bluuebunny/crossref_metadata_2025 huggingface dataset:
How Much Does Wealth Matter in the Acquisition of Financial Literacy?
Authors: MONTICONE CHIARA
Published: June 2010

The acknowledged widespread lack of financial literacy casts serious doubts on the ability of individuals to make financial decisions. Some studies suggest that financial experience can affect financial knowledge and that household financial wealth can be a factor leading to the acquisition of financial literacy. This article investigated the determinants of financial literacy using the 2006 wave of the Italian survey on household income and wealth. Empirical results indicated that wealth has a positive but small effect on the degree of financial knowledge.
Implications for cardiology nurse practitioner billing: A comparison of hospital versus office practice
Authors: Hull‐Grommesh Lori , Ellis Elizabeth Fuselier , Mackey Thomas A.
Published: June 2010

Purpose: To discuss the implications for cardiology nurse practitioner (NP) billing and compare and contrast inpatient Medicare billing practices versus outpatient Medicare billing practices.

Data sources: Selected articles, text books, and government websites.

Conclusions: In today's complex and expensive healthcare system, there has been a steady decline in the reimbursement rate for professional services to hospitals and physicians. NPs can have a significant impact on reducing this decline by billing for services provided.

Implications for practice: The cardiology NP can enhance institutional reimbursement quality and patient safety. The different billing methods such as independent billing, shared billing, and incident to billing by the cardiology NP can be complex.
Mondor's disease: A case study
Authors: Paniagua Carmen T. , Negron Zuleika Diaz
Published: June 2010

Purpose: To provide an overview of the clinical presentation, diagnosis, management, and treatment with advanced practice nursing implications of Mondor's disease.

Data sources: Case presentation and comprehensive literature review on Mondor's disease.

Conclusions: Mondor's disease is a rare disorder that can present after breast surgery. Patients present with a painful cord‐like structure that can take weeks to heal.

Implications for practice: An understanding of the pathophysiology, clinical presentation, treatment, and management of this uncommon disease is important for the advanced nurse practitioner. The practitioner's recognition and differentiation of it from a breast abscess or a primary, recurrent or metastatic carcinoma is paramount.
Comparative QSAR Studies on Toxicity of Phenol Derivatives Using Quantum Topological Molecular Similarity Indices
Authors: Hemmateenejad Bahram , Mehdipour Ahmad R. , Miri Ramin , Shamsipur Mojtaba
Published: June 2010

Quantitative structure activity relationship (QSAR) analyses using a novel type of electronic descriptors called quantum topological molecular similarity (QTMS) indices were operated to describe and compare the mechanisms of toxicity of phenols toward five different strains (i.e., Tetrahymena pyriformis, L1210 Leukemia, Pseudomonas putida,Raja japonicaandCucumis sativus). The appropriate QSAR models for the toxicity data were obtained separately employing partial least squares (PLS) regression combined with genetic algorithms (GA), as a variable selection method. The resulting QSAR models were used to identify molecular fragments of phenol derivatives whose electronic properties contribute significantly to the observed toxicities. Using this information, it was feasible to discriminate between the mechanisms of action of phenol toxicity to the studied strains. It was found that toxicities of phenols to all strains, except with L1210 Leukemia, are significantly affected by electronic features of the phenolic hydroxyl group (C‐O‐H). Meanwhile, the resulting models can describe the inductive and resonance effects of substituents on various toxicities.
Inhibition of Tubulogenesis and of Carcinogen‐mediated Signaling in Brain Endothelial Cells Highlight the Antiangiogenic Properties of a Mumbaistatin Analog
Authors: Tahanian Elizabeth , Lord‐Dufour Simon , Das Abhirup , Khosla Chaitan , Roy René , Annabi Borhane
Published: June 2010

A better understanding of the metabolic adaptations of the vascular endothelial cells (EC) that mediate tumor vascularization would help the development of new drugs and therapies. Novel roles in cell survival and metabolic adaptation to hypoxia have been ascribed to the microsomal glucose‐6‐phosphate translocase (G6PT). While antitumorigenic properties of G6PT inhibitors such as chlorogenic acid (CHL) have been documented, those of the G6PT inhibitor and semi‐synthetic analog AD4‐015 of the polyketide mumbaistatin are not understood. In the present study, we evaluated the in vitro antiangiogenic impact of AD4‐015 on human brain microvascular endothelial cells (HBMEC), which play an essential role as structural and functional components in tumor angiogenesis. We found that in vitro HBMEC migration and tubulogenesis were reduced by AD4‐015 but not by CHL. The mumbaistatin analog significantly inhibited the phorbol 12‐myristate 13‐acetate (PMA)‐induced matrix‐metalloproteinase (MMP)‐9 secretion and gene expression as assessed by zymography and RT‐PCR. PMA‐mediated cell signaling leading to cyclooxygenase (COX)‐2 expression and IκB downregulation was also inhibited, further confirming AD4‐015 as a cell signaling inhibitor in tumor promoting conditions. G6PT functions may therefore account for the metabolic flexibility that enables EC‐mediated neovascularization. This process could be specifically targeted within the vasculature of developing brain tumors by G6PT inhibitors.
Neurological, imaging and pathological features of a meningeal inflammatory pseudotumour in a Maltese terrier
Authors: Loderstedt S. , Walmsley G. L. , Summers B. A. , Cappello R. , Volk H. A.
Published: June 2010

