bluuebunny/crossref_metadata_2025 huggingface dataset:
When the Critically Ill Patient Requires Surgery: A Review of Perioperative Considerations for the Surgical Patient With ALI/ARDS
Authors: Donovan Anne L. , Haight Matthew
Published: October 2012

Patients with acute lung injury or acute respiratory distress syndrome present many challenges in the perioperative setting. Maintaining oxygenation and hemodynamic stability requires a comprehensive plan for both transport and intraoperative management. Many factors are important to consider when choosing a mechanical ventilation strategy, including tidal volume, ventilation mode, and maintenance of positive end-expiratory pressure. The goals of care include maintenance of lung protective strategies during surgery and avoidance of adverse events during transport. Considerations for ventilation unique to the intraoperative setting and situations requiring use of a transport ventilator or an ICU ventilator are discussed. Overall, providing safe and high-quality perioperative care to a critically ill patient requires communication and collaboration among a multidisciplinary team.
Sustainable Development and Governance: Complex Processes and Unpredictable Outcomes
Authors: Sinha Anup
Published: October 2012

This article tries to demonstrate how the concept of sustainable development is fraught with tensions that are political and ethical in nature. In trying to implement any notion of sustainability the agenda for policy action would be quite different in different contexts. The complex set of problems to be addressed would differ considerably in countries with different levels of economic development. Similarly, on certain issues global governance is called for. In other contexts, local conditions and culture must be understood before any policy intervention can be thought of. This is the first level of complexity with which any governance mechanism for sustainability must come to terms with. Governance itself is also inherently complex. It is an unfolding of a complicated interaction between different participants such as policy-makers, the wide variety of agencies which come together in the process of implementation and the beneficiaries themselves. Policy, and its outcomes, should not be viewed as a linear process. It is argued that governance is the result of the interaction between the processes of implementation and the outcomes that are possible. Governance, in this sense, is both complex and unpredictable. Unintended consequences are more the rule than the exception. The complexity of governance is a result of the interplay of knowledge and culture in a variety of power relations. The dominant narrative of sustainability and its associated pathway may not be the only alternative available. It is important to hear out suppressed and appropriated narratives and what they imply for sustainability.
Evolution of residual stress distribution and microstructure in a platinum-aluminide coating
Authors: Liu D , Flewitt P E J , Pavier M
Published: October 2012

In the present paper, we consider the evolution of residual stress and the corresponding microstructure in the thermally grown oxide (TGO) formed on a type of platinum-aluminide coating, RT22, on a single crystal superalloy CMSX4. Eight coated specimens were oxidised in a simulated gas turbine environment at 850, 950, 1000 and 1050°C for periods of time extended up to 10 000 h. Photo-stimulated luminescence piezo-spectroscopy (PLPS) was used to measure the residual stress in the TGO in order to provide a detailed evaluation of the stress developed at each temperature. The stress variation was evaluated using a random measurement approach, which demonstrated that up to 100 measurements provide data that allows the stress distributions to be determined with high confidence. Scanning electron microscope (SEM) and energy dispersive X-ray (EDX) microanalysis have been adopted to investigate microstructural and compositional changes in the TGO and the coating as a function of time and temperature. The results are discussed with respect to the correlation between the statistically analysed stress distribution, degradation of the TGO and coating overall integrity.
Thermodynamic model of reactive sputtering process
Authors: Faddeeva S , Oseguera J
Published: October 2012

A new approach in describing the reactive sputtering process is developed by applying a mass balance and the first and second laws of thermodynamics. The developed model involves macroparameters versus microparameters involved in the widely accepted model of Berg et al. The hysteresis loop produced during the PVD process is explained using this new approach. The numerical simulations of the Ti reactive sputtering process in the presence of N2 and the Al reactive sputtering process in the presence of O2 in an Ar atmosphere are performed, and the results are compared to the experimental data reported in the literature.
In aggressive forms of mastocytosis, TET2 loss cooperates with c-KITD816V to transform mast cells
Authors: Soucie Erinn , Hanssens Katia , Mercher Thomas , Georgin-Lavialle Sophie , Damaj Gandhi , Livideanu Cristina , Chandesris Maria Olivia , Acin Yolène , Létard Sebastien , de Sepulveda Paulo , Hermine Olivier , Bernard Olivier A. , Dubreuil Patrice
Published: October 2012

Although a role for oncogenic KIT in driving mast cell disease is clear, the mechanisms driving the multiple phenotypic and clinical manifestations of this disorder are not well elucidated. We now show, using a large cohort of mastocytosis patients, including an almost equal number of aggressive and nonaggressive cases of systemic mastocytosis, that in contrast to the oncogenic KITD816V, TET2 mutation statistically associates with aggressive forms of the disease. By infecting primary murine bone marrow–derived mast cells with KITD816V, we also observe a significant and competitive growth advantage for KITD816V in Tet2-nullizygous compared with wild-type cells. TET2-deficient cells display increased proliferation and can survive in the absence of cytokines. Taken together, these data demonstrate a oncogenic cooperation in mast cells and reveal TET2 mutation as a potential marker to diagnose and predict severe forms of mastocytosis.
Humans with chronic granulomatous disease maintain humoral immunologic memory despite low frequencies of circulating memory B cells
Authors: Moir Susan , De Ravin Suk See , Santich Brian H. , Kim Jin Young , Posada Jacqueline G. , Ho Jason , Buckner Clarisa M. , Wang Wei , Kardava Lela , Garofalo Mary , Marciano Beatriz E. , Manischewitz Jody , King Lisa R. , Khurana Surender , Chun Tae-Wook , Golding Hana , Fauci Anthony S. , Malech Harry L.
Published: October 2012

