bluuebunny/crossref_metadata_2025 huggingface dataset:
Theory, simulation and experimental results of the acoustic detection of magnetization changes in superparamagnetic iron oxide
Authors: Gleich Bernhard , Weizenecker Jürgen , Borgert Jörn
Published: June 2011

Background

Magnetic Particle Imaging is a novel method for medical imaging. It can be used to measure the local concentration of a tracer material based on iron oxide nanoparticles. While the resulting images show the distribution of the tracer material in phantoms or anatomic structures of subjects under examination, no information about the tissue is being acquired. To expand Magnetic Particle Imaging into the detection of soft tissue properties, a new method is proposed, which detects acoustic emissions caused by magnetization changes in superparamagnetic iron oxide.

Methods

Starting from an introduction to the theory of acoustically detected Magnetic Particle Imaging, a comparison to magnetically detected Magnetic Particle Imaging is presented. Furthermore, an experimental setup for the detection of acoustic emissions is described, which consists of the necessary field generating components, i.e. coils and permanent magnets, as well as a calibrated microphone to perform the detection.

Results

The estimated detection limit of acoustic Magnetic Particle Imaging is comparable to the detection limit of magnetic resonance imaging for iron oxide nanoparticles, whereas both are inferior to the theoretical detection limit for magnetically detected Magnetic Particle Imaging. Sufficient data was acquired to perform a comparison to the simulated data. The experimental results are in agreement with the simulations. The remaining differences can be well explained.

Conclusions

It was possible to demonstrate the detection of acoustic emissions of magnetic tracer materials in Magnetic Particle Imaging. The processing of acoustic emission in addition to the tracer distribution acquired by magnetic detection might allow for the extraction of mechanical tissue parameters. Such parameters, like for example the velocity of sound and the attenuation caused by the tissue, might also be used to support and improve ultrasound imaging. However, the method can also be used to perform imaging on its own.
Molecular diagnosis of hereditary inclusion body myopathy by linkage analysis and identification of a novel splice site mutation in GNE
Authors: Boyden Steven E , Duncan Anna R , Estrella Elicia A , Lidov Hart GW , Mahoney Lane J , Katz Jonathan S , Kunkel Louis M , Kang Peter B
Published: June 2011

Background

Many myopathies share clinical features in common, and diagnosis often requires genetic testing. We ascertained a family in which five siblings presented with distal muscle weakness of unknown etiology.

Methods

We performed high-density genomewide linkage analysis and mutation screening of candidate genes to identify the genetic defect in the family. Preserved clinical biopsy material was reviewed to confirm the diagnosis, and reverse transcriptase PCR was used to determine the molecular effect of a splice site mutation.

Results

The linkage scan excluded the majority of known myopathy genes, but one linkage peak included the gene GNE, in which mutations cause autosomal recessive hereditary inclusion body myopathy type 2 (HIBM2). Muscle biopsy tissue from a patient showed myopathic features, including small basophilic fibers with vacuoles. Sequence analysis of GNE revealed affected individuals were compound heterozygous for a novel mutation in the 5' splice donor site of intron 10 (c.1816+5G>A) and a previously reported missense mutation (c.2086G>A, p.V696M), confirming the diagnosis as HIBM2. The splice site mutation correlated with exclusion of exon 10 from the transcript, which is predicted to produce an in-frame deletion (p.G545_D605del) of 61 amino acids in the kinase domain of the GNE protein. The father of the proband was heterozygous for the splice site mutation and exhibited mild distal weakness late in life.

Conclusions

Our study expands on the extensive allelic heterogeneity of HIBM2 and demonstrates the value of linkage analysis in resolving ambiguous clinical findings to achieve a molecular diagnosis.
Safety of phosphatidylserine containing omega-3 fatty acids in non-demented elderly: a double-blind placebo-controlled trial followed by an open-label extension
Authors: Vakhapova Veronika , Richter Yael , Cohen Tzafra , Herzog Yael , Korczyn Amos D
Published: June 2011

Background

Phosphatidylserine (PS) is a naturally occurring phospholipid present in the inner leaflet of mammalian plasma membranes. Administration of PS extracted from bovine cortex (BC-PS), which contains high levels of omega-3 long chain polyunsaturated fatty acid (LC-PUFA) attached to its backbone, resulted in positive effects on brain functions such as learning and memory. Recently, a novel marine-sourced PS with omega-3 LC-PUFA attached to its backbone was developed (PS-DHA). In the present study, we evaluated the safety profile of the novel PS preparation in non-demented elderly with memory complaints. The efficacy study of this novel formulation indicated that PS-DHA may ameliorate cognitive deficits in non-demented elderly population.

Methods

157 non-demented elderly participants with memory complaints were randomized to receive either PS-DHA (300 mg PS/day) or placebo for 15 weeks. Standard biochemical and hematological safety parameters, blood pressure and heart rate were evaluated at baseline and endpoint. 122 participants continued into an open-label extension for additional 15 weeks, in which they all consumed PS-DHA (100 mg PS/day) and were evaluated for their blood pressure, heart rate and weight at endpoint. Adverse events were monitored throughout the double-blind and open-label phases.

Results

131 participants completed the double-blind phase. No significant differences were found in any of the tested safety parameters between the study groups, or within each group. 121 participants completed the open-label phase. At the end of this phase, there was a reduction in resting diastolic blood pressure and a slight weight gain among participants who consumed PS-DHA for 30 weeks.

