bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic inequality and population health: looking beyond aggregate indicators
Authors: Böckerman Petri , Johansson Edvard , Helakorpi Satu , Uutela Antti
Published: February 2009

This paper studies the sensitivity of various health indicators to income inequality as measured by regional Gini coefficients, using individual microdata from Finland over the period 1993–2005. There is no overall association between income and health at the regional level. We discovered that, among men, there are no significant associations between income inequality and several measures of health status. Among women or among both sexes combined, there are some indications of associations in the predicted direction between income inequality and physical health, disability retirement, sick leave, and consumption of medicines, but none are robust to different model specifications. Only among the population aged less than 30 there is some indication that mental health is associated with inequality. Our findings confirm that income inequality in small populations (not large enough to measure the overall class pyramid of the society) is often immaterial for health outcomes.
‘Futureless persons’: shifting life expectancies and the vicissitudes of progressive illness
Authors: Gibson Barbara E. , Zitzelsberger Hilde , McKeever Patricia
Published: February 2009

Medical technological advances can have profound effects on people's lives by extending the life course and creating uncertain futures. This is the case for a number of persons with ‘diseases of childhood’ who can now survive well into adulthood with technological support. This paper draws on a Canadian qualitative study of young men with Duchenne muscular dystrophy (DMD) which examined the effects of a shifting life expectancy on personal identities. Engaging with Pierre Bourdieu's central concept of habitus, we discuss the temporal dimensions of social exclusion and marginalised identities. Participants’ narrative accounts revealed how their dispositions were orientated to a shortened lifespan that exerted damaging effects regardless of actual lifespan. Compounding their material, social and symbolic isolation was a temporal isolation whereby the men had lived every day anticipating that it could be their last for as much as a decade. The findings suggest a need to re‐orient medical and social discourses to serve and include adults with DMD and other conditions previously limited to childhood in their communities.
The effects of natalizumab on inflammatory mediators in multiple sclerosis: prospects for treatment‐sensitive biomarkers
Authors: Khademi M. , Bornsen L. , Rafatnia F. , Andersson M. , Brundin L. , Piehl F. , Sellebjerg F. , Olsson T.
Published: February 2009

Background:  Natalizumab affects systemic cytokine expressions and clinical course in relapsing–remitting multiple sclerosis (RRMS). We analyzed levels of inflammatory cytokines in cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMCs), levels of matrix metalloproteinase (MMP)‐9 and osteopontin (OPN) in CSF, and clinical outcome measures in 22 natalizumab‐treated RRMS patients.

Methods:  mRNA levels of cytokines in cells were detected with real‐time RT‐PCR. Protein levels of OPN and MMP‐9 were measured by ELISA.

Results:  Natalizumab reduced CSF cell counts (P < 0.0001). Tumor necrosis factor (TNF) and interferon‐γ (IFN‐γ) mRNAs were significantly increased in PBMCs. In contrast, expressions of IFN‐γ and interleukin (IL)‐23 were decreased but IL‐10 increased in the CSF cells. OPN and MMP‐9 were reduced in the CSF. Patients being in remission at baseline showed the same deviations of mediators as those in relapse after natalizumab treatment. The open label clinical outcome measures were either stable or improved during therapy.

Conclusions:  Natalizumab attenuates pro‐inflammatory mediators intrathecally and the reduced pro‐inflammatory milieu may allow increased production of the anti‐inflammatory mediator IL‐10. The increased systemic cytokines may impede the improvement of certain clinical measures like fatigue. The affected mediators seem to be sensitive to an immune‐modifying treatment which could be used as biomarkers for this therapy.
Recurrent Thunderclap Headaches and Multilobar Intracerebral Haemorrhages: Two Cases of Reversible Cerebral Vasoconstriction Syndrome (RCVS)
Authors: Wong SH , Dougan C , Chatterjee K , Fletcher NA , White RP
Published: February 2009

We describe two patients with thunderclap headaches due to reversible cerebral vasoconstriction syndrome (RCVS). The first patient illustrates multilobar intracerebral haemorrhages as an under-appreciated feature of RCVS, and the second illustrates recurrent thunderclap headache (presumed recurrent RCVS) after a long interval of 4 years. These cases demonstrate the spectrum of presentation of RCVS, a clinically under-recognized condition.
Maternal methadone use in pregnancy: factors associated with the development of neonatal abstinence syndrome and implications for healthcare resources
Authors: Dryden C , Young D , Hepburn M , Mactier H
Published: February 2009

Objectives  The objectives of this study were to investigate factors associated with the development of neonatal abstinence syndrome (NAS) and to assess the implications for healthcare resources of infants born to drug‐misusing women.

Design  Retrospective cohort study from 1 January 2004 to 31 December 2006.

Setting  Inner‐city maternity hospital providing dedicated multidisciplinary care to drug‐misusing women.

Population  Four hundred and fifty singleton pregnancies of drug‐misusing women prescribed substitute methadone in pregnancy.

Methods  Case note review.

Main outcome measures  Development of NAS and duration of infant hospital stay.

Results  45.5% of infants developed NAS requiring pharmacological treatment. The odds ratio of the infant developing NAS was independently related to prescribed maternal methadone dose rather than associated polydrug misuse. Breastfeeding was associated with reduced odds of requiring treatment for NAS (OR 0.55, 95% CI 0.34–0.88). Preterm birth did not influence the odds of the infant receiving treatment for NAS. 48.4% infants were admitted to the neonatal unit (NNU) 40% of these primarily for treatment of NAS. The median total hospital stay for all infants was 10 days (interquartile range 7–17 days). Infants born to methadone‐prescribed drug‐misusing mothers represented 2.9% of hospital births, but used 18.2% of NNU cot days.

