Flurbiprofen-Loaded Solid SNEDDS Preconcentrate for the Enhanced Solubility, In-Vitro Dissolution and Bioavailability in Rats.
The aim of this work was to prepare and optimize a solid self-nanoemulsifying drug delivery system pre-concentrate (SSP) containing water-insoluble flurbiprofen (FL) using a novel pseudo-ternary phase diagram. The pseudo-ternary phase diagram, composed of FL as the drug and dispersion core, Kollisolv MCT 70 as the oil phase, and TPGS (tocopherol polyethylene glycol 1000 succinate) as the surfactant, was constructed for the determination of the SSP region. SSP was investigated in terms of particle size, physical state by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD), in vitro dissolution and oral pharmacokinetics in rats. The determined SSP (FL/Kollisolv MCT 70/TPGS = 10/10/80, weight %) in the pseudo-ternary phase diagram had the melting point of 32.37 °C and uniform mean particle size of below 30 nm without any precipitation of FL in the dispersion. In the dissolution test, the SSP exhibited 95.70 ± 3.40% of release at 15 min, whereas the raw FL showed poor dissolution (i.e., 6.75 ± 1.30%) at that time point. In addition, the SSP showed the enhanced oral absorption (i.e., 1.93-fold increase in AUCinfinite) as compared to the suspension group of raw FL. Therefore, the developed SSP would be a promising drug delivery system with excellent solubilization, dissolution, and bioavailability for FL.


The Shishu Pushti Trial-Extended Peer Counseling for Improving Feeding Practices and Reducing Undernutrition in Children Aged 0-48 Months in Urban Bangladesh: Protocol for a Cluster-Randomized Controlled Trial.
The aim of this study is to assess if peer counseling of women improves breastfeeding, complementary feeding practices, and child growth, and thus reduces the prevalence of undernutrition in children up to 4 years of age. Lack of exclusive breastfeeding and inappropriate complementary feeding are critical factors in reducing child undernutrition, morbidity, and mortality. There are reported trials of peer counseling to improve breastfeeding; however, they did not examine the efficacy of peer counseling to improve complementary feeding or the long-term impacts on child growth and development. This study has used a community-based, cluster-randomized controlled trial with a superiority design and 2 parallel treatment arms. It is assessing the impact of peer counseling, starting in late pregnancy up to 1 year after delivery, on child feeding practices, growth, and development with follow-up until 48 months of age. The study site was Mirpur, a densely populated area in Dhaka. Using satellite maps and geographic information system mapping, we constructed 36 clusters with an average population of 5000 people. We recruited pregnant women in the third trimester aged 16-40 years, with no more than 3 living children. Trained peer counselors visited women at home twice before delivery, 4 times in the first month, monthly from 2 to 6 months, and again at 9 and 12 months. Trained research assistants collected anthropometric measurements. The primary outcome will be differences in child stunting and mean length for age at 6, 12, 15, and 18 months. Secondary outcomes will be differences in the percentage of women exclusively breastfeeding in the mean duration of any breastfeeding and in the percentage of children at 6 and 9 months of age who receive solid, semisolid, or soft foods; and the percentage of children consuming foods from 4 or more food groups at 9, 12, 15, and 18 months. We will assess the mean cognitive function scores from the Ages and Stages Questionnaire (9 and 18 months) and Bayley tests (24 and 36 months). We identified 65,535 people in mapped residences, from which we defined 36 clusters and randomly allocated them equally to intervention or control groups stratified by cluster socioeconomic status. From July 2011 to May 2013, we identified 1056 pregnant women and 993 births in the intervention group and 994 pregnancies and 890 births in the control group. At 18 months, 692 children remained in the intervention group and 551 in the control group. From January 2015 to February 2017, we conducted the long-term follow-up of the cohort. We have now completed the data collection and processing and have started analyses. This study will help fill the evidence gap about the short- and long-term impact of peer counseling on improving infant feeding, preventing childhood undernutrition, and enhancing child cognitive development. ClinicalTrials.gov NCT01333995; https://clinicaltrials.gov/ct2/show/NCT01333995. DERR1-10.2196/31475.


Deletion mapping and heterogenote analysis of a mutation responsible for osmosis-sensitive growth, spectinomycin resistance, and alteration of cytoplasmic membrane in Escherichia coli.
Lambda transducing phages carrying Escherichia coli deoxyribonucleic acid of various lengths from the aroE-rpsL region were lysogenized into the F'3 plasmid and were used for heterogenote analysis of YM101, a sucrose-dependent, spectinomycin-resistant mutant of E. coli. Three characteristics of the mutant strain, resistance to spectinomycin, sucrose dependence of growth, and lack of I-19 protein in the cytoplasmic membrane, were shown to be the result of a mutation in a region designated delta 53-spcl. This region extends over 3.6-kilobase pairs and is located within a cluster of ribosomal genes. The mutation is recessive to the wild-type allele.


Synchronization between background activity and visually evoked potential is not mirrored by focal hyperoxygenation: implications for the interpretation of vascular brain imaging.
We performed an electroencephalography and optical topography study simultaneously exploring electrophysiological and vascular response magnitude as a function of stimulus frequency. To elicit a response in the visual cortex, subjects were exposed to flicker frequencies varying from 1 to 25 Hz (1 Hz steps, eyes closed). Extending the standard view to compare magnitudes of the evoked neuronal to the evoked vascular response, we additionally investigated modulations of alpha-power, a marker of "background" EEG activity. The results show two discrepancies between the electrophysiological and vascular response: (1) VEP and alpha-power exhibit a discontinuous peak when stimulating at the individual alpha-frequency (IAF) (approximately 10-11 Hz), indicating resonance between background oscillations and evoked response; this is not mirrored by the vascular response. (2) The vascular response, in contrast, steadily increases up to a maximum at 7-8 Hz and slightly decreases with higher frequencies. This continuous frequency dependence is partly reflected by the decrease in alpha-power up to frequencies of 8-9 Hz and a slight increase in alpha-power beyond the IAF resonance. Although indicating an inverse relationship between alpha-power and vascular response, the frequency dependence of the evoked response does not show such a correlation. Thus, electrophysiological resonance between an individual's alpha-frequency and isofrequent stimulation is not mirrored by the vascular response. Also, spontaneous background EEG activity is an important modulator of the vascular response magnitude. We discuss these deviations from a simple one-to-one translation between evoked potential and vascular response amplitude in the light of questions concerning synchronization, attenuation, and induction of background oscillations such as the alpha-rhythm.


Elicitor-Induced l-Tyrosine Decarboxylase from Plant Cell Suspension Cultures : I. Induction and Purification.
l-Tyrosine decarboxylase (EC 22.214.171.124) activity was induced in cell suspension cultures of Thalictrum rugosum Ait. and Eschscholtzia californica Cham. with a yeast polysaccharide preparation (elicitor). The highest l-tyrosine decarboxylase activity in extracts from 7-day-old cell cultures of E. californica was observed 5 hours after addition of 30 to 40 micrograms elicitor per gram cell fresh weight. The enzyme extracted from cells of E. californica was purified 1540-fold to a specific activity of 2.6 micromoles CO(2) produced per minute per milligram protein at pH 8.4 and 30 degrees C. Purified enzyme from T. rugosum showed a specific activity of 0.18 micromoles per minute per milligram protein. The purification procedure involved ammonium sulfate fractionation, anion-exchange fast protein liquid chromatography, ultrafiltration, and hydrophobic interaction chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the enzyme from the two plant cell cultures had subunits of identical molecular weight (56,300 +/- 300 daltons.


Incidence densities in a competing events analysis.
Epidemiologists often study the incidence density (ID; also known as incidence rate), which is the number of observed events divided by population-time at risk. Its computational simplicity makes it attractive in applications, but a common concern is that the ID is misleading if the underlying hazard is not constant in time. Another difficulty arises if competing events are present, which seems to have attracted less attention in the literature. However, there are situations in which the presence of competing events obscures the analysis more than nonconstant hazards do. The authors illustrate such a situation using data on infectious complications in patients receiving stem cell transplants, showing that a certain transplant type reduces the infection ID but eventually increases the cumulative infection probability because of its effect on the competing event. The authors investigate the extent to which IDs allow for a reasonable analysis of competing events. They suggest a simple multistate-type graphic based on IDs, which immediately displays the competing event situation. The authors also suggest a more formal summary analysis in terms of a best approximating effect on the cumulative event probability, considering another data example of US women infected with human immunodeficiency virus. Competing events and even more complex event patterns may be adequately addressed with the suggested methodology.


Cyclic pentapeptide analogs based on endomorphin-2 structure: cyclization studies using liquid chromatography combined with on-line mass spectrometry and tandem mass spectrometry.
The cyclization of linear analogs based on endomorphin-2 structure, Tyr/Dmt-d-Lys-Phe-Phe-Asp-NH2 and Tyr/Dmt-d-Cys-Phe-Phe-Cys-NH2 (where Dmt=2',6'-dimethyltyrosine), resulting in obtaining lactam or disulfide derivatives, was studied using liquid chromatography combined with on-line mass spectrometry (LC-MS) and tandem mass spectrometry (LC-MS/MS). In case of cyclization via an amide bond, the formation of the cyclic monomers, cyclic but not linear dimers and even traces of cyclic trimers was observed. Disulfide bridge containing peptides was obtained by the solid-phase synthesis of the linear sequences, followed by either in-solution or on-resin cyclization. In case of the in-solution cyclization, the expected cyclic monomers were the only products. When oxidation of the cysteine residues was performed when the peptides were still on the resin, cyclic monomer and two cyclodimers, parallel and antiparallel, were found. Digestion of the isolated cyclodimers with α-chymotrypsin allowed for their unambiguous identification. The comparison of the cyclic monomer/dimer ratios for analogs with Tyr versus Dmt in position 1 revealed that the presence of the exocyclic Dmt favored formation of the cyclic monomer, most likely due to the increased steric bulk of this amino acid side-chain as compared with Tyr.


