bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta‐analysis: the association of hepatitis B virus genotypes and hepatocellular carcinoma
Authors: Wong G. L.‐H. , Chan H. L.‐Y. , Yiu K. K.‐L. , Lai J. W.‐Y. , Chan V. K.‐K. , Cheung K. K.‐C. , Wong E. W.‐N. , Wong V. W.‐S.
Published: January 2013

Background

A meta‐analysis on the risk of hepatocellular carcinoma (HCC) among hepatitis B virus (HBV) genotypes is warranted as the current data are conflicting.

Aim

To investigate the relative risk of HCC among the four major HBV genotypes (A–D).

Methods

A meta‐analysis was performed based on literature search from electronic databases and bibliography between 1950 and 2012. All abstracts with keywords ‘hepatitis B’, ‘hepatocellular carcinoma’ and ‘genotype’ were screened. Studies were included if they reported HBV genotype as an exposure and HCC as an outcome.

Results

Nine hundred and eighty‐eight abstracts were found through literature search, among them 43 studies were eligible for this meta‐analysis. A total of 14 545 patients with an average age of 43 years were included; 71% were male patients and 17% had cirrhosis. In 33 studies, HCC was found in 1541/6060 (25%) genotype C vs. 550/4417 (12%) genotype B HBV‐infected patients [odds ratio (OR) = 2.05, 95% confidence interval (CI) = 1.52–2.76, P < 0.001]. No difference in the risk of HCC was found among genotype A (71/517, 14%) vs. genotype D (170/1506, 11%) HBV‐infected patients in 14 studies (OR = 0.94, 95% CI = 0.67–1.32). In 10 studies, the risk of HCC was also found higher among genotype C (498/1659, 30%) than genotype A&D (103/1403, 7%) HBV‐infected patients (OR = 2.34, 95% CI = 1.63–3.34, P < 0.001). Subgenotype Ce and Cs HBV‐infected patients had similar risk on HCC (OR = 1.13, 95% CI = 0.76–1.67, P = 0.54). On funnel plot analysis, there was no significant publication bias in all comparisons.

Conclusion

Genotype C hepatitis B virus is associated with a higher risk of hepatocellular carcinoma than other major hepatitis B virus genotypes.
The effects of obesity on oesophageal function, acid exposure and the symptoms of gastro‐oesophageal reflux disease
Authors: Anggiansah R. , Sweis R. , Anggiansah A. , Wong T. , Cooper D. , Fox M.
Published: January 2013

Background

Obese patients have an increased risk of gastro‐oesophageal reflux disease; however, the mechanism underlying this association is uncertain.

Aim

To test the hypothesis that mechanical effects of obesity on oesophageal function increase acid exposure and symptoms.

Methods

Height, weight and waist circumference (WC) were measured in patients with typical reflux symptoms referred for manometry and 24 h ambulatory pH studies. Symptom severity was assessed by questionnaire. The association between obesity [WC, body mass index (BMI)], oesophageal function, acid exposure and reflux symptoms was assessed.

Results

Physiological measurements were obtained from 582 patients (median age 48, 56% female) of whom 406 (70%) completed symptom questionnaires. The prevalence of general obesity was greater in women (BMI ≥ 30 kg/m2; F 23%:M 16%; P = 0.056), however more men had abdominal obesity (WC ≥ 99 cm (M 41%:F 28%; P = 0.001)). Oesophageal acid exposure increased with obesity (WC: R = 0.284, P < 0.001) and was associated also with lower oesophageal sphincter (LOS) pressure, reduced abdominal LOS length and peristaltic dysfunction (all P < 0.001). Univariable regression showed a negative association of WC with both LOS pressure and abdominal LOS length (R = −0.221 and −0.209 respectively; both P < 0.001). However, multivariable analysis demonstrated that the effects of increasing WC on oesophageal function do not explain increased acid reflux in obese patients. Instead, independent effects of obesity and oesophageal dysfunction on acid exposure were present. Reflux symptoms increased with acid exposure (R = 0.300; P < 0.001) and this association explained increased symptom severity in obese patients.

Conclusions

Abdominal obesity (waist circumference) is associated with oesophageal dysfunction, increased acid exposure and reflux symptoms; however, this analysis does not support the mechanical hypothesis that the effects of obesity on oesophageal function are the cause of increased acid exposure in obese patients.
Co‐administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects
Authors: Mueck Wolfgang , Kubitza Dagmar , Becka Michael
Published: January 2013

Aims

The anticoagulant rivaroxaban is an oral, direct Factor Xa inhibitor for the management of thromboembolic disorders. Metabolism and excretion involve cytochrome P450 3A4 (CYP3A4) and 2J2 (CYP2J2), CYP‐independent mechanisms, and P‐glycoprotein (P‐gp) and breast cancer resistance protein (Bcrp) (ABCG2).

Methods

The pharmacokinetic effects of substrates or inhibitors of CYP3A4, P‐gp and Bcrp (ABCG2) on rivaroxaban were studied in healthy volunteers.

Results

Rivaroxaban did not interact with midazolam (CYP3A4 probe substrate). Exposure to rivaroxaban when co‐administered with midazolam was slightly decreased by 11% (95% confidence interval [CI] −28%, 7%) compared with rivaroxaban alone. The following drugs moderately affected rivaroxaban exposure, but not to a clinically relevant extent: erythromycin (moderate CYP3A4/P‐gp inhibitor; 34% increase [95% CI 23%, 46%]), clarithromycin (strong CYP3A4/moderate P‐gp inhibitor; 54% increase [95% CI 44%, 64%]) and fluconazole (moderate CYP3A4, possible Bcrp [ABCG2] inhibitor; 42% increase [95% CI 29%, 56%]). A significant increase in rivaroxaban exposure was demonstrated with the strong CYP3A4, P‐gp/Bcrp (ABCG2) inhibitors (and potential CYP2J2 inhibitors) ketoconazole (158% increase [95% CI 136%, 182%] for a 400 mg once daily dose) and ritonavir (153% increase [95% CI 134%, 174%]).

