bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling of Partially Hydrolyzed Polyacrylamide-Hexamine-Hydroquinone Gel System Used for Profile Modification Jobs in the Oil Field
Authors: Singh Yadav Upendra , Mahto Vikas
Published: December 2012

The cross-linked polymer gel systems are being used increasingly to redirect or modify reservoir fluid movement in the vicinity of injection wells for the purpose of permeability/profile modification job in the oil field due to their high temperature stability and capability to provide rigid gel having high mechanical strength. In this study, a partially hydrolyzed polyacrylamide-hexamine-hydroquinonegel is used for the development of polymer gel system. The experimental investigation demonstrates that the gelation time varies with polymer and crosslinker concentration and the temperature. The mathematical model is developed with the help of gelation kinetics of polymer gel and using Arrhenius equation, which relates the gelation time with polymer, crosslinker concentrations, and temperature. The developed model is solved with the help of multivariate regression method. It is observed in this study that the theoretical values of gelation time have good agreement with the experimental values.
Healthcare Utilization and Costs of Systemic Lupus Erythematosus in Medicaid
Authors: Kan Hong J. , Song Xue , Johnson Barbara H. , Bechtel Benno , O'Sullivan Donna , Molta Charles T.
Published: December 2012

Objective. Healthcare utilization and costs associated with systemic lupus erythematosus (SLE) in a US Medicaid population were examined.Methods. Patients ≥ 18 years old with SLE diagnosis (ICD-9-CM 710.0x) were extracted from a large Medicaid database 2002–2009. Index date was date of the first SLE diagnosis. Patients with and without SLE were matched. All patients had a variable length of followup with a minimum of 12 months. Annualized healthcare utilization and costs associated with SLE and costs of SLE flares were assessed during the followup period. Multivariate regressions were conducted to estimate incremental healthcare utilization and costs associated with SLE.Results. A total of 14,777 SLE patients met the study criteria, and 14,262 were matched to non-SLE patients. SLE patients had significantly higher healthcare utilization per year than their matched controls. The estimated incremental annual cost associated with SLE was $10,984, with the highest increase in inpatient costs (P<0.001). Cost per flare was $11,716 for severe flares, $562 for moderate flares, and $129 for mild flares. Annual total costs for patients with severe flares were $49,754.Conclusions. SLE patients had significantly higher healthcare resource utilization and costs than non-SLE patients. Patients with severe flares had the highest costs.
Influence of Air Temperature and Humidity on Dehydration Equilibria and Kinetics of Theophylline
Authors: Touil Amira , Peczalski Roman , Timoumi Souad , Zagrouba Fethi
Published: December 2012

The effect of hygrothermal conditions (air temperature and relative humidity) on the dehydration of theophylline monohydrate was investigated. Firstly, the equilibrium states of theophylline were investigated. The data from gravimetric analysis at constant temperature and humidity were reported as desorption isotherms. The PXRD analysis was used to identify the different polymorphic forms of theophylline: the monohydrate, the metastable anhydrate, and the stable anhydrate. Solid-solid phase diagrams for two processing times were proposed. Secondly, the dehydration kinetics were studied. The water content evolutions with time were recorded at several temperatures from 20°C to 80°C and several relative humidities from 4% to 50%. Different mathematical models were used to fit the experimental data. The spatially averaged solution of 2D Fickian transient diffusion equation best represented the water mass loss versus time experimental relationship. The dehydration rate constant was found to increase exponentially with air temperature and to decrease exponentially with air relative humidity.
Impact of Cardiac Devices on the Quality of Life in Pediatric Patients
Authors: Czosek Richard J. , Bonney William J. , Cassedy Amy , Mah Douglas Y. , Tanel Ronn E. , Imundo Jason R. , Singh Anoop K. , Cohen Mitchell I. , Miyake Christina Y. , Fawley Kara , Marino Bradley S.
Published: December 2012

Background—

Cardiac rhythm devices are increasingly used in the pediatric population, although their impact on quality of life (QOL) is poorly understood. The purpose of this study was to compare (QOL) scores among pediatric device patients, healthy controls, and congenital heart disease (CHD) patients and determine the key drivers of QOL in pediatric device patients.

Methods and Results—

Multicenter, cross-sectional study at 8 pediatric centers of subjects aged 8 to 18 years with either a pacemaker or defibrillator was carried out. Patient–parent pairs completed the Pediatric Quality of Life Inventory and Pediatric Cardiac Quality of Life Inventory. QOL outcomes in device patients were compared with healthy controls and patients with various forms of CHD. Structural equation modeling was used to test for differences in Pediatric Cardiac Quality of Life Inventory scores among (1) device type, (2) presence of CHD, and (3) hypothesized key drivers of QOL. One hundred seventy-three patient–parent pairs (40 defibrillators/133 pacemakers) were included. Compared with healthy controls, patients with devices and their parents reported significantly lower Pediatric Quality of Life Inventory scoring. Similarly, compared with patients with mild forms of CHD, parents and patients with devices reported significantly lower Pediatric Cardiac Quality of Life Inventory scores and were similar to patients with more severe CHD. Key drivers of patient QOL were presence of implantable cardioverter-defibrillator and CHD. For patients, self-perception was a key driver of lower QOL, whereas for parents behavioral issues were associated with lower QOL.