A five‐year eight‐month‐old Maltese terrier was presented with a 3‐week history of progressive paraparesis and pelvic limb ataxia. Neurological examination was consistent with a lesion involving the T3‐L3 spinal cord segments. Myelogram and magnetic resonance imaging revealed a spherical, intradural‐extramedullary mass lesion at T13/L1. A dorsal laminectomy, durotomy and debulking of the mass were performed. Histopathologic examination revealed a highly cellular tissue, most likely of mesenchymal origin, infiltrated by many lymphocytes, macrophages and neutrophils. The pathological diagnosis of an inflammatory pseudotumour was made. Postsurgical analgesia was achieved with opioids and 2 mg/kg carprofen twice daily for 5 days. When the histopathological diagnosis was made, a tapering course of 1 mg/kg prednisolone twice daily was prescribed, with dose reduction by approximately 50% every 4 to 6 weeks over a 4‐month period. Magnetic resonance imaging was repeated at 22, 32 and 85 weeks postsurgery; no signs of regrowth could be detected and the patient recovered with residual mild paraparesis. Inflammatory pseudotumour has not been documented previously at this site in dogs and, although rare, should be considered in the differential diagnosis of a focal mass lesion affecting the spinal cord. Surgical debulking and immunomodulatory therapy can be curative.
Ecometrics: The traits that bind the past and present together
Authors: ERONEN Jussi T. , POLLY P. David , FRED Marianne , DAMUTH John , FRANK David C. , MOSBRUGGER Volker , SCHEIDEGGER Christoph , STENSETH Nils Chr. , FORTELIUS Mikael
Published: June 2010

We outline here an approach for understanding the biology of climate change, one that integrates data at multiple spatial and temporal scales. Taxon‐free trait analysis, or “ecometrics,” is based on the idea that the distribution in a community of ecomorphological traits such as tooth structure, limb proportions, body mass, leaf shape, incubation temperature, claw shape, any aspect of anatomy or physiology can be measured across some subset of the organisms in a community. Regardless of temporal or spatial scale, traits are the means by which organisms interact with their environment, biotic and abiotic. Ecometrics measures these interactions by focusing on traits which are easily measurable, whose structure is closely related to their function, and whose function interacts directly with local environment. Ecometric trait distributions are thus a comparatively universal metric for exploring systems dynamics at all scales. The main challenge now is to move beyond investigating how future climate change will affect the distribution of organisms and how it will impact ecosystem services and to shift the perspective to ask how biotic systems interact with changing climate in general, and how climate change affects the interactions within and between the components of the whole biotic‐physical system. We believe that it is possible to provide believable, quantitative answers to these questions. Because of this we have initiated an IUBS program iCCB (integrative Climate Change Biology).
Climate change and invasive species: double jeopardy
Authors: MAINKA Susan A. , HOWARD Geoffrey W.
Published: June 2010

Two of the key drivers of biodiversity loss today are climate change and invasive species. Climate change is already having a measurable impact on species distributions, reproduction and behavior, and all evidence suggests that things will get worse even if we act tomorrow to mitigate any future increases in greenhouse gas emissions: temperature will increase, precipitation will change, sea level will rise and ocean chemistry will change. At the same time, biological invasions remain an important threat to biodiversity, causing species loss, changes in distribution and habitat degradation. Acting together, the impacts of each of these drivers of change are compounded and interactions between these two threats present even greater challenges to field conservationists as well as policymakers. Similarly, the social and economic impacts of climate change and invasive species, already substantial, will be magnified. Awareness of the links between the two should underpin all biodiversity management planning and policy.
Some biological consequences of environmental change: A study using barnacles (Cirripedia: Balanomorpha) and gum trees (Angiospermae: Myrtaceae)
Authors: BUCKERIDGE John S.
Published: June 2010

Uniformitarianism permits understanding of the past on the basis of the present, and modeling the future through consideration of the fossil record. The present paper addresses the impact environmental (climatic) change has had on acorn barnacles and eucalyptus trees. Acorn barnacles (Balanomorpha) are first recorded after the K/T mass‐extinction event. In the Paleogene, rapid radiation resulted in their occupying most marine environments. That balanomorphs survived both the Paleocene–Eocene thermal maximum and the Pleistocene glaciation is testament to their ability to adapt to opportunities; they are known from the littoral (Chamaesipho) to depths of 3600 m (Tetrachaelasma) and within this from diverse substrates: rock, wood and miscellaneous flotsam, plus in symbiosis or commensalism with most larger marine organisms. Darwin's (1854) view of the late Tertiary as the age of barnacles is reflected in their diversity, distribution and biomass. Barnacles are contrasted with the Australian Myrtaceae: plants ranging from woody shrubs to tall trees. The most significant is Eucalyptus sensu lato, which typifies Australia's flora, and is characterized by aromatic leaves that produce eucalyptol. Eucalyptus has evolved strategies that result in its domination of Australian open woodlands: these include production of highly flammable eucalyptol oil (with a flashpoint of 49 °C) and an unprecedented ability to regenerate following forest fires. Gum trees and barnacles first appear in the Paleogene, their earliest records are Australasian, and they both demonstrate extraordinary resilience when environmental conditions are optimal.
Direct impacts of recent climate warming on insect populations
Authors: ROBINET Christelle , ROQUES Alain
Published: June 2010

