bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidative stress modulation by Rosmarinus officinalis in creosote‐induced hepatotoxicity
Authors: El‐Demerdash Fatma M. , Abbady Ehab A. , Baghdadi Hoda H.
Published: July 2014

Coal tar is a significant product generated from coal pyrolysis. Coal tar can be utilized as raw materials for various industries. It is also a type of raw material from which phenols, naphthalenes, and anthracene can be extracted. The present study was designed to investigate the possibility of coal tar creosote to induce oxidative stress and biochemical perturbations in rat liver and the role of rosemary (Rosmarinus officinalis) in ameliorating its toxic effects. Male Wister Albino rats were randomly divided into four groups of seven each, group I served as control; group II treated with rosemary (10 mL of water extract/kg BW for 21 days), group III received coal tar creosote (200 mg/4 mL olive oil/kg BW for 3 days), and group IV treated with both rosemary and coal tar creosote. The administration of coal tar creosote significantly caused elevation in lipid peroxidation (LPO) and reduction in the activities of glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and glutathione S‐transferase (GST). A significant decrease in reduced glutathione (GSH) content was also observed. Liver aminotransferases aspartate transaminase (AST) and alanine transaminase (ALT)] and alkaline phosphatase (AlP) were significantly decreased while lactate dehydrogenase (LDH) was increased. Rosemary pretreatment to coal tar creosote‐treated rats decreased LPO level and normalized GPx, GR, SOD, CAT, and GST activities, while GSH content was increased. Also, liver AST, ALT, AlP, and LDH were maintained near normal level due to rosemary treatment. In conclusion, rosemary has beneficial effects and could be able to antagonize coal tar creosote toxicity. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 85–92, 2016.
Nitric oxide increases the invasion of pancreatic cancer cells via activation of the PI3K–AKT and RhoA pathways after carbon ion irradiation
Authors: Fujita Mayumi , Imadome Kaori , Endo Satoshi , Shoji Yoshimi , Yamada Shigeru , Imai Takashi
Published: July 2014

Previous studies have shown that serine proteases and Rho‐associated kinase contribute to carbon ion radiation‐enhanced invasion of the human pancreatic cancer cell line PANC‐1. The results presented here show that nitric oxide synthase (NOS) also plays a critical role in this process. Irradiation of PANC‐1 cells promoted invasion and production of nitric oxide (NO), which activated the PI3K–AKT signaling pathway, while independently activating RhoA. Inhibition of PI3K, Rho‐associated kinase, and serine protease alone or in conjunction with NOS suppressed the radiation‐enhanced invasion of PANC‐1 cells, suggesting that they could serve as possible targets for the management of tumor metastasis.
A 2000-yr reconstruction of air temperature in the Great Basin of the United States with specific reference to the Medieval Climatic Anomaly
Authors: Reinemann Scott A. , Porinchu David F. , MacDonald Glen M. , Mark Bryan G. , DeGrand James Q.
Published: July 2014

A sediment core representing the past two millennia was recovered from Stella Lake in the Snake Range of the central Great Basin in Nevada. The core was analyzed for sub-fossil chironomids and sediment organic content. A quantitative reconstruction of mean July air temperature (MJAT) was developed using a regional training set and a chironomid-based WA-PLS inference model (r2jack= 0.55, RMSEP = 0.9°C). The chironomid-based MJAT reconstruction suggests that the interval between AD 900 and AD 1300, corresponding to the Medieval Climate Anomaly (MCA), was characterized by MJAT elevated 1.0°C above the subsequent Little Ice Age (LIA), but likely not as warm as recent conditions. Comparison of the Stella Lake temperature reconstruction to previously published paleoclimate records from this region indicates that the temperature fluctuations inferred to have occurred at Stella Lake between AD 900 and AD 1300 correspond to regional records documenting hydroclimate variability during the MCA interval. The Stella Lake record provides evidence that elevated summer temperature contributed to the increased aridity that characterized the western United States during the MCA.
Gemcitabine/5-flourouracil/leucovorin for the treatment of advanced pancreatic carcinoma
Authors: Malayeri Reza , Ghassemboland Mehrdad , Ranjpoor Faraz , Maadi Abdolreza
Published: July 2014

BACKGROUND AND OBJECTIVE:

The response rate and median survival with gemcitabine monotherapy, al-though considered the standard treatment for inoperable and metastatic pancreatic cancer, is relatively poor. We tested the efficacy and toxicity of a chemotherapy protocol consisting of gemcitabine, 5-fluorouracil (5-FU) and leucovorin in patients with inoperable or metastatic pancreatic cancer, which was shown to improve median survival in a small phase II trial.

PATIENTS AND METHODS:

patients older than 18 years of age with histologically or cytologically confirmed adenocarcinoma of the pancreas and bidimensionally measurable disease, and who were chemotherapy- and radiotherapy-naive, were treated with a chemotherapy protocol consisting of gemcitabine 1250 mg/m2 on day 1, 5-FU 450 mg/m2 and leucovorin 1 00 mg/m2 on days 1 -3. The treatment was repeated every 2 weeks.

RESULTS:

In an-intention-to-treat analysis, of 37 patients with pancreatic cancer (27 males, 10 females) (67.6% stage IVb) there were 7 (18.9%) objective partial responses (95% confidence interval, 8.33% to 29), 14 (37.8%) patients had stable disease and 16 (43.2%) had progressive disease. The median response time was 3 months (range, 1.5 to 7.0 months). Median overall survival time was 6.5 months (range, 1.0 to 15.5 months). The response to chemotherapy was not different between males and females (P=.971). No grade III/IV toxicities were seen.

