bluuebunny/crossref_metadata_2025 huggingface dataset:
A Topical Negative-Pressure Technique With Skin Flap Transplantation to Repair Lower-Limb Wounds With Bone Exposure
Authors: Jianbing Tang , Biao Cheng , Jiangting Zhu , Qin Li , Bin Zhang
Published: December 2012

The treatment of chronic skin ulcers with exposed bone in the lower extremity is difficult. The development of topical negative pressure (TNP) technology and microsurgical techniques have achieved good clinical results in the repair of such ulcers. Between January 2007 and March 2012, TNP combined with flap transfer was applied to repair lower-limb skin and soft-tissue defects associated with exposed bone in 22 cases at our hospital, and good results were achieved that are reported herein.
Mesenchymal Stem Cells/Multipotent Mesenchymal Stromal Cells (MSCs)
Authors: Zou Ji-Ping , Huang Sha , Peng Yan , Liu Hong-Wei , Cheng Biao , Fu Xiao-Bing , Xiang Xiao-Fei
Published: December 2012

Chronic wounds remain a major challenge in modern medicine and represent a significant health care burden. Several treatments have been suggested, but without a full understanding of the exact mechanism by which chronic wound occurs. Numerous studies have shown that mesenchymal stem cells/multipotent mesenchymal stromal cells (MSCs) may have therapeutic potential in healing cutaneous chronic wounds through various mechanisms. So far, a series of hypotheses have been proposed, but a holistic image of them is lacking. This review provides a systematic analysis of recent research in animal models and preclinical or clinic trails to evaluate the potential role of MSCs in chronic cutaneous wound healing. Most important, we highlight how mesenchymal stem cells could potentially revolutionize our approach to treating cutaneous chronic wounds. Special attention should be focused on ongoing research regarding the challenges in using and prospects of MSCs in clinical settings.
Coblation Technology for Surgical Wound Debridement
Authors: Trial Chloé , Brancati Antonio , Marnet Olivier , Téot Luc
Published: December 2012

Debridement is required to prepare the wound bed, essentially in removing undesired tissues observed both in acute wound after burns or trauma and in chronic wounds such as pressure ulcers, leg ulcers, and diabetic foot ulcers. Surgical debridement has been described as one of the most effective methods but can be contraindicated in the elderly, arteriopathic context, or patients under effective anticoagulation. Recently described debridement technologies are based on application of important mechanical severing forces over the wound surface using high-power hydrojets. High water flux acts as a vector for separating necrotic and sloughy tissues from the wound bed and aspirates them out of the wound immediately. Electrical powered techniques and lasers were also scarcely described. The Coblation debridement technology presented here is based on the local induction of a focused plasma field chemically deleting undesired tissues. This technique is a modification of conventional electrosurgical devices, developed in 1928 where tissue excision and coagulation of tissues were observed. Principles of plasma-mediated debridement are based on a bipolar radiofrequency energizing the molecules, thus creating a plasma field. This glow discharge plasma produces chemically active radical species from dissociation of water, breaking molecular bonds, and causing tissue dissolution. The thermal effects are a by-product, which can be modulated by modifying the electrode construction, limiting the local temperature to less than 50°C in order not to induce wound bed renecrosis. The authors describe here the principle, the first technical adaptation for wound debridement, and the potential clinical interest of the Coblation technology
American Labor and American Law: Exceptionalism and its Politics in the Decline of the American Labor Movement
Authors: Friedman Gerald
Published: December 2012

Since Werner Sombart visited the United States at the beginning of the 20th century, scholars and activists have debated whether the American labor movement is “exceptionally” weak and conservative, and why. While some have accepted Exceptionalism and attributed it to the conservative values of American workers, others have attributed it instead to the power of business and the repressive posture of the American government. This article argues that the American legal tradition contributed to “exceptionalism” by privileging individual rights over collective action, and by limiting the power of organizations, including governments as well as unions, over individual choice. While this individualist bias was modified in the 1930s, the Supreme Court quickly restored the individual bias in American labor law, leading to the collapse of unions in the later 20th century.
Jacques-Louis David’s Adieux: The Micropolitics of Sovereignty at the Bourbon Restoration
Authors: Klausen Jimmy Casas
Published: December 2012

In 1816, the restored Bourbon regime banished a group of French Revolutionary politicians from French soil. Although Louis XVIII created an exception for France’s premier painter Jacques-Louis David, David contested this exercise of sovereignty by refusing to be the beneficiary of a monarchic decision on the exception. In rewriting exile as exit, David alters the Revolutionary conception of national sovereignty he subscribed to decades earlier and enacts self-sovereignty instead. David’s painting Les Adieux de Télémaque et d’Eucharis (1818) confirms the artist’s self-sovereign affirmation of responsibility, potential undecidability, and autonomous error in defiance of Bourbon unaccountability, decisionism, and infallibility.
Perceptions of assertiveness among women: Triggering and managing conflict in reality television
Authors: Gómez Antonio García
Published: December 2012

