bluuebunny/crossref_metadata_2025 huggingface dataset:
Decellularized extracellular matrix microparticles as a vehicle for cellular delivery in a model of anastomosis healing
Authors: Hoganson David M. , Owens Gwen E. , Meppelink Amanda M. , Bassett Erik K. , Bowley Chris M. , Hinkel Cameron J. , Finkelstein Eric B. , Goldman Scott M. , Vacanti Joseph P.
Published: March 2016

Extracellular matrix (ECM) materials from animal and human sources have become important materials for soft tissue repair. Microparticles of ECM materials have increased surface area and exposed binding sites compared to sheet materials. Decellularized porcine peritoneum was mechanically dissociated into 200 µm microparticles, seeded with fibroblasts and cultured in a low gravity rotating bioreactor. The cells avidly attached and maintained excellent viability on the microparticles. When the seeded microparticles were placed in a collagen gel, the cells quickly migrated off the microparticles and through the gel. Cells from seeded microparticles migrated to and across an in vitro anastomosis model, increasing the tensile strength of the model. Cell seeded microparticles of ECM material have potential for paracrine and cellular delivery therapies when delivered in a gel carrier. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1728–1735, 2016.
The Androgen Receptor Regulates PPARγ Expression and Activity in Human Prostate Cancer Cells
Authors: Olokpa Emuejevoke , Bolden Adrienne , Stewart LaMonica V.
Published: March 2016

The peroxisome proliferator activated receptor gamma (PPARγ) is a ligand‐activated transcription factor that regulates growth and differentiation within normal prostate and prostate cancers. However the factors that control PPARγ within the prostate cancers have not been characterized. The goal of this study was to examine whether the androgen receptor (AR) regulates PPARγ expression and function within human prostate cancer cells. qRT‐PCR and Western blot analyses revealed nanomolar concentrations of the AR agonist dihydrotestosterone (DHT) decrease PPARγ mRNA and protein within the castration‐resistant, AR‐positive C4‐2 and VCaP human prostate cancer cell lines. The AR antagonists bicalutamide and enzalutamide blocked the ability of DHT to reduce PPARγ levels. In addition, siRNA mediated knockdown of AR increased PPARγ protein levels and ligand‐induced PPARγ transcriptional activity within the C4‐2 cell line. Furthermore, proteasome inhibitors that interfere with AR function increased the level of basal PPARγ and prevented the DHT‐mediated suppression of PPARγ. These data suggest that AR normally functions to suppress PPARγ expression within AR‐positive prostate cancer cells. To determine whether increases in AR protein would influence PPARγ expression and activity, we used lipofectamine‐based transfections to overexpress AR within the AR‐null PC‐3 cells. The addition of AR to PC‐3 cells did not significantly alter PPARγ protein levels. However, the ability of the PPARγ ligand rosiglitazone to induce activation of a PPARγ‐driven luciferase reporter and induce expression of FABP4 was suppressed in AR‐positive PC‐3 cells. Together, these data indicate AR serves as a key modulator of PPARγ expression and function within prostate tumors. J. Cell. Physiol. 231: 2664–2672, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.
Prevalence and genotype distribution of cytomegalovirus UL55 sequence in renal transplant recipients in north west of Iran
Authors: Khalafkhany Davod , Makhdoomi Khadijeh , Taghizadeh Afshari Ali , Motazakker Morteza
Published: March 2016

Cytomegalovirus (CMV) is one of the most important infections in renal transplant recipients. Kidney transplant is the last hope for the patients with end stage renal diseases. Cytomegalovirus infection can threaten patients and graft survival after transplantation. Four hundred and thirty‐four renal transplant recipients contributed to this study. PCR and RFLP analyses were performed in order to determine CMV viremia and its genotypes. CMV viremia was detected in 68 (15.9%) recipients. The mean post‐transplantation time in our recipients was 50 months, ranging from 1 to 354 months. Viremia was detected in 31.2%, 30.7%, 17.5%, 10.2%, and 6.4% of the recipients in 0–3, 4–6, 7–12, 13–24, and more than 24 months post‐transplantation, respectively. The distribution of gB1, gB2, gB3, and gB4 genotypes was detected as 26.5%, 20.5%, 17.6%, and 5.9%, respectively. Mixed genotype infection was observed in 29.4% of the recipients. Incidence of viremia was higher in the first 6 months after the transplantation compared with the later stages. Moreover, CMV gB1 and mixed genotype infection were more common in our recipients. J. Med. Virol. 88:1622–1627, 2016. © 2016 Wiley Periodicals, Inc.
Hypochlorhydria‐induced calcium malabsorption does not affect fracture healing but increases post‐traumatic bone loss in the intact skeleton
Authors: Haffner‐Luntzer Melanie , Heilmann Aline , Heidler Verena , Liedert Astrid , Schinke Thorsten , Amling Michael , Yorgan Timur Alexander , vom Scheidt Annika , Ignatius Anita
Published: March 2016

