bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of corypalmine in mouse blood by UPLC–MS/MS and its application to a pharmacokinetic study
Authors: Wu Haiya , Yan Qizhi , Fan Zhehua , Huang Miaoling , He Jiamin , Ma Jianshe , Wang Xianqin
Published: April 2018

In this work, a selective and sensitive ultra‐performance liquid chromatography tandem mass spectrometry method was established and validated for determination of corypalmine in mouse blood after oral or intravenous administration. A UPLC BEH C18 column was used to separate corypalmine and berberrubine (internal standard) at 40°C. The mobile phase was composed of acetonitrile and 10 mmol/L ammonium acetate (containing 0.1% formic acid) at a flow rate of 0.4 mL/min, and the total run time was 4.0 min. Electrospray ionization in positive ion mode was applied; target fragment ions m/z 342.2 → 178.0 for corypalmine and m/z 322.1 → 307.0 for berberrubine were identified with multiple reaction monitoring mode. The linear range was 1–1000 ng/mL (r > 0.995) and the lower limit of quantification for corypalmine in plasma was 1.0 ng/mL. The intra‐ and inter‐day precisions were both <14%. The range of accuracy in this method was 97.5–109.0%. Mean recovery was >69.6%, and the matrix effect was 96.8–107.6%. Based on its high sensitivity, specificity and reliability, this method was successfully applied to study the pharmacokinetic parameters of corypalmine in mouse by oral and intravenous administration, and finally, the bioavailability of corypalmine was identified at 4.6%.
Development and validation of a HPLC‐UV assay for quantification of levetiracetam concentrations in critically ill patients undergoing continuous renal replacement therapy
Authors: Kalaria Shamir N. , Dahmane Elyes , Armahizer Michael , McCarthy Paul , Gopalakrishnan Mathangi
Published: April 2018

Limited clinical data exists on the effects of continuous renal replacement therapy (CRRT) on drug pharmacokinetics. A high‐performance liquid chromatography with ultraviolet detection method was developed and validated to determine levetiracetam concentrations in human plasma and CRRT effluent samples. Five hundred microliters of human plasma and 250 μL effluent samples were used to quantify levetiracetam. Plasma samples were purified by protein precipitation, evaporated under nitrogen gas at room temperature and reconstituted in 50 mm potassium dihydrogen phosphate buffer (pH of 4.5). Reverse‐phase chromatographic separation was achieved within 20 min using a mobile phase eluting gradient of 50 mm potassium dihydrogen phosphate and acetonitrile. UV detection was set at 195 nm. The calibration curve was found to be linear over the range of 2–80μg/mL. Inter‐ and intra‐day precisions were < 8% for both plasma and effluent samples. The accuracy was determined to be within −12–10% of nominal concentrations. The method was selective and sensitive with a lower limit of quantification of 2 μg/mL. Overall recovery of levetiracetam from plasma was ~100%. The validated assay was successfully applied in a pharmacokinetic study to determine potential dose adjustments in patients undergoing CRRT and receiving levetiracetam.
A two‐dimensional, two‐level framework for achieving corporate sustainable development: Assessing the return on sustainability initiatives
Authors: Wu Lin , Subramanian Nachiappan , Gunasekaran Angappa , Abdulrahman Muhammad Dan‐Asabe , Pawar Kulwant Singh , Doran Des
Published: April 2018

Sustainability studies in operations management have reported the positive effects of lean, green and social management systems on various dimensions of a firm's sustainability performance. However, despite its importance and relevance, the time dimension of sustainability has not been systematically considered. This paper recategorizes the well‐identified sustainability initiatives based on a time dimension and empirically validates the categorization. Structural equation modeling analyses were performed using data collected from 284 Chinese automotive firms. The results suggest that various lean and reactive green practices can be categorized as “short‐term sustainability initiatives” because the effects of implementing these practices can be seen in a short time. Specifically, the benefits of implementing short‐term sustainability initiatives can be further strengthened and reinforced in the long run by implementing corporate social responsibility (CSR) practices. In addition, our findings demonstrate that to fully realize the potential associated with CSR practices, firms need to be orientated to the long term and adopt a wait and watch approach.
Photoactivatable Adhesive Ligands for Light‐Guided Neuronal Growth
Authors: Farrukh Aleeza , Fan Wenqiang , Zhao Shifang , Salierno Marcelo , Paez Julieta I. , del Campo Aránzazu
Published: April 2018

Neuro‐regeneration after trauma requires growth and reconnection of neurons to reestablish information flow in particular directions across the damaged tissue. To support this process, biomaterials for nerve tissue regeneration need to provide spatial information to adhesion receptors on the cell membrane and to provide directionality to growing neurites. Here, photoactivatable adhesive peptides based on the CASIKVAVSADR laminin peptidomimetic are presented and applied to spatiotemporal control of neuronal growth to biomaterials in vitro. The introduction of a photoremovable group [6‐nitroveratryl (NVOC), 3‐(4,5‐dimethoxy‐2‐nitrophenyl)butan‐2‐yl (DMNPB), or 2,2′‐((3′‐(1‐hydroxypropan‐2‐yl)‐4′‐nitro‐[1,1′‐biphenyl]‐4‐yl)azanediyl)bis(ethan‐1‐ol) (HANBP)] at the amino terminal group of the K residue temporally inhibited the activity of the peptide. The bioactivity was regained through controlled light exposure. When used in neuronal culture substrates, the peptides allowed light‐based control of the attachment and differentiation of neuronal cells. Site‐selective irradiation activated adhesion and differentiation cues and guided seeded neurons to grow in predefined patterns. This is the first demonstration of ligand‐based light‐controlled interaction between neuronal cells and biomaterials.
Calcium‐Mobilizing Behaviors of Neutral Cyclic ADP‐Ribose Mimics that Integrate Modifications to the Nucleobase, Northern Ribose and Pyrophosphate
Authors: Wang Xuan , Zhang Xiaoyan , Zhang Kehui , Hu Jianxing , Liu Zhenming , Jin Hongwei , Zhang Liangren , Zhang Lihe
Published: April 2018