Since the 1990s, the reality television phenomenon has transformed the face of television in many countries (O’Loughlin, 2004). In Spain, for instance, the private domain has gradually invaded the public domain in an attempt to increase audience ratings and also reflect patterns of asymmetrical societal organization (García-Gómez, 2009). Different television formats, which range from docusoaps to the most blatant examples of so-called ‘voyeur television’ (Higgins, 2009), have occupied the prime-time hours. In particular, a wide range of reality television shows has taken the place that mini-series, sitcoms and films of the week used to occupy. These reality television programmes show the transformation of the private domain into one which can be manipulated and incorporated as an essential element in the theatricalization of the intimate experiences of anonymous people (Myers, 2001). By addressing the relationship between mothering and gendered styles, this study adds to the field of research on reality television research by investigating language and gender within the institutional setting of a docusoap and throwing light on the discursive strategies which two different generations of women use to express anger and assertiveness and impose on others. The study reveals that the strategies used by the Spanish female teenagers under scrutiny are associated with hostile laddish verbal behaviour, whereas the mothers’ strategies relate to an instrumental view of aggression.
Peripheral compartment innate immune response to Haemophilus influenzae and Streptococcus pneumoniae in chronic obstructive pulmonary disease patients
Authors: Francis Santiyagu M Savarimuthu , Tan Maxine E , Fung Pamela R , Shaw Janet G , Semmler Annalese BT , Nataatmadja Maria , Bowman Rayleen V , Fong Kwun M , Yang Ian A
Published: December 2012

Alterations in innate immunity that predispose to chronic obstructive pulmonary disease (COPD) exacerbations are poorly understood. We examined innate immunity gene expression in peripheral blood polymorphonuclear leukocytes (PMN) and monocytes stimulated by Haemophilus influenzae and Streptococcus pneumoniae. Thirty COPD patients (15 rapid and 15 non-rapid lung function decliners) and 15 smokers without COPD were studied. Protein expression of IL-8, IL-6, TNF-α and IFN-γ (especially monocytes) increased with bacterial challenge. In monocytes stimulated with S. pneumoniae, TNF-α protein expression was higher in COPD (non-rapid decliners) than in smokers. In co-cultures of monocytes and PMN, mRNA expression of TGF-β1 and MYD88 was up-regulated, and CD14, TLR2 and IFN-γ down-regulated with H. influenzae challenge. TNF-α mRNA expression was increased with H. influenzae challenge in COPD. Cytokine responses were similar between rapid and non-rapid decliners. TNF-α expression was up-regulated in non-rapid decliners in response to H. influenzae (monocytes) and S. pneumoniae (co-culture of monocytes and PMN). Exposure to bacterial pathogens causes characteristic innate immune responses in peripheral blood monocytes and PMN in COPD. Bacterial exposure significantly alters the expression of TNF-α in COPD patients, although not consistently. There did not appear to be major differences in innate immune responses between rapid and non-rapid decliners.
Sodium reduction and the correction of iodine intake in Belgium: Policy options
Authors: Vandevijvere Stefanie
Published: December 2012

Many studies suggest that high salt intakes are related to high blood pressure and consequently cardiovascular diseases. In addition salt intake was found to be related with obesity, renal stones, osteoporosis and stomach cancer. Belgium, such as other European countries, is suffering from both salt intakes that are twice as high as the recommended intakes and mild iodine deficiency. No comprehensive strategy encompassing both public health problems has been developed. While specific salt reduction targets for processed foods are still under discussion using a consensus approach with industry, an agreement was signed between the bakery sector and the Ministry of Health in April 2009, to encourage and increase the use of iodised salt in the production of bread. Based on results of recent surveys on population iodine status it is advised not to currently revise iodine concentrations in salt in bread but to advocate for a higher percentage of bakers using iodised salt and to install a good monitoring system to control the percentage of bakers effectively using adequately iodised salt. With regard to salt reduction, it is of utmost importance that all companies contribute and harmonise the salt content of their products according to the lowest possible thresholds in a first step. In order to achieve this goal, it will be necessary, in addition to the consensus approach, to come up with at least some legislative tools such as a salt tax or mandatory labelling of foods exceeding a specific sodium concentration. Once salt reduction targets have been clearly defined in Belgium over the longer term, a legal framework should be set in place where iodine concentration in salt for the production of bread and household salt is strictly regulated by law, to avoid a large variability in the iodine content of salt brands consumed. In conclusion, it is possible to tackle salt reduction and iodine deficiency at the same time on the condition that the approach is coordinated and well monitored. All the interventions and measures taken should clearly include education and communication directed towards consumers, food producers, public health professionals, pharmacists, healthcare workers, and media representatives.
A novel method to identify high order gene-gene interactions in genome-wide association studies: Gene-based MDR
Authors: Oh Sohee , Lee Jaehoon , Kwon Min-Seok , Weir Bruce , Ha Kyooseob , Park Taesung
Published: December 2012

Background

Because common complex diseases are affected by multiple genes and environmental factors, it is essential to investigate gene-gene and/or gene-environment interactions to understand genetic architecture of complex diseases. After the great success of large scale genome-wide association (GWA) studies using the high density single nucleotide polymorphism (SNP) chips, the study of gene-gene interaction becomes a next challenge. Multifactor dimensionality reduction (MDR) analysis has been widely used for the gene-gene interaction analysis. In practice, however, it is not easy to perform high order gene-gene interaction analyses via MDR in genome-wide level because it requires exploring a huge search space and suffers from a computational burden due to high dimensionality.

