bluuebunny/crossref_metadata_2025 huggingface dataset:
Ritonavir inhibits intratumoral docetaxel metabolism and enhances docetaxel antitumor activity in an immunocompetent mouse breast cancer model
Authors: Hendrikx Jeroen J.M.A. , Lagas Jurjen S. , Song Ji‐Ying , Rosing Hilde , Schellens Jan H.M. , Beijnen Jos H. , Rottenberg Sven , Schinkel Alfred H.
Published: August 2015

Docetaxel (Taxotere®) is currently used intravenously as an anticancer agent and is primarily metabolized by Cytochrome P450 3A (CYP3A). The HIV protease inhibitor ritonavir, a strong CYP3A4 inhibitor, decreased first‐pass metabolism of orally administered docetaxel. Anticancer effects of ritonavir itself have also been described. We here aimed to test whether ritonavir co‐administration could decrease intratumoral metabolism of intravenously administered docetaxel and thus increase the antitumor activity of docetaxel in an orthotopic, immunocompetent mouse model for breast cancer. Spontaneously arising K14cre;Brca1F/F;p53F/F mouse mammary tumors were orthotopically implanted in syngeneic mice lacking Cyp3a (Cyp3a−/−) to limit ritonavir effects on systemic docetaxel clearance. Over 3 weeks, docetaxel (20 mg/kg) was administered intravenously once weekly, with or without ritonavir (12.5 mg/kg) administered orally for 5 days per week. Untreated mice were used as control for tumor growth. Ritonavir treatment alone did not significantly affect the median time of survival (14 vs. 10 days). Median time of survival in docetaxel‐treated mice was 54 days. Ritonavir co‐treatment significantly increased this to 66 days, and substantially reduced relative average tumor size, without altering tumor histology. Concentrations of the major docetaxel metabolite M2 in tumor tissue were reduced by ritonavir co‐administration, whereas tumor RNA expression of Cyp3a was unaltered. In this breast cancer model, we observed no direct antitumor effect of ritonavir alone, but we found enhanced efficacy of docetaxel treatment when combined with ritonavir. Our data, therefore, suggest that decreased docetaxel metabolism inside the tumor as a result of Cyp3a inhibition contributes to increased antitumor activity.
Statins and the risk of pancreatic cancer in Type 2 diabetic patients—A population‐based cohort study
Authors: Chen Mei‐Jyh , Tsan Yu‐Tse , Liou Jyh‐Ming , Lee Yi‐Chia , Wu Ming‐Shiang , Chiu Han‐Mo , Wang Hsiu‐Po , Chen Pau‐Chung
Published: August 2015

The aim of this study was to determine whether statin use exerts a protective effect against pancreatic cancer in Type 2 diabetic patients. A retrospective population‐based cohort study was designed to analyze the National Health Insurance Research database (NHIRD) from 1997–2010 in Taiwan. A total of 1,140,617 patients with a first‐time diagnosis of Type 2 diabetes were enrolled. The event was defined as newly diagnosed pancreatic cancer. A Cox proportional hazards regression model with time‐dependent covariates was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of pancreatic cancer associated with statin use in the diabetic cohort. A total of 2,341 patients with newly diagnosed pancreatic cancer were identified in the diabetic cohort during the follow‐up period of 6,968,217.1 person‐years. In this cohort, 450,282 patients were defined as statin users (statin use ≥28 cumulative defined daily dose [cDDD] in 1 year) and 0.14% had pancreatic cancer; 690,335 patients were statin nonusers (statin use <28 cDDD in 1 year) and 0.25% had pancreatic cancer. Statin use significantly decreased the risk of pancreatic cancer (adjusted HRs: 0.78 in 28–83 cDDD per year; 0.48 in 84–180 cDDD per year; and 0.33 in >180 cDDD per year) after adjusting for multiple confounders. There was a significant dose‐effect of statin use for the risk of pancreatic cancer (p for trend: <0.001). Statin use may be associated with a reduced risk of pancreatic cancer in Type 2 diabetic patients. More research is needed to clarify this association.
Generation and characterization of a breast carcinoma model by PyMT overexpression in mammary epithelial cells of tree shrew, an animal close to primates in evolution
Authors: Ge Guang‐Zhe , Xia Hou‐Jun , He Bao‐Li , Zhang Hai‐Lin , Liu Wen‐Jing , Shao Ming , Wang Chun‐Yan , Xiao Ji , Ge Fei , Li Fu‐Bing , Li Yi , Chen Ceshi
Published: August 2015

The tree shrew is becoming an attractive experimental animal model for human breast cancer owing to a closer relationship to primates/humans than rodents. Tree shrews are superior to classical primates because tree shrew are easier to manipulate, maintain and propagate. It is required to establish a high‐efficiency tree shrew breast cancer model for etiological research and drug assessment. Our previous studies suggest that 7,12‐dimethylbenz(a)anthracene (DMBA) and medroxyprogesterone acetate (MPA) induce breast tumors in tree shrews with a low frequency (<50%) and long latency (∼7‐month), making these methods less than ideal. We induced mammary tumors in tree shrew (Tupaia belangeri chinensis) by injection of lentivirus expressing the PyMT oncogene into mammary ducts of 22 animals. Most tree shrews developed mammary tumors with a latency of about three weeks, and by 7 weeks all injected tree shrews had developed mammary tumors. Among these, papillary carcinoma is the predominant tumor type. One case showed lymph node and lung metastasis. Interestingly, the expression levels of phosphorylated AKT, ERK and STAT3 were elevated in 41–68% of PyMT‐induced mammary tumors, but not all tumors. Finally, we observed that the growth of PyMT‐induced tree shrew mammary tumors was significantly inhibited by Cisplatin and Epidoxorubicin. PyMT‐induced tree shrew mammary tumor model may be suitable for further breast cancer research and drug development, due to its high efficiency and short latency.
An infection of human adenovirus 31 affects the differentiation of preadipocytes into fat cells, its metabolic profile and fat accumulation
Authors: Bil‐Lula Iwona , Krzywonos‐Zawadzka Anna , Sawicki Grzegorz , Woźniak Mieczysław
Published: August 2015

