bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Multilevel Intervention to Increase HIV Clinical Trial Participation Among Rural Minorities
Authors: Corbie-Smith Giselle , Odeneye Ebun , Banks Bahby , Shandor Miles Margaret , Roman Isler Malika
Published: September 2012

Minorities are disproportionately affected by HIV/AIDS in the rural Southeast; therefore, it is important to develop targeted, culturally appropriate interventions to support rural minority participation in HIV/AIDS research. Using intervention mapping, we developed a comprehensive multilevel intervention for service providers (SPs) and people living with HIV/AIDS (PLWHA). The authors collected data from both groups through 11 focus groups and 35 individual interviews. Resultant data were used to develop matrices of behavioral outcomes, performance objectives, and learning objectives. Each performance objective was mapped with changeable, theory-based determinants to inform components of the intervention. Behavioral outcomes for the intervention included the following: (a) eligible PLWHA will enroll in clinical trials and (2) SPs will refer eligible PLWHA to clinical trials. The ensuing intervention consists of four SPs and six PLWHA educational sessions. Its contents, methods, and strategies were grounded in the theory of reasoned action, social cognitive theory, and the concept of social support. All materials were pretested and refined for content appropriateness and effectiveness.
Apps of Steel: Are Exercise Apps Providing Consumers With Realistic Expectations?
Authors: Cowan Logan T. , Van Wagenen Sarah A. , Brown Brittany A. , Hedin Riley J. , Seino-Stephan Yukiko , Hall P. Cougar , West Joshua H.
Published: September 2012

Objective. To quantify the presence of health behavior theory constructs in iPhone apps targeting physical activity. Methods. This study used a content analysis of 127 apps from Apple’s (App Store) Health & Fitness category. Coders downloaded the apps and then used an established theory-based instrument to rate each app’s inclusion of theoretical constructs from prominent behavior change theories. Five common items were used to measure 20 theoretical constructs, for a total of 100 items. A theory score was calculated for each app. Multiple regression analysis was used to identify factors associated with higher theory scores. Results. Apps were generally observed to be lacking in theoretical content. Theory scores ranged from 1 to 28 on a 100-point scale. The health belief model was the most prevalent theory, accounting for 32% of all constructs. Regression analyses indicated that higher priced apps and apps that addressed a broader activity spectrum were associated with higher total theory scores. Conclusion. It is not unexpected that apps contained only minimal theoretical content, given that app developers come from a variety of backgrounds and many are not trained in the application of health behavior theory. The relationship between price and theory score corroborates research indicating that higher quality apps are more expensive. There is an opportunity for health and behavior change experts to partner with app developers to incorporate behavior change theories into the development of apps. These future collaborations between health behavior change experts and app developers could foster apps superior in both theory and programming possibly resulting in better health outcomes.
Urinary cytokine levels in apparently healthy cats and cats with chronic kidney disease
Authors: Habenicht Lauren M , Webb Tracy L , Clauss Laurie A , Dow Steven W , Quimby Jessica M
Published: September 2012

Chronic kidney disease (CKD) is a common cause of illness and death in cats. The hallmark of CKD in cats is chronic tubulointerstitial nephritis, and inflammation contributes to the progression of renal fibrosis. However, at present, it is difficult to assess directly the degree of intra-renal inflammation without renal biopsy. Measurement of inflammatory cytokine levels in urine may provide a non-invasive means of assessing intra-renal inflammation. Urine cytokine levels (urine cytokine/urine creatinine ratio) were measured in 18 healthy cats and 26 cats with CKD. When urine cytokine levels in healthy and CKD cats were compared, we found significantly higher levels of IL-8 and transforming growth factor-β1 (TGF-β1) in urine of CKD cats, along with significantly lower vascular endothelial growth factor (VEGF) levels. A significant positive correlation between serum creatinine and TGF-β1 levels was found in CKD cats. Urinary cytokine measurement may, potentially, be a useful means of assessing intra-renal inflammation, fibrosis and vascular health in cats with CKD.
Facebook and the engineering of connectivity
Authors: van Dijck José
Published: September 2012

This article aims to explain how Web 2.0 platforms in general, and Facebook in particular, engineers online connections. Connectivity has become the material and metaphorical wiring of our culture, a culture in which technologies shape and are shaped not only by economic and legal frames, but also by users and content. The emergence of social media platforms is at the heart of a shifting dynamic, where various actors (technology, users, content, legal and economic actors) are building a connective space for communication and information. In order to comprehend this interwovenness, Bruno Latour’s actor-network theory will be invoked to explore how social media platforms can be analysed as techno-socio-cultural artefacts; this theoretical framework will be complemented by Castells’ political-economy approach to arrive at a fuller understanding of how social media operate. The documentary Catfish (2010) serves as an illustration to explore social media platforms in their multiple dimensions.
Splenocolonic fistula following non-operative management of splenic rupture
Authors: McCrystal Shaun , Hatzifotis Michael
Published: September 2012