Cyclic adenosine diphosphate ribose (cADPR) is an endogenous Ca2+ mobilizer involved in diverse cellular processes. Mimics of cADPR play a crucial role in investigating the molecular mechanism(s) of cADPR‐mediated signaling. Here, compound 3, a mimic of cADPR in which a neutral triazole moiety and an ether linkage were introduced to substitute the pyrophosphate and “northern” ribose components, respectively, was synthesized for the first time. The pharmacological activities in Jurkat cells indicated that this mimic is capable of penetrating plasma membrane and inciting Ca2+ release from the endoplasmic reticulum (ER) through the action of ryanodine receptors (RyRs) and triggering Ca2+ influx. Furthermore, a uridine moiety was introduced in place of adenine and the new cADPR mimics 4 and 5 were synthesized. The results of biological investigation showed that these mimics also targeted RyRs and retained moderate Ca2+ agonistic activities. The results indicated that the neutral cADPR mimics had the same targets for inducing Ca2+ signaling.
The under‐appreciated and still under‐investigated consequences of “supersized” access and closure
Authors: Turi Zoltan G.
Published: April 2018

Key Points

Large bore access and closure of the femoral artery has the potential to cause or accelerate local vascular disease

The implications of accelerated disease could be substantial

Further investigation is needed to assess the true short‐ and long‐term effects
Unilateral upper extremity lymphedema in metastatic prostate cancer
Authors: Mupamombe Charles T. , LoGiurato Brendan , Kampel Lewis , Cohen Jean Marc
Published: April 2018

Key Clinical Message

Upper extremity lymphedema and cutaneous spread are atypical behavior of prostate disease and should be kept in the differential for selected patients. This presentation in these patients may be underdiagnosed and potentially an ominous sign. Our case adds to our continued learning of possible prostate malignancy behavior.
Hematopoietic cell transplantation for myeloid/NK cell precursor acute leukemia in second remission
Authors: Noguchi Yusuke , Tomizawa Daisuke , Hiroki Haruka , Miyamoto Satoshi , Tezuka Mari , Miyawaki Reiji , Tanaka‐Kubota Mari , Okano Tubasa , Kobayashi Chika , Mitsuiki Noriko , Aoki Yuki , Imai Kohsuke , Kajiwara Michiko , Kanegane Hirokazu , Morio Tomohiro , Takagi Masatoshi
Published: April 2018

Key Clinical Message

Myeloid/natural killer cell precursor acute leukemia (MNKPL) is a rare leukemia subtype characterized by a high incidence of extramedullary infiltration. No appropriate treatment strategy has so far been developed. Acute myelogenous leukemia‐type chemotherapy combined with L‐Asparaginase is an effective treatment for MNKPL. Hematopoietic cell transplantation is a second option in refractory cases.
Colonic bleeding from migrated cement
Authors: Sotiropoulos Georgios C. , Garoufalia Zoe , Klonaris Christos , Machairas Nikolaos
Published: April 2018

Key Clinical Message

Migration of foreign bodies through the colonic wall can be the result of inflammation or effect of radiotherapy. Patients with such condition may remain asymptomatic. Careful assessment of patient' history can provide valuable information in symptomatic cases such as colonic obstruction or bleeding.
Merkel cell carcinoma with intramedullary spinal cord metastasis: a very rare clinical finding
Authors: Haykal Tarek , Towfiq Basim
Published: April 2018

Key Clinical Message

This clinical image teaches readers that a rare finding such as intramedullary spinal metastasis could exist even in the rarest tumors. It adds to the literature how it was managed. It also might reflect the improvement of our cancer treatment allowing us to follow patients longer to find those rare findings in rare tumors.
Morel‐Lavallee injury a case study
Authors: Myrick Karen M. , Davis Stephen
Published: April 2018

Key Clinical Message

Morel‐Lavallee lesions are post‐traumatic, soft‐tissue degloving injuries commonly misdiagnosed as hematomas or ruptured bursa. The clinician needs to be aware of this injury, in order to provide appropriate patient care and treatment. If not treated early, risks include superinfection, continued expansion, overlying tissue necrosis, and suboptimal patient outcomes.
Phenol Catalytic Hydrogenation over Palladium Nanoparticles Supported on Metal‐Organic Frameworks in the Aqueous Phase
Authors: Chen Hao , He Yulian , Pfefferle Lisa D. , Pu Weihua , Wu Yulong , Qi Suitao
Published: April 2018

Metal‐organic frameworks (MOFs) have been extensively applied as supports in hydrogenation catalysis owing to their topological structure and high hydrogen storage capabilities. Pd nanoparticles (NPs) supported on a hollow box‐shaped MOF were prepared for phenol hydrogenation in the aqueous phase. The MOF preparation modulated by monocarboxylic acids grow into different structures. MOF140‐AA, modulated by acetic acid at 140 °C, presents the structure of regular cube with a smooth surface. Compared to other supports, Pd NPs supported on MOF140‐AA presents high phenol conversion due to the high hydrogen storage capability of MOF140‐AA. Phenol is completely converted to cyclohexanol over Pd/MOF140‐AA reacted at 260 °C for 2 h with high selectivity. The reaction mechanism of phenol hydrogenation is studied by density functional theory (DFT). The phenol hydrogenation mechanism is calculated on a Pd38 cluster, which describes the reaction pathway consistent with experimental results.
Simple Green Synthesis and Electrochemical Performance of a New Fluorinated Carbonate as Additive for Lithium‐Ion Batteries
Authors: Beichel Witali , Klose Petra , Blattmann Hannes , Hoecker Johannes , Kratzert Daniel , Krossing Ingo
Published: April 2018