CD27+ memory B cells are reduced in the blood of patients with chronic granulomatous disease (CGD) for reasons and consequences that remain unclear. Here we confirm not only decreased CD27+ but also IgG+ B cells in the blood of CGD patients compared with healthy donors (HDs). However, among IgG+ B cells, the ratio of CD27− to CD27+ was significantly higher in CGD patients compared with HDs. Similar to conventional memory B cells, CD27−IgG+ B cells of CGD patients expressed activation markers and had undergone somatic hypermutation, albeit at levels lower than their CD27+ counterparts. Functional analyses revealed slight reductions in frequencies of total IgG but not influenza-specific memory B-cell responses, as measured by Elispot in CGD patients compared with HDs. Serum IgG levels and influenza-specific antibodies were also normal in these CGD patients. Finally, we provide evidence that influenza-specific memory B cells can be present within the CD27−IgG+ B-cell compartment. Together, these findings show that, despite reduced circulating CD27+ memory B cells, CGD patients maintain an intact humoral immunologic memory, with potential contribution from CD27− B cells.
CaMKII γ, a critical regulator of CML stem/progenitor cells, is a target of the natural product berbamine
Authors: Gu Ying , Chen Ting , Meng Zhipeng , Gan Yichao , Xu Xiaohua , Lou Guiyu , Li Hongzhi , Gan Xiaoxian , Zhou Hong , Tang Jinfen , Xu Genbo , Huang Liansheng , Zhang Xiaohong , Fang Yongming , Wang Kai , Zheng Shu , Huang Wendong , Xu Rongzhen
Published: October 2012

Bcr-Abl tyrosine kinase inhibitors (TKIs) have been a remarkable success for the treatment of Ph+ chronic myeloid leukemia (CML). However, a significant proportion of patients treated with TKIs develop resistance because of leukemia stem cells (LSCs) and T315I mutant Bcr-Abl. Here we describe the unknown activity of the natural product berbamine that efficiently eradicates LSCs and T315I mutant Bcr-Abl clones. Unexpectedly, we identify CaMKII γ as a specific and critical target of berbamine for its antileukemia activity. Berbamine specifically binds to the ATP-binding pocket of CaMKII γ, inhibits its phosphorylation and triggers apoptosis of leukemia cells. More importantly, CaMKII γ is highly activated in LSCs but not in normal hematopoietic stem cells and coactivates LSC-related β-catenin and Stat3 signaling networks. The identification of CaMKII γ as a specific target of berbamine and as a critical molecular switch regulating multiple LSC-related signaling pathways can explain the unique antileukemia activity of berbamine. These findings also suggest that berbamine may be the first ATP-competitive inhibitor of CaMKII γ, and potentially, can serve as a new type of molecular targeted agent through inhibition of the CaMKII γ activity for treatment of leukemia.
Prospective serial evaluation of 2-hydroxyglutarate, during treatment of newly diagnosed acute myeloid leukemia, to assess disease activity and therapeutic response
Authors: Fathi Amir T. , Sadrzadeh Hossein , Borger Darrell R. , Ballen Karen K. , Amrein Philip C. , Attar Eyal C. , Foster Julia , Burke Meghan , Lopez Hector U. , Matulis Christina R. , Edmonds Katherine M. , Iafrate A. John , Straley Kimberly S. , Yen Katharine E. , Agresta Samuel , Schenkein David P. , Hill Cedric , Emadi Ashkan , Neuberg Donna S. , Stone Richard M. , Chen Yi-Bin
Published: October 2012

Mutations of genes encoding isocitrate dehydrogenase (IDH1 and IDH2) have been recently described in acute myeloid leukemia (AML). Serum and myeloblast samples from patients with IDH-mutant AML contain high levels of the metabolite 2-hydroxyglutarate (2-HG), a product of the altered IDH protein. In this prospective study, we sought to determine whether 2-HG can potentially serve as a noninvasive biomarker of disease burden through serial measurements in patients receiving conventional therapy for newly diagnosed AML. Our data demonstrate that serum, urine, marrow aspirate, and myeloblast 2-HG levels are significantly higher in IDH-mutant patients, with a correlation between baseline serum and urine 2-HG levels. Serum and urine 2-HG, along with IDH1/2-mutant allele burden in marrow, decreased with response to treatment. 2-HG decrease was more rapid with induction chemotherapy compared with DNA-methyltransferase inhibitor therapy. Our data suggest that serum or urine 2-HG may serve as noninvasive biomarkers of disease activity for IDH-mutant AML.
How air pollution influences clinical management of respiratory diseases. A case-crossover study in Milan
Authors: Santus Pierachille , Russo Antonio , Madonini Enzo , Allegra Luigi , Blasi Francesco , Centanni Stefano , Miadonna Antonio , Schiraldi Gianfranco , Amaducci Sandro
Published: October 2012

Background

Environmental pollution is a known risk factor for multiple diseases and furthermore increases rate of hospitalisations. We investigated the correlation between emergency room admissions (ERAs) of the general population for respiratory diseases and the environmental pollutant levels in Milan, a metropolis in northern Italy.

Methods

We collected data from 45770 ERAs for respiratory diseases. A time-stratified case-crossover design was used to investigate the association between air pollution levels and ERAs for acute respiratory conditions. The effects of air pollutants were investigated at lag 0 to lag 5, lag 0–2 and lag 3–5 in both single and multi-pollutant models, adjusted for daily weather variables.

