bluuebunny/crossref_metadata_2025 huggingface dataset:
A Case Study Assessing the Auditory and Speech Development of Four Children Implanted with Cochlear Implants by the Chronological Age of 12 Months
Authors: May-Mederake Birgit , Shehata-Dieler Wafaa
Published: February 2013

Children with severe hearing loss most likely receive the greatest benefit from a cochlear implant (CI) when implanted at less than 2 years of age. Children with a hearing loss may also benefit greater from binaural sensory stimulation. Four children who received their first CI under 12 months of age were included in this study. Effects on auditory development were determined using the German LittlEARS Auditory Questionnaire, closed- and open-set monosyllabic word tests, aided free-field, the Mainzer and Göttinger speech discrimination tests, Monosyllabic-Trochee-Polysyllabic (MTP), and Listening Progress Profile (LiP). Speech production and grammar development were evaluated using a German language speech development test (SETK), reception of grammar test (TROG-D) and active vocabulary test (AWST-R). The data showed that children implanted under 12 months of age reached open-set monosyllabic word discrimination at an age of 24 months. LiP results improved over time, and children recognized 100% of words in the MTP test after 12 months. All children performed as well as or better than their hearing peers in speech production and grammar development. SETK showed that the speech development of these children was in general age appropriate. The data suggests that early hearing loss intervention benefits speech and language development and supports the trend towards early cochlear implantation. Furthermore, the data emphasizes the potential benefits associated with bilateral implantation.
Instantaneous Granger Causality with the Hilbert-Huang Transform
Authors: Rodrigues João , Andrade Alexandre
Published: February 2013

Current measures of causality and temporal precedence have limited frequency and time resolution and therefore may not be viable in the detection of short periods of causality in specific frequencies. In addition, the presence of nonstationarities hinders the causality estimation of current techniques as they are based on Fourier transforms or autoregressive model estimation. In this work we present a combination of techniques to measure causality and temporal precedence between stationary and nonstationary time series, that is sensitive to frequency-specific short episodes of causality. This methodology provides a highly informative time-frequency representation of causality with existing causality measures. This is done by decomposing each time series into intrinsic oscillatory modes with an empirical mode decomposition algorithm and, subsequently, calculating their complex Hilbert spectrum. At each time point the cross-spectrum is calculated between time series and used to measure coherency and compute the transfer function and error covariance matrices using the Wilson-Burg method for spectral factorization. The imaginary part of coherency can then be computed as well as several Granger causality measures in the previous matrices. This work covers the most important theoretical background of these techniques and tries to prove the usefulness of this new approach while pointing out some of its qualities and drawbacks.
A Comparative Efficacy of Low-Dose Combined Oral Contraceptives Containing Desogestrel and Drospirenone in Premenstrual Symptoms
Authors: Wichianpitaya Jirath , Taneepanichskul Surasak
Published: February 2013

Objective. To compare the efficacy of low-dose COC containing desogestrel (DSG) with drospirenone (DRSP) in the changes of premenstrual symptoms.Methods. In an open-label randomized controlled trial, 90 women with premenstrual syndrome who required COC were randomly recruited and allocated equally to receive either 6 cycles of 20 micrograms ethinyl estradiol (EE)/150 micrograms DSG (DSG group) or 20 micrograms EE/3 mg DRSP (DRSP group) in 24/4 extended regimen. Analysis of covariance and repeated analysis of variance were used to determine the difference of mean Women's Health Assessment Questionnaire (WHAQ) scores changes between groups, within group, and in premenstrual, menstrual, and postmenstrual phases.Results. Baseline characteristics and WHAQ scores were comparable. At the ends of the 3rd and the 6th cycles, mean WHAQ scores of all the 3 phases in DRSP group showed significant reduction and were significantly lower than those in DSG group. DSG group showed significant reduction in both premenstrual and menstrual phases after the 6th cycle. Adverse effects were comparable in both groups. In conclusion, low-dose COC containing either DSG or DRSP reduced premenstrual symptoms, but the latter showed greater efficacy and earlier reduction.
Determinants of Mortality among HIV Positives after Initiating Antiretroviral Therapy in Western Ethiopia: A Hospital-Based Retrospective Cohort Study
Authors: Hambisa Mitiku Teshome , Ali Ahmed , Dessie Yadeta
Published: February 2013

Studies revealed that there are various determinants of mortality among HIV positives after ART initiation. These determinants are so variable with context and dynamic across time with the advancement of cares and treatments. In this study we tried to identify determinants of mortality among HIV positives after initiating ART. A retrospective cohort study was conducted among 416 ART attendees enrolled between July 2005 to January 2012 in Nekemte Referral Hospital, Western Ethiopia. Actuarial table was used to estimate survival of patients after ART initiation and log rank test was used to compare the survival curves. Cox proportional-hazard regression was applied to determine the independent determinants of time to death. The estimated mortality was 4%, 5%, 6%, 7%, and 7% at 6, 12, 24, 36 and 48 months respectively with mortality incidence density of 1.89 deaths per 100 person years (95% CI 1.74, 3.62). Forty years and above AHR = 3.055 (95% CI 1.292, 7.223), low baseline hemoglobin level (AHR = 0.523 (95% CI .335, 0.816)), and poor ART adherence (AHR 27.848 (95% CI 8.928, 86.8)) were found to be an independent determinants of mortality. These determinants of mortality have to be taken into account to enhance better clinical outcomes of ART attendees.
The Comparison of Photocatalytic Degradation and Decolorization Processes of Dyeing Effluents
Authors: Adamek Ewa , Baran Wojciech , Ziemiańska Justyna , Sobczak Andrzej
Published: February 2013

