bluuebunny/crossref_metadata_2025 huggingface dataset:
Two EguCBF1 genes overexpressed in Eucalyptus display a different impact on stress tolerance and plant development
Authors: Navarro Marie , Ayax Céline , Martinez Yves , Laur Joan , El Kayal Walid , Marque Christiane , Teulières Chantal
Published: May 2010

Two C‐repeat binding factor genes (EguCBF1a/b), isolated from E. gunnii and differentially cold‐regulated, were constitutively overexpressed in a cold‐sensitive Eucalyptus hybrid. In addition to the expected improvement on freezing tolerance, some resulting transgenic lines (EguCBF1a‐OE and EguCBF1b‐OE) exhibited a decrease in stomata density and an over‐accumulation of anthocyanins also observed to a lesser extent in a cold‐acclimated control plant. Given that the induction of five putative CBF target genes was observed in CBF‐overexpressing lines as well as in the cold‐acclimated control line, these phenotypes might be related to cold acclimation. In comparison with the control plant, the most altered transgenic line (EguCBF1a‐OE A1 line), exhibited reduced growth and better water retention capacity. This modified phenotype includes reduced leaf area and thickness associated with a decrease in cell size, as well as a higher oil gland density and a wax deposition on the cuticle. Surprisingly, the EguCBF1b‐OE B9 line, with a level of transgene expression equivalent to the A1 line, showed a less marked phenotype, suggesting a difference in transactivation efficiency between EguCBF1A and B factors. The features of these transgenic lines provide the first signs of adaptive mechanisms controlled by CBF transcription factors in an evergreen broad‐leaved tree. These data also open new prospects towards genetic improvement on Eucalyptus for freezing tolerance.
Expression of the P1B‐type ATPase AtHMA4 in tobacco modifies Zn and Cd root to shoot partitioning and metal tolerancea
Authors: Siemianowski Oskar , Mills Rebecca Fay , Williams Lorraine Elizabeth , Antosiewicz Danuta Maria
Published: May 2010

Genetic modification of Zn/Cd accumulation in roots and shoots for biofortification or phytoremediation is a focus of this manuscript. We expressed AtHMA4 (a P1BATPase involved in Zn and Cd transport), AtHMA4‐trunc (lacking the C‐terminal region) and AtHMA4‐C terminus (the C‐terminal region alone) in tobacco under the CaMV 35S constitutive promoter and examined accumulation and tolerance to both metals. Expression of AtHMA4 enhanced Zn translocation to the shoots only at 10 μm Zn but not at 0.5, 100 and 200 μm Zn. AtHMA4‐trunc did not show this effect and instead reduced Zn translocation to the shoot. AtHMA4‐expressing plants showed a decrease in cadmium uptake when exposed to 0.25 and 5 μm Cd; this was also observed with AtHMA4‐trunc‐expressing lines, although to a lesser extent. Expression of AtHMA4‐C‐terminus containing potential metal binding sites increased cadmium and zinc concentrations in roots and shoots up to fourfold. We have demonstrated that both AtHMA4 and AtHMA4 C‐terminus could be candidate genes/sequences for engineering modifications of zinc and cadmium root/shoot partitioning. However, the phenotype of transformants depended on the external metal concentration, thus it might be difficult to engineer a plant displaying the desired metal‐related phenotype when grown under varying conditions of metal supply.
Expression of an Arabidopsis vacuolar H+‐pyrophosphatase gene (AVP1) in cotton improves drought‐ and salt tolerance and increases fibre yield in the field conditions
Authors: Pasapula Vijaya , Shen Guoxin , Kuppu Sundaram , Paez‐Valencia Julio , Mendoza Marisol , Hou Pei , Chen Jian , Qiu Xiaoyun , Zhu Longfu , Zhang Xianlong , Auld Dick , Blumwald Eduardo , Zhang Hong , Gaxiola Roberto , Payton Paxton
Published: May 2010

The Arabidopsis gene AVP1 encodes a vacuolar pyrophosphatase that functions as a proton pump on the vacuolar membrane. Overexpression of AVP1 in Arabidopsis, tomato and rice enhances plant performance under salt and drought stress conditions, because up‐regulation of the type I H+‐PPase from Arabidopsis may result in a higher proton electrochemical gradient, which facilitates enhanced sequestering of ions and sugars into the vacuole, reducing water potential and resulting in increased drought‐ and salt tolerance when compared to wild‐type plants. Furthermore, overexpression of AVP1 stimulates auxin transport in the root system and leads to larger root systems, which helps transgenic plants absorb water more efficiently under drought conditions. Using the same approach, AVP1‐expressing cotton plants were created and tested for their performance under high‐salt and reduced irrigation conditions. The AVP1‐expressing cotton plants showed more vigorous growth than wild‐type plants in the presence of 200 mm NaCl under hydroponic growth conditions. The soil‐grown AVP1‐expressing cotton plants also displayed significantly improved tolerance to both drought and salt stresses in greenhouse conditions. Furthermore, the fibre yield of AVP1‐expressing cotton plants is at least 20% higher than that of wild‐type plants under dry‐land conditions in the field. This research indicates that AVP1 has the potential to be used for improving crop’s drought‐ and salt tolerance in areas where water and salinity are limiting factors for agricultural productivity.
Prevalence of obesity in Dakar
Authors: Macia E. , Duboz P. , Gueye L.
Published: May 2010

