bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling the “Known Unknowns”: Lessons and Reflections from the New Directions in Leukemia Research 2012 Conference
Authors: White Deborah L. , Brown Anna L. , D'Andrea Richard J. , Rice Alison M.
Published: June 2012

Patients diagnosed with leukemia approach their treatment with the hope of cure despite the effect on their quality of life. Some patients will be cured, others will die from treatment, and some will die of their disease. A common theme at the New Directions in Leukemia Research (NDLR 2012) meeting was that cure will come if the drivers of the disease are better understood. Key messages included the power of combination platforms to understand the genetic and epigenetic modifications in leukemia to enable development of rational therapies, which can be tested via new clinical trial designs ensuring rapid clinical implementation. Cancer Res; 72(17); 4300–3. ©2012 AACR.
The Role of Radiation Therapy for Uterine Cervical Cancer with Distant Metastasis
Authors: Hata Masaharu , Omura Motoko , Miyagi Etsuko , Koike Izumi , Numazaki Reiko , Asai-Sato Mikiko , Tayama Yoshibumi , Ogino Ichiro , Hirahara Fumiki , Inoue Tomio
Published: June 2012

Objective: We carried out a review to determine the role of radiation therapy in uterine cervical cancer with distant metastasis. Methods: Forty-four patients with uterine cervical cancer with distant metastasis underwent radiation therapy; 29 of these also underwent chemotherapy. A total dose of 19.8–90.4 Gy (median 62.9 Gy) was delivered to the cervical tumors. Results: Thirty-three patients died during the follow-up period of 1–94 months (median 10 months) after irradiation. The overall survival rate at 3 years was 20%, and the estimated median survival time was 15 months. Ten patients developed primary tumor progression, and the primary tumor control rate at 3 years was 49%. A distant metastatic site and primary tumor size were significant prognostic factors for their survival. Total radiation dose was considered a significant and useful variable for primary tumor control. With the exception of transient hematologic reactions and hemorrhagic cystitis, there were no therapy-related toxicities of grade 3 or greater. Conclusions: Radiation therapy was safe and effective for local control in patients with uterine cervical cancer with distant metastasis. More aggressive treatment, including radiation therapy with a curative radiation dose, should be considered for patients with favorable prognostic factors for survival.
Polymorphisms in the CTNND2 Gene and 11q24.1 Genomic Region Are Associated with Pathological Myopia in a Chinese Population
Authors: Yu Zhiqiang , Zhou Jiaqi , Chen Xueli , Zhou Xingtao , Sun Xinghuai , Chu Renyuan
Published: June 2012

Pathological myopia is a refractive error that can result in legal blindness and is prevalent in China. A number of genomic loci have been associated with pathological myopia, but only a few have been validated. This study further evaluated the association of polymorphisms in the CTNND2 gene and the 11q24.1 genomic region with pathological myopia. Both regions had previously been implicated in carrying susceptibility genes for this eye disorder. Genotypic and association analyses were performed on 24 single-nucleotide polymorphisms (SNPs) in the CTNND2 and 11q21.1 genomic regions of 321 subjects with pathological myopia and 310 control subjects with normal vision using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Allele and genotype frequency analyses found that the distribution of variants of the SNP rs1479617 located in the CTNND2 gene significantly differed between the pathological myopia and control groups. Haplotype linkage analysis identified 2 genomic blocks in 11q24.1 that were independently associated with pathological myopia. Specific polymorphisms in the CTNND2 gene and 11q24.1 genomic region were found to be significantly associated with pathological myopia in this Chinese population, further supporting the idea that these genomic regions carry susceptibility loci for this disease.
Biomarkers in Neonatology: The Next Generation of Tests
Authors: Ng Pak C. , Lam Hugh S.
Published: June 2012

Over the past two decades, neonatal clinicians have commonly used host response biomarkers to diagnose and assess the severity of systemic infection. Most of these biomarkers, such as acute-phase proteins or cytokines, are non-specific immunomodulating mediators of the inflammatory cascade. With advances in biochemical/genetic research, it is anticipated that future biomarkers will be ‘organ and/or disease specific’. There is also the quest for discovery of ‘novel’ biomarkers to assist diagnosis and prognosis of neonatal diseases using powerful mass-screening techniques, e.g. the next-generation sequencing, proteomics and arrays. This article aims to introduce the concept of the next generation of biomarkers to practising neonatal clinicians, and, hopefully, to integrate basic science research into day-to-day clinical practice in the future.
Outcome of Infusional 5-Fluorouracil, Doxorubicin, and Mitomycin-C (iFAM) Chemotherapy and Analysis of Prognostic Factors in Patients with Refractory Advanced Biliary Tract Cancer
Authors: Lim Kyu-Hyoung , Han Sae-Won , Oh Do-Youn , Im Seock-Ah , Kim Tae-You , Bang Yung-Jue
Published: June 2012

