Sedentary behaviors (involving prolonged sitting time) are associated with deleterious health consequences, independent of (lack of) physical activity. To inform interventions, correlates of prevalent sedentary behaviors need to be identified. We examined associations of socio-demographic, home-environmental and psychosocial factors with adults' TV viewing time and leisure-time Internet use; and whether psychosocial and environmental correlates differed according to gender, age and educational attainment.This cross-sectional study was conducted in Ghent, Belgium, between March and May 2010. Respondents to a mail-out survey  completed a questionnaire on sedentary behaviors and their potential socio-demographic, psychosocial and home environmental correlates. Statistical analyses were performed using multiple linear regression models.The independent variables explained 31% of the variance in TV viewing time and 38% of the variance in leisure-time Internet use. Higher education, greater perceived pros of and confidence about reducing TV time were negatively associated with TV viewing time; older age, higher body mass index, larger TV set size and greater perceived cons of reducing TV time showed positive associations. Perceived pros of and confidence about reducing Internet use were negatively associated with leisure-time Internet use; higher education, number of computers in the home, positive family social norms about Internet use and perceived cons of reducing Internet use showed positive associations. None of the socio-demographic factors moderated these associations.Educational level, age, self-efficacy and pros/cons were the most important correlates identified in this study. If further cross-sectional and longitudinal research can confirm these findings, tailored interventions focusing on both psychosocial and environmental factors in specific population subgroups might be most effective to reduce domestic screen time. Over the past years, much research has focused on the health benefits and determinants of regular physical activity (PA) in adults . To gainRecently, sedentary behaviors  also have been found to be associated with elevated risk of obesity, cardio-metabolic risk profile, diabetes, cardiovascular disease, specific cancers and overall and cardiovascular mortality -7. Thesehttp://www.internetworldstats.com 2010, Miniwatts Marketing Group; accessed June 13, 2011). Furthermore, changing these types of leisure-time SB might be more susceptible to individuals' own choice compared to for example occupational sitting. Therefore, TV viewing and leisure-time Internet use are target behaviors of interest when developing SB-reducing interventions. Nonetheless, before interventions can be developed, the crucial determinants of these behaviors need to be understood.Domestic screen time (TV viewing and leisure-time Internet use at home) has been related to negative health outcomes -9 and isWhen investigating determinants and correlates of SB, ecological models of health behaviors can be used as a theoretical basis. However, since socio-demographic, psychosocial and physical environmental correlates of PA are poorly associated with SB, the PA-related ecological models should be adjusted, using SB-specific variables -19. To oConsequently the main aim of this study was to examine the associations of socio-demographic and sedentary-specific home-environmental and psychosocial factors with TV viewing time and leisure-time Internet use in Belgian adults. Moreover, since behavioral correlates can differ between men and women, younger and older adults and those of higher and lower educational attainment -22, an a2, 1468 inhabitants/km2), Belgium. Data were collected between March and May 2010. In total, 419 adults (20-65 years) participated in the study. To recruit participants, a questionnaire on SB and possible correlates and a letter explaining the purpose of the study were mailed to 1200 randomly selected (based on publicly available population data) urban and suburban adults. A prepaid and preaddressed envelope was provided to return the questionnaire. Fifty-three questionnaires (4.4%) were returned because people no longer lived at the address. After six weeks, 347 completed questionnaires were received and a second letter was sent to non-responders to ask for participation. After another six weeks, a total of 419 completed questionnaires (response rate 36.5%) was sent back. Informed consent was obtained from all participants and the study protocol was approved by the ethics committee of Ghent University Hospital.The present study was conducted in Ghent  and leisure-time internet use at home (min/day). Leisure-time internet use included visiting websites, emailing, and Facebook, Twitter, Netlog at home during leisure-time. These behaviors were determined using an adjusted version of the leisure-time SB questionnaire developed by Salmon and colleagues . The oriThese included self-reported gender, age, educational attainment , employment status , and body mass index . For the analyses, education was dichotomized into having college/university