bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of severity, duration, and etiology of hyperthyroidism on bone turnover markers and bone mineral density in men
Authors: El Hadidy El Hadidy M , Ghonaim Mohamed , El Gawad Soma Sh Abd , El Atta Mohamed Abou
Published: August 2011

Background

Hyperthyroidism is accompanied by osteoporosis with higher incidence of fracture rates. The present work aimed to study bone status in hyperthyroidism and to elucidate the impact of severity, duration, and etiology of hyperthyroidism on biochemical markers of bone turnover and bone mineral density (BMD).

Methods

Fifty-two male patients with hyperthyroidism, 31 with Graves' disease (GD) and 21 with toxic multinodular goiter (TNG), with an age ranging from 23 to 65 years were included, together with 25 healthy euthyroid men with matched age as a control group. In addition to full clinical examination, patients and controls were subjected to measurement of BMD using dual-energy X-ray absorptiometery scanning of the lower half of the left radius. Also, some biochemical markers of bone turnover were done for all patients and controls.

Results

Biochemical markers of bone turnover: included serum bone specific alkaline phosphatase, osteocalcin, carboxy terminal telopeptide of type l collagen also, urinary deoxypyridinoline cross-links (DXP), urinary DXP/urinary creatinine ratio and urinary calcium/urinary creatinine ratio were significantly higher in patients with GD and TNG compared to controls (P < 0.01). However, there was non-significant difference in these parameters between GD and TNG patients (P > 0.05). BMD was significantly lower in GD and TNG compared to controls, but the Z-score of BMD at the lower half of the left radius in patients with GD (-1.7 ± 0.5 SD) was not significantly different from those with TNG (-1.6 ± 0.6 SD) (>0.05). There was significant positive correlation between free T3 and free T4 with biochemical markers of bone turnover, but negative correlation between TSH and those biochemical markers of bone turnover. The duration of the thyrotoxic state positively correlated with the assessed bone turnover markers, but it is negatively correlated with the Z-score of BMD in the studied hyperthyroid patients (r = -0.68, P < 0.0001).

Conclusion

Men with hyperthyroidism have significant bone loss with higher biochemical markers of bone turnover. The severity and the duration of the thyrotoxic state are directly related to the derangement of biochemical markers of bone turnover and bone loss.
Association between statin therapy and outcomes in critically ill patients: a nested cohort study
Authors: Al Harbi Shmeylan A , Tamim Hani M , Arabi Yaseen M
Published: August 2011

Background

The effect of statin therapy on mortality in critically ill patients is controversial, with some studies suggesting a benefit and others suggesting no benefit or even potential harm. The objective of this study was to evaluate the association between statin therapy during intensive care unit (ICU) admission and all-cause mortality in critically ill patients.

Methods

This was a nested cohort study within two randomised controlled trials conducted in a tertiary care ICU. All 763 patients who participated in the two trials were included in this study. Of these, 107 patients (14%) received statins during their ICU stay. The primary endpoint was all-cause ICU and hospital mortality. Secondary endpoints included the development of sepsis and severe sepsis during the ICU stay, the ICU length of stay, the hospital length of stay, and the duration of mechanical ventilation. Multivariate logistic regression was used to adjust for clinically and statistically relevant variables.

Results

Statin therapy was associated with a reduction in hospital mortality (adjusted odds ratio [aOR] = 0.60, 95% confidence interval [CI] 0.36-0.99). Statin therapy was associated with lower hospital mortality in the following groups: patients >58 years of age (aOR = 0.58, 95% CI 0.35-0.97), those with an acute physiology and chronic health evaluation (APACHE II) score >22 (aOR = 0.54, 95% CI 0.31-0.96), diabetic patients (aOR = 0.52, 95% CI 0.30-0.90), patients on vasopressor therapy (aOR = 0.53, 95% CI 0.29-0.97), those admitted with severe sepsis (aOR = 0.22, 95% CI 0.07-0.66), patients with creatinine ≤100 μmol/L (aOR = 0.14, 95% CI 0.04-0.51), and patients with GCS ≤9 (aOR = 0.34, 95% CI 0.17-0.71). When stratified by statin dose, the mortality reduction was mainly observed with statin equipotent doses ≥40 mg of simvastatin (aOR = 0.53, 95% CI 0.28-1.00). Mortality reduction was observed with simvastatin (aOR = 0.37, 95% CI 0.17-0.81) but not with atorvastatin (aOR = 0.80, 95% CI 0.84-1.46). Statin therapy was not associated with a difference in any of the secondary outcomes.

Conclusion

Statin therapy during ICU stay was associated with a reduction in all-cause hospital mortality. This association was especially noted in high-risk subgroups. This potential benefit needs to be validated in a randomised, controlled trial.
A new adaptive testing algorithm for shortening health literacy assessments
Authors: Kandula Sasikiran , Ancker Jessica S , Kaufman David R , Currie Leanne M , Zeng-Treitler Qing
Published: August 2011

Background

Low health literacy has a detrimental effect on health outcomes, as well as ability to use online health resources. Good health literacy assessment tools must be brief to be adopted in practice; test development from the perspective of item-response theory requires pretesting on large participant populations. Our objective was to develop a novel classification method for developing brief assessment instruments that does not require pretesting on large numbers of research participants, and that would be suitable for computerized adaptive testing.