CONCLUSION:

Despite our poor survival data, the combination of gemcitabine with 5-FU and leucovorin is an active and well-tolerated regimen in patients with pancreatic cancer that merits further evaluation in prospective randomized studies. This combination may be considered a valuable alternative to gemcitabine alone.
Biological features and outcome of biphenotypic acute leukemia
Authors: Mikulic Mirta , Batinic Drago , Sucic Mirna , Davidovic-Mrsic Sanja , Dubravcic Klara , Nemet Damir , Serventi-Seiwerth Ranka , Sertic Dubravka , Labar Boris
Published: July 2014

BACKGROUND:

Biphenotypic acute leukemia (BAL) is a distinct entity that is immunophenotypically defined by the European Group for the Immunological Classification of Leukemia (EGIL) scoring system and accounts for less than 5% of all acute leukemia cases. since it is a rare and heterogeneous form of acute leukemia with an allegedly poor outcome, there is no consensus on the best treatment approach in these patients. our objective was to analyze the biological features and outcome of patients diagnosed with BAL in our institution.

PATIENTS AND METHODS:

using the EGIL system, we identified 21 cases (3.9%) of BAL from 535 newly diag-nosed acute leukemia patients in an 11-year period.

RESULTS:

There were ten cases of myeloid+B-lymphoid leukemia, eight cases of myeloid+t-lymphoid, one case of B+t-lymphoid and two cases of trilineage (myeloid+B+t-lymphoid leukemia). The complete remission (GR) rate with high-dose chemotherapy was 72% and overall survival at 5 years was 21%. Patients that received acute lymphoblastic leukemia-oriented chemotherapy had a higher CR rate compared with those who received acute myeloid leukemia-oriented chemotherapy (100% vs. 60%, P=.007). The white blood cell count at diagnosis was found to have statistically significant impact on survival.

CONCLUSION:

Despite the progress in the treatment of acute leukemia, the prognosis of BAL remains poor and treatment protocols devised explicitly for this entity should be investigated in prospective collaborative studies.
Serum prostate-specific antigen, radiologic findings and Gleason score in prostate biopsies in Jordan
Authors: Farsakh Mohammed G. Abu , Farsakh Hussam A. A. Abu
Published: July 2014

BACKGROUND AND OBJECTIVES:

Prostate-specific antigen (PSA) and the PSA ratio are good screening tests for prostate carcinoma. The significance of PSA may be different from one ethnic group to another. Radiologic findings may be helpful in detecting prostate carcinoma.

METHODS:

We reviewed the findings of 348 prostate biopsies performed in a 4-year period. Of these, 278 cases were performed under ultrasound guidance and 70 were performed transrectally under digital guidance. PSA, PSA ratio, Gleason score and radiology findings were determined.

RESULTS:

Forty -three percent of the cases were diagnosed as having adenocarcinoma. The mean age for cancer patients was 68.4 years. The mean PSA level for patients with carcinoma was 23.4 ng/mL compared to 11.2 ng/mL for benign cases. carcinoma occurred in 11% (PSA <4 ng/mL); 48.7% (PSA=4-10 ng/mL); 50.6% (PSA= 10-30 ng/mL); 72% (PSA >30 ng/mL). The PSA ratio for cancer cases was 9.9% compared to 13.7% for benign cases. The average Gleason score for all cancers was 7 of 10. There was no relationship between PSA level and Gleason score. The higher the Gleason score, the higher the percentage of carcinoma present in the cores. Most of the carcinomas (100/122) showed hypoechoic areas on ultrasound exam, while heterogeneous areas favored a benign lesion in 54/76, with a sensitivity of 82% and specificity of 38%.

CONCLUSIONS AND IMPLICATIONS:

The higher the PSA, the greater the chance of having cancer. PSA has a low positive predictive value for prostate carcinoma. Twenty-eight percent of PSA >30 can be attributed to benign conditions. A PSA ratio <10 is suggestive of carcinoma. A radiologic finding of a hypoechoic lesion is a sensitive tool for detecting prostate carcinoma, but its specificity is low.
Cancer incidence among the Bahraini population
Authors: Alsayyad Jamal , Hamadeh Randah
Published: July 2014

BACKGROUND:

Cancer is the second leading cause of death, following cardiovascular diseases, accounting for 12% of annually reported deaths in Bahrain. We determined the epidemiological patterns of malignancies in Bahrain and compared them with those of other Gulf cooperation council (GCC) countries and other developed countries.

SUBJECTS AND METHODS:

Data for the study were obtained from the Bahrain cancer Registry (BCR) database. The overall and type-specific 5-year average incidence rates were calculated for the years 1998-2002 and derived using the CANREG software formula. The incidence rates for the year 2000 were used for comparing Bahrain with those of other countries in the Arabian Gulf using the statistics of the Gulf centre for cancer Registration.

RESULTS:

During the 5-year period there were 2405 cancer cases in Bahrain (1239 males and 1166 females), with an annual average of 481 cases. The world age-standardized incidence rates (ASR) were 162.3 and 145.2 per 100 000 for Bahraini males and females, respectively. Generally, Bahraini men had a higher ASR for most cancer types, and the most common type of cancer| was lung for males (35.2 per 100 000), followed by bladder (14.5) and prostate (14.3), and breast for females (46.8), followed by lung (12.2) and ovary (7.7).

