bluuebunny/crossref_metadata_2025 huggingface dataset:
Concurrent chemoradiotherapy compared with surgery and adjuvant radiotherapy for oral cavity squamous cell carcinoma
Authors: Gore Sinclair M. , Crombie Anthony K. , Batstone Martin D. , Clark Jonathan R.
Published: February 2014

Background

The purpose of this study was to compare survival and functional outcomes in patients with advanced oral cavity squamous cell carcinoma (SCC) treated with either surgery + adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CRT).

Methods

Patients treated with curative intent by either surgery + RT or concurrent CRT were identified over a 6‐year period (2001–2007). Disease and functional outcomes were analyzed on an intention‐to‐treat basis.

Results

Fifty‐four patients underwent surgical excision and received postoperative RT. Fifty patients underwent concurrent CRT. Overall survival (OS) and disease‐specific survival (DSS) was significantly higher in the surgically treated group (p < .001). Long‐term enteral feeding tube support was more commonly required in those treated with CRT, whereas osteoradionecrosis rates were comparable between the 2 groups.

Conclusion

Treatment by surgery + adjuvant RT for advanced oral cavity SCC resulted in better disease control than treatment with CRT. This supports traditional surgical treatment algorithms for oral cavity cancer. © 2014 Wiley Periodicals, Inc. Head Neck 37: 518–523, 2015
Activin A immunoexpression as predictor of occult lymph node metastasis and overall survival in oral tongue squamous cell carcinoma
Authors: Kelner Natalie , Rodrigues Priscila Campioni , Bufalino Andreia , Fonseca Felipe Paiva , dos Santos‐Silva Alan Roger , Miguel Marcia Cristina Costa , Pinto Clóvis Antonio Lopes , Leme Adriana Franco Paes , Graner Edgard , Salo Tuula , Kowalski Luiz Paulo , Coletta Ricardo D.
Published: February 2014

Background

The presence of regional lymph node metastasis has an important impact on clinical management and prognostication of patients with oral tongue squamous cell carcinoma (SCC). Approximately 30% to 50% of patients with oral tongue SCC have regional metastasis at diagnosis, but the limited sensibility of the current diagnostic methods used for neck staging does not allow detection of all cases, leaving a significant number of undiagnosed metastasis (occult lymph node metastasis). In this study, we evaluated whether clinicopathologic features and immunohistochemical detection of carcinoma‐associated fibroblasts (CAFs) and activin A could be predictive markers for occult lymph node metastasis in oral tongue SCC.

Methods

One hundred ten patients with primary oral tongue SCC, who were classified with early stage tumor (stage I and II) and received surgical treatment with elective neck dissection, were enrolled in the study.

Results

Among all examined features, only high immunohistochemical expression of activin A was significantly associated with presence of occult lymph node metastasis (p = .006). Multivariate survival analysis using the Cox proportional hazard model showed that the expression of activin A was an independent marker of reduced overall survival with a 5‐year survival of 89.7% for patients with low expression compared to 76.5% for those with high expression (hazard ratio [HR], 2.44; 95% confidence interval [CI], 1.55–3.85; p = .012).

Conclusion

Our results demonstrated that immunodetection of activin A can be useful for prognostication of oral tongue SCC, revealing patients with occult lymph node metastasis and lower overall survival. © 2014 Wiley Periodicals, Inc. Head Neck 37: 479–486, 2015
Surgical treatment for recurrent solitary fibrous tumor invading atlas
Authors: Tsutsumi Nao , Kojima Yasutaka , Nishida Kotaro , Maeno Koichiro , Kakutani Kenichiro , Kawakami Fumi , Kanzawa Maki , Itoh Tomoo , Otsuki Naoki , Nibu Ken‐ichi
Published: February 2014

Background

Solitary fibrous tumor (SFT), a rare neoplasm, usually originates in the pleura. Extrapleural SFTs occasionally occur in the head and neck.

Methods

In this study, the extirpation of a rare case of recurrent SFT invading the atlas is discussed.

Results

Ten years after surgical resection of an SFT in the right parapharyngeal space, the patient returned with a complaint of swelling sensation in the right neck. MRI and CT showed an enhanced lobulated mass invading the right lateral C1 vertebral body and canal and encasing the right vertebral artery. Extirpation of the recurrent tumor with a combined transcervical and midline posterior approach was successful. The surgical margin was negative for cancer and the postoperative course was uneventful.

Conclusion

Although an SFT is generally benign, recurrence can occur even after several years, therefore, careful long‐term follow‐up is essential for early detection. A combined transcervical and midline posterior approach proved useful for resection of the atlas body. © 2014 Wiley Periodicals, Inc. Head Neck 36: E121–E124, 2014
Pilot study: Raman spectroscopy in differentiating premalignant and malignant oral lesions from normal mucosa and benign lesions in humans
Authors: Guze Kevin , Pawluk Hanna C. , Short Michael , Zeng Haishan , Lorch Jochen , Norris Charles , Sonis Stephen
Published: February 2014

Background

Current practice for differentiating tissue lesions are based on histopathological criteria. This process is subject to error. The purpose of this study was to test whether an alternative, tissue‐based molecular signatures Raman spectra could be used to differentiate premalignant and malignant lesions from normal mucosa or benign lesions.

Methods

Eighteen treatment naive subjects with histologically diagnosed oral disease were studied by comparing the Raman spectra of lesions with contralateral healthy sites. Principle component and multivariate analysis were used to predict which of the tissue groups the average spectrum of each lesion or normal tissue belonged.

Results

The average spectra were clearly different between premalignant and malignant lesions and those derived from normal, benign tissues. Premalignant and malignant lesions could be predicted with 100% sensitivity and 77% specificity.

