Impact of melatonin and tryptophan on water stress tolerance in white lupine (Lupinus termis L.).
Melatonin has been identified as a signal molecule that regulates plant responses to different abiotic and biotic stresses. Melatonin (MT) and its precursor tryptophan (Try) have a major role in improving plant stress tolerance to different environmental stresses such as water deficiency. The rapid increase in the Egyptian population caused insufficient protein sources, especially those of animal origin, in their diet. The possible solution is to augment the diet with legumes such as white lupine which are relatively rich in protein. Thus, the current experimental work was carried out to find changes in growth, biochemical aspects and yield quantity and quality of white lupine plant with spraying of both MT and Try at different concentrations on plant shoot under water deficit stress conditions. Results showed that water deficit (75 or 50% of water irrigation requirements; WIR) caused significant reduction in growth, photosynthetic pigments, indole acetic acid and yield compared with those received 100% WIR. Seed yield significantly decreased (p < 0.05) by 26.98 and 41.64% by decreasing WIR to 75 and 50%. The decrease was accompanied by significant increase in phenolic contents, hydrogen peroxide, lipid peroxidation and some antioxidant enzymes, while nitrate reductase enzyme was decreased. However, external application of either MT or Try significantly alleviated the adverse effects of water deficit (growth suppression), since MT or Try-treated plants recovered more quickly than untreated plants. Moreover, MT or Try-treated plants had higher photosynthetic pigments, indole acetic acid, phenolic, as well as yield quantity and quality under the three WIR as compared with untreated plants. Melatonin treatment at 100 µM and Tryptophan at 200 µM increased weight of seeds/plant by 78.29 and 52.19%, 71.49 and 43.78% and 41.21 and 13.07% in plants irrigated with 100, 75 and 50% WIR, respectively. Exogenous MT and Try significantly reduced hydrogen peroxide and malondialdehyde content, while markedly increased the activities of antioxidant enzymes and nitrate reductase under different WIR. Finally, the current study concluded that MT and Try treatments alleviated the detrimental effects of water deficiency and accelerated the recovery mainly via improving white lupine plants tolerance in forms of enhancing photosynthetic pigments, indole acetic acid, phenolic and antioxidant capacity.


The correlation of sagittal osteotomy inclination and the anteroposterior translation in medial open-wedge high tibial osteotomy-one of the causes affecting the patellofemoral joint?
For opening-wedge high tibial osteotomy, previous studies have shown that most osteotomies were anterior-inclined. The purpose of this study was to determine the effect of sagittal osteotomy inclination on the anteroposterior translation of osteomized fragments and discuss its possible impact on the patellofemoral joint. We retrospectively measured the angle between the joint line and the sagittal osteotomy line. We also evaluated the anteroposterior translation of osteomized fragments by measuring the distance from the most posterior point of the tibial plateau to the tibial tuberosity and the anterior cortical line. Correlation between the sagittal osteotomy inclination and the anteroposterior translation of fragments was analyzed. The mean sagittal osteotomy inclination was 6.3 ± 8.4° anteriorly to the joint line and 82% of osteotomies were anterior-inclined. The anteroposterior translation of the osteomized fragments was moderately correlated to the sagittal inclination. Anterior-inclined osteotomy tends to result in the anterior translation of the proximal fragment. High rates of anterior-inclined osteotomy have been described previously as well as in this study. Anterior-inclined osteotomy tends to result in the anterior translation of the proximal fragment. This may result in increased vertical vector force onto the patellofemoral joint, which further accelerates patellofemoral joint degeneration. Therefore, surgeons should attempt to perform parallel osteotomy or avoid anterior displacement of the proximal fragment if there is concern of anterior-inclined osteotomy.


Evaluation of the motion of surgical instruments during intraocular surgery.
Robot assistance in ocular microsurgery could improve precision, dexterity, save time or prevent complications by task automation, and provide access to ocular surgery in undeserved countries by teleoperation. However, to design robotic devices, the range of motion of surgical instruments needs to be precisely quantified. An electromagnetic tracking system was developed for intraocular surgery in order to quantify the movements of ophthalmic surgeons. Kinematics of surgical steps during phacoemulsification and pars plana vitrectomy procedures were determined by measuring the maximum translation and angular range of motion of intraocular surgical tools in the three planes. Important variations in amplitudes of rotation and translation were measured between both hands and between surgical tasks. These parameters may be used to develop a robotic intraocular surgical system or to improve training.


Effects of phenylpropanoids on human organic anion transporters hOAT1 and hOAT3.
Human organic anion transporters hOAT1/SLC22A6 and hOAT3/SLC22A8 are highly expressed on the basolateral membrane of renal proximal tubules and mediate tubular uptake of anionic drugs from blood. They play an important role for drug disposition, and therefore close studies of their ligand recognition are important for drug therapy and development. In this study, we performed uptake experiments using HEK293 and fluorescent anion 6-carboxyfluorescein to asses the effects of phenylpropanoids on hOAT1 and hOAT3. We found that phenylpropanoids, 3-(4'-isopentenyloxyphenyl)-benzoic acid (IBA), 3-(4'-isopentenyloxy-3'-methoxyphenyl)-benzoic acid (IMBA), and 3-(4'-geranyloxy-3'-methoxy phenyl)-benzoic acid (GMBA) inhibited hOAT1 and hOAT3. The Ki values for hOAT1 were comparable to that of probenecid, a strong inhibitor of hOAT1 and hOAT3. While IBA demonstrated competitive inhibition, IMBA and GMBA showed mixed-type inhibition. After preincubation and washout, the inhibitory effects remained with IMBA and GMBA but not IBA, suggesting that the functional group at 3'-position is responsible for these differences. In conclusion, IBA, IMBA, and GMBA are inhibitors of hOAT1 and hOAT3.


Gold-conjugated arabinogalactan-protein and other lectins as ultrastructural probes for the wheat/stem rust complex.
Arabinogalactan-protein (AGP, "beta-lectin") was isolated from leek seeds, tested for specificity, conjugated with gold colloids, and used as a cytochemical probe to detect beta-linked bound sugars in ultrathin sections of wheat leaves infected with a compatible race of stem rust fungus. Similar sections were probed with other gold-labeled lectins to detect specific sugars. AGP-gold detected beta-glycosyl in all fungal walls and in the extrahaustorial matrix. Other lectin gold conjugates localized galactose in all fungal walls except in walls of the haustorial body. Limulus polyphemus lectin bound only to the outermost layer of intercellular hyphal walls of the fungus. Binding of these lectins was inhibited by their appropriate haptens and was diminished or abolished in specimens pretreated with protease, indicating that the target substances in the tissue were proteinaceous or that polysaccharides possessing affinity to the lectin probes had been removed by the enzyme from a proteinaceous matrix by passive escape. Binding of Lotus tetragonolobus lectin was limited to the two outermost fungal wall layers but was not hapten-inhibitable. Limax flavus lectin, specific for sialic acids, had no affinity to any structure in the sections. In the fungus, the most complex structure was the outermost wall layer of intercellular hyphal cells; it had affinity to all lectins tried so far, except to Limax flavus lectin and to wheat germ lectin included in an earlier study. In the host, AGP and the galactose-specific lectins bound to the inner domain of the wall in areas not in contact with the fungus. At host cell penetration sites, affinity to these lectins often extended throughout the host wall, confirming that it is modified at these sites. Pre-treatment with protease had no effect on lectin binding to the host wall. After protease treatment, host starch granules retained affinity to galactose-specific lectins, but lost affinity for AGP.


Alloscardovia omnicolens emerging presence in premature rupture of membranes.
Alloscardovia omnicolens is a recently-reported microorganism with unknown pathogenic implications. It has been isolated in various clinical localizations but not in the endocervix. We isolated A. omnicolens in an endocervical sample from a 31-yr-old patient with preterm premature rupture of membranes (PPROM) in week 33+3 of pregnancy. The main risk of PPROM is prematurity and the possibility of developing infectious chorioamnionitis, which can be lethal for the mother and newborn. This is the first report of an association between A. omnicolens and PPROM, although its pathogenic role has not yet been elucidated.


Improved accuracy in multicomponent surface complexation models using surface-sensitive analytical techniques: Adsorption of arsenic onto a TiO2/Fe2O3 multifunctional sorbent.
Novel composite materials are increasingly developed for water treatment applications with the aim of achieving multifunctional behaviour, e.g. combining adsorption with light-driven remediation. The application of surface complexation models (SCM) is important to understand how adsorption changes as a function of pH, ionic strength and the presence of competitor ions. Component additive (CA) models describe composite sorbents using a combination of single-phase reference materials. However, predictive adsorption modelling using the CA-SCM approach remains unreliable, due to challenges in the quantitative determination of surface composition. In this study, we test the hypothesis that characterisation of the outermost surface using low energy ion scattering (LEIS) improves CA-SCM accuracy. We consider the TiO2/Fe2O3 photocatalyst-sorbents that are increasingly investigated for arsenic remediation. Due to an iron oxide surface coating that was not captured by bulk analysis, LEIS significantly improves the accuracy of our component additive predictions for monolayer surface processes: adsorption of arsenic(V) and surface acidity. We also demonstrate non-component additivity in multilayer arsenic(III) adsorption, due to changes in surface morphology/porosity. Our results demonstrate how surface-sensitive analytical techniques will improve adsorption models for the next generation of composite sorbents.


Redox reactive reagents inhibiting and inactivating choline acetyltransferase.
3-Trimethylammoniomethyl catechol and N,N-dimethylepinephrine (catecholine) are redox reactive reagents which possess quaternary ammonium functional groups and the capacity to inhibit or inactivate choline binding macromolecules which mediate cholinergic neuronal function. Earlier studies reported the synthesis of 3-trimethylammoniomethyl catechol and demonstrated its redox-dependent covalent inactivation of the nicotinic acetylcholine receptor (Nickoloff et al., Biochemistry 24, 999-1007 (1985)]. Here we present the synthesis of catecholine and show that both 3-trimethylammoniomethyl catechol and catecholine are weak noncompetitive inhibitors (Ki = 15 +/- 6 and 25 +/- 4 mM, respectively) of choline acetyltransferase (EC 184.108.40.206). Both agents irreversibly inactivate the enzyme.


Aligning Solution-Derived Carbon Nanotube Film with Full Surface Coverage for High-Performance Electronics Applications.
The main challenge for application of solution-derived carbon nanotubes (CNTs) in high performance field-effect transistor (FET) is how to align CNTs into an array with high density and full surface coverage. A directional shrinking transfer method is developed to realize high density aligned array based on randomly orientated CNT network film. Through transferring a solution-derived CNT network film onto a stretched retractable film followed by a shrinking process, alignment degree and density of CNT film increase with the shrinking multiple. The quadruply shrunk CNT films present well alignment, which is identified by the polarized Raman spectroscopy and electrical transport measurements. Based on the high quality and high density aligned CNT array, the fabricated FETs with channel length of 300 nm present ultrahigh performance including on-state current Ion of 290 µA µm-1 (Vds = -1.5 V and Vgs = -2 V) and peak transconductance gm of 150 µS µm-1 , which are, respectively, among the highest corresponding values in the reported CNT array FETs. High quality and high semiconducting purity CNT arrays with high density and full coverage obtained through this method promote the development of high performance CNT-based electronics.