Non-operative management has become the preferred treatment for splenic trauma in the absence of haemodynamic instability. The reported complications of non-operative management of splenic trauma may include pseudoaneurysm formation, delayed splenic rupture and splenic abscess formation. Splenocolonic fistula is a finding that has only previously been described in association with Crohn’s disease, pancreatitis, malignancy and haematological disorders. We present the case of a 16-year-old male who suffered a blunt traumatic injury to the spleen, was haemodynamically stable and successfully managed non-operatively. He represented 1 month later following a single episode of per-rectum bleeding. A CT scan of his abdomen revealed a pseudoaneurysm within the spleen, a splenic abscess and a splenocolonic fistula. He proceeded to emergency laparotomy for splenectomy and colonic resection and had an uneventful recovery. The history of management of blunt traumatic splenic injury is discussed, along with the associated risks of operative and conservative management. Methods predicting the success of non-operative management are explored, along with their application and relevance to this particular case.
Doing age: methodological reflections on interviewing
Authors: Lundgren Anna Sofia
Published: September 2012

The aim of this article is not only to discuss how the interview method has implications for the construction of aged identities, but also how the research area conditions the positionings that are made within the interview. Drawing on a set of qualitative semi-structured interviews with persons identifying as, and having experiences of volunteering as ‘class grandparents’ in schools for children, this article highlights and investigates three regimes that proved central in these interviews and that affected the construction of the data: the ‘confessional mode’, the ‘use of life scripts’ and the ‘theoretical identifications’ affecting the interview conversations.
Ideologies of nationhood in sending-state transnationalism: Comparing Surinam and Turkey
Authors: Mügge Liza
Published: September 2012

Why do some sending states encourage continued emigrant involvement whereas others do not? And to what extent does sending-state transnationalism lead to a redefinition of borders? Although research on sending-state transnationalism is flourishing, so far it only covers the positive cases and remains silent on states inactive in this respect. This article addresses this lacuna by comparing transnational costs, benefits and strategies of two radically different sending states, Surinam and Turkey, including one that never reached out to its emigrants. The two sending states have very different ideologies of nationhood: one based on ‘unity in diversity’ on one territory (Surinam), the other based on ethnic nationalism (Turkey). Homeland ideologies of nationhood, this article argues, play a significant role in including or excluding emigrants and their descendants. In this way sending states reinforce rather than deterritorialize their national borders.
Empowering newly married women in Iran: A new method of social work intervention that uses a client-directed problem-solving model in both group and individual sessions
Authors: Rasi Hamideh Addelyan , Moula Alireza , Puddephatt Antony J , Timpka Toomas
Published: September 2012

We set out to assess the processes by which a personal empowerment-oriented intervention based on learning spaces and the Rahyab problem-solving model can help newly married women in Iran to gain more control over their life situations. Learning to use the problem-solving model independently was an important component of this seven months’ educational program. A descriptive field study design based on qualitative methods was employed for data collection and analysis. The analysis of these processes showed how, through group and individual interventions, these women could influence their intimate relationships by altering their thoughts, their management of emotions, and their overt behavior. We invite more research on how empowerment-oriented interventions can be used to support newly married women as a part of family educational programs.
Massacres as process: A micro-sociological theory of internal patterns of mass atrocities
Authors: Klusemann Stefan
Published: September 2012

Mass atrocities are episodes of violence that do not unfold at random: (a) there are recurrent patterns in the forms that violent behavior takes; (b) the chain of events in which violence unfolds is patterned internally, that is, there are processual patterns. These patterns are not the mere outcome or reflection of larger structures such as ethnic conflict; violence instead has patterns (including processual patterns) with a logic of their own. By tracing the onset and early phases of massacres in Srebrenica and Rwanda, it is shown that patterns of violence are shaped by local emotional dynamics. The paper builds on recent findings in the micro-sociology of violence by Collins and others and on Horowitz’s research on the processual character of violence in riots.
Atrocity victimization and the costs of economic conflict crimes in the battle for Baghdad and Iraq
Authors: Hagan John , Kaiser Joshua , Rothenberg Daniel , Hanson Anna , Parker Patricia
Published: September 2012

Economic conflict crimes are defined in this paper as violations of international human rights and humanitarian law, as well as domestic law, associated with military and political conflict and producing significant monetary as well as other forms of suffering for civilians. Criminologists are well positioned by disciplinary emphasis to document and explain military and political violence resulting in economic conflict crimes. Criminal victimization associated with the US-led invasion of Iraq imposed an enormous toll on civilians. Yet there is little attention by criminologists or others to the profound economic costs to Iraqis, whether through lost property, life, or opportunities. We cautiously estimate that the economic losses for households in the city of Baghdad alone were almost US$100 billion, and more than three times this amount for the entire country, with Sunni groups experiencing significantly greater losses than others. So far as we know, our article presents the first estimates of civilian losses from economic conflict crimes that followed the US-led invasion of Iraq. These losses were widespread and systematic, the hallmarks of crimes against humanity.
Victimology in transitional justice: Victimhood, innocence and hierarchy
Authors: McEvoy Kieran , McConnachie Kirsten
Published: September 2012

Although addressing the needs of victims is increasingly proffered as the key rationale for transitional justice, serious critical discussion on the political and social construction of victimhood is only tentatively emerging in the field. Drawing from Anglo-American victimology, the first part of this paper suggests that victims of crime as a category are often perceived as the mirror opposite of perpetrators of crime. It suggests that such a perspective narrows the notion of victims’ rights or needs so they become intrinsically linked to the punishment of perpetrators; that victims and perpetrators are reified and distinct categories; and that ‘true’ victim status demands innocence. The second part of the paper takes these insights and applies them to the context of transitional justice. In particular, it questions the notion of ‘innocence’ as a prerequisite for victim recognition and explores the ways in which victims and perpetrators are not always easily identified as distinct categories in conflicted or transitional societies. The paper concludes that incorporating blame in the calibration of human suffering results in the morally corrosive language of a ‘hierarchy of victims’.
Contextualizing mass atrocity crimes: The dynamics of ‘extremely violent societies’
Authors: Karstedt Susanne
Published: September 2012

