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We derive new QCD sum rules for B→ D and B→ D* form factors. The underlying correlation functions are expanded near the light-cone in terms of B-meson distribution amplitudes defined in HQET, whereas the c-quark mass is kept finite. The leading-order contributions of two- and three-particle distribution amplitudes are taken into account. From the resulting light-cone sum rules we calculate all B→ D(*) form factors in the region of small momentum transfer (maximal recoil). In the infinite heavy-quark mass limit the sum rules reduce to a single expression for the Isgur–Wise function. We compare our predictions with the form factors extracted from experimental B→(*) l ν l decay rates fitted to dispersive parameterizations. [ABSTRACT FROM AUTHOR]

To date, the investigation of the antisaccade task, simple test of "executive functions," in children with ADHD has yielded inconsistent results. The present study aimed at contributing to this issue by (a) the investigation of a large sample of carefully diagnosed ADHD patients aged 7-15 years, and (b) the analyses of differential age effects in patients and controls. Healthy control children were pairwise matched with patients (N = 46; age = 136 ± 24 months) for age and gender, and did not significantly differ in IQ. Horizontal pro- and antisaccades were elicited under the 200-ms gap and overlap conditions (blocks of 100 trials each). Overall, patients exhibited (a) augmented pro- and antisaccadic reaction times, (b) augmented error rates (antitasks), (c) augmented proportions of early responses (all conditions), and (d) reduced proportions of express saccades under the prosaccadic gap condition.The greater decline in anti-as compared to pro-SRT with increasing age that characterized controls was missing in patients. Confirming Barkley's (1997) neuropsychological theory of ADHD, these results altogether point to alterations in "executive functions" in ADHD patients that are presumably supported by frontal lobe structures, in particular the lateral prefrontal cortex nd the frontal eye fields. [ABSTRACT FROM AUTHOR]

Rheo-optics is a method that allows the analysis of optical properties, like birefringence and dichroism under steady and oscillatory shear. It is possible to correlate macroscopic mechanical responses with induced microscopic changes in the material. We describe how this method was improved several fold and implemented on a commercially available setup. However, the here presented ideas are applicable to any rheo-optical setup, based on modulation of the laser light. Additionally it does not need a lock-in amplifier and therefore reduces the costs of the setup.

Abstract Background Genome-wide methylation profiling has led to more comprehensive insights into gene regulation mechanisms and potential therapeutic targets. Illumina Human Methylation BeadChip is one of the most commonly used genome-wide methylation platforms. Similar to other microarray experiments, methylation data is susceptible to various technical artifacts, particularly batch effects. To date, little attention has been given to issues related to normalization and batch effect correction for this kind of data. Methods We evaluated three common normalization approaches and investigated their performance in batch effect removal using three datasets with different degrees of batch effects generated from HumanMethylation27 platform: quantile normalization at average β value (QNβ); two step quantile normalization at probe signals implemented in "lumi" package of R (lumi); and quantile normalization of A and B signal separately (ABnorm). Subsequent Empirical Bayes (EB) batch adjustment was also evaluated. Results Each normalization could remove a portion of batch effects and their effectiveness differed depending on the severity of batch effects in a dataset. For the dataset with minor batch effects (Dataset 1), normalization alone appeared adequate and "lumi" showed the best performance. However, all methods left substantial batch effects intact in the datasets with obvious batch effects and further correction was necessary. Without any correction, 50 and 66 percent of CpGs were associated with batch effects in Dataset 2 and 3, respectively. After QNβ, lumi or ABnorm, the number of CpGs associated with batch effects were reduced to 24, 32, and 26 percent for Dataset 2; and 37, 46, and 35 percent for Dataset 3, respectively. Additional EB correction effectively removed such remaining non-biological effects. More importantly, the two-step procedure almost tripled the numbers of CpGs associated with the outcome of interest for the two datasets. Conclusion Genome-wide methylation data from Infinium Methylation BeadChip can be susceptible to batch effects with profound impacts on downstream analyses and conclusions. Normalization can reduce part but not all batch effects. EB correction along with normalization is recommended for effective batch effect removal.