Conclusions—

Patient QOL is significantly affected by the presence of cardiac rhythm devices. Whether these effects can be mitigated through the use of psychotherapy needs to be assessed.
The Effect of Excess Weight Gain With Intensive Diabetes Mellitus Treatment on Cardiovascular Disease Risk Factors and Atherosclerosis in Type 1 Diabetes Mellitus
Authors: Purnell Jonathan Q. , Zinman Bernard , Brunzell John D.
Published: December 2012

Background—

Intensive diabetes mellitus therapy of type 1 diabetes mellitus reduces diabetes mellitus complications but can be associated with excess weight gain, central obesity, and dyslipidemia. The purpose of this study was to determine whether excessive weight gain with diabetes mellitus therapy of type 1 diabetes mellitus is prospectively associated with atherosclerotic disease.

Methods and Results—

Subjects with type 1 diabetes mellitus (97% white, 45% female, mean age 35 years) randomly assigned to intensive or conventional diabetes mellitus treatment during the Diabetes Control and Complications Trial (DCCT) underwent intima-media thickness (n = 1015) and coronary artery calcium score (n = 925) measurements during follow-up in the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. Intensive treatment subjects were classified by quartile of body mass index change during the DCCT. Excess gainers (4th quartile, including conventional treatment subjects meeting this threshold) maintained greater body mass index and waist circumference, needed more insulin, had greater intima-media thickness (+5%,
P
< 0.001 EDIC year 1,
P
= 0.003 EDIC year 6), and trended toward greater coronary artery calcium scores (odds ratio, 1.55; confidence interval, 0.97 to 2.49;
P
= 0.07) than minimal gainers. DCCT subjects meeting metabolic syndrome criteria for waist circumference and blood pressure had greater intima-media thickness in both EDIC years (
P
= 0.02 to < 0.001); those meeting high-density lipoprotein criteria had greater coronary artery calcium scores (odds ratio, 1.6; confidence interval, 1.1 to 2.4;
P
= 0.01) during follow-up. Increasing frequency of a family history of diabetes mellitus, hypertension, and hyperlipidemia was associated with greater intima-media thickness with intensive but not conventional treatment.

Conclusions—

Excess weight gain in DCCT is associated with sustained increases in central obesity, insulin resistance, dyslipidemia and blood pressure, as well as more extensive atherosclerosis during EDIC.

Clinical Trial Registration—

URL for DCCT:
http://clinicaltrials.gov
; Unique identifier: NCT00360815. URL for EDIC:
http://clinicaltrials.gov
; Unique identifier: NCT00360893.
Toxicopathological evaluation in Wistar rats (Rattus norvegicus) following repeated oral exposure to acephate
Authors: Bhadaniya Amit R , Kalariya Vinay A , Joshi Dilip V , Patel Bakor J , Chaudhary Sandhya , Patel Hitesh B , Patel Jignesh M , Patel Urvesh D , Patel Harshad B , Ghodasara Sanjay N , Savsani Harish H
Published: December 2012

The present study was carried out to evaluate the effects of exposure at different doses of acephate on hematology, blood biochemistry, oxidative stress and immune system of Wistar rats. The experiment was carried out on 40 Wistar rats, which were divided in four groups. Animals of the three treatment groups were given with different sublethal doses (1/40th, 1/20th, 1/10th of lethal dose 50 value) of acephate by oral gavage. The hematology, blood biochemistry, oxidative stress marker, humoral immune response and cell-mediated immunity were evaluated following acephate exposure. Significant alteration in hematological parameters was not observed following different doses of acephate; however, significant alteration in alkaline phosphatase, gamma glutamyl transferase, acetyl cholinesterase, lipid peroxidase and superoxide dismutase was observed in medium- and high-dose group animals. Nonsignificant decrease in antibody titer in animals exposed to high dose has been observed compared with animals of control group. However, significant alteration in cell-mediated immunity was not observed in animals treated with acephate at different doses.
Youth, waste and work in Mathare: whose business and whose politics?
Authors: Thieme Tatiana
Published: December 2012

In Nairobi’s Mathare Valley, one of the largest and oldest informal settlements in East Africa, waste has become a source of income generation for youth and a means of asserting slum dwellers’ rights to the city. While waste management has become a platform for engaging with the broader politics of basic services, it also interfaces with “sustainability” initiatives that invite alternative market-based approaches to address the challenges of poverty. It is at once a critique and an enabler of the excesses of modernity, at once a business and a form of political mobilization and contestation. The politics of work and waste among youth reflects alternative modes of urbanization grounded in both the dynamics of youth culture among the urban poor and grassroots market-based approaches to the provision of basic services.
Can the Elderly Handle the Heat? A Retrospective Case-Control Study of the Impact of Heat Waves on Older Patients Attending an Inner City Australian Emergency Department
Authors: Dalip Janelle , Phillips Georgina A. , Jelinek George A. , Weiland Tracey J.
Published: December 2012