Effects of recent climate change have already been detected in many species, and, in particular, in insects. The present paper reviews the key impacts of global warming on insect development and dispersal. The effects of climate change appear to be much more complex than a simple linear response to an average increase in temperature. They can differ between seasons and bioclimatic regions. Earlier flight periods, enhanced winter survival and acceleration of development rates are the major insect responses. Differential response of insects and hosts to warming up might also lead to disruption of their phenological synchrony, but adaptive genetic processes are likely to quickly restore this synchrony. In a number of cases, warming results in removing or relocating the barriers that limit present species' ranges. It is also likely to facilitate the establishment and spread of invasive alien species. Finally, knowledge gaps are identified and future research interests are suggested.
Decreasing the aging velocity in industry workers
Authors: Kristjuhan Ülo
Published: June 2010

We carried out physiological and ergonomic studies in industry from 1965 to 2000. Participants (2147) were workers in different jobs, such as light industry and the dairy, automotive, and building materials industries. Most of the groups studied included 30–50 male and female workers. In the studies we used a combination of methods and paid much attention to the quantitative assessment of discomfort during working hours. One of the aims was to avoid or postpone various age‐related diseases (cardiovascular, musculoskeletal, etc.) of workers. We provided recommendations to managers and individuals: changing the technology, work organization, corrective measures of ergonomics, self‐care procedures or doctor visits, correct diet, preventive exercises, and improving labor productivity. Changes based on our studies postponed age‐related changes up to 20 years and pointed to close connections between the environment and aging peculiarities in the human organism.
Hyperbaric oxygen treatment induces antioxidant gene expression
Authors: Godman Cassandra A. , Joshi Rashmi , Giardina Charles , Perdrizet George , Hightower Lawrence E.
Published: June 2010

Although the underlying molecular causes of aging are not entirely clear, hormetic agents like exercise, heat, and calorie restriction may generate a mild pro‐oxidant stress that induces cell protective responses to promote healthy aging. As an individual ages, many cellular and physiological processes decline, including wound healing and reparative angiogenesis. This is particularly critical in patients with chronic non‐healing wounds who tend to be older. We are interested in the potential beneficial effects of hyperbaric oxygen as a mild hormetic stress on human microvascular endothelial cells. We analyzed global gene expression changes in human endothelial cells following a hyperbaric exposure comparable to a clinical treatment. Our analysis revealed an upregulation of antioxidant, cytoprotective, and immediate early genes. This increase coincided with an increased resistance to a lethal oxidative stress. Our data indicate that hyperbaric oxygen can induce protection against oxidative insults in endothelial cells and may provide an easily administered hormetic treatment to help promote healthy aging.
Synchronization of posttranslational modifications during aging
Authors: Schrattenholz André , Šoškić Vukić , Groebe Karlfried
Published: June 2010

There is an urgent need for surrogate biomarkers in clinical diagnostics but also preclinical in toxicology of chemicals and efficacy testing of pharmaceuticals. On the background of the emerging fields of systems biology and theranostics, the importance of time scales and the synchronization of complex biological readouts become increasingly obvious. Systemic effects such as responses to stimuli, medical intervention, cellular stress, or toxicity elicit immediate molecular changes on the protein level. Early events include phosphorylation and oxidation of proteins. These posttranslational modifications have a direct impact on enzyme activities and protein–protein interactions. Only at downstream stages is gene transcription activated. Here we outline the analytical and statistical requirements dealing with complex patterns of protein expression and the extraction of protein surrogate biomarkers defining specific early stages of biological responses. We also present successful examples from research on aging and discuss prerequisites and necessary considerations while moving candidates to validation.
Why aging research?
Authors: Farrelly Colin
Published: June 2010

The American philosopher John Rawls describes a fair system of social cooperation as one that is both rational and reasonable. Is it rational and reasonable for societies that (1) are vulnerable to diverse risks of morbidity (e.g., cancer, heart disease) and mortality and (2) are constrained by limited medical resources, to prioritize aging research? In this paper I make the case for answering “yes” on both accounts. Focusing on a plausible example of an applied gerontological intervention (i.e., an antiaging pharmaceutical), I argue that the goal of decelerating the rate of human aging would be a more effective strategy for extending the human health span than the current strategy of just tackling each specific disease of aging. Furthermore, the aspiration to retard human aging is also a reasonable aspiration, for the principle that underlies it (i.e., the duty to prevent harm) is one that no one could reasonably reject.
Mitochondrial pathways governing stress resistance, life, and death in the fungal aging model Podospora anserina
Authors: Osiewacz Heinz D. , Brust Diana , Hamann Andrea , Kunstmann Birgit , Luce Karin , Müller‐Ohldach Mathis , Scheckhuber Christian Q. , Servos Jörg , Strobel Ingmar
Published: June 2010

Work from more than 50 years of research has unraveled a number of molecular pathways that are involved in controlling aging of the fungal model system Podospora anserina. Early research revealed that wild‐type strain aging is linked to gross reorganization of the mitochondrial DNA. Later it was shown that aging of P. anserina does also take place, although at a slower pace, when the wild‐type specific mitochondrial DNA rearrangements do not occur. Now it is clear that a network of different pathways is involved in the control of aging. Branches of these pathways appear to be connected and constitute a hierarchical system of responses. Although cross talk between the individual pathways seems to be fundamental in the coordination of the overall system, the precise underlying interactions remain to be unraveled. Such a systematic approach aims at a holistic understanding of the process of biological aging, the ultimate goal of modern systems biology.
Targeting the age‐related occurrence, removal, and accumulation of molecular damage by hormesis
Authors: Rattan Suresh I. S.
Published: June 2010