Conclusions  Higher maternal methadone dose is associated with a higher incidence of NAS. Pregnant drug‐misusing women should be encouraged and supported to breastfeed. Their infants are extremely vulnerable and draw heavily on healthcare resources.
Tissue plasminogen activator promotes axonal outgrowth on CNS myelin after conditioned injury
Authors: Minor Kenneth , Phillips Jacob , Seeds Nicholas W.
Published: February 2009

J. Neurochem. (2009) 109, 706–715.

Following CNS injury, myelin‐associated inhibitors represent major obstacles to axonal regeneration and functional recovery. The following study suggests that the proteolytic enzyme tissue plasminogen activator (tPA) plays a major function in ‘conditioning‐injury induced’ axon regeneration. In this paradigm, prior peripheral nerve injury leads to an enhanced ability of sensory neurons to regenerate their central axons in the presence of the CNS inhibitory microenvironment. tPA is widely expressed by CNS and PNS neurons and plays major roles in synaptic reorganization and plasticity. This study shows that cultured neurons from mice deficient in tPA, in contrast to wild‐type mice, fail to undergo conditioning‐injury induced axonal regeneration in the presence of purified myelin membranes. Interestingly, neurons from mice deficient in plasminogen, the best known substrate for tPA, showed active axon regeneration. These results suggest a novel plasminogen‐independent role for tPA in promoting axonal regeneration on CNS myelin.
Cerebral inflammation contributes to encephalopathy and brain edema in acute liver failure: protective effect of minocycline
Authors: Jiang Wenlei , Desjardins Paul , Butterworth Roger F.
Published: February 2009

Encephalopathy and brain edema are serious complications of acute liver failure (ALF). The precise pathophysiologic mechanisms responsible have not been fully elucidated but it has been recently proposed that microglia‐derived proinflammatory cytokines are involved. In the present study we evaluated the role of microglial activation and the protective effect of the anti‐inflammatory drug minocycline in the pathogenesis of hepatic encephalopathy and brain edema in rats with ALF resulting from hepatic devascularisation. ALF rats were killed 6 h after hepatic artery ligation before the onset of neurological symptoms and at coma stages of encephalopathy along with their appropriate sham‐operated controls and in parallel with minocycline‐treated ALF rats. Increased OX‐42 and OX‐6 immunoreactivities confirming microglial activation were accompanied by increased expression of interleukins (IL‐1β, IL‐6) and tumor necrosis factor‐alpha (TNF‐α) in the frontal cortex at coma stage of encephalopathy in ALF rats compared with sham‐operated controls. Minocycline treatment prevented both microglial activation as well as the up‐regulation of IL‐1β, ΙL‐6 and TNF‐α mRNA and protein expression with a concomitant attenuation of the progression of encephalopathy and brain edema. These results offer the first direct evidence for central proinflammatory mechanisms in the pathogenesis of brain edema and its complications in ALF and suggest that anti‐inflammatory agents may be beneficial in these patients.
Stability of international environmental agreements: an illustration with asymmetrical countries
Authors: Bahn Olivier , Breton Michèle , Sbragia Lucia , Zaccour Georges
Published: February 2009

In this paper we use a dynamic model to analyze the composition and stability of international environmental agreements (IEAs) in an asymmetrical framework. Signatory countries are assumed to optimize the total welfare of the international agreement's members, while non‐signatory countries optimize their own individual welfare, taking into account the dynamics of the pollution stock. Our model is calibrated using data from the MERGE climate policy assessment model. We briefly review two contrasting approaches to define stability of IEAs, and provide a numerical illustration in each case.
Applying path‐counting methods for measuring the robustness of the network‐structured system
Authors: Kobayashi Kazuhiro , Morohosi Hozumi , Oyama Tatsuo
Published: February 2009

We consider the path‐counting problem that asks how many paths exist between any two different nodes in a network after deleting an arbitrary number of edges or nodes from the original network. Using path‐counting methods, we propose a quantitative method for measuring the robustness of the network‐structured system. First we define the connectivity function and attempt to obtain the expected connectivity function for the network. Applying the Monte Carlo method, we estimate expected edge deletion and node deletion connectivity functions when an arbitrary number of edges or nodes are deleted from the original network. We attempt to approximate the expected edge deletion connectivity function using an appropriate nonlinear function with two parameters. We also show the numerical results of applying the path‐counting method with their analysis in order to quantitatively evaluate the connectivity for some special types of networks.
Mild Head Trauma and Chronic Headaches in Returning US Soldiers
Authors: Theeler Brett J. , Erickson Jay C.
Published: February 2009

Objective.— To determine the incidence and types of head or neck trauma and headache characteristics among US Army soldiers evaluated for chronic headaches at a military neurology clinic following a combat tour in Iraq.

Background.— Head or neck trauma and headaches are common in US soldiers deployed to Iraq. The temporal association between mild head trauma and headaches, as well as the clinical characteristics of headaches associated with mild head trauma, has not been systematically studied in US soldiers returning from Iraq.

Methods.— A retrospective cohort study was conducted with 81 US Army soldiers from the same brigade who were evaluated at a single military neurology clinic for recurrent headaches after a 1‐year combat tour in Iraq. All subjects underwent a standardized interview and evaluation to determine the occurrence of head or neck trauma during deployment, mechanism and type of trauma, headache type, and headache characteristics.

