bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacodynamics of Echinocandins against Candida glabrata: Requirement for Dosage Escalation To Achieve Maximal Antifungal Activity in Neutropenic Hosts
Authors: Howard Susan J. , Livermore Joanne , Sharp Andrew , Goodwin Joanne , Gregson Lea , Alastruey-Izquierdo A. , Perlin D. S. , Warn Peter A. , Hope William W.
Published: August 2011

Candida glabrata
is a leading cause of disseminated candidiasis. The echinocandins are increasingly used as first-line agents for the treatment of patients with this syndrome, although the optimal regimen for the treatment of invasive
Candida glabrata
infections in neutropenic patients is not known. We studied the pharmacokinetics (PK) and pharmacodynamics (PD) of micafungin, anidulafungin, and caspofungin in a neutropenic murine model of disseminated
Candida glabrata
infection to gain further insight into optimal therapeutic options for patients with this syndrome. A mathematical model was fitted to the data and used to bridge the experimental results to humans. The intravenous inoculation of
Candida glabrata
in mice was followed by logarithmic growth throughout the experimental period (101 h). A dose-dependent decline in fungal burden was observed following the administration of 0.1 to 20 mg/kg of body weight every 24 h for all three agents. The exposure-response relationships for each drug partitioned into distinct fungistatic and fungicidal components of activity. Surprisingly, the average human drug exposures following currently licensed regimens were predicted to result in a fungistatic antifungal effect. Higher human dosages of all three echinocandins are required to induce fungicidal effects in neutropenic hosts.
Engineering and Preclinical Evaluation of Attenuated Nontyphoidal Salmonella Strains Serving as Live Oral Vaccines and as Reagent Strains
Authors: Tennant Sharon M. , Wang Jin-Yuan , Galen James E. , Simon Raphael , Pasetti Marcela F. , Gat Orit , Levine Myron M.
Published: August 2011

While nontyphoidal
Salmonella
(NTS) has long been recognized as a cause of self-limited gastroenteritis, it is becoming increasingly evident that multiple-antibiotic-resistant strains are also emerging as important causes of invasive bacteremia and focal infections, resulting in hospitalizations and deaths. We have constructed attenuated
Salmonella enterica
serovar Typhimurium and
Salmonella enterica
serovar Enteritidis strains that can serve as live oral vaccines and as “reagent strains” for subunit vaccine production in a safe and economical manner. Prototype attenuated vaccine strains CVD 1921 and CVD 1941, derived from the invasive wild-type strains
S. Typhimurium
I77 and
S. Enteritidis
R11, respectively, were constructed by deleting
guaBA
, encoding guanine biosynthesis, and
clpP
, encoding a master protease regulator. The
clpP
mutation resulted in a hyperflagellation phenotype. An additional deletion in
fliD
yielded reagent strains CVD 1923 and CVD 1943, respectively, which export flagellin monomers. Oral 50% lethal dose (LD
50
) analyses showed that the NTS vaccine strains were all highly attenuated in mice. Oral immunization with CVD 1921 or CVD 1923 protected mice against lethal challenge with wild-type
S. Typhimurium
I77. Immunization with CVD 1941 but not CVD 1943 protected mice against lethal infection with
S. Enteritidis
R11. Immune responses induced by these strains included high levels of serum IgG anti-lipopolysaccharide (LPS) and anti-flagellum antibodies, with titers increasing progressively during the immunization schedule. Since
S. Typhimurium
and
S. Enteritidis
are the most common NTS serovars associated with invasive disease, these findings can pave the way for development of a highly effective, broad-spectrum vaccine against invasive NTS.
Localized Suppression of Inflammation at Sites of Helicobacter pylori Colonization
Authors: Every Alison L. , Ng Garrett Z. , Skene Caroline D. , Harbour Stacey N. , Walduck Anna K. , McGuckin Michael A. , Sutton Philip
Published: August 2011

While gastric adenocarcinoma is the most serious consequence ofHelicobacter pyloriinfection, not all infected persons develop this pathology. Individuals most at risk of this cancer are those in whom the bacteria colonize the acid-secreting region of the stomach and subsequently develop severe inflammation in the gastric corpus. It has been reported anecdotally that male mice become infected with greater numbers ofH. pyloribacteria than female mice. While investigating this phenomenon, we found that increasedH. pyloriinfection densities in male mice were not related to antibody production, and this phenomenon was not normalized by gonadectomy. However, the gastric pH in male 129/Sv mice was significantly elevated compared with that in female mice. Differences in colonization were evident within 1 day postinfection and significantly arose due to colonization of the gastric corpus region in male mice. This provided a potential model for comparing the effect of corpus colonization on the development of gastritis. This was explored using two models ofH. pylori-induced inflammation, namely, 2-month infections ofMuc1−/−mice and 6-month infections of wild-type 129/Sv mice. WhileH. pyloriinfection of female mice induced a severe, corpus-predominant atrophic gastritis, to our surprise, male mice developed minimal inflammation despite being colonized with significantly moreH. pyloribacteria than female controls. Thus, colonization of the gastric corpus in male mice was associated with a loss of inflammation in that region. The suppression of inflammation concomitant with infection of the gastric corpus in male mice demonstrates a powerful localized suppression of inflammation induced at sites ofH. pyloricolonization.
Physical activity and mental health in children and adolescents: a review of reviews
Authors: Biddle Stuart J H , Asare Mavis
Published: August 2011

Objective

To synthesise reviews investigating physical activity and depression, anxiety, self-esteem and cognitive functioning in children and adolescents and to assess the association between sedentary behaviour and mental health by performing a brief review.

Methods

Searches were performed in 2010. Inclusion criteria specified review articles reporting chronic physical activity and at least one mental health outcome that included depression, anxiety/stress, self-esteem and cognitive functioning in children or adolescents.