A fluorinated carbonate (4‐(2,2,3,3,4,4,5,5,5‐nonafluoro‐pentyl)‐1,3‐dioxolan‐2‐one, 1) was synthesized from the corresponding oxirane through a one‐step carbonation reaction. The compound was obtained in quantitative yield with battery‐grade purity on a 50 g scale. Carbonate 1 was fully characterized by NMR, IR, MS, and crystal structure analysis. The compound melts at 98 °C and decomposes at 168 °C. When used as additive in lithium‐ion half‐ and full‐cell tests, 1 exhibited no reactivity toward the graphite anode, no participation in the solid‐electrolyte interphase (SEI) formation and led to a higher oxidation stability of the electrolyte against a carbon black electrode, compared to 4‐fluoro‐ethylenecarbonate and 4‐trifluoromethyl‐1,3‐dioxolan‐2‐one. The facile, clean, and scalable one‐step synthesis of 1 combined with its electrochemical behavior characterizes it as a promising additive for high voltage applications in lithium‐ion batteries.
Non‐Heme Iron Catalysts for Olefin Epoxidation: Conformationally Rigid Aryl–Aryl Junction To Support Amine/Imine Multidentate Ligands
Authors: Park Hyunchang , Ahn Hye Mi , Jeong Ha Young , Kim Cheal , Lee Dongwhan
Published: April 2018

Atom‐transfer chemistry represents an important class of reactions catalyzed by metalloenzymes. As a functional mimic of non‐heme iron enzymes that deliver oxygen atoms to olefins, we have designed monoiron complexes supported by new N‐donor chelates. These ligands take advantage of heme‐like conformational rigidity of the π‐conjugated molecular backbone, and synthetic flexibility of tethering non‐heme donor groups for additional steric and electronic control. Iron complexes generated in situ can be used to carry out catalytic epoxidation of a wide range of olefin substrates by using mCPBA as a terminal oxidant. The fate of initial iron‐peracid adduct and the involvement of iron‐oxo species in this process were investigated further by mechanistic probes and isotope exchange studies. Our findings suggest that anilidopyridyl‐derived [N,N]‐bidentate motif could serve as a versatile structural platform to build non‐heme ligands for catalytic oxidation chemistry.
Ist Mycel das Material der Zukunft?
Authors: Dänzer Tatjana
Published: April 2018

Nein, Myzel (engl. Mycelium) ist kein neuentdecktes chemisches Element. Aber es könnte die Lösung für Alternativen zu erdölbasierten Materialien sein.
Overcoming the gamma‐ray computed tomography data processing pitfalls for bubble column equipped with vertical internal tubes
Authors: Sultan Abbas J. , Sabri Laith S. , Shao Jianbin , Al‐Dahhan Muthanna H.
Published: April 2018

This study identifies and addresses some major pitfalls that are involved in the visualization and quantification of the gas‐liquid distributions and their profiles in a bubble column with internals using the gamma‐ray computed tomography (CT) technique. Some of these pitfalls encountered in the scanning of bubble columns with internals are using an improper reference scan, and applying the same experimental scanning procedure and mathematical relationships for estimating the gas holdup in the column without internals to the column with internals. The experimental results revealed that the selection of the inappropriate reference scan for CT experiments would significantly affect the reconstructed linear attenuation coefficient values and consequently the gas holdup results. Additionally, the reconstructed linear attenuation values showed good agreement with theoretical values when considering air as reference scans. However, disagreement is observed when using the empty column with internals as a reference scan. Moreover, it was found that using the proper reference scan eliminated the errors not only for the reconstructed linear attenuation coefficients but also for the gas holdup values near the wall region. Furthermore, the CT technique was capable of capturing the small thickness (5 mm) of the wall for phantom and bubble columns as well as the internals when the air was used as the reference scan. Finally, a new methodology has been implemented to exclude the internals from the cross‐sectional images, and the azimuthally averaged gas holdup profiles to provide accurate and reliable results for comparison and validation purposes for the bubble column with internals.
Anaplastic lymphoma kinase (ALK) gene rearrangements in radiation‐related human papillary thyroid carcinoma after the Chernobyl accident
Authors: Arndt Annette , Steinestel Konrad , Rump Alexis , Sroya Manveer , Bogdanova Tetiana , Kovgan Leonila , Port Matthias , Abend Michael , Eder Stefan
Published: April 2018

Childhood radiation exposure has been associated with increased papillary thyroid carcinoma (PTC) risk. The role of anaplastic lymphoma kinase (ALK) gene rearrangements in radiation‐related PTC remains unclear, but STRN‐ALK fusions have recently been detected in PTCs from radiation exposed persons after Chernobyl using targeted next‐generation sequencing and RNA‐seq. We investigated ALK and RET gene rearrangements as well as known driver point mutations in PTC tumours from 77 radiation‐exposed patients (mean age at surgery 22.4 years) and PTC tumours from 19 non‐exposed individuals after the Chernobyl accident. ALK rearrangements were detected by fluorescence in situ hybridisation (FISH) and confirmed with immunohistochemistry (IHC); point mutations in the BRAF and RAS genes were detected by DNA pyrosequencing. Among the 77 tumours from exposed persons, we identified 7 ALK rearrangements and none in the unexposed group. When combining ALK and RET rearrangements, we found 24 in the exposed (31.2%) compared to two (10.5%) in the unexposed group. Odds ratios increased significantly in a dose‐dependent manner up to 6.2 (95%CI: 1.1, 34.7; p = 0.039) at Iodine‐131 thyroid doses >500 mGy. In total, 27 cases carried point mutations of BRAF or RAS genes, yet logistic regression analysis failed to identify significant dose association. To our knowledge we are the first to describe ALK rearrangements in post‐Chernobyl PTC samples using routine methods such as FISH and IHC. Our findings further support the hypothesis that gene rearrangements, but not oncogenic driver mutations, are associated with ionising radiation‐related tumour risk. IHC may represent an effective method for ALK‐screening in PTCs with known radiation aetiology, which is of clinical value since oncogenic ALK activation might represent a valuable target for small molecule inhibitors.
Effect of Catch‐Can Spacing on Calculation of Sprinkler Irrigation Application Uniformity
Authors: Zhang Lin , Merkley Gary P. , Wu Pute , Zhu Delan
Published: April 2018

