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Introduction: Lumen apposing metal stents (LAMS) have been used increasingly for drainage of pancreatic fluid collections (PFC). We present an international, multicenter study evaluating the safety and efficacy of LAMS in PFCs., Methods: Consecutive patients undergoing LAMS placement for PFC at 12 international centers were included (ClinicalTrials.gov NCT01522573). Demographics, clinical history, and procedural details were recorded. Technical success was defined as successful LAMS deployment. Clinical success was defined as PFC resolution at three-month follow-up., Results: 192 patients were included (140 males (72.9%), mean-age 53.8 years), with mean follow-up of 4.2 months ± 3.8. Mean PFC size was 11.9 cm (range 2-25). The median number of endoscopic interventions was 2 (range 1-14). Etiologies for PFC were gallstone (n = 82, 42.7%), alcohol (n = 50, 26%), idiopathic (n = 26, 13.5%), and other (n = 34, 17.7%). Technical success was achieved in 189 patients (98.4%). Clinical success was observed in 125 of 135 patients (92.6%). Adverse events included bleeding (n = 11, 5.7), infection (n = 2, 1%), and perforation (n = 2, 1%). Three or more endoscopy sessions were a positive predictor for PFC resolution and the only significant predictor for AEs., Conclusion: LAMS has a high technical and clinical success rate with a low rate of AEs. PFC drainage via LAMS provides a minimally invasive, safe, and efficacious procedure for PFC resolution., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Loneliness is connected to poorer health outcomes with stress reactivity proposed as an underlying mechanism. The present study explored whether the relationship between loneliness and cardiovascular reactivity (CVR) varies across acute psychological stress tasks. Eighty-eight healthy younger adults completed a psychometric measure of loneliness and participated in a standardised cardiovascular stress-testing protocol, with a public speaking and a mental arithmetic task. Cardiovascular functioning was assessed before and during the acute stress exposure. Higher levels of loneliness significantly predicted lower total peripheral resistance (TPR) reactivity to the public speaking task but not to the arithmetic challenge. This suggests that the effect of loneliness on cardiovascular reactivity to acute stress may vary by stressor type. These findings are discussed in relation to future research., (Copyright © 2018 Elsevier B.V. All rights reserved.)

All influenza viral neuraminidases (NA) of both type A and B viruses have only one universally conserved sequence located between amino acids 222-230. A monoclonal antibody against this region has been previously reported to provide broad inhibition against all nine subtypes of influenza A NA; yet its inhibitory effect against influenza B viral NA remained unknown. Here, we report that the monoclonal antibody provides a broad inhibition against various strains of influenza B viruses of both Victoria and Yamagata genetic lineage. Moreover, the growth and NA enzymatic activity of two drug resistant influenza B strains (E117D and D197E) are also inhibited by the antibody even though these two mutations are conformationally proximal to the universal epitope. Collectively, these data suggest that this unique, highly-conserved linear sequence in viral NA is exposed sufficiently to allow access by inhibitory antibody during the course of infection; it could represent a potential target for antiviral agents and vaccine-induced immune responses against diverse strains of type B influenza virus., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

The only universally conserved sequence amongst all influenza A viral neuraminidase (NA) is located between amino acids 222-230 and plays crucial roles in viral replication. However, it remained unclear as to whether this universal epitope is exposed during the course of infection to allow binding and inhibition by antibodies. Using a monoclonal antibody (MAb) targeting this specific epitope, we demonstrated that all nine subtypes of NA were inhibited in vitro by the MAb. Moreover, the antibody also provided heterosubtypic protection in mice challenged with lethal doses of mouse-adapted H1N1 and H3N2, which represent group I and II viruses, respectively. Furthermore, we report amino acid residues I222 and E227, located in close proximity to the active site, are indispensable for inhibition by this antibody. This unique, highly-conserved linear sequence in viral NA could be an attractive immunological target for protection against diverse strains of influenza viruses., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

