Molecular dynamics simulation of three plastic additives' diffusion in polyethylene terephthalate.
Accurate diffusion coefficient data of additives in a polymer are of paramount importance for estimating the migration of the additives over time. This paper shows how this diffusion coefficient can be estimated for three plastic additives [2-(2'-hydroxy-5'-methylphenyl) (UV-P), 2,6-di-tert-butyl-4-methylphenol (BHT) and di-(2-ethylhexyl) phthalate (DEHP)] in polyethylene terephthalate (PET) using the molecular dynamics (MD) simulation method. MD simulations were performed at temperatures of 293-433 K. The diffusion coefficient was calculated through the Einstein relationship connecting the data of mean-square displacement at different times. Comparison of the diffusion coefficients simulated by the MD simulation technique, predicted by the Piringer model and experiments, showed that, except for a few samples, the MD-simulated values were in agreement with the experimental values within one order of magnitude. Furthermore, the diffusion process for additives is discussed in detail, and four factors - the interaction energy between additive molecules and PET, fractional free volume, molecular shape and size, and self-diffusion of the polymer - are proposed to illustrate the microscopic diffusion mechanism. The movement trajectories of additives in PET cell models suggested that the additive molecules oscillate slowly rather than hopping for a long time. Occasionally, when a sufficiently large hole was created adjacently, the molecule could undergo spatial motion by jumping into the free-volume hole and consequently start a continuous oscillation and hop. The results indicate that MD simulation is a useful approach for predicting the microstructure and diffusion coefficient of plastic additives, and help to estimate the migration level of additives from PET packaging.


[Agrobacterium-mediated genetic transformation of secondary somatic embryos in alfalfa].
We describe a genetic transformation method of secondary somatic embryogenesis in alfalfa through cotyledon-stage somatic embryos of alfalfa infected by Agrobacterium strain GV3101. The Agrobacterium strain GV3101 contained binary vector pCAMBIA2301 that had gus gene as reporter and npt II gene as selectable marker. The infected primary embryos were induced through series of medium under 75 mg/L kanamycin selection. We obtained the transgenic alfalfa plants. Then, GUS expression in different tissue of transgenic alfalfa was tested by GUS histochemical analysis. Further, the stable integration and transformation efficiency were tested by polymerase chain reaction and Southern blotting hybridization. The result showed that GUS expression was different in different organs of transgenic alfalfa; the copy number of integrated npt II gene was from 1 to 4; the transformation efficiency via primary somatic embryogenesis was 65.82%.


Stochastic resonance in the presence of spatially localized structures.
Stable spatially localized structures exist in a wide variety of spatially extended nonlinear systems, including nonlinear optical devices. We study stochastic resonance (SR) in models of optical parametric oscillators in the presence of a spatially uniform time-periodic driving and in a regime where two equivalent states with equal intensity but opposite phase exist. Diffraction and nonlinearity enable the existence of localized states, formed by the locking of kinks and antikinks and displaying spatially damped oscillatory tails (in one dimension) or the stabilization of dark ring cavity solitons (in two dimensions). We show that SR is inhibited at low driving amplitudes by the presence of localized states which obstruct the front motion. For larger driving amplitudes, in the regime where localized states cease to be stable, we observe instead an enhancement of SR.


Effects of current and potential dental etchants on nerve compound action potentials.
In this study, a 35% phosphoric acid gel (3M Scotchbond etchant), a nonrinse etchant (NRC), and two EDTA-containing conditioners (RC-Prep and File-Eze) were tested in vitro for blocking nerve conductance evoked in the rat sciatic nerve after local application. The phosphoric acid gel and NRC completely and irreversibly inhibited conductance. On the other hand, RC-Prep reduced the compound action potentials (cAPs) by 50% in 120 min. With File-Eze, the reduction in cAPs was less than 50% after an application time of 160 min (61.8 +/- 1.8%). At 160 min the cAPs in the RC-Prep group had been inhibited by 62.4%. These results indicated strong neurotoxic effects of phosphoric acid and NRC when applied directly on exposed pulp in the total etch procedure.


Plasmonic Absorption Enhancement in Elliptical Graphene Arrays.
In this paper, we come up with a wavelength tunable absorber which is made up of periodically elliptical graphene arrays in the far-infrared and terahertz regions. Through simulation, we find that we can increase the length of long axis of the ellipse, raise the incidence angles of TM- and TE-polarization (TM- and TE-polarization indicate the direction of the incident electric field along the direction of the x and the y axis, respectively.) within certain limits, and increase the chemical potential of graphene, so as to enhance the absorption of light in the elliptical graphene arrays. We also compare the absorption spectra of the original structure and the complementary structure, and find that the absorption of the original structure is higher than that of the complementary structure. In the end, we study the changes in the absorption rate of the double layer structure of the elliptical array with the increase in the thickness of SiO₂. The elliptical array structure can be applied to tunable spectral detectors, filters and sensors at far-infrared and terahertz wavelengths.


Study on catalytic incineration of methane using Cr2O3/gamma-Al2O3 as the catalyst.
A fixed bed reactor was employed to investigate the catalytic incineration of CH4 by various supported transition metal oxide catalysts, with a view of finding the optimal one. Results indicated that the active species, the support, the metal content, the weight hourly space velocity (WHSV), and the inlet CH4 concentration were all important factors affecting CH4 oxidation. Cr2O3/gamma-Al2O3 was found to be the most active catalyst among the seven gamma-Al2O3-supported metal oxide catalysts tested. With Cr2O3 as the active species, gamma-Al2O3 was the most suitable of six supports tested. Furthermore, the optimal Cr content of Cr2O3/ gamma-Al2O3 was 9 wt.%. X-ray diffraction (XRD) patterns showed that it was formation of CrO3 crystals that caused a decline in catalyst activity at Cr content above 9wt.%. Using the optimal Cr2O3/gamma-Al2O3 catalyst, CH4 was completely oxidized at about 390 degrees C. much lower than the temperature required by noble metal catalysts for the same outcome. The stability of Cr2O3/gamma-Al2O3 was good and was not affected by the reaction temperature, demonstrated by a nearly constant conversion rate of CH4 of 57% at 350 degrees C and 97% at 380 degrees C during a 20 h on-stream test. However, WHSV and inlet concentration of CH4 did affect CH4 conversion noticeably. For complete oxidation of CH4, the reaction temperature required increased with WHSV and inlet CH4 concentration.


Rheumatology Image of the Month: A Low Resource Innovation With Measurable Results.
Strategies to increase confidence in rheumatology knowledge are valuable for medical trainees and residents. A web-based teaching innovation was implemented in an attempt to increase rheumatology exposure for internal medicine residents. An Image of the Month webpage was established, where a practicing rheumatologist would post a new image that could be answered online by internal medicine residents. Cumulative data was analyzed to determine the extent and change in rheumatology exposure. The Image of the Month webpage posted images for a total of 76 months between July 2010 to May 2017, with a total of 1326 submitted responses. The proportion of residents who only participated in Image of the Month and only did a rheumatology rotation averaged 36.1% and 16.5%, respectively. The proportion of residents who only participated in Image of the Month was higher than the proportion who only did a rheumatology rotation for all of the 7 time periods assessed. A total of 491 residents participated in Image of the Month, with an average of 54.9% of residents participating each year. Overall, on average, 52 residents had 1 or more submissions, 3.6 entries were submitted per resident, and 17.4 entries were submitted per month. Junior residents (PGY1) participated more often than senior residents (PGY3). The Image of the Month webpage successfully improves internal medicine resident exposure to rheumatology with minimal resources and manpower required. Further study is necessary to determine the impact this exposure may have on the abilities and confidence levels of internal medicine residents.


Racial Prejudice Predicts Police Militarization.
In the United States, police are becoming increasingly militarized. Whereas the racialized nature of police militarization has been documented, the relationship between racial prejudice and police militarization is less understood. We assessed the link between racial prejudice against Black and Native Americans and police militarization at individual and regional levels. Study 1 (N = 765) recruited a nationally representative sample of White Americans and found a positive association between racial prejudice and support for police militarization. Study 2 (N = 3,129,343) sourced regional aggregates of prejudice among White Americans from Project Implicit and policing data from the Defense Logistics Agency and found that police departments in states higher in prejudice acquired greater amounts of militarized equipment. Together, these studies demonstrate that, in terms of attitudes and policies, racial prejudice predicts police militarization.


Hypersensitivity pneumonitis: a complex lung disease.
Hypersensitivity pneumonitis (HP), also called extrinsic allergic alveolitis, is a respiratory syndrome involving the lung parenchyma and specifically the alveoli, terminal bronchioli, and alveolar interstitium, due to a delayed allergic reaction. Such reaction is secondary to a repeated and prolonged inhalation of different types of organic dusts or other substances to which the patient is sensitized and hyper responsive, primarily consisting of organic dusts of animal or vegetable origin, more rarely from chemicals. The prevalence of HP is difficult to evaluate because of uncertainties in detection and misdiagnosis and lacking of widely accepted diagnostic criteria, and varies considerably depending on disease definition, diagnostic methods, exposure modalities, geographical conditions, agricultural and industrial practices, and host risk factors. HP can be caused by multiple agents that are present in work places and in the home, such as microbes, animal and plant proteins, organic and inorganic chemicals. The number of environment, settings and causative agents is increasing over time. From the clinical point of view HP can be divided in acute/subacute and chronic, depending on the intensity and frequency of exposure to causative antigens. The mainstay in managing HP is the avoidance of the causative antigen, though the complete removal is not always possible due to the difficulties to identify the agent or because its avoidance may lead to major changes in life style or occupational settings. HP is a complex syndrome that needs urgently for more stringent and selective diagnostic criteria and validation, including wider panels of IgG, and a closer collaboration with occupational physicians, as part of a multidisciplinary expertise.


