bluuebunny/crossref_metadata_2025 huggingface dataset:
The Significance of Microthrombosis and fgl2 in No-Reflow Phenomenon of Rats With Acute Myocardial Ischemia/Reperfusion
Authors: Shao Liang , Wu Daying , Zhang Ping , Li Wenzhu , Wang Jue , Su Guanhua , Liao Yuhua , Wang Zhaohui , Liu Kun
Published: March 2012

No-reflow phenomenon due to cardiac microvascular dysfunction or disturbance aggravates clinic outcomes of a portion of patients with acute myocardial infarction undergoing percutaneous coronary intervention or thrombolytic therapy. Our working hypothesis was that cardiac microthrombosis would play an important role in the pathogenesis. We investigated that cardiac microthrombi were observed by Martius, Scarlet, Blue methocl (MSB) and Masson trichrome staining. Furthermore, we investigated the expression of fibrinogen-like protein 2 (fgl2) in rats with acute myocardial ischemia/reperfusion (MI/R) and its possible pathological and clinical significance. The fgl2 was highly expressed in myocardium of rats with acute MI/R and located at cardiac microvascular walls. We found that the expression of fgl2 in peripheral mononuclear cells of rats with acute MI/R significantly increased correspondingly with its cardiac expression. Expression of cardiac fgl2 was correlated with no-reflow size of rats with acute MI/R, which was detected and calculated by thioflavin S staining. No-reflow size was in line with cardiac diastolic dysfunction of rats with acute MI/R monitored by hemodynamics. Thus, microthrombosis is involved in cardiac microvascular dysfunction or disturbance of rats with acute MI/R as one cause, and fgl2 may emerge as a predictor of the occurrence of no-reflow phenomenon.
The Efficacy and Safety of Pharmacological Prophylaxis of Venous Thromboembolism Following Elective Knee or Hip Replacement
Authors: Cohen Alexander , Drost Pieter , Marchant Nick , Mitchell Stephen , Orme Michelle , Rublee Dale , Simon Teresa A. , Sutton Alex
Published: March 2012

The present systematic review was conducted to assess the efficacy and safety of apixaban versus other anticoagulants, for the prevention of venous thromboembolism (VTE) following total hip replacement (THR) and total knee replacement (TKR) surgery. Electronic databases were interrogated to identify relevant randomized controlled trials. A series of direct/indirect comparisons and a network meta-analysis were conducted. Indirect comparisons found that the odds ratio of “all VTE and all-cause death” were significantly higher for dabigatran than for apixaban in patients with THR (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.50-4.21) and TKR (OR, 1.72; 95% CI, 1.22-2.42). Rivaroxaban showed similar efficacy to apixaban in patients with THR and TKR (OR, 0.69; 95% CI, 0.38-1.25 and OR, 0.83; 95% CI, 0.57-1.19, respectively). No significant differences were observed in bleeding outcomes between treatments. The novel anticoagulants apixaban, rivaroxaban, and dabigatran demonstrated similar or improved efficacy and similar safety compared with current therapies in this indication.
MRI-based analysis of the natalizumab therapeutic window in multiple sclerosis
Authors: Grimaldi Luigi ME , Prosperini Luca , Vitello Gaetano , Borriello Giovanna , Fubelli Federica , Pozzilli Carlo
Published: March 2012

The recommended natalizumab dosage is 300 mg every 4 weeks. We evaluated radiological activity at various times from the last natalizumab infusion by examining 386 magnetic resonance imaging (MRI) scans from 166 natalizumab-treated patients with relapsing–remitting MS. Of 113 scans performed >4 weeks after last natalizumab infusion, 26 were active (i.e. had ≥1 contrast-enhancing lesions). Risk of radiological activity increased by 1.34 fold for each week of delay with respect to the recommended 4-week dosing interval, compared with schedule-adherent patients ( p<0.0001). Our data suggest that an increased MRI activity ≥7 weeks from the last infusion of natalizumab should be considered in cases of therapy discontinuation.
Enhancement of the surface electrical conductivity of thermoplastic composite matrices
Authors: Kilbride Marianne , Pethrick Richard A
Published: March 2012

Enhancement of the surface electrical conductivity is desirable in a number of applications where composite structures are exposed to environments with high electrical activity. A high surface conductivity is desirable on aircraft that can be subject to lightning strikes or in manufacturing environments where static build up can produce safety issues. This article considers the addition of various conducting fillers to a thermoplastic to enhance the conductivity of the polymer matrix. The thermoplastic is one which is conventionally used to toughen epoxy resin composites. It was found that enhancement of the resin matrix depends on the filler, method of processing and subsequent thermal treatment. Conducting data are presented on the blends containing carbon nanotubes, nanographite and carbon black in various proportions and doped and undoped with additional conducting salts. The latter have been added to the resin so as to enhance conduction between the filler particles. While the levels of conductivity are significantly lower than those observed with a pure metal skin, values are achieved, which would allow discharge of electricity within relatively short periods of time.
Cardiorenal disease development under chronic renin–angiotensin–aldosterone system suppression
Authors: Sarafidis Pantelis A , Ruilope Luis M
Published: March 2012

