bluuebunny/crossref_metadata_2025 huggingface dataset:
CYP1, a hypovirus‐regulated cyclophilin, is required for virulence in the chestnut blight fungus
Authors: CHEN MIN‐MEI , JIANG MINGGUO , SHANG JINJIE , LAN XIUWAN , YANG FENG , HUANG JINGKUAN , NUSS DONALD L. , CHEN BAOSHAN
Published: October 2010

Cyclophilins are peptidyl‐prolyl cis–trans isomerases that are highly conserved throughout eukaryotes and are the cellular target of the immunosuppressive drug cyclosporin A (CsA). We cloned cyp1, a cyclophilin A‐encoding gene in the phytopathogenic fungus Cryphonectria parasitica, and showed that this gene was downregulated following infection by a virulence‐attenuating hypovirus. The function of cyp1 was further investigated by construction of a cyp1 deletion mutant. Although the wild‐type C. parasitica strain EP155 was sensitive to CsA, the Δcyp1 strain was highly tolerant to CsA, indicating that CYP1 was the target of CsA. Deletion of cyp1 resulted in reduced virulence when inoculated to chestnut stems. Transcriptional analysis revealed that deletion of cyp1 also reduced transcript levels for genes encoding key components of the heterotrimeric guanosine triphosphate‐binding protein signalling pathway that are essential for sensing environmental cues and are involved in C. parasitica development and virulence.
Combination of FVIII and by‐passing agent potentiates in vitro thrombin production in haemophilia A inhibitor plasma
Authors: Klintman Jenny , Astermark Jan , Berntorp Erik
Published: October 2010

The by‐passing agents, recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrate (APCC), are important tools in the treatment of patients with haemophilia A and high‐responding inhibitory antibodies. It has been observed clinically that in some patients undergoing immune tolerance induction the bleeding frequency decreases, hypothetically caused by a transient haemostatic effect of infused FVIII not measurable ex vivo. We evaluated how by‐passing agents and factor VIII (FVIII) affect thrombin generation (TG) in vitro using plasma from 11 patients with severe haemophilia A and high titre inhibitors. Samples were spiked with combinations of APCC, rFVIIa and five different FVIII products. Combination of APCC and FVIII showed a synergistic effect in eliciting TG (P < 0·005) for four FVIII products. When rFVIIa and FVIII were combined the interaction between the preparations was found to be additive. APCC and rFVIIa were then combined without FVIII, resulting in an additive effect on thrombin production. Each product separately increased TG above baseline. In conclusion, the amount of thrombin formed in vitro by adding a by‐passing agent, was higher in the presence of FVIII. Our findings support the use of FVIII in by‐passing therapy to optimize the haemostatic effect.
A novel HLA‐A*31 allele, A*31:34, identified by sequence‐based typing
Authors: Ko S.‐Y. , Oh H.‐B. , Heo Y.‐S. , Jun J. H. , Kwon O.‐J.
Published: October 2010

New allele A*31:34 showed one nucleotide difference with A*31:01:02 at codon 166 (GAG/CAG).
A novel HLA‐DPB1 allele, DPB1*125:01, identified by sequence‐based typing in an Indian individual
Authors: Kanga U. , McWhinnie A. J. , Mourya M. , Shaw B. E. , Madrigal J. A. , Mehra N. K.
Published: October 2010

A novel DPB1*125:01 allele differs from DPB1*26:01:02 at two positions in exon 2, leading to changes at codons 9 and 35.
Identification of a novel HLA‐C*08 variant allele, C*08:31. Sequence analysis from exons 1 through 8
Authors: Iliescu A. , Nesci S. , Manfroi S. , Buffi O. , Bontadini A.
Published: October 2010

A novel allele, HLA‐ C*08:31 has been identified by sequence based typing in an Italian hematological patient undergoing bone marrow transplantation.
Association of the CD226 single nucleotide polymorphism with systemic lupus erythematosus in the Chinese Han population
Authors: Du Y. , Tian L. , Shen L. X. , Wang F. , Yu L. K. , Song Y. , Zhu J. F. , Du R.
Published: October 2010

A novel non‐synonymous (Gly307Ser) variant, rs763361, of the CD226 gene on chromosome 18q22 was recently shown to be associated with multiple autoimmune diseases. Taking into consideration that different autoimmune diseases may share some common pathogenic pathways, in this study we performed case–control studies to assess any genetic linkage with systemic lupus erythemtosus (SLE). An association between the Gly307Ser single nucleotide polymorphism (SNP) and susceptibility to SLE was identified. The TT genotype [odds ratio (OR) = 1.79, 95% confidence interval (CI) = 1.07–3.01, P = 0.025] and the T allele (OR = 1.34, 95% CI = 1.05–1.74, P = 0.018) of the rs763361 SNP were associated with the risk of SLE. This finding indicates that polymorphism of Gly307Ser (rs763361) in exon 7 of the CD226 gene may be associated with the development of SLE.
Sequence‐based typing showed a novel HLA‐DQB1*05 allele, DQB1*05:01:03
Authors: Jakubauskas A. , Griskevicius L.
Published: October 2010

The novel allele HLA‐DQB1*05:01:03 differs from HLA‐DQB1*05:01:01 by a silent nucleotide substitution at codon 77R (AGG to AGA).
Sutureless total thyroidectomy: a safe and cost‐effective alternative
Authors: Chang Ling‐Yun , O'Neill Christine , Suliburk James , Sidhu Stan , Delbridge Leigh , Sywak Mark
Published: October 2010

Background:  Advanced vessel sealing devices provide an alternative to conventional ligation techniques for thyroidectomy. To date, most studies have been inadequately powered to explore differences in the infrequent post‐operative complications following thyroidectomy. This study is designed to compare the outcomes of sutureless thyroidectomy and conventional thyroidectomy for recurrent laryngeal nerve (RLN) injury, permanent hypoparathyroidism, and haematoma formation.