Results

We propose dimensional reduction analysis, Gene-MDR analysis for the fast and efficient high order gene-gene interaction analysis. The proposed Gene-MDR method is composed of two-step applications of MDR: within- and between-gene MDR analyses. First, within-gene MDR analysis summarizes each gene effect via MDR analysis by combining multiple SNPs from the same gene. Second, between-gene MDR analysis then performs interaction analysis using the summarized gene effects from within-gene MDR analysis. We apply the Gene-MDR method to bipolar disorder (BD) GWA data from Wellcome Trust Case Control Consortium (WTCCC). The results demonstrate that Gene-MDR is capable of detecting high order gene-gene interactions associated with BD.

Conclusion

By reducing the dimension of genome-wide data from SNP level to gene level, Gene-MDR efficiently identifies high order gene-gene interactions. Therefore, Gene-MDR can provide the key to understand complex disease etiology.
High-throughput comparison of gene fitness among related bacteria
Authors: Canals Rocio , Xia Xiao-Qin , Fronick Catrina , Clifton Sandra W , Ahmer Brian MM , Andrews-Polymenis Helene L , Porwollik Steffen , McClelland Michael
Published: December 2012

Background

The contribution of a gene to the fitness of a bacterium can be assayed by whether and to what degree the bacterium tolerates transposon insertions in that gene. We use this fact to compare the fitness of syntenic homologous genes among related Salmonella strains and thereby reveal differences not apparent at the gene sequence level.

Results

A transposon Tn5 derivative was used to construct mutants in Salmonella Typhimurium ATCC14028 (STM1) and Salmonella Typhi Ty2 (STY1), which were then grown in rich media. The locations of 234,152 and 53,556 integration sites, respectively, were mapped by sequencing. These data were compared to similar data available for a different Ty2 isolate (STY2) and essential genes identified in E. coli K-12 (ECO). Of 277 genes considered essential in ECO, all had syntenic homologs in STM1, STY1, and STY2, and all but nine genes were either devoid of transposon insertions or had very few. For three of these nine genes, part of the annotated gene lacked transposon integrations (yejM, ftsN and murB). At least one of the other six genes, trpS, had a potentially functionally redundant gene encoded elsewhere in Salmonella but not in ECO. An additional 165 genes were almost entirely devoid of transposon integrations in all three Salmonella strains examined, including many genes associated with protein and DNA synthesis. Four of these genes (STM14_1498, STM14_2872, STM14_3360, and STM14_5442) are not found in E. coli. Notable differences in the extent of gene selection were also observed among the three different Salmonella isolates. Mutations in hns, for example, were selected against in STM1 but not in the two STY strains, which have a defect in rpoS rendering hns nonessential.

Conclusions

Comparisons among transposon integration profiles from different members of a species and among related species, all grown in similar conditions, identify differences in gene contributions to fitness among syntenic homologs. Further differences in fitness profiles among shared genes can be expected in other selective environments, with potential relevance for comparative systems biology.
Losing identity: structural diversity of transposable elements belonging to different classes in the genome of Anopheles gambiae
Authors: Fernández-Medina Rita D , Ribeiro José M C , Carareto Claudia M A , Velasque Luciane , Struchiner Cláudio J
Published: December 2012

Background

Transposable elements (TEs), both DNA transposons and retrotransposons, are genetic elements with the main characteristic of being able to mobilize and amplify their own representation within genomes, utilizing different mechanisms of transposition. An almost universal feature of TEs in eukaryotic genomes is their inability to transpose by themselves, mainly as the result of sequence degeneration (by either mutations or deletions). Most of the elements are thus either inactive or non-autonomous. Considering that the bulk of some eukaryotic genomes derive from TEs, they have been conceived as “TE graveyards.” It has been shown that once an element has been inactivated, it progressively accumulates mutations and deletions at neutral rates until completely losing its identity or being lost from the host genome; however, it has also been shown that these “neutral sequences” might serve as raw material for domestication by host genomes.

Results

We have analyzed the sequence structural variations, nucleotide divergence, and pattern of insertions and deletions of several superfamilies of TEs belonging to both class I (long terminal repeats [LTRs] and non-LTRs [NLTRs]) and II in the genome ofAnopheles gambiae, aiming at describing the landscape of deterioration of these elements in this particular genome. Our results describe a great diversity in patterns of deterioration, indicating lineage-specific differences including the presence of Solo-LTRs in the LTR lineage, 5′-deleted NLTRs, and several non-autonomous and MITEs in the class II families. Interestingly, we found fragments of NLTRs corresponding to the RT domain, which preserves high identity among them, suggesting a possible remaining genomic role for these domains.

Conclusions

We show here that the TEs in theAn. gambiaegenome deteriorate in different ways according to the class to which they belong. This diversity certainly has implications not only at the host genomic level but also at the amplification dynamic and evolution of the TE families themselves.
Staphylococcus aureus autoinducer-2 quorum sensing decreases biofilm formation in an icaR-dependent manner
Authors: Yu Dan , Zhao Liping , Xue Ting , Sun Baolin
Published: December 2012

Background

Staphylococcus aureus is an important pathogen that causes biofilm-associated infection in humans. Autoinducer 2 (AI-2), a quorum-sensing (QS) signal for interspecies communication, has a wide range of regulatory functions in both Gram-positive and Gram-negative bacteria, but its exact role in biofilm formation in S. aureus remains unclear.