Efficient calcium absorption is essential for skeletal health. Patients with impaired gastric acidification display low bone mass and increased fracture risk because calcium absorption is dependent on gastric pH. We investigated fracture healing and post‐traumatic bone turnover in mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells. Cckbr−/− mice display hypochlorhydria, calcium malabsorption, and osteopenia. Cckbr−/− and wildtype (WT) mice received a femur osteotomy and were fed either a standard or calcium‐enriched diet. Healed and intact bones were assessed by biomechanical testing, histomorphometry, micro‐computed tomography, and quantitative backscattering. Parathyroid hormone (PTH) serum levels were determined by enzyme‐linked immunosorbent assay. Fracture healing was unaffected in Cckbr−/− mice. However, Cckbr−/− mice displayed increased calcium mobilization from the intact skeleton during bone healing, confirmed by significantly elevated PTH levels and osteoclast numbers compared to WT mice. Calcium supplementation significantly reduced secondary hyperparathyroidism and bone resorption in the intact skeleton in both genotypes, but more efficiently in WT mice. Furthermore, calcium administration improved bone healing in WT mice, indicated by significantly increased mechanical properties and bone mineral density of the fracture callus, whereas it had no significant effect in Cckbr−/− mice. Therefore, under conditions of hypochlorhydria‐induced calcium malabsorption, calcium, which is essential for callus mineralization, appears to be increasingly mobilized from the intact skeleton in favor of fracture healing. Calcium supplementation during fracture healing prevented systemic calcium mobilization, thereby maintaining bone mass and improving fracture healing in healthy individuals whereas the effect was limited by gastric hypochlorhydria. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1914–1921, 2016.
Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers
Authors: op den Dries Sanna , Karimian Negin , Westerkamp Andrie C. , Sutton Michael E. , Kuipers Michiel , Wiersema‐Buist Janneke , Ottens Petra J. , Kuipers Jeroen , Giepmans Ben N. , Leuvenink Henri G. D. , Lisman Ton , Porte Robert J.
Published: March 2016

Bile duct injury may occur during liver procurement and transplantation, especially in livers from donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury compared to static cold storage (SCS). However, it is unknown whether NMP provides better preservation of bile ducts. The aim of this study was to determine the impact of NMP on bile duct preservation in both DCD and non‐DCD livers. DCD and non‐DCD livers obtained from Lewis rats were preserved for 3 hours using either SCS or NMP, followed by 2 hours ex vivo reperfusion. Biomarkers of bile duct injury (gamma‐glutamyltransferase and lactate dehydrogenase in bile) were lower in NMP‐preserved livers compared to SCS‐preserved livers. Biliary bicarbonate concentration, reflecting biliary epithelial function, was 2‐fold higher in NMP‐preserved livers (P < 0.01). In parallel with this, the pH of the bile was significantly higher in NMP‐preserved livers (7.63 ± 0.02 and 7.74 ± 0.05 for non‐DCD and DCD livers, respectively) compared with SCS‐preserved livers (7.46 ± 0.02 and 7.49 ± 0.04 for non‐DCD and DCD livers, respectively). Scanning and transmission electron microscopy of donor extrahepatic bile ducts demonstrated significantly decreased injury of the biliary epithelium of NMP‐preserved donor livers (including the loss of lateral interdigitations and mitochondrial injury). Differences between NMP and SCS were most prominent in DCD livers. Compared to conventional SCS, NMP provides superior preservation of bile duct epithelial cell function and morphology, especially in DCD donor livers. By reducing biliary injury, NMP could have an important impact on the utilization of DCD livers and outcome after transplantation. Liver Transplantation 22 994–1005 2016 AASLD
Helical Polymers Showing Inverse Helicity and Synergistic Effect in Chiral Catalysis: Catalytic Functionality Determining Enantioconfiguration and Helical Frameworks Providing Asymmetric Microenvironment
Authors: Zhang Haiyang , Deng Jianping
Published: March 2016

This article reports optically active helical polymers showing inverse helicity, which is controlled by copolymer composition. L‐Proline‐derived monomer and an achiral monomer have been copolymerized, affording copolymers with optical activity and remarkable catalytic ability. By adjusting relative content of the two monomers, a series of copolymers with varied optical activity has been obtained. More notably, the handedness of the macromolecular helices inverses at specific monomer feed ratios. Copolymers with opposite helicity have been applied as chiral catalysts for asymmetric aldol reaction to investigate the exact role of helical structures in catalysis. The variation in the stereoselectivity of product has demonstrated an intriguing synergistic effect occurring between the helical macromolecular frameworks and pendent prolineamide groups. The macromolecular helices provide asymmetric microenvironment for the reaction while enantioconfiguration of the product is determined by the specific catalytic functionality. This study opens up new opportunities for manufacturing macromolecules as mimetic enzymes catalyzing asymmetric reactions.

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Validation and optimization of adiabatic T1ρ and T2ρ for quantitative imaging of articular cartilage at 3 T
Authors: Casula Victor , Autio Joonas , Nissi Mikko J. , Auerbach Edward J. , Ellermann Jutta , Lammentausta Eveliina , Nieminen Miika T.
Published: March 2016

Purpose

The aim of the present work was to validate and optimize adiabatic T1ρ and T2ρ mapping for in vivo measurements of articular cartilage at 3 Tesla (T).

Methods

Phantom and in vivo experiments were systematically performed on a 3T clinical system to evaluate the sequences using hyperbolic secant HS1 and HS4 pulses. R1ρ and R2ρ relaxation rates were studied as a function of agarose and chondroitin sulfate concentration and pulse duration. Optimal in vivo protocol was determined by imaging the articular cartilage of two volunteers and varying the sequence parameters, and successively applied in eight additional subjects. Reproducibility was assessed in phantoms and in vivo.