Treatment of dye effluents resulting from the industrial scale dyeing of cotton, polyacrylic fibres, leather, and flax fabrics by photocatalytic methods was investigated. Photocatalytic processes were initiated by UV-a light (λmax366 nm) and were conducted in the presence of TiO2, TiO2/FeCl3, or FeCl3as photocatalysts. It was found that the photocatalytic process carried out with TiO2and TiO2/FeCl3was the most effective method for decolorization of textile dyeing effluents and degradation of dyes, except for effluents containing very high concentrations of stable azo dyes. During the photocatalytic degradation of anionic dyes, a mixture of TiO2/FeCl3was more effective, while in the case of cationic dyes, more suitable seems to be TiO2alone.
Sequence Determination of a Novel Tripeptide Isolated from the Young Leaves ofAzadirachta indicaA. Juss
Authors: Rajeswari Prabha M. , Ramachandramurty B.
Published: February 2013

The neem tree has long been recognized for its unique properties, both against insects and in improving human health. Every part of the tree has been used as a traditional medicine for household remedy against various human ailments, from antiquity. Although the occurrence of various phytochemicals in neem has been studied, we have identified the presence of a novel tripeptide in the young leaves of neem using a simple and inexpensive paper chromatographic method, detected by Cu(II)-ninhydrin reagent. The peptide nature of the isolated compound is confirmed by spectral studies. The sequence of the peptide is determined using de novo sequencing by tandem MS after purification.
Expression ofN-Acetylgalactosamine 4-Sulfate 6-O-Sulfotransferase Involved in Chondroitin Sulfate Synthesis Is Responsible for Pulmonary Metastasis
Authors: Mizumoto Shuji , Watanabe Moto , Yamada Shuhei , Sugahara Kazuyuki
Published: February 2013

Chondroitin sulfate (CS) containing E-disaccharide units, glucuronic acid-N-acetylgalactosamine(4, 6-O-disulfate), at surfaces of tumor cells plays a key role in tumor metastasis. However, the molecular mechanism of the metastasis involving the CS chain-containing E-units is not fully understood. In this study, to clarify the role of E-units in the metastasis and to search for potential molecular targets for anticancer drugs, the isolation and characterization of Lewis lung carcinoma (LLC) cells stably downregulated by the knockdown for the gene encodingN-acetylgalactosamine 4-O-sulfate 6-O-sulfotransferase (GalNAc4S-6ST), which is responsible for the formation of E-units in CS chains, were performed. Knockdown ofGalNAc4S-6STin LLC cells resulted in a reduction in the proportion of E-units, in adhesiveness to extracellular matrix adhesion molecules and in proliferationin vitro. Furthermore, the stable downregulation ofGalNAc4S-6STexpression in LLC cells markedly inhibited the colonization of the lungs by inoculated LLC cells and invasive capacity of LLC cells. These results provide clear evidence that CS chain-containing E-units and/or GalNAc4S-6ST play a crucial role in pulmonary metastasis at least through the increased adhesion and the invasive capacity of LLC cells and also provides insights into future drug targets for anticancer treatment.
Bilateral Asymmetric Dislocations of Hip Joints: An Unusual Mechanism of Injury
Authors: Kanojia Rajesh Kumar , Patra Satya Ranjan , Gupta Sumit
Published: February 2013

Asymmetric bilateral dislocations of the hips are rare injuries. Among the small number of reports in the literature, most have attributed the cause to high-velocity motor crashes. These dislocations are often seen to be associated with fractures of the proximal femur or the acetabulum. We present a case of a 45-year-old man with bilateral asymmetric dislocation of hips which were purely ligamentous in nature, without any fracture. He sustained his injuries due to a fall while getting on a moving bus. It was an unusual mechanism of injury as compared to the other cases of asymmetric hip dislocations reported in published studies. Both hips were reduced under general anaesthesia within three hours of the trauma. Skin traction and non-weight-bearing rehabilitation were continued for six weeks. After 35 months of followup, the patient remains asymptomatic. Early diagnosis and timely reduction of such dislocations under anaesthesia are necessary for prevention of complications.
May-Thurner Syndrome: A Case Report and Review of the Literature
Authors: Kalu Shivani , Shah Payal , Natarajan Aparna , Nwankwo Nwabundo , Mustafa Usman , Hussain Nasir
Published: February 2013

May-Thurner syndrome (MTS) has been recognized as a clinical entity for almost six decades. The true incidence rate of MTS is unknown and perhaps ranges from 22 to 32% according to the autopsy studies in the early twentieth century. However, MTS related deep venous thrombosis (DVT) accounts for only 2%-3% of all lower limb DVTS. In MTS, the left common iliac vein is compressed against the fifth lumbar vertebrae by the right common iliac artery, as it crosses in front of the vein. Chronic pulsation of the artery is thought to cause elastin, collagen deposition, and intimal fibrosis leading to formation of venous spur and venous thrombosis. MTS can present as acute or chronic DVT leading to pulmonary embolism (PE), chronic leg pain, chronic ulcers, or skin pigmentation changes. In this case report we have described an interesting case of a 28-year-old Caucasian female who presented for evaluation of shortness of breath (SOB) associated with cough for one week. SOB was found to be secondary to massive bilateral pulmonary embolism resulting from extensive MTS related DVT of the left lower extremity. Patient underwent pharmacomechanical treatment with local thrombolysis, thrombectomy, and venoplasty along with stent placement that extended to inferior vena caval junction. Subsequently patient was discharged on coumadin. MTS should be considered in differentials when faced with a case of unilateral DVT particularly in younger age group.
Posterior Reversible Leukoencephalopathy Syndrome in a Pre-Eclamptic Woman
Authors: Thakur Raghvendra , Sharma Bhoj Raj , Yuan Tian , Guiying Zheng
Published: February 2013

