bluuebunny/crossref_metadata_2025 huggingface dataset:
A mechanical model for predicting the probability of osteoporotic hip fractures based in DXA measurements and finite element simulation
Authors: López Enrique , Ibarz Elena , Herrera Antonio , Mateo Jesús , Lobo-Escolar Antonio , Puértolas Sergio , Gracia Luis
Published: November 2012

Background

Osteoporotic hip fractures represent major cause of disability, loss of quality of life and even mortality among the elderly population. Decisions on drug therapy are based on the assessment of risk factors for fracture, from BMD measurements. The combination of biomechanical models with clinical studies could better estimate bone strength and supporting the specialists in their decision.

Methods

A model to assess the probability of fracture, based on the Damage and Fracture Mechanics has been developed, evaluating the mechanical magnitudes involved in the fracture process from clinical BMD measurements. The model is intended for simulating the degenerative process in the skeleton, with the consequent lost of bone mass and hence the decrease of its mechanical resistance which enables the fracture due to different traumatisms. Clinical studies were chosen, both in non-treatment conditions and receiving drug therapy, and fitted to specific patients according their actual BMD measures. The predictive model is applied in a FE simulation of the proximal femur. The fracture zone would be determined according loading scenario (sideway fall, impact, accidental loads, etc.), using the mechanical properties of bone obtained from the evolutionary model corresponding to the considered time.

Results

BMD evolution in untreated patients and in those under different treatments was analyzed. Evolutionary curves of fracture probability were obtained from the evolution of mechanical damage. The evolutionary curve of the untreated group of patients presented a marked increase of the fracture probability, while the curves of patients under drug treatment showed variable decreased risks, depending on the therapy type.

Conclusion

The FE model allowed to obtain detailed maps of damage and fracture probability, identifying high-risk local zones at femoral neck and intertrochanteric and subtrochanteric areas, which are the typical locations of osteoporotic hip fractures.

The developed model is suitable for being used in individualized cases. The model might better identify at-risk individuals in early stages of osteoporosis and might be helpful for treatment decisions.
Neurobehavioral function and low-level exposure to brominated flame retardants in adolescents: a cross-sectional study
Authors: Kiciński Michał , Viaene Mineke K , Den Hond Elly , Schoeters Greet , Covaci Adrian , Dirtu Alin C , Nelen Vera , Bruckers Liesbeth , Croes Kim , Sioen Isabelle , Baeyens Willy , Van Larebeke Nicolas , Nawrot Tim S
Published: November 2012

Background

Animal and in vitro studies demonstrated a neurotoxic potential of brominated flame retardants, a group of chemicals used in many household and commercial products to prevent fire. Although the first reports of detrimental neurobehavioral effects in rodents appeared more than ten years ago, human data are sparse.

Methods

As a part of a biomonitoring program for environmental health surveillance in Flanders, Belgium, we assessed the neurobehavioral function with the Neurobehavioral Evaluation System (NES-3), and collected blood samples in a group of high school students. Cross-sectional data on 515 adolescents (13.6-17 years of age) was available for the analysis. Multiple regression models accounting for potential confounders were used to investigate the associations between biomarkers of internal exposure to brominated flame retardants [serum levels of polybrominated diphenyl ether (PBDE) congeners 47, 99, 100, 153, 209, hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA)] and cognitive performance. In addition, we investigated the association between brominated flame retardants and serum levels of FT3, FT4, and TSH.

Results

A two-fold increase of the sum of serum PBDE’s was associated with a decrease of the number of taps with the preferred-hand in the Finger Tapping test by 5.31 (95% CI: 0.56 to 10.05, p = 0.029). The effects of the individual PBDE congeners on the motor speed were consistent. Serum levels above the level of quantification were associated with an average decrease of FT3 level by 0.18 pg/mL (95% CI: 0.03 to 0.34, p = 0.020) for PBDE-99 and by 0.15 pg/mL (95% CI: 0.004 to 0.29, p = 0.045) for PBDE-100, compared with concentrations below the level of quantification. PBDE-47 level above the level of quantification was associated with an average increase of TSH levels by 10.1% (95% CI: 0.8% to 20.2%, p = 0.033), compared with concentrations below the level of quantification. We did not observe effects of PBDE’s on neurobehavioral domains other than the motor function. HBCD and TBBPA did not show consistent associations with performance in the neurobehavioral tests.

Conclusions

This study is one of few studies and so far the largest one investigating the neurobehavioral effects of brominated flame retardants in humans. Consistently with experimental animal data, PBDE exposure was associated with changes in the motor function and the serum levels of the thyroid hormones.
A gender-related action of IFNbeta-therapy was found in multiple sclerosis
Authors: Contasta Ida , Totaro Rocco , Pellegrini Patrizia , Del Beato Tiziana , Carolei Antonio , Berghella Anna Maria
Published: November 2012

Background

Understanding how sexual dimorphism affects the physiological and pathological responses of the immune system is of considerable clinical importance and could lead to new approaches in therapy. Sexual dimorphism has already been noted as an important factor in autoimmune diseases: the aim of this study was to establish whether sexual dimorphism in autoimmune diseases is the result of differing pathways being involved in the regulation of T-helper (Th) cell network homeostasis.