The elderly have a higher mortality rate during heat waves and may, therefore, have higher morbidity. We investigated the effects of high ambient environmental temperature on emergency department (ED) function and patient (age >64 years) morbidity. A retrospective case-control study of ED presentations at an Australian metropolitan hospital from September 2005 to May 2010 was undertaken. Cases comprised 1297 ED presentations surrounding heat threshold days. These were compared with randomly selected presentations on nonthreshold days (3 controls: 1 case), analyzing patient morbidity and ED function variables: triage category, presenting complaint, demographics, arrival mode, time to doctor, ED length of stay (LOS), ED disposition, and discharge diagnoses. A greater proportion of cases presented with “weakness,” and were diagnosed with “dehydration.” There was little effect on ED function, with ED LOS 24 minutes longer for cases and time to doctor 3 minutes shorter. This study found limited evidence of increased morbidity in the elderly during heat wave conditions.
A Heuristic Tool for Teaching Business Writing
Authors: Ortiz Lorelei A.
Published: December 2012

To teach effective business communication, instructors must target students’ current weaknesses in writing. One method for doing so is by assigning writing exercises. When used heuristically, writing exercises encourage students to practice self-assessment, self-evaluation, active learning, and knowledge transfer, all while reinforcing the basics of good writing. Using writing exercises as a diagnostic or maintenance tool at different stages in the semester, in addition to the core assignments, can drastically improve undergraduate and graduate student writing and increase the probability that these students will transfer that writing knowledge into other courses and into their practices as professional writers in industry.
Deficient Emotional Self-Regulation in ADHD Assessed Using a Unique Profile of the Child Behavior Checklist (CBCL)
Authors: Donfrancesco R. , Innocenzi M. , Marano A. , Biederman J.
Published: December 2012

Objective: A unique profile of the empirically derived Child Behavior Checklist–anxious/depressed, attention, and aggression–deficient emotional self-regulation (CBCL-AAA-DESR profile: ≥180 and ≤210) may be used to identify a sizable minority of children with ADHD with associated DESR. The main aim of this study was to replicate these findings in an Italian sample. Method: The sample consisted of 358 children and teenagers aged 6 to 17 years of both sexes with ( n = 190) and without a diagnosis of ADHD ( n = 168). Results: In all, 40.0% of children with ADHD had a positive CBCL-DESR profile compared with 3.5% of controls. Receiver-operating characteristic analysis showed that the CBCL-DESR profile cut-off (sensitivity = 97.33, specificity = 79.66, criterion ≥179, ≤210) discriminated the two subsamples. Conclusion: The findings replicate previous results highlighting the utility of the CBCL as a means of identifying DESR in children with ADHD.
A Computing Model for Lifecycle Health Performance Evaluations of Sustainable Healthy Buildings
Authors: Lee Goonjae , Na Youngju , Kim Jeong Tai , Kim Sunkuk
Published: December 2012

As hazardous substances generated indoors are becoming a greater social issue, sustainable healthy buildings are being increasingly spotlighted. Sustainable healthy buildings refer to those buildings that maintain a certain level of health performance for their lifecycle. The health performance can be evaluated in terms of time, space and health factors. Previous studies on healthy buildings have mostly focused on pollutant emissions from materials and evaluation indicators, and the studies conducted on performance evaluations have been limited to specific areas such as indoor air quality (IAQ). However, it is necessary to assess the lifecycle health performance of health factors including IAQ, temperature, humidity, noise and lighting. In addition, a computing model is required to easily and promptly calculate the health factors and share health performance evaluation results during the planning, design, construction and operation and maintenance (O & M) phases. The purpose of this study is to propose a computing model for lifecycle health performance evaluation (LHPE model) of sustainable healthy buildings. The LHPE model consists of a lifecycle health performance tree (LHT) model, a process model and an information model. The LHPE model is intended to be used as a tool to draw out the comprehensive health performance of buildings with ease and quickness, when the evaluation indicators of the factors are completed in the near future.
Convergence of iterative sequences for fixed points of an infinite family of nonexpansive mappings based on a hybrid steepest descent methods
Authors: Onjai-uea Nawitcha , Jaiboon Chaichana , Kumam Poom , Humphries Usa Wannasingha
Published: December 2012

The propose of this article is to consider the strong convergence of an iterative sequences for finding a common element of the set of fixed points of an infinite family of nonexpansive mappings, the set of solutions of the variational inequalities for inverse strongly monotone mappings, and the set of solutions of system of equilibrium problems in Hilbert spaces by using a hybrid steepest descent methods. Our results improve and generalize many known corresponding results.

AMS (2000) Subject Classification: 46C05; 47H09; 47H10.
Genome plasticity and systems evolution in Streptomyces
Authors: Zhou Zhan , Gu Jianying , Li Yong-Quan , Wang Yufeng
Published: December 2012

Background

Streptomycetes are filamentous soil-dwelling bacteria. They are best known as the producers of a great variety of natural products such as antibiotics, antifungals, antiparasitics, and anticancer agents and the decomposers of organic substances for carbon recycling. They are also model organisms for the studies of gene regulatory networks, morphological differentiation, and stress response. The availability of sets of genomes from closely relatedStreptomycesstrains makes it possible to assess the mechanisms underlying genome plasticity and systems adaptation.