Conclusion

Raman spectroscopy (RS) offers the potential to provide point of care diagnosis of oral disease using a noninvasive, convenient, and relatively inexpensive technology. © 2014 Wiley Periodicals, Inc. Head Neck, 2014 © 2014 Wiley Periodicals, Inc. Head Neck 37: 511–517, 2015
Potential Impacts of the Affordable Care Act on the Clinical Practice of Hepatology
Authors: Talwalkar Jayant A.
Published: February 2014

The Patient Protection and Affordable Care Act (ACA), along with the Health Care and Education Reconciliation Act, was signed into law and upheld by the Supreme Court earlier this year. The ACA contains a variety of reforms that, if implemented, will significantly affect current models of healthcare delivery for patients with acute and chronic hepatobiliary diseases. One of the Act's central reforms is the creation of accountable care organizations (ACOs) whose mission will be to integrate different levels of care to improve the quality of services delivered and outcomes among populations while maintaining, or preferably reducing, the overall costs of care. Currently, there are clinical practice areas within hepatology, such as liver transplantation, that already have many of the desired features attributed to ACOs. The ACA is sure to affect all fields of medicine, including the practice of clinical hepatology. This article describes the components of the ACA that have the greatest potential to influence the clinical practice of hepatology.

Conclusion:

Ultimately, it will be the responsibility of our profession to identify optimal healthcare delivery models for providing high-value, patient-centered care. (Hepatology 2014;59:1681–1687)
Cognitive effects of pregabalin in the treatment of long‐term benzodiazepine‐use and dependence
Authors: Oulis Panagiotis , Kalogerakou Stamatina , Anyfandi Eleni , Konstantakopoulos George , Papakosta Vassiliki‐Maria , Masdrakis Vasilios , Tsaltas Eleftheria
Published: February 2014

Objective

Long‐term benzodiazepine (BDZ) use and dependence affect cognitive functioning adversely and partly irreversibly. Emerging evidence suggests that pregabalin (PGB) might be a safe and efficacious treatment of long‐term BDZ use. The aim of the present study was to investigate the changes in several core cognitive functions after successful treatment of long‐term BDZ use and dependence with PGB.

Methods

Fourteen patients with long‐term BDZ use (mean duration >15 years) underwent neuropsychological assessment with the mini‐mental state examination and four tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) battery before the initiation of PGB treatment and at a two months follow‐up after the cessation of BDZs. Patients' CANTAB percentile score distributions were compared with normative CANTAB data.

Results

Patients improved on cognitive measures of global cognitive functioning, time orientation, psychomotor speed, and visuospatial memory and learning with strong effect sizes. By contrast, they failed to improve on measures of attentional flexibility. Despite their significant improvement, patients' scores on most tests remained still at the lower percentiles of CANTAB normative scores.

Conclusions

Although preliminary, our findings suggest that successful treatment of long‐term BDZ use with PGB is associated with a substantial, though only partial, recovery of BDZ‐compromised neuropsychological functioning, at least at a 2‐month follow‐up. Copyright © 2014 John Wiley & Sons, Ltd.
Therapeutic potential of highly cytotoxic natural killer cells for gastric cancer
Authors: Mimura Kousaku , Kamiya Takahiro , Shiraishi Kensuke , Kua Ley‐Fang , Shabbir Asim , So Jimmy , Yong Wei‐Peng , Suzuki Yoshiyuki , Yoshimoto Yuya , Nakano Takashi , Fujii Hideki , Campana Dario , Kono Koji
Published: February 2014

To develop more effective therapies for patients with advanced gastric cancer, we examined the potential of ex vivo expanded natural killer (NK) cells. We assessed the expression of ligands for NK Group 2 Member D (NKG2D, an important NK activation molecule) in primary tumors from 102 patients with gastric cancer by immunohistochemistry and determined their prognostic value. We then examined the in vitro and in vivo cytotoxicity of NK cells from healthy donors and patients with gastric cancer. The cytotoxicity of resting and of interleukin (IL)‐2‐activated NK cells was compared to that of NK cells expanded for 7 days by coculture with the K562‐mb15‐4.1BBL cell line. As a result, the expression of NKG2D ligands in primary tumors was correlated with favorable presenting features and outcomes, suggesting that gastric cancer may be sensitive to NK cell cytotoxicity. Although resting NK cells showed minimal cytotoxicity against gastric cancer cells, K562‐mb15‐4.1BBL‐expanded NK cells were highly cytotoxic and significantly more powerful than IL‐2‐activated NK cells. Cytotoxicity was correlated with NKG2D ligand expression and could be modulated by mitogen‐activated protein kinase and AKT‐PI3 kinase inhibitors. The cytotoxicity of expanded NK cells against HER2‐positive gastric cancer cells could be increased by Herceptin and further augmented by Lapatinib. Finally, expanded NK cells exhibited strong antitumor activity in immunodeficient mice engrafted with a gastric cancer cell line. In conclusion, gastric cancer tumors express NKG2D ligands and are highly susceptible to killing by NK cells stimulated by K562‐mb15‐4.1BBL. These results provide a strong rationale for clinical testing of these NK cells in patients and suggest their use to augment the effects of antibody therapy.
Dietary effect of selenium‐fortified Chlorella vulgaris on reproduction of Brachionus plicatilis species complex (Rotifera: Monogononta)
Authors: Kim Hee‐Jin , Nakamura Koh , Hagiwara Atsushi
Published: February 2014