Conclusions

The results of this study indicate that consumption of PS-DHA at a dosage of 300 mg PS/day for 15 weeks, or 100 mg PS/day for 30 weeks, is safe, well tolerated, and does not produce any negative effects in the tested parameters.

Trial registration

clinicaltrials. gov, identifier: NCT00437983
Equity in the delivery of community healthcare to older people: findings from 10/66 Dementia Research Group cross-sectional surveys in Latin America, China, India and Nigeria
Authors: Albanese Emiliano , Liu Zhaorui , Acosta Daisy , Guerra Mariella , Huang Yueqin , Jacob KS , Jimenez-Velazquez Ivonne Z , Llibre Rodriguez Juan J , Salas Aquiles , Sosa Ana L , Uwakwe Richard , Williams Joseph D , Borges Guilherme , Jotheeswaran AT , Klibanski Milagros G , McCrone Paul , Ferri Cleusa P , Prince Martin J
Published: June 2011

Background

To describe patterns of recent health service utilisation, and consequent out-of-pocket expenses among older people in countries with low and middle incomes, and to assess the equity with which services are accessed and delivered.

Methods

17,944 people aged 65 years and over were assessed in one-phase population-based cross-sectional surveys in geographically-defined catchment areas in nine countries - urban and rural sites in China, India, Mexico and Peru, urban sites in Cuba, Dominican Republic, Puerto Rico and Venezuela, and a rural site in Nigeria. The main outcome was use of community health care services in the past 3 months. Independent associations were estimated with indicators of need (dementia, depression, physical impairments), predisposing factors (age, sex, and education), and enabling factors (household assets, pension receipt and health insurance) using Poisson regression to generate prevalence ratios and fixed effects meta-analysis to combine them.

Results

The proportion using healthcare services varied from 6% to 82% among sites. Number of physical impairments (pooled prevalence ratio 1.37, 95% CI 1.26-1.49) and ICD-10 depressive episode (pooled PR 1.21, 95% CI 1.07-1.38) were associated with service use, but dementia was inversely associated (pooled PR 0.93, 95% CI 0.90-0.97). Other correlates were female sex, higher education, more household assets, receiving a pension, and health insurance. Standardisation for age, sex, physical impairments, depression and dementia did not explain variation in service use. There was a strong borderline significant ecological correlation between the proportion of consultations requiring out-of-pocket costs and the prevalence of health service use (r = -0.50, p = 0.09).

Conclusions

While there was little evidence of ageism, inequity was apparent in the independent enabling effects of education and health insurance cover, the latter particularly in sites where out-of-pocket expenses were common, and private health insurance an important component of healthcare financing. Variation in service use among sites was most plausibly accounted for by stark differences in the extent of out-of-pocket expenses, and the ability of older people and their families to afford them. Health systems that finance medical services through out-of-pocket payments risk excluding the poorest older people, those without a secure regular income, and the uninsured.
Co-cultivation of murine BMDCs with 67NR mouse mammary carcinoma cells give rise to highly drug resistant cells
Authors: Nagler Christa , Hardt Cornelia , Zänker Kurt S , Dittmar Thomas
Published: June 2011

Background

Tumor tissue resembles chronically inflamed tissue. Since chronic inflammatory conditions are a strong stimulus for bone marrow-derived cells (BMDCs) it can be assumed that recruitment of BMDCs into cancer tissue should be a common phenomenon. Several data have outlined that BMDC can influence tumor growth and metastasis, e.g., by inducing a paracrine acting feedback loop in tumor cells. Likewise, cell fusion and horizontal gene transfer are further mechanisms how BMDCs can trigger tumor progression.

Results

Hygromycin resistant murine 67NR-Hyg mammary carcinoma cells were co-cultivated with puromycin resistant murine BMDCs from Tg(GFPU)5Nagy/J mice. Isolation of hygromycin/puromycin resistant mBMDC/67NR-Hyg cell clones was performed by a dual drug selection procedure. PCR analysis revealed an overlap of parental markers in mBMDC/67NR-Hyg cell clones, suggesting that dual resistant cells originated by cell fusion. By contrast, both STR and SNP data analysis indicated that only parental 67NR-Hyg alleles were found in mBMDC/67NR-Hyg cell clones favoring horizontal gene transfer as the mode of origin. RealTime-PCR-array analysis showed a marked up-regulation of Abcb1a and Abcb1b ABC multidrug transporters in mBMDC/67NR-Hyg clones, which was verified by Western Blot analysis. Moreover, the markedly increased Abcb1a/Abcb1b expression was correlated to an efficient Rhodamine 123 efflux, which was completely inhibited by verapamil, a well-known Abcb1a/Abcb1b inhibitor. Likewise, mBMDCs/67NR-Hyg clones revealed a marked resistance towards chemotherapeutic drugs including 17-DMAG, doxorubicin, etoposide and paclitaxel. In accordance to Rhodamine 123 efflux data, chemotherapeutic drug resistance of mBMDC/67NR-Hyg cells was impaired by verapamil mediated blockage of Abc1a/Abcb1b multidrug transporter function.