Results

We present the results of a comprehensive analysis of the genomes of fiveStreptomycesspecies with distinct phenotypes. These streptomycetes have a pan-genome comprised of 17,362 orthologous families which includes 3,096 components in the core genome, 5,066 components in the dispensable genome, and 9,200 components that are uniquely present in only one species. The core genome makes up about 33%-45% of each genome repertoire. It contains important genes forStreptomycesbiology including those involved in gene regulation, secretion, secondary metabolism and morphological differentiation. Abundant duplicate genes have been identified, with 4%-11% of the whole genomes composed of lineage-specific expansions (LSEs), suggesting that frequent gene duplication or lateral gene transfer events play a role in shaping the genome diversification within this genus. Two patterns of expansion, single gene expansion and chromosome block expansion are observed, representing different scales of duplication.

Conclusions

Our results provide a catalog of genome components and their potential functional roles in gene regulatory networks and metabolic networks. The core genome components reveal the minimum requirement for streptomycetes to sustain a successful lifecycle in the soil environment, reflecting the effects of both genome evolution and environmental stress acting upon the expressed phenotypes. A better understanding of the LSE gene families will, on the other hand, bring a wealth of new insights into the mechanisms underlying strain-specific phenotypes, such as the production of novel antibiotics, pathogenesis, and adaptive response to environmental challenges.
Gene expression and proteomic analysis of the formation of Phakopsora pachyrhizi appressoria
Authors: Stone Christine L , McMahon Michael B , Fortis Laurie L , Nuñez Alberto , Smythers Gary W , Luster Douglas G , Frederick Reid D
Published: December 2012

Background

Phakopsora pachyrhizi is an obligate fungal pathogen causing Asian soybean rust (ASR). A dual approach was taken to examine the molecular and biochemical processes occurring during the development of appressoria, specialized infection structures by which P. pachyrhizi invades a host plant. Suppression subtractive hybridization (SSH) was utilized to generate a cDNA library enriched for transcripts expressed during appressoria formation. Two-dimensional gel electrophoresis and mass spectroscopy analysis were used to generate a partial proteome of proteins present during appressoria formation.

Results

Sequence analysis of 1133 expressed sequence tags (ESTs) revealed 238 non-redundant ESTs, of which 53% had putative identities assigned. Twenty-nine of the non-redundant ESTs were found to be specific to the appressoria-enriched cDNA library, and did not occur in a previously constructed germinated urediniospore cDNA library. Analysis of proteins against a custom database of the appressoria-enriched ESTs plus Basidiomycota EST sequences available from NCBI revealed 256 proteins. Fifty-nine of these proteins were not previously identified in a partial proteome of P. pachyrhizi germinated urediniospores. Genes and proteins identified fell into functional categories of metabolism, cell cycle and DNA processing, protein fate, cellular transport, cellular communication and signal transduction, and cell rescue. However, 38% of ESTs and 24% of proteins matched only to hypothetical proteins of unknown function, or showed no similarity to sequences in the current NCBI database. Three novel Phakopsora genes were identified from the cDNA library along with six potentially rust-specific genes. Protein analysis revealed eight proteins of unknown function, which possessed classic secretion signals. Two of the extracellular proteins are reported as potential effector proteins.

Conclusions

Several genes and proteins were identified that are expressed in P. pachyrhizi during appressoria formation. Understanding the role that these genes and proteins play in the molecular and biochemical processes in the infection process may provide insight for developing targeted control measures and novel methods of disease management.
The Madagascar hissing cockroach as a novel surrogate host for Burkholderia pseudomallei, B. mallei and B. thailandensis
Authors: Fisher Nathan A , Ribot Wilson J , Applefeld Willard , DeShazer David
Published: December 2012

Background

Burkholderia pseudomallei and Burkholderia mallei are gram-negative pathogens responsible for the diseases melioidosis and glanders, respectively. Both species cause disease in humans and animals and have been designated as category B select agents by the Centers for Disease Control and Prevention (CDC). Burkholderia thailandensis is a closely related bacterium that is generally considered avirulent for humans. While it can cause disease in rodents, the B. thailandensis 50% lethal dose (LD50) is typically ≥ 104-fold higher than the B. pseudomallei and B. mallei LD50 in mammalian models of infection. Here we describe an alternative to mammalian hosts in the study of virulence and host-pathogen interactions of these Burkholderia species.

Results

Madagascar hissing cockroaches (MH cockroaches) possess a number of qualities that make them desirable for use as a surrogate host, including ease of breeding, ease of handling, a competent innate immune system, and the ability to survive at 37°C. MH cockroaches were highly susceptible to infection with B. pseudomallei, B. mallei and B. thailandensis and the LD50 was <10 colony-forming units (cfu) for all three species. In comparison, the LD50 for Escherichia coli in MH cockroaches was >105 cfu. B. pseudomallei, B. mallei, and B. thailandensis cluster 1 type VI secretion system (T6SS-1) mutants were all attenuated in MH cockroaches, which is consistent with previous virulence studies conducted in rodents. B. pseudomallei mutants deficient in the other five T6SS gene clusters, T6SS-2 through T6SS-6, were virulent in both MH cockroaches and hamsters. Hemocytes obtained from MH cockroaches infected with B. pseudomallei harbored numerous intracellular bacteria, suggesting that this facultative intracellular pathogen can survive and replicate inside of MH cockroach phagocytic cells. The hemolymph extracted from these MH cockroaches also contained multinuclear giant cells (MNGCs) with intracellular B. pseudomallei, which indicates that infected hemocytes can fuse while flowing through the insect’s open circulatory system in vivo.