Results

Relaxation rates depended on agarose and chondroitin sulfate concentration. The sequences were able to generate relaxation time maps with pulse lengths of 8 and 6 ms for HS1 and HS4, respectively. In vivo findings were in good agreement with the phantoms. The implemented adiabatic T1ρ and T2ρ sequences demonstrated regional variation in relaxation time maps of femorotibial cartilage. Reproducibility in phantoms and in vivo was good to excellent for both adiabatic T1ρ and T2ρ.

Conclusions

The findings indicate that sequences are suitable for quantitative in vivo assessment of articular cartilage at 3 T. Magn Reson Med 77:1265–1275, 2017. © 2016 International Society for Magnetic Resonance in Medicine
Monomer volume fraction profiles in pH responsive planar polyelectrolyte brushes
Authors: Mahalik J. P. , Yang Yubo , Deodhar Chaitra , Ankner John F. , Lokitz Bradley S. , Kilbey S. Michael , Sumpter Bobby G. , Kumar Rajeev
Published: March 2016

Spatial dependencies of monomer volume fraction profiles of pH responsive polyelectrolyte brushes were investigated using field theories and neutron reflectivity experiments. In particular, planar polyelectrolyte brushes in good solvent were studied and direct comparisons between predictions of the theories and experimental measurements are presented. The comparisons between the theories and the experimental data reveal that solvent entropy and ion‐pairs resulting from adsorption of counterions from the added salt play key roles in affecting the monomer distribution and must be taken into account in modeling polyelectrolyte brushes. Furthermore, the utility of this physics‐based approach based on these theories for the prediction and interpretation of neutron reflectivity profiles in the context of pH responsive planar polyelectrolyte brushes such as polybasic poly(2‐(dimethylamino)ethyl methacrylate) (PDMAEMA) and polyacidic poly(methacrylic acid) (PMAA) brushes is demonstrated. The approach provides a quantitative way of estimating molecular weights of the polymers polymerized using surface‐initiated atom transfer radical polymerization. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 956–964
Blind testing of cross‐linking/mass spectrometry hybrid methods in CASP11
Authors: Schneider Michael , Belsom Adam , Rappsilber Juri , Brock Oliver
Published: March 2016

Hybrid approaches combine computational methods with experimental data. The information contained in the experimental data can be leveraged to probe the structure of proteins otherwise elusive to computational methods. Compared with computational methods, the structures produced by hybrid methods exhibit some degree of experimental validation. In spite of these advantages, most hybrid methods have not yet been validated in blind tests, hampering their development. Here, we describe the first blind test of a specific cross‐link based hybrid method in CASP. This blind test was coordinated by the CASP organizers and utilized a novel, high‐density cross‐linking/mass‐spectrometry (CLMS) approach that is able to collect high‐density CLMS data in a matter of days. This experimental protocol was developed in the Rappsilber laboratory. This approach exploits the chemistry of a highly reactive, photoactivatable cross‐linker to produce an order of magnitude more cross‐links than homobifunctional cross‐linkers. The Rappsilber laboratory generated experimental CLMS data based on this protocol, submitted the data to the CASP organizers which then released this data to the CASP11 prediction groups in a separate, CLMS assisted modeling experiment. We did not observe a clear improvement of assisted models, presumably because the properties of the CLMS data—uncertainty in cross‐link identification and residue‐residue assignment, and uneven distribution over the protein—were largely unknown to the prediction groups and their approaches were not yet tailored to this kind of data. We also suggest modifications to the CLMS‐CASP experiment and discuss the importance of rigorous blind testing in the development of hybrid methods. Proteins 2016; 84(Suppl 1):152–163. © 2016 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.
Mechanisms of the gabapentinoids and α2δ‐1 calcium channel subunit in neuropathic pain
Authors: Patel Ryan , Dickenson Anthony H.
Published: March 2016

The gabapentinoid drugs gabapentin and pregabalin are key front‐line therapies for various neuropathies of peripheral and central origin. Originally designed as analogs of GABA, the gabapentinoids bind to the α2δ‐1 and α2δ‐2 auxiliary subunits of calcium channels, though only the former has been implicated in the development of neuropathy in animal models. Transgenic approaches also identify α2δ‐1 as key in mediating the analgesic effects of gabapentinoids, however the precise molecular mechanisms remain unclear. Here we review the current understanding of the pathophysiological role of the α2δ‐1 subunit, the mechanisms of analgesic action of gabapentinoid drugs and implications for efficacy in the clinic. Despite widespread use, the number needed to treat for gabapentin and pregabalin averages from 3 to 8 across neuropathies. The failure to treat large numbers of patients adequately necessitates a novel approach to treatment selection. Stratifying patients by sensory profiles may imply common underlying mechanisms, and a greater understanding of these mechanisms could lead to more direct targeting of gabapentinoids.
Pharmacological evaluation of a series of smoothened antagonists in signaling pathways and after topical application in a depilated mouse model
Authors: Lauressergues Emilie , Heusler Peter , Lestienne Fabrice , Troulier David , Rauly‐Lestienne Isabelle , Tourette Amélie , Ailhaud Marie‐Christine , Cathala Claudie , Tardif Stéphanie , Denais‐Laliève Delphine , Calmettes Marie‐Thérèse , Degryse Anne‐Dominique , Dumoulin Antoine , De Vries Luc , Cussac Didier
Published: March 2016

