bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasminogen activator inhibitor‐1 deficiency suppresses osteoblastic differentiation of mesenchymal stem cells in mice
Authors: Takafuji Yoshimasa , Tatsumi Kohei , Ishida Masayoshi , Kawao Naoyuki , Okada Kiyotaka , Matsuo Osamu , Kaji Hiroshi
Published: November 2018

Plasminogen activator inhibitor‐1 (PAI‐1) is known as an inhibitor of fibrinolytic system. Previous studies suggest that PAI‐1 is involved in the pathogenesis of osteoporosis induced by ovariectomy, diabetes, and glucocorticoid excess in mice. However, the roles of PAI‐1 in early‐stage osteogenic differentiation have remained unknown. In the current study, we investigated the roles of PAI‐1 in osteoblastic differentiation of mesenchymal stem cells (MSCs) using wild‐type (WT) and PAI‐1‐deficient (PAI‐1 KO) mice. PAI‐1 mRNA levels were increased with time during osteoblastic differentiation of MSCs or mesenchymal ST‐2 cells. However, the increased PAI‐1 levels declined at the mineralization phase in the experiment using MC3T3‐E1 cells. PAI‐1 deficiency significantly blunted the expression of osteogenic gene, such as osterix and alkaline phosphatase enhanced by bone morphogenetic protein (BMP)‐2 in bone marrow‐derived MSCs (BM‐MSCs), adipose‐tissue‐derived MSCs (AD‐MSCs), and bone marrow stromal cells of mice. Moreover, a reduction in endogenous PAI‐1 levels by small interfering RNA significantly suppressed the expression of osteogenic gene in ST‐2 cells. Plasmin did not affect osteoblastic differentiation of AD‐MSCs induced by BMP‐2 with or without PAI‐1 deficiency. PAI‐1 deficiency and a reduction in endogenous PAI‐1 levels did not affect the phosphorylations of receptor‐specific Smads by BMP‐2 and transforming growth factor‐β in AD‐MSCs and ST‐2 cells, respectively. In conclusion, we first showed that PAI‐1 is crucial for the differentiation of MSCs into osteoblasts in mice.
G Protein α Subunit 14 Mediates Fibroblast Growth Factor 2‐Induced Cellular Responses in Human Endothelial Cells
Authors: Zou Qing‐yun , Zhao Ying‐jie , Zhou Chi , Liu Ai‐xia , Zhong Xin‐qi , Yan Qin , Li Yan , Yi Fu‐xian , Bird Ian M. , Zheng Jing
Published: November 2018

During pregnancy, a tremendous increase in fetoplacental angiogenesis is associated with elevated blood flow. Aberrant fetoplacental vascular function may lead to pregnancy complications including pre‐eclampsia. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are crucial regulators of fetoplacental endothelial function. G protein α subunit 14 (GNA14), a member of Gαq/11 subfamily is involved in mediating hypertensive diseases and tumor vascularization. However, little is known about roles of GNA14 in mediating the FGF2‐ and VEGFA‐induced fetoplacental endothelial function. Using human umbilical vein endothelial cells (HUVECs) cultured under physiological chronic low oxygen (3% O2) as a cell model, we show that transfecting cells with adenovirus carrying GNA14 complementary DNA (cDNA; Ad‐GNA14) increases (p < 0.05) protein expression of GNA14. GNA14 overexpression blocks (p < 0.05) FGF2‐stimulated endothelial migration, whereas it enhances (p < 0.05) endothelial monolayer integrity (maximum increase of ~35% over the control at 24 hr) in response to FGF2. In contrast, GNA14 overexpression does not significantly alter VEGFA‐stimulated cell migration, VEGFA‐weakened cell monolayer integrity, and intracellular Ca++ mobilization in response to adenosine triphosphate (ATP), FGF2, and VEGFA. GNA14 overexpression does not alter either FGF2‐ or VEGFA‐induced phosphorylation of ERK1/2. However, GNA14 overexpression time‐dependently elevates (p < 0.05) phosphorylation of phospholipase C‐β3 (PLCβ3) at S1105 in response to FGF2, but not VEGFA. These data suggest that GNA14 distinctively mediates fetoplacental endothelial cell migration and permeability in response to FGF2 and VEGFA, possibly in part by altering activation of PLCβ3 under physiological chronic low oxygen.
Effect of manufacturing temperature and storage duration on stability of chemically defined media measured with LC‐MS/MS
Authors: Krattenmacher Florian , Heermann Tamara , Calvet Amandine , Krawczyk Bartlomiej , Noll Thomas
Published: November 2018

BACKGROUND

Chemically defined media (CDM) are used routinely in industrial settings for the production of biopharmaceuticals from mammalian cells, so attention has shifted to understanding their chemical behavior and impact on process robustness. In this context, one particular problem is the risk of cross reactivity and instability in complex mixtures of chemicals at high concentrations.

RESULTS

In order to characterize potentially unstable medium compounds in feed media, we developed and validated a novel liquid chromatography tandem mass spectrometry (LC‐MS/MS) method to simultaneously quantify the majority of medium compounds. We used this application advantage to provide the following insights into molecular processes occurring in CDM prepared at different temperatures and during storage: Concentration profiles of critical compounds in CDM are independent of preparation temperature and storage material but show significant alterations over time. In particular l‐cysteine, l‐proline, vitamin B6, thiamine and cyanocobalamin were found to be rather unstable. Using mixed mode chromatography allows expansion of the method to cover additional analytes of interest, as demonstrated by inclusion of seven additional CDM reaction products.