CONCLUSION:

Compared to other Gulf countries, Bahrain had higher incidence rates for cancers of the lung, prostate, colorectum, bladder, kidney, pancreas and leukemia among males and for cancers of the breast, lung, bladder, thyroid, uterus and ovary among females. A rising trend in cancer incidence is likely to continue for years or even decades to come.
Inhibition of Akt pathway phosphorylation as a mechanism in the pathogenesis of functional intestinal obstruction in carcinomatosis peritonei
Authors: Poon Donald , Le Hoang-Vinh , Chanh Ngo Van , Tham Chee-Kian , Poh Benjamin , Koo Wen-Hsin , Hung Huynh
Published: July 2014

BACKGROUND AND OBJECTIVES:

The purpose of this study was to confirm our hypothesis that the develop-ment of functional intestinal obstruction in carcinomatosis peritonei (CP) is related to cytokine-mediated inhibition of the Akt pathway and to investigate the phenomenon of relative adrenal insufficiency in CP.

METHODS:

Human adrenocortical cells (NCI-H295R) were treated with serum derived from eight cancer patients who had intestinal obstruction and functional adrenal insufficiency. serum from three normal healthy subjects and three who had CP but without intestinal obstruction or adrenal insufficiency were used as controls. The differential effects of serum on the treated cells were studied using Western blot analysis. cortisol production of these treated cells was assayed with cortisol ELISA kits.

RESULTS:

phosphorylation of Akt at Ser473 and Ser308 in cells was significantly reduced when treated with serum from patients with intestinal obstruction but not controls. phosphorylation of PDK1 at Ser241, mTOR downstream targets like p70S6 atThr421/Ser424 and Thr389, and lastly 4EBP-1 at Ser70 a downstream target of p70S6 was reduced by approximately 50%, 40%, and 70%, respectively. There was enhanced phosphorylation of elF4E an initiating factor in protein translation in cells treated with patient serum compared to controls. Cortisol synthesis was stimulated upon treatment with patient serum but not with control serum.

CONCLUSION:

Inhibition of Akt phosphorylation is a mechanism that could play a major role in the development of intestinal obstruction in carcinomatosis peritonei. The identification of the mediating cytokines will lead to the development of cogent targeted therapeutic strategies.
Preliminary report on tumor stem cell/B cell hybridoma vaccine for recurrent glioblastoma multiforme
Authors: Moviglia Gustavo A. , Carrizo Antonio G. , Varela Gabriela , Gaeta Carlos A. , Lima Andrea Paes de , Farina Pablo , Molina Hugo
Published: July 2014

BACKGROUND:

Glioblastoma multiforme (GBM), the most aggressive glioma, presents with a rapid evolution and relapse within the first year, which is attributed to the persistence of tumor stem cells (TSC) and the escape of immune surveillance. Mixed leukocyte culture (MLC) cytoimplant has been shown to function as a powerful intratumor pro-inflammatory cytokine pump. tumor B-cell hybridoma (TBH) vaccines have been shown to function as antigen-presenting cells. We evaluated the toxicity and efficiency of each treatment alone and in combination.

PATIENTS AND METHODS:

In an open study, 12 consecutive patients were evenly divided into 3 groups, each group receiving 3 different treatments. Patients in Group 1 were treated, after diagnosis, with debulking surgery (DS)+radiotherapy (Rx), and after the first relapse underwent DS+MLC treatment. Patients in Group 2 were similarly treated but after the first relapse underwent DS+MLC+TBH. Finally, patients in Group 3 were similarly treated but after the first relapse underwent DS+TBH. Nestin PAP stain assessed TSC participation in TBH.

RESULTS:

Treatment with MLC had strong and rapid therapeutic effects, but was limited in duration and induced various degrees of brain inflammation. Treatment with MLC+TBH acted synergistically, provoking a rapid, strong and lasting therapeutic response but also generating different degrees of brain inflammation. A lasting therapeutic effect without generating high degrees of brain inflammation occurred in patients treated with TBH vaccine alone.

CONCLUSION:

TSC vaccine consisting of TBH alone seems to have potent adjuvant reactions overcoming both persistence of tumor stem cells and immune escape of GBM without provoking an encephalitic reaction.
Thyroid carcinoma in the United Arab Emirates
Authors: Al-Zaher Nabil , Al-Salam Suhail , Teraifi Hassan El
Published: July 2014

BACKGROUND:

Although the distribution of thyroid carcinoma in the Arab Gulf States has been described, no previous study has examined the characteristic clinicopathologic features of thyroid carcinoma cases in the united Arab Emirates.

METHODS:

The medical records of 135 patients with thyroid carcinoma diagnosed over a 15-year period (1991-2005) at Tawam Hospital, the national referral oncology center in the UAE, were retrospectively studied and the cases classified according to the histologic classification of the World Health organization (WHO).

RESULTS:

Seventy-eight patients (58%) were diagnosed before the age of 45 years with an overall peak incidence in the fourth and fifth decades. The female to male ratio was 2.4:1. Eighty-four percent had papillary thyroid carcinoma (PTC), while follicular thyroid carcinoma (FTC), anaplastic thyroid carcinoma and medullary carcinoma comprised 14%, 1.4% and 0.6%, respectively. The conventional classical variant of papillary carcinoma was the most common type. Three-quarters of the papillary carcinomas presented as multinodular goiter, while one-fifth presented as a solitary thyroid nodule. Minimal invasive follicular carcinoma was the most common variant of follicular carcinoma.

CONCLUSION:

Thyroid carcinoma in the united Arab Emirates seems to be more common among females and female gender may be a risk factor. Age <45 years can be considered an important prognostic factor as well as a possible risk factor. PTC predominates the histologic pattern of thyroid carcinoma, which is usually associated with an iodide-sufficient area.
Morphologic, immunphenotypic and clinical discriminators between T-cell/histiocyterich large B-cell lymphoma and lymphocytepredominant Hodgkin lymphoma
Authors: Mourad Walid A. , Thani Sheikha Al , Tbakhi Abdelghani , Omari Mohamed Al , Khafaga Yasser , Shoukri Mohamed , Weshi Amr El , Shabana Mohamed Al , Ezzat Adnan
Published: July 2014

BACKGROUND:

Features of T-cell/histiocyte rich large B-cell lymphoma (THRLBCL) overlap with those of lym-phocyte predominant Hodgkin lymphoma (LPHL). The two lymphomas may represent a spectrum of the same disease, and differentiation between the two can sometimes be difficult. We looked at histomorphologic, im- munophenotypic and clinical information that may help differentiate the two entities.

