[Selective induction of effector functions in a T cell clone following antigen presentation in the presence of thymic epithelial cells].
Selective induction of effector functions in a T cell clone, DB14, specific for pigeon cytochrome c 43-58 (p43-58) and restricted to I Ab was analyzed using professional antigen presenting cells (APC), B hybridoma (Th2.58), and various non professional APC, L cells transfected with I Ab (I-Ab L cells), a medullary thymic epithelial cell line (m-TEC) and a cortical thymic epithelial cell line (c-TEC). The m-TEC and c-TEC (m, c-TEC) expressed I-Ab after culturing with interferon-gamma (IFN-gamma). When stimulated with p43-58 in the presence of I-Ab L cells as well as Th2.58 cells, the DB14 cells showed marked proliferation and exhibited significant cytotoxicity against these APC after 18 hr of culture. By contrast, in the presence of m, c-TEC the DB14 cells showed neither proliferation nor cytotoxicity against these TEC but exhibited considerable detachment activity against them. Furthermore DB14 cells became expressed activation markers (CD69 and CD44) after antigen (p43-58) stimulation with m-TEC or c-TEC. Addition of rIL-2 to the culture of DB14 cells, p43-58 and m, c-TEC restored the proliferative responses. However, it was shown that anergy was not involved in the lack of proliferative response of DB14 cells after antigen stimulation with m, c-TEC. The present findings indicate that differences in APC function are present among non-professional APC and suggest that the selective induction of T cell functions can be achieved using appropriate non-professional APC. The characteristic activation of T cells by TEC may be related to their functional roles in situ.


Interaction between Cu and Thiols of Biological and Environmental Importance: Case Study Using Combined Spectrophotometric/Bathocuproine Sulfonate Disodium Salt Hydrate (BCS) Assay.
Considering the biological and ecological importance of Cu-thiol interactions and the discrepancies in previous research, this study focuses on Cu interactions with biologically and ecologically relevant thiols: glutathione (GSH), L-cysteine (L-cys), 3-mercaptopropionic acid (MPA), and thioacetic acid (TAA) in aqueous solution. The addition of Cu(II) to a thiol-containing solution led to a rapid reduction of Cu(II) and the formation of a Cu(I)-thiol complex. The mechanism of Cu(II) reduction and Cu(I) complex formation as well as the kinetics of Cu(I) oxidation strongly depend on the structural properties of the individual thiols investigated. The reducing power of the investigated thiols can be summarized as follows: L-cys ≅ GSH > MPA > TAA. The reaction order, with respect to Cu(I) oxidation, also changes over the time of the reaction course. The deviation of the reaction kinetics from the first order with respect to Cu(I) in the later stages of the reaction course can be attributed to a Fenton-like reaction occurring under low thiol concentration conditions. At high Cu:thiol ratios, in the case of GSH, L-cys, and MPA, the early stage of the reaction course is characterized by high Cu(I) stability, most likely as a result of Cu(I) complexation by the thiols present in excess in the reaction mixture.


Protein phosphorylation and its role in archaeal signal transduction.
Reversible protein phosphorylation is the main mechanism of signal transduction that enables cells to rapidly respond to environmental changes by controlling the functional properties of proteins in response to external stimuli. However, whereas signal transduction is well studied in Eukaryotes and Bacteria, the knowledge in Archaea is still rather scarce. Archaea are special with regard to protein phosphorylation, due to the fact that the two best studied phyla, the Euryarchaeota and Crenarchaeaota, seem to exhibit fundamental differences in regulatory systems. Euryarchaeota (e.g. halophiles, methanogens, thermophiles), like Bacteria and Eukaryotes, rely on bacterial-type two-component signal transduction systems (phosphorylation on His and Asp), as well as on the protein phosphorylation on Ser, Thr and Tyr by Hanks-type protein kinases. Instead, Crenarchaeota (e.g. acidophiles and (hyper)thermophiles) only depend on Hanks-type protein phosphorylation. In this review, the current knowledge of reversible protein phosphorylation in Archaea is presented. It combines results from identified phosphoproteins, biochemical characterization of protein kinases and protein phosphatases as well as target enzymes and first insights into archaeal signal transduction by biochemical, genetic and polyomic studies.


Comparative analysis of the retrosigmoid and lateral supracerebellar infratentorial approaches along the lateral surface of the pontomesencephalic junction: a different perspective.
To quantitatively assess the working distance and angle of attack among the retrosigmoid (RS), lateral supracerebellar (LS), and extreme lateral supracerebellar (EL) views on the lateral surface of the pontomesencephalic junction. Eight sides of silicone-injected fixed cadaveric heads were dissected using the three approaches. All predetermined anatomic points were collected by use of a frameless stereotactic device. The length of exposure and the angle of attack were calculated and compared. Predissection imaging was obtained for illustration. The LS and EL approaches created a horizontal working space as compared with the vertical working space created by the RS approach. The RS view gained less posterior exposure margin than the LS and EL views (posterosuperior margin values: RS, 4.3 +/- 1.7 mm; LS, 6.4 +/- 2.0 mm; EL, 7.3 +/- 2.0 mm; P < 0.001; posteroinferior margin: RS, 2.7 +/- 2.7 mm; LS, 4.9 +/- 2.8 mm; EL, 8.3 +/- 2.5 mm; P < 0.001). When the tentorium is intact, transverse sinus retraction significantly accentuates the field of view by the EL approach compared with the LS approach at both the anteroinferior (P < 0.05) and posteroinferior (P < 0.001) margins. Between the supracerebellar types, the vertical angle of attack was significantly improved and the horizontal angle was significantly decreased when complete venous retraction was performed. The supracerebellar views offer greater advantage over the RS view when the surgeon is working more posteriorly on the pontomesencephalic junction. Between the supracerebellar views, venous retraction creates a significantly wider vertical angle and also improves the exposure when the surgeon is working more inferiorly.


Safety and effectiveness of topical dry mouth products containing olive oil, betaine, and xylitol in reducing xerostomia for polypharmacy-induced dry mouth.
Polypharmacy is a common cause of salivary hypofunction, producing symptoms of dry mouth or xerostomia, especially among older populations. As the number of older people continues to increase, polypharmacy-induced salivary hypofunction is becoming an increasing problem. Many over-the-counter products are available for relieving symptoms of dry mouth, but few have been tested in controlled clinical investigations. The purpose of this investigation was to evaluate the safety and efficacy of a group of topical dry mouth products (toothpaste, mouth rinse, mouth spray and gel) containing olive oil, betaine and xylitol. Forty adults were entered into this single-blinded, open-label, cross-over clinical study and 39 completed all the visits. Subjects were randomly assigned at baseline to using the novel topical dry mouth products daily for 1 week, or to maintain their normal dry mouth routine care. After 1 week, they were crossed over to the other dry mouth regimen. The results demonstrated that the use of the novel topical dry mouth products increased significantly unstimulated whole salivary flow rates, reduced complaints of xerostomia and improved xerostomia-associated quality of life. No clinically significant adverse events were observed. These data suggest that the daily use of topical dry mouth products containing olive oil, betaine and xylitol is safe and effective in relieving symptoms of dry mouth in a population with polypharmacy-induced xerostomia.


[Effect of specific placental proteins--trophoblastic beta 1-glycoprotein chorionic alpha 1-microglobulin--on the proliferation of lymphocytes and malignant fibroblasts in vitro].
A study was made of the action of trophoblastic beta 1-glycoprotein (TBG) and chorionic alpha 1-microglobulin (CAG1) on proliferation of malignant fibroblasts (transplanted L line) and on phytohemagglutinin-stimulated lymphocytes. TBG depressed proliferation of the stimulated lymphocytes and transformed fibroblasts (according to 3H-thymidine incorporation). A dose-response dependence was ascertained. CAG1 did not affect cell division. The inhibitory effect of TBG was seen to be reversed or decreased provided the lymphocyte culture was supplemented with CAG1. The decreased inhibitory effect of TBG in the presence of CAG1 was also noted in the L cell culture. It is likely that in vivo protection of intensely proliferating fetal tissues or tumor from the inhibitors is effected just in this way since placental proteins are synthesized both by embryonic and tumorous cells.


Differential effects of neonatal endotoxemia on heart and kidney carnitine palmitoyl transferase I.
The heart and kidney are both affected in sepsis-related multiple organ failure. Both utilize fatty acid substrates during the neonatal period, and impairment of oxidative metabolism during sepsis could lead to bioenergetic failure. The enzyme carnitine palmitoyl transferase I (CPT I) is important in the control of fat oxidation in the neonatal period. The aim of this study was to determine the effects of sepsis on neonatal cardiac and renal CPT I. Suckling rats received 300 microgram/kg lipopolysaccharide intraperitoneally. Mitochondria were isolated from the heart and kidney after 2 hours. CPT I and II activity were measured radiochemically. Protein levels of M- and L- isoforms of CPT I, both of which are present in heart, were determined by Western blotting. CPT I activity was decreased significantly in the heart but not in the kidney by endotoxemia, whereas CPT II activity was the same in each organ. To investigate the mechanism of this decrease, we carried out Western blotting of the CPT I isoforms in heart mitochondria. Neither M- nor L- isoform was decreased in amount. To determine whether free-radical attack could directly inhibit CPT I activity, control heart mitochondria were incubated with free-radical generating systems. Although hydrogen peroxide had no effect on CPT I activity, the reactive oxygen species nitric oxide, superoxide, and peroxynitrite, all of which are generated in the heart during sepsis, significantly inhibited CPT I activity. The activity of CPT I, a rate-controlling step of fat oxidation, is significantly impaired in heart but not in kidney during neonatal sepsis. This may be caused by direct attack by free radicals, suggesting that antioxidant strategies could be of use in preventing sepsis-related cardiac damage.


A cadmium hydroxide complex of a N3S-donor ligand containing two hydrogen bond donors: synthesis, characterization, and CO2 reactivity.
Treatment of the ebnpa (N-2-(ethylthio)ethyl-N,N-bis((6-neopentylamino-2-pyridyl)methyl)amine) ligand with a molar equivalent amount of Cd(ClO(4))(2).5H(2)O in CH(3)CN followed by the addition of [Me(4)N]OH.5H(2)O yielded the cadmium hydroxide complex [(ebnpaCd)(2)(mu-OH)(2)](ClO(4))(2) (1). Complex 1 has a binuclear cation in the solid-state with secondary hydrogen-bonding and CH/pi interactions involving the ebnpa ligand. In acetonitrile, 1 forms a binuclear/mononuclear equilibrium mixture. The formation of a mononuclear species has been confirmed by conductance measurements of 1 at low concentrations. Variable temperature studies of the binuclear/mononuclear equilibrium provided the standard enthalpy and entropy associated with the formation of the monomer as DeltaH degrees = +31(2) kJ mol(-1) and DeltaS degrees = +108(8) J mol(-1) K(-1), respectively. Enhanced secondary hydrogen-bonding interactions involving the terminal Cd-OH moiety may help to stabilize the mononuclear complex. Treatment of 1 with CO(2) in acetonitrile results in the formation of a binuclear cadmium carbonate complex, [(ebnpaCd)(2)(mu-CO(3))](ClO(4))(2) (2).