Conclusions

Results suggest that rivaroxaban may be co‐administered with CYP3A4 and/or P‐gp substrates/moderate inhibitors, but not with strong combined CYP3A4, P‐gp and Bcrp (ABCG2) inhibitors (mainly comprising azole‐antimycotics, apart from fluconazole, and HIV protease inhibitors), which are multi‐pathway inhibitors of rivaroxaban clearance and elimination.
Reduced indinavir exposure during pregnancy
Authors: Cressey Tim R. , Best Brookie M. , Achalapong Jullapong , Stek Alice , Wang Jiajia , Chotivanich Nantasak , Yuthavisuthi Prapap , Suriyachai Pornnapa , Prommas Sinart , Shapiro David E. , Watts D. Heather , Smith Elizabeth , Capparelli Edmund , Kreitchmann Regis , Mirochnick Mark ,   IMPAACT P1026s team
Published: January 2013

Aim

To describe the pharmacokinetics and safety of indinavir boosted with ritonavir (IDV/r) during the second and third trimesters of pregnancy and in the post‐partum period.

Methods

IMPAACT P1026s is an on‐going, prospective, non‐blinded study of antiretroviral pharmacokinetics (PK) in HIV‐infected pregnant women with a Thai cohort receiving IDV/r 400/100 mg twice daily during pregnancy through to 6–12 weeks post‐partum as part of clinical care. Steady‐state PK profiles were performed during the second (optional) and third trimesters and at 6–12 weeks post‐partum. PK targets were the estimated 10th percentile IDV AUC (12.9 μg ml−1 h) in non‐pregnant historical Thai adults and a trough concentration of 0.1 μg ml−1, the suggested minimum target.

Results

Twenty‐six pregnant women were enrolled; thirteen entered during the second trimester. Median (range) age was 29.8 (18.9–40.8) years and weight 60.5 (50.0–85.0) kg at the third trimester PK visit. The 90% confidence limits for the geometric mean ratio of the indinavir AUC(0,12 h) and Cmax during the second trimester and post‐partum (ante : post ratios) were 0.58 (0.49, 0.68) and 0.73 (0.59, 0.91), respectively; third trimester/post‐partum AUC(0,12 h) and Cmax ratios were 0.60 (0.53, 0.68) and 0.63 (0.55, 0.72), respectively. IDV/r was well tolerated and 21/26 women had a HIV‐1 viral load < 40 copies ml−1 at delivery. All 26 infants were confirmed HIV negative.

Conclusion

Indinavir exposure during the second and third trimesters was significantly reduced compared with post‐partum and ∼30% of women failed to achieve a target trough concentration. Increasing the dose of IDV/r during pregnancy to 600/100 mg twice daily may be preferable to ensure adequate drug concentrations.
Trimethoprim–metformin interaction and its genetic modulation by OCT2 and MATE1 transporters
Authors: Grün Barbara , Kiessling Michael K. , Burhenne Jürgen , Riedel Klaus‐Dieter , Weiss Johanna , Rauch Geraldine , Haefeli Walter E. , Czock David
Published: January 2013

Aims

Metformin pharmacokinetics depends on the presence and activity of membrane‐bound drug transporters and may be affected by transport inhibitors. The aim of this study was to investigate the effects of trimethoprim on metformin pharmacokinetics and genetic modulation by organic cation transporter 2 (OCT2) and multidrug and toxin extrusion 1 (MATE1) polymorphisms.

Methods

Twenty‐four healthy volunteers received metformin 500 mg three times daily for 10 days and trimethoprim 200 mg twice daily from day 5 to 10. Effects of trimethoprim on steady‐state metformin pharmacokinetics were analysed.

Results

In the population as a whole, trimethoprim significantly reduced the apparent systemic metformin clearance (CL/F) from 74 to 54 l h−1 and renal metformin clearance from 31 to 21 l h−1, and prolonged half‐life from 2.7 to 3.6 h (all P < 0.01). This resulted in an increase in the maximal plasma concentration by 38% and in the area under the plasma concentration–time curve by 37%. In volunteers polymorphic for both OCT2 and MATE1, trimethoprim had no relevant inhibitory effects on metformin kinetics. Trimethoprim was associated with a decrease in creatinine clearance from 133 to 106 ml min−1 (P < 0.01) and an increase in plasma lactate from 0.94 to 1.2 mmol l−1 (P = 0.016).

Conclusions

The extent of inhibition by trimethoprim was moderate, but might be clinically relevant in patients with borderline renal function or high‐dose metformin.
Responses of Aquatic Insect Functional Diversity to Landscape Changes in Atlantic Forest
Authors: Colzani Emílio , Siqueira Tadeu , Suriano Marcia T. , Roque Fabio O.
Published: January 2013