CONCLUSION

The successful development of a new LC‐MS/MS method allowed us to show the impact of storage duration on the stability of CDM compounds. Furthermore, the results suggest that essential parameters for medium preparation (e.g. temperature) and storage upscaling (e.g. vessel material) are not impacting upon the chemical composition of CDM. © 2018 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
A novel allele of the goldfish chdB gene: Functional evaluation and evolutionary considerations
Authors: Abe Gembu , Li Ing‐Jia , Lee Shu‐Hua , Ota Kinya G.
Published: November 2018

The twin tail of ornamental goldfish is known to be caused by a nonsense mutation in one chordin paralogue gene. Our previous molecular studies in goldfish revealed that the ancestral
chordin gene was duplicated, creating the
chdA and
chdB genes, and the subsequent introduction of a stop codon allele in the
chdA gene (
chdA
E127X) caused the twin‐tail morphology. The
chdA
E127X allele was positively selected by breeders, and the allele was genetically fixed in the ornamental twin‐tail goldfish population. However, little is known about the evolutionary history of the
chdB paralogue, begging the question: are there the functionally distinct alleles at the
chdB locus, and if so, how did they evolve? To address these questions, we conducted molecular sequencing of the
chdB gene from five different goldfish strains and discovered two alleles at the
chdB gene locus; the two alleles are designated
chdB
1 and
chdB
2. The
chdB
1 allele is the major allele and was found in all investigated goldfish strains, whereas the
chdB
2 allele is minor, having only been found in one twin‐tail strain. Genetic analyses further suggested that these two alleles are functionally different with regard to survivability (
chdB
1 > 
chdB
2). These results led us to presume that in contrast to the
chdA locus, the
chdB locus has tended to be eliminated from the population. We also discuss how the
chdB
2 allele was retained in the goldfish population, despite its disadvantageous function. This study provides empirical evidence of the long‐term retention of a disadvantageous allele under domesticated conditions.
On the decadal predictability of the frequency of flood events across the U.S. Midwest
Authors: Neri Andrea , Villarini Gabriele , Salvi Kaustubh A. , Slater Louise J. , Napolitano Francesco
Published: November 2018

Skilful predictions of the frequency of flood events over long lead times (e.g., from 1 to 10 years ahead) are essential for governments and institutions making near‐term flood risk plans. However, little is known about current flood prediction capabilities over annual to decadal timescales. Here we address this knowledge gap at 286 U.S. Geological Survey gaging stations across the U.S. Midwest using precipitation and temperature decadal predictions from the Coupled Model Intercomparison Project (CMIP) phase 5 models. We use the 1–10‐year predictions of precipitation and temperature as inputs to statistical models that have significant skill in reproducing inter‐annual and decadal changes in the observed frequency of flood events. Our results indicate that the limited skill of basin‐averaged precipitation predictions suppresses the skill of flood event frequency predictions, even at the shortest lead time, but downscaling and bias correction improves predictions across all lead times and especially in spring.
Periodontitis as another comorbidity associated with psoriasis: A case‐control study
Authors: Mendes Victor Silva , Cota Luís Otávio Miranda , Costa Amanda Almeida , Oliveira Alcione Maria Soares Dutra , Costa Fernando Oliveira
Published: November 2018

Background

The association between periodontitis and immuno‐mediated inflammatory diseases has been widely studied and recognized each more over the past few years. The aim of this study was to evaluate the potential association between psoriasis and periodontitis, as well as the influence of risk variables in this association.

Methods

This case‐control study included 756 individuals, 397 with psoriasis, and 359 controls. A full‐mouth periodontal examination was performed, recording therefore plaque index, probing depth, clinical attachment level, and bleeding on probing. The influence of risk variables was tested by univariate analysis and multivariate logistic regression.

Results

A high prevalence of periodontitis was observed among cases (46.1%) when compared to controls (33.1%). Individuals with psoriasis presented a 1.72 higher chance of having periodontitis than controls (OR = 1.72; 95% CI 1.28–2.32; p < 0.001) in the univariate analysis, but with no significance in the multivariate model. The prevalence of periodontitis increased significantly according to the severity of psoriasis [mild form (44.4%); moderate (46.3%); and advanced (47.1%)] when compared to the control group (33.1%). The final multivariate logistic model showed that the number of teeth (OR = 1.08; 95% CI 1.01–1.14; p = 0.018), smoking (OR = 1.91; 95% CI 1.19–3.07; p = 0.008), and body mass index (OR = 1.13; 95% CI 1.11–1.16; p < 0.001) remained significantly associated with the occurrence of periodontitis.

