bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissecting LSD1‐Dependent Neuronal Maturation in the Olfactory Epithelium
Authors: Coleman Julie H. , Lin Brian , Schwob James E.
Published: September 2017

Neurons in the olfactory epithelium (OE) each express a single dominant olfactory receptor (OR) allele from among roughly 1,000 different OR genes. While monogenic and monoallelic OR expression has been appreciated for over two decades, regulators of this process are still being described; most recently, epigenetic modifiers have been of high interest as silent OR genes are decorated with transcriptionally repressive trimethylated histone 3 lysine 9 (H3K9me3) whereas active OR genes are decorated with transcriptionally activating trimethylated histone 3 lysine 4 (H3K4me3). The lysine specific demethylase 1 (LSD1) demethylates at both of these lysine residues and has been shown to disrupt neuronal maturation and OR expression in the developing embryonic OE. Despite the growing literature on LSD1 expression in the OE, a complete characterization of the timing of LSD1 expression relative to neuronal maturation and of the function of LSD1 in the adult OE have yet to be reported. To fill this gap, the present study determined that LSD1 (1) is expressed in early dividing cells before OR expression and neuronal maturation and decreases at the time of OR stabilization; (2) colocalizes with the repressor CoREST (also known as RCOR1) and histone deacetylase 2 in these early dividing cells; and (3) is required for neuronal maturation during a distinct time window between activating reserve stem cells (horizontal basal cells) and Neurogenin1 (+) immediate neuronal precursors. Thus, this study clarifies the role of LSD1 in olfactory neuronal maturation.
Heuristics, Protocol, and Considerations for Flow Chemistry in Photoredox Catalysis
Authors: Moschetta Eric G. , Richter Steven M. , Wittenberger Steven J.
Published: September 2017

Heuristics for employing photoredox catalysts in coiled‐tube LED reactors for flow chemistry are presented. These heuristics focus on common reaction parameters (for example, reagent concentration, tube diameter and light intensity) designed to encompass as many photoredox systems as possible. A chemical actinometer based on a common photocatalyst, [Ru(bpy)3Cl2], is used to determine how each parameter affects the observed rate of reaction and the photon flux received in the reactor. These heuristics are then demonstrated using a photoredox reaction to see if they accurately predict flow reaction conditions that correspond to increased rates of reaction.
Methyl Jasmonate Ameliorates Unpredictable Chronic Mild Stress‐Induced Behavioral and Biochemical Alterations in Mouse Brain
Authors: Adebesin Adaeze , Ajayi Abayomi M. , Olonode Elizabeth O. , Omorogbe Osarume , Umukoro Solomon
Published: September 2017

Preclinical Research

The effects of methyl jasmonate (MJ; 5, 10, 20 mg/kg, i.p), a natural product widely used for the relief of stress, depression, and exhaustion on unpredictable chronic mild stress (UCMS)‐induced depression‐like behaviors in mice was assessed and compared to those of imipramine (IMP; 10 mg/kg, i.p). MJ and IMP were given 30 min before exposure to UCMS with the procedure repeated daily for 2 weeks; 24 h after the stress session, the tail suspension test (TST) and sucrose preference test were assessed. MJ decreased immobility time in the TST and reversed impaired intake of sucrose relative to the stressed control suggesting antidepressant‐like activity. MJ also reduced UCMS‐induced increases in corticosterone and MDA (malondialdehyde) levels and attenuated UCMS‐induced decreases in GSH and TNF‐α levels and SOD activity. These findings suggest that MJ attenuated UCMS‐induced depressive‐like behaviors through decreased levels of corticosterone and decreasing oxidative stress and neuroinflammation in mouse brain.Drug Dev Res 78 : 381‐389, 2017. © 2017 Wiley Periodicals, Inc.
What can Parents' Self‐report of Reading Difficulties Tell Us about Their Children's Emergent Literacy at School Entry?
Authors: Esmaeeli Zahra , Lundetræ Kjersti , Kyle Fiona E.
Published: September 2017

Research has linked family risk (FR) of reading difficulties (RD) with children's difficulties in emergent literacy development. This study is the first to apply parents' self‐report of RD as a proxy for FR in a large sample (n = 1171) in order to test group differences in children's emergent literacy. Emergent literacy, the home literacy environment and children's interest in literacy and letters were compared across different groups of FR children around the school entry. The FR children performed lower in emergent literacy compared with not‐FR children. Furthermore, when comparing FR children with one parent reporting RD and children with both parents reporting RD, moderate group differences were found in Emergent Literacy. Finally, parents' self‐report of RD was a significant contributor of emergent literacy after controlling for the home literacy environment, children's gender, their interest in literacy and letters, months in kindergarten, vocabulary and parents' education. Our findings suggest that schools should monitor the reading development of children with parents self‐reporting RD closely – especially if both parents self‐report RD. © 2017 The Authors. Dyslexia published by John Wiley & Sons Ltd.
Assessing fire impacts on the carbon stability of fire‐tolerant forests
Authors: Bennett Lauren T. , Bruce Matthew J. , Machunter Josephine , Kohout Michele , Krishnaraj Saravanan Jangammanaidu , Aponte Cristina
Published: September 2017

