bluuebunny/crossref_metadata_2025 huggingface dataset:
Responses to the Acupuncture Trialists— Collaboration Individual Patient Data Meta-Analysis
Authors: Vickers Andrew J , Maschino Alexandra C , Lewith George , MacPherson Hugh , Sherman Karen J , Witt Claudia M ,   on behalf of the Acupuncture Trialists’ Collaboration
Published: February 2013

In September 2012 the Acupuncture Trialists’ Collaboration published the results of an individual patient data meta-analysis of almost 18 000 patients in high quality randomised trials. The results favoured acupuncture. Although there was little argument about the findings in the scientific press, a controversy played out in blog posts and the lay press. This controversy was characterised by ad hominem remarks, anonymous criticism, phony expertise and the use of opinion to contradict data, predominantly by self-proclaimed sceptics. There was a near complete absence of substantive scientific critique. The lack of any reasoned debate about the main findings of the Acupuncture Trialists’ Collaboration paper underlines the fact that mainstream science has moved on from the intellectual sterility and ad hominem attacks that characterise the sceptics’ movement.
Injury rates, types, mechanisms and risk factors in female youth ice hockey
Authors: Decloe Melissa D , Meeuwisse Willem H , Hagel Brent E , Emery Carolyn A
Published: February 2013

Background

The objectives of this cohort study were to examine the rate, types, mechanisms and risk factors for injury in female youth (ages 9–17) ice hockey players in the Girls Hockey Calgary Association.

Methods

The main outcome was ice hockey injury, defined as any injury occurring during the 2008/2009 season that required medical attention, and/or removal from a session and/or missing a subsequent session. Potential risk factors included age group, level of play, previous injury, ice hockey experience, physical activity level, weight, height, position of play and menarche. Incidence rate ratios (IRR) were estimated with Poisson Regression adjusted for cluster (team). Exposure data were collected for every session for each participating player.

Results

Twenty-eight teams (n=324) from Atom (ages 9–10), PeeWee (11–12), Bantam (13–14) and Midget (15–17) participated with 53 reported injuries. The overall injury rate was 1.9 injuries/1000 player-hours (95% CI 1.4 to 2.7). Previous injury (IRR=2.7, 95% CI 1.7 to 4.3), games (IRR=2.1, 95% CI 1.1 to 4.2), menarche (PeeWee) (IRR=4.1, 95% CI 1.0 to 16.8) were significant risk factors. In Midget, the more elite divisions were associated with a lower injury risk (A-IRR=0.2, 95% CI 0.1 to 0.5) (AAA-IRR=0.5, 95% CI 0.2 to 0.9).

Conclusions

Injury rates were lower in this study than previously found in male youth and women's ice hockey populations. Previous injury and game play as risk factors are consistent with the literature. Menarche as a risk factor is a new finding in this study. This research will inform future studies of the development of injury prevention strategies in this population.
Facies and climate changes across the Permian–Triassic boundary in the North German Basin: insights from a high-resolution organic carbon isotope record
Authors: Hiete Michael , Röhling Heinz-Gerd , Heunisch Carmen , Berner Ulrich
Published: February 2013

The transition from the uppermost Permian Zechstein Group to the lowermost Triassic Lower Buntsandstein Subgroup in the North German Basin is characterized by a shift from sabkha to playa and to fluviatile facies indicative of a shift to a more humid climate and associated with a major reorganization of the sedimentary system. These changes are recorded in a high-resolution carbon isotope profile of bulk organic matter spanning from the upper Zechstein Group of Changhsingian age to the Calvörde Formation of the Lower Buntsandstein Subgroup of Changhsingian–Indusian age. The organic carbon isotopes reflect a varying composition of the organic matter. Dependent on the facies type, which is mainly controlled by humidity, the proportions of cyanobacterial, phytoplankton and land-plant-derived organic matter with differing organic carbon isotope values change in the samples. A negative organic carbon isotope excursion shortly below the supposed Permian–Triassic Boundary (PTB) is interpreted as a horizon rich in isotopically light phytoplankton, representing a perennial playa lake stage. Although certain effects of global carbon cycle perturbations around the PTB on the analysed organic carbon isotope profile cannot be excluded, the facies and climatic changes associated with the PTB events are thought to be more important.
Hypoxic depression of PKG-mediated inhibition of serotonergic contraction in ovine carotid arteries
Authors: Thorpe Richard B. , Stockman Sara L. , Williams James M. , Lincoln Thomas M. , Pearce William J.
Published: February 2013