Ligand effects on the fluorescence properties of tyrosine-9 in alpha 1-1 glutathione S-transferase.
A conserved tyrosine plays a critical role in catalysis by mammalian glutathione S-transferases (GSTs) of the alpha-, mu-, and pi-classes, by forming a hydrogen bond to and stabilizing the thiolate form of glutathione. The hydrogen bonding properties of this tyrosine in the rat A1-1 GST (Tyr-9), in the absence and presence of ligands, have been studied by steady state and time-resolved fluorescence spectroscopy. In order to achieve this, the single tryptophan (Trp 21) found in the rat A1-1 GST has been replaced with the fluorometrically silent phenylalanine (W21F). Additionally, a double mutant lacking this tryptophan and the catalytic tyrosine (W21F:Y9F) has been constructed, and these mutants have been used as probes of ligand effects at Tyr-9. A comparison of the correlated excitation--emission spectra of the W21F mutant and the W21F-Y9F indicates that a red-shifted emission component is contributed by Tyr-9 with excitation bands at 255 and 300 nm, in the ligand-free enzyme. The pH-dependence of the intensity of these spectral cross-peaks is consistent with an active site tyrosine with a pKa of 8.1-8.3. Upon addition of GSH, the red-shifted component is quenched. Multifrequency phase/modulation fluorescence experiments qualitatively demonstrate that GSH causes a decrease in the average excited state lifetime on the red-edge of the spectrum of W21F but not of the W21F:Y9F spectrum. Steady state correlated difference spectra (W21F-W21F:Y9F) have been used to obtain a model for the excitation-emission correlated spectrum of Tyr-9, which indicates that Tyr-9 is heterogeneous at pH 7.5, with properties of both tyrosinate and "normal tyrosine". The tyrosinate fraction is eliminated, and the blue-shifted component becomes more intense upon addition of GSH conjugates, indicating that the weak hydrogen bond between Tyr-9 and thioethers has little charge-transfer character. The S-methyl GSH yields an "anomalous" spectrum at pH 7.5, which retains cross-peaks consistent with ionized tyrosinate. These results indicate that, in the absence of ligand, Tyr-9 forms a strongly polarized hydrogen bond or a fraction of the phenolic hydroxyl group is partially deprotonated. However, when a GSH conjugate with a sufficiently large hydrophobic group occupies the H-site, Tyr-9 is fully protonated, with little charge-transfer character.


Paternity frequency and maternity of males in some stingless bee species.
In monogynous hymenopteran societies, the number of mates of a queen strongly influences the potential for conflict between workers and queens over the maternity of males. Queens always 'prefer' their own sons to sons of workers, regardless of queen mating frequency. When a queen mates once, workers are more closely related to, and therefore are expected to prefer, their own sons and then sons of sisters to sons of the queen. However, if effective paternity frequency exceeds 2, workers on average should prefer queen-produced males to males produced by their sisters. We studied the queen mating frequency of seven stingless bee species: the Mexican species Scaptotrigona mexicana, S. pectoralis and the Australian species Austroplebeia symei, Trigona clypearis, T. hockingsi, T. mellipes and T. sapiens. We then determined whether males arise from eggs laid by workers or queens in A. symei, T. clypearis, T. hockingsi and T. mellipes. We show that all seven species investigated are most likely singly mated and that the queen dominates reproduction. This indicates that the queen's mating frequency alone does not determine whether workers or the queen produces the males.


Investigation of frontal lobe subregions in first-episode schizophrenia.
The evidence for frontal lobe structural abnormalities in schizophrenia using magnetic resonance (MR) imaging has been mixed, but most studies used either single slice measures or total volumes of a single frontal region, neither of which is sensitive to potential volume differences in more specific subregions. This study employed reliable methods for parcellation of the frontal lobes from MR images based on the sulcal anatomy. Following a cytoarchitectonic theory that distinguishes dorsomedial (archicortically derived) from ventrolateral (paleocortically derived) frontal subregions, we measured the superior frontal gyrus, anterior cingulate gyrus, and orbital frontal region in 19 first-episode schizophrenia patients and 26 healthy comparison subjects. Results indicated that male patients had significantly larger right orbital frontal volume compared to their left orbital frontal volume and compared to healthy men. Among male patients larger right orbital frontal volume was significantly correlated with smaller right 'archicortical' (i.e. anterior cingulate and superior frontal gyri) volume. Furthermore, the ratio of right orbital frontal to right 'archicortical' volume was significantly and positively correlated with level of delusions among male patients. These findings suggest that there may be reciprocal controls on 'archicortical' and 'paleocortical' neurodevelopment among men with schizophrenia, and that larger paleocortical relative to archicortical volumes may be associated with increased delusions.


[THE INFLUENCE OF THE HISTO- AND ULTRASTRUCTURE ON THE REPRODUCTIVE FUNCTION IN MAN 22-35 YEARS AT VARICOCELE].
To find out whether histo- and ultrastructural changes which occurs in men 22-35 years old with varicocele that could lead to infertility? Used 12 testicular biopsy specimens collected from males 22 to 35 years old for diagnostic purposes with varicocele fixed in Buen's solution. Sections of paraffin blocks 7 to 8 micrometers thick were stained with hematoxylin and eosin with Ehrlich hematoxylin staining. To assess the activity of interstitial endocrinocytes, the volume of nuclei was calculated using an ellipse V=π/б х LB2 (L.E. Hesin, 1967), where V - is the volume of the nucleus, L - is the maximum diameter, B - is the minimum diameter. The results obtained were determined in micrometers. Part of the material for electron microscopic examination of the testicular structures was performed according to generally accepted rules. The TeslaBS-490A ultramicrotome made ultra-thin sections, mounted them on copper apertures, further contrasted with lead citrate and studied in a PEM-125K electron microscope with an accelerating voltage of 75 kV and subsequent photography at magnification from 4000 to 16000 times. Statistical processing of materials was performed using a computer system STATISTICA for Windows R. As a result of ultrastructural examination of the testicle, the narrowing of the lumen of the blood vessels due to the swelling of the endothelial cells cytoplasm, the inner cytolemus of which forms different shapes and the height of the projection, the nuclei of which cells are deformed, indicating significant ultrastructural changes in varicocele were established. The effect of changes in histo- and ultrastructure on varicocele and on spermatogenesis is determined. We found changes of different nature with negative quantitative composition of cells at different stages of their development, to a greater extent in spermatocytes and spermatids, their pronounced cytolysis, atrophy of a part of the meandering tubules, in 28.2% of which there is a severe degree of spermatogenesis disorders, and 23.6% of the tubules were emptied. Also, the number of spermatocytes and spermatids decreased significantly (р<0.05). We found a significant reduction in the diameter of the meandering tubules in men 22-35 years of age with varicocele 163.91±4.24 micrometers3 compared with the control 218.63±2.95 micrometers3 (p<0.05). The spermatogenic epithelium cells in the meandering tubules in this pathology were quantitatively reduced by 78%, especially spermatocytes at the pachytene stage and spermatids of the 7th stage of development (98.94±2.79 and 187.45±5.32 respectively р<0.05). The number of interstitial endocrinocytes in the testicle at varicocele was reduced, and the volume of their nuclei averaged 69.37±1.0 micrometers. All of the above adversely affects the male reproductive function, and is a cause of infertility, as evidenced by the atrophy found in the part of the meandering tubules. In conditions of varicose veins of the spermatic cord in men aged 22 - 35 years there is a significant decrease in the diameter of the meandering tubules, a decrease in the number of spermatocytes (up to 60%), spermatids (up to 50%), as well as the volume of nuclei interstitial endocrinocytes (up to 70%), which contributes to the development of male infertility.


Composition of psoas major muscle fibers compared among humans, orangutans, and monkeys.
In primate species the m. psoas major, the only muscle simultaneously controlling the spinal column and lower extremity, is expected to reflect morpho-functional adaptation to diversified locomotor behavior. By using histochemical analysis with Sudan black B staining, composition of different types of muscle fibers in the psoas major was compared between 2 Japanese macaques, 2 hamadryas baboons, 2 anubis baboons, 2 orangutans, and 17 humans. The comparison has revealed unique features of this muscle in humans: 1) Type 1 or red fibers are thicker than Type 2 or white fibers in humans but vice versa in nonhumans; 2) among the species examined the number of the muscle fibers per unit cross-sectional area is largest, implying the fibers are thinnest, in humans; 3) frequency of Type 1 fibers is highest in humans, intermediate in monkeys, and lowest in the orangutan, whereas Type 2 fibers show an inverse trend among the species. These results suggest a correspondence in primates between the composition of the psoas major muscle fibers and difference in substrates inhabited as well as in their positional behaviors.


Multiple chondrosarcomas of the hand.
An unusual case of multiple chondrosarcomas of the hand arising from multiple enchondromas is presented. Chondrosarcoma is an unusual tumor of the hand that requires careful clinical, radiological, and pathological examination for accurate diagnosis. These tumors can usually be managed successfully by wide local excision or ray amputation. However, long follow-up is indicated.


Split-thickness skin grafts and negative-pressure dressings in the treatment of axillary hidradenitis suppurativa.
Although a number of different reconstructive techniques have been described for the treatment of axillary skin defects, split-thickness skin grafting continues to be the most common surgical modality. Here, we present our recent experience of using split-thickness skin grafts together with negative-pressure dressings for the management of defects following wide surgical excision of severe hidradenitis suppurativa. This technique ensures complete skin-graft take whilst allowing full shoulder mobility, thereby minimising the undesirable sequelae associated with split-thickness skin grafting alone.


Interaction Between Diet and Microbiota in the Pathophysiology of Alzheimer's Disease: Focus on Polyphenols and Dietary Fibers.
Animal studies increasingly indicate that the gut microbiota composition and function can be involved in the pathophysiology and progression of Alzheimer's disease (AD) at multiple levels. However, few studies have investigated this putative gut-brain axis in human beings, and none of them considered diet as a determinant of intestinal microbiota composition. Epidemiological studies highlight that a high intake of fruit and vegetables, such as that typical of the Mediterranean diet, can modulate AD progression. Thus, nutritional interventions are being increasingly studied as a possible non-pharmacological strategy to slow down the progression of AD. In particular, polyphenols and fibers represent the nutritional compounds with the higher potential of counterbalancing the pathophysiological mechanisms of dementia due to their antioxidant, anti-inflammatory, and anti-apoptotic properties. These actions are mediated by the gut microbiota, that can transform polyphenols and fibers into biologically active compounds including, among others, phenyl-γ-valerolactones, urolithins, butyrate, and other short-chain fatty acids. In this review, the complex mechanisms linking nutrition, gut microbiota composition, and pathophysiology of cognitive decline in AD are discussed, with a particular focus on the role of polyphenols and fibers. The gaps between pre-clinical and clinical studies are particularly emphasized, as well as the urgent need for studies comprehensively evaluating the link between nutrition, microbiome, and clinical aspects of AD.