The carbon stability of fire‐tolerant forests is often assumed but less frequently assessed, limiting the potential to anticipate threats to forest carbon posed by predicted increases in forest fire activity. Assessing the carbon stability of fire‐tolerant forests requires multi‐indicator approaches that recognize the myriad ways that fires influence the carbon balance, including combustion, deposition of pyrogenic material, and tree death, post‐fire decomposition, recruitment, and growth. Five years after a large‐scale wildfire in southeastern Australia, we assessed the impacts of low‐ and high‐severity wildfire, with and without prescribed fire (≤10 yr before), on carbon stocks in multiple pools, and on carbon stability indicators (carbon stock percentages in live trees and in small trees, and carbon stocks in char and fuels) in fire‐tolerant eucalypt forests. Relative to unburned forest, high‐severity wildfire decreased short‐term (five‐year) carbon stability by significantly decreasing live tree carbon stocks and percentage stocks in live standing trees (reflecting elevated tree mortality), by increasing the percentage of live tree carbon in small trees (those vulnerable to the next fire), and by potentially increasing the probability of another fire through increased elevated fine fuel loads. In contrast, low‐severity wildfire enhanced carbon stability by having negligible effects on aboveground stocks and indicators, and by significantly increasing carbon stocks in char and, in particular, soils, indicating pyrogenic carbon accumulation. Overall, recent preceding prescribed fire did not markedly influence wildfire effects on short‐term carbon stability at stand scales. Despite wide confidence intervals around mean stock differences, indicating uncertainty about the magnitude of fire effects in these natural forests, our assessment highlights the need for active management of carbon assets in fire‐tolerant eucalypt forests under contemporary fire regimes. Decreased live tree carbon and increased reliance on younger cohorts for carbon recovery after high‐severity wildfire could increase vulnerabilities to imminent fires, leading to decisions about interventions to maintain the productivity of some stands. Our multi‐indicator assessment also highlights the importance of considering all carbon pools, particularly pyrogenic reservoirs like soils, when evaluating the potential for prescribed fire regimes to mitigate the carbon costs of wildfires in fire‐prone landscapes.
Water regime of reclaimed and unreclaimed post‐mining sites
Authors: Cejpek Jiří , Kuráž Václav , Vindušková Olga , Frouz Jan
Published: September 2017

Water regime, throughfall, stemflow, soil water storage, subsurface runoff, and meteorological parameters were studied during 2 years (2011–2012) in 2 reclaimed and 2 unreclaimed post‐mining sites near Sokolov (Czech Republic). All sites were 25–35 years old, covered by woody vegetation, and developed on the same overburden consisting of tertiary clays. Interception of water by vegetation was about one third of precipitation in both reclaimed and unreclaimed sites; stemflow also did not differ significantly between sites and represented less than 10% of interception. Both reclaimed and unreclaimed sites have stable amount of soil water in the soil profile independent of precipitation, but water storage in reclaimed sites was significantly higher. The results suggest that after 25–35 years, there is no major difference in water budget of reclaimed and unreclaimed sites that develop by unassisted natural succession.
Clinical practices and attitudes regarding the diagnosis and management of heart failure: findings from the CORE Needs Assessment Survey
Authors: Howlett Jonathan , Comin‐Colet Josep , Dickstein Kenneth , Fuat Ahmet , Pölzl Gerhard , Delaney Sean
Published: September 2017

Aims

CORE is a continuing medical education initiative designed to support the evidence‐based management of heart failure (HF) in the primary and secondary care settings. The goal of the CORE Needs Assessment Survey is to describe current clinical practice patterns and attitudes among global stakeholders in HF care.

Methods and results

The CORE Steering Committee guided the development of survey questions to assess clinical practice, confidence, and attitudes/perceptions among cardiologists, primary care physicians, and nurses involved in HF management. In total, 346 healthcare professionals from Australia (n = 59), Austria (n = 59), Canada (n = 60), Spain (n = 58), Sweden (n = 52), and the UK (n = 58) contributed survey data. Results revealed multiple gaps over the spectrum of HF care, including diagnosis (low recognition of the signs and symptoms of HF and limited use of diagnostic tests), treatment planning (underuse of recommended agents and subtherapeutic dosing), treatment monitoring and adjustment (lack of adherence to recommendations), and long‐term management (low confidence in providing patient education). Although primary care and specialist physicians and nurses shared common unmet needs, healthcare professional‐specific clinical gaps were also identified.

Conclusions

The CORE Needs Assessment Survey provides timely data describing current clinical practices and attitudes among physicians and nurses regarding key aspects of HF care. These findings will be useful for guiding the development of interventions tailored to the specific educational needs of different provider types and designed to support the evidence‐based care of patients with HF.
Selective Carboxylate Directed ortho Functionalization in Copper Catalyzed Reactions of Polyiodo Aromatics: A Straightforward Preparation of 5,7‐Diiodo‐1H‐isochromen‐1‐ones
Authors: Anselmi Elsa , Bahlaouan Zineb , Inack Ngi Samuel , Parrain Jean Luc , Magnier Emmanuel , Abarbri Mohamed
Published: September 2017

A facile, and totally regioselective one‐pot approach to synthesize 5,7‐diiodo‐3‐substituted‐isocoumarins is described. This reaction was realized by using copper iodide as the catalyst under mild reaction conditions. The methodology was used to design a wide variety of compounds and was tolerant to a large number of functional groups. Interestingly, among the three possible carbon–iodine bonds, only one was reactive, which left the two others intact for further functionalization.
Structure and Conformational Studies of Aza‐Crown 8‐Amino‐BODIPY Derivatives: Influence of Steric Hindrance on Their Photophysical Properties
Authors: Costero Ana M. , Betancourt‐Mendiola María L. , Gaviña Pablo , Ochando Luis E. , Gil Salvador , Chulvi Katherine , Peña‐Cabrera Eduardo
Published: September 2017