Chronic hypoxia attenuates soluble guanylate cyclase-induced vasorelaxation in serotonin (5-HT)-contracted ovine carotid arteries. Because protein kinase G (PKG) mediates many effects of soluble guanylate cyclase activation through phosphorylation of multiple kinase targets in vascular smooth muscle, we tested the hypothesis that chronic hypoxia reduces the ability of PKG to phosphorylate its target proteins, which attenuates the ability of PKG to induce vasorelaxation. We also tested the hypothesis that hypoxia attenuates PKG expression and/or activity. Arteries from normoxic and chronically hypoxic (altitude of 3,820 m for 110 days) fetal and adult sheep were denuded of endothelium and equilibrated with 95% O2-5% CO2in the presence of nitro-l-arginine methyl ester (l-NAME) and NG-nitro-l-arginine (l-NNA) to inhibit residual endothelial nitric oxide synthase. Concentration-response relations for 5-HT were determined in the presence of prazosin to minimize activation of α-adrenergic receptors. The PKG activator 8-( p-chlorophenylthio)-guanosine 3′,5′-cyclic monophosphate (8-pCTP-cGMP) reduced agonist binding affinity of the 5-HT receptor in a concentration-dependent manner that was attenuated by hypoxia. Expression and activity of PKG-I was not significantly affected by chronic hypoxia in either fetal or adult arteries, although PKG-I abundance was greater in fetal arteries. Pretreatment with the large conductance calcium-sensitive potassium channel (BK) inhibitor iberiotoxin attenuated the vasorelaxation induced by 8-pCPT-cGMP in normoxic but not chronically hypoxic arteries. These results support the hypothesis that hypoxia attenuates the vasorelaxant effects of PKG through suppression of the ability of PKG to activate large conductance calcium-sensitive potassium channels in arterial smooth muscle. The results also reveal that this hypoxic effect is greater in fetal than adult arteries and that chronic maternal hypoxia can profoundly affect fetal vascular function.
Kinetic Modeling–Based Detection of Genetic Signatures That Provide Chemoresistance via the E2F1-p73/DNp73-miR-205 Network
Authors: Vera Julio , Schmitz Ulf , Lai Xin , Engelmann David , Khan Faiz M. , Wolkenhauer Olaf , Pützer Brigitte M.
Published: February 2013

Drug resistance is a major cause of deaths from cancer. E2F1 is a transcription factor involved in cell proliferation, apoptosis. and metastasis through an intricate regulatory network, which includes other transcription factors like p73 and cancer-related microRNAs like miR-205. To investigate the emergence of drug resistance, we developed a methodology that integrates experimental data with a network biology and kinetic modeling. Using a regulatory map developed to summarize knowledge on E2F1 and its interplay with p73/DNp73 and miR-205 in cancer drug responses, we derived a kinetic model that represents the network response to certain genotoxic and cytostatic anticancer drugs. By perturbing the model parameters, we simulated heterogeneous cell configurations referred to as in silico cell lines. These were used to detect genetic signatures characteristic for single or double drug resistance. We identified a signature composed of high E2F1 and low miR-205 expression that promotes resistance to genotoxic drugs. In this signature, downregulation of miR-205, can be mediated by an imbalance in the p73/DNp73 ratio or by dysregulation of other cancer-related regulators of miR-205 expression such as TGFβ-1 or TWIST1. In addition, we found that a genetic signature composed of high E2F1, low miR-205, and high ERBB3 can render tumor cells insensitive to both cytostatic and genotoxic drugs. Our model simulations also suggested that conventional genotoxic drug treatment favors selection of chemoresistant cells in genetically heterogeneous tumors, in a manner requiring dysregulation of incoherent feedforward loops that involve E2F1, p73/DNp73, and miR-205. Cancer Res; 73(12); 3511–24. ©2013 AACR.
TNRC9 Downregulates BRCA1 Expression and Promotes Breast Cancer Aggressiveness
Authors: Shan Jingxuan , DSouza Shoba P. , Bakhru Sasha , Al-Azwani Eman K. , Ascierto Maria L. , Sastry Konduru S. , Bedri Shahinaz , Kizhakayil Dhanya , Aigha Idil I. , Malek Joel , Al-Bozom Issam , Gehani Salah , Furtado Stacia , Mathiowitz Edith , Wang Ena , Marincola Francesco M. , Chouchane Lotfi
Published: February 2013

Although the linkage between germline mutations of BRCA1 and hereditary breast/ovarian cancers is well established, recent evidence suggests that altered expression of wild-type BRCA1 might contribute to the sporadic forms of breast cancer. The breast cancer gene trinucleotide-repeat-containing 9 (TNRC9; TOX3) has been associated with disease susceptibility but its function is undetermined. Here, we report that TNRC9 is often amplified and overexpressed in breast cancer, particularly in advanced breast cancer. Gene amplification was associated with reduced disease-free and metastasis-free survival rates. Ectopic expression of TNRC9 increased breast cancer cell proliferation, migration, and survival after exposure to apoptotic stimuli. These phenotypes were associated with tumor progression in a mouse model of breast cancer. Gene expression profiling, protein analysis, and in silico assays of large datasets of breast and ovarian cancer samples suggested that TNRC9 and BRCA1 expression were inversely correlated. Notably, we found that TNRC9 bound to both the BRCA1 promoter and the cAMP-responsive element-binding protein (CREB) complex, a regulator of BRCA1 transcription. In support of this connection, expression of TNRC9 downregulated expression of BRCA1 by altering the methylation status of its promoter. Our studies unveil a function for TNRC9 in breast cancer that highlights a new paradigm in BRCA1 regulation. Cancer Res; 73(9); 2840–9. ©2013 AACR.
Aberrant Expression of Mucin Core Proteins and O-Linked Glycans Associated with Progression of Pancreatic Cancer
Authors: Remmers Neeley , Anderson Judy M. , Linde Erin M. , DiMaio Dominick J. , Lazenby Audrey J. , Wandall Hans H. , Mandel Ulla , Clausen Henrik , Yu Fang , Hollingsworth Michael A.
Published: February 2013

Purpose: Mucin expression is a common feature of most adenocarcinomas and features prominently in current attempts to improve diagnosis and therapy for pancreatic cancer and other adenocarcinomas. We investigated the expression of a number of mucin core proteins and associated O-linked glycans expressed in pancreatic adenocarcinoma—sialyl Tn (STn), Tn, T antigen, sialyl Lewis A (CA19-9), sialyl Lewis C (SLeC), Lewis X (LeX), and sialyl LeX (SLeX)—during the progression of pancreatic cancer from early stages to metastatic disease.