Methods

We present a new algorithm that uses principles of measurement decision theory (MDT) and Shannon's information theory. As a demonstration, we applied it to a secondary analysis of data sets from two assessment tests: a study that measured patients' familiarity with health terms (52 participants, 60 items) and a study that assessed health numeracy (165 participants, 8 items).

Results

In the familiarity data set, the method correctly classified 88.5% of the subjects, and the average length of test was reduced by about 50%. In the numeracy data set, for a two-class classification scheme, 96.9% of the subjects were correctly classified with a more modest reduction in test length of 35.7%; a three-class scheme correctly classified 93.8% with a 17.7% reduction in test length.

Conclusions

MDT-based approaches are a promising alternative to approaches based on item-response theory, and are well-suited for computerized adaptive testing in the health domain.
Comparison of the antibody responses to Plasmodium vivax and Plasmodium falciparum antigens in residents of Mandalay, Myanmar
Authors: Kim Tong-Soo , Kim Hyung-Hwan , Kim Jung-Yeon , Kong Yoon , Na Byoung-Kuk , Lin Khin , Moon Sung-Ung , Kim Yeon-Joo , Kwon Myoung-Hee , Sohn Youngjoo , Kim Hyuck , Lee Hyeong-Woo
Published: August 2011

Background

The aim of this study was to investigate the profile of antibodies against several antigens of Plasmodium vivax and Plasmodium falciparum in Mandalay, Myanmar.

Methods

Malaria parasites were identified by microscopic examination. To test the antibodies against P. vivax and P. falciparum in sera, an indirect immunofluorescence antibody test (IFAT) was performed using asexual blood parasite antigens. An enzyme-linked immunosorbent assay (ELISA) was performed with circumsporozoite protein (CSP), Pvs25 and Pvs28 recombinant proteins of transmission-blocking vaccine candidates for P. vivax, and liver stage specific antigen-1 and -3 (PfLSA-1, PfLSA-3) for P. falciparum.

Results

Fourteen patients among 112 were found to be infected with P. vivax and 26 with P. falciparum by thick smear examination. Twenty-three patients were found to be infected with P. vivax, 19 with P. falciparum and five with both by thin smear examination. Blood samples were divided into two groups: Group I consisted of patients who were positive for infection by microscopic examination, and Group II consisted of those who showed symptoms, but were negative in microscopic examination. In P. falciparum, IgG against the blood stage antigen in Group I (80.8%) was higher than in Group II (70.0%). In P. vivax, IgG against the blood stage antigen in Group I (53.8%) was higher than in Group II (41.7%). However, the positivity rate of the PvCSP VK210 subtype in Group II (40.0%) was higher than in Group I (23.1%). Similarly for the PvCSP VK247 subtype, Group II (21.7%) was higher than that for Group I (9.6%). A similar pattern was observed in the ELISA using Pvs25 and Pvs28: positive rates of Group II were higher than those for Group I. However, those differences were not shown significant in statistics.

Conclusions

The positive rates for blood stage antigens of P. falciparum were higher in Group I than in Group II, but the positive rates for antigens of other stages (PfLSA-1 and -3) showed opposite results. Similar to P. falciparum, the positive rate of pre-blood stage (CSP VK210 and 247 subtype) and post-blood stage (Pvs25 and 28) antigens of P. vivax were higher in Group II than in Group I. Therefore, sero-diagnosis is not helpful to discriminate between malaria patients and symptomatic individuals during the epidemic season in Myanmar.
LXR agonist increases apoE secretion from HepG2 spheroid, together with an increased production of VLDL and apoE-rich large HDL
Authors: Kurano Makoto , Iso-O Naoyuki , Hara Masumi , Ishizaka Nobukazu , Moriya Kyoji , Koike Kazuhiko , Tsukamoto Kazuhisa
Published: August 2011

Background

The physiological regulation of hepatic apoE gene has not been clarified, although the expression of apoE in adipocytes and macrophages has been known to be regulated by LXR.

Methods and Results

We investigated the effect of TO901317, a LXR agonist, on hepatic apoE production utilizing HepG2 cells cultured in spheroid form, known to be more differentiated than HepG2 cells in monolayer culture. Spheroid HepG2 cells were prepared in alginate-beads. The secretions of albumin, apoE and apoA-I from spheroid HepG2 cells were significantly increased compared to those from monolayer HepG2 cells, and these increases were accompanied by increased mRNA levels of apoE and apoA-I. Several nuclear receptors including LXRα also became abundant in nuclear fractions in spheroid HepG2 cells. Treatment with TO901317 significantly increased apoE protein secretion from spheroid HepG2 cells, which was also associated with the increased expression of apoE mRNA. Separation of the media with FPLC revealed that the production of apoE-rich large HDL particles were enhanced even at low concentration of TO901317, and at higher concentration of TO901317, production of VLDL particles increased as well.