Mass violence and genocidal events are presently characterized by new patterns that clearly set them apart from previous genocides and mass atrocities. These changes in the nature of mass atrocity events have necessarily shifted perspectives and conceptualizations of genocide and mass atrocities. Gerlach’s (2006, 2010) concept of ‘extremely violent societies’ seeks to deconstruct conventional understandings of genocidal mass violence and to re-contextualize it within a larger framework of conflict and in the ‘grassroots nature’ of other types of violence from which these events emerge. Based on his concept, I constructed a ‘Violent Societies Index’ (VSI), which offers a new approach to the multifaceted nature of contemporary mass violence and provides a new tool for a contextual and pattern analysis: it is the ‘how’ of extreme levels of violence that is addressed rather than the ‘why’.
Do Professional Golf Tour Caddies Improve Player Scoring?
Authors: Coate Douglas , Toomey Michael
Published: September 2012

In this article, we compare daily scoring from the 1980s in periods when professional golfers were required to use local caddies at the Western Open professional golf tournament at Butler National and at the Masters professional golf tournament at Augusta National with daily scoring in adjoining periods when golfers could use their tour caddies in these tournaments. We have found daily scoring to be approximately one stroke lower in the tour caddy periods after controlling for player quality, weather, tournament round, and course changes.
Ultrasound-Guided Interstitial Laser Ablation for Thyroid Nodules Is Effective Only at High Total Amounts of Energy
Authors: Gambelunghe Giovanni , Fede Raffaela , Bini Vittorio , Monacelli Massimo , Avenia Nicola , D’Ajello Michele , Colella Renato , Nasini Giovanni , De Feo Pierpaolo
Published: September 2012

Objective. According to cross-sectional surveys, the prevalence of nontoxic nodular goiter appears to be higher in the adult population. Surgical intervention is indicated for the following: ( a) progressive goiter growth, ( b) compression of organs such as the trachea and esophagus, and ( c) significant aesthetic disfigurement. Ultrasound-guided laser photocoagulation for the treatment of benign thyroid nodules is a viable alternative to traditional surgery. However, studies that have appeared in literature since the introduction of ultrasound-guided laser photocoagulation for the treatment of benign thyroid nodules report contradictory data concerning the energy required for nodule ablation. The aim of the present trial was to evaluate retrospectively the efficacy of percutaneous laser thermal ablation in 2 groups of patients, one treated with low, and the other with high, total amount of energy. Design. Forty euthyroid patients were treated with 1 session of percutaneous laser photocoagulation treatment at low (median = 71 J/mL; 20 patients) and high (median = 578 J/mL; 20 patients) energy. The volume of the nodules was measured by the same investigator, blinded for treatment, using the ellipsoid formula before treatment, at 2, 4, 8, and 30 weeks, and every 6 months for 3 years thereafter. Results. Thyroid nodule ablation is effective over time only if a sufficient amount of energy (>400-500 J/mL for the nodular tissue to be treated) is given, although it incurs proportionate side effects. Conclusions. Percutaneous laser thermal ablation is a viable alternative to traditional surgery for the treatment of benign nodular thyroid disease only if a sufficient amount of energy is delivered.
Analysis of failed Van Straten LPM proximal interphalangeal prostheses
Authors: Bone M. C. , Cunningham J. L. , Lord J. , Giddins G. , Field J. , Joyce T. J.
Published: September 2012

The two-piece Van Straten Leuwen Poeschmann Metal (LPM) prosthesis was intended for the proximal interphalangeal joints. However, revision rates of 29% after 19 months were reported, as well as massive osteolysis. Five failed LPM titanium–niobium coated cobalt chromium components were obtained, three distal and two proximal, and subjected to a forensic retrieval analysis. Components were analyzed using a Talysurf contacting profilometer, ZYGO noncontacting profilometer, and environmental-scanning electron microscope. All components were heavily worn. In some regions the titanium–niobium coating had been scratched and penetrated. Elsewhere this coating had been removed where there was minimal scratching, which may have been due to corrosion between the coating and substrate. The osteolysis reported clinically was likely to be linked to the wear debris from the failed titanium–niobium coating and substrate.
Results of surgical techniques for re-innervation of the triceps as additional procedures for patients with upper root injuries
Authors: Flores L. Pretto
Published: September 2012

Patients with injuries restricted to the upper and middle trunks of the brachial plexus may obtain recovery of elbow extension via the lower trunk, which makes it difficult to assess the real effect of interventions to restore the triceps function in such cases. This study aimed to determine the impact of surgical strategies for re-innervation of the triceps in individuals with partial injuries of the brachial plexus. Patients were divided into two groups. Group 1 consisted of 21 participants in whom the surgery included one technique for re-innervation of elbow extension. In this group, six different extra- or intra-plexal donors were targeted to one of the motor branches of the triceps muscle. Group 2 was composed of 24 controls in which the reconstruction did not include any intervention for recovering triceps function. The individuals who underwent intervention for re-innervation of the triceps obtained significantly better outcomes for elbow extension than the controls.
Mining and characterization of ubiquitin E3 ligases expressed in the mouse testis
Authors: Hou Xiaojun , Zhang Wei , Xiao Zhenyu , Gan Haiyun , Lin Xiwen , Liao Shangying , Han Chunsheng
Published: September 2012

Background

Ubiquitin-mediated protein modification and degradation are believed to play important roles in mammalian spermatogenesis. The catalogues of ubiquitin activating enzymes, conjugating enzymes, and ligases (E3s) have been known for mammals such as mice and humans. However, a systematic characterization of E3s expressed during spermatogenesis has not been carried out.

