Evidence for recovery of body mass and haptoglobin values of river otters following the Exxon Valdez oil spill.
Levels of blood haptoglobin (Hp) and interleukin-6 immunoreactive protein (IL-6 ir) were significantly elevated in river otters (Lutra canadensis) inhabiting oiled areas of Prince William Sound, Alaska (USA) following the Exxon Valdez oil spill in 1989. By May and June 1992, however, such differences were not apparent. Mean body mass of otters, adjusted for sex, age-class, and total length with analysis of covariance, differed between oiled and non-oiled areas from 1990 to 1992, but were nearly identical by May and June 1992. We propose that river otters may be recovering from chronic effects that we observed in 1990 and 1991 following the 1989 Exxon Valdez oil spill, but further research is necessary to test this hypothesis.


Immunohistochemical localization of inhibin/activin subunits in the wild ground squirrel (Citellus dauricus Brandt) ovary.
The intraovarian function of gonadally produced inhibin and activin has been extensively studied in experimental models for decades, yet their presence and function have been rarely reported in wild rodents. With our seasonal breeding model, the wild ground squirrel, we aimed to investigate the possible roles of these peptides in the seasonal folliculogenesis. Immunohistochemical staining and Western blotting have been used to detect the cellular localization and expression patterns of inhibin/activin subunits (α, β(A) and β(B)). In the breeding season ovary, all three subunits were present in granulosa cells, theca cells of antral follicles and interstitial cells, with the strongest immunostaining in granulosa cells. Following ovulation, the corpora lutea become a major site of inhibin/activin synthesis. In the nonbreeding season ovary, inhibin/activin α and β(A) subunits were weakly immunopositive in granulosa cells of early stage follicles, while β(B) subunit was undetectable. The expression level of inhibin/activin subunit proteins were generally higher in the ovaries of the breeding season, and then decreased to a relatively low level during the nonbreeding season. The dynamic expression of inhibin/activin subunits indicated that they might play important paracrine and/or autocrine roles during the seasonal folliculogenesis of the wild ground squirrel.


A Validation Study of the BRIEF-2 Among Kindergarteners and First Graders At-Risk for Behavior Problems.
Early identification of executive dysfunction and timely school-based intervention efforts are critical for students at risk for problematic behaviors during early elementary school. The original Behavior Rating Inventory of Executive Functioning (BRIEF) was designed to measure real-world behavioral manifestations of executive functioning, neurocognitive processes critical for school success. With the updated BRIEF-2, independent validation is needed with kindergarten and first grade students at risk for emotional and behavioral disorders. Thus, using item level analyses, we examined the factor structure of the BRIEF-2 Teacher Rating form with 1,112 students. Results indicated little evidence for the original three-index model and supported a modified two-index model, with a Cognitive Regulation Index and an overall Behavior-Emotion Regulation Index. Criterion related validity indicated positive relationships with performance-based executive functioning (Head-Toes-Knees-Shoulders) and later internalizing and externalizing behaviors. We discuss implications of findings for early identification and school-based intervention efforts, as well as future research.


Diminishing returns? Risk and the duty to care in the SARS epidemic.
The seriousness of the risk that healthcare workers faced during SARS, and their response of service in the face of this risk, brings to light unrealistic assumptions about duty and risk that informed the debate on duty to care in the early years of HIV/AIDS. Duty to care is not based upon particular virtues of the health professions, but arises from social reflection on what response to an epidemic would be consistent with our values and our needs, recognizing our shared vulnerability to disease and death. Such reflection underwrites a strong duty of care, but one not to be borne solely by the altruism and heroism of individual healthcare workers.


[The blood supply of the semitendinosus, gracilis and sartorius muscles and surgical applications (author's transl)].
The vascular pedicles of the semitendinosus, gracilis and sartorius muscles were identified by the authors. Although devascularisation of the tendons is of no importance in plastic operations, any technic using the fleshy part of these muscles should take care to preserve the blood supply. It is therefore important to know their anatomy.


Ethical review in Pakistan: the credibility gap.
The concept of mandatory ethical review of research involving human participants is gradually taking root in Pakistani institutions. Based on the opinions of Institutional Review Board (IRB) members from institutions across the country, the process faces several challenges which threaten its integrity. The lack of registration or accreditation for IRBs has resulted in a wide variation in the calibre and working of such Boards. Despite the recent growth in numbers of people with formal bioethics degrees in the country, a majority of membership remains without any formal training for the work expected from them in ethical review. External pressures to influence deliberations, conflict of interest issues within board leadership and inconsistent application of review requirements all contribute in undermining the reliability of the process. Some of the most significant threats to independent and uninfluenced functioning of such boards arise from institutional leadership itself. In the opinions of IRB members, the review process has to be uniform, consistent and trustworthy if it is to gain the respect of researchers, and IRB need to be given the autonomous space to make independent decisions. Otherwise there is a real danger of IRBs being relegated to being no more than rubber stamping committees.


Contrast Between Orange- and Black-Colored Sclerotial Isolates of Botrytis cinerea: Melanogenesis and Ecological Fitness.
Botrytis cinerea usually produces grayish mycelia and conidia as well as black-colored sclerotia (BS) due to accumulation of melanin. An isolate (XN-1) of B. cinerea producing orange-colored sclerotia (OS) on agar media was obtained from an orange-colored apothecium of an uncultured soil fungus. Whether or not the OS B. cinerea occurs on plants and how they differ from the BS isolates in melanogensis and ecological fitness remained unknown. This study, for the first time, confirmed the presence of the OS B. cinerea in strawberry and tomato plants that were surveyed in Hubei Province of China. Only five OS isolates were obtained from a total of 2,031 isolates surveyed from the two crops. The OS isolate XN-1 was compared and contrasted with the BS isolate B05.10 in sclerotial melanogenesis and ecological fitness. Sclerotial melanogenesis was evident in B05.10 but was deficient in XN-1. The OS were more susceptible to the two mycoparasites Trichoderma koningiopsis and Clonostachys rosea than the BS. The percentage of viable sclerotia after the mycoparasitism study was significantly (P < 0.01) lower in OS (21%) than in BS (48%). This study also reaffirmed the importance of melanization for survival of B. cinerea sclerotia.


Cardiac mast cell-mediated activation of gelatinase and alteration of ventricular diastolic function.
Mast cells contain proteases capable of activating matrix metalloproteinases (MMPs). However, given the relatively low density of mast cells in the myocardium (i.e., 1.5-5.3 cells/mm(2)), it is unknown whether these enzymes are present in sufficient quantities in the normal heart to mediate MMP activation. Accordingly, this study sought to determine whether chemically induced degranulation of cardiac mast cells (with compound 48/80) would have an effect in isolated, blood-perfused, functioning rat hearts. Mast cell degranulation produced a 15% increase in histamine levels present in the coronary efflux, a significant increase in myocardial water (i.e., edema) relative to normal values (80.1 +/- 3.4% vs. 77.4 +/- 1.08%, P < or = 0.03), a substantial activation of MMP-2 (126% increase relative to controls, P < or = 0.02), and a marked decrease in myocardial collagen volume fraction (0.46 +/- 0.10% vs. 0.97 +/- 0.33%, P < or = 0.001). Furthermore, although an increase in ventricular stiffness was expected due to the extent of edema resulting from mast cell degranulation, modest ventricular dilatation was observed. These findings clearly demonstrate that the number of mast cells present in normal hearts is sufficient to mediate activation of MMPs and produce extracellular matrix degradation, thereby potentially causing subsequent ventricular dilatation.


[Preparation and investigation of novel pyrrolidinium-bonded stationary phase for reversed-phase high-performance liquid chromatography].
A new ionic liquid-based high-performance liquid chromatography stationary phase is reported. A derivative of N-methyl pyrrolidinium tetrafluoroborate was covalently immobilized on the surface of silica particles to prepare silica-based N-methyl pyrrolidinium tetrafluoroborate (SilprMP BF4) stationary phase. The obtained ionic liquid-modified silica was evaluated and confirmed by elemental analysis, infrared spectroscopy, and thermogravimetric analysis. A column was packed with the modified particles. The retention behavior of aromatic compounds, alkyl benzenes, and acidic and basic compounds on the SilprMP BF4 stationary phase was studied under reversed-phase liquid chromatography conditions. The effect of the eluent pH on the separation of the acidic and basic compounds was also studied. The new stationary phase involves multiple retention mechanisms, such as electrostatic, hydrophobic, ion-dipole, and anion-exchange interactions, which might lead to multipurpose separation media.


Retinopathy of prematurity blindness worldwide: phenotypes in the third epidemic.
Blindness due to retinopathy of prematurity (ROP) is an increasing problem worldwide as improved levels of neonatal care are provided in countries with developing neonatal intensive care units. The occurrence of ROP blindness varies dramatically with the socioeconomic development of a country. In regions with high levels of neonatal care and adequate resources, ROP blindness is largely restricted to premature infants with very low birth weight and low gestational age while in middle- and low-income countries with regional variation in technology and capacity, limited health resources may well limit the care of the premature newborn.


[Apolipoprotein B and small, dense LDL-C].
Apolipoprotein B-100 (apo B-100) and small, dense LDL-C (sdLDL-C) are beneficial risk markers for CHD. Apo B-100 indicates the number of LDL particles that reflect the risk of CHD better than the LDL-C concentration. SdLDL is a lipoprotein subclass that causes arteriosclerosis with a much higher risk than large LDL. Apo B-100 is measured by a fully automated turbidimetric immunoassay, while small-dense LDL-C is measured by an enzymatic homogeneous assay with an automated analyzer. Elevated apo B-100 and sdLDL-C are observed among people with familial hypercholesterolemia, familial combined hyperlipidemia, diabetes mellitus, or metabolic syndrome, all of which lead to CHD with high probability. Although both apo B-100 and sdLDL-C are high in all of these cases, the two markers show noticeably different tendencies for each case. Familial hypercholesterolemia patients have higher apo B-100 than sdLDL-C; in contrast, people with diabetes mellitus or metabolic syndrome have higher sdLDL-C than apo B-100. Familial combined hyperlipidemia cases do not show much difference between the two values. The results of both apo B-100 or sdLDL-C can be good risk markers of CHD when tested individually, whereas the cause of CHD may be further clarified by assessing them in combination. By identifying the cause, patients can receive appropriate medical treatments. In conclusion, measuring both apo B-100 and sd LDL-C potentially implies further additional information on clinical utility.