[Effects of acupuncture on TCD and BAEP in the patient of vertebrobasilar insufficiency].
To explore mechanisms of acupuncture in treatment of vertebrobasilar insufficiency. Forty cases of vertebrobasilar insufficiency (VBI) were divided into an acupuncture group and a routine treatment group, 20 cases in each group. The acupuncture group were treated by routine treatment plus acupuncture. Transcranial Doppler ultrasonography and brain stem auditory evoked potentials (BAEP) before treatment and 2 weeks after treatment were determined to investigate the effects of acupuncture on blood flow velocity and brain electrophysiology in the patient of VBI. Before treatment, the blood velocity of vertebral artery and vertebrobasilar artery at bilateral sides in the patient of VBI decreased as compared with the control group, and the abnormal rate of TCD was 75.0% (30/40) and the abnormal rate of BAEP was 70.0% (28/40), characterized with brainstem abnormality type; after treatment, the blood velocity in the two groups was improved and the abnormal rate of TCD was 47.5% (19/40), and the abnormal rate of BEAP was 45.0% (18/40). The nerve conduction of the two groups was improved, the peak latency of V wave and interpeak latency of III-V and I -V in the acupuncture group were improved significantly as compared with the routine treatment group (P < 0.05). Acupuncture can improve the blood velocity of vertebrobasilar artery and the nerve conduction function of brainstem in the patient of vertebrobasilar insufficiency.


Purification and Properties of Glutamine Synthetase in Leaves and Roots of Pinus banksiana Lamb.
A method is described for the purification of glutamine synthetase (GS; EC. 126.96.36.199) from the leaves and roots of Pinus banksiana Lamb., a conifer which utilizes ammonium as its primary nitrogen source. The enzyme was purified to apparent homogeneity by a procedure involving salt fractionation as well as ion-exchange, size exclusion, and affinity chromatography. Since the final preparation produced two bands on SDS polyacryamide gels but only one band on a nondenaturating gel, it is concluded that the two subunits (44 and 40 kilodaltons, respectively) are part of a single enzymatic protein which shows GS activity. The pH optimum for leaf GS ranged between 6.2 and 6.5, one pH unit lower than the values reported for higher plants which utilize primarily nitrate nitrogen. Magnesium requirements for GS in P. banksiana were different for leaves and roots, showing V(max)/2 values of 2.5 and 8 millimolar, respectively at 5 millimolar ATP. Furthermore, K(m) values for ammonium were higher for the enzyme in leaves (33.1 micromolar) than in roots (19.2 micromolar). K(m) values for ATP and for glutamate, on the other hand, were similar for the two tissues. A polyclonal antibody was produced against the purified leaf GS. Western blots of leaf homogenates produced two bands, the lighter one being more abundant. The same pattern was found when immunodetection was performed using an anti GS IgG produced against purified GS from Phaseolus nodules thus indicating common antigenic determinants. At least 30% of total GS was recovered in a plastid-fraction of dark-grown calli produced from the basal part of P. banksiana hypocotyls.


Culture of one-cell hamster embryos with water soluble vitamins: pantothenate stimulates blastocyst production.
The effects of water-soluble vitamins, singly or in combinations, on development of hamster 1-cell embryos were examined in a protein-free, chemically defined culture medium, HECM-6. Pantothenate significantly stimulated blastocyst development compared to the vitamin-free control and to every other single vitamin, except thiamine. Ascorbic acid, biotin, choline, folic acid, inositol, niacinamide, pyridoxal, riboflavin and thiamine had no detectable stimulation or inhibition on cleavage stage development or morula/blastocyst formation. When combinations of vitamins were tested, embryo development was either unchanged or significantly greater than in the control, but never significantly greater than development with pantothenate alone. A dose response to pantothenate indicated that 3 micromol/l was the optimum concentration. After embryo transfer, the percentage of live fetuses recovered per 100 1-cell embryos cultured in HECM-6 plus pantothenate (now designated HECM-9) was 24%, significantly higher than the 11% recovered from 100 1-cell embryos cultured in HECM-6 alone. This is the first report to show a stimulatory effect of a single vitamin on in-vitro development of preimplantation embryos in any mammalian species.


Wide-field f /3.5 Rosin camera.
Modification of Rosin's [J. Opt. Soc. Am. 51, 331-335 (1961)] simple design yields an f/3.5 camera that gives 2.5-arcsec resolution over a flat field that is 5 degrees in diameter.


A biochemical rationale for the anticancer effects of Hsp90 inhibitors: slow, tight binding inhibition by geldanamycin and its analogues.
Heat shock protein (Hsp)90 is emerging as an important therapeutic target for the treatment of cancer. Two analogues of the Hsp90 inhibitor geldanamycin are currently in clinical trials. Geldanamycin (GA) and its analogues have been reported to bind purified Hsp90 with low micromolar potency, in stark contrast to their low nanomolar antiproliferative activity in cell culture and their potent antitumor activity in animal models. Several models have been proposed to account for the approximately 100-fold-greater potency in cell culture, including that GA analogues bind with greater affinity to a five-protein Hsp90 complex than to Hsp90 alone. We have determined that GA and the fluorescent analogue BODIPY-GA (BDGA) both demonstrate slow, tight binding to purified Hsp90. BDGA, used to characterize the kinetics of ligand-Hsp90 interactions, was found to bind Hsp90alpha with k(off) = 2.5 x 10(-3) min(-1), t(1/2) = 4.6 h, and Ki* = 10 nM. It was found that BDGA binds to a functional multiprotein Hsp90 complex with kinetics and affinity identical to that of Hsp90 alone. Also, BDGA binds to Hsp90 from multiple cell lysates in a time-dependent manner with similar kinetics. Therefore, our results indicate that the high potency of GA in cell culture and in vivo can be accounted for by its time-dependent, tight binding to Hsp90 alone. In the broader context, these studies highlight the essentiality of detailed biochemical characterization of drug-target interactions for the effective translation of in vitro pharmacology to cellular and in vivo efficacy.


Comparison between placental and skeletal muscle ECM: in vivo implantation.
Several tissues have been decellularized and their extracellular matrices used as allogeneic or xenogeneic scaffolds, either in orthotopic or heterotopic implantations, for tissue engineering purposes. Placentas have abundant matrix, extensive microvascular structure, immunomodulatory properties, growth factors and are discarded after birth, representing an interesting source of extracellular matrix. This study aimed at comparing decellularized canine placentas and murine skeletal muscles to regenerate skeletal muscles in a rat model. Muscle pockets were created at the posterior limbs of male Wistar rats, where the muscle- and placenta-derived extracellular matrices were implanted. Macroscopic, histological, and immunohistochemical analyses were performed after 3, 15, and 45 days of surgeries. On the third day, intense inflammatory reaction, with macrophages (CD163+) and proliferative cells (PCNA+) being observed in control group and adjacent to the decellularized matrices. The percentage of proliferative cells was higher in placenta than in muscle matrices. Macrophages CD163+ high were higher in muscles than in placentas, whereas CD163+ low were higher in placentas than in muscle ECM, at days 3 and 15. Placental matrices were not completely degraded at day 15, as opposed to the muscular ones. After 45 days, both matrices were resorbed and morphologically normal myofibers, with reduction of cell infiltration, were observed. These results demonstrated that xenogeneic placental ECM, implanted heterotopically (representing a biologically critical and challenging microenvironment), induced local inflammatory reactions similar to the allogeneic muscle ECM, implanted orthotopically. Thus, placenta-derived extracellular matrix must be further explored in regenerative medicine.


Role of intraluminal brachytherapy in extrahepatic bile duct and pancreatic cancers: is it just for palliation?
To evaluate intraluminal brachytherapy (ILBT) in patients with extrahepatic bile duct or pancreatic cancers. Thirty-one patients (aged 33-87 years) with unresectable extrahepatic bile duct (n = 18) or pancreatic (n = 13) cancer received ILBT exclusively or as part of a definitive treatment regimen. ILBT was performed with transhepatic percutaneous drainage in four patients and with endoscopic retrograde cholangiopancreatography in 27. Fourteen patients with no metastases, an Eastern Cooperative Oncology Group performance score of < or = 2, and good hematologic parameters received combined modality treatment: 30-Gy ILBT and 45-Gy external-beam radiation therapy with continuous infusion of fluorouracil. Seventeen patients underwent 50-Gy ILBT alone for palliation. No direct treatment-related acute toxic reactions were seen. Three patients had cholangitis early in the study. Three patients had late gastrointestinal bleeding. Jaundice was palliated in all patients (n = 29); pain, in 11 of 13 patients. The survival rate in patients with extrahepatic bile duct cancer was 62% (five of eight) at 2 years for combined modality treatment. No patient with pancreatic cancer lived for longer than 2 years. ILBT is an effective palliative treatment of unresectable extrahepatic bile duct and pancreatic cancers. Results suggest a possible "curative" role in specific clinical settings when properly integrated with other treatments.


Adoptive transfer of infectious bronchitis virus primed alphabeta T cells bearing CD8 antigen protects chicks from acute infection.
Infectious bronchitis virus (IBV) infection and associated illness may be dramatically modified by passive transfer of immune T lymphocytes. Lymphocytes collected 10 days postinfection were transferred to naive chicks before challenge with virus. As determined by respiratory illness and viral load, transfer of syngeneic immune T lymphocytes protected chicks from challenge infection, whereas no protection was observed in the chicks receiving the MHC compatible lymphocytes from uninfected chicks. Protection following administration of T lymphocytes could be observed in chicks with three distinct MHC haplotypes: B(8)/B(8), B(12)/B(12), and B(19)/B(19). Nearly complete elimination of viral infection and illness was observed in chicks receiving cells enriched in alphabeta lymphocytes. In contrast, removal of gammadelta T lymphocytes had only a small effect on their potential to protect chicks. The adoptive transfer of enriched CD8(+) or CD4(+) T lymphocytes indicated that protection was also a function primarily of CD8-bearing cells. These results indicated that alphabeta T lymphocytes bearing CD8(+) antigens are critical in protecting chicks from IBV infection.