Experimental Design: Immunohistochemical analyses of mucin and associated glycan expression on primary tumor and liver metastatic tumor samples were conducted with matched sets of tissues from 40 autopsy patients diagnosed with pancreatic adenocarcinoma, 14 surgically resected tissue samples, and 8 normal pancreata.

Results: There were significant changes in mucin expression patterns throughout disease progression. MUC1 and MUC4 were differentially glycosylated as the disease progressed from early pancreatic intraepithelial neoplasias to metastatic disease. De novo expression of several mucins correlated with increased metastasis indicating a potentially more invasive phenotype, and we show the expression of MUC6 in acinar cells undergoing acinar to ductal metaplasia. A “cancer field-effect” that included changes in mucin protein expression and glycosylation in the adjacent normal pancreas was also seen.

Conclusions: There are significant alterations in mucin expression and posttranslational processing during progression of pancreatic cancer from early lesions to metastasis. The results are presented in the context of how mucins influence the biology of tumor cells and their microenvironment during progression of pancreatic cancer. Clin Cancer Res; 19(8); 1981–93. ©2013 AACR.
Hematoma Expansion following Acute Intracerebral Hemorrhage
Authors: Brouwers H. Bart , Greenberg Steven M.
Published: February 2013

Intracerebral hemorrhage (ICH), the most devastating form of stroke, has no specific therapy proven to improve outcome by randomized controlled trial. Location and baseline hematoma volume are strong predictors of mortality, but are nonmodifiable by the time of diagnosis. Expansion of the initial hematoma is a further marker of poor prognosis that may be at least partly preventable. Several risk factors for hematoma expansion have been identified, including baseline ICH volume, early presentation after symptom onset, anticoagulation, and the CT angiography spot sign. Although the biological mechanisms of hematoma expansion remain unclear, accumulating evidence supports a model of ongoing secondary bleeding from ruptured adjacent vessels surrounding the initial bleeding site. Several large clinical trials testing therapies aimed at preventing hematoma expansion are in progress, including aggressive blood pressure reduction, treatment with recombinant factor VIIa guided by CT angiography findings, and surgical intervention for superficial hematomas without intraventricular extension. Hematoma expansion is so far the only marker of outcome that is amenable to treatment and thus a potentially important therapeutic target.
Serum levels of vitamin D are not associated with future risk of venous thromboembolism
Authors: Lerstad Gunhild , Grimnes Guri , Brækkan Sigrid K. , Vik Anders , Brox Jan , Svartberg Johan , Jorde Rolf , Hansen John-Bjarne , Brodin Ellen E.
Published: February 2013

Previous studies have provided indirect evidence for a possible association between vitamin D status and risk of venous thromboembolism (VTE). However, no study has so far investigated the association between serum levels of 25-hydroxyvitamin D (25(OH)D), the biomarker of vitamin D status, and risk of VTE. The aim of our study was to investigate whether high levels of 25(OH)D were associated with decreased risk of VTE in a prospective population-based study. Serum levels of 25(OH)D were measured in 6,021 men and women, aged 25–84 years, who participated in the Tromsø Study in 1994–1995. Incident VTE-events were registered from date of inclusion through the end of follow-up, September 1, 2007. Cox-regression models were used to calculate hazard ratios (HR) with 95% confidence interval (CI) for VTE. There were 201 incident VTE-events during a median of 10.7 years of follow-up. The risk of VTE did not decrease per one standard deviation (SD) (19.8 nmol/l) increase in serum 25(OH)D (multivariable HR 1.02; 95% CI 0.91–1.22). Moreover, subjects with serum 25(OH)D ≥ 70 nmol/l (upper quartile) did not have decreased risk of VTE compared to those ≤ 44 nmol/l (lower quartile) in age- and sex-adjusted analysis (HR 0.91, 95% CI: 0.60–1.37, p for trend across quartiles 0.9) or multivariable analysis adjusted for age, sex, body mass index, smoking, and physical activity (HR 0.76, 95% CI: 0.45–1.28, p for trend across quartiles 0.9). Subgroup analyses showed no associations between serum levels of 25(OH)D and unprovoked or provoked VTE. In conclusion, in our study, normal serum levels of 25(OH)D were not associated with future risk of VTE, suggesting that vitamin D status does not play an important role in the pathogenesis of VTE. However, our findings did not apply to subjects with vitamin D deficiency (< 30 nmol/l) due to lack of statistical power among these subjects.
CD4+ T cells in atherosclerosis: Regulation by platelets
Authors: Li Nailin
Published: February 2013