Conclusion

Co-cultivation of mBMDCs and mouse 67NR-Hyg mammary carcinoma cells gave rise to highly drug resistant cells. Even though it remains unknown whether mBMDC/67NR-Hyg clones originated by cell fusion or horizontal gene transfer, our data indicate that the exchange of genetic information between two cellular entities is crucial for the origin of highly drug resistant cancer (hybrid) cells, which might be capable to survive chemotherapy.
Dynamin inhibitors induce caspase-mediated apoptosis following cytokinesis failure in human cancer cells and this is blocked by Bcl-2 overexpression
Authors: Joshi Sanket , Braithwaite Antony W , Robinson Phillip J , Chircop Megan
Published: June 2011

Background

The aim of both classical (e.g. taxol) and targeted anti-mitotic agents (e.g. Aurora kinase inhibitors) is to disrupt the mitotic spindle. Such compounds are currently used in the clinic and/or are being tested in clinical trials for cancer treatment. We recently reported a new class of targeted anti-mitotic compounds that do not disrupt the mitotic spindle, but exclusively block completion of cytokinesis. This new class includes MiTMAB and OcTMAB (MiTMABs), which are potent inhibitors of the endocytic protein, dynamin. Like other anti-mitotics, MiTMABs are highly cytotoxic and possess anti-proliferative properties, which appear to be selective for cancer cells. The cellular response following cytokinesis failure and the mechanistic pathway involved is unknown.

Results

We show that MiTMABs induce cell death specifically following cytokinesis failure via the intrinsic apoptotic pathway. This involves cleavage of caspase-8, -9, -3 and PARP, DNA fragmentation and membrane blebbing. Apoptosis was blocked by the pan-caspase inhibitor, ZVAD, and in HeLa cells stably expressing the anti-apoptotic protein, Bcl-2. This resulted in an accumulation of polyploid cells. Caspases were not cleaved in MiTMAB-treated cells that did not enter mitosis. This is consistent with the model that apoptosis induced by MiTMABs occurs exclusively following cytokinesis failure. Cytokinesis failure induced by cytochalasin B also resulted in apoptosis, suggesting that disruption of this process is generally toxic to cells.

Conclusion

Collectively, these data indicate that MiTMAB-induced apoptosis is dependent on both polyploidization and specific intracellular signalling components. This suggests that dynamin and potentially other cytokinesis factors are novel targets for development of cancer therapeutics.
Establishment of stable Huh-7 cell lines expressing various hepatitis C virus genotype 3a protein: an in-vitro testing system for novel anti-HCV drugs
Authors: Butt Sadia , Idrees Muhammad , Rehman Irshad-ur , Ali Liaqat , Hussain Abrar , Ali Muhammad , Ahmed Naveed , Saleem Sana , Fayyaz Madiha
Published: June 2011

Background

Hepatitis C virus (HCV) infection is the leading cause of chronic hepatitis which progresses to hepatocellular carcinoma (HCC) afflicting > 170 million people worldwide. HCV 3a is the most common genotype (about 70% of all genotypes) circulating in Pakistan. Expression of HCV individual gene of 3a would facilitate therapeutic and vaccines strategies against chronic HCV and liver Cirrhosis. The aim of the present study was the establishment of stable Huh-7 cell lines expressing structural and non structural proteins of HCV Genotype 3a Pakistani isolate obtained from chronic HCV patients.

Methods

Blood samples were obtained from chronic HCV-3a positive patients. HCV individual genes were amplified using PCR with gene specific primers having restriction sites. These gene amplicons were cloned in mammalian expression vector PcDNA3.1+. Huh-7 cell lines were transfected with these constructed plasmids having structural or non-structural HCV genes in confluent cells with lipofectamine. Positive clones were selected with G418 and then confirmed by genome PCR. Subsequently, transcription and expression of the integrated genes were demonstrated by RT-PCR, sequencing and Western blot analysis.

Results

We successfully cloned and express five HCV-3a genes in PcDNA3.1+ mammalian expression vector. Results of western blot and sequencing PCR confirmed the stable expression of these five genes.

Conclusion

The stable cell-lines expressing HCV-3a individual genes would be a useful tool to investigate the role of various HCV proteins on HCV disease outcome and testing of new therapeutic strategies against HCV.
Effect of spinal manipulation on sensorimotor functions in back pain patients: study protocol for a randomised controlled trial
Authors: Wilder David G , Vining Robert D , Pohlman Katherine A , Meeker William C , Xia Ting , DeVocht James W , Gudavalli R Maruti , Long Cynthia R , Owens Edward F , Goertz Christine M
Published: June 2011

Background

Low back pain (LBP) is a recognized public health problem, impacting up to 80% of US adults at some point in their lives. Patients with LBP are utilizing integrative health care such as spinal manipulation (SM). SM is the therapeutic application of a load to specific body tissues or structures and can be divided into two broad categories: SM with a high-velocity low-amplitude load, or an impulse "thrust", (HVLA-SM) and SM with a low-velocity variable-amplitude load (LVVA-SM). There is evidence that sensorimotor function in people with LBP is altered. This study evaluates the sensorimotor function in the lumbopelvic region, as measured by postural sway, response to sudden load and repositioning accuracy, following SM to the lumbar and pelvic region when compared to a sham treatment.