TGF-beta1 and IL-6 expression in rat pineal gland is regulated by norepinephrine and interleukin-1beta.
The pineal gland is part of the neuroendocrine system that modulates immune functions. Because the gland is outside the blood-brain barrier, it is accessible to direct feedback from circulating cytokines that affect the synthesis and secretion of melatonin. Recent studies have suggested that intrinsic immunoregulatory cytokines mediate these neuro-immune interactions under the control of sympathetic innervation to the pineal. This study focused on the expression of transforming growth factor-beta1 (TGF-beta1) and interleukin-6 (IL-6), two cytokines that have important regulatory functions on both neurons and immune cells. Northern blot RNA analysis showed that TGF-beta1, but not IL-6, was expressed in freshly dissected rat pineal glands from neonatal age (1-day-old) into adults. Immunocytochemistry for TGF-beta1 in adult glands revealed localization of this protein in astrocyte-like cells. The sympathetic neurotransmitter norepinephrine (NE) increased transcript levels for both TGF-beta1 and IL-6 in adult pineal organ cultures. The effect of NE on IL-6 expression was not found in dispersed cell cultures established from neonatal pineal glands. The immunoregulatory molecule interleukin-1beta (IL-1beta) up-regulated the expression of both IL-6 and TGF-beta1 in adult pineal organ cultures, but not in neonate pineal organ cultures. These findings suggest that TGF-beta1 and IL-6 have intrinsic regulatory roles in the pineal gland and that both neural and immune factors are important mechanisms of regulation.


Auditing the use and assessing the clinical utility of microscopy as a point-of-care test for Neisseria gonorrhoeae in a Sexual Health clinic.
We assessed whether urethral microscopy was performed as per clinic protocol for male clinic attendees reporting contact with Neisseria gonorrhoeae (GC), urethral symptoms or given a diagnosis of epididymo-orchitis (EO) over a 12-month period (9732 patients). Prevalence of gonorrhoea in the contacts, urethral symptoms and EO groups was 50, 12.7 and 1.6%, respectively. Microscopy was performed reliably for contacts (96%), those with discharge/dysuria with evidence of urethritis on examination (98%), but not those with EO (43%). We explored the clinical utility of microscopy as a point-of-care test for identifying urethral GC in each subgroup, using the APTIMA Combo 2 CT/GC nucleic acid amplification test as the comparator (1710 patients). Sensitivity of microscopy for each subgroup was good; there was no statistical difference between subgroup sensitivity using Fisher's exact test. Microscopy is valuable to ensure prompt diagnosis and contact tracing. All GC contacts were treated 'epidemiologically'; however, half of GC contacts did not have GC. Microscopy identified the majority of GC cases, including amongst contacts (71% of heterosexual contacts, 66% of contacts reporting sex with men). We propose that epidemiological treatment for GC contacts should be reconsidered on the grounds of antibiotic stewardship, favouring use of microscopy to guide treatment decisions.


Theoretical study on the interaction of pyrrolopyrimidine derivatives as LIMK2 inhibitors: insight into structure-based inhibitor design.
LIM kinases (LIMKs), downstream of Rho-associated protein kinases (ROCKs) and p21-activated protein kinases (PAKs), are shown to be promising targets for the treatment of cancers. In this study, the inhibition mechanism of 41 pyrrolopyrimidine derivatives as LIMK2 inhibitors was explored through a series of theoretical approaches. First, a model of LIMK2 was generated through molecular homology modeling, and the studied inhibitors were docked into the binding active site of LIMK2 by the docking protocol, taking into consideration the flexibility of the protein. The binding poses predicted by molecular docking for 17 selected inhibitors with different bioactivities complexed with LIMK2 underwent molecular dynamics (MD) simulations, and the binding free energies for the complexes were predicted by using the molecular mechanics/generalized born surface area (MM/GBSA) method. The predicted binding free energies correlated well with the experimental bioactivities (r(2) = 0.63 or 0.62). Next, the free energy decomposition analysis was utilized to highlight the following key structural features related to biological activity: (1) the important H-bond between Ile408 and pyrrolopyrimidine, (2) the H-bonds between the inhibitors and Asp469 and Gly471 which maintain the stability of the DFG-out conformation, and (3) the hydrophobic interactions between the inhibitors and several key residues (Leu337, Phe342, Ala345, Val358, Lys360, Leu389, Ile408, Leu458 and Leu472). Finally, a variety of LIMK2 inhibitors with a pyrrolopyrimidine scaffold were designed, some of which showed improved potency according to the predictions. Our studies suggest that the use of molecular docking with MD simulations and free energy calculations could be a powerful tool for understanding the binding mechanism of LIMK2 inhibitors and for the design of more potent LIMK2 inhibitors.


[Treatment of uremic sympathicopathy with levodopa].
Two patients with chronic uremia suffering from postural hypotension and hypotensive episodes during hemodialysis have been successfully treated with L-DOPA. In one patient the autonomic insufficiency and the beneficial effect of L-DOPA has been demonstrated by tests of the autonomic nervous system. The action of L-DOPA remains unclear. It is possible that the administration of L-DOPA results in increased synthesis of norepinephrine.


Complete localization of disulfide bonds in GM2 activator protein.
Lysosomal degradation of ganglioside GM2 by hexosaminidase A requires the presence of a small, non-enzymatic cofactor, the GM2-activator protein (GM2AP). Lack of functional protein leads to the AB variant of GM2-gangliosidosis, a fatal lysosomal storage disease. Although its possible mode of action and functional domains have been discussed frequently in the past, no structural information about GM2AP is available so far. Here, we determine the complete disulfide bond pattern of the protein. Two of the four disulfide bonds present in the protein were open to classical determination by enzymatic cleavage and mass spectrometry. The direct localization of the remaining two bonds was impeded by the close vicinity of cysteines 136 and 138. We determined the arrangement of these disulfide bonds by MALDI-PSD analysis of disulfide linked peptides and by partial reduction, cyanylation and fragmentation in basic solution, as described recently (Wu F, Watson JT, 1997, Protein Sci 6:391-398).


[Permanent central venous access in chronically-ill children].
15 patients aged 8 months to 18 years received implanted venous access catheters. Blood sampling and continuous infusions up to 52 days were performed via these devices. The systems were used for 18-166+ days and implanted for 18-635+ days. The complication rate was low and seems to be dependent on the experience of the caretaker. The systems are a valuable addition in the care of chronic sick children and offer new perspectives of therapy.


Maintenance of genome stability in plants: repairing DNA double strand breaks and chromatin structure stability.
Plant cells are subject to high levels of DNA damage resulting from plant's obligatory dependence on sunlight and the associated exposure to environmental stresses like solar UV radiation, high soil salinity, drought, chilling injury, and other air and soil pollutants including heavy metals and metabolic by-products from endogenous processes. The irreversible DNA damages, generated by the environmental and genotoxic stresses affect plant growth and development, reproduction, and crop productivity. Thus, for maintaining genome stability, plants have developed an extensive array of mechanisms for the detection and repair of DNA damages. This review will focus recent advances in our understanding of mechanisms regulating plant genome stability in the context of repairing of double stand breaks and chromatin structure maintenance.


Multiregional genetic evolution of metastatic uveal melanoma.
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and leads to deadly metastases for which there is no approved treatment. Genetic events driving early tumor development are well-described, but those occurring later during metastatic progression remain poorly understood. We performed multiregional genomic sequencing on 22 tumors collected from two patients with widely metastatic UM who underwent rapid autopsy. We observed multiple seeding events from the primary tumors, metastasis-to-metastasis seeding, polyclonal seeding, and late driver variants in ATM, KRAS, and other genes previously unreported in UM. These findings reveal previously unrecognized temporal and anatomic complexity in the genetic evolution of metastatic uveal melanoma, and they highlight the distinction between early and late phases of UM genetic evolution with implications for novel therapeutic approaches.


Role of intestinal efflux transporters in the intestinal absorption of methotrexate in rats.
The role of intestinal efflux transporters such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs) in intestinal absorption of methotrexate was examined in rats. In everted intestine, the mucosal efflux of methotrexate after application to serosal side was higher in jejunum than ileum, and the efflux in jejunum was suppressed by pantoprazole, a BCRP inhibitor, and probenecid, an MRP inhibitor, but not by verapamil, a P-gp inhibitor. The mucosal methotrexate efflux in ileum was suppressed by pantoprazole, but not by other inhibitors. On the other hand, the serosal efflux of methotrexate after application to mucosal side was greater in ileum than jejunum, and was suppressed by probenecid. In in-vivo rat studies, the intestinal absorption of methotrexate was significantly higher when methotrexate was administered to ileum than jejunum. Pantoprazole increased methotrexate absorption from jejunum and ileum. Probenecid increased the absorption of methotrexate from jejunum but decreased the absorption from ileum, as evaluated by peak plasma methotrexate levels. In conclusion, BCRP and MRPs are involved in the regional difference in absorption of methotrexate along the intestine, depending on their expression sites.


Local steroid injection into the artificial ulcer created by endoscopic submucosal dissection for gastric cancer: prevention of gastric deformity.
Endoscopic submucosal dissection (ESD) of large gastric lesions results in an extensive artificial ulcer that can lead to marked gastric deformity. The aim of the current study was to evaluate therapeutic efficacy in the prevention of gastric deformity of local triamcinolone acetonide (TCA) injection into the extensive artificial ulcer following ESD. A total of 45 patients who were diagnosed with early gastric cancer were enrolled. Patients were randomly assigned by the sealed-envelope randomization method to either local TCA injections (n = 21) or sham-control (n = 20) groups. Two clips were placed at the two maximum outer edges of the artificial ulcer after the lesion had been resected (Day 0). Local TCA injections were performed on postoperative Day 5 and Day 12. The distance between the two clips was measured by endoscopic measuring forceps on Days 5, 12, 30, and 60. Granulation formation and gastric deformity were evaluated by visual analog scale (VAS) on Days 30 and 60. Local TCA injection did not alter clip-to-clip distance on postoperative Day 60, and formation of flat granulation tissue over the ulcer was followed by regenerative mucosa without any gastric deformity. The sham-control group showed significant shortening of clip-to-clip distance compared with the local steroid-injected group and protruded forms of granulation tissue with mucosal convergence. Histological evaluation revealed prominent growth of neovessels, swelling, and marked increases in endothelial cells in the local steroid-injected group compared with the sham-control group. Local steroid injection into the floor of a post-ESD artificial ulcer promotes the formation of granulation tissue at an early stage of the healing process leading to regeneration of gastric mucosa without mucosal convergence or gastric deformity.