Intravesical potassium chloride sensitivity test in men with chronic pelvic pain syndrome.
Intravesical potassium chloride has been reported to cause pain in patients with interstitial cystitis and male chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS). We performed the potassium chloride sensitivity test (PST) in subjects with CP/CPPS and healthy men without pelvic pain. We recruited 40 men with CP/CPPS and 63 healthy men. The National Institutes of Health CPPS symptom index was used to measure the severity of symptoms. We instilled 100 ml physiological saline (NaCl 0.9%) intravesically. The bladder was emptied and 100 ml potassium chloride solution (KCl 40 mEq) were instilled. The subjects were asked to score urgency (0 to 10) and pain (0 to 10) sensations after each instillation. A positive PST was defined by 5 different cut-off points as the difference in score between KCl and NaCl instillations. Logistic regression analyses and area under the receiver operating characteristics curve were used to determine the predictive power of PST in CP/CPPS. There was no difference in pain and urgency scores between the men with CP/CPPS and controls (p >0.05 for each). Men with CP/CPPS had higher pain and urgency scores with KCl than with NaCl (p = 0.011 and 0.033, respectively). The rates of positive PST were 50% and 36.5% in the CP/CPPS and control groups, respectively (p = 0.160). There was no significant correlation of potassium chloride sensitivity scores with National Institutes of Health symptom scores (p >0.05 for each). The sensitivity, specificity, and positive predictive and negative predictive values of PST were 50%, 63.5%, 46.5% and 66.7%, respectively. Although there was a significant increase in pain and urgency scores following KCl instillation in patients with CP/CPPS, these scores and the rate of positive PST were not statistically different from those of healthy subjects. Thus, PST does not have a good predictive value in the diagnosis of CP/CPPS.


Interleukin-2-collagen chimeric protein which liberates interleukin-2 upon collagenolysis.
Interleukin-2 (IL-2) is a potent activator of cellular immunity and has been utilized as an immunotherapeutic agent. We stably immobilized human IL-2 to collagen by covalently binding it to the N-terminus of human type III collagen (3A1) as IL2-3A1 chimeric protein using recombinant technology. The present study was aimed at liberating IL-2 from the immobilized chimeric protein by treating the chimera with bacterial collagenase. These IL2-3A1 chimeras were synthesized in insect cells which had been infected with baculovirus vectors carrying IL2-3A1 cDNA. The IL2-3A1 protein produced was shown to be in a pepsin-resistant triple helical structure and exhibited IL-2 activity to a similar extent as IL-2 itself. IL2-3A1 could be immobilized on the surface of plastic dishes by incubating it in the dishes. The IL-2 region of the immobilized IL2-3A1 was liberated to culture media by collagenase treatment and this freed IL-2 stimulated the growth of lined T cells. Thus, IL2-3A1 chimeric protein could be utilized as an IL-2 deliverer whose T cell mitogenic activity can be liberated by a collagenolytic environment.


Langmuir probes for SPIDER (Source for the production of Ions of Deuterium Extracted from Radio Frequency plasma) experiment: tests in BATMAN (BAvarian Test Machine for Negative ions).
A prototype system of the Langmuir probes for SPIDER (Source for the production of Ions of Deuterium Extracted from RF plasma) was manufactured and experimentally qualified. The diagnostic was operated in RF (Radio Frequency) plasmas with cesium evaporation on the BATMAN (BAvarian Test MAchine for Negative ions) test facility, which can provide plasma conditions as expected in the SPIDER source. A RF passive compensation circuit was realised to operate the Langmuir probes in RF plasmas. The sensors' holder, designed to better simulate the bias plate conditions in SPIDER, was exposed to a severe experimental campaign in BATMAN with cesium evaporation. No detrimental effect on the diagnostic due to cesium evaporation was found during the exposure to the BATMAN plasma and in particular the insulation of the electrodes was preserved. The paper presents the system prototype, the RF compensation circuit, the acquisition system (as foreseen in SPIDER), and the results obtained during the experimental campaigns.


Structural characterization and discrimination of the Paris polyphylla var. yunnanensis and Paris vietnamensis based on metabolite profiling analysis.
This study aimed to distinguish the rhizomes of Paris polyphylla var. yunnanensis (Franch) Hand Mazz (PPY) and Paris veitnamensis (Takht.) H. Li (PV) using metabolomics-based ultra high-performance liquid chromatography coupled with quadrupole time-of-fligh mass spectrometry (UHPLC/Q-TOF MS). First, the UHPLC/Q-TOF MS approach was optimized for metabolite profiling. Then, the MS data were processed using UNIFI™ combined with an in-house library to automatically characterize the metabolites. Based on the exact mass information, the fragmentation characteristics, and the retention time of compounds, and the fragmentation mechanism and retention behavior of steroidal glycosides in the references, the structures identified by UNIFI were further verified. Overall, 146 metabolites, including 42 potential new compounds, were identified or tentatively identified. Pattern recognition analysis of the PPY and PV MS data revealed that they were clearly separated, and 15 potential biomarkers for differentiating between them were selected. These biomarkers were subsequently used to successfully predict the genus of PPY and PV samples. These results indicated that metabolite profiling by UHPLC/Q-TOF MS is an effective, robust approach for determining the characteristic biomarkers that differentiate between TCM species with multiple botanical origins.


Maturation-related changes of carrot lignins.
Lignified cell walls are important factors for textural and physiological properties of plant-based foods. However, carrot lignins and their modifications during maturation are poorly described. The objective of this study was to describe carrot lignins in detail and to study lignin structural alterations at later stages of maturity. Klason and acetyl bromide soluble lignin contents of insoluble fibers of carrots harvested at different times (26, 29 and 35 weeks after seeding) ranged between 46.38 and 62.68 g kg-1 and between 19.79 and 28.08 g kg-1 , respectively. As determined by both 2D-nuclear magnetic resonance and the derivatization followed by reductive cleavage method, coniferyl alcohol heavily dominated the traditional monolignol composition in carrot lignins, independently of harvest times. By using 2D-nuclear magnetic resonance experiments on isolated lignins, p-hydroxybenzoate was identified as a less common lignin constituent, attached to lignin γ-hydroxyl groups and being increasingly incorporated with maturation. β-Aryl ethers, phenylcoumaran, resinol and dibenzodioxocin structures were identified as lignin interunit linkages, largely independent of harvest times and with β-aryl ethers being expectedly dominant. Carrots contain guaiacyl-rich lignins that incorporate increasing amounts of p-hydroxybenzoate with maturation. All other lignin characteristics appear to be widely independent of harvest times. © 2017 Society of Chemical Industry.


A Review of the Potential of Phytochemicals from Prunus africana (Hook f.) Kalkman Stem Bark for Chemoprevention and Chemotherapy of Prostate Cancer.
Prostate cancer remains one of the major causes of death worldwide. In view of the limited treatment options for patients with prostate cancer, preventive and treatment approaches based on natural compounds can play an integral role in tackling this disease. Recent evidence supports the beneficial effects of plant-derived phytochemicals as chemopreventive and chemotherapeutic agents for various cancers, including prostate cancer. Prunus africana has been used for generations in African traditional medicine to treat prostate cancer. This review examined the potential roles of the phytochemicals from P. africana, an endangered, sub-Saharan Africa plant in the chemoprevention and chemotherapy of prostate cancer. In vitro and in vivo studies have provided strong pharmacological evidence for antiprostate cancer activities of P. africana-derived phytochemicals. Through synergistic interactions between different effective phytochemicals, P. africana extracts have been shown to exhibit very strong antiandrogenic and antiangiogenic activities and have the ability to kill tumor cells via apoptotic pathways, prevent the proliferation of prostate cancer cells, and alter the signaling pathways required for the maintenance of prostate cancer cells. However, further preclinical and clinical studies ought to be done to advance and eventually use these promising phytochemicals for the prevention and chemotherapy of human prostate cancer.


Pre-clinical delivery of gene therapy products to the cerebrospinal fluid: challenges and considerations for clinical translation.
While the majority of gene therapy studies in neurological indications have focused on direct gene transfer to the central nervous system (CNS), there is growing interest in the delivery of therapeutics using the cerebrospinal fluid (CSF) as a conduit. Historically, direct CNS routes-of-administration (RoAs) have relied on tissue dynamics, displacement of interstitial fluid, and regional specificity to achieve focal delivery into regions of interest, such as the brain. While intraparenchymal delivery minimizes peripheral organ exposure, one perceived drawback is the relative invasiveness of this approach to drug delivery. In this mini review, we examine the CSF as an alternative RoA to target CNS tissue and discuss considerations associated with the safety of performing such procedures, biodistribution of therapeutics following single administration, and translation of findings given differences between small and large animals. These factors will help delineate key considerations for translating data obtained from animal studies into clinical settings that may be useful in the treatment of neurological conditions.


Motility induced phase separation of deformable cells.
Using a multi-phase field model, we examine how particle deformability, which is a proxy for cell stiffness, affects motility induced phase separation (MIPS). We show that purely repulsive deformable, i.e., squishy, cells phase separate more effectively than their rigid counterparts. This can be understood as due to the fact that deformability increases the effective duration of collisions. In addition, the dense regions become increasingly disordered as deformability increases. Our results contextualize the applicability of MIPS to biological systems and have implications for how cells in biological systems may self-organize.


Bone regeneration after radicular cyst removal with and without guided bone regeneration.
In order to determine the degree of bone regeneration after removal of radicular cysts using guided bone regeneration (GBR), a prospective, controlled and randomized clinical study was performed. Thirty patients with radicular cysts were divided into three groups. One group, the control group (n=10 patients), was treated by enucleation and primary closure. The other two groups were treated by enucleation and primary closure but GBR was used in addition, using a resorbable membrane (n=10) and a nonresorbable membrane (n=10). The membranes were fixed with nonresorbable Memfix System screws. The residual volume and the density of the newly formed tissue was measured by computer-assisted tomography and computer-assisted digital image analysis before enucleation and three and six months postoperatively. No statistical significance was found in density and residual volume between the three treatment groups after six months. These results suggest that GBR using membranes does not contribute to increased bone regeneration.


