bluuebunny/crossref_metadata_2025 huggingface dataset:
An update on vaccines against Shigella
Authors: Ashkenazi Shai , Cohen Dani
Published: August 2013

Despite intensive research efforts for more than 60 years, utilizing diverse vaccine strategies, a safe and efficacious vaccine against shigellosis is not available yet. We are currently witnessing innovative approaches based on elucidation of the virulence mechanisms of Shigella, understanding the immune response to the pathogen and progress in molecular technology for developing Shigella vaccines. It is hoped that these will lead to a licensed effective Shigella vaccine to protect humans against the significant worldwide morbidity and mortality caused by this microorganism.
RCircos: an R package for Circos 2D track plots
Authors: Zhang Hongen , Meltzer Paul , Davis Sean
Published: August 2013

Background

Circos is a Perl language based software package for visualizing similarities and differences of genome structure and positional relationships between genomic intervals. Running Circos requires extra data processing procedures to prepare plot data files and configure files from datasets, which limits its capability of integrating directly with other software tools such as R. Recently published R Bioconductor package ggbio provides a function to display genomic data in circular layout based on multiple other packages, which increases its complexity of usage and decreased the flexibility in integrating with other R pipelines.

Results

We implemented an R package, RCircos, using only R packages that come with R base installation. The package supports Circos 2D data track plots such as scatter, line, histogram, heatmap, tile, connectors, links, and text labels. Each plot is implemented with a specific function and input data for all functions are data frames which can be objects read from text files or generated with other R pipelines.

Conclusion

RCircos package provides a simple and flexible way to make Circos 2D track plots with R and could be easily integrated into other R data processing and graphic manipulation pipelines for presenting large-scale multi-sample genomic research data. It can also serve as a base tool to generate complex Circos images.
Nrf2 is required to maintain the self-renewal of glioma stem cells
Authors: Zhu Jianhong , Wang Handong , Sun Qing , Ji Xiangjun , Zhu Lin , Cong Zixiang , Zhou Yuan , Liu Huandong , Zhou Mengliang
Published: August 2013

Background

Glioblastomas are deadly cancers that display a functional cellular hierarchy maintained by self-renewing glioma stem cells (GSCs). Self-renewal is a complex biological process necessary for maintaining the glioma stem cells. Nuclear factor rythroid 2-related factor 2(Nrf2) plays a significant role in protecting cells from endogenous and exogenous stresses. Nrf2 is a key nuclear transcription factor that regulates antioxidant response element (ARE)-containing genes. Previous studies have demonstrated the significant role of Nrf2 in the proliferation of glioblastoma, and in their resistance to radioactive therapies. We examined the effect of knocking down Nrf2 in GSCs.

Methods

Nrf2 expression was down-regulated by shRNA transinfected with lentivirus. Expression levels of Nestin, Nrf2, BMI-1, Sox2 and Cyclin E were assessed by western blotting, quantitative polymerase chain reaction (qPCR) and immunohistochemistry analysis. The capacity for self-renewalin vitrowas assessed by genesis of colonies. The capacity for self-renewalin vivowas analyzed by tumor genesis of xenografts in nude mice.

Results

Knockdown of Nrf2 inhibited the proliferation of GSCs, and significantly reduced the expression of BMI-1, Sox2 and CyclinE. Knocking down of Nrf2 changed the cell cycle distribution of GSCs by causing an uncharacteristic increase in the proportion of cells in the G2 phase and a decrease in the proportion of cells in the S phase of the cell cycle.

Conclusions

Nrf2 is required to maintain the self-renewal of GSCs, and its down-regulation can attenuate the self-renewal of GSCs significantly.
Efavirenz-induced gynecomastia in a prepubertal girl with human immunodeficiency virus infection: a case report
Authors: van Ramshorst Mette S , Kekana Magdeline , Struthers Helen E , McIntyre James A , Peters Remco PH
Published: August 2013

Background

Prepubertal gynecomastia is a rare condition and most frequently classified as idiopathic. In HIV-infected adults gynecomastia is a recognised but infrequent side-effect of antiretroviral treatment (ART) and mostly attributed to efavirenz use. Gynecomastia should be distinguished from pseudogynecomastia as part of the lipodystrophy syndrome caused by Nucleoside Reverse Transcriptase Inhibitors (NRTIs) to avoid incorrect substitution of drugs. In the medical literature only five cases of prepubertal gynecomastia in children taking ART are described and underlying pathogenesis was unknown. The occurrence of adverse effects of ART may interfere with therapy adherence and long-term prognosis and for that reason requires attention. We report the first case of prepubertal gynecomastia in a young girl attributed to efavirenz use.

Case presentation

A seven-year-old African girl presented with true gynecomastia four months after initiation on ART (abacavir, lamivudine, efavirenz). History, physical examination and laboratory tests excluded known causes of gynecomastia and efavirenz was considered as the most likely cause. Six weeks after withdrawal of efavirenz the breast enlargement had completely resolved.

Conclusions

Efavirenz-induced gynecomastia may occur in children as well as in adults. With the increasing access to ART, the possibility of efavirenz-exposure and the potential occurrence of its associated side-effects may be high. In resource-poor settings, empirical change from efavirenz to nevirapine may be considered, providing no other known or alarming cause is identified, as efavirenz-induced gynecomastia can resolve quickly after withdrawal of the drug. Timely recognition of gynecomastia as a side-effect of efavirenz is important in order to intervene while the condition may still be reversible, to sustain adherence to ART and to maintain the sociopsychological health of the child.
‘It is like a tomato stall where someone can pick what he likes’: structure and practices of female sex work in Kampala, Uganda
Authors: Mbonye Martin , Nakamanya Sarah , Nalukenge Winifred , King Rachel , Vandepitte Judith , Seeley Janet
Published: August 2013

Background

Effective interventions among female sex workers require a thorough knowledge of the context of local sex industries. We explore the organisation of female sex work in a low socio-economic setting in Kampala, Uganda.