Drugs suppressing the renin-angiotensin-aldosterone system (RAAS) are now widely used to treat patients all along the cardiorenal continuum. It supposes that many patients, in particular those with arterial hypertension are treated with converting-enzyme inhibitors and angiotensin receptor blockers for years during which the development and prograssion of cardiorenal disease can be observed. The meaning of this progression in the presence of RAAS suppression requires to be clarified and to be treated in order to diminish the velocity of progression of cardiorenal disease.
Dipeptidyl peptidase-IV is a potential molecular biomarker in diabetic kidney disease
Authors: Sun Ai-li , Deng Jing-ti , Guan Guang-ju , Chen Shi-hong , Liu Yuan-tao , Cheng Jing , Li Zhen-wei , Zhuang Xiang-hua , Sun Fu-dun , Deng Hao-ping
Published: March 2012

The present study was designed to identify the changes in microvesicle-dipeptidyl peptidase-IV (DPP IV) levels in human urine and serum, and to determine whether there were correlations with the severity of diabetic kidney disease (DKD). A total of 127 patients with type 2 diabetes mellitus (T2DM) were divided into three groups according to the urinary albumin/ creatinine ratio (UACR): microalbuminuria group ( n = 50); macroalbuminuria group ( n = 34) and normoalbuminuria group ( n = 43), and 34 age- and sex-matched non-diabetic healthy subjects were selected as controls. Microvesicle-bound DPP IV and free urinary DPP IV were separated by a filtra-centrifugation method. The total microvesicles were captured by a specific monoclonal antibody, AD-1. DPP IV activity was determined by measuring the cleavage of chromogenic free 4-nitroaniline from Gly-Pro-p-nitroanilide at 405 nm with an ELISA plate reader. DPP IV protein levels were determined by ELISA and Western blot. Our results showed that the microvesicle-bound type was the major form of DPP IV in urine; the urinary microvesicle-DPP IV excretion of each T2DM group was significantly higher compared with controls. The urinary microvesicle-DPP IV level was positively correlated with UACR in patients with T2DM. These findings suggest that the urinary level of microvesicle-bound DPP IV is associated with the severity of DKD.
Defining the Urological Chronic Pelvic Pain Syndromes
Authors: Baranowski Andrew
Published: March 2012

From an international symposium by the National Institutes of Health, June 16–17, 2008, the mechanisms around urogenital pain (UGP) are now much more clearly understood, with a move away from considering the ‘end-organ’ as being responsible towards a central neuroplasticity theory and as a consequence both a multidisciplinary and interdisciplinary approach to management.
The Cost and Burden of Chronic Pain
Authors: Phillips Ceri J.
Published: March 2012

• There are enormous costs which society has to bear as a result of the burden of chronic pain and its suffering. • Policy makers at governmental level and commissioners, and health care decision-makers alike should adopt a broad, strategic and coherent perspective in determining issues relating to service provision and resource allocation.
Insights into Pain: A Review of Qualitative Research
Authors: Osborn Mike , Rodham Karen
Published: March 2012

• Qualitative research exposes and explores important aspects of the pain experience that are inaccessible to other approaches. • Qualitative work adopts a different epistemological and ontological perspective to quantitative work. • Qualitative research is not well established in the field of pain, but is growing. • More interpretative engagement with qualitative data is required.
The Self in Pain
Authors: Morley Stephen
Published: March 2012

• The self is not a unitary concept but has different facets, encompassing potentially contradictory states, intentions or desires. • The ensuing contradictory facets of the self lead to internal discrepancies which can have both motivational and emotional consequences. • Self-Discrepancy Theory (SDT) explains emotional consequences by considering discrepancies between the actual, ideal or ought self. • Depression can be part predicted by considering the extent an individual regards their self as enmeshed with their pain. • Individuals who place a high value on independence or social interaction are more likely to experience a high anxious state in the presence of the “mere threat” of pain enmeshment. • Consequently pain can rapidly come to infiltrate and affect a person's sense of self.
Transdermal Opioids for Cancer Pain Management
Authors: Vithlani Rohan Hasmukh , Baranidharan Ganesan
Published: March 2012

• The prevalence of pain in cancer is up to 90%, more than 45% of this can be adequately managed using the World Health Organisation three step analgesic ladder. • Transdermal opioids are safe, effective, and produce significantly fewer side effects than oral morphine when used for moderate to severe cancer pain. • Transdermal buprenorphine has a lower incidence of systemic side effects than transdermal fentanyl and it is indicated for use in cancer patients with neuropathic pain and renal dysfunction. • Transdermal opioids require a long lag period for dose stabilisation and elimination, hence are unsuitable for acute or unstable pain, and may result in prolonged side effects. • Transdermal analgesics reduce the need for frequent dosing, clock watching and are more convenient for patients, physicians and carers, hence increasing treatment compliance.
Back Pain in Malignant Disease—Metastatic Spinal Cord Compression?
Authors: Lawrie Iain
Published: March 2012

• Be alert to possible spinal cord compression in patients who are at risk and who present with warning signs and symptoms • Maintain a low threshold for further investigation of such patients and for discussing them with specialist colleagues • If MSCC is suspected, commence high dose steroids (16mg dexamethasone orally in the morning) immediately • Ensure imaging to confirm diagnosis of MSCC is carried out within 24 hours of clinical suspicion • Ensure prompt treatment within 24 hours of diagnosis
Recent Advancements in Temporomandibular Disorders (TMDs)
Authors: Durham J , Wassell RW
Published: March 2012