Results.— In total, 33 of 81 (41%) soldiers evaluated for headaches reported a history of head or neck trauma while deployed to Iraq. A total of 18 (22%) subjects had concussion without loss of consciousness and 15 (19%) had concussion with loss of consciousness. Ten subjects also had an accompanying traumatic neck injury. No subjects had moderate or severe traumatic brain injury. Exposure to blasts was the most common cause of trauma, accounting for 67% of head and neck injuries. Headaches began within one week after trauma in 12 of 33 (36%) soldiers with head or neck injury. Another 12 (36%) reported worsening of pre‐existing headaches after trauma. Headaches were classified as migraine type in 78% of soldiers with head or neck trauma. Headache types, frequency, severity, duration, and disability were similar for soldiers with and without a history of head or neck trauma.

Conclusion.— A history of mild head trauma, usually caused by exposure to blasts, is found in almost half of returning US combat troops who receive specialized care for headaches. In many cases, head trauma was temporally associated with either the onset of headaches or the worsening of pre‐existing headaches, implicating trauma as a precipitating or exacerbating factor, respectively. Headaches in head trauma‐exposed soldiers are usually migraine type and are similar to nontraumatic headaches encountered at a military specialty clinic.
Toxicology and Circumstances of Completed Suicide by Means Other than Overdose*
Authors: Darke Shane , Duflou Johan , Torok Michelle
Published: February 2009

Abstract:  To determine the prevalence and circumstances of psychoactive substances amongst nonoverdose completed suicide, 1436 consecutive cases autopsied at the NSW Department of Forensic Medicine over the period 1/1/1997–12/31/2006 were analyzed. Substances were detected in 67.2% of cases, and illicit drugs in 20.1%. Alcohol was present in 40.6% of cases. Males were more likely to be positive for alcohol, cannabis, and psychostimulants, and females for pharmaceuticals. Illicits were associated with younger age. Alcohol was most prominent amongst toxicity cases, as were opioids, psychostimulants amongst gunshot cases, and pharmaceuticals amongst drownings. Cases in which drug and alcohol histories were noted were more likely to have a substance detected. Alcohol was more common where a suicide note was left and where relationship problems were involved. Pharmaceuticals were more common where a previous attempt was noted. Licit and illicit substances are strongly associated with suicide, even when the method does not involve drug overdose.
Evaluation of the Photodegradation of Crystal Violet upon Light Exposure by Mass Spectrometric and Spectroscopic Methods
Authors: Weyermann Céline , Kirsch Dieter , Costa Vera César , Spengler Bernhard
Published: February 2009

Abstract: Crystal violet is a very common dye in ballpoint ink. Recent research suggests that the degradation of triarylmethane dyes gives an indication of the age of a ballpoint pen entry on a document. The main problem for the quantitative evaluation of the degradation is that it is highly dependent on the exposure to light. Moreover additional factors, such as additives and substrate play an important role in this process. The aim of this work is to compare the degradation pathways of the pure dye in water and ethanol upon exposure to xenon light by UV/VIS spectrophotometry and laser desorption ionization. Significant differences have been observed in the products and the kinetics of the degradation. N‐demethylation, an expected decomposition process, was found to take place only in aqueous solution and kinetics calculations showed that the degradation occurred 2.5 times faster in ethanol compared to water. The degradation of crystal violet in inks from four ballpoint pens on paper was also studied for entries made over 2–3 years. It was observed that degradation reactions were quenched by the presence of another dye due to competitive absorption. It was also observed that the thickness of a stroke (concentration of ink) influenced the degradation process. In the absence of light only one ballpoint pen showed slight degradation. A better understanding of the influence of the paper, ink composition, and storage conditions is necessary to interpret correctly the age of an ink based on the degradation of dyes.
Igf1r+/CD34+immature ICC are putative adult progenitor cells, identified ultrastructurally as fibroblast‐like ICC in Ws/Ws rat colon
Authors: Wang X.Y. , Albertí E. , White E.J. , Mikkelsen H.B. , Larsen J.O. , Jiménez M. , Huizinga J.D.
Published: February 2009

The colon of Ws/Ws mutant rats shows impairment of pacemaker activity and altered inhibitory neurotransmission. The present study set out to find structural correlates to these findings to resolve mechanisms. In the colon of Ws/Ws rats, interstitial cells of Cajal associated with Auerbach’s plexus (ICC‐AP) were significantly decreased and ICC located at the submuscular plexus and intramuscular ICC were rarely observed based on immunohistochemistry and electron microscopy. Ultrastructural investigations revealed that there was no overall loss of all types of interstitial cells combined. Where loss of ICC was observed, a marked increase in fibroblast‐like ICC (FL‐ICC) was found at the level of AP. Immunoelectron microscopy proved FL‐ICC to be c‐Kit–but gap junction coupled to each other and to c‐Kit+ICC; they were associated with enteric nerves and occupied space normally occupied by ICC in the wild‐type rat colon, suggesting them to be immature ICC. In addition, a marked increase in immunoreactivity for insulin‐like growth factor 1 receptor (Igf1r) occurred, co‐localized with CD34 but not with c‐Kit. A significantly higher number of Igf1r+/CD34+cells were found in Ws/Ws compared to wild‐type rat colons. These CD34+/Igf1r+cells in the Ws/Ws colon occupied the same space as FL‐ICC. Hence we propose that a subset of immature ICC (FL‐ICC) consists of adult progenitor cells. Immunohistochemistry revealed a reduction of neurons positive for neuronal nitric oxide synthase. The functional capabilities of the immature ICC and the regenerative capabilities of the adult progenitor cells need further study. The morphological features described here show that the loss of pacemaker activity is not associated with failure to develop a network of interstitial cells around AP but a failure to develop this network into fully functional pacemaker cells. The reduction in nitrergic innervation associated with the Ws mutation may be the result of a reduction in nitrergic neurons.
The R439C mutation in LMNA causes lamin oligomerization and susceptibility to oxidative stress
Authors: Verstraeten Valerie L.R.M. , Caputo Sandrine , Van Steensel Maurice A.M. , Duband‐Goulet Isabelle , Zinn‐Justin Sophie , Kamps Miriam , Kuijpers Helma J.H. , Östlund Cecilia , Worman Howard J. , Briedé Jacob J. , Le Dour Caroline , Marcelis Carlo L.M. , Van Geel Michel , Steijlen Peter M. , Van Den Wijngaard Arthur , Ramaekers Frans C.S. , Broers Jos L.V.
Published: February 2009

