bluuebunny/crossref_metadata_2025 huggingface dataset:
Life-Threatening Hemopericardium Associated with Rivaroxaban
Authors: Basnet Sijan , Tachamo Niranjan , Tharu Biswaraj , Dhital Rashmi , Ghimire Sushil , Poudel Dilli Ram
Published: April 2017

Rivaroxaban is a novel oral anticoagulant used in the treatment of venous thromboembolism. The use of this medication has expanded over the recent years with resultant expansion of side effect profile. We present a case of a 56-year-old female who presented with shortness of breath and chest pain 12 weeks after starting rivaroxaban for left upper extremity deep vein thrombosis. She was later diagnosed with spontaneous hemopericardium requiring pericardial fluid drainage. Rarer side effects like this will be encountered more often with the increasing use of novel oral anticoagulants. The clinicians should be cognizant of this entity among patients with shortness of breath and chest pain for timely diagnosis and intervention.
Oral Administration of Tualang and Manuka Honeys Modulates Breast Cancer Progression in Sprague‐Dawley Rats Model
Authors: Ahmed Sarfraz , Sulaiman Siti Amrah , Othman Nor Hayati
Published: April 2017

Breast cancer has been recognized as the leading cause of death in women worldwide. Research has shown the importance of complementary and alternative therapies in cancer. In this study, we investigated the antitumoural therapeutic effects of Malaysian Tualang honey (TH) and Australian/New Zealand Manuka honey (MH) against breast cancer in rats. Thirty syngeneic virgin female Sprague‐Dawley (SD) rats were induced by the carcinogen 1‐methyl‐1‐nitrosourea (MNU) 80 mg/kg. The treatment started when first palpable tumour reached 10–12 mm in size by dividing rats into following groups: Group 0 (negative control); Group 1 (positive control); and Groups 2 and 3 which received 1.0 g/kg body weight/day of TH and MH, respectively, for 120 days. The data demonstrate that cancer masses in TH and MH treated groups showed a lower median tumour size, weight, and multiplicity compared with the nontreated positive control (p < 0.05). Treatment also showed a dramatic slower growth rate (up to 70.82%) compared with the nontreated control (0%) (p < 0.05). The antitumoural effect was mediated through modulation of tumour growth, tumour grading, estrogenic activity, and haematological parameters. Our findings demonstrate that systemic administration of TH and MH increases the susceptibility of expression of proapoptotic proteins (Apaf‐1, Caspase‐9, IFN‐γ, IFNGR1, and p53) and decreases the expression of antiapoptotic proteins (TNF‐α, COX‐2, and Bcl‐xL 1) in its mechanism of action. This highlights a potential novel role for TH and MH in alleviating breast cancer.
Investigations of a Gas Turbine Low-Emission Combustor Operating on the Synthesis Gas
Authors: Serbin Serhiy , Goncharova Nataliia
Published: April 2017

Investigations of the working processes in a gas turbine low-emission combustor operating on the synthesis gas, in which the principle of RQL (Rich-Burn, Quick-Mix, and Lean-Burn) combustion technology is realized, have been performed. Selected concept of a gas turbine combustor can provide higher performance and lower emission of nitrogen oxides and demonstrates satisfactory major key parameters. Obtained results and recommendations can be used for the gas turbine combustor operation modes modeling, geometry optimization, and prospective power generation units design and engineering.
The Effect of Acepromazine Alone or in Combination with Methadone, Morphine, or Tramadol on Sedation and Selected Cardiopulmonary Variables in Sheep
Authors: Nishimura Lilian Toshiko , Villela Isadora Oliveira Junqueira , Carvalho Leonardo Lamarca , Borges Luisa Pucci Bueno , Silva Marcos Augusto Machado , Mattos-Junior Ewaldo
Published: April 2017

The sedative and selected cardiopulmonary effects of acepromazine alone or in combination with methadone, morphine, or tramadol were compared in sheep. Six ewes were randomly assigned to treatments: A (0.05 mg/kg acepromazine), AM (A plus 0.5 mg/kg methadone), AMO (A plus 0.5 mg/kg morphine), and AT (A plus 5 mg/kg tramadol). Parameters were assessed before sedative drug administration (baseline) and every 15 minutes thereafter, for two hours. Treatments A and AM were associated with increases in sedation score for 60 minutes and treatments AMO and AT for 30 minutes; however, there were no significant differences between treatments. There was a decrease in mean arterial pressure compared to baseline values in treatment A at 15, 45, 60, and 90 minutes, in treatment AM at 15 minutes, and in treatment AT from 45 to 120 minutes. Arterial blood carbon dioxide pressure increased at all time points in all treatments. Arterial oxygen pressure decreased in treatment AMO at 15, 30, and 120 minutes and in treatment AT at 15–45, 105, and 120 minutes, compared to baseline. Acepromazine alone causes a level of sedation similar to that observed when it is coadministered with opioids methadone, morphine, and tramadol. These combinations did not cause clinical cardiopulmonary changes.
Bacteremia and Urinary Tract Infection Caused byChromobacterium violaceum: Case Reports from a Tertiary Care Hospital in Kathmandu, Nepal
Authors: Pant Narayan Dutt , Acharya Subhash Prasad , Bhandari Raju , Yadav Uday Narayan , Saru Dil Bahadur , Sharma Manisha
Published: April 2017

Chromobacterium violaceumis ubiquitous in the environment of tropical and subtropical regions but the infections caused by this organism are rare and the urinary tract infections caused by it are even rarer. Due to the propensity for hematogenous spread leading to fatal sepsis, the infections caused byChromobacterium violaceumhave high mortality rate (65–80%) with death occurring in as less as one week of acquiring infection. So, prompt proper treatment is necessary for successful treatment of the infections but, due to the rarity of the infections caused by the organism, there is limited awareness among the clinicians regarding the infections caused by this organism. Here, we reported a case of urinary tract infection caused byChromobacterium violaceumin a 84-year-old male, who was a kidney patient, and another case of bacteremia caused by the same bacterium in a road traffic accident patient (22-year-old male), both of which were managed with the timely suitable treatment.
Atraumatic Acromioclavicular Dislocation: A Case Report and Review of the Literature
Authors: Sadeghi Nasrat , Haen Pieter Stijn , Onstenk Ron
Published: April 2017