Conclusions

LXR activation enhanced the expression of hepatic apoE, together with the alteration of lipoprotein particles produced from the differentiated hepatocyte-derived cells. HepG2 spheroids might serve as a good model of well-differentiated human hepatocytes for future investigations of hepatic lipid metabolism.
Neutralizing activities of caprine antibodies towards conserved regions of the HCV envelope glycoprotein E2
Authors: El Abd Yasmine S , Tabll Ashraf A , El Din Noha G Bader , Hosny Alaa El-Dien S , Moustafa Rehab I , El-Shenawy Reem , Atef Khaled , El-Awady Mostafa K
Published: August 2011

Anti HCV vaccine is not currently available and the present antiviral therapies fail to cure approximately half of the treated HCV patients. This study was designed to assess the immunogenic properties of genetically conserved peptides derived from the C-terminal region of HVR-1 and test their neutralizing activities in a step towards developing therapeutic and/or prophylactic immunogens against HCV infection. Antibodies were generated by vaccination of goats with synthetic peptides derived from HCV E2. Viral neutralizing capacity of the generated anti E2 antibodies was tested using in vitro assays. Goats immunized with E2 synthetic peptides termed p412 [a.a 412-419], p430 [a.a 430-447] and p517 [a.a 517-531] generated high titers of antibody responses 2 to 4.5 fold higher than comparable titers of antibodies to the same epitopes in chronic HCV patients. In post infection experiments of native HCV into cultured Huh7.5 cells anti p412 and anti p 517 were proven to be neutralizing to HCV genotype 4a from patients' sera (87.5% and 75% respectively). On the contrary anti p430 exhibited weak viral neutralization capacity on the same samples (31.25%). Furthermore Ab mixes containing anti p430 exhibited reduced viral neutralization properties. From these experiments one could predict that neutralization by Abs towards different E2-epitopes varies considerably and success in the enrichment of neutralization epitope-specific antibodies may be accompanied by favorable results in combating HCV infection. Also, E2 conserved peptides p517 and p412 represent potential components of a candidate peptide vaccine against HCV infection.
Molecular analysis of the membrane insertion domain of proteinase 3, the Wegener's autoantigen, in RBL cells: implication for its pathogenic activity
Authors: Kantari Chahrazade , Millet Arnaud , Gabillet Julie , Hajjar Eric , Broemstrup Torben , Pluta Paula , Reuter Nathalie , Witko-Sarsat Véronique
Published: August 2011

PR3, also called myeloblastin, is a neutrophil serine protease that promotes myeloid cell proliferation by cleaving the cyclin-dependent kinase inhibitor p21cip1/waf1. In addition, it is the target of ANCA in GPA, a necrotizing vasculitis. Anti-PR3 ANCA binding to membrane-expressed PR3 triggers neutrophil activation, potentiating vascular inflammation. This study performed in RBL cells identifies the structural motifs of PR3 membrane anchorage and examines its impact on PR3 proinflammatory and proliferative functions. With the use of MD simulations and mutagenesis, we demonstrate that the mutations of four hydrophobic (F180, F181, L228, F229) or four basic (R193, R194, K195, R227) amino acids abrogated PR3 membrane anchorage. The hydrophobic patch-deficient PR3 mutant (PR34H4A) was still able to cleave the synthetic substrate Boc-Ala-Pro-Val in cell lysates. However, in contrast to WT PR3, PR34H4A was not expressed at the plasma membrane after degranulation and failed to cleave extracellular fibronectin, was not externalized after apoptosis and did not impair macrophage phagocytosis of apoptotic cells, did not promote myeloid cell proliferation and failed to cleave p21/waf1. PR3 membrane insertion appears to be pivotal for its proinflammatory activities, such as extracellular proteolysis and impairment of apoptotic cell clearance, but also for myeloid cell proliferation. Targeting membrane-associated PR3 might constitute a novel, anti-inflammatory therapeutic strategy in inflammatory disease especially in vasculitis, but this approach has to be validated in mature neutrophils.
Reported Antiplatelet Use Influences Long-Term Outcome Independently in Deep Intracerebral Hemorrhage
Authors: Kuramatsu Joji B. , Mauer Christoph , Kiphuth Ines-Christine , Lücking Hannes , Kloska Stephan P. , Köhrmann Martin , Huttner Hagen B.
Published: August 2011

BACKGROUND:

Recent studies have focused on antiplatelet (AP) use in intracerebral hemorrhage (ICH) patients. Several outcome predictors have been debated, but influences on mortality and outcome still remain controversial, especially for different ICH locations.

OBJECTIVE:

To investigate the characteristics and functional outcome of ICH patients with reported regular AP use according to hemorrhage locations.

METHODS:

This retrospective analysis included 210 consecutive spontaneous ICH patients. Clinical data including the preadmission status, initial presentation, neuroradiological data, treatment, and outcome were evaluated. Analyses were calculated for AP use vs non-AP use according to hematoma locations, and multivariate models were calculated for hematoma expansion and unfavorable (modified Rankin Scale = 4–6) long-term functional outcome (at 1 year).

RESULTS:

For all AP users ICH volume was significantly larger, 27.7 mL (interquartile range 7.4-66.1) vs 16.8 mL (interquartile range 4.2-44.7); (P = .032). Analyses showed an increased mortality for AP users at 90 days and 1 year (P = .036; P = .008). Multivariately, for all ICH patients, prior AP use was independently associated with hematoma expansion (odds ratio [OR] 3.61; P = .026) and poorer functional outcome at 1 year (OR 3.82, P = .035). In deep ICH patients, AP use was an independent predictor of an unfavorable functional outcome at 1 year (OR 4.75, P = .048).