We investigated the effects of fortifying a diet of Chlorella vulgaris with Selenium (Se) on sexual and asexual reproduction of rotifers in the Brachionus plicatilis species complex: i.e. two strains of B. plicatilis sensu stricto and one of Brachionus rotundiformis. These rotifers were cultured for 8–10 days on one of three different diets that were adjusted to provide the same dry weight of food: non‐fortified Chlorella, Se‐fortified Chlorella, and Nannochloropsis oculata. B. plicatilis (Makishima strain), which is obligatorily asexual, showed no difference in population growth rate among the three different diets (r = 0.55–0.61). On the other hand, B. plicatilis (NH17L strain), which reproduces by cyclical parthenogenesis, showed higher population growth (r = 0.25) and also higher rates of fertilization (35.9%) and absolute resting egg production (2803.9 eggs/g food) with the Se‐fortified Chlorella diet than with other foods. Although B. rotundiformis (Kochi strain), which also exhibits cyclical parthenogenesis, showed no differences in population growth among the three different diets (r = 0.42–0.48), sexual reproduction parameters were different depending on the feeding regime. The highest mixis (26.2%), fertilization (72.6%), and resting egg production (3489.9 eggs/g food) were observed with the Se‐fortified Chlorella diet. We posit that the effect of Se‐fortified diet was greater on the resting egg production by enhancing male fertility than on population growth.
Nitroaromatic compounds: Environmental toxicity, carcinogenicity, mutagenicity, therapy and mechanism
Authors: Kovacic Peter , Somanathan Ratnasamy
Published: February 2014

Vehicle pollution is an increasing problem in the industrial world. Aromatic nitro compounds comprise a significant portion of the threat. In this review, the class includes nitro derivatives of benzene, biphenyls, naphthalenes, benzanthrone and polycyclic aromatic hydrocarbons, plus nitroheteroaromatic compounds. The numerous toxic manifestations are discussed. An appreciable number of drugs incorporate the nitroaromatic structure. The mechanistic aspects of both toxicity and therapy are addressed in the context of a unifying mechanism involving electron transfer, reactive oxygen species, oxidative stress and antioxidants. Copyright © 2014 John Wiley & Sons, Ltd.
Preliminary safety evaluation of a taurocholate‐conjugated low‐molecular‐weight heparin derivative (LHT7): a potent angiogenesis inhibitor
Authors: Alam Farzana , Chung Seung Woo , Hwang Seung Rim , Kim Ji‐young , Park Jooho , Moon Hyun Tae , Byun Youngro
Published: February 2014

In our previous studies, taurocholic acid (TA)‐conjugated low‐molecular‐weight heparin derivative (LHT7) has been proven to be a potent anti‐angiogenic agent by demonstrated successful blockage capability of vascular endothelial growth factors (VEGF). Preliminary safety evaluations were conducted based on its mechanism of action and chemical behavior. For this purpose, acute toxicity study, and hematological and serological evaluations were carried out. Additionally, in order to evaluate mechanism‐related side effects, both blood pressure and the occurrence of proteinuria were measured using a treatment regime of multiple high doses of LHT7 in a biodistribution study. LD50 values for LHT7 in female and male mice were 56.9 and 64.7 mg kg–1 doses, respectively. There were no vital fluctuations in the serological and hematological parameters, except for the elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) at 100 and 200 mg kg–1 doses of LHT7, representing vital changes in the liver function. Moreover, the results of mechanism‐related studies showed that blood pressure at 50 mg kg–1 did not change but showed elevated levels of protein in urine. In the biodistribution study, a slight accumulation of LHT7 in the kidney and the liver were observed at the 50 mg kg–1 repeated dose owing to the presence of bile acid. No fatal damage was observed in this study; most observations were related to the chemical composition or the mechanism of action of the material. Copyright © 2014 John Wiley & Sons, Ltd.
Biomechanical and antibacterial properties of Tobramycin loaded hydroxyapatite coated fixation pins
Authors: Sörensen Jan Henrik , Lilja Mirjam , Sörensen Torben Christian , Åstrand Maria , Procter Philip , Fuchs Sabine , Strømme Maria , Steckel Hartwig
Published: February 2014

The present study investigates the use of nanoporous, biomimetic hydroxyapatite (HA) coatings deposited on TiO2 coated fixation pins as functional implant surfaces for the local release of Tobramycin in order to prevent bacterial colonization. The impact of HA‐coating thickness, coating morphology and biomechanical forces during insertion into synthetic bone on the drug loading and release properties are analyzed. The coatings are shown to exhibit bactericidal effects against Staphylococcus aureus in agar medium for a duration of 6 days after loading by adsorption with Tobramycin for only 5 min at elevated temperature and pressure. Furthermore, high performance liquid chromatography analysis shows a drug release in phosphate buffered saline for 8 days with antibiotic concentration remaining above the minimal inhibitory concentration for S. aureus during the entire release period. Biomechanical insertion tests into synthetic bone and conventional scratch testing demonstrate adhesive strength at the HA/TiO2 interface. Biocompatibility is verified by cell viability tests. Outgrowth endothelial cells, as well as primary osteoblasts, are viable and firmly attached to both HA and TiO2 surfaces. The results presented are encouraging and support the concept of functional HA coatings as local drug delivery vehicles for biomedical applications to treat as well as to prevent post‐surgical infections. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1381–1392, 2014.
Transcriptional Activation by NFκB Increases Perlecan/HSPG2 Expression in the Desmoplastic Prostate Tumor Microenvironment
Authors: Warren Curtis R. , Grindel Brian J. , Francis Lewis , Carson Daniel D. , Farach‐Carson Mary C.
Published: February 2014