Results

In present study, we set out to mine E3s from the mouse genome and to characterize their expression pattern, subcellular localization, and enzymatic activities based on microarray data and biochemical assays. We identified 398 putative E3s belonging to the RING, U-box, and HECT subfamilies and found that most genes were conserved between mice and humans. We discovered that 73 of them were highly or specifically expressed in the testes based on the microarray expression data. We selected 10 putative E3 genes to examine their mRNA expression pattern, and several genes to study their subcellular localization and E3 ligase activity. RT-PCR results showed that all the selected genes were predominately expressed in the testis. Some putative E3s were localized in the cytoplasm while others were in both the cytoplasm and the nucleus. Moreover, all the selected proteins were enzymatically active as demonstrated by in vitro and in vivo assays.

Conclusions

We have identified a large number of putative E3s that are expressed during mouse spermatogenesis. Among these, a significant portion is highly or specifically expressed in the testis. Subcellular localization and enzymatic activity assays suggested that these E3s might execute diverse functions in mammalian spermatogenesis. Our results may serve as an initial guide to the field for further functional analysis.
Cul4B regulates neural progenitor cell growth
Authors: Liu Helio C , Enikolopov Grigori , Chen Yuzhi
Published: September 2012

Background

Cullin ubiquitin ligases are activated via the covalent modification of Cullins by the small ubiquitin-like protein nedd8 in a process called neddylation. Genetic mutations of cullin-4b (cul4b) cause a prevalent type of X-linked intellectual disability (XLID) in males, but the physiological function of Cul4B in neuronal cells remains unclear.

Results

There are three major isoforms of Cul4B (1, 2, and 3) in human and rodent tissues. By examining the endogenous Cul4B isoforms in the brain, this study demonstrates that Cul4B-1 and Cul4B-2 isoforms are unneddylated and more abundant in the brain whereas the lesser species Cul4B-3 that misses the N-terminus present in the other two isoforms is neddylated. The data suggest that the N-terminus of Cul4B inhibits neddylation in the larger isoforms. Immunostaining of human NT-2 cells also shows that most Cul4B is unneddylated, especially when it is localized in the process in G0-synchronized cells. This study demonstrates that Cul4B accumulates during mitosis and downregulation of Cul4B arrests NPCs and NT-2 cells in the G2/M phase of the cell cycle. In both human and rodent brain tissues, Cul4B-positive cells accumulate β-catenin in the dentate subgranular zone and the subventricular zone. These Cul4B-positive cells also co-express the MPM-2 mitotic epitope, suggesting that Cul4B is also necessary for mitosis progression in vivo.

Conclusions

This study provides first evidence that unneddylated Cul4B isoforms exist in the brain and are necessary for mitosis progression in NPCs. The data suggest that unneddylated Cul4B isoforms specifically inhibits β-catenin degradation during mitosis. Furthermore, unneddylated Cul4B may play a role in addition to cell cycle since it is exclusively localized to the processes in starved NT-2 cells. Further analyses of the different isoforms of Cul4B will help understand the cognitive deficits in Cul4B-linked XLID and give insights into drug and biomarker discoveries.
Seroprevalence of anti-hepatitis E virus (HEV) in a Korean population: comparison of two commercial anti-HEV assays
Authors: Park Hyun Kyung , Jeong Sook-Hyang , Kim Jin-Wook , Woo Byung-Hyun , Lee Dong Ho , Kim Hyun Young , Ahn Soyeon
Published: September 2012

Background

Hepatitis E virus (HEV) has emerged as an important cause of epidemic and sporadic acute viral hepatitis worldwide. This study investigated the seroprevalence of anti-HEV in a Korean population and compared the performance of two commercially available anti-HEV assays.

Methods

A total 147 health-check examinees were randomly sampled as matched to the age- and sex- adjusted standard population based on the Korean National Census of 2007. Serum immunoglobulin G anti-HEV was determined by using the Genelabs assay (Genelabs, Singapore) and the Wantai assay (Wantai, Beijing, China).

Results

The overall anti-HEV seroprevalence was 23.1% (95% CI, 16.1-30.1%) using the Wantai assay and 14.3% (95% CI, 8.3-20.3%) using the Genelabs assay. Only 12 samples (8.1%) were positive for anti-HEV as measured by both assays; agreement between the two assays was poor (kappa value of 0.315). The anti-HEV seroprevalence increased with age from 2% and 3% in the people younger than 20-years-of-age to 34.6% and 42.3% in those over 59-years-of-age by the Genelabs and Wantai assay, respectively.