Caprine arthritis encephalitis: an example of risk assessment for embryo trading.
The risk of transmission of caprine arthritis encephalitis virus (CAEV) during embryo transfer has been demonstrated in vivo through the detection of CAEV proviral DNA in: (1) flushing media for embryo collection; (2) cells of the cumulus oophorus surrounding the oocytes, ovarian follicle, oviduct and uterine tissues; and (3) testis, epididymis, vas deferens and vesicular glands. Experimentally infected embryos without a zona pellucida (ZP), washed 10 times with Minimum Essential Media (MEM) and 5% Fetal Calf Serum (FCS) solution, were capable of transmitting CAEV. In vitro we demonstrated that granulosa, oviductal, epididymal and embryo cells are fully susceptible to CAEV infection and allow active replication. However, AI with in vitro-infected semen can result in the production, after ten washing, of CAEV-free embryos, and ten washing in vitro- or in vivo-infected embryos with an intact ZP, or ten washing oocytes with an intact ZP, resulted in the production of virus-free female gametes or embryos that can be used for IVF or embryo transfer. Therefore, we have demonstrated that: (1) that CAEV-free embryos can be produced by IVF using spermatozoa infected in vitro by CAEV; and (2) embryo transfer can be used under field conditions to produce CAEV-free kids from CAEV-infected biological mothers.


Effects of solution conditions, processing parameters, and container materials on aggregation of a monoclonal antibody during freeze-thawing.
Freeze-thawing is a potentially damaging stress to which therapeutic proteins can be exposed deliberately during storage of bulk drug substance, and accidentally because of mishandling of commercial product during shipping and/or storage. The primary route of degradation induced by freeze-thawing is protein aggregation. We studied the effects of freeze-thawing on aggregation of an IgG2 monoclonal antibody, examining solution conditions (pH, and the presence or absence of 150 mM KCl), protein concentration, cooling and warming rates, and container type and material. In addition, we determined the effect of pH and KCl on protein tertiary structure and thermal stability with second derivative UV spectroscopy. In general, aggregation of the antibody during freeze-thawing increased with decreasing pH, which correlated well with Tm values. Aggregation was most prevalent at pH 3 and 4, with potential mechanisms involving both the formation of aggregation-prone conformational states as well as adsorption to and denaturation at various interfaces. Although all the parameters examined demonstrated some effect on the formation of soluble aggregates, the effect of container material was especially pronounced. Samples stressed in plastic or glass containers contained low amounts of aggregate. Storage in Teflon or commercial freezing containers, however, led to significantly higher levels of aggregate formation.


Malformations in newborns associated to anticonvulsant consumption during pregnancy. experience in third level hospital of Mexico.
The purpose of the present study is to determine the relationship between the anticonvulsant drug use during pregnancy and the presence of malformations in the newborns. The frequency of malformations in the neonates of epileptic mothers under anticonvulsant treatment was analyzed in two periods, one from 1988 to 1992, which included 76 epileptic mothers, and another from 1996 to 2003 with 170 patients. In the first period, 51 (67.1%) of mothers received monotherapy and 25 (32.9%) received polytherapy of phenytoin with carbamazepine, valproic acid or phenobarbital. In this period, 4 newborns (16%) with congenital malformations were registered. In the second period, 159 (93.5%) of the epileptic mothers received monotherapy and 11 (6.5%) received polytherapy of valproic acid with carbamazepine or phenytoin. During this period only 3 newborns 27.3% with malformations were registered. Clinical treatment should consider the risk of using polytherapy, mainly if phenytoin or valproic acid are combined with other anticonvulsants.


[Effects of exogenous ABA on translocation of photosynthate to fruit of Fuji apple during late stage of fruit rapid-swelling.]
To clarify the effects and underlying mechanism of ABA on sugar accumulation in apple fruits, 13C trace technique was used to examined the effects of different ABA levels (0, 50, 100 and 150 mg·L-1) and fluoridone (ABA biosynthesis inhibitor) on translocation of photosynthate to fruit during late stage of fruit rapid-swelling in five-year-old 'Yanfu3'/M26/Malus hupehensis Rehd. The results showed that the activities of related enzyme in sugar metabolism, the relative expression of sucrose transporter gene MdSUT1, MdSUT2.2 and sorbitol transporter gene MdSOT3 tended to increase first and then decrease with increasing ABA concentration, with a peak in 100 mg·L-1ABA treatment. Fluridone treatment significantly inhibited the enzymes activities of sugar metabolism and the relative expression of sugar transporters. The treatment of 100 mg·L-1ABA significantly reduced leaf 13C content, increased fruit 13C content and increased the transport rate of photosynthate from leaves to fruits compared with other treatments. Our results indicated that exogenous ABA enhanced sink strength of fruit and promoted the transportation of more photosynthate to fruits, which increased the soluble sugar content in fruits.


Preparation of primary amine derivatives of the magic-size nanocluster (CdSe)13.
Four [(CdSe)13(RNH2)13] derivatives (R = n-propyl, n-pentyl, n-octyl, and oleyl) are prepared by reaction of Cd(OAc)2·2H2O and selenourea in the corresponding primary-amine solvent. Nanoclusters grow in spontaneously formed amine-bilayer templates and are characterized by elemental analysis, IR spectroscopy, UV-vis spectroscopy, TEM, and low-angle XRD. Derivative [(CdSe)13(n-propylamine)13] is isolated as a yellowish-white solid (MP 98 °C) on the gram scale. These compounds are the first derivatives of magic-size CdSe nanoclusters to be isolated in purity.


Identification and validation of potential novel biomarkers to predict distant metastasis in differentiated thyroid cancer.
Distant metastasis (DM) is not common in differentiated thyroid cancer (DTC). However, it is associated with a significantly poor prognosis. Early detection of high-risk DTC patients is difficult, and the molecular mechanism is still unclear. Therefore, the present study aims to establish a novel predictive model based on clinicopathological parameters and DM-related gene signatures to provide guidelines for clinicians in decision making. Weighted gene co-expression network analysis (WGCNA) was performed to discover co-expressed gene modules and hub genes associated with DM. Univariate and multivariate analyses were carried out to identify independent clinicopathological risk factors based on The Cancer Genome Atlas (TCGA) database. An integrated nomogram prediction model was established. Finally, real hub genes were validated using the GSE60542 database and various thyroid cell lines. The midnightblue module was most significantly positively correlated with DM (R=0.56, P=9e-06) by as per WGCNA. DLX5 (AUC: 0.769), COX6B2 (AUC: 0.764), and LYPD1 (AUC: 0.760) were determined to be the real hub genes that play a crucial role in predicting DM. Meanwhile, univariate and multivariate analyses demonstrated that T-stage (OR, 15.03; 95% CI, 1.75-319.40; and P=0.024), histologic subtype (OR, 0.17; 95% CI, 0.03-0.92; and P=0.042) were the independent predictors of DM. Subsequently, a nomogram model was constructed based on gene signatures and independent clinical risk factors exhibited good performance. Additionally, the mRNA expressions of real hub genes in the GSE60542 dataset were consistent with TCGA. The present study has provided a reliable model to predict DM in patients with DTC. This model is likely to serve as an individual risk assessment tool in therapeutic decision-making.


Ethnic disparities in the prevalence of periodontitis among high school students in Sudan.
There are limited data on the epidemiology and risk factors of periodontitis in young populations in developing nations. This study assesses the prevalence of periodontal attachment loss and aggressive periodontitis and the association with ethnicity among high school students in Sudan. The study sample consisted of 1,200 students, 13 to 19 years old, selected from 38 public and private high schools using a multistage, stratified sampling design. The subjects were interviewed and examined clinically. Periodontal parameters were assessed at six sites per tooth. Subjects with aggressive periodontitis were identified. A total of 3.4% of the subjects had aggressive periodontitis, and 16.3% and 8.2% of the subjects had at least one tooth with > or = 4 and > or = 5 mm attachment loss, respectively. A significantly higher percentage of subjects of African tribal ethnicity had attachment loss > or = 4 and > or = 5 mm compared to Afro-Arab tribes (19.8% versus 14.7%, P = 0.02; and 12% versus 6.4%, P = 0.004, respectively), and had a higher prevalence of aggressive periodontitis (6% versus 2.3%; P = 0.01) and higher risk of being diagnosed with this disease (odds ratio = 2.7; P <0.0001). African ethnicity was also associated with a significantly higher number of teeth with attachment loss than in Afro-Arabs (P <0.01). Comparison by gender showed a significantly higher percentage of males with aggressive periodontitis (4.9% versus 2%; P <0.01) and a higher risk for this disease (odds ratio = 2.5; P = 0.01) than in females. However, the prevalence of subjects with attachment loss > or = 4 and > or = 5 mm was comparable in the two gender groups. Our results show that aggressive periodontitis is highly prevalent in this population. African ethnicity (versus Afro-Arab) and male gender were risk factors for aggressive periodontitis.


Studies on effects of lactose on experimental Trypanosoma vivax infection in Zebu cattle. 2. Packed cell volume.
The ability of intravenously administered lactose in normal saline to prevent a decline in packed cell volume (PCV) during experimental trypanosomosis was studied in Zebu cattle. During the lactose infusion period, the PCV was stable up to Day 5 post-infection (p.i.) in a lactose-infused group, compared to that in an uninfused group in which the PCV dropped significantly (P < 0.05) as shown by the values of cumulative percentage change. Furthermore the mean rate of change in PCV was significantly (P < 0.05) higher in the uninfused group relative to the lactose-infused group during the same period. While the PCV fell markedly in the lactose-infused group a day after lactose infusion was stopped (Day 13 p.i.), subsequent PCV values were significantly (P < 0.05) higher compared to those in the uninfused group, up to the end of experiment on Day 17 p.i. However the mean rates of change in PCV did not vary significantly (P > 0.05) between the groups during the period in which lactose infusion was stopped. The mean levels of parasitaemic waves and parasitaemia were higher, more prolonged and more frequent in the lactose-infused group. It was inferred that the lactose was able to prevent an early onset of anaemia in the Trypanosoma vivax-infected Zebu cattle.