Objective: The purpose of this study was to determine the efficacy and safety of infusional 5-fluorouracil (5-FU), doxorubicin, and mitomycin-C (iFAM) as salvage chemotherapy in biliary tract cancer (BTC) and to identify prognostic factors. Methods: Fifty patients received 5-FU 800 mg/m2 over 10 h on days 1–5, doxorubicin 30 mg/m2 on day 1 and mitomycin-C 8 mg/m2 on day 1, every 4 weeks. The primary endpoint was the overall survival (OS) rate at 6 months. Results: The responses to iFAM were as follows: partial response in 2 patients (4.2%) and stable disease in 9 patients (18.7%). The median progression-free survival and OS were 2.2 months and 5.6 months, respectively. The 6-month OS rate was 48%. Grade 3/4 adverse events included neutropenia (10%), thrombocytopenia (8%), and anemia (2%). Based on multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status, serum albumin, and response to previous chemotherapy were significantly associated with OS. Three risk groups based on the number of 3 poor prognostic factors (0 vs. 1 vs. 2–3) were well correlated to OS (8.7 vs. 5.5 vs. 2.4 months, respectively; p = 0.0002). Conclusions: iFAM as salvage regimen has modest effect and tolerable toxicity in advanced BTC. The described risk group classification may help guide treatment plans.
Cerebrovascular Function in Aging and Dementia: A Systematic Review of Transcranial Doppler Studies
Authors: Keage Hannah A.D. , Churches Owen F. , Kohler Mark , Pomeroy Danielle , Luppino Rocco , Bartolo Michelle L. , Elliott Scott
Published: June 2012

Background/Aim: The contribution of cerebrovascular dysfunction to the manifestation of dementia and cognitive decline in late life is gaining increased attention. We aimed to systematically review evidence for associations between dementia or aging and cerebrovascular function as measured using transcranial Doppler (TCD) examination. Methods: A total of 1,172 articles were retrieved from PsychInfo and PubMed searches, and 34 relevant articles were identified using a variety of TCD methods. Results: The pulsatility index (vessel resistance), spontaneous emboli and cerebrovascular reactivity to hyper-/hypocapnia appeared good discriminators of dementia. Aging was associated with a slowing in blood flow velocity. Conclusion: TCD ultrasonography is inexpensive, portable and well tolerated by aged and demented subjects. The technique stands to make a valuable contribution to the knowledge regarding the underlying functional biology of age-related cognitive change and dementia.
Facial Basal Cell Carcinomas Recurring after Photodynamic Therapy: A Retrospective Analysis of Histological Subtypes
Authors: Fiechter Sabine , Skaria André , Nievergelt Helga , Anex Romain , Borradori Luca , Parmentier Laurent
Published: June 2012

Background: Photodynamic therapy (PDT) is an established treatment for basal cell carcinomas (BCCs). Although recurrences are sometime observed, their histological patterns have never been specifically studied or compared with the one of the initial tumor. Objective: To compare the histopathological aggressiveness of BCCs recurring after PDT with that of the primary tumors. Methods: The study population included 12 patients with 16 post PDT recurrent BCCs. Outcome measures were proportion of histologically aggressive subtypes in BCC recurrences vs. primary tumor. Results: 62.5% of recurrent BCCs displayed a transition from a non-aggressive to an aggressive subtype. Conclusions: Post PDT recurrences appear to display an increased histological aggressiveness, although the latter may reflect the natural course of tumor progression. Despite the presence of potential biases, our study raises the possibility that PDT favors the selection of more aggressive tumor cells. Better systematic large-scale follow-up studies are required to assess the exact frequency and histological types of BCC recurrences after PDT.
Cathepsin G Inhibitor Prevents Ultraviolet B- Induced Photoaging in Hairless Mice via Inhibition of Fibronectin Fragmentation
Authors: Son E.D. , Shim J.H. , Choi H. , Kim H. , Lim K.M. , Chung J.H. , Byun S.Y. , Lee T.R.
Published: June 2012

Background: Cathepsin G, a serine protease that is activated by ultraviolet (UV) radiation, increases matrix metalloproteinase-1 (MMP-1) expression in fibroblasts through fibronectin (Fn) fragmentation and promotes the conversion of proMMP-1 to active MMP-1. Objectives: This study investigated whether [2-[3-[[(1-benzoyl-4-piperidinyl)methylamino]carbonyl]-2-naphthalenyl]-1-(1-naphthalenyl)-2-oxoethyl]-phosphonic acid (KPA), a cathepsin G inhibitor, plays any role in extracellular matrix (ECM) damage in an in vitro 3D dermal equivalent (DE) and an in vivo ultraviolet B (UVB)-irradiated hairless mice. Methods: We examined the potential ECM-protective effects of a cathepsin G inhibitor in an in vitro 3D DE model and an in vivo UVB-irradiated hairless mouse skin model. Results: Among five known serine protease inhibitors, KPA showed the strongest potency and selectivity against cathepsin G. KPA inhibited the cathepsin G-mediated MMP-1 increase and alleviated the downregulation of mRNAs encoding collagen and tissue inhibitor of matrix metalloproteinase-1 in an in vitro 3D DE model. Most importantly, topical application of KPA (0.025%) to the dorsal skin of hairless mice enhanced collagen expression and attenuated UVB-induced Fn fragmentation and upregulation of MMP-2 and MMP-9 activities. Conclusions: Cathepsin G inhibitors may be useful for the prevention of UVB-induced photoaging through amelioration of ECM damage and MMP upregulation.
Venous thromboembolism: Annualised United States models for total, hospital-acquired and preventable costs utilising long-term attack rates
Authors: Borrego Matthew E. , Woersching Alex L. , Federici Robert , Downey Ross , Tiongson Jay , Bieniarz Mark C. , Cavanaugh Brendan J. , Spyropoulos Alex C. , Mahan Charles E.
Published: June 2012

