bluuebunny/crossref_metadata_2025 huggingface dataset:
Interspinous Spacer Implant in Patients with Lumbar Spinal Stenosis: Preliminary Results of a Multicenter, Randomized, Controlled Trial
Authors: Miller Larry E. , Block Jon E.
Published: February 2012

A prospective, randomized, controlled trial was conducted to compare clinical outcomes in patients treated with an investigational interspinous spacer (Superion) versus those treated with an FDA-approved spacer (X-STOP). One hundred sixty-six patients with moderate lumbar spinal stenosis (LSS) unresponsive to conservative care were treated randomly with the Superion (n=80) or X-STOP (n=86) interspinous spacer. Study subjects were followed through 6 months posttreatment. Zurich Claudication Questionnaire (ZCQ) symptom severity scores improved 30% with Superion and 25% with X-STOP (both P<0.001). Similar changes were noted in ZCQ physical function with improvements of 32% with Superion and 27% with X-STOP (both P<0.001). Mean ZCQ patient satisfaction score ranged from 1.7 to 2.0 in both groups at all follow-up visits. The proportion of subjects that achieved at least two of three ZCQ clinical success criteria at 6 months was 75% with Superion and 67% with X-STOP. Axial pain decreased from 55±27 mm at pretreatment to 22±26 mm at 6 months in the Superion group (P<0.001) and from 54±29 mm to 32±31 mm with X-STOP (P<0.001). Extremity pain decreased from 61±26 mm at pretreatment to 18±27 mm at 6 months in the Superion group (P<0.001) and from 64±26 mm to 22±30 mm with X-STOP (P<0.001). Back function improved from 38±13% to 21±19% with Superion (P<0.001) and from 40±13% to 25±16% with X-STOP (P<0.001). Preliminary results suggest that the Superion interspinous spacer and the X-STOP each effectively alleviate pain and improve back function in patients with moderate LSS who are unresponsive to conservative care.
Solving the Short‐Term Scheduling Problem of Hydrothermal Systems via Lagrangian Relaxation and Augmented Lagrangian
Authors: Rodrigues Rafael N. , da Silva Edson L. , Finardi Erlon C. , Takigawa Fabricio Y. K.
Published: February 2012

This paper addresses the short‐term scheduling problem of hydrothermal power systems, which results in a large‐scale mixed‐integer nonlinear programming problem. The objective consists in minimizing the operation cost over a two‐day horizon with a one‐hour time resolution. To solve this difficult problem, a Lagrangian Relaxation (LR) based on variable splitting is designed where the resulting dual problem is solved by a Bundle method. Given that the LR usually fails to find a feasible solution, we use an inexact Augmented Lagrangian method to improve the quality of the solution supplied by the LR. We assess our approach by using a real‐life hydrothermal configuration extracted from the Brazilian power system, proving the conceptual and practical feasibility of the proposed algorithm. In summary, the main contributions of this paper are (i) a detailed and compatible modelling for this problem is presented; (ii) in order to solve efficiently the entire problem, a suitable decomposition strategy is presented. As a result of these contributions, the proposed model is able to find practical solutions with moderate computational burden, which is absolutely necessary in the modern power industry.
Rapamycin Resistance Is Linked to Defective Regulation of Skp2
Authors: Totary-Jain Hana , Sanoudou Despina , Dautriche Cula N. , Schneller Hillary , Zambrana Lester , Marks Andrew R.
Published: February 2012

The mammalian target of rapamycin (mTOR) plays a role in controlling malignant cellular growth. mTOR inhibitors, including rapamycin (sirolimus), are currently being evaluated in cancer trials. However, a significant number of tumors are rapamycin resistant. In this study, we report that the ability of rapamycin to downregulate Skp2, a subunit of the ubiquitin protein ligase complex, identifies tumors that are sensitive to rapamycin. RNA interference (RNAi)–mediated silencing of Skp2 in human tumor cells increased their sensitivity to rapamycin in vitro and inhibited the growth of tumor xenografts in vivo. Our findings suggest that Skp2 levels are a key determinant of antitumor responses to mTOR inhibitors, highlighting a potentially important pharmacogenomic marker to predict sensitivity to rapamycin as well as Skp2 silencing strategies for therapeutic purposes. Cancer Res; 72(7); 1836–43. ©2012 AACR.
Dissection of T-cell Antigen Specificity in Human Melanoma
Authors: Andersen Rikke Sick , Thrue Charlotte Albæk , Junker Niels , Lyngaa Rikke , Donia Marco , Ellebæk Eva , Svane Inge Marie , Schumacher Ton N. , thor Straten Per , Hadrup Sine Reker
Published: February 2012

Tumor-infiltrating lymphocytes (TIL) isolated from melanoma patients and expanded in vitro by interleukin (IL)-2 treatment can elicit therapeutic response after adoptive transfer, but the antigen specificities of the T cells transferred have not been determined. By compiling all known melanoma-associated antigens and applying a novel technology for high-throughput analysis of T-cell responses, we dissected the composition of melanoma-restricted T-cell responses in 63 TIL cultures. T-cell reactivity screens against 175 melanoma-associated epitopes detected 90 responses against 18 different epitopes predominantly from differentiation and cancer-testis antigens. Notably, the majority of these responses were of low frequency and tumor-specific T-cell frequencies decreased during rapid expansion. A further notable observation was a large variation in the T-cell specificities detected in cultures established from different fragments of resected melanoma lesions. In summary, our findings provide an initial definition of T-cell populations contributing to tumor recognition in TILs although the specificity of many tumor-reactive TILs remains undefined. Cancer Res; 72(7); 1642–50. ©2012 AACR.
Estimating Causal Effects of Genetic Risk Variants for Breast Cancer Using Marker Data from Bilateral and Familial Cases
Authors: Dudbridge Frank , Fletcher Olivia , Walker Kate , Johnson Nichola , Orr Nick , dos Santos Silva Isabel , Peto Julian
Published: February 2012

