bluuebunny/crossref_metadata_2025 huggingface dataset:
Voluminous Extracardiac Adult Rhabdomyoma of the Neck: A Case Presentation
Authors: Maglio Riccardo , Francesco Scicchitano , Paolo Magistri , Stefano Valabrega , Francesco D'Angelo , Giovanni Ramacciato
Published: December 2012

Introduction. Rhabdomyomas of the head and neck are exceptionally rare benign mesenchymal tumors. Rare cases have been reported to involve other sites of the body including the head and neck regions.Case Presentation. We report a case of voluminous extracardiac adult rhabdomyoma affecting adult patients and initially seen as slowly growing, indolent neoplasms. The patient is a seventy-year old male Italian patient.Conclusion. Adult extracardiac rhabdomyoma is a rare benign tumor that may present with symptoms that vary from aerodigestive tract obstruction to remaining asymptomatic for many years. Although histology is very characteristic, several differential diagnoses have to be considered. To our knowledge, this is the first case of voluminous adult-type symptomless rhabdomyoma.
In Vitro and In Vivo Evaluation of Oxatomide β-Cyclodextrin Inclusion Complex
Authors: Hashem Fahima M. , Mostafa Mohamed , Shaker Mahmoud , Nasr Mohamed
Published: December 2012

The objective of this study was to evaluate the influence of oxatomide β-cyclodextrin inclusion complex on the physicochemical properties and bioavailability of the drug. Oxatomide β-cyclodextrin solid complex was prepared with equimolar ratio of both oxatomide and β-cyclodextrin in presence or absence of water soluble polymers using different techniques. The coevaporated complex prepared in presence of PVP-K15 showed a prompt drug release and significantly increased % dissolution efficiency compared to the pure oxatomide. Moreover, the results of bioavailability evaluation of this complex in rabbits compared to commercial drug product indicated a 73.15% increase in the oral bioavailability of oxatomide. In conclusion, inclusion complex of oxatomide with β-cyclodextrin prepared by coevaporation in presence of PVP-K15 not only results in an enhancement of the oxatomide dissolution rate but also improves the bioavailability of oxatomide.
Homing of Human B Cells to Lymphoid Organs and B-Cell Lymphoma Engraftment Are Controlled by Cell Adhesion Molecule JAM-C
Authors: Doñate Carmen , Ody Christiane , McKee Thomas , Ruault-Jungblut Sylvie , Fischer Nicolas , Ropraz Patricia , Imhof Beat A. , Matthes Thomas
Published: December 2012

Junctional adhesion molecule C (JAM-C) is expressed by vascular endothelium and human but not mouse B lymphocytes. The level of JAM-C expression defines B-cell differentiation stages and allows the classification of marginal zone–derived (JAM-C–positive) and germinal center–derived (JAM-C–negative) B-cell lymphomas. In the present study, we investigated the role of JAM-C in homing of human B cells, using a xenogeneic nonobese diabetic/severe combined immunodeficient mouse model. Treatment with anti-JAM-C antibodies in short-term experiments reduced migration of normal and malignant JAM-C–expressing B cells to bone marrow, lymph nodes, and spleen. Blocking homing to the spleen is remarkable, as most other antiadhesion antibodies reduce homing of B cells only to bone marrow and lymph nodes. Long-term administration of anti-JAM-C antibodies prevented engraftment of JAM-Cpos lymphoma cells in bone marrow, spleen, and lymph nodes of mice. Plasmon resonance studies identified JAM-B as the major ligand for JAM-C, whereas homotypic JAM-C interactions remained at background levels. Accordingly, anti-JAM-C antibodies blocked adhesion of JAM-C–expressing B cells to their ligand JAM-B, and immunofluorescence analysis showed the expression of JAM-B on murine and human lymphatic endothelial cells. Targeting JAM-C could thus constitute a new therapeutic strategy to prevent lymphoma cells from reaching supportive microenvironments not only in the bone marrow and lymph nodes but also in the spleen. Cancer Res; 73(2); 640–51. ©2012 AACR.
Therapeutic Effects of Deleting Cancer-Associated Fibroblasts in Cholangiocarcinoma
Authors: Mertens Joachim C. , Fingas Christian D. , Christensen John D. , Smoot Rory L. , Bronk Steven F. , Werneburg Nathan W. , Gustafson Michael P. , Dietz Allan B. , Roberts Lewis R. , Sirica Alphonse E. , Gores Gregory J.
Published: December 2012

Cancer-associated fibroblasts (CAF) are abundant in the stroma of desmoplastic cancers where they promote tumor progression. CAFs are “activated” and as such may be uniquely susceptible to apoptosis. Using cholangiocarcinoma as a desmoplastic tumor model, we investigated the sensitivity of liver CAFs to the cytotoxic drug navitoclax, a BH3 mimetic. Navitoclax induced apoptosis in CAF and in myofibroblastic human hepatic stellate cells but lacked similar effects in quiescent fibroblasts or cholangiocarcinoma cells. Unlike cholangiocarcinoma cells, neither CAF nor quiescent fibroblasts expressed Mcl-1, a known resistance factor for navitoclax cytotoxicity. Explaining this paradox, we found that mitochondria isolated from CAFs or cells treated with navitoclax both released the apoptogenic factors Smac and cytochrome c, suggesting that they are primed for cell death. Such death priming in CAFs appeared to be due, in part, to upregulation of the proapoptotic protein Bax. Short hairpin RNA-mediated attenuation of Bax repressed navitoclax-mediated mitochondrial dysfunction, release of apoptogenic factors, and apoptotic cell death. In a syngeneic rat model of cholangiocarcinoma, navitoclax treatment triggered CAF apoptosis, diminishing expression of the desmoplastic extracellular matrix protein tenascin C, suppressing tumor outgrowth, and improving host survival. Together, our findings argue that navitoclax may be useful for destroying CAFs in the tumor microenvironment as a general strategy to attack solid tumors. Cancer Res; 73(2); 897–907. ©2012 AACR.
CYP2D6 Metabolism and Patient Outcome in the Austrian Breast and Colorectal Cancer Study Group Trial (ABCSG) 8
Authors: Goetz Matthew P. , Suman Vera J. , Hoskin Tanya L. , Gnant Michael , Filipits Martin , Safgren Stephanie L. , Kuffel Mary , Jakesz Raimund , Rudas Margaretha , Greil Richard , Dietze Otto , Lang Alois , Offner Felix , Reynolds Carol A. , Weinshilboum Richard M. , Ames Matthew M. , Ingle James N.
Published: December 2012