Healthcare reform is upon the United States (US) healthcare system. Prioritisation of preventative efforts will guide necessary transitions within the US healthcare system. While annual deep-vein thrombosis (DVT) costs have recently been defined at the US national level, annual pulmonary embolism (PE) and venous thromboembolism (VTE) costs have not yet been defined. A decision tree and cost model were developed to estimate US health care costs for total PE, total hospital-acquired PE, and total hospital-acquired “preventable” PE. The previously published DVT cost model was modified, updated and combined with the PE cost model to elucidate the same three categories of costs for VTE. Direct and indirect costs were also delineated. For VTE in the base model, annual cost ranges in 2011 US dollars for total, hospital-acquired, and hospital-acquired “preventable” costs and were $13.5-$27.2, $9.0-$18.2, and $4.5-$14.2 billion, respectively. The first sensitivity analysis, with higher incidence rates and costs, demonstrated annual US total, hospital-acquired, and hospital-acquired “preventable” VTE costs ranging from $32.1-$69.3, $23.7-$51.5, and $11.9-$39.3 billion, respectively. The second sensitivity analysis with long-term attack rates (LTAR) for recurrent events and post-thrombotic syndrome and chronic pulmonary thromboembolic hypertension demonstrated annual US total, hospital-acquired, and hospital-acquired “preventable” VTE costs ranging from $15.4-$34.4, $10.3-$25.4, and $5.1-$19.1 billion, respectively. PE costs comprised a majority of the VTE costs. Prioritisation of effective VTE preventative strategies will reduce significant costs, morbidity and mortality within the US healthcare system. The cost models may be utilised to estimate other countries’ costs or VTE-specific disease states.
Fractalkine – a local inflammatory marker aggravating platelet activation at the vulnerable plaque
Authors: Flierl Ulrike , Schäfer Andreas
Published: June 2012

Chemokines play an important role in inducing chemotaxis of cells, piloting white blood cells in immune surveillance and are crucial parts in the development and progression of atherosclerosis. Platelets are mandatory players in the initiation of atherosclerotic lesion formation and are susceptible targets for and producers of chemokines. Several chemokine receptors on platelets have been described previously, amongst them CX3CR1, the receptor for fractalkine. The unique chemokine fractalkine (CX3CL1, FKN) exists as a soluble as well as a membrane-anchored glycoprotein. Its essential role in the formation of atherosclerotic lesions and atherosclerosis progression has been impressively described in mouse models. Moreover, fractalkine induces platelet activation and adhesion via a functional fractalkine receptor (CX3CR1) expressed on the platelet surface. Platelet activation via the FKN/CX3CR1-axis triggers leukocyte adhesion to activated endothelium, and fractalkine-induced platelet P-selectin is mandatory for leukocyte recruitment under arterial flow conditions. This review summarises the role of fractalkine as a potential local inflammatory mediator which influences platelet activation in the setting of atherosclerosis. Beyond that, aspects of a potential interaction between fractalkine and platelet responsiveness to antiplatelet drugs are described. Furthermore, the possible impact of high-density lipoprotein cholesterol (HDL-C) on atherosclerosis progression, platelet activation and fractalkine signalling are discussed.
Aberrant Neurogenesis After Stroke
Authors: Niv Fanny , Keiner Silke , Krishna -K , Witte Otto W. , Lie Dieter Chichung , Redecker Christoph
Published: June 2012

Background and Purpose—

Adult neurogenesis in the dentate gyrus is a unique form of brain plasticity that is strongly stimulated after stroke. We investigate the morphological properties of new granule cells, which are born and develop after the ischemic insult, and query whether these adult-born neurons properly integrate into the pre-existing hippocampal circuitries.

Methods—

Two well-established models were used to induce either small cortical infarcts (photothrombosis model) or large territorial infarcts (transient middle cerebral artery occlusion model). New granule cells were labeled 4 days after the initial insult by intrahippocampal injection of a retroviral vector encoding green fluorescent protein and newborn neurons were morphologically analyzed using a semiautomatic Neurolucida system and confocal laser scanning microscopy at 6 weeks.

Results—

Approximately 5% to 10% of newborn granule cells displayed significant morphological abnormalities comprising additional basal dendrites and, after middle cerebral artery occlusion, also ectopic cell position. The extent of morphological abnormalities was higher after large territorial infarcts and seems to depend on the severity of ischemic damage. An increased portion of mushroom spines in aberrant neurons suggests stable synaptic integration. However, poststroke generated granule cells with regular appearance also demonstrate alterations in dendritic complexity and spine morphology.