Sprinkler irrigation application uniformity is an important indicator for sprinkler irrigation system design, which can be expressed by the Christiansen uniformity coefficient (CU). The calculated accuracy of CU is closely related with catch‐can spacing and grid size. In theory, the smaller the catch‐can spacing and grid size are, the more accurate the calculation of CU is. However, smaller catch‐can spacing needs more labor in water distribution measurement, and smaller grid size needs more computer runtime to calculate CU. In order to recommend the proper catch‐can spacing and grid size, an experiment is carried out to obtain four different water distribution patterns, and data characteristics for water distribution with various catch‐can spacing and the effect of catch‐can spacing and grid size on CU are studied in the paper. The results show that CU is overestimated for the larger catch‐can spacing, especially when the distribution of water for the pattern is non‐uniformity. CU changes very little within a certain catch‐can spacing and grid size for all the four patterns. Considering the accuracy of CU calculation, labor cost, and the computational runtime, the recommended catch‐can spacing is 1.96 m for pattern I, 0.92 m for patterns III and IV, and the recommended grid size in the calculation of CU is 1.25, 1.0, and 0.5 m for patterns I, III, and IV, respectively.
A novel map of the mouse eye for orienting retinal topography in anatomical space
Authors: Stabio Maureen E. , Sondereker Katelyn B. , Haghgou Sean D. , Day Brittany L. , Chidsey Berrien , Sabbah Shai , Renna Jordan M.
Published: April 2018

Functionally distinct retinal ganglion cells have density and size gradients across the mouse retina, and some degenerative eye diseases follow topographic‐specific gradients of cell death. Hence, the anatomical orientation of the retina with respect to the orbit and head is important for understanding the functional anatomy of the retina in both health and disease. However, different research groups use different anatomical landmarks to determine retinal orientation (dorsal, ventral, temporal, nasal poles). Variations in the accuracy and reliability in marking these landmarks during dissection may lead to discrepancies in the identification and reporting of retinal topography. The goal of this study was to compare the accuracy and reliability of the canthus, rectus muscle, and choroid fissure landmarks in reporting retinal orientation. The retinal relieving cut angle made from each landmark during dissection was calculated based on its relationship to the opsin transition zone (OTZ), determined via a custom MATLAB script that aligns retinas from immunostained s‐opsin. The choroid fissure and rectus muscle landmarks were the most accurate and reliable, while burn marks using the canthus as a reference were the least. These values were used to build an anatomical map that plots various ocular landmarks in relationship to one another, to the horizontal semicircular canals, to lambda–bregma, and to the earth's horizon. Surprisingly, during normal locomotion, the mouse's opsin gradient and the horizontal semicircular canals make equivalent 6° angles aligning the OTZ near the earth's horizon, a feature which may enhance the mouse's ability to visually navigate through its environment.
A comparative study on pathological features of transgenic rat lines expressing either three or four repeat misfolded tau
Authors: Valachova Bernadeta , Brezovakova Veronika , Bugos Ondrej , Jadhav Santosh , Smolek Tomas , Novak Petr , Zilka Norbert
Published: April 2018

Human tauopathies represent a heterogeneous group of neurodegenerative disorders characterized by distinct clinical features, typical histopathological structures, and defined ratio(s) of three‐repeat and four‐repeat tau isoforms within pathological aggregates. How the optional microtubule‐binding repeat of tau influences this differentiation of pathologies is understudied. We have previously generated and characterized transgenic rodent models expressing human truncated tau aa151–391 with either three (SHR24) or four microtubule‐binding repeats (SHR72). Here, we compare the behavioral and neuropathological hallmarks of these two transgenic lines using a battery of tests for sensorimotor, cognitive, and neurological functions over the age range of 3.5–15 months. Progression of sensorimotor and neurological deficits was similar in both transgenic lines; however, the lifespan of transgenic line SHR72 expressing truncated four‐repeat tau was markedly shorter than SHR24. Moreover, the expression of three or four‐repeat tau induced distinct neurofibrillary pathology in these lines. Transgenic lines displayed different distribution of tau pathology and different type of neurofibrillary tangles. Our results suggest that three‐ and four‐repeat isoforms of tau may display different modes of action in the diseased brain.
Drinking Ethanol Has Few Acute Effects on CYP2C9, CYP2C19, NAT2, and P‐Glycoprotein Activities but Somewhat Inhibits CYP1A2, CYP2D6, and Intestinal CYP3A: So What?
Authors: Gazzaz Malaz , Kinzig Martina , Schaeffeler Elke , Jübner Martin , Hsin Chih‐hsuan , Li Xia , Taubert Max , Trueck Christina , Iltgen‐Breburda Juliane , Kraus Daria , Queckenberg Christian , Stoffel Marc , Schwab Matthias , Sörgel Fritz , Fuhr Uwe
Published: April 2018