Methods

We focused on sexually dimorphic changes in the immune response in multiple sclerosis (MS) patients in order to ascertain how these alterations relate to the pathway regulation of the cytokine homeostasis and the Th cell networks. We studied antigen presenting cell (APC)-dependent T cell activation in groups of healthy subjects, in patients under interferon (IFN) β-therapy and untreated. Cytokines, soluble (s) CD30 and the expanded disability status scale (EDSS) were used as biomarkers for T cell differentiation and neurological deficit.

Results

The data confirm our belief that sexual dimorphism in autoimmune diseases is the result of differing pathways that regulate Th cell network homeostasis: interleukin (IL) 6 pathways in women and IFNγ pathways in men. Given the increased susceptibility of women to MS and the significance of IL6 in the autoimmune process compared to IFNγ, it is logical to assume that IL6 pathways are in some way implicated in the prevalence of autoimmune diseases in women. Indeed, our data indicate that IL6 pathways are also involved in T regulatory (Treg) cell imbalance and an increase in neurological deficit in both men and women groups of MS patients, underlining the autoimmune etiology of multiple sclerosis. In further support of differing cytokine pathways in men and women, we noted that the efficacy of IFNβ-treatment in the re-establishment of Th-network balance and in the delaying of the neurological disability progression is linked to the IL6 pathway in women, but to the IFNγ pathway in men. Lastly, we also identified specific gender biomarkers for the use in therapy.

Conclusions

The identification of gender-specific drugs is of considerable importance in translational medicine and will undoubtedly lead to more appropriate therapeutic strategies and more successful treatment.
RMol: a toolset for transforming SD/Molfile structure information into R objects
Authors: Grabner Martin , Varmuza Kurt , Dehmer Matthias
Published: November 2012

Background

The graph-theoretical analysis of molecular networks has a long tradition in chemoinformatics. As demonstrated frequently, a well designed format to encode chemical structures and structure-related information of organic compounds is the Molfile format. But when it comes to use modern programming languages for statistical data analysis in Bio- and Chemoinformatics, as one of the most powerful free languages lacks tools to process Molfile data collections and import molecular network data into .

Results

We design an object which allows a lossless information mapping of structural information from Molfiles into objects. This provides the basis to use the object as an anchor for connecting Molfile data collections with libraries for analyzing graphs. Associated with the objects, a set of functions completes the toolset to organize, describe and manipulate the converted data sets. Further, we bypass -typical limits for manipulating large data sets by storing objects in -compressed serialized files instead of employing files.

Conclusions

By design, is a toolset without dependencies to other libraries or programming languages. It is useful to integrate into pipelines for serialized batch analysis by using network data and, therefore, helps to process sdf-data sets in efficiently. It is freely available under the BSD licence. The script source can be downloaded fromhttp://sourceforge.net/p/rmol-toolset
Diversity and transmission competence in lymphatic filariasis vectors in West Africa, and the implications for accelerated elimination of Anopheles-transmitted filariasis
Authors: de Souza Dziedzom K , Koudou Benjamin , Kelly-Hope Louise A , Wilson Michael D , Bockarie Moses J , Boakye Daniel A
Published: November 2012

Lymphatic Filariasis (LF) is targeted for elimination by the Global Programme for the Elimination of Lymphatic Filariasis (GPELF). The strategy adopted is based on the density dependent phenomenon of Facilitation, which hypothesizes that in an area where the vector species transmitting Wuchereria bancrofti are Anopheles mosquitoes, it is feasible to eliminate LF using Mass Drug Administration (MDA) because of the inability of Anopheles species to transmit low-density microfilaraemia. Even though earlier studies have shown Anopheles species can exhibit the process of Facilitation in West Africa, observations point towards the process of Limitation in certain areas, in which case vector control is recommended. Studies on Anopheles species in West Africa have also shown genetic differentiation, cryptic taxa and speciation, insecticide resistance and the existence of molecular and chromosomal forms, all of which could influence the vectorial capacity of the mosquitoes and ultimately the elimination goal. This paper outlines the uniqueness of LF vectors in West Africa and the challenges it poses to the 2020 elimination goal, based on the current MDA strategies.
TGF beta1 and related-Smads contribute to pulmonary metastasis of hepatocellular carcinoma in mice model
Authors: Li Guo-Cai , Ye Qing-Hai , Dong Qiong-Zhu , Ren Ning , Jia Hu-Liang , Qin Lun-Xiu
Published: November 2012

Background

Recent studies indicate that Transforming Growth Factor beta (TGF β) correlated with pulmonary metastasis of cancers. However, the correlation between TGF β and pulmonary metastasis of hepatocellular carcinoma (HCC) is till unknown.

Methods

We detected the in vitro and in vivo expression levels of TGF β1/Smads by Real-time PCR and Western blot in MHCC97-H and MHCC97–L cell lines, which are HCC cell lines and have higher and lower pulmonary metastatic potential respectively.

Results

TGF β1 mRNA level in MHCC97-L tumors were higher than that in MHCC97-H tumors, (2.81±1.61 vs. 1.24±0.96, P=0.002), TGF β1 protein level in MHCC97-L tumors were also higher than that in MHCC97-H tumors (1.37±0.95 vs. 0.32±0.22, P<0.001). In addition, the TGF β1 mRNA level positively correlated with pulmonary metastasis, and the relations between TGF β1 and Smads were also found (R2=0.12 and 0.40, respectively).