Conclusions

The results demonstrate that MH cockroaches are an attractive alternative to mammals to study host-pathogen interactions and may allow the identification of new Burkholderia virulence determinants. The importance of T6SS-1 as a virulence factor in MH cockroaches and rodents suggests that the primary role of this secretion system is to target evasion of the innate immune system.
QTL mapping reveals the genetic architecture of loci affecting pre- and post-zygotic isolating barriers in Louisiana Iris
Authors: Ballerini Evangeline S , Brothers Amanda N , Tang Shunxue , Knapp Steven J , Bouck Amy , Taylor Sunni J , Arnold Michael L , Martin Noland H
Published: December 2012

Background

Hybridization among Louisiana Irises has been well established and the genetic architecture of reproductive isolation is known to affect the potential for and the directionality of introgression between taxa. Here we use co-dominant markers to identify regions where QTL are located both within and between backcross maps to compare the genetic architecture of reproductive isolation and fitness traits across treatments and years.

Results

QTL mapping was used to elucidate the genetic architecture of reproductive isolation between Iris fulva and Iris brevicaulis. Homologous co-dominant EST-SSR markers scored in two backcross populations between I. fulva and I. brevicaulis were used to generate genetic linkage maps. These were used as the framework for mapping QTL associated with variation in 11 phenotypic traits likely responsible for reproductive isolation and fitness. QTL were dispersed throughout the genome, with the exception of one region of a single linkage group (LG) where QTL for flowering time, sterility, and fruit production clustered. In most cases, homologous QTL were not identified in both backcross populations, however, homologous QTL for flowering time, number of growth points per rhizome, number of nodes per inflorescence, and number of flowers per node were identified on several linkage groups.

Conclusions

Two different traits affecting reproductive isolation, flowering time and sterility, exhibit different genetic architectures, with numerous QTL across the Iris genome controlling flowering time and fewer, less distributed QTL affecting sterility. QTL for traits affecting fitness are largely distributed across the genome with occasional overlap, especially on LG 4, where several QTL increasing fitness and decreasing sterility cluster. Given the distribution and effect direction of QTL affecting reproductive isolation and fitness, we have predicted genomic regions where introgression may be more likely to occur (those regions associated with an increase in fitness and unlinked to loci controlling reproductive isolation) and those that are less likely to exhibit introgression (those regions linked to traits decreasing fitness and reproductive isolation).
Dosing practice of low molecular weight heparins and its efficacy and safety in cardiovascular inpatients: a retrospective study in a Chinese teaching hospital
Authors: Xu Huimin , Cai Hongwen , Qian Zhongshu , Xu Geng , Yan Xiaofeng , Dai Haibin
Published: December 2012

Background

Low-molecular-weight heparins (LMWHs) are safe and effective anticoagulant options for cardiovascular patients when applied as body weight-adjusted doses. However, there are some barriers that make it difficult to implement weight-adjusted doses in clinical practice. Therefore, it is vital to learn the dosing practices of LMWH and its efficacy and safety in clinical practice.

Methods

A retrospective study was conducted in cardiovascular inpatients who had received at least one dose of LMWH during a 6-month period. Appropriateness of LMWH dosing was determined and major clinical outcomes (major adverse vascular events and major bleeding) during hospitalization were evaluated.

Results

A total of 376 admissions representing 364 patients received LMWH treatment. Of these, 17.0% (64/376) of admissions did not have body weight records. Of the 312 admissions included for the outcome study, only 34 cases (10.9%) received the recommended doses of LMWH, while 51 cases (16.3%) received mild underdoses, 223 cases (71.5%) received major underdoses and 4 (1.3%) received excess doses. There were 10 major adverse vascular events, which occurred more often in patients receiving excess doses of LMWH than in patients receiving recommended, mild or major underdoses (50%, 2.9%, 2.0% and 2.7%, respectively, P < 0.001). After multivariable analysis, severe renal insufficiency was an independent risk factor for major adverse vascular events [odds ratio (OR), 31.93; 95% confidence interval (CI), 5.99-170.30; P < 0.001]. No major bleeding was recorded.