Cortical correlates of fitts' law.
Fitts' law describes the fundamental trade-off between movement accuracy and speed: it states that the duration of reaching movements is a function of target size (TS) and distance. While Fitts' law has been extensively studied in ergonomics and has guided the design of human-computer interfaces, there have been few studies on its neuronal correlates. To elucidate sensorimotor cortical activity underlying Fitts' law, we implanted two monkeys with multielectrode arrays in the primary motor (M1) and primary somatosensory (S1) cortices. The monkeys performed reaches with a joystick-controlled cursor toward targets of different size. The reaction time (RT), movement time, and movement velocity changed with TS, and M1 and S1 activity reflected these changes. Moreover, modifications of cortical activity could not be explained by changes of movement parameters alone, but required TS as an additional parameter. Neuronal representation of TS was especially prominent during the early RT period where it influenced the slope of the firing rate rise preceding movement initiation. During the movement period, cortical activity was correlated with movement velocity. Neural decoders were applied to simultaneously decode TS and motor parameters from cortical modulations. We suggest that sensorimotor cortex activity reflects the characteristics of both the movement and the target. Classifiers that extract these parameters from cortical ensembles could improve neuroprosthetic control.


CYP4A11 gene T8590C polymorphism is associated with essential hypertension in the male western Chinese Han population.
CYP4A11 is a member of the cytochrome P450 enzymes and is responsible for metabolizing arachidonic acid to 20-hydroxyeicosatetraenoic acid, a metabolite involved in the regulation of blood pressure. This study aimed to evaluate whether or not the CYP4A11 gene polymorphism T8590C (rs1126742) is involved in essential hypertension in the western Chinese Han population. In a case-control study, the participants included 864 (523 males and 341 females) patients with essential hypertension and 661 (422 males and 239 females) healthy subjects. The T8590C polymorphism of the CYP4A11 gene was analyzed by using the TaqMan® SNP Genotyping Assay. For men, the frequencies of the CC genotype and the C allele were higher in essential hypertension than in the control group (p=0.022 and p=0.016, respectively). After adjustment of confounding factor such as diabetes, smoking, BMI, TG and TC, the significant difference was observed in CC genotype (OR=1.897, 95% confidence interval [CI] 1.026-3.508; p=0.041). No difference was found in all participants and females. The CC genotype and C allele were associated with essential hypertension in the male western Chinese Han population.


A quantitative approach to lower extremity vein repair.
We prospectively investigated the patency of venous repair in a quantitative fashion with measurement of vein blood flow velocities after lower extremity injuries caused by either military or civilian trauma. During a 10-year study period (March 1990 to December 2000), surgical intervention was performed after lower extremity vascular injuries in 130 patients. Most of these patients were men (n = 125), with a mean age of 23 +/- 5 years (range, 17 to 44 years). One hundred ten direct venous injuries were identified in 97 patients, involving the common femoral vein in seven, the deep femoral vein in three, the superficial femoral vein in nine, the popliteal vein in 46, and the posterior tibial (n = 21), anterior tibial (n = 17), or peroneal veins (n = 7) in 45. Popliteal vein thrombosis without apparent venous injury was found in seven patients. Bone fractures (n = 45), nerve injuries (n = 27), or extensive tissue loss (n = 7) often were associated with vascular injuries. Duplex color ultrasonography was used to evaluate patency and to measure blood flow velocity in repaired veins during the early postoperative period and at the time of late follow-up examinations. Significant differences were seen in venous blood flow velocities between severe (extremity diameter more than twice normal) and moderate (diameter 1.5 to 2 times normal) reperfusion injuries. The mean flow velocity in repaired popliteal veins was 15 +/- 2 cm/s with severe reperfusion injuries compared with 8.4 +/- 1.1 cm/s with moderate reperfusion injuries (P <.0001). Flow velocities were lower than 5 cm/s in repaired infrapopliteal veins, and most of these veins occluded on the first postoperative day. Amputations were necessary in 11 patients, all of whom had both tibial fractures and extensive tissue loss. Sodium warfarin therapy was routinely administrated before hospital discharge. The mean follow-up period was 6.2 years (range, 1.3 to 10 years). Repaired common femoral and superficial femoral veins had relatively high patency rates (100% and 89% at 1 year, 100% and 78% at 6 years, respectively), whereas the patency rates for repaired popliteal veins were disappointing (86% at 1 year, 60% at 6 years). All seven popliteal veins that required thrombectomy in the absence of direct injuries remained patent, however. Patch angioplasty had the highest 6-year patency rate (75%) in comparison with all other techniques that were used for venous injuries (lateral repair, 58%; end-to-end anastomosis, 43%; saphenous vein graft interposition, 36%). Venous repair has a high patency rate at the femoral and popliteal levels, but the patency rate for infrapopliteal venous repair is extremely poor because of low flow velocities. Therefore, we conclude that repair of infrapopliteal venous injuries is unnecessary.


An automated algorithm to improve the precision of basilar artery diameter measurements before and after subarachnoid hemorrhage-induced vasospasm in an animal model.
Quantifying vasospasm has traditionally been performed manually, a method prone to imprecision and user bias. An alternative approach is to use computerized image analysis techniques to define and quantify the diameter of a vessel. The goal of this article is to demonstrate a novel automated vessel measurement algorithm specific to the needs of vasospasm studies and to compare it with traditional manual measurements in an animal model of vasospasm. A total of 576 arterial diameter measurements were collected by 4 independent, blinded examiners from 24 angiograms in a rabbit subarachnoid hemorrhage (SAH) model. Measurements were taken from 3 segments of the basilar artery in anteroposterior and lateral projections, both before SAH and after SAH-induced vasospasm. Means and standard deviations of 288 manual measurements were compared with 288 automated measurements. The precision of automated measurements was significantly improved compared with standardized manual measurements (85.7% decrease in variation; P < .001). When using automated measurements, the precision was not affected by vessel size, but when using manual measurements, smaller arteries were less precise (P = .04). There was no significant difference in precision between 2 different contrast concentrations (P = .32). Automated measurements of basilar artery diameters are more precise than manual measurements, both before and after SAH-induced vasospasm. The variability in the manual group worsens when the artery is smaller secondary to vasospasm, indicating a need for the use of this segmentation method.


A comparison of photosynthetic characteristics of encelia species possessing glabrous and pubescent leaves.
Measurements of the dependence of photosynthesis on light, CO(2), and temperature are reported for two species of Encelia (Compositae) which differ in leaf pubescence and in geographical distribution. Encelia californica is glabrous and occurs in relatively mild, but arid habitats and Encelia farinosa is heavily pubescent and occurs in hot, arid habitats. Both species possess the C(3) photosynthetic pathway. Under high irradiances and normal atmospheric conditions the two species have high photosynthetic rates, exceeding 3 nanomoles of CO(2) per square centimeter per second (48 milligrams of CO(2) per square decimeter per hour) and complete light saturation does not occur by full noon sunlight. The high photosynthetic capacity is related to a high efficiency of utilization of intercellular CO(2) combined with high stomatal conductance. Leaf estimates of total soluble protein and fraction I protein are higher in these species than in most plants, although the proportion of fraction I protein is not higher. Both E. californica and E. farinosa attain a maximum rate of photosynthesis between 25 and 30 C, despite the fact that the two species grow in very different thermal habitats. Neither E. californica nor E. farinosa shows significant acclimation in the temperature dependence of photosynthesis when grown under different temperature regimes. The presence of leaf hairs which reduce leaf absorptance and consequently leaf temperature plays an important part in the ability of E. farinosa to survive in its native high temperature environment. When the effects of pubescence are taken into account, there are few if any significant differences in the photosynthetic characteristics of the two species.


Residue Dynamics and Risk Assessment of Prochloraz and Its Metabolite 2,4,6-Trichlorophenol in Apple.
The residue dynamics and risk assessment of prochloraz and its metabolite 2,4,6-trichlorophenol (2,4,6-TCP) in apple under different treatment concentrations were investigated using a GC-ECD method. The derivatization percent of prochloraz to 2,4,6-TCP was stable and complete. The recoveries of prochloraz and 2,4,6-TCP were 82.9%-114.4%, and the coefficients of variation (CV) were 0.7%-8.6% for the whole fruit, apple pulp, and apple peel samples. Under the application of 2 °C 2.0 g/L, 2 °C 1.0 g/L, 20 °C 2.0 g/L, and 20 °C 1.0 g/L treatment, the half-life for the degradation of prochloraz was 57.8-86.6 d in the whole fruit and apple peel, and the prochloraz concentration in the apple pulp increased gradually until a peak (0.72 mg·kg-1) was reached. The concentration of 2,4,6-TCP was below 0.1 mg·kg-1 in four treatment conditions and not detected (<LOD) in apple pulp. Finally, based on the detection of market samples in Hefei (China), we believe that the residual level of prochloraz in apples meets the requirements of the Chinese standards.


Long Non-Coding RNA FENDRR: Gene Structure, Expression, and Biological Relevance.
The FOXF1 Adjacent Noncoding Developmental Regulatory RNA (Fendrr) plays an important role in the control of gene expression in mammals. It is transcribed in the opposite direction to the neighboring Foxf1 gene with which it shares a region containing promoters. In humans, FENDRR is located on chromosome 16q24.1, and is positively regulated both by the FOXF1 distant lung-specific cis-acting enhancer and by trans-acting FOXF1. Fendrr has been shown to function as a competing endogenous RNA, sponging microRNAs and protein factors that control stability of mRNAs, and as an epigenetic modifier of chromatin structure around gene promoters and other regulatory sites, targeting them with histone methyltrasferase complexes. In mice, Fendrr is essential for development of the heart, lungs, and gastrointestinal system; its homozygous loss causes embryonic or perinatal lethality. Importantly, deregulation of FENDRR expression has been causatively linked also to tumorigenesis, resistance to chemotherapy, fibrosis, and inflammatory diseases. Here, we review the current knowledge on the FENDRR structure, expression, and involvement in development and tissue maintenance.


Fetal signaling through placental structure and endocrine function: illustrations and implications from a nonhuman primate model.
The placenta is a transmitter of fetal need and fetal quality, interfacing directly with maternal physiology and ecology. Plasticity of placental structure and function across the developmental timeframe of gestation may serve as an important tool by which a fetus calibrates its growth to shifting maternal ecology and resource availability, and thereby signals its quality and adaptability to a changing environment. Signals of this quality may be conveyed by the size of the placental interface, an important marker of fetal access to maternal resources, or by production of placental insulin-like growth factor-II, a driver of fetoplacental growth. Litter size variation in the common marmoset monkey offers the opportunity to explore intrauterine resource allocation and placental plasticity in an important nonhuman primate model. Triplet marmosets are born at lower birth weights and have poorer postnatal outcomes and survivorship than do twins; triplet placentas differ in placental efficiency, microscopic morphology, and endocrine function. Through placental plasticity, triplet fetuses are able to adjust functional access to maternal resources in a way that allows pregnancy to proceed. However, the costs of such mechanisms may relate to reduced fetal growth and altered postnatal outcomes, with the potential to lead to adverse adult health consequences, suggesting an important link between the placenta itself and the developmental origins of health and disease.