• TMDs are a group of conditions affecting the joint and or the muscles of mastication. • TMDs consist of three main groups of conditions: myofascial pain; disc disorders; TMJ arthritides. • The gold standard diagnostic criteria for research involving TMDs are the Research Diagnostic Criteria for TMDs (RDC/TMD). A pragmatic clinically applicable alternative is the Clinical examination protocol for TMDs (CEP-TMD). • Signs and symptoms can include: pain in masticatory musculature and or the joint; noises associated with joint movements; locking; headache; otalgia. • TMDs' aetiology is multifactorial and biopsychosocial in nature. • Reversible conservative management as defined by the American Association of Dental Research is the initial management of choice for all subgroups of TMDs.
Pain Assessment with Cognitively Impaired Older People in the Acute Hospital Setting
Authors: Brown Donna
Published: March 2012

• Research reveals that older people continue to experience much suffering from acute and chronic pain conditions. • People with cognitive impairment receive less analgesia than their cognitively intact peers. • Postoperative pain assessment with older people in the acute hospital setting remains a challenge. • Context and culture have a significant impact of pain assessment practices. • Due to a paucity of research exploring how pain assessment and management practices with cognitively impaired older people may be realised in the acute hospital setting, there is a need for further research to be conducted.
Identification of tumor epithelium and stroma in tissue microarrays using texture analysis
Authors: Linder Nina , Konsti Juho , Turkki Riku , Rahtu Esa , Lundin Mikael , Nordling Stig , Haglund Caj , Ahonen Timo , Pietikäinen Matti , Lundin Johan
Published: March 2012

Background

The aim of the study was to assess whether texture analysis is feasible for automated identification of epithelium and stroma in digitized tumor tissue microarrays (TMAs). Texture analysis based on local binary patterns (LBP) has previously been used successfully in applications such as face recognition and industrial machine vision. TMAs with tissue samples from 643 patients with colorectal cancer were digitized using a whole slide scanner and areas representing epithelium and stroma were annotated in the images. Well-defined images of epithelium (n = 41) and stroma (n = 39) were used for training a support vector machine (SVM) classifier with LBP texture features and a contrast measure C (LBP/C) as input. We optimized the classifier on a validation set (n = 576) and then assessed its performance on an independent test set of images (n = 720). Finally, the performance of the LBP/C classifier was evaluated against classifiers based on Haralick texture features and Gabor filtered images.

Results

The proposed approach using LPB/C texture features was able to correctly differentiate epithelium from stroma according to texture: the agreement between the classifier and the human observer was 97 per cent (kappa value = 0.934, P < 0.0001) and the accuracy (area under the ROC curve) of the LBP/C classifier was 0.995 (CI95% 0.991-0.998). The accuracy of the corresponding classifiers based on Haralick features and Gabor-filter images were 0.976 and 0.981 respectively.

Conclusions

The method illustrates the capability of automated segmentation of epithelial and stromal tissue in TMAs based on texture features and an SVM classifier. Applications include tissue specific assessment of gene and protein expression, as well as computerized analysis of the tumor microenvironment.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4123422336534537
The effect of a complementary e-learning course on implementation of a quality improvement project regarding care for elderly patients: a stepped wedge trial
Authors: Van de Steeg Lotte , Langelaan Maaike , Ijkema Roelie , Wagner Cordula
Published: March 2012

Background

Delirium occurs frequently in elderly hospitalised patients and is associated with higher mortality, increased length of hospital stay, functional decline, and admission to long-term care. Healthcare professionals frequently do not recognise delirium, indicating that education can play an important role in improving delirium care for hospitalised elderly. Previous studies have indicated that e-learning can provide an effective way of educating healthcare professionals and improving quality of care, though results are inconsistent.

Methods and design

This stepped wedge cluster randomised trial will assess the effects of a complementary delirium e-learning course on the implementation of quality improvement initiative, which aims to enhance the recognition and management of delirium in elderly patients. The trial will be conducted in 18 Dutch hospitals and last 11 months. Measurements will be taken in all participating wards using monthly record reviews, in order to monitor delivered care. These measurements will include the percentage of elderly patients who were screened for the risk of developing delirium, use of the Delirium Observation Screening scale, use of nursing or medical interventions, and the percentage of elderly patients who were diagnosed with delirium. Data regarding the e-learning course will be gathered as well. These data will include user characteristics, information regarding use of the course, delirium knowledge before and after using the course, and the attitude and intentions of nurses concerning delirium care.

Setting

The study will be conducted in internal medicine and surgical wards of eighteen hospitals that are at the beginning stages of implementing the Frail Elderly Project in the Netherlands.

Discussion

Better recognition of elderly patients at risk for delirium and subsequent care is expected from the introduction of an e-learning course for nurses that is complementary to an existing quality improvement project. This trial has the potential to demonstrate that e-learning can be a vital part of the implementation process, especially for quality improvement projects aimed at complex health issues such as delirium. The study will contribute to a growing body of knowledge concerning e-learning and the effects it can have on knowledge as well as delivered care.

Trial registration

Netherlands Trial Register (NTR): NTR2885
Clinical significance of SOX9 in human non-small cell lung cancer progression and overall patient survival
Authors: Zhou Chun-Hui , Ye Li-Ping , Ye Shi-Xing , Li Yan , Zhang Xin-Yin , Xu Xin-Yu , Gong Li-Yun
Published: March 2012

Background

Sex determining region Y (SRY)-related high mobility groupbox 9 (SOX9) is an important transcription factor required for development, which regulates the expression of target genes in the associated pathway. The aim of this study was to describe the expression of SOX9 in human non-small cell lung cancer (NSCLC) and to investigate the association between SOX9 expression and progression of NSCLC.