The primary issue undertaken in this study was to test the hypothesis that preadipocytes would have intrinsically elevated propensity to differentiate into mature adipocytes due to HAdV31 infection. To prove that, the metabolic and molecular mechanisms responsible for HAdV31‐induced adipogenesis were examined. 3T3L1 cells (mouse embryonic fibroblast, adipose like cell line) were used as a surrogate model to analyze an increased proliferation, differentiation, and maturation of preadipocytes infected with human adenovirus. An expression of E4orf1, C/EBP‐β, PPAR‐γ, GAPDH, aP2, LEP, and fatty acid synthase genes, intracellular lipid accumulation as well as cytokine release from the fat cells were assessed. Data showed that HAdV31 increased an expression of C/EBP‐β and PPAR‐γ genes leading to an enhanced differentiation of preadipocytes into fat cells. Besides, overexpression of GAPDH and fatty acid synthase, and decreased expression of leptin caused an increased accumulation of intracellular lipids. Secretion of TNF‐α and IL‐6 from HAdV31‐infected cells was strongly decreased, leading to unlimited virus replication. The results obtained from this study provided the evidences that HAdV31, likewise previously documented HAdV36, is a subsequent human adenovirus affecting the differentiation and lipid accumulation of 3T3L1 cells. J. Med. Virol. 88:400–407, 2016. © 2015 Wiley Periodicals, Inc.
Expression quantitative trait loci for TNFRSF10 influence both HBV infection and hepatocellular carcinoma development
Authors: Wen Juan , Song Ci , Liu Jibin , Chen Jianguo , Zhai Xiangjun , Hu Zhibin
Published: August 2015

Tumor necrosis factor receptor superfamily member 10 (TNFRSF10) is a death domain‐containing receptor for the apoptotic ligand TNFSF10, which involves multiple processes, including hepatocarcinogenesis and immune response against HBV infection. Several single nucleotide polymorphisms (SNPs) were identified as expression quantitative trait loci (eQTLs) for TNFRSF10. To assess the association of TNFRSF10 eQTL SNPs with the risk of hepatocellular carcinoma (HCC) and chronic HBV infection, we designed a case–control study that included 1,300 HBV‐related HCC patients, 1,344 chronic HBV carriers, and 1,344 subjects with HBV natural clearance, and then genotyped two TNFRSF10 eQTL SNPs (rs79037040 and rs2055822). We found that rs79037040 GT/TT genotypes were associated with a decreased HCC risk (adjusted odds ratio [OR] = 0.83, 95% confidence intervals [CIs] = 0.71–0.97, P = 0.021) but an increased chronic HBV infection risk of borderline significance (adjusted OR = 1.14, 95%CIs = 0.98–1.33, P = 0.085). In contrast, the rs2055822 G allele was a risk factor for HCC (adjusted OR = 1.12, 95%CIs = 1.00–1.25, P = 0.041) but a protective factor for chronic HBV infection (adjusted OR = 0.89, 95%CIs = 0.80–0.99, P = 0.038). Furthermore, we observed a dose‐dependent relationship between the number of alleles (rs79037040‐T and rs2055822‐A) and the risk of HCC and chronic HBV infection. In comparison with “0” alleles, having “1–4” alleles was significantly associated with decreased HCC risk and increased HBV infection risk. These findings suggest that eQTL SNPs for TNFRSF10 may be susceptibility markers for HCC and chronic HBV infection. J. Med. Virol. 88:474–480, 2016. © 2015 Wiley Periodicals, Inc.
Water retention properties of a sandy soil with superabsorbent polymers as affected by aging and water quality
Authors: Banedjschafie Schahram , Durner Wolfgang
Published: August 2015

Hydraulic properties, specifically the water holding capacity of soils, play a key role in the ability of soils to sustain plant growth. Additions of hydrophilic polymers (superabsorbents) can improve the water holding capacity of sandy soils. This has led to practical applications of these materials particularly in arid regions and countries, where water is the limiting factor for plant production. The objectives of this study are to investigate how effective hydraulic properties of polymer‐soil mixtures are affected by addition of absorbents in different concentrations. Novel aspects are the investigation of aging under repeated wetting–drying‐cycles over an appreciable time in the field and a systematic investigation of the salt influence on the water uptake of polymers. We added the polymer Super AB, A‐200 (Iran Polymer Institute), to dune sand in ratios of 0.3%, 0.6%, and 1% w/w. We found that the effective water retention characteristics of the soil–absorbent mixtures were improved with respect to plant‐available water compared to the pure sand, and the improvement was related to the respective amount of absorbent in the mixture. The plant available water content (PAW) increased from 0.005 for the untreated sand to 0.06, 0.20, and 0.28 g g−1, respectively, for the sand with the three polymer additions. Due to aging of the polymers, PAW decreased after 6 months of cyclic drying and wetting to about half of the value immediately after the initial treatment. We attribute this to the effect of salts. This is corroborated by the results from water uptake experiments by the pure polymers. Repeated cycles of water uptake showed that salts in the water greatly reduced the uptake capacity of the polymers after few cycles. The effect was strong for bivalent cations and less pronounced for monovalent cations.
Space use by white‐headed woodpeckers and selection for recent forest disturbances
Authors: Lorenz Teresa J. , Vierling Kerri T. , Kozma Jeffrey M. , Millard Janet E. , Raphael Martin G.
Published: August 2015