Results

Four review articles reported evidence concerning depression, four for anxiety, three for self-esteem and seven for cognitive functioning. Nine primary studies assessed associations between sedentary behaviour and mental health. Physical activity has potentially beneficial effects for reduced depression, but the evidence base is limited. Intervention designs are low in quality, and many reviews include cross-sectional studies. Physical activity interventions have been shown to have a small beneficial effect for reduced anxiety, but the evidence base is limited. Physical activity can lead to improvements in self-esteem, at least in the short term. However, there is a paucity of good quality research. Reviews on physical activity and cognitive functioning have provided evidence that routine physical activity can be associated with improved cognitive performance and academic achievement, but these associations are usually small and inconsistent. Primary studies showed consistent negative associations between mental health and sedentary behaviour.

Conclusions

Association between physical activity and mental health in young people is evident, but research designs are often weak and effects are small to moderate. Evidence shows small but consistent associations between sedentary screen time and poorer mental health.
Physical activity in childhood and bone health
Authors: Boreham Colin A G , McKay Heather A
Published: August 2011

The aim of this review is to provide a concise overview and update on recent advances in the field of physical activity in childhood and its effects on bone growth with an emphasis on the potential to prevent fractures. In addition, the review poses several unresolved questions in the field for future research.
A CACHING TECHNIQUE FOR OPTIMIZING AUTOMATED SERVICE DISCOVERY
Authors: STOLLBERG MICHAEL , HOFFMANN JÖRG , FENSEL DIETER
Published: August 2011

The development of sophisticated technologies for service-oriented architectures (SOA) is a grand challenge. A promising approach is the employment of semantic technologies to better support the service usage cycle. Most existing solutions show significant deficits in the computational performance, which hampers the applicability in large-scale SOA systems. We present an optimization technique for automated service discovery — one of the central operations in semantically enabled SOA environments — that can ensure a sophisticated performance while maintaining a high retrieval accuracy. The approach is based on goals that formally describe client objectives, and it employs a caching mechanism for enhancing the computational performance of a two-phased discovery framework. At design time, the suitable services for generic and reusable goal descriptions are determined by semantic matchmaking. The result is captured in a continuously updated graph structure that organizes goals and services with respect to the requested and provided functionalities. This is exploited at runtime in order to detect the suitable services for concrete client requests with minimal effort. We formalize the approach within a first-order logic framework, and define the graph structure along with the associated storage and retrieval algorithms. An empirical evaluation shows that significant performance improvements can be achieved.
MODULAR KNOWLEDGE REPRESENTATION IN ADVISOR AGENTS FOR SITUATION AWARENESS
Authors: PILATO GIOVANNI , AUGELLO AGNESE , GAGLIO SALVATORE
Published: August 2011

A modular knowledge representation framework for conversational agents is presented. The approach has been realized to suit the situation awareness paradigm. The modularity of the framework makes possible the composition of specific modules that deal with particular features, simplifying both the chatbot design process and its smartness. As a proof of concepts we have developed a modular, situation awareness oriented, KB for a conversational agent, which plays the role of an advisor aimed at helping a user to be in charge of a virtual town, inspired to the SimCity series game. The agent makes an extensive use of semantic computing techniques and is able to perceive, comprehend and project consequences of actions in order to handle strategic decision under uncertainty conditions.
SEMANTIC COMPUTING AND COMPUTER SCIENCE
Authors: HAO KE , GONG ZHIYUAN , HUO CHENGJIA , SHEU PHILLIP C.-Y.
Published: August 2011

Semantic Computing is an emerging research field that has drawn much attention from both academia and industry. It addresses the derivation and matching of semantics of computational "content" where "content" may be anything including text, multimedia, hardware, network, etc. which can be mapped to many areas in Computer Science that involve analyzing and processing the intentions of humans with computational content. This paper discusses some potential applications of Semantic Computing in Computer Science.
Short-term exercise training early in life restores deficits in pancreatic β-cell mass associated with growth restriction in adult male rats
Authors: Laker Rhianna C. , Gallo Linda A. , Wlodek Mary E. , Siebel Andrew L. , Wadley Glenn D. , McConell Glenn K.
Published: August 2011

Fetal growth restriction is associated with reduced pancreatic β-cell mass, contributing to impaired glucose tolerance and diabetes. Exercise training increases β-cell mass in animals with diabetes and has long-lasting metabolic benefits in rodents and humans. We studied the effect of exercise training on islet and β-cell morphology and plasma insulin and glucose, following an intraperitoneal glucose tolerance test (IPGTT) in juvenile and adult male Wistar-Kyoto rats born small. Bilateral uterine vessel ligation performed on day 18 of pregnancy resulted in Restricted offspring born small compared with sham-operated Controls and also sham-operated Reduced litter offspring that had their litter size reduced to five pups at birth. Restricted, Control, and Reduced litter offspring remained sedentary or underwent treadmill running from 5 to 9 or 20 to 24 wk of age. Early life exercise increased relative islet surface area and β-cell mass across all groups at 9 wk, partially restoring the 60–68% deficit ( P < 0.05) in Restricted offspring. Remarkably, despite no further exercise training after 9 wk, β-cell mass was restored in Restricted at 24 wk, while sedentary littermates retained a 45% deficit ( P = 0.05) in relative β-cell mass. Later exercise training also restored Restricted β-cell mass to Control levels. In conclusion, early life exercise training in rats born small restored β-cell mass in adulthood and may have beneficial consequences for later metabolic health and disease.
Bilateral Subclavian Steal Syndrome
Authors: Amini Reza , Gornik Heather L. , Gilbert Leslie , Whitelaw Sue , Shishehbor Mehdi
Published: August 2011