Dunnigan‐type familial partial lipodystrophy (FPLD) is a laminopathy characterized by an aberrant fat distribution and a metabolic syndrome for which oxidative stress has recently been suggested as one of the disease‐causing mechanisms. In a family affected with FPLD, we identified a heterozygous missense mutation c.1315C>T in the LMNA gene leading to the p.R439C substitution. Cultured patient fibroblasts do not show any prelamin A accumulation and reveal honeycomb‐like lamin A/C formations in a significant percentage of nuclei. The mutation affects a region in the C‐terminal globular domain of lamins A and C, different from the FPLD‐related hot spot. Here, the introduction of an extra cysteine allows for the formation of disulphide‐mediated lamin A/C oligomers. This oligomerization affects the interaction properties of the C‐terminal domain with DNA as shown by gel retardation assays and causes a DNA‐interaction pattern that is distinct from the classical R482W FPLD mutant. Particularly, whereas the R482W mutation decreases the binding efficiency of the C‐terminal domain to DNA, the R439C mutation increases it. Electron spin resonance spectroscopy studies show significantly higher levels of reactive oxygen species (ROS) upon induction of oxidative stress in R439C patient fibroblasts compared to healthy controls. This increased sensitivity to oxidative stress seems independent of the oligomerization and enhanced DNA binding typical for R439C, as both the R439C and R482W mutants show a similar and significant increase in ROS upon induction of oxidative stress by H2O2.
Extracellular calcium increases CXCR4 expression on bone marrow‐derived cells and enhances pro‐angiogenesis therapy
Authors: Wu Quiling , Shao Hongwei , Darwin Eton D.  , Li Jiahui , Li Jie , Yang Bing , Webster Keith A. , Yu Hong
Published: February 2009

Cell surface receptors play major roles in the mobilization and homing of progenitor cells from the bone marrow to peripheral tissues. CXCR4 is an important receptor that regulates homing of leucocytes and endothelial progenitors in response to the chemokine stromal cell‐derived factor‐1 (SDF‐1). Ionic calcium is also known to regulate chemotaxis of selective bone marrow cells (BMCs) through the calcium‐sensing receptor, CaR. Here we show that calcium regulates CXCR4 expression and BMC responses to SDF‐1. CaCl2 treatment of BMC induced a time‐ and dose‐dependent increase in both the transcription and cell surface expression of CXCR4. BMC subpopulations expressing VEGFR2+, CD34+ and cKit+/Sca‐1+ were especially sensitive to calcium. The effects were blocked by calcium influx inhibitors, anti‐CaR antibody and the protein synthesis inhibitor cycloheximide, but not by the CXCR4 antagonist AMD3100. Calcium treatment also enhanced SDF‐1‐mediated CXCR4 internalization. These changes were reflected in significantly improved chemotaxis by SDF‐1, which was abolished by AMD3100 and by antibody against CXCR4. Calcium pre‐treatment improved homing of CD34+ BMCs to ischemic muscle in vivo, and enhanced revascularization in ischemic mouse hindlimbs. Our results identify calcium as a positive regulator of CXCR4 expression that promotes stem cell mobilization, homing and therapy.
Sorafenib and rapamycin induce growth suppression in mouse models of hepatocellular carcinoma
Authors: Huynh Hung , Ngo Van Chanh , Koong Heng Nung , Poon Donald , Choo Su Pin , Thng Choon Hua , Chow Pierce , Ong Hock Soo , Chung Alexander , Soo Khee Chee
Published: February 2009