Residue of thiram in food, suppresses immune system stress signals and disturbs sphingolipid metabolism in chickens.
Thiram, a well-known sulfur containing organic compound is frequently and extensively used in agriculture because of high biological activity to control different pests. In certain cases, due to long persistence in the environment pesticides and other environmental contaminants induce undesirable toxic impacts to public health and environment. To ascertain the potential mechanisms of toxicity of thiram on different immune organs of broilers, a total of 100 one-day-old chicks were obtained and randomly divided into two groups including thiram group (50 mg/kg) and untreated control group. Thymus and spleen tissues were collected at the age of 14 days from the experimental birds. At necropsy level, thymus was congested, enlarged and hyperemic while spleen had no obvious lesions. The results on mechanisms (apoptosis and autophagy) of immunotoxicity showed significantly increased expression of bax, caspase3, cytc, ATG5, beclin1 and p62 in spleen of treated mice. Results indicated significantly decreased expression of m-TOR and bcl2 to activate apoptosis and autophagy. The expressions of bax, p53 and m-TOR were up-regulated in the thymus while the expressions of ATG5 and Beclin1 were down-regulated to mediate cell apoptosis and inhibit autophagy. The results on different metabolome investigation showed that the sphingolipid metabolism in the thymus of chicks exposed to thiram was disrupted resulting in up-regulation of metabolites related to cell membrane components such as SM, galactosylceramide and lactosylceramide. The results of our experimental research suggest that thiram can interfere with the sphingolipid metabolism in thymus and angiogenesis, inhibit the proliferation of vascular endothelial cells to induce potential toxic effects in chicken.


Physician payments under health care reform.
This study examines the impact of major health insurance reform on payments made in the health care sector. We study the prices of services paid to physicians in the privately insured market during the Massachusetts health care reform. The reform increased the number of insured individuals as well as introduced an online marketplace where insurers compete. We estimate that, over the reform period, physician payments increased at least 11 percentage points relative to control areas. Payment increases began around the time legislation passed the House and Senate-the period in which their was a high probability of the bill eventually becoming law. This result is consistent with fixed-duration payment contracts being negotiated in anticipation of future demand and competition.


Pregnancy Options Counseling and Abortion Referrals Among US Primary Care Physicians: Results From a National Survey.
Primary care physicians (PCPs) can play a critical role in addressing unintended pregnancy through high-quality options counseling and referrals. We surveyed a nationally representative sample of 3,000 PCPs in general, family, and internal medicine on practices and opinions related to options counseling for unintended pregnancy. We assessed predictors of physician practices using multivariable logistic regression weighted for sampling design and differential non-response. Response rate was 29%. Seventy-one percent believed residency training in options counseling should be required, and 69% believed PCPs have an obligation to provide abortion referrals even in the presence of a personal objection to abortion. However, only 26% reported routine options counseling when caring for women with unintended pregnancy compared to 60% who routinely discuss prenatal care. Among physicians who see women seeking abortion, 62% routinely provide referrals, while 14% routinely attempt to dissuade women. Family physicians were more likely to provide routine options counseling when seeing patients with unintended pregnancy than internal medicine physicians (32% vs 21%, P=0.002). In multivariable analyses, factors associated with higher odds of routine abortion referrals were more years in practice (OR=1.03 for each additional year, 95% CI: 1.00-1.05), identifying as a woman vs a man (OR=2.11, 95% CI: 1.31-3.40), practicing in a hospital vs private primary care/multispecialty setting (OR=3.17, 95% CI: 1.10-9.15), and no religious affiliation of practice vs religious affiliation (OR for Catholic affiliation=0.27, 95% CI: 0.11-0.66; OR for other religious affiliation=0.36, 95% CI: 0.15-0.83). Personal Christian religious affiliation among physicians who regularly attend religious services vs no religious affiliation was associated with lower odds of counseling (OR=0.48, 95% CI: 0.26-0.90) and referrals (OR=0.31, 95% CI: 0.15-0.62), and higher odds of abortion dissuasion (OR=4.03, 95% CI: 1.46-11.14). Findings reveal the need to support fuller integration of options counseling and abortion referrals in primary care, particularly through institutional and professional society guidelines and training opportunities to impart skills and highlight the professional obligation to provide non-directive information and support to women with unintended pregnancy.


CD40 ligand binds to alpha5beta1 integrin and triggers cell signaling.
It was originally thought that the critical role of the CD40 ligand (CD40L) in normal and inflammatory immune responses was mainly mediated through its interaction with the classic receptor, CD40. However, data from CD40L(-/-) and CD40(-/-) mice suggest that the CD40L-induced inflammatory immune response involves at least one other receptor. This hypothesis is supported by the fact that CD40L stabilizes arterial thrombi through an alphaIIbbeta3-dependent mechanism. Here we provide evidence that soluble CD40L (sCD40L) binds to cells of the undifferentiated human monocytic U937 cell line in a CD40- and alphaIIbbeta3-independent manner. Binding of sCD40L to U937 cells was inhibited by anti-CD40L monoclonal antibody 5C8, anti-alpha5beta1 monoclonal antibody P1D6, and soluble alpha5beta1. The direct binding of sCD40L to purified alpha5beta1 was confirmed in a solid phase binding assay. Binding of sCD40L to alpha5beta1 was modulated by the form of alpha5beta1 expressed on the cell surface as the activation of alpha5beta1 by Mn(2+) or dithiothreitol resulted in the loss of sCD40L binding. Moreover, sCD40L induced the translocation of alpha5beta1 to the Triton X-100-insoluble fraction of U937 cells, the rapid activation of the MAPK pathways ERK1/2, and interleukin-8 gene expression. The binding of sCD40L to CD40 on BJAB cells, an alpha5beta1-negative B cell line, and the resulting activation of ERK1/2 was not inhibited by soluble alpha5beta1, suggesting that sCD40L can bind concomitantly to both receptors. These results document the existence of novel CD40L-dependent pathways of physiological relevance for cells expressing multiple receptors (CD40, alpha5beta1, and alphaIIbbeta3) for CD40L.


ERK mediates inhibition of Na(+)/H(+) exchange and HCO(3)(-) absorption by nerve growth factor in MTAL.
Mitogen-activated protein (MAP) kinases mediate a variety of critical cellular events, but their role in the regulation of epithelial transport is largely undefined. Recently, we demonstrated that nerve growth factor (NGF) inhibits HCO(3)(-) absorption in the rat medullary thick ascending limb (MTAL) through an unusual mechanism: 1) NGF inhibits basolateral membrane Na(+)/H(+) exchange activity, an effect opposite to the stimulation of Na(+)/H(+) exchange by growth factors in other cells; and 2) inhibition of basolateral Na(+)/H(+) exchange results secondarily in inhibition of apical Na(+)/H(+) exchange, thereby inhibiting HCO(3)(-) absorption. In this study, we examined the role of MAP kinases in mediating inhibition by NGF. In tissue strips from the inner stripe of the outer medulla and in microdissected MTALs, NGF increased extracellular signal-regulated kinase (ERK) activity twofold but had no effect on c-Jun NH(2)-terminal kinase (JNK) or p38 MAP kinase activity. The selective MAP kinase kinase (MEK1/2) inhibitors U0126 and PD-98059 abolished the NGF-induced ERK activation and largely eliminated (> or = 60%) the effects of NGF to inhibit basolateral Na(+)/H(+) exchange activity and transepithelial HCO absorption in perfused MTALs. The MEK1/2 inhibitors did not affect inhibition of HCO(3)(-) absorption by bath ethylisopropyl amiloride, indicating that ERK activation is not involved in mediating interaction between the basolateral and apical Na(+)/H(+) exchangers. These results demonstrate that NGF inhibits basolateral Na(+)/H(+) exchange activity and HCO(3)(-) absorption in the MTAL through activation of the ERK signaling pathway. These findings identify a novel action of ERK to inhibit Na(+)/H(+) exchange activity and establish a role for MAP kinase pathways in the acute regulation of Na(+)/H(+) exchange activity and transepithelial acid secretion in renal tubules.


Canine Brachycephaly: Anatomy, Pathology, Genetics and Welfare.
Brachycephalic dog breeds have experienced a marked rise in popularity in recent years. While numerous people clearly desire this phenotype in their pets, many of these dogs unfortunately experience several concomitant sequelae, including major problems with respiration and thermoregulation, as well as gastrointestinal, ophthalmological, dermatological, reproductive and even dental problems. This mini review focuses on the anatomical and pathological changes associated with brachycephalic skull shape, including brachycephalic obstructive airway syndrome and other co-existent disorders. It then details the known genetic contributors to brachycephaly, and concludes with a brief discourse on the welfare of these animals.


Financial development, energy consumption, and economic growth in the ASEAN countries: evidence from the PVAR approach.
The Association of Southeast Asian Nations (ASEAN), a new global economic force, has struggled to achieve a dual objective of enhanced economic growth and improved environmental quality. Financial development is generally considered an important tool in achieving these simultaneous objectives. This paper examines the response mechanism and the inter-relationship between the ASEAN region's financial development, energy consumption, and economic growth. Unlike previous studies, the paper uses a generalized method of moments panel vector autoregression (GMM-panel VAR) framework for the 1981-2021 period. The second-generation Granger causality test is used to identify their causality relationship. Economic growth supports financial development and reduces energy consumption from fossil fuel sources in the ASEAN countries. Financial development also reduces fossil fuel energy consumption. The bi-directional relationship between economic growth and fossil fuel energy consumption exists. Energy consumption and financial development are also bi-directionally linked. However, only the unidirectional Granger causality from economic growth to financial development is found. The variance decomposition analysis results confirm that economic growth accounts for the most significant variance in fossil fuel energy consumption and financial development in the ASEAN countries. Policy implications have emerged based on these findings.


Endowing Perovskite Nanocrystals with Circularly Polarized Luminescence.
Perovskite nanocrystals are attracting great interest due to their excellent photonic properties. Here, through a supramolecular self-assembly approach, the perovskite nanocrystals (NCs) with a novel circularly polarized luminescence (CPL) are successfully endowed. It is found that the achiral perovskite NCs can coassemble with chiral gelator in nonpolar solvents, in which the gelator molecules modify the surface of the perovskite NCs. Through such cogelation, the molecular chirality can transfer to the NCs resulting in CPL signals with a dissymmetric factor (glum ) up to 10-3 . Furthermore, depending on the molecular chirality of the gelator, the CPL sense can be selected and the mirror-imaged CPL is obtained. Such gels can be further embedded into the polymer film to facilitate flexible CPL devices. It is envisaged that this approach will afford a new insight into the designing of the functional chiroptical materials.