Methods/Design

A total of 219 participants with acute, subacute or chronic low back pain are being recruited from the Quad Cities area located in Iowa and Illinois. They are allocated through a minimization algorithm in a 1:1:1 ratio to receive either 13 HVLA-SM treatments over 6 weeks, 13 LVVA-SM treatments over 6 weeks or 2 weeks of a sham treatment followed by 4 weeks of full spine "doctor's choice" SM. Sensorimotor function tests are performed before and immediately after treatment at baseline, week 2 and week 6. Self-report outcome assessments are also collected. The primary aims of this study are to 1) determine immediate pre to post changes in sensorimotor function as measured by postural sway following delivery of a single HVLA-SM or LVVA-SM treatment when compared to a sham treatment and 2) to determine changes from baseline to 2 weeks (4 treatments) of HVLA-SM or LVVA-SM compared to a sham treatment. Secondary aims include changes in response to sudden loads and lumbar repositioning accuracy at these endpoints, estimating sensorimotor function in the SM groups after 6 weeks of treatment, and exploring if changes in sensorimotor function are associated with changes in self-report outcome assessments.

Discussion

This study may provide clues to the sensorimotor mechanisms that explain observed functional deficits associated with LBP, as well as the mechanism of action of SM.

Trial registration

This trial is registered in ClinicalTrials.gov, with the ID number of NCT00830596, registered on January 27, 2009. The first participant was allocated on 30 January 2009 and the final participant was allocated on 17 March 2011.
Ethnobotany, diverse food uses, claimed health benefits and implications on conservation of barley landraces in North Eastern Ethiopia highlands
Authors: Shewayrga Hailemichael , Sopade Peter A
Published: June 2011

Background

Barley is the number one food crop in the highland parts of North Eastern Ethiopia produced by subsistence farmers grown as landraces. Information on the ethnobotany, food utilization and maintenance of barley landraces is valuable to design and plan germplasm conservation strategies as well as to improve food utilization of barley.

Methods

A study, involving field visits and household interviews, was conducted in three administrative zones. Eleven districts from the three zones, five kebeles in each district and five households from each kebele were visited to gather information on the ethnobotany, the utilization of barley and how barley end-uses influence the maintenance of landrace diversity.

Results

According to farmers, barley is the "king of crops" and it is put for diverse uses with more than 20 types of barley dishes and beverages reportedly prepared in the study area. The products are prepared from either boiled/roasted whole grain, raw- and roasted-milled grain, or cracked grain as main, side, ceremonial, and recuperating dishes. The various barley traditional foods have perceived qualities and health benefits by the farmers. Fifteen diverse barley landraces were reported by farmers, and the ethnobotany of the landraces reflects key quantitative and qualitative traits. Some landraces that are preferred for their culinary qualities are being marginalized due to moisture shortage and soil degradation.

Conclusions

Farmers' preference of different landraces for various end-use qualities is one of the important factors that affect the decision process of landraces maintenance, which in turn affect genetic diversity. Further studies on improving maintenance of landraces, developing suitable varieties and improving the food utilization of barley including processing techniques could contribute to food security of the area.
Evidence Coupling Increased Hexosamine Biosynthesis Pathway Activity to Membrane Cholesterol Toxicity and Cortical Filamentous Actin Derangement Contributing to Cellular Insulin Resistance†
Authors: Bhonagiri Padma , Pattar Guruprasad R. , Habegger Kirk M. , McCarthy Alicia M. , Tackett Lixuan , Elmendorf Jeffrey S.
Published: June 2011

Hyperinsulinemia is known to promote the progression/worsening of insulin resistance. Evidence reveals a hidden cost of hyperinsulinemia on plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate (PIP2)-regulated filamentous actin (F-actin) structure, components critical to the normal operation of the insulin-regulated glucose transport system. Here we delineated whether increased glucose flux through the hexosamine biosynthesis pathway (HBP) causes PIP2/F-actin dysregulation and subsequent insulin resistance. Increased glycosylation events were detected in 3T3-L1 adipocytes cultured under conditions closely resembling physiological hyperinsulinemia (5 nm insulin; 12 h) and in cells in which HBP activity was amplified by 2 mm glucosamine (GlcN). Both the physiological hyperinsulinemia and experimental GlcN challenge induced comparable losses of PIP2 and F-actin. In addition to protecting against the insulin-induced membrane/cytoskeletal abnormality and insulin-resistant state, exogenous PIP2 corrected the GlcN-induced insult on these parameters. Moreover, in accordance with HBP flux directly weakening PIP2/F-actin structure, pharmacological inhibition of the rate-limiting HBP enzyme [glutamine-fructose-6-phosphate amidotransferase (GFAT)] restored PIP2-regulated F-actin structure and insulin responsiveness. Conversely, overexpression of GFAT was associated with a loss of detectable PM PIP2 and insulin sensitivity. Even less invasive challenges with glucose, in the absence of insulin, also led to PIP2/F-actin dysregulation. Mechanistically we found that increased HBP activity increased PM cholesterol, the removal of which normalized PIP2/F-actin levels. Accordingly, these data suggest that glucose transporter-4 functionality, dependent on PIP2 and/or F-actin status, can be critically compromised by inappropriate HBP activity. Furthermore, these data are consistent with the PM cholesterol accrual/toxicity as a mechanistic basis of the HBP-induced defects in PIP2/F-actin structure and impaired glucose transporter-4 regulation.
Carotid Artery Dissection-Related Intracranial Aneurysm Development
Authors: Esposito Giuseppe , Sabatino Giovanni , Lofrese Giorgio , Albanese Alessio
Published: June 2011

BACKGROUND AND IMPORTANCE:

We analyzed the physiopathology of the association between cervical artery dissections (CADs), intracranial aneurysms (IAs), and aneurysmal subarachnoid hemorrhage.