Conclusions

The HEV seroprevalence in Korean population is about 20% overall, with seroprevalence increasing in this population with increasing age. There was poor concordance in the results of the Genelabs and Wantai assays, which warrants further study concerning a reliable diagnostic test for the diagnosis of hepatitis E.
Design and rationale of FOCUS (PX-171-011): A randomized, open-label, phase 3 study of carfilzomib versus best supportive care regimen in patients with relapsed and refractory multiple myeloma (R/R MM)
Authors: Hájek Roman , Bryce Richard , Ro Sunhee , Klencke Barbara , Ludwig Heinz
Published: September 2012

Background

Carfilzomib is a next-generation proteasome inhibitor with single-agent activity in patients with relapsed and refractory multiple myeloma (R/R MM). In PX-171-003-A1, a single-arm phase 2 study of carfilzomib monotherapy in heavily pretreated patients, the overall response rate was 23.7%, 37% of patients achieved ≥ minimal response and median overall survival (OS) was 15.6 months. Based on this study, carfilzomib was recently approved by the US Food and Drug Administration for the treatment of R/R MM. Herein we describe the trial design and rationale for a phase 3 randomized study, FOCUS (CarFilzOmib for AdvanCed Refractory MUltiple Myeloma European Study), being conducted to compare OS after treatment with single-agent carfilzomib to best supportive care (BSC) regimen in R/R MM.

Methods

Patients must have received ≥3 prior regimens, must be responsive to at least 1 line of therapy, and be refractory to their most recent therapy. Eligible patients are randomized 1:1 to receive either carfilzomib (28-day cycles at 20 mg/m2 IV on Days 1–2 of Cycle 1, escalating to 27 mg/m2 IV on Days 8, 9, 15, and 16 and continuing at 27 mg/m2 through Cycle 9 and Days 1, 2, 15, and 16 ≥ Cycle 10) or an active BSC regimen (corticosteroid treatment of prednisolone 30 mg, dexamethasone 6 mg, or equivalent every other day with optional cyclophosphamide 50 mg PO once daily). Patients will continue treatment until disease progression, unacceptable toxicity, or treatment discontinuation and will then enter long-term follow-up for survival. The primary endpoint is OS and secondary endpoints include progression-free survival, overall response rate, and safety. Disease assessments will be determined according to the International Myeloma Working Group Uniform Response Criteria with minimal response per European Blood and Marrow Transplantation Group criteria.

Conclusions

This phase 3 trial will provide more rigorous data for carfilzomib, as this is the first carfilzomib study with OS as the primary endpoint and will not be confounded by crossover and will provide more robust secondary response and safety results that will add to the data set from prior phase 2 studies. FOCUS will facilitate regulatory approvals around the world and expand treatment options for patients with R/R MM.

Trial registration

EudraCT No. 2009-016840-38; NCT01302392.
Alpha-lipoic acid attenuates cardiac fibrosis in Otsuka Long-Evans Tokushima Fatty rats
Authors: Lee Jung Eun , Yi Chin-ok , Jeon Byeong Tak , Shin Hyun Joo , Kim Soo Kyoung , Jung Tae Sik , Choi Jun Young , Roh Gu Seob
Published: September 2012

Background

Hyperglycemia leads to cardiac oxidative stress and an imbalance in glucose homeostasis. Diabetic cardiomyopathy is characterised by cardiac hypertrophy and fibrosis. However, the underlying mechanisms of diabetic cardiomyopathy are not fully understood. This study aimed to investigate the effects of alpha-lipoic acid (ALA) on cardiac energy metabolism, antioxidant effect, and fibrosis in the hearts of Otsuka Long-Evans Tokushima fatty (OLETF) rats.

Methods

Animals were separated into non-diabetic Long-Evans Tokushima Otsuka (LETO) rats and diabetes-prone OLETF rats with or without ALA (200 mg/kg/day) administration for 16 weeks. Diabetic cardiomyopathy was assessed by staining with Sirius Red. The effect of ALA on AMPK signalling, antioxidant enzymes, and fibrosis-related genes in the heart of OLETF rats were performed by Western blot analysis or immunohistochemistry.

Results

Western blot analysis showed that cardiac adenosine monophosphate-activated kinase (AMPK) signalling was lower in OLETF rats than in LETO rats, and that ALA treatment increased the signalling in OLETF rats. Furthermore, the low antioxidant activity in OLETF rats was increased by ALA treatment. In addition to increased Sirius red staining of collagen deposits, transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) were expressed at higher levels in OLETF rat hearts than in LETO rat hearts, and the levels of these factors were decreased by ALA.

Conclusions

ALA enhances AMPK signalling, antioxidant, and antifibrogenic effect. Theses findings suggest that ALA may have beneficial effects in the treatment of diabetic cardiomyopathy.
Effect of Porphyromonas gingivalis infection on post-transcriptional regulation of the low-density lipoprotein receptor in mice
Authors: Miyazawa Haruna , Tabeta Koichi , Miyauchi Sayuri , Aoki-Nonaka Yukari , Domon Hisanori , Honda Tomoyuki , Nakajima Takako , Yamazaki Kazuhisa
Published: September 2012

Background

Periodontal disease is suggested to increase the risk of atherothrombotic disease by inducing dyslipidemia. Recently, we demonstrated that proprotein convertase subtilisin/kexin type 9 (PCSK9), which is known to play a critical role in the regulation of circulating low-density lipoprotein (LDL) cholesterol levels, is elevated in periodontitis patients. However, the underlying mechanisms of elevation of PCSK9 in periodontitis patients are largely unknown. Here, we explored whether Porphyromonas gingivalis, a representative periodontopathic bacterium, -induced inflammatory response regulates serum PCSK9 and cholesterol levels using animal models.