Background: Cases with a family history are enriched for genetic risk variants, and the power of association studies can be improved by selecting cases with a family history of disease. However, in recent genome-wide association scans utilizing familial sampling, the excess relative risk for familial cases is less than predicted when compared with unselected cases. This can be explained by incomplete linkage disequilibrium between the tested marker and the underlying causal variant.

Methods: We show that the allele frequency and effect size of the underlying causal variant can be estimated by combining marker data from studies that ascertain cases based on different family histories. This allows us to learn about the genetic architecture of a complex trait, without having identified any causal variants. We consider several validated common marker alleles for breast cancer, using our own study of high risk, predominantly bilateral cases, cases preferentially selected to have at least two affected first- or second-degree relatives, and published estimates of relative risk from standard case–control studies.

Results: To obtain realistic estimates and to accommodate some prior beliefs, we use Bayesian estimation to infer that the causal variants are probably common, with minor allele frequency >5%, and have small effects, with relative risk around 1.2.

Conclusion: These results strongly support the common disease common variant hypothesis for these specific loci associated with breast cancer.

Impact: Our results agree with recent assertions that synthetic associations of rare variants are unlikely to account for most associations seen in genome-wide studies. Cancer Epidemiol Biomarkers Prev; 21(2); 262–72. ©2011 AACR.
The Impact of Obesity on Follow-Up after an Abnormal Screening Mammogram
Authors: Schur Ellen A. , Elmore Joann E. , Onega Tracy , Wernli Karen J. , Sickles Edward A. , Haneuse Sebastien
Published: February 2012

Background: Effective breast cancer screening and early detection are crucial for obese women, who experience a higher incidence of the disease and present at later stages.

Methods: We examined the association between body mass index (BMI) and timeliness of follow-up after 241,222 abnormal screening mammograms carried out on 201,470 women in the Breast Cancer Surveillance Consortium. Each mammogram had one of three recommendations for follow-up: short-interval follow-up, immediate additional diagnostic imaging, and biopsy/surgical consultation. We used logistic regression to estimate the adjusted effect of BMI on any recorded follow-up within 270 days of the recommendation; linear regression was used to model the mean follow-up time among those with recorded follow-up.

Results: As compared with normal-weight women, higher BMI was associated with slightly increased odds of follow-up among women who received a recommendation for short-interval follow-up (ORs: 1.03–1.10; P = 0.04) or immediate additional imaging (ORs: 1.03–1.09; P = 0.01). No association was found for biopsy/surgical consultation recommendations (P = 0.90). Among those with recorded follow-up, higher BMI was associated with longer mean time to follow-up for both short-interval (3–10 days; P < 0.001) and additional imaging recommendations (2–3 days; P < 0.001) but not biopsy/surgical consultation (P = 0.06). Regardless of statistical significance, actual differences in days to follow-up across BMI groups were small and unlikely to be clinically significant.

Conclusions: Once obese women access screening mammography, their follow-up after abnormal results is similar to that of normal-weight women.

Impact: Efforts to improve early detection of breast cancer in obese women should focus elsewhere, such as improving participation in screening mammography. Cancer Epidemiol Biomarkers Prev; 21(2); 327–36. ©2011 AACR.
Use of Metformin Is Not Associated with a Decreased Risk of Colorectal Cancer: A Case–Control Analysis
Authors: Bodmer Michael , Becker Claudia , Meier Christian , Jick Susan S. , Meier Christoph R.
Published: February 2012

Background: To explore the association between use of metformin or other antidiabetic drugs and the risk of colorectal cancer.

Methods: Using the United Kingdom–based General Practice Research Database (GPRD), we conducted a nested case–control analysis in patients with diabetes mellitus. Cases had an incident diagnosis of colorectal cancer, and up to 6 controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the GPRD prior to the index date. Results were adjusted for multiple potential confounders.

Results: We identified 920 diabetic patients with colorectal cancer. Mean age ± SD was 70.2 ± 8.6 years and 63.3% were male. Extensive use (≥50 prescriptions) of metformin was associated with a slightly increased risk of colorectal cancer (adjusted OR = 1.43, 95% CI: 1.08–1.90) as compared with non use, with an adjustment of OR = 1.81 (95% CI: 1.25–2.62) in men and of 1.00 (95% CI: 0.63–1.58) in women. Neither extensive use of sulfonylureas (adjusted OR = 0.79, 95% CI: 0.60–1.03) nor insulin (adjusted OR = 0.90, 95% CI: 0.63–1.28) were associated with an increased risk of colorectal cancer. A long-term history of diabetes (>10 years) was not associated with a materially increased risk of colorectal cancer compared with short-term diabetes duration (<2 years; adjusted OR = 1.14, 95% CI: 0.90–1.46).

Conclusion: Use of metformin was linked to an increased risk of colorectal cancer in men. Use of sulfonylureas or insulin was not associated with an altered risk of colorectal cancer.