The present study is to our knowledge the first to evaluate the prevalence of obesity among both men and women in Dakar. It was carried out on a sample of 600 dwellers of the Senegalese capital. The prevalence of general obesity is 8.3%, and that of overweight is 22.3%. The underweight rate remains high, given that 12.3% of the adults in this sample show a body mass index (BMI) of <18.5 kg/m2. The prevalence of central obesity is 41.2% according to waist to hip ratio (WHR), and 21.2% according to waist circumference (WC). These figures mask considerable differences between men and women and between generations. For instance, women are often more obese than men, whether it is a question of general obesity (13% and 3.9% respectively) or central obesity (37.5% and 5.5% by WC respectively). Moreover, prevalence of general and central obesity rise drastically with age, irrespective of gender. Thus, in addition to combating infectious disease and undernutrition, Senegal must now face problems associated with overweight and obesity.
WHEN CONCRETIZED EMOTION‐BELIEF COMPLEXES DERAIL DECISION‐MAKING CAPACITY
Authors: HALPERN JODI
Published: May 2010

There is an important gap in philosophical, clinical and bioethical conceptions of decision‐making capacity. These fields recognize that when traumatic life circumstances occur, people not only feel afraid and demoralized, but may develop catastrophic thinking and other beliefs that can lead to poor judgment. Yet there has been no articulation of the ways in which such beliefs may actually derail decision‐making capacity. In particular, certain emotionally grounded beliefs are systematically unresponsive to evidence, and this can block the ability to deliberate about alternatives. People who meet medico‐legal criteria for decision‐making capacity can react to health and personal crises with such capacity‐derailing reactions. One aspect of this is that a person who is otherwise cognitively intact may be unable to appreciate her own future quality of life while in this complex state of mind. This raises troubling ethical challenges. We cannot rely on the current standard assessment of cognition to determine decisional rights in medical and other settings. We need to understand better how emotionally grounded beliefs interfere with decision‐making capacity, in order to identify when caregivers have an obligation to intervene.
WHICH BENEFITS OF RESEARCH PARTICIPATION COUNT AS ‘DIRECT’?
Authors: FRIEDMAN ALEXANDER , ROBBINS EMILY , WENDLER DAVID
Published: May 2010

It is widely held that individuals who are unable to provide informed consent should be enrolled in clinical research only when the risks are low, or the research offers them the prospect of direct benefit. There is now a rich literature on when the risks of clinical research are low enough to enroll individuals who cannot consent. Much less attention has focused on which benefits of research participation count as ‘direct’, and the few existing accounts disagree over how this crucial concept should be defined. This disagreement raises concern over whether those who cannot consent, including children and adults with severe dementia, are being adequately protected. The present paper attempts to address this concern by considering first what additional protections are needed for these vulnerable individuals. This analysis suggests that the extant definitions of direct benefits either provide insufficient protection for research subjects or pose excessive obstacles to appropriate research. This analysis also points to a modified definition of direct benefits with the potential to avoid these two extremes, protecting individuals who cannot consent without blocking appropriate research.
The para‐aortic ridge plays a key role in the formation of the renal, adrenal and gonadal vascular systems
Authors: Isogai Sumio , Horiguchi Mayuko , Hitomi Jiro
Published: May 2010

Renal, adrenal, gonadal, ureteral and inferior phrenic arteries vary in their level of origin and in their calibre, number and precise anatomical relationship to other structures. Studies of the origin and early development of these arteries have evoked sharp disputes. The ladder theory of Felix, which states that ‘All the mesonephric arteries may persist; from them are formed the phrenic, suprarenal, renal and internal spermatic arteries’ has been generally quoted in the anatomical textbooks without rigorous verification for 100 years. In this study, we re‐examined this theory by performing micro‐injection of dye and resin into rat (Rattus norvegicus) embryos. Our results revealed that most of the mesonephric arteries had degenerated before the metanephros started its ascent. The definitive renal, adrenal, gonadal, ureteral and inferior phrenic arteries appeared as new branches from the gonadal artery and/or directly from the abdominal aorta to the para‐aortic ridge. Coincidental to this, the anatomical architecture of the inter‐renal vascular cage, which consists of the interlobar and arcuate arteries and their collateral veins, was completed within the developing metanephros. We demonstrated that the delicate renal vascular cage switched from the primary renal artery to the definitive renal artery and that the route of venous drainage changed from the posterior cardinal vein to the inferior (caudal) vena cava.
Trends in adolescent emotional problems in England: a comparison of two national cohorts twenty years apart
Authors: Collishaw Stephan , Maughan Barbara , Natarajan Lucy , Pickles Andrew
Published: May 2010

Background: Evidence about trends in adolescent emotional problems (depression and anxiety) is inconclusive, because few studies have used comparable measures and samples at different points in time. We compared rates of adolescent emotional problems in two nationally representative English samples of youth 20 years apart using identical symptom screens in each survey.

Methods: Nationally representative community samples of 16–17‐year‐olds living in England in 1986 and 2006 were compared. In 1986, 4524 adolescents and 7120 parents of young people participated in the age‐16‐year follow‐up of the 1970 British Cohort Study. In 2006, 719 adolescents and 734 parents participated in a follow‐up of children sampled from the 2002/2003 Health Surveys for England. Adolescents completed the Malaise Inventory and 12‐item General Health Questionnaire. Parents completed the Rutter‐A scale. Individual symptoms of depression and anxiety were coded combining across relevant questionnaire items. Young people also reported frequency of feeling anxious or depressed.

Results: Youth‐ and parent‐reported emotional problems were more prevalent in 2006 for girls, and rates of parent‐reported problems increased for boys. Twice as many young people reported frequent feelings of depression or anxiety in 2006 as in 1986. Some symptoms showed marked change in prevalence over time (e.g., worry, irritability, fatigue), whereas others showed no change (e.g., loss of enjoyment, worthlessness). There was no evidence of differential trends in emotional problems for young people from socially advantaged and disadvantaged or intact and non‐intact families. Changes in family structure and ethnic composition did not account for trends in youth emotional problems.