Atherosclerosis is an inflammatory and thrombotic disease, in which both CD4+ T cells and platelets play important roles throughout all stages of atherogenesis. CD4+ T cells are the most abundant T cells present in atherosclerotic lesions. They are primarily seen as type 1 T helper (Th1) cells, while the other CD4+ T cell subsets Th2, Th17, and regulatory T (Treg) cells are also found in the lesions with lower frequencies. CD4+ T effector cells release various cytokines, which exert paracrine or autocrine effects among different CD4+ T cell subsets and other lesional cells and subsequently modulate inflammatory processes in the lesions. Platelets are instrumental in thrombosis and haemostasis, but also play important regulatory roles in immune response, inflammation, and angiogenesis. The present review summarises the current knowledge and/or understanding on how platelets regulate recruitment, activation, differentiation, and cytokine production of different CD4+ T cell subsets, as well as impacts of the platelet-CD4+ T cell interactions on atherogenesis. The research perspectives of platelet-CD4+ T cell interaction in atherosclerosis are also discussed.
From mice to men – mouse models in obesity research: What can we learn?
Authors: Scroyen Ilse , Hemmeryckx Bianca , Lijnen H. Roger
Published: February 2013

summary

Obesity has become a world-wide epidemic and is associated with diseases such as diabetes, dyslipidaemia, cardiovascular disease and certain types of cancers. Understanding the adipose tissue developmental process, involving adipogenesis, angiogenesis and extracellular matrix remodelling, is therefore crucial to reveal the pathobiology of obesity. Experimental mouse models are extensively used to gain new insights into these processes and to evaluate the role of new key players, in particular proteolytic system components, in adipose tissue development and obesity. In this paper, we will review available in vitro and in vivo murine models of obesity and discuss their value in understanding the mechanisms contributing to obesity.
Rapid Feature-driven Changes in the Attentional Window
Authors: Leonard Carly J. , Lopez-Calderon Javier , Kreither Johanna , Luck Steven J.
Published: February 2013

Spatial attention must adjust around an object of interest in a manner that reflects the object's size on the retina as well as the proximity of distracting objects, a process often guided by nonspatial features. This study used ERPs to investigate how quickly the size of this type of “attentional window” can adjust around a fixated target object defined by its color and whether this variety of attention influences the feedforward flow of subsequent information through the visual system. The task involved attending either to a circular region at fixation or to a surrounding annulus region, depending on which region contained an attended color. The region containing the attended color varied randomly from trial to trial, so the spatial distribution of attention had to be adjusted on each trial. We measured the initial sensory ERP response elicited by an irrelevant probe stimulus that appeared in one of the two regions at different times after task display onset. This allowed us to measure the amount of time required to adjust spatial attention on the basis of the location of the task-relevant feature. We found that the probe-elicited sensory response was larger when the probe occurred within the region of the attended dots, and this effect required a delay of approximately 175 msec between the onset of the task display and the onset of the probe. Thus, the window of attention is rapidly adjusted around the point of fixation in a manner that reflects the spatial extent of a task-relevant stimulus, leading to changes in the feedforward flow of subsequent information through the visual system.
A new species of the Callophrys mystaphia Miller, 1913—group from Iran (Lepidoptera: Lycaenidae: Eumaeini)
Authors: KRUPITSKY ANATOLY V. , KOLESNICHENKO KIRILL A.
Published: February 2013

A new species, recently misinterpreted as Callophrys mystaphia Miller, 1913, Callophrys mystaphioides Krupitsky & Kolesnichenko sp. n., is described from Central Iran (Esfahan Province). The new species differs from C. mystaphia in the combination of external characters and morphology of genitalia. Possible relations of C. mystaphia—species group with other Palaearctic Callophrys are discussed.
Cognitive Rest and School-Based Recommendations Following Pediatric Concussion
Authors: Arbogast Kristy B. , McGinley Alexander D. , Master Christina L. , Grady Matthew F. , Robinson Roni L. , Zonfrillo Mark R.
Published: February 2013

Objectives. (1) Assess pediatric primary care providers’ understanding of cognitive rest for concussion and (2) describe their concussion management practices. Methods. This study included (1) a survey of general pediatric providers and (2) an electronic medical record (EMR) review of children 5 to 18 years old treated for concussion from September 1, 2010, to May 31, 2011. The survey asked about treatment recommendations for concussion, and results were coded to identify cognitive rest recommendations. The EMR review included the following: injury details, medical evaluation, and recommendations for resuming school and sports/recreation. Results. In all, 89 of 201 providers responded to the survey, and 52 of the 84 clinicians who included comments about concussion management mentioned cognitive rest (62%, 95% confidence interval [CI] = 51%-72%). Of the 91 EMRs reviewed for patients’ first visits following the concussion, only 10 (11%, 95% CI = 6%-19%) included written cognitive rest recommendations. Conclusions. Although the majority of pediatric providers identified cognitive rest as important in pediatric concussion management, few provided written recommendations in the EMR.
Activising Space: The Spatial Politics of the 2011 Protest Movement in Israel
Authors: Marom Nathan
Published: February 2013

In summer 2011, Israel was swept by unprecedented political protest as multiple encampments occupied streets and mass rallies were held weekly in Tel Aviv and other cities. The article focuses on the spatial politics of this protest, analysing the particular strategies it used to activise urban public space. The protest initially reflected a specific urban context and limited agenda—namely, the lack of affordable housing in Tel Aviv. However, as it materialised and expanded in public space, it also became more inclusive, incorporating more marginalised publics and places, addressing long-standing socio-spatial inequalities between Israel’s ‘centre’ and ‘periphery’, and advancing a message of ‘social justice’—with the noted exception of Palestinians in the Occupied Territories. The analysis of the Israeli protest foregrounds some dynamics that it shares with other ‘global’ protests in 2011, from Tahrir Square to Occupy Wall Street, pointing to the spatial politics of centrality, multiplicity and ‘media-space’, a mutually enforcing relationship between physical public space and mainstream and social media.
Morphological Study of Progressive Glomerulonephropathy in Common Marmosets (Callithrix jacchus)
Authors: Yamada Naoaki , Sato Junko , Kanno Takeshi , Wako Yumi , Tsuchitani Minoru
Published: February 2013