Conclusions—

The remarkable stimulation of dentate neurogenesis after stroke coincides with an increased rate of aberrantly integrated neurons, which may contribute to functional impairments and, hypothetically, favor pathogenesis of adjustment disorders, cognitive deficits, or epilepsy often seen in stroke patients.
Hysteretic properties of metal rubber particles
Authors: Hong Jie , Chen LuLu , Ma Yanhong , Tomlinson Geoffrey R , Rongong Jem A
Published: June 2012

The hysteresis behaviour of metal rubber particles has been characterised. A quasi-static experiment was conducted to measure the damping behaviour of metal rubber particles. The effects of imposed displacement and filling density were examined. A mathematic model has been established to characterise the damping behaviour of metal rubber particles. A single-helix spring model was used to represent the microelement of the metal rubber material. This was composed of three contact states: open, slipping and sticking. The stiffness properties for the three cases were derived. The arrangement and spatial distribution of the microsprings were assumed to be uniform and periodic inside the metal rubber particles component. The test results were compared with the simulation results which showed a good correspondence.
An investigation on microstructure and mechanical properties of post-weld heat-treated friction stir welds in aluminum alloy 2024-W
Authors: Aydın Hakan , Bayram Ali , Durgun İsmail
Published: June 2012

The present work describes the results obtained from microstructural and mechanical evaluation of post-weld heat treated friction stir welds of 2024 aluminum alloys in the W temper state. Post-weld heat treatments have been carried out at 510 °C for 2.5 h followed by ageing at room temperature for 6 months, at 100 °C and 190 °C for 10 h, and by cooling in static air (O-temper). The solution treatment caused abnormal coarsening of the grains in the stir zone, which resulted in a drop in microhardness. The strength of the as-welded joint was significantly incrased by post weld heat treatments. The maximum hardness and strength values were obtained in T6 (190 °C, 10 h) treated joint. However, the T6 (190 °C, 10 h) treated joint had the lowest ductility. On the other hand, the tensile properties of the post-weld heat treated joints were far lower than those of the unwelded base materials in the same temper states. In addition, the post-weld heat treatments did not significantly change the fracture locations of the friction stir welds.
Adding Constructive Competition to Enhance a Cooperative Learning Experience
Authors: Rosol Sarah B.
Published: June 2012

This article reviews a classroom application titled “The Quest for Kudos Challenge,” which is a long-term, multitask, large group competition to attain a reward that was designed to adhere to the recommendations for creating a cooperative learning experience while maintaining the elements of a constructive competition. The application was implemented in a course mid-semester, allowing for a comparison of the results before and after the introduction of the Kudos Challenge. Furthermore, the outcomes for the classes that participated in the Kudos Challenge are compared with classes from a previous semester that did not implement the application. Results show that students in the Kudos Challenge classes received higher exam scores, increased classroom participation, and made more voluntary contributions than the Comparison classes from the previous semester. Qualitative feedback from the Kudos classes was overwhelmingly positive. Furthermore, several positive instructor outcomes resulted from the implementation of the Kudos Challenge, including positive feedback from the students, colleagues, and school administrators; higher student evaluations; and an innovative teaching award.
Towards a reorientation in land reform: From a market to locality-driven approach in South Africa’s land restitution programme
Authors: Logan B. Ikubolajeh , Tengbeh George , Petja Brilliant
Published: June 2012

Despite general agreement that land reform can be a catalyst for positive rural change in sub-Saharan Africa, the means towards this end are frequently coloured in ideological hues, which manifest themselves in confounding binaries like racial justice/environmental justice, market/state and equity/efficiency. The fractures surrounding sub-Saharan land reform are most obvious in the south, where the land question traces its roots to racially motivated colonial policies. The South African government, like others in the region, is attempting to combat landlessness through market-led land reform. This article assesses the implementation of the country’s Land Restitution Programme in the Polokwane district. Its main argument is that the modernist mega-narratives, which inform the programme, create a disconnect between the state and the landless. To address this problem, the article proposes a reorientation in which local narratives will replace theoretical mega-narratives at the centre of land reform programmes.
A Gender Analysis of NBC’s Coverage of the 2008 Summer Olympics
Authors: Davis Kelly K. , Tuggle C.A.
Published: June 2012

This study examines National Broadcasting Company (NBC)’s U.S. broadcast coverage of the 2008 Summer Olympic Games for gender equality and compares that coverage to previous years. Olympics coverage is particularly important to female athletes because many receive little media attention beyond Olympic competition. The study found that, while female participation in the Olympics has increased, NBC’s coverage of women’s events has not, and 97% of airtime devoted to women’s events was confined to six “socially acceptable” sports.
Intracellular cyclophilin A is an important Ca2+ regulator in platelets and critically involved in arterial thrombus formation
Authors: Elvers Margitta , Herrmann Annika , Seizer Peter , Münzer Patrick , Beck Sandra , Schönberger Tanja , Borst Oliver , Martin-Romero Francisco Javier , Lang Florian , May Andreas E. , Gawaz Meinrad
Published: June 2012