Purpose: Controversy exists about CYP2D6 genotype and tamoxifen efficacy.

Experimental Design: A matched case–control study was conducted using the Austrian Breast and Colorectal Cancer Study Group Trial 8 (ABCSG8) that randomized postmenopausal women with estrogen receptor (ER)-positive breast cancer to tamoxifen for 5 years (arm A) or tamoxifen for 2 years followed by anastrozole for 3 years (arm B). Cases had disease recurrence, contralateral breast cancer, second non–breast cancer, or died. For each case, controls were identified from the same treatment arm of similar age, surgery/radiation, and tumor–node—metastasis (TNM) stage. Genotyping was conducted for alleles associated with no (PM; *3, *4, *6), reduced (IM; *10, and *41), and extensive (EM: absence of these alleles) CYP2D6 metabolism.

Results: The common CYP2D6*4 allele was in Hardy–Weinberg equilibrium. In arm A during the first 5 years of therapy, women with two poor alleles [PM/PM: OR, 2.45; 95% confidence interval (CI), 1.05–5.73, P = 0.04] and women with one poor allele (PM/IM or PM/EM: OR, 1.67; 95% CI, 0.95–2.93; P = 0.07) had a higher likelihood of an event than women with two extensive alleles (EM/EM). In years 3 to 5 when patients remained on tamoxifen (arm A) or switched to anastrozole (arm B), PM/PM tended toward a higher likelihood of a disease event relative to EM/EM (OR, 2.40; 95% CI, 0.86–6.66; P = 0.09) among women on arm A but not among women on arm B (OR, 0.28; 95% CI, 0.03–2.30).

Conclusion: In ABCSG8, the negative effects of reduced CYP2D6 metabolism were observed only during the period of tamoxifen administration and not after switching to anastrozole. Clin Cancer Res; 19(2); 500–7. ©2012 AACR.
BMS-936564/MDX-1338: A Fully Human Anti-CXCR4 Antibody Induces Apoptosis In Vitro and Shows Antitumor Activity In Vivo in Hematologic Malignancies
Authors: Kuhne Michelle R. , Mulvey Tanya , Belanger Blake , Chen Sharline , Pan Chin , Chong Colin , Cao Fei , Niekro Wafa , Kempe Tom , Henning Karla A. , Cohen Lewis J. , Korman Alan J. , Cardarelli Pina M.
Published: December 2012

Purpose: CXCR4 has been identified as a prognostic marker for acute myeloid leukemia (AML) and other malignancies. We describe the development and characterization of a fully human antibody to CXCR4 and its application for therapy of AML, non–Hodgkin lymphoma (NHL), chronic lymphoid leukemia (CLL), and multiple myeloma.

Experimental Design: Human transgenic mice were immunized with CXCR4-expressing cells, and antibodies reactive with CXCR4 were analyzed for apoptosis induction and ability to interfere with CXCL12-induced migration and calcium flux. In vivo efficacy was determined in multiple AML, NHL, and multiple myeloma xenograft tumors in severe combined immunodeficient mice.

Results: BMS-936564/MDX-1338 is a fully human IgG4 monoclonal antibody that specifically recognizes human CXCR4. In vitro studies show that MDX-1338 binds to CXCR4-expressing cells with low nanomolar affinity, blocks CXCL12 binding to CXCR4-expressing cells, and inhibits CXCL12-induced migration and calcium flux with low nanomolar EC50 values. When given as monotherapy, MDX-1338 exhibits antitumor activity in established tumors including AML, NHL, and multiple myeloma xenograft models. In addition, we show that MDX-1338 induced apoptosis on a panel of cell lines and propose that antibody-induced apoptosis is one of the mechanisms of tumor growth inhibition.

Conclusions: BMS-936564/MDX-1338 is a potent CXCR4 antagonist which is efficacious as monotherapy in tumor-bearing mice and is currently in phase I for the treatment of relapsed/refractory AML, NHL, CLL, and multiple myeloma. Clin Cancer Res; 19(2); 357–66. ©2012 AACR.
SLC1A5 Mediates Glutamine Transport Required for Lung Cancer Cell Growth and Survival
Authors: Hassanein Mohamed , Hoeksema Megan D. , Shiota Masakazu , Qian Jun , Harris Bradford K. , Chen Heidi , Clark Jonathan E. , Alborn William E. , Eisenberg Rosana , Massion Pierre P.
Published: December 2012

Purpose: We have previously identified solute-linked carrier family A1 member 5 (SLC1A5) as an overexpressed protein in a shotgun proteomic analysis of stage I non–small cell lung cancer (NSCLC) when compared with matched controls. We hypothesized that overexpression of SLC1A5 occurs to meet the metabolic demand for lung cancer cell growth and survival.