Herein, we report the synthesis, X‐ray crystal structure and photophysical studies of six new 8‐amino‐BODIPY derivatives containing crown or azo‐crown ether moieties. The influence of steric hindrance, caused by the crown ether, on the planarity of the BODIPY core and its relationship with the fluorescent properties has been established. 1H NMR spectroscopic studies were undertaken to clarify the changes in fluorescence observed in the presence of ZnII.
A Highly Regioselective Palladium‐Catalyzed O,S Rearrangement of Cyclic Thiocarbonates
Authors: Mahy William , Cabezas‐Hayes Sinéad , Kociok‐Köhn Gabriele , Frost Christopher G.
Published: September 2017

This work describes an operationally simple catalytic synthesis of cyclic S‐thiocarbonates with predictable regioselectivity in good yields. The reaction utilizes substrates derived from ubiquitous 1,2‐diols in an atom economical intramolecular rearrangement, catalysed by an inexpensive and simple catalyst–ligand system. A crystal structure is presented that clearly confirms the regioselectivity of the reaction.
Preparation of Organophilic Nanohybrid Kaolinite and Application to the Electrochemical Detection of Organic Pesticide
Authors: Ngassa Guy B. P. , Fafard Jonathan , Detellier Christian
Published: September 2017

Novel organophilic nanohybrid materials (K‐TDD) were obtained by the grafting of 1,2‐tetradecanediol (TDD) onto the surface of kaolinite (K). XRD, IR, TGA‐DTG, and SEM characterization showed that TDD grafting results in a partial exfoliation of kaolinite layers. This material was used to modify a glassy carbon electrode (GCE/K‐TDD) and applied for the trace analysis of methyl parathion (MP). The signal of MP recorded on GCE/K‐TDD was more intense compared to the unmodified GCE or to one modified with a film of natural kaolinite. Several parameters that can affect the stripping response were systematically investigated to optimize the sensitivity of the organokaolinite‐modified electrode. A linear calibration curve for MP was obtained in the concentration range from 2×10−6 to 14×10−6 mol .L−1 in acetate buffer (pH 6), giving a detection limit of 9×10−8 mol .L−1. The sensitivity of the method was found to be 2.42 μA/μM for the range of concentrations that gives a linear calibration curve. The electrode was shown to be very stable, with the electrochemical response of MP decreasing by only 1.5 % after a series of nine measurements. The interference of various inorganic ions and organic compounds likely to influence the stripping determination of the MP were also examined. The results showed that the GCE/K‐TDD electrode was effective in solutions containing interfering species and could be applied for the quantification of MP pesticide in natural water.
A Comparison between the electrocoagulation and the metal dissolution method in the process of phosphorus compounds removal from brewery wastewater
Authors: Wysocka Izabela , Masalski Wojciech
Published: September 2017

This manuscript provides a comparative analysis of metal dissolution method of metal dissolution method (Fe0) based on spontaneous corrosive processes and the electrocoagulation method in the process of phosphorus compounds removal from brewery wastewater. Differences were demonstrated in the effectiveness of both methods and in changes of selected parameters of treated wastewater (total iron content, pH value, redox potential, and total suspended matter content). Additional costs linked with the use of electrocoagulation (higher costs of energy and faster wearing out of electrodes) and the metal dissolution method (longer contact time) were mentioned as well. © 2017 American Institute of Chemical Engineers Environ Prog, 37: 975–979, 2018
Inhibition shapes the organization of hippocampal representations
Authors: McKenzie Sam
Published: September 2017

Hippocampal neurons become tuned to stimuli that predict behaviorally salient outcomes. This plasticity suggests that memory formation depends upon shifts in how different anatomical inputs can drive hippocampal activity. Here, I present evidence that inhibitory neurons can provide such a mechanism for learning‐related changes in the tuning of pyramidal cells. Inhibitory currents arriving on the dendrites of pyramidal cells determine whether an excitatory input can drive action potential output. Specificity and plasticity of this dendritic modulation allows for precise, modifiable changes in how afferent inputs are integrated, a process that defines a neuron's receptive field. In addition, feedback inhibition plays a fundamental role in biasing which excitatory neurons may be co‐active. By defining the rules of synchrony and the rules of input integration, interneurons likely play an important role in the organization of memory representation within the hippocampus.
miR‐122 promotes metastasis of clear‐cell renal cell carcinoma by downregulating Dicer
Authors: Fan Yang , Ma Xin , Li Hongzhao , Gao Yu , Huang Qingbo , Zhang Yu , Bao Xu , Du Qingshan , Luo Guoxiong , Liu Kan , Meng Qingyu , Zhao Chaofei , Zhang Xu
Published: September 2017

Although overall downregulation of microRNAs (miRNAs) is a general feature of clear‐cell renal cell carcinoma (ccRCC), several miRNAs are consistently upregulated, among which miR‐122 was markedly increased in ccRCC tissues. Our study aims to determine the functional importance and underlying mechanism of miR‐122 in ccRCC metastasis. Here, we demonstrate that the expression of miR‐122 increased in ccRCC tissues, and higher miR‐122 expression was found in ccRCC tissues with metastatic disease than in those without metastasis. The increased miR‐122 levels were associated with poor metastasis‐free survival in ccRCC patients with localized disease. Dicer was validated as a direct functional target of miR‐122. Overexpression of miR‐122 promoted migration and invasion of ccRCC cells in vitro and metastatic behavior of ccRCC cells in vivo. Inhibition of miR‐122 attenuated this metastatic phenotype in vitro. Importantly, miR‐122 exerted its pro‐metastatic properties in ccRCC cells by downregulating Dicer and its downstream effector, the miR‐200 family, thereby inducing epithelial–mesenchymal transition (EMT). Our results suggest an important role of the miR‐122/Dicer/miR‐200s/EMT pathway in ccRCC metastasis. Furthermore, miR‐122 may serve as a biomarker for discriminating ccRCC with metastatic potential.
Neuroblastoma cells undergo transcriptomic alterations upon dissemination into the bone marrow and subsequent tumor progression
Authors: Rifatbegovic Fikret , Frech Christian , Abbasi M. Reza , Taschner‐Mandl Sabine , Weiss Tamara , Schmidt Wolfgang M. , Schmidt Iris , Ladenstein Ruth , Ambros Inge M. , Ambros Peter F.
Published: September 2017