We quantified the effect of acute ethanol exposure (initial blood concentrations 0.7 g/L) on major drug metabolizing enzymes and p‐glycoprotein. Sixteen healthy Caucasians participated in a randomized crossover study with repeated administration of either vodka or water. Enzyme/transporter activity was assessed by a cocktail of probe substrates, including caffeine (CYP1A2/NAT2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and digoxin (P‐glycoprotein). The ratio of AUC0‐t of dextromethorphan for ethanol/water coadministration was 1.95 (90% confidence interval (CI) 1.48–2.58). The effect was strongest in individuals with a CYP2D6 genotype predicting high activity (n = 7, ratio 2.66, 90% CI 1.65–4.27). Ethanol increased caffeine AUC0‐t 1.38‐fold (90% CI 1.25–1.52) and reduced intestinal midazolam extraction 0.77‐fold (90% CI 0.69–0.86). The other probe drugs were not affected by ethanol. The results suggest that acute ethanol intake typically has no clinically important effect on the enzymes/transporters tested.
Compensation method of phase‐locked loop under unbalanced grid condition based on harmonic linearization
Authors: Zha Xiaoming , Cen Yang , Huang Meng , Peng Dongdong
Published: April 2018

The voltage source converter (VSC) is often faced with unbalanced grid conditions that will degrade its performance because of the distorted current with a large amount of harmonics. One of the main parts of current distortion is the third‐order harmonics caused by the negative‐sequence voltage component at the fundamental frequency. The distorted output of the synchronous reference frame phase‐locked loop (SRF‐PLL) due to the unbalanced grid voltage is the main reason for the existence of the harmonics. This paper analyzes the mechanism of the generation of harmonics currents and proposes a compensation method for the PLL in VSCs based on the harmonic linearization method without changing the structure of SRF‐PLL. The proposed PLL can work properly under unbalanced grid conditions and has a good dynamic response. The third‐order current harmonics are reduced significantly by using the proposed PLL instead of the conventional SRF‐PLL without changing the current control strategy of VSC. The compensation method is verified by cycle‐by‐cycle circuit simulations and controller hardware‐in‐the‐loop experiments.
Emerging therapeutic potential for xenin and related peptides in obesity and diabetes
Authors: Craig Sarah L. , Gault Victor A. , Irwin Nigel
Published: April 2018

Xenin‐25 is a 25‐amino acid peptide hormone co‐secreted from the same enteroendocrine K‐cell as the incretin peptide glucose‐dependent insulinotropic polypeptide. There is no known specific receptor for xenin‐25, but studies suggest that at least some biological actions may be mediated through interaction with the neurotensin receptor. Original investigation into the physiological significance of xenin‐25 focussed on effects related to gastrointestinal transit and satiety. However, xenin‐25 has been demonstrated in pancreatic islets and recently shown to possess actions in relation to the regulation of insulin and glucagon secretion, as well as promoting beta‐cell survival. Accordingly, the beneficial impact of xenin‐25, and related analogues, has been assessed in animal models of diabetes‐obesity. In addition, studies have demonstrated that metabolically active fragment peptides of xenin‐25, particularly xenin‐8, possess independent therapeutic promise for diabetes, as well as serving as bioactive components for the generation of multi‐acting hybrid peptides with antidiabetic potential. This review focuses on continuing developments with xenin compounds in relation to new therapeutic approaches for diabetes‐obesity.
Cohort study to determine the waist circumference cutoffs for predicting type 2 diabetes mellitus in rural China
Authors: Ren Yongcheng , Liu Yu , Sun Xizhuo , Wang Bingyuan , Zhao Yang , Luo Xinping , Wang Chongjian , Li Linlin , Zhang Lu , Zhou Junmei , Han Chengyi , Liu Xuejiao , Zhang Dongdong , Zhao Jingzhi , Zhang Ming , Hu Dongsheng
Published: April 2018

Background

Limited information is available on the cutoffs of waist circumference (WC) for predicting type 2 diabetes mellitus (T2DM). We aimed to define the optimal WC cutoffs for predicting T2DM among rural Chinese people.

Methods

A cohort of 11 968 participants (732 new‐onset T2DM) from a rural area in China with age 18 to 87 years was established at baseline during July to August of 2007 and 2008 and followed up during July to August of 2013 and 2014. Scatterplot, X‐tile plot, and receiver operating characteristic (ROC) curve analyses were used to determine WC cutoffs for predicting T2DM.

Results

The WC cutoffs for males and females were 84 and 86 cm (scatterplot), 83 and 88 cm (X‐tile plot), and 87 and 88 cm (ROC curve). According to the highest risk score, the optimal WC cutoffs were 87 cm for males and 88 cm for females. With the optimal WC cutoffs, the sensitivity, specificity, positive likelihood ratio, area under the ROC curve, and population‐attributable risk proportions were 67.9%, 67.0%, 2.06%, 0.70%, and 46%, respectively, for males and 52.5%, 75.0%, 2.10%, 0.69%, and 34%, respectively, for females; the corresponding adjusted hazard ratio for WC predicting T2DM was 3.66 (95% confidence interval 2.80‐4.78) for males and 2.55 (2.08‐3.12) for females.