Methods:  A cohort study of consecutive patients undergoing total thyroidectomy using conventional versus sutureless techniques was performed. Sutureless thyroidectomy was performed using either Ligasure Precise (Covidien) or Harmonic Focus (Johnson and Johnson) devices. The primary outcome measures were post‐operative haemorrhage, permanent RLN injury and hypoparathyroidism. Secondary outcome measures were operative time, temporary hypoparathyroidism and vocal cord dysfunction. A cost minimization analysis comparing the two techniques was performed.

Result:  From January 2006 to July 2009, 1935 consecutive patients underwent total thyroidectomy. Of these, 772 underwent conventional thyroidectomy and 1163 were performed using a sutureless technique. The mean operative time was significantly lower in the sutureless group (71 versus 86 min, P= 0.02). There was no difference in the post‐operative complications of haematoma (0.78% conventional versus 1.12% sutureless, P= 0.46), permanent hypoparathyroidism (1.30% conventional versus 0.52% sutureless, P= 0.06) or permanent RLN injury (0.26% conventional versus 0.52% sutureless, P= 0.39). There was an overall cost saving of AUD$14 300 per 100 total thyroidectomy cases performed using the sutureless technique.

Conclusions:  Sutureless thyroidectomy is a safe and efficient way of performing total thyroidectomy and has the potential to reduce operating room costs.
Autologous chondrocyte implantation: an overview of technique and outcomes
Authors: Batty Lachlan , Dance Samuel , Bajaj Sarvottam , Cole Brian J.
Published: October 2010

Articular cartilage is susceptible to damage; however, it has limited capacity for repair. Damage can lead to persistent symptoms including pain, swelling, and loss of function and may ultimately progress to symptomatic degeneration of the joint. To restore function and minimize symptoms, many advocate surgical intervention in selected candidates, which can range from arthroscopic debridement to restorative procedures depending on patient and lesion characteristics. Autologous Chondrocyte Implantation (ACI) is a two‐stage, typically second‐line intervention where cultured autologous chondrocytes are used with the aim of resurfacing symptomatic chondral defects with hyaline or hyaline‐like cartilage. Careful patient selection is important. We present an overview of this procedure including indications and contraindications, surgical technique, and post‐operative management. A review of published ACI outcomes is then presented.
Mitochondrial uncoupling protein 2 in pancreatic β‐cells
Authors: Brand M. D. , Parker N. , Affourtit C. , Mookerjee S. A. , Azzu V.
Published: October 2010

Pancreatic β‐cells have remarkable bioenergetics in which increased glucose supply upregulates the cytosolic ATP/ADP ratio and increases insulin secretion. This arrangement allows glucose‐stimulated insulin secretion (GSIS) to be regulated by the coupling efficiency of oxidative phosphorylation. Uncoupling protein 2 (UCP2) modulates coupling efficiency and may regulate GSIS. Initial measurements of GSIS and glucose tolerance in Ucp2−/− mice supported this model, but recent studies show confounding effects of genetic background. Importantly, however, the enhancement of GSIS is robustly recapitulated with acute UCP2 knockdown in INS‐1E insulinoma cells. UCP2 protein level in these cells is dynamically regulated, over at least a fourfold concentration range, by rapid proteolysis (half‐life less than 1 h) opposing regulated gene transcription and mRNA translation. Degradation is catalysed by the cytosolic proteasome in an unprecedented pathway that is currently known to act only on UCP2 and UCP3. Evidence for proteasomal turnover of UCP2 includes sensitivity of degradation to classic proteasome inhibitors in cells, and reconstitution of degradation in vitro in mitochondria incubated with ubiquitin and the cytosolic 26S proteasome. These dynamic changes in UCP2 content may provide a fine level of control over GSIS in β‐cells.
Redox compartmentalization and cellular stress
Authors: Jones D. P. , Go Y.‐M.
Published: October 2010

Mammalian cells are highly organized to optimize function. For instance, oxidative energy‐producing processes in mitochondria are sequestered away from plasma membrane redox signalling complexes and also from nuclear DNA, which is subject to oxidant‐induced mutation. Proteins are unique among macromolecules in having reversible oxidizable elements, ‘sulphur switches', which support dynamic regulation of structure and function. Accumulating evidence shows that redox signalling and control systems are maintained under kinetically limited steady states, which are highly displaced from redox equilibrium and distinct among organelles. Mitochondria are most reducing and susceptible to oxidation under stressed conditions, while nuclei are also reducing but relatively resistant to oxidation. Within compartments, the glutathione and thioredoxin systems serve parallel and non‐redundant functions to maintain the dynamic redox balance of subsets of protein cysteines, which function in redox signalling and control. This organization allows cells to be poised to respond to cell stress but also creates sites of vulnerability. Importantly, disruption of redox organization is a common basis for disease. Research tools are becoming available to elucidate details of subcellular redox organization, and this development highlights an opportunity for a new generation of targeted antioxidants to enhance and restore redox signalling and control in disease prevention.
Impact of nitric oxide on metabolism in health and age‐related disease
Authors: Knott A. B. , Bossy‐Wetzel E.
Published: October 2010