Results

Here we demonstrate that mutation of the AI-2 synthase gene luxS in S. aureus RN6390B results in increased biofilm formation compared with the wild-type (WT) strain under static, flowing and anaerobic conditions and in a mouse model. Addition of the chemically synthesized AI-2 precursor in the luxS mutation strain (ΔluxS) restored the WT phenotype. Real-time RT-PCR analysis showed that AI-2 activated the transcription of icaR, a repressor of the ica operon, and subsequently a decreased level of icaA transcription, which was presumably the main reason why luxS mutation influences biofilm formation. Furthermore, we compared the roles of the agr-mediated QS system and the LuxS/AI-2 QS system in the regulation of biofilm formation using the ΔluxS strain, RN6911 and the Δagr ΔluxS strain. Our data indicate a cumulative effect of the two QS systems on the regulation of biofilm formation in S. aureus.

Conclusion

These findings demonstrate that AI-2 can decrease biofilm formation in S. aureus via an icaR-activation pathway. This study may provide clues for therapy in S. aureus biofilm-associated infection.
Molecular insights into how a deficiency of amylose affects carbon allocation – carbohydrate and oil analyses and gene expression profiling in the seeds of a rice waxy mutant
Authors: Zhang Ming-Zhou , Fang Jie-Hong , Yan Xia , Liu Jun , Bao Jin-Song , Fransson Gunnel , Andersson Roger , Jansson Christer , Åman Per , Sun Chuanxin
Published: December 2012

Background

Understanding carbon partitioning in cereal seeds is of critical importance to develop cereal crops with enhanced starch yields for food security and for producing specified end-products high in amylose, β-glucan, or fructan, such as functional foods or oils for biofuel applications. Waxy mutants of cereals have a high content of amylopectin and have been well characterized. However, the allocation of carbon to other components, such as β-glucan and oils, and the regulation of the altered carbon distribution to amylopectin in a waxy mutant are poorly understood. In this study, we used a rice mutant, GM077, with a low content of amylose to gain molecular insight into how a deficiency of amylose affects carbon allocation to other end products and to amylopectin. We used carbohydrate analysis, subtractive cDNA libraries, and qPCR to identify candidate genes potentially responsible for the changes in carbon allocation in GM077 seeds.

Results

Carbohydrate analysis indicated that the content of amylose in GM077 seeds was significantly reduced, while that of amylopectin significantly rose as compared to the wild type BP034. The content of glucose, sucrose, total starch, cell-wall polysaccharides and oil were only slightly affected in the mutant as compared to the wild type. Suppression subtractive hybridization (SSH) experiments generated 116 unigenes in the mutant on the wild-type background. Among the 116 unigenes, three, AGP, ISA1 and SUSIBA2-like, were found to be directly involved in amylopectin synthesis, indicating their possible roles in redirecting carbon flux from amylose to amylopectin. A bioinformatics analysis of the putative SUSIBA2-like binding elements in the promoter regions of the upregulated genes indicated that the SUSIBA2-like transcription factor may be instrumental in promoting the carbon reallocation from amylose to amylopectin.

Conclusion

Analyses of carbohydrate and oil fractions and gene expression profiling on a global scale in the rice waxy mutant GM077 revealed several candidate genes implicated in the carbon reallocation response to an amylose deficiency, including genes encoding AGPase and SUSIBA2-like. We believe that AGP and SUSIBA2 are two promising targets for classical breeding and/or transgenic plant improvement to control the carbon flux between starch and other components in cereal seeds.
Chronic HCV infection: epidemiological and clinical relevance
Authors: Zaltron S , Spinetti A , Biasi L , Baiguera C , Castelli F
Published: December 2012

Hepatitis C virus (HCV), first recognized as a cause of transfusion-associated acute and chronic hepatitis in 1989, plays a major role as a cause of chronic liver injury, with potential for neoplastic degeneration. It is mainly transmitted by the parenteral route. However, although with lower efficiency, it may be also transmitted by sexual intercourses and by the mother-to-child route. Epidemiological evidence shows that a wave of infection occurred in the 1945-65 period (baby boomers) in western countries. After acute infection, as many as 50-85% of the patients fail to clear the virus resulting in chronic liver infection and/or disease. It is estimated that, on a global scale, about 170 million people are chronically infected with HCV, leading to about 350.000 deaths yearly. Among western countries southern Europe, and particularly Italy, is among the most affected areas. The impact on the public health systems is noteworthy, with high number of hospitalizations due to chronic liver disease, cirrhosis or hepatocellular carcinoma. While waiting for a safe and effective vaccine to be made available, new promising direct-acting antiviral (DAA) drugs offer a better therapeutic scenario than in the past even for the poor responder genotypes 1 and 4, provided that effective screening and care is offered. However, the long and aspecific prodromic period before clinical symptoms develop is a major obstacle to early detection and treatment. Effective screening strategies may target at-risk groups or age specific groups, as recently recommended by the CDC.
A case of focal segmental glomerulosclerosis in an adult patient with hypogammaglobulinemia superimposed on membranoproliferative glomerulonephritis in childhood
Authors: Tsuji Kenji , Uchida Haruhito Adam , Ono Tetsuichirou , Inoue Tatsuyuki , Shinagawa Katsuji , Kitamura Shinji , Maeshima Yohei , Sugiyama Hitoshi , Makino Hirofumi
Published: December 2012

Background

Common variable immunodeficiency (CVID) is a disorder characterized by hypogammaglobulinemia without a known predisposing cause.

