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In microarray data analysis, we are often required to combine several dependent partial test results. To overcome this, many suggestions have been made in previous literature; Tippett’s test and Fisher’s omnibus test are most popular. Both tests have known null distributions when the partial tests are independent. However, for dependent tests, their (even, asymptotic) null distributions are unknown and additional numerical procedures are required. In this paper, we revisited Stouffer’s test based on z-scores and showed its advantage over the two aforementioned methods in the analysis of large-scale microarray data. The combined statistic in Stouffer’s test has a normal distribution with mean 0 from the normality of the z-scores. Its variance can be estimated from the scores of genes in the experiment without an additional numerical procedure. We numerically compared the errors of Stouffer’s test and the two p-value based methods, Tippett’s test and Fisher’s omnibus test. We also analyzed our microarray data to find differentially expressed genes by non-genotoxic and genotoxic carcinogen compounds. Both numerical study and the real application showed that Stouffer’s test performed better than Tippett’s method and Fisher’s omnibus method with additional permutation steps. [ABSTRACT FROM AUTHOR]

Background: Despite the popularity of modern medicine, medicinal plants remain a cornerstone of treatment for numerous diseases, particularly among ethnic groups and tribal communities around the globe. Ethnomedicine offers advantages such as ease of use, convenience, and economic benefits. Medicinal plant knowledge within Bulang ethnic community of southwest China is a valuable complement to Chinese ethnomedicine systems. Accumulated medical knowledge is due to the extensive length of occupation by Bulang People, considered the earliest inhabitants of Xishuangbanna; this has resulted in the development of various traditional treatment methods with local characteristics and unique curative effects. Therefore, there is exceeding value in exploring the medical knowledge of Bulang. Methods: A total of 175 local informants participated in the interviews and distribution of questionnaires in 10 Bulang villages in Menghai County, Xishuangbanna Prefecture, Yunnan Province, China. We documented the community of Bulang's use of medicinal herbs, and we used both the informant consensus factor (ICF) and use value (UV) methodologies to analyze the data. Furthermore, we conducted a comparative study to explore the potential of Bulang traditional medicine by comparing it to traditional Dai medicine. Results: The study recorded 60 medicinal plant species belonging to 41 families and 59 genera, including 22 species of herb, 22 species of shrub, nine species of trees, and seven species of liana. Araceae, Compositae, Lamiaceae and Leguminosae were found to have the highest number of species. The affordability and cultural heritage of Bulang medicine make it advantageous, Investigated Informants report that increased usage of Western medicine (88%), less availability of herbal medicine (95.43%), and the reduction in medicinal plant resources (80.57%) pose significant threats to Bulang medicine. All Bulang medicinal plants are naturally grown, with only 22 per cent being cultivated. Camellia sinensis (0.94) and Zingiber officinale (0.89) showed the highest UV values, while the function of Phyllanthus emblica L. and Houttuynia cordata Thunb. were also noted. The ICF revealed digestive system related diseases were the most commonly treated, with conditions of the motor system using the highest number of plant species. Finally, a comparison with traditional Dai medicine determined that 22 plants (36.67%) of the 60 surveyed had higher medicinal value in Bulang medicine. Conclusion: Bulang communities primarily source medicinal plants from the wild. Should environmental damage lead to the extinction of these medicinal plants, it could result in a shift toward modern Western medicine as a preferred medical treatment. Bulang ethnomedicine is a vital supplement to China's traditional medicine, particularly aspects of ethnic medicine relevant to daily life. Future research should emphasize inter-ethnic medical studies to reveal the untapped potential of medicinal plants. [ABSTRACT FROM AUTHOR]

During the last decade markerless motion capture techniques have gained an increasing interest in the biomechanics community. In the clinical field, however, the application of markerless techniques is still debated. This is mainly due to a limited number of papers dedicated to the comparison with the state of the art of marker based motion capture, in term of repeatability of the three dimensional joints' kinematics. In the present work the application of markerless technique to data acquired with a marker-based system was investigated. All videos and external data were recorded with the same motion capture system and included the possibility to use markerless and marker-based methods simultaneously. Three dimensional markerless joint kinematics was estimated and compared with the one determined with traditional marker based systems, through the evaluation of root mean square distance between joint rotations. In order to compare the performance of markerless and marker-based systems in terms of clinically relevant joint angles estimation, the same anatomical frames of reference were defined for both systems. Differences in calibration and synchronization of the cameras were excluded by applying the same wand calibration and lens distortion correction to both techniques. Best results were achieved for knee flexion-extension angle, with an average root mean square distance of 11.75 deg, corresponding to 18.35% of the range of motion. Sagittal plane kinematics was estimated better than on the other planes also for hip and ankle (root mean square distance of 17.62 deg e.g. 44.66%, and 7.17 deg e.g. 33.12%), meanwhile estimates for hip joint were the most incorrect. This technique enables users of markerless technology to compare differences with marker-based in order to define the degree of applicability of markerless technique. [ABSTRACT FROM AUTHOR]

Public health surveillance systems provide valuable data for reliable predication of future epidemic events. This paper describes a study that used nine types of infectious disease data collected through a national public health surveillance system in mainland China to evaluate and compare the performances of four time series methods, namely, two decomposition methods (regression and exponential smoothing), autoregressive integrated moving average (ARIMA) and support vector machine (SVM). The data obtained from 2005 to 2011 and in 2012 were used as modeling and forecasting samples, respectively. The performances were evaluated based on three metrics: mean absolute error (MAE), mean absolute percentage error (MAPE), and mean square error (MSE). The accuracy of the statistical models in forecasting future epidemic disease proved their effectiveness in epidemiological surveillance. Although the comparisons found that no single method is completely superior to the others, the present study indeed highlighted that the SVMs outperforms the ARIMA model and decomposition methods in most cases. [ABSTRACT FROM AUTHOR]

Accurate and robust brain extraction is a critical step in most neuroimaging analysis pipelines. In particular, for the large-scale multi-site neuroimaging studies involving a significant number of subjects with diverse age and diagnostic groups, accurate and robust extraction of the brain automatically and consistently is highly desirable. In this paper, we introduce population-specific probability maps to guide the brain extraction of diverse subject groups, including both healthy and diseased adult human populations, both developing and aging human populations, as well as non-human primates. Specifically, the proposed method combines an atlas-based approach, for coarse skull-stripping, with a deformable-surface-based approach that is guided by local intensity information and population-specific prior information learned from a set of real brain images for more localized refinement. Comprehensive quantitative evaluations were performed on the diverse large-scale populations of ADNI dataset with over 800 subjects (55∼90 years of age, multi-site, various diagnosis groups), OASIS dataset with over 400 subjects (18∼96 years of age, wide age range, various diagnosis groups), and NIH pediatrics dataset with 150 subjects (5∼18 years of age, multi-site, wide age range as a complementary age group to the adult dataset). The results demonstrate that our method consistently yields the best overall results across almost the entire human life span, with only a single set of parameters. To demonstrate its capability to work on non-human primates, the proposed method is further evaluated using a rhesus macaque dataset with 20 subjects. Quantitative comparisons with popularly used state-of-the-art methods, including BET, Two-pass BET, BET-B, BSE, HWA, ROBEX and AFNI, demonstrate that the proposed method performs favorably with superior performance on all testing datasets, indicating its robustness and effectiveness. [ABSTRACT FROM AUTHOR]

In this paper we provide normative data along multiple cognitive and affective variable dimensions for a set of 110 sounds, including living and manmade stimuli. Environmental sounds are being increasingly utilized as stimuli in the cognitive, neuropsychological and neuroimaging fields, yet there is no comprehensive set of normative information for these type of stimuli available for use across these experimental domains. Experiment 1 collected data from 162 participants in an on-line questionnaire, which included measures of identification and categorization as well as cognitive and affective variables. A subsequent experiment collected response times to these sounds. Sounds were normalized to the same length (1 second) in order to maximize usage across multiple paradigms and experimental fields. These sounds can be freely downloaded for use, and all response data have also been made available in order that researchers can choose one or many of the cognitive and affective dimensions along which they would like to control their stimuli. Our hope is that the availability of such information will assist researchers in the fields of cognitive and clinical psychology and the neuroimaging community in choosing well-controlled environmental sound stimuli, and allow comparison across multiple studies. [ABSTRACT FROM AUTHOR]