Increasing Vitamin D Serum Levels Is Associated With Reduced Pulmonary Exacerbations in Patients With Cystic Fibrosis.
In 2012, The North American Cystic Fibrosis Foundation (NACFF) published new guidelines for the treatment of vitamin D deficiency in individuals with cystic fibrosis (CF). The objectives of our study were to assess the efficacy of these guidelines, and to test the effect of increasing vitamin D dosage on pulmonary function and exacerbations. Pulmonary function tests and serum concentrations of 25-hydroxyvitamin D [25(OH)D] were measured 1 year before increasing vitamin D dosage according to the guidelines and at least 1 year later. In addition, days of hospitalization and pulmonary exacerbations were counted and an average per year (average number of days of hospitalization and average number of pulmonary exacerbations [PEA], respectively) was calculated. A total of 90 patients from The Cystic Fibrosis Clinic at Hadassah Mount-Scopus Hospital, Jerusalem, Israel. The mean serum concentration of vitamin D increased significantly from 20.97 ng/mL (52.34 nmol/L) at baseline to 25.41 ng/mL (63.42 nmol/L) at the end of follow-up (P < 0.001). The number of PEA decreased significantly from 2.79 ± 3.96 to 2.15 ± 2.91 (P = 0.007). The change in vitamin D levels was correlated with a decrease in PEA (correlation coefficient = -0.318, P = 0.002). The NACFF guidelines for management of vitamin D deficiency improve vitamin D levels in patients with CF but did not reach the normal values in most patients. The increase in vitamin D serum levels was, however, associated with a decrease in number of pulmonary exacerbations.


Diplotriaena darnaudii sp. n. (Nematoda: Diplotriaenidae) from D'Arnaud's barbet, Trachyphonus darnaudii.
Diplotriaena darnaudii sp. n. is described from 13 specimens collected from the thoracic air sacs of a D'Arnaud's barbet (Trachyphonus darnaudii) originating in the Lake Baringo area of Kenya and which died in captivity in Canada. In morphology it is similar to D. bargusinica Skrjabin 1917, D. campanae Anderson 1959, D. dollfusi Anderson 1959, and D. epsilon Johnston and Mawson 1940, but can be separated from these species by combinations of trident size and spicule size and morphology.


Introduction: mediator assays and inflammatory events in asthma and allergic disease (Immunology Research Institute of New England Symposium).
The growing recognition of asthma as an immunologic disease mediated by inflammatory cells and mediators has changed the nature of therapy and monitoring of this disease. Modulation of inflammatory mediators such as leukotrienes, prostaglandins, and adenosine by specific immunoregulatory pharmacotherapy is now becoming well-recognized as essential for proper management of allergic diseases, including asthma. The newly-developed immunoassays for specific inflammatory cell activation markers, such as tryptase for mast cell activation, myeloperoxidase for neutrophil activation, and eosinophilic cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) for eosinophil activation, may significantly enhance the ability to both determine the cellular etiology of allergic inflammation and also to monitor the efficacy of antiinflammatory therapies in suppressing cell-specific immunologic events.


Effects of sclerotic changes on stress concentration in early-stage osteonecrosis: A patient-specific, 3D finite element analysis.
Stress distribution remains unclear in early-stage osteonecrosis of the femoral head (ONFH). To clarify this issue, we generated patient-specific finite element models (FEMs) from 51 patients with ONFH. Patients' hips were classified into three groups: ONFH without a sclerotic boundary (Stage 1, n = 6), ONFH with a sclerotic boundary (Stage 2, n = 10), and ONFH with both a sclerotic boundary and <2 mm collapse (Stage 3, n = 35). Four hips without ONFH were used as controls. Stress distribution in each FEM was compared with magnetic resonance imaging (MRI) and computed tomography (CT) results. Fifteen wholly resected femoral heads in Stage 3 hips were assessed by micro-CT. Furthermore, we histologically examined three Stage 2 femoral heads that subsequently developed subchondral fractures after FEM analyses. In all FEMs of both control and Stage 1 hip, stress was equally distributed on the femoral head surface. However, in all FEMs of both Stages 2 and 3 hips, stress was concentrated at the lateral boundary of the femoral head surface, corresponding to both a low-intensity band on T1-weighted MRI images and sclerotic changes on CT. On micro-CT, subchondral fractures consistently began at the lateral boundary with sclerotic changes, in which bone volume fraction was increased. Histology showed breakage of subchondral plates at the junction between necrotic and reparative zones. In early-stage ONFH, sclerotic changes caused stress concentration, which can trigger subchondral fractures at the lateral boundary. Clinical Significance: Our results will clarify the pathogenic mechanism of collapse in ONFH. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3169-3177, 2018.


Emergence of non-artificial intelligence digital health innovations in ophthalmology: A systematic review.
The prominent rise of digital health in ophthalmology is evident in the current age of Industry 4.0. Despite the many facets of digital health, there has been a greater slant in interest and focus on artificial intelligence recently. Other major elements of digital health like wearables could also substantially impact patient-focused outcomes but have been relatively less explored and discussed. In this review, we comprehensively evaluate the use of non-artificial intelligence digital health tools in ophthalmology. 53 papers were included in this systematic review - 25 papers discuss virtual or augmented reality, 14 discuss mobile applications and 14 discuss wearables. Most papers focused on the use of technologies to detect or rehabilitate visual impairment, glaucoma and age-related macular degeneration. Overall, the findings on patient-focused outcomes with the adoption of these technologies are encouraging. Further validation, large-scale studies and earlier consideration of real-world barriers are warranted to enable better real-world implementation.


Immune responses elicited against rotavirus middle layer protein VP6 inhibit viral replication in vitro and in vivo.
Rotavirus (RV) is a common cause of severe gastroenteritis (GE) in children worldwide. Live oral RV vaccines protect against severe RVGE, but the immune correlates of protection are not yet clearly defined. Inner capsid VP6 protein is a highly conserved, abundant, and immunogenic RV protein, and VP6-specific mucosal antibodies, especially IgA, have been implicated to protect against viral challenge in mice. In the present study systemic and mucosal IgG and IgA responses were induced by immunizing BALB/c mice intranasally with a combination of recombinant RV VP6 protein (subgroup II [SGII]) and norovirus (NoV) virus-like particles (VLPs) used in a candidate vaccine. Following immunization mice were challenged orally with murine RV strain EDIMwt (SG non-I-non-II, G3P10[16]). In order to determine neutralizing activity of fecal samples, sera, and vaginal washes (VW) against human Wa RV (SGII, G1P1A[8]) and rhesus RV (SGI, G3P5B[3]), the RV antigen production was measured with an ELISA-based antigen reduction neutralization assay. Only VWs of immunized mice inhibited replication of both RVs, indicating heterotypic protection of induced antibodies. IgA antibody depletion and blocking experiments using recombinant VP6 confirmed that neutralization was mediated by anti-VP6 IgA antibodies. Most importantly, after the RV challenge significant reduction in viral shedding was observed in feces of immunized mice. These results suggest a significant role for mucosal RV VP6-specific IgA for the inhibition of RV replication in vitro and in vivo. In addition, these results underline the importance of non-serotype-specific immunity induced by the conserved subgroup-specific RV antigen VP6 in clearance of RV infection.


Familial renal disease in soft-coated wheaten terriers.
To review what is known about the familial renal diseases in soft-coated wheaten terriers (SCWT), provide an update in developments in this field including the relationship with protein-losing nephropathy (PLN) and the potential association with protein-losing enteropathy (PLE). Information was derived from studies of dogs maintained in the North Carolina State University colony, information contained within an open registry of affected dogs, and data gathered from the general population of wheaten terriers at risk as well as studies performed on banked DNA samples from affected SCWT in the general population and normal geriatric dogs seen at the University of Pennsylvania (PennVet). A two-hit pathogenesis has been proposed in some types of human focal segmental glomerulosclerosis, specifically the subset of cases that are associated with a podocytopathy. At risk podocytes may be predisposed to injury by disease processes that would be reversible in other patients. Mutations were found in association with PLN in SCWT, indicating a podocytopathy that causes a change in glomerular permselectivity. This podocytopathy leads to the development of lesions resembling focal segmental glomerulosclerosis. There is also strong evidence supporting a high prevalence of food hypersensitivity reactions in SCWT, although it is unclear if these reactions have a primary or secondary role in the development of PLE. There are also suggestions of immunodysregulation in affected SCWT. PLN in SCWT is due to a podocytopathy. The cause of PLE has not been identified; however, it is possible that PLE develops from a functional-structural abnormality in the intestines and food allergies develop as secondary phenomena. It is also possible that inflammatory events that are the result of either immunodysregulation or food allergies might lead to the development of PLE. In either case, PLE most likely exacerbates PLN in affected SCWT.


Tinea axillaris, a variant of intertriginous tinea, due to non-occupational infection with Trichophyton verrucosum.
The term tinea axillaris has been used only a few times in the literature. In this paper we describe a male patient with widespread tinea corporis and unguium affecting also both axillary regions. Trichophyton verrucosum was isolated as the causative agent. The patient admitted to no direct contact with infected animals, but had lived in a rural area until a year before the infection became widespread. Topical treatment with glucocorticosteroids probably promoted propagation over large parts of his body and may have led to the infection of the axillary region, an unusual site for fungal infection. Treatment with itraconazole over 4 weeks led to complete clearing of all lesions on glabrous skin. Thereafter, itraconazole pulse therapy was used to treat the nail infection.


Fluid-phase SC5b-8 complex of human complement: generation and isolation from serum.
A rapid, simple method for isolating SC5b-9 generated in human serum, and SC5b-8 generated in C9-depleted serum is described. The procedure leads to approximately 30% recovery of either complex and consists of polyethyleneglycol precipitation followed by 1 DEAE ion exchange chromatography and a sucrose density gradient ultracentrifugation. The SC5b-8 complex is a water-soluble macromolecular of alpha-electrophoretic mobility. Apart from the absence of C9, it exhibits an identical SDS-gel electrophoresis polypeptide pattern as SC5b-9. A sedimentation coefficient of 19 to 20S and an effective molecular radius of approximately 10 nm were determined by sucrose density gradient centrifugation and gel filtration, respectively. From these values, a m.w. of 800 to 850,000 is tentatively assigned to the SC5b-8 complex. The S-protein was not dissociable from either SC5b-8 or SC5b-9 through treatment with desoxycholate and no alterations in the hydrodynamic properties of either complex were discernible after action of this detergent.