Platelet adhesion and aggregation play a critical role in primary hemostasis. Uncontrolled platelet activation leads to pathologic thrombus formation and organ failure. The decisive central step for different processes of platelet activation is the increase in cytosolic Ca2+ activity ([Ca2+]i). Activation-dependent depletion of intracellular Ca2+ stores triggers Ca2+ entry from the extracellular space. Stromal interaction molecule 1 (STIM1) has been identified as a Ca2+ sensor that regulates store-operated Ca2+ entry through activation of the pore-forming subunit Orai1, the major store-operated Ca2+ entry channel in platelets. In the present study, we show for the first time that the chaperone protein cyclophilin A (CyPA) acts as a Ca2+ modulator in platelets. CyPA deficiency strongly blunted activation-induced Ca2+ mobilization from intracellular stores and Ca2+ influx from the extracellular compartment and thus impaired platelet activation substantially. Furthermore, the phosphorylation of the Ca2+ sensor STIM1 was abrogated upon CyPA deficiency, as shown by immunoprecipitation studies. In a mouse model of arterial thrombosis, CyPA-deficient mice were protected against arterial thrombosis, whereas bleeding time was not affected. The results of the present study identified CyPA as an important Ca2+ regulator in platelets, a critical mechanism for arterial thrombosis.
Identifying promoter features of co-regulated genes with similar network motifs
Authors: Harari Oscar , del Val Coral , Romero-Zaliz Rocío , Shin Dongwoo , Huang Henry , Groisman Eduardo A , Zwir Igor
Published: June 2012

Background

A large amount of computational and experimental work has been devoted to uncovering network motifs in gene regulatory networks. The leading hypothesis is that evolutionary processes independently selected recurrent architectural relationships among regulators and target genes (motifs) to produce characteristic expression patterns of its members. However, even with the same architecture, the genes may still be differentially expressed. Therefore, to define fully the expression of a group of genes, the strength of the connections in a network motif must be specified, and the cis-promoter features that participate in the regulation must be determined.

Results

We have developed a model-based approach to analyze proteobacterial genomes for promoter features that is specifically designed to account for the variability in sequence, location and topology intrinsic to differential gene expression. We provide methods for annotating regulatory regions by detecting their subjacent cis-features. This includes identifying binding sites for a transcriptional regulator, distinguishing between activation and repression sites, direct and reverse orientation, and among sequences that weakly reflect a particular pattern; binding sites for the RNA polymerase, characterizing different classes, and locations relative to the transcription factor binding sites; the presence of riboswitches in the 5'UTR, and for other transcription factors. We applied our approach to characterize network motifs controlled by the PhoP/PhoQ regulatory system of Escherichia coli and Salmonella enterica serovar Typhimurium. We identified key features that enable the PhoP protein to control its target genes, and distinct features may produce different expression patterns even within the same network motif.

Conclusion

Global transcriptional regulators control multiple promoters by a variety of network motifs. This is clearly the case for the regulatory protein PhoP. In this work, we studied this regulatory protein and demonstrated that understanding gene expression does not only require identifying a set of connexions or network motif, but also the cis-acting elements participating in each of these connexions.
Prevalence and type of monoclonal gammopathy of undetermined significance in an apparently healthy Nigerian population: a cross sectional study
Authors: Onwah A Lawretta , Adeyemo Titilope A , Adediran Adewumi , Ajibola Sarah O , Akanmu Alani S
Published: June 2012

Background

The prevalence of monoclonal gammopathy of undetermined significance (MGUS), a premalignant plasma-cell disorder has not been determined in our geographic area Nigeria.

Methods

A cross sectional survey was carried on apparently healthy Nigerians selected by multistage sampling technique from the cosmopolitan city of Lagos, Nigeria. Subjects enrolled into the study had 2-step screening for the presence, type and concentration of monoclonal band. Agarose-gel electrophoresis was performed on all serum samples, and any serum sample with a discrete band of monoclonal protein or thought to have a localized band was subjected to Immunofixation. Subjects were also evaluated for Bence jones proteinuria, haematological and biochemical parameters.

Results

Four hundred and ten subjects with a mean age of 45.68 ± 10.3 years, a median of 45.00 years and a range of 20 to 80 years were enrolled into the study. MGUS was identified in only one (0.24 percent) of the 410 study subject. This subject was demonstrated to have a double monoclonal gammopathy; IgGλ at 16.9 g/L and IgAκ at 8.5 g/L. None of them including the sole subject with MGUS had a monoclonal urinary light chain.

Conclusion

Among residents of Lagos, Nigeria, MGUS was found in only 0.24% percent of apparently normal persons with a median age of 45 years. This suggests that MGUS which represents the earliest stage of monoclonal plasma/lymphoid cell proliferation is not a common finding in the relatively young population of Nigeria. Future epidemiologic studies dealing with plasma cell disorders in older people are required to carefully examine the relationship between environmental factors and prevalence of MGUS and its ultimate progression to MM.
Incidence and risk factors of severe adverse events with nevirapine-based antiretroviral therapy in HIV-infected women. MTCT-Plus program, Abidjan, Côte d'Ivoire
Authors: Coffie Patrick A , Tonwe-Gold Besigin , Tanon Aristophane K , Amani-Bosse Clarisse , Bédikou Gédéon , Abrams Elaine J , Dabis François , Ekouevi Didier K
Published: June 2012

Background

In resource-limited settings where nevirapine-containing regimen is the preferred regimen in women, data on severe adverse events (SAEs) according to CD4 cell count are limited. We estimated the incidence of SAEs according to CD4 cell count and identify their risk factors in nevirapine-treated women.