Dietary Protein Regulates Female Estrous Cyclicity Partially via Fibroblast Growth Factor 21.
Fibroblast growth factor 21 (FGF21), a hormone predominantly released in the liver, has emerged as a critical endocrine signal of dietary protein intake, but its role in the control of estrous cyclicity by dietary protein remains uncertain. To investigated the role of FGF21 and hypothalamic changes in the regulation of estrous cyclicity by dietary protein intake, female adult Sprague-Dawley rats with normal estrous cycles were fed diets with protein contents of 4% (P4), 8% (P8), 13% (P13), 18% (P18), and 23% (P23). FGF21 liver-specific knockout or wild-type mice were fed P18 or P4 diets to examine the role of liver FGF21 in the control of estrous cyclicity. Dietary protein restriction resulted in no negative effects on estrous cyclicity or ovarian follicular development when the protein content was greater than 8%. Protein restriction at 4% resulted in decreased bodyweight, compromised Kiss-1 expression in the hypothalamus, disturbed estrous cyclicity, and inhibited uterine and ovarian follicular development. The disturbed estrous cyclicity in rats that received the P4 diet was reversed after feeding with the P18 diet. Liver Fgf21 mRNA expressions and serum FGF21 levels were significantly increased as dietary protein content decreased, and loss of hepatic FGF21 delayed the onset of cyclicity disruption in rats fed with the P4 diet, possibly due to the regulation of insulin-like growth factor-1. Collectively, severe dietary protein restriction results in the cessation of estrous cyclicity and ovarian follicle development, and hepatic FGF21 and hypothalamic Kiss-1 were partially required for this process.


[Initial experiences with VATS lobectomy].
The authors analyse the experience of videothoracoscopic (VATS) lung lobectomies performed since December 2010 at the Thoracic Surgery Department of Markusovszky University Teaching Hospital. 78 patients (44 men and 34 women) underwent VATS lobectomy. The average age was 61.2 years ranging from 30 to 80. The indications were peripheral malignancy (35 cases) or the suspicion of that (43 cases), presence of curable distant metastasis was not considered as contraindication. In the initial period the operation time was quite long, but shortly after the duration of surgery became almost similar to lobectomies via thoracotomy. Late reoperation was performed in two cases, one for chronic pneumothorax and one for port-site metastasis. 10 vessel and two bronchial injuries occurred, eight of them needed conversion into axillary thoracotomy (conversion rate 10.26%). The postoperative pain was significantly less than after thoracotomy. VATS lobectomy is a safe procedure with less surgical stress and without oncological compromise.


Prevention of Rotavirus Diarrhea in Suckling Rats by a Specific Fermented Milk Concentrate with Prebiotic Mixture.
Several microbial modulatory concepts, such as certain probiotics and prebiotics, confer protection against gastrointestinal infections, among which is acute diarrhea caused by the rotavirus (RV). Other microbiota modulators, such as postbiotics, produced during fermentation, might also have the potential to counteract RV infection. In light of this, a fermented milk, made by using Bifidobacterium breve C50 (BbC50) and Streptococcus thermophilus 065 (St065) with a prebiotic mixture-short chain galactooligosaccharides/long chain fructooligosaccharides (scGOS/lcFOS 9:1)-with potential to impact the intestinal microbiota composition was tested. An RV infected rat model was used to evaluate the amelioration of the infectious process and the improvement of the immune response induced by the fermented milk with prebiotic mixture. The dietary intervention caused a reduction in the clinical symptoms of diarrhea, such as severity and incidence. Furthermore, a modulation of the immune response was observed, which might enhance the reduction of the associated diarrhea. In addition, the fermented milk with prebiotic mixture was able to bind the virus and reduce its clearance. In conclusion, the postbiotic components in the fermented milk in combination with the prebiotics used here showed protective properties against RV infection.


Invited Article: Deep Impact instrument calibration.
Calibration of NASA's Deep Impact spacecraft instruments allows reliable scientific interpretation of the images and spectra returned from comet Tempel 1. Calibrations of the four onboard remote sensing imaging instruments have been performed in the areas of geometric calibration, spatial resolution, spectral resolution, and radiometric response. Error sources such as noise (random, coherent, encoding, data compression), detector readout artifacts, scattered light, and radiation interactions have been quantified. The point spread functions (PSFs) of the medium resolution instrument and its twin impactor targeting sensor are near the theoretical minimum [ approximately 1.7 pixels full width at half maximum (FWHM)]. However, the high resolution instrument camera was found to be out of focus with a PSF FWHM of approximately 9 pixels. The charge coupled device (CCD) read noise is approximately 1 DN. Electrical cross-talk between the CCD detector quadrants is correctable to <2 DN. The IR spectrometer response nonlinearity is correctable to approximately 1%. Spectrometer read noise is approximately 2 DN. The variation in zero-exposure signal level with time and spectrometer temperature is not fully characterized; currently corrections are good to approximately 10 DN at best. Wavelength mapping onto the detector is known within 1 pixel; spectral lines have a FWHM of approximately 2 pixels. About 1% of the IR detector pixels behave badly and remain uncalibrated. The spectrometer exhibits a faint ghost image from reflection off a beamsplitter. Instrument absolute radiometric calibration accuracies were determined generally to <10% using star imaging. Flat-field calibration reduces pixel-to-pixel response differences to approximately 0.5% for the cameras and <2% for the spectrometer. A standard calibration image processing pipeline is used to produce archival image files for analysis by researchers.


Inactivation of the constitutively active ghrelin receptor attenuates limbic seizure activity in rodents.
Ghrelin is a pleiotropic neuropeptide that has been recently implicated in epilepsy. Animal studies performed to date indicate that ghrelin has anticonvulsant properties; however, its mechanism of anticonvulsant action is unknown. Here we show that the anticonvulsant effects of ghrelin are mediated via the growth hormone secretagogue receptor (GHSR). To our surprise, however, we found that the GHSR knockout mice had a higher seizure threshold than their wild-type littermates when treated with pilocarpine. Using both in vivo and in vitro models, we further discovered that inverse agonism and desensitization/internalization of the GHSR attenuate limbic seizures in rats and epileptiform activity in hippocampal slices. This constitutes a novel mechanism of anticonvulsant action, whereby an endogenous agonist reduces the activity of a constitutively active receptor.


Recurrent selection for corn earworm (Lepidoptera: Noctuidae) resistance in three closely related corn southern synthetics.
Plant resistance offers a good alternative to pesticides for protecting corn (Zea mays L.) from attack by corn earworm, Helicoverpa zea (Boddie). The GT-CEW-RS8 synthetic is a breeding population with some resistance to corn earworm, but based on variability for this trait, further improvement was possible in this population. S1 recurrent selection for corn earworm resistance was conducted to improve three synthetics derived from GT-CEW-RS8. The objective of this research was to study the effectiveness of these selection programs to increase insect resistance and maintain agronomic performance. Cycles of selection for each population were evaluated under four environments. Significant gains in resistance were realized, but all three synthetics derived from GT-CEW-RS8 showed a negative response for yield. However, yield losses were not very dramatic for 66RM4 and inbreeding depression would not affect the yield performance in hybrid combination. Selection for yield done simultaneously with selection for reducing ear damage by corn earworm and husk tightness could assist in avoiding decreased yield.


Plasma 25-hydroxyvitamin D and regulation of the renin-angiotensin system in humans.
Vitamin D regulates the renin-angiotensin system (RAS) in experimental animals, but corresponding human data are limited. We examined the relation between plasma 25-hydroxyvitamin D and elements of the RAS in 184 normotensive individuals in high sodium balance; these included circulating levels of plasma renin activity and angiotensin II (Ang II) and the renal plasma flow response to infused Ang II, which is an indirect measure of the intrinsic RAS activity in the kidney. Compared with individuals with sufficient 25-hydroxyvitamin D levels (> or = 30.0 ng/mL), those with insufficiency (15.0 to 29.9 ng/mL) and deficiency (<15.0 ng/mL) had higher circulating Ang II levels (P for trend=0.03). Moreover, those with vitamin D deficiency had significantly blunted renal plasma flow responses to infused Ang II (mean decrease of 115 mL/min per 1.73 m(2) in renal plasma flow versus 145 mL/min per 1.73 m(2) among those with sufficient vitamin D levels; P for trend=0.009). Although plasma renin activity was higher among individuals with insufficient levels of vitamin D, the result was not statistically significant. These data suggest that low plasma 25-hydroxyvitamin D levels may result in upregulation of the RAS in otherwise healthy humans.


Cytokine profile as diagnostic and prognostic factor in neonatal sepsis.
Antecedents: The serum levels of some cytokines can be useful in the diagnosis of neonatal sepsis; the prognostic value of a cytokine profile has not, to our knowledge, been explored in this disease. Objective: The objective of this study is to evaluate the diagnostic value of the serum levels of cytokines IL-1, -2, -4, -5, -6, -7, -8, -10, -12, -13, and -17, TNF, IFNγ, G-CSF, GM-CSF, MCP1, and MIP1β in neonates with high risk of developing sepsis. Methods: Sepsis was evaluated in 96 high-risk neonates. We assessed cytokine levels on hospital admission and during or not during sepsis. Results: Fifty (52%) presented sepsis (26 early and 24 late). Sepsis was associated with high levels of IL-6, IL-10, G-CSF, and MCP1 and low levels of IFNγ, early sepsis with high levels of IL-6 and G-CSF, severe sepsis with high levels of IL-6 and IL-10, while deaths or sequelae was associated with low levels of IL-4, IL-12, IFNγ, and high levels of GM-CSF. IL-6 values of ≥40.1 pg/mL were associated with the development of any type of sepsis (relative risk [RR]: 1.70; 95% confidence interval [95% CI]: 1.18-2.24; p = .01), while IL-6 values of ≥44.9 pg/mL were associated with early sepsis (RR: 1.29; 95% CI: 1.29-4.56; p = .01). Conclusion: In neonates with high risk for the development of sepsis, there is an association between levels of IL-6, IL-10, and G-SCF and the disease development/outcome.