MRL1, a conserved Pentatricopeptide repeat protein, is required for stabilization of rbcL mRNA in Chlamydomonas and Arabidopsis.
We identify and functionally characterize MRL1, a conserved nuclear-encoded regulator of the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase. The nonphotosynthetic mrl1 mutant of Chlamydomonas reinhardtii lacks ribulose-1,5-bisphosphate carboxylase/oxygenase, and the resulting block in electron transfer is partially compensated by redirecting electrons toward molecular oxygen via the Mehler reaction. This allows continued electron flow and constitutive nonphotochemical quenching, enhancing cell survival during illumination in spite of photosystem II and photosystem I photoinhibition. The mrl1 mutant transcribes rbcL normally, but the mRNA is unstable. The molecular target of MRL1 is the 5 ' untranslated region of rbcL. MRL1 is located in the chloroplast stroma, in a high molecular mass complex. Treatment with RNase or deletion of the rbcL gene induces a shift of the complex toward lower molecular mass fractions. MRL1 is well conserved throughout the green lineage, much more so than the 10 other pentatricopeptide repeat proteins found in Chlamydomonas. Depending upon the organism, MRL1 contains 11 to 14 pentatricopeptide repeats followed by a novel MRL1-C domain. In Arabidopsis thaliana, MRL1 also acts on rbcL and is necessary for the production/stabilization of the processed transcript, presumably because it acts as a barrier to 5 ' >3 ' degradation. The Arabidopsis mrl1 mutant retains normal levels of the primary transcript and full photosynthetic capacity.


The Continuous Evolution of Composites for Direct Restorations.
Restorative dentistry without the use of composite materials has become unthinkable. This is a result of numerous improvements in this field, as over the past five decades, the indications for composites have expanded and excellent clinical results have been consistently achieved. The term "composite material" refers to the union of at least two distinct components, insoluble in each other. The resulting product is a material with different, often better, characteristics than the single components. Three main ingredients of dental composites are: the organic resin matrix, inorganic filler particles that are distributed in the resin matrix, and the silane coupling agent used to coat these particles for chemical bonding to the resin matrix. Dental composites also need other components, such as initiators for the polymerization reaction, inhibitors to avoid spontaneous polymerization, and pigments to create a tooth-matching color range.


Spin transport through metal-dichalcogenides layers: a study from first-principles calculations.
Spin transport through monolayer and trilayers of molybdenum dichalcogenides were studied considering Co as leads. Detailed investigations of the electronic structure of the Co/MoS2 interface and magnetic tri-junctions are carried out by using density functional theory calculations to understand transport behavior. The study revealed that new spin-polarized hybridized states appeared at the Fermi level due to the formation of Co/MoS2 interface that effectively acted as a spin filter and enhanced the spin injection efficiency of the systems. Spin-polarized current through the system as well as the magnetoresistance (MR) was estimated at different applied bias voltages. Large MR up to 78% was calculated for the trilayer MoS2 system at a relatively high applied bias voltage. The MR values are further improved by tuning the structure of the scattering region. A very large MR of 123% for MoS2/MoSe2/MoS2 trilayer at an applied bias 0.8 V was observed, which is much higher than the previously reported bias dependent MR values in similar systems.


Suppression of phase transitions in a confined rodlike liquid crystal.
The nematic-to-isotropic, crystal-to-nematic, and supercooled liquid-to-glass temperatures are studied in the liquid crystal 4-pentyl-4'-cyanobiphenyl (5CB) confined in self-ordered nanoporous alumina. The nematic-to-isotropic and the crystal-to-nematic transition temperatures are reduced linearly with the inverse pore diameter. The finding that the crystalline phase is completely suppressed in pores having diameters of 35 nm and below yields an estimate of the critical nucleus size. The liquid-to-glass temperature is reduced in confinement as anticipated by the model of rotational diffusion within a cavity. These results provide the pertinent phase diagram for a confined liquid crystal and are of technological relevance for the design of liquid crystal-based devices with tunable optical, thermal, and dielectric properties.


Equations for the transfer of neutral molecules and ionic species from water to organic phases.
Equations that can be used for partition coefficients of both neutral molecules and ions have been revised, and the term that is specific to ions has been re-evaluated. A new method has been devised for the determination of partition coefficients from water to organic solvents for carboxylate anions that is based on the variation of pK(a) for carboxylic acids with solvent. Using these partition coefficients, descriptors for carboxylate anions, on the same scale as descriptors for neutral molecules, have been obtained for 71 such anions. For 13 carboxylate anions in a test set, descriptors could be predicted that in turn led to predictions of 78 log P values over six water-solvent systems with an absolute error of 0.13 and a standard deviation of only 0.55 log units. Descriptors have been obtained for 26 protonated amines as a training set and descriptors predicted for 17 protonated amines as a test set. The predicted descriptors in turn led to the prediction of 18 log P values for protonated amines with an absolute error of 0.09 and a standard deviation of 0.39 log units. The carboxylate anions are the strongest monofunctional hydrogen bond bases, and the protonated amines are the strongest monofunctional hydrogen bond acids that we have studied.


Mosaicing of confocal microscopic in vivo soft tissue video sequences.
Fibered confocal microscopy allows in vivo and in situ imaging with cellular resolution. The potentiality of this imaging modality is extended in this work by using video mosaicing techniques. Two novelties are introduced. A robust estimator based on statistics for Riemannian manifolds is developed to find a globally consistent mapping of the input frames to a common coordinate system. A mosaicing framework using an efficient scattered data fitting method is proposed in order to take into account the non-rigid deformations and the irregular sampling implied by in vivo fibered confocal microscopy. Results on 50 images of a live mouse colon demonstrate the effectiveness of the proposed method.


SIN1 interacts with a protein that binds the URS1 region of the yeast HO gene.
Evidence has recently been mounting suggesting that a number of chromatin components previously thought to primarily or exclusively have structural function, also have a regulatory role in eukaryotic transcription. Notably, in yeast, histone H4 N-terminal sequence has been shown to be required for promoter activation of certain genes in vivo, and mutations in histone H3 (SIN2) or in SIN1 (which has some sequence similarity to HMG1) are able to suppress swi1, swi2, and swi3 mutations, restoring transcription to HO as well as a number of other genes. In this paper we report the identification of a novel protein or protein complex that specifically binds a short sequence in the HO regulatory region on the one hand, and on the other somehow appears to contact the SIN1 protein. We have shown that the DNA binding activity itself does not contain SIN1, since extracts from sin1 delta strains retain the activity. Interestingly, extracts made from cells carrying the dominant sin1-2 point mutation lack the binding activity. Furthermore, bacterially produced sin1-2 protein can dissociate a DNA/protein complex while a similarly produced SIN1 protein has no effect on the complex at similar concentrations. When the DNA sequence to which the protein complex binds is placed in a CYC1 promoter lacking a UAS (upstream activating sequence), it can serve as a weak UAS in a SIN1 dependent way. Our data imply that a sequence specific DNA binding protein(s) may mediate between the SIN1 protein and the basal transcription apparatus transcribing HO.


Evaluation of biochars and activated carbons for in situ remediation of sediments impacted with organics, mercury, and methylmercury.
In situ amendment of activated carbon (AC) to sediments can effectively reduce the bioavailability of hydrophobic organic contaminants. While biochars have been suggested as low-cost and sustainable alternatives to ACs, there are few comparative sorption data especially for mercury (Hg) and methylmercury (MeHg) at the low porewater concentrations in sediments. Here we compare the ability of a wide range of commercially available and laboratory synthesized ACs and biochars to sorb PAHs, PCBs, DDTs, inorganic Hg, and MeHg at environmentally relevant concentrations. Compared to natural organic matter, sorption capacity for most organic compounds was at least 1-2 orders of magnitude higher for unactivated biochars and 3-4 orders of magnitude higher for ACs which translated to sediment porewater PCB concentration reductions of 18-80% for unactivated biochars, and >99% for ACs with 5% by weight amendment to sediment. Steam activated carbons were more effective than biochars in Hg sorption and translated to modeled porewater Hg reduction in the range of 94-98% for sediments with low native Kd and 31-73% for sediments with high native Kd values for Hg. Unactivated biochars were as effective as the steam activated carbons for MeHg sorption. Predicted reductions of porewater MeHg were 73-92% for sediments with low native Kd and 57-86% for sediment with high native K(d). ACs with high surface areas therefore are likely to be effective in reducing porewater concentrations of organics, Hg, and MeHg in impacted sediments. Unactivated biochars had limited effectiveness for organics and Hg but can be considered when MeHg exposure is the primary concern.


Changes in Behaviors and Attitudes in Response to COVID-19 Pandemic and Vaccination in Healthcare Workers and University Students in Italy.
The objectives of the cross-sectional study were to measure how behaviors and attitudes about preventive measures toward COVID-19 changed over time among Italian vaccinated healthcare workers and university students, and the associated characteristics. The study was carried out between February and March 2021 in the city of Naples, Campania region, Southern Italy. The perceived personal risk of being infected by SARS-CoV-2 after the vaccination was significantly higher among males, in those having a higher perceived personal risk of being infected by SARS-CoV-2 before the vaccination, and in those who were more concerned about the efficacy of the vaccination. The fear of getting the disease as reason to have the COVID-19 vaccination was reported more frequently in younger participants, in those with at least one chronic medical condition, in those with a higher concern about the severity of COVID-19, in those with a higher level of trust in the information received, and in those who acquired information from scientific journals. Overall, 21.3% were willing to engage the three main public health measures (wearing a mask, careful hand washing, physical distancing) after receiving the second dose of the vaccination compared to the behavior before the pandemic began. This willingness was predicted by a higher level of trust in the information received and by a lower self-rated health status. Only 0.1% of participants were willing to engage all three measures after receiving the second dose of the vaccination compared to the behavior before receiving the first dose. These findings are useful in order to develop information strategies regarding vaccine safety and efficacy and the importance of public health measures against COVID-19.