Posterior reversible leukoencephalopathy syndrome (PRLS) is a neurologic condition, often presents with various clinical manifestations. It is rare during pregnancy. We herein report a case of PRLS in a 31-year-old woman, presented with preeclampsia, diagnosed by computer tomography, and successfully delivered the baby with caesarean section. At discharge, patient was fully recovered without any complication.
Development and Evaluation of a Computer-Based Learning Environment for Teachers: Assessment of Learning Strategies in Learning Journals
Authors: Glogger Inga , Holzäpfel Lars , Kappich Julian , Schwonke Rolf , Nückles Matthias , Renkl Alexander
Published: February 2013

Training teachers to assess important components of self-regulated learning such as learning strategies is an important, yet somewhat neglected, aspect of the integration of self-regulated learning at school. Learning journals can be used to assess learning strategies in line with cyclical process models of self-regulated learning, allowing for rich formative feedback. Against this background, we developed a computer-based learning environment (CBLE) that trains teachers to assess learning strategies with learning journals. The contents of the CBLE and its instructional design were derived from theory. The CBLE was further shaped by research in a design-based manner. Finally, in two evaluation studies, student teachers (N1=44;N2=89) worked with the CBLE. We analyzed satisfaction, interest, usability, and assessment skills. Additionally, in evaluation study 2, effects of an experimental variation on motivation and assessment skills were tested. We found high satisfaction, interest, and good usability, as well as satisfying assessment skills, after working with the CBLE. Results show that teachers can be trained to assess learning strategies in learning journals. The developed CBLE offers new perspectives on how to support teachers in fostering learning strategies as central component of effective self-regulated learning at school.
Limiting Excess Weight Gain in Healthy Pregnant Women: Importance of Energy Intakes, Physical Activity, and Adherence to Gestational Weight Gain Guidelines
Authors: Cohen Tamara R. , Koski Kristine G.
Published: February 2013

Few studies have investigated if compliance with energy intakes, physical activity, and weight gain guidelines attenuate postpartum weight retention (PPWR) in mothers attending prenatal classes. We investigated whether (a) daily energy intakes within 300 kcal of estimated energy requirements (EERs), (b) walking more than 5000 steps/day, (c) targeting the recommended weight gain goals for prepregnancy BMI, and/or (d) achieving weekly or total gestational weight gain (GWG) recommendations minimized PPWR in 54 women attending prenatal classes in Montreal/Ottawa, Canada. Participants completed a validated pregnancy physical activity questionnaire (PPAQ), 3 telephone-validated 24-hr dietary recalls, and wore a pedometer for one week. PPWR was measured 6 weeks after delivery. Results showed that 72% had healthy prepregnancy BMIs. However, 52% consumed>300 kcal/day in excess of their EER, 54% exceeded recommended GWG, and more overweight (93%) than normal weight women (38%) cited nonrecommended GWG targets. Following delivery, 33% were classified as overweight, and 17% were obese. Multiple logistic regressions revealed that women targeting “recommended weight gain advice” were 3 times more likely to meet total GWG recommendations (OR: 3.2,P<0.05); women who complied with weekly GWG goals minimized PPWR (OR: 4.2,P<0.02). In conclusion, appropriate GWG targets, lower energy intakes, and physical activity should be emphasized in prenatal education programs.
Levels of Organochlorine Pesticides and Heavy Metals in Surface Waters of Konya Closed Basin, Turkey
Authors: Aydin Mehmet Emin , Ozcan Senar , Beduk Fatma , Tor Ali
Published: February 2013

The concentrations of organochlorine pesticides (OCPs), including α‐, β‐, γ‐, and δ‐hexachlorocyclohexane (HCH), heptachlor, heptachlor epoxide, dieldrin, aldrin, endrin, endrin aldehyde, endrin ketone, endosulfan I, endosulfan II, endosulfan sulfate, p,p′‐DDE, p,p′‐DDD, p,p′‐DDT, methoxychlor, chlordane I, chlordane II, and heavy metals, such as As, Cr, Cu, Fe, Mn, and Ni in surface water samples from the Konya closed basin were determined to evaluate the level of contamination. Among all HCH isomers, β‐HCH is the main isomer with a concentration range of 0.015–0.065 μg/L. DDE, DDD, and DDT were almost determined in all samples, in which DDE isomer had the highest concentration ranged from not detected to 0.037 μg/L. In all studied OCPs, aldrin showed the highest concentration at 0.220 μg/L. The concentrations of heavy metals in water samples were observed with order: Mn < Cu < Ni < As < Cr < Fe. In some samples, As, Fe, and Cr concentrations exceeded the drinking water quality recommended by EU, US EPA, WHO, and Turkish Regulation, while Cu, Ni, and Mn concentrations are below the guideline values. The levels of both OCPs and heavy metals were also compared with other previously published data.
Combined Sales Effort and Inventory Control under Demand Uncertainty
Authors: Xue Weili , Xu Xiaolin , Wang Ruxian
Published: February 2013