Results

An increase in ozone (O3) levels at lag 3–5 was associated with a 78% increase in the number of ERAs for asthma, especially during the warm season. Exposure to carbon monoxide (CO) proved to be a risk factor for pneumonia at lag 0–2 and in the warm season increased the risk of ERA by 66%. A significant association was found between ERAs for COPD exacerbation and levels of sulphur dioxide (SO2), CO, nitrate dioxide (NO2), and particulate matter (PM10 and PM2.5). The multipollutant model that includes all pollutants showed a significant association between CO (26%) and ERA for upper respiratory tract diseases at lag 0–2. For chronic obstructive pulmonary disease (COPD) exacerbations, only CO (OR 1.19) showed a significant association.

Conclusions

Exposure to environmental pollution, even at typical low levels, can increase the risk of ERA for acute respiratory diseases and exacerbation of obstructive lung diseases in the general population.
Wnt5a promotes ewing sarcoma cell migration through upregulating CXCR4 expression
Authors: Jin Zhe , Zhao Chenghai , Han Xiaorui , Han Yaxin
Published: October 2012

Background

As one of the malignant tumors most often affecting children and young adults, Ewing sarcoma (ES) is characterized by early metastasis contributing to unfavorable prognosis. However, the molecular mechanisms responsible for ES metastasis remain poorly understood. In this study, we aimed to explore whether Wnt5a, a putative pro-metastatic factor, plays a role in ES metastasis.

Methods

Expression of Wnt5a and CXCR4 was determined by real-time PCR or Western blot in 15 ES specimens and 4 ES cell lines, A-673, RD-ES, SK-N-MC and SK-ES-1. Expression of Wnt antagonists, SFRP1, SFRP2 and SFRP5, and some components in noncanonical Wnt pathway (p-JNK, p-cJUN and p-PKC) was also analyzed in this study. Methylation status of SFRP1, SFRP2 and SFRP5 was detected by Methylation-specific PCR (MSP). Wnt5a shRNA and pcDNA3.1 SFRP5 vector were used to abrogate Wnt5a expression and overexpress SFRP5 in ES cells, respectively.

Results

Wnt5a expression was positively correlated with CXCR4 expression in ES specimens. Levels of both Wnt5a mRNA and CXCR4 mRNA were significantly higher in specimens from ES patients with metastasis at diagnosis compared with specimens from those without metastasis. Recombinant Wnt5a enhanced CXCR4 expression in ES cells, which was accompanied by increased ES cell migration, whereas Wnt5a shRNA has opposite effects. SFRP5 was methylated and silenced in ES cells, and both recombinant SFRP5 and pcDNA3.1 SFRP5 vector suppressed CXCR4 expression as well as ES cell migration. Wnt5a shRNA and recombinant SFRP5 inhibited phosphorylation of JNK and cJUN, and JNK inhibitor also reduced CXCR4 expression and cell migration in ES cells.

Conclusions

Wnt5a increases ES cell migration via upregulating CXCR4 expression in the absence of Wnt antagonist SFRP5, suggesting that Wnt5a overexpression and SFRP5 deficiency may jointly promote ES metastasis.
A novel tool for assessing and summarizing the built environment
Authors: Kroeger Gretchen L , Messer Lynne , Edwards Sharon E , Miranda Marie Lynn
Published: October 2012

Background

A growing corpus of research focuses on assessing the quality of the local built environment and also examining the relationship between the built environment and health outcomes and indicators in communities. However, there is a lack of research presenting a highly resolved, systematic, and comprehensive spatial approach to assessing the built environment over a large geographic extent. In this paper, we contribute to the built environment literature by describing a tool used to assess the residential built environment at the tax parcel-level, as well as a methodology for summarizing the data into meaningful indices for linkages with health data.

Methods

A database containing residential built environment variables was constructed using the existing body of literature, as well as input from local community partners. During the summer of 2008, a team of trained assessors conducted an on-foot, curb-side assessment of approximately 17,000 tax parcels in Durham, North Carolina, evaluating the built environment on over 80 variables using handheld Global Positioning System (GPS) devices. The exercise was repeated again in the summer of 2011 over a larger geographic area that included roughly 30,700 tax parcels; summary data presented here are from the 2008 assessment.

Results

Built environment data were combined with Durham crime data and tax assessor data in order to construct seven built environment indices. These indices were aggregated to US Census blocks, as well as to primary adjacency communities (PACs) and secondary adjacency communities (SACs) which better described the larger neighborhood context experienced by local residents. Results were disseminated to community members, public health professionals, and government officials.

Conclusions

The assessment tool described is both easily-replicable and comprehensive in design. Furthermore, our construction of PACs and SACs introduces a novel concept to approximate varying scales of community and describe the built environment at those scales. Our collaboration with community partners at all stages of the tool development, data collection, and dissemination of results provides a model for engaging the community in an active research program.
Item and response-category functioning of the Persian version of the KIDSCREEN-27: Rasch partial credit model
Authors: Jafari Peyman , Bagheri Zahra , Safe Mozhgan
Published: October 2012

Background

The purpose of the study was to determine whether the Persian version of the KIDSCREEN-27 has the optimal number of response category to measure health-related quality of life (HRQoL) in children and adolescents. Moreover, we aimed to determine if all the items contributed adequately to their own domain.

Findings

The Persian version of the KIDSCREEN-27 was completed by 1083 school children and 1070 of their parents. The Rasch partial credit model (PCM) was used to investigate item statistics and ordering of response categories. The PCM showed that no item was misfitting. The PCM also revealed that, successive response categories for all items were located in the expected order except for category 1 in self- and proxy-reports.