Conclusions

The prevalence of periodontitis was higher in individuals with psoriasis than in controls. Severity of psoriasis also presented a strong relationship with all periodontal clinical parameters.
Surface Charge Reversible Polymeric Micelle‐Laden Hydrogels for Drug Delivery and 3D Cell Culture
Authors: Wang Kang , Zhang Yuchen , Jiang Sirui , Wu Dengjin , Dai Yu , Zhang Xiaojin , Xia Fan
Published: November 2018

Hydrogels have significant advantages in the local treatment of diseases. However, improving the solubility of hydrophobic drugs and enhancing cell targeting of drug delivery remain significant challenges in the application of such hydrogels. Surface charge reversible polymeric micelle‐laden hydrogels are developed for drug delivery and 3D cell culture. Borax is added into the system to form borate with hydroxyl groups of alginate for rapid gelation. Decreasing pH surrounding the hydrogels facilitates the degradation of the hydrogels and charge reversal of polymeric micelles. The negative‐to‐positive charge reversal endows polymeric micelles with cell targeting and enhanced cell uptake of polymeric micelles. A potential and effective in situ drug delivery system for the local treatment of diseases is provided.
Ultra‐Fast Microwave Assisted Self‐Healing of Covalent Adaptive Polyurethane Networks with Carbon Nanotubes
Authors: Solouki Bonab Vahab , Karimkhani Vahid , Manas‐Zloczower Ica
Published: November 2018

Vitrimers are a class of covalent adaptive networks which, unlike other covalent networks, can be thermally reprocessed, recycled, and are self‐healing. In this research, a polyurethane vitrimer network is prepared using 1,4‐phenylene diisocyanate and excess amount of polycaprolactone polyol. The dynamic nature of this network is provided by a dual effect of dynamic transesterification reactions as well as dynamic transcarbamoylation reactions. This vitrimer can be reshaped, be recycled, and heal potential defects at high enough temperatures. A fast healing strategy is developed by the addition of small amounts (0.05 wt%) of carbon nanotubes (CNTs) which enables the use of microwave radiation for an efficient fast healing process. Using this strategy the healing time decreases more than 30 times compared to using a conventional oven. CNTs also enhance the vitrimer mechanical properties and compensate for the mechanical property loss of the dynamic PU network in comparison to the permanent PU network.
Wire Melt Electrospinning of Thin Polymeric Fibers via Strong Electrostatic Field Gradients
Authors: Morikawa Kai , Vashisth Aniruddh , Grimme Christian J. , Green Micah J. , Naraghi Mohammad
Published: November 2018

Here, a novel melt electrospinning method to produce few‐micron and nanometer thick fibers is presented, in which a polymer‐coated wire with a sharp tip is used as the polymer source. The polymer coating is melted via Joule heating of the source wire and extracted toward the target via electrostatic forces. The high viscosity and low charge density of polymer melts lower their stretchability in melt. The method relies on confining the Taylor cone and reducing initial jet diameter via concentrated electrostatic fields as a means to reduce the diameter of fibers. As a result, the initial jet diameter and the final fiber diameter are reduced by an order of magnitude of three to ten times, respectively, using wire melt electrospinning compared to syringe‐ and edge‐based electrospinning. The fiber diameter melt electrospun via this novel method is 1.0 ± 0.9 µm, considerably thinner than conventional melt electrospinning techniques. The generation of thin fibers are explained in terms of the electrostatic field around the wire tip, as obtained from finite element analysis (FEA), which controls the size and shape of the melt electrospun jet.
Pimavanserin for Parkinson's Disease psychosis: Effects stratified by baseline cognition and use of cognitive‐enhancing medications
Authors: Espay Alberto J. , Guskey Michael T. , Norton James C. , Coate Bruce , Vizcarra Joaquin A. , Ballard Clive , Factor Stewart A. , Friedman Joseph H. , Lang Anthony E. , Larsen Niccole J. , Andersson Candace , Fredericks Doral , Weintraub Daniel
Published: November 2018

Background: PD psychosis is often associated with cognitive impairment, including dementia, and involves dopaminergic, serotonergic, and cholinergic mechanisms.

Objective: To evaluate the differential effect of the antipsychotic pimavanserin, a selective serotonin 2A receptor inverse agonist, in PD psychosis patients with versus without cognitive impairment and in those receiving versus not receiving cognitive‐enhancing medications.

Methods: Data from the pivotal randomized clinical trial of pimavanserin for PD psychosis were stratified by (1) screening MMSE score as cognitively impaired (21‐24) versus unimpaired (≥25) and (2) concomitant use versus nonuse of cognitive‐enhancing medications. The primary outcome measure was change in the PD‐adapted Scale for the Assessment of Positive Symptoms.

Results: Mean (pimavanserin vs. placebo) change from baseline was larger in the cognitively impaired (n = 50; –6.62 vs. –0.91; P = 0.002) versus the cognitively unimpaired (n = 135; –5.50 vs. –3.23; p = 0.046) group. The comparable change was –6.04 versus –2.18 (P = 0.012) and –5.66 versus –3.15 (P = 0.041) in patients treated (n = 69) and not treated (n = 116) with concomitant cognitive‐enhancing medication. Pimavanserin was similarly tolerated across all cognitive groups with no additional safety concerns identified. Overall adverse event rates were comparable across the concomitant cognitive‐enhancing medication groups; however, rates of serious adverse events and discontinuations attributed to adverse events were increased in patients taking cholinesterase inhibitors.