We study the joint inventory and sales effort management problems of a retailer in a broad context and investigate the optimal policies for a single item, periodic-review system. In each period, the demand is uncertain depending on the sales effort level exerted by the retailer, which incurs an associated cost. The retailer’s objective is to find a joint optimal inventory replenishment and sales effort policy to maximize the discounted profit over a finite horizon. We first consider a basic setting with zero setup cost and no batch ordering, under which the base stock list sales effort policy is optimal. Two extensions are then investigated: (1) the case with nonzero setup cost, under which we show that(s,S,e)policy is optimal; and (2) the case with batch ordering, under which we prove the optimality of the(r,Nq,e)policy. Finally, we conduct numerical studies to provide additional managerial insights.
Selective Blockade of Matrix Metalloprotease-14 with a Monoclonal Antibody Abrogates Invasion, Angiogenesis, and Tumor Growth in Ovarian Cancer
Authors: Kaimal Rajani , Aljumaily Raid , Tressel Sarah L. , Pradhan Rutika V. , Covic Lidija , Kuliopulos Athan , Zarwan Corrine , Kim Young B. , Sharifi Sheida , Agarwal Anika
Published: February 2013

Most patients with ovarian cancer are diagnosed late in progression and often experience tumor recurrence and relapses due to drug resistance. Surface expression of matrix metalloprotease (MMP)-14 on ovarian cancer cells stimulates a tumor–stromal signaling pathway that promotes angiogenesis and tumor growth. In a cohort of 92 patients, we found that MMP-14 was increased in the serum of women with malignant ovarian tumors. Therefore, we investigated the preclinical efficacy of a MMP-14 monoclonal antibody that could inhibit the migratory and invasive properties of aggressive ovarian cancer cells in vitro. MMP-14 antibody disrupted ovarian tumor–stromal communication and was equivalent to Avastin in suppressing blood vessel growth in mice harboring Matrigel plugs. These effects on angiogenesis correlated with downregulation of several important angiogenic factors. Furthermore, mice with ovarian cancer tumors treated with anti–MMP-14 monotherapy showed a marked and sustained regression in tumor growth with decreased angiogenesis compared with immunoglobulin G (IgG)-treated controls. In a model of advanced peritoneal ovarian cancer, MMP-14–dependent invasion and metastasis was effectively inhibited by intraperitoneal administration of monoclonal MMP-14 antibody. Together, these studies provide a preclinical proof-of-concept for MMP-14 targeting as an adjuvant treatment strategy for advanced ovarian cancer. Cancer Res; 73(8); 2457–67. ©2013 AACR.
Higher Frequencies of GARP+CTLA-4+Foxp3+ T Regulatory Cells and Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma Patients Are Associated with Impaired T-Cell Functionality
Authors: Kalathil Suresh , Lugade Amit A. , Miller Austin , Iyer Renuka , Thanavala Yasmin
Published: February 2013

The extent to which T-cell–mediated immune surveillance is impaired in human cancer remains a question of major importance, given its potential impact on the development of generalized treatments of advanced disease where the highest degree of heterogeneity exists. Here, we report the first global analysis of immune dysfunction in patients with advanced hepatocellular carcinoma (HCC). Using multi-parameter fluorescence-activated cell sorting analysis, we quantified the cumulative frequency of regulatory T cells (Treg), exhausted CD4+ helper T cells, and myeloid-derived suppressor cells (MDSC) to gain concurrent views on the overall level of immune dysfunction in these inoperable patients. We documented augmented numbers of Tregs, MDSC, PD-1+–exhausted T cells, and increased levels of immunosuppressive cytokines in patients with HCC, compared with normal controls, revealing a network of potential mechanisms of immune dysregulation in patients with HCC. In dampening T-cell–mediated antitumor immunity, we hypothesized that these processes may facilitate HCC progression and thwart the efficacy of immunotherapeutic interventions. In testing this hypothesis, we showed that combined regimens to deplete Tregs, MDSC, and PD-1+ T cells in patients with advanced HCC restored production of granzyme B by CD8+ T cells, reaching levels observed in normal controls and also modestly increased the number of IFN-γ producing CD4+ T cells. These clinical findings encourage efforts to restore T-cell function in patients with advanced stage disease by highlighting combined approaches to deplete endogenous suppressor cell populations that can also expand effector T-cell populations. Cancer Res; 73(8); 2435–44. ©2013 AACR.
Dynamics of Senescent Cell Formation and Retention Revealed by p14ARF Induction in the Epidermis
Authors: Tokarsky-Amiel Ronit , Azazmeh Narmen , Helman Aharon , Stein Yan , Hassan Alia , Maly Alexander , Ben-Porath Ittai
Published: February 2013

Cellular senescence, a state of cell-cycle arrest accompanied by dramatic morphologic and metabolic changes, is a central means by which cells respond to physiologic stress and oncogene activity. Senescence is thought to play important roles in aging and in tumor suppression, yet the dynamics by which senescent cells are formed, their effects on tissue function and their eventual fate are poorly understood. To study cellular senescence within an adult tissue, we developed transgenic mice inducibly expressing p14ARF (human ortholog of murine p19ARF), a central activator of senescence. Induction of p14ARF in the epidermis rapidly led to widespread apoptosis and cell-cycle arrest, a stage that was transient, and was followed by p53-dependent cellular senescence. The endogenous Cdkn2a products p19ARF and p16Ink4a were activated by the transgenic p14ARF through p53, revealing a senescence-promoting feed-forward loop. Commitment of cells to senescence required continued p14ARF expression, indicating that entry into this state depends on a persistent signal. However, once formed, senescent cells were retained in the epidermis, often for weeks after transgene silencing, indicating an absence of an efficient rapidly acting mechanism for their removal. Stem cells in the hair follicle bulge were largely protected from apoptosis upon p14ARF induction, but irreversibly lost their ability to proliferate and initiate follicle growth. Interestingly, induction of epidermal hyperplasia prevented the appearance of senescent cells upon p14ARF induction. Our findings provide basic insights into the dynamics of cellular senescence, a central tumor- suppressive mechanism, and reveal the potential for prolonged retention of senescent cells within tissues. Cancer Res; 73(9); 2829–39. ©2013 AACR.
Chemoprevention of Head and Neck Cancer by Simultaneous Blocking of Epidermal Growth Factor Receptor and Cyclooxygenase-2 Signaling Pathways: Preclinical and Clinical Studies
Authors: Shin Dong M. , Zhang Hongzheng , Saba Nabil F. , Chen Amy Y. , Nannapaneni Sreenivas , Amin A.R.M. Ruhul , Müller Susan , Lewis Melinda , Sica Gabriel , Kono Scott , Brandes Johann C. , Grist William J. , Moreno-Williams Rachel , Beitler Jonathan J. , Thomas Sufi M. , Chen Zhengjia , Shin Hyung Ju C. , Grandis Jennifer R. , Khuri Fadlo R. , Chen Zhuo Georgia
Published: February 2013

