bluuebunny/crossref_metadata_2025 huggingface dataset:
Tolerance to high‐internalizing δ opioid receptor agonist is critically mediated by arrestin 2
Authors: Vicente‐Sanchez Ana , Dripps Isaac J , Tipton Alycia F , Akbari Heba , Akbari Areeb , Jutkiewicz Emily M , Pradhan Amynah A
Published: May 2018

Background and Purpose

Opioid δ receptor agonists are potent antihyperalgesics in chronic pain models, but tolerance develops after prolonged use. Previous evidence indicates that distinct forms of tolerance occur depending on the internalization properties of δ receptor agonists. As arrestins are important in receptor internalization, we investigated the role of arrestin 2 (β‐arrestin 1) in mediating the development of tolerance induced by high‐ and low‐internalizing δ receptor agonists.

Experimental Approach

We evaluated the effect of two δ receptor agonists with similar analgesic potencies, but either high‐(SNC80) or low‐(ARM390) internalization properties in wild‐type (WT) and arrestin 2 knockout (KO) mice. We compared tolerance to the antihyperalgesic effects of these compounds in a model of inflammatory pain. We also examined tolerance to the convulsant effect of SNC80. Furthermore, effect of chronic treatment with SNC80 on δ agonist‐stimulated [35S]‐GTPγS binding was determined in WT and KO mice.

Key Results

Arrestin 2 KO resulted in increased drug potency, duration of action and decreased acute tolerance to the antihyperalgesic effects of SNC80. In contrast, ARM390 produced similar effects in both WT and KO animals. Following chronic treatment, we found a marked decrease in the extent of tolerance to SNC80‐induced antihyperalgesia and convulsions in arrestin 2 KO mice. Accordingly, δ receptors remained functionally coupled to G proteins in arrestin 2 KO mice chronically treated with SNC80.

Conclusions and Implications

Overall, these results suggest that δ receptor agonists interact with arrestins in a ligand‐specific manner, and tolerance to high‐ but not low‐internalizing agonists are preferentially regulated by arrestin 2.
Administration of Cripto in GRP78 overexpressed human MSCs enhances stem cell viability and angiogenesis during human MSC transplantation therapy
Authors: Kim S. , Yoon Y.M. , Han Y.‐S. , Lee J. H. , Hur J. , Lee S. H.
Published: May 2018

Objectives

The purpose of this study was to explore the effectiveness of concurrent GRP78 overexpression combined with Cripto on hMSC proliferation and migration both in vitro and in vivo. Specifically, we explored whether the treatment enhances effectiveness of hMSC transplantation in ischaemic tissue.

Materials and methods

Human MSCs obtained from human adipose tissue were cultured in α‐minimum essential medium (Hyclone, Logan, UT, USA) supplemented with 10% (v/v) foetal bovine serum (Hyclone), 100 U mL−1 penicillin and 100 μg mL−1 streptomycin. Murine hindlimb ischaemic model was generated with 8‐week‐old male nude BALB/c mice (Biogenomics, Seoul, Korea) maintained under a 12‐h light/dark cycle following the established protocol with minor modification. Cellular injection was performed no later than 3 hour after surgery. Lipofectamine transfection, single‐cell cultivation assay, transwell assay, scratch wound‐healing migration assay, immunohistochemistry and western blotting assays were performed.

Results

Overexpression of GRP78 along with Cripto enhanced hMSC proliferation, migration and invasion. It increased interaction of surface GRP78 receptor with Cripto via JAK2/STAT3 pathway. We confirmed our proposed mechanism by showing that treatment with GRP78 antibody blocks the enhancement in vitro. In vivo, we observed that Cripto induced by the hypoxic environment in hindlimb ischaemic model interacts with the overexpressed GRP78 and increases hMSC proliferation, migration and invasion potentials as well as angiogenesis around transplanted ischaemic site via cytokine secretions.

Conclusions

These results demonstrate supporting evidences that GRP78‐Cripto combination technique offers novel strategy to enhance MSC proliferation, migration and invasion potentials as well as angiogenesis around ischaemic site, ultimately facilitating MSC‐based transplantation therapy in ischaemic conditions.
Rapid on‐site evaluation facilitated the diagnosis of a rare case of Talaromyces marneffei infection
Authors: Ma W. , Thiryayi S. A. , Holbrook M. , Shelton D. , Narine N. , Sweeney L. C. , Augustine T. , Bailey S. , Al‐Najjar H. , Rana D. N.
Published: May 2018

This article describes how rapid on‐site evaluation helped to diagnose a very rare infection and allow early treatment.
SurePath® LBC improves the diagnostic accuracy of intrahepatic and hilar cholangiocarcinoma
Authors: Naito Y. , Kawahara A. , Okabe Y. , Ishida Y. , Sadashima E. , Murata K. , Takase Y. , Abe H. , Yamaguchi T. , Tanigawa M. , Mihara Y. , Kondo R. , Kusano H. , Nakayama M. , Shimamatsu K. , Yano H. , Akiba J.
Published: May 2018

Introduction

The current study aimed to compare cytology using SurePath® (SP)‐LBC and biliary tissue histology (BTH) for the diagnosis of biliary disease.

Methods

Between January 2014 and December 2016, 57 patients underwent endoscopic retrograde cholangiopancreatography for the diagnosis of biliary disease. Biliary cytological samples were processed using SP‐LBC and subsequently BTH was performed. A final diagnosis was confirmed by surgery (23 malignant cases) and clinical follow‐up (34 benign and malignant cases): 18 extrahepatic cholangiocarcinoma; 17 intrahepatic/hilar cholangiocarcinoma (intra/H‐CC); eight other malignant disease; and 14 benign biliary disease. The diagnoses made using SP‐LBC and BTH were classified into four categories: (1) benign; (2) indeterminate; (3) suspicious for malignancy/malignant; and (4) inadequate. In addition, diagnostic accuracy was compared between SP‐LBC and BTH.