Conclusions: The antipsychotic effect of pimavanserin is robust in PD patients with cognitive impairment and may be enhanced by concomitant cognitive‐enhancing medication use. Future prospective studies are needed to confirm these preliminary findings. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Robustness of the projection method for an asymmetrically deformed planar antenna array
Authors: Rigobello Francesco , Mansutti Giulia , Asif Sajid , Khan Muhammad S. , Capobianco Antonio D. , Galtarossa Andrea
Published: November 2018

Antenna arrays capable of adapting to surfaces that change shape in time are strongly required in modern wireless communication systems. The projection method is a cost‐effective pattern recovery technique that allows to correct the radiation pattern of the deformed array by just applying a phase compensation to the input signal of each array element. However, the implementation of this methodology can face some limitation that this letter is going to investigate. First, a study on the main lobe gain of the retrieved pattern will highlight the limit on the deformation that can be impressed to the surface. Later, an analysis on the phase approximation that can be tolerated by the method will be illustrated. In fact, the phase resolution required for the instruments (ie, the phase shifters) to be used in a practical setup, can impact considerably on the overall cost. For these purposes, a numerical analysis in CST Microwave Studio is initially performed on a 4 × 4 antenna array. Finally, a prototype was fabricated and measured in an anechoic chamber.
Higher isolation dual‐frequency distinct coupled antennas based on integrated filtering structures
Authors: Li Jiaxu , Zhai Huiqing , Shi Junhao , Liu Longhua , Nie Zhenghang , Hu Diwei
Published: November 2018

This letter proposes a new higher isolation dual‐frequency distinct coupled monopole antenna system by using integrated low‐pass and high‐pass filtering structures. The isolation of the dual‐frequency distinct antennas at 2.4 GHz and 3.6 GHz can be successfully improved by 24 dB under the stable radiation performances. The measurement results are consistent with the simulation results of the fabricated prototype, which verifies the feasibility of this method. The present compact higher isolation frequency distinct antennas could be chosen as a new candidate for integrated multiband anti‐interference terminal systems.
Antenna with a reactive impedance substrate for mine rescue applications
Authors: Roestorff Martin , Odendaal Johann W. , Joubert Johan
Published: November 2018

Two electrically small, reactive impedance surface (RIS) backed, antennas are presented that can be used by rescue workers to locate miners in emergency situations in underground mines. One antenna was designed for optimum impedance bandwidth and the other for compact size, with at least 5% impedance bandwidth. At 433 MHz both antennas have maximum gain values above 5 dBi, and both antennas radiate on average at least 10 dB more power in the front hemisphere than in the rear hemisphere, to reduce interaction with the wearer and aid in locating the missing miners. The first antenna, a planar monopole antenna with RIS backplane had a −10 dB reflection coefficient bandwidth of 25.1%, and a form factor of 0.4 λ0 by 0.4 λ0 by 0.069 λ0. The second antenna, a loaded planar monopole antenna with RIS backplane had a −10 dB reflection coefficient bandwidth of 5.3%, and a form factor of 0.346 λ0 by 0. 346 λ0 by 0.107 λ0. Measured and simulated results for the two antennas are presented.
A novel and individualized robust optimization method using normalized dose interval volume constraints (NDIVC) for intensity‐modulated proton radiotherapy
Authors: Shan Jie , Sio Terence T. , Liu Chenbin , Schild Steven E. , Bues Martin , Liu Wei
Published: November 2018

Purpose

Intensity‐modulated proton therapy (IMPT) is known to be sensitive to patient setup and range uncertainty issues. Multiple robust optimization methods have been developed to mitigate the impact of these uncertainties. Here, we propose a new robust optimization method, which provides an alternative way of robust optimization in IMPT, and is clinically practical, which will enable users to control the balance between nominal plan quality and plan robustness in a user‐defined fashion.

Method

We calculated nine individual dose distributions which corresponded to one nominal and eight extreme scenarios caused by patient setup and proton beam's range uncertainties. For each voxel, the normalized dose interval (NDI) is defined as the full dose range variation divided by the maximum dose in all uncertainty scenarios (NDI = [max – min dose]/max dose), which was then used to calculate the normalized dose interval volume histogram (NDIVH) curves. The areas under the NDIVH curves were used to quantify plan robustness. A normalized dose interval volume constraint (NDIVC) applied to the target was incorporated to specify the desired robustness which was user‐defined. Users could then explore the trade‐off between nominal plan quality and plan robustness by adjusting the position of the NDIVCs on the NDIVH curves freely. We benchmarked our method using one lung, five head and neck (H&N), and three prostate cases by comparing our results to those derived using the voxel‐wise worst‐case robust optimization.

Results

Using the benchmark cases, our new method achieved quality IMPT plans comparable to those derived from the voxel‐wise worst‐case robust optimization for both nominal plan quality and plan robustness in general; even more conformal and more homogeneous target dose distributions in some cases, if proper NDIVCs were applied. The AUC under NDIVH, as a precise quantitative index of plan robustness, was consistent with DVH bandwidths. Additionally, we demonstrated the feasibility of adjusting the position of NDIVCs in the NDIVH curves which allowed users to explore the trade‐off between nominal plan quality and plan robustness.

Conclusions

The NDIVH‐based robust optimization method provided a novel and individualized way of robust optimization in IMPT, and enables users to adjust the balance between nominal plan quality and plan robustness in a user‐defined fashion. This method is applicable for continued improvement and developing the next generation of IMPT planning algorithms in the future.
Hyperpolarized [1‐13C]pyruvate MRI can image the metabolic shift in cardiac metabolism between the fasted and fed state in a porcine model
Authors: Tougaard Rasmus Stilling , Szocska Hansen Esben Søvsø , Laustsen Christoffer , Nørlinger Thomas Stokholm , Mikkelsen Emmeli , Lindhardt Jakob , Nielsen Per Mose , Bertelsen Lotte Bonde , Schroeder Marie , Bøtker Hans Erik , Kim Won Yong , Wiggers Henrik , Stødkilde‐Jørgensen Hans
Published: November 2018

Purpose

Owing to its noninvasive nature, hyperpolarized MRI may improve delineation of myocardial metabolic derangement in heart disease. However, consistency may depend on the changeable nature of cardiac metabolism in relation to whole‐body metabolic state. This study investigates the impact of feeding status on cardiac hyperpolarized MRI in a large animal model resembling human physiology.