Methods

We conducted a qualitative study with 101 participants selected from an epidemiological cohort of 1027 women at high risk of HIV in Kampala. Repeat in-depth life history and work practice interviews were conducted from March 2010 to June 2011. Context specific factors of female sex workers’ day-to-day lives were captured. Reported themes were identified and categorised inductively.

Results

Of the 101 women, 58 were active self-identified sex workers operating in different locations within the area of study and nine had quit sex work. This paper focuses on these 67 women who gave information about their involvement in sex work. The majority had not gone beyond primary level of education and all had at least one child. Thirty one voluntarily disclosed that they were HIV-positive. Common sex work locations were streets/roadsides, bars and night clubs. Typically sex occurred in lodges near bars/night clubs, dark alleyways or car parking lots. Overall, women experienced sex work-related challenges at their work locations but these were more apparent in outdoor settings. These settings exposed women to violence, visibility to police, a stigmatising public as well as competition for clients, while bars provided some protection from these challenges. Older sex workers tended to prefer bars while the younger ones were mostly based on the streets. Alcohol consumption was a feature in all locations and women said it gave them courage and helped them to withstand the night chill. Condom use was determined by clients’ willingness, a woman’s level of sobriety or price offered.

Conclusions

Sex work operates across a variety of locations in the study area in Kampala, with each presenting different strategies and challenges for those operating there. Risky practices are present in all locations although they are higher on the streets compared to other locations. Location specific interventions are required to address the complex challenges in sex work environments.
Improving access to care in low and middle-income countries: institutional factors related to enrollment and patient outcome in a cancer drug access program
Authors: Tekinturhan Ebru , Audureau Etienne , Tavolacci Marie-Pierre , Garcia-Gonzalez Patricia , Ladner Joël , Saba Joseph
Published: August 2013

Background

Limited access to drugs is a crucial barrier to reducing the growing impact of cancer in low- and middle-income countries. Approaches based on drug donations or adaptive pricing strategies yield promising but varying results across countries or programs, The Glivec International Patient Assistance Program (GIPAP) is a program designed to provide imatinib free of charge to patients with chronic myeloid leukemia (CML) or gastrointestinal stromal tumors (GIST). The objective of this work was to identify institutional factors associated with enrollment and patient survival in GIPAP.

Methods

We analyzed follow-up data from 4,946 patients participating in 47 institutions within 44 countries between 2003 and 2010. Active status in the program was considered as a proxy for survival.

Results

Presence of ≥1 hematologist or oncologist at the institution was associated with increased patient enrollment. After adjusting for individual factors such as age (>55 years: Hazard Ratio [HR] = 1.42 [1.16; 1.73]; p = 0.001) and initial stage of disease (accelerated or blast crisis at diagnosis: HR = 4.16 [1.87; 9.25]; p < 10-4), increased survival was found in institutions with research capabilities (HR = 0.55 [0.35; 0.86]; p = 0.01) and those with enrollment of >5 patients/year into GIPAP (HR = 0.48 [0.35; 0.67]; p < 10-4), while a non-significant trend for decreased survival was found for treatment at a public institution (HR = 1.32 [0.95; 1.84]; p = 0.10). The negative impact of an accelerated form of CML was attenuated by the presence of ≥1 hematologist or oncologist at the institution (interaction term HR = 0.43 [0.18; 0.99]; p = 0.05).

Conclusions

Application of these findings to the support and selection of institutions participating in GIPAP may help to optimize care and outcomes for CML and GIST patients in the developing world. These results may also be applicable to the treatment of patients with other forms of cancer, due to the overlap of infrastructure and staff resources used to treat a variety of cancer indications. A multi-sector approach is required to address these barriers.
Plasmodium knowlesi and HIV co-infection in a German traveller to Thailand
Authors: Ehrhardt Jonas , Trein Andreas , Kremsner Peter Gottfried , Frank Matthias
Published: August 2013

A case of Plasmodium knowlesi and HIV co-infection is reported in a German traveller returning from Thailand. The 54 year-old patient presented to the Institute of Tropical Medicine in Tübingen with a 11-day history of daily fever and chills. Initial microscopic evaluation of Giemsa-stained thin blood smears was suggestive of a mixed infection with Plasmodium falciparum and Plasmodium malariae. However, PCR amplification of small subunit ribosomal RNA gene revealed a P. knowlesi infection. Parasitaemia was 473 parasites/μl and the platelet count was within the normal range. Oral treatment with Malarone® was initiated and resulted in a fast recovery without any complications.