Results

Although 23% (13/57) of BTH samples were classified as inadequate, all SP‐LBC cases were classified as adequate. Among 43 malignant cases, 11 normal, four indeterminate and 28 suspicious for malignancy/malignant were found using SP‐LBC (26%, 9% and 65%, respectively), in contrast to 10 inadequate, nine normal, 10 indeterminate and 14 suspicious for malignancy/malignant observed using BTH (23%, 21%, 23%, and 33%, respectively). The identification of malignant cells was strikingly different between SP‐LBC and BTH. Furthermore, limited to intra/H‐CC, accuracy was significantly higher using SP‐LBC than using BTH (P < .001).

Conclusions

SP‐LBC of the biliary tract is a useful and reliable method for diagnosing biliary malignant disease and has an advantage over BTH for detecting malignant cells and accurately diagnosing intra/H‐CC.
Complications related to chronic supratherapeutic use of codeine containing compound analgesics in a cohort of patients presenting for codeine withdrawal
Authors: Cock Victoria , Edmonds Carolyn , Cock Charles
Published: May 2018

Introduction and Aims

This study aimed to compare complications arising due to the supratherapeutic use of paracetamol/codeine or ibuprofen/codeine containing compound analgesics in primary codeine‐dependent patients presenting to a drug and alcohol withdrawal service. Data was compared to determine if there was any difference in the number of complications observed between the two groups.

Design and Methods

A retrospective case review of patients presenting for primary codeine dependence from 2009 to 2014. Sixty patients (42F, 36 ± 10 years) using ibuprofen/codeine and 46 (26F, 39 ± 10 years) using paracetamol/codeine containing compound analgesics were compared. A P value of <0.05 was considered significant.

Results

Patients consumed similar daily doses of codeine (699 ± 45 vs. 636 ± 50 mg) with those consuming ibuprofen/codeine containing compound analgesics ingesting twice as many tablets daily (median 60 vs. 30 tablets; P < 0.0001). Complications related to supratherapeutic use of codeine containing compound analgesics occurred more commonly in patients taking ibuprofen/codeine (52/60; 87%) versus paracetamol/codeine compound analgesics (30/46; 65%) (P < 0.01). Patients taking ibuprofen/codeine containing compound analgesics were more likely to have gastrointestinal bleeding (P < 0.05), anaemia (P < 0.0001) and renal tubular acidosis (P < 0.05). There were two deaths in the group abusing ibuprofen/codeine compound analgesics.

Discussion and Conclusions

In patients with primary codeine dependence, there were more complications related to the supratherapeutic use of ibuprofen/codeine versus paracetamol/codeine containing compound analgesics. The patients in both groups ingested similar total daily codeine amounts. Increased daily tablet intake in the ibuprofen/codeine group could possibly have been linked to lower codeine content per tablet.
Measures of Father Engagement for Nonresident Fathers
Authors: Dyer W. Justin , Kauffman Rebecca , Fagan Jay , Pearson Jessica , Cabrera Natasha
Published: May 2018

Objective

To develop reliable and valid measures of nonresident father engagement.

Background

Although engagement measures exist for resident fathers, they have not been validated for nonresident fathers. Without valid and reliable measures, research on and programs for these fathers are limited in their ability to capture this salient dimension of fathering.

Method

From a focus group of 71 nonresident biological fathers, father–child engagement scales were created. Separate scales were created for fathers of children aged 0 to 1 years, 1 to 5 years, 6 to 11 years, and 12 to 18 years. Scales were administered to 542 nonresident (primarily low income) fathers to test reliability and convergent and predictive validity.

Results

Analyses identified a “caregiving play” domain of engagement across all age groups. For fathers of children 0 to 1 years, a “cognitive stimulation” domain emerged. For all age groups, a “support” domain emerged. All measures had acceptable reliability and (except in 1 instance) were related to at least 1 validity construct. Measures were nonequivalent across groups except for support in 2 groups.

Conclusion

Measures of nonresident father engagement had good reliability and validity. Further, with a minimal number of items, the scales are relatively easy and cost‐effective to administer.

Implications

With reliable and valid measures of engagement, those researching or intervening with nonresident fathers can more accurately capture this highly relevant construct.
Phospho‐regulation of intrinsically disordered proteins for actin assembly and endocytosis
Authors: Miao Yansong , Tipakornsaowapak Teepiyanut , Zheng Liangzhen , Mu Yuguang , Lewellyn Eric
Published: May 2018