The Atlantic Forest domain, one of the 25 world's hotspots for biodiversity, has experienced dramatic changes in its landscape. While the loss of species diversity is well documented, functional diversity has not received the same amount of attention. In this study, we evaluated functional diversity of insects in streams utilizing three indices: functional diversity (FD), functional dispersion (FDis), and functional divergence (FDiv), seeking to understand the roles of three predictor sets in explaining functional patterns: (1) bioclimatic and landscape variables; (2) spatial variables; and (3) local environmental variables. We determined the amount of variation in different measures of functional diversity that was explained by each predictor set and their interplays using variation partitioning. Our study showed that variation in functional diversity is better explained by a set of variables linked to different scales dependent on spatial structures, indicating the importance of landscape and mainly environmental variables in the functional organization of aquatic insect communities, and that the relative importance of predictor sets depends on the indices considered. Variation in FD was better explained by the interplay among the three predictor sets and by local environmental variables, whereas variation in FDis was better explained by spatial variables and by the interplay between environmental and spatial variables. Variation in FDiv was not significantly explained by any predictors. Our study adds more evidence on the harmful effects caused by landscape changes on biodiversity in the Atlantic Forest, suggesting that these effects also influence the functional organization of stream insect communities.
Little Evidence That Time in Child Care Causes Externalizing Problems During Early Childhood in Norway
Authors: Zachrisson Henrik D. , Dearing Eric , Lekhal Ratib , Toppelberg Claudio O.
Published: January 2013

Associations between maternal reports of hours in child care and children's externalizing problems at 18 and 36 months of age were examined in a population‐based Norwegian sample (n = 75,271). Within a sociopolitical context of homogenously high‐quality child care, there was little evidence that high quantity of care causes externalizing problems. Using conventional approaches to handling selection bias and listwise deletion for substantial attrition in this sample, more hours in care predicted higher problem levels, yet with small effect sizes. The finding, however, was not robust to using multiple imputation for missing values. Moreover, when sibling and individual fixed‐effects models for handling selection bias were used, no relation between hours and problems was evident.
Dual Routes to Cognitive Flexibility: Learning and Response‐Conflict Resolution in the Dimensional Change Card Sort Task
Authors: Ramscar Michael , Dye Melody , Gustafson Jessica W. , Klein Joseph
Published: January 2013

Cognitive control, the ability to align our actions with goals or context, is largely absent in children under four. How then are preschoolers able to tailor their behavior to best match the situation? Learning may provide an alternative route to context‐sensitive responding. This study investigated this hypothesis in the Dimensional Change Card Sort (DCCS), a classic test of cognitive control that most under‐fours fail. A training intervention based on learning theoretic principles proved highly effective: Three‐year‐olds who learned about DCCS rules and game contexts in a card‐labeling task, subsequently transferred this knowledge to sorting in the DCCS, passing at more than 3 times the rate of controls (N = 47). This surprising finding reveals much about the nature of the developing mind.
The Utility of Chromosomal Microarray Analysis in Developmental and Behavioral Pediatrics
Authors: Beaudet Arthur L.
Published: January 2013

Chromosomal microarray analysis (CMA) has emerged as a powerful new tool to identify genomic abnormalities associated with a wide range of developmental disabilities including congenital malformations, cognitive impairment, and behavioral abnormalities. CMA includes array comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays, both of which are useful for detection of genomic copy number variants (CNV) such as microdeletions and microduplications. The frequency of disease‐causing CNVs is highest (20%–25%) in children with moderate to severe intellectual disability accompanied by malformations or dysmorphic features. Disease‐causing CNVs are found in 5%–10% of cases of autism, being more frequent in severe phenotypes. CMA has replaced Giemsa‐banded karyotype as the first‐tier test for genetic evaluation of children with developmental and behavioral disabilities.
Impact of body mass index on thyroid functions in Indian children
Authors: Marwaha Raman K. , Tandon Nikhil , Garg M. K. , Ganie Mohd Ashraf , Narang A. , Mehan Neena , Bhadra Kuntal
Published: January 2013

Objective

There is controversy about the relation of thyroid functions and body mass index. The present study was aimed to assess the relationship between thyroid function and body mass index in Indian school children.

Design

Population survey.

Patients

Data were collected from 25 schools in 19 cities across five different geographical zones of India. Children, who consented, were evaluated for anthropometry and blood tests. Children were categorized as overweight and obese based on standard BMI criteria.

Measurements

Serum samples were analysed for free T3, free T4, TSH and anti‐TPO antibodies.

Results

A total of 13 691 children in the age group of 5–18 years formed the study population. The mean age and mean BMI were 11·9 ± 3·0 years and 18·48 ± 3·89 kg/m2 respectively. Among these, 2119 (15·5%) children were overweight and 536 (3·9%) were obese. Subclinical hypothyroidism was present in 943 (6·9%) children.FT3 and TSH levels increased and FT4 levels decreased with increasing BMI in euthyroid boys and girls. Prevalence of SCH was significantly higher in obese/overweight children (9·0%, vs 6·5%; P = 0·034) as compared with normal BMI children.

Conclusions

Serum FT3 and TSH were positively while FT4 was negatively associated with BMI in apparently healthy euthyroid children.
Robust Image Denoising Using a Virtual Flash Image for Monte Carlo Ray Tracing
Authors: Moon Bochang , Jun Jong Yun , Lee JongHyeob , Kim Kunho , Hachisuka Toshiya , Yoon Sung‐Eui
Published: January 2013

We propose an efficient and robust image‐space denoising method for noisy images generated by Monte Carlo ray tracing methods. Our method is based on two new concepts: virtual flash images and homogeneous pixels. Inspired by recent developments in flash photography, virtual flash images emulate photographs taken with a flash, to capture various features of rendered images without taking additional samples. Using a virtual flash image as an edge‐stopping function, our method can preserve image features that were not captured well only by existing edge‐stopping functions such as normals and depth values. While denoising each pixel, we consider only homogeneous pixels—pixels that are statistically equivalent to each other. This makes it possible to define a stochastic error bound of our method, and this bound goes to zero as the number of ray samples goes to infinity, irrespective of denoising parameters. To highlight the benefits of our method, we apply our method to two Monte Carlo ray tracing methods, photon mapping and path tracing, with various input scenes. We demonstrate that using virtual flash images and homogeneous pixels with a standard denoising method outperforms state‐of‐the‐art image‐space denoising methods.
In Vivo Evaluation of a Novel Implant Coating Agent: Laminin‐1
Authors: Bougas Kostas , Jimbo Ryo , Vandeweghe Stefan , Tovar Nick , Baldassarri Marta , Alenezi Ali , Janal Malvin , Coelho Paulo G. , Wennerberg Ann
Published: January 2013

Purpose

The aim of this study was to assess the effect of implant coating with laminin‐1 on the early stages of osseointegration in vivo.