Impact: Metformin does not prevent colorectal cancer. Cancer Epidemiol Biomarkers Prev; 21(2); 280–6. ©2011 AACR.
Infusion of a Lipid Emulsion in Healthy Men Decreases the Serotonergic Response
Authors: Sondermeijer Brigitte M. , Klein Twennaar Christian F. , Kastelein John J.P. , Franssen Eric J.F. , Hutten Barbara A. , Dallinga-Thie Geesje M. , Stroes Erik S.G. , Fliers Eric , Twickler Marcel T.B. , Serlie Mireille J.
Published: February 2012

Subjects with obesity and insulin resistance display a low response to a serotonergic challenge test. One of the hallmarks of obesity and insulin resistance is elevated plasma free fatty acids (FFAs). We hypothesize that increasing plasma FFA by infusion of a lipid emulsion, may be a contributing component leading to decreased serotonergic responsivity in healthy young men. Ten lean healthy men, 23.6 ± 5.0 years and BMI 22.6 ± 1.9 kg/m2, were included. Serotonergic responsivity was assessed using the prolactin response to infusion with citalopram, a selective serotonin reuptake inhibitor, which is a validated tool to assess serotonergic tone. All participants received a lipid/heparin emulsion (Intralipid) infusion during 6 h. Saline infusion was used as a control. To evaluate a possible effect of heparin per se on prolactin, four out of the ten subjects also received heparin only during 6 h without the serotonergic challenge test. Plasma prolactin increased by 74.3 ± 15.5% during saline infusion. Intralipid infusion increased plasma FFA from 0.5 ± 0.05 to 2.3 ± 0.2 mmol/l (p < 0.001). The increase in plasma prolactin during Intralipid infusion was significantly lower (39.3 ± 10%; p < 0.001 compared to saline infusion). Heparin infusion per se increased plasma prolactin by 14.0 ± 1.9%. We found that during the Intralipid infusion with concomitant high plasma FFA levels the serotonergic response was decreased in healthy young men. Higher FFA levels may be the mediator of the decreased serotonergic response reported in patients with insulin resistance and obesity.
Involvement of α2-Adrenoceptor Subtypes A and C in Glucose Homeostasis and Adrenaline-Induced Hyperglycaemia
Authors: Ruohonen Suvi T. , Ruohonen Saku , Gilsbach Ralf , Savontaus Eriika , Scheinin Mika , Hein Lutz
Published: February 2012

Background and Aims: Insulin secretion is controlled by pancreatic α2A-adrenoceptors. Mice lacking α2A-adrenoceptors (α2AAR–/– mice) show hyperinsulinaemia, reduced blood glucose levels and improved glucose tolerance. Methods: In the present study, we used α2ACAR–/–, α2CAR–/– and α2AAR–/– mice and a mouse line with adrenergic cell-specific expression of α2A-adrenoceptors (lacking these receptors in non-adrenergic cells), and their wild-type (WT) controls, to assess the glucoregulatory role of the α2C-adrenoceptor subtype in vivo. Glucose and insulin tolerance tests were performed and blood glucose and serum insulin levels were determined after fasting and glucose stimulation. Plasma catecholamines were also measured. In addition, the effect of pretreatment with (±)-propranolol was determined in α2CAR–/– mice. Results: α2ACAR–/– mice had a similar glucose and insulin phenotype as α2AAR–/– mice and mice with restored α2A-autoreceptors, suggesting that only deletion of postsynaptic α2A-adrenoceptors has major effects on glucose disposition. However, α2ACAR–/– mice were more sensitive to the glucose-lowering effect of insulin than WT mice. This was not observed in α2AAR–/– mice. The α2CAR–/– mice showed impaired glucose tolerance that was reversed by pretreatment with (±)-propranolol. No difference in insulin secretion was observed in α2CAR–/– mice compared with WT animals. Conclusion: The results underline that depletion of postsynaptic pancreatic α2A-adrenoceptors has major effects on the regulation of glucose homeostasis in α2ACAR–/– and α2AAR–/– mice. Deletion of the α2C subtype leads to increased adrenaline secretion and has the potential to increase blood glucose levels via enhanced glycogenolysis.
Prevalence of Urinary Tract Infections and Its Risk Factors in Elementary School Students
Authors: Zincir Handan , Kaya Erten Zeliha , Özkan Filiz , Seviğ Ümit , Başer Mürüvvet , Elmalı Ferhan
Published: February 2012

Background: Childhood urinary tract infections (UTI) are one of the most important factors affecting adult health. Aim: The study was a cross-sectional investigation to identify the prevalence of UTI and its risk factors. Methods: The study included 2,511 6–8th grade elementary school students. Data were collected by questionnaire form and medical diagnosis. Descriptive statistics and logistic regression analyses were performed. Results: 7.1% of all participating students had UTI (10.1% girls, 4.2% boys). Students with a family history of UTI had a 3.763-fold risk of developing UTI (p < 0.05) compared to those without. Students who drank <1 liter of water daily had a 1.077 times higher risk of having the infection than those who drank >1 liter of water daily (p < 0.05). Conclusion: Students drinking an inadequate amount of water and having a family history had a high prevalence of UTI.
Suboptimal Inhibition of Platelet Cyclooxygenase-1 by Aspirin in Metabolic Syndrome
Authors: Smith James P. , Haddad Elias V. , Taylor Mary B. , Oram Denise , Blakemore Dana , Chen Qingxia , Boutaud Olivier , Oates John A.
Published: February 2012

