0.05). Parental satisfaction of crown esthetics was evaluated by questionnaire. Results: Children were, on average, 3.4 years old, female (55 percent), and had a mean decayed, missing, and filled primary teeth (dmft) index score of 10.6. At 12 months, crown retention was significantly lower for CSCs versus PVSSCs or ZCs (79 percent, 100 percent, and 95 percent, respectively; P=0.002). Partial and complete loss of material was significantly higher in CSCs than PVSSCs or ZCs (29 percent, 11 percent, and zero percent, respectively; P<0.001). CSCs presented with increased marginal discrepancies and color change (P<0.001). Most parents were very satisfied (87 percent); those dissatisfied were concerned with the color of CSCs and PVSSCs (63 percent versus 37 percent; P=0.005). Conclusions: Composite strip crowns showed significantly reduced clinical success in retention, durability, marginal adaptation, and color compared to preveneered stainless steel crowns or zirconia crowns. Parental esthetic satisfaction was highest for NuSmile ZCs.


Chromosomal instability and telomere length variations during the life span of human fibroblast clones.
Growth characteristics, karyotype changes, and telomere length variations were analyzed during the life span of 12 anchorage-independent clones isolated from a xeroderma pigmentosum fibroblast strain. After an initial period of comparable active growth, all the clones showed a decline in the growth rate and finally entered a phase of replicative senescence; however, the number of population doublings and the time required to enter senescence varied among the clones. Repeated cytogenetic analyses during culture propagation showed the appearance of chromosome anomalies, mainly telomeric association (tas) and unbalanced translocations. In all the clones the percentage of abnormal mitoses increased with culture passage, but reached different levels (from less than 10% to about 100%). This finding indicates that the replicative block may be associated with differently altered cytogenetic patterns. Specific chromosome arms (5p, 16q, 19q, and 20q) were preferentially involved in tas, suggesting that alterations in chromosome ends may occur which predispose to fusion. In some clones it was possible to demonstrate the origin of marker chromosomes from the evolution of tas. Telomere length analysis by Southern blotting on DNA samples prepared from 7 clones and from the parental cell lines showed that the terminal restriction fragment (TRF) profiles were homogeneous in senescent parental cells and in the clones during the last part of their life in culture, regardless of the degree of karyotype abnormalities. The homogeneity of the TRF profiles supports the hypothesis of a critical telomere length at senescence.


Practice effects in three-dimensional sequential rapid aiming in Parkinson's disease.
One hypothesized role of the basal ganglia, based largely on findings in Parkinson's disease (PD) patients, is the control of movement sequences. We examined changes in performance with practice of a movement sequence in PD patients and age-matched controls (n = 8 per group). Subjects practiced a complex three-dimensional sequential aiming task over 2 days, completing 180 trials, with the goal to minimize response time within specified accuracy limits. The results indicated that both groups became faster in planning the movement, and both groups moved more quickly through the sequence with practice. The PD group's decrease in movement time occurred primarily within the first 45 trials, whereas the control group continued to improve through the first 150 trials. Flight time (time between targets) to a small target decreased with practice in both groups, but flight time to a large target decreased only in the control group. This finding indicates that error corrective processes are more amenable to practice than ballistic processes in people with PD. There was little evidence that either group improved their performance by planning shorter (lower) trajectories, but rather increased mean velocity. Contact time (time on target) decreased with practice in both groups, and there were no group differences. These data indicate that practice can improve performance, both in planning and in specific execution processes.


Coverage statistics for sequence census methods.
We study the statistical properties of fragment coverage in genome sequencing experiments. In an extension of the classic Lander-Waterman model, we consider the effect of the length distribution of fragments. We also introduce a coding of the shape of the coverage depth function as a tree and explain how this can be used to detect regions with anomalous coverage. This modeling perspective is especially germane to current high-throughput sequencing experiments, where both sample preparation protocols and sequencing technology particulars can affect fragment length distributions. Under the mild assumptions that fragment start sites are Poisson distributed and successive fragment lengths are independent and identically distributed, we observe that, regardless of fragment length distribution, the fragments produced in a sequencing experiment can be viewed as resulting from a two-dimensional spatial Poisson process. We then study the successive jumps of the coverage function, and show that they can be encoded as a random tree that is approximately a Galton-Watson tree with generation-dependent geometric offspring distributions whose parameters can be computed. We extend standard analyses of shotgun sequencing that focus on coverage statistics at individual sites, and provide a null model for detecting deviations from random coverage in high-throughput sequence census based experiments. Our approach leads to explicit determinations of the null distributions of certain test statistics, while for others it greatly simplifies the approximation of their null distributions by simulation. Our focus on fragments also leads to a new approach to visualizing sequencing data that is of independent interest.