Overexpression of E2F1 in clear cell renal cell carcinoma: a potential impact of erroneous regulation by thyroid hormone nuclear receptors.
We show here that the promoter of E2F1 gene, encoding one of the key regulators of cell proliferation, is overly active in the presence of low amounts of triiodothyronine (T3) and in the presence of mutant thyroid hormone receptor. We also show that T3-thyroid hormone receptor pathway of regulation of molecular processes is disturbed in clear cell renal cell carcinoma (ccRCC) on several levels, including overexpression of thyroid hormone receptors and the disturbance of their binding to DNA and to the hormone. In comparison to the cancer-free kidneys and peritumoral respective control tissues, E2F1 mRNA and protein levels are significantly increased in cancer tissues. A significant correlation between E2F1 mRNA and protein levels has been found in both control types and ccRCCs. No correlation was observed between the amount of E2F1 mRNA and the amount of thyroid hormone receptors or their DNA or T3 binding activity, suggesting that the function of thyroid hormone receptors could be markedly disturbed in both tumor and peritumoral cells. In summary, we show that ccRCC is characterized by the overexpression of E2F1, which is likely a result of a deregulated control of T3-dependent molecular processes.


Comparison of a new enzymatic assay with a high-performance liquid chromatography/ ultraviolet detection method for therapeutic drug monitoring of mycophenolic acid in adult liver transplant recipients.
Mycophenolic acid (MPA) is used to prevent graft rejection. The methods used for determining the plasma MPA concentration in liver transplant recipients are the enzyme-multiplied immunoassay technique (EMIT), high-performance liquid chromatography with ultraviolet detection (HPLC-UV), and most recently mass spectrometry. EMIT has been reported to overestimate the MPA concentration by 30% to 35% in comparison with HPLC-UV. Recently, a new automated enzymatic assay based on inosine monophosphate dehydrogenase inhibition has been designed. The aim of the present investigation was to compare this technique with validated HPLC-UV in adult liver transplant recipients treated with tacrolimus or cyclosporine. One hundred seventy-six samples from 50 adult liver transplant recipients were analyzed with both techniques. Patients received mycophenolate mofetil (2 or 3 times daily) coadministered with cyclosporine microemulsion (n = 18) or tacrolimus (n = 32). Samples were drawn over an interdose interval during the early or late posttransplantation period. The Passing-Bablok regression and Bland-Altman plot were used to compare the 2 techniques. The Passing-Bablock regression, calculated from 166 samples, showed very good agreement between the enzymatic assay and the HPLC-UV method: enzymatic assay = 1.0204 (95% confidence interval, 0.9942, 1.0478) x HPLC-UV + 0.0201 (-0.0442, 0.0882). No significant bias was found between the techniques (Bland-Altman plot), and the median relative difference was 2.7% (95% confidence interval, -0.4, 6.6). In conclusion, the enzymatic assay showed an excellent correlation with HPLC-UV. Therefore, this method was proved valid and reliable for the monitoring of the plasma MPA concentration in adult liver transplant recipients treated with cyclosporine microemulsion or tacrolimus.


Recovery and distribution of biosolids-derived trace metals in a clay loam soil.
The long-term mobility of trace metals has been cited as a potential hazard by critics of EPA 503 rule governing the land application of biosolids. The objectives of this study were to assess the accumulation of Cu, Ni, Cd, and Zn within the soil profile; the distribution of exchangeable, specifically adsorbed, organic, and oxide fractions of each metal; and mass balance of Cu, Ni, and Zn 17 yr after a single biosolids application. Biosolids were applied to 1.5- x 2.3-m confined plots of a Davidson clay loam (fine, kaolinitic, thermic Rhodic Kandiudult) in 1984 at 0, 42, 84, 126, 168, and 210 Mg ha(-1). The highest biosolids application supplied 4.5, 750, 43, and 600 kg ha(-1) of Cd, Cu, Ni, and Zn, respectively. Soils were sampled to a depth of 0.9 m and sectioned into 5-cm increments after separating the Ap horizon. Total (EPA-3050B), bioavailable (Mehlich-I), sequential extraction, and dispersible clay analyses were performed on samples from the control, 126 Mg ha(-1), and 210 Mg ha(-1) treatments. Trace metals are still concentrated in the top 0.2 m with slight enrichment down to 0.3 m. More than 85% of applied Cu, Ni, and Zn are still found in the topsoil where biosolids was incorporated and 95% or more of the applied metals were accounted for with mass balance calculations. Mehlich-I results showed a slight increase in metal concentration down to 0.35 m. Biosolids application increased the concentrations of trace metals in all the extracted fractions. The major portions of Cu, Zn, and Ni are associated with the metal-oxides fraction. Dispersible clay content and water-soluble metal contents were low and except for water-soluble Zn they were not affected by biosolids application. Results from this study showed that 17 yr after biosolids application there was negligible movement of trace metals through the soil profile and consequently there is little risk of contamination of ground water at this site.


Factors related to the adoption of exercise among older women.
The role of exercise in promoting health is well documented; however, older women have the lowest rates of aerobic exercise of any community group. This paper examines psychological variables relevant to women's initial adoption of exercise. While the evidence is limited, it appears that middle-aged and older women have positive attitudes to exercise but seem unable or unwilling to take action. The influence of practical barriers and of broader social attitudes is considered. It is concluded that social psychological variables have had limited success in explaining sex differences in physical activity. An understanding of practical and societal constraints on behavior choice in a broader social context may provide direction for the development of strategies to improve the exercise levels of this community group.


Identification of differentially expressed genes in salivary adenoid cystic carcinoma cells associated with metastasis.
Salivary adenoid cystic carcinoma (SACC) is a frequent type of salivary gland cancer which is characterized by slow growth but high incidence of distant metastasis. We aimed to identify therapeutic targets which are associated with metastasis of SACC. Total RNA was isolated from a low metastatic SACC cell line (ACC-2) and a highly metastatic SACC cell line (ACC-M), which was screened from ACC-2 by combination of in vivo selection and cloning in vitro. Then the total RNA was subjected to microarray analysis. Differentially expressed genes (DEGs) were screened from ACC-M compared with ACC-2, followed by Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Function annotation for DEGs also was performed. A protein-protein interaction network (PPI) was constructed for DEGs. A total of 1128 DEGs were identified from ACC-M cells compared with ACC-2 cells. Both up- and down-regulated DEGs were enriched in different functions in biological process (BP), cellular component (CC) and molecular function (MF). Additionally, down-regulated DEGs were mainly enriched in "Apoptosis" and "Cytokine-cytokine receptor interaction" pathways which involved IFN-α1, NTRK1 and TGF-β1. In the PPI network, PIK3CA, PTPN11 and PIK3R1 had a number of nodes greater than 10. Transforming growth factor β1 might play a pivotal role during lung metastasis of SACC and be selected as a candidate target for treatment of metastatic SACC. IFNA1, NTRK1 and PIK3CA were also associated with tumor metastasis.


Bradykinin-related compounds as new drugs for cancer and inflammation.
Bradykinin (BK) (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) is an important growth factor for small-cell lung cancer (SCLC) and prostate cancer (PC). These cancers have cells of neuroendocrine origin and express receptors for a variety of neuropeptides. BK receptors are expressed on almost all lung cancer cell lines and on many PC cells. Our very potent BK antagonist B9430 (D-Arg-Arg-Pro-Hyp-Gly-lgl-Ser-D-Igl-Oic-Arg) (Hyp, trans-4-hydroxy-L-proline; Ig1, alpha-2-indanylglycine; Oic, octahydroindole-2-carboxylic acid) is a candidate anti-inflammatory drug but does not inhibit growth of SCLC or PC. When B9430 is dimerized by N-terminal cross-linking with a suberimide linker, the product B9870 is a potent growth inhibitor for SCLC both in vitro and in vivo in athymic nude mice. Daily i.p. injection at 5 mg x kg(-1) day(-1) beginning on day 8 after SCLC SHP-77 cell implantation gave 65% inhibition of tumor growth. B9870 stimulates apoptosis in SCLC by a novel "biased agonist" action. We have also developed new small mimetic antagonists. BKM-570 (F5C-OC2Y-Atmp) (F5C, pentafluorocinnamic acid; OC2Y, O-2,6-dichlorobenzyl tyrosine; Atmp, 4-amino-2,2,6,6-tetramethylpiperidine) is very potent for inhibition of SHP-77 growth in nude mice. When injected daily i.p. at 5 mg x kg(-1), M-570 gave 90% suppression of tumor growth. M-570 is more potent than the well-known anticancer drug cisPlatin (60% inhibition) or the recently developed SU5416 (40% inhibition) in this model. M-570 also showed activity against various other cancer cell lines in vitro (SCLC, non-SCLC, lung, prostate, colon, cervix) and inhibited growth of prostate cell line PC3 in nude mice. M-570 and related compounds evidently act in vivo through pathways other than BK receptors. These compounds have clinical potential for treatment of human lung and prostate cancers.


Effects of aortic valve replacement on exercise duration and functional status in adults with valvular aortic stenosis.
To evaluate the effect of aortic valve replacement on left ventricular function, functional status and exercise duration in an adult population with valvular aortic stenosis. Prospective study of initially asymptomatic patients with pre- and postvalve replacement echocardiography, functional status score and exercise data. University-affiliated, tertiary care teaching hospital. Valvular aortic stenosis patients referred from academic and private practice internists and cardiologists (n = 34, 65% men, mean age 68 +/- 11 years, preoperative aortic valve area 0.9 +/- 0.4 cm2). Annual Doppler echocardiography, functional status questionnaires and, if possible, Bruce protocol maximal exercise tolerance tests. Aortic valve replacement resulted in a decrease in maximum jet velocity (pre 4.7 +/- 0.7 versus post 2.9 +/- 0.7 m/s, P = 0.0001) and left ventricular mass (pre 167 +/- 37 versus post 134 +/- 32 g, P = 0.0001) and an increase in left ventricular ejection fraction (pre 65 +/- 11 versus post 69 +/- 10%, P = 0.05) at rest. However, there was no change in the ratio of early to atrial diastolic filling velocities (pre 1.2 +/- 0.5 versus post 1.4 +/- 0.8, not significant), exercise tolerance as assessed by estimated functional aerobic impairment (pre 26 +/- 32 versus post 22 +/- 27%, not significant) or functional status score (pre 89 +/- 13 versus post 91 +/- 11, not significant). When the aortic valve is replaced promptly at symptom onset, despite improvement in resting left ventricular systolic performance, there is no evidence of improvement in exercise capacity or functional status.