Methods

SOX9 protein and mRNA expression in normal human pneumonocytes, lung cancer cell lines, and eight pairs of matched lung cancer tissues and their adjacent normal lung tissues were detected by Western blotting and real-time reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemistry was used to determine SOX9 protein expression in 142 cases of histologically characterized NSCLC. Statistical analyses were applied to test for prognostic and diagnostic associations.

Results

SOX9 in lung cancer cell lines was upregulated at both mRNA and protein levels, and SOX9 mRNA and protein were also elevated in NSCLC tissues compared with levels in corresponding adjacent non-cancerous lung tissues. Immunohistochemical analysis demonstrated a high expression of SOX9 in 74/142 (52.1%) paraffin-embedded archival lung cancer biopsies. Statistical analysis indicated that upregulation of SOX9 was significantly correlated with the histological stage of NSCLC (P = 0.017) and that patients with a high SOX9 level exhibited a shorter survival time (P < 0.001). Multivariate analysis illustrated that SOX9 upregulation might be an independent prognostic indicator for the survival of patients with NSCLC.

Conclusions

This work shows that SOX9 may serve as a novel and prognostic marker for NSCLC, and play a role during the development and progression of the disease.
The role of immunosuppression of mesenchymal stem cells in tissue repair and tumor growth
Authors: Han Zhipeng , Jing Yingying , Zhang Shanshan , Liu Yan , Shi Yufang , Wei Lixin
Published: March 2012

Mesenchymal stem cells (MSCs) have acquired great interests for their potential use in the clinical therapy of many diseases because of their functions including multiple lineage differentiation, low immunogenicity and immunosuppression. Many studies suggest that MSCs are strongly immunosuppressivein vitroandin vivo. MSCs exert a profound inhibitory effect on the proliferation of T cells, B cells, dendritic cells and natural killer cells. In addition, several soluble factors have been reported to involved in the immunosuppressive effects by MSCs such as TGF-β, HGF, PGE2, IDO and iNOS. These results suggest that MSCs can be used in the therapy of immune disorder diseases, prevention of organ transplantation rejection and tissue injury. In recent study, we demonstrated that MSCs in tumor inflammatory microenvironment might be elicited of immunosuppressive function. Thus, the application of MSCs in cancer therapy might have negative effect by helping tumor cells escaping from the immune surveillance.
Hypogalactosylation of serum N-glycans fails to predict clinical response to methotrexate and TNF inhibition in rheumatoid arthritis
Authors: Ercan Altan , Cui Jing , Hazen Melissa M , Batliwalla Franak , Royle Louise , Rudd Pauline M , Coblyn Jonathan S , Shadick Nancy , Weinblatt Michael E , Gregersen Peter , Lee David M , Nigrovic Peter A
Published: March 2012

Introduction

Rheumatoid arthritis (RA) is associated with hypogalactosylation of immunoglobulin G (IgG). We examined whether a proxy measure for galactosylation of IgG N-glycans could predict response to therapy or was differentially affected by methotrexate (MTX) or TNF blockade.

Methods

Using a previously defined normal phase high-performance liquid chromatography approach, we ascertained the galactosylation status of whole serum N-glycans in two well-defined RA clinical cohorts: the Autoimmune Biomarkers Collaborative Network (n = 98) and Nested I (n = 64). The ratio of agalactosylated to monogalactosylated N-glycans in serum (sG0/G1) was determined before and during therapy with MTX or TNF inhibition and correlated with anticitrullinated peptide antibody (ACPA) status and clinical response as assessed by 28-joint Disease Activity Score utilizing C-reactive peptide and European League Against Rheumatism response criteria.

Results

RA patients from both cohorts exhibited elevation of sG0/G1 at baseline. Improvement in clinical scores correlated with a reduction in sG0/G1 (Spearman's ρ = 0.31 to 0.37; P < 0.05 for each cohort). However, pretreatment sG0/G1 was not predictive of clinical response. Changes in sG0/G1 were similar in the MTX and TNF inhibitor groups. Corrected for disease activity, ACPA positivity correlated with higher sG0/G1.

Conclusions

Baseline serum N-glycan hypogalactosylation, an index previously correlated with hypogalactosylation of IgG N-glycans, did not distinguish patients with rheumatoid arthritis who were likely to experience a favorable clinical response to MTX or TNF blockade. Clinical improvement was associated with partial glycan normalization. ACPA-positive patients demonstrated enhanced N-glycan aberrancy compared with ACPA-negative patients.
Negative- versus positive-pressure ventilation in intubated patients with acute respiratory distress syndrome
Authors: Raymondos Konstantinos , Molitoris Ulrich , Capewell Marcus , Sander Björn , Dieck Thorben , Ahrens Jörg , Weilbach Christian , Knitsch Wolfgang , Corrado Antonio
Published: March 2012

Introduction

Recent experimental data suggest that continuous external negative-pressure ventilation (CENPV) results in better oxygenation and less lung injury than continuous positive-pressure ventilation (CPPV). The effects of CENPV on patients with acute respiratory distress syndrome (ARDS) remain unknown.