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. Vascular endothelial growth factor, platelet derived growth factor and the Raf/mitogen‐activated protein kinase/extracellular signal regulated kinase (Raf/MEK/ERK) signalling pathway regulates the growth, neovascularization, invasiveness and metastatic potential of HCC. In this study, we investigated the in vivo antitumour activity and mechanisms of action of sorafenib tosylate on four patient‐derived HCC xenografts. Sorafenib dosed at 50 mg/kg and 100 mg/kg inhibited tumour growth by 85% and 96%, respectively. Sorafenib‐induced growth suppression and apoptosis were associated with inhibition of angiogenesis, down‐regulation of phospho‐platelet‐derived growth factor receptor β Tyr1021, phospho‐eIF4E Ser209, phospho‐c‐Raf Ser259, c‐Raf, Mcl‐1, Bcl‐2, Bcl‐x and positive cell cycle regulators, up‐regulation of apoptosis signalling kinase‐1, p27 and p21. Expression of IGF‐1Rβ and phosphorylation of c‐Raf Ser338, MEK1/2 Ser217/221 and ERK1/2 Thr202/Tyr204 were increased by sorafenib treatment. Phosphorylation of mammalian target‐of‐rapamycin (mTOR) targets (p70S6K, S6R and 4EBP1) was reduced by sorafenib in sorafenib‐sensitive lines but activated in sorafenib‐less‐sensitive 10–0505 xenograft. Sorafenib‐induced phosphorylation of c‐met, p70S6K and 4EBP1 was significantly reduced when 10–0505 cells were co‐treated with anti‐human anti‐HGF antibody, suggesting that treatment with sorafenib leads to increased HGF secretion and activation of c‐met and mTOR targets. Treatment of 10–0505 tumours with sorafenib plus rapamycin resulted in growth inhibition, inhibition of vascular endothelial growth factor receptor‐2 phosphorylation, increased apoptosis and completely blocked sorafenib‐induced phosphorylation of mTOR targets and cyclin B1 expression. These data also provide a strong rationale for clinical investigation of sorafenib in combination with mTOR inhibitors in patients with HCC.
Phenoxodiol, an anticancer isoflavene, induces immunomodulatory effects in vitro and in vivo
Authors: Georgaki Sylvianna , Skopeliti Margarita , Tsiatas Marinos , Nicolaou Katerina A. , Ioannou Kyriaki , Husband Alan , Bamias Aristotelis , Dimopoulos Meletios A. , Constantinou Andreas I. , Tsitsilonis Ourania E.
Published: February 2009

Phenoxodiol (PXD) is a synthetic analogue of the plant isoflavone genistein with improved anticancer efficacy. Various properties and mechanisms of action have been attributed to the drug, the most important being its ability to sensitize resistant tumour cells to chemotherapy, which led to its fast track FDA approval for phase II/III clinical trials. In this study, we examined the effects of PXD on human peripheral blood mononuclear cells (PBMC) and its potential role in regulating immune responses. We show that PXD, at concentrations ≥1 μg/ml (4 μM), inhibited proliferation and reduced the viability of healthy donor‐derived PBMC. In contrast, lower PXD concentrations (0.05–0.5 μg/ml) augmented, upon 3‐day incubation, PBMC cytotoxicity. Experiments with purified CD56+ lymphocytes revealed that PXD enhanced the lytic function of natural killer (NK) cells by directly stimulating this lymphocytic subpopulation. Furthermore, in an in vivo colon cancer model, Balb/C mice administered low‐dose PXD, exhibited significantly reduced tumour growth rates and prolonged survival (in 40% of the animals). Ex vivo results showed that PXD stimulated both NK and tumour‐specific cell lytic activity. We conclude that PXD, when administered at low concentrations, can act as an immunomodulator, enhancing impaired immune responses, often seen in cancer‐bearing individuals.
MicroRNAs and micromanaging the skeleton in disease, development and evolution
Authors: He Xinjun , Eberhart Johann K. , Postlethwait John H.
Published: February 2009

Introduction

The skeleton in evolution, health and disease

An overview of skeletal development

miRNA biogenesis

miRNAs and genome evolution

microRNAs and the micromanagement of development

Micromanaging skeletal system development

Candidate miRNAs controlling skeletal development

The function of mirn140 in skeletal development: a case study

miRNAs and Hox gene patterning of the axial skeleton

microRNAs and microevolution: a hypothesis

Skeletal miRNAs and skeletal disease

Conclusions

MicroRNAs (miRNAs) are short, non‐protein‐encoding RNAs that effect post‐transcriptional gene regulation by targeting messenger RNAs. miRNAs are associated with specific human diseases and help regulate development. Here we review recent advances in understanding the roles of miRNAs in skeletal malformations, including cleft palate, and in the evolution of skeletal morphologies. We propose the hypothesis that evolutionary variation in miRNA expression patterns or structural variation in miRNA binding sites in messenger RNAs can help explain the evolution of craniofacial variation among species, the development of human craniofacial disease and physiological changes leading to osteopenia that increases with ageing.
Tooth loss and osteoporosis: the osteodent study
Authors: Nicopoulou‐Karayianni Kety , Tzoutzoukos Panagiotis , Mitsea Anastasia , Karayiannis Athanasios , Tsiklakis Kostas , Jacobs Reinhilde , Lindh Christina , Van Der Stelt Paul , Allen Philip , Graham Jim , Horner Keith , Devlin Hugh , Pavitt Susan , Yuan Jingsong
Published: February 2009

Aim: To determine the cross‐sectional association of the osteoporotic status of patients with the number of their teeth, with and without taking into account age and/or smoking.

Material & Methods: At four centres, the study recruited 665 females aged 45–70 years and the number of teeth was counted for 651 subjects. Bone density was measured at the total hip, femoral neck and lumbar spine.

Results: The mean number of teeth in the osteoporotic subjects was 3.3 fewer than normal subjects and 2.1 fewer if those with no teeth were excluded. The association between osteoporosis and having <6 or having <28 teeth remained significant after adjusting for age, smoking and centre with p‐values of 0.016 and 0.011, respectively. A single regression model for tooth count with normal errors would not fit all the data. By fitting mixture regression models to subjects with tooth count >0, three clusters were identified corresponding to different degrees of tooth loss. The overall effect of osteoporosis was as follows: −1.8 teeth before and after adjusting for smoking, −1.2 teeth after adjusting for age, and −1.1 teeth after adjusting for both age and smoking.