In vivo modeling of human neuron dynamics and Down syndrome.
Harnessing the potential of human stem cells for modeling the physiology and diseases of cortical circuitry requires monitoring cellular dynamics in vivo. We show that human induced pluripotent stem cell (iPSC)-derived cortical neurons transplanted into the adult mouse cortex consistently organized into large (up to ~100 mm3) vascularized neuron-glia territories with complex cytoarchitecture. Longitudinal imaging of >4000 grafted developing human neurons revealed that neuronal arbors refined via branch-specific retraction; human synaptic networks substantially restructured over 4 months, with balanced rates of synapse formation and elimination; and oscillatory population activity mirrored the patterns of fetal neural networks. Lastly, we found increased synaptic stability and reduced oscillations in transplants from two individuals with Down syndrome, demonstrating the potential of in vivo imaging in human tissue grafts for patient-specific modeling of cortical development, physiology, and pathogenesis.


High RAD18 Expression is Associated with Disease Progression and Poor Prognosis in Patients with Gastric Cancer.
RAD18 plays an important role in DNA damage repair by inducing monoubiquitinated PCNA (mUB-PCNA) in both cancer and normal tissues. Previous studies have not determined the significance of RAD18 expression in clinical gastric cancer (GC) samples. Thus, this study aimed to clarify the expression and functional significance of RAD18 in GC. Overall, 96 resected GC samples were subjected to an immunohistochemical analysis of RAD18. GC cell lines were also subjected to functional RNA interference analyses of RAD18. RAD18 expression was predominantly nuclear and was observed at higher levels in GC tissues than in normal tissues. In GC tissues, strong RAD18 expression was associated with progression of lymph node metastasis (p = 0.0001), lymphatic invasion (p = 0.0255), venous invasion (p < 0.0001), recurrence (p = 0.028), and disease stage (p = 0.0253). Moreover, GC patients with high tumor RAD18 expression had shorter overall survival (p = 0.0061) and recurrence-free survival durations (p = 0.035) than those with low tumor RAD18 expression. RAD18 knockdown inhibited GC proliferation and invasiveness and increased chemosensitivity by suppressing mUB-PCNA. RAD18 expression may be a useful marker of progression and poor prognosis of GC. Moreover, therapeutic strategies that target RAD18 might be a novel chemosensitizer to eradicate the refractory GC.


[Primary large cell neuroendocrine carcinoma of the breast: a rare tumor in humans].
Primitive large cell neuroendocrine tumor of the breast is an extremely rare entity. Less than ten cases have been reported in the literature. We report a new case of a 61-year old male patient presenting with locally advanced tumor of the right breast, immediately metastasized to the lungs and pleura, staged cT4bN1M1. The patient received eight cycles of Docetaxel-based chemotherapy every 21 days, with a good clinical and radiological response (>50%), followed by adjuvant tamoxifen with disease stabilization for 18 months. Immunohistochemistry is still essential to determine the neuroendocrine nature of this tumor. Treatment is not well codified due to the rarity of this type of cancer.


How decaying wood affects the accumulation of polycyclic aromatic hydrocarbons in soil of temperate mountain forest.
The aim of our research was to determine the role of heavily decomposed deadwood in the shaping of accumulation of polycyclic aromatic hydrocarbons (PAHs) in mountain forest ecosystems. The study included heavily decomposed spruce wood located in lower and higher mountain locations (600 and 1200 m a.s.l.) and at the south (S) and north (N) exposure. The accumulation of PAHs in deadwood was compared to the accumulation of PAHs in surface soil horizons in the immediate vicinity of decaying wood and in soils unaffected by decaying wood. Basic chemical properties and enzymatic activity were determined in wood and soil samples. The conducted research indicates the importance of decaying wood for the formation of PAHs accumulation in mountain forest soils. The lowest content of PAHs was recorded in samples of heavily decomposed wood, which at the same time was characterized by the highest enzymatic activity. Significantly higher PAHs content was recorded in soils unaffected by components released from decaying wood. Our research confirmed the importance of location conditions (exposure, altitude) in shaping PAHs accumulation. The highest mountain locations (1200 m a.s.l.) to N exposure were characterized by the highest accumulation of PAHs.


Ejaculatory dysfunction as a cause of infertility.
Ejaculatory dysfunction (EjD), the most prevalent male sexual disorder, is clearly different from erectile dysfunction (ED). EjD is divided into 4 categories: premature ejaculation, delayed ejaculation, retrograde ejaculation and anejaculation. EjD-related infertility is one of the most serious problems in young patients. If sexual intercourse is achieved successfully without any ejaculate sexual partners/wives will not be able to conceive. Therefore, establishment of management of EjD as well as ED is increasingly crucial for couples wishing for a baby. The therapeutic approach of EjD-related infertility is based upon two scenarios: (1) if EjD alone is the reason for having no children, adequate treatment for EjD alone is required, or (2) if EjD is not the only reason and is combined with a worsening of semen quality, total management for male infertility (including EjD treatment) is needed. In this article, the background of EjD-related infertility is presented briefly, followed by a review of treatment modalities.


Developing a framework to inform scale-up success for population health interventions: a critical interpretive synthesis of the literature.
Population health interventions (PHIs) have the potential to improve the health of large populations by systematically addressing underlying conditions of poor health outcomes (i.e., social determinants of health) and reducing health inequities. Scaling-up may be one means of enhancing the impact of effective PHIs. However, not all scale-up attempts have been successful. In an attempt to help guide the process of successful scale-up of a PHI, we look to the organizational readiness for change theory for a new perspective on how we may better understand the scale-up pathway. Using the change theory, our goal was to develop the foundations of an evidence-based, theory-informed framework for a PHI, through a critical examination of various PHI scale-up experiences documented in the literature. We conducted a multi-step, critical interpretive synthesis (CIS) to gather and examine insights from scale-up experiences detailed in peer-reviewed and grey literatures, with a focus on PHIs from a variety of global settings. The CIS included iterative cycles of systematic searching, sampling, data extraction, critiquing, interpreting, coding, reflecting, and synthesizing. Theories relevant to innovations, complexity, and organizational readiness guided our analysis and synthesis. We retained and examined twenty different PHI scale-up experiences, which were extracted from 77 documents (47 peer-reviewed, 30 grey literature) published between 1995 and 2013. Overall, we identified three phases (i.e., Groundwork, Implementing Scale-up, and Sustaining Scale-up), 11 actions, and four key components (i.e., PHI, context, capacity, stakeholders) pertinent to the scale-up process. Our guiding theories provided explanatory power to various aspects of the scale-up process and to scale-up success, and an alternative perspective to the assessment of scale-up readiness for a PHI. Our synthesis provided the foundations of the Scale-up Readiness Assessment Framework. Our theoretically-informed and rigorous synthesis methodology permitted identification of disparate processes involved in the successful scale-up of a PHI. Our findings complement the guidance and resources currently available, and offer an added perspective to assessing scale-up readiness for a PHI.


Chick embryo myotubes contain transferrin receptors and internalize and recycle transferrin.
Embryonic chick skeletal myotubes grown in cell culture require transferrin to provide iron for proliferation and differentiation. We demonstrate here that cultured myotubes contain transferrin receptors as demonstrated by the finding of specific, saturable, and reversible high-affinity binding sites. Scatchard analysis of equilibrium binding data indicates an apparent Kd of 37 nM and one muscle cell equivalent contains 7,500 transferrin receptors. Myotubes exhibit a Kd 100 times higher for apotransferrin than for iron-saturated transferrin. Internalization of specifically bound transferrin is temperature dependent and occurs rapidly at 37 degrees C with a steady state reached after 10 min. Internalization studies using either 125I-ovotransferrin or 55Fe-ovotransferrin suggest that transferrin is internalized, depleted of iron, and recycled intact to the extracellular medium as shown in other cell systems. Autoradiography of muscle cell cultures incubated with 125I-ovotransferrin at 4 degrees C reveals clusters of receptors along the myotubes. The possible mechanisms by which transferrin is supplied to muscle in vivo are discussed in light of the evidence that motor neurons contain transferrin.


Design of a multi-epitope vaccine (vme-VAC/MST-1) against cholera and vibriosis based on reverse vaccinology and immunoinformatics approaches.
Vibriosis and cholera are serious diseases distributed worldwide and caused by six marine bacteria of the Vibrio genus. Thousands of deaths occur each year due to these illnesses, necessitating the development of new preventive measures. Presently, the existing cholera vaccine demonstrates an effectiveness of approximately 60%. Here we describe a new multi-epitope vaccine, 'vme-VAC/MST-1' based on vaccine targets identified by reverse vaccinology and epitopes predicted by immunoinformatics, two currently effective tools for predicting new vaccines for bacterial pathogens. The vaccine was designed to combat vibriosis and cholera by incorporating epitopes predicted for CTL, HTL, and B cells. These epitopes were identified from six vaccine targets revealed through subtractive genomics, combined with reverse vaccinology, and were further filtered using immunoinformatics approaches based on their predicted immunogenicity. To construct the vaccine, 28 epitopes (24 CTL/B and 4 HTL/B) were linked to the sequence of the cholera toxin B subunit adjuvant. In silico analyses indicate that the resulting immunogen is stable, soluble, non-toxic, and non-allergenic. Furthermore, it exhibits no homology to the host and demonstrates a strong capacity to elicit innate, B-cell, and T-cell immune responses. Our analysis suggests that it is likely to elicit immune reactions mediated through the TLR5 pathway, as evidenced by the molecular docking of the vaccine with the receptor, which revealed high affinity and a favorable reaction. Thus, vme-VAC/MST-1 is predicted to be a safe and effective solution against pathogenic Vibrio spp. However, further experimental analyses are required to measure the vaccine's effects In vivo.Communicated by Ramaswamy H. Sarma.


Inhibition of equine S-adenohomocysteine hydrolase by 2'-deoxyadenosine.
2'-Deoxyadenosine and 9-beta-D-arabinofuranosyladenine (ARA) are apparent suicide inhibitors for equine S-adenosylhomocysteine hydrolase. In initial velocity studies of the synthetic reaction converting adenosine and homocysteine to S-adenosylhomocysteine, adenine, adenosine 5'-triphosphate, and 9-beta-D-arabinofuranosyladenine were found to be competitive inhibitors with Kis of 3.8 microM, 1.1 mM, and 30 microM, respectively. In contrast, linear mixed inhibition was observed for 2'-deoxyadenosine, indicating that 2'-deoxyadenosine must bind in more than one fashion to the enzyme.