Silencing a phloretin-specific glycosyltransferase perturbs both general phenylpropanoid biosynthesis and plant development.
The polyphenol profile of apple (Malus × domestica) is dominated by the dihydrochalcone glycoside phloridzin, but its physiological role is yet to be elucidated. Biosynthesis of phloridzin occurs as a side branch of the main phenylpropanoid pathway, with the final step mediated by the phloretin-specific glycosyltransferase UGT88F1. Unexpectedly, given that UGTs are sometimes viewed as 'decorating enzymes', UGT88F1 knockdown lines were severely dwarfed, with greatly reduced internode lengths, narrow lanceolate leaves, and changes in leaf and fruit cellular morphology. These changes suggested that auxin transport had been altered in the knockdown lines, which was confirmed in assays showing that auxin flux from the shoot apex was increased in the transgenic lines. Metabolite analysis revealed no accumulation of the phloretin aglycone, as well as decreases in many non-target phenylpropanoid compounds. This decreased accumulation of metabolites appeared to be mediated by the repression of the phenylpropanoid pathway via a reduction in key transcript levels (e.g. phenylalanine ammonia lyase, PAL) and enzyme activities (PAL and chalcone synthase). Application of exogenous phloridzin to the UGT88F1 knockdown lines in tissue culture enhanced axial leaf growth and partially restored some aspects of 'normal' apple leaf growth. Together, our results strongly implicate dihydrochalcones as critical compounds in modulating phenylpropanoid pathway flux and establishing auxin patterning early in apple development.


Viruses of Entamoeba histolytica. IV. Studies on the nucleic acids of the filamentous and polyhedral viruses.
The nucleic acids of two amoebal viruses were studied by several independent methods. The filamentous virus, V(ABRM), was shown to be inhibited by bromodeoxyuridine, iododeoxyuridine, and cytosine arabinoside. With acridine orange staining, V(ABRM) inclusions appeared greenish-yellow, indicating that these contained double-stranded nucleic acid. The polyhedral virus, V(301), was also inhibited by bromodeoxyuridine, iododeoxyuridine, and cytosine arabinoside. In addition, nucleic acid hybridization showed that a new DNA species was synthesized in infected amoebal cultures. The intracellular localization of this new DNA was consistent with previous electron microscope studies of the cytoplasmic maturation of V(301).


Association Between Human Leukocyte Antigen Class I and II Diversity and Non-virus-associated Solid Tumors.
Homozygosity at human leukocyte antigen (HLA) loci might lead to reduced immunosurveillance and increased disease risk, including cancers caused by infection or of hematopoietic origin. To investigate the association between HLA zygosity and risk of non-virus-associated solid tumors, we leveraged genome-wide association study (GWAS) data from over 28,000 individuals of European ancestry who participated in studies of 12 cancer sites (bladder, brain, breast, colon, endometrial, kidney, lung, ovary, pancreas, prostate, skin, and testis). Information on HLA zygosity was obtained by imputation; individuals were classified as homozygotes at a given locus when imputed to carry the same four-digit allele at that locus. We observed no evidence for an association between zygosity at six HLA loci and all cancers combined. Increase in number of homozygous at HLA class I loci, class II loci, or class I and II loci was also not associated with cancer overall (P trend = 0.28), with adjusted odds ratios (ORs) for risk-per-locus of 1.00 [95% confidence intervals (CIs) = 0.97, 1.03], 1.02 (0.99, 1.04), and 1.01 (0.99, 1.02), respectively. This study does not support a strong role for HLA zygosity on risk of non-virus-associated solid tumors.


Urinary gamma-glutamyl transferase-to-creatinine ratio as an indicator of tubular function in Bence Jones proteinuria.
Increased urinary gamma-glutamyl transferase (GGT) activity suggests early renal tubular damage. The aim of this study was to evaluate the urinary GGT activity as a marker of renal injury in different types of Bence Jones Proteinuria (BJP). One hundred and three individuals with BJP were included in the study. Urinary GGT activity, urinary GGT-to-creatinine ratio and urinary protein-to-creatinine ratio were studied. Urine samples were tested by immunofixation agarose gel electrophoresis. Total urinary excretion of kappa and lambda light chains were measured by nephelometric method. There were no significant differences in demographic characteristics of the patients in Lambda BJP, Kappa BJP and Control groups. GGT-to-creatinine ratio of the Lambda BJP group was significantly higher than Kappa BJP group and controls (p = 0.018 and 0.002, respectively). There was no correlation between the quantitative kappa and lambda BJP and urinary GGT-to-creatinine ratio. Our data have demonstrated that urinary GGT-to-creatinine ratio could be a tubular damage marker of lambda light chain proteinuria.


Favorable Loci Identified for Stripe Rust Resistance in Chinese Winter Wheat Accessions Via Genome-Wide Association Study.
Stripe rust (or yellow rust), caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most devastating diseases of wheat worldwide. Currently, the utilization of resistant cultivars is the most viable way to reduce yield loss. In this study, a panel of 188 wheat accessions from China were evaluated for stripe rust resistance, and genome-wide association studies (GWAS) were performed using high-quality Diversity Arrays Technology (DArT) markers. According to the phenotype and genotype data, a total of 26 significant marker-trait associations were identified, representing 18 quantitative trait loci (QTLs) on chromosomes 1B, 2A, 2B, 3A, 3B, 5A, 5B, 6B, 7B, and 7D. Of the 18 QTLs, almost all were associated with adult plant resistance (APR) except QYr.nwsuaf-6B.2, which was associated with all-stage resistance (ASR, also known as seedling resistance). Three of the 18 QTLs were mapped far from previously identified Pst resistance genes/QTLs and were considered potentially new loci. The other 15 QTLs mapped close to known resistance genes/QTLs. Subsequent haplotype analysis for QYr.nwsuaf-2A and QYr.nwsuaf-7B.3 revealed the degrees of resistance of the panel in the APR stage. In summary, the favorable alleles identified in this study may be useful in breeding for disease resistance to stripe rust.


Implementing Measurement-Based Care to Determine and Treat Inadequate Response.
 Measurement-based care (MBC) is an important strategy in the treatment of patients with major depressive disorder who have inadequate antidepressant response. The rating scales used in MBC can assist clinicians at critical decision points, such as when to declare a treatment failure, what to do with partial improvement, and how long to continue successful treatment. Measurement has two benefits: it gives the clinician an objective basis for comparison of symptom severity over time, and it helps patients to have insight into their illness course. Further, many of these tools do not add substantially to the length of the clinical visit. MBC can also be used to monitor and address residual symptoms such as fatigue and irritability that impact patients' functioning and quality of life. .


A computational model of the progression of Alzheimer's disease.
Computational modeling allows analysis of the role of network dynamics in the initiation and progression of neuropathology in Alzheimer's disease. The model focuses on a final common breakdown in function, termed runaway synaptic modification. This phenomenon could account for evidence that neuropathological markers associated with neuronal death in Alzheimer's disease first appear and attain their highest concentration in subregions of the hippocampal formation, and then successively spread into the temporal lobe cortex and the cortex of the frontal and parietal lobes. The model demonstrates how the spread of neuropathology from the hippocampus into neocortical structures could result from the mechanisms of consolidation. Initial sensitivity of the hippocampus and entorhinal cortex to the neuropathological process is proposed to result from an imbalance of variables regulating the influence of synaptic transmission on synaptic modification. Memory deficits are described as due to increased interference effects on recent memory caused by runaway synaptic modification, which ultimately leads to impairments of remote and semantic memory.


Physical Accessibility of Routine Prenatal Care for Women with Mobility Disability.
Routine prenatal care includes physical examinations and weight measurement. Little is known about whether access barriers to medical diagnostic equipment, such as examination tables and weight scales, affect prenatal care among pregnant women with physical disabilities. We conducted 2-hour, in-depth telephone interviews with 22 women using a semistructured, open-ended interview protocol. All women had significant mobility difficulties before pregnancy and had delivered babies within the prior 10 years. We recruited most participants through social networks. We sorted interview transcript texts using used NVivo software and conducted conventional content analyses to identify major themes. Interviewee's mean (standard deviation) age was 34.8 (5.3) years. Most were white, well-educated, and higher income; 8 women had spinal cord injuries, 4 cerebral palsy, and 10 had other conditions; 18 used wheeled mobility aids. Some women's obstetricians had height adjustable examination tables, which facilitated transfers for physical examinations. Other women had difficulty transferring onto fixed height examination tables and were examined while sitting in their wheelchairs. Family members and/or clinical staff sometimes assisted with transfers; some women reported concerns about transfer safety. No women reported being routinely weighed on an accessible weight scale by their prenatal care clinicians. A few were never weighed during their pregnancies. Inaccessible examination tables and weight scales impede some pregnant women with physical disabilities from getting routine prenatal physical examinations and weight measurement. This represents substandard care. Adjustable height examination tables and wheelchair accessible weight scales could significantly improve care and comfort for pregnant women with physical disabilities.


Carotenoids as protection against disability in older persons.
The purpose was to examine the relationship of total plasma carotenoids, an indicator of fruit and vegetable intake, with walking speed and severe walking disability in older adults. Nine hundred twenty-eight men and women aged 65 to 102 years from the Invecchiare in Chianti (Aging in the Chianti Area [InCHIANTI]) study, a population-based cohort in Tuscany, Italy, were studied. Plasma carotenoids were measured at enrollment (1998-2000), and walking speed over 4 meters and 400 meters distance were assessed at enrollment and 6 years later (2004-2006). At enrollment, 85 of 928 (9.2%) participants had severe walking disability (defined as being unable to walk or having a walking speed at the 4-meter walking test < 0.4 m/sec). After adjusting for potential confounders, participants with high total plasma carotenoids were significantly less likely to have prevalent severe walking disability (odds ration [OR] 0.59, 95% confidence interval [CI] 0.38-0.90, p = 0.01) and had higher walking speed over 4 meters (beta = 0.024, standard error [SE] = 0.011, p = 0.03) and over 400 meters (beta = 0.019, SE = 0.010, p = 0.04). Of 621 participants without severe walking disability at enrollment who were seen 6 years later, 68 (11.0%) developed severe walking disability. After adjusting for potential confounders, higher total plasma carotenoids were associated with a significantly lower risk of developing severe walking disability (OR 0.51, 95% CI 0.30-0.86, p = 0.01) and were associated with a less steep decline in 4-meter walking speed over a 6-year follow-up (n = 579; beta = 0.026, SE = 0.012, p = 0.03) and with lower incidence rates of being unable to successfully complete the 400-meter walking test at the 6-year follow-up visit (beta = -0.054, SE = 0.03, p = 0.04). High plasma carotenoids concentrations may be protective against the decline in walking speed and the development of severe walking disability in older adults.


No effect of recall period length on prevalence of self-reported haematuria in Schistosoma haematobium-endemic areas.
Assessing prevalence of haematuria by interview is commonly used as a rapid method to identify communities for mass treatment of Schistosoma haematobium infection. We analysed, using 21 published studies, to what extent the prevalence estimates of haematuria were affected by the length of the recall period for which respondents were requested to report symptoms. There was a strong positive association between prevalence of haematuria and infection, but no effect of recall period length. This suggests that the choice of recall period is of minor importance in control programmes or studies based on reported haematuria.