Experimental Design: To test our hypothesis, we first analyzed the protein expression of SLC1A5 in archival lung cancer tissues by immunohistochemistry and immunoblotting (N = 98) and in cell lines (N = 36). To examine SLC1A5 involvement in amino acid transportation, we conducted kinetic analysis of l-glutamine (Gln) uptake in lung cancer cell lines in the presence and absence of a pharmacologic inhibitor of SLC1A5, gamma-l-Glutamyl-p-Nitroanilide (GPNA). Finally, we examined the effect of Gln deprivation and uptake inhibition on cell growth, cell-cycle progression, and growth signaling pathways of five lung cancer cell lines.

Results: Our results show that (i) SLC1A5 protein is expressed in 95% of squamous cell carcinomas (SCC), 74% of adenocarcinomas (ADC), and 50% of neuroendocrine tumors; (ii) SLC1A5 is located at the cytoplasmic membrane and is significantly associated with SCC histology and male gender; (iii) 68% of Gln is transported in a Na+-dependent manner, 50% of which is attributed to SLC1A5 activity; and (iv) pharmacologic and genetic targeting of SLC1A5 decreased cell growth and viability in lung cancer cells, an effect mediated in part by mTOR signaling.

Conclusions: These results suggest that SLC1A5 plays a key role in Gln transport controlling lung cancer cells' metabolism, growth, and survival. Clin Cancer Res; 19(3); 560–70. ©2012 AACR.
Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma: A Review of the Current Understanding of Epidemiology, Biology, Risk Stratification, and Management of Myeloma Precursor Disease
Authors: Agarwal Amit , Ghobrial Irene M.
Published: December 2012

The term monoclonal gammopathy of undetermined significance (MGUS) was coined in 1978. The recent advances in our knowledge about MGUS and smoldering multiple myeloma (SMM) have helped us better understand the pathogenesis of myeloma. It seems that myeloma evolves from a precursor state in almost all cases. We do not completely understand the multistep process from the precursor state to myeloma, but studies like whole genome sequencing continue to improve our understanding of this process. The process of transformation may not be linear acquisition of changes, but rather a branched heterogeneous process. Clinical features that are prognostic of rapid transformation have been identified, but no specific molecular markers have been identified. Even with recent advances, multiple myeloma remains an incurable disease in the vast majority, and intervening at the precursor state provides a unique opportunity to alter the natural history of the disease. A limitation is that a vast majority of patients with precursor disease, especially low-risk MGUS, will never progress to myeloma in their lifetime, and treating these patients is not only unnecessary but may be potentially harmful. The challenge is to identify a subset of patients with the precursor state that would definitely progress to myeloma and in whom interventions will have a meaningful impact. As our understanding of the molecular and genetic processes improves, these studies will guide the selection of high-risk patients more appropriately and ultimately direct a tailored management strategy to either delay progression to symptomatic myeloma or even “cure” a person at this premalignant stage. Clin Cancer Res; 19(5); 985–94. ©2012 AACR.
A Randomized, Placebo-Controlled, Preoperative Trial of Allopurinol in Subjects with Colorectal Adenoma
Authors: Puntoni Matteo , Branchi Daniela , Argusti Alessandra , Zanardi Silvia , Crosta Cristiano , Meroni Emanuele , Munizzi Francesco , Michetti Paolo , Coccia Gianni , De Roberto Giuseppe , Bandelloni Roberto , Turbino Laura , Minetti Egle , Mori Marco , Salvi Sandra , Boccardo Simona , Gatteschi Beatrice , Benelli Roberto , Sonzogni Angelica , DeCensi Andrea
Published: December 2012

Inflammation and oxidative stress play a crucial role in the development of colorectal cancer (CRC) and interference with these mechanisms represents a strategy in CRC chemoprevention. Allopurinol, a safe molecular scavenger largely used as antigout agent, has been shown to increase survival of patients with advanced CRC and to reduce CRC incidence in long-term gout users in epidemiologic studies. We conducted a randomized, double-blind, placebo-controlled preoperative trial in subjects with colorectal adenomatous polyps to assess the activity of allopurinol on biomarkers of colorectal carcinogenesis.

After complete colonoscopy and biopsy of the index polyp, 73 subjects with colorectal adenomas were assigned to either placebo or one of two doses of allopurinol (100 mg or 300 mg) and treated for four weeks before polyp removal. Change of Ki-67 labeling index in adenomatous tissue was the primary endpoint. Secondary endpoints were the immunohistochemical (IHC) expression of NF-κB, β-catenin, topoisomerase-II-α, and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL) in adenomatous polyps and normal adjacent colonic tissue.

Compared with placebo, Ki-67 levels were not significantly modulated by allopurinol, whereas β-catenin and NF-κB expression levels decreased significantly in adenomatous tissue, with a mean change from baseline of −10.6%, 95% confidence interval (CI), −20.5 to −0.7, and −8.1%, 95% CI, −22.7 to 6.5, respectively. NF-κB also decreased significantly in normal adjacent tissue (−16.4%; 95% CI, −29.0 to −3.8). No dose–response relationship was noted, except for NF-κB expression in normal tissue.