Perlecan/HSPG2, a heparan sulfate proteoglycan typically found at tissue borders including those separating epithelia and connective tissue, increases near sites of invasion of primary prostatic tumors as previously shown for other proteins involved in desmoplastic tissue reaction. Studies of prostate cancer cells and stromal cells from both prostate and bone, the major site for prostate cancer metastasis, showed that cancer cells and a subset of stromal cells increased production of perlecan in response to cytokines present in the tumor microenvironment. In silico analysis of the HSPG2 promoter revealed two conserved NFκB binding sites, in addition to the previously reported SMAD3 binding sites. By systematically transfecting cells with a variety of reporter constructs including sequences up to 2.6 kb from the start site of transcription, we identified an active cis element in the distal region of the HSPG2 promoter, and showed that it functions in regulating transcription of HSPG2. Treatment with TNF‐α and/or TGFβ1 identified TNF‐α as a major cytokine regulator of perlecan production. TNF‐α treatment also triggered p65 nuclear translocation and binding to the HSPG2 regulatory region in stromal cells and cancer cells. In addition to stromal induction of perlecan production in the prostate, we identified a matrix‐secreting bone marrow stromal cell type that may represent the source for increases in perlecan in the metastatic bone marrow environment. These studies implicate perlecan in cytokine‐mediated, innate tissue responses to cancer cell invasion, a process we suggest reflects a modified wound healing tissue response co‐opted by prostate cancer cells. J. Cell. Biochem. 115: 1322–1333, 2014. © 2014 Wiley Periodicals, Inc.
The total Position Spread in mixed‐valence compounds: A study on the model system
Authors: Bendazzoli Gian Luigi , El Khatib Muammar , Evangelisti Stefano , Leininger Thierry
Published: February 2014

The behavior of the Total Position Spread (TPS) tensor, which is the second moment cumulant of the total position operator, is investigated in the case of a mixed‐valence model system. The system consists of two H2 molecules placed at a distance D. If D is larger than about 4 bohr, the singly ionized system shows a mixed‐valence character. It is shown that the magnitude of the TPS has a strong peak in the region of the avoided crossing. We believe that the TPS can be a powerful tool to characterize the behavior of the electrons in realistic mixed‐valence compounds. © 2014 Wiley Periodicals, Inc.
Properties of atoms in electronically excited molecules within the formalism of TDDFT
Authors: Sánchez‐Flores Eric Iván , Chávez‐Calvillo Rodrigo , Keith Todd A. , Cuevas Gabriel , Rocha‐Rinza Tomás , Cortés‐Guzmán Fernando
Published: February 2014

The topological analysis of the electron density for electronic excited states under the formalism of the quantum theory of atoms in molecules using time‐dependent density functional theory (TDDFT) is presented. Relaxed electron densities for electronic excited states are computed by solving a Z‐vector equation which is obtained by means of the Sternheimer interchange method. This is in contrast to previous work in which the electron density for excited states is obtained using DFT instead of TDDFT, that is, through the imposition of molecular occupancies in accordance with the electron configuration of the excited state under consideration. Once the electron density of the excited state is computed, its topological characterization and the properties of the atoms in molecules are obtained in the same manner that for the ground state. The analysis of the low‐lying
singlet and triplet vertical excitations of CO and C6H6 are used as representative examples of the application of this methodology. Altogether, it is shown how this procedure provides insights on the changes of the electron density following photoexcitation and it is our hope that it will be useful in the study of different photophysical and photochemical processes. © 2014 Wiley Periodicals, Inc.
1,4‐Bis((1H‐pyrrol‐2‐yl)methylene)thiosemicarbazide Complexes of Zn(II), Cd(II) and Hg(II): Single Source Precursor in Thermal Synthesis of Nanoparticle
Authors: Shukla Satyendra N. , Gaur Pratiksha , Rai Nidhi , Mehrotra Ripul
Published: February 2014

Six complexes of Zn(II), Cd(II) and Hg(II) with sulphur containing Schiff base ligand, 1,4‐bis((1H‐pyrrol‐2‐yl)methylene)thiosemicarbazide in 1:1 and 1:2 ratio has been synthesized. Complexes were characterized by molar conductance measurement, elemental analyses, FT‐IR, 1H‐NMR, and FAB/ESI‐Mass. The complexes were used as a single source precursor for the synthesis of ZnS/CdS/HgS nanoparticles by their thermal decomposition in the presence of different surfactants. The precursor: surfactant ratio and temperature plays important role in determining the size of the nanoparticles. The size and morphology of nanoparticles has been ascertained by UV‐Vis spectroscopy, XRD measurements and Transmission Electron Microscopy (TEM). Schiff base, complexes and nanoparticles were tested for antibacterial activity and MIC values against E. coli. The complexes were found more potent than the corresponding Schiff bases and nanoparticles.
Effects of Core‐modification on Porphyrin Sensitizers to the Efficiencies of Dye‐sensitized Solar Cells
Authors: Mane Sandeep B. , Luo Liyang , Chang Gao‐Fong , Diau Eric Wei‐Guang , Hung Chen‐Hsiung
Published: February 2014

To study dye‐sensitized solar cells (DSSCs) with core‐modified porphyrins as the sensitizing dyes, three porphyrins with an ethynyl benzoic acid as an anchoring group are prepared. The properties of free‐base regular porphyrin (N4), thiaporphyrin (N3S) and oxaporphyrin (N3O) were thoroughly studied by spectroscopic methods, DFT calculations, and photovoltaic measurements. Replacing one of the porphyrinic core nitrogen atoms by oxygen or sulfur considerably changes the absorption spectra. The Soret band of the N3O and N3S observed bathochromic shifts of 3‐9 nm while the Q band reaches 700 nm to the near‐infrared region. The overall conversion efficiencies of the DSSCs based on these porphyrins are in the order N4 (3.66%) ≫ N3S (0.22%) > N3O (0.01%). The time‐correlated single photon counting observed short fluorescence lifetimes for N3O adsorbed both on TiO2 and Al2O3 which explicates the poor efficiency of DSSC using N3O as the photosensitizer.
[C12mim]Br: A Temperature‐dependent Phase Transfer Catalyst and Its Application for Aerobic Oxidative Synthesis of 2‐Aryl Benzimidazoles, Benzoxazoles or Benzothiozoles Catalyzed by TEMPO Based Ionic Liquid
Authors: Yu Jiatao , Lu Ming
Published: February 2014