Nitric oxide (NO) serves as a messenger molecule in a variety of physiological systems and also converts into toxic radical species that can damage cells through a process known as nitrosative stress. While the physiological roles of NO in blood vessel dilation, the nervous system and the immune system are well established, recent studies have begun to investigate the role of NO in metabolism and energy expenditure through modulation of mitochondria. NO appears to stimulate mitochondrial biogenesis in certain situations through activation of proteins such as peroxisome proliferator‐activated receptor γ (PPARγ) co‐activator 1α (PGC1‐α). Because of this link between NO and mitochondrial biogenesis, the role of NO in certain aspects of metabolism, including exercise response, obesity, fat cell differentiation and caloric restriction, are the subject of increasing investigation. In addition to its role in mitochondrial biogenesis, NO also stimulates mitochondrial fragmentation, which can be caused by too much mitochondrial fission or inhibition of mitochondrial fusion and can result in bioenergetic failure. While the contribution of NO‐mediated mitochondrial fragmentation to neurodegenerative diseases seems clear, the mechanisms by which NO causes fragmentation are uncertain and controversial. In this review, we discuss the role of NO in manipulation of mitochondrial biogenesis and dynamics and how these events contribute to human health‐ and age‐related disease.
The role of autophagy in β‐cell lipotoxicity and type 2 diabetes
Authors: Las G. , Shirihai O. S.
Published: October 2010

Autophagy, a ubiquitous catabolic pathway involved in both cell survival and cell death, has been implicated in many age‐associated diseases. Recent findings have shown autophagy to be crucial for proper insulin secretion and β‐cell viability. Transgenic mice lacking autophagy in their β‐cells showed decreased β‐cell mass and suppressed glucose‐stimulated insulin secretion. Several studies showed that stress can stimulate autophagy in β‐cells: the number of autophagosomes is increased in different in vivo models for diabetes, such as db/db mice, mice fed high‐fat diet, pdx‐1 knockout mice, as well as in in vitro models of glucotoxicity and lipotoxicity. Pharmacological and molecular inhibition of autophagy increases the susceptibility to cell stress, suggesting that autophagy protects against diabetes‐relevant stresses. Recent findings, however, question these conclusions. Pancreases of diabetics and β‐cells exposed to fatty acids show accumulation of abnormal autophagosome morphology and suppression of lysosomal gene expression suggesting impairment in autophagic turnover. In this review we attempt to give an overview of the data generated by others and by us in view of the possible role of autophagy in diabetes, a role which depending on the conditions, could be beneficial or detrimental in coping with stress.
The endoplasmic reticulum stress response in the pancreatic β‐cell
Authors: Volchuk A. , Ron D.
Published: October 2010

Eukaryotic cells respond to stress in the endoplasmic reticulum (ER) resulting from insufficient protein folding capacity or altered ER homeostasis by activating the unfolded protein response (UPR). In mammalian cells the UPR is mediated by at least three ER‐localized sensors/transducers, and the cellular response and susceptibility to ER stress is likely to be cell‐type specific to some degree. Here, we review the response of pancreatic β‐cells or islets to ER stress induced by pharmacological agents, misfolded insulin expression, excessive nutrient exposure and in animal models of type 2 diabetes. This review highlights the particular importance of PERK‐mediated translational control and the transcriptional response in pancreatic β‐cells and how these relate to the highly specialized function of β‐cells, namely glucose‐regulated insulin secretion and production. We examine how chronic ER stress may prematurely ‘age’ the β‐cell or cause its genetic reprogramming to either reduce its ability to mount a cell survival response to ER stress, or impair normal function. Both could contribute to β‐cell failure in diabetes. We also explore the therapeutic potential of targeting the UPR to preserve β‐cell function.
Leadership in Organizational Knowledge Creation: A Review and Framework
Authors: von Krogh Georg , Nonaka Ikujiro , Rechsteiner Lise
Published: October 2010

abstract

Organizational knowledge creation integrates context, knowledge assets, and knowledge creation processes throughout the organization. Using organizational knowledge creation theory as an organizing framework, we conduct a literature review that shows prior work has focused on the role of central, upper‐echelon, leadership in knowledge creation processes, without devoting much attention to context and knowledge assets. To remedy these weaknesses, we develop a new framework for situational leadership in organizational knowledge creation. The framework is based on a continuum that ranges from centralized to distributed leadership at three layers of activity: a core layer of local knowledge creation; a conditional layer that provides the resources and context for knowledge creation; and a structural layer that forms the overall frame and direction for knowledge creation in the organization. We discuss the implications of this framework for theory and practice.
Role of astrocytic leptin receptor subtypes on leptin permeation across hCMEC/D3 human brain endothelial cells
Authors: Hsuchou Hung , Kastin Abba J. , Tu Hong , Joan Abbott N. , Couraud Pierre‐Olivier , Pan Weihong
Published: October 2010