Conclusions

Although Rasch analysis confirms that all the items belong to their own underlying construct, response categories should be reorganized and evaluated in further studies, especially in children with chronic conditions.
Immunohistochemical consistency between primary tumors and lymph node metastases of gastric neuroendocrine carcinoma
Authors: Uchiyama Chieko , Tamura Shigeyuki , Nakatsuka Shinichi , Takeno Atsushi , Miki Hirofumi , Kanemura Takashi , Nakahira Shin , Suzuki Rei , Nakata Ken , Takeda Yutaka , Kato Takeshi
Published: October 2012

Background

Gastric neuroendocrine carcinoma (G-NEC) is a rare, highly malignant tumor that exhibits aggressive growth leading to vascular invasion, distant metastasis and extremely poor prognosis. We studied the clinicopathological findings of seven patients at our institute to better under this disease.

Methods

Seven cases of G-NEC were identified among 1,027 cases of gastric carcinoma that underwent gastrectomy at Kansai Rousai Hospital between 2002 and 2010. We studied the pathological and immunohistochemical features of gastric neuroendocrine carcinomas at both the primary site and metastatic lymph nodes.

Results

The mean patient age was 73 years (range 63 to 86 years). There were no females in this series. The final staging was Stage I in one case, Stage II in two, Stage III in two and Stage IV in two. A total of 31 metastatic lymph nodes were found in these patients. This study revealed that the ratio of neuroendocrine cells was similar between the primary and metastatic sites, which tended to show the same expression patterns of neuroendocrine markers.

Conclusions

Metastatic lymph nodes showed heterogeneous immunohistochemical expression patterns similar to the primary sites. G-NEC is far advanced at diagnosis and rapidly reaches the lymph nodes retaining its heterogeneity, carrying a worse prognosis than common gastric cancer.

Mini abstract

G-NEC grows rapidly and metastasizes to the lymph nodes, retaining its pathological and immunohistochemical heterogeneity even at the metastatic sites.
Molecular response of Escherichia coli adhering onto nanoscale topography
Authors: Rizzello Loris , Galeone Antonio , Vecchio Giuseppe , Brunetti Virgilio , Sabella Stefania , Pompa Pier Paolo
Published: October 2012

Bacterial adhesion onto abiotic surfaces is an important issue in biology and medicine since understanding the bases of such interaction represents a crucial aspect in the design of safe implant devices with intrinsic antibacterial characteristics. In this framework, we investigated the effects of nanostructured metal substrates on Escherichia coli adhesion and adaptation in order to understand the bio-molecular dynamics ruling the interactions at the interface. In particular, we show how highly controlled nanostructured gold substrates impact the bacterial behavior in terms of morphological changes and lead to modifications in the expression profile of several genes, which are crucially involved in the stress response and fimbrial synthesis. These results mainly demonstrate that E. coli cells are able to sense even slight changes in surface nanotopography and to actively respond by activating stress-related pathways. At the same time, our findings highlight the possibility of designing nanoengineered substrates able to trigger specific bio-molecular effects, thus opening the perspective of smartly tuning bacterial behavior by biomaterial design.
Clinical course of chronic hepatitis B patients who were off-treated after lamivudine treatment: analysis of 138 consecutive patients
Authors: Jin Young-Joo , Kim Kang Mo , Yoo Dong-jun , Shim Ju Hyun , Lee Han Chu , Chung Young-Hwa , Lee Yung Sang , Suh Dong Jin
Published: October 2012

Background/aims

Little is known about the long-term outcome of chronic hepatitis B (CHB) patients who discontinued antiviral therapy. We intended to analyze the long-term outcome of CHB patients who discontinued lamivudine therapy and to evaluate predictors for post-treatment outcome.

Material/methods

From 2007 to 2008, 138 lamivudine off-treated CHB patients with alanine aminotransferase normalization were consecutively enrolled. Post-treatment virologic relapse, biochemical breakthrough, hepatitis flare, and retreatment results were retrospectively analyzed.

Results

Among 138 patients, 102 were initially HBeAg-positive at the start of lamivudine treatment. Virologic relapse, biochemical breakthrough, and hepatitis flare were observed in 45.2, 52.9, and 12.7% of HBeAg-positive and 29.4, 30.6, and 8.3% of HBeAg-negative patients during the median follow-up of 28 and 30 months, respectively. The cumulative virologic relapse and biochemical breakthrough rates were significantly lower in patients with HBV DNA <50 copies/mL than 50-104copies/mL at lamivudine cessation. Hepatitis flare was observed in 4.8 and 11.8% of HBeAg-positive and HBeAg-negative patients with HBV DNA <50copies/mL, respectively. Thirty-eight among 138 patients received retreatment and most of them achieved biochemical (37/38) and virologic response (35/38) within 1 year of retreatment. Undetectable serum HBV DNA (<50 copies/mL) and young age at lamivudine cessation were inversely associated with virologic relapse. Undetectable HBV DNA at cessation, female, and initial HBeAg-negative were inversely associated with biochemical breakthrough.