Conclusions

Our results suggest that TGF β/ Smads promote pulmonary metastasis of HCC.
Evaluation of primary adnexal masses by 3T MRI: categorization with conventional MR imaging and diffusion-weighted imaging
Authors: Zhang He , Zhang Guo-Fu , He Zhi-Yan , Li Zheng-Yu , Zhu Ming , Zhang Gui-Xiang
Published: November 2012

Background

To investigate the 3.0-Tesla (3 T) magnetic resonance imaging (MRI) characteristics of primary adnexal lesions for discriminating benign from malignant lesions.

Methods

One hundred thirty-nine patients with pathologically proven primary adnexal masses referred for 3 T MRI assessment preoperatively were included. Baseline characteristics, components, and conventional MRI and diffusion-weighted imaging (DWI-MRI) signals were recorded and compared.

Results

There were 22 ovarian cysts, 33 endometriomas, 43 benign tumors and 42 malignant tumors. When ovarian cyst and endometrioma were excluded, there were no significant differences in patients’ age between benign and malignant tumor (P = 0.235). There were no significant differences (P = 0.606) in the conventional MRI signals and significant difference (P = 0.008) in DWI-MRI signal between the non-malignant and malignant lesions. There was a significant difference (P = 0.000) in the apparent diffusion coefficient values (ADCs) between the non-malignant and malignant lesions.

Conclusions

3 T MRI categorized the characteristics of primary adnexal lesions. Conventional MRI signals were not useful for characterizing between benign and malignant lesions. DWI-MRI and ADCs were helpful for distinguishing malignant from benign ovarian lesions.
Biocidal activity of metalloacid-coated surfaces against multidrug-resistant microorganisms
Authors: Tétault Nathalie , Gbaguidi-Haore Houssein , Bertrand Xavier , Quentin Roland , van der Mee-Marquet Nathalie
Published: November 2012

Background

The antimicrobial effects of a coating of molybdenum trioxide (MoO3) has been recently described. The metalloacid material produces oxonium ions (H3O+), which creates an acidic pH that is an effective, non specific antimicrobial. We determined the in vitro antimicrobial activity of molybdenum trioxide metalloacid-coated surfaces.

Methods

Metalloacid-coated and non-coated (control) surfaces were contaminated by exposing them for 15 minutes to microbial suspensions containing 105 cfu/mL. Eleven microorganisms responsible for nosocomial infections were tested: two Staphylococcus aureus strains (the hetero-vancomycin intermediate MRSA Mu50 strain and a ST80-PVL-producing MRSA strain); a vancomycin-resistant van A Enterococcus faecium strain; three extended-spectrum beta-lactamase-producing Enterobacteriaceae strains; a MBL-producing Pseudomonas aeruginosa strain; a multidrug-resistant Acinetobacter baumannii strain; a toxin-producing Clostridium difficile strain; and two fungi (Candida albicans and Aspergillus fumigatus). The assay tested the ability of the coated surfaces to kill microorganisms.

Results

Against all non-sporulating microorganisms tested, metalloacid-coated surfaces exhibited significant antimicrobial activity relative to that of the control surfaces within two to six hours after contact with the microorganisms (p < 0.001). Microorganism survival on the coated surfaces was greatly impaired, whereas microorganism survival on control surfaces remained substantial.

Conclusions

We suggest that, facing the continuing shedding of microorganisms in the vicinity of colonized or infected patients, the continuous biocidal effect of hydroxonium oxides against multidrug-resistant microorganisms may help limit environmental contamination between consecutive cleaning procedures.
Can neonatal lung ultrasound monitor fluid clearance and predict the need of respiratory support?
Authors: Raimondi Francesco , Migliaro Fiorella , Sodano Angela , Umbaldo Angela , Romano Antonia , Vallone Gianfranco , Capasso Letizia
Published: November 2012

Introduction

At birth, lung fluid is rapidly cleared to allow gas exchange. As pulmonary sonography discriminates between liquid and air content, we have used it to monitor extrauterine fluid clearance and respiratory adaptation in term and late preterm neonates. Ultrasound data were also related to the need for respiratory support.

Methods

Consecutive infants at 60 to 120 minutes after birth underwent lung echography. Images were classified using a standardized protocol of adult emergency medicine with minor modifications. Neonates were assigned to type 1 (white lung image), type 2 (prevalence of comet-tail artifacts or B-lines) or type 3 profiles (prevalence of horizontal or A lines). Scans were repeated at 12, 24 and 36 hours. The primary endpoint was the number of infants admitted to the neonatal ICU (NICU) by attending staff who were unaware of the ultrasound. Mode of respiratory support was also recorded.

Results

A total of 154 infants were enrolled in the study. Fourteen neonates were assigned to the type 1, 46 to the type 2 and 94 to the type 3 profile. Within 36 hours there was a gradual shift from types 1 and 2 to type 3. All 14 type 1 and 4 type 2 neonates were admitted to the NICU. Sensitivity was 77.7%, specificity was 100%, positive predictive value was 100%, negative predictive value was 97%. Four type 1 infants were mechanically ventilated.