Actin filament assembly contributes to the endocytic pathway pleiotropically, with active roles in clathrin‐dependent and clathrin‐independent endocytosis as well as subsequent endosomal trafficking. Endocytosis comprises a series of dynamic events, including the initiation of membrane curvature, bud invagination, vesicle abscission and subsequent vesicular transport. The ultimate success of endocytosis requires the coordinated activities of proteins that trigger actin polymerization, recruit actin‐binding proteins (ABPs) and organize endocytic proteins (EPs) that promote membrane curvature through molecular crowding or scaffolding mechanisms. A particularly interesting phenomenon is that multiple EPs and ABPs contain a substantial percentage of intrinsically disordered regions (IDRs), which can contribute to protein coacervation and phase separation. In addition, intrinsically disordered proteins (IDPs) frequently contain sites for post‐translational modifications (PTMs) such as phosphorylation, and these modifications exhibit a high preference for IDR residues [Groban ES et al. (2006) PLoS Comput Biol 2, e32]. PTMs are implicated in regulating protein function by modulating the protein conformation, protein–protein interactions and the transition between order and disorder states of IDPs. The molecular mechanisms by which IDRs of ABPs and EPs fine‐tune actin assembly and endocytosis remain mostly unexplored and elusive. In this review, we analyze protein sequences of budding yeast EPs and ABPs, and discuss the potential underlying mechanisms for regulating endocytosis and actin assembly through the emerging concept of IDR‐mediated protein multivalency, coacervation, and phase transition, with an emphasis on the phospho‐regulation of IDRs. Finally, we summarize the current understanding of how these mechanisms coordinate actin cytoskeleton assembly and membrane curvature formation during endocytosis in budding yeast.
« For the women » ‐ In Memoriam Simone Veil (1927–2017)
Authors: Barthold Charles , Corvellec Hervé
Published: May 2018

This In Memoriam presents the life of Simone Veil, an influential French politician, remembered for a law that made abortion legal in 1974. Simone Veil's contribution to the rights of women is featured as an instance of parrhesia (Foucault, 2011) that was able to establish a new regime of truth about the body, sexuality, and reproductive capacities of French women.
Key roles of hepatologists in successful liver transplantation
Authors: Kogiso Tomomi , Tokushige Katsutoshi
Published: May 2018

Liver transplantation (LT) has been carried out for acute liver failure, end‐stage liver disease, and congenital metabolic disease in more than 7000 cases in Japan. Liver transplantation has been established as a treatment option, and survival rates have improved. In 2016, a new registration/allocation policy and a new scoring system for deceased donor LT were established. The management of perioperative patients and preoperative therapy for liver failure, nutrition, and preventing infection were upgraded. Moreover, methods for preventing disease recurrence, and treating hepatitis C and B have been developed and are particularly crucial for good outcomes in LT. Treatment of the complications of obesity, lifestyle‐related diseases, and malignancy is also required post‐LT. Managing patients after LT contributes to better survival and quality of life. The role of hepatologists is becoming broader and more important.
Antimicrobia activity of garlic (Allium sativum L.) and holy basil (Ocimum sanctum L.) essential oils applied by liquid vs. vapour phases
Authors: Torpol Kittikoon , Wiriyacharee Pairote , Sriwattana Sujinda , Sangsuwan Jurmkwan , Prinyawiwatkul Witoon
Published: April 2018

Antimicrobial activity of garlic (Allium sativum L.) and holy basil (Ocimum sanctum L.) essential oils (GEO and HBEO, respectively) was evaluated in liquid vs. vapour phases. Diallyl disulphide and diallyl trisulphide in GEO while eugenol, caryophyllene and methyl eugenol in HBEO were predominant active compounds. Individually, GEO was highly effective in the vapour phase, showing the greatest antimicrobial activity (P ≤ 0.05) against Bacillus cereus and Staphylococcus aureus with complete inhibition, followed by Salmonella typhimurium and Pseudomonas fluorescens, but had no effect on Escherichia coli, Lactobacillus plantarum or Listeria monocytogenes. The combined GEO:HBEO (a 1:1 ratio) at 30 μL demonstrated inhibitive activity against all bacteria tested with complete inhibition against B. cereus and S. aureus. Minimum bactericidal concentration (MBC) of the combined oil was <0.4% v/v, except for P. fluorescens requiring a higher MBC (1.5%, v/v). This study demonstrated potential of the combined GEO:HBEO to be used for food preservation applications.
Emergency department presentations in early stage breast cancer patients receiving adjuvant and neoadjuvant chemotherapy
Authors: Tang Monica , Horsley Patrick , Lewis Craig R.
Published: May 2018

(Neo)adjuvant chemotherapy for early stage breast cancer is associated with side‐effects, resulting in increased emergency department (ED) presentations. Treatment‐related toxicity can affect quality of life, compromise chemotherapy delivery and treatment outcomes, and increase healthcare use. We performed a retrospective study of ED presentations in patients receiving curative chemotherapy for early breast cancer to identify factors contributing to ED presentations. Of 102 patients, 39 (38%) presented to ED within 30 days of chemotherapy, resulting in 63 ED presentations in total. Most common reasons were non‐neutropenic fever (17 presentations/27%), neutropenic fever (15/24%), pain (9/14%), drug reaction (6/10%) and infection (4/6%). Factors significantly associated with ED presentation were adjuvant chemotherapy timing compared to neoadjuvant timing (P = 0.031), prophylactic antibiotics (P = 0.045) and docetaxel‐containing regimen (P = 0.018).
Hypothalamic demyelination causing panhypopituitarism
Authors: Dixon‐Douglas Julia , Burgess John , Dreyer Michael
Published: May 2018

Hypothalamic involvement in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is rare and endocrinopathies involving the hypothalamic–pituitary axis in patients with demyelinating conditions have rarely been reported. We present two cases of MS/NMOSD with associated hypothalamic–pituitary involvement and subsequent hypopituitarism, including the first report of a patient with hypothalamic demyelination causing panhypopituitarism. Differential diagnoses, including alemtuzumab‐related and primary pituitary pathology are discussed.
Interleukin‐23 promotes intestinal T helper type17 immunity and ameliorates obesity‐associated metabolic syndrome in a murine high‐fat diet model
Authors: Martins Larissa M. S. , Perez Malena M. , Pereira Camila A. , Costa Frederico R. C. , Dias Murilo S. , Tostes Rita C. , Ramos Simone G. , de Zoete Marcel R. , Ryffel Bernhard , Silva João S. , Carlos Daniela
Published: May 2018