Calcineurin B1 Deficiency in Glial Cells Reduces Gastrointestinal Motility and Results in Maldigestion and/or Malabsorption in Mice.
Calcineurin is a Ca2+/calmodulin-dependent protein phosphatase abundantly expressed in the nervous system. To investigate the roles of calcineurin in glial cells, we previously generated glial calcineurin B1-conditional knockout (CKO) mice and found that these mice displayed dysfunction of enteric glial cells, mucosal degeneration and inflammation in the small intestine, and growth retardation and postweaning death, suggesting a novel role of calcineurin in enteric glial cells. Although these findings raised a possibility that abnormalities in calcineurin B1-deficient enteric glial cells may cause dysregulation of gastrointestinal motility and result in maldigestion and/or malabsorption in the CKO mice, these issues remain to be elucidated. In the present study, we showed that gastrointestinal motility was reduced in the CKO mice. Degeneration of mucosal epithelium was observed in the small intestine. Glucose levels were decreased in serum, whereas starch, glucose, and lipid levels were increased in feces. Thus, calcineurin B1 deficiency in glial cells reduces gastrointestinal motility, induces mucosal epithelium degeneration in the small intestine, and results in maldigestion and/or malabsorption in mice, further supporting the important role of calcineurin in enteric glial cells.


Aging and the production effect: a test of the distinctiveness account.
The production effect refers to the benefit in memory for items read aloud relative to items read silently during study. Previous research has explained this benefit as due to distinctiveness, attributable to the additional dimension of encoding for the aloud items that is later used during retrieval. We investigated the production effect in older adults, a population known to have difficulty using distinctiveness to assist remembering. Results showed a production benefit for both younger and older adults on both recall and recognition tests; however, this benefit was reliably smaller for older adults on both measures of memory. This pattern addresses both a theoretical issue and an applied issue: (1) that the role of distinctiveness is pivotal in the production effect, and (2) that production does assist older people in remembering.


The impact of uphill cycling and bicycle suspension on downhill performance during cross-country mountain biking.
Non-propulsive work demand has been linked to reduced energetic economy of cross-country mountain biking. The purpose of this study was to determine mechanical, physiological and performance differences and observe economy while riding a downhill section of a cross-country course prior to and following the metabolic "load" of a climb at race pace under two conditions (hardtail and full suspension) expected to alter vibration damping mechanics. Participants completed 1 lap of the track incorporating the same downhill section twice, under two conditions (hardtail and full suspension). Performance was determined by time to complete overall lap and specific terrain sections. Power, cadence, heart rate and oxygen consumption were sampled and logged every second while triaxial accelerometers recorded accelerations (128 Hz) to quantify vibration. No differences between performance times (P = 0.65) or power outputs (P = 0.61) were observed while physiological demand of loaded downhill riding was significantly greater (P < 0.0001) than unloaded. Full suspension decreased total vibrations experienced (P < 0.01) but had no effect on performance (P = 0.97) or physiological (P > 0.05) measures. This study showed minimal advantage of a full suspension bike in our trial, with further investigations over a full race distance warranted.


Simultaneous separation of atenolol enantiomers and its acid/alkaline degradation impurities on mixed-mode chiral ligand exchange stationary phases.
Simultaneous separation of the enantiomer and impurities is a huge challenge for the quality control of the chiral drug. In this work, mixed-mode chiral ligand exchange stationary phases (CSPs) modified by octyl and sulfhydryl ligands were prepared by vapor deposition and click chemistry methods. Qualitative and quantitative determination of the prepared CSPs were achieved by Fourier transform infrared spectroscopy, solid-state 13 C CP/MAS NMR, and elemental analysis. The chiral resolution of CSPs was investigated through a comprehensively chromatographic evaluation of various racemates. Besides, the thermodynamic experiment was carried out to elucidate the contribution of hydrophobic ligand to the improvement of chiral recognition and selectivity. Atenolol and its degradation products were analyzed on the synthesized CSPs and compared with the commercial chiral column. A good separation of atenolol enantiomers from its acid and alkaline degradation impurities was simultaneously achieved on the C8 /L-Hypro CSP. This new CSP is expected to have more applications in the quality control of other chiral drugs.


[Differential-diagnostic value of changes in nuclear ploidy of prostate epithelial cells during the carcinogenesis process].
Ploidometry of prostatic cell nuclei at different stages of carcinogenesis was made in 80 patients using 8 mcm histological sections stained by Felgen. Ploidy of 1332 nuclei of prostatic epithelial cells and 396 lymphocytes (tissue ploidy standard) was studied on computer image analyser "Imager-CG (computer program version Avtan-San). The study covered interphasic nuclei of the cells of the germinative zones of normal and hyperplastic structures, areas of intraepithelial neoplasia and adenocarcinoma with various disdifferentiation degree. Significant differences in ploidy and proliferative activity of prostatic cells at different carcinogenesis stages were revealed. Ploidometry data may help to take decision in differential histopathological diagnosis of benign and malignant tumors of the prostate.


High-resolution laser surface scanning for patient registration in cranial computer-assisted surgery.
Markerless patient registration is a new procedure that may reduce logistical efforts and possibly also the radiation load on the patients prior to a computer-assisted intervention. Congruent surfaces, such as bone surfaces or skin surfaces, represented in a data set and in the surgical site, can be overlapped using surface-matching. Previous studies describing this kind of markerless registration, however, show inaccuracies of up to 10 mm during computer-assisted navigation. Furthermore, these systems use less than 1000 surface points of the soft tissue surface in order to establish a correlation between the patient and the data set. Previous papers did not answer the question whether it is this scanning resolution that induces these inaccuracies in registration or rather intraoperative skin deformations. In the present study therefore a new navigation system (SSN++) was used which is able to register up to 180,000 surface points of the surgical site. SSN++ is an infrared navigation system enlarged by a Minolta VI 900 3D volume digitizer. Three different kinds of laser scan-resolution were used for data correlation. An additional congruence analysis was performed in order to assess the geometry of the matched skin surfaces. 22 patients suffering from different cranial diseases (tumors, bony malformations, foreign bodies) were prepared for a computer-assisted intervention. Intraoral titanium-markers, rigidly fixed on the patients by a maxillary splint, were placed as targets while the CT data sets were made. These targets were - after markerless laser scan registration of the patients - supposed to serve for validating the new high-resolution navigation system SSN++. The accuracy of markerless laser scan registration depends on the intraoperative laser scan's resolution. A high accuracy of the data correlation can be achieved if the number of the laser scan cloud points is about the same as the number of voxels of the corresponding surface on the CT data set. A reduction of the laser scan cloud points to less than 10 % compared to the number of voxels of the CT surface, however, leads to a significant loss of accuracy after markerless patient registration. The markerless laser scan registration of the surgical site may achieve the same accuracy as a patient registration made by rigidly fixed titanium screws (mean accuracy: 1.2 mm) as long as a high-resolution laser scan is being used.


Polyselenide Anchoring Using Transition-Metal Disulfides for Enhanced Lithium-Selenium Batteries.
While selenium has recently been proposed as a lithium battery cathode as a promising alternative to a lithium-sulfur battery, dissolution of intermediate species should be resolved to improve its cycle stability. Here, we report the promising results of transition-metal disulfides as an anchoring material and the underlying origin for preventing active material loss from the electrode using density functional theory calculations. Group 5 and 4 disulfides (VS2, NbS2, TaS2, TiS2, ZrS2, and HfS2) in particular show anchoring capabilities superior to those of group 6 disulfides (CrS2, MoS2, and WS2). The governing interaction controlling the latter relative anchoring strengths is shown to be charge transfer as understood by crystal-field theory. The current findings and methodologies provide novel chemical insight for the further design of inorganic anchoring materials for both lithium-selenium and lithium-sulfur batteries.


Forced Interactions: Ionic Polymers at Charged Surfactant Interfaces.
Characterizing electrostatic interactions at heterogeneous interfaces is critical for developing a fundamental description of the dynamic processes at charged interfaces. Water-in-oil reverse micelles (RMs) offer a high degree of tunability across composition, polarity, and temperature, making them ideal systems for studying interactions at heterogeneous liquid-liquid interfaces. In the present study, we use a combination of ultrafast two-dimensional infrared spectroscopy and molecular dynamics (MD) simulations to determine the picosecond interfacial dynamics in RMs containing binary compositions of sorbitan monostearate and anionic or cationic cosurfactants, which are used to tune the ratio of charged to nonionic surfactants at the interface. The positively charged polyethylenimine (PEI) polymer is encapsulated within the RMs, and the carbonyl stretching mode of sorbitan monostearate reports on the interfacial hydrogen-bond populations and dynamics. The results show that hydrogen-bond populations are altered through the inclusion of both negatively and positively charged cosurfactants. Charged surfactants increase interfacial water penetration into the surfactant layer, and the surface localization of polymers decreases water penetration. Local hydrogen-bond dynamics undergo a slowdown with the inclusion of charged surfactants, and the encapsulation of polymers results in similar effects, irrespective of the charge.


[Observation of Child Development in a Uterine Cervical Cancer Patient Who Received Chemotherapy during Pregnancy].
This report describes the case of a 36-year-old woman with stage ⅠB1 cervical adenocarcinoma that was diagnosed when her fetus was at 19 weeks of gestation. Both she and her family strongly hoped that her pregnancy could continue. After approval by the Ethics Committee of our hospital, she was treated with paclitaxel and carboplatin. At 32 weeks of gestation, the patient delivered a 1,518 g female newborn via cesarean section. A radical hysterectomy with pelvic lymphadenectomy was performed after delivery. The newborn had Apgar scores of 3 at 1 minute and 5 at 5 minutes. No external malformations were observed. The Kyoto Scale of Psychological Development 2001 was used for cognitive assessment. Although the Language-Social Developmental Quotient score was 65 and developmental delay was observed at 1 year 8 months, the score improved to 98 at 3 years 5 months. The child was followed up until the age of 6 years 2 months and showed no developmental delay. Presentation of this case is important because there are few reports in Japan about the development of children of cancer patients who are exposed to anticancer drugs during pregnancy.