Provitamin A-biofortified maize consumption increases serum xanthophylls and 13C-natural abundance of retinol in Zambian children.
Plants that undergo C4 photosynthesis, such as maize, are enriched in the stable isotope of carbon (13C) compared with other dietary plants and foods. Consumption of maize that has been biofortified to contain elevated levels of provitamin A carotenoids (orange maize) increased the abundance of 13C in serum retinol of Mongolian gerbils. We evaluated this method in humans to determine if it has potential for further use in intervention effectiveness studies. A random subset of samples from a two-month randomized controlled feeding trial of rural three- to five-year old Zambian children were used to determine the impact of orange maize intake on serum carotenoid concentrations ( n = 88) and 13C-natural abundance in serum retinol ( n = 77). Concentrations of β-cryptoxanthin (a xanthophyll provitamin A carotenoid) and the dihydroxy xanthophylls lutein and zeaxanthin, which do not have vitamin A activity, were elevated in children consuming orange maize compared with those consuming a white maize control ( P < 0.001), while β-carotene was not different ( P > 0.3). Furthermore, 13C natural abundance was higher after two months' intervention in the orange maize group compared with the white maize group ( P = 0.049). Predictions made from equations developed in the aforementioned gerbil study estimated that maize provided 11% (2-21%, 95% confidence interval) of the recent dietary vitamin A to these children. These results demonstrate that orange maize is efficacious at providing retinol to the vitamin A pool in children through provitamin A carotenoids, as monitored by the change in 13C enrichment, which was not reflected in serum β-carotene concentrations. Further effectiveness studies in countries who have adopted orange maize should consider determining differences in retinol 13C-enrichment among target groups in addition to profiling serum xanthophyll carotenoids with specific emphasis on zeaxanthin. Impact statement Maize biofortified with provitamin A carotenoids (orange) has been released in some African markets. Responsive and sensitive methods to evaluate dissemination effectiveness are needed. This study investigated methods to evaluate effectiveness of orange maize consumption using serum from Zambian children fed orange maize for two months. Many varieties of orange maize contain higher amounts of the xanthophyll carotenoids in addition to β-carotene compared with typical varieties. This study uniquely showed higher concentrations of the maize xanthophylls lutein, zeaxanthin, and β-cryptoxanthin in children who consumed orange maize compared with white. Furthermore, maize is a C4 plant and is therefore naturally enriched with 13C. Higher 13C was detected in the serum retinol of the orange maize consumers with no change in serum β-carotene concentration suggesting preferential bioconversion to retinol. The combined analyses of serum zeaxanthin specifically and 13C-natural abundance of retinol could prove useful in effectiveness studies between orange maize adopters and non-adopters.


Bioactivity of Hydrolysates Obtained from Chicken Egg Ovalbumin Using Artichoke (Cynara scolymus L.) Proteases.
The aim of this work was to obtain chicken egg ovalbumin hydrolysates using aspartic proteinases present in extracts from the artichoke flower (Cynara scolymus L.) and evaluate their antioxidant, antimicrobial, and angiotensin I-converting enzyme (ACE) inhibitory activity in vitro. Hydrolysis time and molecular weight (<3 kDa) had a significant influence on the hypertensive and antioxidant activity of the hydrolysates. The <3 kDa fraction of the 16 h hydrolysate had an ACE inhibitory activity with an IC50 of 64.06 µg peptides/mL. The fraction <3 kDa of ovalbumin hydrolysate at 2 h of hydrolysis showed a DPPH radical scavenging activity of 30.27 µM of Trolox equivalents/mg peptides. The fraction <3 kDa of the hydrolysate of 16 h had an ABTS+ caption activity of 4.30 mM of Trolox equivalents/mg peptides. The fraction <3 kDa of the hydrolysate of 2 h had an iron (II) chelating activity of 32.18 µg peptides/mL. From the peptide sequences identified in the hydrolysates, we detected four peptides (from the BIOPEP database) that were already in their bioactive form (IAAEVYEHTEGSTTSY, HLFGPPGKKDPV, PIAAEVYEHTEGSTTSY, and YAEERYPIL), and are reported to display antioxidant and ACE inhibitory activity.