The application of [C12mim]Br ionic liquid/o‐xylene temperature‐dependent biphasic system into the [Imim‐TEMPO][Cl]/O2‐promoted condensation between o‐phenylenediamines, o‐aminophenol or o‐aminothiophenol with aldehydes for preparing benzimidazoles, benzoxazoles or benzothiozoles is described. Several aldehydes and o‐phenylenediamines, o‐aminophenol or o‐aminothiophenol were reacted efficiently to form corresponding products in excellent yields. Both the [Imim‐TEMPO][Cl] and [C12mim]Br could be reused at least eight times without significantly decreasing the catalytic activity.
Link Between DNA Damage and Centriole Disengagement/Reduplication in Untransformed Human Cells
Authors: Douthwright Stephen , Sluder Greenfield
Published: February 2014

The radiation and radiomimetic drugs used to treat human tumors damage DNA in both cancer cells and normal proliferating cells. Centrosome amplification after DNA damage is well established for transformed cell types but is sparsely reported and not fully understood in untransformed cells. We characterize centriole behavior after DNA damage in synchronized untransformed human cells. One hour treatment of S phase cells with the radiomimetic drug, Doxorubicin, prolongs G2 by at least 72 h, though 14% of the cells eventually go through mitosis in that time. By 72 h after DNA damage we observe a 52% incidence of centriole disengagement plus a 10% incidence of extra centrioles. We find that either APC/C or Plk activities can disengage centrioles after DNA damage, though they normally work in concert. All disengaged centrioles are associated with γ‐tubulin and maturation markers and thus, should in principle be capable of reduplicating and organizing spindle poles. The low incidence of reduplication of disengaged centrioles during G2 is due to the p53‐dependent expression of p21 and the consequent loss of Cdk2 activity. We find that 26% of the cells going through mitosis after DNA damage contain disengaged or extra centrioles. This could produce genomic instability through transient or persistent spindle multipolarity. Thus, for cancer patients the use of DNA damaging therapies raises the chances of genomic instability and evolution of transformed characteristics in proliferating normal cell populations. J. Cell. Physiol. 229: 1427–1436, 2014. © 2014 Wiley Periodicals, Inc.
Pancreatic Cancer‐Induced Cachexia Is Jak2‐Dependent in Mice
Authors: Gilabert Marine , Calvo Ezequiel , Airoldi Ana , Hamidi Tewfik , Moutardier Vincent , Turrini Olivier , Iovanna Juan
Published: February 2014

Cancer cachexia syndrome is observed in 80% of patients with advanced‐stage cancer, and it is one of the most frequent causes of death. Severe wasting accounts for more than 80% in patients with advanced pancreatic cancer. Here we wanted to define, by using an microarray approach and the Pdx1‐cre;LSL‐KrasG12D;INK4a/arffl/fl mice model, the pathways involved in muscle, liver, and white adipose tissue wasting. These mice, which develop systematically pancreatic cancer, successfully reproduced many human symptoms afflicted with this disease, and particularly cachexia. Using the profiling analysis of pancreatic cancer‐dependent cachectic tissues we found that Jak2/Stat3 pathways, p53 and NFkB results activated. Thus, our interest was focused on the Jak2 pathways because it is pharmacologically targetable with low toxicity and FDA approved drugs are available. Therefore, Pdx1‐cre;LSL‐KrasG12D;INK4a/arffl/fl mice were treated with the Jak2 inhibitor AG490 compound daily starting at 7 weeks old and for a period of 3 weeks and animals were sacrificed at 10 weeks old. Body weight for control mice was 27.84 ± 2.14 g, for untreated Pdx1‐cre;LSL‐KrasG12D;INK4a/arffl/fl was 14.97 ± 1.99 g, whereas in animals treated with the AG490 compound the weight loss was significantly less to 24.53 ± 2.04 g. Treatment with AG490 compound was efficient since phosphorylation of Jak2 and circulating interleukin‐6 (IL6) levels were significantly reduced in cachectic tissues and in mice respectively. In conclusion, we found that Jak2/Stat3‐dependent intracellular pathway plays an essential role since its pharmacological inhibition strongly attenuates cachexia progression in a lethal transgenic pancreatic cancer model. J. Cell. Physiol. 229: 1437–1443, 2014. © 2014 Wiley Periodicals, Inc.
Improved frequency selective fat suppression in the posterior neck with tissue susceptibility matched pyrolytic graphite foam
Authors: Lee Gary , Jordan Caroline , Tiet Pamela , Ruiz Carlos , McCormick Jeff , Phuong Kevin , Hargreaves Brian , Conolly Steven
Published: February 2014

Purpose

To demonstrate improved frequency selective fat suppression in MRI using a magnetic susceptibility matching foam by reducing B0 inhomogeneities induced within the body by air–tissue interfaces.

Materials and Methods

Flexible pyrolytic graphite (PG) composite foam was tailored to match the magnetic susceptibility of human tissue and was shaped to surround the cervical spine region. Field maps and frequency selective fat suppressed T1‐weighted FLASH images were acquired at 3 Tesla in both phantoms and six healthy necks.

Results

B0 field uniformity was shimmed to a target critical threshold of 1 ppm for fat suppression. The percentage of voxels in the phantom that did not achieve the critical threshold was reduced from 64% without the PG foam to only 1% with the foam. A similar decrease from 16% to 2% was observed in the in vivo region of interest.