Allopurinol can inhibit biomarkers of oxidative activation in colon adenomatous polyps and normal adjacent tissue. Further studies should define its potential chemopreventive activity. Cancer Prev Res; 6(2); 74–81. ©2012 AACR.
Ovarian Serous Borderline Tumor Detected by Conventional Papanicolaou Smear: A Case Report
Authors: Tepeoğlu Merih , Özen Özlem , Ayhan Ali
Published: December 2012

Background: Although the Papanicolaou (Pap) smear was originally designed to detect premalignant cervical lesions and cancer, it has become apparent that malignant cells from extrauterine primaries may also appear in the smears. Here, we report a case of a serous borderline tumor (SBT) of the ovary that was detected by a conventional Pap smear. Case Report: In a 34-year-old woman, who was operated on for a left borderline ovarian tumor 2 years ago, glandular dysplasia was discovered in a Pap smear screening. The Pap smear showed a large number of atypical glandular cells forming 3-dimensional papillary clusters. The cell clusters were enlarged and had variably sized round or oval nuclei. The background was clean, and this finding pointed to the noncervical origin of the malignant cells. A right ovarian cystic mass was discovered and a laparotomy performed. A histologic examination of the ovarian mass revealed a SBT of the ovary. Conclusion: This case illustrates the value of the Pap smear in discovering unsuspected extrauterine malignancies, including SBTs of the ovary.
Stem Cell Therapy for Male Urinary Incontinence
Authors: Giberti C. , Gallo F. , Schenone M. , Cortese P. , Ninotta G.
Published: December 2012

Introduction: Among the medical and surgical options which have been proposed in the last years for the management of male stress urinary incontinence (SUI), stem cell therapy represents a new frontier treatment. The aim of this paper is to update the current status of stem cell therapy in animal and human studies for the management of iatrogenic male SUI. Material and Methods: A PubMed review of the literature on stem cell therapy for the treatment of male SUI was performed. Results: Regarding animal studies, bone marrow-, muscle- and adipose-derived stem cells have been widely studied, showing regeneration of the urethral sphincter and recovery of the damaged pelvic nerves. With regard to human studies, only four papers are available in the literature using muscle- and adipose-derived stem cells which reported a significant improvement in sphincteric function and incontinence with no severe side effects. Conclusions: In spite of these promising results, further studies are needed with longer follow-ups and larger numbers of patients in order to clarify the potential role of stem cell therapy for the treatment of male SUI.
Metrical Structure and Production of English Rhythm
Authors: Erickson Donna , Suemitsu Atsuo , Shibuya Yoshiho , Tiede Mark
Published: December 2012

This paper examines kinematic patterns of jaw opening and associated F1 values of 4 American English speakers in productions of the sentence ‘I saw five bright highlights in the sky’. Results show strong-weak jaw opening alternations during the production of the utterance, and significant correlation of F1 with jaw opening for 3 of the 4 speakers. The observed jaw opening patterns correspond to metrically generated syllable stress levels for productions of the sentence by these 4 speakers.
p16INKa Immunocytochemistry in Fine-Needle Aspiration Cytology Smears of Metastatic Head and Neck Squamous Cell Carcinoma
Authors: Grimes Reni , Garcia-Buitrago Monica T. , Jorda Merce , Ganjei-Azar Parvin , Ferrell Annapoorna , Gomez-Fernandez Carmen
Published: December 2012

Objectives: Patients with head and neck squamous cell carcinoma (HNSCC) may initially present with neck metastases diagnosed by fine-needle aspiration (FNA). In these patients, it is critical to locate the primary site so that targeted therapy can be administered. Nearly a quarter of HNSCC are associated with human papillomavirus (HPV) infection. The great majority of HPV-related primaries originate in the oropharynx. p16INKa (p16) functions as a surrogate marker of HPV infection. We sought to determine if expression of p16 by immunocytochemistry (ICC) in neck metastases could assist in localizing the primary site to the oropharynx. Study Design: Diagnostic FNA cytology smears of neck metastases from 90 patients with biopsy-proven primary HNSCC were reviewed. Papanicolaou-stained slides were directly subjected to ICC, using p16 antibody. Results: Twenty-seven (30%) tumors expressed p16 by ICC; 74% of these p16-positive tumors were metastases from oropharynx. There was a significantly higher proportion of p16 expression in patients with primary oropharyngeal carcinoma (47%) versus those whose primary tumor was non-oropharyngeal (15%; p = 0.0013). Conclusions: p16 expression in FNA cytology smears of metastatic HNSCC is a useful indicator of oropharyngeal origin and can be used to help localize the primary site in cases where this is not clinically evident.
The Unique Liquid-Based Cytologic Findings of Thyroid Signet-Ring Follicular Adenoma: A Report of Two Cases with Fine Needle Aspiration Cytology
Authors: Jung Yoon Yang , Kim Mi Kyung , Lee Tae Jin , Lee Chung Hun , Lee Chae Young , Lee Hyebin , Ryu Han Suk
Published: December 2012

Background: Signet-ring follicular adenoma is a rare variant of follicular neoplasm, which has only been described using the conventional smear cytologic preparation. Here we report the unique cytologic findings of two cases of signet-ring follicular adenoma using liquid-based samples and corresponding histologic features and results of ancillary tests. Cases: Case 1: A 65-year-old man presented with a solitary nodule in the right lobe of the thyroid. Ultrasound-guided fine needle aspiration (FNA) yielded several groups of microfollicles containing colloid or mucin-like globules. The tumor cells had eccentrically located nuclei compressed by distended luminal globules. Case 2: A 51-year-old woman presented with a nodule in the left lobe of the thyroid. On liquid-based cytology, cord-like arrangements of microfollicules were noted. The tumor cells had large, clear vacuoles, but the nuclei maintained their round shape and central location. Conclusion: The liquid-based cytologic characteristics are quite different from those encountered in the conventional smear of FNA; therefore, pathologists must also be familiar with the cytomorphologic characteristics of liquid-based preparations. In addition, given the distinctive cytological and histological appearance and the benign clinical course, signet-ring follicular adenoma should be distinguished from other metastatic neoplasms displaying signet-ring cell features.
Twelve Cases of Neuroendocrine Carcinomas of the Uterine Cervix: Cytology, Histopathology and Discussion of Their Histogenesis
Authors: Li Shuxia , Zhu Huiting
Published: December 2012