Conclusions: The study provides evidence for a substantial increase in adolescent emotional problems in England over recent decades, especially among girls.
Viability of microencapsulated Bifidobacterium animalis ssp. lactis BB12 in kefir during refrigerated storage
Authors: GONZÁLEZ‐SÁNCHEZ FERNANDO , AZAOLA ALEJANDRO , GUTIÉRREZ‐LÓPEZ GUSTAVO F , HERNÁNDEZ‐SÁNCHEZ HUMBERTO
Published: May 2010

The viability of free and immobilized cells of  Bifidobacterium animalis ssp. lactis BB12 incorporated into kefir was studied for 28 days during refrigerated storage. The immobilized bifidobacteria were added directly to previously prepared kefir. Titratable acidity, pH, ethanol, fat, protein and lactose were evaluated in the kefir with bifidobacteria after the storage. The survival of the free and microencapsulated bifidobacteria was evaluated during the storage period and in simulated gastric juice. The pH of kefirs ranged from 4.3 to 4.6. Encapsulation improved significantly the survival of bifidobacteria during exposure to nisin, during the storage period and in simulated gastric juice.
Do tubers contain function? Resection of epileptogenic foci in perirolandic cortex in children with tuberous sclerosis complex
Authors: Moshel Yaron A. , Elliott Robert , Teutonico Federica , Sellin Jonathan , Carlson Chad , Devinsky Orrin , Weiner Howard L.
Published: May 2010

Summary

Purpose: Surgical resection of single, dominant, epileptogenic lesions in patients with tuberous sclerosis complex (TSC) is now accepted as an effective therapy. However, patients with symptomatic tubers in eloquent cortex are sometimes not offered surgery because of the concern for postoperative neurologic morbidity. In this study, we examine our results in children undergoing surgery for resection of tubers and associated seizure foci in rolandic and perirolandic cortex.

Methods: Between 1998 and 2008, 52 pediatric patients (mean age 4 years) with TSC underwent epilepsy surgery at the NYU Comprehensive Epilepsy Center. Fifteen of these patients underwent multistage surgery for invasive mapping of seizure foci and surrounding functional cortex followed by resection of tubers/seizure foci in or near rolandic cortex. Data were retrospectively collected and neurologic outcomes were tabulated.

Results: Postoperatively, four patients (27%) had either new hemiparesis or worsening of a preexisting hemiparesis. However, all patients were back to their neurologic baselines at 3‐month follow‐up, yielding no permanent postoperative deficits. The modified Engel outcome was class I in nine patients (60%), class II in three patients (20%), class III in two patients (13%), and class IV in one patient (7%) after 40 months mean follow‐up.

Discussion: Surgical resection of tubers and associated epileptogenic foci in rolandic and perirolandic cortex in children with TSC is feasible, with low neurologic morbidity, and yields good seizure control. These results suggest that tubers and perituberal epileptogenic foci can be safely resected even in eloquent regions because of reorganization of functional cortex or because these lesions contain no neurologic function.
Anticonvulsant and proconvulsant actions of 2‐deoxy‐d‐glucose
Authors: Gasior Maciej , Yankura Jessica , Hartman Adam L. , French Amy , Rogawski Michael A.
Published: May 2010

Purpose: 2‐Deoxy‐d‐glucose (2‐DG), a glucose analog that accumulates in cells and interferes with carbohydrate metabolism by inhibiting glycolytic enzymes, has anticonvulsant actions. Recognizing that severe glucose deprivation can induce seizures, we sought to determine whether acute treatment with 2‐DG can promote seizure susceptibility by assessing its effects on seizure threshold. For comparison, we studied 3‐methyl‐glucose (3‐MG), which like 2‐DG accumulates in cells and reduces glucose uptake, but does not inhibit glycolysis.

Methods: Mice were treated with 2‐DG or 3‐MG and the seizure threshold determined in the 6‐Hz test, the mouse electroshock seizure threshold (MEST) test, and the intravenous pentylenetetrazol (i.v. PTZ) or kainic acid (i.v. KA) seizure threshold tests. 2‐DG was also tested in fully amygdala‐kindled rats.

Results: 2‐DG (125–500 mg/kg, i.p., 30 min before testing) significantly elevated the seizure threshold in the 6‐Hz seizure test. 2‐DG (250–500 mg/kg) decreased the threshold in the MEST and i.v. PTZ and i.v. KA tests. 3‐MG had no effect on seizure threshold in the 6‐Hz test but, like 2‐DG, decreased seizure threshold in the i.v. PTZ test. 2‐DG (250 and 500 mg/kg, i.p., 30 min before testing) had no effect on amygdala‐kindled seizures.

Conclusions: Although 2‐DG protects against seizures in the 6‐Hz seizure test, it promotes seizures in some other models. The proconvulsant action may relate to reduced glucose uptake, whereas the anticonvulsant action may require inhibition of glycolysis and shunting of glucose metabolism through the pentose phosphate pathway.
Is the Full Version of the AUDIT Really Necessary? Study of the Validity and Internal Construct of Its Abbreviated Versions
Authors: Meneses‐Gaya Carolina , Zuardi Antonio W. , Loureiro Sonia R. , Hallak Jaime E. C. , Trzesniak Clarissa , De Azevedo Marques João M. , Machado‐de‐Sousa João P. , Chagas Marcos H. N. , Souza Roberto M. , Crippa José A. S.
Published: May 2010

Background:  This study was aimed at assessing the psychometric qualities of the abbreviated versions of the Alcohol Use Disorders Identification Test (AUDIT‐3, AUDIT‐4, AUDIT‐C, AUDIT‐PC, AUDIT‐QF, FAST, and Five‐Shot) and at comparing them to the 10‐item AUDIT and the CAGE in 2 samples of Brazilian adults.

