HLA-DRB1 polymorphism in recurrent pregnancy loss: New evidence for an association to HLA-DRB1*07.
Many cases of recurrent pregnancy loss (RPL) defined as ≥3 consecutive pregnancy losses are suggested to be caused by an aberrant maternal immune response against the fetus or trophoblast. Human leukocyte antigen (HLA)-DRB1 and -DQB1 polymorphisms are associated with most autoimmune disorders and studies of HLA-DBB1 polymorphism in RPL patients are thus relevant. In previous studies, the HLA-DRB1*03 allele was found with increased prevalence in RPL patients. We wanted to clarify whether HLA-DRB1 alleles indeed were associated with RPL among women of Caucasian descent. A total of 1078 women with unexplained RPL and 2066 bone marrow donors were HLA-DRB1-typed and subsets were also HLA-DQB1 typed. All patients were initially HLA-DRB1-typed by DNA-based low-resolution techniques and subsets of patients and all controls were typed by high-resolution techniques. Among patients, the HLA-DRB1*07 allele frequency was significantly increased compared with controls; OR 1.29 (95 % CI 1.09-1.52), p < 0.0025; after correction for multiple comparisons pc = 0.031. The HLA-DRB1*07/*07 genotype was highly increased in patients with RPL compared with controls: OR 2.27 (1.31-3.93), p = 0.0027. The frequency of the HLA-DRB1*07 phenotype in RPL patients had increased significantly (p = 0.002) in three studies from our group published 1994-2021. The allele frequency of HLA-DRB1*03 was not increased in RPL patients compared with controls; OR 0.96 (0.83-1.12). In conclusion, the previous association between HLA-DRB1*03 and RPL could not be confirmed in our study whereas an association to HLA-DRB1*07 was detected for the first time. Since the latter association is a new finding, it should be confirmed in future studies.


Does pretreatment with omeprazole decrease the chance of eradication of Helicobacter pylori in peptic ulcer patients?
It has been reported that pretreatment with omeprazole could decrease the efficacy of Helicobacter pylori eradication. Our aim was to compare the efficacy, safety, and tolerability of the eradicating regimen, omeprazole/amoxicillin/metronidazole. The two antibiotics were scheduled either during the first or during the last 2 wk of omeprazole administration. In this prospective controlled study conducted in a single center, 78 symptomatic peptic ulcer patients were treated for 4 wk with omeprazole 40 mg o.m.; the patients were randomly assigned to receive amoxicillin 1 g t.i.d. postprandially and metronidazole 250 mg t.i.d. postprandially, either during the first 2 wk (group A, n = 40) or the last 2 wk of therapy with omeprazole (group B, n = 38). H. pylori status was assessed by culture, histology, urease test, and IgG antibodies. Each patient's course was followed for 1 yr. H. pylori infection was cured in 97.4% of group A (95% CI: 0.84-0.99) and in 89% of group B (95% CI: 0.73-0.96, p = 0.28). Healing was achieved in 80% of the patients in group A (95% CI: 0.63-0.90) and in 75.7% of patients in group B (95% CI: 0.60-0.90, p = 0.60) At 12-month follow-up, 72 patients were evaluated: 37/38 (97%) of patients in group A and 33/33 (100%) in group B were confirmed as cured of the infection (NS). Peptic ulcer healing rate reached 100% in the two groups. Furthermore, between the two groups, there were no significant differences in symptom relief or improvement. Both regimens were well tolerated, and no patient had to be withdrawn from therapy because of an adverse event. Minor side-effects appeared to be similar in the two groups (40% vs. 38%). This randomized study clearly indicates that omeprazole pretreatment does not significantly reduce the efficacy of eradicating therapy for H. pylori in peptic ulcer patients.


The antagonism of cholecystokinin octapeptide-8 to the peroxynitrite oxidation on a diabetic cataractal rat model.
Cataracts is considered be formed because of an abnormal glucose metabolic pathway or oxidative stress. We explored the damaging role of ONOO- and antagonism of cholecystokinin octapeptide-8 (CCK-8) in diabetic cataractal rat lenses. A diabetic cataractal animal model was established by peritoneal injection of streptozotocine (STZ). Thirty-six normal SD rats were taken as control group; seventy-two were given STZ (45 mg/kg) and then divided into STZ group and CCK-8 group (peritoneal injection CCK-8). STZ induced diabetic rats were treated with CCK-8 for 60 days. Lenses were examined with slit lamp at 20, 40 and 60 days. Immunofluorescent staining and Western blot analysis were used for determining nitrotyrosine (NT, a marker for ONOO-). PT-PCR and gene array analysis were used for determining the expression of inducible nitric oxide synthetase mRNA (iNOS mRNA) in lens epithelium (LEC). STZ group rats developed lens opacity by 20 days that reached a high level by 60 days after STZ injection. CCK-8 group rats delayed the cataract formation. CCK-8 group rats delayed the cataract formation. There was no distinct expression of NT and iNOS mRNA in control group. In STZ group, there were distinct expression of NT and upregulation of iNOS mRNA; however, CCK-8 group showed weak expression of NT and downregulation of iNOS mRNA. NT, which may be a new form of oxidative stress, was expressed in diabetic rat LEC although CCK-8 could reverse NT damage in LEC. The results suggested that CCK-8 might be a useful therapeutic agent against diabetic cataract. The antagonizing mechanism of CCK-8 may be related to direct antagonism of ONOO- as well as its inhibition of the expression of iNOS mRNA for production of NO and therefore decrease in the formation of ONOO-.


Process for the Purification of cis-p-Coumaric Acid by Cellulose Column Chromatography after the Treatment of the trans Isomer with Ultraviolet Irradiation.
A methanolic solution of trans-p-coumaric acid was exposed to ultraviolet radiation and a mixture solution of the trans and cis isomers was subjected to cellulose column chromatography, eluting with an aqueous 0.1% trifluoroacetic acid solution containing methanol (90:10, v/v). Separation of the trans and cis isomers was achieved. The identity of the cis isomer was confirmed by TLC, HPLC, and NMR. Since both the support and eluent are inexpensive, the cis isomers can be obtained economically on both the laboratory and industrial scales.


Cloning of cDNA and genomic DNA for human von Willebrand factor.
The recent isolation of cDNA and genomic DNA clones for human vWF by ourselves and others has finally laid to rest the historical notion that factor VIII and vWF might have a precursor-product or other complex relationship. These two hemostatic activities are clearly present on two distinct proteins, each encoded by a separate gene. Whether ther is coordinate regulation of the factor VIII and vWF genes is still unknown. The structure and structure-function relationships of the vWF protein have been elucidated by many investigators, only some of whom can be cited in this short paper. Together, these molecular biology and protein chemistry studies have shown that vWAgII is the amino-terminal propeptide of vWF, explaining the proportional deficiency of these two plasma proteins in von Willebrand disease (type I). In addition, sites of proteolytic processing, glycosylation, and disulfide bond formation have been defined, and some of the binding functions of mature vWF have been identified with specific amino acid sequences. The protein has a highly repeated structure, suggesting a complex evolutionary history. The A domains of vWF appear to be homologous to complement factor B, and perhaps to component C2, although the biological meaning of this similarity is unknown. Genomic DNA clones have been isolated corresponding to approximately one third of the vWF gene on chromosome 12, and a fragment of the cDNA also hybridizes to uncharacterized sequences on chromosome 22. Preliminary studies in von Willebrand disease have revealed two patients with very large deletions in the vWF gene.(ABSTRACT TRUNCATED AT 250 WORDS)


Radiographic analysis of neuroforaminal and central canal decompression following lateral lumbar interbody fusion.
Lateral lumbar interbody fusion (LLIF) is a minimally invasive surgical option for treating symptomatic degenerative lumbar spinal stenosis (DLSS) in select patients. However, the efficacy of LLIF for indirectly decompressing the lumbar spine in DLSS, as well as the best radiographic metrics for evaluating such changes, are incompletely understood. A single-institutional cohort of patients who underwent LLIF for DLSS between 5/2015 - 12/2019 was retrospectively reviewed. Diameter, area, and stenosis grades were measured for the central canal (CC) and neural foramina (NF) at each LLIF level based on preoperative and postoperative T2-weighted MRI. Baseline facet joint (FJ) space, degree of FJ osteoarthritis, presence of spondylolisthesis, interbody graft position, and posterior disc height were analyzed as potential predictors of radiographic outcomes. Changes to all metrics after LLIF were analyzed and compared across lumbar levels. Preoperative and intraoperative predictors of decompression were then assessed using multivariate linear regression. A total of 102 patients comprising 153 fused levels were analyzed. Pairwise linear regression of stenosis grade to diameter and area revealed significant correlations for both the CC and NF. All metrics except CC area were significantly improved after LLIF (p < 0.05, 2-tailed t-test). Worse FJ osteoarthritis ipsilateral to the surgical approach was predictive of greater post-operative CC and NF stenosis grade (p < 0.05, univariate and multivariate ordinary least squares linear regression). Lumbar levels L3-5 had significantly higher absolute postoperative CC stenosis grades while relative change in CC stenosis at the L2-3 was significantly greater than other lumbar levels (p < 0.05, one-way ANOVA). There were no baseline or postoperative differences in NF stenosis grade across lumbar levels. Radiographically, LLIF is effective at indirect compression of the CC and NF at all lumbar levels, though worse FJ osteoarthritis predicted higher degrees of post-operative stenosis.


Revisiting a sample of U.S. billionaires: how sample selection and timing of maternal condition influence findings on the Trivers-Willard effect.
Based on evolutionary theory, Trivers & Willard (TW) predicted the existence of mechanisms that lead parents with high levels of resources to bias offspring sex composition to favor sons and parents with low levels of resources to favor daughters. This hypothesis has been tested in samples of wealthy individuals but with mixed results. Here, I argue that both sample selection due to a high number of missing cases and a lacking specification of the timing of wealth accumulation contribute to this equivocal pattern. This study improves on both issues: First, analyses are based on a data set of U.S. billionaires with near-complete information on the sex of offspring. Second, subgroups of billionaires are distinguished according to the timing when they acquired their wealth. Informed by recent insights on the timing of a potential TW effect in animal studies, I state two hypotheses. First, billionaires have a higher share of male offspring than the general population. Second, this effect is larger for heirs and heiresses who are wealthy at the time of conception of all of their children than for self-made billionaires who acquired their wealth during their adult lives, that is, after some or all of their children have already been conceived. Results do not support the first hypothesis for all subgroups of billionaires. But for males, results are weakly consistent with the second hypothesis: Heirs but not self-made billionaires have a higher share of male offspring than the U.S. population. Heiresses, on the other hand, have a much lower share of male offspring than the U.S. average. This hints to a possible interplay of at least two mechanisms affecting sex composition. Implications for future research that would allow disentangling the distinct mechanisms are discussed.