Interindividual variation in the ability of aspirin to inhibit platelet cyclooxygenase-1 (COX-1) could account for some on-treatment cardiovascular events. Here, we sought to determine whether there are clinical phenotypes that are associated with a suboptimal pharmacological effect of aspirin. In a prospective, 2-week study, we evaluated the effect of aspirin (81 mg) on platelet COX-1 in 135 patients with stable coronary artery disease by measuring serum thromboxane B
2
(sTxB
2
) as an indicator of inhibition of platelet COX-1. A nested randomized study compared enteric-coated with immediate-release formulations of aspirin. We found that sTxB
2
was systematically higher among the 83 patients with metabolic syndrome than among the 52 patients without (median: 4.0 versus 3.02 ng/mL;
P
=0.013). Twelve patients (14%) with metabolic syndrome, but none without metabolic syndrome, had sTxB
2
levels consistent with inadequate inhibition of COX (sTxB
2
≥13 ng/mL). In linear regression models, metabolic syndrome (but none of its individual components) significantly associated with higher levels of log-transformed sTxB
2
(
P
=0.006). Higher levels of sTxB
2
associated with greater residual platelet function measured by aggregometry-based methods. Among the randomized subset, sTxB
2
levels were systematically higher among patients receiving enteric-coated aspirin. Last, urinary 11-dehydro thromboxane B
2
did not correlate with sTxB
2
, suggesting that the former should not be used to quantitate aspirin's pharmacological effect on platelets. In conclusion, metabolic syndrome, which places patients at high risk for thrombotic cardiovascular events, strongly and uniquely associates with less effective inhibition of platelet COX-1 by aspirin.
Gender-Specific Differences in Myocardial Deformation and Aortic Stiffness at Rest and Dobutamine Stress
Authors: Puntmann Valentina O. , Nagel Eike , Hughes Alun D. , Gebker Rolf , Gaddum Nicholas , Chowienczyk Phil , Jahnke Cosima , Mirelis Jesus , Schnackenburg Bernhard , Paetsch Ingo , Fleck Eckart
Published: February 2012

Elderly women have increased aortic and ventricular stiffness but preserved global systolic function. Possible gender differences in ventricular deformation attributed to increased aortic stiffness at rest or with positive inotropic stress remain unknown. Eighty-four subjects (mean age: 63±8 years) were assessed for aortic stiffness by pulse wave velocity and ventricular deformation at rest and during dobutamine stress using magnetic resonance. At rest, women (n=40) had greater aortic stiffness and ventricular deformation than men (
P
<0.05). In men, dobutamine increased longitudinal (mean±SD: 3.3±4.1%;
P
<0.01) and circumferential deformation (2.9±5.1%;
P
=0.007), whereas women showed an increase in circumferential deformation only (4.8±6.3%;
P
<0.01). In men there was an inverse association between longitudinal deformation and pulse wave velocity at rest (
r
=−0.51;
P
=0.002) and linear at stress (
r
=0.52;
P
=0.001). In women there were no significant relations at rest, whereas at stress longitudinal deformation was inversely associated with pulse wave velocity (
r
=−0.43;
P
=0.02). We demonstrate gender-specific differences in the relationship between aortic stiffness and ventricular deformation at rest and during dobutamine stress. Although at rest longitudinal deformation is inversely related to aortic stiffness in men, there is no such relationship in women. At stress, men improve longitudinal function, whereas in women such response is limited.
"GOLD or lower limit of normal definition? a comparison with expert-based diagnosis of chronic obstructive pulmonary disease in a prospective cohort-study"
Authors: Güder Gülmisal , Brenner Susanne , Angermann Christiane E , Ertl Georg , Held Matthias , Sachs Alfred P , Lammers Jan-Willem , Zanen Pieter , Hoes Arno W , Störk Stefan , Rutten Frans H
Published: February 2012

Background

The Global initiative for chronic Obstructive Lung Disease (GOLD) defines COPD as a fixed post-bronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below 0.7. Age-dependent cut-off values below the lower fifth percentile (LLN) of this ratio derived from the general population have been proposed as an alternative. We wanted to assess the diagnostic accuracy and prognostic capability of the GOLD and LLN definition when compared to an expert-based diagnosis.

Methods

In a prospective cohort study, 405 patients aged ≥ 65 years with a general practitioner's diagnosis of COPD were recruited and followed up for 4.5 (median; quartiles 3.9; 5.1) years. Prevalence rates of COPD according to GOLD and three LLN definitions and diagnostic performance measurements were calculated. The reference standard was the diagnosis of COPD of an expert panel that used all available diagnostic information, including spirometry and bodyplethysmography.

Results

Compared to the expert panel diagnosis, 'GOLD-COPD' misclassified 69 (28%) patients, and the three LLNs misclassified 114 (46%), 96 (39%), and 98 (40%) patients, respectively. The GOLD classification led to more false positives, the LLNs to more false negative diagnoses. The main predictors beyond the FEV1/FVC ratio for an expert diagnosis of COPD were the FEV1 % predicted, and the residual volume/total lung capacity ratio (RV/TLC). Adding FEV1 and RV/TLC to GOLD or LLN improved the diagnostic accuracy, resulting in a significant reduction of up to 50% of the number of misdiagnoses. The expert diagnosis of COPD better predicts exacerbations, hospitalizations and mortality than GOLD or LLN.