Bilateral subclavian steal syndrome is a rare condition. It is usually due to reversal of vertebral blood flow in the setting of bilateral proximal subclavian or left subclavian plus innominate artery severe stenosis or occlusion. This finding may cause cerebral ischemia related to upper extremities exercise. We report a case of bilateral subclavian steal secondary to total occlusion of the innominate and left subclavian arteries in a patient who presented with cardiomyopathy and flow reversal in the right carotid and bilateral vertebral arteries.
Inheritance of a Ring Chromosome 21 in a Couple UndergoingIn VitroFertilization (IVF): A Case Report
Authors: Mazzaschi Roberto L. P. , Love Donald R. , Hayes Ian , George Alice
Published: August 2011

An amniotic fluid sample from anin vitrofertilized pregnancy was referred for cytogenetic analysis based on a Down syndrome screening risk of 1 : 21. Routine cytogenetic analysis showed a nonmosaic karyotype of 46,XX,r(21)(p11.2q22.3), with partial monosomy for chromosome 21 due to a ring chromosome replacing one of the normal homologues. Detailed ultrasound scanning for the remainder of the pregnancy did not reveal any unusual findings. Parental bloods showed that the mother was mosaic for the ring 21 with a karyotype of 46,XX,r(21)(p11.2q22.3)/46,XX and the father had an unrelated Robertsonian translocation, with a karyotype of 45,XY,rob(13;14)(q10;q10). Microarray analysis of cultured amniocytes determined the extent of the deletion of chromosome 21 material in the ring. The parents were given genetic counselling, and a phenotypically normal female baby was delivered at term. This case highlights the importance of karyotyping as an initial step in the management of couples referred forin vitrofertilization.
A Compact Low-Permittivity Dual-Layer EBG Structure for Mutual Coupling Reduction
Authors: Azarbar A. , Ghalibafan J.
Published: August 2011

Electromagnetic bandgap (EBG) structures can help in the reduction of mutual coupling by their capabilities of suppressing surface wave's propagation in a specific frequency range. In this work, a dual-layer EBG structure, which had a lower resonant frequency than the single-layer one, is proposed in order to reduce the mutual coupling between -plane coupled microstrip antenna array. As this EBG structure significantly made the series capacitance between neighbor cells larger, a drastic reduction of the unit cell size was achieved. The simulated and experimental results show that the proposed structure has a significant 19 dB mutual coupling reduction.
Successful Administration of Recombinant Human Soluble Thrombomodulinα(Recomodulin) for Disseminated Intravascular Coagulation during Induction Chemotherapy in an Elderly Patient with Acute Monoblastic Leukemia Involving the t(9;11)(p22;q23)MLL/AF9Translocation
Authors: Takagi Kazutaka , Tasaki Toshiki , Yamauchi Takahiro , Iwasaki Hiromichi , Ueda Takanori
Published: August 2011

Patients with acute myelogenous leukemia complicate with disseminated intravascular coagulation (DIC), not only at the time of the initially leukemia diagnosis, but also during induction chemotherapy. In Japan, recently, a recombinant human soluble thrombomodulin alpha (Recomodulin) has been introduced as a new type of anti-DIC agent for clinical use in patients with hematological cancer or infectious disease. We describe a 67-year-old female case in which 25,600 units of Recomodulin for 6 days were successfully administered for both initially complicating and therapy-induced DIC without any troubles of bleeding in an acute monoblastic leukemia (AML-M5a) patient with theMLL genetranslocation. Furthermore, the levels of DIC biomarkers recovered rapidly after the Recomodulin treatment. Our case suggests that DIC control using Recomodulin is one of the crucial support-therapies during remission induction chemotherapy in patients with acute leukemia of which type tends to complicate extramedullary or extranodal infiltration having potential to onset DIC.
Angiogenic Factors and Renal Disease in Pregnancy
Authors: Rhee Julie S. , Young Brett C. , Rana Sarosh
Published: August 2011

Background. Preeclampsia is difficult to diagnose in patients with underlying renal disease and proteinuria. Prior studies show that there is an angiogenic factor imbalance with elevated levels of antiangiogenic proteins soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng) and reduced levels of the proangiogenic protein, placental growth factor (PlGF) in women with preeclampsia. These angiogenic biomarkers may be useful in distinguishing preeclampsia from other conditions of pregnancy, which may present with overlapping clinical characteristics.Cases. Case 1: A multiparous woman at 18 weeks gestation with nephrotic syndrome presented with hypertensive emergency and worsening renal insufficiency. She underwent induction of labor for severe preeclampsia. Her sFlt1 and sEng levels were at the 97 percentile while her PlGF level was undetectable (less than the 1st percentile). Case 2: A nulliparous woman with lupus nephritis at 22 weeks gestation presented with fetal demise and heart failure. Three weeks previously, the patient had developed thrombocytopenia and hypertensive urgency. She underwent dilation and evacuation. Her angiogenic profile was consistent with severe preeclampsia.Conclusion. Angiogenic factors may provide evidence to support a diagnosis of preeclampsia in patients with preexisting renal disease and proteinuria, conditions in which the classical definition of hypertension and proteinuria cannot be used.
Genome‐Based Studies of Marine Microorganisms to Maximize the Diversity of Natural Products Discovery for Medical Treatments
Authors: Zhao Xin-Qing
Published: August 2011