White‐headed woodpeckers (Picoides albolarvatus) are important cavity excavators that recently have become the focus of much research because of concerns over population declines. Past studies have focused on nest site selection and survival but information is needed on factors influencing their space use when away from the nest. We examined space use by white‐headed woodpeckers during the nesting (May–Jul) and post‐nesting (Jul–Oct) periods and compared the role of environmental factors (e.g., landcover) and socio‐demographic factors (e.g., age, breeding success) in home range size and selection of location. Average size of 99% kernel home ranges was 125 ha (SD ± 59 ha; n = 19) in the nesting period and 137 ha (SD ± 70 ha; n = 30) in the post‐nesting period. Minimum convex polygons were generally comparable to or smaller than ranges reported from previous radio‐telemetry studies with this species. Although bird weight and age best explained variation in home range size compared to other factors, neither parameter estimate was significant in our models. Thus, even though weight and age were the most‐supported factors in our analysis, home range size was largely influenced by factors that we did not measure. We found that most woodpeckers selected home ranges within forest patches that had undergone a recent disturbance; these areas included forests that had recently been burned with prescribed fire by the United States Forest Service (82%) or subject to disease (16%). Most burned patches in our study were small (approx. 4.8 ha) and occurred within otherwise live forest but had nearly complete mortality of adult trees. We suggest that recent forest disturbances, especially mixed‐severity prescribed burns, may have been selected by white‐headed woodpeckers because they created snags for nesting and future studies should explore this hypothesis. Because home range size was variable and not linked with productivity, it should not be used as an indication of habitat quality without more detailed studies on causal factors that affect space use in this species. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
A multisensor approach to improve manometric analysis of the upper esophageal sphincter
Authors: Jones Corinne A. , Ciucci Michelle R. , Hammer Michael J. , McCulloch Timothy M.
Published: August 2015

Objectives/Hypothesis

High‐resolution manometry (HRM) improves on previous manometric systems by including a greater number of sensors that are more densely placed. Due to deglutitive movement of the HRM catheter and upper esophageal sphincter (UES), it is unclear which HRM sensors capture pressure in the UES. To address this issue, we present two complementary studies to describe UES pressure patterns using HRM + videofluoroscopy and HRM + electromyography (EMG).

Study Design

Case series involving a new analysis method.

Methods

Study 1: Simultaneous HRM + videofluoroscopy were performed in 11 healthy subjects swallowing five 10‐mL thin‐liquid boluses. HRM catheter and UES movement were tracked to identify UES pressure patterns over multiple HRM sensors. Study 2: Simultaneous HRM + cricopharyngeal EMGs were performed in six healthy subjects swallowing five 10‐mL water boluses. HRM and EMG outputs were correlated over individual and multiple HRM sensors.

Results

HRM sensors move prior to UES movement (P < .001) and to a lesser extent in rostral and ventral directions (P ≤ .01) than the UES. UES closure pressure is captured with two distinct patterns: 1) a rostral UES pattern with short durations and fast rate of pressure release, depicting UES descent along the catheter as it closes; and 2) a caudal UES pattern with tonic pressures at baseline and a deglutitive nadir. The HRM + EMG multisensor correlation (r = 0.88) was significantly stronger than the single‐sensor correlation (r = 0.80; P = .02).

Conclusions

During deglutition, the HRM catheter and the UES rise above baseline positions and create a distinctive, multisensor manometric trace. Accurate deglutitive UES pressure evaluation must include multiple manometric sensors.

Level of Evidence

4 Laryngoscope, 126:657–664, 2016
Squamous cell carcinoma of the nasal cavity: A population‐based analysis
Authors: Unsal Aykut A. , Dubal Pariket M. , Patel Tapan D. , Vazquez Alejandro , Baredes Soly , Liu James K. , Eloy Jean Anderson
Published: August 2015

Objectives/Hypothesis

Squamous cell carcinoma of the nasal cavity (NCSCC) is an infrequent malignancy that has been historically difficult to characterize. This study provides new insight into NCSCC utilizing a population‐based database. We analyze the propensity for cervical and distant metastasis from NCSCC, as well as survival outcomes.

Study Design

Retrospective database analysis.

Methods

The Surveillance, Epidemiology, and End Results (SEER) database (2004–2012) was queried for NCSCC cases. Data were analyzed with respect to various demographic and clinicopathologic factors. The results were further examined for regional and distant metastasis. Survival was analyzed using the Kaplan‐Meier model.

Results

A total of 1,180 cases of NCSCC were identified in the SEER database between 2004 and 2012. The mean age at diagnosis was 65.8 years. American Joint Committee on Cancer stage was known in 1,050 cases, of which 53.4% were stage I, 13.3% were stage II, 10.2% were stage III, and 23.0% were stage IV. By tumor (T) stage classification, T1 was the most common (56.6%), followed by T4 (19.3%). Most cases had no nodal (N) involvement at diagnosis (90.8%). Cervical nodal involvement was present in 9.1% of cases, while distant metastasis was seen in 1.9%. Five‐year disease‐specific survival was 69.5% overall, 39.6% in cases with neck involvement and 0.0% for metastatic cases.

Conclusions

This study represents the only known population‐based investigation of NCSCC. Metastasis to cervical nodes or distant sites, especially with T1 tumors, is rare. However, any cervical involvement or distant metastasis discovered on presentation is a poor prognostic indicator.