J. Neurochem.(2010)115, 1288–1298.

Astrocytic leptin receptors (ObR) can be up‐regulated in conditions such as adult‐onset obesity. To determine whether the levels and subtypes of astrocytic ObR modulate leptin transport, we co‐cultured hCMEC/D3 human brain endothelial cells and C6 astrocytoma cells in the Transwell system, and tested leptin permeation from apical to basolateral chambers. In comparison with hCMEC alone, co‐culture of C6 cells reduced the permeability of paracellular markers and leptin. Unexpectedly, ObRb over‐expression in C6 cells increased leptin permeation whereas ObRa over‐expression showed no effect when compared with the control group of pcDNA‐transfected C6 cells. By contrast, the paracellular permeability to the sodium fluorescein control was unchanged by over‐expression of ObR subtypes. Leptin remained intact after crossing the monolayer as shown by HPLC and acid precipitation, and this was not affected by C6 cell co‐culture or the over‐expression of different ObR subtypes. Thus, increased expression of ObRb (and to a lesser extent ObRe) in C6 cells specifically increased the permeation of leptin across the hCMEC monolayer. Consistent with the evidence that the most apparent regulatory changes of ObR during obesity and inflammation occur in astrocytes, the results indicate that astrocytes actively regulate leptin transport across the blood–brain barrier, a mechanism independent of reduction of paracellular permeability.
Trauma‐associated acute mesenteric ischemia in a dog
Authors: Hamilton Todd R. , Thacher Christopher W. , Forsee Kara M. , Nakamura Reid K.
Published: October 2010

Objective
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To describe the successful management of acute mesenteric ischemia (AMI) in a dog.

Case Summary
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An 11‐year‐old, 21.4 kg, male castrated Rough‐Coated Collie was referred for evaluation of an acute abdomen following sustaining injuries in a vehicular accident. On presentation to the hospital, clinicopathologic assessments were within normal limits and distended intestinal loops were evident on abdominal palpation. Plain and contrast radiography demonstrated diffusely distended gas‐filled intestinal loops with a delayed barium transit time. Emergency surgical exploration was performed. The cecum and the proximal two‐thirds of the colon were dark purple to black in color and there were no palpable pulses in the mesenteric arteries associated with the cecum and colon. The cecum and proximal two‐thirds of the colon were resected and an ileocolic anastomosis was performed. The dog recovered well from surgery and was discharged 2 days later. Histopathologic examination was consistent with AMI.

New or Unique Information Provided
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AMI is uncommonly reported in human medicine and is a rare complication from even minor blunt abdominal trauma. This is the first reported case of trauma‐associated AMI in a dog.
Geodynamic regimes of subduction under an active margin: effects of rheological weakening by fluids and melts
Authors: GERYA T. V. , MEILICK F. I.
Published: October 2010

The dynamics of subduction under an active margin are analysed by using a 2D‐coupled petrological–thermomechanical numerical model of an oceanic–continental subduction system. The model includes spontaneous slab bending, dehydration of the subducted crust, aqueous fluid transport, partial melting of both crustal and mantle rocks as well as melt extraction processes resulting in magmatic arc crust growth. Based on our models, the following five geodynamic regimes of subduction, which may potentially form at active margins, are identified: (i) stable subduction with no backarc spreading centre and without plumes in the mantle wedge; (ii) retreating subduction with a focused backarc spreading centre and without plumes; (iii) retreating subduction with distributed intra‐arc extension and trans‐lithospheric sedimentary plumes; (iv) advancing subduction with underplating (laterally extending) sub‐lithospheric plumes; and (v) stable to advancing subduction with stationary (laterally limited) sub‐lithospheric plumes. Transitions between these different regimes are mainly caused by the concurrence of rheological weakening effects of (i) aqueous fluids percolating from the subducting slab into the mantle wedge and (ii) melts propagating from the partially molten areas formed in the mantle wedge towards the surface. The aqueous fluids mainly affect the forearc region. Strong fluid‐related weakening promotes plate decoupling and reduces subduction drag and thus results in stacking of sediments in the accretion prism. In contrast, reduced weakening by fluids results in strong coupling of the plates and leads to advancing collision‐like subduction with enhanced subduction erosion. Thickening of the overriding plate and large sedimentary plumes in the mantle wedge are the consequences. On the other hand, melts, extracted from the hot regions above the slab, rheologically weaken the lithosphere below the arc, which thus controls overriding plate extension and shortening. Strong rheological weakening by melts in combination with weak plate coupling trigger retreating subduction with a pronounced backarc spreading centre. Also, weakening of the continental lithosphere by melts extracted from trans‐lithospheric sedimentary plumes generate a weak channel through which these structures may be emplaced into subarc crust. If there is insufficient melt‐related weakening, plumes cannot ascend but extend horizontally and thus underplate the lithosphere.
On the interpretation of retrograde reaction textures in granulite facies rocks
Authors: WHITE R. W. , POWELL R.
Published: October 2010