Microvesicles released from hormone-refractory prostate cancer cells facilitate mouse pre-osteoblast differentiation.
Bone metastasis is often occurs in patients with prostate cancer. There is a vicious cycle for bone metastases involving prostate cancer cells, osteoblasts, and osteoclasts. Acting among those cells during the process of metastasis are several molecules such as bone morphogenetic proteins, platelet-derived growth factor, endothelin-1, matrix metalloproteases, vascular endothelial growth factor, transforming growth factor-β, and insulin-like growth factors. Cell-derived microvesicles are endogenous carriers transporting proteins, mRNAs and miRNAs between cells, which is a candidate for participation in the bone metastasis of these cells. Here, we demonstrated that prostate cancer cells in vitro released microvesicles into the culture medium (PCa-MVs), which was shown by electron microscopic study and nanoparticle tracking analysis. In this study, we found for the first time that these PCa-MVs enhanced osteoblast differentiation mainly through the delivery of PCa cell-derived v-ets erythroblastosis virus E26 oncogene homolog 1, which is an osteoblast differentiation related-transcriptional factor.


Non-alcoholic fatty liver disease (NAFLD) is associated with an increased incidence of chronic kidney disease (CKD).
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the western world. The excess mortality in NAFLD patients is strongly related to extrahepatic comorbidities. Recently, an association between NAFLD and chronic kidney disease (CKD) has been reported in various populations. Based on the IQVIA Disease Analyzer database, this retrospective study examined two cohorts from Germany matched for sex, age, index year, annual visit frequency, hypertension, and diabetes, including 92,225 patients with and without NAFLD. The incidence of CKD was assessed as a function of NAFLD using Cox regression models. A total of 92,225 NAFLD patients as well as 92,225 patients without NAFLD were included into analyses. CKD was diagnosed in 19.1% vs. 11.1% of patients with and without NAFLD within the 10 years observation period (p < 0.001). Cox regression confirmed a significant association between NAFLD and CKD with a hazard ratio (HR) of 1.80 (95%CI: 1.73-1.86, p < 0.001). Subgroup analyses revealed that this association was most pronounced in the age group of 18 to 50 years (HR: 2.13, 95%CI: 1.91-2.37, p < 0.001) and among female NAFLD patients (HR 1.85, 95%CI: 1.76-1.95, p < 0.001). The results of this study confirm a significantly increased risk of developing CKD in a large, real-world cohort of adult NAFLD patients in Germany. Interdisciplinary care of NAFLD patients, which is currently gaining importance worldwide, should be considered to include systematic measures for prevention and/or early detection of CKD with the aim of minimizing long-term renal complications.


Behavior of tight-junction, adherens-junction and cell polarity proteins during HNF-4alpha-induced epithelial polarization.
We previously reported that expression of tight-junction molecules occludin, claudin-6 and claudin-7, as well as establishment of epithelial polarity, was triggered in mouse F9 cells expressing hepatocyte nuclear factor (HNF)-4alpha [H. Chiba, T. Gotoh, T. Kojima, S. Satohisa, K. Kikuchi, M. Osanai, N. Sawada. Hepatocyte nuclear factor (HNF)-4alpha triggers formation of functional tight junctions and establishment of polarized epithelial morphology in F9 embryonal carcinoma cells, Exp. Cell Res. 286 (2003) 288-297]. Using these cells, we examined in the present study behavior of tight-junction, adherens-junction and cell polarity proteins and elucidated the molecular mechanism behind HNF-4alpha-initiated junction formation and epithelial polarization. We herein show that not only ZO-1 and ZO-2, but also ZO-3, junctional adhesion molecule (JAM)-B, JAM-C and cell polarity proteins PAR-3, PAR-6 and atypical protein kinase C (aPKC) accumulate at primordial adherens junctions in undifferentiated F9 cells. In contrast, CRB3, Pals1 and PATJ appeared to exhibit distinct subcellular localization in immature cells. Induced expression of HNF-4alpha led to translocation of these tight-junction and cell polarity proteins to beltlike tight junctions, where occludin, claudin-6 and claudin-7 were assembled, in differentiated cells. Interestingly, PAR-6, aPKC, CRB3 and Pals1, but not PAR-3 or PATJ, were also concentrated on the apical membranes in differentiated cells. These findings indicate that HNF-4alpha provokes not only expression of tight-junction adhesion molecules, but also modulation of subcellular distribution of junction and cell polarity proteins, resulting in junction formation and epithelial polarization.


Intrauterine Instillation of Tranexamic Acid in Hysteroscopic Myomectomy: A Double-Blind, Placebo-Controlled, Parallel-Group Randomized Clinical Trial.
To evaluate the hemostatic effect of intrauterine instillation of tranexamic acid (TXA) with the distention medium during hysteroscopic myomectomy. Prospective, parallel-group, double-blind, placebo-controlled randomized clinical trial. Early Cancer Detection Unit in Ain Shams University Maternity Hospital, Cairo, Egypt. Eighty women with type 0 or I submucous myoma undergoing hysteroscopic myomectomy using unipolar resectoscope. The participants were randomly assigned to receive either 1 g of TXA for every 1000 mL of the distending medium (intervention group) or 10 mL of placebo (10 mL of 1.5% glycine) in the same form inside every 1000 mL of the distention medium. The primary outcome was a change in hemoglobin level 24 hours after surgery compared with preoperative values, and the secondary outcomes were the surgeon's rating of intraoperative bleeding and the quality of operative view, the duration of surgery, the volume of injected media, intraoperative complications, and the completion of myomectomy in 1 procedure. The mean difference in hemoglobin level was 1.11 ±.58 g/dL in the TXA group and 1.46 ± 0.61 g/dL in the placebo group (p = .015). The quality of hysteroscopic view was better in the TXA group (p = .001), with good operative view in 23 (60.5%) cases in TXA vs 8 (20.5%) in the placebo group. The surgeon's rating of bleeding as excessive was reported in 1 (2.6%) case in the TXA group and in 9 (23.1%) cases in the placebo group. There was no difference between the groups regarding the duration of surgery, the volume of injected media, completion of myoma resection in 1 session, and intraoperative complications. Three cases of uterine perforation with the thermal loop were reported, and all were associated with poor operative field in the placebo group. Intrauterine instillation of TXA with the distention medium during hysteroscopic myomectomy resulted in a statistically significant decrease in hemoglobin level 24 hours after surgery, albeit with minimal clinical significance. TXA resulted in better visualization of the field throughout the procedure.


Spider bites in the United States.
The bite of the brown recluse spider rapidly causes an infarction in skin that is painful and can be slow to heal. This is the only North American spider to cause such severe necrosis. The bite sometimes can produce a sudden, severe hemolysis. Conservative care without drugs is the safest proven treatment.


Indoxyl sulfate enhances endothelin-1-induced contraction via impairment of NO/cGMP signaling in rat aorta.
The microbiome-derived tryptophan metabolite, indoxyl sulfate, is considered a harmful vascular toxin. Here, we examined the effects of indoxyl sulfate on endothelin-1 (ET-1)-induced contraction in rat thoracic aortas. Indoxyl sulfate (10-3 M, 60 min) increased ET-1-induced contraction but did not affect isotonic high-K+-induced contraction. The ET-1-induced contraction was enhanced by endothelial denudation in both control and indoxyl sulfate-treated groups. BQ123 (10-6 M), an ETA receptor antagonist, reduced the ET-1-induced contraction in both control and indoxyl sulfate groups. BQ788 (10-6 M), an ETB receptor antagonist, increased the contraction in the control group but had no effect on the indoxyl sulfate group. Conversely, indoxyl sulfate inhibited relaxation induced by IRL1620, an ETB receptor agonist. L-NNA, an NO synthase (NOS) inhibitor, increased the ET-1-induced contractions in both the control and indoxyl sulfate groups, whereas L-NPA (10-6 M), a specific neuronal NOS inhibitor, did not affect the ET-1-induced contraction in both groups. However, ODQ, an inhibitor of soluble guanylyl cyclase, increased the ET-1-induced contraction in both groups. Organic anion transporter (OAT) inhibitor probenecid (10-3 M) and antioxidant N-acetyl-L-cysteine (NAC; 5 × 10-3 M) inhibited the effects of indoxyl sulfate. A cell-permeant superoxide scavenger reduced the ET-1-induced contraction in the indoxyl sulfate group. The aortic activity of SOD was reduced by indoxyl sulfate. The present study revealed that indoxyl sulfate augments ET-1-induced contraction in rat aortae. This enhancement may be due to the impairment of NO/cGMP signaling and may be attributed to impairment of the antioxidant systems via cellular uptake through OATs.


Effect of residence time during hydrothermal carbonization of biogas digestate on the combustion characteristics of hydrochar and the biogas production of process water.
The biogas digestate from anaerobic digestion of cow manure and energy crops was treated by hydrothermal carbonization (HTC) at 210 °C for 0.5 to 5 h to understand the effect of HTC residence time on the combustion characteristics of hydrochar and the biogas production of process water. The increase in HTC residence time slightly reduced the higher heating values (16.3-16.0 MJ/kg) but improved most slagging and fouling indices of the hydrochar. However, the slagging and fouling during hydrochar combustion were almost impossible to avoid. The specific methane yield of the process water was not significantly influenced by the HTC residence time. Energy assessment demonstrated that HTC for 0.5 h achieved the highest process efficiency and net energy gain when the combustion energy was obtained from hydrochar and CH4 (from process water). Therefore, the HTC condition of 210 °C, 0.5 h is suggested to valorize biogas digestate for energy production.


Movement related cortical potentials of cued versus self-initiated movements: double dissociated modulation by dorsal premotor cortex versus supplementary motor area rTMS.
The dorsal premotor cortex (PMd) is thought to play a significant role in movement preparation cued by sensory information rather than in self-initiated movements. The evidence in humans for this contention is still circumstantial. Here we explored the effects of modulation of PMd by excitability decreasing 1 Hz repetitive transcranial magnetic stimulation (rTMS) versus excitability increasing 5 Hz rTMS on two forms of movement related cortical potentials: contingent negative variation (CNV) versus Bereitschaftspotential (BP) reflecting externally cued versus self-triggered movement preparation. Ten healthy right-handed subjects performed visually cued or self-triggered simple sequential finger movements with their right hand. CNV and BP were recorded by 25 EEG electrodes covering the fronto-centro-parietal cortex and divided into an early (1500-500 ms before a go-signal or movement onset) and a late potential (500-0 ms). MRI-navigated 1 Hz rTMS of the left PMd resulted in significant increase of the late CNV over the left central region predominantly contralateral to the prepared right hand movement, while 5 Hz rTMS had no effect on CNV. In contrast, 1 and 5 Hz rTMS did not modify BP. Control experiments of 1 Hz rTMS of the supplementary motor area (SMA) and of low-intensity 1 Hz rTMS of the left primary motor cortex did not change CNV, but 1 Hz SMA-rTMS increased late BP. This double dissociation of effects of PMd-rTMS versus SMA-rTMS on CNV versus BP provides direct evidence that the left PMd in humans is more involved in preparatory processes of externally cued rather than self-initiated movements, contrasting with an opposite role of the SMA.