The Hedgehog (HH) pathway has been linked to the formation of basal cell carcinoma (BCC), medulloblastoma, and other cancers. The recently approved orally active drugs vismodegib (GDC‐0449) and sonidegib (LDE–225) were not only efficacious for the treatment of advanced or metastatic BCC by antagonizing the smoothened (SMO) receptor, but also produced important side effects, limiting their use for less invasive BCC. Herein, we compared a large series of SMO antagonists, including GDC‐0449 and LDE‐225, the clinically tested BMS‐833923, CUR‐61414, cyclopamine, IPI‐926 (saridegib), itraconazole, LEQ‐506, LY‐2940680 (taladegib), PF‐04449913 (glasdegib), and TAK‐441 as well as preclinical candidates (PF‐5274857, MRT‐83) in two SMO‐dependent cellular assays and for G‐protein activation. We report marked differences in inhibitor potencies between compounds as well as a notable disparity between the G‐protein assay and the cellular tests, suggesting that classification of drugs is assay dependent. Furthermore, we explored topical efficacies of SMO antagonists on depilated mice using Gli1 and Ptch1 mRNA quantification in skin as biomarkers of the HH signaling inhibition. This topical model rapidly discriminated drugs in terms of efficacies and potencies for inhibition of both biomarkers. SMO antagonists showed also a large variation in their blood and skin partition, suggesting that some drugs are more favorable for topical application. Overall, our data suggested that in vitro and in vivo efficacious drugs such as LEQ‐506 and TAK‐441 may be of interest for topical treatment of less invasive BCC with minimal side effects.
Gastrointestinal safety, chemotherapeutic potential, and classic pharmacological profile of NOSH‐naproxen (AVT‐219) a dual NO‐ and H2S‐releasing hybrid
Authors: Chattopadhyay Mitali , Kodela Ravinder , Duvalsaint Pascale L. , Kashfi Khosrow
Published: March 2016

Naproxen (NAP) is a potent nonsteroidal anti‐inflammatory drug (NSAID) with a favorable cardiovascular profile. However, its long‐term use may lead to serious gastrointestinal and renal side effects. NOSH‐ (nitric oxide and hydrogen sulfide) releasing naproxen (NOSH‐NAP, AVT‐219) belongs to a new class of anti‐inflammatory agents designed to overcome these limitations. We compared the gastrointestinal safety, anti‐inflammatory, analgesic, antipyretic, and antiplatelet properties of AVT‐219 to that of NAP in preclinical animal models. We also evaluated its anticancer effects in 11 human cancer cell (HCC) lines of six different tissue origins and in a chemotherapeutic xenograft mouse model of colon cancer. AVT‐219: (1) was orders of magnitude more potent than NAP in inhibiting the growth of cultured HCC; (2) was safe to the stomach, whereas NAP caused significant ulceration; (3) showed strong anti‐inflammatory, analgesic, antipyretic, and antiplatelet properties comparable to NAP; and (4) NAP caused a significant rise in plasma tumor necrosis factor‐alpha (TNFα), whereas in the AVT‐219‐treated rats this rise was significantly less. Mechanistically, AVT‐219 was a strong antioxidant, inhibited cyclooxygenase (COX)‐1 and ‐2, thus reducing prostaglandin (PG) E2. In xenografts, AVT‐219 significantly reduced tumor growth and tumor mass with no sign of GI toxicity, whereas NAP‐treated mice died due to GI bleeding. AVT‐219 displayed considerable safety and potency in inhibiting HCC growth; was an effective analgesic, antipyretic, antiplatelet, and anti‐inflammatory; and was significantly more efficacious than NAP in reducing the growth of established tumors in a xenograft mouse model.
Effect of yeast assimilable nitrogen on the synthesis of phenolic aroma compounds by Hanseniaspora vineae strains
Authors: Martin Valentina , Boido Eduardo , Giorello Facundo , Mas Albert , Dellacassa Eduardo , Carrau Francisco
Published: March 2016

In several grape varieties, the dominating aryl alkyl alcohols found are the volatile group of phenylpropanoid‐related compounds, such as glycosylated benzyl and 2‐phenylethyl alcohol, which contribute to wine with floral and fruity aromas after being hydrolysed during fermentation. Saccharomyces cerevisiae is largely recognized as the main agent in grape must fermentation, but yeast strains belonging to other genera, including Hanseniaspora, are known to predominate during the first stages of alcoholic fermentation. Although non‐Saccharomyces yeast strains have a well‐recognized genetic diversity, understanding of their impact on wine flavour richness is still emerging. In this study, 11 Hansenisapora vineae strains were used to ferment a chemically defined simil‐grape fermentation medium, resembling the nutrient composition of grape juice but devoid of grape‐derived secondary metabolites. GC–MS analysis was performed to determine volatile compounds in the produced wines. Our results showed that benzyl alcohol, benzyl acetate and 2‐phenylethyl acetate are significantly synthesized by H. vineae strains. Levels of these compounds found in fermentations with 11 H. vineae different strains were one or two orders of magnitude higher than those measured in fermentations with a known S. cerevisiae wine strain. The implications for winemaking in response to the negative correlation of benzyl alcohol, benzyl acetate and 2‐phenylethyl acetate production with yeast assimilable nitrogen concentrations are discussed. Copyright © 2016 John Wiley & Sons, Ltd.
On the Pragmatic Equivalence between Representing Data and Phenomena
Authors: Nguyen James
Published: March 2016