Conclusion

PG foam improved B0 field uniformity by moving air–tissue field gradients outside of the neck where they cannot cause MRI artifacts. The PG foams consistently mitigated signal dropout, improved overall SNR, and enabled more robust frequency selective fat suppression. J. Magn. Reson. Imaging 2015;41:684–693. © 2014 Wiley Periodicals, Inc.
In Vivo 31P magnetic resonance spectroscopic imaging (MRSI) for metabolic profiling of human breast cancer xenografts
Authors: Esmaeili Morteza , Moestue Siver A. , Hamans Bob C. , Veltien Andor , Kristian Alexandr , Engebråten Olav , Mælandsmo Gunhild M. , Gribbestad Ingrid S. , Bathen Tone F. , Heerschap Arend
Published: February 2014

Purpose

To study cancer associated with abnormal metabolism of phospholipids, of which several have been proposed as biomarkers for malignancy or to monitor response to anticancer therapy. We explored 3D 31P magnetic resonance spectroscopic imaging (MRSI) at high magnetic field for in vivo assessment of individual phospholipids in two patient‐derived breast cancer xenografts representing good and poor prognosis (luminal‐ and basal‐like tumors).

Materials and Methods

Metabolic profiles from luminal‐like and basal‐like xenograft tumors were obtained in vivo using 3D 31P MRSI at 11.7T and from tissue extracts in vitro at 14.1T. Gene expression analysis was performed in order to support metabolic differences between the two xenografts.

Results

In vivo 31P MR spectra were obtained in which the prominent resonances from phospholipid metabolites were detected at a high signal‐to‐noise ratio (SNR >7.5). Metabolic profiles obtained in vivo were in agreement with those obtained in vitro and could be used to discriminate between the two xenograft models, based on the levels of phosphocholine, phosphoethanolamine, glycerophosphocholine, and glycerophosphoethanolamine. The differences in phospholipid metabolite concentration could partly be explained by gene expression profiles.

Conclusion

Noninvasive metabolic profiling by 3D 31P MRSI can discriminate between subtypes of breast cancer based on different concentrations of choline‐ and ethanolamine‐containing phospholipids. J. Magn. Reson. Imaging 2015;41:601–609. © 2014 Wiley Periodicals, Inc.
Molecular detection and characterization of aichivirus A in adult patients with diarrhea in Thailand
Authors: Saikruang Wilaiporn , Khamrin Pattara , Suantai Boonpa , Ushijima Hiroshi , Maneekarn Niwat
Published: February 2014

Viral gastroenteritis is a common public health problem that causes morbidity and mortality worldwide. Recently, new viruses causing gastroenteritis have been identified. Among these, Aichivirus has also been proposed as a causative agent of gastroenteritis in human. Most studies have been conducted in infants and children, the information in adults is limited. Therefore, the purpose of this study was to investigate the epidemiology and molecular characterization of Aichivirus in adult patients with diarrhea. A total of 332 fecal specimens collected from January to December 2008 were screened for the presence of Aichivirus by reverse transcription‐PCR (RT‐PCR) method. Out of 332 fecal specimens tested, Aichivirus was detected with the prevalence of 0.9% (3/332). The data indicate that the prevalence of Aichivirus in adults was as low as those reported in children in Thailand. Phylogenetic analysis of the VP1 sequence revealed that one Aichivirus belonged to genotype A, while other two Aichiviruses were genotype B. In conclusion, this study provided the molecular epidemiological data of Aichivirus circulating in adult patients with diarrhea at low prevalence and the viruses were genetically variable as both genotypes A and B were found in this population. J. Med. Virol. 86:983–987, 2014. © 2014 Wiley Periodicals, Inc.
The significance of cellulolytic enzymes produced by Trichoderma in opportunistic lifestyle of this fungus
Authors: Strakowska Judyta , Błaszczyk Lidia , Chełkowski Jerzy
Published: February 2014

The degradation of native cellulose to glucose monomers is a complex process, which requires the synergistic action of the extracellular enzymes produced by cellulolytic microorganisms. Among fungi, the enzymatic systems that can degrade native cellulose have been extensively studied for species belonging to the genera of Trichoderma. The majority of the cellulolytic enzymes described so far have been examples of Trichoderma reesei, extremely specialized in the efficient degradation of plant cell wall cellulose. Other Trichoderma species, such as T. harzianum, T. koningii, T. longibrachiatum, and T. viride, known for their capacity to produce cellulolytic enzymes, have been isolated from various ecological niches, where they have proved successful in various heterotrophic interactions. As saprotrophs, these species are considered to make a contribution to the degradation of lignocellulosic plant material. Their cellulolytic potential is also used in interactions with plants, especially in plant root colonization. However, the role of cellulolytic enzymes in species forming endophytic associations with plants or in those existing in the substratum for mushroom cultivation remains unknown. The present review discusses the current state of knowledge about cellulolytic enzymes production by Trichoderma species and the encoding genes, as well as the involvement of these proteins in the lifestyle of Trichoderma.
Validation of GAITRite and PROMIS as high‐throughput physical function outcome measures following ACL reconstruction
Authors: Papuga M. Owen , Beck Christopher A. , Kates Stephen L. , Schwarz Edward M. , Maloney Michael D.
Published: February 2014