Level of Evidence

4. Laryngoscope, 126:560–565, 2016
Endoscopic surgery of the orbital apex: Outcomes and emerging techniques
Authors: Stokken Janalee , Gumber Divya , Antisdel Jastin , Sindwani Raj
Published: August 2015

Objectives/Hypothesis

To review our experience with endoscopic orbital apex surgery.

Study Design

Retrospective review.

Methods

All cases with Current Procedural Terminology codes for endoscopic orbital decompression between 2002 and 2011 at two institutions were reviewed. Patients with a diagnosis of Graves orbitopathy or an orbital complication of sinusitis were excluded. Presenting symptoms, lesion location, pathology, surgical outcomes, and complications were examined.

Results

A total of 27 patients were identified. Seventeen (63%) of the patients were men, and the average age was 56 (range = 14–82) years. Eighteen patients had primary orbital apex lesions, and nine patients had sinonasal lesions that predominantly involved the medial orbital apex. The lesions were found to be on the right in 59% of cases. The etiologies include benign (40.7%), malignant (44%), infectious (7.4%), and metastatic (7.4%) lesions. Obtaining a pathologic diagnosis was successful endoscopically in all but two (7.4%) patients, both with lateral lesions. The two‐surgeon, four‐handed technique and intraoperative image guidance employing fused computed tomography/magnetic resonance imaging were used in the majority of intraconal cases. Complications occurred in three patients (11%) and included myocardial infarction, deep venous thrombosis, and vision loss. There were no cerebrospinal fluid leaks or postoperative hemorrhages. Notably, vision remained stable or improved in all but one patient (3.7% risk of vision decline). Average follow‐up was 4 years (range = 1 month–8 years).

Conclusions

The endoscopic approach to the orbit apex offers significant advantages over traditional external approaches, and should be the preferred approach for all medial and inferior lesions. A two‐surgeon multihanded technique can help facilitate difficult cases.

Level of Evidence

4. Laryngoscope, 126:20–24, 2016
Otolaryngological manifestations of Measles (Rubeola): A case report and brief review
Authors: Bhatt Jay M. , Huoh Kevin C.
Published: August 2015

Measles is an acute viral respiratory illness caused by a virus of the Paramyxoviridae family. Despite being eliminated from the United States, small outbreaks across the country continue to occur. The United States experienced a record number of cases in 2014, with 668 cases seen across the country, a record since its elimination in 2000. Here, we present a case of an acute presentation of measles illness and discuss the otolaryngologic manifestation of the disease. Laryngoscope, 126:1481–1483, 2016
Oxidation‐Responsive Polymer–Drug Conjugates with a Phenylboronic Ester Linker
Authors: Qiu Fang‐Yi , Zhang Mei , Ji Ran , Du Fu‐Sheng , Li Zi‐Chen
Published: August 2015

Polymer–drug conjugates have attracted great interest as one category of various promising nanomedicines due to the advantages of high drug‐loading capacity, negligible burst release, and improved pharmacokinetics as compared with the small molecular weight drugs or the polymeric delivery systems with physically encapsulated drugs. Herein, a new type of oxidation‐responsive polymer–drug conjugates composed of a poly(ethylene glycol) (PEG) block and a hydrophobic polyacrylate block to which Naproxen is attached through a phenylboronic ester linker is reported. The amphiphilic block copolymers are synthesized through the reversible addition–fragmentation chain transfer polymerization of the Naproxen‐containing acrylic monomer using a PEG chain transfer agent. In neutral aqueous buffer, the conjugates formed nanoparticles with diameters of ≈150–300 nm depending on the length of the hydrophobic segment. The dynamic covalent bond of the phenylboronic ester is stabilized due to the hydrophobic microenvironment inside the nanoparticles. Upon exposure to H2O2, the phenylboronic ester is oxidized rapidly into the phenol derivative which underwent a 1,6‐elimination reaction, releasing the intact Naproxen. The rate of drug release is influenced by the concentration of H2O2 and the hydrophobic block length. This type of oxidation‐responsive polymer–drug conjugate is feasible for other drugs containing hydroxyl group or amino group.

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Preparation of Polyamide‐6 Submicrometer‐Sized Spheres by In Situ Polymerization
Authors: Zhao Xingke , Xia Housheng , Fu Xubing , Duan Jianping , Yang Guisheng
Published: August 2015

Polyamide‐6 (PA6) submicron‐sized spheres are prepared by two steps: (1) anionic ring‐opening polymerization of ε‐caprolactam in the presence of poly(ethylene glycol)‐block‐poly‐(propylene glycol)‐block‐poly(ethylene glycol)(PEG‐b‐PPG‐b‐PEG) and (2) separation of PA6 spheres by dissolving PEG‐b‐PPG‐b‐PEG from the prepared blends. The PA6 microspheres obtained are regular spherical, with diameter ranging from 200 nm to 2 μm and narrow size distribution, as confirmed by scanning electron microscopy. By comparison with PA6/PS and PA6/PEG systems, it is denominated that the PEG blocks in PEG‐b‐PPG‐b‐PEG can effectively reduce the surface tension of PA6 droplets and further decrease the diameter of the PA6 microspheres. The PPG block in PEG‐b‐PPG‐b‐PEG can prevent the PA6 droplets coalescing with each other, and isolated spherical particles can be obtained finally. The phase inversion of the PA6/PEG‐b‐PPG‐b‐PEG blends occurs at very low PEG‐b‐PPG‐b‐PEG content; the PEG‐b‐PPG‐b‐PEG phase can be removed by water easily. The whole experiment can be finished in a short time (approximately in half an hour) without using any organic solvents; it is an efficient strategy for the preparation of submicron‐sized PA6 microspheres.