Methods

Thirteen 30‐kg pigs were subjected to an overnight fast, and 5 pigs were fed a carbohydrate‐rich meal on the morning of the experiments. Vital parameters and blood samples were registered. All pigs were then scanned by hyperpolarized [1‐13C]pyruvate cardiac MRI, and results were compared between the 2 groups and correlated with circulating substrates and hormones.

Results

The fed group had higher blood glucose concentration and mean arterial pressure than the fasted group. Plasma concentrations of free fatty acids (FFAs) were decreased in the fed group, whereas plasma insulin concentrations were similar between groups. Hyperpolarized MRI showed that fed animals had increased lactate/pyruvate, alanine/pyruvate, and bicarbonate/pyruvate ratios. Metabolic ratios correlated negatively with FFA levels.

Conclusion

Hyperpolarized MR can identify the effects of different metabolic states on cardiac metabolism in a large animal model. Unlike previous rodent studies, all metabolic derivatives of pyruvate increased in the myocardium of fed pigs. Carbohydrate‐rich feeding seems to be a feasible model for standardized, large animal hyperpolarized MRI studies of myocardial carbohydrate metabolism.
The relationship between residual sphincter damage after primary repair, faecal incontinence, and anal sphincter function in primiparous women with an obstetric anal sphincter injury
Authors: Patton Vicki , Kumar Swetha , Parkin Katrina , Karantanis Emmanuel , Dinning Phil
Published: November 2018

Background and Aims

Anal sphincter injury has been identified as a primary cause of post‐partum fecal incontinence in women with obstetric anal sphincter injury. However, women without obstetric anal sphincter injury may also develop fecal incontinence. The aim is to determine the relationship between fecal incontinence severity; and i) residual anal sphincter injury, quantified by the Starck score, and ii) anal sphincter tone.

Methods

Consecutive case series of prospectively collected data set in a Pelvic Floor Unit within a tertiary teaching hospital in Australia. Population 181 primiparous women with Sultan classification Grade 3 and 4 sphincter injuries. Main outcome measures: Sultan classification, anal manometry, pudendal nerve terminal motor latency, St Mark's fecal incontinence score, and Starck ultrasound score.

Results

45% of women reported some degree of fecal incontinence. One third of women with normal external sphincter tone were incontinent. Those with higher Starck score had higher St Mark's scores. A higher Sultan classification correlated with more severe incontinence regardless if the repair was complete. Forceps delivery had a twofold risk of incontinence when compared to non‐forceps delivery.

Conclusion

The importance of an effective anal sphincter repair is confirmed. However, overall there is no direct relationship between residual sphincter damage, anal sphincter tone, and fecal incontinence severity. These data indicate that anal sphincter integrity alone is not the sole mechanism for maintaining fecal continence. Rectal and colonic motor function may also play a role and investigation into these components may provide greater insight into the effect of vaginal delivery upon fecal continence mechanisms
Characterizing pelvic floor muscles activities using magnetomyography
Authors: Escalona‐Vargas Diana , Oliphant Sallie , Siegel Eric R. , Eswaran Hari
Published: November 2018

Aims

To characterize levator ani muscle (LAM) activity in nulligravidas using magnetomyography (MMG) and define MMG characteristics associated with LAM activity with and without accessory muscle contributions.

Methods

MMG data were collected from eight nulligravidas during rest and voluntary LAM contractions (Kegels) of varying intensity. We utilized simultaneous vaginal manometry and surface electromyography (sEMG) to evaluate for accessory muscle recruitment. Moderate Kegel (MK) MMG trials were sub‐selected based on the presence or absence of accessory muscle interaction. Amplitude and spectral‐related indicators were calculated across MK epochs: root‐mean square (RMS) amplitude, percentage amplitude relative to rest, and relative power spectrum density (rPSD) in three frequency bands (low, middle, high). Ternary diagram characterized rPSD from selected Kegels and ROC analysis was performed to identify cut‐points to differentiate MKs from interacting MKs.

Results

Nineteen MMG recordings were obtained. Amplitude and spectral parameters were significantly different between isolated and interacting MK epochs. Mean RMS and power values of the isolated MK were, respectively, 120.66 ± 43.8 fT and 1.72 ± 1.44 (T2/Hz)*10−28. Amplitudes of MK were 64% and 117 higher than baseline activities for the isolated and interacting epochs, respectively. ROC curves reveled cut‐off points on low and middle frequency bands that achieved perfect separation (ROC‐AUC = 1.0) between isolated and interacting MK.

Conclusions

Our study demonstrates that MMG, a novel biomagnetic technique, allows precise detection and characterization of normal female pelvic floor function. Results show that isolated moderate voluntary contraction of the LAMs produces distinct MMG amplitude and spectral characteristics compared with Kegels involving co‐activation of other muscle groups.
Student perspectives on managing sickle cell disease at school
Authors: Haridasa Naeha , DeBaun Michael R. , Sanger Maureen , Mayo‐Gamble Tilicia L.
Published: November 2018

Objective

The study objective was to identify the perceptions of children with sickle cell disease (SCD) in the school environment.