CLINICAL PRESENTATION:

A 43-year-old woman presented with diffuse subarachnoid hemorrhage (Fisher 3; Hunt-Hess 1). computed tomography angiography revealed a cervical internal carotid artery dissection and 2 IAs: right paraclinoid and right posterior communicating artery. The patient underwent surgical clipping of the 2 aneurysms. CAD was managed conservatively. Postoperative course was initially uneventful. After 24 hours, digital subtraction angiography (DSA) documented the exclusion of the aneurysms and an improvement of the CAD. After 3 days, the patient's neurological condition suddenly worsened; CT scan documented a subarachnoid rebleeding (Hunt-Hess 4) and DSA revealed the recurrence of CAD and a new right internal carotid artery aneurysm. The patient underwent clipping of the new aneurysm and decompressive craniectomy because of severe brain swelling. Postoperative neurological conditions remained poor. DSA showed the exclusion of the aneurysms and improvement of CAD. Three days later, CT scan performed after a sudden raise in intracranial pressure documented a wide intracerebral hematoma. Computed tomography angiography did not show new vascular malformations. Surgical removal of the hematoma was performed, but poor neurological conditions persisted.

CONCLUSION:

CAD-related hemodynamic changes may play a role in the development of IAs. The presence of IAs must be screened carefully in case of CAD, because the dynamic behavior of CAD definitively increases the risk of IA formation, enlargement, and rupture.
A role for noncanonical microRNAs in the mammalian brain revealed by phenotypic differences in Dgcr8 versus Dicer1 knockouts and small RNA sequencing
Authors: Babiarz Joshua E. , Hsu Ruby , Melton Collin , Thomas Molly , Ullian Erik M. , Blelloch Robert
Published: June 2011

Noncanonical microRNAs (miRNAs) and endogenous small interfering RNAs (endo-siRNAs) are distinct subclasses of small RNAs that bypass the DGCR8/DROSHA Microprocessor but still require DICER1 for their biogenesis. What role, if any, they have in mammals remains unknown. To identify potential functional properties for these subclasses, we compared the phenotypes resulting from conditional deletion of Dgcr8 versus Dicer1 in post-mitotic neurons. The loss of Dicer1 resulted in an earlier lethality, more severe structural abnormalities, and increased apoptosis relative to that from Dgcr8 loss. Deep sequencing of small RNAs from the hippocampus and cortex of the conditional knockouts and control littermates identified multiple noncanonical microRNAs that were expressed at high levels in the brain relative to other tissues, including mirtrons and H/ACA snoRNA-derived small RNAs. In contrast, we found no evidence for endo-siRNAs in the brain. Taken together, our findings provide evidence for a diverse population of highly expressed noncanonical miRNAs that together are likely to play important functional roles in post-mitotic neurons.
RNA molecules with conserved catalytic cores but variable peripheries fold along unique energetically optimized pathways
Authors: Mitra Somdeb , Laederach Alain , Golden Barbara L. , Altman Russ B. , Brenowitz Michael
Published: June 2011

Functional and kinetic constraints must be efficiently balanced during the folding process of all biopolymers. To understand how homologous RNA molecules with different global architectures fold into a common core structure we determined, under identical conditions, the folding mechanisms of three phylogenetically divergent group I intron ribozymes. These ribozymes share a conserved functional core defined by topologically equivalent tertiary motifs but differ in their primary sequence, size, and structural complexity. Time-resolved hydroxyl radical probing of the backbone solvent accessible surface and catalytic activity measurements integrated with structural-kinetic modeling reveal that each ribozyme adopts a unique strategy to attain the conserved functional fold. The folding rates are not dictated by the size or the overall structural complexity, but rather by the strength of the constituent tertiary motifs which, in turn, govern the structure, stability, and lifetime of the folding intermediates. A fundamental general principle of RNA folding emerges from this study: The dominant folding flux always proceeds through an optimally structured kinetic intermediate that has sufficient stability to act as a nucleating scaffold while retaining enough conformational freedom to avoid kinetic trapping. Our results also suggest a potential role of naturally selected peripheral A-minor interactions in balancing RNA structural stability with folding efficiency.
Systematic Review of the Safety of Regular Preventive Asthma Medications During Pregnancy
Authors: Lim Angelina , Stewart Kay , König Kai , George Johnson
Published: June 2011

Objective:

To review the safety of regular preventive asthma medications during pregnancy.

Data Sources:

The following databases were searched from inception to February 2011: Ovid MEDLINE, PubMed, Cochrane Library, EMBASE and CINAHL Plus.

Study Selection and Data Extraction:

The search was limited to human studies published in the English language. Titles of all articles were screened for relevance. Abstracts of relevant articles were scrutinized to confirm relevance before obtaining full text.

Data Synthesis:

Selected articles were read by 2 authors and the accuracy of the data extracted was confirmed.

Results:

Thirty-three articles were included in the final review. Small sample size, missing data, inadequate control for confounding factors, and poor documentation of dosage range were common limitations of the studies reviewed. The use of inhaled corticosteroids, cromolyns, and long-acting β2 agonists during pregnancy was not associated with any particular adverse event, although the fluticasone/salmeterol combination has been associated with poor outcomes in postmarketing studies. Congenital malformations have been reported with leukotriene receptor antagonist exposure during pregnancy, but those women also had exposure to other medications, including oral corticosteroids.