Graph theoretical approaches have successfully revealed abnormality in brain connectivity, in particular, for contrasting patients from healthy controls. Besides the group comparison analysis, a correlational study is also challenging. In studies with patients, for example, finding brain connections that indeed deepen specific symptoms is interesting. The correlational study is also beneficial since it does not require controls, which are often difficult to find, especially for old-age patients with cognitive impairment where controls could also have cognitive deficits due to normal ageing. However, one of the major difficulties in such correlational studies is too conservative multiple comparison correction. In this paper, we propose a novel method for identifying brain connections that are correlated with a specific cognitive behavior by employing cluster-based statistics, which is less conservative than other methods, such as Bonferroni correction, false discovery rate procedure, and extreme statistics. Our method is based on the insight that multiple brain connections, rather than a single connection, are responsible for abnormal behaviors. Given brain connectivity data, we first compute a partial correlation coefficient between every edge and the behavioral measure. Then we group together neighboring connections with strong correlation into clusters and calculate their maximum sizes. This procedure is repeated for randomly permuted assignments of behavioral measures. Significance levels of the identified sub-networks are estimated from the null distribution of the cluster sizes. This method is independent of network construction methods: either structural or functional network can be used in association with any behavioral measures. We further demonstrated the efficacy of our method using patients with subcortical vascular cognitive impairment. We identified sub-networks that are correlated with the disease severity by exploiting diffusion tensor imaging techniques. The identified sub-networks were consistent with the previous clinical findings having valid significance level, while other methods did not assert any significant findings. [ABSTRACT FROM AUTHOR]

Evidence of clinical utility is a key issue in translating pharmacogenomics into clinical practice. Appropriately designed randomized controlled trials generally provide the most robust evidence of the clinical utility, but often only data from a pharmacogenomic association study are available. This paper details a method for reframing the results of pharmacogenomic association studies in terms of the comparative treatment effect for a pharmacogenomic subgroup to provide greater insight into the likely clinical utility of a pharmacogenomic marker, its’ likely cost effectiveness, and the value of undertaking the further (often expensive) research required for translation into clinical practice. The method is based on the law of total probability, which relates marginal and conditional probability. It takes as inputs: the prevalence of the pharmacogenomic marker in the patient group of interest, prognostic effect of the pharmacogenomic marker based on observational association studies, and the unstratified comparative treatment effect based on one or more conventional randomized controlled trials. The critical assumption is that of exchangeability across the included studies. The method is demonstrated using a case study of cytochrome P450 (CYP) 2C19 genotype and the anti-platelet agent clopidogrel. Indirect subgroup analysis provided insight into relationship between the clinical utility of genotyping CYP2C19 and the risk ratio of cardiovascular outcomes between CYP2C19 genotypes for individuals using clopidogrel. In this case study the indirect and direct estimates of the treatment effect for the cytochrome P450 2C19 subgroups were similar. In general, however, indirect estimates are likely to have substantially greater risk of bias than an equivalent direct estimate. [ABSTRACT FROM AUTHOR]

Accurate incidence forecasting of infectious disease is critical for early prevention and for better government strategic planning. In this paper, we present a comprehensive study of different forecasting methods based on the monthly incidence of typhoid fever. The seasonal autoregressive integrated moving average (SARIMA) model and three different models inspired by neural networks, namely, back propagation neural networks (BPNN), radial basis function neural networks (RBFNN), and Elman recurrent neural networks (ERNN) were compared. The differences as well as the advantages and disadvantages, among the SARIMA model and the neural networks were summarized and discussed. The data obtained for 2005 to 2009 and for 2010 from the Chinese Center for Disease Control and Prevention were used as modeling and forecasting samples, respectively. The performances were evaluated based on three metrics: mean absolute error (MAE), mean absolute percentage error (MAPE), and mean square error (MSE). The results showed that RBFNN obtained the smallest MAE, MAPE and MSE in both the modeling and forecasting processes. The performances of the four models ranked in descending order were: RBFNN, ERNN, BPNN and the SARIMA model. [ABSTRACT FROM AUTHOR]

A variety of cardiac arrhythmias are initiated by a focal excitation that disrupts the regular beating of the heart. In some cases it is known that these excitations are due to calcium (Ca) release from the sarcoplasmic reticulum (SR) via propagating subcellular Ca waves. However, it is not understood what are the physiological factors that determine the timing of these excitations at both the subcellular and tissue level. In this paper we apply analytic and numerical approaches to determine the timing statistics of spontaneous Ca release (SCR) in a simplified model of a cardiac myocyte. In particular, we compute the mean first passage time (MFPT) to SCR, in the case where SCR is initiated by spontaneous Ca sparks, and demonstrate that this quantity exhibits either an algebraic or exponential dependence on system parameters. Based on this analysis we identify the necessary requirements so that SCR occurs on a time scale comparable to the cardiac cycle. Finally, we study how SCR is synchronized across many cells in cardiac tissue, and identify a quantitative measure that determines the relative timing of SCR in an ensemble of cells. Using this approach we identify the physiological conditions so that cell-to-cell variations in the timing of SCR is small compared to the typical duration of an SCR event. We argue further that under these conditions inward currents due to SCR can summate and generate arrhythmogenic triggered excitations in cardiac tissue. [ABSTRACT FROM AUTHOR]

Abstract The prevalence of pathological germline mutations in colorectal cancer has been widely studied, as germline mutations in the DNA mismatch repair genes hMLH1 and hMSH2 confer a high risk of colorectal cancer. However, because the sample size and population of previous studies are very different from each other, the conclusions still remain controversial. In this paper, Databases such as PubMed were applied to search for related papers. The data were imported into Comprehensive Meta-Analysis V2, which was used to estimate the weighted prevalence of hMLH1 and hMSH2 pathological mutations and compare the differences of prevalence among different family histories, ethnicities and related factors. This study collected and utilized data from 102 papers. In the Amsterdam-criteria positive group, the prevalence of pathological germline mutations of the hMLH1 and hMSH2 genes was 28.55% (95%CI 26.04%–31.19%) and 19.41% (95%CI 15.88%–23.51%), respectively, and the prevalence of germline mutations in hMLH1/hMSH2 was 15.44%/10.02%, 20.43%/13.26% and 15.43%/11.70% in Asian, American multiethnic and European/Australian populations, respectively. Substitution mutations accounted for the largest proportion of germline mutations (hMLH1: 52.34%, hMSH2: 43.25%). The total prevalence of mutations of hMLH1 and hMSH2 in Amsterdam-criteria positive, Amsterdam-criteria negative and sporadic colorectal cancers was around 45%, 25% and 15%, respectively, and there were no obvious differences in the prevalence of germline mutations among different ethnicities. [ABSTRACT FROM AUTHOR]

This paper aims to study the abnormal patterns of brain glucose metabolism co-variations in Alzheimer disease (AD) and Mild Cognitive Impairment (MCI) patients compared to Normal healthy controls (NC) using the Alzheimer Disease Neuroimaging Initiative (ADNI) database. The local cerebral metabolic rate for glucose (CMRgl) in a set of 90 structures belonging to the AAL atlas was obtained from Fluro-Deoxyglucose Positron Emission Tomography data in resting state. It is assumed that brain regions whose CMRgl values are significantly correlated are functionally associated; therefore, when metabolism is altered in a single region, the alteration will affect the metabolism of other brain areas with which it interrelates. The glucose metabolism network (represented by the matrix of the CMRgl co-variations among all pairs of structures) was studied using the graph theory framework. The highest concurrent fluctuations in CMRgl were basically identified between homologous cortical regions in all groups. Significant differences in CMRgl co-variations in AD and MCI groups as compared to NC were found. The AD and MCI patients showed aberrant patterns in comparison to NC subjects, as detected by global and local network properties (global and local efficiency, clustering index, and others). MCI network’s attributes showed an intermediate position between NC and AD, corroborating it as a transitional stage from normal aging to Alzheimer disease. Our study is an attempt at exploring the complex association between glucose metabolism, CMRgl covariations and the attributes of the brain network organization in AD and MCI. [ABSTRACT FROM AUTHOR]

A large number of nucleotide sequences of various pathogens are available in public databases. The growth of the datasets has resulted in an enormous increase in computational costs. Moreover, due to differences in surveillance activities, the number of sequences found in databases varies from one country to another and from year to year. Therefore, it is important to study resampling methods to reduce the sampling bias. A novel algorithm–called the closest-neighbor trimming method–that resamples a given number of sequences from a large nucleotide sequence dataset was proposed. The performance of the proposed algorithm was compared with other algorithms by using the nucleotide sequences of human H3N2 influenza viruses. We compared the closest-neighbor trimming method with the naive hierarchical clustering algorithm and -medoids clustering algorithm. Genetic information accumulated in public databases contains sampling bias. The closest-neighbor trimming method can thin out densely sampled sequences from a given dataset. Since nucleotide sequences are among the most widely used materials for life sciences, we anticipate that our algorithm to various datasets will result in reducing sampling bias. [ABSTRACT FROM AUTHOR]