An Australian profile on the use of cocaine.
Data collected on cocaine in Australia in the mid to late 1980s, when law enforcement and treatment centres were concerned with possible increases in cocaine use, indicated a low prevalence of use. This article reports findings from the Australian component of the 1993-94 World Health Organization study entitled "Initiative on Cocaine", which provides an updated analysis of cocaine use patterns and consequences. The two components of this study were a "country profile" which summarized existing health, law enforcement and survey data on cocaine use from national, regional and city level records, and a key informant study which consisted of interviews with people from Sydney and Melbourne who were familiar with cocaine use through personal, professional and observational experience. Findings show that the prevalence of cocaine use has remained low among the general population in Australia (around 2%), and few people present to treatment services with primary cocaine problems or are arrested. However, the use of cocaine seems to have increased among inner Sydney injecting drug users. There have also been indications of larger police seizures of cocaine, reflecting a possible increase in availability. Recommendations are made to provide relevant interventions and continually monitor patterns of cocaine use, particularly among at-risk groups.


Final report on the safety assessment of ethoxyethanol and ethoxyethanol acetate.
Ethoxyethanol is an ether alcohol described as a solvent and viscosity-decreasing agent for use in cosmetics. Ethoxyethanol Acetate is the ester of Ethoxyethanol and acetic acid described as a solvent for use in cosmetics. Although these ingredients have been used in the past, neither ingredient is in current use. Ethoxyethanol is produced by reacting ethylene oxide with ethyl alcohol. Ethoxyethanol Acetate is produced via an esterification of Ethoxyethanol and acetic acid, acetic acid anhydride, or acetic chloride. Ethoxyethanol is metabolized to ethoxyacetaldehyde, which is further metabolized to ethoxyacetic acid, which is also a metabolite of Ethoxyethanol Acetate. Low to moderate acute inhalation toxicity is seen in animals studies. Acute oral toxicity studies in several species reported kidney damage, including extreme tubular degeneration. Kidney damage was also seen in acute dermal toxicity studies in rats and rabbits. Minor liver and kidney damage was also seen in short-term studies of rats injected subcutaneously with Ethoxyethanol, but was absent in dogs dosed intravenously. Mixed toxicity results were also seen in subchronic tests in mice and rats. Ethoxyethanol and Ethoxyethanol Acetate were mild to moderate eye irritants in rabbits; mild skin irritants in rabbits, and nonsensitizing in guinea pigs. Most genotoxicity tests were negative, but chromosome aberrations and sister-chromatid exchanges were among the positive results seen. Numerous reproductive and developmental toxicity studies, across several species, involving various routes of administration, indicate that Ethoxyethanol and Ethoxyethanol Acetate are reproductive toxicants and teratogens. Mild anemia was reported in individuals exposed occupationally to Ethoxyethanol, which resolved when the chemical was not used. Reproductive effects have been noted in males exposed occupationally to Ethoxyethanol. Although there are insufficient data to determine the potential carcinogenic effects of Ethoxyethanol or Ethoxyethanol Acetate, there is evidence that these chemicals are absorbed across human skin and that they are reproductive and developmental toxicants via dermal exposure. Therefore, these ingredients are unsafe for use in cosmetic formulations.


Hepatitis C virus-induced oxidative stress and mitochondrial dysfunction: a focus on recent advances in proteomics.
The natural history of chronic hepatitis C virus (HCV) infection presents two major aspects. On one side, the illness is by itself benign, whereas, on the other side, epidemiological evidence clearly identifies chronic HCV infection as the principal cause of cirrhosis, hepatocellular carcinoma, and extrahepatic diseases, such as autoimmune type II mixed cryoglobulinemia and some B cell non-Hodgkin's lymphomas. The mechanisms responsible for the progression of liver disease to severe liver injury are still poorly understood. Nonetheless, considerable biological data and studies from animal models suggest that oxidative stress contributes to steatohepatitis and that the increased generation of reactive oxygen and nitrogen species, together with the decreased antioxidant defense, promotes the development of hepatic and extrahepatic complications of HCV infection. The principal mechanisms causing oxidative stress in HCV-positive subjects have only been partially elucidated and have identified chronic inflammation, iron overload, ER stress, and a direct activity of HCV proteins in increasing mitochondrial ROS production, as key events. This review summarizes current knowledge regarding mechanisms of HCV-induced oxidative stress with its long-term effects in the context of HCV-related diseases, and includes a discussion of recent contributions from proteomics studies.


Case study of bovine dermatitis caused by oat straw infected with Fusarium sporotrichioides.
A dermatitis characterised by discrete, raised, plaque-like and cracked skin lesions of variable sizes on the udder, the hind quarters, the lips and muzzle of all the cows in a herd was suspected of being caused by the oat straw used in bedding, after initial feed analysis and skin culture were negative for toxins and dermatophytes. Mycological analysis indicated an extensive infestation of the oat straw by Fusarium sporotrichioides, a toxic mould, and an immunochemical assay indicated dermatotoxic trichothecenes in the straw (0.22 microgram/g dried straw). An ethyl acetate extract of the straw induced a necrotic response on shaved rat skin. Ingestion of the toxic bedding straw and inhalation of toxic straw dust probably also caused the internal haemorrhage and lung emphysema observed in the two cows that died. The regression of the dermatitis and the recovery of general herd health after the withdrawal of the oat straw further supported the diagnosis.


Ten Unsolved Questions About Neuroinflammation in Parkinson's Disease.
Parkinson's disease is a progressive and debilitating disorder that has so far eluded attempts to develop disease-modifying treatment. Both epidemiological and genetic studies support a role of neuroinflammation in the pathophysiology of Parkinson's disease. Postmortem studies and experimental analyses suggest the involvement of both innate and adaptive immunity in the degenerative process. There is also some circumstantial evidence for effects of immune therapies on the disease. In the present article, we review 10 unanswered questions related to neuroinflammatory processes in Parkinson's disease with the goal of stimulating research in the field and accelerating the clinical development of neuroprotective therapies based on anti-inflammatory strategies. © 2020 International Parkinson and Movement Disorder Society.


Microdialysis reveals changes in extracellular opioid peptide levels in the amygdala induced by amygdaloid kindling stimulation.
Enkephalins released in basolateral nucleus of the amygdala in response to electrical stimulation were determined in amygdala kindled and nonkindled freely moving rats using microdialysis. Enkephalin release was enhanced after a single and repetitive electrical stimulation (233 and 130% above control levels, respectively) in nonkindled rats. In fully kindled rats, the extracellular enkephalin levels decreased (35% below the control levels) within the first 20 min after onset of stage V kindled seizures, reaching baseline level 40 to 60 min following the generalized seizure activity. HPLC analysis identified the majority of recovered immunoreactive material from the amygdala as Met-enkephalin. On the basis of our results it is suggested that the enhanced enkephalin release in the amygdala during the early kindling stages might have a suppressive effect which may represent a homeostatic mechanism to avoid the spread of the afterdischarge to other structures. The decreased extracellular level of enkephalin in the amygdala after stage V kindled seizures could reflect a general impairment of inhibitory mechanisms in this structure with subsequent production of seizure activity.


[Berberine hydrochloride inhibits benign prostatic hyperplasia in rats by activating the Nrf2/ARE pathway].
To study the inhibitory effect of berberine hydrochloride (BBR) on BPH and its underlying mechanism in male rats. Forty male rats were randomly divided into a normal control, a BPH model control, a BBR intervention, and a BBR+Bruceol intervention group, and the BPH model was established in the latter three groups. The animals in the normal and BPH model control groups were treated intragastrically with normal saline, and those in the BBR and BBR+Bruceol intervention groups with BBR at 200 mg/kg and BBR plus Bruceol at 1 mg/kg, respectively, once a day for 14 consecutive days. The prostates of the rats were harvested for measurement of their wet weight and prostatic index, detection of the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) and determination of the protein expressions of nuclear factor E2-related factor 2 (Nrf2), antioxidant response element (ARE) and reduced coenzyme I quinone oxidoreductase (NQO1) in the prostate tissue by Western blot. The wet weights of the prostate in the normal control, BPH model control, BBR intervention, and BBR+Bruceol intervention groups were (715.63 ± 28.57) mg, (1118.93 ± 36.41) mg, (896.21 ± 20.24) mg and (967.23 ± 24.98) mg, the prostate indexes were 2.10 ± 0.13, 3.45 ± 0.22, 2.75 ± 0.19 and 3.01 ± 0.14, the SOD contents in the prostate tissue were (38.54 ± 5.12) U/mg, (13.98 ± 2.01) U/mg, (26.75 ± 3.19) U/mg and (20.16 ± 4.10) U/mg, and the MDA contents were (3.59 ± 0.83) nmol/mg, (12.63 ± 3.26) nmol/mg, (7.20 ± 1.69) nmol/mg and (9.85 ± 1.71) nmol/mg, respectively. The relative expressions of the Nrf2 protein in the four groups were 0.53 ± 0.06, 0.12 ± 0.03, 0.36 ± 0.04 and 0.25 ± 0.03, those of the ARE protein were 0.69 ± 0.07, 0.21 ± 0.02, 0.50 ± 0.06 and 0.30 ± 0.04, and those of the NQO1 protein were 0.44 ± 0.05, 0.15 ± 0.03, 0.30 ± 0.04 and 0.22 ± 0.03, respectively. There were statistically significant differences in all the above indicators between the normal and BPH model control groups (P < 0.05), as well as between the BPH model control and BBR intervention groups (P < 0.05) and between the BPH model control and the BBR+Bruceol intervention groups (P < 0.05). BBR hydrochloride can inhibit prostatic hyperplasia in BPH rats and reduce oxidative stress and pathological changes by activating the Nrf2/ARE pathway.