Neuroblastoma is the most common extracranial solid tumor in childhood. The vast majority of metastatic (M) stage patients present with disseminated tumor cells (DTCs) in the bone marrow (BM) at diagnosis and relapse. Although these cells represent a major obstacle in the treatment of neuroblastoma patients, insights into their expression profile remained elusive. The present RNA‐Seq study of stage 4/M primary tumors, enriched BM‐derived diagnostic and relapse DTCs, as well as the corresponding BM‐derived mononuclear cells (MNCs) from 53 patients revealed 322 differentially expressed genes in DTCs as compared to the tumors (q < 0.001, |log2FC|>2). Particularly, the levels of transcripts encoded by mitochondrial DNA were elevated in DTCs, whereas, for example, genes involved in angiogenesis were downregulated. Furthermore, 224 genes were highly expressed in DTCs and only slightly, if at all, in MNCs (q < 8 × 10−75 log2FC > 6). Interestingly, we found the transcriptome of relapse DTCs largely resembling those of diagnostic DTCs with only 113 differentially expressed genes under relaxed cut‐offs (q < 0.01, |log2FC|>0.5). Notably, relapse DTCs showed a positional enrichment of 31 downregulated genes on chromosome 19, including five tumor suppressor genes: SIRT6, BBC3/PUMA, STK11, CADM4 and GLTSCR2. This first RNA‐Seq analysis of neuroblastoma DTCs revealed their unique expression profile in comparison to the tumors and MNCs, and less pronounced differences between diagnostic and relapse DTCs. The latter preferentially affected downregulation of genes encoded by chromosome 19. As these alterations might be associated with treatment failure and disease relapse, further functional studies on DTCs should be considered.
Ingested nitrate and nitrite, disinfection by‐products, and pancreatic cancer risk in postmenopausal women
Authors: Quist Arbor J.L. , Inoue‐Choi Maki , Weyer Peter J. , Anderson Kristin E. , Cantor Kenneth P. , Krasner Stuart , Freeman Laura E. Beane , Ward Mary H. , Jones Rena R.
Published: September 2017

Nitrate and nitrite are precursors of N‐nitroso compounds (NOC), probable human carcinogens that cause pancreatic tumors in animals. Disinfection by‐products (DBP) exposures have also been linked with digestive system cancers, but few studies have evaluated relationships with pancreatic cancer. We investigated the association of pancreatic cancer with these drinking water contaminants and dietary nitrate/nitrite in a cohort of postmenopausal women in Iowa (1986–2011). We used historical monitoring and treatment data to estimate levels of long‐term average nitrate and total trihalomethanes (TTHM; the sum of the most prevalent DBP class) and the duration exceeding one‐half the maximum contaminant level (>½ MCL; 5 mg/L nitrate‐nitrogen, 40 µg/L TTHM) among participants on public water supplies (PWS) >10 years. We estimated dietary nitrate and nitrite intakes using a food frequency questionnaire. We computed hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression and evaluated nitrate interactions with smoking and vitamin C intake. We identified 313 cases among 34,242 women, including 152 with >10 years PWS use (N = 15,710). Multivariable models of average nitrate showed no association with pancreatic cancer (HRp95 vs. Q1 = 1.16, 95% CI: 0.51–2.64). Associations with average TTHM levels were also null (HRQ4 vs. Q1 = 0.70, 95% CI:0.42–1.18). We observed no trend with increasing years of exposure to either contaminant at levels >½ MCL. Positive associations were suggested in the highest dietary nitrite intake from processed meat (HRp95 vs. Q1 = 1.66, 95% CI 1.00–2.75;ptrend = 0.05). We found no interactions of nitrate with known modifiers of endogenous NOC formation. Our results suggest that nitrite intake from processed meat may be a risk factor for pancreatic cancer.
Neurologic injury and patient displacement in gynecologic laparoscopic surgery using a beanbag and shoulder supports
Authors: Treszezamsky Alejandro D. , Fenske Suzanne , Moshier Erin L. , Ascher‐Walsh Charles J.
Published: September 2017

Objective

To quantify the incidence of peripheral neuropathy in gynecologic laparoscopic surgery using a combination of beanbag, eggcrate foam, and shoulder supports; and to assess patient displacement during surgery in a steep Trendelenburg position and determine variables correlated with displacement.

Methods

A retrospective study included all gynecologic laparoscopic surgeries performed by one high‐volume surgeon at a US center between September 15, 2007, and September 15, 2012. Data included neurologic deficits or extremity pain, any other complications, and—for the final study year—surgical time as well as patient and beanbag displacement.

Results

Among 967 patients, no long‐term neuropathy was reported, 6 (0.6%) patients had transient shoulder pain beyond the first 24 hours (resolved by initial postoperative visit), and 7 (0.7%) were lost to follow‐up. No neurologic complications were reported. Median beanbag and total patient displacement were 0 cm (interquartile range 0–0) and 0 cm (interquartile range 0–2), respectively. Patient displacement relative to the table was correlated with the total surgical time (P=0.025) and patient weight (P=0.023). The median displacement was greater in hysterectomy than non‐hysterectomy procedures (P=0.003).