Conclusions:

Some negative outcomes of preventive asthma medications have been reported, although their direct link with medication use is inconclusive. Selection of preventive medications for asthma management during pregnancy should be based on an assessment of the risks and benefits of medication use versus the risks of poorly controlled asthma.
Medication Utilization and Illness Management Study in Nigeria
Authors: Enato Ehijie FO , Sounyo Adebukola A , Einarson Thomas R
Published: June 2011

Background:

Little is known about rates of illness, illness management, or drug utilization in developing countries.

Objective:

To determine patterns of illness and drug utilization in urban and rural households in Nigeria.

Methods:

A survey was developed and validated for data collection. A random sample from some communities in Owan East Local Government Area (LGA) of Edo State, Nigeria, was selected, based on a national population survey, using both the supervisory and enumeration areas of the LGA. We determined the sample size using methods described by Cochran, including 5% precision, 5% α, and allowing for 5% data error. Respondents were queried in face-to-face interviews about illnesses in their households during the previous 2 weeks; demographic information; how they were treated; and where they sought treatment, advice, and medicines. As well, we determined how they kept families well. Descriptive statistics were used to summarize data.

Results:

Out of 549 persons, 497 completed the questionnaires, giving a response rate of 90.5%. Of these respondents, 395 (79.5%) reported 517 illnesses during the previous 2 weeks. The average age of the ill person was 30.6 ± 24.3 years (range 3 months to 95 years). Percentages by age were: infants younger than 1 year 1.0%, children aged 1-17 years 36.0%, and adults aged ≥18 years 63.0%. Average monthly income per household was low (13,247 naira/88.31 US$). Malaria and its symptoms (fever, chills, joint pain, headache, gastrointestinal problems) and upper respiratory symptoms were most common. A majority (44.8%) of the ill persons self-treated, with 93.6% using antibiotic and antimalarial drugs. Among the households surveyed, 42.1% had drugs on hand (average 2.3 ± 1.3, range 1-7, median 2) for disease prevention, and the most used drugs were analgesics (46.2%) and antimalarial drugs (37.3%).

Conclusions:

Illness is frequent in Nigeria and is usually self-treated with antibiotic and antimalarial drugs. Medications were reported to be the most frequently used measure to prevent household illness. The implications of these findings are discussed.
Rapid Onset of Iatrogenic Adrenal Insufficiency in a Patient with Cystic Fibrosis–Related Liver Disease Treated with Inhaled Corticosteroids and a Moderate CYP3A4 Inhibitor
Authors: Hoover Wynton C , Britton LaCrecia J , Gardner Jay , Jackson Tracy , Gutierrez Hector
Published: June 2011

Objective:

To report the rapid onset of adrenal insufficiency and subsequent development of Cushing syndrome precipitated by a CYP3A4-mediated drug-drug interaction that may have been enhanced by the presence of cystic fibrosis (CF)-related liver disease.

Case Summary:

A 9-year-old girl with CF and cirrhosis experienced a decline in lung function that led to a diagnosis of asthma. After initiation of asthma therapy with inhaled fluticasone 110 μg/actuation, the patient experienced improvement in lung function to baseline. Seven weeks after the initiation of inhaled fluticasone, she developed vaginal candidiasis and was prescribed fluconazole 100 mg/day, a CYP3A4 inhibitor. Three days after starting fluconazole, she developed polyuria and polydipsia and was found to have severe hyperglycemia, which led to the diagnosis of Cushing syndrome. Fluticasone was discontinued, and the patient's adrenal function normalized.

Discussion:

Patients with CF are commonly prescribed complex medication regimens that may affect drug metabolism. CYP3A4 inhibitors may significantly decrease metabolic clearance in patients using chronic inhaled corticosteroids. Iatrogenic Cushing syndrome has been reported in patients with CF treated concomitantly, and for extended duration, with inhaled corticosteroids and CYP3A4 inhibitors. This case highlights rapid onset of adrenal insufficiency in a patient with CF-related liver disease treated briefly with a moderate CYP3A4 inhibitor. Use of the Horn drug interaction probability scale indicates that the interaction between fluticasone and fluconazole was probable.

Conclusions:

CYP3A4-mediated drug interactions represent a significant risk in patients treated with long-term inhaled corticosteroids. The presence of clinically significant CF-related liver disease may enhance this risk.
Dofetilide Dose Calculation Errors in Elderly Associated with Use of the Modification of Diet in Renal Disease Equation
Authors: Denetclaw Tina H , Oshima Nancy , Dowling Thomas C
Published: June 2011

Objective:

To report 2 cases of drug dosage calculation errors that occurred when the Modification of Diet in Renal Disease (MDRD) equation was used for initiating drug therapy with dofetilide in eiderly patients with chronic kidney disease.

Case Summary:

An 83-year-old woman and a 92-year-old man were admitted for dofetilide treatment initiation and cardioversion for atrial fibrillation. The estimated glomerular filtration rate (eGFR) determined with use of the MDRD equation was significantly higher than the estimated creatinine clearance (eCrCl) determined with use of the Cockcroft-Gault equation for both cases (85 vs 43 mL/min for the man and 40 vs 24 mL/min for the woman). Initial dofetilide dosages calculated by the MDRD equation were 2-fold higher than those calculated by eCrCl in both cases. Initiation of dose based on the MDRD in the first patient ted to a 32% increase in the QTc interval from baseline. Dofetilide therapy was adjusted for QTc interval prolongation based on eCrCl and reinitiated at a lower dose, and the patient did not develop further significant increases in the QTc interval. In the second patient, the lower dose based on eCrCl was initiated and the QTc interval remained within an acceptable range.