Acromioclavicular dislocation (AC dislocation) is a common injury of the shoulder. In contrast to a traumatic cause, nontraumatic dislocation is very rare. We report on a 17-year-old female that presented with voluntary recurrent dislocation of the right AC joint followed by recurrent pain without instability of the ipsilateral shoulder. Clinical examination showed crepitation as well as palpitation pain and dislocation of the AC joint. There were no symptoms of Marfan or Ehlers-Danlos syndrome as other joint examinations were also negative for hypermobility. Considering age as well as minor complaints, nonoperative treatment by postural therapy without taping was recommended. After one year, the patient experienced fewer symptoms and she was able to participate in daily activities.
Self-Medication in University Students from the City of Mansoura, Egypt
Authors: Helal R. M. , Abou-ElWafa H. S.
Published: April 2017

Background. Self-medication is a common practice in developed and developing countries.Objectives. To explore the prevalence of self-medication practices among university students, probable reasons, symptoms requiring self-medication, and sources of advice.Methods. A descriptive cross-sectional study was carried out in Mansoura University, Egypt, and included 1st and last year students of both medical and nonmedical faculties.Results. Prevalence of self-medication was 62.9%. Younger age, female, medical, and ever-married students and those having home pharmacy tended to self-medicate more than their peers with significant difference between them. Being medical student, being from urban area, having good current health condition, being careless about health, and having drugs stored at home pharmacy were independently associated with the likelihood of self-medicating.Conclusion. Prevalence of self-medication among university students is high which constitutes a health problem that needs intervention.
4‐Hydroxynonenal Contributes to Angiogenesis through a Redox‐Dependent Sphingolipid Pathway: Prevention by Hydralazine Derivatives
Authors: Camaré Caroline , Vanucci-Bacqué Corinne , Augé Nathalie , Pucelle Mélanie , Bernis Corinne , Swiader Audrey , Baltas Michel , Bedos-Belval Florence , Salvayre Robert , Nègre-Salvayre Anne
Published: April 2017

The neovascularization of atherosclerotic lesions is involved in plaque development and may contribute to intraplaque hemorrhage and plaque fragilization and rupture. Among the various proangiogenic agents involved in the neovascularization process, proatherogenic oxidized LDLs (oxLDLs) contribute to the formation of tubes via the generation of sphingosine 1‐phosphate (S1P), a major mitogenic and proangiogenic sphingolipid mediator. In this study, we investigated whether 4‐hydroxynonenal (4‐HNE), an aldehydic lipid oxidation product abundantly present in oxLDLs, contributes to their proangiogenic properties. Immunofluorescence analysis of human atherosclerotic lesions from carotid endarterectomy showed the colocalization of HNE‐adducts with CD31, a marker of endothelial cells, suggesting a close relationship between 4‐HNE and neovessel formation. In vitro, low 4‐HNE concentration (0.5–1 µM) elicited the formation of tubes by human microvascular endothelial cells (HMEC‐1), whereas higher concentrations were not angiogenic. The formation of tubes by 4‐HNE involved the generation of reactive oxygen species and the activation of the sphingolipid pathway, namely, the neutral type 2 sphingomyelinase and sphingosine kinase‐1 (nSMase2/SK‐1) pathway, indicating a role for S1P in the angiogenic signaling of 4‐HNE. Carbonyl scavengers hydralazine and bisvanillyl‐hydralazone inhibited the nSMase2/SK1 pathway activation and the formation of tubes on Matrigel® evoked by 4‐HNE. Altogether, these results emphasize the role of 4‐HNE in the angiogenic effect of oxLDLs and point out the potential interest of pharmacological carbonyl scavengers to prevent the neovascularization process.
Prevalence of Dietary Supplements Use among Gymnasium Users
Authors: Jawadi Ayman H. , Addar Abdulmalik M. , Alazzam Abdulaziz S. , Alrabieah Fahad O. , Al Alsheikh Abdullah S. , Amer Roaa R. , Aldrees Al Anoud S. , Al Turki Maha A. , Osman Ali K. , Badri Motasim
Published: April 2017

Background.Several studies showed that regular gymnasium users use various dietary supplements without comprehension of their potential risks.Objective.To determine the prevalence and dietary supplement intake and assess the awareness of supplement use among regular gymnasium users in Riyadh, Saudi Arabia.Methods.A descriptive cross-sectional study was conducted among regular gymnasium users in Riyadh, Saudi Arabia, between April 2015 and June 2015. A validated structured questionnaire was used.Results.The study included 299 participants. Of these 113 (37.8%) were dietary supplements users and this was more common among males than females (44.7% versus 16.4%). Gender based analysis showed that males were exercising more frequently than females and the type of cardiovascular exercise was more among them. The most commonly used supplements were whey protein (22.1%), amino acids (16.8%), multivitamins (16.8%), creatine (11.5%), and omega 3 (11.5%). The reasons for taking dietary supplements were to improve body shape (47.7%), increase health (44.2%), and improve performance (41.5%).Conclusion.Most of the information about supplements was obtained from unreliable sources. More studies are needed to better understand supplements use and their impact on health in Saudi Arabia.
Laboratory Diagnosis of Malaria: Comparison of Manual and Automated Diagnostic Tests
Authors: Mukry Samina Naz , Saud Madiha , Sufaida Gul , Shaikh Kashif , Naz Arshi , Shamsi Tahir Sultan
Published: April 2017