Retrograde reaction textures, such as partial pseudomorphs, coronae and symplectic coronae are a relatively common feature of granulite facies rocks and represent evidence of change of mineral modes or assemblages. Thus, such reaction textures represent one of the more potentially useful indicators of retrograde P–T evolutions. However, the interpretation of such textures requires the simultaneous consideration of the formation of the texture itself in terms of the spatial relationships in a rock, and of the changes in P–T conditions that drove the development of the reaction texture. Calculated phase diagrams provide a robust framework in which to consider reaction textures, especially via the combined use of pseudosections to understand the P–T changes and μ–μ diagrams to understand the spatial arrangement of the minerals. Consideration of the chemical potential gradients that may exist across a given texture means that elucidating P–T conditions and P–T paths must be done with care. The evolution of a given reaction texture may be complex with different layers or individual minerals in a texture forming at different times. Thus, the approach of writing a reaction to represent the inferred local reactant and product phases and simply ascribing such reaction textures to crossing equivalent univariant reactions from petrogenetic grids or traversing through fields in pseudosections without due consideration of chemical potential gradients may result in an incorrect interpretation. Furthermore, the potential for a non‐continuous metamorphic evolution of a rock by polymetamorphism or some other hiatus in the textural/mineral‐assemblage evolution creates further uncertainty in the interpretation of a texture in terms of its reaction history and P–T path. A common interpretation of coronae and symplectic coronae, on the basis of the preservation of the apparent reactants, is that they represent reactions that failed to go to completion for various kinetic reasons. While this may be true in some cases, many other textures may actually represent reaction having gone to completion with, for example, silicate melt being the phase completely consumed. Furthermore, even where a reaction has failed to go to completion, the possible reasons for this may be different for different rocks.
Frovatriptan for Prophylactic Treatment of Cluster Headache: Lessons for Future Trial Design
Authors: Pageler Lutz , Katsarava Zaza , Lampl Christian , Straube Andreas , Evers Stefan , Diener Hans‐Christoph , Limmroth Volker
Published: October 2010

(Headache 2011;51:129‐134)

Objective.— The aim of this study was to determine whether frovatriptan would show efficacy in short term prophylactic treatment of episodic cluster headache (ECH) in comparison to placebo.

Background.— The 5‐hydroxytryptamine1B/d (5‐HT1B/d)‐agonists naratriptan, eletriptan, and frovatriptan have been shown to reduce the frequency of ECH. So far, no double‐blind placebo‐controlled trials have investigated the potential prophylactic effects of 5‐HT1B/d‐agonists in ECH.

Methods.— The trial was conducted as a multi‐center, placebo‐controlled, randomized, double‐blind, prospective phase III parallel‐group trial with two independent treatment groups (5 mg frovatriptan vs placebo). It was planned to randomize about 96 patients (48 patients per group) into the trial to obtain 80 evaluable patients (40 patients per group).

Results.— The study was prematurely discontinued after 13 months and enrollment of 11, instead of the planned 80 patients, by the sponsor due to infeasibility. Recruitment was slow and each of the patients included conducted major protocol violations. The differences in the primary and secondary endpoints were not significant.

Conclusion.— This study shows that particular therapeutic aims are impossible to be addressed in a double‐blind, randomized, parallel group, study design with specific inclusion and exclusion criteria according to the International Headache Society (IHS) guidelines for controlled trials of drugs in cluster headache. Further studies are required to evaluate the potential efficacy of triptans in the prophylactic treatment of ECH. The outcome of the trial suggests that the recommendations of the Guidelines for controlled Trials of Drugs in Cluster Headache from the IHS should be revised.
The Energetic Pathway to Mobility Loss: An Emerging New Framework for Longitudinal Studies on Aging
Authors: Schrack Jennifer A. , Simonsick Eleanor M. , Ferrucci Luigi
Published: October 2010

The capacity to walk independently is a central component of independent living. Numerous large and well‐designed longitudinal studies have shown that gait speed, a reliable marker of mobility, tends to decline with age and as a consequence of chronic disease. This decline in performance is of utmost importance because slow walking speed is a strong, independent predictor of disability, healthcare utilization, nursing home admission, and mortality. Based on these robust findings, it has been postulated that age‐associated decline in walking speed is a reliable barometer of the effect of biological aging on health and functional status. Despite the extraordinary prognostic information that walking speed provides, which is often superior to traditional medical information, there is a limited understanding of the mechanisms that underlie age‐ and disease‐related gait speed decline. Identifying the mechanisms that underlie the prognostic value of walking speed should be a central theme in the design of the next generation of longitudinal studies of aging, with appropriate measures introduced and analytical approaches incorporated.