[Efficacy of coarctation resection and aortoplasty with autologous pulmonary artery patch strategy for treating coarctation of the aorta combined with hypoplastic aortic arch in infants].
Objective: To investigate the outcomes of coarctation resection and aortoplasty with autologous pulmonary artery patch for treating coarctation of the aorta combined with hypoplastic aortic arch in infants. Methods: Clinical data of 21 infants with coarctation of the aorta and hypoplastic aortic arch, who underwent coarctation resection and aortoplasty with autologous pulmonary artery patch in Fuwai hospital from January 2009 to June 2016 were retrospectively analyzed. The age of the patients was 4 (2, 5) months,and the body weight of the patients was (5.3±1.6) kg. The patients were followed up to observe the surgery effect. Results: No perioperative death and serious complications occurred. When the patients were discharged,the systolic blood pressure of the right upper limb was lower than the preoperative systolic blood pressure ((85.7±5.9) mmHg(1 mmHg=0.133 kPa) vs. (100.7±16.6) mmHg, P<0.001),and the systolic blood pressure of the right lower limb was higher than the preoperative systolic blood pressure ((98.7±13.3) mmHg vs. (85.6±20.8) mmHg, P<0.001). The pressure gradient of aortic coarctation detected by echocardiography was lower than the preoperative pressure gradient ((13.1±3.8) mmHg vs. (46.2±17.1) mmHg, P<0.001). No restenosis was detected by echocardiography at discharge. Follow-up data were obtained in 19 patients, and the follow-up time was 18 (8, 45) months.The patients grew well, and no death occurred. Restenosis occurred in 3 cases, 1 patient underwent aortic balloon dilatation and the remaining 2 patients were under follow up observation. Computed tomography angiography showed that the morphology of aortic arch was normal without signs of aortic aneurysm. Conclusion: Coarctation resection with autologous pulmonary artery patch aortoplastystrategy is considered as a safe and effective surgical method for management of infant coarctation with hypoplastic aortic arch, and this surgery method is related with satisfactory early and mid-term outcomes in this patient cohort.


Expression of the metastasis suppressor KAI1 in decidual cells at the human maternal-fetal interface: Regulation and functional implications.
At the human maternal-fetal interface, the decidua forms a dense matrix that is believed to limit trophoblast invasion. We investigated whether the metastasis suppressor KAI1 (CD82) is expressed at the maternal-fetal interface. Immunohistochemistry showed strong expression of KAI1 in decidual cells, whereas trophoblast cells were negative for KAI1. In luteal phase endometrium, KAI1 was present in decidualizing endometrial stromal cells. We investigated whether KAI1 expression in endometrial stromal cells is regulated by the decidualizing stimuli cAMP and progesterone or by the cytokine interleukin (IL)-1beta. Western blot analysis revealed induction of KAI1 protein by cAMP analog, but not by progesterone, in a delayed fashion. In contrast, IL-1beta rapidly stimulated KAI1 expression at the transcript level and at the protein level. Cultured decidual cells from term placenta expressed a basal level of KAI1 protein that was elevated on cAMP stimulation. Silencing of KAI1 by RNA interference attenuated expression of decorin, a decidual product implicated in limiting trophoblast invasion. This study shows for the first time the expression of KAI1 in decidual cells at the human maternal-fetal interface, where the metastasis suppressor might participate in intercellular communication with trophoblast cells and the control of trophoblast invasion.


Inhibition of ribonucleic acid polymerase by a bacteriocin from Bacteroides fragilis.
The Bacteroides fragilis bacteriocin which inhibits ribonucleic acid (RNA) polymerase activity had a narrow activity spectrum in vivo and only inhibited the growth of certain B. fragilis strains. In vitro the bacteriocin was not specific and inhibited RNA polymerases from widely diverse bacterial genera. RNA polymerases from rifampin-resistant strains of Bacteroides thetaiotaomicron and Clostridium acetobutylicum were resistant to the bacteriocin in vitro. Purified bacteriocin bound to partially purified RNA polymerase, and both proteins were cosedimented in a glycerol gradient. In the RNA polymerase reaction, the bacteriocin acted as a competitive inhibitor for adenosine, cytidine, and uridine 5'-triphosphates and as a noncompetitive inhibitor for guanosine 5'-triphosphate. The bacteriocin did not inhibit RNA polymerase from chicken embryos.


Local Administration of Interleukin-1 Receptor Antagonist Improves Diabetic Wound Healing.
Impaired healing of the skin is a notable cause of patient morbidity and mortality. In diabetic individuals, dysregulated inflammation contributes to delayed wound healing. Specific immunomodulatory agents may have a role in the treatment of diabetic wounds. One of these molecules is interleukin-1 receptor antagonist (Anakinra; Amgen Corp.). Although interleukin-1 receptor antagonist (Anakinra; Amgen Corp.) is approved by the Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis and neonatal-onset multisystem inflammatory disease, little is known about the local use this drug in cutaneous wound healing. Therefore, the aim of this study is to determine the effect of locally administered interleukin-1 receptor antagonist on delayed wound healing, specifically, in a diabetic mouse model. Two 6-mm full-thickness wounds were created on the dorsa of diabetic (db/db) mice and stented. One-hour postwounding, wound margins were subcutaneously injected with either (1) low-dose interleukin-1 receptor antagonist in a gelatin-transglutaminase gel vehicle or (2) the gel vehicle only. Wounds were imaged on days 0, 7, 14, and 21 postwounding, and wound area was determined. Wound biopsies were collected on day 21 and immunohistochemically stained for neutrophil and macrophage infiltration. Wounds treated with interleukin-1 receptor antagonist had significantly smaller wound area than nontreated wounds on day 7 and day 14 postwounding. Treated wounds also showed significantly less neutrophil and macrophage infiltration. These findings support the hypothesis that interleukin-1 receptor antagonist may have an important role in cutaneous wound healing, possibly by promoting successful resolution of acute inflammation and hence accelerating wound closure. Thereby, administration of IL-1Ra may be useful in the treatment of nonhealing wounds.


Metabolic and Risk Profiles of Lean and Non-Lean Hepatic Steatosis among US Adults.
Hepatic steatosis can occur in lean individuals, while its metabolic and risk profiles remain unclear. We aimed to characterize the clinical and risk profiles of lean and non-lean steatosis. This cross-sectional study included 1610 patients with transient elastography-assessed steatosis. The metabolic and risk profiles were compared. Compared to their non-lean counterparts, lean subjects with steatosis had a lower degree of fibrosis (F0-F1: 91.9% vs. 80.9%), had a lower prevalence of diabetes (27.9% vs. 32.8%), dyslipidemia (54.7% vs. 60.2%) and hypertension (50.0% vs. 51.3%), and had higher levels of high-density lipoprotein cholesterol while lower fasting insulin and homeostatic model assessment for insulin resistance (all p < 0.05). Of the 16 potential risk factors, being Hispanic was associated with higher odds of non-lean steatosis but not with lean steatosis (odds ratio (OR): 2.07 vs. 0.93), while excessive alcohol consumption had a different trend in the ratio (OR: 1.47 vs.6.65). Higher waist-to-hip ratio (OR: 7.48 vs. 2.45), and higher waist circumference (OR: 1.14 vs. 1.07) showed a stronger positive association with lean steatosis than with non-lean steatosis (all Pheterogeneity < 0.05). Although lean individuals with steatosis presented a healthier metabolic profile, both lean and non-lean steatosis had a significant proportion of metabolic derangements. In addition, the etiological heterogeneity between lean and non-lean steatosis may exist.


Human acute myelogenous leukemia stem cells are rare and heterogeneous when assayed in NOD/SCID/IL2Rγc-deficient mice.
Human leukemic stem cells, like other cancer stem cells, are hypothesized to be rare, capable of incomplete differentiation, and restricted to a phenotype associated with early hematopoietic progenitors or stem cells. However, recent work in other types of tumors has challenged the cancer stem cell model. Using a robust model of xenotransplantation based on NOD/SCID/IL2Rγc-deficient mice, we confirmed that human leukemic stem cells, functionally defined by us as SCID leukemia-initiating cells (SL-ICs), are rare in acute myelogenous leukemia (AML). In contrast to previous results, SL-ICs were found among cells expressing lineage markers (i.e., among Lin+ cells), CD38, or CD45RA, all markers associated with normal committed progenitors. Remarkably, each engrafting fraction consistently recapitulated the original phenotypic diversity of the primary AML specimen and contained self-renewing leukemic stem cells, as demonstrated by secondary transplants. While SL-ICs were enriched in the Lin-CD38- fraction compared with the other fractions analyzed, SL-ICs in this fraction represented only one-third of all SL-ICs present in the unfractionated specimen. These results indicate that human AML stem cells are rare and enriched but not restricted to the phenotype associated with normal primitive hematopoietic cells. These results suggest a plasticity of the cancer stem cell phenotype that we believe has not been previously described.


Endodontic and periodontal treatments of a geminated mandibular first premolar.
To describe a rare case of gemination involving a mandibular first premolar. The complex morphology of geminated teeth renders their endodontic and periodontal management difficult. Root canal and periodontal treatments were performed on a geminated mandibular first premolar with three canals. Clinical examination showed two separated crowns with united roots. Radiographically, two distinct pulp chambers with two joined and a third independent canal were seen. Conventional root canal treatment resulted in complete healing of the apical lesion. However, the occurrence of a vertical fracture led to the extraction of the mesial segment. At the follow-up visit, the distal segment was clinically healthy and continued to satisfy functional demands.


Patch clamp studies of the amphibian nephron.
Transepithelial transport, intracellular ion activities and membrane potentials are all affected by changes in the conductive properties of the membranes of polarised epithelial cells. Conventional electrophysiological techniques have already determined the major conductances of the apical and basolateral membranes of the various nephron segments. These conductances are presently being studied at the molecular level with the aid of the patch clamp technique. In the case of the amphibian nephron, single-channel studies have been carried out in the proximal and early distal (diluting) segments. Almost all of the channels described so far have been selective for potassium, and the properties of these channels are described in this review. In addition, the basic electrophysiological and transport properties of these two general nephron segments are briefly described. From the physiological stand-point, the results of single-channel studies are providing us with information concerning the regulation of the conductances by intracellular mediators, allowing us to make predictions about the effects of various perturbations on cell membrane conductances. On the other hand, biophysical analysis is giving information ranging from the voltage dependence and ion selectivity of the channels to clues concerning their submicroscopic structure.