CONCLUSION:

Hematoma expansion and more frequent unfavorable long-term functional outcome were independently associated with prior AP use for all patients, and in deep ICH patients AP use was an independent predictor of an unfavorable long-term functional outcome.
The deep venous system of the lower extremity: new nomenclature
Authors: Kachlik D , Pechacek V , Musil V , Baca V
Published: August 2011

The correct and precise nomenclature of the veins of the lower extremity is a necessary tool for communication. Three important changes have been done over the last 13 years. Terminologia Anatomica, the latest version of the Latin anatomical nomenclature, was published in 1998, extended in the area of the lower extremity veins with two consensus documents, in 2001, during the 14th World Congress of the International Union of Phlebology and in 2004 during the 21st World Congress of the International Union of Angiology. This article is a free continuation of two previous articles, reviewing the detailed anatomy and correct nomenclature of the superficial veins of the lower extremities and veins of pelvis. Now, it is concentrated on the deep venous system, in which 15 new terms have been added in both Latin and English languages.
Bupropion-Induced Generalized Exanthematous Pustulosis; Azathioprine-Induced Fever; Reversible Posterior Leukoencephalopathy Syndrome with Sunitinib Therapy; Ketoprofen-Associated Nonalcoholic Fatty Liver Disease and Steatohepatitis; Glomerulosclerosis with Acute Renal Failure Associated with Eltrombopag; Anaphylaxis from Passive Transfer of Peanut Allergen in a Blood Product; Early Detection and Prediction of Cardiotoxicity in Chemotherapy-Treated Patients
Authors: Shuster Joel
Published: August 2011

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers.
Hospital Strategies for Insulin Therapy with Rapid-Acting Insulin Analogs
Authors: Campbell R. Keith
Published: August 2011

This article presents strategies on how to meet the challenges presented by the use of insulin in the hospital setting and describes trends seen in current hospital practice. Insulin provides the greatest flexibility in the hospital setting to achieve optimal blood glycemic control in patients with known type 2 diabetes, thereby reducing complications and death. Important challenges include implementing protocols for use of subcutaneous insulin injection (including optimal use of insulin pens), conversion from continuous subcutaneous insulin infusion or intravenous infusion to subcutaneous administration by multiple injections, and dosing of insulin in patients receiving corticosteroids. One important trend is a move away from the use of sliding-scale insulin to the use of correction-dose insulin as an adjunct to basal/bolus insulin. In this approach, insulin treatment is closely tailored to changing levels of glycemia, and a protocol is put in place for administration of a correction dose of rapid-acting insulin in response to a glycemic excursion. Insulin analogs can more closely mimic physiological insulin profiles than regular insulin, and rapid-acting analogs are invaluable agents as correction insulin administered by pump or in transition to multiple daily injections and as part of basal/bolus therapy. Good glycemic control can improve outcomes of hospital patients in several ways, including facilitating more rapid recovery from infections, shortening intensive care stays, and minimizing costs. Strategies employed to meet the challenges of insulin use in the hospital setting include the increasing use of continuous glucose monitoring systems and the development of insulin dosing algorithms.
Roflumilast
Authors: Cada Dennis J. , Levien Terri L. , Baker Danial E.
Published: August 2011

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. Subscribers to The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The August 2011 monograph topics are on fidaxomicin, boceprevir, telaprevir, rilpivirine hydrochloride, and gabapentin enacarbil. The DUE/MUE is on fidaxomicin.
New Drugs Approved by the FDA; New Dosage Forms and Indications Approved by the FDA; Agents Pending FDA Approval; New Drug/Biologics License Applications Filed by Manufacturer; Significant Labeling Changes or “Dear Health Professional” Letters Related to Safety
Authors: Baker Danial E.
Published: August 2011

This monthly feature will help readers keep current on new drugs, new indications, dosage forms, and safety-related changes in labeling or use. Efforts have been made to ensure the accuracy of this information; however, if there are any questions, please let me know at bakerdan@wsu.edu .
Google on Steroids: An Advanced Search Engine Primer
Authors: Felkey Bill G. , Fox Brent I.
Published: August 2011

The evolution of the Internet is a rather fascinating piece of history. Even in the early days of use by the general public, Internet users quickly realized that tools were needed to find the information that they sought. Today, search engines are those tools, and Google is the most popular. The Google.com page is simple and to the point: enter your search terms and press the Enter key. In this installment, we provide tips that go beyond simply entering a search term.
Lectin-like Oxidized LDL Receptor 1 Is Involved in CRP-Mediated Complement Activation
Authors: Fujita Yoshiko , Yamaguchi Saburo , Kakino Akemi , Iwamoto Shin , Yoshimoto Ryo , Sawamura Tatsuya
Published: August 2011

BACKGROUND

C-reactive protein (CRP) is purported to be a risk factor that acts independently of LDL cholesterol in predicting all-cause mortality in patients with ischemic heart disease. Lectin-like oxidized LDL receptor 1 (LOX-1) impairs endothelial function and exacerbates myocardial injury. We recently demonstrated that CRP increased vascular permeability through direct binding to LOX-1. Here we examined, using a hypertensive rat model, whether LOX-1 is involved in CRP-induced complement activation.