Conclusions

GOLD criteria over-diagnose COPD, while LLN definitions under-diagnose COPD in elderly patients as compared to an expert panel diagnosis. Incorporating FEV1 and RV/TLC into the GOLD-COPD or LLN-based definition brings both definitions closer to expert panel diagnosis of COPD, and to daily clinical practice.
Developing community-based preventive interventions in Hong Kong: a description of the first phase of the family project
Authors: Stewart Sunita M , Fabrizio Cecilia S , Hirschmann Malia R , Lam Tai Hing
Published: February 2012

Background

This paper describes the development of culturally-appropriate family-based interventions and their relevant measures, to promote family health, happiness and harmony in Hong Kong. Programs were developed in the community, using a collaborative approach with community partners. The development process, challenges, and the lessons learned are described. This experience may be of interest to the scientific community as there is little information currently available about community-based development of brief interventions with local validity in cultures outside the West.

Methods

The academic-community collaborative team each brought strengths to the development process and determined the targets for intervention (parent-child relationships). Information from expert advisors and stakeholder discussion groups was collected and utilized to define the sources of stress in parent-child relationships.

Results

Themes emerged from the literature and discussion groups that guided the content of the intervention. Projects emphasized features that were appropriate for this cultural group and promoted potential for sustainability, so that the programs might eventually be implemented at a population-wide level. Challenges included ensuring local direction, relevance and acceptability for the intervention content, engaging participants and enhancing motivation to make behavior changes after a brief program, measurement of behavior changes, and developing an equal partner relationship between academic and community staff.

Conclusions

This work has public health significance because of the global importance of parent-child relationships as a risk-factor for many outcomes in adulthood, the need to develop interventions with strong evidence of effectiveness to populations outside the West, the potential application of our interventions to universal populations, and characteristics of the interventions that promote dissemination, including minimal additional costs for delivery by community agencies, and high acceptability to participants.
Systemic air embolism during percutaneous core needle biopsy of the lung: frequency and risk factors
Authors: Freund Martin C , Petersen Johannes , Goder Katharina C , Bunse Tillmann , Wiedermann Franz , Glodny Bernhard
Published: February 2012

Background

Detection of risk factors for an air embolism in the left atrium, left ventricle, or systemic circulation (systemic air embolism, SAE) during a percutaneous core needle biopsy (PCNB) of the thorax.

Methods

In a retrospective observational study, all PCNBs of the thorax in 610 patients between 2007 and 2009 were analyzed. The SmartStep™ technique (General Electric) was used for the biopsy, with which the examiner can prepare a batch of three 1.25-mm or 2.5-mm collimated slices within a second using a foot switch in the CT room to check the needle position. The image data thus generated and the control CT scans that followed were examined retrospectively for the presence of intravascular air. Intravascular air was defined as two or more adjacent voxels with absorption values of < -200 HU in the left atrium, left ventricle, aorta, or arteries during or after the procedure. The univariate statistical analysis of categorical variables was made using 2 by 2 tables and the Fisher test. The groups were compared using the Mann-Whitney test. Finally, a multivariate logistic regression analysis was used to identify independent risk factors for the occurrence of an SAE.

Results

The radiological incidence of an SAE during a PCNB was 3.8% (23/610 patients), whereas the clinically apparent incidence was 0.49%. Two patients developed clinical symptoms consisting of transient hemiplegia or transient amaurosis; one died due to a fatal SAE of the coronary arteries. The mortality was thus 0.16%. The depth of the needle in the lesion (Wald: 6.859), endotracheal anesthesia (Wald: 5.721), location of the lesion above the level of the left atrium (Wald: 5.159), and prone position of the patients (Wald: 4.317) were independent risk factors for the incidence of an SAE (p < 0.05 each). Using explorative criteria, the acute angle of the needle to the tumor surface, and the transition of ventilated lung were independent factors. The frequency of biopsies, needle penetration depth, and tumor location near the diaphragm or in the lower lobe also played a subordinate role, not however, the needle penetration depth through the lung.

Conclusion

If possible, the PCNB should be performed under local anesthesia. We recommend avoiding endotracheal anesthesia and prone position. Whenever possible, patients should be positioned on the back in such a way that the tumor is lower than the left atrium. The tip of the needle should be within the tumor during the biopsy procedure.
Radiographic knee osteoarthritis in ex-elite table tennis players
Authors: Rajabi Reza , Johnson Gillian M , Alizadeh Mohammad H , Meghdadi Nazanin
Published: February 2012

Background

Table tennis involves adoption of the semi-flexed knee and asymmetrical torsional trunk movements creating rotational torques on the knee joint which may predispose players to osteoarthritis (OA) of the knee. This study aims to compare radiographic signs of knee OA and associated functional levels in ex-elite male table tennis players and control subjects.

Methods

Study participants were 22 ex-elite male table tennis players (mean age 56.64 ± 5.17 years) with 10 years of involvement at the professional level and 22 non-athletic males (mean age 55.63 ± 4.08 years) recruited from the general population. A set of three radiographs taken from each knee were evaluated by an experienced radiologist using the Kellgren and Lawrence (KL) scale (0-4) to determine radiographic levels of OA severity. The intercondylar distance was taken as a measure of lower limb angulation. Participants also completed the pain, stiffness, and physical function categories of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) 3.1 questionnaire.