Malaria is the second most prevalent disease in Pakistan resulting in ~30,000 annual deaths. In endemic countries like Pakistan precise and timely diagnosis of malaria is imperative to overcome the associated risks of fatal outcomes. Malarial parasite was screened in 128 malaria suspected patients and 150 healthy controls, by species-specific PCR, microscopy of blood smears, hemoanalyzer Sysmex XE-2100, and rapid test devices (First Response Malaria® and ICT Malaria Combo®). The microscopy detected MP in 126 samples (parasite load/µl 386–53712/µl); 71.094% were infected withPlasmodium vivaxand 14.844% withP. falciparumwhile 14.062% had mixedP. vivaxandP. falciparuminfection. The mean parasite load forP. vivaxandP. falciparumwas 14496/µl and 24410/µl, respectively. The abnormal scattergrams of DIFF, WBC/ Baso, IMI channel, and RET-EXT on Sysmex XE-2100 supported 99.2% parasite detection, whereas only 93% of confirmed malaria cases were detected by both rapid tests. About 127 samples were positive by PCR. Since Sysmex XE-2100 automatically detected the presence of malarial parasite with high sensitivity, it can be a good option for presumptive diagnosis in endemic areas. Microscopy remains the gold standard to confirm MP in suspected patients. Rapid diagnostic tests have acceptable sensitivity and specificity.
Asphalt Mixture Segregation Detection: Digital Image Processing Approach
Authors: Baqersad Mohamadtaqi , Hamedi Amirmasoud , Mohammadafzali Mojtaba , Ali Hesham
Published: April 2017

Segregation determination in the asphalt pavement is an issue causing many disputes between agencies and contractors. The visual inspection method has commonly been used to determine pavement texture and in-place core density test used for verification. Furthermore, laser-based devices, such as the Florida Texture Meter (FTM) and the Circular Track Meter (CTM), have recently been developed to evaluate the asphalt mixture texture. In this study, an innovative digital image processing approach is used to determine pavement segregation. In this procedure, the standard deviation of the grayscale image frequency histogram is used to determine segregated regions. Linear Discriminate Analysis (LDA) is then implemented on the obtained standard deviations from image processing to classify pavements into the segregated and nonsegregated areas. The visual inspection method is utilized to verify this method. The results have demonstrated that this new method is a robust tool to determine segregated areas in newly paved FC9.5 pavement types.
Medical and Periodontal Clinical Parameters in Patients at Different Levels of Chronic Renal Failure
Authors: Perozini Caroline , Ruivo Gilson Fernandes , Ricardo Lucilene Hernandes , Pavesi Larissa Avance , Kim Yeon Jung , Pallos Debora
Published: April 2017

Aim. To assess the clinical periodontal and medical parameters in patients with chronic renal failure (CRF) at different levels of renal disease.Background. CRF is a progressive and irreversible loss of renal function associated with a decline in the glomerular filtration rate. Periodontal disease is a destructive inflammatory disease affecting periodontal tissues that shows high prevalence in patients with CRF.Materials and Methods. 102 CRF patients were included and divided into an early stage group (EG), predialysis group (PDG), and hemodialysis group (HDG). The medical parameters were taken from the patients’ records.Results. Periodontal clinical condition differed among the CRF groups. Clinical attachment loss was greater in the HDG and PDG group compared to the EG (p=0.0364); the same was observed in the Plaque Index (p=0.0296); the others periodontal parameters did not show any differences. Ferritin levels were significantly higher in the HDG when compared to the EG and PGD (p<0.0001), and fibrinogen was higher in PDG compared with the others (p<0.0001); the triglycerides also showed higher values in the HDG compared with the other groups (p<0.0001).Conclusion. The patients with renal involvement should have a multidisciplinary approach to an improvement in their oral and systemic health.
Combination Therapy Targeting BCL6 and Phospho-STAT3 Defeats Intratumor Heterogeneity in a Subset of Non–Small Cell Lung Cancers
Authors: Deb Dhruba , Rajaram Satwik , Larsen Jill E. , Dospoy Patrick D. , Marullo Rossella , Li Long Shan , Avila Kimberley , Xue Fengtian , Cerchietti Leandro , Minna John D. , Altschuler Steven J. , Wu Lani F.
Published: April 2017

Oncogene-specific changes in cellular signaling have been widely observed in lung cancer. Here, we investigated how these alterations could affect signaling heterogeneity and suggest novel therapeutic strategies. We compared signaling changes across six human bronchial epithelial cell (HBEC) strains that were systematically transformed with various combinations of TP53, KRAS, and MYC—oncogenic alterations commonly found in non–small cell lung cancer (NSCLC). We interrogated at single-cell resolution how these alterations could affect classic readouts (β-CATENIN, SMAD2/3, phospho-STAT3, P65, FOXO1, and phospho-ERK1/2) of key pathways commonly affected in NSCLC. All three oncogenic alterations were required concurrently to observe significant signaling changes, and significant heterogeneity arose in this condition. Unexpectedly, we found two mutually exclusive altered subpopulations: one with STAT3 upregulation and another with SMAD2/3 downregulation. Treatment with a STAT3 inhibitor eliminated the upregulated STAT3 subpopulation, but left a large surviving subpopulation with downregulated SMAD2/3. A bioinformatics search identified BCL6, a gene downstream of SMAD2/3, as a novel pharmacologically accessible target of our transformed HBECs. Combination treatment with STAT3 and BCL6 inhibitors across a panel of NSCLC cell lines and in xenografted tumors significantly reduced tumor cell growth. We conclude that BCL6 is a new therapeutic target in NSCLC and combination therapy that targets multiple vulnerabilities (STAT3 and BCL6) downstream of common oncogenes, and tumor suppressors may provide a potent way to defeat intratumor heterogeneity. Cancer Res; 77(11); 3070–81. ©2017 AACR.
Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry
Authors: Feng Ye , Rhie Suhn Kyong , Huo Dezheng , Ruiz-Narvaez Edward A. , Haddad Stephen A. , Ambrosone Christine B. , John Esther M. , Bernstein Leslie , Zheng Wei , Hu Jennifer J. , Ziegler Regina G. , Nyante Sarah , Bandera Elisa V. , Ingles Sue A. , Press Michael F. , Deming Sandra L. , Rodriguez-Gil Jorge L. , Zheng Yonglan , Yao Song , Han Yoo-Jeong , Ogundiran Temidayo O. , Rebbeck Timothy R. , Adebamowo Clement , Ojengbede Oladosu , Falusi Adeyinka G. , Hennis Anselm , Nemesure Barbara , Ambs Stefan , Blot William , Cai Qiuyin , Signorello Lisa , Nathanson Katherine L. , Lunetta Kathryn L. , Sucheston-Campbell Lara E. , Bensen Jeannette T. , Chanock Stephen J. , Marchand Loic Le , Olshan Andrew F. , Kolonel Laurence N. , Conti David V. , Coetzee Gerhard A. , Stram Daniel O. , Olopade Olufunmilayo I. , Palmer Julie R. , Haiman Christopher A.
Published: April 2017