Conclusions

Post-treatment virologic relapse and biochemical breakthrough incidence were low in patients who achieved undetectable viral titer at lamivudine cessation. Retreatment after biochemical breakthrough or virologic relapse was safe and effective. Intermittent antiviral therapy might be cautiously considered in appropriately selected CHB patients.
In defense of adolescents: They really do use braces for the hours prescribed, if good help is provided. Results from a prospective everyday clinic cohort using thermobrace
Authors: Donzelli Sabrina , Zaina Fabio , Negrini Stefano
Published: October 2012

Background

The effectiveness of bracing relies on the quality of the brace, compliance of the patient, and some disease factors. Patients and parents tend to overestimate adherence, so an objective assessment of compliance has been developed through the use of heat sensors. In 2010 we started the everyday clinical use of a temperature sensor, and the aim of this study is to present our initial results.

Methods

Population: A prospective cohort of 68 scoliosis patients that finished at least 4 months of brace treatment on March 31, 2011: 48 at their first evaluation (79% females, age 14.2±2.4) and 20 already in treatment.

Treatment: Bracing (SPoRT concept); physiotherapic specific exercises (SEAS School); team approach according to the SOSORT Bracing Management Guidelines.

Methods. A heat sensor, “Thermobrace” (TB), has been validated and applied to the brace. The real (measured by TB) and referred (reported by the patient) compliances were calculated.

Statistics. The distribution was not normal, hence median and 95% interval confidence (IC95) and non-parametric tests had to be used.

Results

Average TB use: 5.5±1.5 months. Brace prescription was 23 hours/day (h/d) (IC95 18–23), with a referred compliance of 100% (IC95 70.7-100%) and a real one of 91.7% (IC95 56.6-101.7%), corresponding to 20 h/d (IC95 11–23). The more the brace was prescribed, the more compliant the patient was (94.8% in 23 h/d vs. 73.2% in 18 h/d, P < 0.05). Sixty percent of the patients had at least 90% compliance, and 45% remained within 1 hour of what had been prescribed. Non-wearing days were 0 (IC95 0–12.95), and involved 29% of patients.

Conclusion

This is the first study using a TB in a setting of respect for the SOSORT criteria for bracing, and it states that it is possible to achieve a very good compliance, even with a full time prescription, and better than what was previously reported (80% maximum). We hypothesize that the treating team (SOSORT criteria) plays a major role in our results. This study suggests that compliance is neither due to the type of treatment only nor to the patient alone. According to our experience, TB offers valuable insights and do not undermine the relationship with the patients.
An epidemiological and clinical analysis of craniomaxillofacial fibrous dysplasia in a Chinese population
Authors: Cheng Jie , Wang Yanling , Yu Hongbo , Wang Dongmiao , Ye Jinhai , Jiang Hongbin , Wu Yunong , Shen Guofang
Published: October 2012

Background

Craniomaxillofacial fibrous dysplasia (FD) is a benign bone lesion characterized by facial disfigurement and functional impairment. The aim of this study was to characterize the epidemiological and clinical features of craniomaxillofacial FD by presenting data from a representative Chinese population during a 15-year period (1994–2009).

Method

The craniomaxillofacial disease registries of two Chinese tertiary referral hospitals (Shanghai Ninth People’s Hospital and Stomatological hospital of Jiangsu Province) were searched and reviewed to collect relevant information for patients with craniomaxillofacial FD between Jan.1994 and Dec.2009. All included cases were further analyzed with regard to associated epidemiological and clinicopathological variables.

Results

A total number of 266 cases with definitive diagnosis were identified with 219 primary cases and 47 recurrent cases. There were 111 males and 155 females with a male to female ratio of 0.716:1. They were clinically categorized into three groups: monostotic (71.1%), polysotic (27.4%) and Albright syndrome (1.5%). Maxilla alone or with adjacent bones was the most common affected site. The serum alkaline phosphatase (ALP) in patients was much higher than that in healthy control, whereas comparable between primary patients and recurrent ones. Three patients (3/266, 1.1%) with polysotic lesions underwent spontaneous malignant transformation into osteosarcoma. The majority of patients underwent conservative surgery, while the others received radical resection with or without reconstruction.

Conclusions

Craniomaxillofacial FD is a rare bony disorder with defined epidemiological and clinicopathological features in Chinese population. Further investigations are warranted to establish the optimized timing, treatment strategy and prognostic prediction for this clinical entity.
MicroRNAs and Toll-like Receptor/Interleukin-1 Receptor Signaling
Authors: Virtue Anthony , Wang Hong , Yang Xiao-feng
Published: October 2012

The discovery of miRNAs has revolutionized the way we examine the genome, RNA products, and the regulation of transcription and translation. Their ability to modulate protein expression through mRNA degradation and translation repression resulted in avid scientific interest in miRNAs over the past decade. This research has led to findings that indicate miRNAs can regulate an array of cellular functions such as cellular apoptosis, proliferation, differentiation, and metabolism. Specifically, the capability of miRNAs to finely-tune gene expression naturally lends itself to immune system regulation which requires precise control for proper activity. In fact, abnormal miRNAs expression is often seen with inflammatory disorders like rheumatoid arthritis, systemic lupus erthematosus, experimental autoimmune encephalomyelitis, and inflammatory cancers. As a result, research investigating miRNAs modulation of immune cell proliferation, differentiation, and cellular signaling has yielded fruitful results. Specifically, in this review, we will examine the impact of miRNAs on toll-like receptor (TLRs) and interleukin-1β (IL-1β) signaling, which are integral in the proper functioning of the innate immune system. These signaling pathways share several key downstream signaling adaptors and therefore produce similar downstream effects such as the production of pro-inflammatory cytokines, chemokines, and interferons. This review will examine in depth the specific interactions of miRNAs with receptors, adaptor molecules, and regulator molecules within these cellular pathways. In addition, we will discuss the modulation of miRNAs’ expression by TLR and IL-1R signaling through positive and negative feedback loops.
Humeral head osteonecrosis in an adolescent amateur swimming athlete: a case report
Authors: Zuo Jianlin , Sano Hirotaka , Yamamoto Nobuyuki , Sakoma Yoshimasa , Shinozaki Nobuhisa , Itoigawa Yoshiaki , Omi Rei , Itoi Eiji
Published: October 2012