Methods:  The validity and internal consistency of the scales were assessed in a sample of 530 subjects attended at an emergency department and at a Psychosocial Care Center for Alcohol and Drugs. The Structured Clinical Interview for DSM‐IV was used as the diagnostic comparative measure for the predictive validity assessment. The concurrent validity between the scales was analyzed by means of Pearson’s correlation coefficient.

Results:  The assessment of the predictive validity of the abbreviated versions showed high sensitivity (of 0.78 to 0.96) and specificity (of 0.74 to 0.94) indices, with areas under the curve as elevated as those of the AUDIT (0.89 and 0.92 to screen for abuse and 0.93 and 0.95 in the screening of dependence). The CAGE presented lower indices: 0.81 for abuse and 0.87 for dependence. The analysis of the internal consistency of the AUDIT and its versions exhibited Cronbach’s alpha coefficients between 0.83 and 0.94, while the coefficient for the CAGE was 0.78. Significant correlations were found between the 10‐item AUDIT and its versions, ranging from 0.91 to 0.99. Again, the results for the CAGE were satisfactory (0.77), although inferior to the other instruments.

Conclusions:  The results obtained in this study confirm the validity of the abbreviated versions of the AUDIT for the screening of alcohol use disorders and show that their psychometric properties are as satisfactory as those of the 10‐item AUDIT and the CAGE.
11. Lumbosacral Radicular Pain
Authors: Van Boxem Koen , Cheng Jianguo , Patijn Jacob , Van Kleef Maarten , Lataster Arno , Mekhail Nagy , Van Zundert Jan
Published: May 2010

Lumbosacral radicular pain is characterized by a radiating pain in one or more lumbar or sacral dermatomes; it may or may not be accompanied by other radicular irritation symptoms and/or symptoms of decreased function. The annual prevalence in the general population, described as low back pain with leg pain traveling below the knee, varied from 9.9% to 25%, which means that it is presumably the most commonly occurring form of neuropathic pain.

The patient's history may give a suggestion of lumbosacral radicular pain. The best known clinical investigation is the straight‐leg raising test. Final diagnosis is made based on a combination of clinical examination and potentially additional tests. Medical imaging studies are indicated to exclude possible serious pathologies and to confirm the affected level in patients suffering lumbosacral radicular pain for longer than 3 months. Magnetic resonance imaging is preferred. Selective diagnostic blocks help confirming the affected level.

There is controversy concerning the effectiveness of conservative management (physical therapy, exercise) and pharmacological treatment.

When conservative treatment fails, in subacute lumbosacral radicular pain under the level L3 as the result of a contained herniation, transforaminal corticosteroid administration is recommended (2 B+). In chronic lumbosacral radicular pain, (pulsed) radiofrequency treatment adjacent to the spinal ganglion (DRG) can be considered (2 C+). For refractory lumbosacral radicular pain, adhesiolysis and epiduroscopy can be considered (2 B±), preferentially study‐related.

In patients with a therapy‐resistant radicular pain in the context of a Failed Back Surgery Syndrome, spinal cord stimulation is recommended (2 A+). This treatment should be performed in specialized centers.
Parcs nationaux et populations locales dans l’ouest canadien : de l’exclusion à la participation
Authors: HÉRITIER STÉPHANE
Published: May 2010

Les parcs nationaux du Canada sont réputés pour avoir été développés afin de protéger des espaces de nature destinés ‘au bénéfice et à la jouissance du peuple canadien’. L’histoire des parcs nationaux témoigne de l’évolution du rapport à la nature, d’une approche fonctionnelle à une approche environnementale fondée sur la protection des écosystèmes et de la biodiversité. Les quatre parcs nationaux des lacs Waterton, de Banff et de Wood Buffalo en Alberta, ainsi que celui de Kootenay en Colombie‐Britannique (quatre des quatorze parcs créés avant 1930, année de la Première loi sur les Parcs Nationaux) sont étudiés afin de cerner les évolutions de l’exclusion puis de l’implication progressive des populations locales dans la gestion des parcs. L’inclusion des populations locales et les processus de gestion collaborative ont été développés dans les parcs nationaux du Nord du Canada au milieu des années 1980. Ces pratiques ont été considérées comme des réussites dans ces régions du pays, mais la situation s’avère très différente dans le sud du pays, notamment dans les parcs créés avant 1930. Mais les choses ont changé depuis que la culture et les droits autochtones ont été reconnus dans des jugements rendus par la Cour Suprême du Canada et dans la Loi constitutionnelle. Dans les quatre parcs servant de support à cette étude, l’implication des communautés locales et le développement de la participation s’avèrent assez lents. Des actions telles que des tables rondes et la participation à l’élaboration de sites d’interprétation et d’expositions sur l’histoire des Autochtones apparaissent comme les prémices d’une coopération encore à construire.
Metropolis on the margins: talent attraction and retention to the St. John's city‐region
Authors: LEPAWSKY JOSH , PHAN CHRYSTAL , GREENWOOD ROB
Published: May 2010