Background: Environmental nontuberculous mycobacteria (NTM) are ubiquitous organisms with which humans commonly interact. The epidemiologic characteristics of NTM diseases including mortality rate and its associated factors remain largely unknown. In this study, we explored the geographical area of exposure and mortality and comorbid conditions of affected persons to determine environment, host, and host-pathogen interactive factors. Methods: We analyzed mortality related to nontuberculous mycobacterial infections from 1999 through 2010 by examining multiple-cause-of-death data from the National Center for Health Statistics. Among those who died with these diseases, we analyzed age-adjusted mortality rates, trends, associations with demographic variables, and comorbid conditions and correlated this information with similar data for tuberculosis-related mortality during the same time. Measurements and Mean Results: From 1999 through 2010, nontuberculous mycobacterial disease was reported as an immediate cause of death in 2,990 people in the United States with a combined overall mean age-adjusted mortality rate of 0.1 per 100,000 person-years. A significant increase in the number of NTM related deaths was seen from 1999 through 2010 (R2 = 0.72, p<0.0001), but it was not significant after adjustment for age. Persons aged 55 years and older, women, those living in Hawaii and Louisiana, and those of non-Hispanic, white ethnicity had higher mortality rates. Compared to tuberculosis-related mortality, chronic obstructive pulmonary disease, bronchiectasis, HIV, interstitial lung diseases, and tobacco use were significantly more common in persons with nontuberculous mycobacteria-related deaths. Conclusions: Nontuberculous mycobacteria-related death numbers are rising and are unevenly distributed. The strong association of nontuberculous mycobacterial disease with age suggests that its prevalence will increase as the United States population ages. [ABSTRACT FROM AUTHOR]

Background: Comparative analysis of the cellular biology of the microvasculature in different tissues requires the availability of viable primary endothelial cells (ECs). This study describes a novel method to isolate primary ECs from healthy organs, repair blastemas and tumors as examples of non-proliferating and proliferating benign and malignant tissues and their functional characterization. Methodology/Principal Findings: Single cell suspensions from hearts, lungs, repair blastemas and tumors were incubated consecutively with an anti-CD31 antibody and magnetic micro-beads, coupled to a derivative of biotin and streptavidin, respectively. Following magnetic bead separation, CD31-positive ECs were released by biotin-streptavidin competition. In the absence of micro-beads, ECs became adherent to plastic surfaces. ECs from proliferating repair blastemas and tumors were larger and exhibited higher expression densities of CD31, CD105 and CD102 compared to those from non-proliferating normal tissues such as heart and lung. The expression density of CD34 was particularly high in tumor-derived ECs, and that of CD54 and CD144 in ECs of repair blastemas. Functionally, ECs of non-proliferating and proliferating tissues differed in their capacity to form tubes in matrigel and to align under flow conditions. Conclusions/Significance: This method provides a powerful tool to generate high yields of viable, primary ECs of different origins. The results suggest that an altered expression of adhesion molecules on ECs in proliferating tissues contribute to loss of EC function that might cause a chaotic tumor vasculature. [ABSTRACT FROM AUTHOR]

Background: Although male circumcision (MC) is recommended as an HIV prevention option, the religious, cultural and biomedical dimensions of its feasibility, acceptability and practice in India have not been explored till date. This study explores beliefs, experiences and understanding of the community and healthcare providers (HCPs) about adult MC as an HIV prevention option in India. Methods: This qualitative study covered 134 in-depth interviews from Belgaum, Kolkata, Meerut and Mumbai cities of India. Of these, 62 respondents were the members of circumcising (CC)/non-circumcising communities (NCC); including medically and traditionally circumcised men, parents of circumcised children, spouses of circumcised men, and religious clerics. Additionally, 58 registered healthcare providers (RHCPs) such as general and pediatric surgeons, pediatricians, skin and venereal disease specialists, general practitioners, and operation theatre nurses were interviewed. Fourteen traditional circumcisers were also interviewed. The data were coded and analyzed in QSR NUD*IST ver. 6.0. The study has not explored the participants' views about neonatal versus adult circumcision. Results: Members of CC/NCC, traditional circumcisers and RCHPs expressed sharp religious sensitivities around the issue of MC. Six themes emerged: Male circumcision as the religious rite; Multiple meanings of MC: MC for ‘religious identity/privilege/sacrifice’ or ‘hygiene’; MC inflicts pain and cost; Medical indications outweigh faith; Hesitation exists in accepting ‘foreign’ evidence supporting MC; and communication is the key for acceptance of MCs. Medical indications could make members of NCC accept MC following appropriate counseling. Majority of the RHCPs demanded local in-country evidence. Conclusion: HCPs must educate high-risk groups regarding the preventive and therapeutic role of MC. Communities need to discuss and create new social norms about male circumcision for better societal acceptance especially among the NCC. Feasibility studies on MC as an individual specific option for the high risk groups in health care setting needs to be explored. [ABSTRACT FROM AUTHOR]

Objective: To evaluate and compare the distribution and density of primordial follicles within a whole sheep ovary and to gain insight into how to overcome the impact of natural follicular heterogeneity on the experimental results. Design: Histological study. Setting: Academic research center. Animals: Five- to nine-month-old ewes. Interventions: Freshly sampled whole sheep ovaries were collected and prepared for histological analysis. Main Outcome Measure(s): The follicular densities and distributions were determined for hematoxylin and eosin sections. A mathematical model was derived based on the follicle counts and Monte-Carlo simulations. Results: Heterogeneous distributions and densities of primordial follicles were identified 1) for distinct areas of the same ovarian cortex, 2) between the ovaries of the same animal and 3) across different ewes. A mathematical model based on the analysis of 37,153 primordial follicles from 8 different ovaries facilitated the estimation of the number of cortical biopsies and sections that had to be analyzed to overcome such heterogeneity. Conclusion: The influence of physiological follicular heterogeneity on experimental and clinical results can be overcome when a definite number of cortical pieces and sections are taken into consideration. [ABSTRACT FROM AUTHOR]

Close adaptation of the prosthesis to the bone is the key to achieving optimal stability and fixation for total hip arthroplasty (THA). However, there have been no adequate studies of bone morphology, especially in different races. The aim of this study was to analyze the geometry of the acetabulum and proximal femur of people from South China, based on three-dimensional reconstruction, and to detect differences between different population subsets. CT scans were performed on 80 healthy volunteers (160 hips) from South China, comprising 40 males (80 hips) and 40 females (80 hips). The images were imported into Mimics 10.01 to perform 3D reconstruction. THA-associated anatomical parameters were measured and compared with other published data. In comparison with published data, it seemed that people from South China have smaller acetabular abduction angle, larger acetabular supro-inferior diameter, larger neck-shaft angle, smaller offset, thinner femoral shaft and more proximal isthmus, which needed to be further confirmed. There were significant differences between the genders in most parameters. As significant differences in canal flare index (CFI) and distal canal flare index (DCFI) were found between genders, it was concluded the most significant differences lay in the isthmus of the femur. Among the femora, according to Noble’s classification we identified more normal types and fewer stovepipe and champagne-flute types than expected from the literature, indicating that uncemented prostheses would be suitable for most people from South China. Our findings reveal that simply choosing the smallest of a series of prostheses would not necessarily provide a good fit, due to the different trends from the proximal to the distal part of the femur. Significant variation exists in THA-associated anatomy between genders and population subsets. It is therefore imperative that each patient receives individual consideration rather than assuming all patients have the same anatomy, especially for different races. [ABSTRACT FROM AUTHOR]

Transient painful stimuli could induce suppression of alpha oscillatory activities and enhancement of gamma oscillatory activities that also could be greatly modulated by attention. Here, we attempted to characterize changes in cortical activities during tonic heat pain perception and investigated the influence of directed/distracted attention on these responses. We collected 5-minute long continuous Electroencephalography (EEG) data from 38 healthy volunteers during four conditions presented in a counterbalanced order: (A) resting condition; (B) innoxious-distracted condition; (C) noxious-distracted condition; (D) noxious-attended condition. The effects of tonic heat pain stimulation and selective attention on oscillatory activities were investigated by comparing the EEG power spectra among the four experimental conditions and assessing the relationship between spectral power difference and subjective pain intensity. The change of oscillatory activities in condition D was characterized by stable and persistent decrease of alpha oscillation power over contralateral-central electrodes and widespread increase of gamma oscillation power, which were even significantly correlated with subjective pain intensity. Since EEG responses in the alpha and gamma frequency band were affected by attention in different manners, they are likely related to different aspects of the multidimensional sensory experience of pain. The observed contralateral-central alpha suppression (conditions D vs. B and D vs. C) may reflect primarily a top-down cognitive process such as attention, while the widespread gamma enhancement (conditions D vs. A) may partly reflect tonic pain processing, representing the summary effects of bottom-up stimulus-related and top-down subject-driven cognitive processes. [ABSTRACT FROM AUTHOR]