Conclusion

Use of beanbags with shoulder supports and convoluted foam armboard pads was associated with minimal patient displacement and risk of arm and leg neurologic injury.
Synthesis and bioactivity assessment of high silica content quaternary glasses withCa:Pratios of 1.5 and 1.67, made by a rapid sol‐gel process
Authors: Ben‐Arfa Basam A. E. , Fernandes Hugo R. , Miranda Salvado Isabel M. , Ferreira José M. F. , Pullar Robert C.
Published: September 2017

Sol‐gel glasses in quaternary silica–sodium–calcium–phosphorous systems have been synthesized using a rotary evaporator for rapid drying without ageing. This novel fast drying method drastically decreases the total drying and ageing time from several weeks to only 1 hour, thus overcoming a serious drawback in sol‐gel preparation procedures for bioglasses. This work investigates the bioactivity behavior of two glasses synthesized by this fast method, with Ca:P ratios of 1.5, and 1.67. X‐ray diffraction (XRD), Inductive coupled plasma, Fourier‐transform infrared, and Raman spectroscopy were used to confirm the bioactivity of the synthesized powders. MAS‐NMR was also used to assess the degree of silica polymerization. The composition with a higher Ca:P = 1.67 ratio showed better bioactivity in comparison to the one with Ca:P = 1.5, which exhibited little bio‐response with up to 4 weeks of immersion in SBF (simulated body fluid). It was also found that an orbital agitation rate of 120 rpm favors the interfacial bio‐mineralization reactions, promoting the formation of a crystalline hydroxyapatite (HAp) layer at the surface of the (Ca:P = 1.67) composition after 2 weeks immersion in SBF. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 510–520, 2018.
N,N'‐methylenebis(acrylamide)‐crosslinked poly(acrylic acid) particles as doxorubicin carriers: A comparison between release behavior of physically loaded drug and conjugated drug via acid‐labile hydrazone linkage
Authors: Modarresi‐Saryazdi Seyedeh Mahnaz , Haddadi‐Asl Vahid , Salami‐Kalajahi Mehdi
Published: September 2017

N,N'‐methylenebis(acrylamide) (MBA)‐crosslinked poly(acrylic acid) (PAA) particles with low degree of cross‐linking were synthesized using distillation precipitation polymerization. Size and size distribution of particles were obtained using dynamic light scattering and field emission scanning electron microscopy( and results showed that microspheres had a narrow size dispersity. Proton nuclear magnetic resonance results indicated that amount of cross‐linker in structure of particles is a little more than the molar percentage of feeded MBA because of greater activity ratio of MBA than AA. pH‐responsive behavior of samples was investigated using UV‐vis. absorption at 480 nm where each sample showed a sudden deplete in UV absorbance at a peculiar pH. Synthesized particles were used as carriers of anti‐cancer drug doxorubicin using two different approaches including physically loading of drug and drug conjugation via an acid‐labile hydrazone linkage. Release results showed that in the first case, amount of released drug has an inverse relationship with the amount of cross‐linker in the structure and also, by adding an acid‐labile linkage, the amount of burst release decreased drastically. Also, the amount of released drug for conjugated systems was much lesser than particles with physically loaded drug. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 342–348, 2018.
Biomechanical properties and healing effects of chitin patch in a rat full‐thickness abdominal wall defect model
Authors: Qiao Jing , Jiang Zhiwen , Liang Xuyue , Yang Yan , Liu Wanshun , Han Baoqin
Published: September 2017

Hernia repair is usually accompanied with the implantation of a synthetic mesh, which frequently results in a foreign body response and serious complications. In the present study, a novel biodegradable chitin‐based hernia patch was prepared and characterized. Biomechanical properties and biodegradability of the chitin patch were quantifiedin vitroandin vivo. In repair of the rat abdominal wall full‐thickness defect model, the chitin patch induced more abundant new blood vessels with milder tissue inflammation and fibrosis compared with polypropylene mesh. Chitin patch effectively inhibited excessive secretion of inflammation‐associated cytokines (IL‐6 and TNF‐α) (p < 0.01) and significantly increased the secretion of healing‐related cytokines (FGF1 and TGF‐β1) (p < 0.01). Accompanied by biodegradation of the chitin patch, intra‐abdominal adhesions caused by the chitin patch decreased significantly, and the tensile strength of the repaired site could meet the biomechanical requirements of human abdominal wall. After the one‐year observation period, the defected abdominal wall returned to the appropriate thickness with no obvious complication or hernia occurrence. In a conclusion, the newly designed chitin patch showed good biomechanical properties and satisfactory healing effects on the full‐thickness defect of abdominal wall, which makes it promising candidate for clinical hernia treatment. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1349–1357, 2018.
Reference intervals for serum bilirubin, urea, and uric acid in healthy Chinese geriatric population
Authors: Yang Yuanqing , Jiang Hongmin , Tang Aiguo , Xiang Zhongyuan
Published: September 2017

Objectives

The study aims to establish the reference intervals (RIs) for total bilirubin (TBIL), direct bilirubin (DBIL), urea (UR), and uric acid (UA) in healthy Chinese geriatric population.

Methods

Eight hundred and twenty cases from six representative geographical regions in China (including male 413 cases and female 407 cases) of apparently healthy individuals aged 60‐96 years were recruited. Serum TBIL, DBIL, UR, and UA were analyzed by automatic biochemical analyzer and RIs were determined following CLSI C28‐A3 guidelines using a non‐parametric method.