Discussion:

The initial dosing of dofetilide is based on eCrCl as specified by the drug manufacturer. Recent widespread use and automated reporting of the eGFR by clinical laboratories has tempted some clinicians to consider using eGFR for calculating drug doses. However, recent data suggest that the eGFR, calculated by the MDRD equation, consistently overestimates eCrCl, leading to dose discrepancies, particularly in the elderly. The cases reported here illustrate the drug dose calculation errors that may occur when using the MDRD equation for initiating doses of dofetilide.

Conclusions:

Use of the eGFR or MDRD equation for calculation of doses in renal dysfunction has not been validated, and significant drug dose errors have been reported. The use of eGFR to calculate doses of dofetilide should be avoided.
Interoperabilität von Manufacturing Execution Systems (MES)
Authors: Schleipen Miriam , Münnemann Ansgar , Sauer Olaf
Published: June 2011

Informationstechnik befähigt moderne Produktionssysteme dazu, sich entsprechend der Marktanforderungen zu wandeln, im Netzwerk zu arbeiten und in Echtzeit Informationen auszutauschen. Die Integration vorhandener und neuer IT-Systeme spielt dabei eine immer bedeutendere Rolle, um Geschäftsprozesse durchgängig zu unterstützen. Basis dieser Integration sind Mechanismen zur Interoperabilität, von denen einige in diesem Heft vorgestellt werden. Die Autoren dieses Betrags beschreiben die Dimensionen der Interoperabilität auf der Fertigungsleitebene.
Diabetes and risk of tumors: oncologic considerations
Authors: Rosta András
Published: June 2011

Type 2 diabetes mellitus and malignant tumors are frequent diseases worldwide. The incidence of these two diseases is growing continuously and causes serious health care problem. Population based epidemiologic studies show that the coexistence of type 2 diabetes and malignant tumors is more frequent than expected by the age-corrected incidence and prevalence of each disease. Epidemiologic studies and meta-analyses show that type 2 diabetes increases the risk and tumor specific mortality of certain cancers. The overlapping risk factors of the diseases suggest a relationship between type 2 diabetes and malignant tumors, with a significant role of obesity as a major risk factor. In the pathophysiology of type 2 diabetes there are several biological processes, which may explain the higher cancer risk in type 2 diabetes. In vitro experiments, and in vivo animal studies show that the mitotic effect of hyperinsulinemia plays an important role in the relationship of cancer and type 2 diabetes mellitus. Recent studies show that the different treatment modalities, antidiabetic drugs and their combinations used for the treatment of type 2 diabetes can modify cancer risk. The majority of the data show that metformin therapy decreases, while insulin secretagog drugs slightly increase the risk of certain types of cancers in type 2 diabetes. Metformin can decrease cell proliferation and induce apoptosis in certain cancer cell lines. Endogenous and exogenous (therapy induced) hyperinsulinemia may be mitogenic and may increase the risk of cancer in type 2 diabetes. Human studies showed that the analogue insulin glargin increases the risk of certain cancers. As a result of conceptual weaknesses in study design, data collection, and statistical methods the results of these studies are questionable. According to present knowledge, obtaining and maintaining optimal metabolic target values with the appropriate choice of treatment modality is the aim of treatment in type 2 diabetes. Presently, study results showing elevated mitogenic potential with some antidiabetic treatment modalities are not taken into account, when considering the choice of antidiabetic treatment in type 2 diabetic patients. In the care of patients with increased cancer risk, oncologic considerations should be taken into account. Well designed, prospective, clinical studies would be necessary to demonstrate the possible correlation between treatment modalities of type 2 diabetes and change of cancer risk in type 2 diabetes mellitus. Orv. Hetil., 2011, 152, 1144–1155.
Secondary aggregate from waste treated with carbon dioxide
Authors: Gunning Peter J. , Hills Colin D. , Antemir Aurora , Carey Paula J.
Published: June 2011

Secondary aggregate can be made from industrial waste by treatment with carbon dioxide gas (accelerated carbonation). Trials were conducted on bauxite waste, biomass ashes, metal dusts, quarry fines, steel-making waste, and the ashes arising from municipal incineration, paper recycling, sewage sludge incineration, and coal fired power stations. The wastes were formed into pellets using a combined pelletising and accelerated carbonation process with patent pending. The manufactured pellets conformed to the bulk density requirements for lightweight aggregate specified by British Standard. Specification for lightweight aggregate is limited, and two commercial lightweight aggregates were tested alongside the manufactured pellets for comparison. Compressive strength, water absorption and apparent density of the materials were comparable to that of the commercial aggregate. Furthermore, the finished product contained up to 11% of its own weight in carbon dioxide gas, permanently bound as solid minerals. In a series of on-site pilot scale demonstrations, aggregates have been produced in bulk and used in commercial product trials. The aggregates produced by accelerated carbonation appear to be suitable for use in a wide range of applications including concrete, construction blocks, and substrates for green roofs.
Enhancing urban sustainability using 3D visualisation
Authors: Isaacs John P. , Falconer Ruth E. , Gilmour Daniel J. , Blackwood David J.
Published: June 2011