Background: Genome-wide association studies have identified approximately 100 common genetic variants associated with breast cancer risk, the majority of which were discovered in women of European ancestry. Because of different patterns of linkage disequilibrium, many of these genetic markers may not represent signals in populations of African ancestry.

Methods: We tested 74 breast cancer risk variants and conducted fine-mapping of these susceptibility regions in 6,522 breast cancer cases and 7,643 controls of African ancestry from three genetic consortia (AABC, AMBER, and ROOT).

Results: Fifty-four of the 74 variants (73%) were found to have ORs that were directionally consistent with those previously reported, of which 12 were nominally statistically significant (P < 0.05). Through fine-mapping, in six regions (3p24, 12p11, 14q13, 16q12/FTO, 16q23, 19p13), we observed seven markers that better represent the underlying risk variant for overall breast cancer or breast cancer subtypes, whereas in another two regions (11q13, 16q12/TOX3), we identified suggestive evidence of signals that are independent of the reported index variant. Overlapping chromatin features and regulatory elements suggest that many of the risk alleles lie in regions with biological functionality.

Conclusions: Through fine-mapping of known susceptibility regions, we have revealed alleles that better characterize breast cancer risk in women of African ancestry.

Impact: The risk alleles identified represent genetic markers for modeling and stratifying breast cancer risk in women of African ancestry. Cancer Epidemiol Biomarkers Prev; 26(7); 1016–26. ©2017 AACR.
Vulvar Squamous Cell Carcinoma (VSCC) as Two Diseases: HPV Status Identifies Distinct Mutational Profiles Including Oncogenic Fibroblast Growth Factor Receptor 3
Authors: Weberpals Johanne I. , Lo Bryan , Duciaume Marc M. , Spaans Johanna N. , Clancy Aisling A. , Dimitroulakos Jim , Goss Glenwood D. , Sekhon Harman S.
Published: April 2017

Purpose: Patients with advanced or recurrent invasive vulvar squamous cell carcinoma (VSCC) have limited treatment options and a grave prognosis. Understanding the genomic landscape may facilitate the identification of new therapies and improve clinical outcomes.

Experimental Design: A retrospective chart review and molecular analysis of patients with VSCC from 2000 to 2016 was performed at the Ottawa Hospital Research Institute. The presence of oncogenic human papillomavirus (HPV) was determined by nested PCR and amplified DNA was sequenced using the Ion AmpliSeq Cancer Hotspot v2 Panel. The patients were divided into two groups according to HPV status (HPV-positive versus HPV-negative) and clinical outcome correlated with mutation status using descriptive statistics.

Results: In 43 VSCC patients, there was a high mutation rate in both HPV-positive (73%) and HPV-negative (90%) disease with the two subgroups expressing distinct genetic profiles. HPV-positive tumors were characterized by oncogenic mutations in PIK3CA (27%), FGFR3 (14%), and PTEN (9%), whereas HPV-negative tumors were found to have mutations in TP53 (57%), HRAS (24%), PI3KCA (19%), and CDKN2A (14%). Mutation S249C in FGFR3 occurred in 14% of HPV-positive tumors. While there were notable differences in the occurrence of TP53, HRAS, PTEN, and FGFR3 mutations according to HPV status, only the rate of TP53 mutations was statistically significant (P = 0.0004). No significant difference in prognosis was found between patients with HPV-positive and HPV-negative VSCC.

Conclusions: HPV-positive VSCC is characterized by oncogenic FGFR3 mutations that helps classify this subtype as a separate disease. Inhibitors of FGFR3 merit consideration as a therapeutic strategy in this neglected cancer in women. Clin Cancer Res; 23(15); 4501–10. ©2017 AACR.
Phase Ib/II Study of the Safety and Efficacy of Combination Therapy with Multikinase VEGF Inhibitor Pazopanib and MEK Inhibitor Trametinib In Advanced Soft Tissue Sarcoma
Authors: Subbiah Vivek , Meyer Christian , Zinner Ralph , Meric-Bernstam Funda , Zahurak Marianna L. , O'Connor Ashley , Roszik Jason , Shaw Kenna , Ludwig Joseph A. , Kurzrock Razelle , Azad Nilofer A.
Published: April 2017

Purpose: Pazopanib, a multireceptor tyrosine kinase inhibitor targeting primarily VEGFRs1–3, is approved for advanced soft tissue sarcoma (STS) and renal cell cancer. Downstream of VEGFR, trametinib is an FDA-approved MEK inhibitor used for melanoma. We hypothesized that vertical pathway inhibition using trametinib would synergize with pazopanib in advanced STS.