The objective of this research is to examine the factors that influence the attraction and retention of creative and highly educated workers in a small‐sized Canadian city. The study examines two hypotheses: that the social dynamics of city‐regions constitute the foundations of economic success in the global economy; and, that talented, highly educated individuals will be attracted to those city‐regions that offer a richness of employment opportunity, a high quality of life, a critical mass of cultural activity and social diversity. The hypotheses are explored through in‐depth interviews with creative and highly educated workers, employers and intermediary organizations. The evidence from the interviews suggests mixed support for the hypotheses. In view of these findings, we contend that the specificities of place must be more carefully theorized in the creative class literature and be more carefully considered by policy‐makers designing policies directed towards attracting and retaining talented and highly educated workers.
Body Height Estimation from Head and Face Dimensions: A Different Method*
Authors: Pelin Can , Zağyapan Ragıba , Yazıcı Canan , Kürkçüoğlu Ayla
Published: May 2010

Abstract:  As there are cases brought for forensic examination where only the craniofacial region is available, estimation of stature from craniofacial dimensions is without doubt important in forensic cases. The study presented here attempts to estimate stature from craniofacial dimensions in the Turkish population. In the second phase of the study, the correlations between craniofacial dimensions and stature were also evaluated according to different head and face types. All measurements were taken from 286 healthy males with a mean age of 22.71 ± 4.86 years. The sample was then reclassified according to different head and face indexes. For the whole sample, correlation coefficients were low, changing only between 0.012 and 0.229. Thus, no significant increase in correlation coefficients was observed after the samples had been reevaluated according to different head and face types. As a conclusion, craniofacial dimensions are not good predictors for body height for the Turkish population.
Therapeutic approaches for newly diagnosed multiple myeloma patients in the era of novel drugs
Authors: Morabito Fortunato , Gentile Massimo , Mazzone Carla , Bringhen Sara , Vigna Ernesto , Lucia Eugenio , Recchia Anna G. , Raimondo Francesco D. , Musto Pellegrino , Palumbo Antonio
Published: May 2010

The treatment of newly diagnosed multiple myeloma (MM) has evolved rapidly over recent years. The availability of new effective drugs with novel mechanisms of action, such as thalidomide, lenalidomide and bortezomib in the last decade, has resulted in a new scenario expected to impact favorably on the outcome of patients with MM. The introduction of new drugs in the treatment of patients eligible for autologous stem cell transplantation (ASCT) has allowed for a significant increase of complete response rate with a positive impact on progression‐free survival. In patients not eligible for ASCT, randomized trials have shown that both thalidomide and bortezomib when combined with melphalan and prednisone (MP) are superior to MP and are now considered the standard of care. Ongoing trials are assessing whether MP plus lenalidomide or the combination of lenalidomide plus dexamethasone should be considered an attractive treatment option, while additional studies are needed to determine the role of routine maintenance or consolidation therapy with these new drugs. This new therapeutic armamentarium in light of adequate prophylaxis and supportive care allows clinicians to greatly improve the survival perspectives for both young and elderly patients. In this review, we report updated data for the front‐line therapy of MM, examining the role of new drugs either when administered as induction therapy before ASCT in younger patients or when combined with alkylating agents for the treatment of older patients. The most relevant articles on therapy of MM published from November 1982 to January 2010 (selected through PubMed), and recent meeting abstracts were used as sources for this review.
Oral D‐penicillamine for the prevention of retinopathy of prematurity in very low birth weight infants: a randomized, placebo‐controlled trial
Authors: Tandon Manjari , Dutta Sourabh , Dogra Mangat R , Gupta Amod
Published: May 2010

Purpose:  To compare prophylactic enteral D‐penicillamine (DPA) with placebo for prevention of ‘retinopathy of prematurity (ROP) or death’ among very low birth weight (VLBW) infants.

Methods:  This was a double‐blind, single‐centre, randomized, placebo‐controlled trial with stratification (for birth weight <1250 and ≥1250 g) and blocking. Inborn neonates with birth weight 750–1500 g, gestation ≤32 weeks, age ≤5 days, who tolerated feeds were eligible. Neonates with gastro‐intestinal malformations, life‐threatening malformations and necrotizing enterocolitis were excluded. Enrolled subjects were randomly allocated to receive oral DPA suspension at 100 mg/kg/dose 8 h for 3 days, followed by 50 mg/kg/day for another 11 days or placebo. The primary outcome was ‘any ROP or death’. Secondary outcomes included any ROP, treatable ROP, adverse effects and feed intolerance.

Results:  A total of 88 subjects were enrolled. Baseline characteristics were similar with the exception of multiple gestation. There were no significant differences in primary and secondary outcomes, even after adjusting for multiple gestation and on sub‐group analysis. No adverse reaction was noted.

Conclusion:  Prophylactic enterally administered DPA suspension in a dose 100 mg/kg/dose 8 h for 3 days, followed by 50 mg/kg once per day for next 11 days, does not prevent ‘any stage ROP or death’ or ‘ROP requiring treatment’ in VLBW infants. DPA is well tolerated and does not have any major short‐term adverse effects.
Paradoxical interactions between modifiers and elastase‐2
Authors: Schenker Patricia , Baici Antonio
Published: May 2010