This study hypothesized that a scarcity of available energy induces the decline in customary walking speed with aging and disease. Based on work in the Baltimore Longitudinal Study of Aging, examples of measures, operationalized dimensions, and analytical models that may be implemented to address this are provided. The main premise is simple: the biochemical processes that maintain life, secure homeostatic equilibrium, and prevent the collapse of health require energy. If energy becomes deficient, adaptive behaviors develop to conserve energy.
Assessment of Function and Disability in Longitudinal Studies
Authors: Gill Thomas M.
Published: October 2010

Over the past 2 decades, there has been considerable progress in the assessment of function and disability in older persons. Tests of physical performance are now routinely included in longitudinal studies to measure functional limitations, which are considered the building blocks of functioning. In addition, new strategies have been developed to assess the presence and onset of disability and to expand the scope of disability assessments beyond traditional indicators of difficulty and dependence. Contemporary measurement technologies, such as item response theory and computer adaptive testing, show great promise in the assessment of functional status and disability, but prospective studies are needed to demonstrate their true value, particularly to identify the circumstances in which their use will improve the assessment of functional outcomes in older persons. Another high priority for future research is to validate and further refine strategies to more completely and accurately ascertain the occurrence of disability in older persons.
Influence of Age and Health Behaviors on Stroke Risk: Lessons from Longitudinal Studies
Authors: Kelly‐Hayes Margaret
Published: October 2010

Stroke is a major cause of death and serious neurological disability in older adults in the United States today. The most effective means available for reducing the burden of stroke involves risk factor modification. Given the growing number of older adults at risk for stroke, it is increasingly important to identify health behaviors that can produce significant change. Ongoing longitudinal studies have identified several behavioral factors that have been shown to improve overall health and reduce the risk of stroke, including effective management of hypertension, cessation of cigarette smoking for those who smoke, and maintaining a healthy diet and active physical lifestyle. Because modification of risk factors remains a primary intervention for effective prevention of stroke, community‐based studies that address and institute stroke prevention strategies have the best opportunity to reduce or postpone the devastating effect of stroke.
An Overview of the Design, Implementation, and Analyses of Longitudinal Studies on Aging
Authors: Newman Anne B.
Published: October 2010

Longitudinal studies have contributed substantially to understanding of aging and geriatric syndromes. These efforts have provided a base of knowledge of the critical factors to consider in designing and implementing new longitudinal studies in older adults. This review highlights some of the major considerations in planning and implementing this type of study. Longitudinal studies can assess change over time and specific disease endpoints. Such projects require multidisciplinary teams with expertise in the many health and contextual factors that must be considered. Recent advances in study design include the use of imaging and biomarkers to assess mechanisms and approaches that raise the ceiling on measurement and integrate assessment of exposures over time. Study implementation requires careful planning and monitoring to maintain fidelity to the scientific goals. Analysis of longitudinal data requires approaches that account for inevitable missing data. New studies should take advantage of the experience obtained from longitudinal studies on aging already conducted.
A Road Map for the Recruitment and Retention of Older Adult Participants for Longitudinal Studies
Authors: Bonk Janet
Published: October 2010

Cost‐effective recruitment of older adult study participants is essential to geriatric research. Because this age group is particularly challenging to recruit, careful planning and ongoing evaluation is important for successful participant recruitment and retention. Experienced recruitment staff should be involved in a study from the earliest planning stages through the active recruitment phase to the last randomization or enrollment visit. A number of participant burdens are unique to the elderly population. Recruitment staff should be trained to understand and assist with the needs of older research volunteers. Addressing these unique participant burdens can ensure successful study participant recruitment and retention in ongoing and future longitudinal studies on aging.
The Aging Mind: Vascular Health in Normal Cognitive Aging
Authors: Warsch Jessica R. L. , Wright Clinton B.
Published: October 2010

In spite of the breakneck speed at which understanding of the biological basis of the aging process has evolved, the important determinants of aging and longevity have yet to be uncovered. The preservation of cognitive functioning is an essential component of successful aging, and the ability to distinguish those who maintain cognitive health into advanced age from those who experience cognitive decline may influence public health efforts to prevent or delay the onset of cognitive impairment in old age. There is growing evidence implicating vascular risk factors and related subclinical cerebrovascular damage in cognitive impairment and dementia, but Alzheimer's disease is highly prevalent in older populations, and the role of inflammation in vascular and neurodegenerative processes is poorly understood. There is a growing need to examine the effects of these factors on normal cognitive aging. This brief survey of the literature reviews evidence of the roles of subclinical vascular brain damage and exposure to cerebrovascular risk factors in normal cognitive aging.
Long‐Term RV Threshold Behavior by Automated Measurements: Safety is the Standpoint of Pacemaker Longevity!
Authors: BIFFI MAURO , BERTINI MATTEO , MAZZOTTI ANDREA , GARDINI BEATRICE , MANTOVANI VALENTINA , ZIACCHI MATTEO , VALZANIA CINZIA , MARTIGNANI CHRISTIAN , DIEMBERGER IGOR , BORIANI GIUSEPPE
Published: October 2010

Background: We studied long‐term right ventricular (RV) pacing threshold (RVPT) behavior in patients consecutively implanted with pacemakers capable of automatic output reprogramming tracked by automatic RV threshold measurement (automatic verification of capture [AVC]).

Methods: All the patients had state‐of‐the art steroid‐eluting bipolar pacing leads and were RV‐paced by an AVC algorithm from the three American manufacturers. Follow‐up occurred twice in the first year after implantation, then yearly until approaching elective replacement indicator.

Results: Three hundred and twenty‐one patients aged 73 ± 12 years were observed for 49 ± 26 months on average. At implantation, RVPT was 0.54 ± 0.2 V at 0.4 ms at an average 774 ± 217 Ω impedance. Forty‐one of the 321 patients (12.8%) had a permanent RVPT increase above 1.5 V at 0.4 ms: RVPT was between 1.6 and 2.5 V in 29 of 321 (9%) patients, whereas it was between 2.6 and 3.5 V in seven of 321 (2.2%) patients, and >3.5 V in five of 321 (1.5%) patients. No exit block occurred because of automatic RV output adjustment by AVC algorithms. No predictor of RVPT increase was found at multivariable analysis.