Methods

All HIV-infected women who initiated nevirapine-containing regimen in the MTCT-Plus operational program in Abidjan, Côte d'Ivoire, were eligible for this study. Laboratory and clinical (rash) SAEs were classified as grade 3 and 4. Cox models were used to identify factors associated with the occurrence of SAEs.

Results

From August 2003 to October 2006, 290 women initiated a nevirapine-containing regimen at a median CD4 cell count of 186 cells/mm3(IQR 124-266). During a median follow-up on treatment of 25 months, the incidence of all SAEs was 19.5/100 patient-years. The 24-month probability of occurrence of hepatotoxicity or rash was not different between women with a CD4 cell count >250 cells/mm3and women with a CD4 cell count ≤250 cells/mm3(8.3%vs. 9.9%, Log-rank test: p = 0.75). In a multivariate proportional hazard model, neither CD4 cell count >250 cells/mm3at treatment initiation nor initiation NVP-based regimen initiated during pregnancy were associated with the occurrence of SAEs.

Conclusion

CD4 cell count >250 cells/mm3was not associated with a higher risk of severe hepatotoxicity and/or rash, as well as initiation of ART during pregnancy. Pharmacovogilance data as well as meta-analysis on women receiving NVP in these settings are needed for better information about NVP toxicity.
Hypermethylated 14-3-3-σ and ESR1 gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis
Authors: Zurita Mercedes , Lara Pedro C , del Moral Rosario , Torres Blanca , Linares-Fernández José Luis , Arrabal Sandra Ríos , Martínez-Galán Joaquina , Oliver Francisco Javier , Ruiz de Almodóvar José Mariano
Published: June 2012

Background

Numerous hypermethylated genes have been reported in breast cancer, and the silencing of these genes plays an important role in carcinogenesis, tumor progression and diagnosis. These hypermethylated promoters are very rarely found in normal breast. It has been suggested that aberrant hypermethylation may be useful as a biomarker, with implications for breast cancer etiology, diagnosis, and management. The relationship between primary neoplasm and metastasis remains largely unknown. There has been no comprehensive comparative study on the clinical usefulness of tumor-associated methylated DNA biomarkers in primary breast carcinoma and metastatic breast carcinoma. The objective of the present study was to investigate the association between clinical extension of breast cancer and methylation status ofEstrogen Receptor1(ESR1) andStratifin(14-3-3-σ) gene promoters in disease-free and metastatic breast cancer patients.

Methods

We studied two cohorts of patients: 77 patients treated for breast cancer with no signs of disease, and 34 patients with metastatic breast cancer. DNA was obtained from serum samples, and promoter methylation status was determined by using DNA bisulfite modification and quantitative methylation-specific PCR.

Results

Serum levels of methylated gene promoter14-3-3-σsignificantly differed between Control and Metastatic Breast Cancer groups (P < 0.001), and between Disease-Free and Metastatic Breast Cancer groups (P < 0.001). The ratio of the14-3-3-σlevel before the first chemotherapy cycle to the level just before administration of the second chemotherapy cycle was defined as the Biomarker Response Ratio [BRR]. We calculated BRR values for the "continuous decline" and "rise-and-fall" groups. Subsequent ROC analysis showed a sensitivity of 75% (95% CI: 47.6 - 86.7) and a specificity of 66.7% (95% CI: 41.0 - 86.7) to discriminate between the groups for a cut-off level of BRR = 2.39. The area under the ROC curve (Z = 0.804 ± 0.074) indicates that this test is a good approach to post-treatment prognosis.

Conclusions

The relationship of14-3-3-σwith breast cancer metastasis and progression found in this study suggests a possible application of14-3-3-σas a biomarker to screen for metastasis and to follow up patients treated for metastatic breast cancer, monitoring their disease status and treatment response.
Why has the Universal Coverage Scheme in Thailand achieved a pro-poor public subsidy for health care?
Authors: Limwattananon Supon , Tangcharoensathien Viroj , Tisayaticom Kanjana , Boonyapaisarncharoen Tawekiat , Prakongsai Phusit
Published: June 2012

Background

Thailand has achieved universal health coverage since 2002 through the implementation of the Universal Coverage Scheme (UCS) for 47 million of the population who were neither private sector employees nor government employees. A well performing UCS should achieve health equity goals in terms of health service use and distribution of government subsidy on health. With these goals in mind, this paper assesses the magnitude and trend of government health budget benefiting the poor as compared to the rich UCS members.

Method

Benefit incidence analysis was conducted using the nationally representative household surveys, Health and Welfare Surveys, between 2003 and 2009. UCS members are grouped into five different socio-economic status using asset indexes and wealth quintiles.

Findings

The total government subsidy, net of direct household payment, for combined outpatient (OP) and inpatient (IP) services to public hospitals and health facilities provided to UCS members, had increased from 30 billion Baht (US$ 1 billion) in 2003 to 40-46 billion Baht in 2004-2009. In 2003 for 23% and 12% of the UCS members who belonged to the poorest and richest quintiles of the whole-country populations respectively, the share of public subsidies for OP service was 28% and 7% for the poorest and the richest quintiles, whereby for IP services the share was 27% and 6% for the poorest and richest quintiles respectively. This reflects a pro-poor outcome of public subsidies to healthcare. The OP and IP public subsidies remained consistently pro-poor in subsequent years.