Results

The results showed 78.3% of the ex-elite table tennis players and 36.3% of controls had varying signs of radiographic knee OA with a significant difference in the prevalence levels of definite radiographic OA (KL scale > 2) found between the two groups (P ≤ 0.001). Based on the WOMAC scores, 68.2% of the ex-elite table tennis players reported symptoms of knee pain compared with 27.3% of the controls (p = 0.02) though no significant differences were identified in the mean physical function or stiffness scores between the two groups. In terms of knee alignment, 73.7% of the ex-elite athletes and 32% of the control group had signs of altered lower limb alignment (genu varum) (p = 0.01). Statistical differences were found in subjects categorized as having radiographic signs of OA and altered lower limb alignment (p = 0.03).

Conclusions

Ex-elite table tennis players were found to have increased levels of radiological signs of OA in the knee joint though this did not transpire through to altered levels of physical disability or knee stiffness in these players when compared with subjects from the general population suggesting that function in these players is not severely impacted upon.
A direct detection of Escherichia coli genomic DNA using gold nanoprobes
Authors: Bakthavathsalam Padmavathy , Rajendran Vinoth Kumar , Baquir Mohammed Jaffar Ali
Published: February 2012

Background

In situation like diagnosis of clinical and forensic samples there exists a need for highly sensitive, rapid and specific DNA detection methods. Though conventional DNA amplification using PCR can provide fast results, it is not widely practised in diagnostic laboratories partially because it requires skilled personnel and expensive equipment. To overcome these limitations nanoparticles have been explored as signalling probes for ultrasensitive DNA detection that can be used in field applications. Among the nanomaterials, gold nanoparticles (AuNPs) have been extensively used mainly because of its optical property and ability to get functionalized with a variety of biomolecules.

Results

We report a protocol for the use of gold nanoparticles functionalized with single stranded oligonucleotide (AuNP- oligo probe) as visual detection probes for rapid and specific detection ofEscherichia coli. The AuNP- oligo probe on hybridization with target DNA containing complementary sequences remains red whereas test samples without complementary DNA sequences to the probe turns purple due to acid induced aggregation of AuNP- oligo probes. The color change of the solution is observed visually by naked eye demonstrating direct and rapid detection of the pathogenicEscherichia colifrom its genomic DNA without the need for PCR amplification. The limit of detection was ~54 ng for unamplified genomic DNA. The method requires less than 30 minutes to complete after genomic DNA extraction. However, by using unamplified enzymatic digested genomic DNA, the detection limit of 11.4 ng was attained. Results of UV-Vis spectroscopic measurement and AFM imaging further support the hypothesis of aggregation based visual discrimination. To elucidate its utility in medical diagnostic, the assay was validated on clinical strains of pathogenicEscherichia coliobtained from local hospitals and spiked urine samples. It was found to be 100% sensitive and proves to be highly specific without any cross reaction with non-Escherichia colistrains.

Conclusion

This work gives entry into a new class of DNA/gold nanoparticles hybrid materials which might have optical property that can be controlled for application in diagnostics. We note that it should be possible to extend this strategy easily for developing new types of DNA biosensor for point of care detection. The salient feature of this approach includes low-cost, robust reagents and simple colorimetric detection of pathogen.
Characterization of the seminal plasma proteome in men with prostatitis by mass spectrometry
Authors: Kagedan Daniel , Lecker Irene , Batruch Ihor , Smith Christopher , Kaploun Ilia , Lo Kirk , Grober Ethan , Diamandis Eleftherios P , Jarvi Keith A
Published: February 2012

Background

Prostatitis is an inflammation of the prostate gland which affects approximately 10% of men. Despite its frequency, diagnosing prostatitis and monitoring patient response to treatment remains frustrating. As the prostate contributes a substantial percentage of proteins to seminal plasma, we hypothesized that a protein biomarker of prostatitis might be found by comparing the seminal plasma proteome of patients with and without prostatitis.

Results

Using mass spectrometry, we identified 1708 proteins in the pooled seminal plasma of 5 prostatitis patients. Comparing this list to a previously published list of seminal plasma proteins in the pooled seminal plasma of 5 healthy, fertile controls yielded 1464 proteins in common, 413 found only in the control group, and 254 found only in the prostatitis group. Applying a set of criteria to this dataset, we generated a high-confidence list of 59 candidate prostatitis biomarkers, 33 of which were significantly increased in prostatitis as compared to control, and 26 of which were decreased. The candidates were analyzed using Gene Ontology and Ingenuity Pathway analysis to delineate their subcellular localizations and functions.

Conclusions

Thus, in this study, we identified 59 putative biomarkers in seminal plasma that need further validation for diagnosis and monitoring of prostatitis.
A national survey of the availability of intensity-modulated radiation therapy and stereotactic radiosurgery in Canada
Authors: AlDuhaiby Eman Z , Breen Stephen , Bissonnette Jean-Pierre , Sharpe Michael , Mayhew Linda , Tyldesley Scott , Wilke Derek R , Hodgson David C
Published: February 2012

Background

The timely and appropriate adoption of new radiation therapy (RT) technologies is a challenge both in terms of providing of optimal patient care and managing health care resources. Relatively little is known regarding the rate at which new RT technologies are adopted in different jurisdictions, and the barriers to implementation of these technologies.

Methods

Surveys were sent to all radiation oncology department heads in Canada regarding the availability of RT equipment from 2006 to 2010. Data were collected concerning the availability and use of Intensity Modulated Radiation Therapy (IMRT) and stereotactic radiosurgery (SRS), and the obstacles to implementation of these technologies.