Serum anti-Müllerian hormone levels are associated with early miscarriage in the IVF/ICSI fresh cycle.
Anti-Müllerian hormone (AMH) is used as a biomarker to estimate ovarian reserve. The relationship between AMH and early miscarriage of in vitro fertilization (IVF) is still inconclusive. This study aimed to explore whether serum AMH levels are associated with early miscarriage rates after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) with fresh embryo transfer (ET). This retrospective cohort study included 2246 patients undergoing their first oocyte retrievals for IVF/ICSI with fresh embryos transferred to Tianjin Central Hospital of Gynecology Obstetrics between May 2018 and March 2020. The serum AMH levels of the patients were measured within 12 months before the IVF/ICSI cycles. All women were divided into a low-AMH group, medium-AMH group and high-AMH group. Binary logistic regression was applied to confirm whether the serum AMH level was associated with the risk of early miscarriage independent of potential confounders, such as age, body mass index (BMI), duration of infertility, main diagnosis, history of internal medicine diseases, number of oocytes retrieved and high-quality embryo rate. The early miscarriage rate was significantly lower in the medium-AMH group than in either the low-AMH or high-AMH group among young (< 35 years) women (P = 0.015). In women above 35 years of age, the early miscarriage rates in the three AMH groups were not significantly different. Young women with high serum AMH levels had a significantly higher risk of early miscarriage regardless of age or other potential confounders (adjusted odds ratio (OR) 2.382, 95% confidence interval (CI) 1.246 to 4.553, P = 0.009). The results remained similar after restricting the analysis to women without polycystic ovary syndrome (PCOS). With a high AMH level, young women had a higher risk of early miscarriage than women with a medium AMH level in their first IVF/ICSI treatment. In young women, serum AMH levels were independently associated with the risk of early miscarriage after IVF-ET treatment. Serum AMH levels might be a valuable marker to estimate the risk of early miscarriage. It is worth noting to the clinical value of AMH.


[A woman with acute abdominal pain after a gastric bypass].
A 35-year-old woman with a history of gastric bypass presented with acute abdominal pain, nausea and an urge to move. She showed normal vital signs. We found abdominal guarding and elevated ASAT, ALAT and LDH. A CT scan showed the whirl sign, caused by a mesenteric herniation through the Roux-en-Y gastric bypass.


(3R,4S)-3-[4-(4-fluorophenyl)-4-hydroxypiperidin-1-yl]chroman-4,7-diol: a conformationally restricted analogue of the NR2B subtype-selective NMDA antagonist (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)- 1-propanol.
(1S,2S)-1-(4-Hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (CP-101,606, 1) is a recently described antagonist of N-methyl-D-aspartate (NMDA) receptors containing the NR2B subunit. In the present study, the optimal orientation of compounds of this structural type for their receptor was explored. Tethering of the pendent methyl group of 1 to the phenolic aromatic ring via an oxygen atom prevents rotation about the central portion of the molecule. Several of the new chromanol compounds have high affinity for the racemic [3H]CP-101,606 binding site on the NMDA receptor and protect against glutamate toxicity in cultured hippocampal neurons. The new ring caused a change in the stereochemical preference of the receptor-cis (erythro) compounds had better affinity for the receptor than the trans isomers. Computational studies suggest that steric interactions between the pendent methyl group and the phenol ring in the acyclic series determine which structures can best fit the receptor. The chromanol analogue, (3R,4S)-3-[4-(4-fluorophenyl)-4-hydroxypiperidin-1- yl]chroman-4,7-diol (12a, CP-283,097), was found to possess potency and selectivity comparable to CP-101,606. Thus 12a is a new tool to explore the function of the NR2B-containing NMDA receptors.


Fluoroquinolone-Resistant Streptococcus agalactiae Invasive Isolates Recovered in Argentina.
Background: Streptococcus agalactiae or group B Streptococcus (GBS) is an important pathogen in neonates and nonpregnant individuals. Epidemiological studies of GBS resistance to fluoroquinolones (FQs) in Latin America are scarce. This study aimed to determine the local prevalence of FQ resistance in the frame of a national, prospective multicenter study of invasive GBS infections and to investigate mechanisms of resistance, serotype distribution, and clonal relationships among resistant isolates. Methods: From July 2014 to July 2015, 162 invasive GBS isolates were collected from 86 health care centers in 32 Argentinean cities. All isolates were screened for FQ nonsusceptibility using a five-disc scheme: levofloxacin (LVX), ciprofloxacin, norfloxacin (NOR), ofloxacin, and pefloxacin (PF). LVX minimal inhibitory concentration (MIC) was determined by the agar dilution method. Sequencing of internal regions of gyrA and parC genes was performed. Capsular typing and genetic characterization of nonsusceptible isolates were assessed by latex agglutination, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing. Results: Twenty-four of one hundred sixty-two GBS isolates exhibited no inhibition zones to all tested FQs with an MIC range of 16-32 mg/L for LVX, and one isolate with MIC = 1 mg/L showed no inhibition zones around NOR and PF discs. In all resistant isolates, point mutations were detected in both genes. Serotype Ib was prevalent (88%). One PFGE type accounted for 84% of the FQ-resistant isolates and belonged to serotype Ib, sequence type 10. Conclusions: The prevalence of FQ resistance was 14.8% likely to be associated with dissemination of an ST10/serotype Ib clone. The unexpected high rate of resistance emphasizes the relevance for continuous surveillance of GBS epidemiology and antibiotic susceptibility.


Prognostic value of circulating DNA levels in critically ill and trauma patients.
The number of studies investigating circulating nucleic acids as potential biomarkers has increased in recent years. The detection of such biomarkers is a minimally invasive alternative for the diagnosis and prognosis of various clinical conditions. The value of circulating DNA levels as a predictive biomarker has been demonstrated in patients suffering from numerous acute pathologies that have a high risk of intensive care needs and in-hospital deaths. The mechanism by which circulating DNA levels increase in patients with these conditions remains unclear. In this review, we focused on the potential use of this biomarker for prognosis prediction in critically ill and trauma patients. The literature review was performed by searching MedLine using PubMed in the English language.


Clinical trials in cancer screening, prevention and early diagnosis (SPED): a systematic mapping review.
Global annual cancer incidence is forecast to rise to 27.5 M by 2040, a 62% increase from 2018. For most cancers, prevention and early detection are the most effective ways of reducing mortality. This study maps trials in cancer screening, prevention, and early diagnosis (SPED) to identify areas of unmet need and highlight research priorities. A systematic mapping review was conducted to evaluate all clinical trials focused on cancer SPED, irrespective of tumour type. The National Cancer Research Institute (NCRI) portfolio, EMBASE, PubMed and Medline were searched for relevant papers published between 01/01/2007 and 01/04/2020. References were exported into Covidence software and double-screened. Data were extracted and mapped according to tumour site, geographical location, and intervention type. One hundred seventeen thousand seven hundred one abstracts were screened, 5157 full texts reviewed, and 2888 studies included. 1184 (52%) trials focussed on screening, 554 (24%) prevention, 442 (20%) early diagnosis, and 85 (4%) a combination. Colorectal, breast, and cervical cancer comprised 61% of all studies compared with 6.4% in lung and 1.8% in liver cancer. The latter two are responsible for 26.3% of global cancer deaths compared with 19.3% for the former three. Number of studies varied markedly according to geographical location; 88% were based in North America, Europe, or Asia. This study shows clear disparities in the volume of research conducted across different tumour types and according to geographical location. These findings will help drive future research effort so that resources can be directed towards major challenges in cancer SPED.


Egg Allergy in US Children.
Egg allergy is common in young children (<5 years) and has significant negative impacts on quality of life. The objective of this study was to characterize egg allergy prevalence, severity, baked egg tolerance, and other associated factors in a large US cohort. A national cross-sectional survey was administered from October 2015 to September 2016, resulting in complete parent-proxy responses for 38,408 children. Weighted proportions were estimated to compare egg allergy prevalence and characteristics between key subpopulations. The overall prevalence of current, convincingly egg allergy was 0.9% among all children and 1.3% among children <5 years. Black children were over-represented among children with egg allergy, accounting for 23.4% (95% confidence interval: 13.1-38.4) of egg-allergic children despite comprising 13.2% (12.3-14.2) of the US pediatric population. Among children with egg allergy, 64.2% reported baked egg tolerance and 60.2% had allergy to other foods, with 29.3% having peanut allergy. Asthma was more prevalent in children with an egg allergy than children with other top 8 food allergies (46.5% [35.8-57.4] vs 33.2% [29.6-37.0], P < .05). Among children with current egg allergy, those with baked egg tolerance reported that their food allergy resulted in significantly reduced psychosocial burden, relative to their baked egg-allergic counterparts (M = 3.1 [2.9-3.3] vs M = 3.7 [3.5-3.9]). Egg allergy is common amongst young children. Nearly two-thirds of children with egg allergy reported baked egg tolerance. Increased efforts are needed to ensure that children with egg allergy are appropriately evaluated as many have comorbid allergic disease and determination of baked egg tolerance may improve quality of life.


gamma-Glutamyltranspeptidase from Proteus mirabilis: localization and activation by phospholipids.
Antiserum was prepared against the purified gamma-glutamyltranspeptidase (EC 220.127.116.11) of Proteus mirabilis. The antiserum inactivated the gamma-glutamyltranspeptidase activities of both purified enzyme and intact cells. Native cells were agglutinated with the antibody. Immunocytochemical studies with indirect immunofluorescence and electron microscopy analysis suggested that gamma-glutamyltranspeptidase is localized on the surface of the cell. Its distribution in the cell wall or periplasmic space or both was also confirmed by the treatment of cells with lysozyme-EDTA. The purified enzyme was activated by the addition of membrane phospholipids isolated from the same bacterium. The hydrolysis activity was stimulated more than the transpeptidation activity by several phospholipids.


[Timing of food introduction to the infant diet and risk of food allergy: a systematic review and Meta-analysis].
Objective: To evaluate the relationship between the timing of complementary feeding for infants and the occurrence of food allergy. Methods: The PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang Data database were searched for randomized controlled trials (RCTs) about the effects of early introduction of complementary foods in infants on the occurrence of food allergy. Papers published from the establishment of the databases to December 31, 2019 were extracted. The quality of the selected literature was evaluated using the risk-of-bias (ROB) tools in the Cochrane Handbook, and the RevMan 5.3 software was used for meta-analysis. For the complementary food analyzed in a few reports in literature, a systematic review was conducted. Results: A total of 8 RCTs were extracted, and the systematic review and Meta-analysis were carried out according to food types. The results of Meta-analysis showed that compared with late introduction (after 6 months of age), early introduction (before 6 months of age) of eggs (RR=0.60, 95%CI 0.46-0.79) could reduce the risk of egg allergy in infants. The subgroup analysis of the six studies about eggs demonstrated that in infants with a prior or family history of allergic diseases, the introduction of eggs before 6 months of age was associated with reduced risk of egg allergy (RR=0.55, 95%CI 0.40-0.75), and the introduction of raw eggs (RR=0.67, 95%CI 0.49-0.93) and small amount of eggs (equivalent to weekly protein 0-4 g) (RR=0.55, 95%CI 0.36-0.85) before 6 months of age were also associated with reduced risk of egg allergy. In addition, egg supplementation during 4-6 months of age reduced the occurrence of egg allergy compared with supplementation before 4 months of age (RR=0.58, 95%CI 0.43-0.78). The systematic review found no conclusive relationship between early peanut introduction and peanut allergy, nor the correlation between early cow's milk protein introduction and cow's milk protein allergy (P>0.05). Conclusion: Early introduction (before 6 months of age) of eggs in infants' complementary foods can prevent infant egg allergy, but the limitations of the study need to be considered.