Methods

Semistructured interviews (N = 14) were conducted with pediatric patients ages 6 to 10 who attended Metro Nashville Public Schools. These participants were recruited through the Vanderbilt Sickle Cell Disease Clinic. Participants were asked about the perceived efficacy of their teachers to (1) understand SCD; (2) communicate with students regarding SCD; (3) handle an SCD‐related pain episode in school; and (4) identify methods to compensate for school absenteeism associated with an SCD diagnosis. Content analysis identified underlying themes.

Results

Five themes emerged that highlighted the perceptions and recommendations of children with SCD in the school environment: (1) perceptions that allow students to prevent SCD from limiting their school experience; (2) administrator actions to alleviate challenges associated with SCD; (3) communication about SCD; (4) how SCD interferes with school activities; and (5) ways students advocate for themselves. Students also provided four areas of recommendations for school personnel: (1) ways teachers can help with school activities; (2) make‐up work for school absences; (3) empowering students with SCD; and (4) helping with SCD episodes at school.

Conclusions

Students with SCD advocated strongly for their needs at school to attain their education. However, they perceived school personnel to lack knowledge about SCD management. This could be overcome with a handbook specific for teachers of students with SCD that could address each of the five themes.
Pediatric residents’ perceived barriers to opioid use in sickle cell disease pain management
Authors: Fearon Amber , Marsh Anne , Kim Jennifer , Treadwell Marsha
Published: November 2018

Objective

Current guidelines recommend high‐priority treatment of severe sickle cell disease (SCD) pain with opioids; however, patients with SCD have historically been undertreated. We used mixed methods to assess pediatric residents’ perceptions toward opioid use in SCD pain management.

Methods

We distributed a survey to 88 residents at an urban pediatric medical center in a cross‐sectional study. Participants responded to questions about perceived barriers to acute SCD pain management and attitudes toward patients with SCD. Responses were examined using bivariate analyses. Five pediatric residents were interviewed, to provide more in‐depth understanding of barriers to SCD pain management.

Results

Fifty‐three residents (60%) completed the survey. Participants were divided into “more experienced” (had seen ≥ 21 patients with SCD; 45.3%) or “less experienced.” Both groups reported potential for tolerance and dependence as major barriers to opioid use in SCD. Less experienced residents reported a greater need for additional training in SCD pain management (P < 0.05), more concern about addiction, and greater empathy for patients with SCD (P < 0.05). Both groups agreed that patients with SCD were “frustrating to care for.” Thematic analysis revealed that increased patient and provider barriers led to distrust, ultimately leading to undertreatment of pain and inadequate care.

Conclusion

Although more experienced residents reported feeling more comfortable treating acute SCD pain and were less concerned with addiction compared with less experienced residents, certain negative views of patients with SCD were prevalent among all residents. Findings suggest that residency training must address provider attitudes as well as knowledge about SCD.
Temperature Raman Studies of Freestanding and Flexible Thin Films of CdS‐doped PVDF
Authors: Thakur Abhishek , Dam Siddhartha , Dey Rajkumar , Gangavarappu Amarendra , Hussain Shamima
Published: November 2018

Temperature dependent Raman studies have been carried out on free standing thin films of (Poly(vinylidene fluoride)) incorporated with nano‐crystalline (Cadmium sulphide). Well‐defined signatures of both PVDF as well as CdS could be observed from the Raman spectra of the composite films. Peak shifts toward higher wavenumber for modes of CdS were observed at low temperature. Doping dramatically modulates the phases of polyvinyldene fluoride (PVDF). Microstructural studies revealed additional granular structure on incorporation of CdS nanoparticles into the otherwise fibrous PVDF. Energy Dispersive Spectroscopy (EDS) study confirms the elemental composition of the samples. The thermal conductivity of the composite film was obtained from Raman studies. POLYM. COMPOS., 40:2662–2667, 2019. © 2018 Society of Plastics Engineers
Estimating the Reliability of Low‐Abundant Signals and Limited Replicate Measurements through MS2 Peak Area in SWATH
Authors: Limonier Franck , Willems Sander , Waeterloos Geneviève , Sneyers Myriam , Dhaenens Maarten , Deforce Dieter
Published: November 2018

Sequential windows acquisition of all theoretical fragment ions mass spectrometry (SWATH‐MS) provides large‐scale protein quantification with high accuracy and selectivity. Nevertheless, reliable quantification of low‐abundant signals in complex samples remains challenging, as recently illustrated in a multicenter benchmark study of different label‐free software tools. Here, the SWATH Replicates Analysis 2.0 template from Sciex is used to highlight that the relationship between the MS2 peak area and the variability can be described by a function. This functional relationship appears to be largely insensitive to variation in samples or acquisition conditions, suggesting a device‐intrinsic property. By using a power regression, it is shown that the MS2 peak area can be used to predict the quantification repeatability without relying on replicate injections, thus contributing to high‐throughput confident quantification of low‐abundant signals with SWATH‐MS.
On‐Tissue Hydrogel‐Mediated Nondestructive Proteomic Characterization: Application to fr/fr and FFPE Tissues and Insights for Quantitative Proteomics Using a Case of Cardiac Myxoma
Authors: Taverna Domenico , Mignogna Chiara , Santise Gianluca , Gaspari Marco , Cuda Giovanni
Published: November 2018

Purpose

The application of a methodology for quantitative protein analysis from formalin‐fixed and paraffin‐embedded (FFPE) tissue by using hydrogels. Miniaturized polymeric gels are placed onto histologically defined tissue regions in order to perform localized digestion for bottom‐up proteomics. Hydrogel‐extracted peptides are then labeled with tandem mass tags (TMT) reagents for relative protein quantification. A cardiac myxoma biopsy is used.