Van Fraassen argues that data provide the target-end structures required by structuralist accounts of scientific representation. But models represent phenomena not data. Van Fraassen agrees but argues that there is no pragmatic difference between taking a scientific model to accurately represent a physical system and accurately represent data extracted from it. In this article I reconstruct his argument and show that it turns on the false premise that the pragmatic content of acts of representation include doxastic commitments.
Sleeping Beauty’s Credences
Authors: Cisewski Jessi , Kadane Joseph B. , Schervish Mark J. , Seidenfeld Teddy , Stern Rafael
Published: March 2016

The Sleeping Beauty problem has spawned a debate between “thirders” and “halfers” who draw conflicting conclusions about Sleeping Beauty's credence that a coin lands heads. Our analysis is based on a probability model for what Sleeping Beauty knows at each time during the experiment. We show that conflicting conclusions result from different modeling assumptions that each group makes. Our analysis uses a standard “Bayesian” account of rational belief with conditioning. No special handling is used for self-locating beliefs or centered propositions. We also explore what fair prices Sleeping Beauty computes for gambles that she might be offered during the experiment.
On How to Approach the Approach to Equilibrium
Authors: Luczak Joshua
Published: March 2016

This article highlights the limitations of typicality accounts of thermodynamic behavior so as to promote an alternative line of research: understanding and accounting for the success of the techniques and equations physicists use to model the behavior of systems that begin away from equilibrium. This article also takes steps in this promising direction. It examines a technique commonly used to model the behavior of an important kind of system: a Brownian particle that has been introduced to an isolated fluid at equilibrium. It also accounts for the success of the model, by identifying and grounding the technique’s key assumptions.
ThePlasmodium falciparumDrugome And Its Polypharmacological Implications
Authors: Zhang Yinliang , Xie Li , Xie Lei , Bourne Philip E.
Published: March 2016

Malaria is a disease contracted by over 200 million people each year, mostly in developing countries. The primary causative agent,Plasmodium falciparum(P. falciparum) has shown increased resistance to existing drugs, hence new treatments are needed quickly. To this end we performed a high-throughput systems-level analysis, mapping existing FDA drugs with the potential for repurposing against targets from theP. falciparumstructural proteome. The resultingP. falciparumdrugome (P.falciparum-drugome) was used to prioritize potential new anti-malaria candidate targets and highlight some novel FDA approved drugs that have apparent anti-malaria effects for possible use as multi-target therapeutics.
Pre-treatment with the methanol extract ofWithania somniferaprevents Diazinon-induced cardiotoxic effects of organophosphate poisoning
Authors: Eric Mwangi Irungu , Peter Waweru Mwangi , Frederick Bukachi
Published: March 2016

Organophosphate poisoning represents a major and growing global health problem especially in the developing countries and cardiotoxicity is the major cause of death. Thus, a compelling need to develop novel low cost efficacious agents to manage this condition.

Objective

To evaluate the methanol extract ofWithania somniferaas a pre-treatment agent in the prevention of the cardiotoxic effects of diazinon in Sprague Dawley rats

Materials and Methods

Twenty one (21) adult rats were randomized to receive 200 mg/kg methanol extract ofWithania somnifera(test group), vehicle (negative control) or 200 μg/kg Neostigmine as pre-treatment 30 minutes prior to the oral administration of 200 mg/kg Diazinon. Baseline and post-treatment electrocardiograms (ECGs) were recorded by the Powerlab data acquisition system (ML865 AD instruments, Sydney, Australia). The experimental data were expressed as median ± the inter-quartile range and analysed using the Kruskal – Wallis non-parametric test and followed by Mann–Whitney U post hoc test in cases of significance, which was set at p < 0.05. Statistical Package for Social Sciences (SPSS) version 17 software was used for analysis.

Results

Pre-treatment with the methanol extract ofW. somniferahad significant effect on the following diazinon-induced electrocardiographic changes; RR interval (0.026 (0.007 – 0.065) vs. 0.035 (0.019 – 0.050) vs. 0.090 (0.071 – 0.01), p = 0.031),heart rate (-54.235 (-115.317 – (-19.857)) vs. -−96.136 (-96.472 – (-43.879)) vs. -−174.361 (-189.775 – (-129.469)), p = 0.014), PR interval (0.006 (0.004 – 0.008) vs. 0.003 (0.001 – 0.004) vs. 0.009 (0.006 – 0.015), p = 0.019), QRS interval (0.005 (0.001 – 0.008) vs. -−0.002 (-0.005 – 0.001) vs. 0.007 (0.003 – 0.011), p = 0.023) and ST height (-34.830 (-63.578 – 4.215) vs. -−22.330 (-38.383– (-4.159)) vs. -−73.156 (-214.022– (-52.449)), p = 0.023). It however had no significant effect on the QTc interval changes (-0.005 (-0.011 – 0.003) vs. -−0.005 (-0.015 – 0.065) vs. -−0.021 (-0.060– (-0.006)), p = 0.174).