Objective: Neuroendocrine carcinoma (NEC) of the uterine cervix is a highly aggressive type of tumor. Therefore, recognition of its cytology and histopathology is important for early diagnosis. Study Design: We report 6 cases of small-cell and 6 cases of large-cell NEC of the uterine cervix, including 5 cytology slides. AE1/3, CEA, p63, p16, CD56, chromogranin and synaptophysin were detected. Results: Two cytology slides of small-cell NEC showed sheet-like clusters. The tumor cells were uniformly small, with finely granular chromatin, scant cytoplasm and absent nucleoli. Three large-cell NEC smears showed palisading, molding and abortive rosettes with prominent eosinophilic nucleoli. The tumor cells had either abundant cytoplasm or no cytoplasm at all. The histopathology analysis indicated a transition from dysplasia glands or adenocarcinoma in situ glands to NEC in 6 cases. Conclusion: Cervical cytology of NEC has many unique characteristics, distinct from the characteristics of other lesions. We also demonstrated a hypothesis of the histogenesis of some NECs.
Neuroticism Modifies the Association of Vision Impairment and Cognition among Community-Dwelling Older Adults
Authors: Gaynes Bruce I. , Shah Raj , Leurgans Sue , Bennett David
Published: December 2012

Background: Vision impairment (best-corrected binocular visual acuity worse than 20/40) is a common age-related health condition requiring adaptation to maintain well-being. Whether neuroticism, a personality trait associated with decreased ability to adapt to change, modifies the association of vision impairment with worse cognition is uncertain. Methods: Using baseline visual acuity, neuroticism and cognitive function data from 714 community-dwelling, older participants in the Rush Memory and Aging Project, we examined whether self-reported neuroticism level modified the cross-sectional association between vision impairment and lower cognitive level. Results: Women represented 76% of the participants. The mean age was 79.6 (SD = 6.9) years and the mean education level was 14.6 (SD = 2.9) years; 26% of the participants had vision impairment. In a linear regression model adjusted for age, sex and education, each unit higher in neuroticism level worsened the association between vision impairment and lower global cognitive function level (parameter estimate for vision impairment and neuroticism interaction term = –0.017; standard error = 0.005; p = 0.001). For participants with vision impairment, a high neuroticism level (50th percentile or above) was associated with a mean global cognitive score that was 0.297 z-score units lower than for participants with a low neuroticism level (p < 0.001). Conclusions: In older persons, neuroticism modifies the association between vision impairment and cognitive function level.
Ultrasound-Guided Fine-Needle Aspiration of Thyroid Nodules Measuring Less than 5 mm: Effects on Specimen Adequacy and Diagnosis
Authors: Kim Dong Wook , Jung Soo Jin , In Hyun Sin , Eom Jae Wook , Ryu Ji Hwa , Kim Young Wook
Published: December 2012

Objective: We aimed to assess the adequacy and efficacy of ultrasound (US)-guided fine-needle aspiration (US-FNA) for small solid thyroid nodules (SSTNs) with the largest diameter <5 mm and compared these according to nodule size. Study Design: Among 656 SSTNs in 569 patients, each SSTN was classified into 1 of 4 groups according to the largest diameter: 1 mm ≤ group A < 2 mm; 2 mm ≤ group B < 3 mm; 3 mm ≤ group C < 4 mm, and 4 mm ≤ group D < 5 mm. We compared the adequacy and efficacy of US-FNA between these groups using histopathologic results as a reference standard. Results: 571 (87.0%) SSTNs were adequately sampled by US-FNA and 200 of these were histopathologically confirmed. The adequacy of US-FNA for SSTNs varied according to the nodule diameter: the smaller the nodule diameter, the lower the diagnostic adequacy. The diagnostic efficacy of US-FNA for SSTNs showed a significant relationship with nodule size: diagnostic efficacy in groups A and B was lower than in groups C and D. Conclusions: The adequacy of US-FNA for SSTNs tended to decrease with decreased nodule size, and diagnostic efficacy of US-FNA for SSTNs with the largest diameter <3 mm was lower than for those ≥3 mm.
Association between Hysterectomy with Ovarian Preservation and Cardiovascular Disease in a Norwegian Population-Based Sample
Authors: Michelsen Trond M. , Dørum Anne , Cvancarova Milada , Liavaag Astrid H. , Dahl Alv A.
Published: December 2012

Background/Aims: Some previous studies have reported that hysterectomy predicts increased prevalence of cardiovascular diseases, but the findings are disputed. We aimed to examine associations between hysterectomy and cardiovascular disease in a Norwegian cross-sectional health study. Methods: The data were obtained from the population-based cross-sectional Nord-Trøndelag Health Study (The HUNT-2 Study). Of 46,709 invited females, 35,280 (76%) participated; 939 (3%) reported hysterectomy without oophorectomy (exposed women). Each exposed woman was age-matched with four randomly chosen women (n = 3,756) without hysterectomy or oophorectomy. Oophorectomy and hysterectomy status was self-reported by the women. Hazard ratio for cardiovascular diseases was calculated by Cox regression analyses with hysterectomy as a time-dependent covariate. Results: Median time since hysterectomy was 14 years (range 0–56 years). We calculated a significantly larger cumulative probability of cardiovascular diseases after hysterectomy with a hazard ratio of 1.92, 95% CI (1.51–2.38) after adjustments for cardiovascular risk factors (diabetes, age, use of hormonal replacement therapy and positive family history of myocardial infarction). Conclusion: Women had a significantly increased risk of cardiovascular diseases after hysterectomy compared to age-matched controls. Studies with longitudinal design and confirmed medical outcome data are needed.
In vitro Analysis of the Impact of Enrofloxacin Residues on the Human Intestinal Microbiota Using 1H-NMR Spectroscopy
Authors: Ahn Youngbeom , Jung Ji Young , Chung Yong Hyun , Chae Minho , Jeon Che Ok , Cerniglia Carl E.
Published: December 2012