Results

IMRT was available in 37% of responding centers in 2006, increasing to 87% in 2010. In 2010, 72% of centers reported that IMRT was available for all patients who might benefit, and 37% indicated that they used IMRT for "virtually all" head and neck patients. SRS availability increased from 26% in 2006 to 42.5% in 2010. Eighty-two percent of centers reported that patients had access to SRS either directly or by referral. The main barriers for IMRT implementation included the need to train or hire treatment planning staff, whereas barriers to SRS implementation mostly included the need to purchase and/or upgrade existing planning software and equipment.

Conclusions

The survey showed a growing adoption of IMRT and SRS in Canada, although the latter was available in less than half of responding centers. Barriers to implementation differed for IMRT compared to SRS. Enhancing human resources is an important consideration in the implementation of new RT technologies, due to the multidisciplinary nature of the planning and treatment process.
Cardiac tamponade from a giant thymoma: case report
Authors: Fazlıoğulları Osman , Atalan Nazan , Gürer Onur , Akgün Serdar , Arsan Sinan
Published: February 2012

Thymoma, the most common neoplasm of the anterior mediastinum especially in adults, accounts for 20-25% of all mediastinal tumors and 50% of anterior mediastinal masses. These tumors are routinely asymptomatic for prolonged periods of time. Pericardial tamponade is a very rare initial manifestation of a thymoma. This report presents a patient who had hemorrhagic pericardial tamponade that likely resulted from the largest symptomatic mixed type (type AB) thymoma described in the literature.
Enumerating metabolic pathways for the production of heterologous target chemicals in chassis organisms
Authors: Carbonell Pablo , Fichera Davide , Pandit Shashi B , Faulon Jean-Loup
Published: February 2012

Background

We consider the possibility of engineering metabolic pathways in a chassis organism in order to synthesize novel target compounds that are heterologous to the chassis. For this purpose, we model metabolic networks through hypergraphs where reactions are represented by hyperarcs. Each hyperarc represents an enzyme-catalyzed reaction that transforms set of substrates compounds into product compounds. We follow a retrosynthetic approach in order to search in the metabolic space (hypergraphs) for pathways (hyperpaths) linking the target compounds to a source set of compounds.

Results

To select the best pathways to engineer, we have developed an objective function that computes the cost of inserting a heterologous pathway in a given chassis organism. In order to find minimum-cost pathways, we propose in this paper two methods based on steady state analysis and network topology that are to the best of our knowledge, the first to enumerate all possible heterologous pathways linking a target compounds to a source set of compounds. In the context of metabolic engineering, the source set is composed of all naturally produced chassis compounds (endogenuous chassis metabolites) and the target set can be any compound of the chemical space. We also provide an algorithm for identifying precursors which can be supplied to the growth media in order to increase the number of ways to synthesize specific target compounds.

Conclusions

We find the topological approach to be faster by several orders of magnitude than the steady state approach. Yet both methods are generally scalable in time with the number of pathways in the metabolic network. Therefore this work provides a powerful tool for pathway enumeration with direct application to biosynthetic pathway design.
High rates of de novo 15q11q13 inversions in human spermatozoa
Authors: Molina Òscar , Anton Ester , Vidal Francesca , Blanco Joan
Published: February 2012

Low-Copy Repeats predispose the 15q11-q13 region to non-allelic homologous recombination. We have already demonstrated that a significant percentage of Prader-Willi syndrome (PWS) fathers have an increased susceptibility to generate 15q11q13 deletions in spermatozoa, suggesting the participation of intrachromatid exchanges. This work has been focused on assessing the incidence of de novo 15q11q13 inversions in spermatozoa of control donors and PWS fathers in order to determine the basal rates of inversions and to confirm the intrachromatid mechanism as the main cause of 15q11q13 anomalies.

Semen samples from 10 control donors and 16 PWS fathers were processed and analyzed by triple-color FISH. Three differentially labeled BAC-clones were used: one proximal and two distal of the 15q11-q13 region. Signal associations allowed the discrimination between normal and inverted haplotypes, which were confirmed by laser-scanning confocal microscopy.

Two types of inversions were detected which correspond to the segments involved in Class I and II PWS deletions. No significant differences were observed in the mean frequencies of inversions between controls and PWS fathers (3.59% ± 0.46 and 9.51% ± 0.87 vs 3.06% ± 0.33 and 10.07% ± 0.74). Individual comparisons showed significant increases of inversions in four PWS fathers (P < 0.05) previously reported as patients with increases of 15q11q13 deletions.

Results suggest that the incidence of heterozygous inversion carriers in the general population could reach significant values. This situation could have important implications, as they have been described as predisposing haplotypes for genomic disorders. As a whole, results confirm the high instability of the 15q11-q13 region, which is prone to different types of de novo reorganizations by intrachromatid NAHR.
Regulation of cochlear convergent extension by the vertebrate planar cell polarity pathway is dependent on p120-catenin
Authors: Chacon-Heszele Maria F. , Ren Dongdong , Reynolds Albert B. , Chi Fanglu , Chen Ping
Published: February 2012