The maximum RVPT increase occurred within 12 months from implantation in 19 of 321 (5.9%) patients, between the first and the second year in 12 of 321 (3.7%), between the second and the sixth year in eight of 321 (2.5%), and after the sixth year in two of 321 (0.6%).

Conclusion: Despite technologic improvement in lead manufacturing, long‐term increase of the RVPT occurs in about 13% of patients, possibly representing a serious safety issue in 3.7% when 2.5 V at 0.4 ms is exceeded. AVC algorithms can improve patients’ safety by automatic tailoring of the pacing output to threshold fluctuations, while maximizing device longevity. (PACE 2011; 89–95)
Expression of CD66 in non‐Hodgkin lymphomas and multiple myeloma
Authors: Josef Karban , Heidi Mocikova , Robert Pytlik , Pavel Klener , Marek Trneny
Published: October 2010

Objectives:  90Y‐labeled anti‐CD66b monoclonal antibody clone BW 250/183 was developed for treatment of tumors. The aim of the study was the analysis of CD66 expression in lymphoproliferative malignancies to expand the potential of anti‐CD66‐based therapy.

Patients and methods:  Bone marrow samples from 260 patients were examined for the expression of CD66 on tumor cells in 104 B‐chronic lymphocytic leukemias (B‐CLL), 28 mantle cell lymphomas (MCL), 22 follicular lymphomas (FCL), 15 marginal zone lymphomas (MZL), 12 lymphoplasmacytic lymphomas (LPL), 13 diffuse large B cell lymphomas (DLBCL), 4 T‐non‐Hodgkin lymphomas (T‐NHL), 3 B‐NHL not otherwise specified (B‐NHL NOS), 3 B acute lymphoblastic leukemias (B‐ALL), and in 56 multiple myelomas (MM) by flow cytometry.

Results:  Positive (≥ 20%) expression of CD66abce clone Kat4c was detected in 76% of B‐CLL and 76.8% of MM. The highest number of CD66abce‐positive samples was in MCL and LPL (96.4% of 28 and 91.7% of 12 patients, respectively). Expression of CD66b clone BW 250/183 was examined in 114 of 260 samples. Positive expression was detected in 23.3% of B‐CLL (6/35), 17.1% of MM (7/30), and 21.4% of MCL (3/14) samples.

Conclusion:  The expression of CD66b compared to CD66abce was lower in all measured samples. Use of radiolabeled anti‐CD66b antibody for the treatment of lymphoproliferative diseases appears to have limited preclinical substantiation.
Oral myiasis in an elderly patient
Authors: Ribeiro Michel Campos , De Oliveira Pepato André , De Matos Fernando Pando , Sverzut Cássio Edvard , Abrahão Ana Amélia Carraro , Trivellato Alexandre Elias
Published: October 2010

doi: 10.1111/j.1741‐2358.2010.00432.x

Oral myiasis in an elderly patient

Background:  Myiasis is the invasion of living tissue of humans and other mammals by eggs or maggots of flies of the order of Diptera. It occurs mainly in the Tropics and is associated with inadequate public and personal hygiene. Oral myiases in an older man appears to be rare.

Objective:  To relate a case of oral myiases in a debilitated older man treated by mechanical removal of the maggots, identifying the adult insect that caused the infestation.

Methods:  The diagnosis of oral myiasis was established by the clinical examination and it was detected that the infestation involved only soft tissue and the sinus cavity. The patient was submitted to two mechanical removal of the visible maggots.

Results:  Total of 110 maggots was removed from the oral cavity of the patient and adult insects was identified as belonging to the Calliphoridae Family, Cochliomyia hominivorax species. The patient died two days after the second procedure by severe systemic complications.

Conclusions:  The mechanic removal and the identification of the maggots must be adopted as soon as possible to prevent further tissue damage and bacterial infection in cases of oral myiasis. Special attention should be given to the debilitated old patients that are particularly susceptible to oral myiasis infestation.
A matrix gene–based multiplex real‐time RT‐PCR for detection and differentiation of 2009 pandemic H1N1 and other influenza A viruses in North America
Authors: Harmon Karen , Bower Leslie , Kim Won‐Il , Pentella Michael , Yoon Kyoung‐Jin
Published: October 2010

Please cite this paper as: Harmon et al. (2010) A matrix gene–based multiplex real‐time RT‐PCR for detection and differentiation of 2009 pandemic H1N1 and other influenza A viruses in North America. Influenza and Other Respiratory Viruses 4(6), 405–410.

Background  The emergence in humans of pandemic (H1N1) 2009 (pH1N1) with similarities to swine influenza viruses (SIVs) caused much concern for both human and animal health as potential for interspecies transmission was initially unknown.

Objectives  The goal of this study was to develop a real‐time RT‐PCR test for the detection and differentiation of 2009 pH1N1 and endemic influenza A viruses in North America.