Symmetry calculation for molecules and transition states.
The symmetry of molecules and transition states of elementary reactions is an essential property with important implications for computational chemistry. The automated identification of symmetry by computers is a very useful tool for many applications, but often relies on the availability of three-dimensional coordinates of the atoms in the molecule and hence becomes less useful when these coordinates are a priori unavailable. This article presents a new algorithm that identifies symmetry of molecules and transition states based on an augmented graph representation of the corresponding structures, in which both topology and the presence of stereocenters are accounted for. The automorphism group order of the graph associated with the molecule or transition state is used as a starting point. A novel concept of label-stereoisomers, that is, stereoisomers that arise after labeling homomorph substituents in the original molecule so that they become distinguishable, is introduced and used to obtain the symmetry number. The algorithm is characterized by its generic nature and avoids the use of heuristic rules that would limit the applicability. The calculated symmetry numbers are in agreement with expected values for a large and diverse set of structures, ranging from asymmetric, small molecules such as fluorochlorobromomethane to highly symmetric structures found in drug discovery assays. The new algorithm opens up new possibilities for the fast screening of the degree of symmetry of large sets of molecules.


How to promote the sustainable development of virtual reality technology for training in construction filed: A tripartite evolutionary game analysis.
In recent years, virtual reality training technology (VRTT) has been considered by many scholars as a new training method instead of traditional training (TT) to reduce unsafe behaviors ascribed to construction workers (CWs) and corporate accident rates. However, in this process, a conflict of interest arises among the government, construction enterprises (CEs), and CWs. Therefore, this study introduces a quantitative research method, the three-party evolutionary game and creatively combining them with the product life cycle (PLC) to solve this problem by analyzing the equilibrium and evolutionarily stable strategies of the system. Finally, collaborative players' decision-making behaviors and their sensitivity to critical factors are examined. This paper will illustrate these in each stage through numerical simulations. The results of the study indicate that the government plays a dominant role in the VRTT introduction stage. When the government gives CEs appropriate subsidies, CEs will eventually realize the importance of VRTT for CWs. Then the government will gradually reduce the amount of the subsidies in this process. In addition, we also find that the continually high cost will lead to negative policies by the government, which requires the active cooperation and attitude change from CEs and CWs. Ultimately, the government, CEs and CWs adopt the best strategy in the evolutionary process to facilitate the promotion, application and sustainability of VRTT in the construction industry.


Synthesis of biocompatible BSA-GMA and two-photon polymerization of 3D hydrogels with free radical type I photoinitiator.
Although the development of three-dimensional (3D) printing technology is growing rapidly in the biomedical field, it remains a challenge to achieve arbitrary 3D structures with high resolution and high efficiency. Protein hydrogels fabricated by two- photon polymerization (TPP) have excellent mechanical properties, high precision, and 3D architecture. However, a large number of the amino acid group in bovine serum albumin (BSA) would be consumed when the protein-based hydrogels use dyes of free radical type II photoinitiators. In this study, we use glycidyl methacrylate (GMA) to modify BSA molecules to obtain a series of BSA-GMA materials, allowing the protein material to be two-photon polymerized with a water-soluble free radical type I photoinitiator. The precisely controllable 3D structure of the BSA-GMA hydrogel was fabricated by adjusting the concentration of the precursor solution, the degree of methacrylation, and the processing parameters of the TPP technique. Importantly, BSA-GMA materials are free of acidic hazardous substances. Meanwhile, the water-soluble initiator lithium phenyl (2,4,6-trimethylbenzoyl) phosphite (LAP) allows TPP on the vinyl group of the GMA chain and thus without consuming its amino acid group. The as-prepared BSA-GMA hydrogel structure exhibits excellent autofluorescence imaging, pH responsiveness, and biocompatibility, which would provide new avenues for potential applications in tissue engineering and biomedical fields to meet specific biological requirements.


Comparing treatment outcome of infliximab and adalimumab in patients with severe hidradenitis suppurativa.
Hidradenitis suppurativa (HS) is a chronic relapsing skin disease. Recent studies have shown promising results of anti-tumor necrosis factor-alpha treatment. To compare the efficacy and safety of infliximab and adalimumab in the treatment of HS. A retrospective study was performed to compare 2 cohorts of 10 adult patients suffering from severe, recalcitrant HS. In 2005, 10 patients were treated with infliximab intravenous (i.v.) (3 infusions of 5 mg/kg at weeks 0, 2, and 6). In 2009, 10 other patients were treated in the same hospital with adalimumab subcutaneous (s.c.) 40 mg every other week. Both cohorts were followed up for 1 year using identical evaluation methods [Sartorius score, quality of life index, reduction of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), patient and doctor global assessment, and duration of efficacy]. Nineteen patients completed the study. In both groups, the severity of the HS diminished. Infliximab performed better in all aspects. The average Sartorius score was reduced to 54% of baseline for the infliximab group and 66% of baseline for the adalimumab group. Adalimumab s.c. 40 mg every other week is less effective than infliximab i.v. 5 mg/kg at weeks 0, 2, and 6.


The TRPM6 kinase domain determines the Mg·ATP sensitivity of TRPM7/M6 heteromeric ion channels.
The transient receptor potential melastatin member 7 (TRPM7) and member 6 (TRPM6) are divalent cation channel kinases essential for magnesium (Mg(2+)) homeostasis in vertebrates. It remains unclear how TRPM6 affects divalent cation transport and whether this involves functional homomeric TRPM6 plasma membrane channels or heteromeric channel assemblies with TRPM7. We show that homomeric TRPM6 is highly sensitive to intracellular free Mg(2+) and therefore unlikely to be active at physiological levels of [Mg(2+)]i. Co-expression of TRPM7 and TRPM6 produces heteromeric TRPM7/M6 channels with altered pharmacology and sensitivity to intracellular Mg·ATP compared with homomeric TRPM7. Strikingly, the activity of heteromeric TRPM7/M6 channels is independent of intracellular Mg·ATP concentrations, essentially uncoupling channel activity from cellular energy status. Disruption of TRPM6 kinase phosphorylation activity re-introduces Mg·ATP sensitivity to the heteromeric channel similar to that of TRPM7. Thus, TRPM6 modulates the functionality of TRPM7, and the TRPM6 kinase plays a critical role in tuning the phenotype of the TRPM7·M6 channel complex.


The ability of consortium wastewater protozoan and bacterial species to remove COD in the presence of nanomaterials under varying pH conditions.
The aim of this study was to ascertain the survival limit and capability of commonly found wastewater protozoan (Aspidisca sp, Trachelophyllum sp and Peranema sp) and bacterial (Bacillus licheniformis, Brevibacillus laterosporus and Pseudomonas putida) species to remove COD while exposed to commercial nanomaterials under varying pH conditions. The experimental study was carried out in modified mixed liquor media adjusted to various pH levels (pH 2, 7 and 10) and a comparative study was performed to determine the difference between the cytotoxicity effects of commercial zinc oxide (nZnO) and silver (nAg) nanomaterials (NMs) on the target wastewater microbial communities using standard methods. The selected microbial communities were exposed to lethal concentrations ranging from 0.015 g/L to 40 g/L for nZnO and from 0.015 g/L to 2 g/L for nAg for a period of 5 days of incubation at 30°C (100 r/min). Compared with the absence of NMs in wastewater mixed liquor, the relevant environmental concentration ranging between 10 µg/L and 100 µg/L, for both nZnO and nAg caused no adverse effects, but the presence of 20 g of nZnO/L and 0.65 g of nAg/L significantly inhibited microbial growth. Statistical evidence showed that nAg was significantly more toxic compared to nZnO, but there was an insignificant difference in toxicity between microbial communities and pH variations. A significant decrease in the removal of COD by microbial populations was observed in the presence of NMs with a moderate correlation of r = 0.3 to r = 0.7 at all pH levels. It was evident that there was a physical interaction between commercial NMs and target wastewater microbial communities; although not quantitatively assessed, cell morphology and cell death were observed. Such phenomena suggest the high resilience of the microbial community, but it is the accumulation of NMs that will have adverse effects on the performance in terms of COD removal.


DNA hypomethylation and aberrant expression of the human endogenous retrovirus ERVWE1/syncytin-1 in seminomas.
Syncytin-1 and 2, human fusogenic glycoproteins encoded by the env genes of the endogenous retroviral loci ERVWE1 and ERVFRDE1, respectively, contribute to the differentiation of multinucleated syncytiotrophoblast in chorionic villi. In non-trophoblastic cells, however, the expression of syncytins has to be suppressed to avoid potential pathogenic effects. Previously, we have shown that the transcriptional suppression of ERVWE1 promoter is controlled epigenetically by DNA methylation and chromatin modifications. In this study, we describe the aberrant expression of syncytin-1 in biopsies of testicular germ cell tumors. We found efficient expression and splicing of syncytin-1 in seminomas and mixed germ cell tumors with seminoma component. Although another fusogenic gene, syncytin-2 was also derepressed in seminomas, its expression was significantly lower than that of syncytin-1. Neither the transcription factor GCM1 nor the increased copy number of ERVWE1 were sufficient for this aberrant expression of syncytin-1 in seminomas. In accordance with our recent finding of the highly increased expression of TET1 dioxygenase in most seminomas, the ERVWE1 promoter was significantly hypomethylated in comparison with the matched controls. In contrast, 5-hydroxymethylcytosine levels were not detectable at the ERVWE1 promoter. We further describe that another endogenous retroviral element adjacent to ERVWE1 remains transcriptionally suppressed and two additional HERV-W family members are only slightly upregulated in seminomas. We conclude that DNA demethylation of the ERVWE1 promoter in seminomas is a prerequisite for syncytin-1 derepression. We propose the spliced syncytin-1 expression as a marker of seminoma and suggest that aberrant expression of endogenous retroviruses might be a correlate of the hypomethylated genome of seminomas.