Results

In apparently healthy Chinese geriatric population of China, the RIs of TBIL, DBIL, UR, and UA were 6.6~21.8 μmol/L, 1.9~8.0 μmol/L, 3.60~9.51 mmol/L, 179.2~460.9 μmol/L in males and 6.1~20.0 μmol/L, 1.8~7.1 μmol/L,3.35~8.89 mmol/L, 130.2~443.4 μmol/L in females, respectively.

Conclusions

The RIs of TBIL, DBIL, UR, and UA were established within apparently healthy geriatric Chinese population according to CLSIC28‐A3 document, providing a reference for the clinical.
Blinatumomab Pharmacodynamics and Exposure–Response Relationships in Relapsed/Refractory Acute Lymphoblastic Leukemia
Authors: Zhu Min , Kratzer Andrea , Johnson Jessica , Holland Chris , Brandl Christian , Singh Indrajeet , Wolf Andreas , Doshi Sameer
Published: September 2017

We evaluated blinatumomab pharmacokinetics, pharmacodynamics (CD3+ T‐cell, CD19+ B‐cell, and cytokine levels), and their associations with efficacy or safety in relapsed/refractory acute lymphoblastic leukemia. Blinatumomab pharmacokinetics (continuous intravenous infusion) from a phase 2 study (n = 189; NCT01466179) were assessed noncompartmentally. Associations between steady‐state concentration (Css) and efficacy (complete remission [CR] or CR with partial hematologic recovery [CRh]) or safety (cytokine release syndrome [CRS] and neurologic events [NEs]) were evaluated with statistical models. Blinatumomab mean ± SD Css was 621 ± 502 pg/mL (28 μg/day dose). Cytokines were transiently elevated in >50% of patients; B‐cell levels decreased in most patients. Lower B‐cell and bone marrow (BM) blast percentages and higher T‐cell percentages were associated with higher CR/CRh (P < .001) in univariate analysis. Higher Css (OR, 1.90; 95%CI, 1.12‒3.21), higher peak IL‐10 level (1.59; 1.13‒2.22), and lower BM blast percentage (0.78; 0.69‒0.89) were associated with higher CR/CRh in multivariate analysis. Higher Css (HR, 1.40; 1.01–1.94) and lower B‐cell level (0.90; 0.84‒0.97) were associated with shorter time to NEs. Cytokine peaks were not associated with NEs or CRS. In conclusion, blinatumomab led to T cell‐mediated depletion of target B cells in blood and blasts in the bone marrow. Immune system effectiveness was important for treatment responses.
RNA Therapeutics in Oncology: Advances, Challenges, and Future Directions
Authors: MacLeod A. Robert , Crooke Stanley T.
Published: September 2017

RNA‐based therapeutic technologies represent a rapidly expanding class of therapeutic opportunities with the power to modulate cellular biology in ways never before possible. With RNA‐targeted therapeutics, inhibitors of previously undruggable proteins, gene expression modulators, and even therapeutic proteins can be rationally designed based on sequence information alone, something that is not possible with other therapeutic modalities. The most advanced RNA therapeutic modalities are antisense oligonucleotides (ASOs) and small interfering RNAs. Particularly with ASOs, recent clinical data have demonstrated proof of mechanism and clinical benefit with these approaches across several nononcology disease areas by multiple routes of administration. In cancer, next‐generation ASOs have recently demonstrated single‐agent activity in patients with highly refractory cancers. Here we discuss advances in RNA therapeutics for the treatment of cancer and the challenges that remain to solidify these as mainstay therapeutic modalities to bridge the pharmacogenomic divide that remains in cancer drug discovery.
Repeated immune challenges affect testosterone but not sperm quality
Authors: Needham Katie B. , Kucera Aurelia C. , Heidinger Britt J. , Greives Timothy J.
Published: September 2017

Mounting an immunological response is energetically demanding and necessarily redirects allocation of resources toward immune system activation and away from other energetically expensive processes, such as reproduction. Lipopolysaccharide (LPS), a major component of the outer membrane of the cell wall of Gram‐negative bacteria Escherichia coli, mimics a bacterial infection without producing the cost of replicating the pathogen and is one of the most commonly used agents to induce an acute phase immune response. Here, we ask if a trade‐off can be induced between activation of the acute phase immune response and sperm function, a key indicator of sperm competitive ability. Further, we ask whether repeated exposure to this endotoxin in a social species such as the house sparrow (Passer domesticus), where repeated pathogen exposure may be common, may have a more pronounced effect. To address our questions, we exposed individuals to two rounds of LPS treatment or control, to mimic a repeated pathogen exposure in the wild. We predicted that repeated pathogen exposure would have detrimental effects on sperm quality, and therefore, reproductive success. We compared a measure of sperm quality (straight‐line velocity) in captive male house sparrows between LPS‐treated and control individuals. We found that although LPS treatment impaired circulating testosterone and induced a hypothermic state when compared with controls, it did not affect sperm quality within days or weeks following a single or repeated LPS exposure.
Analysis of the spotted gar genome suggests absence of causative link between ancestral genome duplication and transposable element diversification in teleost fish
Authors: Chalopin Domitille , Volff Jean‐Nicolas
Published: September 2017

Teleost fish have been shown to contain many superfamilies of transposable elements (TEs) that are absent from most tetrapod genomes. Since theories predict an increase in TE activity following polyploidization, such diversity might be linked to the 3R whole‐genome duplication that occurred approximately 300 million years ago before the teleost radiation. To test this hypothesis, we have analyzed the genome of the spotted gar Lepisosteus oculatus, which diverged from the teleost lineage before the 3R duplication. Our results indicate that TE diversity and copy numbers are similar in gar and teleost genomes, suggesting that TE diversity was ancestral and not linked to the 3R whole‐genome duplication. We propose that about 25 distinct superfamilies of TEs were present in the last ancestor of gars and teleost fish about 300 million years ago in the ray‐finned fish lineage.
Impact of dietary beliefs and practices on patients with inflammatory bowel disease: An observational study from India
Authors: Tomar Sanjeevani K , Kedia Saurabh , Upadhyay Ashish D , Bopanna Sawan , Yadav Dawesh P , Goyal Sandeep , Jain Saransh , Makharia Govind , Ahuja Vineet , Singh Namrata
Published: September 2017

Background and Aim

Patients with inflammatory bowel disease (IBD) are at a risk of nutritional deficits because of poor dietary beliefs and practices. There are no data on this aspect from Asia, which is experiencing a rise in IBD incidence. We aimed to establish dietary beliefs and practices in patients of IBD from India.