degree (yes/no).To assess the number of TVs and computers in the home, questions were derived from a previously validated home electronic equipment scale . All parAll questions on psychosocial variables, except for social norm from family and friends, were derived from a validated questionnaire developed by Norman and colleagues  in the cAll analyses were run using SPSS 16.0 for Windows. Multiple linear regression analyses were executed to investigate associations of socio-demographic, psychosocial and home-environmental factors with the outcome measures. Dependent variables were min/week of TV viewing time and min/week of leisure-time Internet use. Because both dependent variables were positively skewed, logarithmic transformations were applied to improve normality . Indepen2. Of all participants, 56.7% had a college/university degree, 70.6% was employed and 80.3% reported having a white-collar job. Compared with Belgian census data [Socio-demographic characteristics and mean scores for the home-environmental factors, psychosocial factors (sum scores and item level) and SB are shown in Table sus data , the samThe regression analyses showed that 39% of the variance in TV viewing time was explained by the independent variables. Regarding the socio-demographic factors, age (p < 0.001) and BMI (p = 0.030) were positively associated with TV viewing time, while educational level had a negative association (p = 0.001). Size of the largest TV set was the only home-environmental factor that was positively associated with TV viewing time (p = 0.012). For the psychosocial variables, perceiving more cons was associated with more TV viewing time (p = 0.014) while more pros (p < 0.001) and higher self-efficacy about reducing TV viewing time were related to less TV viewing time (p < 0.001). Results of the moderated regression analyses showed that none of the socio-demographic factors  significantly moderated the associations between the psychosocial and home-environmental factors and TV viewing time .In total, 34% of the variance in leisure-time Internet use was explained by the independent variables. Educational level was positively associated with leisure-time Internet use (p = 0.015), while employment status was negatively related to Internet use (p = 0.001). The number of computers was the only home-environmental factor that was positively associated with leisure-time Internet use (p = 0.020). Concerning the psychosocial factors, perception of higher social norm from family towards Internet use (p = 0.011) and more cons (p = 0.002) were related to more leisure-time Internet use. Moreover, more pros (p = 0.009) and higher self-efficacy about reducing leisure-time Internet use were associated with less Internet use (p < 0.001). Results of the moderated regression analyses showed that none of the socio-demographic factors  significantly moderated the associations between the psychosocial and home-environmental factors and leisure-time Internet use .This was the first study to investigate the concurrent contribution of socio-demographic, home-environmental and psychosocial factors to explain variance in domestic screen time in adults. Generally, the included factors explained a large amount (34% and 39%) of the variance in TV viewing and leisure-time Internet use. By conducting analyses that examined sociodemographic attributes as both predictors of the main effects, and as moderators of the relationships of home environmental and psychosocial factors with domestic screen time, we were able to examine specifically whether these associations differed by gender, age and educational attainment. The absence of interaction effects suggested that similar psychosocial and home-environmental factors can be targeted in different subgroups .2 = 9.9, p = .002). Unemployed and retired adults spent more time using Internet in the present study; this could potentially be explained by the higher discretionary time they have available [Detailed interpretation of the correlates showed that educational level and age were the strongest socio-demographic correlates of TV viewing time. Middle-aged and lower-educated adults watched more TV than younger and higher-educated adults. These findings are consistent with other adult studies ,32-34 anvailable . BMI wasvailable ,22,33. Tvailable .Regarding the home-environmental factors, positive associations were found between the size of the largest TV set and TV viewing time and between the number of computers and leisure-time Internet use, although the beta-values were small. However, no association was found between the number of TVs and TV viewing time. Roemmich and colleagues  found thPsychosocial factors were strongly associated with domestic screen time. Self-efficacy about reducing screen time and perceiving pros and cons to reduce screen time were the most consistent correlates. No other adult studies examining these factors were identified, but in adolescents, self-efficacy and decisional balance (pros - cons) have been found to be important correlates of total sedentary time ,42. WhenWhen comparing the present findings to