Therapeutic effects of complex motor training on motor performance deficits induced by neonatal binge-like alcohol exposure in rats: II. A quantitative stereological study of synaptic plasticity in female rat cerebellum.
Twenty days of complex motor skill training in adult rats was previously demonstrated to rehabilitate motor performance deficits induced by binge alcohol exposure in neonatal rats. This follow-up study evaluated morphological plasticity in the paramedian lobule of the cerebellum (PML) using the same treatment and training regimens. On postnatal days (PD) 4-9, female Long-Evans rats were given either alcohol (Alcohol Exposure - AE, 4.5 g/kg/day via artificial rearing), exposure to gastrostomy control (GC) artificial rearing procedures, or reared normally as suckle controls (SC). After weaning, all rats were housed two to three per cage. At 180 days old, rats were randomly assigned either to a rehabilitation condition (RC: given 20 days of complex motor skill training), or to an inactive condition (IC: remained in their home cage). The AE rats were delayed in acquiring the training, but there were no group differences in performance over the last 2 weeks of training. Unbiased stereological techniques were used to evaluate PML volume, Purkinje cell and parallel fiber synapse density. Although total volume of PML was significantly reduced in the AE rats, complex motor skill training resulted in a significant increase in the PML molecular layer in all three postnatal treatment groups. The RC animals from the SC and AE groups had more parallel fiber synapses per Purkinje cell than corresponding IC animals. These data support the hypothesis that 'rehabilitative' motor training stimulates synaptogenesis in the PML, and that Purkinje neurons that survive the early postnatal alcohol insult are capable of substantial experience-induced plasticity.


Clinical-Community Connections: Incorporating Evidence-Based Programs for Improved Patient Outcomes.
Incorporating evidence-based community programs into clinical care recommendations and goals may help bridge the clinic-to-community transition for older adults. Engagement in evidence-based programs can help older adults manage chronic conditions and reduce fall risk through behavior change and self-management following a clinical episode of care. This paper describes evidence-based fall prevention and physical activity programs, provides resources to locate programs, and strategies to match older adults to the right programs.


Gradient electro-processing strategy for efficient conversion of harmful algal blooms to biohythane with mechanisms insight.
Globally eruptive harmful algal blooms (HABs) have caused numerous negative effects on aquatic ecosystem and human health. Conversion of HABs into biohythane via dark fermentation (DF) is a promising approach to simultaneously cope with environmental and energy issues, but low HABs harvesting efficiency and biohythane productivity severely hinder its application. Here we designed a gradient electro-processing strategy for efficient HABs harvesting and disruption, which had intrinsic advantages of no secondary pollution and high economic feasibility. Firstly, low current density (0.888-4.444 mA/cm2) was supplied to HABs suspension to harvest biomass via electro-flocculation, which achieved 98.59% harvesting efficiency. A mathematic model considering coupling effects of multi-influencing factors on HABs harvesting was constructed to guide large-scale application. Then, the harvested HABs biomass was disrupted via electro-oxidation under higher current density (44.44 mA/cm2) to improve bioavailability for DF. As results, hydrogen and methane yields of 64.46 mL/ (g VS) and 171.82 mL/(g VS) were obtained under 6 min electro-oxidation, along with the highest energy yield (50.1 kJ/L) and energy conversion efficiency (44.87%). Mechanisms of HABs harvesting and disruption under gradient electro-processing were revealed, along with the conversion pathways from HABs to biohythane. Together, this work provides a promising strategy for efficient disposal of HABs with extra benefit of biohythane production.


Role of intracellular calcium in acute thermal pain perception.
The role of intracellular calcium in acute thermal nociception was investigated in the mouse hot-plate test. Intracerebroventricular (i.c.v.) administration of TMB-8, a blocker of Ca++ release from intracellular stores, produced hypernociception. By contrast, i.c.v. pretreatment with thapsigargin, a depletor of Ca++ intracellular stores, produced an increase of the mouse pain threshold. Furthermore, non-analgesic doses of thapsigargin prevented the hypernociception produced by TMB-8. In mice undergoing treatment with heparin, an InsP3-receptor antagonist, or ryanodine, a ryanodine receptor (RyR) antagonist, a dose-dependent reduction of the pain threshold was observed. Pretreatment with D-myo inositol, compound which produces InsP3, and 4-chloro-m-cresol, a RyR agonist, induced an antinociceptive effect. The heparin hypernociception was prevented by D-myo inositol, but not by L-myo inositol, used as negative control. In the same experimental conditions, the antinociception induced by D-myo inositol was prevented by a non-hyperalgesic dose of heparin. Similarly, the reduction of pain threshold produced by ryanodine was reversed by non-analgesic doses of 4-chloro-m-cresol, whereas the antinocicpetion induced by 4-chloro-m-cresol was prevented by non-hyperalgesic doses of ryanodine. The pharmacological treatments employed did not produce any behavioral impairment of mice as revealed by the rota-rod and hole-board tests. These results indicate that a variation of intracellular calcium contents at a supraspinal level is involved in the modulation of acute thermal nociception. In particular, the stimulation of both InsP3- and Ry-receptors appears to play an important role in the induction of antinociception in mice, whereas a blockade of these receptors is involved in an hypernociceptive response to acute thermal pain.


The ultrastructural localization of fibronectin in the lining layer of rheumatoid arthritis synovium: the synthesis of fibronectin by type B lining cells.
The distribution of fibronectin in the lining layer of inflamed rheumatoid arthritis (RA) synovium has been ultrastructurally investigated using an anti-human plasma fibronectin antibody. The hyperplasia of lining cells was prominent in the lining layer of the inflamed RA synovium. A high level of fibronectin was localized in this region. Ultrastructurally the fibronectin was observed on the surface of both type A (type M) and type B (type F) cells, and in the extracellular fibrin-like material. This glycoprotein was detectable in rough endoplasmic reticulum (RER), some Golgi apparatus, and peripheral vesicles of type B cells. On the other hand, RER and Golgi apparatus of type A cells failed to be immunostained with the antibody. Type A cells occasionally contacted each other with interdigitation of cytoplasmic processes, and a high amount of fibronectin was localized in this region. These findings indicate that fibronectin is synthesized along the classic secretory pathway through RER and Golgi apparatus of type B cells. On the contrary, type A cells seem not to be associated with the local synthesis of the glycoprotein. Fibronectin may play a structural role in organizing these proliferated lining cells by promoting cell adhesion. The synthesis of fibronectin by proliferated type B cells may be responsible in part for the local increase of this glycoprotein in the lining layer of RA synovium.


An immunochemical method for the detection of the expression of human gene loci in human-rodent somatic cell hybrids with special reference to the GPI locus.
Species-specific antibodies, prepared against unpurified human enzymes in human-hamster somatic cell hybrids. Results of the detection of the expression of the human glucosephosphate isomerase gene locus (GPI) by electrophoretic and immunochemical techniques were concordant in 17 instances. The human GPI synthesized by fibroblasts derived from skin explants and by somatic cell hybrids retaining the human GPI locus, regardless of whether the human parental cells were lymphocytes or fibroblasts, appeared to be antigenically identical.


Impaired recognition of emotional facial expressions in patients with multiple sclerosis.
Disturbances that occur in patients with multiple sclerosis (MS) are not restricted to motor, sensory, or urinary functions; they also include cognitive dysfunction, fatigue, and depression. Moreover, people with MS are known to have fewer social activities and a reduced quality of life. One aspect of social interaction is accurate recognition of facial expressions. Several studies have suggested impairment in the processing of facial expressions in patients with multiple sclerosis, but it is not clear if these deficits are based on cognitive, depressive, or other attendant symptoms. To investigate emotion recognition and facial identity recognition abilities and their relation with cognitive functions, depression, and fatigue in a cohort of MS patients. Emotion recognition and facial identity recognition abilities were investigated in a cohort of 61 MS patients with unimpaired visual acuity and 53 healthy controls using the Florida Affect Battery. Additionally, we investigated possible relationships between impaired facial expression recognition and other clinical features. MS patients were not impaired in facial identity discrimination, but showed a poor performance in all subtests that required emotion recognition. Impaired recognition of facial emotions by patients with MS seems to be associated with both cognitive and affective (depression) aspects of the disease.


Thermophilic 4-α-Glucanotransferase from Thermoproteus Uzoniensis Retards the Long-Term Retrogradation but Maintains the Short-Term Gelation Strength of Tapioca Starch.
Gelation of starch is a process during short-term retrogradation. However, long-term retrogradation always leads to the quality deterioration of starch-based food. In this work, a new type of modified tapioca starch (MTS) gel with maintained short-term gelation strength and retarded long-term retrogradation was prepared using a novel recombinantly produced and characterized 4-α-glucanotransferase (TuαGT). In the resulting MTS, the exterior chains of the amylopectin part were elongated and the content of amylose was reduced because of the disproportionation activity of TuαGT. The retrogradation analysis demonstrated that the MTS possessed highly weakened long-term retrogradation characteristics as compared to the native starch. Most importantly, the strength of the gel formed by regelatinized MTS is very close to that of gelatinized native tapioca starch when storing below 30 °C. These findings provide a starting point for developing a novel method for the enzymatic modification of the starch-based gels.


Indication for Antibiotic Prescription Among Children Attending Primary Healthcare Services in Rural Burkina Faso.
Of 61 355 visits by children <5 years old to 48 government-run primary healthcare facilities in Nouna District, Burkina Faso, 30 975 had an antibiotic prescribed (58% for pneumonia diagnoses). A minority of prescriptions were for diagnoses not requiring antibiotics, including malaria, nonbloody diarrhea, and cough without pneumonia.


Dental Health Status and Oral Health Care in Nursery School-Aged Children and their Parents Living in Poznan (Poland).
The aim of this study was to evaluate the dental health status of nursery age children and parents. The use of dental services was assessed. The study was performed in nursery schools located in Poznan, Western Poland. Clinical examination was carried out in 157 children (48.41% males and 51.59% females), aged 10-42 months. Dental health status (the number of teeth with caries, fillings and extracted) of their parents was determined on the basis of data obtained from a questionnaire. The questions also concerned information on child's and parents' dental check-ups and opinion on their predisposition to dental caries. Clinical examination revealed that 21.05% of boys and 18.51% of girls had dental caries. Most mothers had from 1 to 5 either carious and/or filled teeth (47.13%) or extracted teeth due to carious process (61.15%); the fathers' values were similar at 46.50 and 66.24%, respectively. More mothers (84.71%) than fathers (72.62%) had regular dental check-ups (p = 0.02). The analysis of mother-father-child triads showed that when both parents visited the dentist regularly, more children were free of caries (56.68%) in comparison to those with the disease (13.38%; p < 0.001). This study showed that the dental health status, as well as oral care of nursery school children and their parents, is unsatisfactory. Therefore, there is a need to introduce an intensive dental educational program focusing on dental prophylaxis for nursery age children and their parents or caregivers.