Conclusion

The efficacy of pre-treatment with the methanol extract ofWithania somniferawas comparable to that of pre-treatment with Neostigmine a commonly used carbamate drug. Thus, it is a potentially viable low cost treatment option for organophosphate poisoning in resource-limited settings.
Pemphigus with features of both vulgaris and foliaceus variants localized to the nose
Authors: Mandel Victor Desmond , Farnetani Francesca , Vaschieri Cristina , Manfredini Marco , Cesinaro Anna Maria , Giusti Francesca , Pellacani Giovanni
Published: March 2016

We report the case of a 74‐year‐old man affected by an unusual variant of pemphigus. He presented with a crusty and scaly lesion of the nose. We performed reflectance confocal microscopy and optical coherence tomography on the lesion, which suggested an unexpected diagnosis of pemphigus. Therefore, to confirm our diagnostic suspicions, we executed indirect immunofluorescence and two biopsies, one for histopathological examination and one for direct immunofluorescence. Histopathological evaluation showed acantholysis with formation of clefts in the granular and spinous layers of the epidermis. Direct immunofluorescence revealed immunoglobulin G and C3 deposit to the full thickness of the epidermis. Indirect immunofluorescence showed intercellular antibodies at a titer of 1:40 in the suprabasal epidermis. The immunoblot analysis using epidermal extract revealed the presence of circulating antibodies directed to 130‐ and 160‐kDa antigens in the patient's serum. These two antigens were evidenced from nitrocellulose membrane with colorimetric AP systems, which highlighted the presence of autoantibodies against desmoglein (Dsg)1 and Dsg3 (sodium dodecylsulfate polyacrylamide gel electrophoresis). We also performed an enzyme‐linked immunoassay. All these findings suggested that this patient's pemphigus had features of both vulgaris and foliaceus variants.
Assessing the Composition and Diversity of the Australian Interest Group System
Authors: Fraussen Bert , Halpin Darren
Published: March 2016

Any democratic society requires mechanisms for citizens to have effective political voice. Clearly, political parties provide a key channel for expressing views and preferences. However, organised interests provide another important mechanism for such representation. A crucial question in this regard is whether the interest group system is capable of ensuring the representation of a variety of public and private interests. Resolving these debates requires data that map the terrain and also are attentive to organisational diversity. This article takes up this challenge through exploring the composition and diversity of the Australian system of organised interests, using a new data set based on the Directory of Australian Associations. This system‐level approach delivers important insights into the nature of the Australian interest group system, as well as provides a framework for subsequent work interpreting and contextualising advocacy activities of particular groups, or lobbying dynamics in specific policy domains.
Detecting and quantifying introgression in hybridized populations: simplifying assumptions yield overconfidence and uncertainty
Authors: Della Croce Patrick , Poole Geoffrey C. , Luikart Gordon
Published: March 2016

A growing threat to the conservation of many native species worldwide is genetic introgression from non‐native species. Although improved molecular genetic techniques are increasing the availability of species‐diagnostic markers for many species, efficient field sampling design and reliable data interpretation require accurate estimates of uncertainty associated with the detection of non‐native alleles and the quantification of introgression in native populations. Using fish populations as examples, we developed a simulation model of an age‐structured population that tracks the introduction and inheritance of non‐native alleles across generations by simulating stochastic mating and survival of individual fish and the resulting transmission of diagnostic markers. To simulate detection and quantification of introgression, we sampled varying combinations of n fish and m diagnostic markers to detect and quantify introgression from thousands of virtual, independent fish populations for a wide range of hybridization scenarios. Using the results of simulated sampling, we quantified the extent to which common simplifying assumptions regarding population structure and inheritance mechanisms can lead to the following: (i) overconfidence in our ability to detect non‐native alleles and (ii) unrealistically narrow confidence intervals for estimates of the proportion of non‐native alleles present. Under many circumstances, commonly used simplifying assumptions underestimate the probability of failing to detect ongoing introgression and the uncertainty associated with estimates of introgression by orders of magnitude. Such overconfidence in our ability to detect and quantify introgression can affect critical conservation and management decisions regarding native species undergoing or at risk of introgression from non‐native species.
Hemodynamic Effects, Safety, and Feasibility of Intravenous Esmolol Infusion During Takotsubo Cardiomyopathy With Left Ventricular Outflow Tract Obstruction: Results From A Multicenter Registry
Authors: Santoro Francesco , Ieva Riccardo , Ferraretti Armando , Fanelli Mario , Musaico Francesco , Tarantino Nicola , Martino Luigi Di , Gennaro Luisa De , Caldarola Pasquale , Biase Matteo Di , Brunetti Natale Daniele
Published: March 2016

Background

Left ventricular outflow tract obstruction (LVOTO) may complicate an episode of Takotsubo cardiomyopathy (TTC), potentially leading to cardiogenic shock. Beta‐blockers are considered the most suitable treatment for such complication.

Aim of the study

The objective of this study was to evaluate the hemodynamic effects, safety, and feasibility of a selective beta‐blocker (β1) with a short half‐life, esmolol, in subjects with a TTC episode.

Methods

Ninety‐six consecutive patients with TTC were enrolled in a multicenter registry. The hemodynamic and echocardiographic effects of esmolol (0.15–0.3 mg/kg/min) were analyzed in nine consecutive patients with LVOTO. Clinical course of patients, hemodynamics, days of hospitalization, LV function, and adverse events at follow‐up were recorded.

Results

Left ventricular outflow tract obstruction was present in 10 (10.4%) of 96 patients. Patients with LVOTO were older and had higher values of troponin‐I at admission. LV ejection fraction at admission (36.1 ± 8.4%) significantly improved at discharge (51.4 ± 6.9%, P = 0.001). Among patients treated with esmolol infusion, LVOT pressure gradient before treatment was 47.6 ± 16.6 mmHg and after 18.2 ± 2.3 mmHg (P = 0.0091). Systolic blood pressure decreased from 123.8 ± 29.1 to 112.6 ± 12.7 mmHg (P = 0.1537). Mean hospital stay was 9 ± 2 days. No adverse events were observed during hospitalization and at follow‐up.