Marine microorganisms are rich source for natural products which play important roles in pharmaceutical industry. Over the past decade, genome‐based studies of marine microorganisms have unveiled the tremendous diversity of the producers of natural products and also contributed to the efficiency of harness the strain diversity and chemical diversity, as well as the genetic diversity of marine microorganisms for the rapid discovery and generation of new natural products. In the meantime, genomic information retrieved from marine symbiotic microorganisms can also be employed for the discovery of new medical molecules from yet‐unculturable microorganisms. In this paper, the recent progress in the genomic research of marine microorganisms is reviewed; new tools of genome mining as well as the advance in the activation of orphan pathways and metagenomic studies are summarized. Genome‐based research of marine microorganisms will maximize the biodiscovery process and solve the problems of supply and sustainability of drug molecules for medical treatments.
Fatal H1N1-Related Acute Necrotizing Encephalopathy in an Adult
Authors: Lee Yu-Jin , Smith D. Scott , Rao Vivek A. , Siegel Robert D. , Kosek Jon , Glaser Carol A. , Flint Alexander C.
Published: August 2011

Acute necrotizing encephalopathy (ANE) is a severe neurological complication of influenza infection, including H1N1 influenza. Many cases of ANE have been reported in the pediatric literature, but very few cases have been described in adults. The cause of ANE remains unknown—the influenza virus is not known to be neurotropic, and evidence of direct viral involvement of the central nervous system (CNS) has not been demonstrated in the limited cases of ANE in which pathological specimens have been obtained. Here we report a fatal case of ANE from H1N1 influenza infection in an adult. Neuroimaging and postmortem analysis both showed widespread brain edema, necrosis, and hemorrhage, but molecular studies and postmortem pathology revealed no evidence of direct viral involvement of the CNS. This case of fatal ANE in an adult is consistent with the hypothesis generated from pediatric cases that the host immune response, and not direct viral invasion of the CNS, is responsible for pathogenesis of ANE.
An Early Diagnosis of Gastroepiploic Arterial Aneurysm during a Routine Abdominal Ultrasound Study
Authors: Casella Giovanni , Sartirana Adriana , Vandoni Pietro , Di Bella Camillo , Pagni Fabio , Nobili Paolo
Published: August 2011

Gastroepiploic arterial aneurysm (GEAA) is a rare condition, but the rupture risk is very high. We report the case of a patient with incidental finding of GEAA during US examination. The diagnosis was confirmed by a computed tomography and an angiographic study. A classic laparotomy with aneurysmectomy has been successfully performed.
Dynamic Analysis of Electrostatic Microactuators Using the Differential Quadrature Method
Authors: Hsu Ming-Hung
Published: August 2011

This work studies the dynamic behavior of electrostatic actuators using finite‐element package software (FEMLAB) and differential quadrature method. The differential quadrature technique is used to transform partial differential equations into a discrete eigenvalue problem. Numerical results indicate that length, width, and thickness significantly impact the frequencies of the electrostatic actuators. The thickness could not affect markedly the electrostatic actuator capacities. The effects of varying actuator length, width, and thickness on the dynamic behavior and actuator capacities in electrostatic actuator systems are investigated. The differential quadrature method is an efficient differential equation solver.
An Unusual Case of Myonecrosis
Authors: Mukhopadhyay P. , Barai R. , Philips C. A. , Ghosh J. , Saha S.
Published: August 2011

Diabetic Myonecrosis is a rare complication of long-standing Diabetes Mellitus Type 1 and 2. The most likely affected areas are of proximal lower limbs, mostly the quadriceps muscle. The presenting features are myriad and a diagnostic conundrum for the physician. There has been previously mentioned, through few case reports, the classical presentation of diabetes-related muscle infarction. Here we present a patient of diabetic myonecrosis, in whom the initial presentation of diabetes mellitus was that of bilateral symmetric proximal upper limb predominant muscle infarction, which has never been reported before.
Fanconi Bickel Syndrome: Novel Mutations inGLUT 2Gene Causing a Distinguished Form of Renal Tubular Acidosis in Two Unrelated Egyptian Families
Authors: Al-Haggar Mohammad , Sakamoto Osamu , Shaltout Ali , El-Hawary Amany , Wahba Yahya , Abdel-Hadi Dina
Published: August 2011

Background. Fanconi-Bickel syndrome (FBS) is an autosomal recessive disorder caused by defects in facilitative glucose transporter 2 (GLUT2 or SLC2A2) gene mapped on chromosome 3q26.1-26.3, that codes for the glucose transporter protein 2.Methods. Two unrelated Egyptian families having suspected cases of FBS were enrolled after taking a written informed consent; both had positive consanguinity, and index cases had evidences of proximal renal tubular defects with hepatomegaly; they were subjected to history taking, signs of rickets as well as anthropometric measurements. Laboratory workup included urinalysis, renal and liver function tests including fasting and postprandial blood sugar; serum calcium, phosphorus, alkaline phosphatase, sodium and potassium, lipid profile, and detailed blood gas. Imaging including bone survey and abdominal ultrasound, and liver biopsy were done to confirm diagnosis. Molecular analysis of the GLUT2 gene was done for DNA samples extracted from peripheral blood leukocyte. All coding sequences, including flanking introns in GLUT2 gene, were amplified using PCR followed by direct sequencing.Results. Two new mutations had been detected, one in each family, in exon 3 two bases (GA) were deleted (c.253 254delGA) and in exon 6 in the second family, G-to-C substitution at position-1 of the splicing acceptor site (c.776-1G>C or IVS5-1G>A).Conclusion. FBS is a rare disease due to mutation in GLUT2 gene; many mutations were reported, about half were novel mutations; yet none of these mutations is more frequent. A more extensive survey for the most frequent mutations among FBS has to be contemplated to allow for use of molecular screening tests like ARMS.
Influence of Welding Parameters on Weld Formation and Microstructure of Dual-Laser Beams Welded T-Joint of Aluminum Alloy
Authors: Li Min , Li Zhuguo , Zhao Yong , Li Hao , Wang Yuhua , Huang Jian
Published: August 2011