Exposure of humans to antimicrobial residues in food-producing animals may alter the intestinal microbiota which could result in a potential risk to human health. To determine the effect of enrofloxacin on the human intestinal microbiota, fecal suspensions (25%) were cultured in the presence of 0.06–5 µg/ml enrofloxacin. The bacterial community was analyzed by plating on selective culture media, pyrosequencing and nuclear magnetic resonance (NMR) spectroscopy. Pyrosequencing analysis of 16S rRNA genes and viable counts on Bacteroides sp., Enterococcus sp., and Bifidobacterium sp. selection medium indicated that there were no significant changes in the bacteria numbers at the selected enrofloxacin concentrations (0.06, 0.1, and 1 µg/ml) relative to the control samples after a 48 h incubation. NMR analysis showed remarkably similar spectra in cultures treated with 0.06, 0.1, and 1 µg/ml enrofloxacin, with some slight differences in peak heights. However, hierarchical clustering analysis indicated significant differences in metabolite concentrations between the control and those samples treated with 1 µg/ml enrofloxacin. Leucine, phenylalanine, proline, and 2-oxovalerate were positively correlated with the concentration of enrofloxacin. NMR analysis is a potentially useful tool to monitor changes of the human intestinal microbiota, in addition to traditional culture methods and pyrosequencing.
The Mimic Chain Reaction
Authors: Norris Vic , Thierry Alain , Amar Patrick , Holland I. Barry , Molina Franck
Published: December 2012

It is sometimes speculated that the equivalent of the polymerase chain reaction might be developed for identification of peptides, proteins or other molecules. In general, though, it is believed that there can be no way to amplify targets such as proteins. Natural amplification systems do, however, exist as in the case of certain autoinducer systems in bacteria. Here, we outline a possible, generic method, the mimic chain reaction, for obtaining peptides with 3-D structures that mimic the 3-D structure of their targets. These targets would include a variety of molecules, including proteins. There are therefore two categories of applications: the ability via amplification firstly to detect a known protein or other target at an extremely low concentration, and secondly to obtain a set of peptides that mimic the structure of an unknown target and that can be used to obtain a ‘photofit’.
Serum D-Dimer Concentrations in Nephrotic Syndrome Track with Albuminuria, Not Estimated Glomerular Filtration Rate
Authors: Sexton D.J. , Clarkson M.R. , Mazur M.J. , Plant W.D. , Eustace J.A.
Published: December 2012

Background: The nephrotic syndrome is associated with an increased risk of venous and arterial thrombosis. There are little published data on the distribution, interpretation or determinants of serum D-dimer levels in patients with the nephrotic syndrome. We aimed to describe this relationship. Methods: This was a cross-sectional study of 100 patients with the nephrotic syndrome. Multivariate linear regression was used to evaluate for independent predictors of elevated D-dimer levels. Patients were observed for a period of 2 years after the baseline measurement of D-dimer level to assess for subsequent clinically evident thrombosis. Results: On univariate linear regression, D-dimer elevation was associated with age in years β (95% CI) 0.02 (0.016, 0.03), log-transformed urinary protein:creatinine ratio in g/g 0.439 (0.32, 0.558) and inversely with serum albumin in g/l –0.05 (–0.073, –0.035) and estimated glomerular filtration rate (eGFR) in ml/min/1.73 m2 –0.01 (–0.016, –0.003). On multivariate linear regression, age in years β (95% CI) 0.019 (0.012, 0.026), serum albumin in g/l –0.023 (–0.043, –0.003), and log-transformed urinary protein:creatinine ratio in g/g 0.266 (0.124, 0.408) were independently associated with elevated D-dimer levels. Conclusion: D-dimer levels are commonly raised in the nephrotic syndrome in the absence of clinically evident thrombosis, and are independently associated with age, degree of proteinuria and serum albumin, but not with eGFR. Baseline levels of D-dimer did not predict subsequent episodes of clinically evident thrombosis after 2 years of follow-up.
Adriamycin-Induced Models of VACTERL Association
Authors: Mc Laughlin D. , Hajduk P. , Murphy P. , Puri P.
Published: December 2012

Animal models are of great importance for medical research. They have enabled analysis of the aetiology and pathogenesis of complex congenital malformations and have also led to major advances in the surgical and therapeutic management of these conditions. Animal models allow us to comprehend the morphological and molecular basis of disease and consequently to discover novel approaches for both surgical and medical therapy. The anthracycline antibiotic adriamycin was incidentally found to have teratogenic effects on rats, producing a range of defects remarkably similar to the VACTERL association of congenital anomalies in humans, providing a reproducible animal model of this condition. VACTERL association is a spectrum of birth defects which includes vertebral, anal, cardiovascular, tracheo-oesophageal, renal and limb anomalies. In recent years, adriamycin rodent models of VACTERL have provided valuable insights into the pathogenesis of this complex association, particularly in relation to tracheo-oesophageal malformations. The adriamycin rat model and adriamycin mouse model are now well established in the investigation of the morphology of faulty organogenesis and the regulation of gene expression in tracheo-oesophageal anomalies.
Preterm Heart in Adult Life
Authors: Lewandowski Adam J. , Augustine Daniel , Lamata Pablo , Davis Esther F. , Lazdam Merzaka , Francis Jane , McCormick Kenny , Wilkinson Andrew R. , Singhal Atul , Lucas Alan , Smith Nic P. , Neubauer Stefan , Leeson Paul
Published: December 2012

Background—

Preterm birth leads to an early switch from fetal to postnatal circulation before completion of left ventricular in utero development. In animal studies, this results in an adversely remodeled left ventricle. We determined whether preterm birth is associated with a distinct left ventricular structure and function in humans.