Complete Genome Sequence of a Novel Variant Strain of Peste des Petits Ruminants Virus, China/XJYL/2013.
Here, we announce the complete genome sequence of a novel variant strain of peste des petits ruminants virus, termed China/XJYL/2013. The genome is 15,954 nucleotides long with a 6-nucleotide insertion in the 5' untranslated region of the F gene. This strain is phylogenetically classified as a lineage IV virus.


An improved technique for prolonged arterial catheterization in infants and children.
Arterial catheterization for blood gas analysis and direct monitoring of blood pressure in infants and children can be attended by a variety of complications, which limit its use to short periods of time. An improved technique, consisting of elimination of stopcocks, the use of a continuous flushing system adapted for infants and children, and meticulous care of the system, was used in 57 children whose ages ranged from the neonatal period to 16 years. The mean duration of cannulation was 5.5 days (range, 1-31 days). All but one of the catheters were functional at the time of discontinuation. There were no thromboembolic phenomena, local or systemic infections or accidental bleeding. We feel that our approach to prolonged arterial cannulation can be an extremely valuable aid in the management of critically ill children.


Interaction of BMP10 with Tcap may modulate the course of hypertensive cardiac hypertrophy.
Elevated wall stress by hypertension induces an adaptive myocardial hypertrophy via releasing prohypertrophic hormones such as angiotensin II. In this study, we investigated the involvement of bone morphogenetic protein-10 (BMP10) in hypertension-induced cardiac hypertrophy. Expression of BMP10 was increased in the hypertrophied ventricles from hypertensive rats. BMP10 localized on cell surface and at stretch-sensing Z disc of cardiomyocytes, where BMP10 interacted with a protein called titin-cap (Tcap). A rare variant of the human BMP10 gene, Thr326Ile, was found to be associated with hypertensive dilated cardiomyopathy. The variant BMP10 demonstrated decreased binding to Tcap and increased extracellular secretion. Conditioned medium from cells transfected with wild-type or variant BMP10 induced hypertrophy in rat neonatal cardiomyocytes, except that medium from variant BMP10-carrying cells showed an enhanced effect reflecting the increased secretion. These observations suggested that hypertension induced expression of prohypertrophic BMP10, and the hypertrophic effect of BMP10 was modulated, at least in part, by its binding to Tcap at the Z disc.


Enzyme-free, signal-amplified nucleic acid circuits for biosensing and bioimaging analysis.
Enzyme-free, signal-amplified nucleic acid circuits utilize programmed assembly reactions between nucleic acid substrates to transduce a chemical input into an amplified detection signal. These circuits have shown great potential for developing biosensors for high-sensitivity and high-selectivity detection of varying targets including nucleic acids, small molecules and proteins in vitro and for high-contrast in situ visualization and imaging of these targets in tissues and living cells. We review the background of the enzyme-free, signal-amplified nucleic acid circuits, including their mechanism, significance, types and development. We also review current applications of these circuits for biosensors and bioimaging.


Organizational Justice and Employee Readiness for Change: The Mediating Role of Perceived Organizational Support.
Recent studies have shown that an organization must adapt to change to succeed in a constantly changing market. However, most change efforts fail due to employee resistance to change. It is critical to address employee readiness for change to avoid employee resistance. Employees' perceptions of fair treatment by their organizations have positively predicted their Readiness for organizational change. This research aims to investigate the influence of organizational justice on employee readiness for change using perceived organizational support (POS) as a mediator. This study was carried out on the Ethiopian Revenue and Customs Authority (ERCA) and conducted with 359 employees. The study used a structural equation model and multiple regression analysis to analyze the data. The model developed explains how POS mediates the positive relationship between organizational justice and employee readiness for change. The result shows that organizational justice is a significant influencing factor on employee readiness for change. Furthermore, POS mediates the positive influence of organizational justice on employee readiness for change. This study can assist public and private organizations, as well as policymakers and practitioners, in improving and encouraging different organizational change practices in Ethiopia. Moreover, this study can also contribute to the literature on organizational change by filling the gaps in the relationship between organizational justice and employees' Readiness for organizational change. Overall, this study concludes that organizations in Ethiopia, including ERCA, should investigate the influence of organizational justice on employee readiness for change to have successful organizational change.


Analytical prediction of the breakout noise from a rectangular cavity with one compliant wall.
This paper describes an analytical calculation of breakout noise by incorporating three-dimensional effects along with the acoustical and structural wave coupling phenomena. The breakout noise phenomena from cavities are important at low frequencies, and the coupling between acoustic waves and structural waves plays a critical role in prediction of the transverse transmission loss. The first step in the breakout noise prediction is to calculate the inside cavity pressure field and the normal cavity wall vibration by using an impedance-mobility approach, which results in a compact matrix formulation. The second step is to calculate the radiated sound power from an unbaffled plate formulation that poses formidable challenges on computational time. The proposed formulation helps in reducing the computational time substantially by converting quadruple integrals into single integrals using an appropriate coordinate transformation technique. Analytical results are validated with the finite element/boundary element numerical models.


Comparison of Balloon Dilation and Laser Eustachian Tuboplasty in Patients with Eustachian Tube Dysfunction: A Meta-analysis.
Objective We aimed to perform a meta-analysis examining balloon dilatation and laser tuboplasty for the treatment of eustachian tube dysfunction (ETD). Data Sources PubMed, Cochrane, and Embase search up to April 18, 2016, with the following keywords: eustachian, middle-ear, eustachian tuboplasty, balloon tuboplasty, laser tuboplasty, laser dilatation, and balloon dilatation. Review Methods Randomized controlled trials and prospective, retrospective, and 1-arm studies of patients with ETD treated with balloon dilatation or laser tuboplasty were included. Outcome measures were improvement of eustachian tube score (ETS) and tympanometry and Valsalva maneuver results. Results Two retrospective and 11 prospective studies were included (1063 patients; 942 treated with balloon and 121 with laser tuboplasty). Balloon tuboplasty resulted in a significant improvement of ETS (pooled standardized mean difference [SMD], 0.94; 95% confidence interval [CI], 0.23-1.66; P = .009) and, compared with laser tuboplasty, a greater tympanometry improvement rate (pooled event rate = 73% vs 13%; P = .001). Valsalva maneuver improvement rate was not different between the group results (pooled event rate = 67% vs 50%; P = .472). The maximum number of studies that provided outcome data for any one measure was only 4, and sensitivity analysis indicated ETS results may have been overly influenced by 2 studies. No balloon tuboplasty studies reported ETS data, preventing comparison between the 2 procedures. Conclusion Both procedures can improve symptoms of ETD; however, because of the limited numbers of studies reporting data of the outcomes of interest, it remains unclear if one procedure provides greater benefits.


Human T-lymphotropic virus type-1 (HTLV-1) in Israeli patients and their family relatives and its transmission to rats.
We tested the possibility that lymphocytes, sera and saliva, obtained directly from healthy human T-lymphotropic virus type 1 (HTLV-1) carriers and patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) of Iranian Mashhadi origin, as well as lymphocytes from patients with mycosis fungoides (MF) and their family relatives (MFR), may be infective. Peripheral blood mononuclear cells (PBMC), sera, PBMC cultured with phytohaemagglutinin A and phorbol myristate acetate, cell-free supernatant from these cultures, saliva cells and cell-free saliva were injected into adult WKA (n=107) and F344 (n=47) female rats. The appearance of anti-HTLV-1 antibodies in the rat sera was tested by particle agglutination assay and ELISA, and positive results were confirmed by western blot assay. Higher titers (1:1024) of anti-HTLV-1 antibodies were found in the F344 rats as compared to the WKA rats (1:256). The PA agglutination test was the most sensitive for the detection of HTLV-1 antibody. The HTLV-1 provirus was detected in both strains of rats infected with body fluids and cells from the Iranian Mashhadi Jews, in various organs (PBMC, spleen, thymus, salivary glands, spinal cord, kidney and brain) by nested PCR. However, the HTLV-1 provirus was not detected in 100% of the rats. The negative rats were only immunized and not infected. The spleen, thymus, spinal cord and salivary glands of the seropositive rats were found to be infectious and to transmit the HTLV-1 to healthy rats. F344 rats infected with PBMC cultures obtained from HTLV-1 antibody positive MF patients and their MFR who were only 20% positive showed anti-HTLV-1 antibodies, but only in 20% of rats without showing the HTLV-1 provirus; these rats were probably not infected but only immunized. This is one of the few studies on the transmission of HTLV-1 to rats by inoculation with human infectious fluids or cells from HTLV-1 infected healthy carriers (42%), HAM/TSP patients of Iranian Mashhadi origin (58%) as well as lymphocyte cultures obtained from HTLV-1 antibody positive MF and MFR of nonIranian origin.


Insulin analogues in pregnancy and specific congenital anomalies: a literature review.
Insulin analogues are commonly used in pregnant women with diabetes. It is not known if the use of insulin analogues in pregnancy is associated with any higher risk of congenital anomalies in the offspring compared with use of human insulin. We performed a literature search for studies of pregnant women with pregestational diabetes using insulin analogues in the first trimester and information on congenital anomalies. The studies were analysed to compare the congenital anomaly rate among foetuses of mothers using insulin analogues with foetuses of mothers using human insulin. Of 29 studies, we included 1286 foetuses of mothers using short-acting insulin analogues with 1089 references of mothers using human insulin and 768 foetuses of mothers using long-acting insulin analogues with 685 references of mothers using long-acting human insulin (Neutral Protamine Hagedorn). The congenital anomaly rate was 4.84% and 4.29% among the foetuses of mothers using lispro and aspart. For glargine and detemir, the congenital anomaly rate was 2.86% and 3.47%, respectively. No studies on the use of insulin glulisine and degludec in pregnancy were found. There was no statistically significant difference in the congenital anomaly rate among foetuses exposed to insulin analogues (lispro, aspart, glargine or detemir) compared with those exposed to human insulin or Neutral Protamine Hagedorn insulin. The total prevalence of congenital anomalies was not increased for foetuses exposed to insulin analogues. The small samples in the included studies provided insufficient statistical power to identify a moderate increased risk of specific congenital anomalies.