New healthcare demands for quality measures of elective procedures, such as anterior cruciate ligament (ACL) reconstructive surgery, warrant the establishment of high throughput outcomes for high volume clinics. To this end, we evaluated the PROMIS and GAITRite as physical function outcome measures to quantify early healing and post‐operative complications in 106 patients at pre‐operative and 3, 10, 20 and 52 weeks post‐ACL reconstruction with bone‐tendon‐bone autograft, and compared the results to the current IKDC validated outcome measure. The results showed that both PROMIS and GAITRite were significantly quicker to administer versus IKDC (p < 0.0001). Additional advantages were that PROMIS and GAITRite detected a significant decrease in physical function at 3 weeks post‐operative, and a significant improvement at 10 weeks post‐operative versus pre‐operative (p < 0.001), which were not detected with IKDC. GAITRite was limited by a low ceiling that could not detect improvement of physical function beyond 20 weeks, while both PROMIS and IKDC detected significant improvement out to 52 weeks post‐operative (p < 0.001). Linear regressions demonstrated a significant relationship between IKDC and PROMIS, with a combined correlation value of 0.8954 (p < 0.001) for all time points. Finally, ROC curve analysis demonstrated that PROMIS is a diagnostic test for poor outcomes. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:793–801, 2014.
Controlled‐release of bone morphogenetic protein‐2 from a microsphere coating applied to acid‐etched Ti6AL4V implants increases biological bone growth in vivo
Authors: Fu Yangmu , Zhang Qiang , Sun Yong , Liao Weixiong , Bai Xiaowei , Zhang Lili , Du Lina , Jin Yiguang , Wang Qi , Li Zhongli , Wang Yan
Published: February 2014

A central clinical challenge regarding the surgical treatment of bone and joint conditions is the eventual loosening of an orthopedic implant as a result of insufficient bone ingrowth at the bone–implant interface. We investigated the in vivo effectiveness of a coating containing recombinant human bone morphogenetic protein‐2 (rhBMP‐2)‐loaded microspheres applied to acid‐etched Ti6Al4V cylinders for implantation. Three groups of rabbits (24 per group) were used for implantation: (1) acid‐etched Ti6Al4V implants coated with a mixture of rhBMP‐2‐loaded microspheres (125 ng rhBMP‐2/mg microspheres) and α‐butyl cyanoacrylate; (2) acid‐etched, uncoated implants; and (3) bare, smooth uncoated implants. After implantation, 12 rabbits from each group were used for bone ingrowth determination at 4, 5, 6, 7, 8, and 12 weeks (2 rabbits per time point), while the remainder were used for histological analysis and push‐out testing at 12 weeks. Scanning electron microscopy showed significant improvement in bone growth of the rhBMP‐2 microspheres/α‐butyl cyanoacrylate group compared with the other groups (p < 0.01). Histological analysis and push‐out testing also demonstrated enhanced bone growth of the rhBMP‐2 group over that in the other two groups (p < 0.01). The rhBMP‐2 group showed the most significant bone growth, suggesting that coating acid‐etched implants with a mixture of rhBMP‐2‐loaded microspheres and α‐butyl cyanoacrylate may be an effective method to improve the osseointegration of orthopedic implants. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:744–751, 2014.
Proteomic identification of 14‐3‐3ϵ as a linker protein between pERK1/2 inhibition and BIM upregulation in human osteosarcoma cells
Authors: Kim Kyung Ok , Hsu Anny C. , Lee Heon Goo , Patel Neel , Chandhanayingyong Chandhanarat , Hickernell Thomas , Lee Francis Young‐In
Published: February 2014

Despite advancements in multimodality chemotherapy, conventional cytotoxic treatments still remain ineffective for a subset of patients with aggressive metastatic or multifocal osteosarcoma. It has been shown that pERK1/2 inhibition enhances chemosensitivity to doxorubicin and promotes osteosarcoma cell death in vivo and in vitro. One of the pro‐apoptotic mechanisms is upregulation of Bim by pERK1/2 inhibitors. To this end, we examined proteomic changes of 143B human osteosarcoma cells with and without treatment of PD98059, pERK1/2 inhibitor. Specifically, we identified 14‐3‐3ϵ protein as a potential mediator of Bim expression in response to inhibition of pERK1/2. We hypothesized that 14‐3‐3ϵ mediates upregulation of Bim expression after pERK1/2 inhibition. We examined the expression of Bim after silencing 14‐3‐3ϵ using siRNA. The 14‐3‐3ϵ gene silencing resulted in downregulation of Bim expression after PD98059 treatment. These data indicate that 14‐3‐3ϵ is required for Bim expression and that it has an anti‐cancer effect under pERK1/2 inhibition in 143B cells. By playing an essential role upstream of Bim, 14‐3‐3ϵ may potentially be a coadjuvant factor synergizing the effect of pERK1/2 inhibitors in addition to conventional cytotoxic agents for more effective osteosarcoma treatments. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:848–854, 2014.
Pathokinematics of precision pinch movement associated with carpal tunnel syndrome
Authors: Nataraj Raviraj , Evans Peter J. , Seitz William H. , Li Zong‐Ming
Published: February 2014

Carpal tunnel syndrome (CTS) can adversely affect fine motor control of the hand. Precision pinch between the thumb and index finger requires coordinated movements of these digits for reliable task performance. We examined the impairment upon precision pinch function affected by CTS during digit movement and digit contact. Eleven CTS subjects and 11 able‐bodied (ABL) controls donned markers for motion capture of the thumb and index finger during precision pinch movement (PPM). Subjects were instructed to repetitively execute the PPM task, and performance was assessed by range of movement, variability of the movement trajectory, and precision of digit contact. The CTS group demonstrated shorter path‐length of digit endpoints and greater variability in inter‐pad distance and most joint angles across the PPM movement. Subjects with CTS also showed lack of precision in contact points on the digit‐pads and relative orientation of the digits at contact. Carpal tunnel syndrome impairs the ability to perform precision pinch across the movement and at digit‐contact. The findings may serve to identify deficits in manual dexterity for functional evaluation of CTS. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:786–792, 2014.
Tracheobronchial injury in the setting of an esophagectomy for cancer: Postoperative discovery a bad omen
Authors: Koshenkov Vadim P. , Yakoub Danny , Livingstone Alan S. , Franceschi Dido
Published: February 2014

Background

A tracheobronchial injury is an uncommon complication of an esophagectomy. Differences in outcomes may exist for patients with injuries detected intraoperatively and postoperatively.