Methods and Results—

A total of 234 individuals 20 to 39 years of age underwent cardiovascular magnetic resonance. One hundred two had been followed prospectively since preterm birth (gestational age=30.3±2.5 week; birth weight=1.3±0.3 kg), and 132 were born at term to uncomplicated pregnancies. Longitudinal and short-axis cine images were used to quantify left ventricular mass, 3-dimensional geometric variation by creation of a unique computational cardiac atlas, and myocardial function. We then determined whether perinatal factors modify these left ventricular parameters. Individuals born preterm had increased left ventricular mass (66.5±10.9 versus 55.4±11.4 g/m
2
;
P
<0.001) with greater prematurity associated with greater mass (
r
= −0.22,
P
=0.03). Preterm-born individuals had short left ventricles with small internal diameters and a displaced apex. Ejection fraction was preserved (
P
>0.99), but both longitudinal systolic (peak strain, strain rate, and velocity,
P
<0.001) and diastolic (peak strain rate and velocity,
P
<0.001) function and rotational (apical and basal peak systolic rotation rate,
P
=0.05 and
P
=0.006; net twist angle,
P
=0.02) movement were significantly reduced. A diagnosis of preeclampsia during the pregnancy was associated with further reductions in longitudinal peak systolic strain in the offspring (
P
=0.02, n=29).

Conclusions—

Individuals born preterm have increased left ventricular mass in adult life. Furthermore, they exhibit a unique 3-dimensional left ventricular geometry and significant reductions in systolic and diastolic functional parameters.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01487824.
The Brewer–Dobson Circulation in a Changing Climate: Impact of the Model Configuration
Authors: Bunzel Felix , Schmidt Hauke
Published: December 2012

Most climate models simulate a strengthening of the Brewer–Dobson circulation (BDC) under a changing climate. However, the magnitude of the trend as well as the underlying mechanisms varies significantly among the models. In this work the impact of both vertical resolution and vertical extent of a model on the simulated BDC change is investigated by analyzing sensitivity simulations performed with the general circulation model ECHAM6 in three different model configurations for three different climate states. Tropical upwelling velocities and age of stratospheric air are used as measures for the strength of the BDC. Both consistently show a BDC strengthening from the preindustrial to the future climate state for all configurations of the model. However, the amplitude and origin of this change vary between the different setups. Analyses of the tropical upward mass flux indicate that in the model with a lid at 10 hPa the BDC strengthening at 70 hPa is primarily produced by resolved wave drag, while in the model with a higher lid (0.01 hPa) the parameterized wave drag yields the main contribution to the BDC increase. This implies that consistent changes in the BDC originate from different causes when the stratosphere is not sufficiently resolved in a model. Furthermore, the effect of enhancing the horizontal diffusion in the upper model layers to avoid resolved wave reflection at the model lid is quantified, and a possible link to the different behavior of the low-top model with regard to the origin of the BDC change is identified.
Characteristics Associated with the Madden–Julian Oscillation at Manus Island
Authors: Deng Liping , McFarlane Sally A. , Flaherty Julia E.
Published: December 2012

Ground-based high temporal and vertical resolution datasets from observations during 2002–07 at the Atmospheric Radiation Measurement (ARM) tropical western Pacific (TWP) site on Manus Island are used to examine the characteristics of clouds and rainfall associated with the active phase of the Madden–Julian oscillation (MJO) passing over Manus. A composite MJO event at Manus is developed based on the NOAA MJO index 4 and precipitation using 13 events. The cloud characteristics associated with the active phase of the MJO at Manus show a two-phase structure as the wave passes over Manus. During the development phase, congestus plays an important role, and the enhanced convection is located between surface westerly and easterly wind anomalies (type-I structure). During the mature phase, deep convection is the dominant cloud type, and the enhanced convection is collocated with the westerly wind anomalies (type-II structure). Consistent with this two-phase structure, the heavy rainfall frequency also shows a two-peak structure during the MJO disturbance, while light rainfall does not show a clear relation to the intraseasonal disturbance associated with the MJO. In addition, a positive relationship between the precipitation rate and precipitable water vapor exists at Manus, and the atmospheric column is less moist after the passing of the MJO convection center than before.
Changes in the Relationship between ENSO and Asia–Pacific Midlatitude Winter Atmospheric Circulation
Authors: He Shengping , Wang Huijun , Liu Jiping
Published: December 2012