The current status and future prospects of altering the pathogenic microflora of periodontal disease.
Modern periodontal therapy aims to suppress or eradicate periodontal pathogens and to maintain a posttreatment flora that is compatible with health. Systemic and local antimicrobial therapies have demonstrated effectiveness against several periodontal pathogens. Sustained-release devices, or irrigators, for local application of antimicrobial agents to periodontal pockets show great promise. Replacement therapy and periodontal vaccines, although still in the early research phase, represent very interesting approaches for preventing periodontitis. Using modern molecular genetic methods, it is theoretically possible to clone virulence determinants of periodontal pathogens into a nonpathogenic organism. The carrier organism with the expressed foreign antigens may be implanted in the oral cavity or the intestinal tract to induce long-lasting immunity against the targeted periodontal pathogens.


Method for Detecting Abnormal Activity in a Group of Mobile Robots.
The range of attacks implemented on wireless networks is quite wide. To avoid or reduce the likelihood of an attack, it is necessary to use various defense mechanisms. Existing protection mechanisms are not always suitable for robotic systems and may not fully provide the necessary level of security. Thus, it is necessary to develop new ways of protection, which would be specific to groups of mobile robots. In this study, we propose an analysis of the following cyber parameters: the power consumption and the residual energy, as well as an in-depth traffic analysis to evaluate the effectiveness of the attack and identify abnormal network. We realized an analysis of the behavior of robotic systems under normal conditions and determined that, by their nature, robotic systems have a static and uniform behavior. We developed an experimental stand, and also conducted a theoretical analysis to confirm our assumptions. We found that some indicators of the components of the robotic system change statically; that is, there was a little deviation from the mean. Thus, we identified a set of metrics that allow us to determine how static the operation of the robotic system and its components is. Metrics allow us to evaluate parameters such as power consumption, and incoming/outgoing/redirected/dropped network packets. The results obtained are important for creating an integrated system for detecting anomalies in robotic systems. At the same time, the robotic node can analyze these parameters independently and make calculations that do not greatly affect performance. The main idea of this paper is to define a set of metrics characterizing the static behavior of a robotic system for the further development of an anomaly detection system.


Computational investigation of molecular structures, spectroscopic properties and antitumor-antibacterial activities of some Schiff bases.
Molecular structures, spectroscopic properties (IR, 1H NMR and 13C NMR, UV-VIS), molecular electrostatic potential maps and some molecular properties (ionization energy, electron affinity, energy gap, hardness, electronegativity, electrophilicity index, static dipole moment and average linear polarizability) of three Schiff bases which are 2-((ethylamino)methyl)-6-methoxyphenol (HL1), 2-((ethylamino) methyl)-6-methylphenol (HL2) and 2-((ethylamino)methyl)-6-chlorophenol (HL3) were computed at B3LYP/6-31G(d) level in aqueous phase. The effects of methoxy, methyl and chloro substituents on Schiff bases were examined and it was found that the electron donating property of methyl and chlorine substituents was higher than the methoxy substituent. In order to investigate the antitumor activities of Schiff bases were docked against the breast cancer (MCF7) cell line. Molecular docking results were compared with antitumor standard 5-fluorouracil. Antitumor activity of HL2 and HL3 molecule was found to be higher than HL1 against MCF-7 cell line. In addition, in order to predict the antibacterial activities of Schiff bases were docked against the Mycobacterium tuberculosis (H37Rv) cell line. Docking results were compared with the antibacterial reference N-(salicylidene)-2-hydroxyaniline. Antibacterial activity of HL2 and HL3 molecules was found to be higher than HL1. It is estimated that the binding of the electron donating group to the ortho position of the hydroxyl group in studied Schiff bases increases both antitumor and antibacterial activity.