Methods

Patients with ulcerative colitis (UC) and Crohn's disease (CD) followed up between November 2016 and March 2017 were included. A questionnaire extracted information on the patients' sociodemographic, nutritional and disease profile, smoking and drinking habits, dietary beliefs and practices, current dietary preferences, intake and avoidance, dietary changes made after diagnosis of IBD, dietary changes made during relapse, frequency of consumption of major food groups, and the attitudes toward dietary advice.

Results

A total of 316 patients (218 UC and 98 CD; mean age: 38.5 ± 12.2 years) were included. Forty‐four percent patients perceived food as a risk factor for IBD, 52% felt dietary habits to have a more important role than medicines in disease control, 77% reported certain foods improve symptoms during relapse, 86% had modified their diet since the diagnosis of IBD (UC > CD, P = 0.04), 90% imposed food restrictions, and <50% had received dietary counseling. About 40% of patients could not meet their dietary requirements and 66% had decreased their dietary intake since diagnosis, which further decreased during relapse (85%).

Conclusion

Dietary beliefs and practices play a central role in perception of disease in IBD patients. A large majority of them make dietary changes which can lead to undernutrition. Proper dietary counseling is required in these patients to prevent malnutrition.
Drug resistance in intestinal tuberculosis: A reason to worry?
Authors: Sonambekar Ajinkya , Desai Devendra , Abraham Philip , Mehta Vatsal , Samant Hrishikesh , Joshi Anand , Gupta Tarun , Rodrigues Camilla
Published: September 2017

Background and Aim

Emergence of drug resistance in intestinal tuberculosis (ITB) makes the treatment of this condition challenging. While there is growing evidence of multiple and extensive drug resistance in pulmonary and glandular tuberculosis (TB), literature regarding susceptibility and resistance patterns in ITB is scarce. The aim of the current paper was to study the prevalence of drug resistance in patients with ITB.

Methods

Among patients presenting to a tertiary care hospital in Mumbai between 2008 and 2016, records of all patients with ITB, whose mucosal biopsy (obtained at ileocolonoscopy) tissue culture was positive for Mycobacterium tuberculosis and in whom drug sensitivity testing was performed, were retrospectively analyzed. Sensitivity and resistance to single or multiple anti‐TB drugs were noted.

Results

A total of 43 patients were included, of whom 10 (23.2%) patients were diagnosed to have resistance to at least one first‐line anti‐TB drug. Resistance to isoniazid was the most common (nine patients), followed by rifampicin (six), pyrazinamide (five), streptomycin and ethionamide (four each), ethambutol, moxifloxacin and ofloxacin (three each), and p‐amino salicylic acid (one). Six patients (13.9%) had multidrug‐resistant TB and needed second‐line anti‐TB therapy as per drug sensitivity pattern. There was no patient with extensive drug‐resistant TB.

Conclusion

Twenty‐three percent of our patients with ITB tested for drug resistance had drug resistance, 13.9% being multidrug resistant and needing second‐line anti‐TB therapy.
Liver stiffness measurement predicts hepatocellular carcinoma development in patients treated with direct‐acting antivirals
Authors: Tachi Yoshihiko , Hirai Takanori , Kojima Yuko , Ishizu Yoji , Honda Takashi , Kuzuya Teiji , Hayashi Kazuhiko , Ishigami Masatoshi , Goto Hidemi
Published: September 2017

Background and Aim

Predictive factors for hepatocarcinogenesis following eradication of hepatitis C virus by direct‐acting antivirals (DAAs) are unknown. The aim of the study was to investigate the relationships between liver stiffness (LS) using acoustic radiation force impulse (ARFI) erastograghy and the development of hepatocellular carcinoma (HCC) in patients who achieved sustained virological response (SVR) treated with DAA.

Methods

In this prospective study, we enrolled 263 hepatitis C patients with SVR who underwent ARFI before DAA treatment. Thirty patients had previous HCC.

Results

The median LS value according to ARFI measurements was 1.34 m/s (range: 0.67–4.35). During the follow‐up period (median: 18.1 months), development of HCC occurred in 19 patients (7.2%; HCC occurrence in 7 patients and HCC recurrence in 12 patients). By multivariate Cox regression analysis, HCC history (hazard ratio [HR]: 10.634; 95% confidence interval [CI]: 4.13–27.37; P = 0.001), older age (HR: 4.638; 95% CI: 1.63–13.61; P = 0.004) and higher total bilirubin levels (HR: 4.189; 95% CI: 1.66–10.60; P = 0.002) were independent predictors for the development of HCC, and higher LS value (≥1.73 m/s) at baseline was an independent predictor for HCC occurrence (HR: 8.350; 95% CI: 1.62–43.09; P = 0.011). The cumulative recurrence of HCC was statistically similar according to the degree of LS in patients who were previously treated for HCC.