[Body composition analysis in patients with cystic fibrosis. Comparison of 3 methods: dual energy x-ray absorptiometry, bioelectrical impedance analysis, and skinfold measurements].
Nutritional status must be closely monitored in cystic fibrosis (CF) patients. This study compared three methods of measuring body composition in CF patients and then examined the relationships between two simple anthropometric markers of nutritional status - tricipital skinfold thickness (TSK) and arm muscular circumference (AMC) - and the results given by each method. Fifty-five patients with CF, 27 females and 28 males, participated in this study. The mean age at the time of the study was 14 ± 5 years, ranging from 4 to 29 years. The four skinfolds (SK) and arm circumference were measured in all patients and fat mass (FM) and AMC were calculated. Fifty patients underwent dual energy x-ray absorptiometry (DEXA) and 38 underwent bioelectrical impedance analysis (BIA). The values for FM as calculated by the three methods were highly correlated, as were the values for lean body mass (LM) (p<0.001). The LM assessed by anthropometry was overestimated by 8 ± 4% compared with DEXA and by 6 ± 7% compared with BIA. BIA overestimated LM by 4 ± 6% compared with DEXA (p<0.001). The LM values measured by SK, DEXA, and BIA were highly correlated with AMC (p<0.001) and FM calculated using these three techniques were highly correlated with TSK (p<0.001). The measurement of TSK and AMC are simple and rapid ways to evaluate body composition. The excellent correlation between the three methods used to measure body composition suggests that they are valid for use in patients with CF, but the results were not identical. The measurement from each technique must be interpreted according to its own norms and comparisons can only be made if the same technique is used in the same patient.


Young adult cancer caregivers' exposure to cancer misinformation on social media.
The objective of this study was to describe young adult cancer caregivers' exposure to cancer misinformation on social media. Eligible participants were 18 to 39 years old, used social media weekly, and cared for an adult patient with cancer diagnosed 6 months to 5 years before (N = 21). Recruitment occurred from August 2017 to June 2018 in person at oncology clinics and online. Semistructured telephone interviews were recorded and analyzed with grounded theory methods through 2 rounds of coding (κ = 0.88). Caregivers were on average 29.1 years old, female (76.2%), non-Hispanic White (90.5%), college educated (57.1%), and caring for a spouse/partner (47.6%). Caregivers were exposed to a variety of cancer misinformation topics; some felt uncertain in their caregiving ability when confronted with cancer misinformation. Caregivers crosschecked online sources and consulted trusted individuals (eg, family, friends, and health care providers) to determine the quality of cancer-related information and manage cancer misinformation. Cancer misinformation on social media may influence caregiving behaviors and decision making. Whether caregivers correctly and consistently identify cancer misinformation on social media is unknown. Supporting digital literacy to mitigate cancer misinformation on social media may improve young cancer caregivers' access to credible cancer information. Cancer misinformation on social media affects young adult cancer caregivers' perceptions of their social support network. Caregivers differ in how they evaluate cancer information for quality and in how this information influences their health behaviors and caregiving decisions.


The Efficiency of Learning Methodology for Privacy Protection in Context-aware Environment during the COVID-19 Pandemic.
When the COVID-19 coronavirus hit, the context-aware application users were willing to relax their context privacy preferences during the lockdown to cope their lives while staying home. Such disturbance in the privacy behavior affected the performance of Machine Learning (ML) algorithm that is trained on normal behavior. In this paper, we present the impact of the pandemic on the efficiency of the learning algorithm implementation of a privacy protection system. The system is composed of three modules, in this work we focus on Privacy Preferences Manager (PPM) module which is implemented using hybrid methodology based on a Statistical Model (SM) and Logistic Regression (LR) learning algorithm. The efficiency of the hybrid methodology is assessed using two real-world datasets collected prior and during the COVID-19 pandemic. The results show that the pandemic significantly impacted the efficiency of the hybrid methodology by 13.05% and 15.22% for the accuracy and F1 score respectively.


A nicking enzyme from trypanosomatids which specifically affects the topological linking of duplex DNA circles. Purification and characterization.
Newly replicated duplex DNA minicircles of trypanosomal kinetoplast DNA are nicked in both their monomeric and catenated topological states, whereas mature ones are covalently sealed. The possibility that nicking may play a role during kinetoplast DNA replication by affecting the topological interconversions of monomeric DNA minicircles and catenane networks was studied here in vitro using Crithidia fasciculata DNA topoisomerase. An enzyme that catalyzes the nicking of duplex DNA circles has been purified to apparent homogeneity from C. fasciculata cell extracts. The native enzyme has a sedimentation coefficient of 6.8 S and was found to be a dimer with a protomer Mr = 60,000. Nicking of kinetoplast DNA networks by the purified enzyme inhibits their decatenation by the Crithidia DNA topoisomerase but has no effect on the catenation of monomeric DNA minicircles into networks. This differential effect on decatenation versus catenation is specific to the purified nicking enzyme. Random nicking of interlocked DNA minicircles has no detectable effect on the reversibility of the topological reaction. The potential role of Crithidia nicking enzyme in the replication of kinetoplast DNA networks in trypanosomatids is discussed.


Preparation of Hydrophobic Film by Electrospinning for Rapid SERS Detection of Trace Triazophos.
For real application, it is an urgent demand to fabricate stable and flexible surface-enhanced Raman scattering (SERS) substrates with high enhancement factors in a large-scale and facile way. Herein, by using the electrospinning technique, a hydrophobic and flexible poly(styrene-co-butadiene) (SB) fibrous membrane is obtained, which is beneficial for modification of silver nanoparticles (Ag NPs) colloid in a small region and then formation of more "hot spots" by drying; the final SERS substrate is designated as Ag/SB. Hydrophobic Ag/SB can efficiently capture heterocyclic molecules into the vicinity of hot spots of Ag NPs. Such Ag/SB films are used to quantitatively detect trace triazophos residue on fruit peels or in the juice, and the limit of detection (LOD) of 2.5 × 10-8 M is achieved. Ag/SB films possess a capability to resist heat. As a case, 6-mercaptopurine (6MP) that just barely dissolves in 90 °C water is picked for conducting Ag/SB-film-based experiments.


The correlation between human plasma melatonin levels and urinary 6-hydroxymelatonin excretion.
A significant correlation (0.76) has been found between nighttime peak plasma melatonin levels and the 24-h urinary excretion totals for conjugated 6-hydroxymelatonin for a group of 22 women. This study validates the comparison of plasma levels of the hormone or urinary levels of its metabolite to assess pineal gland production of melatonin in humans.


Resistance and resilience of genetic and phenotypic diversity to "black swan" flood events: A retrospective analysis with historical samples of guppies.
Rare extreme "black swan" disturbances can impact ecosystems in many ways, such as destroying habitats, depleting resources, and causing high mortality. In rivers, for instance, exceptional floods that occur infrequently (e.g., so-called "50-year floods") can strongly impact the abundance of fishes and other aquatic organisms. Beyond such ecological effects, these floods could also impact intraspecific diversity by elevating genetic drift or dispersal and by imposing strong selection, which could then influence the population's ability to recover from disturbance. And yet, natural systems might be resistant (show little change) or resilient (show rapid recovery) even to rare extreme events - perhaps as a result of selection due to past events. We considered these possibilities in two rivers where native guppies experienced two extreme floods - one in 2005 and another in 2016. For each river, we selected four sites and used archived "historical" samples to compare levels of genetic and phenotypic diversity before vs. after floods. Genetic diversity was represented by 33 neutral microsatellite markers, and phenotypic diversity was represented by body length and male melanic (black) colour. We found that genetic diversity and population structure was mostly "resistant" to even these extreme floods; whereas the larger impacts on phenotypic diversity were short-lived, suggesting additional "resilience". We discuss the determinants of these two outcomes for guppies facing floods, and then consider the general implications for the resistance and resilience of intraspecific variation to black swan disturbances.


Risk factors for the development of secondary malignancies after marrow transplantation.
Bone marrow transplantation is associated with several risk factors that may predispose patients to the development of a new malignancy post-transplant. Several types of malignancies, including lymphoproliferative disorders, new leukemias, and solid tumors have been observed. Risk factors include treatment of acute graft-versus-host disease with monoclonal or polyclonal antibodies, total body irradiation, HLA nonidentity, and T-cell depletion. It is currently unknown whether longer follow-up will show a further increase or decline in the incidence of secondary tumors.


MSC-Derived exosomes suppress colorectal cancer cell proliferation and metastasis via miR-100/mTOR/miR-143 pathway.
Exosomes derived from mesenchymal stem cells (MSCs) are mostly responsible for the therapeutic effects of MSCs. To show the therapeutic effects of the human bone marrow MSC-derived exosomes (MSC-Exos) on colorectal cancer (CRC) and explore the molecular cross-talks between them, CRC cells were treated with the MSC-Exos. We found that MSC-Exos were enriched with miR-100 and miR-143, which effectively downregulated mTOR, Cyclin D1, K-RAS, HK2 while upregulated p-27 expression. All these effects were reversed by concurrent treatment with MSC-Exos and antagomiR-100, confirming that they were caused by exosomal transfer of miR-100 into recipient CRC cells. Moreover, exosomal miR-100 promoted endogenous miR-143 expression. The flow cytometry, MTT and trypan blue assays revealed that MSC-Exos could efficiently suppress proliferation and induce apoptosis of the CRC cells. Furthermore, wound healing, transwell migration and invasion assays confirmed their inhibitory effects on the migration and invasiveness of SW480 cells. We further confirmed these effects by analyzing the expression levels of epithelial to mesenchymal transition (EMT) factors and metastasis-related genes. Results showed that MSC-Exos significantly suppressed the expression of MMP2 and MMP9 (metastasis-related genes), SNAIL and TWIST (EMT-inducing transcription factors), Vimentin and N-cadherin (mesenchymal cell markers), whereas E-cadherin (epithelial cell marker) was remarkably up-regulated. Collectively, our data indicated that MSC-Exos could suppress proliferation, migration, invasion and metastasis while inducing the apoptosis of the CRC cells via miR-100/mTOR/miR-143 axis. Our findings highlight that MSC-Exo treatment as well as miR-100 restoration might be considered as potential therapeutic strategies for CRC.