[The roles of nuclear Ca2+/CaM dependent kinases and calcineurin on the development of myocardial hypertrophy in rat].
To evaluate whether protein phosphorylation and dephosphorylation in nuclei play roles in the development of myocardial hypertrophy, distribution of protein kinases and phosphatases in cell fractions were determined. The model of hypertensive rat was established by abdominal aortic constriction. Velocity and isopyknic gradient centrifugation was employed to fractionate rat myocardium to membrane, cytosol and nuclei. Enzymatic methods were employed to determine kinases and phosphatases. Compare with control group, the activity of CaMK increased by 101.1% (P < 0.01) and 40.16% (P < 0.01) respectively in nuclear and membranous fractions, changed without significance in cytosolic fraction; the activity of calcineurin in nuclei increased by 43.57%, (P < 0.05), lightly changed without significance in membranous and cytosolic fractions. Nuclear translocation of CaMK and calcineurin, might play important roles on overload-induced cardiac hypertrophy.


Triplet photosensitizers: from molecular design to applications.
Triplet photosensitizers (PSs) are compounds that can be efficiently excited to the triplet excited state which subsequently act as catalysts in photochemical reactions. The name is originally derived from compounds that were used to transfer the triplet energy to other compounds that have only a small intrinsic triplet state yield. Triplet PSs are not only used for triplet energy transfer, but also for photocatalytic organic reactions, photodynamic therapy (PDT), photoinduced hydrogen production from water and triplet-triplet annihilation (TTA) upconversion. A good PS should exhibit strong absorption of the excitation light, a high yield of intersystem crossing (ISC) for efficient production of the triplet state, and a long triplet lifetime to allow for the reaction with a reactant molecule. Most transition metal complexes show efficient ISC, but small molar absorption coefficients in the visible spectral region and short-lived triplet excited states, which make them unsuitable as triplet PSs. One obstacle to the development of new triplet PSs is the difficulty in predicting the ISC of chromophores, especially of organic compounds without any heavy atoms. This review article summarizes some molecular design rationales for triplet PSs, based on the molecular structural factors that facilitate ISC. The design of transition metal complexes with large molar absorption coefficients in the visible spectral region and long-lived triplet excited states is presented. A new method of using a spin converter to construct heavy atom-free organic triplet PSs is discussed, with which ISC becomes predictable, C60 being an example. To enhance the performance of triplet PSs, energy funneling based triplet PSs are proposed, which show broadband absorption in the visible region. Applications of triplet PSs in photocatalytic organic reactions, hydrogen production, triplet-triplet annihilation upconversion and luminescent oxygen sensing are briefly introduced.


Natural Tr1-like cells do not confer long-term tolerogenic memory.
IL-10-producing Tr1 cells promote tolerance but their contributions to tolerogenic memory are unclear. Using 10BiT mice that carry a Foxp3-eGFP reporter and stably express CD90.1 following IL-10 production, we characterized the spatiotemporal dynamics of Tr1 cells in a house dust mite model of allergic airway inflammation. CD90.1+Foxp3-IL-10+ Tr1 cells arise from memory cells and rejoin the tissue-resident memory T-cell pool after cessation of IL-10 production. Persistent antigenic stimulation is necessary to sustain IL-10 production and Irf1 and Batf expression distinguishes CD90.1+Foxp3-IL-10+ Tr1 cells from CD90.1+Foxp3-IL-10- 'former' Tr1. Depletion of Tr1-like cells after primary sensitization exacerbates allergic airway inflammation. However, neither transfer nor depletion of former Tr1 cells influences either Tr1 numbers or the inflammatory response during subsequent allergen memory re-challenge weeks later. Together these data suggest that naturally-arising Tr1 cells do not necessarily give rise to more Tr1 upon allergen re-challenge or contribute to tolerogenic memory. This phenotypic instability may limit efforts to re-establish tolerance by expanding Tr1 in vivo.


Containing the cost of care for people living with HIV/AIDS: an examination of the Medicaid managed care approach.
This article examines Medicaid managed care's potential impact on people living with HIV/AIDS. The incongruence of the philosophy behind providing health and social services to people living with HIV/AIDS and with the philosophy behind the medical model of managed care is discussed. Health and social policy issues that various states have had to face concerning Medicaid managed care's administration of health benefits for people living with HIV/AIDS are examined. Research on managed care is employed to extrapolate potential managed care models that states might use to administer the health benefits for people living with HIV/AIDS. Finally, policy and research agendas are proposed to begin investigating Medicaid managed care's potential impact on people living with HIV/AIDS.


Kinetic assembly of near-IR-active gold nanoclusters using weakly adsorbing polymers to control the size.
Clusters of metal nanoparticles with an overall size of less than 100 nm and high metal loadings for strong optical functionality are of interest in various fields including microelectronics, sensors, optoelectronics, and biomedical imaging and therapeutics. Herein we assemble approximately 5 nm gold particles into clusters with controlled size, as small as 30 nm and up to 100 nm, that contain only small amounts of polymeric stabilizers. The assembly is kinetically controlled with weakly adsorbing polymers, PLA(2K)-b-PEG(10K)-b-PLA(2K) or PEG (MW = 3350), by manipulating electrostatic, van der Waals (VDW), steric, and depletion forces. The cluster size and optical properties are tuned as a function of particle volume fractions and polymer/gold ratios to modulate the interparticle interactions. The close spacing between the constituent gold nanoparticles and high gold loadings (80-85 w/w gold) produce a strong absorbance cross section of approximately 9 x 10(-15) m(2) in the NIR at 700 nm. This morphology results from VDW and depletion attractive interactions that exclude the weakly adsorbed polymeric stabilizer from the cluster interior. The generality of this kinetic assembly platform is demonstrated for gold nanoparticles with a range of surface charges from highly negative to neutral with the two different polymers.


Beneficial effects of environmental enrichment on behavior, stress reactivity and synaptophysin/BDNF expression in hippocampus following early life stress.
Exposure to environmental enrichment can beneficially influence the behavior and enhance synaptic plasticity. The aim of the present study was to investigate the mediated effects of environmental enrichment on postnatal stress-associated impact with regard to behavior, stress reactivity as well as synaptic plasticity changes in the dorsal hippocampus. Wistar rat pups were submitted to a 3 h maternal separation (MS) protocol during postnatal days 1-21, while another group was left undisturbed. On postnatal day 23, a subgroup from each rearing condition (maternal separation, no-maternal separation) was housed in enriched environmental conditions until postnatal day 65 (6 weeks duration). At approximately three months of age, adult rats underwent behavioral testing to evaluate anxiety (Elevated Plus Maze), locomotion (Open Field Test), spatial learning and memory (Morris Water Maze) as well as non-spatial recognition memory (Novel Object Recognition Test). After completion of behavioral testing, blood samples were taken for evaluation of stress-induced plasma corticosterone using an enzyme-linked immunosorbent assay (ELISA), while immunofluorescence was applied to evaluate hippocampal BDNF and synaptophysin expression in dorsal hippocampus. We found that environmental enrichment protected against the effects of maternal separation as indicated by the lower anxiety levels and the reversal of spatial memory deficits compared to animals housed in standard conditions. These changes were associated with increased BDNF and synaptophysin expression in the hippocampus. Regarding the neuroendocrine response to stress, while exposure to an acute stressor potentiated corticosterone increases in maternally-separated rats, environmental enrichment of these rats prevented this effect. The current study aimed at investigating the compensatory role of enriched environment against the negative outcomes of adverse experiences early in life concurrently on emotional and cognitive behaviors, HPA function and neuroplasticity markers.


Streamlining the Pipeline for Generation of Recombinant Affinity Reagents by Integrating the Affinity Maturation Step.
Often when generating recombinant affinity reagents to a target, one singles out an individual binder, constructs a secondary library of variants, and affinity selects a tighter or more specific binder. To enhance the throughput of this general approach, we have developed a more integrated strategy where the "affinity maturation" step is part of the phage-display pipeline, rather than a follow-on process. In our new schema, we perform two rounds of affinity selection, followed by error-prone PCR on the pools of recovered clones, generation of secondary libraries, and three additional rounds of affinity selection, under conditions of off-rate competition. We demonstrate the utility of this approach by generating low nanomolar fibronectin type III (FN3) monobodies to five human proteins: ubiquitin-conjugating enzyme E2 R1 (CDC34), COP9 signalosome complex subunit 5 (COPS5), mitogen-activated protein kinase kinase 5 (MAP2K5), Splicing factor 3A subunit 1 (SF3A1) and ubiquitin carboxyl-terminal hydrolase 11 (USP11). The affinities of the resulting monobodies are typically in the single-digit nanomolar range. We demonstrate the utility of two binders by pulling down the targets from a spiked lysate of HeLa cells. This integrated approach should be applicable to directed evolution of any phage-displayed affinity reagent scaffold.


Pathology of human diabetic neuropathy.
Pathologic study of a disease provides insights into the precise mechanisms and targets of damage and may provide insights into new therapies. The main targets in diabetic neuropathy are myelinated and unmyelinated fibers as dysfunction and damage to them explains the symptoms of painful neuropathy and the major end points of foot ulceration and amputation as well as mortality. Demyelination and axonal degeneration are established hallmarks of the pathology of human diabetic neuropathy and were derived from pioneering light and electronmicroscopic studies of sural nerve biopsies in the late 1960s and early 1970s. Additional abnormalities, which are relevant to the pathogenesis of human diabetic neuropathy, include pathology of the microvessels and extracellular space. Intraepidermal and sudomotor nerve quantification in skin biopsies provides a minimally invasive means for the detection of early nerve damage. Studies of muscle biopsies are limited and show significant alterations in the expression of neurotrophins, but limited changes in muscle fiber size and capillary density.


PDL1 expression in desmoplastic melanoma is associated with tumor aggressiveness and progression.
The prognostic role of programmed death ligand 1 (PDL1), CD8, and forkhead box p3 (FoxP3) expression in desmoplastic melanomas is unclear. We correlated PDL1, p53, and Ki-67 expression with CD8+ and FoxP3+ immune infiltrates with clinicopathologic variables and patient outcomes in a series of 66 desmoplastic melanomas. Tumoral PDL1 expression (≥25%), which was seen in 21% of patients (14 of 66), significantly correlated with mixed histology, tumor thickness, mitoses, recurrence, and metastasis. According to linear regression analysis, tumoral PDL1 expression correlated with thickness (P = .0041); p53 expression (P = .019); Ki-67 proliferation index (P = .0018); and tumoral CD8 (P = .0084), stromal CD8 (P < .0001), and FoxP3 (P < .0001) T-cell counts. According to univariate analyses, PDL1 expression of 25% or higher correlated with shorter progression-free survival (P < .0001) and melanoma-specific survival (P = .034). According to multivariate analyses, PDL1 expression of 25% or more (P = .026) and mixed histology (P = .039) independently predicted shorter progression-free survival, and presence of lymphovascular invasion predicted shorter overall survival (P = .018). Small study size. Tumoral and stromal CD8+ and FoxP3+ lymphocyte counts correlated with tumoral PDL1 expression, which is supportive of an adaptive immune response. PDL1 expression in desmoplastic melanoma was associated with tumor aggressiveness and progression. Although PDL1 expression is typically low in melanoma, its frequency and level of expression in desmoplastic melanoma may identify a subset of melanomas that are likely to respond to immunotherapy.