Osteonecrosis of the humeral head in an adolescent without clear pathogenesis has not been reported in the literature. In this case report, we present such a case of humeral head osteonecrosis in a 15-year-old adolescent. The lesion was located at the subchondral area of the medial part of the humeral head with characteristic appearances on MRI. The shoulder was immobilized in a sling until the pain disappeared, and the patient was told to refrain any kind of sport activities. Bone remodeling was noted five months after the first visit, and it took 2 years for the lesion to be totally healed.
Ramipril attenuates lipid peroxidation and cardiac fibrosis in an experimental model of rheumatoid arthritis
Authors: Shi Qin , Abusarah Jamilah , Baroudi Ghayath , Fernandes Julio C , Fahmi Hassan , Benderdour Mohamed
Published: October 2012

Introduction

Recent studies revealed that co-morbidity and mortality due to cardiovascular disease are increased in patients with rheumatoid arthritis (RA) but little is known about factors involved in these manifestations. This study aimed at characterizing the impact of arthritis on oxidative stress status and tissue fibrosis in the heart of rats with adjuvant-induced arthritis (AIA).

Methods

AIA was induced with complete Freund's adjuvant in female Lewis rats. Animals were treated by oral administration of vehicle or angiotensin-converting enzyme inhibitor ramipril (10 mg/kg/day) for 28 days, beginning 1 day after arthritis induction. Isolated adult cardiomyocytes were exposed to 10 μM 4-hydroxynonenal (HNE) for 24 hours in the presence or absence of 10 μM ramipril.

Results

Compared to controls, AIA rats showed significant 55 and 30% increase of 4-HNE/protein adducts in serum and left ventricular (LV) tissues, respectively. Cardiac mitochondrial NADP+-isocitrate dehydrogenase (mNADP-ICDH) activity decreased by 25% in AIA rats without any changes in its protein and mRNA expression. The loss of mNADP-ICDH activity was correlated with enhanced accumulation of HNE/mNADP-ICDH adducts as well as with decrease of glutathione and NADPH. Angiotensin II type 1 receptor (AT1R) expression and tissue fibrosis were induced in LV tissues from AIA rats. In isolated cardiomyocytes, HNE significantly decreased mNADP-ICDH activity and enhanced type I collagen and connective tissue growth factor expression. The oral administration of ramipril significantly reduced HNE and AT1R levels and restored mNADP-ICDH activity and redox status in LV tissues of AIA rats. The protective effects of this drug were also evident from the decrease in arthritis scoring and inflammatory markers.

Conclusion

Collectively, our findings disclosed that AIA induced oxidative stress and fibrosis in the heart. The fact that ramipril attenuates inflammation, oxidative stress and tissue fibrosis may provide a novel strategy to prevent heart diseases in RA.
Prothrombotic effects of tumor necrosis factor alpha in vivo are amplified by the absence of TNF-alpha receptor subtype 1 and require TNF-alpha receptor subtype 2
Authors: Pircher Joachim , Merkle Monika , Wörnle Markus , Ribeiro Andrea , Czermak Thomas , Stampnik Yvonn , Mannell Hanna , Niemeyer Markus , Vielhauer Volker , Krötz Florian
Published: October 2012

Introduction

Elevated serum levels of the proinflammatory cytokine tumor necrosis factor alpha (TNFα) correlate with an increased risk for atherothrombotic events and TNFα is known to induce prothrombotic molecules in endothelial cells. Based on the preexisting evidence for the impact of TNFα in the pathogenesis of autoimmune disorders and their known association with an acquired hypercoagulability, we investigated the effects of TNFα and the role of the TNF receptor subtypes TNFR1 and TNFR2 for arteriolar thrombosis in vivo.

Methods

Arteriolar thrombosis and platelet-rolling in vivo were investigated in wildtype, TNFR1-/-, TNFR2-/- and TNFR1-/R2-/- C57BL/6 mice using intravital microscopy in the dorsal skinfold chamber microcirculation model. In vitro, expression of prothrombotic molecules was assessed in human endothelial cells by real-time PCR and flow cytometry.

Results

In wildtype mice, stimulation with TNFα significantly accelerated thrombotic vessel occlusion in vivo upon ferric chloride injury. Arteriolar thrombosis was much more pronounced in TNFR1-/- animals, where TNFα additionally led to increased platelet-endothelium-interaction. TNFα dependent prothrombotic effects were not observed in TNFR2-/- and TNFR1-/R2- mice. In vitro, stimulation of human platelet rich plasma with TNFα did not influence aggregation properties. In human endothelial cells, TNFα induced superoxide production, p-selectin, tissue factor and PAI-1, and suppressed thrombomodulin, resulting in an accelerated endothelial dependent blood clotting in vitro. Additionally, TNFα caused the release of soluble mediators by endothelial cells which induced prothrombotic and suppressed anticoagulant genes comparable to direct TNFα effects.