Strategies for testing and developing effective means of intervention, prevention, and modulation of aging incorporate means to minimize the occurrence and accumulation of molecular damage, to reduce molecular heterogeneity, and to evaluate the relevance of the type and extent of damage with respect to its role in aging and age‐related diseases. One such approach is that of mild stress‐induced hormesis, which stimulates maintenance and repair systems and strengthens the homeodynamic space of cells and organisms. Hormesis through mild heat shock, natural and synthetic hormetins, and other stressors brings about several antiaging effects in human fibroblasts, keratinocytes, and telomerase‐immortalized bone marrow stem cells. Depending on the cell type, these antiaging hormetic effects include extension of replicative life span, enhanced proteasomal activities, increased chaperone levels, and improved wound healing, angiogenesis, and differentiation. The main molecular pathways for achieving such hormetic effects are through targeting the processes for the repair and removal of molecular damage, which can slow aging.
The marvel of percutaneous cardiovascular devices in the elderly
Authors: Guidoin Robert , Douville Yvan , Clavel Marie‐Annick , Zhang Ze , Nutley Mark , Pîbarot Philippe , Dionne Guy
Published: June 2010

Thanks to minimally invasive procedures, frail and elderly patients can also benefit from innovative technologies. More than 14 million implanted pacemakers deliver impulses to the heart muscle to regulate the heart rate (treating bradycardias and blocks). The first human implantation of defibrillators was performed in early 2000. The defibrillator detects cardiac arrhythmias and corrects them by delivering electric shocks. The ongoing development of minimally invasive technologies has also broadened the scope of treatment for elderly patients with vascular stenosis and aneurysmal disease as well as other complex vascular pathologies. The nonsurgical cardiac valve replacement represents one of the most recent and exciting developments, demonstrating the feasibility of replacing a heart valve by way of placement through an intra‐arterial or trans‐ventricular sheath. Percutaneous devices are particularly well suited for the elderly as the surgical risks of minimally invasive surgery are considerably less as compared to open surgery, leading to a shorter hospital stay, a faster recovery, and improved quality of life.
Isolation and Rheological Properties of Tamarind Seed Polysaccharide from Tamarind Kernel Powder Using Protease Enzyme and High‐Intensity Ultrasound
Authors: Poommarinvarakul Sukhum , Tattiyakul Jirarat , Muangnapoh Chirakarn
Published: June 2010

Abstract:  The effectiveness of using protease and combinations of protease and high‐intensity ultrasound for high‐purity, high‐yield tamarind seed polysaccharide (TSP) production was investigated. Tamarind kernel powder (TKP) suspension was treated with protease alone at 0.16, 0.48, and 0.80 units/mL and with protease‐ultrasound combinations over 3 different orders of sequence (before, simultaneous with, and after protease digestion) using combinations of 0.48 units/mL protease and high‐intensity ultrasound at 25% and 50% amplitude for 15 and 30 min. The long protease digestion time could produce high‐purity isolated TSP, but the polysaccharide yields were lower. The polysaccharide purity and yield were highly improved, even at a shorter protease digestion time, when the protease treatment was combined with high‐intensity ultrasound. The increased amplitude level and sonication time decreased the average molecular weight of the polysaccharide. The rheological properties of the TKP and the isolated TSP, from nondestructive oscillatory measurements, demonstrated that the latter present a viscoelastic solution. The decreasing of protein content resulted in better elasticity of the solution. The power law model could be used to fit the down curve between shear rate and shear stress data. The consistency coefficient (K) increased while the flow behavior index decreased with the increased purity of the polysaccharide as a result of increasing increased digestion time, enzyme concentration, sonication power, and sonication time.
Detecting Food‐ and Waterborne Viruses by Surface‐Enhanced Raman Spectroscopy
Authors: Fan Cui , Hu Zhiqiang , Riley Lela K. , Purdy Gregory A. , Mustapha Azlin , Lin Mengshi
Published: June 2010

Abstract:  Food‐ and waterborne viruses pose serious health risks to humans and were associated with many outbreaks worldwide. Rapid, accurate, and nondestructive methods for detection of viruses are of great importance to protect public health. In this study, surface‐enhanced Raman spectroscopy (SERS) coupled with gold SERS‐active substrates was used to detect and discriminate 7 food‐ and waterborne viruses, including norovirus, adenovirus, parvovirus, rotavirus, coronavirus, paramyxovirus, and herpersvirus. Virus samples were purified and dialyzed in phosphate buffered saline (8 to 9 log PFU/mL) and then further diluted in deionized water for SERS measurement. After capturing the characteristic SERS spectral patterns, multivariate statistical analyses, including soft independent modeling of class analogy (SIMCA) and principal component analysis (PCA), were employed to analyze SERS spectral data for characterization and identification of viruses. The results show that SIMCA was able to differentiate viruses with and without envelope with >95% of classification accuracy, while PCA presented clear spectral data segregations between different virus strains. The virus detection limit by SERS using gold substrates reached a titer of 102.