Methods

A retrospective review was performed for patients who underwent an esophagectomy for cancer at Jackson Memorial Hospital/University of Miami from January 2000 to June 2012.

Results

An injury to the tracheobronchial tree occurred in 7 of 425 patients (1.6%). The majority of the operations were performed via a transhiatal approach (87.8%). Patients with airway injuries were older (median 73 vs. 63), more likely to have squamous cell carcinoma (85.7% vs. 17.9%), and with proximal tumors (85.7% vs. 14.1%). When given, the type of neoadjuvant treatment consisted of chemoradiotherapy in all patients who suffered an injury, whereas it was only administered to 21.3% of patients without an injury. There were no deaths among three patients in whom the injury was identified intraoperatively. Mortality occurred in three of four patients (75.0%) with an injury detected postoperatively.

Conclusions

Patients with proximal tumors and radiation administration as a component of neoadjuvant treatment are more likely to suffer a tracheobronchial injury. An aggressive reoperative approach is warranted in patients with injuries that are discovered postoperatively. J. Surg. Oncol. 2014 109:804–807. © 2014 Wiley Periodicals, Inc.
Determination of endosulfan isomers and their metabolites in tap water and commercial samples using microextraction by packed sorbent and GC–MS
Authors: Kaur Ramandeep , Rani Susheela , Malik Ashok Kumar , Aulakh Jatinder Singh
Published: February 2014

A simple, rapid, accurate and sensitive method using microextraction by packed sorbent (MEPS) followed by GC–MS has been pursued for the determination of organochlorine insecticide endosulfan isomers (α and β) and their metabolites (ether, lactone and sulfate). MEPS is a miniaturised version of SPE employing C18 packing material. It is very efficient technique as it employs as low as 10 μL of sample volume. The distinct feature of MEPS is the magnitude of the elution volume that could be directly injected to GC system. Various parameters such as extraction cycles, washing solvent, elution solvent, elution volume and pH, which influenced the MEPS performance, were tested and optimised. The calibration curves were obtained in the concentration range 1–500 ng/mL. The results showed a close correlation coefficient (R2 > 0.991) for all analytes in the calibration range studied. The LOD and LOQ obtained for GC–MS under selected ion monitoring acquisition are between 0.0038–0.01 and 0.0125–0.033 ng/mL, respectively. The developed method is applicable for the quantification of these compounds in tap water and commercial samples. This method has been shown to be selective as no interferences from endogenous substances were detected by analysis. This method not only decreases sample preparation time but is cheaper, eco‐friendly and easier to perform compared to traditional techniques.
A robust method of enhancement of protection ability of electrodeposited silane film over copper surface using H2O2
Authors: Karthik N. , Sethuraman M. G.
Published: February 2014

The enhancement of protection of copper through pretreatment of metal surface with H2O2 and subsequent addition of H2O2 in the electrodeposition of 3‐mercaptopropyltrimethoxysilane (MPTS) has been investigated in the present work. MPTS films over copper surface with and without H2O2 were investigated by FT‐IR, XRD, Raman spectroscopy and SEM. The protection of copper surface by MPTS in the presence and absence of H2O2 in 1% NaCl medium was also investigated by electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization studies (PDS). The results of the study indicate that MPTS film electrodeposited on pretreated copper with 1000 ppm of H2O2 increases the inhibition efficiency to almost 100%.
The corrosion inhibition behaviors of 2′‐hydroxy‐acetophenone for AZ91D magnesium alloy
Authors: Hu J. Y. , Song X. Q. , Zhang Z. , Zeng D. Z. , Shi T. H. , Gao J. F.
Published: February 2014

The corrosion inhibition behaviors of 2′‐hydroxy‐acetophenone for AZ91D magnesium alloy in ASTM D1384‐87 corrosive water (model water) were investigated using weight loss and electrochemical measurements. The surface morphologies and composition of films formed on magnesium alloy in solutions with and without 2′‐hydroxy‐acetophenone were examined by scanning electron microscope and Fourier transform infrared spectrum. The results show that inhibition efficiency first increases and then decreases with the increasing 2′‐hydroxy‐acetophenone concentration, its maximum value is at 50 ppm. It is considered that 2′‐hydroxy‐acetophenone anions can chelate with the Mg2+ and form a 2′‐hydroxy‐acetophenone–Mg complex on the magnesium alloy surface, hindering the corrosion development of magnesium alloy.
Corrosion resistance of new powder metallurgy boron‐containing stainless steel in the nuclear repository environment
Authors: Stoulil J. , Hemmer V. , Šefl V. , Bystrianský J.
Published: February 2014

The paper studies corrosion resistance of a new type of material in the environment of moist bentonite, which is typical for nuclear waste repository. The material was characterized by measurements of hardness, metallography, and scanning electron microscopy. Methods of impedance spectroscopy, potentiodynamic, and potentiostatic tests were used to assess corrosion resistance. The measurements were carried out in pore solution of Czech bentonite Rokle B75 and model pore solution B1600 of Volclay MX80 bentonite. It is impossible for this material that localized corrosion occur in the environment of Rokle B75. Localized corrosion may occur in the environment of Volclay MX 80 bentonite at temperatures higher than 40 °C, obviously at potentials exceeding red/ox potential of aerated pore solution.