Experimental Design: In an open-label, multicenter, investigator-initiated National Comprehensive Cancer Network (NCCN)-sponsored trial, patients with metastatic or advanced STS received pazopanib 800 mg and 2 mg of trametinib continuously for 28-day cycles. The primary endpoint was 4-month progression-free survival (PFS). Secondary endpoints were overall survival, response rate, and disease control rate.

Results: Twenty-five patients were enrolled. The median age was 49 years (range, 22–77 years) and 52% were male. Median PFS was 2.27 months [95% confidence interval (CI), 1.9–3.9], and the 4-month PFS rate was 21.1% (95% CI, 9.7–45.9), which was not an improvement over the hypothesized null 4-month PFS rate of 28.3% (P = 0.79). Median overall survival was 9.0 months (95% CI, 5.7–17.7). A partial response occurred in 2 (8%) of the evaluable patients (95% CI, 1.0–26.0), one with PIK3CA E542K-mutant embryonal rhabdomyosarcoma and another with spindle cell sarcoma. The disease control rate was 14/25 (56%; 95% CI, 34.9–75.6). The most common adverse events were diarrhea (84%), nausea (64%), and fatigue (56%).

Conclusions: The combination of pazopanib and trametinib was tolerable without indication of added activity of the combination in STS. Further study may be warranted in RAS/RAF aberrant sarcomas. Clin Cancer Res; 23(15); 4027–34. ©2017 AACR.
Preclinical Activity of the Novel Anti-Prolactin Receptor (PRLR) Antibody–Drug Conjugate REGN2878-DM1 in PRLR-Positive Breast Cancers
Authors: Kelly Marcus P. , Hickey Carlos , Makonnen Sosina , Coetzee Sandra , Jalal Sumreen , Wang Yu , Delfino Frank , Shan Jing , Potocky Terra B. , Chatterjee Ishita , Andreev Julian , Kunz Arthur , D'Souza Christopher , Giurleo Jason T. , Nittoli Thomas , Trail Pamela A. , Thurston Gavin , Kirshner Jessica R.
Published: April 2017

The Prolactin Receptor (PRLR) is a type 1 cytokine receptor that is expressed in a subset of breast cancers and may contribute to its pathogenesis. It is relatively overexpressed in approximately 25% of human breast tumors while expressed at low levels in some normal human tissues including the mammary gland. We developed an anti-PRLR antibody-drug conjugate (ADC), to target PRLR-positive breast cancer. REGN2878-DM1 is comprised of a fully human high-affinity function-blocking anti-PRLR IgG1 antibody (REGN2878) conjugated via a noncleavable SMCC linker to the cytotoxic maytansine derivative DM1. Both unconjugated REGN2878 and conjugated REGN2878-DM1 block PRL-mediated activation in vitro and are rapidly internalized into lysosomes. REGN2878-DM1 induces potent cell-cycle arrest and cytotoxicity in PRLR-expressing tumor cell lines. In vivo, REGN2878-DM1 demonstrated significant antigen-specific antitumor activity against breast cancer xenograft models. In addition, REGN2878-DM1 showed additive activity when combined with the antiestrogen agent fulvestrant. These results illustrate promising antitumor activity against PRLR-positive breast cancer xenografts and support the evaluation of anti-PRLR ADCs as potential therapeutic agents in breast cancer. Mol Cancer Ther; 16(7); 1299–311. ©2017 AACR.
Successful Management of a Patient with Autoimmune Hemorrhaphilia due to Anti-Factor XIII/13 Antibodies Complicated by Pulmonary Thromboembolism
Authors: Ogawa Yoshiyuki , Yanagisawa Kunio , Souri Masayoshi , Mihara Masahiro , Naito Chiaki , Takizawa Makiko , Ishizaki Takuma , Mitsui Takeki , Handa Hiroshi , Osaki Tsukasa , Nojima Yoshihisa , Ichinose Akitada
Published: April 2017

Autoimmune hemophilia-like disease (hemorrhaphilia) due to anti-factor XIII (FXIII) antibodies (AH13) is a very rare, life-threatening bleeding disorder. A 77-year-old woman developed macrohematuria and a right renal pelvic hematoma. The coagulation times were not prolonged, but FXIII activity and antigen levels were severely and moderately reduced to 9 and 29% of normal values, respectively. Accordingly, the FXIII-specific activity turned out to be low. FXIII inhibitor and anti-FXIII-A subunit autoantibodies were detected by a 1:1 crossmixing test and immunoblot and immunochromatographic assays. She was therefore diagnosed with “definite AH13” and treated with plasma-derived FXIII concentrates to arrest the hemorrhage. In addition to a highly compressed inferior vena cava by a huge renal pelvic hematoma, deep vein thrombosis (DVT) and pulmonary thromboembolism (PE) were identified by systemic computed tomography. The patient was immediately started on anticoagulation therapy with low-dose heparin. Emboli disappeared quickly, probably because under-crosslinked thrombi caused by severe FXIII deficiency are vulnerable to fibrinolysis. After about 1.5 years, anti-FXIII-A subunit autoantibodies still remained despite the use of rituximab, steroid pulse therapy, oral prednisolone, and oral cyclophosphamide treatments. In conclusion, an extremely rare AH13 case complicated by DVT and PE was successfully managed by balancing anticoagulation therapy with hemostatic therapy.
Long-Term Follow-Up of Children after Venom Immunotherapy: Low Adherence to Anaphylaxis Guidelines
Authors: Fiedler Claudia , Miehe Ulrich , Treudler Regina , Kiess Wieland , Prenzel Freerk
Published: April 2017