Spontaneous progressive glomerulonephropathy often occurs in common marmosets. However, there are few detailed reports concerning the age-related progressive process of glomerular changes. We discuss the glomerular changes in the early stage and the progressive changes in the advanced stage of nephropathy. We investigated the kidneys of common marmosets (2–11 years old; 9 males and 12 females) using hematoxylin and eosin, periodic acid–Schiff, periodic acid–methenamine-silver, and Masson’s trichrome (MT) stains and a transmission electron microscope. There was no remarkable change in urine cytology, hematology, or blood chemistry. In the early stage of nephropathy, effacement of podocyte foot processes was observed ultrastructurally even though there were no marked glomerular lesions in the light microscopy. Subsequently, mesangial proliferation occurred from the hilar to peripheral side along the tuft. In the middle stage, red deposits were visible at the glomerular basement membrane (GBM) and the mesangial region directly under the GBM (paramesangial area) with the MT stain. Electron dense deposits were seen at the same area. In the advanced stage, the irregularity became prominent with or without dense deposits. It is necessary to investigate in detail whether the change of podocyte in the early stage was immuno-mediated or due to podocyte failure.
Development of a short measure of psychological recovery in serious mental illness: the STORI-30
Authors: Andresen Retta , Caputi Peter , Oades Lindsay
Published: February 2013

Objective:

To develop a brief measure of stage of psychological recovery from mental illness by identifying the best-performing items of the 50-item Stages of Recovery Instrument (STORI).

Method:

Item response modelling was used to identify a short form of the full-length STORI. The resulting items were subjected to factor analysis to further refine the subscales. A second data set was used to confirm the construct validity of the new measure. A correlational analysis was conducted to examine relationships among the five subscale scores.

Results:

Analyses identified 30 items that represented the five stages of the full STORI. The five stage subscale scores of the shorter measure, the STORI-30, showed a pattern of correlations that demonstrated an ordinal relationship between the stages.

Conclusions:

There is a need for recovery-oriented measures to augment established clinical assessment tools. The shorter version of the STORI, the STORI-30, shows promise as a brief measure of stage of recovery, more feasible for routine clinical use. Further psychometric and longitudinal testing is recommended. Qualitative research would be valuable in establishing acceptability to consumers and the clinical usefulness of the STORI-30.
Resident-to-Resident Violence Triggers in Nursing Homes
Authors: Snellgrove Susan , Beck Cornelia , Green Angela , McSweeney Jean C.
Published: February 2013

Certified nurses’ assistants (CNAs) employed by a rural nursing home in Northeast Arkansas described their perceptions of resident-to-resident violence in order to provide insight on factors, including unmet needs, that may trigger the phenomenon. Semistructured interviews were conducted with 11 CNAs. Data were analyzed using content analysis and constant comparison. Two categories of triggers emerged from the data—active and passive. Active triggers involved the actions of other residents that were intrusive in nature, such as wandering into a residents’ personal space, taking a resident’s belongings, and so forth. Passive triggers did not involve the actions of residents but related to the internal and external environment of the residents. Examples were factors such as boredom, competition for attention and communication difficulties. Results indicate that there are factors, including unmet needs within the nursing home environment that may be identified and altered to prevent violence between residents.
Effect of Graduated Compression Stockings on Venous Blood Velocity in Supine Resting Hospitalized Patients
Authors: Stein Paul D , Matta Fadi , Akkad Mohamed W , Hoppe Cheryl L , Patel Yash R , Sivakumar Subburaman
Published: February 2013

The effects of graduated compression stockings (GCSs) on venous blood velocity were measured in 26 hospitalized medical patients while supine at rest. Peak blood velocity in the right femoral vein was 21.6 cm/s without GCS and 23.0 cm/s with GCS [not significant (NS)]. Peak blood velocity in the right popliteal vein was 12.5 cm/s without GCS and 15.0 cm/s with GCS (NS). Mean blood velocity in the right femoral vein did not increase significantly with GCS, but mean blood velocity in the right popliteal vein increased marginally from 5.0 cm/s to 5.8 cm/s ( P = .05). Among 11 patients with venous insufficiency (refilling time ≤19 s), neither peak nor mean blood velocity in the femoral or popliteal veins increased significantly with GCS. In conclusion, thigh-length GCS in hospitalized patients had little or no effect on popliteal or femoral vein blood velocity while supine at rest, irrespective of whether the patients had venous insufficiency.
Power and Control in the Legal System
Authors: Watson Laurel B. , Ancis Julie R.
Published: February 2013

The purpose of this study was to examine the ways in which abuse that occurred during marriage/relationship continued within divorce and custody-related legal proceedings. Twenty-seven women participated in semistructured interviews. Interviews were analyzed utilizing a grounded theory approach in order to inductively arrive at a theory explaining how abuse dynamics may continue during legal proceedings. Participants identified child support litigation, custody and visitation battles, intimidation/harassment, deliberately prolonging the case, manipulating finances, and distortions of information as methods by which their exes sought to maintain power and control. Counseling implications are described.
Novel diagnostic assays for heparin-induced thrombocytopenia
Authors: Cuker Adam , Rux Ann H. , Hinds Jillian L. , Dela Cruz May , Yarovoi Serge V. , Brown Isola A. M. , Yang Wei , Konkle Barbara A. , Arepally Gowthami M. , Watson Stephen P. , Cines Douglas B. , Sachais Bruce S.
Published: February 2013

Key Points

The KKO-inhibition ELISA and DT40-luciferase tests are novel laboratory assays for HIT. They showed better discrimination than 2 commercial immunoassays and may improve the specificity and feasibility of HIT laboratory testing.
A Korpelevich-like algorithm for variational inequalities
Authors: Wu Zhitao , Yao Yonghong , Liou Yeong-Cheng , Li Hong-Jun
Published: February 2013

A Korpelevich-like algorithm has been introduced for solving a generalized variational inequality. It is shown that the presented algorithm converges strongly to a special solution of the generalized variational inequality.