Influence of the route of administration on the pharmacokinetics of pirprofen enantiomers in the rat.
The pharmacokinetics of the enantiomers of the non-steroidal anti-inflammatory drug pirprofen were studied in male Sprague-Dawley rats after oral and intravenous (iv) doses of the racemate. No significant differences were detected between the enantiomers after oral or iv dosing in t1/2, Vd, or sigma Xu. However, the R:S area under the plasma concentration (AUC) ratio after oral doses (0.92 +/- 0.13) was slightly but significantly lower than after matching iv doses (1.05 +/- 0.036). The absolute bioavailability of the active S-enantiomer (78.5%) after oral doses was higher than the inactive R-enantiomer (69.3%). The plasma protein binding of both enantiomers was saturable over a fivefold range of plasma concentrations. At higher plasma concentrations, the S-enantiomer was less bound than the R-enantiomer. In an in vitro experiment using everted rat jejunum, no chiral inversion was discernible. The dependency of the AUC ratio of the enantiomers on the route of administration may be due to stereoselective first-pass metabolism.


[Helicobacter pylori and molecular biology--virulence, diagnosis and vaccine development].
The discovery of H. pylori as the etiologic agent of chronic antral type B gastritis and the finding that H.pylori is involved in the pathogenesis of gastroduodenal ulcer disease and gastric carcinoma have triggered intensive research about this organism. After overcoming considerable initial difficulties, researchers succeeded in adapting the instruments of molecular biology to the study of this highly fastidious organism. This has led to a rapid increase of knowledge concerning the basis of H.pylori virulence (as well as that of the related animal pathogens H. mustelae and H. felis) and to the development of molecular methods for the purposes of diagnosis and epidemiological research. The latest application of molecular biology in this area is the use of recombinant proteins for the development of an H.pylori vaccine. This review gives an overview of this rapidly developing field.


Perfusion Index: An Indicator of Success During Endoscopic Thoracic Sympathectomy for Hyperhidrosis.
Endoscopic thoracic sympathectomy (ETS) is indicated for refractory hyperhidrosis. The pulse oximetry-derived perfusion index (PI) quantifies pulsatile blood flow at the oximeter. Thoracic sympathectomy increases blood flow; thus we postulate it will reliably increase PI. We evaluated the ipsilateral finger PI as a predictor of successful sympathectomy during ETS. After institutional review board approval and informed consent, 100 adult patients undergoing bilateral ETS were studied. Finger and earlobe pulse oximetry probes were placed. Hemodynamic variables and PI were continuously monitored. PI data were collected before and every minute after sympathectomy for 5 minutes and then at 10 minutes. We defined a successful sympathectomy by at least a 50% increase of the PI on the ipsilateral arm. A repeated measures analysis of variance was conducted to determine overall model significance (p ≤ 0.05). Left sympathectomy was associated with a mean 240% increase in PI (p < 0.0001) during the first consecutive 10 minutes, whereas the right side exhibited a mean 236% increase in PI (p < 0.0001). Statistically significant differences were observed between the mean baseline PI value ± the standard error of the mean and time intervals (1, 2, 3, 4, 5, and 10 minutes after baseline) on both the left and right sides for all time intervals. The hemodynamics remained constant throughout the study period. All patients had postoperative resolution of their hyperhidrosis symptoms. In patients with hyperhidrosis of the upper extremities, intraoperative PI derived from an ipsilateral finger pulse oximeter is an intraoperative marker for successful thoracic sympathectomy.


Use of animal species data in environmental impact assessments.
Environmental Impact Assessments (EIAs) should ideally help minimize adverse effects on biological diversity by considering impacts of projects on wide ranges of species. This paper investigates how recent Dutch EIAs included the species comprising animal diversity. We present results of two studies on fauna data used in the EIAs. Objectives were to determine for different taxa (a) the relative representation of species in Environmental Impact Statements (EISs); (b) the extent to which EISs referred to specific species and the accuracy of survey data referred to; and (c) apparent roles of different EIA actors in species inclusion. EIAs were found to use data on various taxa but on limited numbers of species. The frequency with which taxa were included varied significantly. Birds were most frequently included, followed by mammals, amphibians, and other species groups. The quality of data on birds exceeded that regarding other vertebrates. Our results indicate that (a) EIA working groups of independent experts were the most influential in determining the data to be used; (b) on average, proponents included data more often than required by guidelines; and (c) in 30 to 40% of the EIAs, the participation of nongovernmental organizations prompted use of data. Despite the key role of experts in data inclusion, the taxon rankings found in the EIAs showed little deviation from those observed in studies on people's preferences for species. Given the limited ranges of species considered, it is doubtful that the EIAs examined effectively contributed to conserving animal species diversity.


Access to Pharmacotherapy Amongst Women with Bipolar Disorder during Pregnancy: a Preliminary Study.
Bipolar disorder among pregnant women has deleterious effects on birth and child outcomes and is currently under-detected, not addressed effectively, or exacerbated through inappropriate treatment. The goal of this study was to identify perspectives of pregnant and postpartum women with bipolar disorder on barriers and facilitators to psychiatric treatment during pregnancy. In-depth interviews were conducted with pregnant and postpartum women who scored ≥ 10 on the Edinburgh Postnatal Depression Scale and met DSM-IV criteria for bipolar disorder I, II or not otherwise specified using the Mini International Neuropsychiatric Interview version 5.0. Interviews were transcribed, and resulting data were analyzed using a grounded theory approach to identify barriers and facilitators to bipolar disorder treatment access in pregnancy. Participant identified barriers included perception that psychiatric providers lack training and experience in the treatment of psychiatric illness during pregnancy, are reluctant to treat bipolar disorder among pregnant women, and believe that pharmacotherapy is not needed for psychiatric illness during pregnancy. Facilitators included participants' perception that providers' acknowledge risks associated with untreated or undertreated psychiatric illness during pregnancy and provide psycho-education about the risks, benefits and alternatives to pharmacotherapy. Psychiatric providers are critically important to the treatment of bipolar disorder and need knowledge and skills necessary to provide care during the perinatal period. Advancing psychiatric providers' knowledge/skills may improve access to pharmacotherapy for pregnant women with bipolar disorder.


Simulation of Phosphorus Chemistry, Uptake and Utilisation by Winter Wheat.
The phosphorus (P) supply from soils is crucial to crop production. Given the complexity involved in P-cycling, a model that can simulate the major P-cycling processes and link with other nutrients and environmental factors, e.g., soil temperature and moisture, would be a useful tool. The aim of this study was to describe a process-based P module added to the SPACSYS (Soil Plant and Atmosphere Continuum System) model and to evaluate its predictive capability on the dynamics of P content in crops and the impact of soil P status on crop growth. A P-cycling module was developed and linked to other modules included in the SPACSYS model. We used a winter wheat (Triticum aestivum, cv Xi-19) field experiment at Rothamsted Research in Harpenden to calibrate and validate the model. Model performance statistics show that the model simulated aboveground dry matter, P accumulation and soil moisture dynamics reasonably well. Simulated dynamics of soil nitrate and ammonium were close to the observed data when P fertiliser was applied. However, there are large discrepancies in fields without P fertiliser. This study demonstrated that the SPACSYS model was able to investigate the interactions between carbon, nitrogen, P and water in a single process-based model after the tested P module was implemented.


Multi-task learning for cross-platform siRNA efficacy prediction: an in-silico study.
Gene silencing using exogenous small interfering RNAs (siRNAs) is now a widespread molecular tool for gene functional study and new-drug target identification. The key mechanism in this technique is to design efficient siRNAs that incorporated into the RNA-induced silencing complexes (RISC) to bind and interact with the mRNA targets to repress their translations to proteins. Although considerable progress has been made in the computational analysis of siRNA binding efficacy, few joint analysis of different RNAi experiments conducted under different experimental scenarios has been done in research so far, while the joint analysis is an important issue in cross-platform siRNA efficacy prediction. A collective analysis of RNAi mechanisms for different datasets and experimental conditions can often provide new clues on the design of potent siRNAs. An elegant multi-task learning paradigm for cross-platform siRNA efficacy prediction is proposed. Experimental studies were performed on a large dataset of siRNA sequences which encompass several RNAi experiments recently conducted by different research groups. By using our multi-task learning method, the synergy among different experiments is exploited and an efficient multi-task predictor for siRNA efficacy prediction is obtained. The 19 most popular biological features for siRNA according to their jointly importance in multi-task learning were ranked. Furthermore, the hypothesis is validated out that the siRNA binding efficacy on different messenger RNAs(mRNAs) have different conditional distribution, thus the multi-task learning can be conducted by viewing tasks at an "mRNA"-level rather than at the "experiment"-level. Such distribution diversity derived from siRNAs bound to different mRNAs help indicate that the properties of target mRNA have important implications on the siRNA binding efficacy. The knowledge gained from our study provides useful insights on how to analyze various cross-platform RNAi data for uncovering of their complex mechanism.


pH tolerance in Bacillus: alkaliphiles versus non-alkaliphiles.
Monovalent cation/proton antiporters that catalyse electrogenic uptake of H+ in exchange for cytoplasmic K+ and/or Na+ are centrally involved in bacterial pH homeostasis under alkaline challenge. Systematic attempts have identified some, but not yet all, of the genes encoding such antiporters that participate in pH homeostasis in the neutrophilic Bacillus subtilis and the extremely alkaliphilic Bacillus firmus OF4. In each organism there are at least three distinct antiporters involved in pH homeostasis. They differ in cation requirement, with pH homeostasis specifically utilizing Na+/H+ antiport in the alkaliphile and using either Na+ or K+/H+ antiport in B. subtilis. Some of the antiporters involved in pH homeostasis are constitutive and are in place to respond to sudden pH shifts, but there is also an inducible component. At least two sets of homologous antiporters (NhaC and Mrp/Pha) function in both alkaliphiles and neutrophiles. An additional antiporter of a different transport protein family, the Gram-positive tetracycline-metal/H+ antiporter, is important in pH homeostasis in B. subtilis but has not yet been shown to be present in any alkaliphile. There are also differences outside of the antiporters themselves that contribute to the greater capacity of the alkaliphiles for pH homeostasis, including cation re-entry capacity and possible surface properties.


Effect of Calcium Foliar Spray Technique on Mechanical Properties of Strawberries.
The calcium fertilization of strawberry plants (Fragaria × ananassa Duchesne) was evaluated using two types of nozzles, with two liquid pressure levels and two driving speeds. The calcium content of the leaves and fruit were analyzed via flame photometry. Higher leaf calcium content was found in plots sprayed with standard nozzles, while higher fruit calcium content was observed for those sprayed with air induction nozzles. The fruit quality was assessed by determining the basic physical and mechanical properties, using uniaxial compression tests integrated with surface pressure measurements. Different spraying techniques influenced the mechanical resistance of the fruit. A spraying speed of 5 km/h and an operating pressure of 0.4 MPa significantly increased the firmness of the fruit by ~66%, the critical load level by 36%, and the maximum surface pressure by up to 38%, but did not increase the geometrical parameters of the strawberries. Regular foliar feeding during harvest could improve the mechanical strength of strawberries. An appropriate spraying technique with a calcium agent could effectively improve the mechanical properties of the delicate fruit, which is particularly important for limiting losses during harvesting, transportation, and storage.