Abstract Background Recent studies have demonstrated the consistently high diagnostic and prognostic value of dobutamine stress cardiovascular magnetic resonance (DCMR). The value of DCMR for clinical decision making still needs to be defined. Hence, the purpose of this study was to assess the utility of DCMR regarding clinical management of patients with suspected and known coronary artery disease (CAD) in a routine setting. Methods and Results We prospectively performed a standard DCMR examination in 1532 consecutive patients with suspected and known CAD. Patients were stratified according to the results of DCMR: DCMR-positive patients were recommended to undergo invasive coronary angiography and DCMR-negative patients received optimal medical treatment. Of 609 (40%) DCMR-positive patients coronary angiography was performed in 478 (78%) within 90 days. In 409 of these patients significant coronary stenoses ≥50% were present (positive predictive value 86%). Of 923 (60%) DCMR-negative patients 833 (90%) received optimal medical therapy. During a mean follow-up period of 2.1 ± 0.8 years (median: 2.1 years, interquartile range 1.5 to 2.7 years) 8 DCMR-negative patients (0.96%) sustained a cardiac event. In 131 DCMR-positive patients who did not undergo invasive angiography, 20 patients (15%) suffered cardiac events. In 90 DCMR-negative patients (10%) invasive angiography was performed within 2 years (range 0.01 to 2.0 years) with 56 patients having coronary stenoses ≥50%. Conclusion In a routine setting DCMR proved a useful arbiter for clinical decision making and exhibited high utility for stratification and clinical management of patients with suspected and known CAD.

Abstract Background Stromal signalling increases the lateral cell adhesions of prostate epithelial cells grown in 3D culture. The aim of this study was to use microarray analysis to identify significant epithelial signalling pathways and genes in this process. Methods Microarray analysis was used to identify genes that were differentially expressed when epithelial cells were grown in 3D Matrigel culture with stromal co-culture compared to without stroma. Two culture models were employed: primary epithelial cells (ten samples) and an epithelial cell line (three experiments). A separate microarray analysis was performed on each model system and then compared to identify tissue-relevant genes in a cell line model. Results TGF beta signalling was significantly ranked for both model systems and in both models the TGF beta signalling gene SOX4 was significantly down regulated. Analysis of all differentially expressed genes to identify genes that were common to both models found several morphology related gene clusters; actin binding (DIAPH2, FHOD3, ABLIM1, TMOD4, MYH10), GTPase activator activity (BCR, MYH10), cytoskeleton (MAP2, MYH10, TMOD4, FHOD3), protein binding (ITGA6, CD44), proteinaceous extracellular matrix (NID2, CILP2), ion channel/ ion transporter activity (CACNA1C, CACNB2, KCNH2, SLC8A1, SLC39A9) and genes associated with developmental pathways (POFUT1, FZD2, HOXA5, IRX2, FGF11, SOX4, SMARCC1). Conclusions In 3D prostate cultures, stromal cells increase lateral epithelial cell adhesions. We show that this morphological effect is associated with gene expression changes to TGF beta signalling, cytoskeleton and anion activity.

Abstract Background Adenosine first pass perfusion cardiovascular magnetic resonance (CMR) yields excellent results for the detection of significant coronary artery disease (CAD). In patients with coronary artery bypass grafts (CABG) the kinetics of a contrast bolus may by altered only due to different distances through the bypass grafts compared to native vessels, thereby possibly imitating a perfusion defect. The aim of the study was to evaluate semiquantitative perfusion parameters in order to assess possible differences in epicardial contrast kinetics in areas supplied by native coronaries and CABG, both without significant stenosis. Methods Twenty patients with invasive exclusion of significant CAD (control group) and 38 patients with CABG without angiographically significant (≥50%) stenosis in unbypassed coronaries or grafts were retrospectively included in the study. They underwent adenosine first pass (0.05 mmol/kg Gd-DTPA) perfusion (3 short axis views/heart beat) and late gadolinium enhancement (LGE) imaging 1 day before invasive coronary angiography. Areas perfused by native coronaries and/or the different bypasses were identified in X-ray angiography using the 16 segment model. In each of these areas upslope and maximal signal intensity (SImax) relative to the left ventricular parameters, time to 50% maximal signal intensity (TSI50%max) and time to maximal signal intensity (TSImax) were calculated. Results In areas perfused by coronary arteries with bypasses compared to native coronaries relative upslope and relative SImax did not show a significant difference. TSI50%max and TSImax in native coronaries and bypasses were 7.2s ± 1.9s vs. 7.5s ± 1.9s (p < 0.05) and 12.6s ± 3.0s vs. 13.1s ± 3.0s (p < 0.05), respectively. The delay in Tmax resulted in a significant (p < 0.05) delay of 0.5 ± 1.1 heart beats (=images) when adjusted to the heart rate. Differences in time were most pronounced in areas perfused by left internal mammary artery grafts rather than by venous CABG, but were also present between native vessel territories in patients without CAD, albeit with smaller variability. Conclusion Adenosine perfusion CMR in patients post CABG may be associated with a short delay in contrast arrival. However, once the contrast is in the myocardium there is similar wash-in kinetics and peak enhancement. Therefore, since the delay is only short, the possibly differing contrast kinetics through grafts and native vessels does not seem to be a limiting factor for the accuracy of first pass adenosine perfusion in patients post CABG.