Materials and Methods

Turned titanium implants were coated with the osteoprogenitor‐stimulating protein, laminin‐1 (TL). Their osteogenic performance was assessed with removal torque, histomorphometry, and nanoindentation in a rabbit model after 2 and 4 weeks. The performance of the test implants was compared with turned control implants (T), alkali‐ and heat‐treated implants (AH), andAHimplants coated with laminin‐1.

Results

After 2 weeks,TLdemonstrated significantly higher removal torque as compared withTand equivalent toAH. Bone area was significantly higher for the test surface after 4 weeks, while no significant changes were detected on the micromechanical properties of the surrounding bone.

Conclusions

Within the limitations of this study, our results suggest a great potential for laminin‐1 as a coating agent. A turned implant surface coated with laminin‐1 could enhance osseointegration comparable with a bioactive implant surface while keeping the surface smooth.
Fibrin Clot Extension on Zirconia Surface for Dental Implants: A Quantitative In Vitro Study
Authors: Traini Tonino , Caputi Sergio , Gherlone Enrico , Degidi Marco , Piattelli Adriano
Published: January 2013

Purpose

The surface chemical and physical properties of materials used for implants have a major influence on blood clot organization. This study aims to evaluate the blood clot extension (bce) on zirconia and titanium. bce was measured in association to surface roughness (Ra) and static contact angle (θ).

Materials and Methods

Forty disk‐shaped samples of sandblasted yttria tetragonal zirconia polycrystal (sb‐YTZP), machined titanium (m‐Ti), and sandblasted, high‐temperature, acid‐etched titanium (p‐Ti) were used in the present study. About 0.2 mL of human blood, immediately dropped onto the specimen's surface and left in contact for 5 minutes at room temperature, was used to measure the bce. Specimens were observed under confocal scanning laser and scanning electron microscopes.

Results

The bce (mean × 107 ± standard deviation [SD] × 106 μm2) was 2.97 ± 6.68 for m‐Ti, 5.64 ± 6.83 for p‐Ti, and 3.61 ± 7.67 for sb‐YTZP. p‐Ti samples showed a significantly higher bce. Ra (mean ± SD [μm]) was 0.56 ± 0.7 for m‐Ti, 3.78 ± 0.8 for p‐Ti, and 2.68 ± 0.6 for sb‐YTZP. The difference was not significant between sb‐YTZP and p‐Ti. θ (mean ± SD) was 55.6 ± 5.6 for m‐Ti, 48.7 ± 2.8 for sb‐YTZP, and 38.0 ± 2.2 for p‐Ti. The difference was not significant between m‐Ti and sb‐YTZP.

Conclusions

The sb‐YTZP demonstrated a significantly lesser amount of bce compared with p‐Ti specimens, notwithstanding that any significant difference was present between Ra and θ.
Reliability of Vertical Jump Performance evaluated with contact mat in elderly women
Authors: Farias Darlan L. , Teixeira Tatiane G. , Madrid Bibiano , Pinho Danilo , Boullosa Daniel A. , Prestes Jonato
Published: January 2013

The aim of this study was to evaluate the reliability of the vertical jump (VJ) using a contact mat in elderly women. Thirty‐one physically active women aged 69·5 ± 5·6 years participated in this study. Jump performance was evaluated with a contact mat. The first testing session (s1) consisted of four countermovement jumps interspersed with 40 s rest intervals. After a period of 5–7 days, volunteers performed the second session (s2) utilizing the same procedures. The intersession statistical analysis was calculated considering the two highest jumps, one obtained in each section. The intra‐session analysis utilized all eight jumps, all four from each section, and the differences between means were calculated by repeated measures ANOVA. Reliability was tested using the intra‐class correlation coefficient (ICC) and agreement by the Bland–Altman method. The intra‐ and inter‐subject variation percentage was calculated by the coefficient of variation (CV). Results: The intersession results displayed a high ICC (0·91; P<0·001) and a good agreement verified by the Bland–Altman method. There was a significant difference in the intra‐session analysis only in s2 between the jumps 2 and 4. Both in s1 and s2, the ICC was high (0·96; P<0·001; 0·95; P<0·001), and the within session reliability CV was low (10·14% and 9·07%). Conclusion: In physically active elderly women, VJ evaluation using a contact mat is a reliable method and could be used to estimate jump height. Additionally, the results of this study could serve as reference values in similar samples evaluated with the same procedures.
Recipient outcomes of dual and multiple renal arteries following 1000 consecutive laparoscopic donor nephrectomies at a single institution
Authors: Cooper Matthew , Kramer Andrew , Nogueira Joseph M. , Phelan Michael
Published: January 2013

Purpose

We examined outcomes of kidney transplant recipients from allografts harvested via laparoscopic donor nephrectomy (LDN) with various arterial anatomies. We examined the risk of slow graft function, delayed graft function (DGF), and postoperative urological complications in recipients of multi‐vessel allografts.

Methods

Donor and recipient records for 1000 consecutive LDN were reviewed (1996–2005). Characteristics examined included donor demographics, intraoperative parameters and complications, recipient post‐operative complications and short‐term recipient allograft function.