Rhizosphere selection of highly motile phenotypic variants of Pseudomonas fluorescens with enhanced competitive colonization ability.
Phenotypic variants of Pseudomonas fluorescens F113 showing a translucent and diffuse colony morphology show enhanced colonization of the alfalfa rhizosphere. We have previously shown that in the biocontrol agent P. fluorescens F113, phenotypic variation is mediated by the activity of two site-specific recombinases, Sss and XerD. By overexpressing the genes encoding either of the recombinases, we have now generated a large number of variants (mutants) after selection either by prolonged laboratory cultivation or by rhizosphere passage. All the isolated variants were more motile than the wild-type strain and appear to contain mutations in the gacA and/or gacS gene. By disrupting these genes and complementation analysis, we have observed that the Gac system regulates swimming motility by a repression pathway. Variants isolated after selection by prolonged cultivation formed a single population with a swimming motility that was equal to the motility of gac mutants, being 150% more motile than the wild type. The motility phenotype of these variants was complemented by the cloned gac genes. Variants isolated after rhizosphere selection belonged to two different populations: one identical to the population isolated after prolonged cultivation and the other comprising variants that besides a gac mutation harbored additional mutations conferring higher motility. Our results show that gac mutations are selected both in the stationary phase and during rhizosphere colonization. The enhanced motility phenotype is in turn selected during rhizosphere colonization. Several of these highly motile variants were more competitive than the wild-type strain, displacing it from the root tip within 2 weeks.


Comparative cognition: Practical shortcomings and some potential ways forward.
The objectives in the field of comparative cognition are clear; efforts are devoted to revealing the selection pressures that shape the brains and cognitive abilities of different species and understanding cognitive processes in differently structured brains. However, our progress on reaching these objectives is slow, mostly because of several major practical challenges. In this review, we discuss 2 major shortcomings: (a) the poor systematics and low magnitude of the phylogenetic comparisons made, and (b) the weak comparability of the results caused by interfering species-specific confounding factors (perceptual, motivational, and morphological) alongside an insufficient level of standardisation of the methodologies. We propose a multiple-level comparative approach that emphasises the importance of achieving more direct comparisons within taxonomic groups at genus or family level as the first step before comparing between distantly related groups. We also encourage increasing interdisciplinary efforts to execute "team-science" approach in building a systematic and direct large-scale phylogenetic comparisons of bigger cognitive test batteries that produce reliable species-representative data. We finally revisit some existing suggestions that allow us to maximise standardisation while minimising species-specific confounding factors. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Role of human chromosome 11 in determining surface antigenic phenotype of normal and malignant cells. Somatic cell genetic analysis of eight antigens, including putative human Thy-1.
The expression of eight serologically and biochemically distinct human cell surface antigens defined by monoclonal antibodies was examined on a panel of rodent-human somatic cell hybrids. Cosegregation was observed for human chromosome 11, and surface expression of all eight antigens was studied. Serological analysis of hybrids containing defined segments of human chromosome 11 permitted the regional assignment of genes controlling antigens JF23 (90 kD glycoprotein), G344 (25 kD), T43 (85 kD), A124, and NP13 to chromosome 11pter-q13, and of genes controlling Q14 (130 kD), MC139 (35 kD), and K117 (25 kD) to chromosome 11q13-qter. K117, the putative human Thy-1 antigen, was expressed at high levels in chromosome 11-containing hybrids constructed with mouse neuroblastoma cells, but showed little or no expression in hybrids constructed with mouse L cells. A similar pattern of expression in hybrids was found for MC139, an antigen shared by neuroectoderm-derived cells and normal and malignant T lymphocytes. T43 is a marker of malignant tumors (but not benign tumors) derived from a number of T43- epithelia, and the regional assignment of the T43 locus on chromosome 11 raises questions about its possible involvement in the specific rearrangements of this chromosome seen in human malignancies.


Acitretin-induced poliosis with concurrent alopecia.
Acitretin, a metabolite of the aromatic retinoid etretinate, has been utilized successfully in the treatment of psoriasis since the late 1980s. Of the oral retinoids available, etretinate and acitretin are the most likely agents to induce various dose-dependent hair changes, but to our knowledge this is the first reported case of acitretin-induced poliosis. Additional cutaneous findings included skin atrophy and stickiness. Here we report a case of full body acitretin-induced poliosis with concurrent alopecia in a patient with psoriasis. A proposed mechanism for the poliosis is also presented here. Closer examination of retinoid-induced hair changes is needed in order to help physicians better counsel their patients regarding the adverse effects of acitretin and to expand the current knowledge on hair follicle biology.


Restriction Fragment Length Polymorphism Linkage Map of Arabidopsis thaliana.
We have constructed a restriction fragment length polymorphism (RFLP) linkage map of the nuclear genome of the small flowering plant Arabidopsis thaliana. The map is based on the meiotic segregation of both RFLP and morphological genetic markers from five independent crosses. The morphological markers on each of the five chromosomes were included in the crosses to allow alignment of the RFLP map with the established genetic map. The map contains 94 new randomly distributed molecular markers (nine identified cloned Arabidopsis genes and 85 genomic cosmid clones) that detect polymorphisms between the Landsberg erecta and Columbia races. In addition, 17 markers from an independently constructed RFLP map of the Arabidopsis genome [Chang, C., Bowman, J.L., DeJohn, A.W., Lander, E.S., and Meyerowitz, E.M. (1988). Proc. Natl. Acad. Sci. USA 85, 6856-6860] have been included to permit integration of the two RFLP maps.


Lower Limb Somatosensory Discrimination Is Impaired in People With Parkinson's Disease: Novel Assessment and Associations With Balance, Gait, and Falls.
People with Parkinson's disease (PD) have often compromised walking and balance. This may be the result of the impaired lower limb tactile and proprioceptive sensation. Existing clinical measures may not be sufficiently sensitive to uncover these sensory impairments. To determine whether novel measures of lower limb somatosensory discrimination are psychometrically robust and associated with mobility outcomes in people with PD. Lower limb somatosensation was assessed on 2 occasions, 3 to 7 days apart, using the following 3 novel tests: gradient discrimination, roughness discrimination, and step height discrimination. Static and dynamic balance (Brief Balance Evaluations Systems Test), falls incidence, falls confidence (Falls Efficacy Scale), and gait (speed and step length) were also obtained. The participants were 27 people with PD and 27 healthy controls. Novel tests showed good to excellent intrarater reliability (intraclass correlation coefficient = 0.72-0.92). Significantly higher gradient and step height discrimination thresholds (P < 0.01) were demonstrated in the participants with PD when compared with the healthy controls, indicating worse position sense at the ankle, knee, and hip. Significant correlations were identified between gradient discrimination and falls incidence (r = 0.55), falls confidence (r = 0.44), and balance (r = 0.63), but not gait (r = 0.21). Step height discrimination was significantly correlated with balance (r = 0.54). Foot roughness discrimination was not significantly different between people with PD and healthy controls and was not significantly correlated with mobility measures (P > .05). These novel tests are psychometrically robust and identify impaired lower limb position sense, which was associated with balance and falls in this sample of PD patients. Interventions targeting somatosensory processing in PD may improve aspects of balance and reduce falls risk. Further research is warranted.


Safety assessment of lauriminodipropionic acid, sodium lauriminodipropionate, and disodium lauriminodipropionate as used in cosmetics.
The Cosmetic Ingredient Review Expert Panel assessed the safety of lauriminodipropionic acid, sodium lauriminodipropionate, and disodium lauriminodipropionate as used in cosmetics. These ingredients function in cosmetics as hair-conditioning agents and surfactant-cleansing agents. The Panel reviewed relevant animal and human data related to the safety of these ingredients in cosmetics. The Panel concluded that lauriminodipropionic acid, sodium lauriminodipropionate, and disodium lauriminodipropionate are safe as cosmetic ingredients in the present practices of use and concentration.


Balloon angioplasty to facilitate autogenous arteriovenous access maturation: a new paradigm for upgrading small-caliber veins, improved function, and surveillance.
Balloon angioplasty maturation is emerging as an important method to increase utilization and improve function of autogenous arteriovenous hemodialysis accesses (AVFs). Through the sequential dilation of small veins, large-diameter AVFs can be created with the inherent benefits of easier cannulation, greater overall surface area, improved patency, and fewer complications. A usable AVF can be created in a shorter amount of time, decreasing the need for dialysis catheters. In addition, selective angioplasty of the AVF inflow and outflow can facilitate improved flow rates and increase access longevity. Our approach, including primary balloon angioplasty during AVF creation, sequential balloon angioplasty maturation, and surveillance fistulagrams will be presented.


Abolition of egg diapause by ablation of suboesophageal ganglion in parental females is compatible with genetic engineering methods.
Microinjection of genetic material into non-diapause eggs is required for genetic engineering of silkworms. Besides diapause could be useful for maintaining transgenic lines, a drawback of this technology is that most standard silkworm strains and experimental lines of interest produce diapausing eggs. Several approaches have been developed to abolish diapause but none are very efficient. Here, we investigated the ablation of the suboesophageal ganglion (SG) in female pupae, which is a source of the hormone required to trigger egg diapause, as a mean to abolish diapause. We showed that SG-ablation is a reliable method to produce nondiapause eggs. Additionally, the challenge associated with lower fecundity of females with SG ablation was resolved by injecting pilocarpine into the mated female. We also investigated the suitability of nondiapause eggs laid by SG-ablated females for transgenesis, targeted mutagenesis, and induction of parthenogenetic development. Our results demonstrated SG-ablation to be a useful and simple method for expanding the possibilities associated with genetic engineering in silkworms.