what has been reported in studies examining correlates of PA in adults, similar patterns can be identified. Self-efficacy is one of the most consistent correlates of PA, together with perceived benefits and barriers and social support . MoreoveThe first study limitation was the cross-sectional study design, inducing that no inferences on causality can be made. Second, both outcome measures and potential correlates were self-reported, so the measures may suffer from social desirability and underestimation. Third, since the study sample was somewhat more likely to be highly-educated and employed compared to the Belgian population, generalizability of the results may be limited. Fourth, some possibly important correlates  were not included in the questionnaire or were only assessed with a limited number of questions . These factors should be investigated more thoroughly in the future. Moreover, the validity of questions to assess social norm from family and friends towards domestic screen time needs to be examined. Strengths of this study included the use of validated psychosocial questionnaires and the inclusion of correlates of multiple domains.In general, these findings are promising, with high proportions of variance in domestic screen time explained by mainly socio-demographic and psychosocial correlates. Future research should keep this focus on different SB  and on multiple levels of determinants, because a wide range of correlates can be important for different types of SB. Moreover, within the ecological perspective , other cIn summary, the present findings show that educational level, age, self-efficacy about reducing screen time and pros and cons for reducing screen time were the most important correlates of TV viewing time and leisure-time Internet use in a sample of Belgian adults. Based on these findings, tailored interventions focusing mainly on psychosocial factors in specific population subgroups might be most effective to reduce domestic screen time. If SB-reducing interventions targeting the most-relevant determinants were to be combined with strategies to increase PA and to develop healthy eating habits in the future, health effects could be reached in large populations.The authors declare that they have no competing interests.All authors contributed to the design of different parts of the study. DVD was responsible for data collection, performed the statistical analyses and drafted the manuscript. IDB, GC and BD helped to prepare the data collection, participated in the interpretation of the data, helped to draft the manuscript and revised the manuscript for important intellectual content. NO, KDC and KW revised the draft for important intellectual content. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/11/668/prepub


Mechanical force is present in all aspects of living systems. It affects the conformation of molecules, the shape of cells, and the morphology of tissues. All of these are crucial in architecture-dependent biological functions. Nanoscience of advanced materials has provided knowledge and techniques that can be used to understand how mechanical force is involved in biological systems, as well as to open new avenues to tailor-made bio-mimetic materials with desirable properties.In this article, we describe models and show examples of how force is involved in molecular functioning, cell shape patterning, and tissue morphology. Life relies on the ability of size and shape control at different scales. At the molecular and sub-cellular levels, chemical signaling relies on conformational changes of molecules. Mutations leading to abnormal conformational changes often cause diseases such as tumors and tissue malfunction. At the cellular and tissue levels, the ability of cells to form specific shapes is of vital importance ,2. This From a theoretical point of view, the control of molecular conformation, cell shape, and tissue morphology relies on how mechanical forces are created, distributed, and transmitted. There is a growing interest in the role of mechanical force in tissue development, remodeling, regeneration, and tumorigenesis -10. In mUnderstanding how cells create, distribute, transmit, and use forces is essential for using nanomaterials technology in biological systems. At the cellular level, the creation of force within single cells depends on the orientation and distribution of cytoskeleton proteins, such as actomyosin filaments, the organization of which is further regulated by chemical signaling that relies on conformational changes of molecules. Likewise, the propagation of force within tissues is parameterized by the distribution and the orientation of extracellular matrix (ECM) molecules.n segments of characteristic length lk (Kuhn length) connected via freely-rotating joints  . T. Tn segmC (eFJC) ,14, whicβ-barrel structure formed from seven anti-parallel β-strands. Domains are linked to neighboring domains via an elastic linker region, which is thought to be the main source contributing to the overall flexibility of the chain [To illustrate how force measurements of molecules are done to obtain