METHODS:

cases of THRLCL and LPHL were blindly reviewed and studied for histological pattern (nodular vs. diffuse), nuclear features and pattern of expression of CD20, CD30, CD57, epithelial membrane antigen (EMA) and Epstein-Barr virus (EBV). A score encompassing diffuse histology, high nuclear grade, CD20 single-cell pattern, CD30+, CD57-, EMA-, and EBV+ was estimated for the diagnosis of TCHRLBCL.

RESULTS:

There were 58 cases, including 30 cases of TCHRLBL and 28 cases of LPHL. The median age was 36 years for TCHRLBCL and 21 years for LPHL (P=0.0001). Three types of nuclei were identified (lymphocytic/his- tocytic, Reed-Sternberg and centroblast-like). The latter two high-grade nuclei were suggestive of TCHRLBCL. TCHRLBCL and LPHL, respectively, showed diffuse histology, 90% vs. 4% (P=0.001), single CD20+ cells, 93% vs. 3.5% (P=0.00004), CD30+ cells, 30% vs. 0% (P=0.01), CD57+ cells, 41% vs. 93% (P=0.008), EMA+ cells, 27% vs. 60% (P=0.113), EBV+ cells, 24% vs. 0% (P=0.117), high nuclear grade, 70% vs. 0% (P=0.001), total score 2-7 (mean 4.68) vs. 0-2 (mean 0.72) (P=0.001), high stage, 86% vs. 7% (P=0.0001).

CONCLUSION:

Our findings indicate that a combination of multiple parameters can help differentiate between the two diseases. Two cases originally diagnosed as LPHL were re-assigned the diagnosis of THRLBCL.
Maternal acute lymphoctic leukemia with rearrangement of the mixed lineage leukemia gene occurring during pregnancy
Authors: Aljurf Mahmoud , Nassar Amr , Saleh Abu Jafar , Almhareb Fahed , Alzahrani Hazzaa , Walter Claudia , Bakr Mohammad , Ahmed Syed Osman , Chaudhri Naeem
Published: July 2014

Acute lymphoblastic leukemia (ALL) is a relatively rare disease during pregnancy, accounting for about 15% of all cases of pregnancy-associated leukemia. Although mixed lineage leukemia gene (MLL) rearrangement is the dominant genetic aberration in infantile acute leukemia, the occurrence of MLL gene rearrangement in maternal ALL occurring during pregnancy has not been reported. Out of 31 cases of maternal leukemia diagnosed during pregnancy at our institution, 5 were ALL cases. Three of the 5 patients had MLL gene rearrangement. The data for these 5 patients are presented in this report. We believe that the association of MLL gene rearrangement with maternal leukemia is biologically plausible and this observation needs to be validated in a larger cohort of pregnancy-associated maternal leukemia cases.
Predictors of severe hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency following exposure to oxidant stresses
Authors: Al-Sweedan Suleimman A. , Jdaitawi Hussein , Khriesat Wadah M. , Khader Yousef Y. , Al-Rimawi Hala S.
Published: July 2014

BACKGROUND AND OBJECTIVES:

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic enzy-matic disorder that affects millions of people worldwide, and is a major health problem in Jordan. We studied factors that may predict severe hemolysis in children with G6PD deficiency.

METHODS:

We reviewed the records of patients with low G6PD activity admitted to a teaching hospital between 1996 to 2007. We collected demographic data, details of sign and symptoms, history and type of fava bean ingestion, blood and Rh group, history of neonatal jaundice, history and type of drug use, abdominal pain at admission and the results of tests for hemoglobin, white blood cells (WBC), and hepatic function. We classified patients into mild and severe groups based on hemoglobin levels at admission.

RESULTS:

Of 428 children with G6PD deficiency, 79 (18%) were severe cases and 349 (82%) patients with mild disease. There were no statistically significant differences in most factors between the two groups. Factors that achieved statistical significance for severe hemolysis included younger age (P<.05), male gender (P<.05), higher alkaline phosphatase (ALP) (P<.05), presence of fever at admission (P<.01), presence of vomiting during the attack (P=.006), and a negative family history for G6PD deficiency (P=.005).

CONCLUSIONS:

Severe hemolysis can be predicted during hemolytic episodes in children with low G6PD by young age, male gender, a negative family history of G6PD deficiency, the presence of fever and vomiting and a high ALP.
The National Oncology Program
Authors: Theodore Vandenberg , Nadeem Nagi , Bertha Garcia , Catherine Kirk , James Gilchrist , Susan Poirier , Hugh Allen , Albert Driedger , Kate Fournie , Mohamed Basahi , Martin Robinsong
Published: July 2014

Cancer in developing countries is growing and will soon be a major problem as life expectancy increases. This article outlines the experience and future objectives of a partnership between Yemeni and Canadian oncology professionals in their attempt to develop a National Oncology Program in Yemen. We review current knowledge of the epidemiology, social, educational and economic challenges as well as sugggested initial steps in developing a relevant oncology program for this society.
Prognostic effect of hormone receptor status in early HER2 positive breast cancer patients
Authors: Gómez Henry L. , Castañeda Carlos A. , Vigil Carlos E. , Vidaurre Tatiana , Velarde Raúl G. , Cruz Wilder R. , Pinto Joseph A. , Suazo Juan F. , Garcés Milko R. , Neciosup Silvia P. , Vallejos Carlos S.
Published: July 2014

BACKGROUND

This study was conducted to determine the prognostic effect hormone receptor (HR) status in early HER2 positive (HER2 +) breast cancer patients, since it has not yet been established whether HR status can be used in the prognosis of patients with (HER2 +) breast cancer.