Enhanced catalytic performance of copper-exchanged SAPO-34 molecular sieve in methanol-to-olefin reaction.
Methanol-to-olefin (MTO) reaction over copper-exchanged SAPO-34 catalysts was investigated in order to extend their catalyst life. The exchange of copper ions into the cages of an SAPO-34 molecular sieve was confirmed by ESR, XPS, and 129Xe NMR techniques. Copper ions located in its cages considerably reduced its deactivation rate in the MTO reaction, while those dispersed on the external surface of the SAPO-34 molecular sieve accelerated the deactivation due to the limited mass transfer through the pore entrances. The 13C NMR and UV-VIS spectroscopy investigations of the materials occluded on the copper-exchanged SAPO-34 catalysts during the MTO reaction clearly showed that the copper ions exchanged in the cages suppressed the further condensation of alkyl aromatics to large, fused polycyclic aromatic hydrocarbons (PAHs). Theoretical calculations for the SAPO-34 and copper-exchanged SAPO-34 molecular sieves supported this observation because copper ions located in the cages stabilized the alkyl aromatics. Therefore, the exchange of copper ions into the SAPO-34 molecular sieve stabilized the reactive intermediates, alkyl aromatics, of the MTO reaction and suppressed their further condensation to PAHs, thereby slowing the deactivation.


Inequality and redistribution behavior in a give-or-take game.
Political polarization and extremism are widely thought to be driven by the surge in economic inequality in many countries around the world. Understanding why inequality persists depends on knowing the causal effect of inequality on individual behavior. We study how inequality affects redistribution behavior in a randomized "give-or-take" experiment that created equality, advantageous inequality, or disadvantageous inequality between two individuals before offering one of them the opportunity to either take from or give to the other. We estimate the causal effect of inequality in representative samples of German and American citizens (n = 4,966) and establish two main findings. First, individuals imperfectly equalize payoffs: On average, respondents transfer 12% of the available endowments to realize more equal wealth distributions. This means that respondents tolerate a considerable degree of inequality even in a setting in which there are no costs to redistribution. Second, redistribution behavior in response to disadvantageous and advantageous inequality is largely asymmetric: Individuals who take from those who are richer do not also tend to give to those who are poorer, and individuals who give to those who are poorer do not tend to take from those who are richer. These behavioral redistribution types correlate in meaningful ways with support for heavy taxes on the rich and the provision of welfare benefits for the poor. Consequently, it seems difficult to construct a majority coalition willing to back the type of government interventions needed to counter rising inequality.


Targeted molecular ablation of cancer stem cells for curing gastrointestinal cancers.
Abundance of the ATPase-binding cassette (ABC) transporters and deranged self-renewal pathways characterize the presence of cancer stem cells (CSCs) in gastrointestinal cancers (GI cancers), which play crucial roles in tumorigenesis, chemotherapy resistance, tumor recurrence, and cancer metastasis. Therefore, in order to ensure high cure rates, chemoquiescence, CSCs should be ablated. Recent advances in either understanding CSCs or biomarker identification enable scientists to develop techniques for ablating CSCs and clinicians to provide cancer cure, especially in GI cancers characterized by inflammation-driven carcinogenesis. Areas covered: A novel approach to ablate CSCs in GI cancers, including esophageal, gastric, and colon cancers, is introduced along with explored underlying molecular mechanisms. Expert commentary: Though CSC ablation is still in the empirical stages and not in clinical practice, several strategies for ablating CSCs in GI cancers had been published, proton-pump inhibitors (PPIs) that regulate the membrane-bound ABC transporters, which underlie drug resistance; chloroquine (CQ) that inhibits autophagy, which is responsible for tumor survival; Hedgehog/Wnt/Notch inhibitors that influence the underlying stem-cell growth, and some natural products including Korean red ginseng, cancer-preventive kimchi, Artemisia extract, EGCG from green tea, and walnut extracts.


Synthesis of highly substituted furans by the electrophile-induced coupling of 2-(1-alkynyl)-2-alken-1-ones and nucleophiles.
[reaction: see text] The coupling of 2-(1-alkynyl)-2-alken-1-ones with nucleophiles, either catalyzed by AuCl3 or induced by an electrophile, provides highly substituted furans in good to excellent yields under very mild reaction conditions. Various nucleophiles, including functionally substituted alcohols, H2O, carboxylic acids, 1,3-diketones, and electron-rich arenes, and a range of cyclic and acyclic 2-(1-alkynyl)-2-alken-1-ones readily participate in these cyclizations. Iodine, NIS, and PhSeCl have proven successful as electrophiles in this process. The resulting iodine-containing furans can be readily elaborated to more complex products using known organopalladium chemistry.


The regeneration with ascorbate of Helix pomatia methaemocyanin mediated by hydrogen peroxide.
The regeneration of the copper bands of H. pomatia haemocyanin proceeds much more slowly with an excess of ascorbate than with a slight excess of hydrogen peroxide. The regenerating agent with ascorbate is hydrogen perioxide, formed in its autoxidation at the air. This was concluded after regeneration experiments with ascorbate under strictly anaerobic conditions and at the air in the presence of catalase. The autoxidation of ascorbate was catalysed by Fe and Cu ions. In the presence of EDTA there is still metal catalysis, especially in slightly alkaline medium, due to the Fe(III)-EDTA complex. Addition of diethylenetriamine pentaacetate completely abolished the metal catalysis.


Acoustic tracking of fin whales: Habitat use and movement patterns within a Canadian Pacific fjord system.
Fin whale 20 Hz calls were detected, localized, and tracked using a 10 km aperture network of three acoustic receivers deployed for 11 months in a Pacific Canadian fjord system. The area has been historically important for fin whales and is located along a route that tankers will begin using in 2024. A total of 6712 calls were localized, and trajectories were fitted for 55 acoustic tracks. Fin whale tracks occurred throughout the monitoring site. Call activity peaked in September and was low during winter months. Swimming characteristics varied significantly between day- and nighttime: at night, whales swam faster (7.1 vs 4.0 km/h median, +75.2%), which resulted in longer (+34.7%), less predictable (-70.6%) tracks as compared to daylight hours. Call frequencies varied between 16 and 32 Hz. Beside stereotypical song frequencies, fin whales also used irregular frequency components, which contributed the majority of calls in the summer but did not occur in the winter. The results suggest that the area is primarily used as a summer feeding ground, where fin whales follow a diel behavioral cycle. The observed activity patterns will aid in the assessment of strike risk and harassment mitigation and provide a baseline to document behavioral change.


Examining associations between value-behavior discrepancy guilt, anxiety, and suicide risk for Mexican descent college students: Resilience through self-compassion.
The present study examines self-compassion (SC) as a potential protective factor in the relationship between value-behavior discrepancy guilt (VBDG) and the mental health outcomes of anxiety and suicide risk in a sample of Mexican-descent college students. Participants consisted of 810 college students of Mexican descent. Students were recruited through a psychology participant pool and completed an online survey. Two regression analyses examined the direct effect of VBDG on anxiety symptoms and suicide risk with SC as a moderator. Results indicated that high levels of SC were protective in the relationship between VBDG and mental health outcomes. On the other hand, lower levels of SC put one at risk for increased anxiety symptoms and higher suicide risk when they experience VBDG. The study shows the need to develop interventions that cultivate a high sense of SC in Mexican-descent college students.


Pretreatment changes in drinking: Theoretical and methodological implications for alcohol use disorder treatment outcome research.
There is a growing recognition of the importance of changes in drinking prior to the first treatment session (i.e., pretreatment change). A major limitation of past studies of pretreatment change is the reliance on retrospective reporting on drinking rates between the baseline assessment and the first treatment session collected at the end of treatment. The present study sought to extend previous findings by examining 12-month treatment outcomes and correlates of pretreatment changes in drinking measured weekly during treatment. Data from a randomized behavioral clinical trial examining the effect of therapeutic alliance feedback on drinking outcomes were analyzed (n = 165). All participants received cognitive behavioral therapy for alcohol dependence, completed pre and posttreatment assessments, and provided weekly measures of drinking during treatment. Results indicated that approximately half of the sample reduced their heavy drinking days by 70% or more and number of drinking days by 50% or more prior to beginning treatment. Further, individuals who reported greater consideration of how their problematic drinking affected their social environment displayed greater changes in drinking days prior to treatment. Changes in heavy drinking days were also related to relationship status, such that individuals who were single/never married were less likely to change prior to treatment than those who were married/cohabitating or separated/divorced. These confirm the importance of pretreatment change in the study of treatment outcomes, and suggest that interpersonal processes, including the appraisal of drinking behavior in a social context, may play an important role in pretreatment changes in drinking.


Nanoparticles-cell association predicted by protein corona fingerprints.
In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a "protein corona" layer. The long-lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (Ø≈ 100-250 nm) and surface chemistry (unmodified and PEGylated) to investigate the relationships between NP physicochemical properties (nanoparticle size, aggregation state and surface charge), protein corona fingerprints (PCFs), and NP-cell association. We found out that none of the NPs' physicochemical properties alone was exclusively able to account for association with human cervical cancer cell line (HeLa). For the entire library of NPs, a total of 436 distinct serum proteins were detected. We developed a predictive-validation modeling that provides a means of assessing the relative significance of the identified corona proteins. Interestingly, a minor fraction of the HC, which consists of only 8 PCFs were identified as main promoters of NP association with HeLa cells. Remarkably, identified PCFs have several receptors with high level of expression on the plasma membrane of HeLa cells.


GABA(B) receptor-mediated increase of neurosteroids by gamma-hydroxybutyric acid.
Among the pharmacological actions of gamma-hydroxybutyric acid (GHB), some may involve GABA(A) receptor-mediated mechanisms. GHB, however, fails to directly interact with sites for agonists and modulators on the GABA(A) receptor complex. We hypothesized that, in vivo, GHB may interfere with GABA(A) receptor function by altering the brain concentrations of the neurosteroids 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone, AP) and 3 alpha,21-dihydroxy-5 alpha-pregnan-20-one (allotetrahydrodeoxycorticosterone, THDOC), positive allosteric modulators of GABA-gated chloride currents. In male Wistar rats, GHB dose-dependently (75-1000 mg/kg, i.p.) increased AP, THDOC and their precursors pregnenolone and progesterone in brain cortex and hippocampus. The increases of AP (4-5 fold) and THDOC (3-4 fold) elicited by 300 mg/kg GHB peaked between 30 and 90 min and abated by 180 min. The selective GABA(B) receptor antagonist SCH 50911 (50 mg/kg, i.p.) prevented the action of GHB, while the GABA(B) receptor agonist baclofen (5-10 mg/kg) mimicked it. NCS-382 (50 mg/kg, i.p.), the purported selective antagonist of the GHB receptor, failed to antagonize GHB, but at 300 mg/kg increased brain cortical neurosteroids to the same extent as 300 mg/kg GHB; coadministration of GHB and NCS-382, however, failed to yield an additive effect. These results strongly suggest that GHB, via a GABA(B) receptor-mediated mechanism, increases the brain concentrations of neurosteroids, whose properties as amplifiers of the GABA-gated chloride conductances may play a role in the GABA(A) receptor-mediated pharmacological actions of GHB.