This paper focused on the welding 1.8 mm thick 6061 aluminum alloy plates in T-joint form using dual lasers that introduced by a Nd: YAG laser and a CO2laser with 4043 aluminum filler wire. The effects of welding parameters on the T-joint weld appearance, microstructure and the joint mechanical properties were studied systematically, The influence of welding parameters included the distance between two laser beams, welding speed, laser power and the laser beam offset toward the stringer. The weld appearance, microstructure, hardness of the joint were evaluated by optical microscope and micro-hardness test. A monotonic quasi-static tensile test was conducted by a self-made clamping device to obtain the tensile property of welded joints. At the optimized parameters, the welded T-joint showed good weld appearance without macro defects; the micro hardness of welds ranged from 75 to 85 HV0.3, and the tensile strength was about 254 MPa with the fracture at the heat affected zone on the stringer side.
Fatal Hemoptysis due to Chronic Cavitary Pulmonary Aspergillosis Complicated by Nontuberculous Mycobacterial Tuberculosis
Authors: Kokkonouzis Ioannis , Athanasopoulos Ioannis , Doulgerakis Nikolaos , Tsonis Grigorios , Lampaditis Ioannis , Saridis Nikolaos , Skoufaras Vasilios
Published: August 2011

A 51-year-old man, with a history of severe COPD and bilateral pneumothorax, who was under treatment for pulmonary tuberculosis due to mycobacterium avium, was admitted due to high-grade fever, weight loss, cough, and production of purulent sputum, for almost one month without any special improvement despite adequate antibiotics treatment in outpatient setting. A CT scan revealed multiple consolidations, fibrosis, scaring, and cavitary lesions in both upper lobes with newly shadows which were fungus balls inside them. Aspergillus flavius was isolated in three sputum samples, a diagnosis of chronic cavitary pulmonary aspergillosis was made, and treatment with intravenous amphotericin B was started. An initially clinical improvement was noted, and a first episode of minor hemoptysis was treated with conservative measures. Unfortunately a second major episode of hemoptysis occurred and he died almost immediately. Aspergilloma is defined as the presence of a fungus ball inside a preexisting pulmonary cavity or dilated airway and is one of the clinical conditions associated with the clinical spectrum of pulmonary colonization. Tuberculosis is the most common underling disease. Hemoptysis is the most common symptom. Antifungal antibiotics, surgical interventions, bronchial arteries embolization, and intracavity infusion of antibiotics have been proposed without always adequate sufficiency.
Splenic Artery Aneurysm Presenting as Extrahepatic Portal Vein Obstruction: A Case Report
Authors: Elamurugan T. P. , Kumar S. Suresh , Muthukumarassamy R. , Kate Vikram
Published: August 2011

Splenic artery aneurysms are the most common visceral aneurysm occuring predominantly in females. They are usually asymptomatic, and the symptomatic presentation includes chronic abdominal pain of varied severity or an acute rupture with hypotension. Splenic artery aneurysm causing extrahepatic portal hypertension is very rare and is due to splenic vein thrombosis that develops secondary to compression by the aneurysm. We report one such rare presentation of splenic artery aneurysms in a pregnant female with the features of EHPVO (variceal bleed, hypersplenism) treated by splenectomy along with excision of the aneurysm.
Research on the Influence of Switching Frequency on Low‐Frequency Oscillation in the Voltage‐Controlled Buck‐Boost Converter
Authors: Wang Faqiang , Ma Xikui
Published: August 2011

The influence of switching frequency on the low‐frequency oscillation in the voltage‐controlled buck‐boost converter is studied in this paper. Firstly, the mathematical model of this system is derived. And then, a glimpse at the influence of switching frequency on the low‐frequency oscillation in this system by MATLAB/Simulink is given. The improved averaged model of the system is established, and the corresponding theoretical analysis is presented. It is found that the switching frequency has an important influence on the low‐frequency oscillation in the system, that is, the low‐frequency oscillation is easy to occur when the switching frequency is low. Finally, the effectiveness of the improved averaged model and the theoretical analysis are confirmed by circuit experiment.
Effects of Glucosamine and Chondroitin Sulfate on Cartilage Metabolism in OA: Outlook on Other Nutrient Partners Especially Omega-3 Fatty Acids
Authors: Jerosch Jörg
Published: August 2011

Osteoarthritis (OA) is a degenerative joint disease that is characterized by increasing loss of cartilage, remodeling of the periarticular bone, and inflammation of the synovial membrane. Besides the common OA therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), the treatment with chondroprotectives, such as glucosamine sulfate, chondroitin sulfate, hyaluronic acid, collagen hydrolysate, or nutrients, such as antioxidants and omega-3 fatty acids is a promising therapeutic approach. Numerous clinical studies have demonstrated that the targeted administration of selected micronutrients leads to a more effective reduction of OA symptoms, with less adverse events. Their chondroprotective action can be explained by a dual mechanism: (1) as basic components of cartilage and synovial fluid, they stimulate the anabolic process of the cartilage metabolism; (2) their anti-inflammatory action can delay many inflammation-induced catabolic processes in the cartilage. These two mechanisms are able to slow the progression of cartilage destruction and may help to regenerate the joint structure, leading to reduced pain and increased mobility of the affected joint.
Epidemiological Survey on the Prevalence of Periodontitis and Diabetes Mellitus in Uyghur Adults from Rural Hotan Area in Xinjiang
Authors: Awuti Gulinuer , Younusi Kurexi , Li Linlin , Upur Halmurat , Ren Jun
Published: August 2011