We addressed the role of interleukin‐23 (IL‐23) in driving the intestinal T helper type 17 (Th17) response during obesity and metabolic syndrome progression induced by a high‐fat diet (HFD). Diet‐induced obese and lean mice received HFD or control diet (CTD), respectively, for 20 weeks. The nutritional, metabolic and immune parameters were examined at weeks 9 and 20. Gene and protein IL‐23p19 and IL‐23 receptor expression was increased in the ileum of obese wild‐type mice (WT) fed the HFD for 9 weeks. Mice lacking IL‐23 and fed the HFD exhibited greater weight gain, higher fat accumulation, adipocyte hypertrophy and hepatic steatosis. Notably, these mice had more glucose intolerance, insulin resistance and associated metabolic alterations, such as hyperinsulinaemia and hyperlipidaemia. IL‐23 deficiency also significantly reduced protein levels of IL‐17, CCL20 and neutrophil elastase in the ileum and reduced Th17 cell expansion in the mesenteric lymph nodes of the HFD mice. Of importance, IL‐23‐deficient mice exhibited increased gut permeability and blood bacterial translocation compared with WT mice fed HFD. Finally, metagenomics analysis of gut microbiota revealed a dramatic outgrowth of Bacteroidetes over Firmicutes phylum with the prevalence of Bacteroides genera in the faeces of IL‐23‐deficient mice after HFD. In summary, IL‐23 appears to maintain the Th17 response and neutrophil migration into the intestinal mucosa, minimizing the gut dysbiosis and protecting against obesity and metabolic disease development in mice.
The WHO global influenza surveillance and response system (GISRS)—A future perspective
Authors: Hay Alan J , McCauley John W
Published: May 2018

In the centenary year of the devastating 1918‐19 pandemic, it seems opportune to reflect on the success of the WHO Global Influenza Surveillance and Response System (GISRS) initiated 70 years ago to provide early warning of changes in influenza viruses circulating in the global population to help mitigate the consequences of such a pandemic and maintain the efficacy of seasonal influenza vaccines. Three pandemics later and in the face of pandemic threats from highly pathogenic zoonotic infections by different influenza A subtypes, it continues to represent a model platform for global collaboration and timely sharing of viruses, reagents and information to forestall and respond to public health emergencies.
Investigation of anisotropic mechanical properties of textured KSr2Nb5O15 ceramics via ab‐initio calculation and nanoindentation
Authors: Chen Qian , Gao Feng , Csanádi Tamás , Xu Jie , Fu Maosen , Wang Min , Dusza Ján
Published: May 2018

Anisotropic mechanical properties of KSr2Nb5O15 (KSN) crystals were investigated through first‐principles calculations based on density functional theory. These properties were experimentally verified via nanoindentation on textured KSN ceramics fabricated, using a reactive template grain growth method. Nanoindentation was performed in directions parallel and perpendicular to the [001] direction of samples consisting of highly oriented grains with tetragonal symmetry. Calculations revealed that Nb‐O yields a relatively strong covalent effect and Nb‐O octahedral distortions induce spontaneous polarization in the KSN crystal. The measured indentation modulus values concurred with the predictions, based on the calculated elastic constants, as indicated by an anisotropic ratio of ~10% between the 2 tested orientations. The hardness exhibited negligible anisotropy. However, the predictions revealed a pronounced anisotropy of the Young's modulus (ratio of ~40% between the [100] direction and a direction tilted by ~45° from the [001] toward the [100]).
Computer‐assisted cognitive behavioural therapy: The experiences of adults who have an intellectual disability and anxiety or depression
Authors: Cooney Patricia , Jackman Catherine , Tunney Conall , Coyle David , O'Reilly Gary
Published: May 2018

Background

Despite its evidence base in the general population, computerized cognitive behavioural therapy (cCBT) has not yet been adapted for use with people with intellectual disability. This study aimed to explore the experiences of adults with an intellectual disability who played a cCBT program.

Method

Twenty‐four adults (with a mild or moderate intellectual disability and clinically significant anxiety or depression) who were in the treatment arm of a pilot randomized controlled trial evaluating the cCBT program were individually interviewed. Thematic analysis was used to analyse and report themes within the data.

Results

Participants found playing the program to be an enjoyable and novel experience and that it was challenging and helpful. It allowed them to develop and reflect on relationships and increased their awareness of thoughts, feelings and behaviours.

Conclusions

Combining technology with CBT is an effective way to reduce barriers to accessing mental health interventions and technology for this population.
The Science of Salt: A focused review on salt‐related knowledge, attitudes and behaviors, and gender differences
Authors: McKenzie Briar , Santos Joseph Alvin , Trieu Kathy , Thout Sudhir Raj , Johnson Claire , Arcand JoAnne , Webster Jacqui , McLean Rachael
Published: May 2018