Conclusions

In the late preterm and term neonate, the lung ultrasound scan follows a reproducible pattern that parallels the respiratory status and can be used as a predictor of respiratory support.
Associations Between End-of-Life Discussion Characteristics and Care Received Near Death: A Prospective Cohort Study
Authors: Mack Jennifer W. , Cronin Angel , Keating Nancy L. , Taback Nathan , Huskamp Haiden A. , Malin Jennifer L. , Earle Craig C. , Weeks Jane C.
Published: November 2012

Purpose

National guidelines recommend that discussions about end-of-life (EOL) care planning happen early for patients with incurable cancer. We do not know whether earlier EOL discussions lead to less aggressive care near death. We sought to evaluate the extent to which EOL discussion characteristics, such as timing, involved providers, and location, are associated with the aggressiveness of care received near death.

Patients and Methods

We studied 1,231 patients with stage IV lung or colorectal cancer in the Cancer Care Outcomes Research and Surveillance Consortium, a population- and health system–based prospective cohort study, who died during the 15-month study period but survived at least 1 month. Our main outcome measure was the aggressiveness of EOL care received.

Results

Nearly half of patients received at least one marker of aggressive EOL care, including chemotherapy in the last 14 days of life (16%), intensive care unit care in the last 30 days of life (9%), and acute hospital-based care in the last 30 days of life (40%). Patients who had EOL discussions with their physicians before the last 30 days of life were less likely to receive aggressive measures at EOL, including chemotherapy (P = .003), acute care (P < .001), or any aggressive care (P < .001). Such patients were also more likely to receive hospice care (P < .001) and to have hospice initiated earlier (P < .001).

Conclusion

Early EOL discussions are prospectively associated with less aggressive care and greater use of hospice at EOL.
Ablation of Egr2-Positive Cells in Male Mouse Anterior Pituitary Leads to Atypical Isolated GH Deficiency
Authors: Bouchoucha Yassine Xavier , Charnay Patrick , Gilardi-Hebenstreit Pascale
Published: November 2012

In this study, we have investigated the expression and function of the transcription factor early growth response factor 2 (Egr2)/Krox20 in the developing anterior pituitary. Egr2 is initially expressed in all differentiating hormonal cells types, but its expression is mostly restricted to the somatotroph lineage after birth. Egr2 knockout results in anterior pituitary hypoplasia. However, the analysis of a conditional mutant demonstrates that this phenotype does not originate from a lack of Egr2 expression in the pituitary. Using an Egr2 allele driving a Cre-activable toxin gene, we performed a genetic ablation of Egr2-positive cells in the pituitary. During the postnatal period, this ablation leads to specific and progressive depletion of the somatotroph population, creating a novel model of early-onset isolated GH deficiency (GHD). Mutant animals were subjected to a complete metabolic analysis, revealing atypical and expected features. Consistent with an adult-onset isolated GHD model, mutant animals are hypoglycemic and display increased insulin sensitivity and glucose clearance. This latter phenotype is in contrast to the glucose intolerance observed in another early-onset GHD model. Surprisingly, increased insulin sensitivity is not accompanied by a modified balance between fat and lean tissues, but by reduced metabolic adaptability between glucose and lipid oxidation conditions. This suggests that the relationship between these metabolic features and insulin sensitivity should be reconsidered. In conclusion, our mutant may be a valuable genetic model with which to study the effects of long-term GH deficiency, in conditions of normal pancreatic function and unaffected balance between fat and glucose metabolism.
Resource Use and Cost Implications of Switching Among Warfarin Formulations in Atrial Fibrillation Patients
Authors: Kwong Winghan Jacqueline , Kamat Siddhesh , Fang Christy
Published: November 2012

Background:

Despite the uncertainty surrounding the safety of switching warfarin formulations, limited data exist on the resource use and costs associated with this switching pattern.

Objective:

To evaluate health care resource use and costs associated with switching warfarin formulations among patients with atrial fibrillation (AF) in a managed care organization.

Methods:

Patients diagnosed with AF (ICD-9 427.31) between July 2004 and August 2008 and who received warfarin therapy were identified in the HealthCore Integrated Research Database and categorized into 3 groups: users of generic warfarin formulations from a single drug manufacturer (generic-only group), users of branded warfarin formulations only (brand-only group), and patients who used generic and branded warfarin therapy interchangeably or who may have used generic drugs from 1 or more manufacturers (generic/brand switching group). Patients were followed 12 months or longer after their index warfarin prescription date to compare all-cause resource use and costs using multivariable regression analysis.

Results:

The analysis included 12,908 patients: 71.82% were in the generic-only group, 9.61% were in the brand-only group, and 18.57% were in the generic/brand switching group. Patients in the generic/brand switching group were more likely to be hospitalized (relative risk [RR] = 1.43, p < 0.0001) or to use emergency department services (RR = 1.20, p < 0.01), compared to the brand-only users. Hospitalizations were more likely (RR = 1.26, p < 0.001) to occur among generic-only users versus brand-only users. Adjusted mean pharmacy costs per member per month were lower in the generic/brand switching group compared to the brand-only group ($257 vs $273, p = 0.038), but inpatient costs were higher ($1250 vs $972, p < 0.001), resulting in higher ($2125 vs $1847, p < 0.001) total costs. Generic-only users had lower pharmacy costs compared to brand-only users ($246 vs $273, p < 0.001), but total health care costs trended to be higher in the generic-only group ($1957 vs $1847, p = 0.053).