The Swedish salmonella control programme has been very successful in reducing the number of salmonella infections in both humans and animals. However, the costs for the control have increased and it has thus been questioned if the control measures could be relaxed and, if so, what effect this would have on human and animal health. The aim of the present study is to evaluate the expected effects on human health of a relaxation of the Swedish control i.e. a substitution of the present programme with a programme similar to the ones present in Denmark or the Netherlands. Data from the year 2010 was used to illustrate this. It was assumed that the domestic exposure to salmonella would then become the same in Sweden as it was in Denmark or the Netherlands in that year. As official statistics on the number of reported salmonella cases are not comparable across European countries, data from five different sources were used to try to obtain comparable estimates of the domestic salmonella exposure in the three countries. The study shows that the number of reported domestic human salmonella cases in Sweden in 2010 would increase by approximately 900 to 2 400 cases in the Danish scenarios and 6 400 to 8 400 in the Dutch scenarios. Although uncertainty exists, it was concluded that the number of reported domestic salmonella cases would increase substantially in Sweden in case of a relaxation of the current control programme. [ABSTRACT FROM AUTHOR]

The attention network test (ANT) is a reliable tool to detect the efficiency of alerting, orienting, and executive control networks. However, studies using the ANT obtained inconsistent relationships between attention networks due to two reasons: on the one hand, the inter-network relationships of attention subsystems were far from clear; on the other hand, ANT scores in previous studies were disturbed by possible inter-network interactions. Here we proposed a new computing method by dissecting cue-target conditions to estimate ANT scores and relationships between attention networks as pure as possible. The method was tested in 36 participants. Comparing to the original method, the new method showed a larger alerting score and a smaller executive control score, and revealed interactions between alerting and executive control and between orienting and executive control. More interestingly, the new method revealed unidirectional influences from alerting to executive control and from executive control to orienting. These findings provided useful information for better understanding attention networks and their relationships in the ANT. Finally, the relationships of attention networks should be considered with more experimental paradigms and techniques. [ABSTRACT FROM AUTHOR]

Childhood family structure has been shown to play an important role in shaping a child's life course development, especially in industrialised societies. One hypothesis which could explain such findings is that parental investment is likely to be diluted in families without both natural parents. Most empirical studies have examined the influence of only one type of family disruption or composition (e.g. father absence) making it difficult to simultaneously compare the effects of different kinds of family structure on children's future outcomes. Here we use a large, rich data source (n = 16,207) collected by Alfred Kinsey and colleagues in the United States from 1938 to 1963, to examine the effects of particular childhood family compositions and compare between them. The dataset further allows us to look at the effects of family structure on an array of traits relating to sexual maturity, reproduction, and risk-taking. Our results show that, for both sexes, living with a single mother or mother and stepfather during childhood was often associated with faster progression to life history events and greater propensity for risk-taking behaviours. However, living with a single father or father and stepmother was typically not significantly different to having both natural parents for these outcomes. Our results withstand adjustment for socioeconomic status, age, ethnicity, age at puberty (where applicable), and sibling configuration. While these results support the hypothesis that early family environment influences subsequent reproductive strategy, the different responses to the presence or absence of different parental figures in the household rearing environment suggests that particular family constructions exert independent influences on childhood outcomes. Our results suggest that father-absent households (i.e. single mothers or mothers and stepfathers) are most highly associated with subsequent fast life history progressions, compared with mother-absent households, and those with two natural parents. [ABSTRACT FROM AUTHOR]

To explore if trypsin could catalyze the degradation of non-protein molecule deltamethrin, we compared in vitro hydrolytic reactions of deltamethrin in the presence and absence of trypsin with ultraviolet-visible (UV/Vis) spectrophotometry and gas chromatography-mass spectrometry (GC/MS). In addition, acute oral toxicity of the degradation products was determined in Wistar rats. The results show that the absorption peak of deltamethrin is around 264 nm, while the absorption peaks of deltamethrin degradation products are around 250 nm and 296 nm. In our GC setting, the retention time of undegraded deltamethrin was 37.968 min, while those of deltamethrin degradation products were 15.289 min and 18.730 min. The LD50 of deltamethrin in Wistar rats is 55 mg/kg, while that of deltamethrin degradation products is 3358 mg/kg in female rats and 1045 mg/kg in male rates (61-fold and 19-fold reductions in toxicity), suggesting that trypsin could directly degrade deltamethrin, which significantly reduces the toxicity of deltamethrin. These results expand people's understanding of the functions of proteases and point to potential applications of trypsin as an attractive agent to control residual pesticides in the environment and on agricultural products. [ABSTRACT FROM AUTHOR]

The recent expansion of Aedes albopictus, a day-biting mosquito, to densely inhabited areas in the northeastern Atlantic states of the USA has dramatically increased the problem that mosquitoes create for urban and suburban residents. We quantified the impact of mosquitoes on residents' quality of life within the context of a comprehensive area-wide integrated pest management program to control Ae. albopictus in two counties (Mercer and Monmouth) in New Jersey. We interviewed residents of 121 randomly selected households in both counties between October and November 2010. We asked residents about their experience with mosquitoes in their neighborhood and the importance of the ability to relax outdoors without mosquitoes compared to other neighborhood characteristics (1 = not important, 5 = extremely important). We rated residents' utility based on paired comparisons to known states from the EuroQol health description system. The majority (54.6%) of respondents considered mosquitoes to be a problem. Respondents reported an average of 7.1 mosquito bites in a typical week during that summer. Mosquitoes prevented 59.5% of residents from enjoying their outdoor activities at least to some extent. Residents rated the mosquito acceptability (mean ± standard deviation) during that summer on a scale of 0 (mosquito invasion) to 100 (no mosquitoes) at 56.7±28.7, and their overall utility at 0.87±0.03. This is comparable to living with up to two risk factors for diabetes (i.e., abdominal obesity, body mass index of 28 or more, reported cholesterol problems, diagnosis of hypertension, or history of cardiovascular disease) or women experiencing menstrual disorders. Respondents rated the importance of enjoying outdoor activities without mosquitoes (4.69±0.80) comparable to that of neighborhood safety (4.74±0.80) and higher than that of a clean neighborhood (4.59±0.94). In conclusion, New Jersey residents reported that mosquitoes decreased their utility by 0.13, comparable to the loss from worrisome health risk factors, underscoring the importance of controlling this problem. [ABSTRACT FROM AUTHOR]

Purpose: When comparing follow-up endothelial cell (EC) density measurements it is only possible to demonstrate cell loss in large cohorts or in pronounced cases due to the standard deviation of measurements. However, especially in clinical studies or refractive surgery patients, EC stability is an important factor. Thus we developed a computer program to achieve cell-by-cell alignment of conventional specular non-contact EC photographs. This is a pilot study to evaluate whether this new diagnostic technique is applicable in postoperative patients. Methods: Digitized endothelial cell photos of 30 eyes following implantation of a phakic posterior chamber intraocular lens for correction of high myopia were analyzed. All EC centroids were dotted on each image, and early and late follow-up pictures were automatically aligned on the basis of these centroids. The tracking results were confirmed via alternating image presentation of the corresponding image areas, and were reviewed for loss of individual cells. In addition, conventional EC density measurements were performed. Results: Mean time interval between first and second postoperative EC image was 1.4 years (range 3 months – 2.2 years), with early images taken at a median of 5.5 months after IOL implantation (lower/upper quartile 1.2–12.3 months). Extrapolated central EC density was 2812±500/mm2 at the first time point, and 2797±524/mm2 at the second time point. In 26 out of 30 image pairs, the EC mosaic was successfully retraced; cell loss in this area was excluded via photo flickering. Only in 4 image pairs, the EC mosaic could not be matched. Conclusions: We demonstrate that the corneal EC mosaic of clinical routine non-contact microscope pictures can be superimposed and compared on single cell level over time with our new computer based program. This new method is valuable to judge on EC stability even in small cohorts since it does not require mean values and standard deviations. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence suggests that mothers show a different pattern of brain responses when viewing their own compared to other infants. However, there is inconsistency across functional imaging studies regarding the key areas involved, and none have examined relationships between brain and behavioural responses to infants. We examined the brain regions activated when mothers viewed videos of their own infant contrasted with an unknown infant, and whether these are associated with behavioural and self-reported measures of mother-infant relations. Method: Twenty right-handed mothers viewed alternating 30-sec blocks of video of own 4–9 month infant and an unfamiliar matched infant, interspersed with neutral video. Whole brain functional magnetic resonance images (fMRI) were acquired on a 1.5T Philips Intera scanner using a TR of 2.55 s. Videotaped mother-infant interactions were systematically evaluated blind to family information to generate behavioural measures for correlational analysis. Results: Enhanced blood oxygenation functional imaging responses were found in the own versus unknown infant contrast in the bilateral precuneus, right superior temporal gyrus, right medial and left middle frontal gyri and left amygdala. Positive mother-infant interaction (less directive parent behaviour; more positive/attentive infant behaviour) was significantly associated with greater activation in several regions on viewing own versus unknown infant, particularly the middle frontal gyrus. Mothers' perceived warmth of her infant was correlated with activations in the same contrast, particularly in sensory and visual areas. Conclusion: This study partially replicates previous reports of the brain regions activated in mothers in response to the visual presentation of their own infant. It is the first to report associations between mothers' unique neural responses to viewing their own infant with the quality of her concurrent behaviour when interacting with her infant and with her perceptions of infant warmth. These findings provide support for developing fMRI as a potential biomarker of parenting risk and change. [ABSTRACT FROM AUTHOR]