Amino acid analysis using core-shell particle column.
In this study, the separation efficiency of a core-shell particle column was compared with particle-packed and monolithic silica columns, which showed that the core-shell particle column had a smaller theoretical plate height and that its separation efficiency was not affected significantly by the increase in flow rate. A fast HPLC method using a core-shell particle column was developed for the determination of amino acids. 4-Fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) was used as a fluorescence derivatization reagent for amino acids, followed by separation on a core-shell Kinetex C18 column. The analysis time for 21 NBD-amino acids was within 7min, which was faster than that in our previous studies with conventional particle-packed columns or monolithic silica columns. The linearities of the calibration curves for all the amino acids were found to be good over a range of injection amounts from 40fmol to 40pmol. The accuracies for the amino acid determinations were 90.9-107%. The method was proved to have potential for the fast determination of amino acids in biological samples.


Critical factors in assessing risk from exposure to nasal carcinogens.
Anatomical, physiological, biochemical and molecular factors that contribute to chemical-induced nasal carcinogenesis are either largely divergent between test species and humans, or we know very little of them. These factors, let alone the uncertainty associated with our knowledge gap, present a risk assessor with the formidable task of making judgments about risks to human health from exposure to chemicals that have been identified in rodent studies to be nasal carcinogens. This paper summarizes some of the critical attributes of the hazard identification and dose-response aspects of risk assessments for nasal carcinogens that must be accounted for by risk assessors in order to make informed decisions. Data on two example compounds, dimethyl sulfate and hexamethylphosphoramide, are discussed to illustrate the diversity of information that can be used to develop informed hypotheses about mode of action and decisions on appropriate dosimeters for interspecies extrapolation. Default approaches to interspecies dosimetry extrapolation are described briefly and are followed by a discussion of a generalized physiologically based pharmacokinetic model that, unlike default approaches, is flexible and capable of incorporating many of the critical species-specific factors. Recent advancements in interspecies nasal dosimetry modeling are remarkable. However, it is concluded that without the development of research programs aimed at understanding carcinogenic susceptibility factors in human and rodent nasal tissues, development of plausible modes of action will lag behind the advancements made in dosimetry modeling.


A gut-brain axis mediates sodium appetite via gastrointestinal peptide regulation on a medulla-hypothalamic circuit.
Salt homeostasis is orchestrated by both neural circuits and peripheral endocrine factors. The colon is one of the primary sites for electrolyte absorption, while its potential role in modulating sodium intake remains unclear. Here, we revealed that a gastrointestinal hormone, secretin, is released from colon endocrine cells under body sodium deficiency and is indispensable for inducing salt appetite. As the neural substrate, circulating secretin activates specific receptors in the nucleus of the solitary tracts, which further activates the downstream paraventricular nucleus of the hypothalamus, resulting in enhanced sodium intake. These results demonstrated a previously unrecognized gut-brain pathway for the timely regulation of sodium homeostasis.


Ex vivo model for elucidating the functional and structural differentiation of the embryonic mouse thyroid.
Terminal thyroid gland differentiation - the last developmental step needed to enable thyroid hormone (T4) synthesis - involves profound structural and biochemical changes in the thyroid follicular cells (TFCs). We aimed to develop an ex vivo thyroid model of embryonic mouse thyroid that would replicate the in vivo TFC differentiation program. E13.5 thyroid explants were cultured ex vivo in chemically defined medium for 7 days. Immunostaining and qPCR of thyroid explants showed thyroglobulin production onset, follicle formation, and T4 synthesis onset in 1-, 3-, and 5-day-old cultures, respectively. Differentiation was maintained and follicular growth continued throughout the 7-day culture period. Pharmacological approaches to culture inhibition were performed successfully in the ex vivo thyroids. Our robust and well described ex vivo thyroid culture model replicates the sequence of thyroid differentiation to T4 synthesis seen in vivo. This model can be used to test the effects of pharmacological inhibitors on thyroid hormone production.


[Quantitative investigations on vitellogenic protein metabolism in the honey bee (Apis mellifica)].
The soluble proteins of the haemolymph, ovary and eggs of the honey bee were separated by electrophoresis on cellulose acetate foils and on polyacrylamide gels. The predominant haemolymph fraction (60-80%) is a female-specific protein. Corresponding fractions are found in the ovary and in uncleaved eggs. According to the results, it is highly probable that these fractions represent the yolk material or vitellogenin. InApis, this vitellogenin is represented by only one protein band which carries no carbohydrate components.The haemolymph titre of vitellogenic protein depends on the physiological state of the female bees. In the worker bees, haemolymph yolk proteins are detectable only during the nurse age, whereas in queens they can be found throughout the year. It may be noted that in the mated and egg producing queens the concentration of vitellogenin in the haemolymph is lower than in virgin queens and in adult non-laying queens.The rate ofin vivo protein synthesis was determined by injecting a mixture of14C-amino acids and measuring the radioactivity in pherogram bands using a methane flow counter. In the actively laying queen the rate of vitellogenin synthesis is 3 times higher than that of the non-sex-specific blood proteins. Approximately 85% of the labeled proteins which are released from the fat body are yolk material. In contrast to other insects, non-laying queens were also found to synthesize vitellogenin; however, the rate did not exceed that of the other serum proteins. The fate of yolk material in such females is unknown. In the ovary, synthesis of the euplasmic proteins occurs at a rate similar to that of the nonspecific haemolyph fractions. The appearance of radioactivity in the ovarian yolk is delayed compared with all other proteins. This indicates that these proteins are labeled byde novo synthesis, whereas the yolk is not built up within the ovary. This conclusion is further supported by the fact that the increase in specific radioactivity of ovarian yolk proteins occurs at a time when free14C-amino acids are no longer available in the haemolymph. Following the maximum intensity of labelling of yolk proteins the specific activity declines. From the data it can be estimated that the period of vitellogenesis for a single follicle is 2 days; 2 additional days of maturation, during which glycogen synthesis and chorion formation occur, are required before oviposition.


Ultrastructure Characteristics of Different Chinese Medicine Syndromes of Helicobacter pylori-Correlated Gastric Diseases.
To explore the ultrastructure characteristics of patients with dampness-heat of Pi (Spleen)-Wei (Stomach) syndrome (DHPW) and Pi-qi deficiency syndrome (PQD), both of which are Helicobacter pylori (Hp)-correlated gastric diseases (HPCG), and implicate a helpful hint for the clinical microcosmic syndrome differentiation. Fourteen gastric mucosa samples from 6 chronic gastritis (CG) and 6 active peptic ulcer (including 8 DHPW, 4 PQD) as well as 2 healthy volunteers were collected and tested for Hp infection. The ultrastructure of gastric mucosa was observed under the transmission electron microscope (TEM). Among 14 gastric mucosa samples, 8 of them were Hp positive (6 DHPW and 2 PQD), which were all accordance with the results screened by supermicro-pathological method. Under TEM, the normal gastric mucosa, with tidy microvilli and abundant in mucus granules, mitochondria and rough endoplasmic reticulum distributed evenly, and with smooth nucleus membrane. But in those specimens of DHPW with Hp infection, microvilli were presented with burr shape. Especially, those samples from dampness-heat syndrome with predominant heat type (DHSH) patients were more obvious, with microvilli damaged, mitochondria concentrated and distributed in disorder, secretory tubule extended. In dampness-heat syndrome with predominant dampness type (DHSD) patients, mucus granules aggregated obviously, mitochondria swelled and blurred, and rough endoplasmic reticulum crowded. For 2 samples of DHPW without Hp infection, their microvilli were intact, with mitochondria increased and gathered but well-distributed, and secretory tubule extended mildly. In 2 PQD patients with Hp positive, the specimens of microvilli were sparse, and their mucus granules and mitochondria were decreased, with fractured crests and vacuole, secretory tubules extension to nucleus membrane, and rough endoplasmic reticulum extension in a pool-like way, and nucleus condensed. The 2 samples from PQD patients without Hp infection were characterized with intact microvilli, decreased mitochondria, fractured crest and extended rough endoplasmic reticulum in a pool-like way. It's obviously different in ultrastructure of DHPW and PQD patients under TEM, which may give a helpful hint for the microcosmic syndrome differentiation of HPCG.


Pharmacological and pharmacokinetic study of olmesartan medoxomil in animal diabetic retinopathy models.
A close relationship between the renin-angiotensin system and the pathophysiology of diabetic retinopathy has been suggested, several angiotensin II type 1 receptor (angiotensin AT1 receptor) antagonists being effective in animal models. Therefore, we examined the efficacy of an angiotensin AT1 receptor antagonist, olmesartan medoxomil (CS-866), in animal retinopathy models. In diabetic stroke-prone spontaneously hypertensive (SHRSP) rats, 4-week treatment with CS-866 prevented the elongation of oscillatory potential peaks dose-dependently which almost normalized at 3 mg/kg/day. Next, in oxygen-induced retinopathy mice, CS-866 at 1 mg/kg significantly prevented the retinal neovascularization. In these animal models, plasma concentrations of CS-866 were comparable to the in vitro IC50 value of the angiotensin AT1 receptor. In summary, our data demonstrated that CS-866 was effective in early and late stage retinopathy models through the inhibition of the angiotensin AT1 receptor. These findings suggest the possibility of CS-866 as a therapeutic agent for diabetic retinopathy.


Rehospitalization in a national population of home health care patients with heart failure.
Patients with heart failure (HF) have high rates of rehospitalization. Home health care (HHC) patients with HF are not well studied in this regard. The objectives of this study were to determine patient, HHC agency, and geographic (i.e., area variation) factors related to 30-day rehospitalization in a national population of HHC patients with HF, and to describe the extent to which rehospitalizations were potentially avoidable. Chronic Condition Warehouse data from the Centers for Medicare & Medicaid Services. Retrospective cohort design. The 2005 national population of HHC patients was matched with hospital and HHC claims, the Provider of Service file, and the Area Resource File. The 30-day rehospitalization rate was 26 percent with 42 percent of patients having cardiac-related diagnoses for the rehospitalization. Factors with the strongest association with rehospitalization were consistent between the multilevel model and Cox proportional hazard models: number of prior hospital stays, higher HHC visit intensity category, and dyspnea severity at HHC admission. Substantial numbers of rehospitalizations were judged to be potentially avoidable. The persistently high rates of rehospitalization have been difficult to address. There are health care-specific actions and policy implications that are worth examining to improve rehospitalization rates.