Practical Application:  SERS is a simple, rapid, and accurate method for detection of food‐ and waterborne viruses. Our results demonstrate that coupled with gold substrates, SERS was able to rapidly detect and discriminate among different food‐ and waterborne viruses, indicating that SERS can provide rapid, sensitive, and reproducible detection results with minimum sample preparation for virus detection.
Viability of Bifidobacteria Strains in Yogurt with Added Oat Beta‐Glucan and Corn Starch during Cold Storage
Authors: Rosburg Valerie , Boylston Terri , White Pamela
Published: June 2010

Abstract:  Probiotics must be consumed at a level of 107 CFU/mL for successful colonization of the gut. In yogurts containing beneficial cultures, the survival of probiotic strains can quickly decline below this critical concentration during cold storage. We hypothesized that beta‐glucan would increase the viability of bifidobacteria strains in yogurt during cold storage. Yogurts were produced containing 0.44% beta‐glucan (concentrated or freeze‐dried) extracted from whole oat flour and/or 1.33% modified corn starch, and bifidobacteria (B. breve or B. longum) at a concentration of at least 109 CFU/mL. All yogurts were stored at 4 °C. Bifidobacteria and yogurt cultures, Streptococcus thermophilus and Lactobacillus delbureckii subsp. bulgaricus, were enumerated from undisturbed aliquots before fermentation, after fermentation, and once a week for 5 wk. S. thermophilus and L. bulgaricus maintained a concentration of at least 108 CFU/mL in yogurts containing concentrated or freeze‐dried beta‐glucan regardless of starch addition, and in the control with no added beta‐glucan or starch. Similarly, the probiotic, Bifidobacterium breve, survived above a therapeutic level in all treatments. The addition of beta‐glucan prolonged the survival of Bifidobacterium longum at a concentration of at least 107 CFU/mL by up to 2 wk on average beyond the control. Further, the inclusion of concentrated beta‐glucan in yogurt improved survival of B. longum above 107 CFU/mL by 1 wk longer than did freeze‐dried beta‐glucan. Study results suggest that beta‐glucan has a protective effect on bifidobacteria in yogurt when stressed by low‐temperature storage.

Practical Application:  This study suggests that beta‐glucan (oat fiber) may improve bifidobacteria survival in yogurt during refrigerated storage.
Sorghum Proteins: The Concentration, Isolation, Modification, and Food Applications of Kafirins
Authors: De Mesa‐Stonestreet Normell Jhoe , Alavi Sajid , Bean Scott R.
Published: June 2010

Abstract:  Celiac disease is a serious condition affecting millions of individuals. Those afflicted with this illness are resigned to a lifelong avoidance of products containing the storage prolamin proteins found in cereal grains wheat, rye, and barley. Since many food products are based on these cereals, especially wheat, celiac patients have very limited food choices, and those that are available to them are generally poor in quality, often nutritionally deficient, and expensive. Furthermore, this condition also indirectly affects their families and friends with whom they share meals. Thus, a burgeoning need exists to develop nutritious, palatable, and affordable foods, especially staples like bread and pasta, for these individuals and their families and friends who are accustomed to wheat based products. Grain sorghum and its proteins are safe for celiac patients and individuals with varying levels of gluten intolerances. However, the main sorghum proteins, kafirins, are resistant to digestion. They are also difficult to extract and modify in an industrial‐scale process and with food‐compatible chemicals, thus limiting their use in foods. This review describes studies on kafirin extraction and methods for modifying sorghum proteins for improved nutrition and functionality, as well as food applications. Armed with this knowledge, scientists and technologists will be in a better position to identify opportunities that will further enhance the nutritional and functional value of sorghum proteins.
Effect of Ambient Humidity on UV/Visible Photodegradation of Melanin Thin Films
Authors: Sharma Anup
Published: June 2010

Photodegradation of spin‐coated thin films of melanin is investigated using UVA and visible light from light‐emitting diodes. The gradual increase in transmitted light through the film is measured as melanin photodegrades over the course of several hours. The photodegradation rate is measured for wavelengths in the 365–600 nm range. It is found that the increase in ambient humidity significantly accelerates the photodegradation process. Implications of these observations for evolution of melanism in biological systems are discussed.
Survival analysis of pancreatic and periampullary collision cancers
Authors: NIU Geng Ming , JIN Da Yong , JI Yuan , HOU Jun , WANG Dan Song , LOU Wen Hui
Published: June 2010

OBJECTIVE:  Collision cancers are malignancies in the same organ or anatomical site that comprises at least two different tumor components, with no mixed or transitional area between two components. Collision cancers are very rare in the pancreas and periampullary region. The aim of this study was to analyze the clinical and pathological features and prognosis of collision cancer in the pancreas and periampullary region.

METHODS:  Patients with collision cancers of the pancreas and periampullary region (n= 10) who had undergone radical surgery were retrospectively studied. Their clinical and pathological features were summarized and the prognostic data were compared with patients with pancreatic adenocarcinomas who underwent radical surgery (n= 87) and with patients with pancreatic or periampullary malignancies who underwent palliative surgery (n= 89).

RESULTS:  Compared with other cancers at these sites, collision cancer presents no specific clinical features. However, the median survival period of patients with such malignancies was only 10.0 months, which was much less than those with pancreatic adenocarcinomas who underwent radical surgery (27.0 months) and those who received a palliative operation (20.9 months) only.