MSC:47H05, 47J25.
Homology-based inference sets the bar high for protein function prediction
Authors: Hamp Tobias , Kassner Rebecca , Seemayer Stefan , Vicedo Esmeralda , Schaefer Christian , Achten Dominik , Auer Florian , Boehm Ariane , Braun Tatjana , Hecht Maximilian , Heron Mark , Hönigschmid Peter , Hopf Thomas A , Kaufmann Stefanie , Kiening Michael , Krompass Denis , Landerer Cedric , Mahlich Yannick , Roos Manfred , Rost Burkhard
Published: February 2013

Background

Any method that de novo predicts protein function should do better than random. More challenging, it also ought to outperform simple homology-based inference.

Methods

Here, we describe a few methods that predict protein function exclusively through homology. Together, they set the bar or lower limit for future improvements.

Results and conclusions

During the development of these methods, we faced two surprises. Firstly, our most successful implementation for the baseline ranked very high at CAFA1. In fact, our best combination of homology-based methods fared only slightly worse than the top-of-the-line prediction method from the Jones group. Secondly, although the concept of homology-based inference is simple, this work revealed that the precise details of the implementation are crucial: not only did the methods span from top to bottom performers at CAFA, but also the reasons for these differences were unexpected. In this work, we also propose a new rigorous measure to compare predicted and experimental annotations. It puts more emphasis on the details of protein function than the other measures employed by CAFA and may best reflect the expectations of users. Clearly, the definition of proper goals remains one major objective for CAFA.
Propolis changes the anticancer activity of temozolomide in U87MG human glioblastoma cell line
Authors: Markiewicz-Żukowska Renata , Borawska Maria H , Fiedorowicz Anna , Naliwajko Sylwia K , Sawicka Diana , Car Halina
Published: February 2013

Background

Propolis is a honey bee product which contains many active compounds, such as CAPE or chrysin, and has many beneficial activities. Recently, its anti-tumor properties have been discussed. We have tested whether the ethanolic extract of propolis (EEP) interferes with temozolomide (TMZ) to inhibit U87MG cell line growth.

Methods

The U87MG glioblastoma cell line was exposed to TMZ (10-100 μM), EEP (10-100 μg/ml) or a mixture of TMZ and EEP during 24, 48 or 72 hours. The cell division was examined by the H3-thymidine incorporation, while the western blot method was used for detection of p65 subunit of NF-κB and ELISA test to measure the concentration of its p50 subunit in the nucleus.

Results

We have found that both, TMZ and EEP administrated alone, had a dose- and time-dependent inhibitory effect on the U87MG cell line growth, which was manifested by gradual reduction of cell viability and alterations in proliferation rate. The anti-tumor effect of TMZ (20 μM) was enhanced by EEP, which was especially well observed after a short time of exposition, where simultaneous usage of TMZ and EEP resulted in a higher degree of growth inhibition than each biological factor used separately. In addition, cells treated with TMZ presented no changes in NF-κB activity in prolonged time of treatment and EEP only slightly reduced the nuclear translocation of this transcription factor. In turn, the combined incubation with TMZ and EEP led to an approximately double reduction of NF-κB nuclear localization.

Conclusions

We conclude that EEP presents cytotoxic properties and may cooperate with TMZ synergistically enhancing its growth inhibiting activity against glioblastoma U87MG cell line. This phenomenon may be at least partially mediated by a reduced activity of NF-κB.
Molecular immunologic correlates of spontaneous latency in a rabbit model of pulmonary tuberculosis
Authors: Subbian Selvakumar , O’Brien Paul , Kushner Nicole L , Yang Guibin , Tsenova Liana , Peixoto Blas , Bandyopadhyay Nirmalya , Bader Joel S , Karakousis Petros C , Fallows Dorothy , Kaplan Gilla
Published: February 2013

Background

Infection of humans withMycobacterium tuberculosis(Mtb) results in latent tuberculosis infection (LTBI) in 90-95% of immune competent individuals, with no symptoms of active disease. The World Health Organization estimates that 1.5 billion people have LTBI, which can reactivate in the setting of waning host immunity, posing a threat to global TB control. Various animal models have been used to study the pathogenesis of TB. However, besides nonhuman primates, rabbits are the only animal model that fully recapitulates the pathological features of human TB, including progressive disease with necrosis and cavitation or establishment of spontaneous latency.