Methods

We compared 2 h CENPV in a tankrespirator ("iron lung") with 2 h CPPV. The six intubated patients developed ARDS after pulmonary thrombectomy (n = 1), aspiration (n = 3), sepsis (n = 1) or both (n = 1). We used a tidal volume of 6 ml/kg predicted body weight and matched lung volumes at end expiration. Haemodynamics were assessed using the pulse contour cardiac output (PiCCO) system, and pressure measurements were referenced to atmospheric pressure.

Results

CENPV resulted in better oxygenation compared to CPPV (median ratio of arterial oxygen pressure to fraction of inspired oxygen of 345 mmHg (minimum-maximum 183 to 438 mmHg) vs 256 mmHg (minimum-maximum 123 to 419 mmHg) (P < 0.05). Tank pressures were -32.5 cmH2O (minimum-maximum -30 to -43) at end inspiration and -15 cmH2O (minimum-maximum -15 to -19 cmH2O) at end expiration. NO Inspiratory transpulmonary pressures decreased (P = 0.04) and airway pressures were considerably lower at inspiration (-1.5 cmH2O (minimum-maximum -3 to 0 cmH2O) vs 34.5 cmH2O (minimum-maximum 30 to 47 cmH2O), P = 0.03) and expiration (4.5 cmH2O (minimum-maximum 2 to 5) vs 16 cmH2O (minimum-maximum 16 to 23), P =0.03). During CENPV, intraabdominal pressures decreased from 20.5 mmHg (12 to 30 mmHg) to 1 mmHg (minimum-maximum -7 to 5 mmHg) (P = 0.03). Arterial pressures decreased by approximately 10 mmHg and central venous pressures by 18 mmHg. Intrathoracic blood volume indices and cardiac indices increased at the initiation of CENPV by 15% and 20% (P < 0.05), respectively. Heart rate and extravascular lung water indices remained unchanged.

Conclusions

CENPV with a tank respirator improved gas exchange in patients with ARDS at lower transpulmonary, airway and intraabdominal pressures and, at least initially improving haemodynamics. Our observations encourage the consideration of further studies on the physiological effects and the clinical effectiveness of CENPV in patients with ARDS.
CASK (LIN2) interacts with Cx43 in wounded skin and their coexpression affects cell migration
Authors: Márquez-Rosado Lucrecia , Singh Deepika , Rincón-Arano Hector , Solan Joell L. , Lampe Paul D.
Published: March 2012

Vertebrate gap junctions are composed of proteins from the connexin family. Co-immunoprecipitation, in vitro binding and far western experiments demonstrate that mammalian CASK (also known as LIN2) directly interacts with Cx43. Immunoprecipitation studies indicate that the CASK mainly interacts with the hypophosphorylated form of Cx43. Functional co-regulation of these proteins was found in MDCK cells migrating into a scratch wound, where expression of either protein individually inhibits migration but their coexpression abrogates this inhibitory effect. Immunofluorescence shows colocalization of Cx43 and CASK in mouse brain astrocytes and in response to wounding in human foreskin. During wounding, CASK is mobilized to the plasma membrane where it colocalizes with Cx43 and CADM1 1 hour after skin explant wounding. Together, these studies indicate that CASK interaction with Cx43 occurs relatively early in the connexin life cycle and imply a plasma membrane targeting role for the interaction that apparently affects cellular processes including cellular migration and wound healing.
No one can whistle a symphony alone – how different ubiquitin linkages cooperate to orchestrate NF-κB activity
Authors: Schmukle Anna C. , Walczak Henning
Published: March 2012

Although it has been known for a long time that ubiquitylation has a major role in the activation and regulation of the nuclear factor kappa B (NF-κB) pathway, recent studies have revealed that the picture is a lot more complex than originally thought. NF-κB and ubiquitylation initially became linked when it was recognised that lysine (K)48-linked ubiquitin chains are involved in the processing of NF-κB precursors and the degradation of inhibitor of kappa B (IκB) proteins. Soon thereafter, it was reported that K63-linked chains were involved in the assembly of IκB kinase (IKK)-activating complexes and required for activation of the NF-κB signalling pathway. Recently, the discovery that atypical ubiquitin linkages, including linear and K11 linkages, are also involved in the activation of NF-κB has led to the need to re-evaluate existing models of how activation of this transcription factor is initiated and regulated. It is now becoming apparent that not only the canonical types of ubiquitin chains but possibly all linkage types have to be investigated in order to fully comprehend NF-κB activation. This can be considered a turning point in our view of the regulation of one of the most important pathways of gene induction. Hence, in this Commentary, we summarise the information that is currently available and incorporate it into a new model of NF-κB activation, thereby highlighting the emerging new challenges in understanding the role of ubiquitylation in NF-κB activation.
Non-canonical ubiquitin-based signals for proteasomal degradation
Authors: Kravtsova-Ivantsiv Yelena , Ciechanover Aaron
Published: March 2012