CONCLUSION:  Collision cancers of the pancreas and periampullary region are difficult to diagnose preoperatively. Their prognosis is poor even after radical resection and adjuvant chemotherapy were given.
Intellectual Property: a powerful tool to develop biotech research
Authors: Giugni Diego , Giugni Valter
Published: June 2010

Today biotechnology is perhaps the most important technology field because of the strong health and food implications. However, due to the nature of said technology, there is the need of a huge amount of investments to sustain the experimentation costs. Consequently, investors aim to safeguard as much as possible their investments. Intellectual Property, and in particular patents, has been demonstrated to actually constitute a powerful tool to help them. Moreover, patents represent an extremely important means to disclose biotechnology inventions. Patentable biotechnology inventions involve products as nucleotide and amino acid sequences, microorganisms, processes or methods for modifying said products, uses for the manufacture of medicaments, etc. There are several ways to protect inventions, but all follow the three main patentability requirements: novelty, inventive step and industrial application.
Outcome of surgery after macula‐off retinal detachment – results from MUSTARD, one of the largest databases on buckling surgery in Europe. Results from a large German case series
Authors: Thelen Ulrich , Amler Susanne , Osada Nani , Gerding Heinrich
Published: June 2010

Purpose:  To evaluate the anatomical success rate of scleral buckling surgery in the treatment of rhegmatogenous retinal detachment and to evaluate the differences in outcome between patients suffering macula‐off retinal detachment and those without a macular involvement.

Methods:  As a retrospective interventional case series, Munster Study on Therapy Achievements in Retinal Detachment (MUSTARD) is one of the largest ever established of retinal detachment patients and their outcome after buckling surgery, with 4325 patients who underwent surgery between 1980 and 2001. In 53.94% (n = 2134) of 3956 patients with nontraumatic retinal detachment, the macula was involved. The main outcome measure was the achievement of dry anatomical attachment of the retina.

Results:  The success rate in patients with macula‐off retinal detachment is 80.46% and thus 7.78% lower (p < 0.01) than that in those patients with their macula intact whose success rate amounted to 88.24%. The overall success rate of all 4325 MUSTARD patients was 83.98%.

Conclusions:  Scleral buckling is an established and mostly successful method for the treatment of retinal detachment. As our case series has demonstrated, even eyes with macula‐off can be treated successfully by this procedure, thereby avoiding the complications of primary vitrectomy.
Development of a questionnaire for identification of the risk factors for osteoarthritis of the knees in developing countries. A pilot study in Iran and Bangladesh. An ILAR–COPCORD phase III study
Authors: HAQ Syed Atiqul , DAVATCHI Fereydoun , DAHAGHIN Saeideh , ISLAM Nazrul , GHOSE Aniruddha , DARMAWAN John , CHOPRA Arvind , YU Zeng Quing , DANS Leonila F. , RASKER Johannes J.
Published: June 2010

Background:  Knee osteoarthritis (OA) is one of the most prevalent rheumatic disorders in the Asia‐Pacific region. Identification of modifiable risk factors is important for development of strategies for primary and secondary prevention of knee OA.

Objective:  Developing a core questionnaire for identification of risk factors of knee OA at the community level.

Methods:  Steps performed: (1) item generation from literature, existing knee OA questionnaires and patient focus group discussions; (2) development of a preliminary APLAR‐COPCORD English questionnaire; (3) translation into target language, back translation and development of a pre‐final target language version; (4) adaptation of the pre‐final target language version through tests of comprehensibility, content validity, test–retest reliability; and (5) finalization of the English questionnaire. Investigators in Bangladesh, Iran, China, Philippines and Indonesia participated in steps 1 and 2. Subsequent steps were carried out by Bangladeshi and Iranian investigators.

Results:  Fifty‐three items were generated. Fourteen were obtainable from physical examination and placed in an examination sheet. Two radiological items were not included. A preliminary English questionnaire comprising the remaining 37 items was constructed and translated into Bengali and Persian. The preliminary Bengali and Persian versions were adapted as a result of tests of comprehensibility, content validity and test–retest reliability. The English questionnaire was adapted through repeated exchange of ideas and experiences among participating investigators. A 35‐item English core questionnaire was finally developed.

Conclusion:  The questionnaires may be used to identify risk factors of knee OA in Asia‐Pacific communities after validation and further adaptation. From these data strategies for primary and secondary prevention of knee OA can be developed.
Association of resistin polymorphism, its serum levels and prevalence of stroke in Japanese type 2 diabetic patients
Authors: Nakashima Eitaro , Watarai Atsuko , Tsukahara Takayoshi , Hamada Yoji , Naruse Keiko , Kamiya Hideki , Kato Jiro , Kato Norihiro , Tomita Makoto , Oiso Yutaka , Nakamura Jiro
Published: June 2010

Aims/Introduction:  Resistin, an inflammatory cytokine, might be involved in the development of atherosclerosis. In a recent paper, we showed that resistin polymorphism might be a risk marker for stroke susceptibility in Japanese type 2 diabetic patients. We tested whether the serum resistin levels might be also a risk marker of stroke independently from RETN polymorphism.

Materials and Methods:  Type 2 diabetic outpatients from our hospitals were enrolled. Patients (n = 89) with a history of coronary heart disease and stroke, and randomly selected controls (n = 178) matched for sex and age, but without a history of coronary heart disease and stroke, were examined for polymorphism ‐420 (C>G) and cytokines levels.