Pediatric pharmacogenomics: challenges and opportunities: on behalf of the Sanford Children's Genomic Medicine Consortium.
The advent of digital, electronic, and molecular technologies has allowed the study of complete genomes. Integrating this information into drug development has opened the door for pharmacogenomic (PGx) interventions in direct patient care. PGx allows clinicians to better identify drug of choice and optimize dosing regimens based on an individual's genetic characteristics. Integrating PGx into pediatric care is a priority for the Sanford Children's Genomic Medicine Consortium, a partnership of ten children's hospitals across the US committed to the innovation and advancement of genomics in pediatric care. In this white paper, we review the current state of PGx research and its clinical utility in pediatrics, a largely understudied population, and make recommendations for advancing cutting-edge practice in pediatrics.


Distribution and effect of galanin on gallbladder and sphincter of Oddi motility in the pig.
This study was designed to determine the occurrence and topographical distribution of galanin-like immunoreactivity (GAL-LI) in the porcine gallbladder and sphincter of Oddi and to investigate the pharmacologic effect of GAL on gallbladder and sphincter of Oddi motility. By radioimmunoassay the concentration of GAL-LI in the gallbladder was 2.75 +/- 0.23, 9.73 +/- 1.33 in the common bile duct and 5.10 +/- 0.37 in the sphincter of Oddi (pmol/g +/- SE). By immunohistochemistry GAL-LI was found exclusively in ganglionic cells and in nerve fibers among the smooth muscle bundles. Gallbladder and sphincter of Oddi pressures were recorded before and during 5-minute local intraarterial infusion of 4, 8, 19, 39, 78 and 194 ng GAL - Kg-1 - min-1 in 12 anaesthetized pigs. GAL in doses greater than or equal to 39 ng.kg-1.min-1 significantly reduced sphincter of Oddi phasic wave frequency (4.8 +/- 0.4 vs. 2.1 +/- 0.5; p = 0.004) and sphincter of Oddi motility index (70.2 +/- 6.02 vs. 27.7 +/- 8.3; p = 0.002) but did not affect gallbladder pressure. We conclude that the distribution of GAL-LI in the sphincter of Oddi and the effect that a pharmacologic dose of GAL has on sphincter of Oddi motor activity, suggests that GAL may be involved in the physiologic control of bile flow in the pig.


Date seed extract-loaded oil-in-water nanoemulsion: Development, characterization, and antioxidant activity as a delivery model for rheumatoid arthritis.
Rheumatoid arthritis is an inflammatory disorder, affecting around 1% of the world population. Antioxidant activity plays important role to overcome the inflammation associated with arthritis. Phoenix dactylifera (date) seeds, generally considered as a waste product or utilized as food for domestic farm animals, have been used as a source of antioxidants at different disease conditions. The aim of the present study was to enhance the release of date seed extract in order to achieve high antioxidant activity. Nanoemulsion of methanolic extract of date seed was prepared by aqueous titration method. The selected formulations were exposed to thermodynamic stability and dispersibility tests. The optimized nanoemulsions were evaluated on the basis of droplet size (23.14 ± 0.055nm), polydispersity index (0.166 ± 0.124), percent transmittance (99.12 ± 0.0163), refractive index (1.36 ± 0.046), viscosity (cP) (12.30 ± 0.75), conductivity (µS/cm) (347.46 ± 1.10), and drug content (%) (99.67 ± 0.11). The in vitro release studies revealed that final optimized formulation has cumulative release of drug (57.51% ± 2.65%), which was more significantly greater as compared to drug suspension (26.44% ± 1.15%). Further in vitro antioxidant activity studies revealed that the developed methanolic extract of date seed-loaded nanoemulsion has more antioxidant potential when compared with methanolic extract.


Autoinhibition of Ethylene Production in Citrus Peel Discs : SUPPRESSION OF 1-AMINOCYCLOPROPANE-1-CARBOXYLIC ACID SYNTHESIS.
Wound ethylene formation induced in flavede tissue of citrus fruit (Citrus paradisi MacFad. cv. Ruby Red) by slicing was almost completely inhibited by exogenous ethylene. The inhibition lasted for at least 6 hours after removal of exogenous ethylene and was then gradually relieved. The extent of inhibition was dependent upon the concentration of ethylene (1 to 10 microliters/liter) and the duration of treatment. The increase in wound ethylene production in control discs was paralleled by an increase in 1-aminocyclopropane-1-carboxylic acid (AAC) content, whereas in ethylene-treated discs there was little increase in ACC content. Application of ACC completely restored ethylene production in ethylene-pretreated discs, indicating that the conversion of ACC to ethylene is not impaired by the presence of ethylene. Thus, autoinhibition of ethylene synthesis was exerted by reducing the availability of ACC. Ethylene treatment resulted in a decrease in extractable ACC synthase activity, but this decrease was too small to account for the marked inhibition of ACC formation. The data indicate that autoinhibition of ethylene production in citrus flavede discs results from suppression of ACC formation through repression of the synthesis of ACC synthase and inhibition of its activity.