The aim of the current review was to examine the scope of studies published in the Science of Salt Weekly that contained a measure of self‐reported knowledge, attitudes, and behavior (KAB) concerning salt. Specific objectives were to examine how KAB measures are used to evaluate salt reduction intervention studies, the questionnaires used, and whether any gender differences exist in self‐reported KAB. Studies were reviewed from the commencement of Science of Salt Weekly, June 2013 to the end of August 2017. Seventy‐five studies had relevant measures of KAB and were included in this review, 13 of these were salt‐reduction intervention‐evaluation studies, with the remainder (62) being descriptive KAB studies. The KAB questionnaires used were specific to the populations studied, without evidence of a best practice measure. 40% of studies used KAB alone as the primary outcome measure; the remaining studies used more quantitative measures of salt intake such as 24‐hour urine. Only half of the descriptive studies showed KAB outcomes disaggregated by gender, and of those, 73% showed women had more favorable KAB related to salt. None of the salt intervention‐evaluation studies showed disaggregated KAB data. Therefore, it is likely important that evaluation studies disaggregate, and are appropriately powered to disaggregate all outcomes by gender to address potential disparities.
Primary aldosteronism in patients with adrenal incidentaloma: Is screening appropriate for everyone?
Authors: Stavropoulos Konstantinos , Imprialos Konstantinos P. , Katsiki Niki , Petidis Konstantinos , Kamparoudis Apostolos , Petras Panagiotis , Georgopoulou Vasiliki , Finitsis Stefanos , Papadopoulos Christodoulos , Athyros Vasilios G. , Doumas Michael , Karagiannis Asterios
Published: May 2018

Primary aldosteronism (PA) is a common form of secondary hypertension. Several guidelines recommend that patients with adrenal incidentaloma have a high probability of suffering from PA. We conducted a prospective study of 269 consecutive adults with adrenal incidentaloma to investigate the prevalence and clinical characteristics of PA. In total, 9 participants were detected with PA, suggesting a prevalence of 3.35% among the study population. PA participants had a higher blood pressure level by 14/20.8 mm Hg and a lower serum potassium level by 0.8 mmol/L (P < .05). Importantly, all patients with PA presented with concurrent indications (hypertension with or without hypokalemia) for screening of the disease, but they have not undergone relative screening by the referring physician, thus casting doubts about the appropriate implementation of current guidelines in real‐life practice. Intense efforts are needed to familiarize physicians with recommendations for PA to minimize undiagnosed cases and the detrimental sequelae of this endocrine form of hypertension.
Toxoplasma gondii Histone 4 Affects Some Functions of Murine Ana‐1 Macrophages In Vitro
Authors: Liu Xinchao , Li Xiaoyu , Wang Qiangqiang , Sun Xiaoni , Lu Mingmin , Ehsan Muhammad , Xu Lixin , Yan RuoFeng , Song XiaoKai , Li XiangRui
Published: May 2018

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan that can infect almost all nucleated cells. Histone proteins and DNA form the nucleosomes, which are the fundamental building blocks of eukaryotic chromatin. Histone 4 is an essential component of a histone octamer. In the present study, T. gondii histone 4 (TgH4) was cloned and the regulatory effect of TgH4 on murine macrophages was characterized. Bioinformatics analysis revealed that TgH4 was highly conserved in structure. Recombinant TgH4 (rTgH4) protein was identified by sera from rats experimentally infected with T. gondii and native TgH4 in the total soluble protein of T. gondii tachyzoites was recognized by polyclonal antibodies against rTgH4, as indicated by immunoblotting analysis. Immunofluorescence assay showed that TgH4 binds to macrophages. Following incubation with rTgH4, the toll‐like receptor 4 (TLR4) level of the macrophages was downregulated. Meanwhile, chemotaxis and the proliferation of macrophages were inhibited. However, rTgH4 can promote phagocytosis, apoptosis, and the secretion of nitric oxide, interleukin‐6, and tumor necrosis factor‐α from macrophages. Just 80 μg/ml rTgH4 can significantly elevate the secretion of interleukin‐10 and interleukin‐1β (p < 0.05 and p < 0.01). Viewed together, these outcomes indicated that rTgH4 can affect the functions of murine macrophages in vitro.
One percent alendronate and aloe vera gel local host modulating agents in chronic periodontitis patients with class II furcation defects: A randomized, controlled clinical trial
Authors: Ipshita Sahu , Kurian Ida G. , Dileep Pankaj , Kumar Shatrughan , Singh Priyanka , Pradeep Avani R.
Published: May 2018

Aim

Alendronate (ALN) has antiresorptive and osteostimulative properties. The major component of aloe vera (AV) gel is acemannan, which has been found to have osteogenic properties. The aim of the present study is to explore the effectiveness of 1% ALN and AV gel as an adjunct to scaling and root planing (SRP) in chronic periodontitis patients with class II furcation defects.

Methods

Ninety volunteers were randomly assigned to three treatment groups: (a) SRP plus placebo gel; (b) SRP plus 1% ALN gel; and (c) SRP plus AV gel. Clinical and radiographic parameters were recorded at baseline and at 6 and 12 months.

Results

The mean probing depth reduction and relative horizontal clinical attachment level (CAL) and relative vertical CAL gains were greater in the ALN group than in the AV and placebo groups at 6 and 12 months. Furthermore, a significantly greater mean percentage of defect depth reduction (DDR) was found in the ALN group (38.09 ± 9.53, 44.86 ± 6.29) than the AV groups (11.94 ± 15.10, 14.59 ± 25.49) at 6 and 12 months, respectively.