As part of routine screening the patient also underwent HIV testing and was found to be HIV positive with a CD4 cell count of 115/μl and a viral load of 34,799 copies/ml. A follow-up measurement of the viral load seven days after the first quantification revealed an increase to 102,000 copies/ml. Three months after the first quantification the viral load had dropped to 10,000 copies/ml without the initiation of antiretroviral treatment. This suggests the possibility of a P. knowlesi malaria-induced temporary elevation of viral load similar to that reported for P. falciparum and HIV co-infection.
USP1 deubiquitinase: cellular functions, regulatory mechanisms and emerging potential as target in cancer therapy
Authors: García-Santisteban Iraia , Peters Godefridus J , Giovannetti Elisa , Rodríguez Jose Antonio
Published: August 2013

Reversible protein ubiquitination is emerging as a key process for maintaining cell homeostasis, and the enzymes that participate in this process, in particular E3 ubiquitin ligases and deubiquitinases (DUBs), are increasingly being regarded as candidates for drug discovery. Human DUBs are a group of approximately 100 proteins, whose cellular functions and regulatory mechanisms remain, with some exceptions, poorly characterized. One of the best-characterized human DUBs is ubiquitin-specific protease 1 (USP1), which plays an important role in the cellular response to DNA damage. USP1 levels, localization and activity are modulated through several mechanisms, including protein-protein interactions, autocleavage/degradation and phosphorylation, ensuring that USP1 function is carried out in a properly regulated spatio-temporal manner. Importantly, USP1 expression is deregulated in certain types of human cancer, suggesting that USP1 could represent a valid target in cancer therapy. This view has gained recent support with the finding that USP1 inhibition may contribute to revert cisplatin resistance in anin vitromodel of non-small cell lung cancer (NSCLC). Here, we describe the current knowledge on the cellular functions and regulatory mechanisms of USP1. We also summarize USP1 alterations found in cancer, combining data from the literature and public databases with our own data. Finally, we discuss the emerging potential of USP1 as a target, integrating published data with our novel findings on the effects of the USP1 inhibitor pimozide in combination with cisplatin in NSCLC cells.
Comparative measurement of aortic root by transthoracic echocardiography in normal Korean population based on two different guidelines
Authors: Son Myoung Kyun , Chang Sung-A , Kwak Ji Hye , Lim Hye Jin , Park Sung-Ji , Choi Jin-Oh , Lee Sang-Chol , Park Seung Woo , Kim Duk-Kyung , Oh Jae K
Published: August 2013

Background

Aortic root size is an important parameter in vascular diseases and can be easily assessed by transthoracic echocardiography. However, measurements values may vary according to cardiac cycle and the definition used for edge. This study aimed to define normal values according to the measurement method specified by two different guidelines to determine the influence of the different methods on echocardiographic measurements.

Methods

Healthy Korean adults were enrolled. The aortic root diameters were measured twice at four levels (aortic annulus, sinuses of Valsalva, sinotubular junction, and ascending aorta) by the 2005 American Society of Echocardiography (ASE) guidelines (measured from leading edge to leading edge during diastole) and the 2010 ASE pediatric guidelines (measured from inner edge to inner edge during systole).

Results

One hundred twelve subjects aged 20–69 years were enrolled. The aortic diameters (cm) determine by the aforementioned two guidelines showed significant difference. Measurements were larger in 2005 ASE guideline at aortic annuls, sinuses of Valsalva, and sinotubular junction level, but smaller at ascending aortic level with 2-3mm of differences. Intraobserver variability was similarly good, but interobserver variability was slightly higher than intraobserver variability in both measurement methods. BSA and age was most important determinant for aortic root size.

Conclusions

The measurement method of aortic root can affect the echocardiographic result. The measurement method should be noted when assessing clinical significance of aortic root measurement.
Radiofrequency ablation versus hepatic resection for the treatment of early-stage hepatocellular carcinoma meeting Milan criteria: a systematic review and meta-analysis
Authors: Duan Chenyang , Liu Mengying , Zhang Zhuohang , Ma Kuansheng , Bie Ping
Published: August 2013

Current options for the treatment of the early-stage HCC conforming to the Milan criteria consist of liver transplantation, hepatic resection (HR), transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) .Whether HR or RFA is the better treatment for early HCC has long been debated. The aim of our paper is to compare the therapeutic effects of radiofrequency ablation (RFA) and hepatic resection (HR) in the treatment of early-stage hepatocellular carcinoma (HCC). Controlled trials evaluating the efficacy between RFA and HR for the treatment of early-stage HCC published before June 2013 were searched electronically using MEDLINE, PubMed, Cochrane Library, and EMBASE databases. Using inclusion and exclusion criteria, two randomized controlled trials and 10 nonrandomized controlled trials were included in the meta- analysis. The results showed that the 3,5-year overall survival rates and 1,3,5 disease-free survival rates were significantly lower after RFA than after HR. However, complications after treatment were less common and the length of hospital stay was significantly shorter after RFA. Additionally, there was no significant difference in the 1-year overall survival rate between RFA and HR. The conclusions of the results show that the difference in the short-term effectiveness of RFA and HR in the treatment of small HCC is not notable, but the long-term efficacy of HR is better than that of RFA. However, HR is associated with more complications and a longer hospital stay.
Two-stage hepatectomy after autologous CD133+ stem cells administration: a case report
Authors: Franchi Eloisa , Canepa Maria C , Peloso Andrea , Barbieri Letizia , Briani Laura , Panyor Gabor , Dionigi Paolo , Maestri Marcello
Published: August 2013