Regulated cellular proteolysis is mediated largely by the ubiquitin–proteasome system (UPS). It is a highly specific process that is time- (e.g. cell cycle), compartment- (e.g. nucleus or endoplasmic reticulum) and substrate quality- (e.g. denatured or misfolded proteins) dependent, and allows fast adaptation to changing conditions. Degradation by the UPS is carried out through two successive steps: the substrate is covalently tagged with ubiquitin and subsequently degraded by the 26S proteasome. The accepted ‘canonical’ signal for proteasomal recognition is a polyubiquitin chain that is anchored to a lysine residue in the target substrate, and is assembled through isopeptide bonds involving lysine 48 of ubiquitin. However, several ‘non-canonical’ ubiquitin-based signals for proteasomal targeting have also been identified. These include chains anchored to residues other than internal lysine in the substrates, chains assembled through linking residues other than lysine 48 in ubiquitin, and mixed chains made of both ubiquitin and a ubiquitin-like protein. Furthermore, some proteins can be degraded following modification by a single ubiquitin (monoubiquitylation) or multiple single ubiquitins (multiple monoubiquitylation). Finally, some proteins can be proteasomally degraded without prior ubiquitylation (the process is also often referred to as ubiquitination). In this Commentary, we describe these recent findings and discuss the possible physiological roles of these diverse signals. Furthermore, we discuss the possible impact of this signal diversity on drug development.
Reevaluation of the Reactivity of Superoxide Radicals by Consideration of Both the Alkalinity of KO2 and the Superoxide-Scavenging Activity of Xanthine Oxidase
Authors: Mitsuta Keiichi
Published: March 2012

The rate constant, kS, for the reaction of scavengers, obtained from a competitive reaction system in which KO2 was used as a superoxide source, with superoxide has been reevaluated in electron spin resonance (ESR) spin-trapping studies. In consequence, it has been found that the local pH in a reaction field of our KO2 system was 12. As a result, the rate constants for the reaction of xanthine oxidase (XOD) with superoxide at pH 7.8 and 12 were established to be 2.1 × 106 and 8.0 × 105 M−1 s−1, respectively. On the basis of these values, discrepancies between reports in the literature have been examined, and it has been found that systematic errors appearing in values of the rate constant, kT, for the reaction of spin-trapping agents with superoxide due to variations in determination method had originated from omission of the superoxide-scavenging activity of XOD and that the errors could be explained almost completely quantitatively. For this reason, the kT values latterly reported by Allouch et al. are inferior to those formerly reported by Finkelstein et al. as reference values when the kS values are determined by the kinetic competition using these kT values.
Menstruation, Perimenopause, and Chaos Theory
Authors: Derry Paula S. , Derry Gregory N.
Published: March 2012

This article argues that menstruation, including the transition to menopause, results from a specific kind of complex system, namely, one that is nonlinear, dynamical, and chaotic. A complexity-based perspective changes how we think about and research menstruation-related health problems and positive health. Chaotic systems are deterministic but not predictable, characterized by sensitivity to initial conditions and strange attractors. Chaos theory provides a coherent framework that qualitatively accounts for puzzling results from perimenopause research. It directs attention to variability within and between women, adaptation, lifespan development, and the need for complex explanations of disease. Whether the menstrual cycle is chaotic can be empirically tested, and a summary of our research on 20- to 40-year-old women is provided.
Pathogenesis of prostatic small cell carcinoma involves the inactivation of the P53 pathway
Authors: Chen Hongbing , Sun Yin , Wu Chengyu , Magyar Clara E , Li Xinmin , Cheng Liang , Yao Jorge L , Shen Steven , Osunkoya Adeboye O , Liang Chaozhao , Huang Jiaoti
Published: March 2012

Small cell neuroendocrine carcinoma (SCNC) of the prostate is a variant form of prostate cancer that occurs de novo or as a recurrent tumor in patients who received hormonal therapy for prostatic adenocarcinoma. It is composed of pure neuroendocrine (NE) tumor cells, but unlike the scattered NE cells in benign prostate and adenocarcinoma that are quiescent, the NE cells in SCNC are highly proliferative and aggressive, causing death in months. In this study, we provide evidence that interleukin 8 (IL8)–CXCR2–P53 (TP53) signaling pathway keeps the NE cells of benign prostate and adenocarcinoma in a quiescent state normally. While P53 appears to be wild-type in the NE cells of benign prostate and adenocarcinoma, immunohistochemical studies show that the majority of the NE tumor cells in SCNC are positive for nuclear p53, suggesting that the p53 is mutated. This observation is confirmed by sequencing of genomic DNA showing p53 mutation in five of seven cases of SCNC. Our results support the hypothesis that p53 mutation leads to inactivation of the IL8–CXCR2–p53 signaling pathway, resulting in the loss of an important growth inhibitory mechanism and the hyper-proliferation of NE cells in SCNC. Therefore, we have identified potential cells of origin and a molecular target for prostatic SCNC that are very different from those of conventional adenocarcinoma, which explains SCNC's distinct biology and the clinical observation that it does not respond to hormonal therapy targeting androgen receptor signaling, which produces short-term therapeutic effects in nearly all patients with prostatic adenocarcinoma.
Atributos críticos de satisfação em serviços de arquitetura: visão do cliente × visão do arquiteto
Authors: Almada Isabela Winter , Tontini Gérson
Published: March 2012