Conclusions

Underdose of LMWH is commonly used in cardiovascular inpatients, which was suboptimal according to guidelines. Using LMWH at a fixed, low dose for treatment purposes in patients without severe renal insufficiency was not associated with a higher risk of adverse vascular events in the current study, though larger studies with extended follow-ups are required to fully assess the long-term consequences of LMWH underdosing.
Natural history and clinical response: “It’s the virus, stupid, or is it the host?”
Authors: Nucara Stefania , Caroleo Benedetto , Guadagnino Vincenzo , Perrotti Nicola , Trapasso Francesco
Published: December 2012

A major goal of modern medicine is the application of personalized therapies, consisting of decisions and practices tailored to the individual patient. Information about genetic variants, either mutant or polymorphic, represents the basis for the development of this clinical approach. Recently, several independent genome-wide association studies (GWAS) have identified two single nucleotide polymorphisms (SNPs) on the IL28B locus associated with HCV containment, spontaneous clearance, treatment response, and disease progression. In this minireview we will concisely discuss some critical genetic concepts that may have possible implications for clinical decisions in the treatment of HCV infection.
Disruption of the endothelin A receptor in the nephron causes mild fluid volume expansion
Authors: Stuart Deborah , Rees Sara , Woodward Stephanie K , Koesters Robert , Strait Kevin A , Kohan Donald E
Published: December 2012

Background

Endothelin, via endothelin A receptors (ETA), exerts multiple pathologic effects that contribute to disease pathogenesis throughout the body. ETA antagonists ameliorate many experimental diseases and have been extensively utilized in clinical trials. The utility of ETA blockers has been greatly limited, however, by fluid retention, sometimes leading to heart failure or death. To begin to examine this issue, the effect of genetic disruption of ETA in the nephron on blood pressure and salt handling was determined.

Methods

Mice were generated with doxycycline-inducible nephron-specific ETA deletion using Pax8-rtTA and LC-1 transgenes on the background of homozygous loxP-flanked ETA alleles. Arterial pressure, Na metabolism and measures of body fluid volume status (hematocrit and impedance plethysmography) were assessed.

Results

Absence of nephron ETA did not alter arterial pressure whether mice were ingesting a normal or high Na diet. Nephron ETA disruption did not detectably affect 24 hr Na excretion or urine volume regardless of Na intake. However, mice with nephron ETA knockout that were fed a high Na diet had mild fluid retention as evidenced by an increase in body weight and a fall in hematocrit.

Conclusions

Genetic deletion of nephron ETA causes very modest fluid retention that does not alter arterial pressure. Nephron ETA, under normal conditions, likely do not play a major role in regulation of Na excretion or systemic hemodynamics.
Insulin-like growth factors in endometrioid adenocarcinoma: Correlation with clinico-pathological features and estrogen receptor expression
Authors: Liang Yuan-Jiao , Hao Qun , Zhang Hui-Ming , Wu Yuan-Zhe , Wang Jian-Dong
Published: December 2012

Background

Endometrial carcinoma is a common malignancy of female genital tract. Insulin-like growth factor is known to elicit estrogen-induced mitogenic activity and anti-apoptotic effect in endometrial tissues.

Methods

The retrospective study investigated the expression of insulin-like growth factors, estrogen receptors and their associations in endometrioid adenocarcinoma (EAC) from 80 EAC patients in immunohistochemistry, and 58 EAC patients and 42 control patients in quantitative RT-PCR. The Pearson correlation analysis was used to analyze their correlations with clinic-pathological parameters.

Results

Our results showed that insulin-like growth factor-1 and insulin-like growth factor-2 mRNA levels were higher in tumor tissues and tumor-adjacent tissues than those in control cells, and were inversely correlated with the malignancy of the tumor with a positive correlation with ERα and ERβ expression. Insulin-like growth factor-1R protein expression was correlated with clinical stage, and insulin-like growth factor-2R protein expression was inversely correlated with histological grade.

Conclusions

Insulin-like growth factor system plays an important role in estrogen-induced endometrial carcinogenesis, and overexpression of insulin-like growth factor-1R in the advanced endometrioid adenocarcinoma is not estrogen-dependent.
Self-reported evaluation of competencies and attitudes by physicians-in-training before and after a single day legislative advocacy experience
Authors: Huntoon Kristin M , McCluney Colin J , Wiley Elizabeth A , Scannell Christopher A , Bruno Richard , Stull Matthew J
Published: December 2012

Background

Advocacy is increasingly being recognized as a core element of medical professionalism and efforts are underway to incorporate advocacy training into graduate and undergraduate medical school curricula. While limited data exist to quantify physician attitudes toward advocacy, even less has been done to assess the knowledge, skills, and attitudes of future physicians. The purpose of this study was to assess students’ experiences and attitudes toward legislative advocacy, cutting out using a convience sample.

Methods

A paper survey based on previously validated surveys was administered to a convenience sample of premedical and medical student participants attending a National Advocacy Day in Washington, DC, in March 2011, both before and after their advocacy experiences. Responses were anonymous and either categorical ( or ordinal, using a 5-point Likert scale. Data were analyzed statistically to evaluate demographics and compare changes in pre- and post-experience attitude and skills.

Results

Data from 108 pre-advocacy and 50 post-advocacy surveys were analyzed yielding a response rate of 46.3%. Following a single advocacy experience, subjects felt they were more likely to contact their legislators about healthcare issues (p = 0.03), to meet in person with their legislators (p < 0.01), and to advocate for populations' health needs (p = 0.04). Participants endorsed an increased perception of the role of a physician advocate extending beyond individual patients (p = 0.03). Participants disagreed with the statement that their formal curricula adequately covered legislative healthcare advocacy. Additionally, respondents indicated that they plan to engage in legislative advocacy activities in the future (p < 0.01).