Liver resection is the mainstay of treatment for patients with primary and metastatic liver tumors. However, a large majority of patients present for initial medical evaluation with primary and metastatic liver tumors when their cancer is unresectable. Several trials have been undertaken to identify alternative treatments and complementary therapies. In the near future, the field of liver surgery will aim to increase the number of patients that can benefit from resection, since radical removal of the tumor currently provides the sole chance of cure. This paper reports the case of a patient with an advanced colonic cancer in the era of stem cell therapyIn 2011, a 57 years old white Caucasian man with a previous history of non-Hodgkin lymphoma (NHL) was diagnosed with colon cancer and bilobar liver metastases. Following neoadjuvant therapy, the patient was enrolled in a protocol of stem cell administration for liver regeneration. Surgery was initially performed on the primary cancer and left liver lobe. An extended right lobectomy to S1 was then performed after a portal vein embolization (PVE) and stem cell stimulation of the remaining liver. The postoperative course was uneventful and the patient was free of disease after 12 months. Extreme liver resection can provide a safer option and a chance of cure to otherwise unresectable patients when liver regeneration is boosted by PVE and stem cell administration.
Plasma procalcitonin is associated with all-cause and cancer mortality in apparently healthy men: a prospective population-based study
Authors: Cotoi Ovidiu S , Manjer Jonas , Hedblad Bo , Engström Gunnar , Melander Olle , Schiopu Alexandru
Published: August 2013

Background

The inflammatory mediator procalcitonin (PCT) has previously been associated with prognosis in myocardial infarction, cancer and sepsis patients. The importance of PCT in the general population is currently unknown. Our aim was to assess the relationship between plasma PCT and the risk of all-cause and cause-specific mortality in apparently healthy individuals with no previous history of cardiovascular disease or cancer.

Methods

We performed a prospective, population-based study on 3,322 individuals recruited from the Malmö Diet and Cancer cohort, with a median follow-up time of 16.2 years. Plasma PCT, high-sensitivity C-reactive protein (hsCRP), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides and cystatin C were measured at baseline and a thorough risk factor assessment was performed for all subjects. The primary end-points of the study were all-cause mortality, cancer mortality and cardiovascular mortality.

Results

Men had higher PCT levels compared to women. In Cox proportional hazard models adjusted for age, sex, hypertension, diabetes, plasma lipids, renal function, body mass index and smoking, baseline PCT was associated with all-cause mortality and cancer mortality in men. The hazard ratio (HR) for men with PCT levels within the highest compared with the lowest quartile was 1.52 (95% confidence interval (CI) 1.07 to 2.16;P= 0.024) for all-cause mortality and 2.37 (95% CI 1.36 to 4.14;P= 0.006) for cancer mortality. Additionally, men with increased plasma PCT were found to be at a higher risk to develop colon cancer (HR per 1 SD increase = 1.49 (95% CI 1.13 to 1.95);P= 0.005). In multivariate Cox regression analyses with mutual adjustments for PCT and hsCRP, PCT was independently associated with cancer death (HR per 1 SD increase = 1.28 (95% CI 1.10 to 1.49);P= 0.001) and hsCRP with cardiovascular death (HR per 1 SD increase = 1.42 (95% CI 1.11 to 1.83);P= 0.006) in men. We found no significant correlations between baseline PCT or hsCRP and incident cancer or cardiovascular death in women.

Conclusions

We disclose for the first time important independent associations between PCT and the risk for all-cause and cancer mortality in apparently healthy men. Our findings warrant further investigation into the mechanisms underlying the relationship between PCT and cancer.
A duplex, SYBR Green I-based RT-qPCR assay for the simultaneous detection of Apple chlorotic leaf spot virus and Cherry green ring mottle virus in peach
Authors: Zhao Zhe , Yu Yun , Zhang Zhixiang , Liang Pengbo , Ma Yuxin , Li Shifang , Wang Hongqing
Published: August 2013

Background

Co-infections ofApple chlorotic leaf spot virus(ACLSV) andCherry green ring mottle virus(CGRMV) in peach is common in China and have resulted in significant yield reductions. A reliable, sensitive and quantitive method is needed to detect and distinguish between ACLSV and CGRMV in peach.

Findings

We developed a sensitive and specific SYBR Green-I based RT-qPCR for the quantification of ACLSV and CGRMV in different peach tissues, and a duplex RT-qPCR system to detect ACLSV and CGRMV simultaneously. The RT-qPCR method was optimized using standard samples transcribed by the T7 Large Scale RNA Production System in vitro. The peach genes,RNA Polymerase subunit II(RPII) andUbiquitin 10(UBQ10), which were used as the internal controls for the quantification assay also showed good expression stability in this system. Single RT-qPCR assays showed that CGRMV in peach accumulates to a higher level than ACLSV. The detection limits of the duplex RT-qPCR assay were 102and 104copies for ACLSV and CGRMV, respectively. The sensitivity of the duplex RT-qPCR was as high as RT-qPCR and higher than RT-PCR.

Conclusions

The SYBR Green-I RT-qPCR assay provided a sensitive, specific and reliable method for the detection and quantification of ACLSV and CGRMV in different peach tissues. The duplex RT-qPCR system provided a sensitive and specific method to detect and differentiate between ACLSV and CGRMV in a single sample. This RT-qPCR assay could be a useful tool for the routine diagnosis of these two viruses and for disease epidemiology studies in peach orchards.
An analysis of the molecular evolution of Hepatitis B viral genotypes A/B/D using a Bayesian evolutionary method
Authors: Xu Guangyu , Wei Chengguo , Guo Yuqi , Zhang Chao , Zhang Nan , Wang Guoqing
Published: August 2013

Background

Hepatitis B virus (HBV) infection is a major global health problem. The infectious virion contains an inner “core particle”, which is made of 180 or 240 copies of core protein, alternatively known as hepatitis B core antigen, or HBcAg which encloses the viral genome.

Method

In this study, we characterized HBV genotypes and used Bayesian analyses to estimate date of emergence of the most recent common ancestor (TMRCA) of three HBV genotypes, A, B, and D.