The pro-poor benefit incidence is determined by higher utilization by the poorest than the richest quintiles, especially at health centres and district hospitals. Thus the probability and the amount of household direct health payment for public facilities by the poorest UCS members were less than their richest counterparts.

Conclusions

Higher utilization and better financial risk protection benefiting the poor UCS members are the results of extensive geographical coverage of health service infrastructure especially at district level, adequate finance and functioning primary healthcare, comprehensive benefit package and zero copayment at points of services.
A 90 day chronic toxicity study of Nigerian herbal preparation DAS-77 in rats
Authors: Afolabi Saheed O , Akindele Abidemi J , Awodele Olufunsho , Anunobi Chidozie C , Adeyemi Olufunmilayo O
Published: June 2012

Background

The herbal preparation DAS-77, used for the treatment of various ailments in Nigeria, contains the milled bark of Mangifera indica L. and root of Carica papaya L. Toxicological assessment of the preparation was carried out in this study.

Methods

In the acute toxicity study, DAS-77 was administered to mice p.o. up to 20 g/kg in divided doses and i.p. at 250–3000 mg/kg. Mortality within 24 h was recorded. In the chronic toxicity study, rats were treated p.o. for 90 days at doses of 80, 400 (therapeutic dose, TD) and 2000 mg/kg. By 90 days, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination, antioxidants and histopathological assessments.

Results

DAS-77 did not produce any lethality administered p.o. up to 20 g/kg in divided doses but the i.p. LD50 was 1122.0 mg/kg. At TD, DAS-77 produced significant (p < 0.05) reductions in body weight, food intake and K+, and increases in ovary weight, neutrophils and HDL, which were reversible. Histopathological presentations were generally normal. Effects at the other doses were comparable to those at TD except for reversible increases in antioxidants in the liver, kidney and testes, and sperm abnormality, and reductions in liver enzymes, sperm motility and count.

Conclusions

Findings in this study revealed that DAS-77 is relatively safe with the potential for enhancing in vivo antioxidant activity. However, possibly reversible side-effects include electrolyte imbalance and sterility in males.
In-silico identification of phenotype-biased functional modules
Authors: Padmanabhan Kanchana , Wilson Kevin , Rocha Andrea M , Wang Kuangyu , Mihelcic James R , Samatova Nagiza F
Published: June 2012

Background

Phenotypes exhibited by microorganisms can be useful for several purposes, e.g., ethanol as an alternate fuel. Sometimes, the target phenotype maybe required in combination with other phenotypes, in order to be useful, for e.g., an industrial process may require that the organism survive in an anaerobic, alcohol rich environment and be able to feed on both hexose and pentose sugars to produce ethanol. This combination of traits may not be available in any existing organism or if they do exist, the mechanisms involved in the phenotype-expression may not be efficient enough to be useful. Thus, it may be required to genetically modify microorganisms. However, before any genetic modification can take place, it is important to identify the underlying cellular subsystems responsible for the expression of the target phenotype.

Results

In this paper, we develop a method to identify statistically significant and phenotypically-biased functional modules. The method can compare the organismal network information from hundreds of phenotype expressing and phenotype non-expressing organisms to identify cellular subsystems that are more prone to occur in phenotype-expressing organisms than in phenotype non-expressing organisms. We have provided literature evidence that the phenotype-biased modules identified for phenotypes such as hydrogen production (dark and light fermentation), respiration, gram-positive, gram-negative and motility, are indeed phenotype-related.

Conclusion

Thus we have proposed a methodology to identify phenotype-biased cellular subsystems. We have shown the effectiveness of our methodology by applying it to several target phenotypes. The code and all supplemental files can be downloaded from (http://freescience.org/cs/phenotype-biased-biclusters/).
Using multitask classification methods to investigate the kinase-specific phosphorylation sites
Authors: Gao Shan , Xu Shuo , Fang Yaping , Fang Jianwen
Published: June 2012

Background

Identification of phosphorylation sites by computational methods is becoming increasingly important because it reduces labor-intensive and costly experiments and can improve our understanding of the common properties and underlying mechanisms of protein phosphorylation.

Methods

A multitask learning framework for learning four kinase families simultaneously, instead of studying each kinase family of phosphorylation sites separately, is presented in the study. The framework includes two multitask classification methods: the Multi-Task Least Squares Support Vector Machines (MTLS-SVMs) and the Multi-Task Feature Selection (MT-Feat3).

Results

Using the multitask learning framework, we successfully identify 18 common features shared by four kinase families of phosphorylation sites. The reliability of selected features is demonstrated by the consistent performance in two multi-task learning methods.

Conclusions

The selected features can be used to build efficient multitask classifiers with good performance, suggesting they are important to protein phosphorylation across 4 kinase families.
IDDI: integrated domain-domain interaction and protein interaction analysis system
Authors: Kim Yul , Min Bumki , Yi Gwan-Su
Published: June 2012

Background

Deciphering protein-protein interaction (PPI) in domain level enriches valuable information about binding mechanism and functional role of interacting proteins. The 3D structures of complex proteins are reliable source of domain-domain interaction (DDI) but the number of proven structures is very limited. Several resources for the computationally predicted DDI have been generated but they are scattered in various places and their prediction show erratic performances. A well-organized PPI and DDI analysis system integrating these data with fair scoring system is necessary.