Influence of salinity and temperature on acute toxicity of cadmium to Mysidopsis bahia molenock.
Acute toxicity tests were conducted to compare estimates of toxicity, as modified by salinity and temperature, based on response surface techniques with those derived using conventional test methods, and to compare effect of a single episodic exposure to cadmium as a function of salinity with that of continuous exposure. Regression analysis indicated that mortality following continuous 96-hr exposure is related to linear and quadratic effects of salinity and cadmium at 20 degrees C, and to the linear and quadratic effects of cadmium only at 25 degrees C. LC50s decreased with increases in temperature and decreases in salinity. Based on the regression model developed, 96-hr LC50s ranged from 15.5 to 28.0 micrograms Cd/L at 10 and 30% salinities, respectively, at 25 degrees C; and from 47 to 85 micrograms Cd/L at these salinities at 20 degrees C. Trimmed Spearman-Karber method used in analysis of a second data set yielded estimates at 20 degrees C and 25 degrees C comparable to those of multiple regression analysis. At 30 degrees C, the 96-hr LC50 was less than 11 micrograms/L. The relationship of median tolerance to cadmium concentration and exposure time was related to the interaction of both factors and independent of salinity between 10 and 30% at 25 degrees C. The quadratic model predicts mortality of 50% following exposures of less than 12 hr to the highest concentration examined (92 micrograms/L). For exposure durations of 16 and 24 hr, 50% mortality is predicted to occur at 78 and 56 micrograms/Cd/L, respectively.


Cytomegalovirus Infection Is Associated With Increased Prevalence of Latent Tuberculosis Infection.
Cytomegalovirus (CMV) increases tuberculosis (TB) risk, but its relationship with latent TB infection (LTBI) is unknown. Using US nationally representative data, we report that CMV was independently associated with LTBI (odds ratio, 2.94; 95% CI, 1.19-7.28; P=.02). CMV and LTBI were associated with higher C-reactive protein, suggesting chronic inflammation.


GlobalSurgBox: A Portable Surgical Simulator for Surgical Trainees Worldwide.
Identify barriers to surgical simulation in multiple countries across the income spectrum. Evaluate whether a novel, portable surgical simulator (GlobalSurgBox) would be valuable to surgical trainees and overcome these barriers. Trainees from high-, middle-, and low-income countries were instructed on how to perform surgical skills using the GlobalSurgBox. Participants were sent an anonymized survey after 1 week to evaluate practicality and helpfulness of the trainer. Academic medical centers in 3 countries: USA, Kenya, and Rwanda. 48 medical students, 48 surgery residents, 3 medical officers, and 3 cardiothoracic surgery fellows. 99.0% of respondents agreed surgical simulation was an important aspect of surgical education. Despite 60.8% having access to simulation resources, only 3 of 40 (7.5%) US trainees, 2 of 12 (16.7%) of Kenyan trainees, and 1 of 10 (10.0%) Rwandan trainees used these resources routinely. 38 (95.0%) US trainees, 9 (75.0%) Kenyan trainees, and 8 (80.0%) Rwandan trainees with access to simulation resources stated there were barriers to using them. The frequently cited barriers included lack of convenient access and lack of time. After using the GlobalSurgBox, 5 (7.8%) US participants, 0 (0%) Kenyan participants, and 5 (38.5%) Rwandan participants reported lack of convenient access as a continued barrier to simulation. 52 (81.3%) US trainees, 24 (96.0%) Kenyan trainees, and 12 (92.3%) Rwandan trainees stated the GlobalSurgBox was a good facsimile of the operating room. 59 (92.2%) US trainees, 24 (96.0%) Kenyan trainees, and 13 (100%) Rwandan trainees stated the GlobalSurgBox better prepared them for clinical settings. A majority of trainees across all 3 countries reported multiple barriers to simulation in their current surgical training. The GlobalSurgBox eliminates many of these barriers by providing a portable, affordable, and realistic way to practice skills needed in the operating room.


Oxidative Coordination versus C3 -C(O)Me Bond Cleavage in Acetylacetonate Iridium Complexes.
Iridabicycles [Ir{κ3 -N,C,O-(pyC(H)=C(C(O)Me)2 }(Cl)(L-L)](L-L=cod (cod=1,5-cyclooctadiene), 1 a; bipy (bipy=2,2'-bipyridine), 1 b) have been obtained by oxidative coordination of 3-(pyridine-2-yl-methylene)pentane-2,4-dione L1, to the complexes [{Ir(μ-Cl)(cod)}2 ] and [{Ir(μ-Cl)(coe)2 }2 ] (coe=cis-cyclooctene), the latter in the presence of bipy. Remarkably, cleavage of the C3 -C(O)Me bond of L1 has instead been achieved in the reaction with [Ir(Cl)(dmb)2 ] (dmb=2,3-dimethylbutadiene), yielding a compound formulated as [Ir{κ2 -N,C-(pyC(H)C(C(O)Me))}(CO)(μ-Cl)(Me)]2 , 2. Treatment of dimer 2 with DMSO or PMe3 produced the complexes[Ir{κ2 -N,C-(pyC(H)C(C(O)Me)}(CO)Cl(Me)L] (L=DMSO, 3 a; PMe3 , 3 b). Plausible mechanisms for the reactions leading to complexes 1 and 2 are proposed by means of DFT calculations.


PCB, PCDD and PCDF congener profiles in two types of Aroclor 1254.
Monsanto produced two distinct variants of Aroclor 1254. The late-production variant resulted from a change in Monsanto's manufacturing process in the early 1970s. Previous literature had reported that the late-production variant was produced from 1974 to 1976, but subsequent work has identified a sample known to be obtained in 1972. In this paper, we present congener-specific PCB and PCDD/F data for this 1972 late-production sample, and a brief historical record of late-production Aroclor 1254.


Sleep deprivation reduces vagal tone during an inspiratory endurance task in humans.
Sleep deprivation alters inspiratory endurance by reducing inspiratory motor output. Vagal tone is involved in exercise endurance. This study aimed to investigate the effect of sleep deprivation on vagal tone adaptation in healthy subjects performing an inspiratory effort. Vagal tone was assessed using Heart Rate Variability normalized units of frequency domain component HF (high frequency) before, at the start, and the end of an inspiratory loading trial performed until exhaustion by 16 volunteers after one night of sleep deprivation and one night of normal sleep, where sleep deprivation reduced the inspiratory endurance by half compared to the normal sleep condition (30 min vs 60 min). At rest, heart rate was similar in sleep deprivation and normal sleep conditions. In normal sleep condition, heart rate increased during inspiratory loading task; this increase was greater in sleep deprivation condition. In normal sleep condition, vagal tone increased at the beginning of the trial. This vagal tone increase was absent in sleep deprivation condition. Sleep deprivation abolished vagal tone response to inspiratory load, possibly contributing to a higher heart rate during the trial and to a reduced inspiratory endurance. NCT02725190.


Exposure and risk assessment of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dl-PCBs) for primiparous mothers and breastfed infants in Penang, Malaysia.
An average 50 ml breast milk samples were collected from 21 lactating primiparous mothers (range 25 to 45 years, mean 33 years), 4-8 weeks after delivery in Penang Island, Malaysia. The geometric mean concentration of the most toxic congeners, 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) was 0.14 pg WHO2005-TEQ g-1 zlipid. The most abundant congeners of PCDD/Fs were octachlorodibenzo-p-dioxin (OCDD) (5.9-75.4%), followed by 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (1,2,3,4,6,7,8-HpCDD) (1.1-30.7%). The geometric mean level of total dioxins and dl-PCBs was 2.2 pg WHO2005-TEQ g-1 lipid, significantly lower than those in developed countries or highly contaminated areas. The total dioxins and dl-PCBs in pg WHO2005-TEQ levels in breast milk were significantly correlated with years of residence at potential contaminated site. The average daily intake of 11.8 pg WHO2005-TEQ kg-1 body weight was estimated for a breastfed infant at 6 months of age. This demonstrates the exposure risk to infants, especially from Penang region, to these pollutants from human milk intake are potentially high during the lactation period.


The prevalence of HR-HPV DNA in ASC-US Pap smears: A military population study.
To determine the prevalence of HR-HPV DNA in ASC-US Pap smears following implementation of the Bethesda 2001 classification system. A computer database of Pap smears obtained within Department of the Army medical facilities was queried for the study period August 2002 to June 2004. All ASC-US Pap smears that underwent reflex testing for HR-HPV DNA were included. Additional clinical and demographic data were obtained from facilities within the US northeast region to evaluate the differences in ASC-US and SIL rates between the current and former Bethesda classification systems. 550,000 Pap smears were collected during the study period. The HR-HPV prevalence was 40.8% (95% confidence interval [CI] = 40.3 to 41.3) among 40,870 patients with ASC-US Pap smears. Within the northeast region, the HR-HPV prevalence in ASC-US Pap smears decreased from 61.2% (95% CI = 57.4 to 64.8%) in patients 18-22 years old to 24.9% (95% CI = 23.1 to 26.8%) in patients age 29 and older. When comparing the two classification systems, significant increases in both ASC-H and SIL and decreases in ASC-US were appreciated after the institution of Bethesda system 2001. In our large, diverse cohort, the implementation of the Bethesda II system has resulted in a decrease in ASC-US Pap smear results. Additionally, the prevalence of HR-HPV in the ASC-US population was 40.8%, significantly lower than the rate noted in the ALTS trial under the Bethesda I classification system.


Short-term effects of air pollution on daily single- and co-morbidity cardiorespiratory outpatient visits.
Several studies have noted that the existence of comorbidities lead to an increase in the risk of premature mortality and morbidity. Most of the studies examining the effects of air pollution on comorbidity visits were from Northern American countries, with scarce literature from Asia. This study contributes to existing, yet limited understanding of air pollution-comorbidity by examining the effects of daily air pollutants on outpatient single morbidity and comorbid cardiorespiratory visits in Japan. A total of 1,452,505 outpatient cardiorespiratory visits were recorded among the 21 Japanese cities from 2013 to 2016. Daily outpatient cardiorespiratory visit data were obtained from a health insurance claims database managed by the Japan Medical Data Center Co., Ltd. (JMDC). A time-stratified case crossover analysis coupled with Generalized Additive Mixed Model was used to analyze the association of daily air pollutants (particulate matter 2.5 μm or less in diameter, ozone and nitrogen dioxide) on daily single (respiratory and cardiovascular) and comorbidity health outcomes. We further examined single and cumulative effects for 0-3 and 0-14 lag periods. Ozone, NO2, and PM2.5 were positively associated with cardiorespiratory visits in either shorter or longer lags, with more apparent comorbidity associations with NO2 exposure. A 10-unit increase in NO2, after adjusting for ozone, was associated with a 2.24% (95% CI: 1.34-3.15) and 6.49% (95% CI: 5.00-8.01) increase in comorbidity visit at Lag 0 (of Lag 0-3) and cumulative lag 0-3, respectively. Our results contribute to existing evidence suggesting that short-term and extended exposure to air pollution elicit health risks on cardiovascular, respiratory and comorbid clinic visits. Exposure to NO2, in particular, was associated with increase in the risk of single and comorbidity cardiorespiratory visits. Results can be potentially utilized for both individual health (e.g. risk population health management) and health facility management (e.g. health visit influx determination).