Lung congestion in chronic heart failure: haemodynamic, clinical, and prognostic implications.
The goal of the study was to examine the prognostic impact, haemodynamic and clinical features associated with lung congestion in patients with chronic heart failure (HF). HF patients (n = 186) and HF-free controls (n = 21) underwent right heart catheterization, echocardiography, pulmonary function testing and chest radiography that was blindly scored for the presence and severity of lung oedema. Lung congestion correlated directly with pulmonary vascular resistance (PVR, P = 0.004) and inversely with pulmonary artery (PA) compliance (P < 0.001) and the diffusion limit for carbon monoxide (DLCO , P = 0.009). Compared with dry lung HF, wet lung HF patients (congestion score > median) had 25% lower PA compliance and 25-35% higher PVR, transpulmonary gradients and PA pressures (40 vs. 32 mmHg, P < 0.001) despite marginally higher PA wedge pressure (PAWP; 22 vs. 19 mmHg, P = 0.002). Wet lung HF patients displayed more right ventricular (RV) dilatation and dysfunction, more restrictive ventilation and greater reduction of DLCO . The strongest correlates of lung congestion were NT-proBNP, haemoglobin, albumin, and glomerular filtration, all surpassing PAWP. After a median of 333 days (interquartile range 80-875), 59 patients (32%) died. Lung congestion was associated with reduced survival (P < 0.0001), even after adjusting for PAWP, NT-proBNP, anaemia, CAD and renal dysfunction. Interstitial lung oedema is associated with pulmonary vascular disease, RV overload and dysfunction and increased mortality in HF. These data reinforce the importance of aggressive decongestion in HF and suggest that novel agents aimed at reducing lung water may help to deter progression of pulmonary vascular disease and biventricular HF.


Proteinases as Biomarkers in Breast Cancer Prognosis and Diagnosis.
Breast cancer is the second leading cause of cancer-related deaths among women in the Western World. Upon diagnosis and treatment in the preinvasive state, the five years survival rate levitate up to 93%, making early detection crucial for dedicative diagnosis and treatment. Currently, mammography is the most efficacious diagnostic modality. However, this technique does not match the ultimate sensitivity. Other routinely used biomarkers include tumor size, histological type, nuclear and cellular characteristics, mitotic index, vascular invasion, hormonal and axillary lymph node status were not good enough to predict the course of cancer. To date, researchers revealed a change in the level of some proteinases in breast cancer tissue and reported the role of these proteinases in tumor aggressiveness and patient response to therapy. This review summarizes the potential role of serine proteinases (including urokinasedependent plasminogen activator and kallikreins) and zinc metalloproteinases (including matrix metalloproteinase and A disintegrin and metalloproteinase) as either a prognostic and/or diagnostic breast cancer biomarkers. These proteinases plus genetic biomarkers could be implemented in the development of multiplex bio sensing platform toward early breast cancer detection, diagnosis, monitor progression and therapeutic success.


Academy of Nutrition and Dietetics: Revised 2012 Standards of Practice in Nutrition Care and Standards of Professional Performance for Registered Dietitians.
RDs face complex situations every day. Competently addressing the unique needs of each situation and applying standards appropriately is essential to providing safe, timely, person-centered quality care and service. All RDs are advised to conduct their practice based on the most recent edition of the Academy's Code of Ethics and the Scope of Practice in Nutrition and Dietetics, the Scope of Practice for the Registered Dietitian, the 2012 Standards of Practice in Nutrition Care and Standards of Professional Performance for RDs, and the applicable focus area SOP and SOPP for RDs. These resources provide minimum standards and tools for demonstrating competence and safe practice, and are used collectively to gauge and guide an RD's performance in nutrition and dietetics practice. The SOP and SOPP for the RD are self-evaluation tools that promote quality assurance and performance improvement. Self-assessment provides opportunities to identify areas for enhancement, new learning, and skill development, and to encourage progression of career growth. All RDs are advised to have in their personal libraries the most recent copy of the Academy's Scope of Practice in Nutrition and Dietetics and its components: The 2012 Academy Standards of Practice in Nutrition Care and Standards of Professional Performance for Registered Dietitians; applicable focus area SOP and SOPP; the Code of Ethics; and the Scope of Practice for the Registered Dietitian. To ensure that credentialed dietetics practitioners always have access to the most current materials, each resource is maintained on the Academy's website. The documents will continue to be reviewed and updated as new trends in the profession of nutrition and dietetics and external influences emerge.


Association of nutritional risk and adverse medical outcomes across different medical inpatient populations.
The aim of this study was to examine the prevalence of nutritional risk and its association with multiple adverse clinical outcomes in a large cohort of acutely ill medical inpatients from a Swiss tertiary care hospital. We prospectively followed consecutive adult medical inpatients for 30 d. Multivariate regression models were used to investigate the association of the initial Nutritional Risk Score (NRS 2002) with mortality, impairment in activities of daily living (Barthel Index <95 points), hospital length of stay, hospital readmission rates, and quality of life (QoL; adapted from EQ5 D); all parameters were measured at 30 d. Of 3186 patients (mean age 71 y, 44.7% women), 887 (27.8%) were at risk for malnutrition with an NRS ≥3 points. We found strong associations (odds ratio/hazard ratio [OR/HR], 95% confidence interval [CI]) between nutritional risk and mortality (OR/HR, 7.82; 95% CI, 6.04-10.12), impaired Barthel Index (OR/HR, 2.56; 95% CI, 2.12-3.09), time to hospital discharge (OR/HR, 0.48; 95% CI, 0.43-0.52), hospital readmission (OR/HR, 1.46; 95% CI, 1.08-1.97), and all five dimensions of QoL measures. Associations remained significant after adjustment for sociodemographic characteristics, comorbidities, and medical diagnoses. Results were robust in subgroup analysis with evidence of effect modification (P for interaction < 0.05) based on age and main diagnosis groups. Nutritional risk is significant in acutely ill medical inpatients and is associated with increased medical resource use, adverse clinical outcomes, and impairments in functional ability and QoL. Randomized trials are needed to evaluate evidence-based preventive and treatment strategies focusing on nutritional factors to improve outcomes in these high-risk patients.


Current progress in inorganic artificial biomaterials.
In this review, recent advances in bioceramics, metallic biomaterials, and their composites are discussed in terms of their material properties and new medical applications. Porous calcium phosphate ceramics have attracted a lot attention as scaffolds for tissue-engineering purposes since the porous structure allows bone ingrowth. The addition of biodegradable polymers like chitosan, gelatin, and collagen have modified the degradability of the ceramics and their mechanical properties. Titanium (Ti) alloys are being developed for the fabrication of medical devices for the replacement of hard tissue such as artificial hip joints, bone plates, and dental implants because they are very reliable from the viewpoint of mechanical performance. Physical treatment such as grooving or setting a spatial gap on the surface of materials is applicable to improve the apatite formation on the Ti alloys. Blood-compatible polymers such as poly(ethylene glycol) have been successfully fixed on the surface of Ti via chemical bonding by an electrodeposition method. New functions have been explored in Ni-free, Co-Cr-Mo alloys and Mg alloys. In addition, yttrium-containing or phosphorus-containing glass microspheres (20-30 μm in diameter) and ferrimagnetic ceramic particles have exhibited great potential to realize minimally invasive treatment of cancer without surgical operation via in situ radiotherapy or hyperthermia of cancer, but it is still a major challenge to clarify the biological reaction between the artificial implants and living body before their application.


Neonatal Group B Streptococcal Infection in Australia: A Case-control Study.
To determine maternal and neonatal risk factors for, and incidence of, neonatal early-onset group B streptococcus (EOGBS) and late-onset (LOGBS) infection in South Australia (SA) and the Northern Territory (NT). A case-control study with 2:1 matched controls to cases. The study included tertiary hospitals in South Australia and the Northern Territory, Australia. Retrospective data were collected from a 16-year epoch (2000-2015). Of a total of 188 clinically suspected or confirmed cases, 139 were confirmed, of which 56.1% (n = 78) were EOGBS and 43.9% (n = 61) were LOGBS. The incidence of clinically suspected and confirmed cases of EOGBS was 0.26/1000 live births in SA and 0.73/1000 live births in the NT, and the incidence of confirmed cases was 0.19/1000 for SA and 0.36/1000 for the NT. The incidence of clinically suspected or confirmed LOGBS was 0.18/1000 live births in SA and 0.16/1000 for the NT. The majority of infants with GBS presented with sepsis, pneumonia, or meningitis. Developmental delay was the most commonly recorded long-term complication at 1 year old. Risk factors for EOGBS included maternal GBS carriage, previous fetal death, identifying as Aboriginal and/or Torres Strait Islander, and maternal fever in labor/chorioamnionitis. GBS remains a leading cause of neonatal morbidity and mortality. Adding previous fetal death to GBS screening guidelines would improve GBS prevention. The introduction of maternal GBS vaccination programs should be guided by country-specific disease epidemiology.


Proteasome Subunit Beta Type 1 P11A Polymorphism Is a New Prognostic Marker in Multiple Myeloma.
Proteasome subunit beta type 1 (PSMB1) rs12717 polymorphism, a single nucleotide polymorphism with unknown functional effect, was recently reported to influence response to bortezomib-based therapy in follicular lymphoma. We retrospectively analyzed the prognostic impact of this polymorphism in 211 consecutively diagnosed multiple myeloma cases, and performed in vitro experiments to look into its functional consequences. On univariate analysis, patients carrying the variant G allele showed significantly shorter progression-free survival (PFS) with a pattern suggestive of a gene-dose effect (PFS 26.4, 22.3, and 16.4 months in C/C, C/G, and G/G patients, respectively, P = .002). On multivariate analysis, carrying the G/G genotype was a significant independent risk factor for relapse (hazard ratio [HR] 2.29, P < .001) with a similar trend in C/G carriers (HR 1.33, P = .097) when compared with the major allele carrier C/C cohort. Our subsequent in vitro analyses demonstrated significantly reduced protease activity in proteasomes of individuals with G/G genotype compared with that of C/C carriers, despite that PSMB1 expression and proteasome assembly remained unaltered. Bortezomib exhibited a lower inhibitory capacity on the caspase- and trypsin-like activity of proteasomes from G/G individuals. Our results show that carriership of PSMB1 rs12717 minor allele is predictive for suboptimal response with bortezomib treatment, which could be explained by less active proteasomes that are less sensitive to bortezomib, and myeloma cells consequently relying on other escape mechanisms to cope with the abundance of misfolded proteins.