Conclusions

A one-time practical advocacy experience has a positive influence on students’ knowledge, skills and attitudes towards legislative advocacy. Practical experience is an important method of furthering medical education in advocacy and further research is necessary to assess its impact in a broader population.
Clinical application of human β-defensin and CD14 gene polymorphism in evaluating the status of chronic inflammation
Authors: Loo Wings TY , Bai Lan-jun , Fan Chang-bin , Yue Yuan , Dou Yi-ding , Wang Min , Liang Hao , Cheung Mary NB , Chow Louis WC , Li Jin-le , Tian Ye , Qing Liu
Published: December 2012

Background

Periodontitis is a common disease that affects the periodontal tissue supporting the teeth. This disease is attributed to multiple risk factors, including diabetes, cigarette smoking, alcohol, pathogenic microorganisms, genetics and others. Human beta-defensin-1 (hBD-1) is a cationic antimicrobial peptide with cysteine-rich ß-sheets and broad-spectrum antimicrobial activity. CD14 is a protein involved in the detection of bacterial lipopolysaccharide (LPS) and has also been associated with periodontitis. This study investigates the single nucleotide polymorphic (SNP) region, -1654(V38I), of the human beta-defensin-1 (hBD-1) gene as well as the -159 region of theCD14gene in subjects with chronic periodontitis.

Methods

Blood samples from periodontally healthy subjects and periodontitis patients were obtained. DNA was extracted from the blood and was used to perform restriction digest at the polymorphic G1654A site ofDEFB1with the enzymeHincII.The polymorphic site 159TT ofCD14was digested with the enzymeAvaII.Enzyme-linked immunosorbent assay (ELISA) was performed on soluble samples to determine the protein expressions.

Results

The control and patient groups expressed 35% and 38% 1654 A/A genotype ofDEFB1, respectively. The A allele frequency of the control group was 40%, while the patient blood group was 54%. The mean hBD-1 protein levels of the control and patient samples were 102.83 pg/mL and 252.09 pg/mL, respectively. The genotype distribution ofCD14in healthy subjects was 16% for C/C, 26% for T/T and 58% for C/T. The genotype frequencies ofCD14in periodontitis patients were 10% for C/C, 43% for T/T and 47% for C/T. The CD14 protein expression determined by ELISA showed a mean protein level of the control samples at 76.28ng/mL and the patient blood samples at 179.27ng/mL with apvalue of 0.001.

Our study demonstrated that patients suffering from chronic periodontitis present more commonly with the 1654A/A genotype on theDEFB1gene and the 159T/T genotype on theCD14gene.

Conclusions

This study purely investigated the association between periodontitis and one polymorphic site on bothDEFB1andCD14gene, with the purpose of expanding knowledge for the future development in diagnostic markers or therapeutic interventions to combat this disease.
Antibacterial activity of silver-doped hydroxyapatite nanoparticles against gram-positive and gram-negative bacteria
Authors: Ciobanu Carmen Steluta , Iconaru Simona Liliana , Le Coustumer Phillippe , Constantin Liliana Violeta , Predoi Daniela
Published: December 2012

Ag-doped nanocrystalline hydroxyapatite nanoparticles (Ag:HAp-NPs) (Ca10-xAgx(PO4)6(OH)2,xAg = 0.05, 0.2, and 0.3) with antibacterial properties are of great interest in the development of new products. Coprecipitation method is a promising route for obtaining nanocrystalline Ag:HAp with antibacterial properties. X-ray diffraction identified HAp as an unique crystalline phase in each sample. The calculated lattice constants ofa = b = 9.435 Å,c = 6.876 Å forxAg = 0.05,a = b = 9.443 Å,c = 6.875 Å forxAg = 0.2, anda = b = 9.445 Å,c = 6.877 Å forxAg = 0.3 are in good agreement with the standard ofa = b = 9.418 Å,c = 6.884 Å (space group P63/m). The Fourier transform infrared and Raman spectra of the sintered HAp show the absorption bands characteristic to hydroxyapatite. The Ag:HAp nanoparticles are evaluated for their antibacterial activity againstStaphylococcus aureus,Klebsiella pneumoniae,Providencia stuartii,Citrobacter freundiiandSerratia marcescens. The results showed that the antibacterial activity of these materials, regardless of the sample types, was greatest againstS. aureus,K. pneumoniae, P. stuartii, andC. freundii. The results of qualitative antibacterial tests revealed that the tested Ag:HAp-NPs had an important inhibitory activity onP. stuartiiandC. freundii. The absorbance values measured at 490 nm of theP. stuartiiandC. freundiiin the presence of Ag:HAp-NPs decreased compared with those of organic solvent used (DMSO) for all the samples (xAg = 0.05, 0.2, and 0.3). Antibacterial activity increased with the increase ofxAgin the samples. The Ag:HAp-NP concentration had little influence on the bacterial growth (P. stuartii).
On "Equation missing" -contractions in ordered metric spaces
Authors: Chaipunya Parin , Sintunavarat Wutiphol , Kumam Poom
Published: December 2012

In this paper, we introduced a new type of a contractive condition defined on an ordered space, namely a

P

-contraction, which generalizes the weak contraction. We also proved some fixed point theorems for such a condition in ordered metric spaces. A supporting example of our results is provided in the last part of our paper as well.