Conclusions:

The use of both generic and branded formulations of warfarin interchangeably, or the use of generics from more than 1 manufacturer, was associated with increased use of all-cause health care resources and total costs in patients with AF.
Understanding Pregnancy‐Related Attitudes and Behaviors: A Mixed‐Methods Study of Homeless Youth
Authors: Tucker Joan S. , Sussell Jesse , Golinelli Daniela , Zhou Annie , Kennedy David P. , Wenzel Suzanne L.
Published: November 2012

CONTEXT

Pregnancy rates are substantially higher among homeless youth than in the general population of youth, yet little is known about homeless adolescents’ and young adults’ pregnancy‐related attitudes and behaviors.

METHODS

Pregnancy‐related attitudes and behaviors were examined among two samples of sexually active homeless 13–24‐year‐olds in Los Angeles County. Data from 37 semistructured interviews conducted in March–April 2011 were analyzed using standard qualitative methods. Data from a structured survey with 277 respondents, conducted between October 2008 and August 2009, were analyzed primarily using regression modeling.

RESULTS

More than half of interview respondents held ambivalent attitudes toward pregnancy, and ambivalent youth reported less contraceptive use than others. The interviews identified several potential influences on pregnancy attitudes: barriers associated with homelessness, readiness to settle down, desire to achieve goals, belief that a child would create something positive in life, and family and partners. In the survey, having positive attitudes toward pregnancy was positively associated with duration of homelessness (odds ratio, 1.6), contact with relatives (1.1) and relationship commitment (1.8); it was negatively associated with frequency of drinking (0.9). Relationship commitment was positively associated with nonuse of an effective contraceptive method at last sex (1.5).

CONCLUSIONS

Effective and accessible pregnancy prevention and family planning programs for homeless youth are needed. Youths’ ambivalence toward pregnancy and feelings of relationship commitment warrant attention as possible areas for programs to address.
Phloroglucinol Protects Small Intestines of Mice from Ionizing Radiation by Regulating Apoptosis-Related Molecules
Authors: Ha Danbee , Bing So Jin , Cho Jinhee , Ahn Ginnae , Kim Dae Seung , Al-Amin Mohammad , Park Suk Jae , Jee Youngheun
Published: November 2012

Phloroglucinol (PG) is a phenolic compound isolated from Ecklonia cava, a brown algae abundant on Jeju island, Korea. Previous reports have suggested that PG exerts antioxidative and cytoprotective effects against oxidative stress. In this study, we confirmed that PG protected against small intestinal damage caused by ionizing radiation, and we investigated its protective mechanism in detail. Regeneration of intestinal crypts in the PG-treated irradiated group was significantly promoted compared with that in irradiated controls. The expression level of proapoptotic molecules such as p53, Bax, and Bak in the small intestine was downregulated and that of antiapoptotic molecules such as Bcl-2 and Bcl-XS/L was augmented in the PG-treated group. On histological observation of the small intestine, PG inhibited the immunoreactivity of p53, Bax, and Bak and increased that of Bcl-2 and Bcl-XS/L. These results demonstrate the protective mechanisms of PG in mice against intestinal damage from ionizing radiation, providing the benefit of raising the apoptosis threshold of jejunal crypt cells.
Relation between Ultrastructural Localization, Changes in Caveolin-1, and Capillarization of Liver Sinusoidal Endothelial Cells in Human Hepatitis C–Related Cirrhotic Liver
Authors: Yamazaki Hitoshi , Oda Masaya , Takahashi Yoshihito , Iguchi Hiroyoshi , Yoshimura Kazunori , Okada Nobuhiko , Yokomori Hiroaki
Published: November 2012

Most vascular endothelial cells are continuously exposed to shear stress in vivo. Caveolae are omega-shaped membrane invaginations in endothelial cells (ECs) and are enriched in cholesterol, caveolins, and signaling molecules. This study was designed to elucidate the ultrastructural localization and change in caveolin-1 expression within human liver sinusoidal endothelial cells (LSECs) during the progression of cirrhosis caused by hepatitis C, using tissue sections prepared via perfusion-fixation. Normal control liver specimens and hepatitis C–related Child-Pugh A and C cirrhotic liver specimens were studied. Caveolin-1 in the liver sinusoids was examined via immunohistochemistry, Western blotting, and immunoelectron microscopy. In control liver tissue, caveolin-1 was localized on caveolae mainly in arterial and portal endothelial cells of the portal tract and was also found on vesicles and some fenestrae in LSECs around the central vein. In cirrhotic liver tissue, aberrant caveolin-1 expression was observed on caveolae-like structures in LSECs. Caveolin-1 was especially overexpressed in late-stage cirrhosis. This study demonstrates that caveolin-1 is strongly expressed within caveolae-like structures and associated vesicles within LSECs of the hepatitis C–related cirrhotic liver. These findings suggest a direct association of caveolin-1 in the process of differentiation of LSECs in cirrhosis-mediated capillarization.
Translating Genomics to the Clinic: Implications of Cancer Heterogeneity
Authors: Samuel Nardin , Hudson Thomas J
Published: November 2012

BACKGROUND

Sequencing of cancer genomes has become a pivotal method for uncovering and understanding the deregulated cellular processes driving tumor initiation and progression. Whole-genome sequencing is evolving toward becoming less costly and more feasible on a large scale; consequently, thousands of tumors are being analyzed with these technologies. Interpreting these data in the context of tumor complexity poses a challenge for cancer genomics.