Conclusions: We have established a significant association between osteoporosis and tooth loss after adjusting the effect for age and smoking.
Three‐dimensional imaging as a pre‐operative tool in decision making for furcation surgery
Authors: Walter Clemens , Kaner Dogan , Berndt Dorothea C. , Weiger Roland , Zitzmann Nicola U.
Published: February 2009

Aim: To investigate the use of cone beam computed tomography (CBCT) in assessing furcation involvement (FI) and concomitant treatment decisions in maxillary molars.

Material and Methods: Twelve patients with generalized chronic periodontitis were consecutively recruited and CBCT was performed in maxillary molars (n=22) with clinical FI and increased probing pocket depths. CBCT images were analysed and FI, root length supported by bone and anatomical features were evaluated. FI and treatment recommendations based on clinical examinations and periapical radiographs were compared with data derived from CBCT images.

Results: The estimated degree of FI based on clinical findings was confirmed in 27% of the sites, while 29% were overestimated and 44% revealed an underestimation according to CBCT analyses. Among degree I FI, 25% were underestimated, among degree II and II–III, the underestimation was as high as 75%, while all sites with degree III FI were confirmed in the CBCT. Discrepancies between clinically and CBCT‐based therapeutic treatment approaches were found in 59–82% of the teeth, depending on whether the less invasive or the most invasive treatment recommendation was selected for comparison.

Conclusions: CBCT images of maxillary molars may provide detailed information of FI and a reliable basis for treatment decision.
Nuclear‐Cytosolic Transport of COMMD1 Regulates NF‐κB and HIF‐1 Activity
Authors: Muller Patricia A. J. , De Sluis Bart van , Groot Arjan J. , Verbeek Dineke , Vonk Willianne I.M. , Maine Gabriel N. , Burstein Ezra , Wijmenga Cisca , Vooijs Marc , Reits Eric , Klomp Leo W. J.
Published: February 2009

Copper metabolism MURR1 domain1 (COMMD1) is a novel inhibitor of the transcription factors NF‐κB and HIF‐1, which play important roles in inflammation and tumor growth, respectively. In this study, we identified two highly conserved nuclear export signals (NESs) in COMMD1 and revealed that these NESs were essential and sufficient to induce maximal nuclear export of COMMD1. Inhibition of CRM1‐mediated nuclear export by Leptomycin B resulted in nuclear accumulation of COMMD1. In addition, low oxygen concentrations induced the active export of COMMD1 from the nucleus in a CRM1‐dependent manner. Disruption of the NESs in COMMD1 increased the repression of COMMD1 in transcriptional activity of NF‐κB and HIF‐1. In conclusion, these data indicate that COMMD1 undergoes constitutive nucleocytoplasmic transport as a novel mechanism to regulate NF‐κB and HIF‐1 signaling.
Parametric and genetic analysis of Drosophila appetitive long‐term memory and sugar motivation
Authors: Colomb J. , Kaiser L. , Chabaud M.‐A. , Preat T.
Published: February 2009

Distinct forms of memory can be highlighted using different training protocols. In Drosophila olfactory aversive learning, one conditioning session triggers memory formation independently of protein synthesis, while five spaced conditioning sessions lead to the formation of long‐term memory (LTM), a long‐lasting memory dependent on de novo protein synthesis. In contrast, one session of odour–sugar association appeared sufficient for the fly to form LTM. We designed and tuned an apparatus that facilitates repeated discriminative conditioning by alternate presentations of two odours, one being associated with sugar, as well as a new paradigm to test sugar responsiveness (SR). Our results show that both SR and short‐term memory (STM) scores increase with starvation length before conditioning. The protein dependency of appetitive LTM is independent of the repetition and the spacing of training sessions, on the starvation duration and on the strength of the unconditioned stimulus. In contrast to a recent report, our test measures an abnormal SR of radish mutant flies, which might initiate their STM and LTM phenotypes. In addition, our work shows that crammer and tequila mutants, which are deficient for aversive LTM, present both an SR and an appetitive STM defect. Using the MB247‐P[switch] system, we further show that tequila is required in the adult mushroom bodies for normal sugar motivation.
Aversive phototaxic suppression: evaluation of a short‐term memory assay in Drosophila melanogaster
Authors: Seugnet L. , Suzuki Y. , Stidd R. , Shaw P. J.
Published: February 2009

Drosophila melanogaster is increasingly being used to model human conditions that are associated with cognitive deficits including fragile‐X syndrome, Alzheimer’s disease, Parkinson’s disease, sleep loss, etc. With few exceptions, cognitive abilities that are known to be modified in these conditions in humans have not been evaluated in fly models. One reason is the absence of a simple, inexpensive and reliable behavioral assay that can be used by laboratories that are not expert in learning and memory. Aversive phototaxic suppression (APS) is a simple assay in which flies learn to avoid light that is paired with an aversive stimulus (quinine/humidity). However, questions remain about whether the change in the fly’s behavior reflects learning an association between light and quinine/humidity or whether the change in behavior is because of nonassociative effects of habituation and/or sensitization. We evaluated potential effects of sensitization and habituation on behavior in the T‐maze and conducted a series of yoked control experiments to further exclude nonassociative effects and determine whether this task evaluates operant learning. Together these experiments indicate that a fly must associate the light with quinine/humidity to successfully complete the task. Next, we show that five classic memory mutants are deficient in this assay. Finally, we evaluate performance in a fly model of neurodegenerative disorders associated with the accumulation of Tau. These data indicate that APS is a simple and effective assay that can be used to evaluate fly models of human conditions associated with cognitive deficits.
FROM COALITIONS TO MOVEMENTS: REALIZING THE PROMISE OF REGIONAL POWER BUILDING
Authors: Dobbie David
Published: February 2009