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Induction of Secondary Structure through Micellization of an Oppositely Charged Pair of Homochiral Block‐ and Homopolypeptides in an Aqueous Medium
Authors: Mutaf Omer F. , Kishimura Akihiro , Mochida Yuki , Kim Ahram , Kataoka Kazunori
Published: August 2015

Polyion complex (PIC) formation is an attractive method for obtaining molecular assemblies owing to their facile fabrication process in aqueous media, but more insights are required in order to control the higher‐dimensional structures of polypeptide‐based PICs. Herein, the PIC formation behavior of oppositely charged homochiral polypeptides, poly‐l‐lysine and poly(ethylene glycol)‐b‐poly(l‐glutamate) (PEG‐PLG), and their secondary structures are carefully studied in water. PIC formation takes place in a polymer concentration‐dependent manner, and clear β‐sheet formation is observed at polymer concentrations ≥0.3 mg mL−1. The results also confirm that multimolecular aggregation is a prerequisite for β‐sheet formation, which indicates that the inner hydrophobic environment of PICs is favorable for β‐sheet formation. Furthermore, the PEG weight fraction, stereoregularity of the polypeptide, and ionic strength of the solutions are found to be key factors for generating a secondary structure, presumably because these factors can contribute to the tuning of the inner environment of PICs. This method of producing water‐soluble nanoassemblies from oppositely charged polypeptides may expedite self‐assembly studies in biological systems and be incorporated into various molecular systems to exploit protein‐mimicking features.

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Mitsunobu Reaction: A Versatile Tool for PEG End Functionalization
Authors: d'Arcy Richard , Tirelli Nicola
Published: August 2015

The Mitsunobu reaction can be efficiently used for the transformation of poly(ethylene glycol) (PEG) terminal OH group(s) into a variety of functions. In comparison to more classical approaches of PEG functionalization, the main advantage of the Mitsunobu reaction attains to the fact that in one step, with no detrimental effect on PEG integrity (e.g., chain cleavage). Here, its quantitative conversion is demonstrated into derivatives that, either directly or after deprotection, are amenable to (bio)conjugation reactions: azides (Huisgen cycloaddition), aldehydes, primary amines (Schiff base formation and reduction), thiols, and N‐oxymaleimide (Michael‐type addition). Therefore this reaction is proposed as a general tool for the preparation of functionalities for the purpose of PEGylation, and more generally for (bio)conjugation purposes.

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Advances in the treatment of cognitive impairment inParkinson's disease
Authors: Goldman Jennifer G. , Weintraub Daniel
Published: August 2015

Cognitive impairment in Parkinson's disease (PD) is a frequent complication, with significant interindividual variability in clinical symptoms, severity, timing, and neural substrates. Recent studies have focused not only on understanding PD dementia, but also mild cognitive impairment in PD, which may represent a prodromal stage for dementia. In recent years, there have been important advances regarding clinical characterizations, definitions, associated biomarkers, and risk factors for both mild cognitive impairment in PD and PD dementia. However, there is a paucity of effective therapies for cognitive impairment in PD, whether for mild symptoms or for moderate to severe dementia. At present, only rivastigmine is U.S. Food and Drug Administration approved for PD dementia, an indication received nearly a decade ago. Given the frequency of PD cognitive impairment and its substantial impact on both patients and families, the lack of available and effective treatments represents a striking gap in the field, especially when compared to the large number of available therapies for PD motor symptoms and complications. Improved symptomatic therapies, as well as potential disease‐modifying agents, for PD cognitive impairment are needed. Most therapeutic trials for PD dementia and mild cognitive impairment in PD have focused on drugs developed for and tested in Alzheimer's disease, such as cholinesterase inhibitors and the N‐methyl‐D‐aspartate receptor antagonist, memantine, though recent and ongoing trials examine the effects of pharmacological agents affecting other neurotransmitters, as well as nonpharmacological therapies, including mental and physical exercise and neurostimulation. This review summarizes the design and outcomes of trials for PD cognitive impairment published since 2013 and highlights future therapeutic research opportunities and challenges. © 2015 International Parkinson and Movement Disorder Society
The gga‐let‐7 family post‐transcriptionally regulates TGFBR1 and LIN28B during the differentiation process in early chick development
Authors: Lee Sang In , Jeon Mi‐hyang , Kim Jeom Sun , Jeon Ik‐Soo , Byun Sung June
Published: August 2015

Early chick embryogenesis is governed by a complex mechanism involving transcriptional and post‐transcriptional regulation, although how post‐transcriptional processes influence the balance between pluripotency and differentiation during early chick development have not been previously investigated. Here, we characterized the microRNA (miRNA) signature associated with differentiation in the chick embryo, and found that as expression of the gga‐let‐7 family increases through early development, expression of their direct targets, TGFBR1 and LIN28B, decreases; indeed, gga‐let‐7a‐5p and gga‐let‐7b miRNAs directly bind to TGFBR1 and LIN28B transcripts. Our data further indicate that TGFBR1 and LIN28B maintain pluripotency by regulating POUV, NANOG, and CRIPTO. Therefore, gga‐let‐7 miRNAs act as post‐transcriptional regulators of differentiation in blastodermal cells by repressing the expression of the TGFBR1 and LIN28B, which intrinsically controls blastodermal cell differentiation in early chick development. Mol. Reprod. Dev. 82: 967–975, 2015. © 2015 Wiley Periodicals, Inc.
Correcting heat‐induced chemical shift distortions in proton resonance frequency‐shift thermometry
Authors: Gaur Pooja , Partanen Ari , Werner Beat , Ghanouni Pejman , Bitton Rachelle , Butts Pauly Kim , Grissom William A
Published: August 2015

Purpose

To reconstruct proton resonance frequency‐shift temperature maps free of chemical shift distortions.