Methods

We infected C57BL/6 mice intraperitoneally with Porphyromonas gingivalis, a representative strain of periodontopathic bacteria, and evaluated serum PCSK9 levels and the serum lipid profile. PCSK9 and LDL receptor (LDLR) gene and protein expression, as well as liver X receptors (Lxrs), inducible degrader of the LDLR (Idol), and sterol regulatory element binding transcription factor (Srebf)2 gene expression, were examined in the liver.

Results

P. gingivalis infection induced a significant elevation of serum PCSK9 levels and a concomitant elevation of total and LDL cholesterol compared with sham-infected mice. The LDL cholesterol levels were significantly correlated with PCSK9 levels. Expression of the Pcsk9, Ldlr, and Srebf2 genes was upregulated in the livers of the P. gingivalis-infected mice compared with the sham-infected mice. Although Pcsk9 gene expression is known to be positively regulated by sterol regulatory element binding protein (SREBP)2 (human homologue of Srebf2), whereas Srebf2 is negatively regulated by cholesterol, the elevated expression of Srebf2 found in the infected mice is thought to be mediated by P. gingivalis infection.

Conclusions

P. gingivalis infection upregulates PCSK9 production via upregulation of Srebf2, independent of cholesterol levels. Further studies are required to elucidate how infection regulates Srebf2 expression and subsequently influences lipid metabolism.
Application of a nanotechnology antimicrobial spray to prevent lower urinary tract infection: a multicenter urology trial
Authors: He Wei , Wang Dongmin , Ye Zhangqun , Qian Weihong , Tao Yan , Shi Xiaofeng , Liu Ling , Chen Jin , Qiu Ling , Wan Peng , Jia Xiaojun , Li Xia , Gao Caixia , Ma Xuexia , Wen Biyan , Chen Nianzhen , Li Ping , Ren Zhengzheng , Lan Li , Li Siyi , Zuo Yi , Zhang Hua , Ma Liming , Zhang Yueping , Li Zhicong , Su Weiping , Yang Qing , Chen Qingli , Wang Xuejing , Ye Zhenni , Chen JP , Loo Wings TY , Chow Louis WC , Yip Adrian YS , Ng Elizabeth LY , Cheung Mary NB , Wang Zhiping
Published: September 2012

Background

Catheter-associated urinary tract infection (CAUTI) is a common nosocomial device-associated infection. It is now recognized that the high infection rates were caused by the formation of biofilm on the surface of the catheters that decreases the susceptibility to antibiotics and results in anti-microbial resistance.

In this study, we performed an in vitro test to explore the mechanism of biofilm formation and subsequently conducted a multi-center clinical trial to investigate the efficacy of CAUTI prevention with the application of JUC, a nanotechnology antimicrobial spray.

Methods

Siliconized latex urinary catheters were cut into fragments and sterilized by autoclaving. The sterilized sample fragments were randomly divided into the therapy and control group, whereby they were sprayed with JUC and distilled water respectively and dried before use.

The experimental standard strains of Escherichia coli (E. coli) were isolated from the urine samples of patients. At 16 hours and 7 days of incubation, the samples were extracted for confocal laser scanning microscopy.

A total of 1,150 patients were accrued in the clinical study. Patients were randomized according to the order of surgical treatment. The odd array of patients was assigned as the therapy group (JUC), and the even array of patients was assigned as the control group (normal saline).

Results

After 16 hours of culture, bacterial biofilm formed on the surface of sample fragments from the control group. In the therapy group, no bacterial biofilm formation was observed on the sample fragments. No significant increase in bacterial colony count was observed in the therapy group after 7 days of incubation.

On the 7th day of catheterization, urine samples were collected for bacterial culture before extubation. Significant difference was observed in the incidence of bacteriuria between the therapy group and control group (4.52% vs. 13.04%, p < 0.001).

Conclusions

In this study, the effectiveness of JUC in preventing CAUTI in a hospital setting was demonstrated in both in vitro and clinical studies.
Overexpression of epithelial growth factor receptor (EGFR) predicts better response to neo-adjuvant chemotherapy in patients with triple-negative breast cancer
Authors: Tang Yiqing , Zhu Li , Li Yafen , Ji Jun , Li Jianfang , Yuan Fei , Wang Dengbin , Chen Weiguo , Huang Ou , Chen Xiaosong , Wu Jiayi , Shen Kunwei , Loo Wings TY , Chow Louis WC
Published: September 2012

Background

Triple negative breast cancer (TNBC) occurs in approximately 10% to 25% of all patients with breast cancer and is associated with poor prognosis. Neo-adjuvant chemotherapy has been reported to produce a higher pathologic complete response (pCR) rate in TNBC. If pCR is achieved, patients with TNBC had a similar survival with non-TNBC patients. The aim of our study was to investigate the protein expression of epithelial growth factor receptor (EGFR) and response to neo-adjuvant chemotherapy and clinical outcome in patients with TNBC compared with non-TNBC.

Methods

A total of 198 locally advanced breast cancer patients who received neo-adjuvant chemotherapy were studied. Immunohistochemistry (IHC) was carried out to detect the protein expression of EGFR in tumor samples. Clinical and pathological parameters, pCR rate and survival data were compared between 40 TNBCs and 158 non-TNBCs.