O presente trabalho tem por objetivo identificar se a percepção sobre os atributos necessários para a satisfação do cliente em projetos residenciais (construção ou reformas) são os mesmos entre clientes e arquitetos. Trata-se de uma pesquisa quantitativa exploratória, que emprega questionários estruturados não disfarçados como instrumento de coleta de dados. Os 15 atributos pesquisados foram definidos por meio da literatura. A coleta de dados foi realizada com 100 clientes pessoas físicas e 30 profissionais. Os resultados da pesquisa indicam que os clientes esperam que o arquiteto resolva o seu problema e consiga entender as suas necessidades, sem necessidade de alterações ou muitas interações com o cliente. Na visão dos clientes, o serviço a ser prestado pelos arquitetos é um serviço técnico. Já os arquitetos percebem que o serviço deve ser construído em conjunto com o cliente e que seu serviço está mais concentrado na criação, no design. Como conclusão, levando em conta a visão dos clientes, o escritório de arquitetura que quiser ter um diferencial competitivo deve entender que seu serviço engloba desde a criação até a entrega da obra, com garantia dos serviços prestados. Deve entender também que o cliente pressupõe que o arquiteto deve saber de suas necessidades e que o atendimento ao cronograma e orçamento iniciais são atributos atrativos.
Processo sustentável de produção de carvão vegetal quanto aos aspectos: ambiental, econômico, social e cultural
Authors: Santos Sueli de Fátima de Oliveira Miranda , Hatakeyama Kazuo
Published: March 2012

O Brasil produz aproximadamente 1/3 da produção mundial de carvão vegetal e sua quase totalidade é destinada à produção brasileira de ferro-gusa, ferro ligas e silício metálico. Quase 75% desse carvão ainda é produzido artesanalmente, utilizando-se principalmente a lenha de mata nativa. A pressão por sistemas produtivos sustentáveis tem dirigido a busca por tecnologias mais limpas e eficientes. A partir de pesquisa numa unidade industrial produtora de carvão vegetal pelo processo de carbonização em cilindros metálicos verticais, localizada no Paraná, este artigo objetiva mostrar que os aspectos de sustentabilidade deste processo estão no atendimento aos requisitos básicos de ser ecologicamente correto, economicamente viável, socialmente justo e culturalmente aceito. Este processo mostrou um potencial de economizar em torno de 25% de lenha, o atendimento à legislação trabalhista vigente e o atendimento aos anseios da sociedade, ao proporcionar aos trabalhadores condições dignas de trabalho e inserção social, quando comparado ao processo artesanal.
Excesso de velocidade no trânsito: análise sob a perspectiva da moralidade
Authors: Polli Gislei Mocelin , Thielen Iara Picchioni , Hartmann Ricardo Carlos , Soares Diogo Picchioni
Published: March 2012

Este trabalho focaliza o desenvolvimento moral como um dos fatores relacionados ao comportamento inadequado no trânsito. O objetivo foi estudar a relação entre o nível de desenvolvimento moral e o comportamento infrator dos motoristas, partindo da hipótese que a infração estaria relacionada com os primeiros estágios de desenvolvimento moral propostos por Kohlberg. Para esta pesquisa, foram analisadas entrevistas qualitativas com 20 motoristas com mais de nove multas por excesso de velocidade, das quais 49 respostas foram selecionadas, já que as demais não possibilitavam análise do nível de desenvolvimento moral. O estudo permitiu verificar que o estágio 1 de desenvolvimento moral predomina em 75,51% das respostas dos motoristas infratores entrevistados. A característica principal desse estágio é a preocupação com a punição, expressa na resposta “eu não sabia que ali tinha radar”. Essa resposta indica que, se não houvesse fiscalização e, em consequência, punição, não haveria motivo para não infringir a lei. Este estudo indica limitações na aplicação da teoria de desenvolvimento moral baseada nas justificativas, pois estas se aplicam a ações infratoras ou não. Além disso, o estudo não focalizou dilemas e privilegiou a análise das respostas, portanto, o estágio 1 foi característico de respostas, e não de sujeitos.
Validação do Questionário de Performance Vocal no Brasil
Authors: Paulinelli Bruna Rabelo , Gama Ana Cristina Côrtes , Behlau Mara
Published: March 2012

OBJETIVO: Realizar a validação do Vocal Performance Questionnaire para o Português Brasileiro. MÉTODOS: Foram seguidos os passos do Scientific Advisory Committee of the Medical Outcomes Trust - SAC. Primeiramente foram analisados os aspectos de modelo conceitual e de medida, confiabilidade, validade, sensibilidade, interpretabilidade e demanda de administração e resposta. O questionário foi traduzido e também retrotraduzido por duas fonoaudiólogas fluentes na língua. As versões foram comparadas e a versão em Português do questionárion foi gerada, recebendo o nome Questionário de Performance Vocal - QPV. O questionário foi aplicado em 325 indivíduos, 160 com queixa vocal e 165 indivíduos sem queixa vocal, com distribuição semelhante de gênero e idade. Posteriormente, os escores dos dois grupos foram comparados e o questionário foi reaplicado em 39 participantes disfônicos, para avaliação da confiabilidade e reprodutibilidade do questionário. O intervalo de confiança considerado foi 95%. RESULTADOS: Todas as 12 questões foram mantidas e o questionário apresentou medidas psicométricas confiáveis de validade, confiabilidade e reprodutibilidade e sensibilidade. CONCLUSÃO: A versão brasileira chamada Questionário de Performance Vocal - QPV, é um protocolo confiável, válido, sensível a mudanças, de fácil aplicação e cálculo de resultados, podendo ser um instrumento importante para compor a avaliação fonoaudiológica do indivíduo disfônico.
Estudo do amortecimento do pêndulo simples: uma proposta para aplicação em laboratório de ensino
Authors: Arnold Francisco José , Arthur Rangel , Bravo-Roger Leonardo Lorenzo , Gonçalves Marcos Sérgio , Oliveira Mário José Garrido de
Published: March 2012