Does an ethene/benzenium ion complex exist? A discrepancy between B3LYP and MP2 predictions.
To investigate the possible existence of a complex between the benzenium ion and ethene, computations employing B3LYP and MP2 were carried out. The two methodologies gave conflicting answers; B3LYP confirmed the existence, but according to MP2, the structure found by B3LYP transforms into an ethylbenzenium ion. Computations utilizing the CCSD and QCISD methods showed the B3LYP result to be correct; 21 kJ/mol is needed to separate the two moieties.


A sequential-move game for enhancing safety and security cooperation within chemical clusters.
The present paper provides a game theoretic analysis of strategic cooperation on safety and security among chemical companies within a chemical industrial cluster. We suggest a two-stage sequential move game between adjacent chemical plants and the so-called Multi-Plant Council (MPC). The MPC is considered in the game as a leader player who makes the first move, and the individual chemical companies are the followers. The MPC's objective is to achieve full cooperation among players through establishing a subsidy system at minimum expense. The rest of the players rationally react to the subsidies proposed by the MPC and play Nash equilibrium. We show that such a case of conflict between safety and security, and social cooperation, belongs to the 'coordination with assurance' class of games, and we explore the role of cluster governance (fulfilled by the MPC) in achieving a full cooperative outcome in domino effects prevention negotiations. The paper proposes an algorithm that can be used by the MPC to develop the subsidy system. Furthermore, a stepwise plan to improve cross-company safety and security management in a chemical industrial cluster is suggested and an illustrative example is provided.


Endoscopic features of suspected precancerous lesions in high-risk areas for esophageal cancer.
A high prevalence of a chronic form of esophagitis was found during two endoscopic surveys carried out in high-incidence areas of esophageal cancer in 430 subjects from Iran, and in 527 individuals from Linxian, Peoples Republic of China, selected from the general population. This high prevalence was present even in the younger age groups. The lesion does not seem to be related to gastro-histological correlation, available for all cases examined, confirmed the chronic nature of the lesion. dysplasia was found in 3 to 8 per cent of the cases. Overall, 21 esophageal cancers were diagnosed, most in a very early phase, and some only at histology. A follow-up of 20 cases after one year, showed the progression of this chronic lesion to cancer in 4 cases. The data available suggest the precancerous nature of the lesion in these high-risk populations.


Evidence of soluble microbial products accelerating chloramine decay in nitrifying bulk water samples.
The discovery of a microbially derived soluble product that accelerates chloramine decay is described. Nitrifying bacteria are believed to be wholly responsible for rapid chloramine loss in drinking water systems. However, a recent investigation showed that an unidentified soluble agent significantly accelerated chloramine decay. The agent was suspected to be either natural organic matter (NOM) or soluble microbial products (SMPs). A laboratory scale reactor was fed chloraminated reverse osmosis (RO) treated water to eliminate the interference from NOM. Once nitrification had set in, experiments were conducted on the reactor and feed waters to determine the identity of the component. The study showed the presence of SMPs released by microbes in severely nitrified waters. Further experiments proved that the SMPs significantly accelerated chloramine decay, probably through catalytic reaction. Moreover, application of common protein denaturing techniques stopped the reaction implying that the compound responsible was likely to be a protein. This significant finding will pave the way for better control of chloramine in the distribution systems.


Tetracycline inducible gene manipulation in serotonergic neurons.
The serotonergic (5-HT) neuronal system has important and diverse physiological functions throughout development and adulthood. Its dysregulation during development or later in adulthood has been implicated in many neuropsychiatric disorders. Transgenic animal models designed to study the contribution of serotonergic susceptibility genes to a pathological phenotype should ideally allow to study candidate gene overexpression or gene knockout selectively in serotonergic neurons at any desired time during life. For this purpose, conditional expression systems such as the tet-system are preferable. Here, we generated a transactivator (tTA) mouse line (TPH2-tTA) that allows temporal and spatial control of tetracycline (Ptet) controlled transgene expression as well as gene deletion in 5-HT neurons. The tTA cDNA was inserted into a 196 kb PAC containing a genomic mouse Tph2 fragment (177 kb) by homologous recombination in E. coli. For functional analysis of Ptet-controlled transgene expression, TPH2-tTA mice were crossed to a Ptet-regulated lacZ reporter line (Ptet-nLacZ). In adult double-transgenic TPH2-tTA/Ptet-nLacZ mice, TPH2-tTA founder line L62-20 showed strong serotonergic β-galactosidase expression which could be completely suppressed with doxycycline (Dox). Furthermore, Ptet-regulated gene expression could be reversibly activated or inactivated when Dox was either withdrawn or added to the system. For functional analysis of Ptet-controlled, Cre-mediated gene deletion, TPH2-tTA mice (L62-20) were crossed to double transgenic Ptet-Cre/R26R reporter mice to generate TPH2-tTA/Ptet-Cre/R26R mice. Without Dox, 5-HT specific recombination started at E12.5. With permanent Dox administration, Ptet-controlled Cre-mediated recombination was absent. Dox withdrawal either postnatally or during adulthood induced efficient recombination in serotonergic neurons of all raphe nuclei, respectively. In the enteric nervous system, recombination could not be detected. We generated a transgenic mouse tTA line (TPH2-tTA) which allows both inducible and reversible transgene expression and inducible Cre-mediated gene deletion selectively in 5-HT neurons throughout life. This will allow precise delineation of serotonergic gene functions during development and adulthood.


Glassy dynamics of water in TIP4P/Ice aqueous solutions of trehalose in comparison with the bulk phase.
We perform molecular dynamics simulations of TIP4P/Ice water in solution with trehalose for 3.65 and 18.57 wt. % concentrations and of bulk TIP4P/Ice water at ambient pressure, to characterize the structure and dynamics of water in a sugar aqueous solution in the supercooled region. We find here that TIP4P/Ice water in solution with trehalose molecules follows the Mode Coupling Theory and undergoes a fragile to strong transition up to the highest concentration investigated, similar to the bulk. Moreover, we perform a Mode Coupling Theory test, showing that the Time Temperature Superposition principle holds for both bulk TIP4P/Ice water and for TIP4P/Ice water in the solutions and we calculate the exponents of the theory. The direct comparison of the dynamical results for bulk water and water in the solutions shows upon cooling along the isobar a fastening of water dynamics for lower temperatures, T < 240 K. We found that the counter-intuitive behavior for the low temperature solutions can be explained with the diffusion anomaly of water leading us to the conclusion that the fastening observed below T = 240 K in water dynamics is only fictitious, due to the fact that the density of water molecules in the solutions is higher than the density of the bulk at the same temperature and pressure. This result should be taken into account in experimental investigations which are often carried out at constant pressure.


CLINICAL AND EPIDEMIOLOGICAL CHARACTERISTICS OF PATIENTS DIAGNOSED WITH COVID-19 IN A TERTIARY CARE CENTER IN MEXICO CITY: A PROSPECTIVE COHORT STUDY.
Regional information regarding the characteristics of patients with coronavirus disease (COVID)-19 is needed for a better understanding of the pandemic. The objective of the study to describe the clinical features of COVID-19 patients diagnosed in a tertiary-care center in Mexico City and to assess differences according to the treatment setting (ambulatory vs. hospital) and to the need of intensive care (IC). We conducted a prospective cohort, including consecutive patients with COVID-19 from February 26, 2020 to April 11, 2020. We identified 309 patients (140 inpatients and 169 outpatients). The median age was 43 years (interquartile range, 33-54), 59.2% men, and 18.6% healthcare workers (12.3% from our center). The median body mass index (BMI) was 29.00 kg/m2 and 39.6% had obesity. Compared to outpatients, inpatients were older, had comorbidities, cough, and dyspnea more frequently. Twenty-nine (20.7%) inpatients required treatment in the IC unit (ICU). History of diabetes (type 1 or 2) and abdominal pain were more common in ICU patients compared to non-ICU patients. ICU patients had higher BMIs, higher respiratory rates, and lower room-air capillary oxygen saturations. ICU patients showed a more severe inflammatory response as assessed by white blood cell count, neutrophil and platelet count, C-reactive protein, ferritin, procalcitonin, and albumin levels. By the end of the study period, 65 inpatients had been discharged because of improvement, 70 continued hospitalized, and five had died. Patients with comorbidities, either middle-age obese or elderly complaining of fever, cough, or dyspnea, were more likely to be admitted. At admission, patients with diabetes, high BMI, and clinical or laboratory findings consistent with a severe inflammatory state were more likely to require IC.


Phase-field modeling of binary alloy solidification with coupled heat and solute diffusion.
A phase-field model is developed for simulating quantitatively microstructural pattern formation in solidification of dilute binary alloys with coupled heat and solute diffusion. The model reduces to the sharp-interface equations in a computationally tractable thin-interface limit where (i). the width of the diffuse interface is about one order of magnitude smaller than the radius of curvature of the interface but much larger than the real microscopic width of a solid-liquid interface, and (ii). kinetic effects are negligible. A recently derived antitrapping current [Phys. Rev. Lett. 87, 115701 (2001)]] is used in the solute conservation equation to recover precisely local equilibrium at the interface and to eliminate interface stretching and surface diffusion effects that arise when the solutal diffusivities are unequal in the solid and liquid. Model results are first compared to analytical solutions for one-dimensional steady-state solidification. Two-dimensional thermosolutal dendritic growth simulations with vanishing solutal diffusivity in the solid show that both the microstructural evolution and the solute profile in the solid are accurately modeled by the present approach. Results are then presented that illustrate the utility of the model for simulating dendritic solidification for the large ratios of the liquid thermal to solutal diffusivities (Lewis numbers) typical of alloys.