A comparison of sexual function in primiparous and multiparous women.
Childbirth is one of the most important influencing factors for sexual function. Therefore, this study was conducted with the aim of comparing sexual function in primiparous and multiparous women. This cross-sectional analytical study was performed using systematic random sampling on 420 women in the postpartum period who referred to Bandar Abbas health Centres in 2018. The data were collected using an interview method which consisted of a Female Sexual Function Index questionnaire and a demographic questionnaire. The data analysis was performed using the SPSS Version 23 software. The results showed that sexual dysfunction was lower in multiparous women compared to primiparous women (p = .006). Low sexual activity in primiparous women can be due to less privacy and more time and energy loss. Several factors including housing situation, monthly income, episiotomy incision, and the education level of the couple were influential in the sexual function of the primiparous women (p < .05). Sexual function differs between primiparous and multiparous women in postpartum period and the number of deliveries can affect sexual performance.IMPACT STATEMENTWhat is already known on this subject? Sexual function in humans is affected by a complexity of interactions. Childbirth is among the most one of the important factors that influences sexual function. Pregnancy and childbirth affect all organs of the female body, especially the genital tract, and the resulting changes may cause problems in sexual intercourse. Negative childbirth experiences from previous deliveries can affect sexual performance.What do the results of this study add? Regarding the high prevalence of sexual problems during the postpartum period and the direct impact of this on spousal relationship, and also given the controversial data on the relationship between parity and sexual dysfunction, the present study was conducted to compare postpartum sexual function between primiparous and multiparous women.What are the implications of these findings for clinical practice and/or further research? The sexual and emotional intimacy of couples may be affected due to the changes in women's sexual function as the result of physiological and anatomical changes during pregnancy and postpartum. Therefore, to improve the quality of sexual relations, screening and counselling for sexual disorders should not be limited to pregnancy and postpartum periods, but should also be included in pre-pregnancy counselling centres.


Acid Hydrolases and Autolytic Properties of Protein Bodies and Spherosomes Isolated from Ungerminated Seeds of Sorghum bicolor (Linn.) Moench.
Protein bodies and spherosomes isolated from mature seeds of Sorghum bicolor (Linn.) Moench have measurable activity of acid protease, alpha-glucosidase, beta-glucosidase, beta-galactosidase, phytase, acid pyrophosphatase, p-nitrophenyl phosphatase, and RNase. Protein bodies have largely insoluble activities, and produce soluble protein and soluble amino nitrogen during autolysis. They have the dual function of protein storage and protein catabolism. Spherosomes have considerable amounts of soluble enzymes and autolytically produce soluble amino nitrogen and inorganic phosphate but release little soluble protein. Spherosomes are similar to animal lysosomes but have an additional storage function for protein, phosphorus, and metals. Mature sorghum seed contains the necessary enzymes and substrates to generate two basic metabolites, amino acids and inorganic phosphate.


Airway allergy and viral infection.
There are complex interactions between airway allergy and viral infection. Available evidence suggests that viral respiratory infection can initiate, maintain and activate exacerbation of allergic conditions in respiratory tract. Innate and inflammatory responses to acute viral infection play important roles in its relationship to allergic reactions. On the other hand, biased immune responses toward Th2 caused by an allergic reaction may make the immune response ineffective in combating viral infection. It was previously shown that allergy can increase the expression level of rhinovirus receptors on mucosal epithelial cells. This suggests that airway allergy may increase the risk of rhinovirus infection. We have recently shown that allergy may also increase the expression level of influenza virus receptors. This suggests that airway allergy and viral infection may have a reciprocal interaction. The effect of allergy on the risk and outcome of viral infection needs to be further confirmed in clinical studies and its potential implication for clinical practice should be considered.


A pedunculated left ventricular thrombus in a women with peripartum cardiomyopathy: evaluation by three dimensional echocardiography.
Peripartum cardiomyopathy is a cardiac condition characterized by development of heart failure during the last month of pregnancy or during the first five months of post partum period without any other identifiable cause of heart failure. The hypercoagulable state in the pregnancy along with left ventricular (LV) systolic dysfunction predisposes the patient to thromboembolic complications like intraventricular thrombi. We report a case of a 30-year-old female with peripartum cardiomyopathy along with a highly mobile mass in the LV cavity on two dimensional echocardiography. Three dimensional transthoracic echocardiography clearly showed the pedicle of the mass attached to the interventricular septum along with internal echolucent areas within the mass. Due to denial of the patient to undergo surgery, she was started on oral anticoagulation, with complete dissolution of the mass within one month.


Luminescent platinum complexes with terdentate ligands forming 6-membered chelate rings: advantageous and deleterious effects in N--N--N and N--C--N-coordinated complexes.
Platinum(II) complexes of the form [PtL(n)Cl](+) are reported, containing the N--N--N-coordinating ligands 2,6-di(8-quinolyl)pyridine (L(1)), 2,6-di(8-quinolyl)-4-methoxypyridine (L(2)), or 2,6-di(7-aza-indolyl)-pyridine (L(3)). Metathesis of the chloride co-ligand in [PtL(1)Cl](+) can be accomplished under mild conditions, as exemplified by the formation of the complexes [PtL(1)OMe](+) and [PtL(1)(C[triple bond]C-tfp)](+), in which L(1) remains bound as a terdentate ligand {HC[triple bond]C-tfp = 3,5-bis(trifluoromethyl)-phenylacetylene}. An N--C--N-coordinated, cyclometalated analogue of [PtL(1)Cl](+) has also been prepared, namely, PtL(4)Cl where HL(4) is 1,3-di(8-quinolyl)benzene. The common feature among the six new complexes described here is that they contain 6-membered chelate rings, rather than the usual 5-membered rings that form when more common N--N--N ligands, such as 2,2':6',2''-terpyridine (tpy), bind to Pt(II). All the quinolyl-based complexes are phosphorescent in solution at room temperature, with quantum yields up to 4%. This contrasts with the well-established lack of emission from [Pt(tpy)Cl](+) under these conditions. Density functional theory calculations suggest that the improvement may stem, at least in part, from the relief of ring strain associated with the larger chelate ring size, leading to a more optimal bite angle at the metal, close to 180 degrees , and hence to a stronger ligand field. Consideration of the luminescence parameters, including data at 77 K, together with absorption and electrochemical data and the results of TD-DFT calculations, suggests that the lowest-lying singlet states have metal-to-ligand charge-transfer (MLCT) character, but that the triplet state from which emission occurs has more predominant ligand-centered character. The azaindolyl complex [PtL(3)Cl](+) is not emissive at room temperature, apparently owing to a particularly small radiative rate constant. The cyclometalated complex PtL(4)Cl emits at lower energy than [PtL(1)Cl](+) but, in this case, the luminescence quantum yield is inferior to related complexes with 5-membered chelate rings.


Healthy and tumoral tissue resistivity in wild-type and sparc-/- animal models.
Despite the technological improvement of radiologic, endoscopic and nuclear imaging, the accuracy of diagnostic procedures for tumors can be limited whenever a mass-forming lesion is identified. This is true also because bioptical sampling cannot be properly guided into the lesions so as to puncture neoplastic tissue and to avoid necrotic areas. Under these circumstances, invasive and expensive procedures are still required to obtain diagnosis which is mandatory to plan the most appropriate therapeutic strategy. In order to test if electrical impedance spectroscopy may be helpful in providing further evidence for cancer detection, resistivity measurements were taken on 22 mice, 11 wild-type and 11 sparc-/- (knock out for the protein SPARC: secreted protein acidic and rich in cysteine), bearing mammary carcinomas, by placing a needle-probe into tumor, peritumoral and contralateral healthy fat areas. Tumor resistivity was significantly lower than both peritumoral fat and contralateral fat tissues. Resistivity in sparc-/- mice was lower than wild-type animals. A significant frequency dependence of resistivity was present in tissues analyzed. We conclude that accurate measurements of resistivity may allow to discriminate between tissues with different pathological and/or structural characteristics. Therefore, resistivity measurements could be considered for in vivo detection and differential diagnosis of tumor masses.


Reversible bilateral ureteric obstruction due to a pancreatic pseudocyst.
An unusual case of bilateral ureteric obstruction and hydronephrosis due to pancreatic pseudocyst formation, after an episode of acute pancreatitis is reported. All abnormalities resolved with conservative management. Possible reasons for such ureteric obstruction include periureteric fat necrosis by pancreatic enzymes and compression by the inflammatory mass.


Ultrastructural changes in the cell walls of ripening apple and pear fruit.
Ultrastructural changes in the cell walls of "Calville de San Sauveur" apples (Malus sylvestris Mill) and "Spadona" pear (Pyrus communis L.) fruit were followed during ripening. In apple, structural alterations in cell walls became apparent at advanced stages of softening and showed predominantly dissolution of the middle lamella. In pears softening was also associated with the dissolution of the middle lamella, and in addition a gradual disintegration of fibrillar material throughout the cell wall. In fully ripe fruit almost all of the fibrillar arrangement in the cell wall was lost. Application of enzyme solutions containing polygalacturonase and cellulase to tissue discs from firm pear fruit led to ultrastructural changes observed in naturally ripening pears. In apple polygalacturonase alone was sufficient to dissolve the middle lamella region of the cell walls, as was also found to occur in naturally ripening fruit. In both apple and pear the cell wall areas containing plasmodesmata maintained their structural integrity throughout the ripening process. At advanced stages of ripening vesicles appeared in the vicinity of plasmodesmata.


Choledochal cysts--report of three cases and review.
Three cases of choledochal cyst are presented, with a review of previous publications. We re-emphasize the diagnostic dilemma involved and discuss current surgical management. A new complication is illustrated and an association with polycystic kidneys is reported. Choledochal cysts are uncommon, but correct management ensures a symptom-free future for the patient. Recent reports support cyst excision if technically feasible.


Bose-Einstein condensation in a dilute gas: the first 70 years and some recent experiments (Nobel Lecture).
Bose-Einstein condensates of dilute gases offer a rich field to study fundamental quantum-mechanical processes, manipulation of the speed at which light propogates, observation of atomic pair-formation and superfluidity, or even simulating white dwarf stars. Still more radical applications are on the horizon. However, their initial creation was a masterpiece of experimental physics. After an initial process of laser cooling (which itself won its developers the 1997 Nobel Prize), atoms in a magnetic-optical trap must be safely transferred into a purely magnetic trap, where the condensation process begins at 170 nK and 20 nK a pure condensate of 2000 atoms could be created. More astonishingly, Wieman and Cornell showed these low temperatures could be achieved in "bench scale" equipment rather than the massive pieces normally demanded by cryoscience. For their 1995 discovery of this new state of matter, they were awarded the 2001 Nobel Prize in Physics.