Purpose: We investigated the efficacy and underlying molecular mechanism of a novel chemopreventive strategy combining EGF receptor (EGFR) tyrosine kinase inhibitor (TKI) with cyclooxygenase-2 inhibitor (COX-2I).

Experimental Design: We examined the inhibition of tumor cell growth by combined EGFR-TKI (erlotinib) and COX-2I (celecoxib) treatment using head and neck cancer cell lines and a preventive xenograft model. We studied the antiangiogenic activity of these agents and examined the affected signaling pathways by immunoblotting analysis in tumor cell lysates and immunohistochemistry (IHC) and enzyme immunoassay (EIA) analyses on the mouse xenograft tissues and blood, respectively. Biomarkers in these signaling pathways were studied by IHC, EIA, and an antibody array analysis in samples collected from participants in a phase I chemoprevention trial of erlotinib and celecoxib.

Results: The combined treatment inhibited head and neck cancer cell growth significantly more potently than either single agent alone in cell line and xenograft models, and resulted in greater inhibition of cell-cycle progression at G1 phase than either single drug. The combined treatment modulated the EGFR and mTOR signaling pathways. A phase I chemoprevention trial of combined erlotinib and celecoxib revealed an overall pathologic response rate of 71% at time of data analysis. Analysis of tissue samples from participants consistently showed downregulation of EGFR, pERK, and pS6 levels after treatment, which correlated with clinical response.

Conclusion: Treatment with erlotinib combined with celecoxib offers an effective chemopreventive approach through inhibition of EGFR and mTOR pathways, which may serve as potential biomarkers to monitor the intervention of this combination in the clinic. Clin Cancer Res; 19(5); 1244–56. ©2013 AACR.
Caloric Restriction Reverses Obesity-Induced Mammary Gland Inflammation in Mice
Authors: Bhardwaj Priya , Du Baoheng , Zhou Xi Kathy , Sue Erika , Harbus Michael D. , Falcone Domenick J. , Giri Dilip , Hudis Clifford A. , Kopelovich Levy , Subbaramaiah Kotha , Dannenberg Andrew J.
Published: February 2013

Obesity is a risk factor for the development of hormone receptor–positive breast cancer in postmenopausal women. Estrogen synthesis is catalyzed by aromatase. Recently, we identified an obesity→inflammation→aromatase axis in mouse models and women. In mouse models of obesity, inflammatory foci characterized by crown-like structures (CLS) consisting of dead adipocytes encircled by macrophages were found in the mammary gland. CLS of the breast were found in most overweight and obese women. CLS were associated with adipocyte hypertrophy, activation of NF-κB, elevated levels of proinflammatory mediators and aromatase, and increased expression of the progesterone receptor (PR). Collectively, these findings provide a plausible explanation for the link between obesity, chronic inflammation, and postmenopausal breast cancer. Here, we investigated whether caloric restriction (CR) reversed the inflammatory state and related molecular changes in the mammary gland of obese mice. Obese ovariectomized C57BL/6J mice were subjected to 30% CR for 7 or 14 weeks. Findings in CR mice were compared with the results in mice fed a high-fat diet ad libitum or with control mice fed a low-fat diet. CR was associated with more than a 75% decrease in mammary CLS/cm2. Reduced histologic inflammation following CR was associated with decreased adipocyte diameter and monocyte chemoattractant protein-1 (MCP-1) levels, reduced NF-κB binding activity, and normalization of levels of proinflammatory mediators, aromatase, and PR. In summary, obesity-related inflammation of the mammary gland and elevated aromatase and PR levels were reversed with CR. Our results provide a rationale for determining whether weight loss can reverse breast inflammation associated with obesity in women. Cancer Prev Res; 6(4); 282–9. ©2013 AACR.
Sorafenib in Elderly Patients with Advanced Hepatocellular Carcinoma: A Case Series
Authors: Montella Liliana , Addeo Raffaele , Cennamo Gregorio , Vincenzi Bruno , Palmieri Rita , Sperlongano Pasquale , Sperlongano Rossella , Iodice Patrizia , Russo Paola , Del Prete Salvatore
Published: February 2013