PATIENTS AND METHODS

We obtained data from 299 patients with early HER 2+ breast cancer who underwwent surgery and received standard adjuvant chemotherapy, hormonal therapy and/or radiation between 2000 and 2002 at the Instituto Nacional de Enfermedades Neoplasicas, Perú. Clinical and pathological features were compared. Endpoints analyzed were disease free survival (DFS) and overall survival (OS).

RESULTS:

Overall, 155 patients were HR -positive (HR +) and 144 were negative (HR-). The two groups had similar characteristics except for histologic grade and extracapsular extension. With a median follow-up of 93 months, 5-year DFS was statistically different between the two groups: 65.0% for (HER 2+/ HR-) and 74.6% for the (HER 2+/ HR +) patients (P=.045). OS at 5 years was not statistically different between the two groups with 75.5% for (HER 2+/ HR-) patients and 82.4% for the (HER 2+/ HR +)(P=.140).

CONCLUSIONS:

Patients with (HER 2+/ HR-) breast cancers treated with surgery and standard adjuvant chemottherapy exhibited a statistically worse DFS compared to those with (HER 2+/ HR +) tumors. However, OS was similar in both groups.
Poor survival outcome of docetaxel every three weeks plus prednisone for treatment of patients with hormone-refractory metastatic prostate cancer
Authors: Abu-Hamar Abd El Halim Mohamed , Mansour Saleh , Shebiney Mohamed El , Abd El Bary Naser Mohamed , Sadaka Emad , Maria Alaa
Published: July 2014

BACKGROUND AND OBJECTIVES:

Since previous studies have indicated there are improvements in overall survival, the aim of this phase II clinical study was to evaluate docetaxel every three weeks plus prednisone as first-line chemotherapy for treatment of hormone-refractory metastatic prostate cancer (HRMPC).

METHODS:

Thirty-five metastatic HRPC patients were treated with docetaxel 70 mg/m2 every 3 weeks plus oral prednisolone 5 mg twice daily at the clinical oncology departments of Tanta, Mansoura and Menofia University Hospitals during the period from June 2006 to December 2008. The primary endpoint was assessment of the overall tumor response rate. Secondary endpoints were assessment of PSA response rate, overall survival rate, and the time to disease progression.

RESULTS:

The median number of cycles administered was 6 cycles. Partial response was observed in 15 patients (42.9%) with evaluable measurable disease. Median survival from protocol entry was 15 months. Median timeto-disease progression was 10 months. Prostate-specific antigen (PSA) declined ≥ 50% in 9 patients (25.7%). The most common grade 3/4 toxicity associated with studied protocol was neutropenia (85.7%).

CONCLUSIONS:

When given with prednisone, treatment with docetaxel every three weeks does not improve survival, so the benefit of docetaxel-based therapy is not clear this high risk and poor prognostic group of pattients.
Carcinosarcoma of the uterus in a woman with Down syndrome
Authors: Al-Badawi Ismail A. , AlOmar Osama , Kornfeld Ianny
Published: July 2014

There are only a few reports of uterine cancers in women with Down syndrome, whose tumor profile is marked by a reduced risk for solid neoplasms. There are no reports of a uterine carcinosarcoma arising in a woman with Down syndrome. In our case, a delayed diagnosis of uterine carcinosarcoma was confirmed in a 38-year-old, nulliparous, single, obese woman with Down syndrome, who presented with irregular vaginal bleeding. Although uterine cancers are underrepresented in women with Down syndrome, uterine malignancy should be considered in the differential diagnosis of abnormal vaginal bleeding. A timely and complete gynecological examination will preclude a delay in diagnosis.
A phase II study of high-dose celecoxib and metronomic ‘low-dose‘ cyclophosphamide and methotrexate in patients with relapsed and refractory lymphoma
Authors: Bary Naser Abd El , Hashem Tarek , Metwally Hasan , Ghany Ashraf Abd , Mageed Hager Abd El
Published: July 2014

BACKGROUND AND OBJECTIVES:

Relapsed, histologically aggressive non-Hodgkin lymphoma (NHL) has a poor prognosis; relapsed patients who do not respond to second line therapy or are unfit for BMT have a worse prognosis. Angiogenesis is increased in aggressive NHL and could be targeted by selective cyclooxygenase-2 inhhibition and metronomic chemotherapy. We assessed the toxicity of metronomic chemotherapy and the response and progression-free survival in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

PATIENTS AND METHODS:

We prospectively studied 41 patients with a diagnosis of relapsed and/or refractory DLBCL who may have received any number of preceding therapies (as long as one included an anthracycline) and were not candidates for bone marrow transplantation. They received oral cyclophosphamide (50 mg every day), oral methotrexate (2.5 mg 4 times/week) and high-dose oral celecoxib (400 mg twice daily) until there was disease progression or unacceptable toxicity.

RESULTS:

All 41 patients (median age, 56 years) were evaluable for toxicity and response, with a median follow up of 9.1 months (range, 4-35 months). At relapse, 51.2% had a high international prognostic index. The treatment protocol was well tolerated with no major toxicities. The most common toxicities were fatigue (61%), nausea (22%), neutropenia (19.5%), and anemia (22%). In 31.7 % there was a partial response and 48.8% had stable disease. Progression-free survival was 12 months. The median response duration was 10 months.