Lung immunopathology is the main cause of influenza-mediated morbidity and death, and much of its molecular mechanisms remain unclear. Whereas tumor necrosis factor-α (TNF-α) is traditionally considered a proinflammatory cytokine, its role in influenza immunopathology is unresolved. We have investigated this issue by using a model of acute H1N1 influenza infection established in wild-type and TNF-α-deficient mice and evaluated lung viral clearance, inflammatory responses, and immunopathology. Whereas TNF-α was up-regulated in the lung after influenza infection, it was not required for normal influenza viral clearance. However, TNF-α deficiency led not only to a greater extent of illness but also to heightened lung immunopathology and tissue remodeling. The severe lung immunopathology was associated with increased inflammatory cell infiltration, anti-influenza adaptive immune responses, and expression of cytokines such as monocyte chemoattractant protein-1 (MCP-1) and fibrotic growth factor, TGF-β1. Thus, in vivo neutralization of MCP-1 markedly attenuated lung immunopathology and blunted TGF-β1 production following influenza infection in these hosts. On the other hand, in vivo transgenic expression of MCP-1 worsened lung immunopathology following influenza infection in wild-type hosts. Thus, TNF-α is dispensable for influenza clearance; however, different from the traditional belief, this cytokine is critically required for negatively regulating the extent of lung immunopathology during acute influenza infection., (Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The expression of platelet-derived growth factor-A (PDGF-A) mRNA was examined in the cotyledons of normal human placentae and those from patients with pre-eclampsia. These patients exhibited pre-delivery blood pressure of 154+/-4/99+/-4 mmHg (mean+/-SEM) and met the criteria established for pre-eclampsia. During labour they received MgSO4 infusion for various time intervals (4-25 h). The PDGF-A message was quantitated to beta-actin by the solution hybridization nuclease protection assay. Since the two groups differed in two parameters (pre-eclampsia and MgSO4 treatment), the direct comparison was not feasible. An analysis of covariance revealed a significant difference in the message between the pre-eclamptic and control groups (P<0.01); the gestational age was not a significant covariate for either group but the time on MgSO4 in pre-eclampsia group was significant (P<0.002). A linear regression analysis of PDGF-A mRNA values for the pre-eclamptic group showed a time-dependent downregulation of the message by MgSO4 (P<0.01, r=- 0.796). These results show a uniform expression of PDGF-A mRNA in cotyledons of normal human placenta between 35 and 40 weeks of gestation. Furthermore, MgSO4 has an inhibitory effect on the expression of this message which may have aside from its anticonvulsive action beneficial effect on the function of pre-eclamptic placenta.

A study was made of the biosynthesis by Anabaena flos-aquae of the tropane-related alkaloid anatoxin-a. Evidence is presented that the toxin arises from ornithine via putrescine (1,4-diaminobutane) and that ornithine decarboxylase (EC 4.1.1.17) is involved. An ornithine decarboxylase preparation, with optimal activity at pH 8, was obtained from Anabaena flos-aquae and partially purified by gel-filtration chromatography on DEAE-cellulose. One major and one minor peak of enzymic activity were obtained with Km values of 1.25 and 2.5 mM, respectively. Plasmid DNA (10 Kb; Mr 6.5 x 10(6] was detected in the toxic strain of Anabaena flos-aquae but not in a non-toxic strain. DNA from the toxin-producing strain of Anabaena flos-aquae transforms the non-toxic into a toxic strain.

The relation of fetal growth and maternal oxygen transport as assessed by red blood cell 2,3-diphosphoglycerate, hemoglobin oxygen affinity, hemoglobin, pH, and PCO2 was evaluated in 21 pregnant women. The study was performed in the third trimester and each subject evaluated had sonographic evidence of fetal growth retardation without other obvious abnormalities. Decreased maternal 2,3-diphosphoglycerate/hemoglobin molar ratio and hemoglobin oxygen affinity were related linearly to the birth weight normalized for the expected sea level values of gestational age expressed as a birth weight (gestational age-normalized) Z score. The correlation coefficients and p values were r = 0.71, p less than 0.001 and r = 0.67, p less than 0.001, respectively. The ponderal index-normalized Z score correlated with the 2,3-diphosphoglycerate/hemoglobin molar ratio (r = 0.46, p less than 0.04), but the relation was not as strong as the birth weight-normalized Z score. The crown-heel length/head circumference ratio did not correlate with the 2,3-diphosphoglycerate/hemoglobin molar ratio (r = 0.29, NS). The birth weight (gestational age)-normalized Z score did not correlate with hemoglobin, PCO2, or pH. In the regulation of hemoglobin oxygen affinity, calculations indicated that the 2,3-diphosphoglycerate/hemoglobin molar ratio played a highly significant role (p less than 0.001), pH was minimally significant (p less than 0.025), but PCO2 had little or no significant effects in this study. It appears that fetal growth is related to the maternal red blood cell oxygen transport parameters 2,3-diphosphoglycerate/hemoglobin molar ratio and hemoglobin oxygen affinity. Moreover, the 2,3-diphosphoglycerate/hemoglobin molar ratio is the principal regulator of hemoglobin oxygen affinity.