Objective: The management of hepatocellular carcinoma (HCC) in elderly patients is significantly more complicated than in younger patients because of medical comorbidities, advanced status at diagnosis, reduced liver function and altered drug pharmacokinetics. Our objective was a revision of the charts of unselected elderly patients with HCC being treated with a reduced starting dose of sorafenib. Methods: Activity, adverse events and quality of life were evaluated during the treatment. Sixty patients (47 males and 13 females) aged more than 70 years old (range 70-90, median 76 years) were retrospectively reviewed. Results: One complete and one partial response were achieved in the series (overall response rate 3.3%). Stable disease accounted for 76.6% (46 out of 60 patients). The disease control rate (complete plus partial response plus stable disease) was 80%. Median time to progression (TTP) was 7.0 months (95% CI, 5.2-8.7 months) and median survival was 10.0 months (95% CI, 5.0-14.9 months). Thrombosis correlated to TTP. Full doses of sora-fenib were reached in 11 out of 60 patients (18.3%). The evaluation of quality of life did not show any significant change during the study. Conclusions: Sorafenib at a reduced dose can be safely used in elderly HCC patients with maintenance of activity and increased tolerability.
Assessment of Liver Fibrosis with Real-Time Tissue Elastography in Chronic Viral Hepatitis
Authors: Yada Norihisa , Kudo Masatoshi , Morikawa Hiroyasu , Fujimoto Kenji , Kato Michio , Kawada Norifumi
Published: February 2013

Objective: The aim of this study was to assess prospectively the accuracy of measurement of liver fibrosis with real-time tissue elastography (RTE) in patients with chronic viral hepatitis. Methods: Two hundred and forty-five patients were prospectively enrolled. Nine image features were measured from strain images, and Liver Fibrosis Index (LFI) was calculated from these features. Fibrosis stage was diagnosed from pathological specimens obtained by ultrasound-guided biopsy. LFI and serological markers were compared with pathological diagnosis, and the diagnostic performance of RTE was compared. Results: LFI in stages F0-F1, F2, F3 and F4 was 1.58, 2.03, 2.40 and 2.86, respectively, demonstrating a stepwise increase with increasing severity of liver fibrosis (p < 0.001). LFI in F2 did not significantly differ from that in F3, whereas for all other combinations of stages, there were significant differences. The area under the receiver operating characteristic curve of the LFI, platelet count, aspartate/alanine aminotransferase ratio, aspartate aminotransferase-to-platelet ratio, and FibroIndex for predicting F3 stage or higher (F0-F2 vs. F3-F4) was 0.865, 0.824, 0.708, 0.789 and 0.828, respectively. Conclusions: RTE is useful for diagnosis of liver fibrosis, regardless of stage, in patients with chronic viral hepatitis.
Role of Gadolinium-Ethoxybenzyl-Diethylenetriamine Pentaacetic Acid-Enhanced Magnetic Resonance Imaging in the Management of Hepatocellular Carcinoma: Consensus at the Symposium of the 48th Annual Meeting of the Liver Cancer Study Group of Japan
Authors: Kudo Masatoshi , Matsui Osamu , Sakamoto Michiie , Kitao Azusa , Kim Tonsok , Ariizumi Shun-ichi , Ichikawa Tomoaki , Kobayashi Satoshi , Imai Yasuharu , Izumi Namiki , Fujinaga Yasunari , Arii Shigeki
Published: February 2013

We summarize here the consensus reached at the Symposium of the 48th Annual Meeting of the Liver Cancer Study Group of Japan held in Kanazawa on July 20th and 21st, 2012, on the role of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) in the management of hepatocellular carcinoma (HCC). Currently, dynamic CT is the first choice of imaging modality when HCC is suspected. EOB-MRI is useful for differentiation and definitive diagnosis of HCC when dynamic CT/MRI does not show conclusive findings for HCC. In addition, contrast- enhanced ultrasound with Sonazoid is useful for making a decision on whether or not to treat a hypovascular lesion <1 cm when the nodules are shown with low intensity in the hepatocyte phase of EOB-MRI. Furthermore, EOB-MRI should be performed in selected cases of HCC ultrahigh-risk groups every 3-4 months, or EOB-MRI should be performed at least once at the first visit in all HCC ultrahigh-risk groups.
Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: Recent Progression and Perspective
Authors: Takayasu Kenichi
Published: February 2013

Transcatheter arterial chemoembolization (TACE) is widely performed in 32% of patients with unresectable hepatocellular carcinoma (HCC) at initial diagnosis and in 58% of those with recurrent HCC in Japan. However, the patient population which undergoes TACE is heterogeneous, and thus the 3-year survival rate varies from 26 to 47%. The selection criteria for TACE is 2-3 tumors >3 cm or 4 or more tumors in patients with liver damage A/B (corresponding well to Child-Pugh class A/B) and absence of vascular invasion and extrahepatic spread, as proposed by Japanese guidelines. The 3-year survival rate of TACE for patients with 2-3 tumors >3 cm or 4 or more tumors was 55 and 46%, respectively, in Child-Pugh A and 30 and 22%, respectively, in class B. These outcomes could help in understanding the various results of TACE in different backgrounds in the East and West. Recently, TACE with calibrated drug-eluting beads loaded with doxorubicin showed a similar tumor response and radioembolization with yttrium-90 microspheres demonstrated a similar median survival compared with conventional TACE. Based on these results, the combination of TACE and novel molecular targeted agents can be used to elucidate the synergic effect on survival.
Yttrium-90 Radioembolization for Hepatocellular Carcinoma: What We Know and What We Need to Know
Authors: Kim Yun Hwan , Kim Do Young
Published: February 2013