The serine endopeptidase elastase‐2 from human polymorphonuclear leukocytes is associated with physiological remodeling and pathological degradation of the extracellular matrix. Glycosaminoglycans bound to the matrix or released after proteolytic processing of the core proteins of proteoglycans are potential ligands of elastase‐2. In vitro, this interaction results in enzyme inhibition at low concentrations of glycosaminoglycans. However, inhibition is reversed and even abolished at high concentrations of the ligands. This behavior, which can be interpreted by a mechanism involving at least two molecules of glycosaminoglycan binding the enzyme at different sites, may cause interference with the natural protein inhibitors of elastase‐2, particularly the α‐1 peptidase inhibitor. Depending on their concentration, glycosaminoglycans can either stimulate or antagonize the formation of the enzyme‐inhibitor complex and thus affect proteolytic activity. This interference with elastase‐2 inhibition in the extracellular space may be part of a finely‐tuned control mechanism in the microenvironment of the enzyme during remodeling and degradation of the extracellular matrix.
The two Caenorhabditis elegans metallothioneins (CeMT‐1 and CeMT‐2) discriminate between essential zinc and toxic cadmium
Authors: Zeitoun‐Ghandour Sukaina , Charnock John M. , Hodson Mark E. , Leszczyszyn Oksana I. , Blindauer Claudia A. , Stürzenbaum Stephen R.
Published: May 2010

The nematode Caenorhabditis elegans expresses two metallothioneins (MTs), CeMT‐1 and CeMT‐2, that are believed to be key players in the protection against metal toxicity. In this study, both isoforms were expressed in vitro in the presence of either Zn(II) or Cd(II). Metal binding stoichiometries and affinities were determined by ESI‐MS and NMR, respectively. Both isoforms had equal zinc binding ability, but differed in their cadmium binding behaviour, with higher affinity found for CeMT‐2. In addition, wild‐type C. elegans, single MT knockouts and a double MT knockout allele were exposed to zinc (340 μm) or cadmium (25 μm) to investigate effects in vivo. Zinc levels were significantly increased in all knockout strains, but were most pronounced in the CeMT‐1 knockout, mtl‐1 (tm1770), while cadmium accumulation was highest in the CeMT‐2 knockout, mtl‐2 (gk125) and the double knockout mtl‐1;mtl‐2  (zs1). In addition, metal speciation was assessed by X‐ray absorption fine‐structure spectroscopy. This showed that O‐donating, probably phosphate‐rich, ligands play a dominant role in maintaining the physiological concentration of zinc, independently of metallothionein status. In contrast, cadmium was shown to coordinate with thiol groups, and the cadmium speciation of the wild‐type and the CeMT‐2 knockout strain was distinctly different to the CeMT‐1 and double knockouts. Taken together, and supported by a simple model calculation, these findings show for the first time that the two MT isoforms have differential affinities towards Cd(II) and Zn(II) at a cellular level, and this is reflected at the protein level. This suggests that the two MT isoforms have distinct in vivo roles.
An allosteric DNAzyme with dual RNA‐cleaving and DNA‐cleaving activities
Authors: Jiang Dazhi , Xu Jiacui , Sheng Yongjie , Sun Yanhong , Zhang Jin
Published: May 2010

A series of RNA‐cleaving or DNA‐cleaving DNAzymes have been obtained by in vitro selection. However, engineering an allosteric DNAzyme with dual RNA‐cleaving and DNA‐cleaving activities is very challenging. We used an in vitro‐selected pistol‐like (PL) DNAzyme as a DNA scaffold for designing a DNAzyme with dual catalytic activities. We prepared the 46‐nucleotide DNAzyme with DNA‐cleaving activity (PL DNAzyme), and then grafted the deoxyribonucleotide residues from an 8–17 variant DNAzyme into the region of stem–loop I and the catalytic core of the PL DNAzyme scaffold. This deoxyribonucleotide residue grafting resulted in a DNAzyme with dual RNA‐cleaving and DNA‐cleaving activities (DRc DNAzyme). Drc DNAzyme has properties different from those of the original PL DNAzyme, including DNA cleavage sites and the required metal ion concentration. Interestingly, the RNA substrate and RNase A can act as effectors to mediate the DNA cleavage. Our results show that RNA‐cleaving and DNA‐cleaving activities simultaneously coexist in DRc DNAzyme, and the DNA cleavage activity can be reversibly regulated by a conformational transition.
ATP allosteric activation of atrial natriuretic factor receptor guanylate cyclase
Authors: Duda Teresa , Yadav Prem , Sharma Rameshwar K.
Published: May 2010

Atrial natriuretic factor receptor guanylate cyclase (ANF‐RGC) is the receptor and the signal transducer of two natriuretic peptide hormones: atrial natriuretic factor and brain natriuretic peptide. It is a single transmembrane‐spanning protein. It binds these hormones at its extracellular domain and activates its intracellular catalytic domain. This results in the accelerated production of cyclic GMP, a second messenger in controlling blood pressure, cardiac vasculature and fluid secretion. ATP is obligatory for the transduction of this hormonal signal. Two models of ATP action have been proposed. In Model 1, it is a direct allosteric transducer. It binds to the defined regulatory domain (ATP‐regulated module) juxtaposed to the C‐terminal side of the transmembrane domain of ANF‐RGC, induces a cascade of temporal and spatial changes and activates the catalytic module residing at the C‐terminus of the cyclase. In Model 2, before ATP can exhibit its allosteric effect, ANF‐RGC must first be phosphorylated by an as yet unidentified protein kinase. This initial step is obligatory in atrial natriuretic factor signaling of ANF‐RGC. Until now, none of these models has been directly validated because it has not been possible to segregate the allosteric and the phosphorylation effects of ATP in ANF‐RGC activation. The present study accomplishes this aim through a novel probe, staurosporine. This unequivocally validates Model 1 and settles the over two‐decade long debate on the role of ATP in ANF‐RGC signaling. In addition, the present study demonstrates that the mechanisms of allosteric modification of ANF‐RGC by staurosporine and adenylyl‐imidodiphosphate, a nonhydrolyzable analog of ATP, are almost (or totally) identical.
The Action of a Novel Fluoroquinolone Antibiotic Agent Antofloxacin Hydrochloride on Human‐Ether‐à‐go‐go‐Related Gene Potassium Channel
Authors: Guo Jia , Han Sheng‐Na , Liu Jin‐Xu , Zhang Xiang‐Mei , Hu Zhen‐Sheng , Shi Jie , Zhang Li‐Rong , Zhao Zhong‐Zhong , Zhang Zhao
Published: May 2010