This paper presents the results of an initial application of a prototype simulation and visualisation tool (S-City VT) that was developed to enable all stakeholders, regardless of background or experience, to understand, interact with and influence decisions made on the sustainability of urban design. The tool takes the unique approach of combining three-dimensional (3D) interactive and immersive technologies with computer modelling to present stakeholders with an interactive virtual development. Use of outputs from the model and a 3D visualisation of the development can help decision-makers judge the relative sustainability of different aspects of a development. The tool employs a number of different methods to present sustainability results to stakeholders. Initial tests on the effectiveness of the different visualisation methods are described and discussed. The paper then presents some conclusions on further development and application of the tool to model and visualise possible results of decisions made at different stages of the project.
Mixing zone regulation for effluent discharges into EU waters
Authors: Bleninger Tobias , Jirka Gerhard H.
Published: June 2011

Environmental standards and their implementation in different countries are reviewed for point source discharges into surface waters. The paper focuses on the analysis of existing mixing zone regulations and recommends procedures to develop and manage mixing zone definitions as required by recent amendments of the ‘combined approach' of the European Community water framework directive. The review shows that only a few mixing zone regulations exist in the European Union member countries, and that some effluent types, such as desalination brine discharges, and some discharge technologies, such as river diffusers, are not yet considered. The paper discusses those two issues in detail. First, by analysing desalination plant discharge characteristics and recommending mixing zone regulations for such multi-component and multi-process discharges. Second, by presenting river diffuser discharge technologies and procedures for demonstrating compliance of discharges that employ these technologies.
Methodology to estimate hydraulic efficiency of drain inlets
Authors: Gómez Manuel , Russo Beniamino
Published: June 2011

Effective drainage of roadway pavements is essential to the maintenance of street service level and traffic safety. Storm drainage inlets are used to collect urban runoff and discharge it to an underground sewer system. Inlet efficiency governs both the rate of water removal from the gutter and the amount of water that can enter into the storm sewer system and it depends upon inlet and road geometry as well as the hydraulics of the approaching flow. In the present study a methodology to assess inlet efficiency from experimental tests is presented. An empirical relationship is proposed to obtain the hydraulic efficiency as a function of inlet and street flow characteristics. According to this procedure inlet efficiency could be estimated on the basis of grate geometry and the hydraulics of the approaching flow. The procedure was compared with other methodologies proposed in recent years in the field of urban hydrology.
From Alleviation to Eradication: A Reassessment of Modernization, Market‐Based, and Communitarian Solutions to Global Poverty
Authors: Roxas Sixto K. , Ungson Gerardo R.
Published: June 2011

Economic growth and modernization are widely held to be the antidote to global poverty, but what if they actually contribute to the problem? A parallel question is whether poverty alleviation and eradication that have been used interchangeably are, in fact, the same. On the first question, extant theories, ranging from modernization to dependency, are limited in delivering a poverty‐free world, and, in some cases, have been more the problem than the solution. On the second question, poverty alleviation and eradication derive from different theoretical interests. Alleviation measures, such as market‐based solutions, are limited by profit‐maximizing objectives of enterprise. In contrast, poverty eradication entails a radical transformation of the poor to become self‐reliant. To meet this requirement, communitarian initiatives anchored on a different valuation, management, and organizational systems are proposed.
Recurrent Johanson-Blizzard Syndrome in a Triplet Pregnancy Complicated by Urethral Obstruction Sequence: A Clinical, Molecular, and Immunohistochemical Approach
Authors: Schoner Katharina , Fritz Barbara , Huelskamp Georg , Louwen Frank , Zenker Martin , Moll Roland , Rehder Helga
Published: June 2011

We report on a triplet pregnancy of consanguineous parents with one fetus being affected by recurrent Johanson-Blizzard syndrome (JBS). At autopsy in the 35th gestational week, the affected triplet presented with an especially severe and lethal manifestation of the disorder as compared to his elder affected brother and to cases in the literature, thus exemplifying great interfamilial and intrafamilial phenotypic variability. Arhinencephaly and cystic renal dysplasia associated with urethral obstruction sequence were features not described previously in the literature. In addition to the lack of exocrine acini as the characteristic feature of JBS, the pancreas revealed a resorptive inflammatory reaction with infiltration by eosinophilic granulocytes that focally dispersed onto islets of Langerhans, thus favoring a progressive destructive rather than primary dysplastic process and possibly explaining the occurrence of diabetes mellitus in later life. JBS maps to chromosome 15q15-q21.1 and is associated with mutations in the UBR1 gene. Testing the fetus and the affected sibling revealed a homozygous truncating mutation in UBR1. The resulting absence of the UBR1 protein was confirmed by Western blot. Immunohistochemical staining using a commercial anti-UBR1 antibody demonstrated staining, presumably artifactual. This finding suggests that, until an appropriately validated antibody has been identified, this modality should not be utilized for diagnosis or confirmation of this disorder.
Localization of energy for a regular black hole solution in an asymptotically de Sitter spacetime geometry
Authors: Radinschi Irina , Grammenos Theophanes , Spanou Andromahi
Published: June 2011

The energy and momentum distributions of a regular black hole in a four-dimensional, asymptotically de Sitter spacetime geometry are computed, whereby the Einstein, Landau-Lifshitz, Weinberg and Møller energy-momentum complexes are utilized. It is found, for all prescriptions applied, that the momentum distribution vanishes, while the energy distribution depends on the mass parameter M, the electric charge Q, and the cosmological constant Λ. In addition, various limiting cases are discussed.