Results

DGF was 5.3% for single; 5.2% for dual; and 9.8% for multiple (p = 0.05). Recipient creatinine (Cr) at one wk and one month was 1.9 + 1.5 and 1.6 + 0.8; 2.1 + 1.6 and 1.7 + 1.2; 2.8 + 2.3 and 1.7 + 0.8 respectively (p = 0.01). Recipient Cr at one year averaged 1.6 mg % with no significant differences between groups, with 48 ureteral complications (4.8%): 32/732 = 4.4% recognized in single arterial allograft recipients; 12/212(5.7%) for dual and 4/43 for multiple (9.3%) (p = 0.03).

Conclusion

Complex vascular anatomy not a contraindication to LDN. Recipients of allograft with >2 arteries experience longer warm and cold ischemia times, greater incidence of DGF, and greater propensity for ureteral complications. Long term recipient outcomes remain excellent.
Molecular genetic system for regenerative studies using newts
Authors: Hayashi Toshinori , Yokotani Naoki , Tane Shoji , Matsumoto Akira , Myouga Ayumi , Okamoto Mitsumasa , Takeuchi Takashi
Published: January 2013

Urodele newts have the remarkable capability of organ regeneration, and have been used as a unique experimental model for more than a century. However, the mechanisms underlying regulation of the regeneration are not well understood, and gene functions in particular remain largely unknown. To elucidate gene function in regeneration, molecular genetic analyses are very powerful. In particular, it is important to establish transgenic or knockout (mutant) lines, and systematically cross these lines to study the functions of the genes. In fact, such systems have been developed for other vertebrate models. However, there is currently no experimental model system using molecular genetics for newt regenerative research due to difficulties with respect to breeding newts in the laboratory. Here, we show that the Iberian ribbed newt (Pleurodeles waltl) has outstanding properties as a laboratory newt. We developed conditions under which we can obtain a sufficient number and quality of eggs throughout the year, and shortened the period required for sexual maturation from 18 months to 6 months. In addition, P. waltl newts are known for their ability, like other newts, to regenerate various tissues. We revealed that their ability to regenerate various organs is equivalent to that of Japanese common newts. We also developed a method for efficient transgenesis. These studies demonstrate that P. waltl newts are a suitable model animal for analysis of regeneration using molecular genetics. Establishment of this experimental model will enable us to perform comparable studies using these newts and other vertebrate models.
Cardiac Lipoma at Unusual Location – Mimicking Atrial Myxoma
Authors: Singh Bhupinder , Bhairappa Shivakumar , Shankar Subramani Khamitkar , Prasad N. M. , Manjunath C. N.
Published: January 2013

Cardiac lipomas are one of the rare primary benign neoplasms composed of mature fat cells. The tumor originates mostly in the subendocardium and subepicardium but very rarely within the myocardium. Clinically, this tumor is asymptomatic and found incidentally in the vast majority of cases. We report a 26‐year‐old female presenting with atypical chest pain. Transthoracic echocardiogram showed a mass in relation to interatrial septum suggestive of atrial myxoma, but was confirmed to be cardiac lipoma on magnetic resonance imaging. Owing to the asymptomatic character and the benign nature of the tumor, a decision for conservative management was made.
Right Ventricular Function Relates to Functional Capacity in Men with Atrial Fibrillation and Preserved Left Ventricular Ejection Fraction
Authors: Cohen Scott , Gaddam Sainath , Gemignani Anthony , Wu Wen‐Chih , Sharma Satish , Choudhary Gaurav
Published: January 2013

Background

While left ventricular (LV) diastolic function (E/e′) is related to functional capacity in patients with atrial fibrillation (AF), the underlying mechanism is unclear. Right ventricular (RV) function is related to prognosis in various diseases, however, its relationship with LV diastolic function is not well‐studied. We sought to examine the reliability of echocardiographic indices of RV function in AF, the relationship between LV diastolic function and RV function, and the relationship between RV function and 6MWT distance in ambulatory patients with AF.

Methods

We designed a retrospective study evaluating 52 veterans with AF and preserved LV ejection fraction (LVEF) who underwent echocardiography and 6MWT at scheduled visits throughout 1 year. We performed pairwise correlation to evaluate reproducibility of echocardiographic indices of RV function measured 1 week apart. Multiple regression was used to assess the association of indices of RV function to LV diastolic function and functional capacity.

Results

Most RV function indices had good to excellent correlation between 2 visits 1 week apart (coefficient 0.50–0.81) with test‐retest variations of <6%, except for tricuspid annular plane systolic excursion (TAPSE), which had a significant variation in 9%. TAPSE, RV S′ and RV e′ were significantly related to LV diastolic function after adjusting for RV systolic pressure. After further adjustment for comorbidities, only RV S′ and RV e′ remained significantly related to 6MWT.

Conclusion

RV tissue Doppler measurements (S′ and e′) had good reproducibility and were independently related to LV diastolic function and 6MWT in men with AF and preserved LVEF.
Evaluation of Atrial Electromechanic Delay and Left Atrial Mechanical Functions in the Patients with Secundum Type Atrial Septal Defect
Authors: Erturk Mehmet , Aslan Muzaffer , Aksu Hale Unal , Akturk Ibrahim Faruk , Gul Mehmet , Uzun Fatih , Surgit Ozgur , Ari Hasan , Uslu Nevzat , Erol Mustafa Kemal
Published: January 2013

Aim

The aim of our study was to evaluate atrial electromechanical delay (AEMD) and left atrial mechanical functions (LAMF) in the patients with secundum‐type atrial septal defect (ASD).

Method

We included 72 patients with secundum type ASD in the study group and 35 gender and age‐matched healthy volunteers for the control group. Maximal, minimal, and presystolic LA volumes were measured by modified Simpson method and indexed to the body surface area (BSA). Inter‐AEMD, right and left intra‐AEMD were measured from the lateral and septal mitral annulus and tricuspid annulus using tissue Doppler imaging (TDI).