Conclusions

Esmolol infusion was temporally associated with reduction in intraventricular gradient and systemic blood pressure in patients with TTC and LVOTO. Further controlled studies are warranted to confirm these preliminary findings.
Distensibility and pain of the uterine cervix evaluated by novel techniques
Authors: Gregersen Hans , Hee Lene , Liao Donghua , Uldbjerg Niels
Published: March 2016

The article serves to review the literature on the human uterine cervix based on a new distension technology named functional luminal imaging probe. This technology was originally developed to study the biomechanical competence of the gastro‐esophageal junction where it provides a geometric profile of the lumen during distension, which can be related to sensory data. We searched and reviewed publications on cervical distention from 2002. The functional luminal imaging probe technology has been used for studying the mechanical and mechano‐sensory properties of the cervix in non‐pregnant women. In early pregnant women and in term pregnant women, the technique provides geometric measurements from the whole cervical canal during distension, which changes dramatically during pregnancy. Furthermore, it has been demonstrated that the technique predicts the outcome of labor induction better than the Bishop score does. The functional luminal imaging probe technology has potential as a research tool as well as for clinical use in gynecology and obstetrics.
Ventricular outputs, central blood flow distribution and flow pattern through the aortic isthmus of fetuses with simple transposition of the great arteries
Authors: Blanc Julie , Fouron Jean‐Claude , Sonesson Sven‐Erik , Raboisson Marie‐Josée , Huggon Ian , Gendron Roxanne , Berger Annie , Brisebois Sophie
Published: March 2016

Introduction

Our objective was to determine the impact of simple transposition of the great arteries (TGA) on fetal left ventricular (LV) and right ventricular (RV) performances and central circulatory dynamics including the aortic isthmus.

Material and methods

Ventricular stroke volumes were calculated as the product of the cross‐sectional area of the corresponding semi‐lunar valve and the flow velocity integral through these valves. Volume flow in ductus arteriosus (QDA) was evaluated using the same technique. Flow through the lungs (QLUNGS) was calculated by subtracting netQDA from flow in main pulmonary artery [netQDA = QDA minus retrograde ductus arteriosus (DA) diastolic flow]. Relative performance of each ventricle expressed as percentage of combined cardiac output was also indirectly assessed by the aortic isthmus systolic index (ISI) (nadir of incisura/peak systolic of the Doppler waveforms in the isthmus); the relation between ISI and QLUNGS was investigated.

Results

Fifty‐one fetuses with TGA were compared with 74 normal controls matched for gestational age. TGA fetuses had higher QLV at T2 (58.6 ± 9.4% vs. 43.4 ± 5.0%, p < 0.001) and T3 (53.7 ± 8.9% vs. 43.9 ± 5.7%, p < 0.001). QLUNGS was higher in fetuses with TGA, in the second (50.4 ± 16.3% vs. 39.0 ± 16.8%, p = 0.007) and third trimesters of gestation (52.8 ± 22.0% vs. 37.1 ± 16.3%, p = 0.005). No difference was found between ISI values from normal and TGA groups. A significant inverse correlation was observed between ISI and QLUNGS (r = −0.55, p = 0.006).

Conclusions

Central distribution of combined cardiac output of fetuses with simple TGA is characterized by a greater QLUNGS leading to a dominant LV. In prenatal TGA, changes in QLUNGS could be monitored by measuring ISI. The clinical importance of this last observation deserves further investigations.
Therapeutic hypothermia for neonatal hypoxic‐ischaemic encephalopathy had favourable outcomes at a referral hospital in a middle‐income country
Authors: Kali Gugulabatembunamahlubi Tenjiwe Jabulile , Martinez‐Biarge Miriam , Van Zyl Jeanetta , Smith Johan , Rutherford Mary
Published: March 2016

Aim

This South African study documented the survival and neurodevelopmental outcomes of infants with hypoxic‐ischaemic encephalopathy (HIE) after introducing cooling to a neonatal intensive care unit and identified early markers for neurodevelopmental outcome.

Methods

We retrospectively reviewed infants that received cooling according to the Total Body Hypothermia trial protocol from 2008 to 2011. Infants were screened with the Bayley Scales of Infant and Toddler Development, Third Edition, at one year of age and underwent neurological and hearing assessments.

Results

Data on 99 infants with HIE showed that 45% of cases were moderate, 23% severe and 32% mild. An abnormal amplitude integrated electro‐encephalogram (aEEG) background was documented in 45 cases within 24 hours. Magnetic resonance imaging (MRI) scans were consistent with HIE in all but one case. We reviewed 50 traceable survivors at one year. Development was significantly impaired in nine and 41 were normal or mildly impaired. A severely abnormal aEEG background, severe HIE and an abnormal MRI were associated with death and severe impairment. A good suck, mild HIE, primiparity and normal MRI were associated with good outcomes.

Conclusion

Most infants with HIE survived without major impairment. Previously described predictors of neurodevelopmental outcome were good surrogate markers in this population.
‘Planning Live’: using a person‐centred intervention to reduce admissions to and length of stay in learning disability inpatient facilities
Authors: Bartle Janet , Crossland Tom , Hewitt Olivia
Published: March 2016

Accessible Summary

Some people with a learning disability need to go to hospital to get help with their mental health or if they have challenging behaviour.

We wanted to see if we could help people get the right support at home so they did not have to go to hospital

We had a special meeting to help this happen called a ‘Planning Live’ meeting

These meetings helped some people stay at home and get support without having to go to hospital.