the parameters that define the mechanical properties of molecules, we use single molecule force studies of a protein with repeated units. The single molecule manipulation studies are performed using an engineered polyprotein consisting of repeats of the I27 domain of human cardiac titin. Titin is a giant muscle protein of 1 μm in length and 3 MDa in size, found in the striated cardiac and skeletal muscle tissue . Titin mhe chain . The A-bhe chain .The mechanical nature of titin's function makes it particularly suitable for single molecule stretch-relaxation studies -26. In pThere has been renewed interest in understanding the details of thermodynamics and kinetics of DNA melting due to recent advances in both single molecule experimental techniques ,28-34 anB form DNA (B-DNA) and S form DNA (S-DNA), prior to dsDNA melting, was observed [B-DNA, S-DNA, and ssDNA, were quantified using the FJC and WLC polymer elasticity models, and were shown to agree well with expectations from previous experiments and theory.AFM is used to pull single-stranded DNA (ssDNA) and dsDNA molecules, and measure the force associated with the conformational changes Figure . DNA melobserved . The mecPoly(dA), a single-stranded DNA composed of uniform A bases , has alsLiving cells continuously consume energy to organize and maintain asymmetric architectures dictating their functions. One specific example is the orientation of myofibrils, which is a cord-like structure consisting of several different types of filamentous proteins that are organized into a regularly repeated subunit, the sarcomere. Myofibril matures in a force-dependent manner . Within In most tissues, cells can iteratively pattern morphogenetic units of similar size into complex forms. This occurs at both single- and multi-cell levels. For example, in the morphogenesis of a growth cone, single neuron cells form multiple, regularly separated neurites, which then differentiate into axon and dendrites . LikewisL, between neighboring activations. In turn, position cues can spontaneously emerge to pattern cell/tissue into regular/periodic shape.One appealing mechanism to control repetitive cell/tissue patterning is the chemical-based reaction–diffusion scheme proposed by Alan Turing  . LateralTo form lateral inhibition, it is required that the activation and the inhibition possess different spatial scales. In chemical-based lateral inhibition, this requirement can be achieved by having different diffusion coefficients for molecules that mediate the activation or the inhibition ,50,53-59Compared with chemical-based processes, several features of mechanical processes make them easier to create patterning cues. One example is that cells use differential motility to pattern tissues. For two types of cells that interact with each other Figure a, they ei.e., spatial anisotropy : S form DNA; (Ig): Immunoglobulin; (FN3): Fibronectin type 3; (BM): Basement membrane; (COL): Collagen.(ECM): Extracellular matrix; (FJC): Freely-jointed chain; (eFJC): Extensible FJC; (WLC): Wormlike chain; (ssDNA): Single-stranded DNA; (dsDNA): Double-stranded DNA; (B-DNA): The authors declare that they have no competing interests.CG conceived the study, participated in its design, and drafted the manuscript. NCH carried out the experiments and drafted the manuscript. SSW and EWF drafted the manuscript. CHK conceived the study, participated in its design, and drafted the manuscript. All authors read and approved the final manuscript.


In functional neuroimaging studies, ventral parietal cortex (VPC) is recruited by very different cognitive tasks. Explaining the contributions of VPC to these tasks has become a topic of intense study and lively debate. Perception studies frequently find VPC activations during tasks involving attention-reorienting, and memory studies frequently find them during tasks involving episodic recollection. According to the Attention to Memory (AtoM) model, both phenomena can be explained by the same VPC function: bottom-up attention. Yet, a recent functional MRI (fMRI) meta-analysis suggested that attention-reorienting activations are more frequent in anterior VPC, whereas recollection activations are more frequent in posterior VPC. Also, there is evidence that anterior and posterior VPC regions have different functional connectivity patterns. To investigate these issues, we conducted a resting-state functional connectivity analysis using as seeds the center-of-mass of attention-reorienting and recollection activations in the meta-analysis, which were located in the supramarginal gyrus  and in the angular gyrus (AG), respectively. The SMG seed showed stronger connectivity with ventrolateral prefrontal cortex (VLPFC) and occipito-temporal cortex, whereas the AG seed showed stronger connectivity with the hippocampus and default network regions. To investigate whether these connectivity differences were graded or sharp, VLPFC and hippocampal connectivity was measured in VPC regions traversing through the SMG and AG seeds. The results showed a graded pattern: VLPFC connectivity gradually decreases from SMG to