Results

The age, gender, systolic and diastolic blood pressure, heart rate (HR), BSA, and body mass index (BMI) parameters were not significantly different between the groups. Left atrial active and total emptying fractions and conduit volumes were significantly lower in the patients with ASD compared with the control group (P = 0.006, P = 0.001, and P = 0.032, respectively). Total emptying volume was increased in patients with ASD (P = 0.021). Passive emptying volume and fraction and active emptying volumes were not different significantly between the groups (P > 0.05). The left intraatrial, right intraatrial, and inter‐AEMDs were significantly longer in the ASD group (P = 0.032, P = 0.013, and P = 0.003, respectively).

Conclusion

The left atrial reservoir and contractile pump functions are reduced; the left intraatrial, right intraatrial, and inter‐AEMDs are increased in the patients with ASD.
Echocardiographic Myocardial Deformation Evaluation of Right Ventricular Function in Comparison with CMRI in Repaired Tetralogy of Fallot: A Cross‐Sectional and Longitudinal Validation Study
Authors: Srivastava Shubhika , Salem Yishay , Chatterjee Samprit , Helen Ko H. , Lai Wyman W. , Parness Ira A. , Nielsen James C. , Lytrivi Irene D.
Published: January 2013

Background

Decreased right ventricular (RV) ejection fraction (EF) increases morbidity in repaired tetralogy of Fallot (rToF). Cardiac magnetic resonance (CMR) is the accepted reference standard for RV EF measurement. There are no established color Doppler tissue imaging (cDTI) values that identify decreased RV EF in rToF. We sought to assess accuracy of cDTI myocardial deformation and velocity indices in predicting CMR‐derived RV EF.

Methods

Retrospective evaluation of CMR and echocardiography studies performed on the same day. cDTI‐derived peak systolic velocity (pkS), isovolumic acceleration (IVA) of the tricuspid valve annulus, strain (ε) and strain rate (SR) of the RV free wall, adjusted for age, volume and pressure overload were used to compute RV EF. The probability of correctly classifying CMR measured RV EF <45% was estimated by logistic regression analysis. The accuracy of the model was tested on 10 prospective patients.

Results

Sixty matched echocardiographic and CMR studies were analyzed. None of the individual cDTI parameters could reliably identify patients with CMR‐derived decreased RV EF. However, when adjusted for age in a logistic model: Y = −0.5 − 0.07 × age + 0.016 × ε + 0.46 × pkS, where Y is the logit (log odds), patients with RV EF <45% were identified with 86% sensitivity, 93.5% specificity. Prospective application of this model correctly identified all subjects with RV EF <45%.

Conclusion

The age‐adjusted logistic model and not individual parameters, derived from cDTI‐derived pkS, and ε can reliably identify patients with decreased RV EF <45%.
Cannabis and other illicit drug use in epilepsy patients
Authors: Hamerle M. , Ghaeni L. , Kowski A. , Weissinger F. , Holtkamp M.
Published: January 2013

Background and purpose

This study aimed to assess the prevalence of illicit drug use among epilepsy patients and its effects on the disease.

Methods

We systematically interviewed epilepsy outpatients at a tertiary epilepsy clinic. Predictors for active cannabis use were analysed with a logistic regression model.

Results

Overall, 310 subjects were enrolled; 63 (20.3%) reported consuming cannabis after epilepsy was diagnosed, and 16 (5.2%) used other illicit drugs. Active cannabis use was predicted by sex (male) [odds ratio (OR) 5.342, 95% confidence interval (95% CI) 1.416–20.153] and age (OR 0.956, 95% CI 0.919–0.994). Cannabis consumption mostly did not affect epilepsy (84.1%). Seizure worsening was observed with frequent illicit (non‐cannabis) drug use in 80% of cases.

Conclusions

Cannabis use does not seem to affect epilepsy; however, frequent use of other drugs increases seizure risk.
Altered sleep regulation in a mouse model of SCN1A‐derived genetic epilepsy with febrile seizures plus (GEFS+)
Authors: Papale Ligia A. , Makinson Christopher D. , Christopher Ehlen J. , Tufik Sergio , Decker Michael J. , Paul Ketema N. , Escayg Andrew
Published: January 2013

Purpose

Mutations in the voltage‐gated sodium channel (VGSC) gene SCN1A are responsible for a number of epilepsy disorders, including genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome. In addition to seizures, patients with SCN1A mutations often experience sleep abnormalities, suggesting that SCN1A may also play a role in the neuronal pathways involved in the regulation of sleep. However, to date, a role for SCN1A in the regulation of sleep architecture has not been directly examined. To fill this gap, we tested the hypothesis that SCN1A contributes to the regulation of sleep architecture, and by extension, that SCN1A dysfunction contributes to the sleep abnormalities observed in patients with SCN1A mutations.

Methods

Using immunohistochemistry we first examined the expression of mouse Scn1a in regions of the mouse brain that are known to be involved in seizure generation and sleep regulation. Next, we performed detailed analysis of sleep and wake electroencephalography (EEG) patterns during 48 continuous hours of baseline recordings in a knock‐in mouse line that expresses the human SCN1A GEFS+ mutation R1648H (RH mutants). We also characterized the sleep–wake pattern following 6 h of sleep deprivation.

Key Findings

Immunohistochemistry revealed broad expression of Scn1a in the neocortex, hippocampus, hypothalamus, thalamic reticular nuclei, dorsal raphe nuclei, pedunculopontine, and laterodorsal tegmental nuclei. Co‐localization between Scn1a immunoreactivity and critical cell types within these regions was also observed. EEG analysis under baseline conditions revealed increased wakefulness and reduced non–rapid eye movement (NREM) and rapid eye movement (REM) sleep amounts during the dark phase in the RH mutants, suggesting a sleep deficit. Nevertheless, the mutants exhibited levels of NREM and REM sleep that were generally similar to wild‐type littermates during the recovery period following 6 h of sleep deprivation.