METHODS AND RESULTS

In the cultured LOX-1–expressing cell line hLOX-1-CHO, CRP increased complement activation, but did not do so in native CHO cells. Depleting C1q from serum abolished CRP-induced complement activation. Incubation of CRP with serum on immobilized recombinant LOX-1 similarly showed that CRP activated C1q-requiring classical complement pathway in a LOX-1–dependent manner. Interestingly, the interaction between CRP and LOX-1 was dependent on Ca2+ ion and competed with phosphocholine, suggesting that LOX-1 bound to the B-face of CRP with a phosphocholine-binding domain. This was in contrast to Fcγ receptors, to which CRP bound in A-face with complement-binding domain. In vivo, intradermal injection of CRP to hypertensive SHRSP rats induced complement activation detected by C3d deposition and leukocyte infiltration around the injected area. Anti–LOX-1 antibody reduced the extent of complement activation and leukocyte infiltration.

CONCLUSIONS

LOX-1 appears to be involved in CRP-induced complement activation, and thus may serve to locate the site of CRP-induced complement activation and inflammation.
Wound degradomics – current status and future perspectives
Authors: Hermes Olivia , Schlage Pascal , dem Keller Ulrich auf
Published: August 2011

Proteases are pivotal modulators of extracellular matrix components and bioactive proteins at all phases of cutaneous wound healing and thereby essentially contribute to the successful reestablishment of skin integrity upon injury. As a consequence, disturbance of proteolytic activity at the wound site is a major factor in the pathology of chronic wounds. A large body of data acquired in many years of research provide a good understanding of how individual proteases may influence the repair process. The next challenge will be to integrate these findings and to elucidate the complex interactions of proteolytic enzymes, their inhibitors and substrates on a system-wide level. Here, we present novel approaches that might help to achieve this ambitious goal in cutaneous wound healing research.
Retinoblastoma family of proteins and chromatin epigenetics: a repetitive story in a few LINEs
Authors: Montoya-Durango Diego E. , Ramos Kenneth S.
Published: August 2011

The retinoblastoma (RB) protein family in mammals is composed of three members: pRB (or RB1), p107, and p130. Although these proteins do not directly bind DNA, they associate with the E2F family of transcription factors which function as DNA sequence-specific transcription factors. RB proteins alter gene transcription via direct interference with E2F functions, as well as recruitment of transcriptional repressors and corepressors that silence gene expression through DNA and histone modifications. E2F/RB complexes shape the chromatin landscape through recruitment to CpG-rich regions in the genome, thus making E2F/RB complexes function as local and global regulators of gene expression and chromatin dynamics. Recruitment of E2F/pRB to the long interspersed nuclear element (LINE1) promoter enhances the role that RB proteins play in genome-wide regulation of heterochromatin. LINE1 elements are dispersed throughout the genome and therefore recruitment of RB to the LINE1 promoter suggests that LINE1 could serve as the scaffold on which RB builds up heterochromatic regions that silence and shape large stretches of chromatin. We suggest that mutations in RB function might lead to global rearrangement of heterochromatic domains with concomitant retrotransposon reactivation and increased genomic instability. These novel roles for RB proteins open the epigenetic-based way for new pharmacological treatments of RB-associated diseases, namely inhibitors of histone and DNA methylation, as well as histone deacetylase inhibitors.
Ageing populations, complex diseases and their challenge to 21st century healthcare: the focus of the European Society for Pharmacogenomics and Theranostics
Authors: Henney Adriano
Published: August 2011

No abstract available
Oxidative stabilisation of kraft lignin for carbon fibre production
Authors: Brodin Ida , Ernstsson Marie , Gellerstedt Göran , Sjöholm Elisabeth
Published: August 2011

With the aim of investigating kraft lignin as a raw material for carbon fibre production, different lignins have been stabilised in air at conditions varied according to a full factorial experimental design. The lignins under examination were purified kraft lignin powders originating from birch, spruce/pine and Eucalyptus globules, as well as lignin fibres originating from birch with 5% poly(ethylene oxide) (PEO) added as a plasticiser. The influence of temperature, time and heating rate on yield and glass-transition temperature (Tg) was investigated. The highest yield was achieved after stabilisation at 280°C during 2 h with a heating rate of 0.2°C min-1. The Tg of all lignin powders was increased when stabilisation occurred under harsher conditions. X-ray photoelectron spectroscopy analysis (XPS) of both the outer surface and the cleaved cross-section of individual lignin/PEO fibres showed a clear gradient in the degree of chemical modification, with the major change occurring on the surface resulting in the appearance of a skin-core structure after stabilisation. The behaviour of the lignin fibres during stabilisation is similar to that of pitch-based fibres, indicating good possibilities for lignin as raw material for carbon fibre production.
Antithrombotic properties of sulfated wood-derived galactoglucomannans
Authors: Doliška Aleš , Willför Stefan , Strnad Simona , Ribitsch Volker , Kleinschek Karin Stana , Eklund Patrik , Xu Chunlin
Published: August 2011