Conclusions

TNFα accelerates thrombus formation in an in vivo model of arteriolar thrombosis. Its prothrombotic effects in vivo require TNFR2 and are partly compensated by TNFR1. In vitro studies indicate endothelial mechanisms to be responsible for prothrombotic TNFα effects. Our results support a more selective therapeutic approach in anticytokine therapy favouring TNFR2 specific antagonists.
Maternal Corticosterone Exposure in the Mouse Has Sex-Specific Effects on Placental Growth and mRNA Expression
Authors: Cuffe J. S. M. , O'Sullivan L. , Simmons D. G. , Anderson S. T. , Moritz K. M.
Published: October 2012

Maternal exposure to increased synthetic glucocorticoids (GC) during pregnancy is known to disturb fetal development and increase the risk of long-term disease. Maternal exposure to elevated levels of natural GC is likely to be common yet is relatively understudied. The placenta plays an important role in regulating fetal exposure to maternal GC but is itself vulnerable to maternal insults. This study uses a mouse model of maternal corticosterone (Cort) exposure to investigate its effects on the developing placenta. Mice were treated with Cort (33 μg/kg·h) for 60 h starting at embryonic d 12.5 (E12.5) before collection of placentas at E14.5 and E17.5. Although Cort exposure did not affect fetal size, placentas of male fetuses were larger at E17.5 in association with changes in placental Igf2. This increase in size was associated with an increase in placental thickness and an increase in placental junctional zone volume. Placentas from female fetuses were of normal size and had no changes in growth factor mRNA levels. The expression of the protective enzyme 11β-hydroxysteroid dehydrogenase type 2 was increased at E14.5 but was decreased in males at E17.5. In contrast, the expression of Nr3c1 (which encodes the GC receptor) was increased during the Cort exposure and remained elevated at E17.5 in the placentas of male fetuses. Our study has shown that maternal Cort exposure infers a sex-specific alteration to normal placental growth and growth factor expression, thus further adding to our understanding of the mechanisms of male dominance of programmed disease.
Calcium Signaling Regulates Trafficking of Familial Hypocalciuric Hypercalcemia (FHH) Mutants of the Calcium Sensing Receptor
Authors: Grant Michael P. , Stepanchick Ann , Breitwieser Gerda E.
Published: October 2012

Calcium-sensing receptors (CaSRs) regulate systemic Ca2+ homeostasis. Loss-of-function mutations cause familial benign hypocalciuric hypercalcemia (FHH) or neonatal severe hyperparathyroidism (NSHPT). FHH/NSHPT mutations can reduce trafficking of CaSRs to the plasma membrane. CaSR signaling is potentiated by agonist-driven anterograde CaSR trafficking, leading to a new steady state level of plasma membrane CaSR, which is maintained, with minimal functional desensitization, as long as extracellular Ca2+ is elevated. This requirement for CaSR signaling to drive CaSR trafficking to the plasma membrane led us to reconsider the mechanism(s) contributing to dysregulated trafficking of FHH/NSHPT mutants. We simultaneously monitored dynamic changes in plasma membrane levels of CaSR and intracellular Ca2+, using a chimeric CaSR construct, which allowed explicit tracking of plasma membrane levels of mutant or wild-type CaSRs in the presence of nonchimeric partners. Expression of mutants alone revealed severe defects in plasma membrane targeting and Ca2+ signaling, which were substantially rescued by coexpression with wild-type CaSR. Biasing toward heterodimerization of wild-type and FHH/NSHPT mutants revealed that intracellular Ca2+ oscillations were insufficient to rescue plasma membrane targeting. Coexpression of the nonfunctional mutant E297K with the truncation CaSRΔ868 robustly rescued trafficking and Ca2+ signaling, whereas coexpression of distinct FHH/NSHPT mutants rescued neither trafficking nor signaling. Our study suggests that rescue of FHH/NSHPT mutants requires a steady state intracellular Ca2+ response when extracellular Ca2+ is elevated and argues that Ca2+ signaling by wild-type CaSRs rescues FHH mutant trafficking to the plasma membrane.
Quantitative kinetics analysis of BMP2 uptake into cells and its modulation by BMP antagonists
Authors: Alborzinia Hamed , Schmidt-Glenewinkel Hannah , Ilkavets Iryna , Breitkopf-Heinlein Katja , Cheng Xinlai , Hortschansky Peter , Dooley Steven , Wölfl Stefan
Published: October 2012

Bone morphogenetic proteins (BMPs) are members of the TGFβ family of signaling proteins and play an important role during development and in tissue formation. BMP signaling is a well-studied process, which is initiated through binding of cognate receptors and processed through activation of Smad downstream mediators. A hallmark of BMP signaling is its modulation at the extracellular level through specific antagonists. Although it had been shown that BMP and TGFβ receptors are internalized following activation, little is known about the fate of BMP ligands. We prepared biologically active fluorescently labeled BMP2 and quantitatively analyzed its binding and uptake in cells using flow cytometry and confocal microscopy. Exogenous BMP2 was rapidly bound to the cell surface and subsequently internalized in a time-dependent manner and accumulated in the cell center. Although binding to the cell surface was limited by binding sites at the beginning, internalization continously increased with time, after a short delay. Using different inhibitors we found that internalization of BMP2 through endosomal particles occurred in a clathrin-dependent pathway. Furthermore, uptake of BMP2 was modulated in strikingly different ways by BMP2 antagonists. Although Noggin and Gremlin increased BMP2 uptake, Chordin blocked BMP2 uptake, which was concentration dependent in both cases. In conclusion, our findings present interesting mechanisms for the modulation of BMP signaling by concentration gradients of BMP ligands and antagonists in a dose- and time-dependent manner, which can provide an explanation of some properties of the BMP regulatory network.
‘Poking’ microtubules bring about nuclear wriggling to position nuclei
Authors: Szikora Szilard , Gaspar Imre , Szabad Janos
Published: October 2012