Conclusion

ALN showed significant improvement in all clinical parameters, along with greater DDR, compared to AV in the treatment of class II furcation defects as an adjunct to SRP.
Tectonometamorphic evolution of the Atbashi high‐Punits (KyrgyzCAOB, Tien Shan): Implications for the closure of the Turkestan Ocean and continental subduction–exhumation of the South Kazakh continental margin
Authors: Loury Chloé , Rolland Yann , Guillot Stéphane , Lanari Pierre , Ganino Clément , Melis Raphael , Jourdon Anthony , Petit Carole , Beyssac Olivier , Gallet Sylvain , Monié Patrick
Published: May 2018

The South Tien Shan (STS) belt results from the last collision event in the western Central Asian Orogenic Belt (CAOB). Understanding its formation is of prime importance in the general framework of theCAOB. The Atbashi Range preserves high‐P(HP) rocks along the STS suture, but still, its global metamorphic evolution remains poorly constrained. SeveralHPunits have been identified: (a) a HP tectonic mélange including boudins of mafic eclogites in a sedimentary matrix, (b) a large (>100 km long) high‐Pmetasedimentary unit (HPMU) and (c) a lower blueschist facies accretionary prism. Raman Spectroscopy on carbonaceous material combined with phengite and chlorite multiequilibria and isochemical phase diagram modelling indicates that theHPMUrecorded homogeneousP–Tconditions of 23–25 kbar and 560–570°C along the whole unit.40Ar/39Ar dating on phengite from theHPMUranges between 328 and 319 Ma at regional scale. These ages are interpreted as (re‐) crystallization ages of phengite duringTmaxconditions at a pressure range of 20–25 kbar. Thermobarometry on samples from the HP tectonic mélange provides similar metamorphic peak conditions. Thermobarometry on the blueschist to lower greenschist facies accretionary prism indicates that it underwentP–Tconditions of 5–6 kbar and 290–340°C, highlighting a 17–20 kbar pressure gap between theHPMU‐tectonic mélange units and the accretionary prism. Comparison with available geochronological data suggests a very short time span between the prograde path (340 Ma),HPmetamorphic peak (330 Ma), theTmax(328–319 Ma) and the final exhumation of theHPMU(303–295 Ma). Extrusion of theHPMU, accommodated by a basal thrust and an upper detachment, was driven by buoyant forces from 70–75 km up to 60 km depth, which directly followed continental subduction and detachment of theHPMU. At crustal depths, extrusion was controlled by collisional tectonics up to shallow levels. Lithological homogeneity of theHPMUand its continental‐derived character from the North Tien Shan suggest this unit corresponds to the hyper‐extended continental margin of the Kazakh continent, subducted southward below the north continental active margin of the Tarim craton. Integration of the available geological data allows us to propose a general geodynamic scenario for Tien Shan during the Carboniferous with a combination of (a) N‐dipping subduction below the Kazakh margin of Middle Tien Shan until 390–340 Ma and (b) S‐dipping subduction of remaining Turkestan marginal basins between 340 and 320 Ma.
Paternity Leave‐Taking and Father Engagement
Authors: Petts Richard J. , Knoester Chris
Published: May 2018

Evidence suggests that paternity leave‐taking is associated with higher levels of father involvement, but research has been limited in its focus on cross‐sectional analyses and indicators of father involvement used. This study uses national longitudinal data to examine whether paternity leave‐taking is associated with 2 indicators of father engagement when children are infants, whether paternity leave‐taking is associated with trajectories of father engagement during the first few years of a child's life, and whether the relationships between paternity leave and father engagement are explained by fathering commitments and attitudes. The results suggest that longer periods of leave are associated with more frequent engagement in developmental tasks and caretaking when children are infants as well as during the first few years of children's lives. There is also evidence that father attitudes partially explain the relationships between length of paternity leave and father engagement.
The effects of maternal risk factors during pregnancy on the onset of sleep difficulties in infants at 3 months old
Authors: Morales‐Muñoz Isabel , Saarenpää‐Heikkilä Outi , Kylliäinen Anneli , Pölkki Pirjo , Porkka‐Heiskanen Tarja , Paunio Tiina , Paavonen E. Juulia
Published: May 2018

Sleep problems in young children are among the most common concerns reported to paediatricians. Sleep is thought to have important regulatory functions, and sleep difficulties in early childhood are linked to several psychosocial and physiological problems. Moreover, several prenatal factors have been found to influence infants’ sleep. Among them, most of the studies have been focused on maternal prenatal depression and/or anxiety as potential risk factors for sleep problems in childhood, whereas other relevant psychological factors during pregnancy have not received as much attention. Therefore, we aimed to examine the effect of several psychiatric maternal risk factors during pregnancy (i.e. symptoms of anxiety, depression, insomnia, alcohol use, seasonality, attention deficit and hyperactivity disorder and/or stressful life events) on the onset of some sleep problems related to sleep quality and sleep practices in 3‐month‐old infants. We examined 1,221 cases from a population‐based birth cohort, with subjective measures during pregnancy in mothers, and at 3 months after birth in the infants. The findings showed that all the maternal risk factors during pregnancy, except for symptoms of alcoholism and sleepiness, were related to sleep difficulties in infants. Interestingly, attention deficit and hyperactivity disorder symptomatology in mothers during pregnancy was the only variable that predicted more than two sleeping difficulties (i.e. long sleep‐onset latency, co‐sleeping with parents and irregular sleeping routines) at 3 months old. Our results highlight the relevance of maternal risk factors during pregnancy, and not only prenatal depression and/or anxiety, as variables to be considered when examining sleep difficulties in infants.
Reproducibility of gastric emptying assessed with scintigraphy in patients with upper GI symptoms
Authors: Desai A. , O'Connor M. , Neja B. , Delaney K. , Camilleri M. , Zinsmeister A. R. , Bharucha A. E.
Published: May 2018

Background

The reproducibility of gastric emptying (GE) measured with scintigraphy in patients is poorly understood. Our aims were to assess the intra and inter‐individual reproducibility of these parameters in patients with upper gastrointestinal symptoms.