The vertebrate planar cell polarity (PCP) pathway consists of conserved PCP and ciliary genes. During development, the PCP pathway regulates convergent extension (CE) and uniform orientation of sensory hair cells in the cochlea. It is not clear how these diverse morphogenetic processes are regulated by a common set of PCP genes. Here, we show that cellular contacts and geometry change drastically and that the dynamic expression of N-cadherin and E-cadherin demarcates sharp boundaries during cochlear extension. The conditional knockout of a component of the adherens junctions, p120-catenin, leads to the reduction of E-cadherin and N-cadherin and to characteristic cochlear CE defects but not misorientation of hair cells. The specific CE defects in p120-catenin mutants are in contrast to associated CE and hair cell misorientation defects observed in common PCP gene mutants. Moreover, the loss-of-function of a conserved PCP gene, Vangl2, alters the dynamic distribution of N-cadherin and E-cadherin in the cochlea and causes similar abnormalities in cellular morphology to those found in p120-catenin mutants. Conversely, we found that Pcdh15 interacts genetically with PCP genes to regulate the formation of polar hair bundles, but not CE defects in the cochlea. Together, these results indicate that the vertebrate PCP pathway regulates CE and hair cell polarity independently and that a p120-catenin-dependent mechanism regulates CE of the cochlea.
Nematostella vectensis achaete-scute homolog NvashA regulates embryonic ectodermal neurogenesis and represents an ancient component of the metazoan neural specification pathway
Authors: Layden Michael J. , Boekhout Michiel , Martindale Mark Q.
Published: February 2012

achaete-scute homologs (ash) regulate neural development in all bilaterian model animals indicating that they represent a component of the ancestral neurogenic pathway. We test this by investigating four ash genes during development of a basal metazoan, the cnidarian sea anemone Nematostella vectensis. Spatiotemporal expression of ash genes in the early embryo and larval stages suggests that they regulate neurogenesis. More specifically, NvashA is co-expressed with neural genes in the embryonic ectoderm. Knockdown of NvashA results in decreased expression of eight neural markers, including the six novel neural targets identified here. Conversely, overexpression of NvashA induces increased expression of all eight genes, but only within their normal axial domains. Overexpression of NvashB-D differentially increases expression of NvashA targets. The expression patterns and differential ability of ash genes to regulate neural gene expression reveals surprising molecular complexity in these ‘simple’ animals. These data suggest that achaete-scute homologs functioned in the ancestral metazoan neurogenic pathway and provide a foundation to investigate further the evolution of neurogenesis and the origin of complex central nervous systems.
Nanobiology and physiology of growth hormone secretion
Authors: Anderson Lloyd L , Scanes Colin G
Published: February 2012

Growth hormone (GH) secretion is controlled by hypothalamic releasing hormones from the median eminence together with hormones and neuropeptides produced by peripheral organs. Secretion of GH involves movement of secretory vesicles along microtubules, transient ‘docking’ with the porosome in the cell membrane and subsequent release of GH. Release of GH is stimulated by GH releasing hormone (GHRH) and inhibited by somatostatin (SRIF). Ghrelin may be functioning to stimulate GH release from somatotropes acting via the GH secretagogue (GHS) receptor (GHSR). However, recent physiological studies militate against this. In addition, ghrelin does influence GH release acting within the hypothalamus. Release of GH from the somatotropes involves the GH-containing secretory granules moving close to the cell surface followed by transitory fusion of the secretory granules with the porosomes located in multiple secretory pits in the cell membrane. Other peptides/proteins can influence GH secretion, particularly in species of non-mammalian vertebrates.
Echocardiography of the weird and wonderful: tarantulas, turtles and tigers
Authors: Pereira Yolanda Martinez , Pizzi Romain
Published: February 2012

Echocardiography is performed routinely in dogs and cats for the investigation of cardiac disease following well-established, published guidelines for the echocardiographic examination. However, such guidelines do not exist for other animal patients such as small pet mammals, zoo animals, wildlife, birds and reptiles. In these species, a detailed knowledge of the widely differing cardiovascular function and cardiac anatomy is necessary in order to interpret the echocardiographic examination. This varies widely, from the four-chambered mammalian heart, the muscular tricuspid valve and right aorta in birds, the three-chambered heart in reptiles and amphibians with intracardiac shunting of blood, to the two-chambered heart in fish. These are adaptations to very different natural histories and ecological niche requirements such as flying, diving and hibernation, and influence echocardiographic interpretation. Modifications to the echocardiographic technique are necessary in order to obtain a feasible acoustic window in view of differences in visceral and skeletal anatomy, such as the shell in tortoises, air sacs in birds and encircling ribs in snakes. The presence of scales, feathers and fur also contribute to difficulties in obtaining diagnostic quality images.
Established and Emerging Markers of Kidney Function
Authors: Ferguson Michael A , Waikar Sushrut S
Published: February 2012

BACKGROUND

The kidney performs a multitude of essential functions to maintain homeostasis. In clinical medicine, glomerular filtration rate (GFR) provides the best index of overall kidney function, and proteinuria adds additional information on renal and nonrenal prognosis. Several novel biomarkers of kidney injury and function are under investigation.

CONTENT

Plasma creatinine concentration is the most widely used measure for estimation of GFR. Plasma cystatin C and β-trace protein may eventually prove to be superior to creatinine. GFR may be measured directly by use of exogenous filtration markers, although their role is primarily limited to the research setting. Real-time, noninvasive measurement of GFR by using fluorescently labeled markers may be available in the future. Novel biomarkers of tubular injury such as neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, liver-type fatty acid binding protein, N-acetyl-β-(D)-glucosaminidase, and interleukin-18 may enable the early detection of acute kidney injury before or in the absence of a change in GFR.

A variety of methods are available to assist clinicians in the assessment of kidney function and injury. Ongoing investigation will help determine the utility of several new markers and clarify their role in the care of patients with and at risk for kidney disease.