CONCLUSIONS:

We conclude that metronomic chemotherapy can be used for patients with relapsed and or refractory DLBCL with reasonable outcome and acceptable toxicity. Standard approaches such as hematopoietic stem cell transplantation and chemo-immunotherapy combinations should be explored prior to a decision on metronomic chemotherapy.
Identification of a novel peptide derived from the M-phase phosphoprotein 11 (MPP11) leukemic antigen recognized by human CD8+ cytotoxic T lymphocytes
Authors: Qudaihi Ghofran Al , Lehe Cynthia , Dickinson Anne , Eltayeb Khaled , Rasheed Walid , Chaudhri Naeem , Aljurf Mahmoud , Dermime Said
Published: July 2014

BACKGROUND AND OBJECTIVES

There is an urgent need for the development of leukemia-targeted im-munotherapeutic approaches using defined leukemia-associated antigens that are preferentially expressed by most leukemia subtypes and absent or minimally expressed in vital tissues. M-phase phosphoprotein 11 protein (MPP11) is extensively overexpressed in leukemic cells and therefore is considered an attractive target for leukemia T cell therapy. We sought to identify potential CD8 + cytotoxic T lymphocytes that specifically recognised peptides derived from the MPP11 antigen.

MATERIALS AND METHODS

A computer-based epitope prediction program SYFPEITHI, was used to predict peptides from the MPP11 protein that bind to the most common HLA- A*0201 molecule. Peptide binding capacity to the HLA-A*0201 molecule was measured using the T2 TAP-deficient, HLA-A*0201-positive cell line. Dendritic cells were pulsed with peptides and then used to generate CD8 + cytotoxic T lymphocytes (CTL). The CML leukemic cell line K562-A2.1 naturally expressing the MPP11 antigen and engineered to express the HLA-A*0201 molecule was used as the target cell.

RESULTS

We have identified a potential HLA-A*0201 binding epitope (STLCQVEPV) named MPP-4 derived from the MPP11 protein which was used to generate a CTL line. Interestingly, this CTL line specifically recognized peptide-loaded target cells in both ELISPOT and cytotoxic assays. Importantly, this CTL line exerted a cytotoxic effect towards the CML leukemic cell line K562-A2.1.

CONCLUSION

This is the first study to describe a novel epitope derived from the MPP11 antigen that has been recognized by human CD8 + CTL.
Feasibility study of dose-dense biweekly administered pemetrexed in patients with non-small cell lung cancer
Authors: Emmanouilides Christos , Yermetaki Theodora , Serpanou Anastasia , Sapountzi Evdoxia , Mantziari Polyxeni , Titopoulos Iraklis , Filippou Dimitrios
Published: July 2014

BACKGROUND AND OBJECTIVES

Pemetrexed is a multitargeted folate pathway inhibitor with documented activity in non-small cell lung cancer (NSCLC). The presumed maximum tolerated dose is 500 mg/m2 every 3 weeks, but pemetrexed-related toxicity is ameliorated when folate and B12 supplementation is provided and therefore a higher dose intensity may be tolerated. The current exploratory study assessed the feasibility of administration of pemetrexed at a fixed dose of 1000 mg every 2 weeks in patients with relapsed or refractory NSCLC.

PATIENTS AND METHODS

The first cohort of 12 patients received pemetrexed monotherapy. No dose-limiting grade 4 toxicity was noted after 4 cycles, so the subsequent cohort of 14 patients received additional anticancer agents (bevacizumab, erlotinib, carboplatin, docetaxel, vinorelbine) given along with dose-dense pemetrexed.

RESULTS

Toxicity overall was reversible and manageable. Among 19 patients who received pemetrexed either alone or with non-myelosuppressive targeted agents, there were only 2 instances of grade 4 neutropenia after prolonged treatment. Grade 3-4 hematologic toxicity was eventually noted in 11 of the 26 patients (42%; 95% confidence interval, 23% to 61%) after a median of 4 cycles (range, 2-14 cycles). There was no significant additional toxicity nor any treatment-related deaths.

CONCLUSION

Our preliminary observations indicate that dose-dense pemetrexed every 2 weeks is feasible and this regimen can be used as monotherapy. These data may serve as a scaffold for combination studies.
Growth and instability of the liquid rim in the crown splash regime
Authors: Agbaglah G. , Deegan R. D.
Published: July 2014

We study the formation, growth and disintegration of jets following the impact of a drop on a thin film of the same liquid for $\def \xmlpi #1{}\def \mathsfbi #1{\boldsymbol {\mathsf {#1}}}\let \le =\leqslant \let \leq =\leqslant \let \ge =\geqslant \let \geq =\geqslant \def \Pr {\mathit {Pr}}\def \Fr {\mathit {Fr}}\def \Rey {\mathit {Re}}\mathit{We}<1000$ and $\mathit{Re}<2000$ using a combination of numerical simulations and linear stability theory (Agbaglah, Josserand & Zaleski, Phys. Fluids, vol. 25, 2013, 022103). Our simulations faithfully capture this phenomena and are in good agreement with experimental profiles obtained from high-speed X-ray imaging. We obtain scaling relations from our simulations and use these as inputs to our stability analysis. The resulting predictions for the most unstable wavelength are in excellent agreement with experimental data. Our calculations show that the dominant destabilizing mechanism is a competition between capillarity and inertia but that deceleration of the rim provides an additional boost to growth. We also predict over the entire parameter range of our study the number and timescale for formation of secondary droplets formed during a splash, based on the assumption that the most unstable mode sets the droplet number.
“Censorship is Official Critique”: Contesting the Limits of Scholarship in the Censorship of the Hallische Jahrbücher
Authors: Bunn Matthew
Published: July 2014