Case presentation

We report a 36-year-old man who had suffered membranoproliferative glomerulonephritis (MPGN) in his childhood, later diagnosed with CVID at 35 years of age. He presented at our hospital with signs of proteinuria. A renal biopsy revealed he suffered from focal segmental glomerulosclerosis (FSGS), possibly due to obesity and hypertension, not CVID - associated MPGN.

Conclusion

This is the first case report of FSGS in a CVID patient. In this case, we have to pay attention not only to the treatment of obesity and hypertension for FSGS but also to the recurrence of immune-complex glomerulonephritis such as MPGN, in case of the restoration of hypogammaglobulinemia.
Potential role of probiotics on colorectal cancer prevention
Authors: Uccello Mario , Malaguarnera Giulia , Basile Francesco , D’agata Velia , Malaguarnera Michele , Bertino Gaetano , Vacante Marco , Drago Filippo , Biondi Antonio
Published: December 2012

Background

Colorectal cancer represents the most common malignancy of the gastrointestinal tract. Owing to differences in dietary habits and lifestyle, this neoplasm is more common in industrialized countries than in developing ones. Evidence from a wide range of sources supports the assumption that the link between diet and colorectal cancer may be due to an imbalance of the intestinal microflora.

Discussion

Probiotic bacteria are live microorganisms that, when administered in adequate amounts, confer a healthy benefit on the host, and they have been investigated for their protective anti-tumor effects. In vivo and molecular studies have displayed encouraging findings that support a role of probiotics in colorectal cancer prevention.

Several mechanisms could explain the preventive action of probiotics against colorectal cancer onset. They include: alteration of the intestinal microflora; inactivation of cancerogenic compounds; competition with putrefactive and pathogenic microbiota; improvement of the host’s immune response; anti-proliferative effects via regulation of apoptosis and cell differentiation; fermentation of undigested food; inhibition of tyrosine kinase signaling pathways.
Effects of Astragalus polysaccharides on P-glycoprotein efflux pump function and protein expression in H22 hepatoma cells in vitro
Authors: Tian Qing E , De Li Huan , Yan Miao , Cai Hua-Lin , Tan Qin-You , Zhang Wen-Yuan
Published: December 2012

Background

Astragalus polysaccharides (APS) are active constituents of Astragalus membranaceus. They have been widely studied, especially with respect to their immunopotentiating properties, their ability to counteract the side effects of chemotherapeutic drugs, and their anticancer properties. However, the mechanism by which APS inhibit cancer and the issue of whether that mechanism involves the reversal of multidrug resistance (MDR) is not completely clear. The present paper describes an investigation of the effects of APS on P-glycoprotein function and expression in H22 hepatoma cell lines resistant to Adriamycin (H22/ADM).

Methods

H22/ADM cell lines were treated with different concentrations of APS and/or the most common chemotherapy drugs, such as Cyclophosphamid, Adriamycin, 5-Fluorouracil, Cisplatin, Etoposide, and Vincristine. Chemotherapeutic drug sensitivity, P-glycoprotein function and expression, and MDR1 mRNA expression were detected using MTT assay, flow cytometry, Western blotting, and quantitative RT-PCR.

Results

When used alone, APS had no anti-tumor activity in H22/ADM cells in vitro. However, it can increase the cytotoxicity of certain chemotherapy drugs, such as Cyclophosphamid, Adriamycin, 5-Fluorouracil, Cisplatin, Etoposide, and Vincristine, in H22/ADM cells. It acts in a dose-dependent manner. Compared to a blank control group, APS increased intracellular Rhodamine-123 retention and decreased P-glycoprotein efflux function in a dose-dependent manner. These factors were assessed 24 h, 48 h, and 72 h after administration. APS down regulated P-glycoprotein and MDR1 mRNA expression in a concentration-dependent manner within a final range of 0.8–500 mg/L and in a time-dependent manner from 24–72 h.

Conclusion

APS can enhance the chemosensitivity of H22/ADM cells. This may involve the downregulation of MDR1 mRNA expression, inhibition of P-GP efflux pump function, or both, which would decrease the expression of the MDR1 protein.
Myocardial dysfunction in patients with type 2 diabetes mellitus: role of endothelial progenitor cells and oxidative stress
Authors: Zhao Chun Ting , Wang Mei , Siu Chung Wah , Hou Ying Long , Wang Tian , Tse Hung Fat , Yiu Kai Hang
Published: December 2012

Background

Endothelial progenitor cells (EPCs) are responsible for angiogenesis and maintenance of microvascular integrity, the number of EPCs is correlated with oxidative stress. Their relation to myocardial dysfunction in patients with type 2 diabetes mellitus (T2DM) is nonetheless unknown.