Galactoglucomannans (GGMs) are water-soluble polysaccharides released and accumulated in process waters in the production of thermomechanical pulp. The general trend in the forestry industry is moving towards bio-refineries, for example utilizing these hemicelluloses as bioactive substances. At present, there is no industrial use of wood-derived mannans. In this study, GGMs extracted from thermomechanical pulp, as well as further carboxymethyl-ated galactoglucomannans (CM-GGMs), were sulfated to increase their antithrombotic properties. The products were characterized with Fourier transform infrared spectroscopy, nuclear magnetic resonance and capillary electrophoresis. The carbohydrate composition and sulfur amounts were determined. The products’ total charges were determined by polyelectrolyte titrations and their antithrombotic effect was measured based on the activated partial thromboplastin time. The results showed a significant increase in the antithrombotic effect of the sulfated galactoglucomannans from spruce wood and thus a potential new use for wood-derived mannans.
Is it possible to improve neurodevelopmental abnormalities in Down syndrome?
Authors: Bartesaghi Renata , Guidi Sandra , Ciani Elisabetta
Published: August 2011

Down syndrome (DS) is a genetic pathology caused by the triplication of human chromosome 21. Although individuals with DS have various medical problems, intellectual disability is the most invalidating aspect of the pathology. Despite numerous efforts, the mechanisms whereby gene triplication leads to the DS phenotype have not been elucidated and there are, at present, no therapies to rescue brain developmental alterations and mental disability in individuals with DS. In this review, we focused on the major defects of the DS brain, comparing data regarding humans with DS and mouse models for DS, and therapeutic interventions attempted on animal DS models. Based on the promising results of pharmacotherapies in these models, we believe that it is possible to conclude that tools to improve brain development in DS are now almost at hand. We now know that it is possible to rescue and/or improve neurogenesis, neuron maturation, connectivity, neurodegeneration and behavior. We believe that the knowledge gained in DS mouse models provides a rational basis to start new clinical trials in infants, children and adults with DS, exploiting drugs that have proved able to rescue various facets of the DS neurologic phenotype. It is not unreasonable to consider that the results of these trials may provide a positive answer to the question: ‘Is it possible to improve brain development in DS?’.
Translational research in transcranial direct current stimulation
(tDCS): a systematic review of studies in animals
Authors: Brunoni Andre Russowsky , Fregni Felipe , Pagano Rosana Lima
Published: August 2011

Recent therapeutic human studies testing transcranial direct current stimulation
(tDCS) have shown promising results, although many questions remain unanswered.
Translational research with experimental animals is an appropriate framework for
investigating its mechanisms of action that are still undetermined.
Nevertheless, animal and human studies are often discordant. Our aim was to
review tDCS animal studies, examining and comparing their main findings with
human studies. We performed a systematic review in Medline and other databases,
screening for animal studies in vivo that delivered tDCS.
Studies in vitro and using other neuromodulatory techniques
were excluded. We extracted data according to Animal Research: Reporting
In Vivo Experiments (ARRIVE) guidelines for reporting
in vivo animal research. Thus, we collected data on sample
characteristics (size, gender, weight and specimen) and methodology
(experimental procedures, experimental animals, housing and husbandry, as well
as analysis). We also collected data on methods for delivering tDCS (location,
size, current and current density of electrodes and electrode montage),
experimental effects (polarity-, intensity- and after-effects) and safety. Only
12 of 48 potentially eligible studies met our inclusion criteria and were
reviewed. Quality assessment reporting was only moderate and studies were
heterogeneous regarding tDCS montage methodology, position of active and
reference electrodes, and current density used. Nonetheless, almost all studies
demonstrated that tDCS had positive immediate and long-lasting effects.
Vis-à-vis human trials, animal studies applied
higher current densities (34.2 vs. 0.4 A/m2, respectively), preferred
extra-cephalic positions for reference electrodes (60% vs. 10%,
respectively) and used electrodes with different sizes more often. Potential
implications for translational tDCS research are discussed.
Modifications of bone material properties in postmenopausal osteoporotic women long-term treated with alendronate
Authors: Bala Yohann , Farlay Delphine , Chapurlat Roland D , Boivin Georges
Published: August 2011

Objective

Given recent concern about long-term safety of bisphosphonate (BP) therapy, the effects of long-term alendronate (ALN) therapy on intrinsic bone properties were studied among postmenopausal osteoporotic (PMOP) women.

Design and methods

Transiliac bone biopsies were obtained from 32 outpatient clinic PMOP women treated with oral ALN for 6.4±2.0 years. Variables reflecting bone mineralization were measured both at tissue level using quantitative microradiography and at crystal level by Fourier transform infrared microspectroscopy. Bone microhardness was investigated by Vickers indentation tests. Results were compared with those from 22 age-matched untreated PMOP women.

Results

Long-term treatment with ALN was associated with a 84% (P<0.001) lower remodeling activity compared with untreated PMOP women, leading to an increased degree of mineralization in both cortical and trabecular bone (+9 and +6%, respectively, P<0.05). Despite a more mature and more mineralized bone matrix, after treatment, cortical and trabecular microhardness and crystallinity were lower than that measured in untreated patients. None of the variables reflecting material properties were significantly correlated to the duration of the treatment.