Isolation and Metagenomic Identification of Avian Leukosis Virus Associated with Mortality in Broiler Chicken.
Avian leukosis virus (ALV) belongs to the family Retroviridae and causes considerable economic losses to the poultry industry. Following an outbreak associated with high mortality in a broiler flock in northern part of Malaysia, kidney tissues from affected chickens were submitted for virus isolation and identification in chicken embryonated egg and MDCK cells. Evidence of virus growth was indicated by haemorrhage and embryo mortality in egg culture. While viral growth in cell culture was evidenced by the development of cytopathic effects. The isolated virus was purified by sucrose gradient and identified using negative staining transmission electron microscopy. Further confirmation was achieved through next-generation sequencing and nucleotide sequence homology search. Analysis of the viral sequences using the NCBI BLAST tool revealed 99-100% sequence homology with exogenous ALV viral envelope protein. Phylogenetic analysis based on partial envelope sequences showed the Malaysian isolate clustered with Taiwanese and Japanese ALV strains, which were closer to ALV subgroup J, ALV subgroup E, and recombinant A/E isolates. Based on these findings, ALV was concluded to be associated with the present outbreak. It was recommended that further studies should be conducted on the molecular epidemiology and pathogenicity of the identified virus isolate.


Educators' perceptions of the D.A.R.E. program.
This study examines the perceptions of educators about the Drug Abuse Resistance Education (D.A.R.E.) program, based on the results of a statewide survey among 286 fifth and sixth grade teachers and principals. Educators gave their highest ratings to teacher/officer interaction, the role playing exercises, and the graduation ceremony. Ratings of overall program quality and the impact of the program on students were both high. Block regression analysis was used to examine factors predictive of educators' views of D.A.R.E. D.A.R.E. program elements were the most important factors explaining variance in educators' ratings of over-all program quality and program impact on students. Altogether, 54 percent and 38 percent of the variance in both dependent variables were explained. The results are discussed in terms of the important role teachers and principals play as stakeholders in prevention education.


Glucokinase and fructokinase of Trichomonas vaginalis and Tritrichomonas foetus.
Trichomonas vaginalis and Tritrichomonas foetus contain glucokinase and not a hexokinase of broad hexose specificity. Tritrichomonas foetus also contains a specific fructokinase which could be resolved from glucokinase by anion exchange chromatography. Native T. vaginalis glucokinase had a Mr of 76,000, and SDS-PAG electrophoresis showed two equally stained bands corresponding to Mr 40,000 and 38,000. Glucose and ATP were by far the best substrates for both trichomonad glucokinases, with Km values as low as 33-35 microM and 75-83 microM, respectively. Substrate saturation curves for these enzymes were all hyperbolic. Tritrichomonas foetus fructokinase required fructose and ATP, with Km values of 200 microM and 81 microM. None of the activities was affected by a number of potential regulatory metabolites, including glucose-6-phosphate. The only exception was AMP which in supraphysiological concentrations had an inhibitory effect on T. foetus fructokinase. In conclusion, the absence of regulation at the hexose phosphorylation step described here, as well as the presence of an easily reversible PPi: fructose-6-phosphate 1-phosphotransferase described previously (Mertens, E., Van Schaftingen, E. & Müller, M. 1989. Mol. Biochem. Parasitol., 37:183-190), suggest that the rate of the 1st part of glycolysis in trichomonads is controlled only by the intracellular availability of hexoses.


Alpha-adrenergic agonist and antagonist activity of dihydroergotoxine in rats.
The alpha-adrenergic activity of dihydroergotoxine had been studied in both pithed and urethane or pentobarbitone anaesthetized rats. In anaesthetized rats, blood pressure effects varied with the anaesthetic agent: hypotension with urethane, hypertension with pentobarbitone. This latter pressor response was a peripheral effect. In pithed rats, the vasopressor response to dihydroergotoxine was reduced competitively by yohimbine, and non-competitively by nifedipine, but not by prazosin or methysergide, showing that the vasoconstriction is mediated by alpha 2-adrenoceptors. Dihydroergotoxine decreases the tachycardia elicited by stimulation of the cardioaccelerator nerves, this effect being antagonized by yohimbine. It also reduced the pressor response to (-)-phenylephrine. These results indicated that, on the peripheral vascular system of the rat, dihydroergotoxine acts as an alpha 1-adrenoceptor blocker and an alpha 2-adrenoceptor agonist.