Targeting Solid Lipid Nanoparticles with Anisamide for Docetaxel Delivery to Prostate Cancer: Preparation, Optimization, and In-vitro Evaluation.
The purpose of the current study was to prepare and characterize the targeted solid lipid nanoparticles (SLNs) containing docetaxel (DTX) for prostate cancer treatment. The goal has been achieved by locating anisamide (Anis) ligand on the surface of SLNs, which can interact with the overexpressed sigma receptor on the prostate cancer cells. DTX loaded SLNs were prepared by high shear homogenization and ultra-sonication method and optimized by applying experimental design. The average particle size and the entrapment efficiency of the optimum DTX-SLN were 174 ± 9.1 nm and 83 ± 3.34%, respectively. The results of differential scanning calorimetry showed that DTX had been dispersed as amorphous in the nanocarriers. Scanning electron microscopy (SEM) images confirmed the nanoscale size and spherical shape of the nanoparticles. The cytotoxicity studies have demonstrated that IC50 of free drug, DTX-SLN and DTX-SLN-Anis was 0.25 ± 0.01, 0.23 ± 0.02, 0.12 ± 0.01 nM on PC3 cell line and 20.9 ± 3.89, 18.74 ± 7.43, and 14.68 ± 5.70 nM on HEK293 cell line, respectively. Targeted DTX-SLN-Anis was acted more effectively on prostate cancer cells in comparison to DTX-SLN and free drug. The results of this study have depicted that the anti-cancer drug loaded in targeted SLNs can be a promising way for cancer treatment. In addition, performing in-vivo studies will be complementary to these findings.


Structural, spectroscopic, and computational characterization of the azide adduct of Fe(III)(2,6-diacetylpyridinebis(semioxamazide)), a functional analogue of iron superoxide dismutase.
We have prepared and thoroughly characterized, using X-ray crystallographic, spectroscopic, and computational methods, the diazide adduct of [Fe(III)(dapsox)(H2O)2](+) [dapsox = 2,6-diacetylpyridinebis(semioxamazide)], (1), a low-molecular weight, functional analogue of iron superoxide dismutase (FeSOD). The X-ray crystal structure of the dimeric form of 1, (Na[Fe(III)(dapsox)(N3)2]·DMF)2 (2) shows two axially coordinated, symmetry inequivalent azides with differing Fe-N3 bond lengths and Fe-N-N2 bond angles. This inequivalence of the azide ligands likely reflects the presence of an interdimer hydrogen bonding interaction between a dapsox NH group and the coordinated nitrogen of one of the two azide ligands. Resonance Raman (rR) data obtained for frozen aqueous solution and solid-state samples of 2 indicate that the azides remain inequivalent in solution, suggesting that one of the azide ligands of 1 engages in an intermolecular hydrogen bonding interaction with a water molecule. Density functional theory (DFT) and time-dependent DFT calculations have been used to study two different computational models of 1, one using coordinates taken from the X-ray crystal structure of 2, and the other generated via DFT geometry optimization. An evaluation of these models on the basis of electronic absorption, magnetic circular dichroism, and rR data indicates that the crystal structure based model yields a more accurate electronic structure description of 1, providing further support for the proposed intermolecular hydrogen bonding of 1 in the solid state and in solution. An analysis of the experimentally validated DFT results for this model reveals that the azides have both σ- and π-bonding interactions with the Fe(III) center and that more negative charge is located on the Fe-bound, rather than on the terminal, nitrogen atom of each azide. These observations are reminiscent of the results previously reported for the azide adduct of FeSOD and provide clues regarding the origin of the high catalytic activity of Fe-dapsox for superoxide disproportionation.


Physicians at risk. Some epidemiologic considerations of alcoholism, drug abuse, and suicide.
Physicians are at high risk of addiction by alcohol and other chemicals. The consequences are costly and disastrous, the scope of the problem is grossly underestimated and underreported, treatment is not overwhelmingly favorable, and prevention is even less successful. A modern treatment facility dealing with the problem is described and suggestions are made regarding the underlying issues and policies that face the administrators of training programs and treatment centers. Even more important is the need to persuade physicians to "cherish themselves" and avoid the dangers of "role strain" - two important self-help behavior modifications that may help lessen an important occupational health risk.


Refractive surgery in children: is it ready for prime time?
Potential indications for excimer laser procedures in children include accommodative esotropia, bilateral high ametropia, and severe anisometropia. Treatment of these conditions has traditionally included spectacle or contact lens use. This treatment, however, is often ineffective in children with severe anisometropia or bilateral ametropia, especially those with neuropsychological disorders. Refractive surgery may be a viable treatment option for these conditions. The visual and refractive results from our studies on photorefractive keratectomy for pediatric anisometropic amblyopia are discussed. Also, I will present a review of the world literature on excimer laser procedures for accommodative esotropia, pediatric high anisometropia, and pediatric bilateral high ametropia. In our study, at 36 months follow-up, 7 of 9 patients who were able to perform psychophysical acuity testing preoperatively had improvement of two or more lines of uncorrected visual acuity and 6 of 9 had improvement of two or more lines of best corrected visual acuity. Fifty percent of the myopic patients and 100% of the hyperopic patients were within 2 D of refractive target at the 36-month follow-up visit. Refractive error stability has been good and corneal haze has been minimal. Refractive surgery in children to reduce amblyopiogenic levels of refractive error is proving to be relatively stable. Best corrected and uncorrected visual acuity has also been shown to improve following the excimer laser procedures. Refractive surgery also appears to be effective for pure accommodative esotropia. Randomized clinical trials are needed to fully establish safety and efficacy. Other refractive procedures, such as clear lens extraction and phakic intraocular lenses, may also prove to be valid treatment options for these conditions in the future.


Importance of ADP-ribosylation in the morphological changes of PC12 cells induced by cholera toxin.
Cholera toxin (CTX) is composed of two subunits, subunit A, which possesses ADP-ribosyltransferase activity, and subunit B, which is responsible for receptor binding. It has previously been shown that agents that increase cyclic AMP (cAMP) levels in cells induce differentiation of PC12 cells into neurite-like cells. In this report, we show that as little as 100 pg of CTX per ml induces such changes. CTX was found to ADP-ribosylate at least four membrane proteins of PC12 cells in vitro and in vivo and to increase intracellular cAMP levels. We have developed an inducible ctx gene expression system in Vibrio cholerae by using the tac promoter. The culture medium of the CTX-producing bacteria was able to induce the morphological changes and the ADP-ribosylation of the PC12 cell membrane proteins. We have constructed two CTX-cross-reactive mutant proteins (CTX-CRM) by site-directed mutagenesis. The choice of glutamic acid 29 as the target amino acid was based on sequence similarities with other bacterial toxins. CTX-CRM-E29 delta, in which the Glu-29 of the A subunit was deleted, showed strongly reduced ADP-ribosyltransferase activity and did not induce significant morphological changes of PC12 cells. In contrast, CTX-CRM-E29D, in which the Glu-29 was replaced by an aspartic acid, was as active as the wild-type protein. We conclude that the ADP-ribosylation activity of CTX is important for the toxin-induced differentiation of PC12 cells. Pertussis toxin, which had no visible effect on PC12 cell morphology, was also able to ADP-ribosylate a membrane-bound protein(s) in vitro and in vivo. Pertussis toxin alone did not significantly increase cAMP levels in PC12 cells, but it acted synergistically with CTX.


Comparing Clinical and Radiological Features in Familial and Sporadic Multiple Sclerosis.
Objective To compare the initial presentation, clinical features, disease courses, and radiological parameters between familial multiple sclerosis (fMS) and sporadic multiple sclerosis (sMS) to determine if the two represent distinct clinical entities. Methods This retrospective study was conducted at the Neurology Clinic at Kocaeli University Hospital. Records of 114 fMS and 150 sMS patients, aged 18-65, diagnosed based on either the Poser criteria or the McDonald 2001 criteria were analyzed. Radiological data and Expanded Disability Status Scale (EDSS) evaluations were conducted by a specialist neurologist. Variables included age at MS onset, first symptoms, relapses, EDSS scores at diagnosis and last examination, and MRI findings. Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 28, Armonk, NY) was utilized for data analysis. Results Both fMS and sMS groups were comparable in age (43.55±12.50 and 42.35±10.61 years, respectively) and gender distribution (females: fMS 71.9%, sMS 71.3%). No significant difference was noted regarding disease onset age (fMS 29.83±10.77, sMS 30.42±9.7). Age of onset, final EDSS, and relapse rate didn't significantly vary among sMS, fMS with first-degree relatives having MS (fMS(1)), and fMS with second or third-degree relatives having MS (fMS(2)). The fMS group showed a significantly higher incidence of initial spinal cord lesions on MRI compared to the sMS group (38.6% vs. 17.3%; p<0.001). Within the fMS group, the presence of spinal cord lesions on initial MRI correlated with a higher relapse rate and elevated initial and final EDSS scores. Conclusion Despite overarching similarities between fMS and sMS, spinal cord lesions' prevalence and implications in fMS may point to a genetic underpinning warranting in-depth exploration.


Photo-Crosslinked Coumarin-Containing Bis-Urea Amphiphile Hydrogels.
The design of photo-responsive supramolecular hydrogels based on coumarin dimerization and de-dimerization is described. The photo-responsive coumarin unit is chemically incorporated into an oligo(ethylene glycol) (OEG) bis-urea amphiphile that is capable of co-assembling with non-functionalized OEG amphiphile, to form supramolecular fibers. UV light with two different wavelengths (365 nm and 254 nm) is employed to induce a photo-reversible dimerization and de-dimerization process of coumarin units, respectively. The co-assembled solutions could be photo-crosslinked to induce a sol-to-gel transition through dimerization of coumarin with 365 nm UV light, and de-dimerization occurs with 254 nm UV light, to provide a weaker gel. In this system, the mechanical strength of supramolecular hydrogels can be tuned using the irradiation time, providing precise control of gelation in a supramolecular hydrogelator.


Role of vimA in cell surface biogenesis in Porphyromonas gingivalis.
The Porphyromonas gingivalis vimA gene has been previously shown to play a significant role in the biogenesis of gingipains. Further, in P. gingivalis FLL92, a vimA-defective mutant, there was increased auto-aggregation, suggesting alteration in membrane surface proteins. In order to determine the role of the VimA protein in cell surface biogenesis, the surface morphology of P. gingivalis FLL92 was further characterized. Transmission electron microscopy demonstrated abundant fimbrial appendages and a less well defined and irregular capsule in FLL92 compared with the wild-type. In addition, atomic force microscopy showed that the wild-type had a smoother surface compared with FLL92. Western blot analysis using anti-FimA antibodies showed a 41 kDa immunoreactive protein band in P. gingivalis FLL92 which was missing in the wild-type P. gingivalis W83 strain. There was increased sensitivity to globomycin and vancomycin in FLL92 compared with the wild-type. Outer membrane fractions from FLL92 had a modified lectin-binding profile. Furthermore, in contrast with the wild-type strain, nine proteins were missing from the outer membrane fraction of FLL92, while 20 proteins present in that fraction from FLL92 were missing in the wild-type strain. Taken together, these results suggest that the VimA protein affects capsular synthesis and fimbrial phenotypic expression, and plays a role in the glycosylation and anchorage of several surface proteins.