Background: Data on the long-term outcome of children after specific venom immunotherapy (VIT) are limited. Therefore, we assessed sting recurrence and anaphylaxis relapse rates as well as adherence to anaphylaxis guidelines with regard to the availability of emergency equipment and education status. Methods: For this long-term survey, data of 311 children with a history of anaphylactic reactions to hymenoptera stings were collected by chart review. We included patients who were treated with a 3-year VIT between 1993 and 2009 and had completed a questionnaire. Results: Forty of the 311 patients were included. Mean VIT duration was 3.1 years. Of the 40 patients included, 29 children (72.5%) received VIT with vespid venom, 9 with bee venom, and 2 patients with both venoms. During a mean follow-up period of 13 years, 20/40 patients (50%) suffered re-stings. Six of the 20 (30%) patients developed again anaphylactic symptoms (grade 1 n = 5, grade 3 n = 1); 2 were allergic to vespid and 4 to bee venom. Of the entire cohort, only 5/40 (12.5%) had appropriate emergency kits according to the guidelines of the European Academy of Allergy and Clinical Immunology. Among the patients who had emergency kits available, one third (5/15) felt uncertain about the correct application of the medication. Less than two thirds of our population (25/40) affirmed that they have been educated in emergency management. The vast majority (95%; 38/40) of our patients did not have allergy follow-ups after VIT completion. Conclusions: Anaphylactic relapses are not uncommon, and there are considerable deficits in the emergency management of patients. Hence, comprehensive standardized anaphylaxis education programs as well as regular follow-ups of the allergy status are crucial.
Risk Factors for Severe Reactions during Double-Blind Placebo-Controlled Food Challenges
Authors: Yanagida Noriyuki , Sato Sakura , Asaumi Tomoyuki , Ogura Kiyotake , Ebisawa Motohiro
Published: April 2017

Background: Severe anaphylactic symptoms can occur during oral food challenges (OFCs). Thus, high-risk patients (e.g., patients with a history of anaphylaxis or high antigen-specific immunoglobulin E [IgE] levels) must carefully undergo OFCs in hospitals. We attempted to identify the risk factors for severe symptoms during OFC testing among high-risk patients. Methods: We retrospectively evaluated patients' characteristics and severe symptoms that were experienced during a double-blind placebo-controlled food challenge test performed before the patients underwent oral immunotherapy between June 2008 and June 2012. Patients were ≥5 years old and had an anaphylactic history or antigen-specific IgE (>30 kUA/L). Severe symptoms were defined using the grading of the Japanese Anaphylaxis Guidelines, which are modified from the European Academy of Allergology and Clinical Immunology Guidelines. Results: We evaluated 393 cases with positive test results, including 98 cases with severe symptoms. The most frequent severe symptoms were respiratory (77%), gastrointestinal (28%), cardiovascular (27%), and neurological (13%) symptoms. Multivariate analysis revealed that the significant factors for a severe reaction were a history of anaphylaxis to the causative food (adjusted odds ratio [OR]: 2.147, p = 0.003), older age (per 1 year increase, adjusted OR: 1.102, p = 0.044), and an egg OFC (adjusted OR: 0.433, p = 0.003). Conclusions: The risk factors for a severe reaction to OFCs were a history of an anaphylactic reaction and older age. An egg OFC was associated with low risk of severe symptoms during OFC. Therefore, OFCs for patients with these risk factors should only be performed under specialist supervision with access to rapid treatment and full resuscitation equipment.
Moyamoya in a Patient with Smith-Magenis Syndrome
Authors: Freeman Jacob , Deleyiannis Frederic , Bernard Timothy J. , Fenton Laura Z. , Somme Steig , Wilkinson C. Corbett
Published: April 2017

Occurrence of moyamoya syndrome in a patient with Smith-Magenis syndrome (SMS) has previously been reported once in a 10-year-old Asian female. We report a second case of moyamoya in a patient with SMS, in a now 25-year-old Asian female diagnosed with both conditions as a child. In addition to describing her medical and surgical history, we provide a detailed report of her omental transposition, in which the omental circulation was anastomosed to the superior thyroid artery and external jugular vein. To our knowledge, this is the first report of omental transposition for moyamoya in which omental vessels are anastomosed to vessels in the neck, as well as the second report of moyamoya in a patient with SMS.
Hodgkin Lymphoma Outcome: A Retrospective Study from 3 Tertiary Centers in Saudi Arabia
Authors: Shafi Ruaa G. , Al-Mansour Mubarak M. , Kanfar Solaf S. , Al Hashmi Hani , Alsaeed Ahmed , Al-Foheidi Meteb , Ibrahim Ezzeldin M.
Published: April 2017

Background: Hodgkin lymphoma (HL) exhibits considerable clinicopathological variations in different parts of the world. This study was prompted by the limited availability of HL data in developing countries (particularly long-term outcomes). Methods: We performed a retrospective review of eligible adult HL patients treated at 3 tertiary centers in Saudi Arabia between January 1997 and December 2012. Results: The review included 340 patients with a median age of 26 years (range 15-82 years); 53% were male, 74% had an advanced stage, 22% had bulky disease, and 70% had low-to-intermediate risk according to the International Prognostic Score. Nodular sclerosis was the most common histological subtype (59%). Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) was offered to 92% and radiotherapy to 43%. Initial therapy outcomes were complete response, partial response, and progressive disease in 91%, 5%, and 2% of patients, respectively. At a median follow-up of 39 months, the actuarial freedom from treatment failure at 5 years was 74%, with a 5-year overall survival of 91%. Multivariate analysis showed that advanced disease stage and high-risk international prognostic index independently predicted an adverse outcome. Conclusion: Our Saudi patient population exhibited outcomes that were comparable to those reported in developed countries.
Comparison of Monopolar and Bipolar Transurethral Resection of Non-Muscle Invasive Bladder Cancer
Authors: Balci Melih , Tuncel Altug , Keten Tanju , Guzel Ozer , Lokman Utku , Koseoglu Ersin , Aslan Yilmaz , Atan Ali
Published: April 2017