AG, whereas hippocampal connectivity gradually increases from SMG to AG. Importantly, both gradients showed an abrupt break when extended beyond VPC borders. This finding suggests that functional differences between SMG and AG are more subtle than previously thought. These connectivity differences can be explained by differences in the input and output to anterior and posterior VPC regions, without the need of postulating markedly different functions. These results are as consistent with integrative accounts of VPC function, such as the AtoM model, as they are with models that ascribe completely different functions to VPC regions. Located ventrally to the intraparietal sulcus, the ventral parietal cortex (VPC) is comprised of the supramarginal gyrus [SMG (BA40)] and angular gyrus [AG (BA39)]. In line with traditional views linking the parietal cortex to attention Mesulam, , there iHowever, the AtoM model's integrative account of VPC function has been recently challenged by a meta-analysis of fMRI studies that reported a difference in the spatial distribution of VPC activations during attention-reorienting and recollection tasks  recruited from the University of Amsterdam community. All participants were in good health and right-handed. Their native language was Dutch and they were paid 25 euro for participation. Participants gave their written informed consent and the study met all criteria for approval of the ethical board of the Amsterdam Medical Center.* sensitive gradient echo sequence . Additionally, a high-resolution T1-weighted structural scan  was collected. Two 8-min rest blocks were administered to each participant. Each block consisted of a black screen with a white fixation cross-hair in the center. Participants were instructed to keep focused on the cross-hair during scanning.fMRI images were collected on a Phillips Intera 3.0T using a 6-channel standard SENSE head coil and a T2http://www.fil.ion.ucl.ac.uk/spm) software was used to preprocess and analyze the MR data. The images were slice-time and motion-corrected, and then normalized. First, individual normalization parameters were obtained by normalizing the segmentedstructural scan of each subject using the Montreal Neurological Institute (MNI) T1 template image. These normalization parameters were then applied to the functional images. Next, the normalized functional images were resliced to a resolution of 3 × 3 × 3 mm and spatially smoothed using an 8-mm isotropic Gaussian kernel. Next, treating the volumes as a time series, the data were temporally smoothed using linear detrending, and a temporal filter (0.01 Hz < f < 0.08 Hz) was applied to remove low-frequency drifts and physiological high-frequency noise.Statistical Parametric Mapping  the center of mass was x, y, z = −48, −45, 34, for recollection studies (N = 20), it was x, y, z = −43, −58, 36, . As can be seen, the attention-reorienting seed (red dot) was located more anteriorly, falling within SMG (BA 40) in a region commonly referred to as the temporo-parietal junction (TPJ)  was located more posteriorly falling within the boundaries of AG (BA 39).For the identification of the seeds, we used the center-of-mass of www.restfmri.net) integrated with SPM5. A seed correlation analysis was performed in a voxel-wise way with the six head motion parameters as covariates. Individual r-maps were normalized to Z-maps by using Fisher's Z transformation. For the seed analysis, two spherical regions of interest  were centered at the MNI coordinates derived from the two meta-analyses of attention-reorienting and recollection. Next, the Z-maps were averaged across runs for each participant. Subsequently, difference maps were created by subtracting the two resulting Z-maps. To assess relative differences in connectivity between the two seeds, we used a random effects analysis on these difference maps with a two-sided one-sample t-test .For analysis of the connectivity differences between the SMG and AG seeds we used the REST toolbox  with 2 intermediate voxels (6-mm). As shown in Figure attention-reorienting  peaks reported in Table P < 0.05 , nor for hippocampal connectivity . However, there was a significant change in slope when exiting VPC . Thus, our results indeed indicate that differences in connectivity patterns between VPC subregions associated with attention-reorienting and recollection are more graded rather than sharp, and that this pattern of gradedness is interrupted when extending the vector outside VPC. This last finding indicates that our results cannot easily be explained by confounding aspects associated with preprocessing of the functional images.To investigate if the connectivity differences between anterior and posterior VPC are graded or sharp, we measured the strength of VLPFC and hippocampal connectivity along a six-point 3D vector stretching throughout VPC, and going through the SMG and AG seeds Figure . As illuattention-reorienting tasks and a posterior seed in AG corresponding to the center-of-mass of activations during recollection tasks  than the AG seed. Most attention-reorienting tasks involve visuospatial