Activity-dependent plasticity of transmitter release from nerve terminals in rat fast and slow muscles.
Neuromuscular junctions (NMJs) on fast and slow muscle fibers display different transmitter release characteristics that appear well adapted to the different patterns of nerve impulses that they transmit in vivo. Here, we ask whether the release properties of such NMJs, termed fast and slow, can be transformed by chronic nerve stimulation. In young adult rats, nerve impulse conduction in the sciatic nerve was blocked by TTX, and the nerve to the fast extensor digitorum longus (EDL) or the slow soleus (SOL) muscle stimulated directly below the block with slow (20 Hz for 10 sec every 30 sec) or fast (150 Hz for 1 sec every 60 sec) stimulus patterns, respectively. After 3-4 weeks, originally fast EDL-NMJs and slow SOL-NMJs had become almost fully transformed to slow and fast NMJs, respectively, with respect to maintenance of transmitter release during tonic 20 Hz stimulation in vitro and ratio of quantal content to vesicle pool size. TTX block alone had no such transforming effect. Vesicle recycle time was unaffected by the stimulation, whereas initial quantal content and vesicle pool size were reduced (by 49% and 57% in EDL and 33% and 67% in SOL). Muscle fiber diameter also declined (by 49% in EDL and 33% in SOL vs 46% in unstimulated SOL; unstimulated EDL was not examined). We conclude that fast and slow NMJs display marked plasticity by being able to adapt important release characteristics to the impulse patterns imposed on them.


Natural killer cells play a key role in the antitumor immunity generated by chaperone-rich cell lysate vaccination.
Tumor derived chaperone-rich cell lysate (CRCL) when isolated from tumor tissues is a potent vaccine that contains at least 4 of the highly immunogenic heat shock proteins (HSP) such as HSP70, HSP90, glucose related protein 94 and calreticulin. We have previously documented that CRCL provides both a source of tumor antigens and danger signals triggering dendritic cell (DC) activation. Immunization with tumor derived CRCL elicits tumor-specific T cell responses leading to tumor regression. In the current study, we further dissect the mechanisms by which CRCL simulates the immune system, and demonstrate that natural killer (NK) cells are required for effective antitumor effects to take place. Our results illustrate that CRCL directly stimulates proinflammatory cytokine and chemokine production by NK cells, which may lead to activation and recruitment of macrophages at the tumor site. Thus, this report provides further insight into the function of CRCL as an immunostimulant against cancer.


Current state of knowledge on neuroendocrine small bowel tumours: non-systematic review of the literature based on one case.
More than 60% of neuroendocrine tumours, also called carcinoids, are localised within the gastrointestinal tract. Small bowel neuroendocrine tumours have been diagnosed with increasing frequency over the past 35 years, being the second most frequent tumours of the small intestine. Ileal neuroendocrine tumours diagnosis is late because patients have non-specific symptoms. We have proposed to illustrate as an example the case of a patient, and on its basis, to make a brief review of the literature on small bowel neuroendocrine tumours, resuming several recent changes in the field, concerning classification criteria of these tumours and new recommendations and current advances in diagnosis and treatment. This patient came to our emergency department with a complete bowel obstruction, along with a 2-year history of peristaltic abdominal pain, vomits and diarrhoea episodes. During emergency laparotomy, an ileal stricture was observed, that showed to be a neuroendocrine tumour of the small bowel.


Diffusion Monte Carlo study of excitons and biexcitons in a mass-asymmetric electron-hole bilayer.
We employed the diffusion Monte Carlo method, under fixed node approximation, to investigate the various ground state properties of a mass-asymmetric electron-hole bilayer system. Particularly, we calculated the ground state energy, the condensation fraction c, and the pair correlation function g(r) at density rs = 5 a.u. for the inter-planer distance d ≤ 0.5 a.u. Based on the characteristics of condensate faction and pair correlation functions, we found the phase transition from the excitonic fluid phase to the biexcitonic fluid phase at d = 0.24 a.u. We also analytically calculated the critical layer separation dcrit for biexciton stability, the value for which was almost double the d = 0.24 a.u.


Bond Performance of CFRP Strands to Grouting Admixture for Prestressed Structure and Development of Their Bond-Slip Constitutive Models.
Prestressed concrete structures have witnessed widespread use in building and infrastructure applications during the last two decades due to their high stiffness and strength indices. However, structural failures caused by the corrosion of steel reinforcing bars or strands have proliferated, opening the door for carbon fibre-reinforced polymer (CFRP) strands as an excellent alternative with high corrosion resistance. The bonding interaction between the CFRP strands and concrete is the fundamental parameter in shaping the structural behaviour of CFRP prestressed concrete structures. In this paper, the bonding behaviour between CFRP strands and concrete with grouting admixture is experimentally investigated based on three groups of standard pull-out tests. The bond strength of CFRP strands was systematically studied and compared against steel strands. The untreated CFRP strands exhibited an inefficient bonding strength with the grouting admixture, equivalent to only 5% compared to steel strands of the same diameter. Surface coating with epoxy quartz sand can significantly improve the anchoring efficiency of CFRP strands up to 14 times compared to the untreated strands, which is approximately as efficient as steel strands. Moreover, the bond-slip curves between CFRP strands and concrete were analysed and were found to be different compared to steel strands. Finally, this study proposed bond-slip constitutive models of CFRP strands with better applicability, using an exponentially damped sine function to fit the residual segment of the curve.


Neutrophils accelerate macrophage-mediated digestion of apoptotic cells in vivo as well as in vitro.
It is generally believed that the clearance of apoptotic cells does not lead to inflammation. In contrast, we previously found that injection of apoptotic cells into the peritoneal cavity induced the expression of an inflammatory chemokine, MIP-2, and infiltration of neutrophils, and that anti-MIP-2 Abs suppressed the infiltration significantly. Because our previous study showed that whole-body x-irradiation caused neutrophil infiltration into the thymus along with T cell apoptosis, we examined the role of neutrophils in apoptotic cell clearance. Neutrophil infiltration reached a peak 12 h after irradiation with 1 Gy of x-rays. Immunohistological analysis revealed that apoptotic cells disappeared dramatically from 10.5 to 12 h after x-irradiation. As neutrophils moved from an inner area of the cortex to the periphery, apoptotic cells disappeared concomitantly. Either anti-MIP-2 or anti-CXCR2 Abs suppressed neutrophil infiltration significantly, and the suppression of neutrophil infiltration by anti-MIP-2 Abs delayed the disappearance of apoptotic cells. Moreover, macrophage-mediated digestion of apoptotic thymocytes was accelerated in vitro on coculturing with neutrophils, even if neutrophils were separated from macrophages. These results suggest that neutrophils are recruited to the thymus mainly by MIP-2 after whole-body x-irradiation and that such neutrophils may not induce inflammation but rather accelerate complete digestion of apoptotic cells by macrophages.


Analysis of immunohistochemical results of the ras oncogene product p21 in myelodysplastic syndromes.
Mutation of the ras oncogenes is the most commonly detected molecular abnormality in acute myelogenous leukemia and myelodysplastic syndromes (MDS). This molecular event may either be acquired by different subclones or by all malignant cells. The availability of the ras p21 monoclonal antibody Y13 259 makes possible the direct study of the distribution of the ras gene product in human malignant cells. The bone marrow smears from 41 patients with MDS were analysed by two independent observers after treatment with MoAb Y13 259, biotinylated goat antirat IgG, streptavidin, peroxidase and staining with diaminobenzidine. A high proportion of strongly positive smears was found among patients with MDS. This positivity was found in 25% of refractory anemia, in 80% of the refractory anemias with excess of blasts, and in 90% of those in transformation, while all 7 cases with chronic myelomonocytic leukemia were found positive. The percentage of positivity may suggest that activation of ras oncogene in associated with disease progression.


Utility of Amsel criteria, Nugent score, and quantitative PCR for Gardnerella vaginalis, Mycoplasma hominis, and Lactobacillus spp. for diagnosis of bacterial vaginosis in human immunodeficiency virus-infected women.
Bacterial vaginosis (BV) is a clinical syndrome presenting with a malodorous vaginal discharge and increased vaginal pH. Diagnosis has been based on clinical Amsel criteria and direct Gram stain of vaginal secretions. Human immunodeficiency virus (HIV)-infected participants in the Women's Interagency HIV Study contributed cervicovaginal lavage (CVL) samples. Lactobacilli, Gardnerella vaginalis, and Mycoplasma hominis in cervicovaginal lavage samples were quantified by PCR. Gynecologic evaluation included Nugent score and Amsel criterion assessment. We compared the gold standard Nugent score to Amsel criteria and quantitative bacterial PCR for diagnosing BV in 203 CVL samples from women with Nugent scores of 7 to 10 (BV group) and 203 samples from women with BV Nugent scores of 0 to 3 ("No-BV" group). Only 75 of the 203 CVL samples from women with Nugent scores of 7 to 10 met positive Amsel criteria. Increasing levels of G. vaginalis and M. hominis and decreasing levels of lactobacilli were significantly associated with BV by Nugent score. Of the group with Nugent scores of 7 to 10, 83% and 81% had log(10) G. vaginalis counts and log(10) M. hominis counts greater than 6.81 and 4.82, respectively, while only 30% and 31% of the group with Nugent scores of 0 to 3 were above these thresholds, respectively. There was significant overlap in the log(10) lactobacillus counts between the two groups. Utilizing all three log(10) bacterial counts (G. vaginalis, M. hominis, and lactobacilli) in our model improved the sensitivity and specificity to 83% and 78%, respectively, in comparison with Nugent score. In this cohort, Amsel criteria were poorly predictive of BV. PCR quantification of G. vaginalis and M. hominis from CVL is significantly more sensitive than Amsel criteria for diagnosing BV.


Differing characteristics in 100 consecutive secondary rhinoplasty patients following closed versus open surgical approaches.
Open rhinoplasty has unquestionably become more popular during the past two decades because of the putative diagnostic and technical advantages that direct transcolumellar access offers. To test the hypothesis that patients initially treated by the opened or closed approaches differed in the secondary deformities that developed, a retrospective study was conducted of 100 consecutive secondary rhinoplasty patients (66 women and 34 men) operated on by the author before February of 1998. Sixty-four percent had previously undergone closed rhinoplasties and 36 had undergone open rhinoplasties; the incidence of prior open rhinoplasty had increased steadily over the survey years, from 21 percent in 1996 to more than 50 percent in 1998, 1999, and 2000 (p < 0.05). The data generated indicate the following. First, the open rhinoplasty patients had undergone more operations (3.1 versus 1.2) and had more presenting complaints (5.8 versus 2.6) than the closed rhinoplasty patients. Second, although the most common presenting complaint among prior closed rhinoplasty patients was an overresected dorsum (50 percent) or tip (33 percent) or internal valvular obstruction (42 percent), prior open rhinoplasty patients complained more frequently than the closed rhinoplasty patients of these problems and also external valvular obstruction (50 percent, p < 0.0001), short nose (39 percent, p < 0.001), wide columella (36 percent, p < 0.001), narrow nose (31 percent, p < 0.001), columellar scar (25 percent, p < 0.001), and symptomatic columellar struts (19 percent, p < 0.001). Only excessive nasal length was more prevalent among closed rhinoplasty patients (20 percent, p < 0.01). Third, ranking of deformities differed significantly (p < 0.0001) between the two groups, so that complaints related to the nostrils, nasal tip, nasal length, or columella were more common among the open rhinoplasty patients than among those previously treated endonasally. Fourth, the relative frequencies of surgical complaints also differed: whereas patients previously treated endonasally were 6.7 times more likely to complain of long noses, patients previously treated by open rhinoplasty complained more frequently of the following: excessive columellar width (open approach, 36 percent of patients; closed approach, none), hard columellar struts (open approach, 19 percent of patients; closed approach, none), external valvular obstruction (4.5 times as frequent with the open approach as it was with the closed approach), alar/nostril distortion (four times as frequent), and narrow nose (3.9 times). Although the most common complaints among all postrhinoplasty patients remain the overresected dorsum, tip, or (internal valvular) airway obstruction, the author's data suggest that patients previously treated by the open approach are more likely to have postsurgical deformities and complaints referable to those anatomic structures most easily reached by transcolumellar exposure and to techniques that can be performed more readily or aggressively through that access route.