Theory and Methods

Tissue heating created by thermal therapies such as focused ultrasound surgery results in a change in proton resonance frequency that causes geometric distortions in the image and calculated temperature maps, in the same manner as other chemical shift and off‐resonance distortions if left uncorrected. We propose an online‐compatible algorithm to correct these distortions in 2DFT and echo‐planar imaging acquisitions, which is based on a k‐space signal model that accounts for proton resonance frequency change‐induced phase shifts both up to and during the readout. The method was evaluated with simulations, gel phantoms, and in vivo temperature maps from brain, soft tissue tumor, and uterine fibroid focused ultrasound surgery treatments.

Results

Without chemical shift correction, peak temperature and thermal dose measurements were spatially offset by approximately 1 mm in vivo. Spatial shifts increased as readout bandwidth decreased, as shown by up to 4‐fold greater temperature hot spot asymmetry in uncorrected temperature maps. In most cases, the computation times to correct maps at peak heat were less than 10 ms, without parallelization.

Conclusion

Heat‐induced proton resonance frequency changes create chemical shift distortions in temperature maps resulting from MR‐guided focused ultrasound surgery ablations, but the distortions can be corrected using an online‐compatible algorithm. Magn Reson Med 76:172–182, 2016. © 2015 Wiley Periodicals, Inc.
A randomized trial of diagnostic ultrasound to improve outcomes in focal neuropathies
Authors: Cartwright Michael S. , Griffin Leah P. , Dowlen Hugh , Bargoil Jessica M. , Caress James B. , Li Zhongyu J. , Defranzo Anthony J. , Wiesler Ethan R. , Tuohy Christopher J. , Balakrishnan Nikhil , Molnar Joseph A. , Baute Vanessa , Koman L. Andrew , Poehling Gary G. , Walker Francis O.
Published: August 2015

Introduction: Neuromuscular ultrasound is valid, reliable, and accurate, but it is not known whether combining it with electrodiagnostic studies leads to better outcomes in individuals with focal neuropathies. Methods: One hundred twenty individuals with focal neuropathy, based on history, examination, and electrodiagnosis, were enrolled in this study. All patients underwent neuromuscular ultrasound and were randomized to either have their ultrasound results sent to the referring physician or not have them sent. Outcomes were assessed at 6 months by evaluators blinded to group assignment. Results: The Overall Disability Sum Score and 7 of 8 domains of the Medical Outcomes Study 36‐item Short‐Form Health Survey (SF‐36) showed more improvement in the “report sent” group, although only the general health perception domain was significant (P = 0.005). Conclusions: Most 6‐month outcomes did not reach statistical significance between the 2 groups. However, the “report sent” group had trends toward better outcomes, with significance being reached in the general health perception domain of the SF‐36. Muscle Nerve 52: 746–753, 2015
Atherosclerosis as a predictor of delayed recovery from lower urinary tract dysfunction after robot‐assisted laparoscopic radical prostatectomy
Authors: Yabe Michihiro , Haga Nobuhiro , Ogawa Soichiro , Kataoka Masao , Akaihata Hidenori , Sato Yuichi , Hata Junya , Ishibashi Kei , Kojima Yoshiyuki
Published: August 2015

Aims

The aim of the present study was to investigate whether atherosclerosis could be associated with lower urinary tract dysfunction in the early postoperative period after robot‐assisted laparoscopic radical prostatectomy (RARP).

Methods

Eighty consecutive patients undergoing RARP were investigated. The severity of atherosclerosis was evaluated by the cardio‐ankle vascular index (CAVI) before RARP. Patients were divided into two groups, the atherosclerotic group (CAVI ≥9.0) and the control group (CAVI <9.0). International Prostate Symptom Score (IPSS), quality of life (QOL) index, uroflowmetry, post‐void residual urine volume (PVR), frequency–volume charts, and the 1‐hr pad test were compared between the two groups. Assessments were performed before RARP, and then at 1, 3, and 6 months after RARP.

Results

Preoperative subjective and objective parameters were not significantly different between the two groups. The voiding symptom score of the IPSS and the QOL index was significantly higher in the atherosclerotic group at 3 months after RARP (P = 0.035, P = 0.001, respectively). The maximum flow rate was consistently lower in the atherosclerotic group, reaching a significant difference at 6 months after RARP (P = 0.027). IPSS total and storage symptom scores, PVR, frequency, and urine loss were not significantly different between the groups after RARP.

Conclusions

Atherosclerosis delayed the improvement of both voiding symptoms and voiding function after RARP, leading to aggravation of QOL in the early postoperative period. Atherosclerosis may be a predictor of slower recovery from transient lower urinary tract dysfunction immediately after RARP. Neurourol. Urodynam. 35:920–925, 2016. © 2015 Wiley Periodicals, Inc.
The prevalence of fecal incontinence and associated risk factors in older adults participating in the SABE study
Authors: Tamanini José Tadeu Nunes , de Jesus Felipe Alves , Castro Rodrigo Aquino , Ferreira Sartori Marair Gracio , Castello Girão Manoel João Batista , dos Santos Jair Lício Ferreita , de Oliveira Duarte Yeda Aparecida , Lebrão Maria Lúcia
Published: August 2015

Aims

To assess the prevalence of fecal incontinence (FI) and associated factors in older adults.