Results

In 198 cases who received neo-adjuvant chemotherapy, significant differences exist in surgical therapy (P=0.005) and pCR rate (P=0.012) between patients with TNBCs and non-TNBCs. Overexpression of EGFR was significantly associated with pCR rate in patients with TNBCs (P < 0.001). Survival analysis revealed that patients with TNBCs had worse DFS and OS than those with non-TNBCs (P = 0.001, P < 0.001 respectively). Furthermore, for patients with non-TNBCs, those who acheived pCR had better DFS and OS than those who acheived RD (both P < 0.001).

Conclusions

Our results suggested that patients with TNBCs had increased pCR rates compared with non-TNBC. Overexpression of EGFR predicted better response to neo-adjuvant chemotherapy in patients with TNBCs.
A cluster randomized controlled trial of the effectiveness and cost-effectiveness of Intermediate Care Clinics for Diabetes (ICCD): study protocol for a randomized controlled trial
Authors: Armstrong Natalie , Baines Darrin , Baker Richard , Crossman Richard , Davies Melanie , Hardy Ainsley , Khunti Kamlesh , Kumar Sudhesh , O’Hare Joseph Paul , Raymond Neil , Saravanan Ponnusamy , Stallard Nigel , Szczepura Ala , Wilson Andrew
Published: September 2012

Background

World-wide healthcare systems are faced with an epidemic of type 2 diabetes. In the United Kingdom, clinical care is primarily provided by general practitioners (GPs) rather than hospital specialists. Intermediate care clinics for diabetes (ICCD) potentially provide a model for supporting GPs in their care of people with poorly controlled type 2 diabetes and in their management of cardiovascular risk factors. This study aims to (1) compare patients with type 2 diabetes registered with practices that have access to an ICCD service with those that have access only to usual hospital care; (2) assess the cost-effectiveness of the intervention; and (3) explore the views and experiences of patients, health professionals and other stakeholders.

Methods/Design

This two-arm cluster randomized controlled trial (with integral economic evaluation and qualitative study) is set in general practices in three UK Primary Care Trusts. Practices are randomized to one of two groups with patients referred to either an ICCD (intervention) or to hospital care (control).

Intervention group:GP practices in the intervention arm have the opportunity to refer patients to an ICCD - a multidisciplinary team led by a specialist nurse and a diabetologist. Patients are reviewed and managed in the ICCD for a short period with a goal of improving diabetes and cardiovascular risk factor control and are then referred back to practice.

or

Control group:Standard GP care, with referral to secondary care as required, but no access to ICCD.

Participants are adults aged 18 years or older who have type 2 diabetes that is difficult for their GPs to control. The primary outcome is the proportion of participants reaching three risk factor targets: HbA1c(≤7.0%); blood pressure (<140/80); and cholesterol (<4 mmol/l), at the end of the 18-month intervention period. The main secondary outcomes are the proportion of participants reaching individual risk factor targets and the overall 10-year risks for coronary heart disease(CHD) and stroke assessed by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Other secondary outcomes include body mass index and waist circumference, use of medication, reported smoking, emotional adjustment, patient satisfaction and views on continuity, costs and health related quality of life. We aimed to randomize 50 practices and recruit 2,555 patients.

Discussion

Forty-nine practices have been randomized, 1,997 patients have been recruited to the trial, and 20 patients have been recruited to the qualitative study. Results will be available late 2012.

Trial registration

[ClinicalTrials.gov: Identifier NCT00945204]
Atrial fibrillation following cardiac surgery: risk analysis and long-term survival
Authors: Helgadottir Solveig , Sigurdsson Martin I , Ingvarsdottir Inga L , Arnar David O , Gudbjartsson Tomas
Published: September 2012

Background

We studied potential risk factors for postoperative atrial fibrillation (POAF) in a large cohort of patients who underwent open-heart surgery, evaluating short- and long-term outcome, and we developed a risk-assessment model of POAF.

Methods

A retrospective study of 744 patients without prior history of AF who underwent CABG (n = 513), OPCAB (n = 207), and/or AVR (n = 156) at Landspitali Hospital in 2002–2006. Logistic regression analysis was used to study risk factors for POAF, comparing patients with and without POAF.

Results

The rate of POAF was 44%, and was higher following AVR (74%) than after CABG (44%) or OPCAB (35%). In general, patients with POAF were significantly older, were more often female, were less likely to be smokers, had a lower EF, and had a higher EuroSCORE. The use of antiarrythmics was similar in the groups but patients who experienced POAF were less likely to be taking statins. POAF patients also had longer hospital stay, higher rates of complications, and operative mortality (5% vs. 0.7%). In multivariate analysis, AVR (OR 4.4), a preoperative history of cardiac failure (OR 1.8), higher EuroSCORE (OR 1.1), and advanced age (OR 1.1) were independent prognostic factors for POAF. Overall five-year survival was 83% and 93% for patients with and without POAF (p <0.001).

Conclusion

POAF was detected in 44% of patients, which is high compared to other studies. In the future, our assessment score will hopefully be of use in identifying patients at high risk of POAF and lower complications related to POAF.
IκBα deficiency in brain leads to elevated basal neuroinflammation and attenuated response following traumatic brain injury: implications for functional recovery
Authors: Lian Hong , Shim David J , Gaddam Samson SK , Rodriguez-Rivera Jennifer , Bitner Brittany R , Pautler Robia G , Robertson Claudia S , Zheng Hui
Published: September 2012

Background

The transcription factor NFκB is an important mediator of cell survival and inflammation in the immune system. In the central nervous system (CNS), NFκB signaling has been implicated in regulating neuronal survival following acute pathologic damage such as traumatic brain injury (TBI) and stroke. NFκB is normally bound by the principal inhibitory protein, IκBα, and sequestered in the cytoplasm. Activation of NFκB requires the degradation of IκBα, thereby freeing NFκB to translocate to the nucleus and activate the target genes. Mice deficient in IκBα display deregulated and sustained NFκB activation and early postnatal lethality, highlighting a critical role of IκBα in NFκB regulation.