Eight-year observation and comparative study of specific pathogen-free cats experimentally infected with feline immunodeficiency virus (FIV) subtypes A and B: terminal acquired immunodeficiency syndrome in a cat infected with FIV petaluma strain.
Three specific pathogen-free cats experimentally infected with feline immunodeficiency virus (FIV) strains Petaluma, TM1 and TM2, respectively were observed for over 8 years. Without showing any significant clinical signs of immunodeficiency syndrome (AIDS) for 8 years and 4 months of asymptomatic phase, the Petaluma-infected cat exhibited severe stomatitis/gingivitis, anorexia, emaciation, hematological and immunological disorders such as severe anemia, lymphopenia, thrombocytopenia, and decrease of CD4/CD8 ratio to 0.075, and finally died with hemoperitoneum at 8 years and 8 months post-infection. Histopathological studies revealed that the cat had systemic lymphoid atrophy and bone marrow disorders indicating acute myelocytic leukemia (aleukemic type). Plasma viral titer of the cat at AIDS phase was considerably high and anti-FIV antibody titer was slightly low as compared with the other FIV-infected cats. In addition, immunoblotting analysis using serially collected serum/plasma samples of these cats revealed that antibodies against FIV proteins were induced in all the infected cats, however in the Petaluma-infected cat anti-Gag antibodies disappeared during the asymptomatic period. These results suggested that plasma viral load and anti-FIV Gag antibody response correlated with disease progression, and supported FIV-infected cats as a suitable animal model of human AIDS.


Catalytic promiscuity in Pseudomonas aeruginosa arylsulfatase as an example of chemistry-driven protein evolution.
In recent years, it has become increasingly clear that many enzymes are catalytically "promiscuous". This can provide a springboard for protein evolution, allowing enzymes to acquire novel functionality without compromising their native activities. We present here a detailed study of Pseudomonas aeruginosa arylsulfatase (PAS), which catalyzes the hydrolysis of a number of chemically distinct substrates, with proficiencies comparable to that towards its native reaction. We demonstrate that the main driving force for the promiscuity is the ability to exploit the electrostatic preorganization of the active site for the native substrate, providing an example of chemistry-driven protein evolution.


Serum albumin level correlates with disease severity in patients with Hemorrhagic Fever with Renal Syndrome.
Hypoalbuminemia frequently occurs in Hemorrhagic Fever with Renal Syndrome (HFRS), but clinical significance of hypoalbuminemia is not well known. This study was designed to evaluate hypoalbuminemia as a marker of severity of disease in patients with HFRS. We evaluated the relationship between the level of serum albumin and clinical parameters representing the severity of disease in 144 patients with HFRS. The patients were divided into three groups based on the level of serum albumin; Group I (normal serum albumin), Group II (serum albumin <3.5 g/dL and >/=3.0 g/dL), and Group III (serum albumin <3.0 g/dL). Of the total of 144 patients, 42 patients (29.2%) were categorized as Group I, 39 patients (27.1%) as Group II, and 63 patients (43.8%) as Group III. Group III had a higher rate of incidence in episode of hypotension, pulmonary edema than did Group I and Group II. The lowest level of serum albumin was positively correlated with platelet count (r=0.505, p<0.001) and was negatively correlated with leukocyte count (r=-0.329, p<0.001), BUN (r=-0.484, p<0.001), serum creatinine (r=-0.394, p<0.001), and AST (r=-0.251, p=0.002). Our data suggest that hypoalbuminemia frequently occurs in the acute stage of HFRS, and level of serum albumin is associated with the disease severity of HFRS.


Low grade inflammation in juvenile obesity and type 1 diabetes associated with early signs of atherosclerosis.
Subclinical inflammation has been implicated in the initiation and/or progression of atherosclerosis. Diabetes mellitus and obesity are risk factors for atherosclerosis, and asymptomatic low grade inflammation occurs prior to overt vascular lesions in these patients. In contrast to adults, little information exists concerning low grade inflammation in young type 1 diabetes and juvenile obesity. To investigate low grade inflammation and immune activation in juvenile diabetes mellitus and obesity. hs-CRP, soluble interleukin-2 receptor (sIL-2R), C-peptide, insulin, cortisol, vitamin B12, folic acid, leptin, and homocysteine were determined in 148 patients with juvenile type 1 diabetes, 86 obese children and 142 normal weighted age-matched healthy controls. Intima-media thickness (IMT) and lumen diameter of both common carotid arteries (CCA) was measured by ultrasonography in 52 healthy pediatric controls, 10 diabetics, and 34 obese juveniles. Serum hs-CRP was significantly elevated in patients with type 1 diabetes (p < 0.0001), and obese children (p < 0.0001) as compared to the control group. The obese juveniles (p < 0.0001) and the diabetics (p < 0.0001) showed significantly increased values for IMT of CAAs. Levels of homocysteine, sIL-2R, insulin, cortisol, vitamin B12, and folic acid did not differ from the controls. The elevation of hs-CRP was more pronounced in obesity as compared to type 1 diabetes (p < 0.0001), and the hs-CRP values correlated significantly with body mass index standard deviation score (BMI-SDS) values. Furthermore, the IMT and the luminal diameter of CCAs showed significant correlations with BMI-SDS values. A low grade inflammation as determined by serum hs-CRP is significantly increased in children with type 1 diabetes, and even more pronounced in apparently healthy juveniles with obesity. The increased IMT of CCAs strongly argues for an association between this low grade inflammation and early atherosclerotic vessel injury.


The direction of the acceleration and rotational forces associated with mild traumatic brain injury in rodents effect behavioural and molecular outcomes.
The translation of research to clinical application is only as good as the modelling platforms employed. This study sought to improve understanding of mild traumatic brain injury (mTBI), by examining the importance of acceleration and rotational force directions on behavioural and molecular outcomes. It is believed that many symptoms associated with concussive forms of mTBI are related to white matter and fibre tract damage. Given that rodents have significantly less white matter, could changes in acceleration/rotational force directionality alter outcomes? Comparison of mTBIs with two distinct injury platforms, the lateral impact (LI) device, which produces horizontal acceleration/rotation; or the modified weight drop (WD) device, which produces sagittal or vertical acceleration/rotation. Male and female rats underwent a behavioural test battery followed by analysis of 5 TBI-associated biomarkers (BDNF, Eno2, GFAP, MAPT, TERT) from the prefrontal cortex and hippocampus. Acute behavioural impairments were similar for both injury models; animals exhibited increased time-to-wake, and deficits of balance and motor control. However, as the post-injury interval increased LI animals displayed deficits on tasks related to emotional functioning, whereas WD animals showed impairment in cognitive measures. Biomarker expression varied as a function of injury platform, sex, and brain region. Just as with humans, the direction of the acceleration and rotational forces produced injuries in different networks and connections, resulting in altered functional deficits for rodents as well. These findings suggest that rodents are a valuable resource for the study of mTBI, when appropriately modelled.


Social science and health services research: contributions to public policy.
Public skepticism of the promised links between research and practical ends, and of the role of natural scientists as the ultimate judges of progress, is not new. After the unprecedented new social legislation and related research of the 1960s, social scientists today are being questioned about their contribution to improved public policy. Government interventions in the health services industry created new needs for information and knowledge, and at the same time altered the institutions and mechanisms through which relevant research is conducted and used. Social scientists and public officials will have to act in concert in response to new policy and research environments.


Getting started in research: designing and preparing to conduct a research study.
To discuss common pitfalls and useful tips in designing a quantitative research study, the importance and process of ethical approval, and consideration of funding. Through careful planning, based on formulation of a research question, early career researchers can design and conduct quantitative research projects within the framework of the Scholarly Project or in their own independent projects.


Amino Acid-Capped Water-Soluble Near-Infrared Region CuInS2/ZnS Quantum Dots for Selective Cadmium Ion Determination and Multicolor Cell Imaging.
Although attractive for their low toxicity, CuInS2/ZnS core/shell quantum dots (CIS/ZnS QDs) still suffer from poor luminescence efficiency and poor water solubility. Herein, two amino acids (AAs), i.e., cysteine (Cys) and threonine (Thr), are used to tune the properties of CIS/ZnS QDs by capping them in both core and shell. It is found that Thr can regulate the density of Cys on the surface of QDs, thus causing a synergistic effect on the enhancement of photoluminescence (PL) intensity. Capping in the shell mainly leads to the enhancement of PL intensity, and capping in the core results in a red-shift of PL wavelength. Accordingly, a new kind of near-infrared region CIS/ZnS QDs with improved optical properties has been prepared. In addition, the Cys- and Thr-capped CIS/ZnS QDs possess outstanding water solubility and biocompatibility. In this work, the QDs are further employed in Cd2+ determination and multicolor imaging, indicating their potential applications. Relying on the enhancement of PL intensity via cation exchange, the Cys- and Thr-capped CIS/ZnS QDs can sense Cd2+ sensitively. Notably, because ZnS shells of the QDs will not be affected by Zn2+, the analytical method can discriminate Cd2+ from Zn2+ depending on the inherent characteristics of QDs. Moreover, intercellular Cd2+ can also be evaluated by the bright PL from the QDs, and the QDs can achieve multicolor imaging. Overall, this work demonstrates that various properties of QDs may be tuned by capping with AAs, and AA-capped QDs are of great value in advanced biosensing and bioimaging.