Methods

The prevalence and factors associated with FI in older adults were studied by means the SABE study (Health, Well‐being, and Aging). A group of 1,345 subjects were interviewed during the third wave of the SABE study performed in Sao Paulo, in 2010. The study included 64.3% females; the mean age of the participants was 70.4 years. The dependent variable was the positive answer for the question “In the last 12 months, have you ever lost control of bowel movements or stools?”. Descriptive analysis and hierarchical logistic regression were performed. The independent variables were as follows: (a) demographics: gender, age and (b) clinical characteristics: self‐reported chronic diseases, presence of cognitive and/or functional decline, depression and urinary incontinence symptoms, and nutritional status.

Results

The overall prevalence of FI was 11,7%, being 8.3% and 13.2% for males and females respectively. Among male subjects, the presence of malnutrition was associated with FI and thus presented a high relative risk index for its occurrence. Among female subjects, age group 70–74 years and some self‐reported diseases or conditions such as mild depression, heart disease, urinary incontinence, and polypharmacy were associated with FI. For the first time in literature, polypharmacy appeared as an associated factor for FI for female older adults.

Conclusions

The prevalence of FI in older adults was 11.7% and was mainly associated with advanced age and presence of heart disease, symptoms of depression, polypharmacy and urinary incontinence and malnutrition. Neurourol. Urodynam. 35:959–964, 2016. © 2015 Wiley Periodicals, Inc.
Balancing the energy equation for healthy kidneys
Authors: Mount Peter F , Power David A
Published: August 2015

The high‐energy requirement of the kidney and the importance of energy metabolism in renal physiology has been appreciated for decades, but only recently has there emerged a strong link between impaired renal energy metabolism and chronic kidney disease (CKD). The mechanisms underlying the association between changes in energy metabolism and progression of CKD, however, remain poorly understood. A new study from Qiu and colleagues reported in the Journal of Pathology has advanced this understanding by showing that, after renal injury, the energy sensor AMPK inhibits epithelial–mesenchymal transition and inflammation, processes important in the pathogenesis of CKD. Furthermore, this study identifies an interaction between AMPK and CK2β as an important mechanism in the anti‐fibrotic effect. CK2β has previously been shown to interact with STK11 (also known as LKB1) to regulate cellular polarity. These findings are consistent with the known roles of the LKB1–AMPK pathway in sustaining cellular energy homeostasis and epithelial cell polarity, and add to growing evidence linking the suppression of energy metabolism to CKD. They emphasize the importance of energy metabolism in general and the LKB1–AMPK axis in particular as key investigational and therapeutic targets in the battle against CKD. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Antiretroviral Pharmacokinetics in Pregnant Women
Authors: Gilbert Elise M. , Darin Kristin M. , Scarsi Kimberly K. , McLaughlin Milena M.
Published: August 2015

For women infected with the human immunodeficiency virus (HIV) who become pregnant, the use of combination antiretroviral therapy (ART) significantly reduces transmission ofHIVfrom mother to child. Selection of an appropriateARTregimen for use among pregnant women requires consideration of numerous factors including maternal and fetal safety, antiretroviral pharmacokinetics, and regimen efficacy. Optimization of antiretroviral pharmacokinetics during pregnancy requires special consideration because pregnancy‐associated changes in drug absorption, distribution, metabolism, and excretion are known to occur throughout pregnancy and postpartum. Understanding antiretroviral placental transfer may offer additional insight into each drug's potential role in preventingHIVtransmission in utero and may also have implications regarding viral resistance in cases where transmission does occur. In this review, we summarize key published data describing antiretroviral pharmacokinetics in pregnant women, providing suggestions for clinical application of these data where appropriate.
Sulfonated dendrimer‐ and hyperbranched polyglycerol‐PBIOO® blend membranes for fuel cells
Authors: Martín‐Zarco Manuela , Titvinidze Giorgi , García‐Martínez Joaquín C. , Rodríguez‐López Julián
Published: August 2015

A new sulfonated dendrimer with an arylene ether sulfone backbone has been synthesized, fully characterized, and blended with PBIOO® to prepare acid‐base proton‐conducting membranes under different conditions and with different composition ratios. Water‐soluble sulfonated hyperbranched polyglycerols of different molecular weights were also used as the acidic components. Membrane properties such as ion‐exchange capacity, water uptake, thermal stability, proton conductivity, and morphology have been studied and discussed. The nature of the acidic component and the morphology of the membranes had a marked influence on the final properties. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 69–80
Synthesis and photovoltaic properties of 2,6‐bis(2‐thienyl) benzobisazole and 4,8‐bis(thienyl)‐benzo[1,2‐B:4,5‐B′]dithiophene copolymers
Authors: Bhuwalka Achala , Ewan Monique D. , Elshobaki Moneim , Mike Jared F. , Tlach Brian , Chaudhary Sumit , Jeffries‐EL Malika
Published: August 2015

In an effort to design efficient low‐cost polymers for use in organic photovoltaic cells the easily prepared donor–acceptor–donor triad of a either cis‐benzobisoxazole, trans‐benzobisoxazole or trans‐benzobisthiazole flanked by two thiophene rings was combined with the electron‐rich 4,8‐bis(5‐(2‐ethylhexyl)‐thien‐2‐yl)‐benzo[1,2‐b:4,5‐b′]dithiophene. The electrochemical, optical, morphological, charge transport, and photovoltaic properties of the resulting terpolymers were investigated. Although the polymers differed in the arrangement and/or nature of the chalcogens, they all had similar highest occupied molecular orbital energy levels (−5.2 to −5.3 eV) and optical band gaps (2.1–2.2 eV). However, the lowest unoccupied molecular orbital energy levels ranged from −3.1 to −3.5 eV. When the polymers were used as electron donors in bulk heterojunction photovoltaic devices with PC71BM ([6,6]‐phenyl C71‐butyric acid methyl ester) as the acceptor, the trans‐benzobisoxazole polymer had the best performance with a power conversion efficiency of 2.8%. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 316–324
Combustion of Aluminum Particles near the Burning Surface in AP/AN Composite Propellants
Authors: Doi Rieko , Kuwahara Takuo
Published: August 2015