Interdecadal changes in the relationship between El Niño–Southern Oscillation (ENSO) and midlatitude atmospheric circulation are investigated in this study. Comparison of associations between ENSO and midlatitude atmospheric circulation anomalies between 1958–76 and 1977–2010 suggest that during 1958–76, ENSO exerted a strong impact on the East Asian winter monsoon (EAWM) and the associated atmospheric circulation pattern was similar to the positive North Pacific Oscillation (NPO). In contrast, during 1977–2010, the NPO-like atmospheric pattern disappeared. Instead, ENSO exerted a strong impact on the eastern North Pacific Ocean (NP) and North America, and the associated atmospheric circulation pattern resembled the Pacific–North America (PNA) teleconnection. Also, significant correlations between ENSO and sea surface temperature anomalies (SSTAs) over the western subtropical NP during 1958–76 became insignificant during 1977–2010, whereas negative correlations between ENSO and SSTAs in the central and northeastern subtropical NP became more significant since the mid-1970s. Further analyses suggest that the interdecadal shift of the Aleutian low, which occurred around the mid-1970s, might be responsible for the identified changes. Before the mid-1970s, warm ENSO events generated an anomalous anticyclone over the western NP, which is a key system bridging ENSO and EAWM-related atmospheric circulation. After the mid-1970s, the Aleutian low intensified and shifted eastward, leading to the impact of ENSO prevailing over the eastern NP. In addition, the weakened (strengthened) ENSO–NPO/EAWM (ENSO–PNA) relationship likely contributed to the weakened (strengthened) relationship between ENSO and SSTAs over the western (central and eastern) subtropical NP.
Comparison of Mobile-Radar Measurements of Tornado Intensity with Corresponding WSR-88D Measurements
Authors: Toth M. , Trapp R. J. , Wurman J. , Kosiba K. A.
Published: December 2012

In the United States, visual observations of tornadoes and/or the existence of tornado damage currently provide the sole evidence of tornadogenesis in association with a mesocyclone or other radar-detected storm-scale vortex. The severity of the tornado damage is currently the only means of estimating the intensity of tornadoes, radar detected or otherwise. The limitations of the damage-based record of tornado occurrence and intensity are well known and motivated this research. Weather Surveillance Radar-1988 Doppler (WSR-88D) measurements of the translating tornadic flow were compared with (semi-) coordinated measurements obtained near the surface with mobile radar. On the basis of a small yet fairly broad sample of tornadoes, high linear correlation was found between the vortex intensity (rotation plus translation) quantified using WSR-88D data and that quantified using Doppler on Wheels data. The possible effects of Doppler radar sampling on these results were explored through experiments with a simple vortex model. These experiments argued that the likelihood is high that a tornado would be sampled in a favorable way during at least one radar scan. Hence, the suggestion from this work is that WSR-88Ds (or similar operational radars) can potentially be used in isolation to estimate low-level tornado intensity. The proposed estimation is by way of a linear regression model, and application of this model is relevant only once a tornado is already confirmed.
Precarious Work in India
Authors: Maiti Dibyendu
Published: December 2012

Workers in India are becoming increasingly precarious in spite of its significant economic growth during the past two decades. The extent of informalization and casualization, used as proxies for precariousness, can be deduced from government sources and shows that the size of the informal sector not only constitutes almost 90% of the working population but also is growing. While the informal sector is not an accurate measure of precarious work, two specific characteristics of Indian precarious work are highlighted. The first deals with nonregistered establishments, unmaintained accounts, and hiring no more than 10 workers, officially defined as the “informal sector.” Individuals engaged in this sector experience precarious employment. The second group involves workers engaged in the formal sector on short-term contracts. Combined, the size of both types of precarious work has increased sharply in the postreform period beginning in the early 1990s. The supposed rigidity of labor laws is often used to explain the rise in precarious employment. However, the article finds that although the numbers of industrial disputes and wage shares have declined, the use of contract work has increased in the formal sector, and thus the labor market has been conducive to industrial expansion in spite of the absence of substantial labor law reform.
With Eloquence and Humanity? Human Factors/Ergonomics in Sustainable Human Development
Authors: Moore Dave , Barnard Tim
Published: December 2012

This article is based on a keynote presentation given at the 18th Congress of the International Ergonomics Association in Recife, Brazil, February 2012. It considers new, and not so new, approaches and practical roles for the emerging field of human factors/ergonomics (HFE) in sustainable development (SD). The material for this article was largely drawn from the literature in the fields of human development, sustainability, climate change mitigation and adaptation, and social/environmental impact assessment. Identifying the role of HFE in SD is not a simple one and from the outset is complicated by the widely differing ideas in the sustainability literature about what exactly it is we are hoping to sustain. Is it individual companies, business models, cultures, or the carrying capacity of our planet? Or combinations of these? For the purposes of this article, certain assumptions are made, and various emerging opportunities and responsibilities associated with our changing world of work are introduced. First, there are new versions of traditional tasks for us, such as working with the people and companies in the renewable energy sectors. Beyond this, however, it is suggested that there are emerging roles for HFE professionals in transdisciplinary work where we might play our part, for example, in tackling the twinned issues of climate change and human development in areas of significant poverty. In particular we have the tools and capabilities to help define and measure what groups have reason to value, and wish to sustain. It is suggested, that to do this effectively, however, will require a philosophical shift, or perhaps just a philosophical restatement at a collective level, regarding who and what we ultimately serve.
Wavelet-based acoustic emission characterization of residual strength of drilled composite materials
Authors: Heidary Hossein , Ahmadi Mehdi , Rahimi Abdolreza , Minak Giangiacomo
Published: December 2012

Drilling composite materials is one of the secondary processes of manufacturing industrial structures. However, drilling composite materials presents a number of problems such as degradation of mechanical behavior. In this study, effects of spindle speed, feed rate, and drill point geometry on residual tensile strength are studied. Acoustic emission technique with a wavelet-based signal processing method is developed to monitor the residual tensile strength of drilled laminates. Cumulative count, amplitude, and energy are used as time-domain parameters to characterize the process. According to wavelet analysis, frequency distribution and energy percentage of each damage mechanism (matrix cracking, fiber breakage, and fiber slipping) during tensile test are determined.