Results

We defined the molecular immunological correlates of LTBI establishment in a rabbit model of pulmonary infection with Mtb CDC1551. After aerosol infection, exponential bacterial growth was noted in the lungs for 4 weeks, followed by a significant decline by 12 weeks, resulting in the absence of cultivable bacilli by 24 weeks. We used rabbit whole genome microarrays to profile the lung transcriptome during the course of infection. At 2 weeks post-infection, gene networks involved in natural killer (NK) and dendritic cell (DC) activation and macrophage antimicrobial activities were highly upregulated. This was followed by upregulation of gene networks involved in macrophage and T cell activation and autophagy, peaking at 4 to 8 weeks. Concomitantly, host Th1, but not Th2 or inflammatory, immune response genes were significantly upregulated. Thus, the expression kinetics of genes involved in cross-talk between innate and adaptive immunity over the first 8 weeks post-infection were consistent with early efficient control of infection in the lungs. Interestingly, expression of many genes of the host innate and adaptive immune response pathways was downregulated at 12 weeks, suggesting that immune activation did not persist once bacilli began to clear from the infected lungs.

Conclusions

Our results suggest that early activation of host innate immunity prior to efficient activation of T cell-mediated adaptive immunity but not inflammation is essential for establishment of LTBI in Mtb CDC1551-infected rabbits. We also show that T cell activation and the host adaptive immune response networks are dampened once bacterial growth is controlled, ultimately resulting in spontaneous LTBI.
Association between peripheral T-Lymphocyte activation and impaired bone mineral density in HIV-infected patients
Authors: Gazzola Lidia , Bellistri Giusi Maria , Tincati Camilla , Ierardi Valentina , Savoldi Alessia , Del Sole Angelo , Tagliabue Luca , d’Arminio Monforte Antonella , Marchetti Giulia
Published: February 2013

Background

HIV-infected patients display an increased and early incidence of osteopenia/osteoporosis. We investigated whether bone metabolism disorders in HIV-infected patients are related to immune hyperactivation and premature immune senescence.

Methods

Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA): low BMD (LBMD) was defined as T-score or z-score < -1. CD4+/CD8+ phenotype (CD38/HLA-DR, CD127, CD28/CD57), and circulating IL-7, TNF-α, RANKL, OPG were measured. The variables with p < .05 were evaluated by multivariate logistic regression.

Results

78 patients were enrolled: 55 were LBMD. LBMD patients showed increased activated HDLADR + CD4+ and CD8+ (p = .03 and p = .002, respectively). Interestingly, no differences in senescent CD28-CD57 + CD4+/CD8+ T-cells were observed between groups. However, LBMD patients displayed a decreased CD4 + CD28- phenotype (p = .04) at the advantage of the CD28+ pool (p = .03), possibly reflecting heightened apoptosis of highly differentiated CD28-negative cells.

Activated HLADR + CD4+/CD8+ and CD28 + CD4+ cells were independently associated with impaired BMD (AOR = 1.08 for each additional HLADR + CD4+ percentage higher; CI 95%,1.01-1.15; p = .02; AOR = 1.07 for each additional HLADR + CD8+ percentage higher; CI 95%,1.01-1.11; p = .01; AOR = 1.06 for each additional CD28 + CD4+ percentage higher; CI 95%,1.0-1.13; p = .05).

Conclusions

Heightened T-cell activation in HIV-infected patients independently predicts BMD disorders, suggesting a critical role of immune activation in the pathogenesis of osteopenia/osteoporosis, even in patients achieving full viral suppression with HAART.
Abattoir-based study on the epidemiology of caprine tuberculosis in Ethiopia using conventional and molecular tools
Authors: Deresa Benti , Conraths Franz J , Ameni Gobena
Published: February 2013

Background

Despite the important role of goats for meat and milk production in Ethiopia, little information is available on the epidemiology of caprine tuberculosis (TB). Caprine TB is important as milk is usually consumed raw particularly by Ethiopian pastoralists. The objectives of the present study were to estimate the prevalence of TB in goats at an abattoir, to evaluate associated risk factors and to characterize the causative mycobacteria.

Methods

A cross-sectional study was conducted on 1990 randomly selected male goats that were slaughtered at Luna Export Abattoir of central Ethiopia. Postmortem examination, mycobacterial culturing and molecular typing techniques like genus typing, deletion typing and spoligotyping were used.

Result

The overall prevalence of caprine TB-like lesions was 3.5%. The lesion prevalence increased significantly with increasing age. Mycobacteria were found by culture and seen as acid fast bacilli in 12% of the goats with TB-like lesions. Characterization of the eight isolates using multiplex polymerase chain reaction (PCR) indicated that five of them belonged to the genus Mycobacterium. Four of the latter were confirmed to be members of the M. tuberculosis complex. Further characterization of the three M. tuberculosis isolates by spoligotyping identified them as type SIT53 and two new spoligotypes.

Conclusion

The isolation of M. tuberculosis from goats in this study indicates a potential risk of transmission of M. tuberculosis between humans and goats.
Novel multi-targeted polymerase chain reaction for diagnosis of presumed tubercular uveitis
Authors: Sharma Kusum , Gupta Vishali , Bansal Reema , Sharma Aman , Sharma Meera , Gupta Amod
Published: February 2013

Background

The objective of this study was to report the use of multi-targeted polymerase chain reaction (PCR) in the diagnosis of presumed tubercular uveitis. Multi-targeted PCR using three targets specific for Mycobacterium tuberculosis, i.e., IS6110, MPB64, and protein b, was performed on intraocular fluid samples of 25 subjects. Nine had presumed tubercular uveitis, six had intraocular inflammation secondary to a nontubercular etiology (disease controls), and ten had no evidence of intraocular inflammation (normal controls). As described previously, response to antitubercular therapy was considered as the gold standard.