Abstract:  The administration of certain fluoroquinolone antibacterials has recently been linked to QT interval prolongation, raising the clinical concerns over the cardiotoxicity of these agents. In this study, the effects of a novel fluoroquinolone, antofloxacin hydrochloride (AX) on human‐ether‐à‐go‐go‐related gene (HERG) encoding potassium channels and the biophysical mechanisms of drug action were performed with whole‐cell patch‐clamp technique in transiently transfected HEK293 cells. The administration of AX caused voltage‐ and time‐dependent inhibition of HERG K+ current (IHERG/MiRP1) in a concentration‐dependent manner but did not markedly modify the properties of channel kinetics, including activation, inactivation, deactivation and recovery from inactivation as well. In comparison with sparfloxacin (SPX), levofloxacin lactate (LVFX), the potency of AX to inhibit HERG tail currents was the least one, with an IC50 value of 460.37 μM. By contrast, SPX was the most potent compound, displaying an IC50 value of 2.69 μM whereas LVFX showed modest potency, with an IC50 value of 43.86 μM, respectively. Taken together, our data suggest that AX only causes a minor reduction of IHERG/MiRP1 at the estimated free plasma level.
Studies on the Acute Toxicity, Pharmacokinetics and Pharmacodynamics of Paliperidone Derivatives – Comparison to Paliperidone and Risperidone in Mice and Rats
Authors: Sun Fengying , Su Zhengxing , Sui Cheng , Zhang Chao , Yuan Lijia , Meng Qingfan , Teng Lirong , Li Youxin
Published: May 2010

Abstract: The objective of this study was to investigate the acute toxicity, pharmacokinetics and pharmacodynamics of paliperidone derivatives (PDs) compared with paliperidone and risperidone. The i.g. LD50and i.v. maximum tolerated doses of PD1, PD5 and PD6 were greater than those of paliperidone and risperidone in mice. Pharmacokinetic study showed that PDs were quickly metabolized to paliperidone to take effect in the treatment of schizophrenia in rats after i.g. administration. Only traces of the parent substances were found. Pharmacodynamic study showed that PDs significantly reduced MK‐801‐induced hyperlocomotion in mice. The electrocardiogram (ECG) was recorded at 0, 5, 10, 15, 20, 25, 30, 45 and 60 min. in anaesthetized rats after i.v. injection of 0.21, 0.59, 1.69 μmol/kg drugs. Heart rate reduction had a linear relation with dose after i.v. injection of PDs, paliperidone and risperidone. No significant change in the ECG parameters was found in all groups after administration of the low dose. Although the reductions in heart rate and the corrected QT interval (QTc) were observed in all drugs at the high dose, PD5 and PD6 were associated with smaller effects on the ECG parameters than other compounds, including paliperidone and risperidone. Therefore, PD5 and PD6 could be potential candidates for the treatment of schizophrenia.
Ginsenoside Rb3 Inhibits Angiotensin II‐Induced Vascular Smooth Muscle Cells Proliferation
Authors: Wang Tian , Yu Xiao‐Feng , Qu Shao‐Chun , Xu Hua‐Li , Sui Da‐Yuan
Published: May 2010

Abstract:  This study was designed to examine the effect of ginsenoside Rb3 on angiotensin (Ang) II‐induced proliferation of cultured rat vascular smooth muscle cells (VSMCs). VSMCs proliferation was evaluated by [3H]Thymidine incorporation. The cell cycle was examined by flow cytometry. The expression of mRNA of proto‐oncogene c‐myc, c‐fos and c‐jun was observed by RT‐PCR. Ginsenoside Rb3 had no effects on VSMCs proliferation in physiological condition. Ang II significantly increased the proliferation of VSMCs and the expression of mRNA of proto‐oncogene c‐myc, c‐fos and c‐jun. Ginsenoside Rb3 markedly inhibited Ang II‐induced VSMCs proliferation. Concomitantly, ginsenoside Rb3 decreased cell cycle progression from G0/G1 to S phase. Furthermore, ginsenoside Rb3 significantly attenuated the expression of mRNA of proto‐oncogene c‐myc, c‐fos and c‐jun. This study showed that ginsenoside Rb3 inhibited Ang II‐induced VSMCs proliferation, at least in part by inhibiting Ang II‐induced G0/G1 to S phase transition and attenuating the expression of mRNA of c‐fos, c‐jun and c‐myc. The findings may explain the beneficial effects of ginsenoside Rb3 in cardiovascular diseases, and it will be useful to develop prevention and therapeutics of cardiovascular diseases.
Genetic Analysis of ele Mutants and Comparative Mapping of ele1 Locus in the Control of Organ Internal Asymmetry in Garden Pea
Authors: Li Xin , Zhuang Li‐Li , Ambrose Mike , Rameau Catherine , Hu Xiao‐He , Yang Jun , Luo Da
Published: May 2010