CONTENT

The sequencing of large numbers of tumors has revealed novel insights into oncogenic mechanisms. In particular, we highlight the remarkable insight into the pathogenesis of breast cancers that has been gained through comprehensive and integrated sequencing analysis. The analysis and interpretation of sequencing data, however, must be considered in the context of heterogeneity within and among tumor samples. Only by adequately accounting for the underlying complexity of cancer genomes will the potential of genome sequencing be understood and subsequently translated into improved management of patients.

The paradigm of personalized medicine holds promise if patient tumors are thoroughly studied as unique and heterogeneous entities and clinical decisions are made accordingly. Associated challenges will be ameliorated by continued collaborative efforts among research centers that coordinate the sharing of mutation, intervention, and outcomes data to assist in the interpretation of genomic data and to support clinical decision-making.
It's Time to Unify Telecommunications Policy
Authors: Macher Jeffrey T. , Mayo John W.
Published: November 2012

Rooted in 20th century legislation, telecommunications policy has historically been conducted in separate wired and wireless silos. The explosion of wireless voice, data and video communications, however, has largely overtaken wired communications, yet these silos persist. This article evaluates the economic foundation for unifying telecommunications policy.
The Effects of Supplemental Fish Oil on Blood Pressure and Morning Cortisol in Normotensive Adults: a Pilot Study
Authors: Noreen Eric E. , Brandauer Josef
Published: November 2012

PURPOSE: To determine the effects of 6wk of supplementation with fish oil (FO) on blood pressure and the morning salivary cortisol concentration in normotensive adults. METHODS: Testing was performed following an overnight fast. Subjects (n=40; 35+/-13y, mean+/-SD) rested supine for 40min, at which time blood pressure and heart rate were measured. Saliva was collected and analyzed for cortisol. Subjects were then randomly assigned to either: 4g/d of Safflower Oil (SO); or 4g/d of FO supplying 1,600mg/d eicosapentaenoic acid and 800mg/d docosahexaenoic acid. Testing was repeated following 6wk of treatment. RESULTS: Compared to SO, there was a significant decrease in systolic blood pressure with FO (SO=1.3+/-5.8 mmHg; FO=-6.8+/-10.2 mmHg; p=0.004), a significant reduction in pulse pressure (SO=0.2+/-7.8 mmHg; FO=-6.4+/-8.8 mmHg; p=0.02), and a tendency for a decrease in mean arterial pressure (SO=1.2+/-5.3 mmHg; FO=-2.5+/-7.3 mmHg; p=0.08). There was a tendency for salivary cortisol to decrease with FO (SO=0.005+/-0.129 µg/dL; FO=-0.068+/-0.148 µg/dL; p=0.072), however, this change was not significantly correlated with the change in systolic blood pressure (r=0.021, p=0.929). CONCLUSION: 6wk of supplementation with FO significantly decreases systolic blood pressure in normotensive adults and this change was not significantly correlated with a reduction in salivary cortisol.
Using Role Substitution To Address The Health Workforce Shortage And To Facilitate Integration?
Authors: Leach Matthew J.
Published: November 2012

The health workforce is perceived to be in short supply in most developed and developing countries. There are concerns that this could result in reduced coverage of health services and the delivery of suboptimal care. Strategies to address the health workforce shortage have focussed predominantly on recruitment and training, with relatively little regard to the equally important issue of retention. One approach that may improve job satisfaction, opportunities for specialisation and the workload of health workers, and thus, improve retention and more importantly, patient outcomes, is role substitution. Many complementary and alternative medicine (CAM) practitioners appear to be well placed in terms of educational preparation to substitute (either horizontally or vertically) a number of roles traditionally performed by conventional health disciplines. As well as the potential benefits to the health workforce and the quality of patient care, role substitution could provide an important first step toward integrating CAM practitioners into mainstream health care settings.
Effect of Smilax zeylanica roots and rhizomes in paracetamol induced hepatotoxicity
Authors: Murali Anita , Ashok Purnima , Madhavan V.
Published: November 2012

Context: Smilax zeylanica L.(Smilacaceae) is a climbing shrub with woody prickly stems. Objective: This study evaluated the hepatoprotective effect of S. zeylanica against paracetamol induced hepatotoxicity in Wistar rats. Materials and methods: The protective effects of the methanol extract (200 and 400 mg/kg) of root and rhizome of S. zeylanica were studied on paracetamol induced (1 g/kg) hepatic damage in Wistar rats by estimating the serum levels of AST, ALT, alkaline phosphatase (ALP), total proteins, total bilirubin and albumin. Sections of liver were observed for histopathological changes in liver architecture. Results: Rats were protected from the hepatotoxic action of paracetamol as evidenced by the significant reduction in the elevated serum levels of ALT (P<0.001), AST (P< 0.01, P< 0.001), ALP (P<0.05, P< 0.001), total bilirubin (P< 0.05) and an increased level of total protein (P< 0.05) and albumin (P< 0.05, P<0.01) with a significant reduction in liver weight (P<0.001), when compared with the paracetamol control. Silymarin (100 mg/kg) was used as the standard. Discussion and conclusion: The biochemical observations were supplemented by the histopathological studies on the liver sections of different groups. The methanol extract of S. zeylanica was found to alter the damage caused to hepatocytes by paracetamol and prevent the leakage of vital serum markers, which confirmed the hepatoprotective effect of this plant.
The Effects of a Motivational General-Mastery Imagery Intervention on the Imagery Ability and Sport Confidence of Inter-Collegiate Golfers
Authors: Hammond Thomas , Gregg Melanie , Hrycaiko Dennis , Mactavish Jennifer , Leslie-Toogood Adrienne
Published: November 2012