Results

Multi-targeted PCR was positive in seven out of nine patients with presumed tubercular uveitis and negative in all normal and disease controls. The sensitivity and specificity were 77.77% and 100%, respectively. For the diagnosis of presumed tubercular uveitis, multi-targeted PCR had a positive predictive value of 100% and a negative predictive value of 88.88%.

Conclusion

Multi-targeted PCR can be a valuable tool for diagnosing presumed tubercular uveitis.
Traditional Chinese medicine: a promising candidate for the treatment of Alzheimer’s disease
Authors: Sun Zhi-Kun , Yang Hong-Qi , Chen Sheng-Di
Published: February 2013

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder, characterized clinically by insidious onset of memory and cognition impairment, emergence of psychiatric symptoms and behavioral disorder, and impairment of activities of daily living (ADL). Traditional Chinese medicine (TCM) is practiced in the Chinese health care system for more than 2,000 years. In recent years, scientists have isolated many novel compounds from herbs, some of which improve dementia with fewer side effects than conventional drugs and are regarded as potential anti-AD drugs. In this review, we summarize the latest research progress on TCM showing their possible role of treatment of AD and other demented diseases and possible pharmacological actions.
TLR2 deletion promotes arthritis through reduction of IL-10
Authors: Huang Qi-Quan , Koessler Renee E , Birkett Robert , Perlman Harris , Xing Lianping , Pope Richard M
Published: February 2013

TLR2 signaling modulates K/BxN serum transfer arthritis by enhancing the expression of immune complex-induced IL-10.

RA is a chronic inflammatory disease characterized by the persistent expression of inflammatory cytokines from macrophages, which may be mediated, in part, through TLR2 signaling. Earlier studies demonstrate a role for TLR2 signaling in dampening the arthritis in IL-1Ra−/− mice, which was mediated through T cells. This study was performed to determine whether TLR2 signaling plays a role in the pathogenesis of T cell-independent arthritis triggered by transferring serum from K/BxN mice. We documented more severe arthritis in Tlr2−/− mice compared with WT controls. The Tlr2−/− mice also demonstrated increased inflammation, erosion, pannus formation, and osteoclastogenesis, as well as increased IL-1β and decreased IL-10 within the joints. In vitro bone marrow-differentiated macrophages expressed comparable levels of activating and inhibitory FcγRs, however when stimulated with immune complexes, the Tlr2−/− macrophages expressed decreased IL-10 and reduced activation of Akt and ERK. Our findings indicate that Tlr2−/− promotes the effector phase of arthritis through decreased IL-10 by macrophages, which is important, not only as an anti-inflammatory cytokine but also in restraining the differentiation and activation of osteoclasts.
Forum Theater in Singapore: Resistance, Containment, and Commodification in an Advanced Industrial Society
Authors: Tan Kenneth Paul
Published: February 2013

Forum theater is an interactive practice whose “third-world” revolutionary origins have been transposed into techniques for dealing with “oppressions” within bourgeois societies. By constructing an analytical framework that articulates a Marcusean “one-dimensional society” approach and a Gramscian “constant struggle for hegemony” approach, this article discusses forum theater's relative autonomy from and susceptibility to the authoritarian and culture-industry logics of advanced industrial society. In 1993, forum theater was successfully introduced to Singapore by local professional theater company The Necessary Stage (TNS) and then quickly proscribed by the state for its Marxist associations and unscripted nature. At the turn of the millennium, however, the state has come to realize more clearly the economic value of the arts, including its “subversive” qualities that may generate excitement and nurture a culture of innovation necessary for the creative economy of renaissance Singapore, a global city for the arts. In the transition to this new climate, TNS and another professional theater company, Drama Box, have attempted to negotiate new forum spaces for critical thinking against the grain of hegemony, without being co-opted by authoritarian capitalism. Both have attempted this in often-contrasting ways: for instance, TNS addresses a mostly English-speaking, theater-attending, middle-class audience, while Drama Box inserts Chinese-language forum theater into the organic everyday-life spaces of working-class communities. While TNS stages most of its forum theater work within the conventional walls of theater space, Drama Box embraces an aesthetic and site specificity that are closer to the form's popular roots. The Marcusean/Gramscian framework presented in this article offers a dynamic approach for critically analyzing the birth, death, and rebirth of forum theater in Singapore, and the contrasting and yet complementary ways in which TNS and Drama Box have negotiated with new opportunities and limitations in their socially conscious artistic practice. That forum theater has “reemerged” — a decade after its proscription by the state — as a “legitimate” part of the global city's state-led and economically driven artistic and cultural “renaissance” calls into question the extent of its radicalism today, but it also offers suggestions for new and more sophisticated modes of resistance and collaboration.
Cementing techniques for the tibial component in primary total knee replacement
Authors: Cawley D. T. , Kelly N. , McGarry J. P. , Shannon F. J.
Published: February 2013

The optimum cementing technique for the tibial component in cemented primary total knee replacement (TKR) remains controversial. The technique of cementing, the volume of cement and the penetration are largely dependent on the operator, and hence large variations can occur. Clinical, experimental and computational studies have been performed, with conflicting results. Early implant migration is an indication of loosening. Aseptic loosening is the most common cause of failure in primary TKR and is the product of several factors. Sufficient penetration of cement has been shown to increase implant stability.

This review discusses the relevant literature regarding all aspects of the cementing of the tibial component at primary TKR.

Cite this article: Bone Joint J 2013;95-B:295–300.