Methods

Eighty-seven patients with T2DM and no history of coronary artery disease were recruited. Transthoracic echocardiography and detailed evaluation of left ventricular (LV) systolic function by 2-dimensional (2D) speckle tracking derived strain analysis in 3 orthogonal directions was performed. Four subpopulations of EPCs, including CD34+, CD133+, CD34+/kinase insert domain-containing receptor (KDR) + and CD133+/KDR + EPCs, were measured by flow cytometry. Oxidative stress was assessed by superoxide dismutase (SOD).

Results

The mean age of the patients was 62 ± 9 years and 39.6% were male. Those with an impaired longitudinal strain had a lower number of CD34+ EPCs (2.82 ± 1.87% vs. 3.74 ± 2.12%, P < 0.05) than those with preserved longitudinal strain. When compared with those with preserved circumferential strain, patients with an impaired circumferential strain had a lower number of CD34+ EPCs (2.63 ± 1.80% vs. 3.87 ± 2.10%, P < 0.01) and SOD level (0.13 ± 0.06U/ml vs. 0.20 ± 0.08U/ml, P < 0.01). Patients with an impaired radial strain nonetheless had a lower number of CD34+ EPCs (2.62 ± 2.08% vs. 3.69 ± 1.99%, P < 0.05). Multivariate analysis demonstrated that only impaired global circumferential strain remained significantly associated with CD34 + EPCs and SOD.

Conclusions

LV global circumferential strain was independently associated with number of CD34+ EPCs and SOD. These findings suggest that myocardial dysfunction in patients with T2DM is related to depletion of EPCs and increased oxidative stress.
Epidemiology of Plasmodium knowlesi malaria in north-east Sabah, Malaysia: family clusters and wide age distribution
Authors: Barber Bridget E , William Timothy , Dhararaj Prabakaran , Anderios Fread , Grigg Matthew J , Yeo Tsin W , Anstey Nicholas M
Published: December 2012

Background

The simian parasite Plasmodium knowlesi is a common cause of human malaria in Malaysian Borneo, with a particularly high incidence in Kudat, Sabah. Little is known however about the epidemiology in this substantially deforested region.

Methods

Malaria microscopy records at Kudat District Hospital were retrospectively reviewed from January 2009-November 2011. Demographics, and PCR results if available, were recorded for each positive result. Medical records were reviewed for patients suspected of representing family clusters, and families contacted for further information. Rainfall data were obtained from the Malaysian Meteorological Department.

Results

“Plasmodium malariae” mixed or mono-infection was diagnosed by microscopy in 517/653 (79%) patients. Of these, PCR was performed in 445 (86%) and was positive for P. knowlesi mono-infection in 339 (76%). Patients with knowlesi malaria demonstrated a wide age distribution (median 33, IQR 20–50, range 0.7-89 years) with P. knowlesi predominating in all age groups except those <5 years old, where numbers approximated those of Plasmodium falciparum and Plasmodium vivax. Two contemporaneous family clusters were identified: a father with two children (aged 10–11 years); and three brothers (aged one-11 years), all with PCR-confirmed knowlesi malaria. Cases of P. knowlesi demonstrated significant seasonal variation, and correlated with rainfall in the preceding three to five months.

Conclusions

Plasmodium knowlesi is the most common cause of malaria admissions to Kudat District Hospital. The wide age distribution and presence of family clusters suggest that transmission may be occurring close to or inside people’s homes, in contrast to previous reports from densely forested areas of Sarawak. These findings have significant implications for malaria control. Prospective studies of risk factors, vectors and transmission dynamics of P. knowlesi in Sabah, including potential for human-to-human transmission, are needed.
Wait, treat and see: echocardiographic monitoring of brain-dead potential donors with stunned heart
Authors: Casartelli Marilena , Bombardini Tonino , Simion Davide , Gaspari Maria Grazia , Procaccio Francesco
Published: December 2012

Background

Heart transplantation is limited by a severe donor organ shortage. Potential donors with brain death (BD) and left ventricular dysfunction due to neurogenic stunning are currently excluded from donation – although such abnormalities can be reversible with aggressive treatment including Hormonal Treatment (HT) and deferred organ retrieval.

Aim

To assess the recovery of left ventricular dysfunction in potential brain-dead donors with hemodynamic instability treated by aggressive treatment and HT.

Methods

In a single-center, observational study design, we evaluated 15 consecutive brain-dead potential donors (DBD) (8 males, age = 48 ± 15 years) with hemodynamic instability. All underwent standard hemodynamic monitoring and transthoracic 2-dimensional echo (2-DE) with assessment of Ejection Fraction (EF). Measurements were obtained before BD and after BD within 6 h, at 24 h and within 48 h. HT (with insulin, methylprednisolone, vasopressin and T3) was started as soon as possible to treat hemodynamic instability and avoid administration of norepinephrine (NE). Eligible potential heart donors underwent coronary angiography.

Results

After HT, we observed a normalization of hemodynamic conditions with improvement of mean arterial pressure (pre = 68 ± 8 mmHg vs post = 83 ± 13 mmHg, p < .01), cardiac index (pre = 2.4 ± 0.6 L/min/m2 vs post 3.7 ± 1.2 L/min/m2, p < .05), EF (pre = 48 ± 15 vs post = 59 ± 3%, p < .01) without administration of norepinephrine (NE) in 67% of cases. Five potential donors were excluded from donation (opposition, n = 3, tubercolosis n = 1, malignancy n = 1). At pre-harvesting angiography, coronary artery stenosis was present in 2 of the 10 consented donors. Eight hearts were uneventfully transplanted. No early graft failure occurred and all eight recipients were alive at 6-month follow-up.