Motivational general-mastery imagery is described as imaging overcoming challenges in sport with confidence and control. Using a single-subject multiple baseline design three male inter-collegiate golfers completed the Motivational Imagery Ability Measure for Sport during baseline and post-intervention phases and completed the Competitive State Anxiety Inventory-2R prior to each competitive round. Golf scores were recorded at the conclusion of each competition. Participants engaged in six sessions of guided motivational general-mastery imagery training over a three-week period. The sport confidence of one participant significantly increased from baseline to intervention. Golf performance (measured by stroke average) of two participants improved. All participants showed improvement in their ability to use imagery and indicated the imagery training program was effective.
Mental Practice is Modifiable: Changes in Perspective Maintenance and Vividness Post-Stroke
Authors: Nobbe, MA Joanna A. , Nilsen, Ed.D., OTL Dawn , Gillen, Ed.D., OTR Glen
Published: November 2012

This exploratory study investigated effects of a mental practice (MP) intervention on imagery vividness and perspective maintenance in post-stroke subjects. Additionally, the relationship between internal and external imagery vividness and kinesthetic imagery was examined. Data were drawn from 17 persons participating in a RCT investigating the effects of perspective use during MP on post-stroke recovery. The Vividness of Movement Imagery Questionnaire-2 (VMIQ-2) and a self-report perspective rating scale were used to examine changes in vividness and perspective maintenance, respectively. Findings indicate improvements in vividness were most evident in those with the weakest initial ability. Perspective maintenance improved significantly from the first score to the last for all groups. Visual imagery vividness was strongly related to kinesthetic imagery regardless of imagery perspective. Preliminary findings suggest certain aspects of imagery ability can be improved with practice post-stroke.
Imagery and Endurance: Does Imagery Impair Performance by Depleting Self-Control Strength?
Authors: Graham Jeffrey D. , Bray Steven R.
Published: November 2012

Although mental imagery has been shown to have beneficial effects on performance, imagery has been shown to negatively affect physical performances under some conditions. The limited strength model of self-regulation posits that self-control strength is depleted when people regulate their thoughts, impulses, emotions, and behaviours. Research shows depletion of self-control strength in one task domain (e.g., controlling thoughts or images) leads to poorer self-control within similar and dissimilar domains (e.g., controlling physical endurance). The purpose of the present study was to investigate the aftereffects of performing mental imagery on two self-control tasks, physical endurance and response inhibition. Sedentary undergraduates (N = 37) were randomly assigned to either an imagery condition (n = 15), attention-placebo condition (n = 13), or a quiet rest control (n = 9). Participants performed two isometric endurance tasks (30% of maximum handgrip squeeze) separated by their respective study manipulation, and followed by the Wisconsin Card Sort Test (WCST). It was expected that participants in the mental imagery condition would show greater decrements in performance on the second endurance trial (when compared to baseline) and more perseverative errors on the WCST compared to the control conditions. All of the participants’ endurance performances declined over time (p < .05), however, no between group differences were found on endurance performances (p > .05) or on WCST scores (p > .05). Performing a basic 6 minute imagery session involving moderately-intense aerobic exercise does not appear to deplete self-control resources when compared to the attention-placebo and quiet rest control groups. However, the unanticipated decline in the endurance performances observed within the control conditions suggests that future research is needed to better understand the relationship between mental imagery and self-control depletion effects.
Therapeutic Equivalence and the Generic Competition Paradox
Authors: Nabin Munirul Haque , Mohan Vijay , Nicholas Aaron , Sgro Pasquale M.
Published: November 2012

Following the passage of the Waxman-Hatch Act (1984), FDA approval for a generic drug requires the establishment of bio-equivalence between the generic drug and an FDA approved branded drug. However, a large body of evidence in the medical community suggests that bio-equivalence does not guarantee therapeutic equivalence; in some instances the lack of therapeutic equivalence can lead to fatal consequences for patients switching to generic products. In this paper, we construct a simple model to analyze the implications of therapeutic non-equivalence between branded and generic drugs. We show, theoretically and empirically, that this distinction can provide a plausible explanation of the generic competition paradox.
Estimating Trends in Incidence, Time-to-Diagnosis and Undiagnosed Prevalence using a CD4-based Bayesian Back-calculation
Authors: Birrell Paul J. , Chadborn Tim R. , Gill O. Noel , Delpech Valerie C. , De Angelis Daniela
Published: November 2012

There has been much recent speculation regarding the potential for HIV test-and-treat strategies to provide control of the HIV endemic. In the UK, despite advanced HIV surveillance and the implementation of a number of testing initiatives and attempts to widen access to antiretroviral drugs, the number of new diagnoses persists at a high level having risen considerably over the course of the last ten years. The extent to which this high level of diagnosis is attributable to levels of HIV transmission or improved rates of testing and diagnosis is unclear. To disentangle these competing factors, we use a Bayesian back-calculation based on HIV and AIDS diagnosis data augmented by observed CD4 count levels at diagnosis. The CD4 count acts as a prognostic marker indicative of the time-since-infection for any new diagnosis. In addition to estimating time-dependent rates of infection and diagnosis, we exploit the model structure to estimate posterior distributions for a number of key epidemiological quantities such as trends in the time-to-diagnosis and the time-since infection distributions as well as the prevalence of undiagnosed infection. These quantities are stratified by CD4 count where possible. The proposed methodology is applied to HIV/AIDS surveillance data from England & Wales uncovering a decreasing trend in the time to diagnosis and stable levels of incidence in recent years.
Contributions of CCLM to advances in quality control
Authors: Kazmierczak Steven C.
Published: November 2012