Results:  Serum resistin levels were significantly higher in patients with cardiovascular diseases (CVD) than in those without CVD (P = 0.024), and were highest in patients with stroke among the CVD. In multiple logistic regression analysis, serum resistin levels was an independent risk marker of stroke even after adjusted by RETN polymorphism, age, sex, body mass index, HbA1c, systolic and diastolic blood pressure, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, creatinine, history of coronary heart disease, treatment of insulin, sulfonylurea and aspirin (odds ratio 1.33, 95% confidence interval [CI] 1.02–1.73, P = 0.039). The enrolled patients were divided by their serum resistin levels (high or low group) and their genotypes (CC, CG, GG at ‐420) into six groups. Patients with the GG genotype and high resistin levels showed the highest odds ratio, 5.69 (95% CI 1.24–26.1), compared with the group with CC and low levels.

Conclusions:  The results suggest that serum resistin levels might be a good marker of susceptibility to stroke as well as RETN polymorphism. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.00040.x, 2010)
Rupture of the mesocolon as a cause of recurrent colic in a showjumper mare
Authors: Torre F. , Gasparin J. , Andreasi M. B.
Published: June 2010

An 11‐year‐old Italian Saddlebred showjumper mare was referred for investigation of recurrent colic. The mare had undergone surgery for left dorsal displacement of the ascending colon 5 years previously and had subsequently experienced several episodes of colic that had responded to medical treatment. Due to deterioration of the mare's clinical condition in the last episode, characterised by unrelenting pain and worsening of the cardiovascular parameters, the mare underwent repeat surgery for suspected colonic displacement. Exploratory laparotomy revealed a complete rupture of the mesocolon of the ascending colon. The mesocolon was repaired and the mare recovered uneventfully. She returned to training and competition and only a single episode of mild transient colic was recorded in the follow‐up.
Cystamine Suppresses Polyalanine Toxicity in a Mouse Model of Oculopharyngeal Muscular Dystrophy
Authors: Davies Janet E. , Rose Claudia , Sarkar Sovan , Rubinsztein David C.
Published: June 2010

Mice with oculopharyngeal muscular dystrophy, caused by aggregation of a nuclear protein, show improvement when treated with cystamine, suggesting a possible therapeutic approach for patients.
Tumor-Penetrating Peptides: A Shift from Magic Bullets to Magic Guns
Authors: Feron Olivier
Published: June 2010

A two-motif cyclic peptide facilitates tumor penetration of conjugated or coadministered drugs.
"Drop-the-Loser" Designs—An Alternative Design for Phase III Studies
Authors: Carlson Nichole
Published: June 2010

"Drop-the-loser" clinical trails offer a useful alternative to classic single-dose phase III designs when phase II data are ambiguous.
Impact of Burden on Granulocyte Clearance of Bacteria in a Mouse Thigh Infection Model
Authors: Drusano G. L. , Fregeau Christine , Liu Weiguo , Brown D. L. , Louie Arnold
Published: June 2010

We wished to delineate granulocytes' impact on the clearance of different bacterial burdens of
Pseudomonas aeruginosa
and
Staphylococcus aureus
in a granulocyte-replete mouse thigh infection model. A mouse thigh model was employed. Bacterial challenges from 10
5
to 3 × 10
7
CFU (
S. aureus
) and from 3 × 10
4
to 3 × 10
8
CFU (
P. aeruginosa
) were injected into murine posterior thighs. Organism quantitation was at baseline, 2 h (
Pseudomonas
only), and 24 h. A Michaelis-Menten population model was fit to the data for each organism. Breakpoints for microbial containment by granulocytes were identified. Bacterial burdens exceeding that breakpoint value resulted in organism multiplication. The Michaelis-Menten model fit the data well. For
P. aeruginosa
, the observed-predicted plot had a regression equation that explained over 98% of the variance (
P
≪ 0.001). For
S. aureus
, this relationship explained greater than 94% of the variance (
P
≪ 0.001). Maximal growth rate constants, maximal population burdens, and the bacterial loads at which granulocytes killed if half-saturated were not different. The kill rate constant for
P. aeruginosa
was almost 10 times that of
S. aureus
. Bacterial kill by granulocytes is saturable. No difference between saturation points of different isolates was seen. A higher bacterial burden means an increasing reliance on chemotherapy to drive bacterial clearance.
Is the Recommended Once-Daily Dose of Lamivudine Optimal in West African HIV-Infected Children?
Authors: Bouazza Naïm , Hirt Déborah , Bardin Christophe , Diagbouga Serge , Nacro Boubacar , Hien Hervé , Zoure Emmanuelle , Rouet François , Ouiminga Adama , Blanche Stephane , Van De Perre Philippe , Tréluyer Jean-Marc , Msellati Philippe , Urien Saik
Published: June 2010