Dynamic transcriptomes of resistant and susceptible peach lines after infestation by green peach aphids (Myzus persicae Sülzer) reveal defence responses controlled by the Rm3 locus.
The green peach aphid (GPA), Myzus persicae (Sülzer), is a widespread phloem-feeding insect that significantly influences the yield and visual quality of peach [Prunus persica (L.) Batsch]. Single dominant gene (Rm3)-based resistance provides effective management of this invasive pest, although little is known about the molecular responses of plants to GPA feeding. To illustrate the molecular mechanisms of monogenic resistance in peach to young tissue-infecting GPAs, aphid-resistant/aphid-susceptible peach lines from a segregating population with Rm3/rm3 and rm3/rm3 genotypes were infested with GPAs for 3 to 72 h. Transcriptome analysis of the infested tissues identified 3854 differentially expressed genes (DEGs). Although the majority of the DEGs in the resistant line also responded to aphid attack in the susceptible line, the overall magnitude of change was greater in the resistant line than in the susceptible line. The enriched gene ontology of the 3854 DEGs involved in plant defence responses included redox situation, calcium-mediated signalling, transcription factor (e.g., WRKY, MYB, and ERF), MAPK signalling cascade, phytohormone signalling, pathogenesis-related protein, and secondary metabolite terms. Of the 53 genes annotated in a 460 kb interval of the rm3 locus, seven genes were differentially expressed between the aphid-resistant and aphid-susceptible peach lines following aphid infestation. Together, these results suggest that the Rm3-dependent resistance relies mainly on the inducible expression of defence-related pathways and signalling elements within hours after the initiation of aphid feeding and that the production of specific secondary metabolites from phenylpropanoid/flavonoid pathways can have major effects on peach-aphid interactions.


Can anecdotes add to an understanding of hypnosis?
This paper emphasizes the importance of anecdotes, in conjunction with experimental data and careful clinical observation,for an understanding of hypnosis. Anecdotes are presented that bear on (a) individual differences in hypnotizability, (b) the stereotypes of hypnosis, (c) the importance of careful wording in preparing experimental subjects and clinical patients for hypnosis, (d) the notion of hypnosis as involving a partial, but not complete, setting aside of critical judgment, which permits the hypnotized person to engage in fantasy and make-believe, (e) confabulation in hypnotic age regression, (f) the differentiation of hypnotic and therapeutic suggestion, (g)the nature of hypnotic suggestion, and (h) some experiences with the posthypnotic persistence of an uncanceled suggestion.


Cytokinins: activity, biosynthesis, and translocation.
Cytokinins (CKs) play a crucial role in various phases of plant growth and development, but the basic molecular mechanisms of their biosynthesis and signal transduction only recently became clear. The progress was achieved by identifying a series of key genes encoding enzymes and proteins controlling critical steps in biosynthesis, translocation, and signaling. Basic schemes for CK homeostasis and root/shoot communication at the whole-plant level can now be devised. This review summarizes recent findings on the relationship between CK structural variation and activity, distinct features in CK biosynthesis between higher plants and Agrobacterium infected plants, CK translocation at whole-plant and cellular levels, and CKs as signaling molecules for nutrient status via root-shoot communication.