Conclusion

The LS value at baseline is useful for predicting HCC occurrence. Thus, even if SVR is achieved, patients with higher LS at baseline must be followed carefully for HCC occurrence.
Thermolysis of Chlorovinyl Imines as an Alternate Route for the Synthesis of Pyranoquinolin‐3‐one and Pyranoacridin‐3‐one Derivatives
Authors: Patra Prasanta
Published: September 2017

Synthesis of 3H‐pyrano[3,2‐f]quinolin‐3‐one and 3H‐benzo[h]pyrano[3,2‐a]acridin‐3‐one derivatives are described by the thermolysis of suitable chlorovinyl imine derivatives. The chlorovinyl imines were obtained by condensation of suitable β‐chloro‐α,β‐unsaturated aldehydes and 6‐aminocoumarin in methanol at 15°C. Compounds showed blue fluorescence in alkaline medium.
Analyzing fatigue in prolonged watching of 3DTV with ReHo approach
Authors: Chen Chunxiao , Wang Jing , Liu Yupin , Chen Xin
Published: September 2017

Fatigue caused by the prolonged watching of 3DTV has been paid great attention about the safety for viewers. We used regional homogeneity (ReHo) to measure the local synchronization of resting‐state functional magnetic resonance imaging signals both before and after watching 2D or 3D television. Twenty normal subjects were all measured four times: scans before watching television (3D‐Pre/2D‐Pre) and immediately after watching television for 1 h (3D‐Post/2D‐Post). The variation of ReHo was investigated in 2D/3D groups, and then the influence of watching 2D/3D TV on the spectators was estimated. Compared with the 3D‐Pre, the 3D‐Post showed significantly higher ReHo in the right inferior occipital gyrus (BA18/19) and right middle occipital gyrus (BA18/19), left postcentral gyrus (BA2/3/4/7), and small area of BA9/10 in left frontal lobe. Additionally, increased ReHo regions in the 2D‐Post was observed in the left medial frontal gyrus (BA9/10/32), left cingulate gyrus (BA24), and right anterior cingulate (BA32) as compared with the 2D‐Pre. For the 2D group, subjects mainly feel mental fatigue, which could be caused by prolonged attention. For the 3D group, watching TV primarily causes visual fatigue because of the constant change of depth of focus and mild mental fatigue. The study indicates the adverse effects of 3DTV on visual function.
A paradigm for evaluation and management of the maxillary sinus before dental implantation
Authors: Chen Yi‐Wei , Lee Fu‐Ying , Chang Po‐Hung , Huang Chi‐Che , Fu Chia‐Hsiang , Huang Chien‐Chia , Lee Ta‐Jen
Published: September 2017

Objectives

To determine a paradigm for evaluating and managing maxillary sinus conditions before dental implantation via preoperative sinonasal assessment.

Study Design

Prospective cohort study.

Methods

Eighty‐four patients who underwent dental implantation with or without sinus augmentation were included. Maxillary sinus conditions were classified into groups 1 to 6 according to cone‐beam computed tomography (CT) findings: 1) nonspecific findings, 2) solitary polyp or cyst, 3) mucosal thickening, 4) air–fluid level or fluid accumulation, 5) near‐total opacification of the maxillary or other paranasal sinus, and 6) calcification spots in the maxillary sinus. Dental implantation with or without sinus augmentation was suggested with postoperative sinus observation (groups 1–3), after medication for acute sinusitis (group 4), and after comprehensive treatment of chronic or fungal sinusitis (groups 5–6). Intraoperative and postoperative sinus‐related complications were recorded.

Results

Two patients (groups 1 and 3) developed acute rhinosinusitis after sinus augmentation; both recovered completely with medical treatment. Schneiderian membrane perforation occurred during sinus lift surgery in six patients (group 1): five recovered after conservative medical therapy and close observation, whereas one required endoscopic sinus surgery and recovered well. No chronic rhinosinusitis developed after dental implantation.

Conclusion

Craniofacial CT is crucial for pre‐dental implantation sinonasal evaluation. The risk of dental implant‐related chronic rhinosinusitis is low for patients with cysts, polyps, or mucosal thickening in the maxillary sinus. However, preventive endoscopic sinus surgery is recommended for patients with incurable chronic rhinosinusitis, fungal sinusitis, and large polyps or cysts.

Level of Evidence

4. Laryngoscope, 128:1261–1267, 2018
Development of microbial community during primary succession in areas degraded by mining activities
Authors: Harantová Lenka , Mudrák Ondřej , Kohout Petr , Elhottová Dana , Frouz Jan , Baldrian Petr
Published: September 2017

Together with plants, soil microbial communities play an essential role in the development of stable ecosystems on degraded lands, such as postmining spoil heaps. Our study addressed concurrent development of the vegetation and soil fungal and bacterial communities in the course of primary succession in a brown coal mine spoil deposit area in the Czech Republic across a chronosequence spanning 54 years. During succession, the plant communities changed from sparse plants over grassland and shrubland into a forest, becoming substantially more diverse with time. Microbial biomass increased until the 21st year of ecosystem development and later decreased. Although there was a close association between fungi and vegetation, with fungi mirroring the differences in plant community assemblages, the development of the bacterial community was different. The early succession community in the barren nonvegetated soil largely differed from that in the older sites, especially in its high abundance of autotrophic and free‐living N2‐fixing bacteria. Later in succession, bacterial community changes were minor and reflected the chemical parameters of the soil, including pH, which also showed a minor change with time. Our results show that complex forest ecosystems developed over 54 years on the originally barren soil of the temperate zone and indicate an important role of bacteria in the initial stage of soil development. Although the arrival of vegetation affects substantially fungal as well as bacterial communities, it is mainly fungi that respond to the ongoing development of vegetation.