Results

We investigated the role of IκBα in regulating NFκB activity in the brain and the effects of the NFκB/IκBα pathway in mediating neuroinflammation under both physiological and brain injury conditions. We report that astrocytes, but not neurons, exhibit prominent NFκB activity, and that basal NFκB activity in astrocytes is elevated in the absence of IκBα. By generating mice with brain-specific deletion of IκBα, we show that IκBα deficiency does not compromise normal brain development. However, basal neuroinflammation detected by GFAP and Iba1 immunoreactivity is elevated. This leads to impaired inflammatory responses following TBI and worsened brain damage including higher blood brain barrier permeability, increased injury volumes and enlarged ventricle volumes.

Conclusions

We conclude that, in the CNS, astrocyte is the primary cell type subject to NFκB regulation. We further demonstrate that IκBα plays an important role in regulating NFκB activity in the brain and a robust NFκB/IκBα-mediated neuroinflammatory response immediately following TBI is beneficial.
Low temperature oxidation of linseed oil: a review
Authors: Juita  , Dlugogorski Bogdan Z , Kennedy Eric M , Mackie John C
Published: September 2012

This review analyses and summarises the previous investigations on the oxidation of linseed oil and the self-heating of cotton and other materials impregnated with the oil. It discusses the composition and chemical structure of linseed oil, including its drying properties. The review describes several experimental methods used to test the propensity of the oil to induce spontaneous heating and ignition of lignocellulosic materials soaked with the oil. It covers the thermal ignition of the lignocellulosic substrates impregnated with the oil and it critically evaluates the analytical methods applied to investigate the oxidation reactions of linseed oil.

Initiation of radical chains by singlet oxygen (1Δg), and their propagation underpin the mechanism of oxidation of linseed oil, leading to the self-heating and formation of volatile organic species and higher molecular weight compounds. The review also discusses the role of metal complexes of cobalt, iron and manganese in catalysing the oxidative drying of linseed oil, summarising some kinetic parameters such as the rate constants of the peroxidation reactions.

With respect to fire safety, the classical theory of self-ignition does not account for radical and catalytic reactions and appears to offer limited insights into the autoignition of lignocellulosic materials soaked with linseed oil. New theoretical and numerical treatments of oxidation of such materials need to be developed. The self-ignition induced by linseed oil is predicated on the presence of both a metal catalyst and a lignocellulosic substrate, and the absence of any prior thermal treatment of the oil, which destroys both peroxy radicals and singlet O2 sensitisers. An overview of peroxyl chemistry included in the article will be useful to those working in areas of fire science, paint drying, indoor air quality, biofuels and lipid oxidation.
Periovulatory Expression of Hydrogen Peroxide-Induced Sulfiredoxin and Peroxiredoxin 2 in the Rat Ovary: Gonadotropin Regulation and Potential Modification
Authors: Park Jae-Il , Jeon Hye-Jeong , Jung Nak-Kyun , Jang You-Jee , Kim Jin-Seon , Seo Young-Woo , Jeong Moonkyung , Chae Ho Zoon , Chun Sang-Young
Published: September 2012

Reactive oxygen species are involved in ovulation. The aim of this study was to examine gonadotropin regulation of antioxidant enzyme sulfiredoxin (Srx) and peroxiredoxin 2 (PRDX2) expressions and modification during the ovulatory process in rats. Administration of antioxidants in vivo reduced ovulation rate and cumulus expansion. LH treatment increased H2O2 levels within 15 min, which, in turn, induced Srx gene expression in cultured preovulatory follicles. Treatment of preovulatory follicles with catalase suppressed the stimulatory effect of LH on Akt phosphorylation. LH- or H2O2-stimulated Srx mRNA levels were suppressed by inhibitors of antioxidant agents and MAPK kinase. An in vivo injection of equine chorionic gonadotropin-human chorionic gonadotropin (hCG) stimulated Srx mRNA within 1 h in granulosa but not thecal cells of preovulatory follicles. Srx protein levels were stimulated from 3 h post-hCG injection. Immunofluorescence analysis revealed that oocytes expressed the Srx protein. Furthermore, hCG treatment increased Srx expression in mural granulosa, theca and cumulus cells, but the Srx protein was not detected in corpora lutea. Gene expression of PRDX2, identified as an Srx-dependent modified enzyme, was stimulated by gonadotropins. In situ hybridization analysis demonstrated that PRDX2 mRNA was detected in oocytes and theca cells as well as granulosa cells of some antral and preovulatory follicles. High levels of PRDX2 mRNA were detected in corpora lutea. Total levels of PRDX2 protein were not changed by gonadotropins. However, levels of hyperoxidized PRDX2 increased within 2–3 h after the hCG injection. Taken together, gonadotropin stimulation of Srx expression and PRDX2 modification in the ovary suggest the existence of an antioxidant system to maintain H2O2 production and elimination during the periovulatory period.