While censorship touched upon the careers of every German writer in the nineteenth century, a few cases stood out to contemporaries, defining their era. If the Demagogenverfolgung stamped the early 1820s and the prohibition of Young Germany the 1830s, the assault on left-wing or “Young” Hegelianism in 1842–43 was the major censorship case of the decade. Banning the Deutsche Jahrbücher, Rheinische Zeitung, and Leipziger Allgemeine Zeitung was part of a significant, coordinated effort to undermine a small but influential faction of radical social critics. This wave of intellectual persecution radicalized the left, sowing the seeds for Marx's thoroughgoing assault on the foundations of European state and society. Understanding these cases in the context of a broader process of the transformation of censorship practices in modern Germany, however, remains an incomplete project for historians.
Sequencing your genome: your future is here, but are you sure you want to know it?
Authors: PILLAR NIR , ISAKOV OFER , SHOMRON NOAM
Published: July 2014

Next-generation sequencing (NGS; also known as deep sequencing or ultra-high throughput sequencing) has probably been the most important tool for genomic research over the past few years. NGS has led to numerous discoveries and scientific breakthroughs in the genetic field. The sequencing technology that has entered the research laboratory in the past decade is now being introduced into the clinical diagnostic laboratory. Consequently, NGS results are becoming available in the medical arena as abundance of clinically relevant variants, conferring predisposition to disease, are being discovered at a growing rate (Stanley, 2014).
INTENTIONS, COMPLIANCE, AND FIDUCIARY OBLIGATIONS
Authors: Galoob Stephen R. , Leib Ethan J.
Published: July 2014

This essay investigates the structure of fiduciary obligations, specifically the obligation of loyalty. Fiduciary obligations differ from promissory obligations with respect to the possibility of “accidental compliance.” Promissory obligations can be satisfied through behavior that conforms to a promise, even if that behavior is done for inappropriate reasons. By contrast, fiduciary loyalty necessarily has an intentional dimension, one that prevents satisfaction through accidental compliance. The intentional dimension of fiduciary loyalty is best described by what we call the “shaping” account. This account both explains the conscientiousness that loyalty demands and improves on other accounts of the intentional dimension of loyalty. Our analysis challenges two of the most prominent ways of conceptualizing fiduciary obligations. “Contractarianism” configures fiduciary obligations as a species of contractual duties. The view that we call “proscriptivism” reduces fiduciary obligations to the juridical prohibitions that apply to fiduciaries. Neither of these approaches is satisfactory, because each neglects the intentional dimension of fiduciary loyalty.
The applicability and application of international humanitarian law to multinational forces
Authors: Ferraro Tristan
Published: July 2014

The multifaceted nature of peace operations today and the increasingly violent environments in which their personnel operate increase the likelihood of their being called upon to use force. It thus becomes all the more important to understand when and how international humanitarian law (IHL) applies to their action. This article attempts to clarify the conditions for IHL applicability to multinational forces, the extent to which this body of law applies to peace operations, the determination of the parties to a conflict involving a multinational peace operation and the classification of such conflict. Finally, it tackles the important question of the personal, temporal and geographical scope of IHL in peace operations.
Zur interindividuellen Variabilität affektiver Reaktionen im Verlauf von Freizeit- und Gesundheitssportprogrammen
Authors: Sudeck Gorden , Conzelmann Achim
Published: July 2014

Positive Effekte sportlicher Aktivität auf das aktuelle Befinden sind meta-analytisch gut dokumentiert. Eine Generalisierung der Befunde wird dadurch eingeschränkt, dass zunehmend eine hohe interindividuelle Variabilität beobachtet wird und Prozesse während der Aktivität defizitär berücksichtigt wurden. Dieser Beitrag geht den Fragen nach, wie groß das Ausmaß interindividueller Variabilität affektiver Reaktionen im Verlauf von gruppenbasierten Freizeit- und Gesundheitssportaktivitäten ist und welchen Einfluss personale Voraussetzungen (Fitnesszustand) und Faktoren der Auseinandersetzung mit der Aktivität (Beanspruchungserleben, Kompetenzwahrnehmung, positives Gruppenerleben) nehmen. Speziell interessiert, inwieweit affektive Reaktionen in Abhängigkeit vom Zeitpunkt sowie in Abhängigkeit der Intensität von unterschiedlichen Faktoren beeinflusst werden. Dazu wurden 110 Universitätsangestellte (M = 49.5 Jahre) wiederholt im Rahmen von mehrwöchigen Programmen befragt. An insgesamt sechs Terminen wurden Handheld-PC-Befragungen vor, zweimal während und nach der Kursstunde durchgeführt, mit denen das aktuelle Befinden und mögliche Einflussfaktoren erfasst wurden. Die Ergebnisse zeigen, dass die Variabilität affektiver Reaktionen im ersten Abschnitt der Sportprogramme am größten ist, während die Reaktionen am Ende der Kursstunde insgesamt positiver und homogener ausfallen. Im ersten Abschnitt sind personale Voraussetzungen noch wichtige Einflussfaktoren, während die Bedeutung der wahrgenommenen Kompetenz und des positiven Gruppenerlebens im Verlauf der Sportaktivität größer wird. Im Einklang mit der Dual Mode Theory weist die Kompetenzwahrnehmung bei anstrengender Intensität im Vergleich zu moderater Intensität einen größeren Zusammenhang mit dem Befinden auf.
Site‐specific host gene modification by zinc finger nucleases: pointing the way to drug free control of HIV‐1?
Authors: Sasson Sarah C , Kelleher Anthony D
Published: July 2014