Significance

These results establish a direct role for SCN1A in the regulation of sleep and suggest that patients with SCN1A mutations may experience chronic alterations in sleep, potentially leading to negative outcomes over time. In addition, the expression of Scn1a in specific cell types/brain regions that are known to play critical roles in seizure generation and sleep now provides a mechanistic basis for the clinical features (seizures and sleep abnormalities) associated with human SCN1A mutations.
The effects of therapeutic concentrations of gentamicin, amikacin and hyaluronic acid on cultured bone marrow‐derived equine mesenchymal stem cells
Authors: Bohannon L. K. , Owens S. D. , Walker N. J. , Carrade D. D. , Galuppo L. D. , Borjesson D. L.
Published: January 2013

Reasons for performing study

Joint inflammation and septic arthritis are both potential complications of intra‐articular injections of bone marrow‐derived mesenchymal stem cells (BM‐MSCs). Clinicians may prophylactically co‐inject BM‐MSCs admixed with either antimicrobials or hyaluronic acid; however, the effect of these agents on cultured BM‐MSCs is unknown.

Objective

To determine the effects of therapeutic levels of gentamicin, amikacin and hyaluronic acid on cultured equine BM‐MSCs in vitro.

Study design

In vitro experimental study.

Methods

Equine BM‐MSCs from 4 healthy mature horses were isolated. Cultured BM‐MSCs from each donor were incubated with gentamicin (150 mg), amikacin (250 mg), hyaluronic acid (22 mg) or 1% penicillin/streptomycin (control) under sterile conditions. Mesenchymal stem cells viability, proliferation, mediator secretion and culture media pH were measured.

Results

Incubation of BM‐MSCs with gentamicin resulted in >95% MSC death after 45 min, and incubation of BM‐MSCs with amikacin resulted in >95% MSC death after 2 h. Incubation of BM‐MSCs with hyaluronic acid or penicillin/streptomycin (control) for up to 6 h resulted in sustained BM‐MSC viability of 80% and >93%, respectively. All additives resulted in decreased media pH in the first minute; however, the pH then remained constant over the 6 h incubation period. No significant differences in BM‐MSC proliferation or mediator secretion between the penicillin/streptomycin (control) and cells treated with hyaluronic acid were observed.

Conclusion

Therapeutic concentrations of aminoglycoside antimicrobials are toxic to cultured equine BM‐MSCs. The effects of hyaluronic acid on cultured MSC viability, proliferation and mediator secretion are minimal.

Potential relevance

Based on these findings, the mixing of aminoglycoside antimicrobials and cultured equine BM‐MSCs prior to therapeutic use is not recommended.
Detection of A/B toxin and isolation of Clostridium difficile and Clostridium perfringens from foals
Authors: Silva R. O. S. , Ribeiro M. G. , Palhares M. S. , Borges A. S. , Maranhão R. P. A. , Silva M. X. , Lucas T. M. , Olivo G. , Lobato F. C. F.
Published: January 2013

Reasons for performing the study

Toxin detection and screening could contribute to knowledge of the transmission patterns, risk factors and epidemiology of Clostridium difficile and Clostridium perfringens.

Objective

To isolate C. difficile and C. perfringens and to detect A/B toxins in faecal samples from diarrhoeic and nondiarrhoeic foals.

Study design

Cross‐sectional observational study.

Methods

A total of 153 samples from foals were collected: 139 samples from farms and 14 samples from diarrhoeic foals admitted to a veterinary hospital. The A/B toxins were detected by cytotoxicity assay. All suspected colonies of C. perfringens were subjected to polymerase chain reaction for detection of the major toxin genes (α, β, ε and ι) and for detection of β2‐, NetB‐ and enterotoxin‐encoding genes. Furthermore, C. difficile and C. perfringens isolates were evaluated for in vitro antimicrobial susceptibility.

Results

Seven of 153 (4.6%) samples, all from diarrhoeic foals, were positive for C. difficile A/B toxin. Of these, 5 of 14 (35.7%) were from hospitalised foals, and only 2 of 63 (3.2%) diarrhoeic foal samples were from farms (P = 0.002). Clostridium perfringens was isolated from 31 (20.3%) foals, of which 21 of 76 (27.6%) were diarrhoeic and 10 of 76 (13.2%) were nondiarrhoeic, demonstrating a difference between these 2 groups (P = 0.045). Only 4 strains were positive for the β2‐encoding gene (cpb2). All C. difficile and C. perfringens isolates were susceptible to metronidazole and vancomycin.

Conclusions

The present report highlights the need for laboratory diagnostics to differentiate C. difficile‐associated infection in foals from other causes of diarrhoea to facilitate adequate antimicrobial therapy.