Conclusions

The optimal WC cutoffs for predicting T2DM were similar between males and females. As well, the criteria of WC for central obesity are no longer practical for predicting T2DM.
Socio‐economic status and HbA1c in type 2 diabetes: A systematic review and meta‐analysis
Authors: Bijlsma-Rutte Anne , Rutters Femke , Elders Petra J.M. , Bot Sandra D.M. , Nijpels Giel
Published: April 2018

Up until now, differences in HbA1c levels by socio‐economic status (SES) have been identified, but not yet quantified in people with type 2 diabetes. The aim of this study was therefore to assess the difference in HbA1c levels between people with type 2 diabetes of different SES in a systematic review and meta‐analysis. A systematic literature search was conducted in MEDLINE, Embase, Ebsco, and the Cochrane Library until January 14, 2018. Included studies described adults with type 2 diabetes in whom the association between SES and HbA1c levels was studied. Studies were rated for methodological quality and data were synthesized quantitatively (meta‐analysis) and qualitatively (levels of evidence), stratified for type of SES variable, i.e., education, income, deprivation, and employment. Fifty‐one studies were included: 15 high, 27 moderate, and 9 of low methodological quality. Strong evidence was provided that people of low SES have higher HbA1c levels than people of high SES, for deprivation, education, and employment status. The pooled mean difference in HbA1c levels between people of low and high SES was 0.26% (95% CI, 0.09‐0.43) or 3.12 mmol/mol (95% CI, 1.21‐5.04) for education and 0.20% (95% CI, −0.05 to 0.46) or 2.36 mmol/mol (95%CI, −0.61 to 5.33) for income. In conclusion, our systematic review and meta‐analysis showed that there was an inverse association between SES and HbA1c levels in people with type 2 diabetes. Future research should focus on finding SES‐sensitive strategies to reduce HbA1c levels in people with type 2 diabetes.
Effects of female preference intensity on the permissiveness of sexual trait polymorphisms
Authors: Ponkshe Aditya , Endler John A.
Published: April 2018

Recent developments in sexual selection theory suggest that on their own, mate preferences can promote the maintenance of sexual trait diversity. However, how mate preferences constrain the permissiveness of sexual trait diversity in different environmental regimes remains an open question. Here, we examine how a range of mate choice parameters affect the permissiveness of sexual trait polymorphism under several selection regimes. We use the null model of sexual selection and show that environments with strong assortative mating significantly increase the permissiveness of sexual trait polymorphism. We show that for a given change in mate choice parameters, the permissiveness of polymorphism changes more in environments with strong natural selection on sexual traits than in environments with weak selection. Sets of nearly stable polymorphic populations with weak assortative mating are more likely to show accidental divergence in sexual traits than sets of populations with strong assortative mating. The permissiveness of sexual trait polymorphism critically depends upon particular combinations of natural selection and mate choice parameters.
Bison body size and climate change
Authors: Martin Jeff M. , Mead Jim I. , Barboza Perry S.
Published: April 2018

The relationship between body size and temperature of mammals is poorly resolved, especially for large keystone species such as bison (Bison bison). Bison are well represented in the fossil record across North America, which provides an opportunity to relate body size to climate within a species. We measured the length of a leg bone (calcaneal tuber, DstL) in 849 specimens from 60 localities that were dated by stratigraphy and 14C decay. We estimated body mass (M) as M = (DstL/11.49)3. Average annual temperature was estimated from δ18O values in the ice cores from Greenland. Calcaneal tuber length of Bison declined over the last 40,000 years, that is, average body mass was 37% larger (910 ± 50 kg) than today (665 ± 21 kg). Average annual temperature has warmed by 6°C since the Last Glacial Maximum (~24–18 kya) and is predicted to further increase by 4°C by the end of the 21st century. If body size continues to linearly respond to global temperature, Bison body mass will likely decline by an additional 46%, to 357 ± 54 kg, with an increase of 4°C globally. The rate of mass loss is 41 ± 10 kg per°C increase in global temperature. Changes in body size of Bison may be a result of migration, disease, or human harvest but those effects are likely to be local and short‐term and not likely to persist over the long time scale of the fossil record. The strong correspondence between body size of bison and air temperature is more likely the result of persistent effects on the ability to grow and the consequences of sustaining a large body mass in a warming environment. Continuing rises in global temperature will likely depress body sizes of bison, and perhaps other large grazers, without human intervention.
Chromocene–Cyclopentadienyltitanium Trichloride Ion Pairs and Their Rearrangement to Titanocene Chloride–Cyclopentadienylchromium Dichlorides – Ethylene Polymerization Tests
Authors: Varga Vojtech , Pinkas Jiří , Císařová Ivana , Kubišta Jiří , Horáček Michal , Mach Karel , Gyepes Róbert
Published: April 2018

Reactions of chromocene [CrCp2] (Cp = η5‐C5H5) with cyclopentadienyltitanium trichlorides [Ti(η5‐C5H5–nMen)Cl3] (n = 0–5) and [Ti(C5Me4Et)TiCl3] in toluene resulted in precipitation of ion pairs of [CrCp2]+[Ti(η5‐C5H5–nMen)Cl3]– (1–6) and [CrCp2]+[Ti(η5‐C5Me4Et)Cl3]– (7). Heating their toluene solutions to 100 °C yielded the titanocene chloride – cyclopentadienylchromium dichloride complexes with the metals linked by bridging chloride ligands. For n = 0–3, the purple‐violet complexes [CpCp′Ti(µ‐Cl)2Cr(Cp)Cl] (Cp′ – cyclopentadienyl ligand of the titanium component) (8–11) were stable at 100 °C, and the single‐crystal structure of [Cp2Ti(µ‐Cl)2Cr(Cp)Cl] (8) was determined. The bridging complexes of the same type for n = 4, 5 and the C5Me4Et ligand (12–14) were contaminated with titanocene dichlorides containing mixed auxiliary ligands [TiCp(C5HMe4)Cl2] (15), [TiCp(C5Me5)Cl2] (16), and [TiCp(C5Me4Et)Cl2] (17), respectively. In addition, they contained the hitherto unknown (CpCrCl)n (18). Heating of 12–14 to 100 °C resulted in their decomposition to 15–17, accompanied with 18 in all cases. The molecular and electronic properties of 1, 4, 5, 8 and both isomers of 13 were investigated by DFT. Complexes 8, 9, and 11 activated with MMAO polymerized ethylene in toluene to very high molecular weights polyethylene (Mn ≥ 500 kg mol–1); upon activation with B(C6F5)3/Et3SiH in dichloromethane they produced Mn = 9–23 kg mol–1. The titanium species was the catalytically dominant one in both cases.
Enhanced Photoelectrochemical Water Oxidation on BiVO4 with Mesoporous Cobalt Nitride Sheets as Oxygen‐Evolution Cocatalysts
Authors: Wan Xiaokang , Su Jinzhan , Guo Liejin
Published: April 2018