Conclusion

Increased degree of mineralization associated with lower crystallinity and microhardness in ALN long-term-treated PMOP women suggests that ALN could alter the quality of bone matrix. The study also suggested that after 3 years of treatment, the changes in material properties are not dependent on the duration of the treatment. Further studies are requested to assess the short-term (<3 years) effects of BPs on bone intrinsic properties.
Granulosal and thecal expression of bone morphogenetic protein- and activin-binding protein mRNA transcripts during bovine follicle development and factors modulating their expression in vitro
Authors: Glister Claire , Satchell Leanne , Knight Phil G
Published: August 2011

Evidence supports local roles for transforming growth factor β superfamily members including activins and bone morphogenetic proteins (BMP) in follicle development. Access of these ligands to signalling receptors is likely modulated by extracellular binding proteins (BP). In this study, we comparedex vivoexpression of four BPs (chordin, gremlin, noggin and follistatin) in granulosal (GC) and theca interna (TC) compartments of developing bovine antral follicles (1–18 mm). Effects of FSH and IGF on BMP and BP expression by cultured GC, and effects of LH and BMPs on BP expression by cultured TC were also examined. Follicular expression of all four BP transcripts was higher in GC than TC compartments (P<0.001) a finding confirmed by immunohistochemistry. Follicle category affected (P<0.01) gremlin and follistatin mRNA abundance, with a significant cell-type×follicle category interaction for chordin, follistatin and noggin. Noggin transcript abundance was lower (P<0.05) in GC of large ‘E-active’ than ‘E-inactive’ follicles while follistatin mRNA level was higher (P<0.01). FSH enhanced CYP19, FSHR, INHBA and follistatin by GC without affecting BMP or BMP–BP expression. IGF increased CYP19 and follistatin, reduced BMP4, noggin and gremlin but did not affect chordin orFSHRmRNA levels. LH increased TC androgen secretion but had no effect on BMP or BP expression. BMPs uniformly suppressed TC androgen production whilst increasing chordin, noggin and gremlin mRNA levels up to 20-fold (P<0.01). These findings support the hypothesis that extracellular BP, mostly from GC, contribute to the regulation of intrafollicular BMP/activin signalling. Enhancement of thecal BP expression by BMP implies an autoregulatory feedback role to prevent excessive signalling.
Characteristics of low-density hemp-lime building materials
Authors: Hirst Edward A. J. , Walker Peter , Paine Kevin A. , Yates Tim
Published: August 2011

Hemp-lime is a sustainable low-carbon composite building material that combines renewably sourced hemp shiv (a co-product of hemp fibre crop production) with formulated lime-based binders. To date, its primary use has been to form solid external walls in timber-framed buildings. This paper reports on the testing of 54 hemp-lime cylinders to compare their strength and stiffness properties at three different densities and at different ages up to 180 days. Three different and widely used formulated lime binders were studied. Phenolphthalein staining was used to map development of the carbonation front across specimen cross-sections. The strength and stiffness properties of the hemp-lime are comparable with other rigid insulation materials such as woodfibre board. The strength of hemp-lime increases with mix density and age. However, the strength of hemp-lime is not directly related to the individual strength of the binder, but rather is a function of complex and dynamic interactions between the hemp and the binder matrix, as well as the density and the percentage of wet binder mix at fabrication.
The internet: a potential factor in socio-spatial disintegration of Riga?
Authors: Nawratek Krzysztof
Published: August 2011

This paper analyses the current and planned urban and social structure of Riga, the capital of Latvia, in the context of language tension. This tension is grounded in the ethnic diversity of the city, in which the number of Russian-speaking inhabitants is almost equal to the number of Latvians. This paper calls for further analysis of the output of contemporary information technologies implemented in post-socialist and bilingual cities. While planners often focus on social and national tensions in such cities, this text investigates the simultaneously underlying and parallel linguistic barrier that impedes communication between different communities. Analysing policy documents and cultural papers, and applying an anthropological approach based on several years of the author’s own residency in Riga, this text conceptualises language in the post-socialist city as one of the fundamental analytic perspectives to adopt in examining the urban realm. It considers the use of ‘transcendent’ (neutral) language (English in Latvia) as a substitute for the neutral public sphere within which everybody could potentially meet and communicate.
A review of road structure data in six European countries
Authors: Žnidarič Aleš , Pakrashi Vikram , O'Brien Eugene , O'Connor Alan
Published: August 2011

The European Union has expanded significantly in recent years. Sustainable trade within the Union, leading to economic growth to the benefit of the ‘old’ and ‘new’ member states is thus extremely important. The road infrastructure is strategic and vital to such development since an uneven transport infrastructure, in terms of capacity and condition, has the potential to reinforce uneven development trends and hinder economic convergence of old and new member states. In the decades since their design and construction, loading conditions have significantly changed for many major highway infrastructure elements/networks owing primarily to increased freight volumes and vehicle sizes. This, coupled with the gradual deterioration of a significant number of highway structures due to their age, and the absence of a pan-European assessment framework, can be expected to affect the smooth functioning of the infrastructure in its as-built condition. Increased periods of reduced flow can be expected owing to planned and unplanned interventions for repair/rehabilitation. This paper reports the findings of a survey regarding the current status of the highway infrastructure elements in six countries within the European Union as reported by the owners/operators. The countries surveyed include a cross-section of ‘existing’ older countries and ‘new’ member states. The current situations for bridges, culverts, tunnels and retaining walls are reported, along with their potential replacement costs. The findings act as a departure point for further studies in support of a centralised and/or synchronised EU approach to infrastructure maintenance management. Information in the form presented in this paper is central to any future decision-making frameworks in terms of trade route choice and operations, monetary investment, optimised maintenance, management and rehabilitation of the built infrastructure and the economic integration of the newly joined member states.
Organoleptic Quality, Minerals, Proteins and Amino Acids from Two Tunisian Commercial Pomegranate Fruits
Authors: Elfalleh Walid , Tlili Nizar , Ying Ma , Sheng-Hua He , Ferchichi Ali , Nasri Nizar
Published: August 2011