Experimental design

Multiple hydrogels, incorporating the proteolytic enzyme trypsin, are placed on serial tissue sections, and processed for digestion and TMT derivatization. SCX fractionation before LC‐MS/MS analysis and bioinformatics analysis are carried out.

Results

Two histologically different areas on both FFPE and frozen sections of the same cardiac myxoma biopsy are compared. In total, 1949 (FFPE) and 2491 (frozen) proteins are identified, with a total overlap of 56%. The quantitative comparison highlighted 15 (FFPE) and 138 (frozen) differentially expressed proteins between myxoma regions.

Conclusion

The methodology successfully detects numerous protein signals from FFPE and frozen specimens and is able to differentiate between tissue regions. A fast and reliable tissue preparation for quantitative protein analysis by minimum sample manipulation is developed. This offers an option for on‐tissue proteomics analysis while preserving the inherent spatial information on the tissue.
RNAi‐knockdown of the Locusta migratoria nuclear export factor protein results in insect mortality and alterations in gut microbiome
Authors: Xie Jiaqin , Li Shangji , Zhang Wei , Xia Yuxian
Published: November 2018

BACKGROUND

The migratory locust Locusta migratoria is one of the most important agricultural pests worldwide. The nuclear export factor 1 (NXF1) protein plays a crucial role in mediating mRNA transport from the nucleus to the cytoplasm. This study evaluates whether NXF1 could be a potential target for RNAi‐mediated pest control of L. migratoria.

RESULTS

We cloned and characterized the nuclear export factor lm‐nxf1 of L. migratoria. Lm‐nxf1 was expressed in all tissues examined, including head, fat body, hemolymph, trunk, leg and midgut, with high expression observed in the hemolymph and fat body. Injection of lm‐nxf1 dsRNA into hemolymph resulted in inhibition of mRNA export in hemocytes, which were used as a target for observing mRNA export. Total hemocyte levels were reduced by ca. 97% in lm‐nxf1‐dsRNA‐treated locusts, and high insect mortality occurred with LT50 = 7.75 day as compared with 18.15 day for gfp‐dsRNA‐treated controls. Further, the locust intestine became atrophy, and the opportunistic pathogens Enterobacter aerogenes, Klebsiella pneumoniae and Enterobacter asburiae were specifically detected in midgut after lm‐nxf1 dsRNA treatment.

CONCLUSIONS

The results reveal that knockdown of the lm‐nxf1 gene affects the survival of L. migratoria, indicating that lm‐nxf1 is a potential target for RNAi‐mediated pest control. © 2018 Society of Chemical Industry
Low Wear and Low Friction DLC Coating With Good Adhesion to CoCrMo Metal Substrates
Authors: Cano David , Lousa Arturo , Esteve Joan , Ferrer‐Anglada Núria
Published: November 2018

A challenge currently facing the orthopedics sector consists in the durability problems posed by joint prosthesis based on metal‐on‐metal contacts. While the diamond‐like carbon (DLC)‐based coating solves the shortcomings of wear and friction found in the uncoated metal parts, they are generally subject to adhesion failures that may prove to be catastrophic. Our coatings were deposited with a specific multilayered composition that changes from highly metallic at the metal interface, up to a DLC at the sliding contact region. These coatings show very good wear performance results when tested in a highly humid air atmosphere as well as when they are tested in water immersion or in bovine serum. The friction coefficients of our DLC‐against‐DLC tribological pair are found to be always less than 0.1, while wear rates are extremely low, under 2.5 × 10−8 mm3/N m, and it produces highly polished surfaces. The compressive stresses of our coatings are always lower than 2.5 GPa, and when combined with good interface adhesion to the CoCrMo metal substrates, make the coatings highly resistant to delamination even after prolonged test runs. Raman analyses do not reveal any detectable changes even after very long test runs, indicating that no tribochemical reactions occur on the DLC coating.
Effects of Cracks on Anomalous Mechanical Behavior and Energy Dissipation of Negative‐Stiffness Plates
Authors: Wang Yun‐Che , Lai Hsiang‐Wei , Shen Meng‐Wei
Published: November 2018

Mechanical behavior of negative‐stiffness (NS) plates containing cracks, under sinusoidal straining, are numerically studied with the phase‐field modeling techniques. Ferroelastic phase transition is triggered by thermal loading with the Landau‐type energy function to generate the double‐well potential. NS arises from regions of the multi‐domain plates, and interacts with surrounding positive‐stiffness neighboring regions to give rise to anomalous mechanical behavior and energy dissipation. It is found that the anomalies in effective elastic modulus and damping are preserved in the presence of cracks, regardless of their shape or tip radius. Cracks do not diminish the negative‐stiffness effects on overall properties; they may provide more enhancement in dissipation. Crack tips concentrate stress, and cause phase transition to start earlier than other regions in the plates. As opposed to passive materials whose overall damping must be positive, we observe negative effective damping in the plates due to generation of energy from the phase transition.
Natural Polymer‐Based Copper/ Sandarac Resin Catalyzed Regioselective One‐Pot Synthesis of 1,4‐Disubstituted 1,2,3‐Triazoles under Ultrasonic Irradiation
Authors: Faeghi Faezeh , Javanshir Shahrzad , Molaei Shiva
Published: November 2018