Abstract Background Wearing shoes of insufficient length during childhood has often been cited as leading to deformities of the foot, particularly to the development of hallux valgus disorders. Until now, these assumptions have not been confirmed through scientific research. This study aims to investigate whether this association can be statistically proven, and if children who wear shoes of insufficient length actually do have a higher risk of a more pronounced lateral deviation of the hallux. Methods 858 pre-school children were included in the study. The study sample was stratified by sex, urban/rural areas and Austrian province. The hallux angle and the length of the feet were recorded. The inside length of the children's footwear (indoor shoes worn in pre-school and outdoor shoes) were assessed. Personal data and different anthropometric measurements were taken. The risk of hallux valgus deviation was statistically tested by a stepwise logistic regression analysis and the relative risk (odds ratio) for a hallux angle ≥ 4 degrees was calculated. Results Exact examinations of the hallux angle could be conducted on a total of 1,579 individual feet. Only 23.9% out of 1,579 feet presented a straight position of the great toe. The others were characterized by lateral deviations (valgus position) at different degrees, equalling 10 degrees or greater in 14.2% of the children's feet. 88.8% of 808 children examined wore indoor footwear that was of insufficient length, and 69.4% of 812 children wore outdoor shoes that were too short. A significant relationship was observed between the lengthwise fit of the shoes and the hallux angle: the shorter the shoe, the higher the value of the hallux angle. The relative risk (odds ratio) of a lateral hallux deviation of ≥ 4 degrees in children wearing shoes of insufficient length was significantly increased. Conclusions There is a significant relationship between the hallux angle in children and footwear that is too short in length. The fact that the majority of the children examined were wearing shoes of insufficient length makes the issue particularly significant. Our results emphasize the importance of ensuring that children's footwear fits properly.

Abstract Background We report age-dependent penetrance estimates for leucine-rich repeat kinase 2 (LRRK2)-related Parkinson's disease (PD) in a large sample of familial PD. The most frequently seen LRRK2 mutation, Gly2019Ser (G2019S), is associated with approximately 5 to 6% of familial PD cases and 1 to 2% of idiopathic cases, making it the most common known genetic cause of PD. Studies of the penetrance of LRRK2 mutations have produced a wide range of estimates, possibly due to differences in study design and recruitment, including in particular differences between samples of familial PD versus sporadic PD. Methods A sample, including 903 affected and 58 unaffected members from 509 families ascertained for having two or more PD-affected members, 126 randomly ascertained PD patients and 197 controls, was screened for five different LRRK2 mutations. Penetrance was estimated in families of LRRK2 carriers with consideration of the inherent bias towards increased penetrance in a familial sample. Results Thirty-one out of 509 families with multiple cases of PD (6.1%) were found to have 58 LRRK2 mutation carriers (6.4%). Twenty-nine of the 31 families had G2019S mutations while two had R1441C mutations. No mutations were identified among controls or unaffected relatives of PD cases. Nine PD-affected relatives of G2019S carriers did not carry the LRRK2 mutation themselves. At the maximum observed age range of 90 to 94 years, the unbiased estimated penetrance was 67% for G2019S families, compared with a baseline PD risk of 17% seen in the non-LRRK2-related PD families. Conclusion Lifetime penetrance of LRRK2 estimated in the unascertained relatives of multiplex PD families is greater than that reported in studies of sporadically ascertained LRRK2 cases, suggesting that inherited susceptibility factors may modify the penetrance of LRRK2 mutations. In addition, the presence of nine PD phenocopies in the LRRK2 families suggests that these susceptibility factors may also increase the risk of non-LRRK2-related PD. No differences in penetrance were found between men and women, suggesting that the factors that influence penetrance for LRRK2 carriers are independent of the factors which increase PD prevalence in men.

Abstract Background Cardiovascular Magnetic Resonance (CMR) imaging offers methods for the detection of ischemia and myocardial infarction as well as visualization of the coronary arteries (MRCA). However, a direct comparison of adenosine perfusion (PERF), late gadolinium enhancement (LGE) and MRCA or the results of their combination has not been performed. Aim of the study was to evaluate the feasibility/diagnostic performance of rest/stress perfusion, late gadolinium enhancement and MRCA and their combination in patients with suspected coronary artery disease (CAD) in comparison to invasive angiography. Methods Fifty-four patients (60 ± 10 years, 35 men, CAD 48%) underwent CMR including MRCA (steady state free precession, navigator whole heart approach, spatial resolution 0.7 × 0.7 × .0.9 mm, trigger delay and temporal resolution adjusted individually), stress PERF (adenosine 140 μg/min/kg), rest PERF (SSFP, 3 short axis, 1 saturation prepulse per slice) and LGE (3D inversion recovery technique) using Gd-BOPTA. Images were analyzed visually. Stenosis >50% in invasive angiography was considered significant. Results Mean study time was 68 ± 11 minutes. Sensitivity for PERF, LGE, MRCA and the combination of PERF/LGE and PERF/LGE/MRCA was 87%, 50%, 91%, 88% and 92%, respectively and specificity 88%, 96%, 46%, 88% and 56%, respectively. If image quality of MRCA was excellent (n = 18) the combination of MRCA/PERF/LGE yield a sensitivity of 86% and specificity of 91%. However, no test or combination improved diagnostic performance significantly compared to PERF alone. Conclusion In patients with CAD, the combination of stress PERF, LGE and MRCA is feasible. When compared to invasive angiography, adenosine stress perfusion outperforms CMR coronary angiography in direct comparison and yields the best results with non-significant improvement in combination with LGE and significant deterioration in combination with MRCA. MRCA may be of additional value only in a minority of patients with excellent image quality.