Background and Aims. This study was designed to explore the relationship between periodontitis and diabetes mellitus (DM) in Uygur adults from Xinjiang.Methods and Results. Data were obtained using questionnaire and oral examination. Participants (48.87 ±13.72 yr) were categorized into periodontitis and non-periodontitis groups in accordance with the chronic periodontitis diagnostic criteria. Based on gum inflammation, bleeding on probing, periodontal pocket depth and attachment loss, patients were further divided into mild, moderate and severe periodontitis groups. Among 962 subjects, 453 (47.1%) suffered from chronic periodontitis with a prevalence of type 2 DM and impaired fasting glucose of 9.5% and 11.4%, respectively. In the periodontitis group, the prevalence of type 2 DM was 75.6% compared with 22.4% in the non-periodontitis group. Likewise, the prevalence of impaired fasting glucose was 71.3% and 28.7% in periodontitis and non-periodontitis groups, respectively. The univariate logistic regression analysis revealed moderate and severe periodontitis as risk factors for DM (OR=3.4,OR=2.9). Multivariate logistic regression analysis showed that moderate periodontitis is independently associated with DM (OR=4).Conclusions. Our data revealed that prevalence of DM is overtly higher in periodontitis patients than in individuals without periodontitis. Furthermore, moderate periodontitis is considered an independent risk factor for type 2 DM.
Evaluation of the Toxicity ofVirola sebiferaCrude Extracts, Fractions and Isolated Compounds on the Nest of Leaf-Cutting Ants
Authors: Bicalho Keylla Utherdyany , Terezan Ana Paula , Martins Denise Cristina , Freitas Taís Garcia , Fernandes João Batista , da Silva Maria Fátima das Graças Fernandes , Vieira Paulo Cezar , Pagnocca Fernando Carlos , Bueno Odair Côrrea
Published: July 2011

The phytochemical study ofVirola sebiferaleaves led to the isolation of three lignans: (+)-sesamin, (−)-hinokinin, and (−)-kusunokinin and three flavonoids: quercetin-3-O-α-L-rhamnoside, quercetin-3-O-β-D-glucoside, and quercetin-3-methoxy-7-O-β-D-glucoside by using techniques as high-speed counter-current chromatography and high-performance liquid chromatography. The crude extracts, fractions, and isolated compounds were evaluated for their insecticidal and fungicidal potential againstAtta sexdens rubropilosaand its symbiotic fungusLeucoagaricus gongylophorus. The bioassay results showed a high insecticidal activity for the methanol crude extract of the leaves ofV. sebiferaand itsn-hexane, dichloromethane and ethyl acetate fractions. The fungicidal bioassay revealed high toxicity of the lignans againstL. gongylophorus.
Resistance to CYP17A1 Inhibition with Abiraterone in Castration-Resistant Prostate Cancer: Induction of Steroidogenesis and Androgen Receptor Splice Variants
Authors: Mostaghel Elahe A. , Marck Brett T. , Plymate Stephen R. , Vessella Robert L. , Balk Stephen , Matsumoto Alvin M. , Nelson Peter S. , Montgomery R. Bruce
Published: August 2011

Purpose: Abiraterone is a potent inhibitor of the steroidogenic enzyme CYP17A1 and suppresses tumor growth in patients with castration-resistant prostate cancer (CRPC). The effectiveness of abiraterone in reducing tumor androgens is not known, nor have mechanisms contributing to abiraterone resistance been established.

Experimental Design: We treated human CRPC xenografts with abiraterone and measured tumor growth, tissue androgens, androgen receptor (AR) levels, and steroidogenic gene expression versus controls.

Results: Abiraterone suppressed serum PSA levels and improved survival in two distinct CRPC xenografts: median survival of LuCaP35CR improved from 17 to 39 days (HR = 3.6, P = 0.0014) and LuCaP23CR from 14 to 24 days (HR = 2.5, P = 0.0048). Abiraterone strongly suppressed tumor androgens, with testosterone (T) decreasing from 0.49 ± 0.22 to 0.03 ± 0.01 pg/mg (P < 0.0001), and from 0.69 ± 0.36 to 0.03 ± 0.01 pg/mg (P = 0.002) in abiraterone-treated 23CR and 35CR, respectively, with comparable decreases in tissue DHT. Treatment was associated with increased expression of full-length AR (ARFL) and truncated AR variants (ARFL 2.3-fold, P = 0.008 and ARdel567es 2.7-fold, P = 0.036 in 23 CR; ARFL 3.4-fold, P = 0.001 and ARV7 3.1-fold, P = 0.0003 in 35CR), and increased expression of the abiraterone target CYP17A1 (∼2.1-fold, P = 0.0001 and P = 0.028 in 23CR and 35CR, respectively) and transcript changes in other enzymes modulating steroid metabolism.

Conclusions: These studies indicate that abiraterone reduces CRPC growth via suppression of intratumoral androgens and that resistance to abiraterone may occur through mechanisms that include upregulation of CYP17A1, and/or induction of AR and AR splice variants that confer ligand-independent AR transactivation. Clin Cancer Res; 17(18); 5913–25. ©2011 AACR.
A New Molecular Predictor of Distant Recurrence in ER-Positive, HER2-Negative Breast Cancer Adds Independent Information to Conventional Clinical Risk Factors
Authors: Filipits Martin , Rudas Margaretha , Jakesz Raimund , Dubsky Peter , Fitzal Florian , Singer Christian F. , Dietze Otto , Greil Richard , Jelen Andrea , Sevelda Paul , Freibauer Christa , Müller Volkmar , Jänicke Fritz , Schmidt Marcus , Kölbl Heinz , Rody Achim , Kaufmann Manfred , Schroth Werner , Brauch Hiltrud , Schwab Matthias , Fritz Peter , Weber Karsten E. , Feder Inke S. , Hennig Guido , Kronenwett Ralf , Gehrmann Mathias , Gnant Michael
Published: August 2011

Purpose: According to current guidelines, molecular tests predicting the outcome of breast cancer patients can be used to assist in making treatment decisions after consideration of conventional markers. We developed and validated a gene expression signature predicting the likelihood of distant recurrence in patients with estrogen receptor (ER)–positive, HER2-negative breast cancer treated with adjuvant endocrine therapy.