The discipline of laboratory medicine is relatively young when considered in the context of the history of medicine itself. The history of quality control, within the context of laboratory medicine, also enjoys a relatively brief, but rich history. Laboratory quality control continues to evolve along with advances in automation, measurement techniques and information technology.Clinical Chemistry and Laboratory Medicine(CCLM) has played a key role in helping disseminate information about the proper use and utility of quality control. Publication of important advances in quality control techniques and dissemination of guidelines concerned with laboratory quality control has undoubtedly helped readers of this journal keep up to date on the most recent developments in this field.
In silico pharmacology for a multidisciplinary drug discovery process
Authors: Ortega Santiago Schiaffino , Cara Luisa Carlota López , Salvador María Kimatrai
Published: November 2012

The process of bringing new and innovative drugs, from conception and synthesis through to approval on the market can take the pharmaceutical industry 8–15 years and cost approximately $1.8 billion. Two key technologies are improving the hit-to-drug timeline: high-throughput screening (HTS) and rational drug design. In the latter case, starting from some known ligand-based or target-based information, a lead structure will be rationally designed to be tested in vitro or in vivo. Computational methods are part of many drug discovery programs, including the assessment of ADME (absorption-distribution-metabolism-excretion) and toxicity (ADMET) properties of compounds at the early stages of discovery/development with impressive results. The aim of this paper is to review, in a simple way, some of the most popular strategies used by modelers and some successful applications on computational chemistry to raise awareness of its importance and potential for an actual multidisciplinary drug discovery process.
Interactions between BdkrB2 and p53 genes in the developing kidney
Authors: El-Dahr Samir S. , Saifudeen Zubaida
Published: November 2012

Gene-environment interactions are implicated in congenital disorders. Accordingly, there is a pressing need to develop animal models of human disease, which are the product of defined gene-environment interactions. Work from our laboratory demonstrates the presence of genetic interactions between the bradykinin B2 receptor (BdkrB2) and the tumor suppressor protein p53 in the developing kidney. Our studies have shown that the Bdkrb2

-/-
embryos exposed to gestational salt stress develop renal dysgenesis. The underlying mechanism is p53 stabilization and mediated apoptosis and repression of the terminal epithelial differentiation program. We also uncovered a novel functional cross-talk between p53 and BdkrB2. Thus, while BdkrB2 is a target for p53-mediated transcriptional activation, BdkrB2 inactivation results in the upregulation of checkpoint kinase 1 (Chk1) levels, thus potentiating phosphorylation of p53 on Ser23 by Chk1, an essential step in the pathway leading to renal dysgenesis in salt-stressed BdkrB2

-/-
mutant mice. Future studies will now focus on defining how this G-protein-coupled receptor is coupled to the activation of p53, a tumor suppressor gene that is mutated in more than 50% of all human cancers.
High-Temperature Oxidation Behavior and Formation Mechanism of Rolling Cracks of Fe-36Ni Invar Alloy
Authors: Yu Yan-chong , Chen Wei-qing , Zheng Hong-guang
Published: November 2012

The oxidation of Fe-36Ni invar alloy in 5%O2-15%CO2-80%N2 atmosphere at 1200 °C for 4 h and the cause of rolling cracks have been investigated using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and Gleeble thermal simulation machine. The result showed that the scales consisted of the external scale and the subscale. The external scale had stratified structures of Fe2O3/Fe3O4 + NiO/Fe3O4 + FeO + NiO from outside to inside. The subscale had a typical substructure of the intra-granular subscale and the inter-granular subscale. Oxidation particles of (Fe3O4 + FeO) were isolated in FeNi3 matrix in the intra-granular subscale zone. The grain boundary was the preferential short-circuit diffusion paths of the diffusing O and was first to be oxidized. The inter-granular subscale led to the subscale and was the origin of rolling cracks. The protective heating measure was put forward to prevent rolling cracks.
Prime-Perfect Numbers
Authors: Pollack Paul , Pomerance Carl
Published: November 2012

We discuss a relative of the perfect numbers for which it is possible to prove that there are infinitely many examples. Call a natural number

as

We conclude by discussing some related problems posed by Harborth and Cohen.
Detection of chemical pollutants in water using gold nanoparticles as sensors: a review
Authors: Wang Chao , Yu Chenxu
Published: November 2012

Rapid and accurate evaluation of pollutant contamination in water is one of the key tasks of environmental monitoring. To make onsite assessment feasible, the analytical tools should be easy to operate, with minimal sample preparation needs. Gold nanoparticle (AuNP)-based sensors have the potential to detect toxins, heavy metals, and inorganic and organic pollutants in water rapidly with high sensitivity, and they are expected to play an increasingly important role in environmental monitoring. In this article, the synthesis, fabrication and functionalization of AuNPs are discussed, and the recent advances in the development and application of AuNP-based sensors for the determination of various pollutants contamination in water are reviewed.