A series of cobalt‐based oxide and nitride sheet electrocatalysts were developed and then coupled with BiVO4 to investigate the cocatalytic effect and the relationship between electrocatalysis and photoelectrochemical (PEC) water oxidation. The cobalt nitride sheets were synthesized by a hydrothermal method before calcination in ammonia and show superior electrocatalytic activities for oxygen evolution. BiVO4 has been reported to be a desirable candidate among semiconductor materials for photoelectrochemical water splitting except for its sluggish surface oxygen‐evolution kinetics. In this work, the PEC performance of BiVO4 was significantly enhanced by efficient oxygen‐evolution catalysts serving as cocatalysts. The enhancement of the PEC performance after cocatalyst loading agrees well with the electrocatalytic activities and can be ascribed to the improved surface kinetics. The photocurrent characteristics combined with the results of the electrochemical tests indicate that favourable overpotential and Tafel slope are both important factors in the role of cocatalysts for efficient photoelectrochemical water oxidation. Benefiting from the cocatalytic effect, Co2N0.67‐loaded BiVO4 exhibited the highest photocurrent of 2.21 mA/cm2 at 1.23 V vs. RHE, which is about 80 % higher than that of bare BiVO4.
Construction of Eu2O3/g‐C3N4 Redox Heterojunctions Containing Eu3+/Eu2+ Self‐Redox Centers for Boosted Visible‐Light Photocatalytic Activity
Authors: Wang Fangzhi , Li Wenjun , Gu Shaonan , Li Hongda , Ren Chaojun , Liu Xintong
Published: April 2018

The in‐built self‐redox couple in a heterojunction can indeed boost its photocatalytic activity. Herein, to obtain highly efficient visible‐light photocatalysis, a new Eu2O3/g‐C3N4 redox heterojunction is designed and fabricated by a facile in situ growth strategy. Compared with pure g‐C3N4, the as‐prepared Eu2O3/g‐C3N4 redox heterojunction shows extremely enhanced photocatalytic performance for the decontamination of organic contaminants under visible‐light irradiation. The presence of the Eu3+/Eu2+ self‐redox couple is identified by X‐ray photoelectron spectroscopy spectra analysis, before and after photoreaction. The boosted photocatalytic mechanism is explored systematically through UV/Vis diffuse reflectance spectroscopy, photoluminescence spectroscopy, and photocurrent measurements. Moreover, the radical trapping and electron paramagnetic resonance experiments reveal that ·O2– and h+ are the main active species, and a small amount of ·OH radical is also generated. The boosted photocatalytic performance is derived from the effective separation of photogenerated e–/h+ pairs by forming a Eu2O3/g‐C3N4 heterostructure with a self‐redox center. In particular, the self‐redox couple of Eu3+/Eu2+ can lead to more effective separation of the photogenerated charge carriers, as well as to sustainable production of ·O2–. It is anticipated that our study could provide new insight into the development of g‐C3N4‐based redox heterojunctions with high visible‐light photocatalytic performance.
Synthesis of a Quaternary N,N′‐Aminal‐Containing A–E Ring System of Palau′amine via an Enamide‐Type Overman Rearrangement Reaction
Authors: Imaoka Takuya , Iwata Makoto , Nagasawa Kazuo
Published: April 2018

We present a synthesis of the pentacyclic A–E ring system of palau′amine, a member of the dimeric pyrrole‐imidazole alkaloid (PIA) family. The synthesis features tandem elimination–Michael addition reaction to obtain cis‐fused bicyclo[3,3,0]octane, followed by stereoselective ketone reduction, and further elaboration to obtain the tetracyclic precursor for the Overman rearrangement reaction. The enamide‐type Overman rearrangement reaction generated the N,N′‐aminal quaternary asymmetric center at C10, and ring closure provided the desired pentacycle.
Unsaturated Derivatives of Trifluoromethanesulfonamide
Authors: Shainyan Bagrat A.
Published: April 2018

Unsaturated derivatives of trifluoromethanesulfonamide (CF3SO2NH2, triflamide, TfNH2) of general formula TfNRR′ where R and/or R′ contain C=C or C≡C bonds, are of particular interest in triflate chemistry because they open the way for further functionalization and provide access to new adducts and cycloadducts. Two approaches to these compounds have been developed in our group. One is treatment of triflic anhydride (or fluoride) with unsaturated amines, or alkylation of triflamide with unsaturated alkyl halides. The second approach consists of oxidative triflamidation of dienes, with one C=C bond remaining intact. Another class of unsaturated triflamide derivatives is that of N‐alkylidenetriflamides (TfN=R). At the time our comprehensive review on triflamides and related compounds covering the literature up to 2012 was published, very little information on unsaturated triflamides was available. Since then, research in this area has expanded. In this review we demonstrate new examples of unusual reactivity of unsaturated triflamides, such as unprecedented splitting of α,ω‐bis(triflamidomethyl)diacetylene, diverse courses of oxidative triflamidation and arenesulfonamidation of dienes, different routes of cycloaddition of fluorinated and non‐fluorinated N‐sulfinylsulfonamides to carbodiimides, isomerization, etc. The high NH‐acidity, the strong electron‐acceptor ability and good nucleofugality of the triflyl and triflamido groups, and the presence of multiple bonds in the unsaturated triflamides all make them both interesting objects for investigations of hydrogen bonding and self‐organization processes, as well as valuable synthons in organic chemistry.
Direct Acetophenone–Acetophenone Crossed Aldol Reaction and Aldol Self‐Reaction Promoted by a Tethered Ru–S Complex
Authors: Pommerening Phillip , Stahl Timo , Oestreich Martin
Published: April 2018