Objective: We aimed to compare the safety and efficacy of monopolar and bipolar transurethral resection (TUR) of bladder tumors (TURBTs). Material and Methods: A total of 240 patients who underwent TURBT were prospectively included in the study from May 2011 to May 2014. All patients with suspected bladder tumors were eligible for study inclusion. Those who refused consent and those undergoing routine restaging TURBT were excluded from analysis. Patients were divided on the basis of the monopolar arm and the bipolar arm. Study outcomes included the incidence of bladder perforation and obturator jerk, decrease in hemoglobin and sodium levels, rates of re-coagulation and blood transfusion, TUR syndrome, and operation time. Results: The mean age of the patients was 62 ± 13.7 years. The incidence of obturator jerk and bladder perforation was greater in the bipolar arm. However, with a decrease in the hemoglobin and sodium levels, rates of re-coagulation and blood transfusion were greater in the monopolar arm. Statistical analysis did not show significant differences with regard to study outcomes between the groups. There was no case of TUR syndrome in the 2 arms. The residual tumors' rate was similar between the 2 groups. Conclusions: Our results showed that efficacy and safety of the monopolar and bipolar methods seems to be comparable in patients with bladder tumors.
Discordant Genotypic Sex and Phenotype Variations in Two Spanish Siblings with 17α-Hydroxylase/17,20-Lyase Deficiency Carrying the Most Prevalent Mutated CYP17A1 Alleles of Brazilian Patients
Authors: Fernández-Cancio Mónica , García-García Emilio , González-Cejudo Carmen , Martínez-Maestre María-Angeles , Mangas-Cruz Miguel-Angel , Guerra-Junior Gil , Pandi de Mello Maricilda , Arnhold Ivo J.P. , Nishi Mirian Y. , Bilharinho Mendonça Berenice , García-Arumí Elena , Audí Laura , Tizzano Eduardo , Carrascosa Antonio
Published: April 2017

17α-hydroxylase/17,20-lyase deficiency is a rare form of congenital adrenal hyperplasia caused by mutations in CYP17A1. Two phenotypic female sisters, aged 17 and 15 years and with 46,XY and 46,XX karyotypes, respectively, presented with primary amenorrhea and absent secondary sexual characteristics. The elder sib also presented with high blood pressure. Both patients had elevated levels of ACTH, gonadotropins, progesterone, corticosterone, and deoxycorticosterone, and reduced levels of estradiol, testosterone, androstenedione, 17-OH-P, DHEA-S, cortisol, aldosterone, and renin activity. The CYP17A1 gene was sequenced, and polymorphic haplotypes were further analyzed in the Spanish family and in Brazilian patients. The 2 sisters were compound heterozygous for p.Arg362Cys and p.Trp406Arg mutations, previously described as the most prevalent mutations in Brazilian families of Spanish (p.Trp406Arg) or Portuguese (p.Arg362Cys) origin. Analysis of polymorphisms in CYP17A1 suggested that the paternal allele with p.Arg362Cys may share a common origin with the Brazilian carriers, while the maternal allele with p.Trp406Arg did not. Hydrocortisone and sex hormone replacement therapy was initiated in both patients. In conclusion, one CYP17A1 mutation (p.Arg362Cys) may share a common ancestry in Brazilian and our present Spanish patients, while p.Trp406Arg may have arisen separately. The elder patient (46,XY) developed a more severe phenotype and a poorer response to estradiol replacement therapy.
Renaissance of Low-Dose Radiotherapy Concepts for Cutaneous Lymphomas
Authors: Dabaja Bouthaina
Published: April 2017

Primary cutaneous B- and T-cell lymphomas are rare types of non-Hodgkin's lymphoma with a unique presentation. This can make it challenging for clinicians to manage these cases, and quite often the management mirrors that of other commonly seen lymphomas. This document summarizes how to manage primary cutaneous lymphoma with specific focus on the role of ultralow-dose radiation.
Shared Decision Making and Treatment Satisfaction in Japanese Patients with Inflammatory Bowel Disease
Authors: Mahlich Jorg , Matsuoka Katsuyoshi , Sruamsiri Rosarin
Published: April 2017

Background: Inflammatory bowel disease (IBD) is a range of complex disorders that imposes a high burden on patients' quality of life and on available health resources. Only 50% of those with this disease appear to be satisfied with the treatment methods. Therefore, this has a negative effect on their willingness to comply with treatment. Objective: This study examined whether patients are more satisfied when they and their doctors agree on how much of their management decisions should be shared. Participants: A nationwide online survey of Japanese patients in treatment for IBD yielded 1,068 respondents. Methods: A scoring system to match patients' preference for shared decision-making and their actual involvement in their treatment decisions was devised. To assess factors that were associated with treatment satisfaction, univariate and multivariate logistic regressions were performed. Results: We found a clear correlation between the extent to which patients and their doctors agreed on decision-sharing and patients' overall satisfaction with their treatment. An excellent fit increased the odds ratio of being satisfied with the treatment by 16.48 (8.31-32.69). Conclusions: Physicians should expect best patient compliance when they and their patients are in agreement with the extent to which treatment decisions are shared. This in turn maximizes the likelihood of successful treatment outcome.
ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Systemic Therapy - Chemotherapy
Authors: Garcia-Carbonero Rocio , Rinke Anja , Valle Juan W. , Fazio Nicola , Caplin Martyn , Gorbounova Vera , O'Connor Juan , Eriksson Barbro , Sorbye Halfdan , Kulke Matthew , Chen Jie , Falkerby Jenny , Costa Frederico , de Herder Wouter , Lombard-Bohas Catherine , Pavel Marianne ,   all other Antibes Consensus Conference participants
Published: April 2017