Methods  Matrix (M) gene sequences from U.S. human pH1N1 cases and U.S. SIVs were aligned to determine a suitable region for an assay target. Primers were selected to amplify all influenza A. Two probes were designed to differentiate pH1N1 (EA matrix) from endemic (NA matrix) SIVs. The assay was validated using the first U.S. pH1N1 strain, 10 human pH1N1‐positive specimens and nine U.S. SIV isolates, then evaluated on 165 specimens of swine and other animal origin submitted to the Iowa State University Veterinary Diagnostic Laboratory. Results were compared to other influenza A PCR assays. Sequences from additional pH1N1 strains and contemporary H1N1 SIVs were used to assess robustness of the selected primers and probes for the intended purpose.

Results  The new assay’s results from clinical specimens concurred with confirmatory PCR testing. The additional probe designed from sequence analysis improved detection of the NA matrix subtype when added to the reaction mixture.

Conclusion  This assay detects and differentiates pH1N1 and US influenza A viruses in various sample matrices and species. Good bioinformatics support is critical when designing RT‐PCR assays and monitoring their performance.
Infectivity of equine H3N8 influenza virus in bovine cells and calves
Authors: Lin Chengbin , Holland Jr Robert E. , McCoy Morgan H. , Donofrio‐Newman Jennifer , Vickers Mary L. , Chambers Thomas M.
Published: October 2010

Please cite this paper as:Linet al.(2010) Infectivity of equine H3N8 influenza virus in bovine cells and calves. Influenza and Other Respiratory Viruses 4(6), 357–361.

Background Serological evidence for influenza A, subtype H1 and H3 virus infections of bovines, associated with respiratory disease and decreased milk production, has been reported. Equine H3N8 influenza virus circulates widely and was responsible for the introduction of H3N8 influenza into canines.

Objective To explore the possibility that equine H3N8 influenza might also infect bovines.

Methods To assess the incidence of seroconversion in the field, a retrospective survey of bovine serum samples was carried out. Also, primary cultures of bovine nasal turbinate cells, and live beef calves, were studied for their permissiveness to infection.

Results and Conclusions We found serological evidence of exposure of bovines in Kentucky to H3 influenza. We demonstrate that cultured bovine respiratory epithelium is permissive for the growth of equine H3N8 influenza virusin vitro, but this virus does not replicate extensively or produce disease in experimentally inoculated cattle.
A new method to assess the risk of local and widespread flooding on rivers and coasts
Authors: Lamb R. , Keef C. , Tawn J. , Laeger S. , Meadowcroft I. , Surendran S. , Dunning P. , Batstone C.
Published: October 2010

To date, national‐ and regional‐scale flood risk assessments have provided valuable information about the annual expected consequences of flooding, but not the exposure to widespread concurrent flooding that could have damaging consequences for people and the economy. We present a new method for flood risk assessment that accommodates the risk of widespread flooding. It is based on a statistical conditional exceedance model, which is fitted to gauged data and describes the joint probability of extreme river flows or sea levels at multiple locations. The method can be applied together with data from models for flood defence systems and economic damages to calculate a risk profile describing the probability distribution of economic losses or other consequences aggregated over a region. The method has the potential to augment national or regional risk assessments of expected annual damage with new information about the likelihoods, extent and impacts of events that could contribute to the risk.
Seroprevalence of Antibodies toEncephalitozoon cuniculiandToxoplasma gondiiin Farmed Domestic Rabbits in Egypt
Authors: Ashmawy K. I. , Abuakkada S. S. , Awad A. M.
Published: October 2010

Rabbit sera from ten commercial farms representing three provinces in Northern Egypt (Behera, Alexandria and Khafr El‐Sheikh) were submitted to serological screening forEncephalitozoon cuniculiusing an enzyme‐linked immunosorbent assay and forToxoplasma gondiiusing an indirect hemagglutination test. Antibodies againstE. cuniculiwere detected in 36/240 (15%) sera examined while antibodies againstT. gondiishowed a seroprevalence of 22/194 (11.34%). Both infections were detected in all of the examined farms. These results are of epidemiological relevance and public health importance because of the recognized susceptibility of humans toE. cuniculiandT. gondiiinfections; therefore, routine screening examinations of farm rabbits are advised considering the zoonotic potential of these parasites.
Comparing spatially‐varying coefficients models for analysis of ecological data with non‐stationary and anisotropic residual dependence
Authors: Finley Andrew O.
Published: October 2010

1. When exploring spatially complex ecological phenomena using regression models it is often unreasonable to assume a single set of regression coefficients can capture space‐varying and scale‐dependent relationships between covariates and the outcome variable. This is especially true when conducting analysis across large spatial domains, where there is an increased propensity for anisotropic dependence structures and non‐stationarity in the underlying spatial processes.

2. Geographically weighted regression (GWR) and Bayesian spatially‐varying coefficients (SVC) are the most common methods for modelling such data. This paper compares these methods for modelling data generated from non‐stationary processes. The comparison highlights some strengths and limitations of each method and aims to assist those who seek appropriate methods to better understand spatially complex ecological systems. Both synthetic and ecological data sets are used to facilitate the comparison.

3. Results underscored the need for the postulated model to approximate the underlying mechanism generating the data. Further, results show GWR and SVC can produce very different regression coefficient surfaces and hence dramatically different conclusions can be drawn regarding the impact of covariates. The trade‐off between the richer inferential framework of SVC models and computational demands is also discussed.