Conclusion

In BD donors, intensive treatment including HT is associated with improvement of regional and global LV function and reverse remodeling detectable by transthoracic 2DE. Donor hearts with recovered LV function may be eligible for uneventful heart transplant. The wait (in brain death), treat (with HT) and see (with 2D echo) strategy can help rescue organs suitable for heart donation.
Glutamate-induced obesity leads to decreased sperm reserves and acceleration of transit time in the epididymis of adult male rats
Authors: Fernandes Glaura SA , Arena Arielle C , Campos Kleber E , Volpato Gustavo T , Anselmo-Franci Janete A , Damasceno Débora C , Kempinas Wilma G
Published: December 2012

Background

Given the established fact that obesity interferes with male reproductive functions, the present study aimed to evaluate sperm production in the testis and storage in the epididymis in a glutamate-induced model of obesity.

Methods

Male rats were treated neonatally with monosodium glutamate (MSG) at doses of 4 mg/kg subcutaneously, or with saline solution (control group), on postnatal days 2, 4, 6, 8 and 10. On day 120, obesity was confirmed by the Lee index in all MSG-treated rats. After this, all animals from the two experimental groups were anesthetized and killed to evaluate body and reproductive organ weights, sperm parameters, plasma hormone levels (FSH, LH and testosterone), testicular and epididymal histo-morphometry and histopathology.

Results

Significant reductions in absolute and relative weights of testis, epididymis, prostate and seminal vesicle were noted in MSG-treated animals. In these same animals plasma testosterone and follicle-stimulating hormone (FSH) concentrations were decreased, as well as sperm counts in the testis and epididymis and seminiferous epithelium height and tubular diameter. The sperm transit time was accelerated in obese rats. However, the number of Sertoli cells per seminiferous tubule and stereological findings on the epididymis were not markedly changed by obesity.

Conclusions

Neonatal MSG-administered model of obesity lowers sperm production and leads to a reduction in sperm storage in the epididymis of adult male rats. The acceleration of sperm transit time can have implications for the sperm quality of these rats.
Overexpression of the secretory small GTPase Rab27B in human breast cancer correlates closely with lymph node metastasis and predicts poor prognosis
Authors: Zhang Jia-Xing , Huang Xiao-Xia , Cai Man-Bo , Tong Zhu-Ting , Chen Jie-Wei , Qian Dong , Liao Yi-Ji , Deng Hai-Xia , Liao Ding-Zhun , Huang Ma-Yan , Zeng Yi-Xin , Xie Dan , Mai Shi-Juan
Published: December 2012

Background

The secretory small GTPase Rab27b was recently identified as an oncogene in breast cancer (BC) in vivo and in vitro studies. This research was designed to further explore the clinical and prognostic significance of Rab27B in BC patients.

Methods

The mRNA/protein expression level of Rab27B was examined by performing Real-time PCR, western blot, and immunohistochemistry (IHC) assays in 12 paired BC tissues and matched adjacent noncancerous tissues (NAT). Then we carried out IHC assay in a large cohort of 221 invasive BC tissues, 22 normal breast tissues, 40 fibroadenoma (FA), 30 ductual carcinoma in situ (DCIS) and 40 metastatic lymph nodes (LNs). The receiver operating characteristic curve method was applied to obtain the optimal cutoff value for high Rab27B expression. Epithelial-mesenchymal transition (EMT) marker expression levels were detected in relation to Rab27B expression.

Results

We observed that the increased expression of Rab27B was dependent upon the magnitude of cancer progression (P < 0.001). The elevated expression of Rab27B was closely correlated with lymph node metastasis, advanced clinical stage, ascending pathology classification, and positive ER status. Furthermore, patients with high expression of Rab27B had inferior survival outcomes. Multivariate Cox regression analysis proved that Rab27B was a significantly independent risk factor for patients’ survival (P < 0.001). Furthermore, a significant positive relationship was observed between Rab27B expression and elevated mesenchymal EMT markers.

Conclusion

Our findings suggest that overexpression of Rab27B in BC coincides with lymph node metastasis and acquisition of a poor prognostic phenotype.
A comparison of the ability of rilpivirine (TMC278) and selected analogues to inhibit clinically relevant HIV-1 reverse transcriptase mutants
Authors: Johnson Barry C , Pauly Gary T , Rai Ganesha , Patel Disha , Bauman Joseph D , Baker Heather L , Das Kalyan , Schneider Joel P , Maloney David J , Arnold Eddy , Thomas Craig J , Hughes Stephen H
Published: December 2012

Background

The recently approved anti-AIDS drug rilpivirine (TMC278, Edurant) is a nonnucleoside inhibitor (NNRTI) that binds to reverse transcriptase (RT) and allosterically blocks the chemical step of DNA synthesis. In contrast to earlier NNRTIs, rilpivirine retains potency against well-characterized, clinically relevant RT mutants. Many structural analogues of rilpivirine are described in the patent literature, but detailed analyses of their antiviral activities have not been published. This work addresses the ability of several of these analogues to inhibit the replication of wild-type (WT) and drug-resistant HIV-1.