stimuli and hence emphasize occipito-temporal input to VPC.In terms of our input/output hypothesis, the strong connectivity of the SMG seed with VLPFC could explain why VPC activations tend to be more anterior for recollection, the stronger connectivity of this seed with the hippocampal formation is consistent with the role of the well-known role of hippocampus in recollection. The AG seed also showed stronger connections with DMN regions, including the posterior cingulate cortex and medial prefrontal cortex. The DMN tends to be more activated during rest than during active task conditions. According to one account, the processes mediated by the DMN represent an internal mode of cognition . As we have argued, this need not be the case. These differences could just as easily reflect differences in applying a common (overarching) function to different domains, in our case perception and memory, about which information is conveyed via different pathways (Cabeza et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


HLA abnormalities on tumour cells for immune escape have been widely described. In addition, cellular components of the tumour microenvironment, in particular myeloid derived suppressor cells (MDSC) and alternatively activated M2 tumour-associated macrophages (TAMs), are involved in tumour promotion, progression, angiogenesis and suppression of anti-tumour immunity. However, the role of HLA in these activities is poorly understood. This review details MHC class I characteristics and describes MHC class I receptors functions. This analysis established the basis for a reflection about the crosstalk among the tumour cells, the TAMs and the cells mediating an immune response.The tumour cells and TAMs exploit MHC class I molecules to modulate the surrounding immune cells. HLA A, B, C and G molecules down-regulate the macrophage myeloid activation through the interaction with the inhibitory LILRB receptors. HLA A, B, C are able to engage inhibitory KIR receptors negatively regulating the Natural Killer and cytotoxic T lymphocytes function while HLA-G induces the secretion of pro-angiogenic cytokines and chemokine thanks to an activator KIR receptor expressed by a minority of peripheral NK cells. The open conformer of classical MHC-I is able to interact with LILRA receptors described as being associated to the Th2-type cytokine response, triggering a condition for the M2 like TAM polarization. In addition, HLA-E antigens on the surface of the TAMs bind the inhibitory receptor CD94/NKG2A expressed by a subset of NK cells and activated cytotoxic T lymphocytes protecting from the cytolysis.Furthermore MHC class II expression by antigen presenting cells is finely regulated by factors provided with immunological capacities. Tumour-associated macrophages show an epigenetically controlled down-regulation of the MHC class II expression induced by the decoy receptor DcR3, a member of the TNFR, which further enhances the M2-like polarization. BAT3, a positive regulator of MHC class II expression in normal macrophages, seems to be secreted by TAMs, consequently lacking its intracellular function, it looks like acting as an immunosuppressive factor.In conclusion HLA could cover a considerable role in tumour-development orchestrated by tumour-associated macrophages. Macrophages are tissue phagocytic cells that display the main activity of clearance independently of immune cells. However, they can be activated in response to either innate or adaptive immune signals and they are able to shape their phenotype to fit the microenvironment. In an attempt to simplify their complexity, activated macrophages can be categorized into two distinct subtypes: classically activated M1) and alternatively activated M2)  Growth Factor; HIV: Human Immunodeficiency Virus; HLA: Human Leucocyte Antigen; ICOS: Inducible T-cell Costimulator; IL: Interleukin; ILT: Immunoglobulin-Like Transcript 2; INF: Interferon; iNOS: inducible NO Synthase; KIR: Killer cell Immunoglobulin-like Receptor; LILR: Leukocyte Immunoglobulin-like Receptor; LPS: Lipopolysaccarhide; M: Macrophage; MHC: Major Histocompatibility Complex; NSLC: Non-Small Lung Cancer; mRNA: messenger RiboNucleoAcid; MSC: Mesenchymal Stem cell; MDSC: Myeloid-derived Suppressor Cell; NHL: Non-Hodgkin Lymphoma; NK: Natural Killer; Stat: Signal transducer and activator of transcription protein; TAP: Transporter associated with antigen processing; TAM: Tumour-Associated Macrophage; TCR: T-Cell Receptor; TGF: Tumour Growth Factor; TNFR: Tumour Necrosis Factor Receptor; VEGF: Vascular Endothelial Growth Factor.The authors declare that they have no competing interests.GVM is the project leader and he has designed the review, contributed with suggestions to the editing; MM has contributed to literature research and writing and concepts development; EA, LV, BS, AL and RK have contributed with specific editing and suggestion that regards their specific area of interest. All authors agreed and contributed to conceived the study, and participated to the final draft the manuscript. All authors read and approved the final manuscript.