For the people who had to come into hospital, they had a shorter stay and could go home more quickly.

Background: Recent government policy has focused on reducing the number of people with a learning disability receiving treatment for challenging behaviour or mental health difficulties in hospitals (including in assessment and treatment units; ATU). People with a learning disability should be supported to remain in their community when receiving support for challenging behaviour or mental health difficulties whenever possible.

Methods: This study considered a novel intervention based on person‐centred planning practice, which aimed to coordinate a person's support, identify outstanding needs and increase communication. This intervention intended to reduce rates of inpatient admission, and support the person to remain in their community, whilst ensuring their needs are met. This intervention was assessed by considering the number of people admitted to the inpatient services before and after the intervention, the length of inpatient admissions before and after the intervention, and by analysing qualitative feedback from participants in the intervention.

Results: ‘Planning Live’ meetings were held for 102 people. Forty‐five meetings were held retrospectively following an emergency admission. Following the ‘Planning Live’ meeting, five people had a planned admission and 52 people did not have an inpatient admission. The median length of inpatient stay fell from 143.5 days before the introduction of ‘Planning Live’ to 66 days (a statistically significant reduction). Qualitative feedback shows that the process was largely seen as helpful by professionals, families and individuals taking part in the meetings.

Conclusions: The results suggest this person‐centred intervention contributed towards a reduction in the amount of time individuals stayed in hospital. However, the total number of hospital admissions rose following the intervention.
Tonsillectomy and inflammatory bowel disease: a meta‐analysis
Authors: Xiong H.‐F. , Wang B. , Zhao Z.‐H. , Hong J. , Zhu Y. , Zhou X. , Xie Y.
Published: March 2016

Aim

The pathogenesis of inflammatory bowel diseases remains unclear. Genetic and environmental factors are involved. Studies of the association between tonsillectomy and inflammatory bowel disease have yielded conflicting results.

Method

PubMed and EMBASE were searched to identify studies evaluating the association between tonsillectomy and inflammatory bowel disease [Crohn's disease (CD) and ulcerative colitis (UC)]. Odds ratios with 95% CI were calculated using a random‐ or fixed‐effects model. The χ2 test and I2 test were used to assess homogeneity. Egger's test was used to evaluate publication bias.

Results

Thirteen observational case–control studies including 4122 patients (3035 UC/1087 CD) and 5103 controls were analysed. The summary odds ratio estimated for UC following a tonsillectomy was 0.932, 95% CI 0.819–1.062. The odds ratio for CD following a tonsillectomy was 1.194, 95% CI 0.992–1.437. Publication bias was not detected (Egger's test coefficient −3.50 to 1.55; P = 0.39).

Conclusion

No obvious association between tonsillectomy and inflammatory bowel disease was identified in our meta‐analysis.
Efficiency of Ipratropium Bromide and Albuterol Deposition in the Lung Delivered via a Soft Mist Inhaler or Chlorofluorocarbon Metered‐Dose Inhaler
Authors: MacGregor TR , ZuWallack R , Rubano V , Castles MA , Dewberry H , Ghafouri M , Wood CC
Published: March 2016

The propellant‐free Combivent Respimat Soft Mist Inhaler (CVT‐R) was developed to replace the chlorofluorocarbon‐propelled Combivent metered‐dose inhaler (CVT‐MDI). This steady‐state pharmacokinetic (PK) substudy evaluated drug lung‐delivery efficiency, using data from two phase III safety and efficacy trials. PK parameters were obtained from well‐controlled population PK analyses. Area under the plasma concentration–time curve (AUC), maximum observed plasma concentration (Cmax), and minimum observed plasma concentration (Cmin) showed systemic exposure to ipratropium bromide and albuterol delivered via the CVT‐R was proportional to ex‐mouthpiece delivered dose. Although the labeled dose of ipratropium bromide in the CVT‐R was half that in the CVT‐MDI, the systemic exposure was comparable. No PK interaction for the ipratropium bromide and albuterol Respimat drug components was demonstrated. Ipratropium bromide alone resulted in similar exposure to the combination of ipratropium bromide and albuterol. These results show that CVT‐R delivers drug more efficiently to the lung than CVT‐MDI.
China's housing bubble burst?
Authors: Liu Tie‐Ying , Chang Hsu‐Ling , Su Chi‐Wei , Jiang Xu‐Zhao
Published: March 2016

In this paper, we developed the recursive unit root tests to identify the beginning and end of potential speculative bubbles in the Chinese housing price cycles during 2006–2013 for the 70 major cities of China. The method is best suited for a practical implementation with a time series and delivers a consistent date‐stamping strategy for the origination and termination of multiple bubbles. Simulations demonstrate that the test significantly improves discriminatory power and leads to distinct power gains when multiple bubbles occur. Overall, the results indicate that the speculative housing price bubbles in China are not bursting, and they indicate that the stationarity of the housing price level varies across the different city sizes. Between the cities, approximately one‐fourth of the bubbles have burst up to December 2013, while the first‐tier city bubble may not burst due to the urbanization process.
A rapid, reliable and less‐destructive method for stem inoculations on trees
Authors: Maschek O. , Halmschlager E.
Published: March 2016

A new stem inoculation method using a gouge and syringe for inoculum application and utilizing the tree transpiration system for the uptake of sap‐compatible liquids was developed. This method is fast, reliable and less‐destructive compared to traditional methods of wound inoculation using a drill, punch, scalpel or a chisel.