Cell-free DNA (cfDNA) in body tissues or fluids is extensively investigated in clinical medicine and other research fields. In this article we provide a direct quantitative real-time PCR (qPCR) as a sensitive tool for the measurement of cfDNA from plasma without previous DNA extraction, which is known to be accompanied by a reduction of DNA yield. The primer sets were designed to amplify a 90 and 222 bp multi-locus L1PA2 sequence. In the first module, cfDNA concentrations in unpurified plasma were compared to cfDNA concentrations in the eluate and the flow-through of the QIAamp DNA Blood Mini Kit and in the eluate of a phenol-chloroform isoamyl (PCI) based DNA extraction, to elucidate the DNA losses during extraction. The analyses revealed 2.79-fold higher cfDNA concentrations in unpurified plasma compared to the eluate of the QIAamp DNA Blood Mini Kit, while 36.7% of the total cfDNA were found in the flow-through. The PCI procedure only performed well on samples with high cfDNA concentrations, showing 87.4% of the concentrations measured in plasma. The DNA integrity strongly depended on the sample treatment. Further qualitative analyses indicated differing fractions of cfDNA fragment lengths in the eluate of both extraction methods. In the second module, cfDNA concentrations in the plasma of 74 coronary heart disease patients were compared to cfDNA concentrations of 74 healthy controls, using the direct L1PA2 qPCR for cfDNA quantification. The patient collective showed significantly higher cfDNA levels (mean (SD) 20.1 (23.8) ng/ml; range 5.1–183.0 ng/ml) compared to the healthy controls (9.7 (4.2) ng/ml; range 1.6–23.7 ng/ml). With our direct qPCR, we recommend a simple, economic and sensitive procedure for the quantification of cfDNA concentrations from plasma that might find broad applicability, if cfDNA became an established marker in the assessment of pathophysiological conditions. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a major human pathogen that elaborates several exotoxins. Among these are the bicomponent leukotoxins (BCLs), which include γ-hemolysin, Panton-Valentine leukocidin (PVL), and LukDE. The toxin components are classified as either F or S proteins, which are secreted individually and assemble on cell surfaces to form hetero-oligomeric pores resulting in lysis of PMNs and/or erythrocytes. F and S proteins of γ-hemolysin, PVL and LukDE have ∼70% sequence homology within the same class and several heterologous combinations of F and S members from these three bicomponent toxin groups are functional. Recently, an additional BCL pair, LukGH (also called LukAB) that has only 30% homology to γ-hemolysin, PVL and LukDE, has been characterized from S. aureus. Our results showed that LukGH was more cytotoxic to human PMNs than PVL. However, LukGH-induced calcium ion influx in PMNs was markedly attenuated and slower than that induced by PVL and other staphylococcal BCLs. In contrast to other heterologous BCL combinations, LukG in combination with heterologous S components, and LukH in combination with heterologous F components did not induce calcium ion entry or cell lysis in human PMNs or rabbit erythrocytes. Like PVL, LukGH induced IL-8 production by PMNs. While individual components LukG and LukH had no cytolytic or calcium influx activity, they each induced high levels of IL-8 transcription and secretion. IL-8 production induced by LukG or LukH was dependent on NF-κB. Therefore, our results indicate LukGH differs functionally from other staphylococcal BCLs. [ABSTRACT FROM AUTHOR]

Objective: Intensive as compared to mild statin therapy has been proven to be superior in improving cardiovascular outcome, whereas the effects of intensive statin therapy on inflammation and lipoprotein biomarkers are not well defined. Methods: This study assigned essential hypertensive patients with dyslipidemia to 6 months administration of mild (1 mg/day, n = 34) or intensive pitavastatin therapy (4 mg/day, n = 29), and various lipid and inflammation biomarkers were measured at baseline, and 3 and 6 months after the start of treatment. Results: Both pitavastatin doses were well tolerated, and there were no serious treatment-related adverse events. After 6 months, significant improvements in total cholesterol, triglycerides, low-density lipoprotein (LDL-) cholesterol, LDL/high-density lipoprotein cholesterol (LDL/HDL), apolipoproteins B, C-II, and E, apolipoprotein-B/apolipoprotein-A-I (Apo B/Apo A-I), and malondialdehyde (MDA-) LDL were observed in both groups. Compared with the mild pitavastatin group, the intensive pitavastatin therapy showed significantly greater decreases in C reactive protein (F = 3.76, p<0.05), total cholesterol (F = 10.65), LDL-cholesterol (F = 23.37), LDL/HDL (F = 12.34), apolipoproteins B (F = 19.07) and E (F = 6.49), Apo B/Apo A-I (F = 13.26), and MDA-LDL (F = 5.76) (p<0.01, respectively). Conclusion: Intensive pitavastatin therapy may have a more favorable effect not only in decreasing LDL-cholesterol but also in pleiotropic benefits in terms of improvement of apolipoproteins, inflammation, or oxidation. [ABSTRACT FROM AUTHOR]

Background: In the beginning of the 1970s, Sweden was the country where both women and men enjoyed the world's longest life expectancy. While life expectancy continues to be high and increasing, Sweden has been losing ground in relation to other leading countries. Methods: We look at life expectancy over the years 1970–2008 for men and women. To assess the relative contributions of age, causes of death, and smoking we decompose differences in life expectancy between Sweden and two leading countries, Japan and France. This study is the first to use this decomposition method to observe how smoking related deaths contribute to life expectancy differences between countries. Results: Sweden has maintained very low mortality at young and working ages for both men and women compared to France and Japan. However, mortality at ages above 65 has become considerably higher in Sweden than in the other leading countries because the decrease has been faster in those countries. Different trends for circulatory diseases were the largest contributor to this development in both sexes but for women also cancer played a role. Mortality from neoplasms has been considerably low for Swedish men. Smoking attributable mortality plays a modest role for women, whereas it is substantially lower in Swedish men than in French and Japanese men. Conclusions: Sweden is losing ground in relation to other leading countries with respect to life expectancy because mortality at high ages improves more slowly than in the leading countries, especially due to trends in cardiovascular disease mortality. Trends in smoking rates may provide a partial explanation for the trends in women; however, it is not possible to isolate one single explanatory factor for why Sweden is losing ground. [ABSTRACT FROM AUTHOR]

The main goal of this study was to investigate how automatic emotion regulation altered the hemispheric asymmetry of ERPs elicited by emotion processing. We examined the effect of individual differences in automatic emotion regulation on the late positive potential (LPP) when participants were viewing blocks of positive high arousal, positive low arousal, negative high arousal and negative low arousal pictures from International affect picture system (IAPS). Two participant groups were categorized by the Emotion Regulation-Implicit Association Test which has been used in previous research to identify two groups of participants with automatic emotion control and with automatic emotion express. The main finding was that automatic emotion express group showed a right dominance of the LPP component at posterior electrodes, especially in high arousal conditions. But no right dominance of the LPP component was observed for automatic emotion control group. We also found the group with automatic emotion control showed no differences in the right posterior LPP amplitude between high- and low-arousal emotion conditions, while the participants with automatic emotion express showed larger LPP amplitude in the right posterior in high-arousal conditions compared to low-arousal conditions. This result suggested that AER (Automatic emotion regulation) modulated the hemispheric asymmetry of LPP on posterior electrodes and supported the right hemisphere hypothesis. [ABSTRACT FROM AUTHOR]