Os pêndulos são muito empregados nas atividades de ensino de cursos introdutórios de física. Nessas atividades, frequentemente, faz-se uso de modelos ideais para estudar o comportamento do pêndulo. Neste trabalho é sugerido um modelo que leva em conta o amortecimento das oscilações. Uma metodologia experimental é proposta com a finalidade de detectar a diminuição da amplitude das oscilações e ajustar estes dados a um modelo matemático. Os resultados demonstram que o pêndulo simples, composto de esferas de pequeno volume e oscilando com baixas velocidades, pode ser estudado por modelos simplificados. A metodologia e o modelo matemático são compatíveis com o nível de conhecimento de alunos de cursos introdutórios de física e oferecem uma visão mais realística sobre o comportamento do pêndulo.
Fifteen-Year Follow-Up Results of Presurgical Orthopedics Followed by Primary Correction for Unilateral Cleft Lip Nose in Program SEHATI in Indonesia
Authors: Sulaiman Farida Kamil , Haryanto Inge Gustiningsih , Hak Syafrudin , Nakamura Norifumi , Sasaguri Masaaki , Ohishi Masamichi
Published: March 2012

Objective

To assess long-term effects of nasal correction in infancy on nasal form and growth in patients with unilateral cleft lip, alveolus, and palate (UCLP).

Design

Retrospective longitudinal study.

Patients

Seventeen patients with complete UCLP treated in Program SEHATI in Harapan Kita Children and Maternity Hospital, Indonesia, and followed for approximately 15 years were enrolled.

Interventions

Subjects received presurgical orthopedics using a Hotz's plate and simultaneous primary lip and nose repair in which the lower lateral cartilage was repositioned through a reverse-U incision.

Main Outcome Measures

Preoperative and postoperative nasal forms, including the nostril height and width ratio, the ratio of the height of the top of the alar groove, and the ratio of nostril surface areas were analyzed using color photos taken serially. One-way analysis of variance was used for statistical analyses.

Results

The nostril height and width ratio and the height of the alar groove were significantly improved postoperatively and maintained for 15 years. The mean ratio of nostril surface areas was 1.01 ± 0.12 fifteen years postoperatively, and there was no significant difference from the ratio 1 year postoperatively. The major persistent deformities were septal deviation and a small skin web on the nostril rim.

Conclusions

Our primary cleft lip nose correction has provided an acceptable nose form and absence of disturbance of the nasal growth in patients with UCLP. However, the repositioning of the nasal cartilage at infancy might not eliminate the need for secondary correction after puberty.
Flow structure around a row of vertical rods in a floodplain
Authors: Keshavarzi Alireza , Esfahani Fariba Sadat
Published: March 2012

This paper presents the results of an experimental study to determine the effect of a row of vertical cylindrical rods on the structure of turbulent flow inside a symmetrical rectangular compound open channel. The coherent turbulent flow structure or bursting events and associated shear stresses play an important role in sediment entrainment and bed instability in an open channel. Therefore, in this study, three-dimensional bursting analysis is used to find the turbulent flow structure at the edge of a floodplain. The study used a model of a symmetrical rectangular compound channel in which ratio of the main channel width B to the floodplain width b was 1·5. A row of cylindrical wooden rods was installed on the floodplain bed at different distances d from the edge of the floodplain (d/b = 0, 0·1, 0·2, 0·3 and 0·4). Three-dimensional flow velocities were measured using an acoustic Doppler velocity meter (micro-ADV). For different experimental tests, the contribution probability of bursting events to the Reynolds shear stress was computed at different points of the flow depth. Minimum values for the contribution probability of shear stress were found for internal, external sweep and ejection events at the edge of floodplain for d/b equal to 0·1. Furthermore, the transition probability of internal, external sweep and external ejection events for d/b = 0·1 decreased at the intersection of the floodplain and main channel. Although scaling of the experimental results requires further study for application to wide rivers, these findings may be useful in practical applications for narrow rivers.
A Simple Method for the Analysis of On‐Farm Strip Trials
Authors: Lawes R. A. , Bramley R. G. V.
Published: March 2012

The design and analysis of experiments in farmers’ fields using commercial yield monitoring equipment has received considerable attention in the last decade. Complex design and analytical techniques have been developed to maximize the utility of the trial to the producer while retaining the potential for robust statistical analysis. However, implementation of such approaches requires access to specialists in spatial analysis, geostatistics, and geographic information systems (GIS) and so is rarely implemented by farmers and their advisors. Here we explore a new and simple approach to the analysis of farmer strip trials and the spatial variability of treatment response. Strip trials evaluating different fertilizer treatments were conducted in farmers’ fields in South Australia and Western Australia. Yield data were subjected to analysis with a linear model that accounted for the spatial autocorrelation in the data, a linear model that did not account for the spatial correlation and a moving pairwise comparison of treatments. Results suggest the pairwise comparison adequately identified treatment differences and their significance. Since this method can be readily implemented in a simple spreadsheet, it offers an important advance in facilitating on‐farm experimentation using precision agriculture technologies.