Method

We integrated three structure-based DDI datasets and twenty computationally predicted DDI datasets and constructed an interaction analysis system, named IDDI, which enables to browse protein and domain interactions with their relationships. To integrate heterogeneous DDI information, a novel scoring scheme is introduced to determine the reliability of DDI by considering the prediction scores of each DDI and the confidence levels of each prediction method in the datasets, and independencies between predicted datasets. In addition, we connected this DDI information to the comprehensive PPI information and developed a unified interface for the interaction analysis exploring interaction networks at both protein and domain level.

Result

IDDI provides 204,705 DDIs among total 7,351 Pfam domains in the current version. The result presents that total number of DDIs is increased eight times more than that of previous studies. Due to the increment of data, 50.4% of PPIs could be correlated with DDIs which is more than twice of previous resources. Newly designed scoring scheme outperformed the previous system in its accuracy too. User interface of IDDI system provides interactive investigation of proteins and domains in interactions with interconnected way. A specific example is presented to show the efficiency of the systems to acquire the comprehensive information of target protein with PPI and DDI relationships. IDDI is freely available at http://pcode.kaist.ac.kr/iddi/.
Quality of life among tuberculosis (TB), TB retreatment and/or TB-HIV co-infected primary public health care patients in three districts in South Africa
Authors: Louw Julia , Peltzer Karl , Naidoo Pamela , Matseke Gladys , Mchunu Gugu , Tutshana Bomkazi
Published: June 2012

Introduction

TB and HIV co-morbidity amount to a massive burden on healthcare systems in many countries. This study investigates health related quality of life among tuberculosis (TB), TB retreatment and TB-HIV co-infected public primary health care patients in three districts in South Africa.

Methods

A cross sectional study was conducted among 4900 TB patients who were in the first month of anti-TB treatment in primary public health care clinics in three districts in South Africa. Quality of life was assessed using the social functioning (SF)-12 Health Survey through face to face interviews. Associations of physical health (Physical health Component Summary = PCS) and mental health (Mental health Component Summary = MCS) were identified using logistic regression analyses.

Results

The overall physical and mental health scores were 42.5 and 40.7, respectively. Emotional role, general health and bodily pain had the lowest sub-scale scores, while energy and fatigue and mental health had the highest domain scores. Independent Kruskal–Wallis tests found significant positive effects of being TB-HIV co-infected on the domains of mental health functioning, emotional role, energy and fatigue, social function and physical role, while significant negative effects were observed on general health, bodily pain and physical function. In multivariable analysis higher educational, lower psychological distress, having fewer chronic conditions and being HIV negative were significantly positively associated with PCS, and low poverty, low psychological distress and being HIV positive were positively significantly associated with MCS.

Conclusion

TB and HIV weaken patients’ physical functioning and impair their quality of life. It is imperative that TB control programmes at public health clinics design strategies to improve the quality of health of TB and HIV co-infected patients.
Primary lung cancer presenting with metastasis to the colon: a case report
Authors: Sakai Hiroshi , Egi Hiroyuki , Hinoi Takao , Tokunaga Masakazu , Kawaguchi Yasuo , Shinomura Manabu , Adachi Tomohiro , Arihiro Koji , Ohdan Hideki
Published: June 2012

Although about 50% of lung cancers have distant metastasis at the time of initial diagnosis, colonic metastases are extremely rare. This report presents a rare clinical case of colonic metastasis from primary squamous cell carcinoma of the lung.

A 60-year-old female with anorexia and fatigue was referred to the department of pulmonary surgery in our hospital. The patient was diagnosed with primary squamous cell carcinoma of the lung, T2b N3 M1b Stage IV, and chemoradiotherapy was initiated. This treatment led to a good partial response in the primary lung lesion without any new metastatic lesions.

The patient developed left abdominal pain due to a bulky sigmoid colon tumor 6 months later, and was preoperatively diagnosed with primary colon cancer. She underwent colonic resection, and the pathology specimen demonstrated poorly differentiated squamous cell carcinoma that was suspected to be colonic metastasis from the primary lung cancer. The postoperative course was uneventful, and she was discharged. Chemotherapy for the lung cancer was scheduled in the department of pulmonary surgery.

This report presented a rare case of colonic metastasis from lung cancer. When patients with advanced primary lung cancer complain of abdominal symptoms, we should consider gastrointestinal tract metastasis from lung cancer.
Laser etching of groove structures with micro-optical fiber-enhanced irradiation
Authors: Liu Dameng , Liu Jiachen , Wang Hui , Shao Tianmin
Published: June 2012

A microfiber is used as a laser-focusing unit to fabricate a groove structure on TiAlSiN surfaces. After one laser pulse etching, a groove with the minimum width of 265 nm is manufactured at the area. This technique of microfabricating the groove in microscale is studied. Based on the near-field intensity enhancement at the contact area between the fiber and the surface during the laser irradiation, simulation results are also presented, which agree well with the experimental results.