Background: Functional activities, such as the sit-to-stand-to-sit (STSTS) task, are often impaired in individuals with chronic obstructive pulmonary disease (COPD). The STSTS task places a high demand on the postural control system, which has been shown to be impaired in individuals with COPD. It remains unknown whether postural control deficits contribute to the decreased STSTS performance in individuals with COPD. Methods: Center of pressure displacement was determined in 18 individuals with COPD and 18 age/gender-matched controls during five consecutive STSTS movements with vision occluded. The total duration, as well as the duration of each sit, sit-to-stand, stand and stand-to-sit phase was recorded. Results: Individuals with COPD needed significantly more time to perform five consecutive STSTS movements compared to healthy controls (19±6 vs. 13±4 seconds, respectively; p = 0.001). The COPD group exhibited a significantly longer stand phase (p = 0.028) and stand-to-sit phase (p = 0.001) compared to the control group. In contrast, the duration of the sit phase (p = 0.766) and sit-to-stand phase (p = 0.999) was not different between groups. Conclusions: Compared to healthy individuals, individuals with COPD needed significantly more time to complete those phases of the STSTS task that require the greatest postural control. These findings support the proposition that suboptimal postural control is an important contributor to the decreased STSTS performance in individuals with COPD. [ABSTRACT FROM AUTHOR]

Campylobacteriosis incited by C. jejuni is a significant enteric disease of human beings. A person working with two reference strains of C. jejuni National Collection of Type Cultures (NCTC) 11168 developed symptoms of severe enteritis including bloody diarrhea. The worker was determined to be infected by C. jejuni. In excess of 50 isolates were recovered from the worker’s stool. All of the recovered isolates and the two reference strains were indistinguishable from each other based on comparative genomic fingerprint subtyping. Whole genome sequence analysis indicated that the worker was infected with a C. jejuni NCTC 11168 obtained from the American Type Culture Collection; this strain (NCTC 11168-GSv) is the genome sequence reference. After passage through the human host, major genetic changes including indel mutations within twelve contingency loci conferring phase variations were detected in the genome of C. jejuni. Specific and robust single nucleotide polymorphism (SNP) changes in the human host were also observed in two loci (Cj0144c, Cj1564). In mice inoculated with an isolate of C. jejuni NCTC 11168-GSv from the infected person, the isolate underwent further genetic variation. At nine loci, mutations specific to inoculated mice including five SNP changes were observed. The two predominant SNPs observed in the human host reverted in mice. Genetic variations occurring in the genome of C. jejuni in mice corresponded to increased densities of C. jejuni cells associated with cecal mucosa. In conclusion, C. jejuni NCTC 11168-GSv was found to be highly virulent in a human being inciting severe enteritis. Host-specific mutations in the person with enteritis occurred/were selected for in the genome of C. jejuni, and many were not maintained in mice. Information obtained in the current study provides new information on host-specific genetic adaptation by C. jejuni. [ABSTRACT FROM AUTHOR]

Background: Individuals with a positive family history for alcoholism (FHP) have shown differences from family-history-negative (FHN) individuals in the neural correlates of reward processing. FHP, compared to FHN individuals, demonstrate relatively diminished ventral striatal activation during anticipation of monetary rewards, and the degree of ventral striatal activation shows an inverse correlation with specific impulsivity measures in alcohol-dependent individuals. Rewards in socially interactive contexts relate importantly to addictive propensities, yet have not been examined with respect to how their neural underpinnings relate to impulsivity-related measures. Here we describe impulsivity measures in FHN and FHP individuals as they relate to a socially interactive functional magnetic resonance imaging (fMRI) task. Methods: Forty FHP and 29 FHN subjects without histories of Axis-I disorders completed a socially interactive Domino task during functional magnetic resonance imaging and completed self-report and behavioral impulsivity-related assessments. Results: FHP compared to FHN individuals showed higher scores (p = .004) on one impulsivity-related factor relating to both compulsivity (Padua Inventory) and reward/punishment sensitivity (Sensitivity to Punishment/Sensitivity to Reward Questionnaire). Multiple regression analysis within a reward-related network revealed a correlation between risk-taking (involving another impulsivity-related factor, the Balloon Analog Risk Task (BART)) and right ventral striatum activation under reward >punishment contrast (p<0.05 FWE corrected) in the social task. Conclusions: Behavioral risk-taking scores may be more closely associated with neural correlates of reward responsiveness in socially interactive contexts than are FH status or impulsivity-related self-report measures. These findings suggest that risk-taking assessments be examined further in socially interactive settings relevant to addictive behaviors. [ABSTRACT FROM AUTHOR]

The putamen has a somatotopic organization of neurons identified by correspondence of firing rates with selected body part movements, as well as by complex, but organized, differential cortical projections onto putamen. In isolated focal dystonia, whole putaminal binding of dopamine D2-like receptor radioligands is quantitatively decreased, but it has not been known whether selected parts of the putamen are differentially affected depending upon the body part affected by dystonia. The radioligand [18F]spiperone binds predominantly to D2-like receptors in striatum. We hypothesized that the spatial location of [18F]spiperone binding within the putamen would differ in patients with dystonia limited to the hand versus the face, and we tested that hypothesis using positron emission tomography and magnetic resonance imaging. To address statistical and methodological concerns, we chose a straightforward but robust image analysis method. An automated algorithm located the peak location of [18F]spiperone binding within the striatum, relative to a brain atlas, in each of 14 patients with cranial dystonia and 8 patients with hand dystonia. The mean (left and right) |x|, y, and z coordinates of peak striatal binding for each patient were compared between groups by t test. The location of peak [18F]spiperone binding within the putamen differed significantly between groups (cranial dystonia z2-like receptors are distributed differently in the putamen depending on the body part manifesting dystonia. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) infection is widespread in China, but few studies have been carried out in Guangdong Province. This study aimed to characterize the prevalence of HEV infections among swine, swine farmers and the general population in Guangdong Province. We conducted an epidemiological study that included swine, swine farmers and health examination attendees in Guangdong from 2011 to 2013. The overall seroprevalence of anti-HEV antibodies in swine was 64.7%. The results revealed that growing pigs, sows and boars (OR ranges from 3.5 to 21.5) have a higher risk than nursery pigs. HEV RNA in swine bile showed that HEV is epidemic in swine in the Pearl River Delta, with the highest prevalence of 22.73% in Foshan. Some genomes of HEV strains from each district were sequenced. Phylogenetic analysis of partial open reading frame 2 (ORF2) shows that they belong to genotype IV and are most closely related to isolates from China. In total, 307 participants were enrolled in the study, including 114 swine farmers and 193 attendees from hospitals. IgG anti-HEV was detected in 48.25% of swine farmers and in 38.34% of the general population. Seroprevalence rates were almost stratified by age, with a higher positive rate for males compared to females across all age groups. Women on swine farms appeared to have a lower risk of infection compared to the general population, revealing that the risk factors for HEV infection are not unique. The results suggested that there were other risk factors for HEV infection. HEV infection is prevalent in Guangdong, but due to the small sample sizes, more investigations are needed to assess the potential impact of HEV infection, and many additional risk factors should be considered. [ABSTRACT FROM AUTHOR]

Background: There are many options for urologists to treat ureteral stones that range from 8 mm to 15 mm, including ESWL and ureteroscopic holmium laser lithotripsy. While both ESWL and ureteroscopy are effective and minimally invasive procedures, there is still controversy over which one is more suitable for ureteral stones. Objective: To perform a retrospective study to compare the efficiency, safety and complications using ESWL vs. ureteroscopic holmium laser lithotripsy in management of ureteral stones. Methods: Between October 2010 and October 2012, 160 patients who underwent ESWL or ureteroscopic holmium laser lithotripsy at Suzhou municipal hospital for a single radiopaque ureteral stone (the size 8–15 mm) were evaluated. All patients were followed up with ultrasonography for six months. Stone clearance rate, costs and complications were compared. Results: Similarity in stone clearance rate and treatment time between the two procedures; overall procedural time, analgesia requirement and total cost were significantly different. Renal colic and gross hematuria were more frequent with ESWL while voiding symptoms were more frequent with ureteroscopy. Both procedures used for ureteral stones ranging from 8 to 15 mm were safe and minimally invasive. Conclusion: ESWL remains first line therapy for proximal ureteral stones while ureteroscopic holmium laser lithotripsy costs more. To determining which one is preferable depends on not only stone characteristics but also patient acceptance and cost-effectiveness ratio. [ABSTRACT FROM AUTHOR]