Potential relevance

More studies are needed to clarify the role of C. perfringens as a primary agent of diarrhoea in foals.
Multiple TSC22D4 iso‐/phospho‐glycoforms display idiosyncratic subcellular localizations and interacting protein partners
Authors: Canterini Sonia , Carletti Valentina , Nusca Stefania , Mangia Franco , Fiorenza Maria Teresa
Published: January 2013

Proteins of the TSC22 domain (TSC22D) family, including TSC22D1 and TSC22D4, play pivotal roles in cell proliferation, differentiation and apoptosis, interacting with other factors in a still largely unknown manner. This study explores this issue by biochemically characterizing various TSC22D4 forms (both iso‐ and glyco‐phospho‐, namely the splice variants 42 and 55 kDa and the post‐translationally modified 67 and 72 kDa forms) and their subcellular localization and protein partners during cerebellar granule neuron (CGN) differentiation. The TSC22D4‐42 form is mostly cytosolic, and is the only TSC22D4 form that associates with TSC22D1.2 in undifferentiated but not differentiated CGNs. In contrast, TSC22D4‐55 is prominently associated with the nuclear matrix in differentiated but not undifferentiated CGNs. As for TSC22D4‐67, it is localized in the cytosol and nuclei of undifferentiated CGNs and enters mitochondria of differentiated CGNs, associating with apoptosis‐inducing factor. TSC22D4‐72 is modified by O‐linked beta‐N‐acetylglucosamine (O‐GlcNAcylated) and phosphorylated and is always associated with chromatin irrespective of CGN differentiation. The various subcellular localization patterns and interacting protein partners of TSC22D4 forms during CGN differentiation suggest the existence of form‐specific function(s) and provide a novel framework to further investigate the biological functions of TSC22D proteins.

Structured digital abstract

AIF and TSC22D4 colocalize by cosedimentation (View interaction).

TSC22D1 physically interacts with TSC22D4 by anti bait coimmunoprecipitation (View Interaction: 1, 2).

TSC22D4 physically interacts with AIF by anti bait coimmunoprecipitation (View Interaction: 1, 2).

AIF and TSC22D4 colocalize by cosedimentation (View interaction).
Caspase‐dependent cleavage of the mono‐ADP‐ribosyltransferase ARTD10 interferes with its pro‐apoptotic function
Authors: Herzog Nicolas , Hartkamp Jörg D. H. , Verheugd Patricia , Treude Fabian , Forst Alexandra H. , Feijs Karla L. H. , Lippok Barbara E. , Kremmer Elisabeth , Kleine Henning , Lüscher Bernhard
Published: January 2013

ADP‐ribosylation is a post‐translational modification that regulates various physiological processes, including DNA damage repair, gene transcription and signal transduction. Intracellular ADP‐ribosyltransferases (ARTDs or PARPs) modify their substrates either by poly‐ or mono‐ADP‐ribosylation. Previously we identified ARTD10 (formerly PARP10) as a mono‐ADP‐ribosyltransferase, and observed that exogenous ARTD10 but not ARTD10‐G888W, a catalytically inactive mutant, interferes with cell proliferation. To expand on this observation, we established cell lines with inducible ARTD10 or ARTD10‐G888W. Consistent with our previous findings, induction of the wild‐type protein but not the mutant inhibited cell proliferation, primarily by inducing apoptosis. During apoptosis, ARTD10 itself was targeted by caspases. We mapped the major cleavage site at EIAMD406↓S, a sequence that was preferentially recognized by caspase–6. Caspase‐dependent cleavage inhibited the pro‐apoptotic activity of ARTD10, as ARTD10(1–406) and ARTD10(407–1025), either alone or together, were unable to induce apoptosis, despite catalytic activity of the latter. Deletion of the N–terminal RNA recognition motif in ARTD10(257–1025) also resulted in loss of pro‐apoptotic activity. Thus our findings indicate that the RNA recognition motif contributes to the pro‐apoptotic effect, together with the catalytic domain. We suggest that these two domains must be physically linked to stimulate apoptosis, possibly targeting ARTD10 through the RNA recognition motif to specific substrates that control cell death. Moreover, we established that knockdown of ARTD10 reduced apoptosis in response to DNA‐damaging agents. Together, these findings indicate that ARTD10 is involved in the regulation of apoptosis, and that, once apoptosis is activated, ARTD10 is cleaved as part of negative feedback regulation.

Structured digital abstract

Caspase-8 cleaves ARTD10 by protease assay (View interaction)

Caspase-6 cleaves ARTD10 by protease assay (View interaction)
Fatigue behaviour of die‐casting aluminum alloy suspension arms for scooters
Authors: BEGHINI M. , BERTINI L. , ROSELLINI W.
Published: January 2013

The aim of the paper is at qualifying a methodology for the fatigue life assessment of structural components obtained by die‐casting for vehicle applications. Full‐scale fatigue tests were conducted on the back suspension arms of mid‐size scooters. Two loading conditions, i.e. bending and combined bending plus torsion, were considered as representative of typical operating conditions. Fatigue tests showed that the locations of failure initiation is different for the two loading configurations. Material was characterized by means of small size standard specimens extracted from the components in order to be representative of the effective material conditions, particularly of the surface. Both static (tensile) and fatigue tests were conducted, making use of three different R‐ratios. A finite element (FEM) model of the suspension arm, representative of full‐scale test conditions was set‐up in order to interpret the tests. The sub‐modelling approach was adopted in order to get accurate evaluations of the stress–strain fields with reasonable computing resources and elaboration time. Combined elastic and elastic–plastic analyses were necessary to estimate the stress cycles in the regions critical for fatigue damage. Employing the material properties given by small‐size specimens and the proposed FE analysis technique, predictions of either the locations of failure initiation and the fatigue strength of the component were obtained, in quite good agreement with full‐scale tests.
The characteristics of an inclined crack in anisotropic paperboard under biaxial loading
Authors: AHMAD F. , PARK M. K.
Published: January 2013

In this paper, a fracture mechanics method was applied for the evaluation of crack behaviour in anisotropic paperboard subjected to biaxial uniform loading. The experiment was performed to determine the crack propagation angle and the fracture strength of paperboard under biaxial loading with the cruciform specimen optimized by FEM simulation. The effects of biaxial loads on the critical stress ratio and crack propagation angle for various inclination angles were investigated. The experimental results were compared with theoretical results, which were calculated by using the Normal Stress Ratio Criteria. The experimental results for crack propagation angle and critical stress show good agreement with theoretical results.