[Augmentation therapy of resistant schizophrenia with rhythmic transcranial magnetic stimulation].
To identify the clinical efficacy of rhythmic transcranial magnetic stimulation (rTMS) in resistant schizophrenia. The study included 44 male patients with resistant schizophrenia, divided into 4 groups: with depressive (group 1; n=11, 25.0%), with hallucinatory (group 2; n=12, 27.3%), with negative (group 3; n=11, 25.0%) and with delusional symptoms (group 4; n=10, 22.7%). Patients received rTMS, the parameters of which were determined depending on the typological variety, for 3 weeks (15 sessions). Psychometric assessment was carried with PANSS, CGI-S, CGI-I, SANS, CDSS, AHRS when included in the study (0 day), after stimulation (21 days) and by the end of the study (42 day) that allowed evaluation of both the severity of the therapeutic effect and its duration. By the end of the course of stimulation, patients of the first three groups developed a distinct positive effect corresponding to a significant reduction in the total PANSS score: group 1 - 24.4% (p=0.002), group 2 - 8.3% (p=0.02), group 3 - 11.7% (p=0.001), which remained stable by day 42 in patients of the first (p=0.001) and second (p=0.005) groups. In patients with delusional symptoms (group 4), a subpsychotic state developed with a corresponding increase in the total PANSS score by 9.7% (p=0.007) requiring a course of relief therapy, which showed effectiveness by the end of the observation (day 42), indicating that resistance was overcome. The study demonstrated the validity of rTMS as an adjuvant method of treatment in the resistant schizophrenia. To implement the potential of rTMS, it is necessary first of all to take into account the structural features of the condition, as well as to continue improving the stimulation technique itself (increasing the duration of the course, developing supportive courses).


Identification and characterization of heat-stable enterotoxin II-producing Escherichia coli from patients with diarrhea.
Stock strains of Escherichia coli isolated from patients with traveller's diarrhea were examined for production of heat-stable enterotoxin II (STII). Of 400 strains examined, 3 were found to produce STII. The nucleotide sequence of the STII gene of these human strains was shown to be identical to that of porcine strains. Cultured cells of these strains induced fluid accumulation in ligated mouse intestinal loops and the activity was neutralized by anti-STII antiserum. These results suggest that STII-producing enterotoxigenic E. coli can cause human diarrhea.


Hematological aspects of Crimean-Congo hemorrhagic fever.
Crimean-Congo hemorrhagic fever (CCHF) is an acute tick-borne viral disease transmitted to humans by Hyalomma ticks or by direct contact with the blood of infected humans or domestic animals. In certain areas of the world, including Africa, Asia, South East Europe and Middle East, sporadic cases or outbreaks of CCHF have been reported. During the last six-year period from 2003 to 2009, CCHF has also occurred endemically in Turkey, particularly during spring and summer, with a case-fatality rate of approximately 5%. The disease is characterized by acute fever, nausea, vomiting, headache, myalgia, elevated liver enzymes and hemorrhagic manifestations ranging from mucocutaneous bleeding to life-threatening massive hemorrhage with disseminated intravascular coagulation (DIC) and hemophagocytosis. As with other viral hemorrhagic diseases, activation of lymphocytes, monocytes, macrophages and oversecretion of cytokines play a pivotal role in the pathogenesis and prognosis of CCHF. Recently an increasing number of publications on CCHF have been emerging in the literature, majority of which have been written by infection specialists. In this article, recent literature on CCHF has been reviewed, with particular emphasis on hematological manifestations, pathogenesis and therapeutic approaches in CCHF from the hematologist's point of view.


Using Quality Tools and Methodologies to Improve a Hospital's Quality Position.
The authors identify the quality tools and methodologies most frequently used by quality-positioned hospitals versus nonquality hospitals. Northeastern U.S. hospitals in both groups received a brief, 12-question survey. The authors found that 93.75% of the quality hospitals and 81.25% of the nonquality hospitals used some form of process improvement methodologies. However, there were significant differences between the groups regarding the impact of quality improvement initiatives on patients. The findings indicate that in quality hospitals the use of quality improvement initiatives had a significantly greater positive impact on patient satisfaction and patient outcomes when compared to nonquality hospitals.


pH dependence of the partitioning of triphenyltin and tributyltin between phosphatidylcholine liposomes and water.
Triorganotin compounds are very toxic contaminants. The site of their basic mechanism of action of acute toxicity is the biomembrane. Liposome-water distribution ratios of triphenyltin and tributyltin were determined between pH 3 and pH 8 with the equilibrium dialysis method in the micromolar concentration range, which is the concentration range where acute toxicity is observed. In addition, biomembrane-water distribution ratios of tributyltin were determined with chromatophores of Rhodobacter sphaeroides that contain approximately 70% protein intercalated in the lipid bilayer. The liposome-water distribution of both compounds showed only weak pH dependence. For tributyltin, the apparent distribution ratio decreased from 4100 at low pH to 2000 at high pH, while this ratio decreased from 70 000 to 22 000 for TPT. The distribution ratio of the triorganotin cation exceeded that of the neutral hydroxo complex by a factor of 2. The distribution ratio of both the cation and the hydroxo complex of triphenyltin exceeded that of tributyltin by a factor of 10. It is postulated that the sorption of the cation is governed by complex formation with ligands in the phospholipids, presumably the phosphate group. The biomembrane-water distribution ratio of tributyltin was found to be lower than the liposome-water distribution ratio at high pH. The hydroxo complex appears to partition only to the lipid fraction of the biomembrane. Yet, at low pH the biomembrane-water distribution ratio exceeded the liposome-water distribution ratio, which is attributed to complex formation of the cationic species with ligands of the protein fraction.


Inconsistencies in a highly polar capillary gas chromatography column and necessity of column performance checks for trans fatty acid measurement.
GC with a capillary column (60-100 m length) is widely used to measure trans fatty acids in dietary fats and biological tissues. Recently, we have occasionally observed that isothermal operation of an SP-2560 column at 180 degrees C results in incomplete separation of gondoic acid (11c-20:1) and one of the geometric isomers of alpha-linolenic acid (9t,12c,15c-18:3), although it has been known to produce their baseline separation in American Oil Chemists' Society Official Method Ce 1h-05, as well as in previous studies. Thus, trans isomer (9t,12c,15c-18:3) is one of the main components of trans fatty acids in refined edible oils, and the baseline separation of this peak from that of 11c-20:1 is indispensable. We demonstrate in this study that an isothermal operating temperature of 175 degrees C for an SP-2560 column results in satisfactory resolution of these two fatty acids. Because of the inconsistency in the separation provided by SP-2560 columns, careful monitoring of the relative elution order of different fatty acid methyl esters using standards is necessary for the exact evaluation of trans fatty acid contents in oils and fats.


Regulation of lysyl oxidase expression in lung fibroblasts by transforming growth factor-beta 1 and prostaglandin E2.
The regulation of lysyl oxidase produced by cultured, lipid-enriched, neonatal rat lung fibroblasts was explored. The presence of 40 pM of transforming growth factor-beta 1 (TGF-beta 1) in overnight cultures increased levels of enzyme secreted into the medium by 1.6-fold while steady-state levels of lysyl oxidase mRNA increased similarly. In contrast, incubation of these cultures with 100 nM of prostaglandin E2 (PGE2) reduced enzyme activity levels by 40 to 50% although steady-state mRNA was not changed. Consistent with the effect of PGE2, the presence of indomethacin stimulated levels of secreted enzyme activity. When present in cultures simultaneously with TGF-beta 1, PGE2 prevented the stimulation beyond control levels seen with TGF-beta 1 alone. Densitometry of protein bands immunoprecipitated by antibody to lysyl oxidase indicated that the degree of conversion of the 50 kD proenzyme to the 29 kD enzyme was not significantly altered by TGF-beta 1 or PGE2. However, the net accumulation of all forms of lysyl oxidase protein was increased by TGF-beta 1 and decreased by PGE2. These results indicate that TGF-beta 1 and specific prostaglandin(s) exert opposing effects on the expression of lysyl oxidase in these lung fibroblasts.


Impact of modifications in acid development on the insoluble calcium content and rheological properties of Cheddar cheese.
Cheddar cheese was made from milk concentrated by reverse osmosis (RO) to increase the lactose content or from whole milk. Manufacturing parameters (pH at coagulant addition, whey drainage, and milling) were altered to produce cheeses with different total Ca contents and low pH values (i.e., <5.0) during ripening. The concentration of insoluble (INSOL) Ca in cheese was measured by cheese juice method, buffering by acid-base titration, rheological properties by small amplitude oscillatory rheometry, and melting properties by UW-Melt Profiler. The INSOL Ca content as a percentage of total Ca in all cheeses rapidly decreased during the first week of aging but surprisingly did not decrease below approximately 41% even in cheeses with a very low pH (e.g., approximately 4.7). Insoluble Ca content in cheese was positively correlated (r = 0.79) with cheese pH in both RO and nonRO treatments, reflecting the key role of pH and acid development in altering the extent of solubilization of INSOL Ca. The INSOL Ca content in cheese was positively correlated with the maximum loss tangent value from the rheology test and the degree of flow from the UW-Melt Profiler. When cheeses with pH <5.0 where heated in the rheometer the loss tangent values remained low (<0.5), which coincided with limited meltability of Cheddar cheeses. We believe that this lack of meltability was due to the dominant effects of reduced electrostatic repulsion between casein particles at low pH values (<5.0).


Role of Kupffer cells in iodized oil embolization.
Iodized oil is a common oily embolic agent used in chemoembolization for treating hepatic tumors. However, how the iodized oil is cleared from the liver has been an unsettled and controversial issue. In this study, the authors attempt to clarify whether Kupffer cells are involved in the clearance of iodized oil and to evaluate the effect of hepatic arterial injection of iodized oil on the functional status of Kupffer cells. Iodized oil was injected into the proper hepatic artery in 42 Fischer 344 rats. In vivo microscopy was performed immediately after and 1, 3, 7, 15, 30, and 60 days after injection. Electron microscopy was performed after in vivo microscopy. Kupffer cells actively captured and phagocytosed iodized oil droplets in the hepatic circulation. The number and functional status of Kupffer cells in the liver were significantly increased after the injection of the iodized oil and returned to normal when the liver was cleared of the oil. Kupffer cells play an important role in clearing iodized oil from the liver. Iodized oil activates the immune defense system in the liver, which may have a synergistic effect in tumor treatment.