Abstract Background Herpes simplex virus type 2 (HSV-2) is a major cofactor of human immunodeficiency virus type 1 (HIV-1) sexual acquisition and transmission. In the present study, we investigated whether HIV-1 and HSV-2 may interact at the cellular level by forming HIV-1 hybrid virions pseudotyped with HSV-2 envelope glycoproteins, as was previously reported for HSV type 1. Methods We evaluated in vitro the production of HSV-2/HIV-1 pseudotypes in mononuclear CEM cells and epithelial HT29 and P4P cells. We analyzed the incorporation into the HIV-1 membrane of HSV-2 gB and gD, two major HSV-2 glycoproteins required for HSV-2 fusion with the cell membrane, in co-infected cells and in HIV-1-infected P4P cells transfected by plasmids coding for gB or gD. Results We show that HSV-2 and HIV-1 co-replicated in dually infected cells, and gB and gD were co-localized with gp160. However, HIV-1 particles, produced in HIV-1-infected cells expressing gB or gD after transfection or HSV-2 superinfection, did not incorporate either gB or gD in the viral membrane, and did not have the capacity to infect cells normally non-permissive for HIV-1, such as epithelial cells. Conclusion Our results do not support the hypothesis of HSV-2/HIV-1 pseudotype formation and involvement in the synergistic genital interactions between HIV-1 and HSV-2.

Black and African American men who have sex with men (Black MSM) experience the greatest proportion of new HIV infections in the United States. To address this challenge, a better understanding of the HIV environment riskscape including both risk and resilience factors is warranted among Black MSM. Research indicates that stress is associated with increased HIV sexual risk behaviors. Further, behavioral factors such as serosorting and community level factors including social support and community connection are resilience factors that protect against risk behaviors. The present study examines whether everyday stress is associated with HIV sexual risk behavior, as well as the role of risk and resilience factors among 125 Black MSM recruited in the Real Talk study. The Real Talk project examined the relationships between resilience, HIV risk behaviors, and HIV prevention strategy among a sample of Black MSM. Using generalized estimating equations, our results indicate a positive association between everyday stress and engaging in condomless anal intercourse only after adjusting for risk, resilience, and correlate variables. Similarly, having multiple sex partners and using substances during sex also show positive associations with condomless anal intercourse. Resilience factors of engaging in serosorting and being connected to both the Black and gay communities were negatively associated with condomless anal intercourse. Future prevention research and programming should focus on both risk and resilience factors to mitigate new HIV infections among Black MSM., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In 2015, the number of infants with congenital malformations (CMs) per 100 000 live births (LBs) was 2368 (7.6%) worldwide, of whom 10.6% died in the first year of life, 43% due to malformations of the circulatory system (MCSs), a scenario similar to what occurs in Brazil., Objective: To assess, per Brazilian macroregion, whether diagnosis of MCS at birth and death due to MCS in the first year of life associate with human development index (HDI) and with technological and human resources., Methods: Ecological study including data available in 2000-2015. Data of LBs, deaths and availability of echocardiography devices were obtained from the DATASUS website. The HDI was obtained from the Atlas of Human Development in Brazil, while other variables were obtained from medical demographic data. Correlation measures between the variables were performed using the Kendall index., Results: The CM rate was 660.8/100 000 LBs, of which 18 444 were due to MCS (diagnosis rate, 38.55/100 000 LBs). Of all Brazilian macroregions, the Southern and Southeastern regions, with the highest HDI values and resources, had the highest MCS diagnosis rates (56.94/100 000 and 62.83/100 000 LBs, respectively). The Northern and Northeastern regions, with the lowest HDI values and resources, had the lowest MCS diagnosis rates (9.77/100 000 and 13.43/100 000 LBs, respectively). The MCS diagnosis rate was 6.4-fold higher in the Southeastern region as compared to the Northern region, but mortality rates were similar in both regions., Conclusion: Of the CMs, the MCS accounted for the highest number of deaths in children under the age of 1 year in Brazil.