Results

We estimated that the rate of evolution of HBV core protein gene to be 1.127 (0.925–1.329, 95% HPD) substitutions per site per year. The TMRCA of HBV for genotypes A, B, D were 118 (54–194, 95% HPD) year, 184 (78–323, 95% HPD) year and 133 (65–230, 95% HPD) year, respectively. Demographic histories of the HBcAg gene showed that the relative genetic diversity had a sharp increase within the first 10 years of its emergence.

Conclusion

Using a bayesian evolutionary method to predict the outbreak trends of HBV through evolutionary trees of HBV, and provide theoretical foundations for clinical prevention and treatment of HBV.
Johan Turi’s animal, mineral, vegetable cures and healing practices: an in-depth analysis of Sami (Saami) folk healing one hundred years ago
Authors: DuBois Thomas A , Lang Jonathan F
Published: August 2013

Background

The healing knowledge of a Sami (Saami) hunter and reindeer herder was surveyed as a window into the concepts of health, healing, and disease in early twentieth-century Sapmi (Northern Sweden). The two books of Johan Turi (1854–1936)—An Account of the Sami(1910) andLappish Texts(1918–19) were examined to determine the varieties of recorded zootherapeutic, mineral, chemical, and ethnobotanical lore, as well as the therapeutic acts, identified conditions, and veterinary knowledge included.

Methods

Tabulation of the materials and species mentioned in Turi’s descriptions (n = 137) permitted analysis of the relative frequency of differing types of healing in Turi’s overall therapeutic repertoire, his relative attention to chronic vs. acute ailments, and the frequency of magic as a component of healing. A qualitative appraisal was made of the degree to which outside influences affected Sami healing of the period. A further assessment of the possible clinical efficacy of the recorded remedies was undertaken.

Results

Turi’s remedies consist most often of zootherapeutics (31%), followed by physical acts such as massage, moxibustion, or manipulation (22%). Ethnobotanical cures make up a significantly smaller portion of his repertoire (17%), followed by mineral and chemical cures (12%). Magic rituals (including incantations and ritual acts) make up a significant portion of Turi’s repertoire, and could be used alone (17%) or in conjunction with other types of healing (38%). Turi’s healing aimed primarily at acute ailments (65%), with chronic conditions addressed less often (35%). A literature review revealed that Turi’s remedies held a marked frequency of likely efficacy, at least in cases in which it was possible to ascertain the precise species, conditions, or substances described. Although it is possible at times to recognize foreign sources in Turi’s repertoire, it is clear that Turi understood all his healing methods as distinctively Sami.

Conclusion

The research illustrates the variety and depth of a single informant’s healing knowledge, and demonstrates the value of both historical sources and in-depth data collection with single experts as useful means of assessing and characterizing an indigenous population’s healing traditions.
Identification of neglected cestode Taenia multicepsmicroRNAs by illumina sequencing and bioinformatic analysis
Authors: Wu Xuhang , Fu Yan , Yang Deying , Xie Yue , Zhang Runhui , Zheng Wanpeng , Nie Huaming , Yan Ning , Wang Ning , Wang Jiahai , Gu Xiaobin , Wang Shuxian , Peng Xuerong , Yang Guangyou
Published: August 2013

Background

Worldwide, but especially in developing countries, coenurosis of sheep and other livestock is caused by Taenia multiceps larvae, and zoonotic infections occur in humans. Infections frequently lead to host death, resulting in huge socioeconomic losses. MicroRNAs (miRNAs) have important roles in the post-transcriptional regulation of a large number of animal genes by imperfectly binding target mRNAs. To date, there have been no reports of miRNAs in T. multiceps.

Results

In this study, we obtained 12.8 million high quality raw reads from adult T. multiceps small RNA library using Illumina sequencing technology. A total of 796 conserved miRNA families (containing 1,006 miRNAs) from 170,888 unique miRNAs were characterized using miRBase (Release 17.0). Here, we selected three conserved miRNA/miRNA* (antisense strand) duplexes at random and amplified their corresponding precursors using a PCR-based method. Furthermore, 20 candidate novel miRNA precursors were verified by genomic PCR. Among these, six corresponding T. multiceps miRNAs are considered specific for Taeniidae because no homologs were found in other species annotated in miRBase. In addition, 181,077 target sites within T. multiceps transcriptome were predicted for 20 candidate newly miRNAs.

Conclusions

Our large-scale investigation of miRNAs in adult T. multiceps provides a substantial platform for improving our understanding of the molecular regulation of T. multiceps and other cestodes development.
Autophagy is involved in oligodendroglial precursor-mediated clearance of amyloid peptide
Authors: Li Wenxia , Tang Yifen , Fan Zhiqin , Meng Ya , Yang Guang , Luo Jia , Ke Zun-Ji
Published: August 2013

Background

Accumulation of β-amyloid peptides is an important hallmark of Alzheimer’s disease (AD). Tremendous efforts have been directed to elucidate the mechanisms of β-amyloid peptides degradation and develop strategies to remove β-amyloid accumulation. In this study, we demonstrated that a subpopulation of oligodendroglial precursor cells, also called NG2 cells, were a new cell type that can clear β-amyloid peptides in the AD transgene mice and in NG2 cell line.

Results

NG2 cells were recruited and clustered around the amyloid plaque in the APPswe/PS1dE9 mice, which is Alzheimer’s disease mouse model. In vitro, NG2 cell line and primary NG2 cells engulfed β-amyloid peptides through the mechanisms of endocytosis in a time dependent manner. Endocytosis is divided into pinocytosis and phagocytosis. Aβ42 internalization by NG2 cells was mediated by actin-dependent macropinocytosis. The presence of β-amyloid peptides stimulated the autophagic pathway in NG2 cells. Once inside the cells, the β-amyloid peptides in NG2 cells were transported to lysosomes and degraded by autophagy.