A field study to assess the role of air-water interfacial sorption on PFAS leaching in an AFFF source area.
Field-deployed lysimeters were used to measure the concentrations of poly- and perfluoroalkyl substances (PFASs) in soil porewater at a site historically impacted with aqueous film forming foam (AFFF). Samples collected over a 49-day period showed that perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were the PFASs with the highest concentrations in porewater, with concentrations of approximately 10,000 and 25,000 ng L-1, respectively. The corresponding average mass flux to underlying groundwater observed for PFOS and PFHxS was 28,000 ± 11,000 and 92,000 ± 32,000 ng m-2 d-1, respectively. Employing the use of batch desorption isotherms (soil:water slurries) to determine desorption Kd values resulted in an overestimation of PFAS porewater concentrations by a factor for 1.4 to 4. However, using the desorption Kd values from the batch desorption isotherms in combination with a PFAS mass balance that incorporated PFAS sorption at the air-water interface resulted in improved predictions of the PFAS porewater concentrations. This improvement was most notable for PFOS, where inclusion of air-water interfacial sorption resulted in a 58% reduction in the predicted PFOS porewater concentration and predicted PFOS porewater concentrations that were identical (within the 95% confidence interval) to the lysimeter measured PFOS porewater concentration. Overall these results highlight the potentially important role of air-water interfacial sorption on PFAS migration in AFFF-impacted unsaturated soils in an in situ field setting.


Influence of sterilization conditions on sulfate-functionalized polyGGE.
Sulfated biomolecules are known to influence numerous biological processes in all living organisms. Particularly, they contribute to prevent and inhibit the hypercoagulation condition. The failure of polymeric implants and blood contacting devices is often related to hypercoagulation and microbial contamination. Here, bioactive sulfated biomacromolecules are mimicked by sulfation of poly(glycerol glycidyl ether) (polyGGE) films. Autoclaving, gamma-ray irradiation and ethylene oxide (EtO) gas sterilization techniques were applied to functionalized materials. The sulfate group density and hydrophilicity of sulfated polymers were decreased while chain mobility and thermal degradation were enhanced post autoclaving when compared to those after EtO sterilization. These results suggest that a quality control after sterilization is mandatory to ensure the amount and functionality of functionalized groups are retained.


Initial stages of SBA-15 synthesis: an overview.
This work presents an overview of the data obtained for SBA-15 synthesis under the reaction conditions using synchrotron based small angle X-ray scattering and small angle neutron scattering. Three major stages in the synthesis of SBA-15 materials proceeding according to the cooperative self-assembly mechanism have been identified, and the structures of the intermediates species have been established. Our in situ time-resolved neutron scattering experiments demonstrate that only spherical micelles of the templating agent are present in the synthesis mixture during the first stage of the reaction. According to the neutron scattering and X-ray scattering data, in the second stage of the reaction the formation of hybrid organic-inorganic micelles is accompanied with the transformation from spherical to cylindrical micelles, which takes place before the precipitation of the ordered SBA-15 phase. During the third stage, these micelles aggregate into a two-dimensional hexagonal structure, confirming that the precipitation takes place as the result of self-assembly of the hybrid cylindrical micelles. As the synthesis proceeds, the voids between the cylinders are filled with the silicate species which undergo condensation reactions resulting in cross-linking and covalent bonding, leading to the formation of highly ordered SBA-15 mesostructure. This work demonstrates that valuable structural information can be obtained from X-ray and neutron scattering characterisation of complex systems containing periodic phases with d-spacing values up to 30 nm, and that both techniques are powerful means for in situ monitoring of the formation of nanostructured materials.


In vivo action of a new octadecaneuropeptide antagonist on neuropeptide Y and corticotropin-releasing hormone mRNA levels in rat.
It has been reported that several of the effects induced by an octadecaneuropeptide (ODN), derived from an 86-amino-acid polypeptide termed diazepam-binding inhibitor, could be mediated by activation of a metabotropic receptor. In order to investigate the role and mechanism of action of ODN in the regulation of corticotropin-releasing factor (CRH) and neuropeptide Y (NPY) expression in the paraventricular nucleus and arcuate nucleus, respectively, we studied the effects of the acute intracerebroventricular administration of ODN (2 microg/rat) and the ODN antagonist to metabotropic receptor, cyclo(1-8)[Dleu5]OP (20 microg/rat), on the gene expression of the two neuropeptides in castrated male rat. ODN administration resulted in a 45% increase in CRH mRNA expression, an effect which was reversed by cyclo(1-8)[Dleu5]OP. When cyclo(1-8)[Dleu5]OP was administered alone, it induced a 19% decrease in CRH mRNA levels. ODN administration induced a 17% decrease in NPY mRNA expression while cyclo(1-8)[Dleu5]OP increased by 21% the hybridization signal. The administration of both ODN and ODN antagonist completely abolished the depressing effect of ODN on NPY mRNA. These data suggest that the effects of ODN on CRH and NPY mRNA might be mediated by interaction with metabotropic receptors. Moreover, since cyclo(1-8)[Dleu5]OP can by itself influence the expression of two peptide mRNAs, it might be suggested that ODN is exerting a tonic influence on NPY and CRH neurons.


The Transthyretin Amyloidosis - Quality of Life (ATTR-QOL) Questionnaire: Development of a Conceptual Model and Disease-Specific Patient-Reported Outcome Measure.
Patients with transthyretin amyloidosis (ATTR) experience a wide variety of symptoms and impacts on health-related quality of life (HRQoL). However, the lack of an ATTR-specific patient-reported outcome (PRO) measure has made consistent measurement of HRQoL in ATTR challenging. This paper describes the development of a conceptual model and subsequent content for the Transthyretin Amyloidosis - Quality of Life Questionnaire (ATTR-QOL), an ATTR-specific PRO measure. This was a cross-sectional, non-interventional, US-based study. The study design included three stages: 1) a targeted literature review followed by qualitative data collection with patients and experts; 2) development of a conceptual model and PRO measure; and 3) review of the PRO measure using a modified Delphi method, translatability assessment, and interviews with patients and experts. Revisions were made to the measure after each round of review. Forty-four patients and 29 experts participated in this study. The conceptual model included two primary concepts of interest: symptoms (cardiac, neuropathic-peripheral, neuropathic-autonomic, and other) and impacts (eg, physical, role, and mental/emotional functioning). Seventy-two items were created (32 symptoms; 40 impacts) to align with the model. A recall period of one month was selected based on participant input. The ATTR-QOL was created with significant patient involvement and guidance from a multidisciplinary group of experts. The mix of patient and clinical perspectives helped to ensure a balanced representation of all relevant disease experiences and clinical specialties. With further refinement from psychometric testing, the ATTR-QOL will provide a standard, comprehensive measure for all ATTR-specific research including both clinical trials and clinical practice.


Effects of TSH receptor mutations on binding and biological activity of monoclonal antibodies and TSH.
The effects of an extensive series of mutations in the TSH receptor (TSHR) leucine-rich domain (LRD) on the ability of thyroid-stimulating monoclonal antibodies (TSMAbs) and TSH to bind to the receptor and stimulate cyclic AMP production in TSHR-transfected CHO cells has been investigated. In addition, the ability of a mouse monoclonal antibody with blocking (i.e., antagonist) activity (RSR-B2) to interact with mutated receptors has been studied. Several amino acids distributed along an extensive part of the concave surface of the LRD were found to be important for binding and stimulation by the thyroid-stimulating human MAb M22 but did not appear to be important for TSH binding and stimulation. Most of these amino acids important for M22 interactions were also found to be important for the stimulating activity of six different mouse TSMAbs and a hamster TSMAb. Furthermore, most of these same amino acids were important for stimulation by TSHR autoantibodies in a panel of sera from patients with Graves' disease. Amino acid R255 was the only residue found to be unimportant for TSH stimulation but critical for stimulation by all thyroid-stimulating antibodies tested (23 patient serum TSHR autoantibodies, M22, and all seven animal TSMAbs). About half the amino acids (all located in the N-terminal part of the LRD) found to be important for M22 activity were also important for the blocking activity of RSR-B2 and although the epitopes for the two MAbs overlap they are different. As the two MAbs have similar affinities, their epitope differences are probably responsible for their different activities. Overall our results indicate that different TSMAbs and different patient sera thyroid-stimulating autoantibodies interact with the same region of the TSHR, but there are subtle differences in the actual amino acids that make contact with the different stimulators.


Effect of Moderate-Intensity Aerobic Exercise on Hepatic Fat Content and Visceral Lipids in Hepatic Patients with Diabesity: A Single-Blinded Randomised Controlled Trial.
Limited studies have assessed the effect of moderate-intensity continuous aerobic exercise on hepatic fat content and visceral lipids in hepatic patients with diabesity. This study was designed to evaluate hepatic fat content and visceral lipids following moderate-intensity continuous aerobic exercise in hepatic patients with diabesity. A single-blinded randomised controlled trial. Thirty-one diabetic obese patients with nonalcoholic fatty liver disease were recruited into this study. The patients were randomly classified into exercise and control groups, fifteen patients in the exercise group and sixteen patients in the control group. The exercise group received an 8-week moderate-intensity continuous aerobic exercise program with standard medical treatment, while the control group received standard medical treatment without any exercise program. Hepatic fat content and visceral lipids were assessed before and after intervention at the end of the study. Baseline and clinical characteristics showed a nonsignificant difference between the two groups (p > 0.05). At the end of the intervention, the aerobic exercise showed significant improvements (serum triglycerides and low-density lipoproteins (LDLs), p ≤ 0.002, total cholesterol, p=0.004, visceral fats, p=0.016, glycated hemoglobin (HbA1C), p=0.022, high-density lipoproteins (HDLs), p=0.038, alanine transaminases (AL), p=0.044, intrahepatic triglyceride and HOMA-IR, p=0.046, and body mass index (BMI), p=0.047), while the control group showed a nonsignificant difference (p > 0.05). The postintervention analysis showed significant differences in favor of the aerobic exercise group (p < 0.05). Moderate-intensity continuous aerobic exercise reduces the hepatic fat content and visceral lipids in hepatic patients with diabesity. Recommendations should be prescribed for encouraging moderate-intensity aerobic exercise training, particularly hepatic patients with diabesity.