Regional power building has helped revitalize working‐class movements across the country, but we lack a systematic understanding of why coalition‐building strategies have been more effective in some regions than others. By comparing efforts to increase labor–community collaboration in several regions, it becomes clear that local activists are more successful when they work simultaneously to change organizational structures and cultures. Their work is facilitated through an intermediary level of “movement hubs” that incubate cross‐cutting cultures of solidarity and strategic evolution within local movements.
Escaping climate policy Groundhog Day
Authors: Lockwood Matthew , Pendleton Andrew
Published: February 2009

Matthew Lockwood and Andrew Pendleton argue that to escape the recurrent nightmare of climate change policy requires a radical revision of priorities
Child protection: crisis management or learning curve?
Authors: Gardner Ruth , Brandon Marian
Published: February 2009

As the media portrays England's child protection system as being in dire straits, Ruth Gardner and Marian Brandon state the case for concentrating resources on improving the amount and quality of contact that professionals have with children and their parents
Ratings war?
Authors: Persaud Avinash
Published: February 2009

Avinash Persaud argues that the proposed regulation of credit rating agencies will do more harm than good
A welfare state as valued as the NHS: the progressive case for reform
Authors: Purnell James
Published: February 2009

James Purnell, the Secretary of State for Work and Pensions, argues that far from being a betrayal of Labour's core values, the Government's welfare reforms are rooted in social democratic principles and aimed at reasserting the best traditions of the welfare state
Minimally Invasive Craniopuncture Therapy vs. Conservative Treatment for Spontaneous Intracerebral Hemorrhage: Results from a Randomized Clinical Trial in China
Authors: Wang Wen-Zhi , Jiang Bin , Liu g-Mei , Li Di , Lu Chuan-Zhen , Zhao Ya-Du , Sander J. W.
Published: February 2009

Background and purposes

To evaluate the effects of minimally invasive craniopuncture therapy compared with conservative treatment in treating intracerebral hemorrhage (25-40 ml) in the basal ganglion.

Methods

A multicenter, randomized control clinical trial comprised 465 cases of hemorrhage in the basal ganglion from 42 hospitals in China. Three hundred and seventy-seven patients with hemorrhage were randomly assigned to receive minimally invasive craniopuncture therapy ( n = 195) or conservative control treatment ( n = 182). The main indices of evaluation were the degree of neurological impairment at the 14th day after treatment, activities of daily living at the end of the 3rd month and the case fatality within 3 months.

Results

Improvement of neurological function in the minimally invasive craniopuncture group was significantly better than that in the control group at the 14th day ( χ2 = 7 93, P = 0 02). At the end of the 3rd month, there was a significant difference between the two groups in activities of daily living score ( χ2 = 2313, P<0·001). The proportion of dependent survival patients (modified Rankin scale > 2) in the craniopuncture group (40·9%) was significantly lower than that in the conservative group (63·0%) at the end of the 3rd month ( χ2 = 16·95, P<0·01). There was no significant difference in the cumulative fatality rates within three months between the two groups [6·7% (13/195) in the craniopuncture group and 8·8% (16/182) in the conservative group].

Conclusions

This minimally invasive craniopuncture technique can improve the independent survival of patients with small basal ganglion hemorrhage. It is a safe and practical technique in treating cerebral hemorrhage.
Antioxidative Activities of Mushroom (Flammulina velutipes) Extract Added to Bigeye Tuna Meat: Dose‐Dependent Efficacy and Comparison with Other Biological Antioxidants
Authors: Bao H.N.D. , Ushio H. , Ohshima T.
Published: February 2009

ABSTRACT:  The ability of a hydrophilic extract prepared from edible mushroom (Flammulina velutipes) to stabilize fresh color of bigeye tuna (Thunnus obesus) meat was evaluated to compare it with certain other antioxidants. The fresh color shelf life of bigeye tuna meats, to which were added as 1, 3, or 5 mL of mushroom extract to 100 g of minced bigeye tuna meat, prolonged duration of ice storage by more than 2, 4, and 6 d, respectively, in comparison with the control tuna meat without mushroom extract. The addition of 5 mL of mushroom extract to 100 g of minced bigeye tuna meat was more effective than adding ascorbic acid sodium salt (500 ppm) or α‐tocopherol (500 ppm) with regard to oxidation of lipid in the tuna meat. The color changes significantly correlated with lipid oxidation as well as metmyoglobin formation in the tuna meat. These results clearly show that the mushroom extract is a potential antioxidant, which has the ability to stabilize fresh color of tuna meat during ice storage.
Equivocal Colonic Carcinogenicity of Aloe arborescens Miller var. natalensis Berger at High‐Dose Level in a Wistar Hannover Rat 2‐y Study
Authors: Yokohira M. , Matsuda Y. , Suzuki S. , Hosokawa K. , Yamakawa K. , Hashimoto N. , Saoo K. , Nabae K. , Doi Y. , Kuno T. , Imaida K.
Published: February 2009