In spite of substantial progress in the management of hepatocellular carcinoma (HCC), suboptimal treatment results are frequently seen in the intermediate and advanced stages of HCC. The current staging system indicates that multinodular HCC without vascular invasion needs to be treated by transarterial chemoembolization (TACE) and HCC with vascular nvasion or distant metastasis is linked to sorafenib, an an-tiangiogenic therapy. Radioembolization with yttrium-90 (90Y) is a recently introduced liver-directed therapy employing a catheter-based approach. Growing data suggest that 90Y radioembolization has a potent anticancer effect with negligible adverse events if appropriate pretreatment evaluations including dosimetry, calculation of lung shunt fraction and assessment of vascular anatomy are performed. Retrospective and small prospective studies have shown response rates and survival after 90Y therapy which are comparable to TACE and sorafenib in the intermediate and advanced stages, respectively. Although a large sample size is necessary to compare the outcome between TACE and radioembolization in intermediate-stage HCC, selected populations, for whom TACE would not be effective, are candidates for testing the role of 90Y radioembolization. A multidisciplinary, combined approach in advanced HCC using loco-regional therapy such as radioembolization and systemic therapy including sorafenib also has to be investigated.
Biomarker Studies on Radiotherapy to Hepatocellular Carcinoma
Authors: Tsai Chiao-Ling , Koong Albert C. , Hsu Feng-Ming , Graber Madeline , Chen I-Sin , Cheng Jason Chia-Hsien
Published: February 2013

Radiotherapy (RT) has been gradually integrated into the multimodality treatment for hepatocellular carcinoma (HCC). The various patterns of failure in HCC patients undergoing RT drive the need of effective biomarkers to guide treatment decisions. Limited numbers of biomarkers have been investigated in HCC, with even fewer of them for patients treated by RT. Serum or plasma biomarkers measured by enzyme-linked immunosorbent assay were the most common practice. Of particular interest are those biomarkers that are detectable early in the course of radiotherapy which correlated with ultimate clinical outcome. Functional magnetic resonance imaging (MRI) is increasingly used to evaluate the imaging pattern indicative of disease control following RT. Positron emission tomography shows that pre-RT standard uptake values associate with various types of recurrence after treatment. Proximity ligation assay (PLA) is evolving with the unique features of dual-probe identification, ligation and amplification to allow the small volume of serum/plasma samples for evaluating multiple biomarkers. We demonstrate the screening work of biomarkers by PLA with pre- and post-RT serum samples from HCC patients undergoing RT. Efforts are being made to search for the potential biomarkers for HCC patients treated by RT.
The Prognostic Value of Vascular Endothelial Growth Factor in Hepatocellular Carcinoma for Predicting Metastasis after Curative Resection
Authors: Minata Mutsuko , Harada Kouji H. , Kudo Masatoshi , Ikai Iwao , Nishida Naoshi
Published: February 2013

Objectives: Hepatocellular carcinoma (HCC) frequently recurs even after curative resection. The purpose of this study was to identify factors predictive for postoperative recurrence of HCC in patients who underwent curative resection using immunohistochemistry. Methods: Expression of vascular endothelial growth factor (VEGF), E-cadherin and cyclin D1 in HCC tissue were analyzed for 133 HCC patients who underwent curative resection of tumors using immunohistochemical analysis. Relationships of expressions and disease-free survival of HCC were evaluated using univariate and multivariate analyses. Results: The average period of follow-up of the patients was 6.7 years. Multivariate analyses revealed that only strong expression of VEGF in HCC tissue was significantly associated with metastatic recurrence (p < 0.001, hazard ratio, HR, 3.32). Conclusions: Evaluating VEGF in HCC tissue after surgical resection has predictive value for metastatic HCC recurrence. The ability to risk stratify should improve the treatment strategies after hepatectomy.
Cerebral Near-Infrared Spectroscopy during Transition of Healthy Term Newborns
Authors: Almaazmi Munira , Schmid Manuel B. , Havers Stefanie , Reister Frank , Lindner Wolfgang , Mayer Benjamin , Hummler Helmut D. , Fuchs Hans
Published: February 2013

Background: Values of regional cerebral tissue oxygen saturation (cStO2) have been described during transition of term and preterm infants after birth. However, use of different devices precludes comparison of measurements. Objective: To measure cStO2 during transition of term infants using a calibrated 4-wavelength laser light source near-infrared spectroscopy oximeter (FORE-SIGHT) to obtain data that allow comparison with cStO2 of very-low-birth-weight (VLBW) infants using this oximeter and with cStO2 of term infants using different oximeters. Methods:cStO2 (FORE-SIGHT oximeter), preductal arterial oxygen saturation and heart rate were measured in 46 healthy term infants (n = 20 spontaneous delivery, n = 22 caesarean section, n = 4 assisted vaginal delivery) during the first 10 min after delivery. Results: The median (interquartile range) cStO2 at 2 min after birth was 42% (39-46) after spontaneous delivery, 42% (30-52) after caesarean section and 36% (20-53) after assisted vaginal delivery (no difference between groups). In association with increasing arterial oxygen saturation and heart rate, cStO2 increased continuously and reached a steady state approximately 8 min after birth of 62-77% (interquartile range) in all three groups. Conclusions: Healthy term newborns had similar cStO2 changes from 2 min after birth regardless of the mode of delivery. cStO2 of healthy term infants was lower than cStO2 of VLBW infants during transition. cStO2 values as measured by the FORE-SIGHT oximeter seem in the range of values as measured by the NIRO 300 oximeter. They were lower than values as measured by the INVOS 5100 oximeter.
Diabetes Does not Affect Outcome of Symptomatic Carotid Stenosis Treated with Endovascular Techniques
Authors: Lago Aida , Parkhutik Vera , Tembl Jose Ignacio , Bermejo Ara , Aparici Fernando , Mainar Esperanza , Vázquez-Añón Víctor
Published: February 2013