The order and relative mobility of proteins on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) is affected by unknown components that are differentially present in SDS preparations obtained from different sources [J.B. Swaney, G.F. Vande Woude, and H.L. Bachrach (1974) Anal. Biochem. 58, 337-346]. The modified separation capabilities of such SDS preparations are useful but the use of this phenomenon in a controlled manner requires that the components responsible for the altered separation be identified. Accordingly, this paper describes a polyacrylamide gel electrophoresis system [mixed alcohol/detergent-polyacrylamide gel electrophoresis (MAD-PAGE)] that employs a mixture of alcohol and detergent instead of SDS alone to modify and enhance protein separation relative to conventional SDS-PAGE. A defined mixture consisting of four sulfated alkyl detergents (dodecyl sulfate, tetradecyl sulfate, hexadecyl sulfate, octadecyl sulfate) as well as the four alcohols of corresponding aliphatic chain length was found to be effective at duplicating the electrophoretic effect of USP-grade SDS and thus changed the relative order and position of polypeptides on electrophoresis relative to conventional SDS-PAGE. This method serves as an adjunct to conventional SDS-PAGE by providing another means of resolving proteins that are not normally resolved by SDS-PAGE. Further, it was found that MAD-PAGE is capable of resolving the NS1 protein of influenza virus into three fractions, whereas conventional SDS-PAGE yields one electrophoretic species. Reelectrophoresis of these novel NS1 bands by conventional SDS-PAGE indicated that they were not modified during MAD-PAGE and probably represented distinct molecular forms present in infected cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Problems encountered in obtaining reliable analytical data by HPLC for the free nucleotide constituents of plant tissues are considered and methods of overcoming them experimentally assessed. Major problems include suppression of residual phosphatase activity during extraction, and removal of pigments, phenolics, alkaloids, and other uv-absorbing nonnucleotides, prior to HPLC. An optimal combination of extraction and pre-HPLC purification techniques is discussed which, in combination with HPLC by anion exchange, yields quantitatively reliable data. The optimized procedure involves extraction with a monophasic mixture of methanol: chloroform:formic acid:water and purification of the nucleotide extract by a batch treatment with poly-N-vinylpyrrolidone, followed by ligand-exchange chromatography. The main HPLC separation uses mu Bondapak NH2 in a linear phosphate gradient and gives good resolution of all the commonly occurring plant nucleotides in a single chromatographic run.

The relationship between cranial ultrasonograms (SONOs) and brain-stem auditory evoked responses (BAERs) was evaluated in 2 independent samples of newborn infants at risk for brain injury (n = 113 and 203). Features of the BAER wave forms subjected to stepwise linear discriminant analysis formed the basis of an algorithm used to detect and follow early brain injury. Using this algorithm, information derived from BAERs reliably predicted SONO abnormalities at least 82.3% of the time in the initial study which was replicated with the second sample (77.3%). The wave I component latency (CL) and the wave III-V inter-peak latency interval (IPL) were independent of each other, and both contributed to a prediction of SONO abnormality. Possible mechanisms for these BAER results include compromise to the cochlear membrane or to the auditory nerve itself as well as prolongation of transmission in the brain-stem due to brain-stem hemorrhage, edema, or compression. Normative BAER values and non-linear regression functions for the wave I, III and V CLs, and the I-III, III-V, and I-V IPLs were calculated across age using data from 109 infants who demonstrated normal BAER patterns and had no history of SONO abnormalities. Our analyses indicate BAER techniques, where a single higher intensity is used to produce the BAER wave form, are both valid and efficient for use in the evaluation of early brain injury.