Chemicals from fresh pomegranates were established. Total sugar of juice extracts are mainly fructose (ca. 7.27 g/100 ml) and glucose (ca. 8.11 g/100 ml). Pulp minerals, expressed as mg/100g are potassium (351.26), magnesium (10.02), calcium (9.26), sodium (7.25), iron (0.15), Zinc (0.10), copper (0.08) and manganese (0.04). Juice proteins are about 7.95 g/l and dry pulp proteins are 24% on a dry-weight basis DW (Kjeldhal assays). Seed proteins are ca. 16.87% DW. Globulins (62.4 mg/g DW) and albumins (54.12 mg/g DW) are the major storage protein fractions, followed by glutelins (33.2 mg/g DW) and prolamins (18.08 mg/g DW). Seed total amino acid content is 14.45 g/100 g DW. Seeds are rich in Glu, Arg, Asp, Leu and Gly amino acids. Essential amino acids average 33.54% of total amino acid. Essential amino acids are mostly all much higher than the requirement of FAO/WHO for adults (but none for preschool children). Most other amino acids have content slightly fewer. All of these findings implied that the content of sugar, mineral and protein maybe included in pomegranate as supplements for commonly diets.
Novel Heuristic for Low-Batch Manufacturing Process Scheduling Optimisation with Reference to Process Engineering
Authors: Maqsood S. , Khan M. K. , Wood A. S.
Published: August 2011

Scheduling is an important element that has a major impact on the efficiency of all manufacturing processes. It plays an important role in optimising the manufacturing times and costs resulting in energy efficient processes. It has been estimated that more than 75% of manufacturing processes occur in small batches. In such environments, processes must be able to perform a variety of operations on a mix of different batches. Batch-job scheduling optimisation is the response to such low batch manufacturing problems. The optimisation of batch-job process scheduling problem is still a challenge to researchers and is far from being completely solved due to its combinatorial nature. In this paper, a novel hybrid heuristic (HybH) solution approach for batch-job scheduling problem is presented with the objective of optimising the overall Makespan (Cmax). The proposed HybH is the combination of Index Based Heuristic (IBH) and the Finished Batch-Job (FBJ) process schedule. The heuristic assigns the first operation to a batch-job using IBH and the remaining operations on the basis FBJ process schedule. The FBJ process schedule gives priority to the batch-job with early finished operations, without violating the constraints of process order. The proposed HybH is explained with the help of a detailed example. Several benchmark problems are solved from the literature to check the validity and effectiveness of the proposed heuristic. The presented HybH has achieved batch-job process schedules which have outperformed the traditional heuristics. The results are encouraging and show that the proposed heuristic is a valid methodology for batch process scheduling optimisation.
The Chad-Cameroon Pipeline Project--Assessing the World Bank's Failed Experiment to Direct Oil Revenues towards the Poor
Authors: Clausen Fabian , Attaran Amir
Published: August 2011

The World Bank's engagement with projects involving extractive industries has not proven particularly successful. Especially in Sub-Saharan Africa, it has actually often made matters worse. Borrower countries' economies failed to grow, and corruption increased; the poor did not benefit from the revenues that were generated. This paper assesses the complex legal and institutional framework of the World Bank project that many hoped would change this bleak record: in the highly publicized and controversial Chad-Cameroon Pipeline Project, the Bank catalyzed the largest private investment in the history of Sub-Saharan Africa. This model project featured new and untested contractual, statutory, institutional and fiscal mechanisms which were intended to make Chad's oil revenues transparent and compel the Government of Chad—one of the world's poorest—to expend its oil revenues on areas consistent with the project's agreed poverty reduction objective, such as education and health.

Despite these heroic measures, in 2008 the revenue allocation program collapsed, and the Bank's projects in Chad terminated prematurely. Not for the first time, the government of Chad had unilaterally altered the underlying laws to enable more security and military spending. Yet again, the poor had not profited from the oil revenues.

We analyse in this paper whether the Bank's failure in the Chad-Cameroon Pipeline Project was due to specific errors in the framework of contracts, laws and institutional structures the Bank deployed—errors which could, in theory, be taken as lessons for a future project making use of an improved revenue allocation system—or whether generally the Bank's entire concept of contractually imposing a revenue allocation system is flawed, such that any attempt to revive such a system on another occasion is misguided and futile.
Ideals in distributive posets
Authors: Batueva Cyndyma , Semenova Marina
Published: August 2011

We prove that any ideal in a distributive (relative to a certain completion) poset is an intersection of prime ideals. Besides that, we give a characterization of n-normal meet semilattices with zero, thus generalizing a known result for lattices with zero.