Effectiveness of an Intervention to Teach Physicians How to Assist Patients to Quit Smoking in Argentina.
We evaluated an intervention to teach physicians how to help their smoking patients quit compared to usual care in Argentina. Physicians were recruited from six clinical systems and randomized to intervention (didactic curriculum in two 3-hour sessions) or usual care. Smoking patients who saw participating physicians within 30 days of the intervention (index clinical visit) were randomly sampled and interviewed by telephone with follow-up surveys at months 6 and 12 after the index clinical visit. Outcomes were tobacco abstinence (main), quit attempt in the past month, use of medications to quit smoking, and cigarettes per day. Repeated measures on the same participants were accommodated via generalized linear mixed models. Two hundred fifty-four physicians were randomized; average age 44.5 years, 53% women and 12% smoked. Of 1378 smoking patients surveyed, 81% were women and 45% had more than 12 years of education. At 1 month, most patients (77%) reported daily smoking, 20% smoked some days and 3% had quit. Mean cigarettes smoked per day was 12.9 (SD = 8.8) and 49% were ready to quit within the year. Intention-to-treat analyses did not show significant group differences in quit rates at 12 months when assuming outcome response was missing at random (23% vs. 24.1%, P = .435). Using missing=smoking imputation rule, quit rates were not different at 12 months (15.6% vs. 16.4% P = .729). Motivated smokers were more likely to quit at 6 months (17.7% vs. 9.6%, P = .03). Training in tobacco cessation for physicians did not improve abstinence among their unselected smoking patients.


Evaluating the mobile heavy metal pool in soak-away sediment, road dust and soil through sequential extraction and isotopic exchange.
Selective sequential dissolution (SSD) and isotopic dilution are two most commonly applied techniques for the measurement of mobile fraction of heavy metal present in the urban environment. This work examined the compliance between SSD proposed by the Community Bureau of Reference (BCR) and isotopic dilution technique (IDT) for determination of mobile pool of heavy metal contained in soakaway sediment, road dust, and soil sample. Heavy metals (Cu, Zn, Cd and Pb) were fractionated using the three-stage BCR protocol, while isotopically exchangeable metal concentrations (E-value) were investigated through isotopic tracers (¹¹¹Cd, ⁶⁵Cu, ²⁰⁷Pb and ⁶⁶Zn). In general, total contamination level, E-value and BCR exchangeable fractions of different samples followed the similar order of road dust > soakaway sediment > soil. Results revealed that the E-value exceeded the BCR exchangeable fraction in all samples. In addition, the first three fractions of BCR which have potential to become mobile under certain environmental conditions were collectively termed as "potential mobile pool" and compared with E-value. It was concluded that metal extracted by weak acid underestimates the exchangeable fraction while the potential mobile pool extracted by three reagents overestimates the real mobile forms of heavy metals. However, better mobility characteristics of heavy metals can be assessed by coupling information obtained through sequential extraction and isotopic exchange.


Dose-dependent cell growth in response to concentration modulated patterns of FGF-2 printed on fibrin.
Immobilized patterns of unmodified fibroblast growth factor-2 (FGF-2), with varying surface concentrations, were inkjet printed onto physiologically relevant fibrin substrates. Printed patterns were characterized using iodinated FGF-2 to determine FGF-2 surface concentration and retention of FGF-2 binding in vitro. MG-63 cells were uniformly seeded onto patterned substrates. Cells were exposed to defined spatial FGF-2 surface concentrations of 1-22 pg/mm(2). Cell numbers were observed to increase in register with the printed FGF-2 patterns from an initial random uniform cell distribution across the patterned and non-patterned regions. Based on time-lapse image analysis, the primary organizational response of the cells was determined to be proliferation and not migration. Cell counts on and off the FGF-2 patterns over time demonstrated an increase in cell density up to a FGF-2 surface concentration of 14 pg/mm(2). Higher surface concentrations did not result in increased cell density. In addition, the cells on the FGF-2 patterns survived longer than the cells off patterns. Our inkjet printing approach permits the systematic study of cellular responses to defined spatial surface concentrations of immobilized growth factors.


Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy for the Quantitative Analysis of Deuterium in Plasma: Application to Total Body Water Determination in Humans and Other Animals.
Conventional methods for measuring the concentration of deuterium in body fluids are by either isotope ratio mass spectrometry or Fourier transform infrared transmission (FT-IR) spectroscopy. The latter method is often preferred as it is less expensive and time consuming; however, having a lower sensitivity means a larger sample volume is required. This study investigated an alternative FT-IR spectroscopic method, attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR), which has the potential to provide shorter analysis times while requiring smaller sample volumes. Deuterium was assayed using ATR FT-IR in plasma in the concentration range 0.5 to 2.5 mg mL-1, typical of those observed in tracer dilution measurements of total body water. Minimal sample preparation was required and analysis time was substantially decreased compared to transmission FT-IR. Samples were analyzed with high precision (coefficient of variation (CV) < 0.5%). Precision of assay was maintained when assaying plasma volumes of only 10 µL. The application of the method to the determination of total body water in humans and animals (horses) was demonstrated. A rapid and simple method for the measurement of deuterium in plasma is described that only requires very small sample volumes, rendering the method suitable for use in pediatrics where blood sampling is required to be kept to a minimum.