Nuclei wriggle in the cells of the follicle epithelium of the Drosophila pre-vitellogenic egg primordia. Although similar phenomena have been reported for a number of cultured cell types and some neurons in the zebrafish embryo, the mechanism and importance of the process have remained unexplained. Wriggling involves successive sudden and random minor turns of the nuclei, approximately three twists per minute with roughly 12° per twist, one of which lasts typically for 14 seconds. Wriggling is generated by the growing microtubules seeded throughout the cell cortex, which, while poking the nuclei, buckle and exert 5–40 piconewtons over ∼16 seconds. While wriggling, the nuclei drift ∼5 µm in a day in the immensely growing follicle cells along the apical–basal axis from the apical to the basal cell region. A >2-fold excess of the microtubules nucleated in the apical cell region, as compared with those seeded in the basal cell cortex, makes the nuclei drift along the apical–basal axis. Nuclear wriggling and positioning appear to be tightly related processes: they cease simultaneously when the nuclei become anchored by the actin cytoskeleton; moreover, colchicine or taxol treatment eliminates both nuclear wriggling and positioning. We propose that the wriggling nuclei reveal a thus far undescribed nuclear positioning mechanism.
Antioxidant and molecular chaperone defenses during estivation and arousal in the South American apple-snailPomacea canaliculata
Authors: Giraud-Billoud Maximiliano , Vega Israel A. , Rinaldi Tosi Martín E. , Abud María A. , Calderón María L. , Castro-Vazquez Alfredo
Published: October 2012

The invasive Pomacea canaliculata estivates during periods of drought and should cope with harmful effects of reoxygenation during arousal. We studied thiobarbituric acid reactive substances (TBARS), enzymatic (superoxide dismutase, SOD and catalase, CAT) and non-enzymatic antioxidants (uric acid and reduced glutathione), and heat shock protein expression (Hsc70, Hsp70 and Hsp90) in (1) active control snails, (2) snails after 45 days of estivation, and (3) aroused snails 20 min and (4) 24 h after water exposure, in midgut gland, kidney and foot. Both kidney and foot (but not the midgut gland) showed a TBARS increase during estivation and a decrease after arousal. Tissue SOD and CAT did not change in any experimental groups. Uric acid increased during estivation in all tissues, and it decreased after arousal in the kidney. Allantoin, the oxidation product of uric acid, remained constant in the midgut gland but it decreased in the kidney until 20 min after arousal; however, allantoin levels rose in both kidney and foot 24 h after arousal. Reduced glutathione decreased during estivation and arousal, in both midgut gland and kidney, and it remained constant in the foot. Hsc70 and Hsp70 kidney levels were stable during the activity-estivation cycle and Hsp90 expression decrease during estivation and recovers in the early arousal. In foot, the expression of Hsp70 and Hsp90 was high during activity and estivation periods and diminished after arousal. Results indicate that a panoply of antioxidant and molecular chaperone defenses may be involved during the estivation-arousal cycle in this freshwater gastropod.
Humoral immune responses are maintained with age in a long-lived ectotherm, the red-eared slider turtle
Authors: Zimmerman Laura M. , Clairardin Sandrine G. , Paitz Ryan T. , Hicke Justin W. , LaMagdeleine Katie A. , Vogel Laura A. , Bowden Rachel M.
Published: October 2012

Aging is typically associated with a decrease in immune function. However, aging does not affect each branch of the immune system equally. Because of these varying effects of age on immune responses, aging could affect taxa differently based on how the particular taxon employs its resources towards different components of immune defense. An example of this is found in the humoral immune system. Specific responses tend to decrease with age while non-specific, natural antibody responses increase with age. Compared with mammals, reptiles of all ages have a slower and less robust humoral immune system. Therefore, they may invest more in non-specific responses and thus avoid the negative consequences of age on the immune system. We examined how the humoral immune system of reptiles is affected by aging and investigated the roles of non-specific, natural antibody responses and specific responses by examining several characteristics of antibodies against lipopolysaccharide (LPS) in the red-eared slider turtle. We found very little evidence of immunosenesce in the humoral immune system of the red-eared slider turtle, which supports the idea that non-specific, natural antibody responses are an important line of defense in reptiles. Overall, this demonstrates that a taxon's immune strategy can influence how the immune system is affected by age.
Lobula-specific visual projection neurons are involved in perception of motion-defined second-order motion in Drosophila
Authors: Zhang Xiaonan , Liu He , Lei Zhengchang , Wu Zhihua , Guo Aike
Published: October 2012

A wide variety of animal species including humans and fruit flies see second-order motion lacking coherent spatiotemporal correlations in luminance. Recent electrophysiological recordings, together with intensive psychophysical studies, are bringing to light the neural underpinnings of second-order motion perception in mammals. However, where and how the higher-order motion signals are processed in the fly brain is poorly understood. Using the rich genetic tools available in Drosophila and examining optomotor responses in fruit flies to several stimuli, we revealed that two lobula-specific visual projection neurons, specifically connecting the lobula and the central brain, are involved in the perception of motion-defined second-order motion, independent of whether the second-order feature is moving perpendicular or opposite to the local first-order motion. By contrast, blocking these neurons has no effect on first-order and flicker-defined second-order stimuli in terms of response delay. Our results suggest that visual neuropils deep in the optic lobe and the central brain, whose functional role in motion processing were previously unclear, may be specifically required for motion-defined motion processing.