Menstrual blood has been introduced as an easily accessible and refreshing stem cell source with no ethical consideration. Although recent works have shown that menstrual blood stem cells (MenSCs) possess multi lineage differentiation capacity, their efficiency of hepatic differentiation in comparison to other stem cell resources has not been addressed so far. The aim of this study was to investigate hepatic differentiation capacity of MenSCs compared to bone marrow-derived stem cells (BMSCs) under protocols developed by different concentrations of hepatocyte growth factor (HGF) and oncostatin M (OSM) in combination with other components in serum supplemented or serum-free culture media. Such comparison was made after assessment of immunophenotye, trans-differentiation potential, immunogenicity and tumorigeicity of these cell types. The differential expression of mature hepatocyte markers such as albumin (ALB), cytokeratin 18 (CK-18), tyrosine aminotransferase and cholesterol 7 alpha-hydroxylase activities (CYP7A1) at both mRNA and protein levels in differentiating MenSCs was significantly higher in upper concentration of HGF and OSM (P1) compared to lower concentration of these factors (P2). Moreover, omission of serum during differentiation process (P3) caused typical improvement in functions assigned to hepatocytes in differentiated MenSCs. While up-regulation level of ALB and CYP7A1 was higher in differentiated MenSCs compared to driven BMSCs, expression level of CK-18, detected level of produced ALB and glycogen accumulation were lower or not significantly different. Therefore, based on the overall comparable hepatic differentiation ability of MenSCs with BMSCs, and also accessibility, refreshing nature and lack of ethical issues of MenSCs, these cells could be suggested as an apt and safe alternative to BMSCs for future stem cell therapy of chronic liver diseases. [ABSTRACT FROM AUTHOR]

The current interest in epigenetic priming is underpinned by the belief that remodelling of the epigenetic landscape will sensitise tumours to subsequent therapy. In this pre-clinical study, paediatric AML cells expanded in culture and primary AML xenografts were treated with decitabine, a DNA demethylating agent, and cytarabine, a frontline cytotoxic agent used in the treatment of AML, either alone or in combination. Sequential treatment with decitabine and cytarabine was found to be more effective in reducing tumour burden than treatment with cytarabine alone suggesting that the sequential delivery of these agents may a have real clinical advantage in the treatment of paediatric AML. However we found no evidence to suggest that this outcome was dependent on priming with a hypomethylating agent, as the benefits observed were independent of the order in which these drugs were administered. [ABSTRACT FROM AUTHOR]

Tetralogy of Fallot (TOF) is one of the most common severe congenital heart malformations. Great progress has been made in identifying key genes that regulate heart development, yet approximately 70% of TOF cases are sporadic and nonsyndromic with no known genetic cause. We created an ultra high-resolution gene centric comparative genomic hybridization (gcCGH) microarray based on 591 genes with a validated association with cardiovascular development or function. We used our gcCGH array to analyze the genomic structure of 34 infants with sporadic TOF without a deletion on chromosome 22q11.2 (n male = 20; n female = 14; age range of 2 to 10 months). Using our custom-made gcCGH microarray platform, we identified a total of 613 copy number variations (CNVs) ranging in size from 78 base pairs to 19.5 Mb. We identified 16 subjects with 33 CNVs that contained 13 different genes which are known to be directly associated with heart development. Additionally, there were 79 genes from the broader list of genes that were partially or completely contained in a CNV. All 34 individuals examined had at least one CNV involving these 79 genes. Furthermore, we had available whole genome exon arrays from right ventricular tissue in 13 of our subjects. We analyzed these for correlations between copy number and gene expression level. Surprisingly, we could detect only one clear association between CNVs and expression (GSTT1) for any of the 591 focal genes on the gcCGH array. The expression levels of GSTT1 were correlated with copy number in all cases examined (r = 0.95, p = 0.001). We identified a large number of small CNVs in genes with varying associations with heart development. Our results illustrate the complexity of human genome structural variation and underscore the need for multifactorial assessment of potential genetic/genomic factors that contribute to congenital heart defects. [ABSTRACT FROM AUTHOR]

Objectives: To systematically review studies comparing peri-operative mortality and length of hospital stay in patients with ruptured abdominal aortic aneurysms (rAAAs) who underwent endovascular aneurysm repair (EVAR) to patients who underwent open surgical repair (OSR). Methods: The Medline, Cochrane, EMBASE, and Google Scholar databases were searched until Apr 30, 2013 using keywords such as abdominal aortic aneurysm, emergent, emergency, rupture, leaking, acute, endovascular, stent, graft, and endoscopic. The primary outcome was peri-operative mortality and the secondary outcome was length of hospital stay. Results: A total of 18 studies (2 randomized controlled trials, 5 prospective studies, and 11 retrospective studies) with a total of 135,734 rAAA patients were included. rAAA patients who underwent EVAR had significantly lower peri-operative mortality compared to those who underwent OSR (overall OR = 0.62, 95% CI = 0.58 to 0.67, P<0.001). rAAA patients with EVAR also had a significantly shorter mean length of hospital stay compared to those with OSR (difference in mean length of stay ranged from −2.00 to −19.10 days, with the overall estimate being −5.25 days (95% CI = −9.23 to −1.26, P = 0.010). There was no publication bias and sensitivity analysis showed good reliability. Conclusions: EVAR confers significant benefits in terms of peri-operative mortality and length of hospital stay. There is a need for more randomized controlled trials to compare outcomes of EVAR and OSR for rAAA. [ABSTRACT FROM AUTHOR]

Dabigatran and rivaroxaban are novel oral anticoagulants that specifically inhibit thrombin and factor Xa, respectively. The aim of this study is to elucidate antithrombotic properties of these anticoagulant agents under arterial and venous shear conditions. Whole blood samples treated with dabigatran or rivaroxaban at 250, 500, and 1000 nM, with/without aspirin and AR-C66096, a P2Y12 antagonist, were perfused over a microchip coated with collagen and tissue thromboplastin at shear rates of 240 and 600 s−1. Fibrin-rich platelet thrombus formation was quantified by monitoring flow pressure changes. Dabigatran at higher concentrations (500 and 1000 nM) potently inhibited thrombus formation at both shear rates, whereas 1000 nM of rivaroxaban delayed, but did not completely inhibit, thrombus formation. Dual antiplatelet agents weakly suppressed thrombus formation at both shear rates, but intensified the anticoagulant effects of dabigatran and rivaroxaban. The anticoagulant effects of dabigatran and rivaroxaban were also evaluated under static conditions using thrombin generation (TG) assay. In platelet-poor plasma, dabigatran at 250 and 500 nM efficiently prolonged the lag time (LT) and moderately reduce peak height (PH) of TG, whereas rivaroxaban at 250 nM efficiently prolonged LT and reduced PH of TG. In platelet-rich plasma, however, both anticoagulants efficiently delayed LT and reduced PH of TG. Our results suggest that dabigatran and rivaroxaban may exert distinct antithrombotic effects under flow conditions, particularly in combination with dual antiplatelet therapy. [ABSTRACT FROM AUTHOR]

Binswanger's disease (BD) is a common cause of vascular dementia in elderly patients; however, few studies have investigated the medial temporal lobe (MTL) atrophy in BD, and the differences in the atrophic patterns between BD and Alzheimer's disease (AD) remain largely unknown. Such knowledge is essential for understanding the pathologic basis of dementia. In this study, we collected structural magnetic resonance imaging (MRI) data from 16 normal controls, 14 patients with AD and 14 patients with BD. The volumes of the hippocampus and amygdala, and morphologic parameters (volume, surface area, cortical thickness and mean curvature) of the entorhinal cortex (ERC) and perirhinal cortex (PRC) were calculated using an automated approach. Volume reduction of the hippocampus, amygdala and ERC, and disturbance of the PRC curvature was found in both AD and BD patients compared with the controls (p<0.05, uncorrected). There were no significant differences among all the structural measures between the AD and BD patients. Finally, partial correlation analyses revealed that cognitive decline could be attributed to ERC thinning in AD and volume reduction of PRC in BD. We conclude that AD and BD exhibit similar atrophy patterns in the medial temporal cortices and deep gray matter but have distinct pathologic bases for cognitive impairments. Although atrophy of the MTL structures is a sensitive biomarker for AD, it is not superior for discrimination between AD and BD. [ABSTRACT FROM AUTHOR]

Background and Aim: Recurrence and metastasis are associated with poor prognosis in hepatocellular carcinoma even in the patients who have undergone radical resection. Therefore, effective treatment is urgently needed for improvement of patients' survival. Previously, we reported that nanosecond pulse electric fields (nsPEFs) can ablate melanoma by induction of apoptosis and inhibition of angiogenesis. This study aims to investigate the in vivo ablation strategy by comparing the dose effect of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma. Materials and Methods: Four hepatocellular carcinoma cell lines HepG2, SMMC7721, Hep1-6, and HCCLM3 were pulsed to test the anti-proliferation and anti-migration ability of 100 ns nsPEFs in vitro. The animal model of human subdermal xenograft HCCLM3 cells into BALB/c nude mouse was used to test the anti-tumor growth and macrophage infiltration in vivo. Results: In vitro assays showed anti-tumor effect of nsPEFs is dose-dependant. But the in vivo study showed the strategy of low dose and multiple treatments is superior to high dose single treatment. The macrophages infiltration significantly increased in the tumors which were treated by multiple low dose nsPEFs. Conclusion: The low dose multiple nsPEFs application is more efficient than high dose single treatment in inhibiting the tumor volume in vivo, which is quite different from the dose-effect relationship in vitro. Beside the electric field strength, the macrophage involvement must be considered to account for effect variability and toxicology in vivo. [ABSTRACT FROM AUTHOR]