Conclusions

Our findings suggest that NG2 cells are a new cell type that can clear β-amyloid peptides through endocytosis and autophagy.
Differential proteomic analysis of the secretome of Irpex lacteus and other white-rot fungi during wheat straw pretreatment
Authors: Salvachúa Davinia , Martínez Angel T , Tien Ming , López-Lucendo María F , García Francisco , de los Ríos Vivian , Martínez María Jesús , Prieto Alicia
Published: August 2013

Background

Identifying new high-performance enzymes or enzyme complexes to enhance biomass degradation is the key for the development of cost-effective processes for ethanol production. Irpex lacteus is an efficient microorganism for wheat straw pretreatment, yielding easily hydrolysable products with high sugar content. Thus, this fungus was selected to investigate the enzymatic system involved in lignocellulose decay, and its secretome was compared to those from Phanerochaete chrysosporium and Pleurotus ostreatus which produced different degradation patterns when growing on wheat straw. Extracellular enzymes were analyzed through 2D-PAGE, nanoLC/MS-MS, and homology searches against public databases.

Results

In wheat straw, I. lacteus secreted proteases, dye-decolorizing and manganese-oxidizing peroxidases, and H2O2 producing-enzymes but also a battery of cellulases and xylanases, excluding those implicated in cellulose and hemicellulose degradation to their monosaccharides, making these sugars poorly available for fungal consumption. In contrast, a significant increase of β-glucosidase production was observed when I. lacteus grew in liquid cultures. P. chrysosporium secreted more enzymes implicated in the total hydrolysis of the polysaccharides and P. ostreatus produced, in proportion, more oxidoreductases.

Conclusion

The protein pattern secreted during I. lacteus growth in wheat straw plus the differences observed among the different secretomes, justify the fitness of I. lacteus for biopretreatment processes in 2G-ethanol production. Furthermore, all these data give insight into the biological degradation of lignocellulose and suggest new enzyme mixtures interesting for its efficient hydrolysis.
Occipital lobe epilepsy secondary to Posterior Reversible Encephalopathy Syndrome (PRES) during a post-partum eclampsia in Mali (West Africa)
Authors: Youssoufa Maïga , Callixte Kuate Tegueu , Christian Napon
Published: August 2013

Background

Eclampsia is known to cause posterior reversible encephalopathy syndrome (PRES) that is often associated with an extensive neurovascular damage affecting preferably posterior regions, often leading to reversible cortical blindness. In spite the magnitude of these lesions, post eclamptic symptomatic epilepsy is rare. We therefore report a case of symptomatic occipital lobe epilepsy secondary to PRES.

Case presentation

A 39-year-old female right handed teacher who presented with headache of progressive onset, phosphenes, rapid decline of visual acuity to blindness, vomiting, repeated generalized tonic-clonic seizures followed by altered consciousness and very high blood pressure (HBP) of 240/120 mmHg, all of which started about 12 hours following a normal delivery. Nine months later, the patient presented with paroxysmal visual symptoms predominating in the right visual field followed by partial tonic clonic seizures with secondary generalization and recurrence of partial occipital lobe seizures. The pathophysiologic mechanism of irreversible tissue damage during PRES syndrome could result from a combination of events including the delay for early treatment, inadequate antihypertensive drugs that could worsen the brain damage by hypo perfusion, inadequate or delayed treatment for seizures or status epilepticus.

Conclusion

Despite its high incidence in the third world, eclampsia is not a usual cause of epilepsy. Our case is the first description of post eclamptic occipital lobe epilepsy in Africa. With this report, we draw practitioners’ attention on this rare complication.
Comparison of whole genome amplification and nested-PCR methods for preimplantation genetic diagnosis for BRCA1 gene mutation on unfertilized oocytes–a pilot study
Authors: Michalska Danuta , Jaguszewska Kinga , Liss Joanna , Kitowska Kamila , Mirecka Agata , Łukaszuk Krzysztof
Published: August 2013

Background

Preimplantation genetic diagnosis (PGD) remains nowadays a valid alternative for couples at high-risk of having a child with a genetic disease and for women older than 37–40 years with the high risk of chromosomal aneuploidies in the embryos. However the use of PGD for high penetrance recessive, dominant and X-liked disorders occurring in early life is documented, debate exists regarding its appropriateness in lower penetrance and late-onset cancer susceptibility syndromes. The data regarding the efficacy of different molecular techniques used in PGD are still lacking. We therefore sought to assess the different molecular techniques used in PGD for detecting three most frequent BRCA1 gene mutations: 5382insC, 185delAG and C61G.

Methods

Anonymous donors of the oocytes and control healthy blood samples were extracted and analyzed in the Fertility and Reproductive Center Invicta in Gdansk. Preimplantation genetic diagnosis for the most frequent mutations: 185delAG, 5382insC, C61G in BRCA 1 gene was carried out on single, unfertilized oocytes, in metaphase of second meiotic division, not qualified to IVF. Positive mutation controls were represented by cell lines from the Coriell Institute for Medical Research: GM14090 (185delAG), GM14097 (C61G), GM13715 (5382insC).

Results

Repeatability of the results acquired from the WGA analysis for the mutation 5382insC was 38%. The repeatability of the nested-PCR analysis in the second round of the amplification was labile for the mutation 5382insC and 185delAG and was ranged from 47% to 57%. However, the repeatability for the mutation C61G was 100%.