Experimental Design: RNA levels assessed by quantitative reverse transcriptase PCR in formalin-fixed, paraffin-embedded tumor tissue were used to calculate a risk score (Endopredict, EP) consisting of eight cancer-related and three reference genes. EP was combined with nodal status and tumor size into a comprehensive risk score, EPclin. Both prespecified risk scores including cutoff values to determine a risk group for each patient (low and high) were validated independently in patients from two large randomized phase III trials [Austrian Breast and Colorectal Cancer Study Group (ABCSG)-6: n = 378, ABCSG-8: n = 1,324].

Results: In both validation cohorts, continuous EP was an independent predictor of distant recurrence in multivariate analysis (ABCSG-6: P = 0.010, ABCSG-8: P < 0.001). Combining Adjuvant!Online, quantitative ER, Ki67, and treatment with EP yielded a prognostic power significantly superior to the clinicopathologic factors alone [c-indices: 0.764 vs. 0.750, P = 0.024 (ABCSG-6) and 0.726 vs. 0.701, P = 0.003 (ABCSG-8)]. EPclin had c-indices of 0.788 and 0.732 and resulted in 10-year distant recurrence rates of 4% and 4% in EPclin low-risk and 28% and 22% in EPclin high-risk patients in ABCSG-6 (P < 0.001) and ABCSG-8 (P < 0.001), respectively.

Conclusions: The multigene EP risk score provided additional prognostic information to the risk of distant recurrence of breast cancer patients, independent from clinicopathologic parameters. The EPclin score outperformed all conventional clinicopathologic risk factors. Clin Cancer Res; 17(18); 6012–20. ©2011 AACR.
Forced Activation of β-Catenin Signaling Supports the Transformation of hTERT-Immortalized Human Fetal Hepatocytes
Authors: Wege Henning , Heim Denise , Lütgehetmann Marc , Dierlamm Judith , Lohse Ansgar W. , Brümmendorf Tim H.
Published: August 2011

Hepatocarcinogenesis is a multistep process driving the progressive transformation of normal liver cells into highly malignant derivatives. Unlimited proliferation and telomere maintenance have been recognized as prerequisites for the development of liver cancer. Moreover, recent studies identified illegitimate β-catenin signaling as relevant hit in a considerable subset of patients. To further investigate the currently not well-understood malignant evolution driven by telomerase and β-catenin, we monitored cytogenetic and phenotypic alterations in untransformed telomerase-immortalized human fetal hepatocytes following forced activation of β-catenin signaling. As expected, constitutive activation of β-catenin signaling significantly enhanced proliferation with decreasing serum dependence. Previously intact contact inhibition was almost completely eliminated. Interestingly, after several passages in cell culture, immortalized clones with dominant-positive β-catenin signaling acquired additional chromosomal aberrations, in particular translocations, anchorage-independent growth capabilities, and formed tumors in athymic nude mice. In further support for the driving role of β-catenin during hepatocarcinogenesis, improved colony growth in soft agar and accelerated tumor formation was also confirmed in Huh7 cells following stable expression of the constitutively active S33Y β-catenin mutant. Telomerase inhibition showed that short-term expansion of transformed clones was not telomerase dependent. Finally, cancer pathway profiling in derived tumors revealed upregulation of characteristic genes associated with invasion and angiogenesis. In conclusion, illegitimate activation of β-catenin signaling enhances the transformation from immortalization to malignant growth in human fetal hepatocytes. Our data functionally confirm a permissive role for β-catenin signaling in the initial phase of hepatocarcinogenesis. Mol Cancer Res; 9(9); 1222–31. ©2011 AACR.
Bleeding Risk in Very Old Patients on Vitamin K Antagonist Treatment
Authors: Poli Daniela , Antonucci Emilia , Testa Sophie , Tosetto Alberto , Ageno Walter , Palareti Gualtiero ,   for the Italian Federation of Anticoagulation Clinics (FCSA)
Published: August 2011

Background—

Vitamin K antagonist (VKA) therapy is increasingly being used for the prevention of venous thromboembolism and stroke in atrial fibrillation. Bleeds are the major concern for VKA prescription, especially in very old patients who carry many risk factors for bleeding. We performed a large multicenter prospective observational study that enrolled very old patients to evaluate the quality of anticoagulation and the incidence of bleedings.

Methods and Results—

The study included 4093 patients ≥80 years of age who were naïve to VKA for thromboprophylaxis of atrial fibrillation or after venous thromboembolism. Patients' demographic and clinical data were collected, and the quality of anticoagulation and the incidence of bleeding were recorded. The follow-up was 9603 patient-years; median age at the beginning of follow-up was 84 years (range, 80 to 102 years). We recorded 179 major bleedings (rate, 1.87 per 100 patient-years), 26 fatal (rate, 0.27 per 100 patient-years). The rate of bleeding was higher in men compared with women (relative risk, 1.4; 95% confidence interval, 1.12 to 1.72;
P
=0.002) and among patients ≥85 years of age compared with younger patients (relative risk, 1.3; 95% confidence interval, 1.0 to 1.65;
P
=0.048). Time in therapeutic range was 62% (interquartile range, 49% to 75%). History of bleeding, active cancer, and history of falls were independently associated with bleeding risk in Cox regression analysis.