Size is a major determinant of dissociation and denaturation behaviour of reconstituted high-density lipoproteins.
Lipid-free apolipoprotein A-I (apoA-I) and A-I(Milano) (A-I(M)) were compared for their denaturation behaviour by running across transverse gradients of a chaotrope, urea, and of a ionic detergent, SDS. For both apo A-I and monomeric apoA-I(M) in the presence of increasing concentrations of urea the transition from high to low mobility had a sigmoidal course, whereas for dimeric A-I(M)/A-I(M) a non-sigmoidal shape was observed. The co-operativity of the unfolding process was lower for dimeric A-I(M)/A-I(M) than for apoA-I or for monomeric apoA-I(M). A slightly higher susceptibility to denaturation was observed for dimeric A-I(M)/A-I(M) than for monomeric apoA-I(M). A similar behaviour of A-I(M)/A-IM versus apoA-I(M) was observed in CD experiments. Large- (12.7/12.5 nm) and small- (7.8 nm) sized reconstituted high-density lipoproteins (rHDL) containing either apoA-I or A-I(M)/A-I(M) were compared with respect to their protein-lipid dissociation behaviour by subjecting them to electrophoresis in the presence of urea, of SDS and of a non-ionic detergent, Nonidet P40. A higher susceptibility to dissociation of small-sized versus large-sized rHDL, regardless of the apolipoprotein component, was observed in all three instances. Our data demonstrate that the differential plasticity of the various classes of rHDL is a function of their size; the higher stability of 12.5/12.7 nm rHDL is likely connected to the higher number of protein-lipid and lipid-lipid interactions in larger as compared with smaller rHDL.


cis rescue of a mutated reverse transcriptase gene of human hepatitis B virus by creation of an internal ATG.
Using mutational analysis, we have investigated the translation strategy of the reverse transcriptase gene (pol) of human hepatitis B virus. It has been proposed that this pol gene product is synthesized as a core-pol fusion protein from a polycistronic mRNA template via ribosomal frameshifting, a mechanism often seen in retroelements. Our data indicate that creation of a novel ATG initiation codon near the original ATG can compensate for a lethal missense mutation at the first ATG position of the pol open reading frame. Genetic analysis has rigorously ruled out the possibilities of frameshifting, non-ATG initiation, or RNA editing. These results are discussed in the context of a 5'-end entry model versus a novel model of direct internal entry of ribosomes.


Deeper penetration of large earthquakes on seismically quiescent faults.
Why many major strike-slip faults known to have had large earthquakes are silent in the interseismic period is a long-standing enigma. One would expect small earthquakes to occur at least at the bottom of the seismogenic zone, where deeper aseismic deformation concentrates loading. We suggest that the absence of such concentrated microseismicity indicates deep rupture past the seismogenic zone in previous large earthquakes. We support this conclusion with numerical simulations of fault behavior and observations of recent major events. Our modeling implies that the 1857 Fort Tejon earthquake on the San Andreas Fault in Southern California penetrated below the seismogenic zone by at least 3 to 5 kilometers. Our findings suggest that such deeper ruptures may occur on other major fault segments, potentially increasing the associated seismic hazard.


Two-Year Outcomes of Orbital Atherectomy Combined With Drug-Coated Balloon Angioplasty for Treatment of Heavily Calcified Femoropopliteal Lesions.
Purpose: To examine whether the combination of orbital atherectomy (OA) and drug-coated balloons (DCB) can lead to superior procedural and 2-year outcomes compared with DCB only in heavily calcified femoropopliteal (FP) lesions. Materials and Methods: A retrospective chart review was conducted to identify patients treated with DCB only or OA+DCB for de novo FP lesions at a single center over a 4-year period (2014-2017). In the observation period, 113 patients met the inclusion criteria: 63 treated with DCB only (mean age 69.0±8.6 years; 62 men) vs 50 treated with OA+DCB (mean age 70.3±7.1 years; 48 men). The OA+DCB group had higher calcification rates (78% with severe calcification vs 37% in the DCB only group). Propensity score matching (PSM) was used to adjust for baseline differences between the 2 groups. Cox regression analysis was used to compare the follow-up outcomes between lesions treated with OA+DCB vs DCB only. Results: No difference in procedural complications or success was found. After PSM adjustment, the OA+DCB group was associated with lower bailout stenting rates (39.4% vs 66.7% in the DCB only group; p=0.026). The 2 groups had similar long-term outcomes, although the OA+DCB arm had a trend toward reduced TLR rates that did not reach statistical significance. The Kaplan-Meier estimates for 2-year freedom from TLR were 76.1% for the OA+DCB group vs 55.5% for the DCB only group (p=0.109). Conclusion: OA+DCB is a safe and effective combination for the treatment of calcified FP lesions. The combined therapy decreased the bailout stenting rates in the adjusted analysis. Larger cohorts and randomized trials are needed to examine OA efficacy in FP lesions.


The Role of Fucoidans Isolated from the Sporophylls of Undaria pinnatifida against Particulate-Matter-Induced Allergic Airway Inflammation: Evidence of the Attenuation of Oxidative Stress and Inflammatory Responses.
Ambient particulate matter (PM) is a critical environment pollutant that promotes the onset and aggravation of respiratory diseases such as asthma through airway inflammation and hypersecretion of mucus. In this study, we aimed to identify the effects of fucoidans isolated from sporophylls of Undaria pinnatifida on asthma symptoms such as the inflammatory response and mucus secretion using a mouse model. Balb/c mice, intraperitoneally sensitized with ovalbumin (OVA, 10 μg) dissolved in 200 µL saline and 2 mg Al(OH)3, were exposed to PM (5 mg/m3) for 7 consecutive days. In parallel, along with PM exposure, we orally administrated fucoidans (100, 400 mg/Kg) or prednisone (5 mg/Kg), an anti-inflammatory drug. We found that oral administration of fucoidans significantly attenuated PM-induced lipid peroxidation and infiltration of inflammatory cells like F4/80+ macrophages, Gr-1+ granulocytes, and CD4+ T lymphocytes. Fucoidans also attenuated the level of PM-exacerbated IL-4, a primitive cytokine released in Th2 mediated eosinophilic asthma. This further suppressed mast cell activation, degranulation and IgE synthesis of PM exposed mice. Interestingly, fucoidans attenuated PM-exacerbated mucus hypersecretion and goblet cell hyperplasia. Therefore, our results suggest that fucoidans are effective at alleviating PM-exacerbated allergic asthma symptoms by attenuating the airway inflammatory response and mucus hypersecretion.


Evidence for symptom management in the child with cancer.
The use of complementary/alternative medicine (CAM) has been well documented among children with cancer. This report summarizes the research evidence on the role of CAM therapies for prevention and treatment of the most commonly reported cancer-related symptoms and late effects among children with cancer. Small clinical trials document evidence of effectiveness for select therapies, such as acupuncture or ginger for nausea and vomiting, TRAUMEEL S for mucositis, and hypnosis and imagery for pain and anxiety. Several relatively small clinical trials of varying quality have been conducted on these CAM therapies in children with cancer. Some herbs have demonstrated efficacy in adults, but few studies of herbs have been conducted in children. Larger randomized clinical trials are warranted for each of these promising therapies. Until the evidence is more conclusive, the providers' role is to assess and document the child's use of CAM, critically evaluate the evidence or lack of evidence, balance the potential risks with possible benefits, and assist the family in their choices and decisions regarding use of CAM for their child with cancer.


Patient Experiences with the Preoperative Assessment Clinic (PEPAC): validation of an instrument to measure patient experiences.
Presently, no comprehensive and validated questionnaire to measure patient experiences of the preoperative assessment clinic (PAC) is available. We developed and validated the Patient Experiences with the Preoperative Assessment Clinic (PEPAC) questionnaire, which can be used for quantitative measurements of patient experiences of the PAC. We adapted the National Health Service outpatient questionnaire, incorporating questions specific for anaesthesiology. To make the PEPAC appropriate for quantitative measurements, dimensions and single items suitable for statistical analysis were constructed. Each dimension consists of multiple items measuring the same aspect of care. Reliability was established by computing Cronbach's alpha coefficients. Construct validity was assessed by correlating the dimensions with the patient's overall appraisal (Pearson's r). These dimensions should explain a substantial level of variance of the patients' overall appraisal; therefore, regression analysis was performed. After a pilot phase, the questionnaire was sent to 700 consecutive patients (response 74%). Five scales measuring five dimensions of patient experiences were constructed. Cronbach's alpha ranged from 0.56 to 0.84, supporting reliability of the PEPAC. Correlations between the dimensions and patients' overall appraisal ranged from 0.22 to 0.56. Collectively, the five scales explained 51% of patients' overall appraisal. The PEPAC is a comprehensive, reliable, and validated questionnaire to measure patient experiences with the PAC. It might be a useful tool to identify the service areas of the PAC that require improvement and to determine which actions can bring about improvement.


Influence of congestive heart failure on endothelin levels and receptors in rabbits.
Congestive heart failure, both in man and in animals is associated with an increased plasma level of endothelin. To investigate further the potential role of the endothelin system, we designed a study to determine the effect of experimental congestive heart failure (CHF) on plasma and tissue immunoreactive-endothelin (irET) and on the density and affinity of endothelin-1 receptors in the heart and kidney. For this purpose, CHF was induced in rabbits by combined aortic valvular insufficiency and stenosis. When CHF was established, plasma and tissue irET levels were measured by radioimmunoassay and density and affinity of endothelin-1 receptors were measured by binding assay on tissue homogenates. Compared to control rabbits, plasma irET was significantly elevated in rabbits with CHF [1.04 +/- 0.15 vs. 0.04 +/- 0.01 fmol/ml, P < 0.001]. Tissue irET concentrations in ventricles and kidney were roughly 4 orders of magnitude higher than plasma concentrations. CHF decreased the tissue irET levels in left ventricle and kidney by 32 and 46%, respectively (P < 0.01), whereas CHF increased it by 58% in the right ventricle (P < 0.005). The density of ET-1 receptors was decreased in the right and left ventricles and in kidneys by 26, 36, and 61%, respectively (P < 0.05). Receptor affinity remained unchanged in response to CHF in both ventricles, whereas it increased in kidney [Kd (pM); 154 +/- 17 vs. 99 +/- 9, P < 0.01]. Thus, this study demonstrates that experimental CHF is not only characterized by elevated plasma irET levels but also by a decrease in tissue irET concentrations in the left ventricle and kidney, and by a down-regulation of ET-1 receptors both in the heart and kidney. Functional consequences of these changes need to be determined.


Perpetrators of Alcohol-Involved Sexual Assaults: How Do They Differ From Other Sexual Assault Perpetrators and Nonperpetrators?
Approximately 50% of sexual assaults involve alcohol. Researchers have documented situational characteristics that distinguish between sexual assaults that do and do not involve alcohol, but little attention has been paid to differences between the perpetrators of these two types of assault. In this study, discriminant function analysis was used to distinguish between college men (N = 356) who reported perpetrating sexual assault that involved alcohol, sexual assault that did not involve alcohol, or no sexual assault. Predictors of sexual assault perpetration that have been documented in past research differentiated nonperpetrators from both types of perpetrators. Perpetrators of sexual assaults that involved alcohol were in most ways similar to perpetrators of sexual assaults that did not, although they did differ on impulsivity, alcohol consumption in sexual situations, and beliefs about alcohol. These findings suggest mechanisms through which alcohol is involved in sexual assault that are relevant to theory and prevention.