Results

We used a combination of structure activity relationships and X-ray crystallography to examine NNRTIs that are structurally related to rilpivirine to determine their ability to inhibit WT RT and several clinically relevant RT mutants. Several analogues showed broad activity with only modest losses of potency when challenged with drug-resistant viruses. Structural analyses (crystallography or modeling) of several analogues whose potencies were reduced by RT mutations provide insight into why these compounds were less effective.

Conclusions

Subtle variations between compounds can lead to profound differences in their activities and resistance profiles. Compounds with larger substitutions replacing the pyrimidine and benzonitrile groups of rilpivirine, which reorient pocket residues, tend to lose more activity against the mutants we tested. These results provide a deeper understanding of how rilpivirine and related compounds interact with the NNRTI binding pocket and should facilitate development of novel inhibitors.
Seroprevalence of porcine torovirus (PToV) in Spanish farms
Authors: Alonso-Padilla Julio , Pignatelli Jaime , Simon-Grifé Meritxell , Plazuelo Susana , Casal Jordi , Rodríguez Dolores
Published: December 2012

Background

Torovirus infections have been associated with gastroenteritis and diarrhea in horses, cows, pigs and humans, especially in young animals and in children. Although asymptomatic in a large percentage of cases, however toroviruses may pose a potential threat to worsen disease outcome in concurrent infections with other enteric pathogens. Previous studies based on the analysis of limited numbers of samples indicated high seroprevalences against porcine torovirus (PToV) in various European countries. The aim of this work was to perform a seroepidemiological survey of PToV in Spanish farms in order to define the seroprevalence against this virus.

Results

Serum samples (n = 2664) from pigs of different ages were collected from 100 Spanish farms coming from 10 regions that concentrate 96.1% of the 3392 farms with 80 or more sows censused in Spain. Samples were screened by means of an indirect enzyme-linked immune-sorbent assay (ELISA) based on a recombinant PToV nucleocapsid protein as antigen. The analysis of the whole serum collection yielded a total of 95.7% (2550/2664) seropositive samples. The highest prevalence (99.6%, 1382/1388) and ELISA values (average O.D. ± standard deviation) were observed in the sows (1.03±0.36) and the lowest prevalence (59.4%, 98/165) and anti-PToV IgG levels (0.45±0.16) were found amongst 3-week-old piglets. Both ELISA reactivity values and seroprevalence percentages rose quickly with piglet’s age from 3 to 11 weeks of age; the seroprevalence was 99.3% (2254/2270) when only the samples from sows and pigs over 11-weeks of age were considered. Antibodies against PToV were detected in all analyzed farms.

Conclusions

This report describes the results of the largest torovirus seroepidemiological survey in farmed swine performed so far. Overall, the seroprevalence against PToV in animals older than 11 weeks of age was >99%, indicating that this virus is endemic in pig herds from Spain.
Strong purifying selection in endogenous retroviruses in the saltwater crocodile (Crocodylus porosus) in the Northern Territory of Australia
Authors: Chong Amanda Yoon-Yee , Atkinson Sarah Jane , Isberg Sally , Gongora Jaime
Published: December 2012

Background

Endogenous retroviruses (ERVs) are remnants of exogenous retroviruses that have integrated into the nuclear DNA of a germ-line cell. Here we present the results of a survey into the ERV complement of Crocodylus porosus, the saltwater crocodile, representing 45 individuals from 17 sampling locations in the Northern Territory of Australia. These retroelements were compared with published ERVs from other species of Crocodylia (Crocodilians; alligators, caimans, gharials and crocodiles) as well as representatives from other vertebrates. This study represents one of the first in-depth studies of ERVs within a single reptilian species shedding light on the diversity of ERVs and proliferation mechanisms in crocodilians.

Results

Analyses of the retroviral pro-pol gene region have corroborated the presence of two major clades of ERVs in C. porosus and revealed 18 potentially functional fragments out of the 227 recovered that encode intact pro-pol ORFs. Interestingly, we have identified some patterns of diversification among those ERVs as well as a novel sequence that suggests the presence of an additional retroviral genus in C. porosus. In addition, considerable diversity but low genetic divergence within one of the C. porosus ERV lineages was identified.

Conclusions

We propose that the ERV complement of C. porosus has come about through a combination of recent infections and replication of ancestral ERVs. Strong purifying selection acting on these clades suggests that this activity is recent or still occurring in the genome of this species. The discovery of potentially functional elements is an interesting development that warrants further investigation.
Verification and validation of ICME methods and models for aerospace applications
Authors: Cowles Bradford , Backman Dan , Dutton Rollie
Published: December 2012

Integrated Computational Materials Engineering (ICME) model verification and validation (V&V) is difficult because materials processing, microstructural evolution, and property development contain a rich mix of length and time scales with an equally complex set of interacting phenomena and mechanisms. Beyond these difficulties, engineers who adapt these models rarely generate independent validation data sets to confirm model adequacy, quantify uncertainty, and identify potential error sources. Even when a validation data set is produced and applied, the range of model applicability is limited by the range on input model parameters contained within the data set. In this paper we provide a summary of a recommended approach to ICME V&V and include descriptions of V&V planning checklists, an ICME Tool Maturity Level assessment guide and examples of how such practitioner aids might be employed.