Purpose: This study was performed to first investigate the morphological differences in the optic nerve head between highly myopic non-glaucomatous controls and highly myopic glaucomatous eyes in comparison with the differences between emmetropic non-glaucomatous controls and emmetropic glaucomatous eyes using confocal scanning laser ophthalmoscopy. Further, the ability of the apparatus in glaucoma diagnosis in highly myopic eyes was compared with that in emmetropic eyes. Methods: Healthy subjects and age-matched patients with early-stage open-angle glaucoma were divided into two groups: emmetropic eyes (−1.0 to +1.0 diopters) and highly myopic eyes (−12.0 to −5.0 diopters).The participants were comprised of 65 emmetropic normal eyes, 59 emmetropic glaucomatous eyes, 62 highly myopic normal eyes, and 68 highly myopic glaucomatous eyes and eyes with pathologic myopia were carefully excluded. Confocal scanning laser tomographic parameters were compared among all subjects after adjustment for age and disc area. The ROC curves and sensitivity and specificity for glaucoma detection using several clinical methods were then compared between the emmetropic and highly myopic eyes. Results: Rim area, cup/disc area ratio, mean cup depth, and cup shape measure of glaucoma eyes are significantly different from those of normal eyes in both highly myopic eyes and emmetropic eyes. Methodological overestimation of retinal nerve fiber layer cross sectional area due to optic disc tilting was suggested in the highly myopic eyes. The diagnostic performance of glaucoma using several discriminant methods significantly deteriorated in the highly myopic eyes. Conclusions: In the highly myopic glaucomatous eyes, confocal scanning laser tomographic parameters were significantly different from that of non-glaucomatous highly myopic eyes but diagnostic performance of glaucoma was deteriorated than that in emmetropic eyes. These findings demonstrate the utility and limitations of the apparatus in diagnosing glaucoma in highly myopic patients. [ABSTRACT FROM AUTHOR]

The rs12979860 single nucleotide polymorphism located on chromosome 19q13.13 near the interferon L3 gene (formerly and commonly known as interleukin 28B gene) has been associated in adults with both spontaneous and treatment induced clearance of hepatitis C virus. Although the exact mechanism of these associations remains unclear, it suggests that variation in genes involved in the immune response against the virus favours viral clearance. Limited and preliminary data are available on this issue in children. The aim of the present study was to evaluate, in a representative cohort of children with perinatal infection, the potential association between rs12979860 single nucleotide polymorphism and the outcome of hepatitis C virus infection. Alleles and genotypes frequencies were evaluated in 30 children who spontaneously cleared the virus and in 147 children with persistent infection and were compared with a population sample of ethnically matched controls with unknown hepatitis C status obtained using the 1000 Genomes Project data. The C allele and the C/C genotype showed greater frequencies in the clearance group (76.7% and 56.7%, respectively) when compared with both children with viral persistence (C allele 56.5%, p = 0.004; C/C genotype 32.7%, p = 0.02) and with the ethnically matched individuals (C allele 59.7%, p = 0.02; C/C genotype 34.7%, p = 0.03). Children with the C/C genotype were 2 times more likely to clear hepatitis C virus relative to children with the C/T and T/T genotypes combined (odds ratio: 2.7; 90% confidence intervals: 1.3–5.8). The present study provides the evidence that the rs12979860 single nucleotide polymorphism influences the natural history of hepatitis C virus in children. [ABSTRACT FROM AUTHOR]

In patients with Parkinson's disease (PD), stem cells can serve as therapeutic agents to restore or regenerate injured nervous system. Here, we differentiated two types of stem cells; mouse embryonic stem cells (mESCs) and protein-based iPS cells (P-iPSCs) generated by non-viral methods, into midbrain dopaminergic (mDA) neurons, and then compared the efficiency of DA neuron differentiation from these two cell types. In the undifferentiated stage, P-iPSCs expressed pluripotency markers as ES cells did, indicating that protein-based reprogramming was stable and authentic. While both stem cell types were differentiated to the terminally-matured mDA neurons, P-iPSCs showed higher DA neuron-specific markers' expression than ES cells. To investigate the mechanism of the superior induction capacity of DA neurons observed in P-iPSCs compared to ES cells, we analyzed histone modifications by genome-wide ChIP sequencing analysis and their corresponding microarray results between two cell types. We found that Wnt signaling was up-regulated, while SFRP1, a counter-acting molecule of Wnt, was more suppressed in P-iPSCs than in mESCs. In PD rat model, transplantation of neural precursor cells derived from both cell types showed improved function. The present study demonstrates that P-iPSCs could be a suitable cell source to provide patient-specific therapy for PD without ethical problems or rejection issues. [ABSTRACT FROM AUTHOR]

Both IgA and IgG antibodies are known to play important roles in protection against influenza virus infection. While IgG is the major isotype induced systemically, IgA is predominant in mucosal tissues, including the upper respiratory tract. Although IgA antibodies are believed to have unique advantages in mucosal immunity, information on direct comparisons of the in vitro antiviral activities of IgA and IgG antibodies recognizing the same epitope is limited. In this study, we demonstrate differences in antiviral activities between these isotypes using monoclonal IgA and IgG antibodies obtained from hybridomas of the same origin. Polymeric IgA-producing hybridoma cells were successfully subcloned from those originally producing monoclonal antibody S139/1, a hemaggulutinin (HA)-specific IgG that was generated against an influenza A virus strain of the H3 subtype but had cross-neutralizing activities against the H1, H2, H13, and H16 subtypes. These monoclonal S139/1 IgA and IgG antibodies were assumed to recognize the same epitope and thus used to compare their antiviral activities. We found that both S139/1 IgA and IgG antibodies strongly bound to the homologous H3 virus in an enzyme-linked immunosorbent assay, and there were no significant differences in their hemagglutination-inhibiting and neutralizing activities against the H3 virus. In contrast, S139/1 IgA showed remarkably higher cross-binding to and antiviral activities against H1, H2, and H13 viruses than S139/1 IgG. It was also noted that S139/1 IgA, but not IgG, drastically suppressed the extracellular release of the viruses from infected cells. Electron microscopy revealed that S139/1 IgA deposited newly produced viral particles on the cell surface, most likely by tethering the particles. These results suggest that anti-HA IgA has greater potential to prevent influenza A virus infection than IgG antibodies, likely due to increased avidity conferred by its multivalency, and that this advantage may be particularly important for heterosubtypic immunity. [ABSTRACT FROM AUTHOR]

Severe asymptomatic stenosis of the internal carotid artery (ICA) leads to increased incidence of mild cognitive impairment (MCI) likely through silent embolic infarcts and/or chronic hypoperfusion, but the brain dysfunction is poorly understood and difficult to diagnose. Thirty cognitively intact subjects with asymptomatic, severe (≧70%), unilateral stenosis of the ICA were compared with 30 healthy controls, matched for age, sex, cardiovascular risk factors and education level, on a battery of neuropsychiatric tests, voxel-based morphometry of magnetic resonance imaging (MRI), diffusion tensor imaging and brain-wise, seed-based analysis of resting-state functional MRI. Multivariate regression models and multivariate pattern classification (support vector machines) were computed to assess the relationship between connectivity measures and neurocognitive performance. The patients had worse dizziness scores and poorer verbal memory, executive function and complex visuo-spatial performance than controls. Twelve out of the 30 patients (40%) were considered to have MCI. Nonetheless, the leukoaraiosis Sheltens scores, hippocampal and brain volumes were not different between groups. Their whole-brain mean fractional anisotropy (FA) was significantly reduced and regional functional connectivity (Fc) was significantly impaired in the dorsal attention network (DAN), frontoparietal network, sensorimotor network and default mode network. In particular, the Fc strength at the insula of the DAN and the mean FA were linearly related with attention performance and dizziness severity, respectively. The multivariate pattern classification gave over 90% predictive accuracy of individuals with MCI or severe dizziness. Cognitive decline in stroke-free individuals with severe carotid stenosis may arise from nonselective widespread disconnections of long-range, predominantly interhemispheric non-hippocampal pathways. Connectivity measures may serve as both predictors for cases at risk and therapeutic targets for mitigating vascular cognitive impairment. [ABSTRACT FROM AUTHOR]