X-ray phase contrast imaging of metallized and non-metallized biological samples.
Imaging of biological samples has been performed with a variety of techniques for example electromagnetic waves, electrons, neutrons, ultrasound and X-rays. Also conventional X-ray imaging represents the basis of medical diagnostic imaging, it remains of limited use in this application because it is based solely on the differential absorption of X-rays by tissues. Coherent and bright photon beams, such as those produced by third-generation synchrotron X-ray sources, provide further information on subtle X-ray phase changes at matter interfaces. This complements conventional X-ray absorption by edge enhancement phenomena. Thus, phase contrast imaging has the potential to improve the detection of structures on images by detecting those structures that are invisible with X-ray absorption imaging. Images of a weakly absorbing nylon fibre were recorded in in-line holography geometry using a high resolution low-noise CCD camera at the ESRF in Grenoble. The method was also applied to improve image contrast for images of biological tissues. This paper presents phase contrast microradiographs of vascular tree casts and images of a housefly. These reveal very fine structures, that remain invisible with conventional absorption contrast only.


Factors affecting dystocia in cattle.
The paper reviews the various factors affecting dystocia in cattle. It is based mainly on the recent studies found in the literature of the subject but refers occasionally to some older papers as well. The factors are grouped into four main categories: direct factors, phenotypic factors related to calf and cow, non-genetic and genetic factors. The first group includes malpresentations and uterine torsion. The second one includes: calf birth weight, multiple calvings, perinatal mortality, cow pelvic area, cow body weight and body condition at calving, gestation length. The non-genetic factors are: cow age and parity, year and season of calving, place of calving, maintenance practises, disorders, calf sex and nutrition. Other non-genetic factors are the level of hormones in the periparturient period, in vitro production of embryos and embryo cloning. Finally, the genotypes of cow, bull and calf, inbreeding, muscular hypertrophy, selection and quantitative trait loci form the fourth group of genetic factors.


Oxyresveratrol suppresses lipopolysaccharide-induced inflammatory responses in murine macrophages.
Excessive inflammation is considered a critical factor in many human diseases. Oxyresveratrol(trans-2,3',4,5'-tetrahydroxystilbene), a natural hydroxystilbene, has been shown to possess antioxidant and free radical-scavenging activity. In this study, we investigated the effects of oxyresveratrol (OxyR) on the lipopolysaccharide (LPS)-induced production of inflammatory cytokines and mediators and further explored the mechanism of action in RAW264.7 murine macrophage cell line. Production of nitric oxide (NO), prostaglandin E2 (PGE2), messenger RNA (mRNA) and protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), and granulocyte macrophage colony-stimulating factor (GM-CSF), phosphorylation of mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38), and the activation of nuclear factor κ-light chain enhancer of activated B cells (NFκB) with OxyR were assayed in LPS-stimulated RAW264.7 cells. OxyR inhibited the productions of NO, PGE2, IL-6, and GM-CSF significantly in LPS-stimulated RAW264.7 cells. OxyR suppressed mRNA and protein expressions of iNOS, COX-2, IL-6, and GM-CSF in LPS-stimulated RAW264.7 cells. OxyR suppressed the phosphorylation of Akt and JNK and p38 MAPKs and the translocation of NFκB p65 subunit into the nucleus. These results indicate that OxyR inhibits LPS-stimulated inflammatory responses though the blocking of MAPK and NFκB signaling pathway in macrophages, and suggest that OxyR possesses anti-inflammatory effects.


[Computed tomography in the exploration of the adrenal gland].
After reviewing their normal procedure (protocole) in studying the suprarenals, the authors will now present their results: --normal anatomy, --normal variants and pit falls, --pathological aspects: masses and other causes. Anyway, computed scanning of the suprarenals should be associated to clinical and biological signs.


Hierarchical Surface Instability in Polymer Films.
This study demonstrates hierarchical instabilities in thin films. The hierarchical instabilities display three morphological characteristics: (1) windmill-like patterns at the macroscale, (2) Bénard cells and striations at the microscale, and (3) holes at the mesoscale. Such hierarchical instabilities occurred when spin coating was performed on high-volatile solutions under a high relative humidity (RH) but were suppressed when spin coating was performed on low-volatile solutions regardless of the RH. The high-volatile solutions comprise poly(4-vinylpyridine) (P4VP) in methanol or ethanol. The low-volatility solutions comprise P4VP in propanol or butanol. P4VP molecular weights, P4VP concentrations, spin rates, and film thicknesses are not vital factors in forming hierarchical instability in spin-coated P4VP films. Instead, the formation of hierarchical instabilities depends on the RH and solvent types. Namely, the hierarchical instabilities are driven by Bénard-Marangoni convection, water vapor condensation, and disturbance of spin-up and spin-off stages during spin coating of highly volatile solutions under high RH. Mechanisms of hierarchical instabilities are interpreted in detail.


The rate-determining steps of aldo-keto reductases (AKRs), a study on human steroid 5β-reductase (AKR1D1).
Aldo-keto reductases (AKRs) are an expanding family of NAD(P)(H)-dependent oxidoreductases that catalyze the reduction of either carbonyl groups or α,β-unsaturated ketones on a variety of endogenous and exogenous substrates. The enzymes catalyze a sequential ordered bi-bi kinetic mechanism, in which cofactor is bound first and released last. Using human steroid 5β-reductase (AKR1D1) as a representative enzyme, the influence of substrate structure on the rate-limiting steps of AKR catalysis has been previously determined. The rate of the chemistry step was found to differ by two orders of magnitude when different steroid substrates were used in single turnover experiments with AKR1D1. This difference was reflected in multiple turnover experiments. C17-C21 steroid substrates exhibited a fast chemistry step followed by slow product release as suggested by "burst" phase kinetics. By contrast, C27 steroids have a slower chemical step that determines the rate of the reaction and "burst-phase" kinetics are no longer observed. Here we present single turnover kinetic experiments and find that they support the existence of two different binding poses for fast substrates due to their biphasic nature. We also re-interpret the loss of "burst-phase" kinetics in the multiple turnover experiments as due to long range effects of the steroid side-chain interacting with distal parts of the steroid pocket to perturb the reaction trajectory for hydride transfer and thus reduce kcat. The ability of steroid structure and hence binding pose to influence rate determination in steroid transforming AKRs is discussed as a general phenomenon.


Evidence and Human Genome Editing.
In July, the United Kingdom's Nuffield Council on Bioethics issued a report on human genome editing in which it said that editing a human embryo's genome to reduce the possibility that the future child will inherit a genetic disorder could be ethically acceptable when certain conditions are met: the intended use of genome-editing interventions secures and is consistent with the "welfare of the future person" and does not "increase disadvantage, discrimination or division in society." Yet the Council noted that if current legal restrictions on the use of heritable genome-editing interventions were lifted, the interventions should be used only in the context of "well-designed and supervised studies" to ensure that they are safe and effective. Some people might contend that it is premature to talk about what kind of evidence-and how much-will be needed to gauge the safety and effectiveness of genome-editing interventions since the United Kingdom, the United States, and several other countries currently prohibit clinical trials that involve transferring into a woman an embryo whose genome was edited. Yet based on an analysis of evidentiary disputes involving several medical technologies (an analysis that I conducted with my Hastings colleague Michael Gusmano for a forthcoming book, Debating Modern Medical Technologies: The Politics of Safety, Effectiveness, and Patient Access), I suggest that now is the time to start the conversation about evidentiary standards for the use of genome editing in reproductive medicine.


Heat capacity, Raman, and Brillouin scattering studies of M2O-MgO-WO3-P2O5 glasses (M=K,Rb).
The authors report the results of temperature-dependent Brillouin scattering from both transverse and longitudinal acoustic waves, heat capacity studies as well as room temperature Raman scattering studies on M2O-MgO-WO3-P2O5 glasses (M=K,Rb). These results were used to obtain information about structure and various properties of the studied glasses such as fragility, elastic moduli, ratio of photoelastic constants, and elastic anharmonicity. They have found that both glasses have similar properties but replacement of K+ ions by Rb+ ions in the glass network leads to decrease of elastic parameters and P44 photoelastic constant due to increase of fragility. Based on Brillouin spectroscopy they show that a linear correlation between longitudinal and shear elastic moduli holds over a large temperature range. This result supports the literature data that the Cauchy-type relation represents a general rule for amorphous solids. An analysis of the Boson peak revealed that the form of the frequency distribution of the excess density of states is in agreement with the Euclidean random matrix theory. The reason of the observed shift of the maximum frequency of the Boson peak when K+ ions are substituted for Rb+ ions is also briefly discussed.


[Gastrointestinal hormones in the blood serum of patients with chronic renal failure].
Content of gastrointestinal hormones (gastrin, insulin, glucagon, C-peptide), beta2-microglobulin, glomerular filtration rate (GFR) were studied in 65 patients with nephrolithiasis (NL) and in 73 patients with chronic renal failure (CRF). It was found that NL with GFR under 80 ml/min runs with elevated insulin, glucagon and C-peptide while CRF with CRF under 30 ml/min is characterized by aggravated disorders of hormonal homeostasis (gastrin, insulin, glucagons, C-peptide elevation). As gastrointestinal hormones in patients with CRF are high, it is recommended to combine medication with diet containing low amount of carbohydrates easy for digestion which is important in the treatment of CRF.