Systemic chemotherapy is indicated in progressive or bulky advanced pancreatic neuroendocrine tumors (NETs) and in grade 3 (G3) neuroendocrine neoplasms (NENs) as per ENETS guidelines. Chemotherapy may be considered in NETs of other sites (lung, thymus, stomach, colon, and rectum) under certain conditions (e.g., when Ki-67 is at a high level [upper G2 range], in rapidly progressive disease and/or after failure of other therapies, or if somatostatin receptor imaging is negative). An ENETS Consensus Conference was held in Antibes (2015) to elaborate guidelines on the standards of care of different diagnostic procedures and therapeutic interventions in NENs. This article provides guidance on chemotherapy including therapeutic indications, dosing schedules, adverse events (including prevention and management), drug interactions, and evaluation of treatment effect for the chemotherapy agents most commonly used in NENs (streptozocin, dacarbazine, fluoropyrimidines, platinum compounds, etoposide, and irinotecan).
Neurokinin 3 Receptor Antagonism Reveals Roles for Neurokinin B in the Regulation of Gonadotropin Secretion and Hot Flashes in Postmenopausal Women
Authors: Skorupskaite Karolina , George Jyothis T. , Veldhuis Johannes D. , Millar Robert P. , Anderson Richard A.
Published: April 2017

Objectives: Neurokinin B (NKB) and kisspeptin are obligate for normal gonadotropin secretion, and links between gonadotropin-releasing hormone (GnRH) pulsatility and vasomotor symptoms have been proposed. Using a selective NKB receptor (NK3R) antagonist, the role of NKB in the hypergonadotropic state in menopausal women was explored. Methods: Eleven postmenopausal women were administered the NK3R antagonist MLE4901 at 40 mg twice daily orally for 7 days. Ten-minute blood sampling for 8 h was performed before and on the last day of NK3R antagonist treatment for luteinising hormone (LH) pulsatility analysis with kisspeptin-10 (0.3 µg/kg i.v. bolus) administered at 6 h on both days. Hot flash frequency and severity were self-reported for 7 days before and during NK3R antagonist administration. Results: LH fell from 29.3 ± 4.1 to 24.4 ± 3.8 IU/L (p < 0.05) after 7 days of NK3R antagonist treatment, with no change in follicle-stimulating hormone (FSH). Basal (non-pulsatile) LH secretion was reduced (549.0 ± 70.8 vs. 366.1 ± 92.1 IU/L/6 h, p = 0.006), and while the LH pulse frequency did not change in the group as a whole (from 0.8 ± 0.1 to 0.7 ± 0.1 pulses/h, ns), it did fall in the 8 women with hot flashes (from 1.0 ± 0.1 to 0.7 ± 0.1 pulses/h, p < 0.05). These women also reported a reduction in hot flash frequency (from 3.4 ± 1.2 to 1.0 ± 0.6 hot flashes/day, p = 0.008) whilst taking the NK3R antagonist. Kisspeptin-10 did not affect LH secretion with or without the NK3R antagonist. Conclusions: The administration of an NK3R antagonist indicates a role for NKB in the regulation of LH/GnRH in postmenopausal women, whereas the lack of response to kisspeptin may reflect the hypo-oestrogenic state. These data support a link of LH/GnRH pulsatility and vasomotor symptoms with NK3R antagonism as a potential therapeutic approach.
Aplicação do mapeamento socioambiental na formação inicial de professores – uma abordagem metodológica crítica e participativa
Authors: Bacci Denise De La Corte , Santos Vânia Maria Nunes dos , Martins Lucelene
Published: April 2017

O mapeamento socioambiental é um instrumento didático-pedagógico de diagnóstico, planejamento e ação que promove a participação dos diferentes atores sociais na busca pela melhoria da qualidade de vida e na promoção da aprendizagem social. Tendo como objetivo a construção do olhar socioambiental na escola, a metodologia foi utilizada em curso de formação inicial em Geociências e Educação Ambiental, do Instituto de Geociências da USP. Focando o desenvolvimento de atividades voltadas ao (re)conhecimento do lugar/ambiente e seus problemas para a formação crítica de professores com capacidade para transformar a realidade socioambiental. O uso do mapeamento socioambiental resultou em processo de aprendizagem participativo, dialógico e interdisciplinar, no qual os futuros professores se apropriaram da metodologia.
Acrobeloides varius sp. n. (Rhabditida: Cephalobidae) from South Korea
Authors: Kim Taeho , Kim Jiyeon , Park Joong-Ki
Published: April 2017

A newAcrobeloidesis described and illustrated from samples collected in rice farmland in South Korea.Acrobeloides variussp. n. exhibits morphological characters of other acrobeloids, including a corpus with elongate spindle-like swelling and lateral incisures that extend to the tail end region. However, this new species is distinguished from other acrobeloids by having lateral incisures that change in number from one to five, three low rounded labial probolae, and a conical pointed tail end with a small spike-shaped mucron. In this study, a detailed morphological comparison ofAcrobeloidesspecies is provided, along with new molecular sequence data from the D2-D3 regions of LSU, SSU and partial mtDNAcox1region from the new species, which can be used as molecular barcode sequences.
Not Just Recycling the Crisis
Authors: Samson Melanie
Published: April 2017

This article contributes to debates on the relationship between waste and value by exploring how the revaluation of waste at a dump in Soweto, South Africa, was transformed during the 2008 economic crisis. It critically engages Herod, Pickren, Rainnie & McGrath-Champ’s differentiation between ‘devalorisation’ due to material degradation and ‘devaluation’ due to prices being too low for recycling to be profitable, in order to develop three arguments. First, it is necessary to recognise how political mobilisation by reclaimers shapes the conditions for devaluation by affecting local prices for recyclables. Second, reclaimers’ struggles to monopolise control over waste as they govern their labour process may lead to materials that could be profitably reclaimed remaining wasted. Third, waste is not only revalued through global production networks. Analysing why reclaimers choose to revalue waste through either formal or informal circuits provides insights into how the economy is constituted and affected by crisis in postcolonial contexts.