We aimed in this study to describe lamivudine concentration-time courses in treatment-naïve children after once-daily administration, to study the effects of body weight and age on lamivudine pharmacokinetics, and to simulate an optimized administration scheme. For this purpose, lamivudine concentrations were measured in 49 children after at least 2 weeks of didanosine-lamivudine-efavirenz treatment. A total of 148 plasma lamivudine concentrations were measured, and a population pharmacokinetic model was developed with NONMEM. The influence of individual characteristics was tested using a likelihood ratio test. Children were divided into two groups, according to their pharmacokinetic parameters, thanks to tree regression analysis. For each patient, the area under the curve was derived from estimated individual pharmacokinetic parameters. Different once-daily doses were simulated in each group, to obtain the same exposure in children as the mean effective exposure in adults (8.9 mg/liter·h). A two-compartment model in which the slope of distribution is assumed to be equal to the absorption rate constant adequately described the data. Parameter estimates were standardized for a mean standard body weight using an allometric model. Children were then divided into 2 groups according to body weight: CL/Fwas significantly higher in children weighing less than 17 kg (1.12 liters/h/kg) than in children over 17 kg (0.95 liters/h/kg;P= 0.01). The target mean AUC of 8.9 mg/liters·h was obtained with a 10-mg/kg once-daily lamivudine (3TC) dose for children below 17 kg; the recommended dose of 8 mg/kg seems to be sufficient in children weighing more than 17 kg. These assumptions should be prospectively confirmed.
Inhibition of Dengue Virus by an Ester Prodrug of an Adenosine Analog
Authors: Chen Yen-Liang , Yin Zheng , Lakshminarayana Suresh B. , Qing Min , Schul Wouter , Duraiswamy Jeyaraj , Kondreddi Ravinder Reddi , Goh Anne , Xu Hao Ying , Yip Andy , Liu Boping , Weaver Margaret , Dartois Veronique , Keller Thomas H. , Shi Pei-Yong
Published: June 2010

Dengue virus (DENV) is the most prevalent mosquito-borne viral pathogen that infects humans. Neither a vaccine nor an antiviral therapy is currently available for DENV. Here, we report an adenosine nucleoside prodrug that potently inhibits DENV replication both in cell culture and in a DENV mouse model. NITD449 (2′-
C
-acetylene-7-deaza-7-carbamoyladenosine) was initially identified as a parental compound that inhibits all four serotypes of DENV with low cytotoxicity. However,
in vivo
pharmacokinetic studies indicated that NITD449 had a low level of exposure in plasma when dosed orally. To increase the oral bioavailability, we covalently linked isobutyric acids to the 3′- and 5′-hydroxyl groups of ribose via ester linkage to NITD449, leading to the prodrug NITD203 (3′,5′-
O
-diisobutyryl-2′-
C
-acetylene-7-deaza-7-carbamoyl-adenosin). Pharmacokinetic analysis showed that upon oral dosing of the prodrug, NITD203 was readily converted to NITD449, resulting in improved exposure of the parental compound in plasma in both mouse and rat. In DENV-infected AG129 mice, oral dosing of the prodrug at 25 mg/kg of body weight reduced peak viremia by 30-fold. Antiviral spectrum analysis showed that NITD203 inhibited various flaviviruses (DENV, yellow fever virus, and West Nile virus) and hepatitis C virus but not Chikungunya virus (an alphavirus). Mode-of-action analysis, using a luciferase-reporting replicon, indicated that NITD203 inhibited DENV RNA synthesis. Although NITD203 exhibited potent
in vitro
and
in vivo
efficacies, the compound could not reach a satisfactory no-observable-adverse-effect level (NOAEL) in a 2-week
in vivo
toxicity study. Nevertheless, our results demonstrate that a prodrug approach using a nucleoside analog could potentially be developed for flavivirus antiviral therapy.
Identification of
Campylobacter jejuni
Genes Involved in Its Interaction with Epithelial Cells
Authors: Novik Veronica , Hofreuter Dirk , Galán Jorge E.
Published: June 2010

Campylobacter jejuni
is the leading cause of infectious gastroenteritis in industrialized nations. Its ability to enter and survive within nonphagocytic cells is thought to be very important for pathogenesis. However, little is known about the
C. jejuni
determinants that mediate these processes. Through an extensive transposon mutagenesis screen, we have identified several loci that are required for
C. jejuni
efficient entry and survival within epithelial cells. Among these loci, insertional mutations in
aspA
,
aspB
, and
sodB
resulted in drastic reduction in
C. jejuni
entry and/or survival within host cells and a severe defect in colonization in an animal model. The implications of these findings for the understanding of
C. jejuni
-host cell interactions are discussed.
Role for CD2AP and Other Endocytosis-Associated Proteins in Enteropathogenic
Escherichia coli
Pedestal Formation
Authors: Guttman Julian A. , Lin Ann E. , Veiga Esteban , Cossart Pascale , Finlay B. Brett
Published: June 2010

Enteropathogenic
Escherichia coli
(EPEC) strains are extracellular pathogens that generate actin-rich structures (pedestals) beneath the adherent bacteria as part of their virulence strategy. Pedestals are hallmarks of EPEC infections, and their efficient formation
in vitro
routinely requires phosphorylation of the EPEC effector protein Tir at tyrosine 474 (Y474). This phosphorylation results in the recruitment and direct attachment of the host adaptor protein Nck to Tir at Y474, which is utilized for actin nucleation through a downstream N-WASP-Arp2/3-based mechanism. Recently, the endocytic protein clathrin was demonstrated to be involved in EPEC pedestal formation. Here we examine the organization of clathrin in pedestals and report that CD2AP, an endocytosis-associated and cortactin-binding protein, is a novel and important component of EPEC pedestal formation that also utilizes Y474 phosphorylation of EPEC Tir. We also demonstrate the successive recruitment of Nck and then clathrin prior to actin polymerization at pedestals during the Nck-dependent pathway of pedestal formation. This study further demonstrates that endocytic proteins are key components of EPEC pedestals and suggests a novel endocytosis subversion strategy employed by these extracellular bacteria.