The serendipitous discovery of aldol reactions of two methyl ketones is reported. The tertiary aldols do form during the dehydrogenative Si–O coupling of the corresponding enolizable ketone and a hydrosilane. The ratio of the expected silyl enol ether and the aldol adduct depends on various reaction parameters but is particularly pronounced with the hydrosilane as the limiting reagent. Aside from aldol self‐reactions, the direct crossed aldol reaction is, in principle, also possible. The hydrosilane can be replaced by a hydroborane, then involving a boron enolate as the enol component.
TBHP Mediated Substrate Controlled Oxidative Dearomatization of Indoles to C2/C3‐Quaternary Indolinones
Authors: Kothandapani Jagatheeswaran , Reddy Singarajanahalli Mundarinti Krishna , Thamotharan Subbiah , Kumar Shankar Madan , Byrappa Kullaiah , Ganesan Subramaniapillai Selva
Published: April 2018

Oxidative dearomatization of indoles with 70 % aqueous tert‐butylhydroperoxide (TBHP) in the absence of any metal salts/organic solvents gave the corresponding C2/C3‐quaternary indolinones under open‐air reaction conditions. The nature of substituent on the indole nitrogen dictates the type of product formed in these reactions. Free (NH)‐indoles gave C2‐quaternary indolinone derivatives whilst (NR)‐indoles yielded C3‐quaternary indolinones as the major product. Moreover, the addition of an excess amount of TBHP also facilitated the one‐pot transformation of (NR)‐indoles to the corresponding isatin derivatives.
Rapid Synthesis of Bicyclic N‐Heterocyclic Cores from N‐Terminal α,β‐Unsaturated Diazoketones
Authors: Santiago João Victor , Burtoloso Antonio C. B.
Published: April 2018

A method for the synthesis of bicyclic N‐heterocyclic cores from N‐terminal α,β‐unsaturated diazoketones has been developed. The transformation involves three sequential steps that include N‐deprotection, an intramolecular aza‐Michael, and a photochemical Wolff rearrangement as a one‐pot protocol. By using this strategy, a series of substituted bicyclic N‐heterocycles, particularly, indolizidines and pyrrolizidines, were synthesize in good yields.
Mental load during cognitive performance in complex regional pain syndrome I
Authors: Breimhorst M. , Dellen C. , Wittayer M. , Rebhorn C. , Drummond P.D. , Birklein F.
Published: April 2018

Background

Complex regional pain syndrome (CRPS) is associated with deficits in limb recognition. The purpose of our study was to determine whether mental load during this task affected performance, sympathetic nervous system activity or pain in CRPS patients.

Methods

We investigated twenty CRPS‐I patients with pain in the upper extremity and twenty age‐ and sex‐matched healthy controls. Each participant completed a limb recognition task. To experimentally manipulate mental load, the presentation time for each picture varied from 2 s (greatest mental load), 4, 6 to 10 s (least mental load). Before and after each run, pain intensity was assessed. Skin conductance was recorded continuously.

Results

Patients with CRPS did not differ from controls in terms of limb recognition and skin conductance reactivity. However, patients with CRPS reported an increase in pain during the task, particularly during high mental load and during the latter stages of the task. Interestingly, state anxiety and depressive symptoms were also associated with increases in pain intensity during high mental load.

Conclusions

These findings indicate that high mental load intensifies pain in CRPS. The increase of pain in association with anxiety and depression indicates a detrimental effect of negative affective states in situations of high stress and mental load in CRPS.

Significance

The effects of mental load need to be considered when patients with CRPS‐I are investigated for diagnostic or therapeutic reasons.
Hyperpolarization‐activated channels shape temporal patterns of ectopic spontaneous discharge in C‐nociceptors after peripheral nerve injury
Authors: Bernal L. , Roza C.
Published: April 2018

Background

Neuropathic pain is thought to be mediated by aberrant impulses from sensitized primary afferents, and the temporal summation of the discharges might also influence nociceptive processing. Hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels (Ih current) generate rhythmic activity in neurons within the central nervous system and contribute to nociceptors excitability in neuropathic pain.

Methods

We searched for single fibres with ectopic spontaneous discharges from an in vitro preparation in mice containing a neuroma formed in a peripheral branch of the saphenous nerve together with the undamaged branches.

Results

Both damaged (axotomized) and undamaged fibres (putative intact) developed ectopic spontaneous activity with different temporal spike trains: Clock‐like, Irregular or Bursts. The Ih current blocker, ZD7288, significantly suppressed ectopic spontaneous discharges in nociceptive fibres (3/5 Aδ‐ and 24/31 C‐units and 1 nonclassified) by 64%. Additionally, ZD7288 changed the spike patterns of 5/7 Clock‐like and 3/4 Burst units to Irregular. Exogenous cAMP produced a significant ~65% increase in the ectopic firing in 5 Irregular fibres, which was restored by ZD7288. In six additional fibres (three Clock‐like and three Irregular), exogenous cAMP had no further effect, but co‐application with ZD7288 decreased their discharge by half. These units showed significant higher levels of discharges than the cAMP‐sensitive ones.

Conclusions

Our data suggest that HCN channels modulate ectopic spontaneous firing in C‐nociceptors and shape their temporal patterns of discharge which will, ultimately, modify the nociceptive message received and processed by second‐order neurons.

Significance

We show an involvement of HCN channels in the modulation of ectopic spontaneous discharges from C‐nociceptors. This finding exposes a mechanism of nociceptive transmission enhancement and highlights the clinical relevance of peripheral HCN blockade for spontaneous pain relief during neuropathy.