Anti‐retroviral therapy (ART) for human immunodeficiency virus‐1 (HIV‐1) infection has transformed its clinical course with spectacular reductions in morbidity and mortality, turning this once fatal diagnosis into a manageable chronic infection. However, ART has its limitations. Current ART does not eliminate the virus. Interruption of therapy results in rapid rebound of the virus, and such rebounds are associated with excess morbidity and mortality. This means that therapy once started is for life. This raises the issues of drug resistance due to suboptimal compliance, cumulative toxicities and mounting costs. Efforts to control the virus through novel interventions, particularly through cell or gene therapy have had a resurgence of interest as a single patient was apparently cured by an allogeneic stem cell transplantation from a donor who carried homozygous mutations that disable expression of the HIV‐1 co‐receptor CCR5. This paper reviews the state of play of gene therapy for HIV infection in the context of a recent paper showing the safety and feasibility of an approach that involves the ex vivo disruption of the ccr5 gene in autologous CD4 T cells using a virally delivered zinc finger nuclease, before their expansion and reinfusion. Although there are still considerable challenges, this approach may point towards a future drug free therapy for HIV‐1 infection.
A critical analysis of calcium carbonate mesocrystals
Authors: Kim Yi-Yeoun , Schenk Anna S. , Ihli Johannes , Kulak Alex N. , Hetherington Nicola B. J. , Tang Chiu C. , Schmahl Wolfgang W. , Griesshaber Erika , Hyett Geoffrey , Meldrum Fiona C.
Published: July 2014

The term mesocrystal has been widely used to describe crystals that form by oriented assembly, and that exhibit nanoparticle substructures. Using calcite crystals co-precipitated with polymers as a suitable test case, this article looks critically at the concept of mesocrystals. Here we demonstrate that the data commonly used to assign mesocrystal structure may be frequently misinterpreted, and that these calcite/polymer crystals do not have nanoparticle substructures. Although morphologies suggest the presence of nanoparticles, these are only present on the crystal surface. High surface areas are only recorded for crystals freshly removed from solution and are again attributed to a thin shell of nanoparticles on a solid calcite core. Line broadening in powder X-ray diffraction spectra is due to lattice strain only, precluding the existence of a nanoparticle sub-structure. Finally, study of the formation mechanism provides no evidence for crystalline precursor particles. A re-evaluation of existing literature on some mesocrystals may therefore be required.
Determinants of PCR performance (Xpert MTB/RIF), including bacterial load and inhibition, for TB diagnosis using specimens from different body compartments
Authors: Theron Grant , Peter Jonny , Calligaro Greg , Meldau Richard , Hanrahan Colleen , Khalfey Hoosain , Matinyenya Brian , Muchinga Tapuwa , Smith Liezel , Pandie Shaheen , Lenders Laura , Patel Vinod , Mayosi Bongani M. , Dheda Keertan
Published: July 2014

The determinants of Xpert MTB/RIF sensitivity, a widely used PCR test for the diagnosis of tuberculosis (TB) are poorly understood. We compared culture time-to-positivity (TTP; a surrogate of bacterial load), MTB/RIF TB-specific and internal positive control (IPC)-specific CT values and clinical characteristics in patients with suspected TB who provided expectorated (n = 438) or induced sputum (n = 128), tracheal aspirates (n = 71), bronchoalveolar lavage fluid (n = 152), pleural fluid (n = 76), cerebral spinal fluid (CSF; n = 152), pericardial fluid (n = 131), or urine (n = 173) specimens. Median bacterial load (TTP in days) was the strongest associate of MTB/RIF positivity in each fluid. TTP correlated with CT values in pulmonary specimens but not extrapulmonary specimens (Spearman's coefficient 0.5043 versus 0.1437; p = 0.030). Inhibition affected a greater proportion of pulmonary specimens than extrapulmonary specimens (IPC CT > 34: 6% (47/731) versus 1% (4/381; p < 0.0001). Pulmonary specimens had greater load than extrapulmonary specimens [TTPs (interquartile range) of 11 (7–16) versus 22 (18–33.5) days; p < 0.0001]. HIV-infection was associated with a decreased likelihood of MTB/RIF-positivity in pulmonary specimens but an increased likelihood in extrapulmonary specimens. Mycobacterial load, which displays significant variation across different body compartments, is the main determinant of MTB/RIF-positivity rather than PCR inhibition. MTB/RIF CT is a poor surrogate of load in extrapulmonary specimens.
Long-lasting changes in brain activation induced by a single REAC technology pulse in Wi-Fi bands. Randomized double-blind fMRI qualitative study
Authors: Rinaldi Salvatore , Mura Marco , Castagna Alessandro , Fontani Vania
Published: July 2014

The aim of this randomized double-blind study was to evaluate in healthy adult subjects, with functional magnetic resonance imaging (fMRI), long lasting changes in brain activation patterns following administration of a single, 250 milliseconds pulse emitted with radio-electric asymmetric conveyer (REAC) technology in the Wi-Fi bands. The REAC impulse was not administered during the scan, but after this, according to a protocol that has previously been demonstrated to be effective in improving motor control and postural balance, in healthy subjects and patients. The study was conducted on 33 healthy volunteers, performed with a 1.5 T unit while operating a motor block task involving cyclical and alternating flexion and extension of one leg. Subsequently subjects were randomly divided into a treatment and a sham treatment control group. Repeated fMRI examinations were performed following the administration of the REAC pulse or sham treatment. The Treated group showed cerebellar and ponto-mesencephalic activation components that disappeared in the second scan, while these activation components persisted in the Sham group. This study shows that a very weak signal, such as 250 milliseconds Wi-Fi pulse, administered with REAC technology, could lead to lasting effects on brain activity modification.