Effect of genetic variants of the heart fatty acid-binding protein gene on intramuscular fat and performance traits in pigs.
In order to find genetic markers to improve the meat quality of pigs by breeding we studied the relationship between variation in the heart fatty acid-binding protein (H-FABP) gene (FABP3) and intramuscular fat (IMF) content. To estimate the effect of H-FABP, pigs from two Duroc populations were selectively mated in such a way that at least two genotypes were present in each litter. In total, data from 983 pigs and pedigree information from three preceding generations were analyzed. Offspring were tested for IMF content as well as backfat thickness (BFT), BW, and drip loss of the meat (DRIP). All pigs were assigned to H-FABP RFLP genotype classes either by the assessed genotype (75%) or based on a probability score determined according to genotypic information of their relatives (25%). Contrasts were detected between homozygous H-FABP RFLP genotype classes for IMF content (.4%, P < .05), BFT (.6 mm, P < .01), and BW (2.4 kg, P < .10). No significant contrasts were detected for DRIP. Results for IMF content, BFT, and BW were confirmed when only genotyped animals were analyzed. Variation in BFT partially explained the effect on IMF content. Although other closely linked genes on porcine chromosome 6 might be responsible for the observed effect, interference of the halothane gene was excluded because all parental animals were noncarriers. In conclusion, H-FABP RFLP can be used as markers to select for increased IMF content and growth in breeding programs.


Calculation of eigenvalues of Sturm-Liouville equation for simulating hydrodynamic soliton generated by a piston wave maker.
This paper focuses on the mathematical study of the existence of solitary gravity waves (solitons) and their characteristics (amplitude, velocity, [Formula: see text]) generated by a piston wave maker lying upstream of a horizontal channel. The mathematical model requires both incompressibility condition, irrotational flow of no viscous fluid and Lagrange coordinates. By using both the inverse scattering method and a given initial potential [Formula: see text] we can transform the KdV equation into Sturm-Liouville spectral problem. The latter problem amounts to find negative discrete eigenvalues [Formula: see text] and associated eigenfunctions [Formula: see text], where each calculated eigenvalue [Formula: see text] gives a soliton and the profile of the free surface. For solving this problem, we can use the Runge-Kutta method. For illustration, two examples of the wave maker movement are proposed. The numerical simulations show that the perturbation of wave maker with hyperbolic tangent displacement under physical conditions affect the number of solitons emitted.


Development of carbazole-bearing pyridopyrimidine-substituted urea/thiourea as polyphenol oxidase inhibitors: synthesis, biochemistry, and theoretical studies.
Polyphenol oxidase (Tyrosinase, PPO) has received considerable attention, since it is the key enzyme in melanin biosynthesis. In this study, we investigated prepared novel carbazole-containing pyridopyrimidine-substituted with urea and thiourea derivatives and their PPO activities on the diphenolase activity of banana tyrosinase. The structures of the compounds synthesized were confirmed by 1 H NMR, 13 C NMR, FTIR and elemental analysis. PPO enzyme was purified from banana on an affinity gel comprised of Sepharose 4B-L-tyrosine-p-amino benzoic acid. For evaluating the enzyme activity, the synthesised compounds were subjected to tyrosinase inhibition assay using catechol as substrate. While some of the compounds (6, 7, 8f, 8h, 8i, 8j) showed enzyme inhibitor effect, some of them (8a, 8b, 8c, 8d, 8e, 8g, 8k) activated the PPO enzyme activity. Gaussian software was used for the molecular calculations to explain the results for the prepared compounds.


Spinal cord injury without radiographic abnormality (SCIWORA).
Spinal cord injury without radiographic abnormality (SCIWORA) is associated with self-reducing transient subluxation or distraction of the juvenile spine. It accounts for about 40% of spinal injuries in children under sixteen. Children's anatomical features increase their susceptibility to hyperflexion, hyperextension and distraction mechanisms. Nursing management includes an awareness of two of its greatest dangers: a delay in onset of symptoms and a possible recurrence. If these dangers are identified early, the child's potential for recovery is maximized.