Methods

Sixty patients (21 diabetics, 39 non‐diabetics) with upper gastrointestinal symptoms underwent scintigraphic‐assessment of GE of a solid meal (296 kcal, 30% fat) over 4 hours on two occasions at an average interval of 15 days. The concordance correlation coefficient (CCC), intra and inter‐individual coefficients of variation (COV) of GE endpoints were analyzed.

Results

The GE t1/2 was 134 ± 8 minutes (mean ± SEM) for the first and 128 ± 6 minutes for the second study. The mean (95% CI) CCC between the two studies was 0.79 (0.67, 0.87) for GE at 1 hour, 0.83 (0.75, 0.9) for GE at 2 hours, 0.54 (0.34, 0.7) for GE at 4 hours, and 0.79 (0.68, 0.86) for GE t1/2. However, in 18 of 60 patients (30%), the characterization of GE as normal, delayed, or rapid differed between the first and second studies. For gastric empting t1/2, the inter‐individual coefficients of variation was 40%; the intra‐individual COV was 20%, comparable in diabetics and non‐diabetics, and greater in patients with rapid (28%) than delayed (18%) or normal GE (12%).

Conclusions & Inferences

Among patients with upper gastrointestinal symptoms, GE measured with scintigraphy is relatively reproducible. In 30% of cases, the interpretation was different between the two assessments. Hence, a diagnosis of gastroparesis based on a single study may occasionally be inaccurate.
Bayesian networks for evaluating climate change influence in olive crops in Andalusia, Spain
Authors: Ropero Rosa F. , Rumí Rafael , Aguilera Pedro A.
Published: May 2018

Olive crops have become a strategic sector in Andalusia, Spain, providing an element of social cohesion and territorial management, but identified as vulnerable under climate change. Their great socioeconomic importance makes the mitigation of climate change effects an important strategy. The main contribution of this paper is to show the application of Bayesian networks into climate change assessment using the evaluation of its impact over olive system in Andalusia. Both classification and regression models were learnt and validated to predict the potential olive grove distribution under an Intergovernmental Panel on Climate Change scenario. A lower error rate was obtained for the regression problem compared to classification. Results predict that climate change will lead to changes into the territorial distribution of olive crops, with a movement from the river valley to the uplands due to the impact of the predicted increase in temperatures.

Recommendations for Resource Managers

Bayesian networks are a powerful tool that allows dealing with both discrete and continuous data. However, if continuous data are available in order to retrieve all statistical information from them, discretization process should be avoided and original continuous data used for modeling purpose.

Olive cropping area follows an altitudinal gradient from the river bed to the mountainous ranges. The minimum temperature limits the establishment of this crop over certain altitude.

Under the scenario of climate change, the altitudinal gradient is lost and the main expanse of olive groves becomes fragmented into smaller patches. Besides, mountainous areas would reach optimal conditions for olive growth due to the increase in temperatures.
Estimating pediatric general anesthesia exposure: Quantifying duration and risk
Authors: Bartels Devan Darby , McCann Mary Ellen , Davidson Andrew J. , Polaner David M. , Whitlock Elizabeth L. , Bateman Brian T.
Published: May 2018

Introduction

Understanding the duration of pediatric general anesthesia exposure in contemporary practice is important for identifying groups at risk for long general anesthesia exposures and designing trials examining associations between general anesthesia exposure and neurodevelopmental outcomes.

Methods

We performed a retrospective cohort analysis to estimate pediatric general anesthesia exposure duration during 2010‐2015 using the National Anesthesia Clinical Outcomes Registry.

Results

A total of 1 548 021 pediatric general anesthetics were included. Median general anesthesia duration was 57 minutes (IQR: 28‐86) with 90th percentile 145 minutes. Children aged <1 year had the longest median exposure duration (79 minutes, IQR: 39‐119) with 90th percentile 210 minutes, and 13.7% of this very young cohort was exposed for >3 hours. High ASA physical status and care at a university hospital were associated with longer exposure times.

Conclusion

While the vast majority (94%) of children undergoing general anesthesia are exposed for <3 hours, certain groups may be at increased risk for longer exposures. These findings may help guide the design of future trials aimed at understanding neurodevelopmental impact of prolonged exposure in these high‐risk groups.
Genome‐wide association analyses of plant growth traits during the stem elongation phase in wheat
Authors: Guo Zifeng , Liu Guozheng , Röder Marion S. , Reif Jochen C. , Ganal Martin W. , Schnurbusch Thorsten
Published: May 2018

One of the primary objectives of wheat breeding was to increase grain yield. Floral abortion during the stem elongation phase (SEP) leads to a loss of more than 50% of the grain number potential. In this study, we quantified 75 plant growth‐associated traits at seven stages during the SEP and mapped 15 696 single nucleotide polymorphism (SNP) markers in 210 accessions of wheat (Triticum aestivum). Our genomewide association study identified trait‐associated SNPs that are shared among various stages of the SEP, as well as SNPs that are shared between plant growth traits and grain yield in the field. The genomic selection analysis shows variation among the prediction abilities of various traits and stages. Furthermore, we found that the allelic variants of Ppd‐D1 (chromosome 2D) and Rht‐D1 (chromosome 4D) loci affect some plant growth traits (e.g. leaf area and spike length). These results have identified a narrow time window within the SEP in which plant growth traits can be manipulated to alter grain yield. This suggests that there may be multiple ways to regulate plant growth during the SEP, to ultimately influence grain number in wheat.
Genotyping genome‐edited mutations in plants using CRISPR ribonucleoprotein complexes
Authors: Liang Zhen , Chen Kunling , Yan Yan , Zhang Yi , Gao Caixia
Published: May 2018