ABSTRACT:  A 2‐y carcinogenicity study of Aloe, Aloe arborescens Miller var. natalensis Berger, a food additive, was conducted for assessment of toxicity and carcinogenic potential in the diet at doses of 4% or 0.8% in groups of male and female Wistar Hannover rats. Both sexes receiving 4% showed diarrhea, with loss of body weight gain. The survival rate in the 4% female group was significantly increased compared with control females after 2 y. Hematological and biochemical examination showed increase of RBC, Hb, and Alb in the 4% males. The cause of these increases could conceivably have been dehydration through diarrhea. AST and Na were significantly decreased in the males receiving 4%, and Cl was significantly decreased in both 4% and 0.8% males. A/G was significantly increased in the 4% females, and Cl was significantly decreased (0.8%) in the female group. Histopathologically, both sexes receiving 4% showed severe sinus dilatation of ileocecal lymph nodes, and yellowish pigmentation of ileocecal lymph nodes and renal tubules. Adenomas or adenocarcinomas in the cecum, colon, and rectum were observed in 4% males but not in the 0.8% and control male groups. Similarly, in females, adenomas in the colon were also observed in the 4% but not 0.8% and control groups. In conclusion, Aloe, used as a food additive, exerted equivocal carcinogenic potential at 4% high‐dose level on colon in the 2‐y carcinogenicity study in rats. Aloe is not carcinogenic at nontoxic‐dose levels and that carcinogenic potential in at 4% high‐dose level on colon is probably due to irritation of the intestinal tract by diarrhea.
Sputum dipalmitoylphosphatidylcholine level as a novel airway inflammatory marker in asthmatic children
Authors: Shaheen Malak Ali , Mahmoud Magdy Ahmed , Abdel Aziz Manal Mohamed , El Morsy Hamam Ibrahim , Abdel Khalik Karima Ahmed
Published: February 2009

Introduction:  Pulmonary surfactant is a unique mixture of lipids and surfactant‐specific proteins. Phosphatidylcholine comprises almost 80% of the total surfactant lipids, about half of which is dipalmitoylphosphatidylcholine (DPPC). Alteration of surfactant composition and function is documented with various airway or lung parenchyma disorders.

Objective:  To assess sputum concentration of DPPC as a major component of airways surfactant in asthmatic children compared to conventional airway inflammatory markers.

Methods:  This case control study included 68 well‐known asthmatic children of different grades of severity and 20 age‐ and sex‐matched normal children as controls. All children were subjected to thorough clinical examination, pulmonary function tests, sputum induction and processing for cytology, DPPC level and eosinophil cationic protein (ECP) level assessment.

Results:  Elevated DPPC levels were evident in all sputum samples of asthmatic children (mean value 626.6 ± 189.7 mcg/mL) compared to controls (mean value 49.3 ± 20.1 mcg/mL). Significant negative correlations (r = −0.83, −0.752 and −0.384) were found between asthmatics sputum DPPC levels and pulmonary function test parameters [% of forced expiratory volume in first second, % of forced vital capacity (FVC) and forced expiratory flow rate over 25%–75% part of FVC], respectively. Meanwhile, significant positive correlations were evident between asthmatics sputum DPPC levels and the sputum inflammatory cells and their sputum ECP levels.

Conclusion:  Elevated DPPC levels are evident in induced sputum of all asthmatic children and they are significantly related to sputum ECP levels and pulmonary function test parameters. Nevertheless, the value of DPPC estimation in the clinical management of children with asthma remains to be determined.

Please cite this paper as: Shaheen MA, Mahmoud MA, Abdel Aziz MM, El Morsy HI and Abdel Khalik KA. Sputum dipalmitoylphosphatidylcholine level as a novel airway inflammatory marker in asthmatic children. The Clinical Respiratory Journal 2009; 3: 95–101.
Fish oil replacement in finfish nutrition
Authors: Turchini Giovanni M. , Torstensen Bente E. , Ng Wing‐Keong
Published: February 2009

Unsustainable fishing practices have placed a heavy emphasis on aquaculture to meet the global shortfalls in the supply of fish and seafood, which are commonly accepted as the primary source of health‐promoting essential omega‐3 (n‐3 highly unsaturated fatty acids). However, dietary fish oil is required for the production of omega‐3‐rich farmed fish and this commodity, in a vicious circle, is at present derived solely from wild fisheries. Decreasing global availability coupled with the highly variable price of this resource has forced the aquaculture industry to investigate the possibilities of alternative dietary lipid sources. This review attempts to compile all principal information available regarding the effects of fish oil replacement for the diets of farmed finfish, analysing the findings using a comparative approach among different cultured fish species. The review initially focuses on the present situation with regard to the production, availability and main nutritional characteristics of fish oil and the principal alternative lipid sources (such as vegetable oils and animal fats). Following this, the effects of fish oil replacement in finfish nutrition on feed quality, fish performance, feed efficiency, fish lipid metabolism, final eating quality and related economic aspects are presented and discussed.
Transboundary management of large carnivores in Europe: from incident to opportunity
Authors: Rosen Tatjana , Bath Alistair
Published: February 2009

Transboundary management of large carnivores, such as that of bears in the human dominated landscapes in Europe is rife with challenges. During summer 2006, brown bear JJ1, one of the 27 cubs born in the Central Alps between 2002 and 2006, as a result of reintroduction efforts carried out in Trentino, Italy, wandered into Austria and Germany. Despite the public outcry he was eventually shot. The death of JJ1 turned into a real international incident that prompted the countries affected to meet and discuss how to manage bears at transboundary level. The author uses the policy sciences approach to map out the social context in which reintroductions and management of large carnivores are occurring and from there suggest possible approaches to improve their success.