MSC:06A05, 06A06, 47H09, 47H10, 54H25.
Bioavailability and pharmacokinetics of oral meloxicam in llamas
Authors: Kreuder Amanda J , Coetzee Johann F , Wulf Larry W , Schleining Jennifer A , KuKanich Butch , Layman Lori L , Plummer Paul J
Published: December 2012

Background

South American camelids in the United States have rapidly developed into an important agricultural industry in need of veterinary services. Pain management is challenging in camelids because there are no drugs currently approved by the U.S. Food and Drug Administration for use in these species. Dosage regimens used for many therapeutic drugs have been extrapolated from other ruminants; however, the pharmacokinetics, in camelids, may differ from those of other species. Studies investigating the pharmacokinetics of cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drugs in camelids are deficient in the published literature. Six adult llamas (121- 168 kg) were administered either a 1 mg/kg dose of oral or a 0.5 mg/kg dose of IV meloxicam in a randomized cross-over design with an 11 day washout period between treatments. Plasma samples collected up to 96 hours post-administration were analyzed by high pressure liquid chromatography and mass spectrometry detection (HPLC-MS) followed by non-compartmental pharmacokinetic analysis.

Results

A mean peak plasma concentration (CMAX) of 1.314 μg/mL (Range: 0.826 – 1.776 μg/mL) was recorded at 21.4 hours (Range: 12.0 – 24.0 hours) with a half-life (T ½ λz) of 22.7 hours (Range: 18.0 – 30.8 hours) after oral meloxicam administration. In comparison, a half-life (T ½ λz) of 17.4 hours (Range: 16.2 – 20.7 hours) was demonstrated with IV meloxicam administration. The oral bioavailability (F) of meloxicam (dose normalized) was 76% (Range: 48 – 92%). No adverse effects associated with either treatment modality were observed in the llamas.

Conclusions

The mean bioavailability (F) of oral meloxicam was 76% indicating a high degree of gastrointestinal absorption. Plasma meloxicam concentrations >0.2 μg/mL were maintained for up to 72 h after oral administration; >0.2 μg/mL is considered to be the concentration of meloxicam required for analgesic effects in other species such as the horse. These data suggest that a single dosage of oral meloxicam at 1 mg/kg could potentially maintain therapeutic concentrations in plasma for up to 3 days in adult llamas.
A novel neural response algorithm for protein function prediction
Authors: Yalamanchili Hari Krishna , Xiao Quan-Wu , Wang Junwen
Published: December 2012

Background

Large amounts of data are being generated by high-throughput genome sequencing methods. But the rate of the experimental functional characterization falls far behind. To fill the gap between the number of sequences and their annotations, fast and accurate automated annotation methods are required. Many methods, such as GOblet, GOFigure, and Gotcha, are designed based on the BLAST search. Unfortunately, the sequence coverage of these methods is low as they cannot detect the remote homologues. Adding to this, the lack of annotation specificity advocates the need to improve automated protein function prediction.

Results

We designed a novel automated protein functional assignment method based on the neural response algorithm, which simulates the neuronal behavior of the visual cortex in the human brain. Firstly, we predict the most similar target protein for a given query protein and thereby assign its GO term to the query sequence. When assessed on test set, our method ranked the actual leaf GO term among the top 5 probable GO terms with accuracy of 86.93%.

Conclusions

The proposed algorithm is the first instance of neural response algorithm being used in the biological domain. The use of HMM profiles along with the secondary structure information to define the neural response gives our method an edge over other available methods on annotation accuracy. Results of the 5-fold cross validation and the comparison with PFP and FFPred servers indicate the prominent performance by our method. The program, the dataset, and help files are available at http://www.jjwanglab.org/NRProF/.
Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle – an update
Authors: Konold Timm , Arnold Mark E , Austin Anthony R , Cawthraw Saira , Hawkins Steve AC , Stack Michael J , Simmons Marion M , Sayers A Robin , Dawson Michael , Wilesmith John W , Wells Gerald AH
Published: December 2012

Background

To provide information on dose–response and aid in modelling the exposure dynamics of the BSE epidemic in the United Kingdom groups of cattle were exposed orally to a range of different doses of brainstem homogenate of known infectious titre from clinical cases of classical bovine spongiform encephalopathy (BSE). Interim data from this study was published in 2007. This communication documents additional BSE cases, which occurred subsequently, examines possible influence of the bovine prion protein gene on disease incidence and revises estimates of effective oral exposure.

Findings

Following interim published results, two further cattle, one dosed with 100 mg and culled at 127 months post exposure and the other dosed with 10 mg and culled at 110 months post exposure, developed BSE. Both had a similar pathological phenotype to previous cases. Based on attack rate and incubation period distribution according to dose, the dose estimate at which 50% of confirmed cases would be clinically affected was revised to 0.15 g of the brain homogenate used in the experiment, with a 95% confidence interval of 0.03–0.79 g. Neither the full open reading frame nor the promoter region of the prion protein gene of dosed cattle appeared to influence susceptibility to BSE, but this may be due to the sample size.

Conclusions

Oral exposure of cattle to a large range of doses of a BSE brainstem homogenate produced disease in all dose groups. The pathological presentation resembled natural disease. The attack rate and incubation period were dependent on the dose.