Aluminum (Al) particles are commonly used in ammonium perchlorate (AP) composite propellants of solid rockets for increasing performance. When propellants including Al particles burn, Al particles easily agglomerate on the burning surface of the propellant. The diameters of agglomerated Al particles are greater than those of mixed particles. The combustion efficiency of the propellant decreases with increasing burning time of the agglomerated Al particles. Therefore, it is important to observe how the agglomerated Al particles burn on the burning surface of AP composite propellant. A lot of researchers have studied Al agglomerate characteristics. Previous studies clarified the relation between the agglomerated Al particle diameter and luminous flame diameter around Al particles near the burning surface. The shapes of luminous flames around agglomerated Al particles are spherical or elliptical. This study evaluates the shapes of the luminous flame around agglomerated Al particles at a constant diameter or a different diameter. When the proportion of the luminous flame diameter (Df) to the diameter of agglomerated Al particles (D0) is 1.54–1.71 at a constant D0, the luminous flames are almost perfectly spherical. Otherwise, the luminous flames are elliptical at a constant D0. Furthermore, when Df/D0 is close to the mean value, the luminous flame is more spherical than elliptical at different D0. The evaporation rate and the burning rate of Al vapor are inversely proportional to D0. The oxidation gas temperatures were changed and the activation energy of Al vapor was obtained as 39.2 kJ mol−1.
Structure of HIV‐1 reverse transcriptase bound to a novel 38‐mer hairpin template‐primer DNA aptamer
Authors: Miller Matthew T. , Tuske Steve , Das Kalyan , DeStefano Jeffrey J. , Arnold Eddy
Published: August 2015

The development of a modified DNA aptamer that binds HIV‐1 reverse transcriptase (RT) with ultra‐high affinity has enabled the X‐ray structure determination of an HIV‐1 RT‐DNA complex to 2.3 Å resolution without the need for an antibody Fab fragment or RT‐DNA cross‐linking. The 38‐mer hairpin‐DNA aptamer has a 15 base‐pair duplex, a three‐deoxythymidine hairpin loop, and a five‐nucleotide 5′‐overhang. The aptamer binds RT in a template‐primer configuration with the 3′‐end positioned at the polymerase active site and has 2′‐O‐methyl modifications at the second and fourth duplex template nucleotides that interact with the p66 fingers and palm subdomains. This structure represents the highest resolution RT‐nucleic acid structure to date. The RT‐aptamer complex is catalytically active and can serve as a platform for studying fundamental RT mechanisms and for development of anti‐HIV inhibitors through fragment screening and other approaches. Additionally, the structure allows for a detailed look at a unique aptamer design and provides the molecular basis for its remarkably high affinity for RT.
Dynamics and thermodynamic properties of CXCL7 chemokine
Authors: Herring Charles A. , Singer Christopher M. , Ermakova Elena A. , Khairutdinov Bulat I. , Zuev Yuriy F. , Jacobs Donald J. , Nesmelova Irina V.
Published: August 2015

Chemokines form a family of signaling proteins mainly responsible for directing the traffic of leukocytes, where their biological activity can be modulated by their oligomerization state. We characterize the dynamics and thermodynamic stability of monomer and homodimer structures of CXCL7, one of the most abundant platelet chemokines, using experimental methods that include circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy, and computational methods that include the anisotropic network model (ANM), molecular dynamics (MD) simulations and the distance constraint model (DCM). A consistent picture emerges for the effects of dimerization and Cys5‐Cys31 and Cys7‐Cys47 disulfide bonds formation. The presence of disulfide bonds is not critical for maintaining structural stability in the monomer or dimer, but the monomer is destabilized more than the dimer upon removal of disulfide bonds. Disulfide bonds play a key role in shaping the characteristics of native state dynamics. The combined analysis shows that upon dimerization flexibly correlated motions are induced between the 30s and 50s loop within each monomer and across the dimer interface. Interestingly, the greatest gain in flexibility upon dimerization occurs when both disulfide bonds are present, and the homodimer is least stable relative to its two monomers. These results suggest that the highly conserved disulfide bonds in chemokines facilitate a structural mechanism that is tuned to optimally distinguish functional characteristics between monomer and dimer. Proteins 2015; 83:1987–2007. © 2015 Wiley Periodicals, Inc.
Detection of the F129L mutation in the cytochrome b gene in Phakopsora pachyrhizi
Authors: Klosowski Ana C , May De Mio Louise L , Miessner Simone , Rodrigues Ronaldo , Stammler Gerd
Published: August 2015

BACKGROUND

Asian soybean rust, caused by Phakopsora pachyrhizi, is mostly controlled by demethylation inhibitor (DMI) and quinone outside inhibitor (QoI) fungicides. Mutations in the cytochrome b (CYTB) gene can lead to pathogen resistance to QoIs. The occurrence of the mutations in codons 129, 137 and 143 in the CYTB gene was investigated, and a pyrosequencing assay was developed for rapid and quantitative detection of the F129L mutation.

RESULTS

Molecular analysis of the CYTB gene showed the presence of the F129L mutation in field samples and monouredinial isolates, while other mutations (G143A and G137R) were not found. The pyrosequencing was an effective method for quantitative detection of the F129L mutation, and many of the P. pachyrhizi samples showed high frequency of F129L.

CONCLUSION

This is the first report of the occurrence of the F129L mutation in P. pachyrhizi. The practical relevance of this mutation for field efficacy of QoIs needs further investigation. © 2015 Society of Chemical Industry