Conclusions

Our results suggest that the nested-PCR technique remains more sensitive and specific method as compared to WGA. WGA performed on the single cells did not reflect expected results. The repeatability of the WGA methodology remains questionable, and any analysis attempt does not guarantee reliable results.

Further evaluation is strongly needed to propose the most accurate molecular technique used in PGD for detecting three most frequent BRCA1 gene mutations: 5382insC, 185delAG and C61G.
Polyvinyl alcohol:starch:carboxymethyl cellulose containing sodium montmorillonite clay blends; mechanical properties and biodegradation behavior
Authors: Taghizadeh Mohammad Taghi , Sabouri Narges , Ghanbarzadeh Babak
Published: August 2013

The focuses of this study were to investigate the effect of sodium montmorillonite clay (MMT-Na) content on the physical properties and extent of enzymatic hydrolysis Polyvinyl Alcohol (PVA): Starch (S): Carboxymethyl Cellulose (CMC) nanocomposites using enzyme −amylase. The results of this work have revealed that films with MMT-Na content at 5 wt% exhibited a significantly reduced rate and extent of starch hydrolysis. The results suggest that this may have been attributed to interactions between PVA:S:CMC and MMT-Na that further prevented enzymatic attack on the remaining starch phases within the blend. The total solids that remained after 4320 min were 65.46 wt% (PVA:S:CMC); 67.91 wt% (PVA:S:CMC:1% MMT-Na); 78.43 wt% (PVA:S:CMC:3% MMT-Na); 80.24 wt% (PVA:S:CMC:5% MMT-Na). The rate of glucose production from each nanocomposite substrates were decresed significantly as the MMT-Na percentage increased from 0 to 5% (W/W). At the level of 5% (W/W) MMT-Na, the films showed the lowest rate of glucose production values (18.95 μg/ml h). With the increase of the MMT concentration from 0 to 5%, the UTS increased 5 from 18.36 to 20.38 MPa, however, the strain to break (SB) decreased noticeably from 35.56 to 5.22%.
Dietary polyphenols as potential nutraceuticals in management of diabetes: a review
Authors: Bahadoran Zahra , Mirmiran Parvin , Azizi Fereidoun
Published: August 2013

In recent years, there is growing evidence that plant-foods polyphenols, due to their biological properties, may be unique nutraceuticals and supplementary treatments for various aspects of type 2 diabetes mellitus. In this article we have reviewed the potential efficacies of polyphenols, including phenolic acids, flavonoids, stilbenes, lignans and polymeric lignans, on metabolic disorders and complications induced by diabetes. Based on several in vitro, animal models and some human studies, dietary plant polyphenols and polyphenol-rich products modulate carbohydrate and lipid metabolism, attenuate hyperglycemia, dyslipidemia and insulin resistance, improve adipose tissue metabolism, and alleviate oxidative stress and stress-sensitive signaling pathways and inflammatory processes. Polyphenolic compounds can also prevent the development of long-term diabetes complications including cardiovascular disease, neuropathy, nephropathy and retinopathy. Further investigations as human clinical studies are needed to obtain the optimum dose and duration of supplementation with polyphenolic compounds in diabetic patients.
G protein-coupled receptor kinase-3-deficient mice exhibit WHIM syndrome features and attenuated inflammatory responses
Authors: Tarrant Teresa K , Billard Matthew J , Timoshchenko Roman G , McGinnis Marcus W , Serafin D Stephen , Foreman Oded , Esserman Denise A , Chao Nelson J , Lento William E , Lee David M , Patel Dhavalkumar , Siderovski David P
Published: August 2013

Chemokine receptor interactions coordinate leukocyte migration in inflammation. Chemokine receptors are GPCRs that when activated, are phosphorylated by GRKs to turn off G protein-mediated signaling yet recruit additional signaling machinery. Recently, GRK3 was identified as a negative regulator of CXCL12/CXCR4 signaling that is defective in human WHIM syndrome. Here, we report that GRK3−/− mice exhibit numerous features of human WHIM, such as impaired CXCL12-mediated desensitization, enhanced CXCR4 signaling to ERK activation, altered granulocyte migration, and a mild myelokathexis. Moreover, GRK3−/− protects mice from two acute models of inflammatory arthritis (K/BxN serum transfer and CAIA). In these granulocyte-dependent disease models, protection of GRK3−/− mice is mediated by retention of cells in the marrow, fewer circulating granulocytes in the peripheral blood, and reduced granulocytes in the joints during active inflammation. In contrast to WHIM, GRK3−/− mice have minimal hypogammaglobulinemia and a peripheral leukocytosis with increased lymphocytes and absent neutropenia. Thus, we conclude that the loss of GRK3-mediated regulation of CXCL12/CXCR4 signaling contributes to some, but not all, of the complete WHIM phenotype and that GRK3 inhibition may be beneficial in the treatment of inflammatory arthritis.
Histologic and Clinical Characteristics Can Guide Staging Evaluations for Children and Adolescents With Rhabdomyosarcoma: A Report From the Children's Oncology Group Soft Tissue Sarcoma Committee
Authors: Weiss Aaron R. , Lyden Elizabeth R. , Anderson James R. , Hawkins Douglas S. , Spunt Sheri L. , Walterhouse David O. , Wolden Suzanne L. , Parham David M. , Rodeberg David A. , Kao Simon C. , Womer Richard B.
Published: August 2013

Purpose

To simplify the recommended staging evaluation by correlating tumor and clinical features with patterns of distant metastasis in newly diagnosed patients with embryonal rhabdomyosarcoma (ERMS) or alveolar rhabdomyosarcoma (ARMS).