Conclusion—

In this large study on very old patients on VKA carefully monitored by anticoagulation clinics, the rate of bleedings was low, suggesting that age in itself should not be considered a contraindication to treatment. Adequate management of VKA therapy in specifically trained center allows very old and frail patients to benefit from VKA thromboprophylaxis.
Involvement of Endoplasmic Stress Protein C/EBP Homologous Protein in Arteriosclerosis Acceleration With Augmented Biological Stress Responses
Authors: Gao Junhong , Ishigaki Yasushi , Yamada Tetsuya , Kondo Keiichi , Yamaguchi Suguru , Imai Junta , Uno Kenji , Hasegawa Yutaka , Sawada Shojiro , Ishihara Hisamitsu , Oyadomari Seiichi , Mori Masataka , Oka Yoshitomo , Katagiri Hideki
Published: August 2011

Background—

The processes of arteriosclerosis, including atherosclerosis and vascular remodeling, are affected by interactions among numerous biological pathways such as responses to inflammation, oxidative stress, and endoplasmic reticulum stress. C/EBP homologous protein (CHOP), which is well known to induce cellular apoptosis in response to severe endoplasmic reticulum stress, is reportedly upregulated in plaque lesions.

Methods and Results—

We examined the effects of CHOP deficiency on 2 types of arteriosclerosis: cuff injury–induced neointimal formation and hypercholesterolemia-induced atherosclerosis. Cuff injury–induced neointimal formation was markedly inhibited in CHOP
−/−
mice with suppressed aortic expression of inflammatory factors and smooth muscle cell proliferation–related proteins. A CHOP deficiency also inhibited aortic plaque formation in hypercholesterolemic apolipoprotein E
−/−
mice with suppressed aortic expression of inflammatory factors and oxidative stress markers. Bone marrow transplantation experiments revealed that recipient CHOP deficiency significantly suppressed both cuff injury–induced neointimal formation and hypercholesterolemia-induced atherosclerotic plaque formation to a greater extent than donor CHOP deficiency, suggesting the importance of CHOP in vascular cells for arteriosclerosis progression. Furthermore, in our in vitro experiments, in not only macrophages but also endothelial and smooth muscle cell lines, endoplasmic reticulum stress inducers upregulated inflammation-, adhesion-, or smooth muscle cell proliferation–related proteins, whereas decreased CHOP expression remarkably suppressed endoplasmic reticulum stress–induced upregulation of these proteins.

Conclusions—

In addition to the well-known signaling for apoptosis induction, CHOP may play important roles in augmenting potentially pathological biological stress responses. This noncanonical role of CHOP, especially that expressed in vascular cells, may contribute to the progression of vascular remodeling and atherosclerosis.
Randomized Comparison of Everolimus-Eluting Stent Versus Sirolimus-Eluting Stent Implantation for De Novo Coronary Artery Disease in Patients With Diabetes Mellitus (ESSENCE-DIABETES)
Authors: Kim Won-Jang , Lee Seung-Whan , Park Seong-Wook , Kim Young-Hak , Yun Sung-Cheol , Lee Jong-Young , Park Duk-Woo , Kang Soo-Jin , Lee Cheol Whan , Lee Jae-Hwan , Choi Si Wan , Seong In-Whan , Lee Bong-Ki , Lee Nae-Hee , Cho Yoon Haeng , Shin Won-Yong , Lee Seung-Jin , Lee Se-Whan , Hyon Min-Su , Bang Duk-Won , Park Woo-Jung , Kim Hyun-Sook , Chae Jei Keon , Lee Keun , Park Hoon-Ki , Park Chang-Bum , Lee Sang-Gon , Kim Min-Kyu , Park Kyoung-Ha , Choi Young-Jin , Cheong Sang-Sig , Yang Tae-Hyun , Jang Jae-Sik , Her Sung Ho , Park Seung-Jung
Published: August 2011

Background—

Drug-eluting stents significantly improved angiographic and clinical outcomes compared with bare metal stents in diabetic patients. However, a comparison of everolimus-eluting stents and sirolimus-eluting stents in diabetic patients has not been evaluated. Therefore we compared effectiveness of everolimus-eluting stents and sirolimus-eluting stents in patients with diabetes mellitus.

Methods and Results—

This prospective, multicenter, randomized study compared everolimus-eluting stent (n=149) and sirolimus-eluting stent (n=151) implantation in diabetic patients. The primary end point was noninferiority of angiographic in-segment late loss at 8 months. Clinical events were also monitored for at least 12 months. Everolimus-eluting stents were noninferior to sirolimus-eluting stents for 8-month in-segment late loss (0.23±0.27 versus 0.37±0.52 mm; difference, −0.13 mm; 95% confidence interval, −0.25 to −0.02; upper 1-sided 95% confidence interval, −0.04;
P
<0.001 for noninferiority), with reductions in in-stent restenosis (0% versus 4.7%;
P
=0.029) and in-segment restenosis (0.9% versus 6.5%;
P
=0.035). However, in-stent late loss (0.11±0.26 versus 0.20±0.49 mm;
P
=0.114) was not statistically different between the 2 groups. At 12 months, ischemia-driven target lesion revascularization (0.7% versus 2.6%;
P
=0.317), death (1.3% versus 3.3%;
P
=0.448), and myocardial infarction (0% versus 1.3%;
P
=0.498) were not statistically different between the 2 groups. Major adverse cardiac events, including death, myocardial infarction, and ischemia-driven target lesion revascularization (2.0% versus 5.3%;
P
=0.218), were also not statistically different between the 2 groups.

Conclusions—

Everolimus-eluting stents were noninferior to sirolimus-eluting stents in reducing in-segment late loss and reduced angiographic restenosis at 8 months in patients with diabetes mellitus and coronary artery disease.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00997763.