Serum autotaxin levels correlate with the severity of pruritus in intrahepatic cholestasis of pregnancy.
This study aimed to examine autotaxin (ATX) concentrations in the serum of pregnant women complicated with intrahepatic cholestasis of pregnancy (ICP) and compare them with individuals with uncomplicated healthy pregnancies. This prospective case-control study took place with 83 pregnant women. The study group included 43 pregnant women presenting with a singleton pregnancy diagnosed with ICP in their third trimester of pregnancy. The diagnostic power of the ATX variable was examined by receiver operating characteristic analysis, and the cut-off value calculated according to the Youden index was summarized with the related sensitivity and specificity points. The mean serum concentration of maternal ATX was significantly higher in the ICP cases (8.91 ± 2.69 pg/mL) compared to the pregnant women in the control group (3.59 ± 1.39 ng/mL, p < 0.001). According to the Youden index, a 5.80 ng/mL cut-off value of serum ATX concentrations can be used to diagnose ICP with 97.7% sensitivity and 97.5% specificity. A significant highly positive correlation was found between maternal serum ATX levels and maternal serum total bile acid levels (r = 0.633 and p < 0.001) and itch intensity, which was objectified by the visual analog scale score (r = 0.951 and p < 0.001). Maternal serum ATX levels were significantly increased in ICP patients as compared with healthy pregnant women. Also, serum ATX activity was highly correlated with the itch intensity. We consider that ATX might represent a robust, accurate, and reliable circulating biomarker to diagnose ICP.


Shedding light on the role of CX3CR1 in the pathogenesis of schizophrenia.
Schizophrenia has a complex and heterogeneous molecular and clinical picture. Over the years of research on this disease, many factors have been suggested to contribute to its pathogenesis. Recently, the inflammatory processes have gained particular interest in the context of schizophrenia due to the increasing evidence from epidemiological, clinical and experimental studies. Within the immunological component, special attention has been brought to chemokines and their receptors. Among them, CX3C chemokine receptor 1 (CX3CR1), which belongs to the family of seven-transmembrane G protein-coupled receptors, and its cognate ligand (CX3CL1) constitute a unique system in the central nervous system. In the view of regulation of the brain homeostasis through immune response, as well as control of microglia reactivity, the CX3CL1-CX3CR1 system may represent an attractive target for further research and schizophrenia treatment. In the review, we described the general characteristics of the CX3CL1-CX3CR1 axis and the involvement of this signaling pathway in the physiological processes whose disruptions are reported to participate in mechanisms underlying schizophrenia. Furthermore, based on the available clinical and experimental data, we presented a guide to understanding the implication of the CX3CL1-CX3CR1 dysfunctions in the course of schizophrenia.


[Clinically pure motor variant of Guillain-Barré polyneuritis. Report of 3 cases].
We report three patients with severe Guillain-Barré syndrome (GBS). On clinical examination, no sensory deficit was elicited. Electromyography (EMG) and motor nerve conduction velocity (NCV) studies were indicative of an axonal lesion. In two patients, we found total peripheral conduction block without volitional EMG activity. Sensory NCV and cortical median nerve evoked potentials remained normal. Sural nerve biopsy revealed unequivocal alterations of sensory nerve fibers, some in the form of primary demyelination. Therefore, these cases must bei classified as combined motor-sensory syndromes despite the clinical and electrophysiological findings. Although total denervation of the extremity muscles occurred, causing tetraparalysis, this manifestation appears to be attributable to the secondary axonal variant. In contrast to positive reports in literature, immunomodulatory treatment proved ineffective in all three cases.


Evaluation of thermal hydrolysis efficiency of mechanically dewatered sewage sludge via rheological measurement.
In this study, laboratory tests of both low temperature (60-90 °C) and high temperature (120-180 °C) thermal hydrolysis (LTHP and HTHP) were performed on mechanically dewatered high-solid sludges (at total solid of 14.2 wt% and 18.2 wt%) to evaluate the extent of organic solubilization through rheological measurements. The effects of treatment temperature and duration on organic solubilization and viscoelastic behavior of the sludge were comprehensively investigated. The results indicated that the organic solubilization contents including soluble chemical oxygen demand, soluble protein, and soluble polysaccharides increased logarithmically with the treatment time. Protein solubilized considerably faster than polysaccharides during thermal hydrolysis. The rheological curves exhibited the Payne effect in the amplitude sweep oscillation test. The elastic modulus in linear viscoelastic regime decreased logarithmically with treatment time. The viscoelastic behavior of sludge was well modeled by the Kaye-Bernstein-Kearsly-Zapas (KBKZ) model with paralleled Maxwell elements to describe the frequency dependence of elastic modulus and viscous modulus. With respect to the relaxation spectrum, the relaxation modulus first decreased with relaxation time and then increased. The relaxation modulus in each Maxwell element decreased with the treatment temperature and duration. Furthermore, in the HTHP, the influence of treatment temperature on enhancing organic solubilization and decreasing viscoelasticity exceeded the influence of treatment duration. In contrast, the treatment duration played a more important role than temperature in the LTHP. The content of organic matters was linearly related and logarithmically related to the elastic modulus in the LTHP and in the HTHP, respectively. The rheology analyses demonstrated that viscoelastic properties could be used as indicators to estimate the extent of organic matter solubilization in thermal hydrolysis process. The developed viscoelastic model provided insights for future research in numerically simulating the fluid dynamics of sludge.


Hypoplastic left heart syndrome, interrupted inferior vena cava, biliary atresia.
A neonate was diagnosed with hypoplastic left heart syndrome, heterotaxy syndrome, and interrupted inferior vena cava soon after birth. At 6 days old she underwent the Norwood procedure using Sano modification. Postoperatively she had persistent direct hyperbilirubinemia and was diagnosed with biliary atresia for which she underwent a Kasai procedure at 29 days old. At 10 months she underwent the Kawashima procedure. She is now 20 months old and has been thriving without any jaundice. This case report illustrates that even in the presence of major multiple congenital anomalies, staged reconstruction for hypoplastic left heart syndrome can be successfully performed.


Zn sorption mechanisms onto sheathed Leptothrix discophora and the impact of the nanoparticulate biogenic Mn oxide coating.
Zinc sorption on sheathed Leptothrix discophora bacterium, the isolated extracellular polymeric substances (EPS) sheath, and Mn oxide-coated bacteria was investigated with macroscopic and spectroscopic techniques. Complexation with L. discophora was dominated by the outer membrane phosphoryl groups of the phospholipid bilayer while sorption to isolated EPS was dominated by carboxyl groups. Precipitation of nanoparticulate Mn oxide coatings on the cell surface increased site capacity by over twenty times with significant increase in metal sorption. XAS analysis of Zn sorption in the coated system showed Mn oxide phase contributions of 18 to 43% through mononuclear inner-sphere complexes. The coordination environments in coprecipitation samples were identical to those of sorption samples, indicating that, even in coprecipitation, Zn is not incorporated into the Mn oxide structure. Rather, through enzymatic oxidation by L. discophora, Mn(II) is oxidized and precipitated onto the biofilm providing a large surface for metal sequestration. The nanoparticulate Mn oxide coating exhibited significant microporosity (75%) suggesting contributions from intraparticle diffusion. Transient studies conducted over 7 months revealed a 170% increase in Zn loading. However, the intraparticle diffusivity of 10(-19) cm(2) s(-1) is two orders of magnitude smaller than that for abiotic Mn oxide which we attribute to morphological changes such as reduced pore sizes in the nanoparticulate oxide. Our results demonstrate that the cell-bound Mn oxide particles can sorb significant amounts of Zn over long periods of time representing an important surface for sequestration of metal contaminants.


[Rabbit coronary vessels following a single irradiation of the heart region with a dose of 2400 rad].
The effect of ionizing radiation on the coronary vessels was studied on rabbits whose cardiac areas were irradiated at a dose of 2400 rads. This exposure led to dilatation and stricture of small vessels. The most significant changes were found in the system of the left coronary artery at an early post-irradiation period.


Previous history of surgery in females and roadside shaving in males are the commonest risk factors for hepatitis C infection: A cross-sectional retrospective study.
Hepatitis C virus (HCV) is a causative agent of hepatitis C disease of the liver. We have analysed the major risk factors including demographic, clinical and genotypic distribution among HCV seropositive patients and their distribution in Uttar Pradesh, India. This study was conducted by a questionnaire-based proforma, filled in Hepatobiliary Clinic, Department of Medicine, King Georg's Medical University, Lucknow, from 2014 to 2017. Demographic, clinical and laboratory data were recorded. Seropositivity was demonstrated through an anti-HCV IgG ELISA kit. Positive patients were further examined for HCV RNA by RT-PCR. A total of 31,440 patients attended the hepatobiliary clinic. Among these, 310 (0.99%) patients were confirmed for HCV infection and there was no significant difference between males and females (50.3% vs. 49.7%). Previous surgery (49.0%), dental extraction (41.0%) and roadside shaving (38.1%) were the major risk factors for HCV infection. We also observed that previous surgery 143/154 (92.9%) in female and roadside shaving 118/156 (75.6%) in male was the commonest factor for HCV, however; dental extraction was comparable among male and female (65 [51.8%] vs 62 [48.2%], P value = 0.818). HCV RNA genotype 3 (81.6%) was the most frequent followed by 3a (11.3%), 3b (5.8%), 1 (0.7%) and 4 (0.7%). In the district-wise analysis, frequent cases were included from Lucknow with previous surgery and dental extraction as the commonest risk factor. Previous surgery among female and roadside shaving among males are the commonest risk factors for HCV. This study suggests a powerful and strict guideline, to avoid HCV infection.


Genetic polymorphism in the transforming growth factor beta1 gene (-509 C/T and -800 G/A) and colorectal cancer.
TGF-beta1 is a multifunctional cytokine that acts as both a tumor suppressor and a stimulator of tumor progression. Susceptibility to colorectal carcinoma may be affected by genetic factors. In this study, the association between -800 G/A and -509 C/T polymorphisms of the transforming growth factor beta1 gene, TGFB1, and susceptibility to colorectal cancer in Iranian patients was investigated. This study was conducted with 134 patients with colorectal carcinoma and 138 healthy controls matched for age and sex. Genotyping was performed on genomic DNA using polymerase chain reaction and restriction fragment length polymorphism. The genotype distributions and allele frequencies of the TGFB1 gene polymorphism at -509 C/T were significantly related to colorectal carcinoma. A lower frequency of 509T allele (41.8%) and TT genotype was observed in patients (21.6%) than in control subjects (52.9% and 29.7%, respectively) (P<0.035). At position 800, no significant differences in genotype distribution and allele frequencies between the patients and healthy controls was found (P>0.05). These data suggest that the genetic polymorphism at -509 C/T but not at -800 G/A of the TGFB1 gene may play a role in susceptibility of Iranian subjects for colorectal carcinoma.