Despite the great achievements in genome editing, accurately detecting mutations induced by sequence‐specific nucleases is still a challenge in plants, especially in polyploidy plants. An efficient detection method is particularly vital when the mutation frequency is low or when a large population needs to be screened. Here, we applied purified CRISPR ribonucleoprotein complexes to cleave PCR products for genome‐edited mutation detection in hexaploid wheat and diploid rice. We show that this mutation detection method is more sensitive than Sanger sequencing and more applicable than PCR/RE method without the requirement for restriction enzyme site. We also demonstrate that this detection method is especially useful for genome editing in wheat, because target sites are often surrounded by single nucleotide polymorphisms. Using this screening method, we were also able to detect foreign DNA‐free tagw2 mutations induced by purified TALEN protein. Finally, we show that partial base editing mutations can also be detected using high‐fidelity SpCas9 variants or FnCpf1. The PCR/RNP method is low‐cost and widely applicable for rapid detection of genome‐edited mutation in plants.
Specialized properties of the triceps surae muscle‐tendon unit in professional ballet dancers
Authors: Moltubakk M. M. , Magulas M. M. , Villars F. O. , Seynnes O. R. , Bojsen‐Møller J.
Published: May 2018

This study compared professional ballet dancers (n = 10) to nonstretching controls (n = 10) with the purpose of comparing muscle and tendon morphology, mechanical, neural, and functional properties of the triceps surae and their role for ankle joint flexibility. Torque‐angle and torque‐velocity data were obtained during passive and active conditions by use of isokinetic dynamometry, while tissue morphology and mechanical properties were evaluated by ultrasonography. Dancers displayed longer gastrocnemius medialis fascicles (55 ± 5 vs 47 ± 6 mm) and a longer (207 ± 33 vs 167 ± 10 mm) and more compliant (230 ± 87 vs 364 ± 106 N/mm) Achilles tendon compared to controls. Greater passive ankle dorsiflexion range of motion (40 ± 7 vs 17 ± 9°) was seen in dancers, resulting from greater fascicle strain and greater elongation of the muscle. Peak electromyographic (EMG) activity recorded during passive stretching was lower in dancers, and at common joint angles, dancers displayed lower EMG amplitude and lower passive joint stiffness. No differences between groups were seen in maximal isometric plantar flexor torque, isokinetic peak torque, angle of peak torque, or work. In conclusion, the greater ankle joint flexibility of professional dancers seems attributed to multiple differences in morphological and mechanical properties of muscle and tendinous tissues, and to factors related to neural activation.
Analysis and comparison of different methods used to extract isoclinic and isochromatic parameters. Application to the determination of the residual stresses inside crystal silicon wafers
Authors: Jagailloux F. , Valle V.
Published: May 2018

The present work focuses on an experimental analysis of different photoelastic extraction methods. An adapted test rig designed in order to evaluate several extraction methods, which come from the literature and 2 new proposed methods. Their comparisons point out dissimilar behaviours between them in an experimental environment. However, some specific cases require the use of most appropriate techniques to minimise the defects influence. Therefore, a specific application of the photoelasticity is presented to illustrate the meaning of the technique used. It mainly focuses on the determination of the residual stresses and their orientation inside photovoltaic crystal silicon wafers.
Heterodimeric O‐methyltransferases involved in the biosynthesis of noscapine in opium poppy
Authors: Park Myung R. , Chen Xue , Lang Dean E. , Ng Kenneth K.S. , Facchini Peter J.
Published: May 2018

Noscapine biosynthesis in opium poppy involves three characterized O‐methyltransferases (OMTs) and a fourth responsible for the 4ʹ‐methoxyl on the phthalide isoquinoline scaffold. The first three enzymes are homodimers, whereas the latter is a heterodimer encoded by two linked genes (OMT2 and OMT3). Neither OMT2 nor OMT3 form stable homodimers, but yield a substrate‐specific heterodimer when their genes are co‐expressed in Escherichia coli. The only substrate, 4ʹ‐O‐desmethyl‐3‐O‐acetylpapaveroxine, is a seco‐berbine pathway intermediate that undergoes ester hydrolysis subsequent to 4ʹ‐O‐methylation leading to the formation of narcotine hemiacetal. In the absence of 4ʹ‐O‐methylation, a parallel pathway yields narcotoline hemiacetal. Dehydrogenation produces noscapine and narcotoline from the corresponding hemiacetals. Phthalide isoquinoline intermediates with a 4ʹ‐hydroxyl (i.e. narcotoline and narcotoline hemiacetal), or the corresponding 1‐hydroxyl on protoberberine intermediates, were not accepted. Norcoclaurine 6OMT, which shares 81% amino acid sequence identity with OMT3, also formed a functionally similar heterodimer with OMT2. Suppression of OMT2 transcript levels in opium poppy increased narcotoline accumulation, whereas reduced OMT3 transcript abundance caused no detectable change in the alkaloid phenotype. Opium poppy chemotype Marianne accumulates high levels of narcotoline and showed no detectable OMT2:OMT3 activity. Compared with the active subunit from the Bea's Choice chemotype, Marianne OMT2 exhibited a single S122Y mutation in the dimerization domain that precluded heterodimer formation based on homology models. Both subunits contributed to the formation of the substrate‐binding domain, although site‐directed mutagenesis revealed OMT2 as the active subunit. The occurrence of physiologically relevant OMT heterodimers increases the catalytic diversity of enzymes derived from a smaller number of gene products.