Osteogenesis imperfecta: from phenotype to genotype and back again.
The presumption that identification of the collagen gene mutations in OI would completely explain the phenotype is unjustified. Full understanding of this fragile bone syndrome will depend on the intelligent interpretation of both the biochemical abnormalities and the clinical features. Between these extremes there is a whole unexplored area of cell biology. To make further progress it seems that we shall have to pay as much attention to the phenotype as to the genotype.


Imaging histologic discordance at MRI-guided 9-gauge vacuum-assisted breast biopsy.
The purpose of this study was to determine the frequency of discordance at MRI-guided vacuum-assisted biopsy and to assess the cancer rate in discordant lesions. With institutional review board approval, retrospective review was performed of a database of 342 lesions that had MRI-guided vacuum-assisted biopsy during a 39-month period. Biopsy samples were obtained in a 1.5-T magnet using a 9-gauge MRI-compatible vacuum-assisted biopsy device. Medical and pathology records were reviewed to determine the number of discordant lesions and surgical outcome. Statistical analysis was performed. Among 342 lesions that had MRI-guided vacuum-assisted biopsy, results were discordant in 24 (7% [95% CI, 3-14%]) lesions. The discordance rate was significantly (p < 0.001) higher among MRI target lesions that were possibly missed rather than sampled. A trend was seen (p < 0.06) toward a higher discordance rate in MRI lesions that were sampled rather than excised at MRI-guided vacuum-assisted biopsy. Subsequent surgery in 20 discordant lesions yielded cancer in six (30% [12-54%]), including ductal carcinoma in situ (DCIS) in two and invasive carcinoma in four (three ductal and one lobular, all with DCIS). The cancer rate among discordant lesions was significantly higher in postmenopausal women than in premenopausal women (p <0.05). Imaging-histologic discordance was found in 7% of lesions that had MRI-guided vacuum-assisted biopsy. Among discordant lesions, surgical excision revealed cancer in 30%. Imaging-histologic correlation is essential after MRI-guided vacuum-assisted biopsy to avoid delay in the diagnosis of breast cancer.


Previously Complicated Nuss Procedure Does Not Preclude Blind Removal of the Bar.
Nuss procedure has become the procedure of choice for well-selected patients with pectus excavatum. Perioperative complications may pose difficulty during the subsequent bar removal due to adhesions and tissue plane disruptions during the initial surgery and repair. This report describes bar removal experience in patients whose Nuss procedures were complicated by cardiac injury, pericardial breach, and lung parenchyma/diaphragm injury during the initial procedure. A total of 529 patients who underwent Nuss procedure between 2007 and 2014 were recorded in a prospective database. Twenty patients with complications (cardiac injury [n = 1], pericardial breach [n = 3], and lung parenchyma/diaphragm injury [n = 16]) were identified. All bars were removed via subcutaneous tissue dissection, without intrathoracic visualization. Average duration of bars was 36 months (±16 months). All bar removal procedures were completed without any need for extra interventions with negligible blood loss. Eighteen patients were able to be discharged within 2 postoperative days. Blind bar removal in patients with previously complicated Nuss procedure seems safe and no other interventions (videothoracoscopy, subxiphoid incision, etc.) during bar removal seem to be necessary.


Intermittency of velocity fluctuations in turbulent thermal convection.
We analyze velocity fluctuations in turbulent Rayleigh-Bénard convection. The velocity measurements were taken at the center of an aspect-ratio-one convection cell filled with water. The measured probability density functions of the velocity difference over a time interval tau are found to change with tau, indicating that the velocity fluctuations are intermittent. The velocity intermittency can be well characterized by the She-Leveque hierarchical structure. Our analyses further show that the vertical velocity component has distinct statistical features from the horizontal components. This result indicates that the vertical direction is special and buoyancy is important even at the center of the convection cell.


Evaluation of vitamin E-diffused highly crosslinked polyethylene wear and porous titanium-coated shell stability: a seven-year randomized control trial using radiostereometric analysis.
Vitamin E-diffused, highly crosslinked polyethylene (VEPE) and porous titanium-coated (PTC) shells were introduced in total hip arthroplasty (THA) to reduce the risk of aseptic loosening. The purpose of this study was: 1) to compare the wear properties of VEPE to moderately crosslinked polyethylene; 2) to assess the stability of PTC shells; and 3) to report their clinical outcomes at seven years. A total of 89 patients were enrolled into a prospective study. All patients received a PTC shell and were randomized to receive a VEPE liner (n = 44) or a moderately crosslinked polyethylene (ModXLPE) liner (n = 45). Radiostereometric analysis (RSA) was used to measure polyethylene wear and component migration. Differences in wear were assessed while adjusting for body mass index, activity level, acetabular inclination, anteversion, and head size. Plain radiographs were assessed for radiolucency and patient-reported outcome measures (PROMs) were administered at each follow-up. In total, 73 patients (82%) completed the seven-year visit. Mean seven-year linear proximal penetration was -0.07 mm (sd 0.16) and 0.00 mm (sd 0.22) for the VEPE and ModXLPE cohorts, respectively (p = 0.116). PROMs (p = 0.310 to 0.807) and radiolucency incidence (p = 0.330) were not different between the polyethylene cohorts. The mean proximal shell migration rate was 0.04 mm per year (sd 0.09). At seven years, patients with radiolucency (34%) demonstrated greater migration (mean difference: 0.6 mm (sd 0.2); p < 0.001). PROMs were lower for patients with radiolucency and greater proximal migration (p = 0.009 to p = 0.045). No implants were revised for aseptic loosening. This is the first randomized controlled trial to report seven-year RSA results for VEPE. All wear rates were below the previously reported osteolysis threshold (0.1 mm per year). PTC shells demonstrated acceptable primary stability through seven years, as indicated by low migration and lack of aseptic loosening. However, patients with acetabular radiolucency were associated with higher shell migration and lower PROM scores. Cite this article: Bone Joint J 2019;101-B:760-767.


Spinal disabilities in military and civil aviators.
The purpose of this study was to analyze the nature and cause of spinal disabilities among military and civil aircrew in India. Studies suggest that military aircrew may be more prone than nonaviators to develop spinal disabilities. An in-depth analysis of such disabilities can enable policy makers to develop data-driven preventive health programs. Extensive literature search did not reveal even a single study focusing on spinal disabilities in symptomatic aircrew. A case record of each aircrew is maintained at the Institute of Aerospace Medicine, Indian Air Force, Bangalore, India These records were accessed for all aircrew evaluated for spinal disabilities from the year 2000 to 2006. The total data comprises of 239 military and 11 civil aircrew. Most of the military aircrew were from the fighter stream. The spectrum of causes for spinal disabilities ranged from ejection, aircraft accidents to road traffic accidents, and falls. Degenerative disc disease was the leading cause in helicopter and transport pilots, whereas fractures were the predominant category in fighter pilots. A total of 153 vertebral fractures and 190 intervertebral discs were involved. There were significant differences in the age and distribution of this aircrew. Spinal disabilities assume significance for variety of reasons. Firstly, a large number of spinal disabilities caused by vehicular trauma are preventable. Second, they generally entail a prolonged course of recovery. Third, they can result in loss of trained human resources, especially when the individual cannot return to his or her original workspace. This study provides insights into the nature of spinal disabilities in civil and military aviation. Ejection and aircraft accidents remain the leading cause of vertebral fractures. Disc degenerative disease is a cause of concern. Physical conditioning and regular physical exercise may possibly minimize spinal disabilities in susceptible aircrew.


Thyroid cancer in Plummer's disease.
Thyroid cancer with concomitant hyperthyroidism is rare. Most foci of malignancy are small and seen postoperatively as incidental findings after surgery for hyperthyroidism. Thyroid masses with clinical features of malignancy and concomitant hyperthyroidism are less-commonly reported. We report two cases of multinodular toxic goitre or Plummer's disease with clinical features of malignancy. Both patients had large multinodular goitres with evidence of metastasis to the manubrium for the first patient and to the lymph node and lungs for the second patient. Both were clinically euthyroid but with free hormone excess and suppressed thyroid stimulating hormone (TSH) on laboratory testing. Both patients received methimazole prior to thyroidectomy. Histopathology revealed follicular variant of papillary cancer with metastasis to the manubrium for the first patient and follicular thyroid cancer with lymph node metastasis for the second. While rare, thyrotoxicosis can occur with malignancy, Plummer's disease may harbour cancer and behave aggressively.


Client participation and provider communication in family planning counselling and the sample study from Turkey.
The family planning program in Turkey was established in 1965 to curb the rapid increase in population growth. The last Demographic and Health Survey showed that about 64 % of married women in Turkey used contraception. This study examines of behaviour of family planning clients and provider in Eskisehir/Turkey, to see whether they can achieve this ideal parnership. Consultation between 83 physicians, 222 nurses and 324 clients requesting family planning methods were audiotaped and analysed for physicians and nurses communication style. Data were collected from 3 hospital and 14 small health units that give services in Eskisehir. The audiotaped consultations were coded using an adaptation of the RIAS which has been used extensively in both developed and developing countries and in statistical analysing chi(2) and t test were utilized. The single strongest factor was providers giving biomedical and technical information. The qualitative analysis of audiotapes found that most of clients' questions concern contraceptive side effects and symptoms. The next category social talk, consisted largely of greetings. Most of the providers (87.6 %) are women. The results show that providers dominate most counselling session and clients rarely take on active role.


Epidemiology of obstructive sleep apnea: a population health perspective.
Population-based epidemiologic studies have uncovered the high prevalence and wide severity spectrum of undiagnosed obstructive sleep apnea, and have consistently found that even mild obstructive sleep apnea is associated with significant morbidity. Evidence from methodologically strong cohort studies indicates that undiagnosed obstructive sleep apnea, with or without symptoms, is independently associated with increased likelihood of hypertension, cardiovascular disease, stroke, daytime sleepiness, motor vehicle accidents, and diminished quality of life. Strategies to decrease the high prevalence and associated morbidity of obstructive sleep apnea are critically needed. The reduction or elimination of risk factors through public health initiatives with clinical support holds promise. Potentially modifiable risk factors considered in this review include overweight and obesity, alcohol, smoking, nasal congestion, and estrogen depletion in menopause. Data suggest that obstructive sleep apnea is associated with all these factors, but at present the only intervention strategy supported with adequate evidence is weight loss. A focus on weight control is especially important given the expanding epidemic of overweight and obesity in the United States. Primary care providers will be central to clinical approaches for addressing the burden and the development of cost-effective case-finding strategies and feasible treatment for mild obstructive sleep apnea warrants high priority.