Patients and Methods

Patient data from the Intergroup Rhabdomyosarcoma Study Group and the Children's Oncology Group over two periods were analyzed: 1991 to 1997 and 1999 to 2004. We used recursive partitioning analyses to identify factors (including histology, age, regional nodal and distant metastatic status, tumor size, local invasiveness, and primary site) that divided patients into subsets with the most different rates of metastatic disease.

Results

Of the 1,687 patients analyzed, 5.7% had lung metastases, 4.8% had bone involvement, and 6% had bone marrow (BM) involvement. Rhabdomyosarcoma (RMS) without local invasion (T1) had a low rate of metastasis for all distant sites, especially ERMS (0% bone, 0% BM). ARMS with local invasion (T2) had a higher rate of metastasis for all distant sites (13% lung, 18% bone, 23% BM). ERMS, T2 also had a higher rate of metastatic lung involvement (9%). The likelihood of bone or BM involvement increased in the presence of lung metastases (41% with, 6% without). Regional nodal metastases (N1) predicted a high rate of metastasis in all distant sites (14% lung, 14% bone, 18% BM). A staging algorithm was developed.

Conclusion

Staging studies in childhood RMS can be tailored to patients' presenting characteristics. Bone marrow aspirate and biopsy and bone scan are unnecessary in at least one third of patients with RMS.
Ten-Year Survival in Patients With BRCA1-Negative and BRCA1-Positive Breast Cancer
Authors: Huzarski Tomasz , Byrski Tomasz , Gronwald Jacek , Górski Bohdan , Domagała Pawel , Cybulski Cezary , Oszurek Oleg , Szwiec Marek , Gugała Karol , Stawicka Malgorzata , Morawiec Zbigniew , Mierzwa Tomasz , Janiszewska Hanna , Kilar Ewa , Marczyk Elzbieta , Kozak-Klonowska Beata , Siołek Monika , Surdyka Dariusz , Wiśniowski Rafal , Posmyk Michal , Sun Ping , Lubiński Jan , Narod Steven A.
Published: August 2013

Purpose

To estimate 10-year overall survival (OS) rates for patients with early-onset breast cancer, with and without a BRCA1 mutation, and to identify prognostic factors among those with BRCA1-positive breast cancer.

Patients and Methods

A total of 3,345 women with stage I to III breast cancer, age ≤ 50 years, were tested for three founder mutations in BRCA1. Information on tumor characteristics and treatments received was retrieved from medical records. Dates of death were obtained from the vital statistics registry. Survival curves for the mutation-positive and -negative subcohorts were compared. Predictors of OS were determined using the Cox proportional hazards model.

Results

Of the 3,345 patients enrolled onto the study, 233 (7.0%) carried a BRCA1 mutation. The 10-year survival rate for mutation carriers was 80.9% (95% CI, 75.4% to 86.4%); for noncarriers, it was 82.2% (95% CI, 80.5% to 83.7%). The adjusted hazard ratio (HR) associated with carrying a BRCA1 mutation was 1.81 (95% CI, 1.26 to 2.61). Among BRCA1 carriers with a small (< 2 cm) node-negative tumor, the 10-year survival rate was 89.9%. Among BRCA1 mutation carriers, positive lymph node status was a strong predictor of mortality (adjusted HR, 4.1; 95% CI, 1.8 to 8.9). Oophorectomy was associated with improved survival in BRCA1 carriers (adjusted HR, 0.30; 95% CI, 0.12 to 0.75).

Conclusion

The 10-year survival rate among women with breast cancer and a BRCA1 mutation is similar to that of patients without a BRCA1 mutation. Among women with a BRCA1 mutation, survival was much improved after oophorectomy.
Explicit Prognostic Information and Reassurance About Nonabandonment When Entering Palliative Breast Cancer Care: Findings From a Scripted Video-Vignette Study
Authors: van Vliet Liesbeth M. , van der Wall Elsken , Plum Nicole M. , Bensing Jozien M.
Published: August 2013

Purpose

When discussing the transition to palliative care for patients with breast cancer, oncologists have to find a balance between giving explicit information while not overwhelming patients and being realistic while remaining hopeful. It is unclear whether patients prefer more or less explicit prognostic information, and reassuring patients that they will not be abandoned may provide realistic hope. We assessed the effect of explicit prognostic information and reassurance about nonabandonment at the transition to palliative care.

Patients and Methods

An experimental 2 × 2 study was used. Four scripted videos of a bad news conversation were created that differed only in the level of “explicitness of prognosis” and “reassurance about nonabandonment” (high v low). Patients with and survivors of breast cancer (n = 51) and healthy women (n = 53) watched the video-vignettes. The effects of the different communications on participants' anxiety, uncertainty, self-efficacy, and satisfaction were assessed by using multilevel analyses that explored the moderating influences of monitoring/blunting scores.

Results

The highly explicit/highly reassuring video yielded the most positive outcomes, and the less explicit/less reassuring video, the most negative (P ≤ .05 for all outcome measures except anxiety). The main effects found were that explicitness and reassurance decreased participants' uncertainty (P < .001 and P = .002, respectively) and anxiety (only after reassurance; P = .001) while increasing self-efficacy (P = .004 and P < .001, respectively) and satisfaction (P < .001 and P < .001, respectively). High monitors seemed least positive, mainly following explicitness.

Conclusion

Explicit prognostic information may lead to better outcomes than general information. In addition, reassurance about nonabandonment might provide realistic hope but should be lived up to. More research is needed to translate these findings into clinical care.