A simple ultrasonic‐assisted method was developed for click synthesize of natural polymer based copper/sandarac resin (CuO/SD) by linking two different unit sandarac resin powder and Cu(CH3COO)2. The CuO/SD nanocomposite was characterized by Fourier‐transform infrared spectroscopy (FT‐IR), scanning electron microscopy (SEM), X‐ray photoelectron spectroscopy (XPS), energy‐dispersive X‐ray spectroscopy (EDX) and X‐ray diffraction (XRD). All these analysis, showed that the surface of sandarac resin was uniformly covered by a layer of CuO nanoplates. Subsequently, its catalytic activity was studied in the synthesis of 1,4‐disubstituted 1,2,3‐triazoles via a one‐pot three‐component reaction among benzyl halides, sodium azide and terminal alkynes in water under ultrasonic irradiation. The reduction of copper (II) complexes of terpene acids to catalytic species Cu (I) occurred under ultrasonic conditions during cavitation. The use of natural CuO/SD catalyst in combination with ultrasonic irradiation eliminated the need of a reducing agent, moreover, it is easily separable, and recyclable so made this already efficacious click reaction, even more user‐friendly.
Thiophene Analogue of Isotanshinone‐II Nucleus: A Novel Approach towards the Synthesis of Phenanthro[4,3‐b]‐thiophene‐4,5‐dione and Phenanthro[3,4‐b]thiophene‐4,5‐dione Derivatives
Authors: Sarkar Aparna , Das Rumpa , Kar Gandhi K.
Published: November 2018

The phenanthraquinone moiety condensed with heteroarene moieties posses various therapeutic activities. In this article, synthesis of some novel thienophenanthraquinones (eg. Phenanthro[4,3‐b]thiophene‐4,5‐dione / phenanthro[3,4‐b]‐thiophene‐4,5‐dione derivatives) is reported using a novel pathway developed by us. 3,4‐Dihydro‐1‐(2‐thienyl)naphthalene‐2‐carbaldehyde derivatives 3 a‐c were aromatized with DDQ to respective 1‐(2‐thienyl)naphthalene‐2‐carbaldehyde derivatives 4 a‐c. Conversion of the CHO functionality to CH2CO2H functionality was achieved in 4 steps to afford 2‐[1‐(2‐thienyl)naphthalene‐2‐yl]acetic acid derivatives 7 a‐c. Intramolecular Friedal‐Crafts acylation of these acids followed by Fremy's salt oxidation of the resulting phenanthro[4,3‐b]thiophene‐4‐ol derivatives 8 a‐c furnished the title compounds 9 a‐c in overall 7 steps. Following a similar route another novel thienophenanthraquinone [10‐methoxyphenanthro[3,4‐b]thiophene‐4,5‐dione 18] has also been synthesized. This synthetic route is very simple with fewer steps and is of good to excellent yields in most of the steps involved.
Grain Size Evolution during Multipass Hot‐Rolling of C‐Mn Steels: Comparison of Phase Field and Extended JMAK Modeling
Authors: Tzini Maria‐Ioanna T. , Karamichailidou Despina A. , Haidemenopoulos Gregory N.
Published: November 2018

The design of multipass hot‐rolling schedules is of great importance to steel industry and an effort is made to predict the microstructure evolution. In the present study, a multi‐phase field model is employed for the simulation of the grain size evolution due to static recrystallization and grain growth during multipass hot‐rolling of C‐Mn steels. A variable stored energy per rolling pass, a temperature dependent interface mobility, and nucleation site density are considered. The model is compared with an extended JMAK model and validated with experimental data obtained from two hot‐rolling schedules. The results indicate that both models describe the experimental data well, however the phase field model avoids certain discontinuities between static recrystallization and grain growth. A statistical analysis is conducted to investigate the effect of the microstructure domain size on the phase field results and grain size distributions. The effect of key process parameters on the kinetics of static recrystallization and grain growth are determined by the temporal evolution of equivalent circular grain diameter distributions. Both approaches have the potential to be used for the computational design of multipass hot‐rolling processes in steels.
Forming a Kanyakla: A qualitative study to develop a novel social support intervention for adolescents living with HIV
Authors: Wolf Hilary T. , Chelliah Shantha S. , Ong'wen Patricia , Tepper Vicki , Kwena Zachary A. , Cohen Craig R.
Published: November 2018

Introduction

HIV is a leading cause of morbidity and mortality among youth in sub Saharan Africa. This study explores the adaptation of an adult social network intervention for adolescents, entitled Kanyakla.

Methods

The study was conducted in Kisumu, Kenya from July to November 2016. Data was collected from: (1) semi‐structured interviews (n = 32) with adolescents living with HIV aged 15–19; and (2) two focus group discussions (n = 21). Transcripts were coded using thematic analysis through the lens of an Adolescent Development Model.

Results

Participants were interested in joining a Kanyakla to build social support, learn new skills, and partake in recreational activities. Many participants feared inadvertent disclosure related to stigma. Certain dichotomous themes emerged including the need for privacy versus the need for social support; and the desire for inclusion of elders versus preference for same‐aged peers in the Kanyaklas.

Conclusions

With this study, we have key information that can be applied to developing the Kanyakla intervention for adolescents. Further study is needed to reconcile the dichotomies that emerged.