Theoretical studies of the potential surface and vibrational spectroscopy of CH3OH and its deuterated analogs.
A potential-energy force field for methanol is calculated at the coupled-cluster singles doubles and noniterative triples correction level using the correlation-consistent polarized valence triple zeta basis set. The force field describes the coupled molecular vibrations, including the cubic and quartic anharmonicites, as a function of the torsional coordinate. The resulting molecular eigenstates are calculated using a combination of perturbative and variation calculations following the approach of Castillo-Chará and Sibert [J. Chem. Phys. 119, 11671 (2003)]. The energies, including torsional tunneling splittings, are compared with available spectroscopic data for all the fundamentals. Excellent agreement is found. Varying the torsional mass, correlation plots are constructed in order to elucidate the complex role of torsion-vibration coupling.


Timescales of Coherent Dynamics in the Light Harvesting Complex 2 (LH2) of Rhodobacter sphaeroides.
The initial dynamics of energy transfer in the light harvesting complex 2 from Rhodobacter sphaeroides were investigated with polarization controlled two-dimensional spectroscopy. This method allows only the coherent electronic motions to be observed revealing the timescale of dephasing among the excited states. We observe persistent coherence among all states and assign ensemble dephasing rates for the various coherences. A simple model is utilized to connect the spectroscopic transitions to the molecular structure, allowing us to distinguish coherences between the two rings of chromophores and coherences within the rings. We also compare dephasing rates between excited states to dephasing rates between the ground and excited states, revealing that the coherences between excited states dephase on a slower timescale than coherences between the ground and excited states.


Phenotyping Sunflower Genetic Resources for Sclerotinia Head Rot Response: Assessing Variability for Disease Resistance Breeding.
Sclerotinia head rot (SHR) is one of the most serious constraints to sunflower (Helianthus annuus L. var. macrocarpus) production worldwide. Here, we evaluated the response to SHR in a sunflower inbred panel from a large INTA germplasm collection, consisting of 137 inbred lines (ILs). Field trials were performed over five consecutive seasons using a twice-replicated randomized complete-block design. Disease incidence, disease severity, incubation period, and area under disease progress curve for disease incidence and severity were determined after controlled inoculation with the pathogen. Statistical analysis using mixed-effect models detected significant differences among ILs for all variables (P < 0.001). In addition, principal component analysis (PCA) and distance-based methods were used to classify the ILs according to their response to SHR, with ILs ALB2/5261 and 5383 emerging as the most resistant. Broad-sense heritability estimates ranged from 20.64% for disease severity to 10.58% for incubation period. The ample phenotypic variability of our collection, along with the moderate heritability estimates, highlight the importance of molecular breeding approaches to gain new insights into the genetic basis of sunflower resistance to SHR. The exhaustive phenotypic characterization presented here provides a reliable set of variables to comprehensively evaluate the disease and identifies two new sources of resistance to SHR.


[Infective endocarditis with a huge mitral vegetation related to atopic dermatitis and high serum level of infection-related antiphospholipid antibody: a case report].
A 24-year-old woman with atopic dermatitis was admitted to our hospital with fever. Echocardiography showed a huge vegetation attached to the posterior mitral commissure without mitral valve dysfunction. Blood culture identified methicillin-sensitive Staphylococcus aureus. The serum level of antiphospholipid antibody was elevated. A splenic infarction occurred on the second hospital day. Surgery to resect the residual mobile vegetation was performed uneventfully on the 6th hospital day. The postoperative course was uneventful, and the patient was discharged after 4 weeks of antibiotic therapy. Preservation of the mitral valve is rare in the face of virulent Staphylococcus infection and the presence of a huge mobile vegetation. These findings were apparently related to the high serum level of infection-related antiphospholipid antibody and atopic dermatitis.


Establishment of Immortalized Primary Human Foreskin Keratinocytes and Their Application to Toxicity Assessment and Three Dimensional Skin Culture Construction.
In spite of frequent usage of primary human foreskin keratinocytes (HFKs) in the study of skin biology, senescence-induced blockage of in vitro proliferation has been a big hurdle for their effective utilization. In order to overcome this passage limitation, we first isolated ten HFK lines from circumcision patients and successfully immortalized four of them via a retroviral transduction of high-risk human papillomavirus (HPV) E6 and E7 oncogenes. We confirmed expression of a keratinocyte marker protein, keratin 14 and two viral oncoproteins in these immortalized HFKs. We also observed their robust responsiveness to various exogenous stimuli, which was evidenced by increased mRNA expression of epithelial differentiation markers and pro-inflammatory genes in response to three reactive chemicals. In addition, their applicability to cytotoxicity assessment turned out to be comparable to that of HaCaT cells. Finally, we confirmed their differentiation capacity by construction of well-stratified three dimensional skin cultures. These newly established immortalized HFKs will be valuable tools not only for generation of in vitro skin disease models but also for prediction of potential toxicities of various cosmetic chemicals.


Determination of pre-pregnancy fear of childbirth levels in Turkish and Syrian refugee individuals with no children: A comparative study.
This study was conducted to determine pre-pregnancy fear of childbirth levels and related factors in Turkish and Syrian refugee individuals with no children. A cross-sectional-descriptive design was used. The study was carried out between September 29 and November 15, 2022 with Turkish and Syrian refugee women with no children who presented to the Obstetrics and Gynecology Polyclinic of a state hospital and their spouses. A total of 545 people, including the spouses of the women who wanted to participate, were included in the study. The data were collected by the researcher in the waiting room of the outpatient clinic by using the face-to-face interview method. A Personal Information Form and the Childbirth Fear-Prior to Pregnancy Scale were used to collect the research data. There was no statistically significant relationship between participants' culture and their age, education level, employment status, family type, income level, and birth preferences (p > 0.05), and the groups were independent and homogeneous in terms of the specified characteristics. It was determined that Syrian refugee women had a significantly higher total score on the Childbirth Fear-Prior to Pregnancy Scale than Turkish women. Also, the score of Syrian refugee men on the same scale was significantly higher than that of Turkish men. A statistically significant difference was found between the total scores of the Turkish and Syrian participants according to age, education level, and preferred mode of birth. In the current study, it was determined that both genders and cultures had a fear of childbirth, although it was more common in women and Syrian refugees. According to the findings of the study, culture, gender, age, education level, and preferred mode of birth were factors related to childbirth fear prior to pregnancy.


Abscisic Acid (ABA ) Promotes the Induction and Maintenance of Pear (Pyrus pyrifolia White Pear Group) Flower Bud Endodormancy.
Dormancy is an adaptive mechanism that allows temperate deciduous plants to survive unfavorable winter conditions. In the present work, we investigated the possible function of abscisic acid (ABA) on the endodormancy process in pear. The ABA content increased during pear flower bud endodormancy establishment and decreased towards endodormancy release. In total, 39 putative genes related to ABA metabolism and signal transductions were identified from pear genome. During the para- to endodormancy transition, PpNCED-2 and PpNCED-3 had high expression levels, while PpCYP707As expression levels were low. However, during endodormancy, the expression of PpCYP707A-3 sharply increased with increasing cold accumulation. At the same time, the ABA content of pear buds declined, and the percentage of bud breaks rapidly increased. On the other hand, the expression levels of PpPYLs, PpPP2Cs, PpSnRK2s, and PpABI4/ABI5s were also changed during the pear flower bud dormancy cycle. Furthermore, exogenous ABA application to para-dormant buds significantly reduced the bud breaks and accelerated the transition to endodormancy. During the whole treatment time, the expression level of PpPP2C-12 decreased to a greater extent in ABA-treated buds than in control. However, the expression levels of PpSnRK2-1, PpSnRK2-4, and PpABI5-1 were higher in ABA-treated buds. Our results indicated that PpCYP707A-3 and PpNCEDs play pivotal roles on the regulation of endodormancy release, while ABA signal transduction pathway also appears to be involved in the process. The present work provided the basic information about the function of ABA-related genes during pear flower bud dormancy process.


The flow field near a venous needle in hemodialysis: a computational study.
The vascular access used in hemodialysis can suffer from numerous complications, which may lead to failure of the access, patient morbidity, and significant costs. The flow field in the region of the venous needle may be a source of damaging hemodynamics and hence adverse effects on the fistula. In this study, the venous needle flow has been considered, using three-dimensional computational methods. Four scenarios where the venous needle flow could potentially influence dialysis treatment outcome were identified and examined: Variation of the needle placement angle (10°, 20°, 30°), variation of the blood flow rate settings (200, 300, 400 mL/min), variation of the needle depth (top, middle, bottom), and the inclusion of a back eye in the needle design. The presence of the needle has significant effect on the flow field, with different scenarios having varying influence. In general, wall shear stresses were elevated above normal physiological values, and increased presence of areas of low velocity and recirculation-indicating increased likelihood of intimal hyperplasia development-were found. Computational results showed that the presence of the venous needle in a hemodialysis fistula leads to abnormal and potentially damaging flow conditions and that optimization of needle parameters could aid in the reduction of vascular access complications. Results indicate shallow needle angles and lower blood flow rates may minimize vessel damage.


Biocontrol of aflatoxins B1, B2, G1, G2, and fumonisin B1 with 6,7-dimethoxycoumarin, a phytoalexin from Citrus sinensis.
Phytoalexins (stress-induced compounds) from Citrus sinensis cultivar Valencia were screened for antifungal and antimycotoxic activity against a test organism (Cladosporium cladosporoides) and mycotoxin-producing fungi Fusarium verticillioides and Aspergillus parasiticus. The active compound, a member of the coumarin family of compounds, has antifungal and antimycotoxic activities and was chemically identified. High-performance liquid chromatography results indicated that Valencia oranges contain a trace amount (0.36 microg/g) of scoparone in untreated fruit, but concentrations increased in UV-irradiated fruit (15.2 microg/g). Infection with Penicillium digitatum, a natural spoilage mold of citrus fruit, caused a 35.51-microg/g increase in the phytoalexin. UV absorption, infrared absorption, and 1H nuclear magnetic resonance spectroscopy revealed that this phytoalexin is identical to 6,7-dimethoxycoumarin. This is the first report indicating that the stress-induced compound, 6,7-dimethoxycoumarin, isolated from P. digitatum-infected Valencia fruit confers resistance against the mycotoxigenic fungi A. parasiticus and F. verticillioides and causes a reduction in production of fumonisin B1 and aflatoxins G1, G2, B1, and B2.