A satellite explosion in the genome of holocentric nematodes.
Centromere sequences in the genome are associated with the formation of kinetochores, where spindle microtubules grow in mitosis. Centromere sequences usually have long tandem repeats (satellites). In holocentric nematodes it is not clear how kinetochores are formed during mitosis; they are distributed throughout the chromosomes. For this reason it appeared of interest to study the satellites in nematodes in order to determine if they offer any clue on how kinetochores are assembled in these species. We have studied the satellites in the genome of six nematode species. We found that the presence of satellites depends on whether the nematode chromosomes are holocentric or monocentric. It turns out that holocentric nematodes are unique because they have a large number of satellites scattered throughout their genome. Their number, length and composition are different in each species: they apparently have very little evolutionary conservation. In contrast, no scattered satellites are found in the monocentric nematode Trichinella spiralis. It appears that the absence/presence of scattered satellites in the genome distinguishes monocentric from holocentric nematodes. We conclude that the presence of satellites is related to the holocentric nature of the chromosomes of most nematodes. Satellites may stabilize a higher order structure of chromatin and facilitate the formation of kinetochores. We also present a new program, SATFIND, which is suited to find satellite sequences.


Effect of Probiotics on the Frequency of CD4+ T-Cells in HIV-Infected Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Depletion of CD4+ T-cells in the gut-associated lymphoid tissue is the hallmark of HIV infection, with only partial restoration by potent antiretroviral therapy (ART). Gut dysbiosis, together with disruption of mucosal integrity contributes to chronic immune activation that further exacerbates the disease. Data from randomized controlled trials in pediatric HIV patients have indicated potential of probiotics in complementing routine ART in managing HIV-associated gastrointestinal complications. We have systematically extracted data from these trials and performed meta-analysis to quantify the effect of probiotics on CD4+ T-cell counts and any adverse events associated with their supplementation. A systematic search through multiple databases yielded three studies that were pooled using fixed-effect model. Risk of bias assessment was done by the Cochrane risk of bias tool and publication bias was assessed by Egger's test. Included studies had moderate risk of bias and Egger's statistics revealed no publication bias (p > 0.05). Pooled analysis showed significant improvement in CD4+ T-cell counts, with mean difference, 123.92 (95% CI: 104.36-143.48), p < 0.0001, no heterogeneity (I2=0) among the included trials. Subgroup analysis also depicted improvement in CD4+ T-cell counts irrespective of treatment duration, in both ART naïve and treated patients. No adverse effects with probiotic consumption were reported. Probiotics supplementation led to an improvement in CD4+ T-cell counts among HIV-infected children with no observed adverse effects. Despite the inherent limitations of included studies, our systematic review would justify more well-designed, large-scale trials in children, which may guide pediatricians on whether to incorporate probiotics as an adjunct therapy to routine ART.


[Cancer of the breast: primary prevention of breast cancer by tamoxifen, eligibility criteria, alternatives to English proposals].
During the spring of 1993, UKCCCR prevention trial group proposed to the french medical community to participate into the international breast cancer prevention trial by tamoxifen set up in Great Britain. In January 1994 this proposal was eventually judged unacceptable in France because of lack of reflexion on primary cancer prevention, medico-legal risks, tamoxifen use risks and the eligibility criteria. A randomized trial could be designed and carried out in France to evaluate the place of tamoxifen in breast cancer prevention in the following settings: post menopausal patient with atypical epithelial hyperplasia or lobular in situ carcinoma.


Wavy line closure for revision of abdominal scars with suture marks in children.
Although various methods are available to treat scars, it is difficult to manage those with suture marks that look like fish-bones, mainly because a large amount of tissue between the suture marks must be discarded with the scar. We report the wavy line closure for revision of abdominal scars with suture marks in three children who were operated on for congenital abdominal diseases. The entire scar, including all the suture marks, was excised using an incision consisting of a pair of smoothly waved lines. This incision makes it possible to reduce the tension on the wound by preserving the normal skin between the suture marks, which is followed by fine scars. The resulting wave-shaped scar is less noticeable and more resistant to postoperative contracture than a straight scar.


Pilot Study of Endothelin Receptor Blockade in Heart Failure with Diastolic Dysfunction and Pulmonary Hypertension (BADDHY-Trial).
In this multi-centre, randomised, placebo-controlled pilot trial, we investigated the clinical and haemodynamic effects of the endothelin-receptor blocker Bosentan in patients with heart failure, preserved ejection fraction and pulmonary hypertension (PH-HFpEF). Eligible patients received either 12 weeks of Bosentan therapy, or a placebo drug. Patients were thereafter followed for a further period of 12 weeks without the study medication. At three points during the study (study Commencement, Week 12 and Week 24), a six-minute walk test (6MWT), echocardiographic and laboratory assessments were performed, as well as a quality of life survey. Right heart catheterisation (RHC) was undertaken at commencement only. The study was aborted early, after an interim analysis favoured the placebo. Six-minute walk distance (6MWD) did not change in the Bosentan group (309.7±96.3m (Commencement), 317.0±126.1m (Week 12), 307.0±84.4m (Week 24); p=0.86), but almost reached statistical significance in the placebo group from 328.8±79.6m, to 361.6±98.2m and 384.0±74.9m (Week 24); p=0.075. In the placebo group, estimated systolic pulmonary artery pressure (measured via echocardiography) significantly decreased (from 62.3±16.7mmHg [Commencement], 45.3±13.9mmHg [Week 12], to 44.6±14.5mmHg [Week 24]; p=0.014) as did right atrial pressure (13.1±5.3 [Commencement], 10.0±3.8 [Week 12], to 9.4±3.2 [Week 24]; p=0.046). Despite this study's limited sample size and premature cessation, it nevertheless suggests that endothelin receptor blockade in patients with PH-HFpEF may have no beneficial effects and could even be detrimental in comparison to a placebo.


More women use prenatal services.
Growing numbers of women understand the importance of prenatal care and are acting to improve their own health and that of their babies, according to a report from the Aga Khan Foundation. In 8 of the foundation's primary health care program areas in Kenya, Bangladesh, India and Pakistan, more women receive prenatal care, more are immunized against tetanus, and more give birth in the presence of a trained attendant than a few years ago. Statistics of improvement vary considerably between programs, not least because of differing levels of acceptance and availability of services when the programs began. However, the overall trend in the 4 countries is towards greater knowledge of health issues and greater readiness to act upon that knowledge. In Mombasa, Kenya, 81% of pregnant women received prenatal care at least once in 1986, and this has since risen to 87%. In Vur, Bangladesh, where only 27% of pregnant women received prenatal care in 1986, this has now risen to 75%.


Cytochemical characterization of mucosubstances in the chick glandular stomach during embryonary and postnatal development.
The chick stomach is composed of two parts: glandular or proventriculus and muscular or gizzard which are morphological and functionally different. Since characterization of the mucosubstances in the adult stomach and its comparison with the embryonary stomach have not been made, we performed the study of the cytochemical characteristics of mucosubstances in the chick glandular stomach during the embryonic and post-natal periods, to obtain information on changes produced in these components during functional differentiation. In this work we established that during development, the epithelial cells of the superficial layer content predominantly glycoproteins and the glycosaminoglycans of the glands decrease when they begin to secrete other compounds, such as proteolytic enzymes necessary for digestion. This sequence of mucosubstances appearance is concordant with the increase of carbonic anhydrase, which reaches its highest specific activity from 15 to 20 days of incubation. In this period hydrochloric acid secretion increases and therefore, glycoprotein secretion becomes necessary to protect the mucous membranes.


Arabidopsis thaliana dehydroascorbate reductase 2: Conformational flexibility during catalysis.
Dehydroascorbate reductase (DHAR) catalyzes the glutathione (GSH)-dependent reduction of dehydroascorbate and plays a direct role in regenerating ascorbic acid, an essential plant antioxidant vital for defense against oxidative stress. DHAR enzymes bear close structural homology to the glutathione transferase (GST) superfamily of enzymes and contain the same active site motif, but most GSTs do not exhibit DHAR activity. The presence of a cysteine at the active site is essential for the catalytic functioning of DHAR, as mutation of this cysteine abolishes the activity. Here we present the crystal structure of DHAR2 from Arabidopsis thaliana with GSH bound to the catalytic cysteine. This structure reveals localized conformational differences around the active site which distinguishes the GSH-bound DHAR2 structure from that of DHAR1. We also unraveled the enzymatic step in which DHAR releases oxidized glutathione (GSSG). To consolidate our structural and kinetic findings, we investigated potential conformational flexibility in DHAR2 by normal mode analysis and found that subdomain mobility could be linked to GSH binding or GSSG release.


Central arterial pressure and arterial pressure pulse: new views entering the second century after Korotkov.
The ubiquitous brachial cuff method gained widespread clinical acceptance for blood pressure recording after confirmation of its prognostic value in 1917. This method displaced radial pulse waveform analysis by sphygmography, which also gave prognostic Information but was difficult to use. Since that time, brachial cuff sphygmomanometry has migrated from the physician's office to 24-hour monitoring and home use, with electronic methods replacing the Korotkov sound technique for determining systolic and diastolic pressure. Detailed instrumental studies, required by regulatory bodies, revealed inaccuracies of all cuff methods for recording true intra-arterial pressure. A major source of inaccuracy in assessing left ventricular load is the amplification of the pressure wave in its transit from the central aorta to upper limb arteries, as extensively studied by Earl H. Wood at the Mayo Clinic in Rochester, Minn, in the 1950s. This limitation can be overcome by combining newer methods using radial artery waveform analysis in conjunction with conventional cuff sphygmomanometry to noninvasively measure the central aortic pressure waveforms. Recent studies using radial tonometry have proved that this is more effective than conventional manometry in predicting cardiovascular events and gauging response to therapy. Measurement of central as well as peripheral arterial pressure and physiology is becoming increasingly used as an office practice and a laboratory procedure.


An in vitro control mechanism for potato stress metabolite biosynthesis.
Ethylene/oxygen (E/O(2)) elevates sesquiterpenoid stress metabolite (SSM) levels in potato (Solanum tuberosum L.) tuber tissue which is reacting hypersensitively. To determine whether E/O(2) retards SSM turnover, a measured amount of rishitin was applied to tuber tissue which was then incubated in air or E/O(2), and rishitin disappearance was monitored. No difference in the rate of rishitin disappearance was detected between air and E/O(2) incubations. However, tissue treated with rishitin and incubated in E/O(2) accumulated intermediates of the katahdinone and phytuberin pathways. This was not the case in rishitin-air treatments. These results suggest the dual involvement of ethylene and SSM intermediates in the regulation of the biosynthesis of SSM, compounds which may serve as phytoalexins.