Background: The influence of diabetes on carotid revascularization techniques is controversial, with few data regarding angioplasty and stenting (CAS). Our purpose was to analyze whether its presence constitutes a risk factor for poor outcome of patients with carotid stenosis treated with CAS. Methods: We compared 30-day and long term morbidity and mortality, as well as restenosis rates, of non diabetic and diabetic patients with symptomatic carotid stenosis treated with endovascular techniques. Results: 318 consecutive patients, 116 (36.5%) of them diabetics, were followed for a median of 56 months. Cumulative 30-day stroke, ischemic cardiopathy and death rate was 4% for non diabetics and 5.2% for diabetics (non significant). Long term stroke and mortality rate was 26.4% for the first group and 34.3% for the second (non significant). The most frequent causes of death were myocardial infarction (17.5% non diabetics, 44% diabetics, p = 0.04), ischemic stroke (12.5% non diabetics, 4% diabetics, non significant) and cancer (30% non diabetics, 16% diabetics, non significant). Twelve patients (6.4%) had restenosis ≥50%, 5.9% non diabetic, 7.4% diabetic, also without statistical significance. Conclusions: In our series, endovascular treatment is both efficient and safe in diabetic patients with symptomatic carotid stenosis; therefore, the presence of diabetes mellitus did not increase the risks linked to CAS procedure.
Ibuprofen and Lipoic Acid Conjugate Neuroprotective Activity Is Mediated by Ngb/Akt Intracellular Signaling Pathway in Alzheimer's Disease Rat Model
Authors: Zara Susi , De Colli Marianna , Rapino Monica , Pacella Stephanie , Nasuti Cinzia , Sozio Piera , Di Stefano Antonio , Cataldi Amelia
Published: February 2013

Background: Alzheimer's disease (AD) is a frequent form of senile dementia. Neuroglobin (Ngb) has a neuroprotective role and decreases Aβ peptide levels. Ngb, promoting Akt phosphorylation, activates cell survival involving cyclic-nucleotide response element-binding protein (CREB). A new molecule (IBU-LA) was synthetized and administered to an AD rat model to counteract AD progression. Objective: The aim of this study was to investigate the IBU-LA-mediated induction of Ngb neuroprotective and antiapoptotic activities. Methods: Brain morphology was analyzed through Bielschowsky staining, Aβ(1-40) and Ngb expression by immunohistochemistry. Akt, p-Akt, CREB and p-CREB expression was evaluated by Western blot, apoptosis through cytochrome C/Apaf 1 immunocomplex formation, and TUNEL analysis. Results: Bielschowsky staining and Aβ(1-40) expression show few nerve connections and Aβ(1-40) expression in an Aβ sample, preserved neuronal cells and Aβ(1-40) expression lowering in an IBU sample, mostly in IBU-LA. The Ngb level decreases in Aβ samples, compared to control and IBU-LA samples. p-Akt/Akt and p-CREB/CREB ratios reveal a reduction in Aβ sample, going back to the basal level in control and IBU-LA samples. Cytochrome C/Apaf 1 co-immunoprecipitate occurs and TUNEL-positive nuclei percentage decreases in Aβ sample. Probe test performance shows an increased spatial reference memory in the IBU-LA compared to the Aβ sample; no significant differences were seen between the IBU-LA and IBU samples. Conclusion: This evidence reveals that IBU-LA administration has the capability to maintain a high Ngb level allowing Ngb to perform a neuroprotective and antiapoptotic role, representing a valid tool in the therapeutic strategy of AD progression.
Serum Ferritin and Vitamin D in Female Hair Loss: Do They Play a Role?
Authors: Rasheed H. , Mahgoub D. , Hegazy R. , El-Komy M. , Abdel Hay R. , Hamid M.A. , Hamdy E.
Published: February 2013

Aim: Evaluation of serum ferritin and vitamin D levels in females with chronic telogen effluvium (TE) or female pattern hair loss (FPHL), in order to validate their role in these common hair loss diseases. Methods: Eighty females (18 to 45 years old) with hair loss, in the form of TE or FPHL, and 40 age-matched females with no hair loss were included in the study. Diagnosis was based upon clinical examination as well as trichogram and dermoscopy. Serum ferritin and vitamin D2 levels were determined for each participant. Results: Serum ferritin levels in the TE (14.7 ± 22.1 μg/l) and FPHL (23.9 ± 38.5 μg/l) candidates were significantly lower than in controls (43.5 ± 20.4 μg/l). Serum vitamin D2 levels in females with TE (28.8 ± 10.5 nmol/l) and FPHL (29.1 ± 8.5 nmol/l) were significantly lower than in controls (118.2 ± 68.1 nmol/l; p < 0.001). These levels decreased with increased disease severity. Serum ferritin cut-off values for TE and FPHL were 27.5 and 29.4 μg/l, respectively, and those for vitamin D were 40.9 and 67.9 nmol/l. Conclusion: Low serum ferritin and vitamin D2 are associated with hair loss in females with TE and FPHL. Screening to establish these levels in cases of hair loss and supplementing with them when they are deficient may be beneficial in the treatment of disease.
Psychological Sweating: A Systematic Review Focused on Aetiology and Cutaneous Response
Authors: Harker M.
Published: February 2013

Psychological sweating in response to emotive stimuli like stress, anxiety and pain occurs over the whole body surface, but is most evident on the palms, soles, face and axilla. This is primarily a consequence of high eccrine sweat gland densities at these body sites. Cholinergic innervation is the primary effector eliciting activation of eccrine sweat glands during periods of acute psychological stress. A dual innervation pathway for eccrine glands (adrenergic and cholinergic) may augment increased sweat output, but this remains to be substantiated. Circulating catecholamines appear not to mediate eccrine gland activity, but may play a role in the activation of apocrine sweat glands. Apocrine sweating is strongly regulated by psychological stimuli and localised to those body sites hosting apocrine glands, with adrenergic peripheral pathways being the primary effector. Accordingly, in the axilla psychological sweating leads to increased sweat output and malodour formation, although this form of sweating at this body site is not observed until puberty.