Previous study has shown that during zygomorphic development in garden pea (Pisum sativum L.), the organ internal (IN) asymmetry of lateral and ventral petals was regulated by a genetic locus, SYMMETRIC PETAL 1 (SYP1), while the dorsoventral (DV) asymmetry was determined by two CYC‐like TCP genes or the PsCYC genes, KEELED WINGS (K) and LOBED STANDARD 1 (LST1). In this study, two novel loci, ELEPHANT EAR‐LIKE LEAF 1 (ELE1) and ELE2 were characterized. These mutants exhibit a similar defect of IN asymmetry as syp1 in lateral and ventral petals, but also display pleiotropic effects of enlarged organ size. Genetic analysis showed that ELE1 and ELE2 were involved in same genetic pathway and the enlarged size of petals but not compound leaves in ele2 was suppressed by introducing k and lst1, indicating that the enlargement of dorsal petal in ele2 requires the activities of K and LST1. An experimental framework of comparative genomic mapping approach was set up to map and clone LjELE1 locus in Lotus japonicus. Cloning the ELE1 gene will shed light on the underlying molecular mechanism during zygomorphic development and further provide the molecular basis for genetic improvement on legume crops.
Dementia and risk: contested territories of everyday life
Authors: Clarke Charlotte L , Keady John , Wilkinson Heather , Gibb Catherine E , Luce Anna , Cook Ailsa , Williams Linda
Published: May 2010

clarke cl, keady j, wilkinson h, gibb ce, luce a, cook a & williams l (2010)
 Journal of Nursing and Healthcare of Chronic Illness 2, 102–112 Dementia and risk: contested territories of everyday life

Aims.  The project aimed to understand the construction of risk in dementia care from the perspective of the person with dementia, family carers and practitioners with the intention of developing negotiated partnerships in risk management.

Background.  This paper addresses a gap in the literature by embedding constructions of risk within everyday events and social contexts, and communicates such constructions through the voices of people with dementia, carers and practitioners.

Method.  This symbolic interactionalist study involved data collection by interview with 55 people with dementia (sometimes twice), and their nominated carer and practitioner. The sample was drawn from three regions of the United Kingdom. Data were collected during 2004.

Conclusions.  Five ‘contested territories’ of everyday living with dementia are outlined in this paper: friendships, smoking, going out, domestic arrangements, and occupation and activity. These contested territories are purposeful and allow for sense making, maintenance of self, claiming and relinquishing decision making, and creating purpose(lessness) in people’s lives.

Relevance to clinical practice.  Assessing and managing risk in a way that respects the dynamics and purposes of contested territories will support care that is person centred, and moreover respectful of the relationships that contribute to maintaining the individual’s sense of self and purpose.
Systematic review: role of health promotion in vascular dementia
Authors: Price Rachel S , Keady John
Published: May 2010

price rs & keady j (2010)
 Journal of Nursing and Healthcare of Chronic Illness 2, 88–101 Systematic review: role of health promotion in vascular dementia

Aims.  This narrative synthesis of the literature investigates the areas of vascular dementia and modifiable risk factors in order to identify the evidence base and opportunities for specific health promotion work and nursing involvement.

Background.  Strategies for well‐being, prevention and health promotion are becoming increasingly important determinants of a quality dementia care service. In England, this emphasis is manifest in the recently launched National Dementia Strategy (February 2009) and areas that address modifiable vascular risk factors are helpful starting points for the enactment of such goals.

Design and methods.  A comprehensive search strategy identified primary and secondary search terms that were used systematically in order to search for relevant information and literature; 128 articles were finally included in the overall design and these were broken down into 116 articles obtained through the formal search process using the online databases and 12 articles from the ‘grey literature’.

Results.  A narrative synthesis of the included material generated a thematic framework that revealed four discrete but overlapping themes: vascular risk factors (1); prevention and reduction of vascular risk factors (2); treatment and intervention in vascular dementia (3); and vascular health promotion (4).

Relevance to clinical practice.  Nursing is in a prime position to undertake health promotion initiatives in modifiable risk behaviours in vascular dementia, an approach that should be commenced for the general population in mid‐life (50 years and over).
The influence of locus of control on risk perception in older South Asian people with Type 2 diabetes in the UK
Authors: Macaden Leah , Clarke Charlotte L
Published: May 2010

macaden l & clarke cl (2010)
 Journal of Nursing and Healthcare of Chronic Illness 2, 144–152 The influence of locus of control on risk perception in older South Asian people with Type 2 diabetes in the UK

Aim of the study.  To analyse risk perception among older South Asian people with Type 2 Diabetes in the UK.

Background.  South Asians living in the UK have an increased predisposition to developing Type 2 diabetes. It usually occurs later in life and has significant long‐term risks that are preventable with life‐style changes. Changes in life‐style practices are likely to be influenced by an individual’s perception of control over his/her health yet perceptions of risk are influenced by sociocultural factors, religious beliefs and gender.

Method.  In this Grounded Theory study, data collection involved: two focus group interviews with health development workers representing ethnic minorities; seven individual interviews with practitioners (three physicians, three nurse specialists and a dietitian); 20 interviews with UK‐resident older South Asians (nine men and eleven women) with Type 2 diabetes together with analysis of their medical records. Data for the study were collected between March 2004–February 2005.

Findings.  Those participants who demonstrated an internal locus of control were proactive in managing their diabetes‐related risks. Participants with an external locus of control in perceiving and managing their risks related to diabetes believed that their diabetes was due to fate, bad luck, divine planning or familial predisposition and were reactive in engaging with diabetes‐related risks.

Relevance to clinical practice.  This study demonstrates the role of affect and external locus of control in risk engagement among older South Asians with Type 2 Diabetes. The appropriateness of the concordance and empowerment model of diabetes care for minority ethnic groups such as the South Asians who engage with diabetes‐related risks reactively driven by external locus of control needs to be carefully assessed.