Atrial arrhythmia (AA) is the most common complication after coronary artery bypass grafting (CABG). Only beta-blockers and amiodarone have been convincingly shown to decrease its incidence. The effectiveness of magnesium on this complication is still controversial. This meta-analysis was performed to evaluate the effect of magnesium as a sole or adjuvant agent in addition to beta-blocker on suppressing postoperative AA after CABG.We searched the PubMed, Medline, ISI Web of Knowledge, Cochrane library databases and online clinical trial database up to May 2012. We used random effects model when there was significant heterogeneity between trials and fixed effects model when heterogeneity was negligible.P = 0.40). Magnesium in addition to beta-blocker did not significantly affect LOS  or the overall mortality . However the risk of postoperative adverse events was higher in the combination of magnesium and beta-blocker group than beta-blocker alone .Five randomized controlled trials were identified, enrolling a total of 1251 patients. The combination of magnesium and beta-blocker did not significantly decrease the incidence of postoperative AA after CABG versus beta-blocker alone (odds ratio (OR) 1.12, 95% confidence interval (CI) 0.86-1.47, This meta-analysis offers the more definitive evidence against the prophylactic administration of intravenous magnesium for prevention of AA after CABG when beta-blockers are routinely administered, and shows an association with more adverse events in those people who received magnesium. Atrial tachyarrhythmias are a common complication of cardiac surgery, with an incidence of 11% to 40% in patients after coronary artery bypass grafting (CABG) and more than 50% in patients after valvular surgery. Atrial fibrillation (AF), flutter, and multifocal atrial tachycardia are different forms of atrial tachyarrhythmias, which have the similar clinical implications in early recovery of patients after cardiac surgery . AF, occHypomagnesemia has been observed after cardiac surgery ,9, and mTo evaluate the effect of magnesium as a sole or adjuvant agent with currently used prophylactic drugs such as beta-blocker in suppressing postoperative AA, several randomized controlled trials (RCTs) have been examined. However, the results were controversial, which could possibly be attributable to lack of statistical power in individual studies. Therefore, we conducted a meta-analysis of RCTs to evaluate the effect of magnesium on the prevention of postoperative AA, the hospital LOS, mortality and adverse effects in addition to beta-blocker after CABG.This meta-analysis of RCTs was performed in accordance with the Quality of Reporting of Meta-analyses (QUOROM) consensus guidelines and according to a protocol that prespecified outcomes, search strategies, inclusion criteria, and statistical analyses . We idenCriteria for study inclusion: (i) the design was a prospective, RCT; (ii) both on-pump and off-pump CABG techniques were included and no limitations were applied to the number of the grafts used; (iii) all patients were in sinus rhythm at the time of surgery; (iv) the intervention was magnesium, as a bolus or continuous infusion, with a total dose beyond 35 mmol, given as a prophylactic measure (before the onset of AA) in the intervention group. The intervention group used magnesium in addition to beta-blocker, and the comparison group just used the same type of beta-blocker; and (v) the primary outcome was the incidence of AA after CABG (measured using a continuous electrocardiogram (ECG) monitoring). Studies that met any one of the following criteria were excluded: (i) unspecified methods of detection of AA or unspecified process of follow-up; (ii) other than magnesium and beta-blocker, the patients using any other anti-arrhythmic drugs (e.g. amiodarone) as prophylactic measures; and (iii) patients with a history of AA or ventricular arrhythmias or any rhythm other than sinus rhythm on the electrocardiogram obtained the evening before surgery.Trials selected for review were screened for information about patient characteristics, details of administration, process of treatment, efficacy in preventing postoperative AA, LOS, mortality and adverse effects. All data were extracted by one author and checked for accuracy by another author independently. Disagreements were resolved by consensus, and if necessary, a third author was required to assess it. We used the Jadad score  to asseshttp://ims.cochrane.org/RevMan). The second author crosschecked the printout against his own data abstraction forms. All statistical analyses were performed using the RevMan5.1 package. Clinical homogeneity of included studies was considered first, by assessing study population, intervention group, comparison group and outcome. For dichotomous outcomes, results are expressed as risk ratio with 95% confidence interval (CI). For continuous outcomes, pooled data are described with the weighted mean difference (WMD) and 95% CI. Where significant heterogeneity was present, the studies were examined in detail for the reasons of heterogeneity. We assessed heterogeneity with I2, which describes the percentage of total variation across studies due to heterogeneity rather than chance. I2 can be calculated as: I2 = 100% × (Q-df)/Q. Negative values of I2 equaled zero, so that I2 ranged between 0%  and 100%. High values would show increased heterogeneity [P value <0.05. Where significant heterogeneity was present, attempts were made to explain the differences based on the patient clinical characteristics and interventions of the included studies. Random effects method was used to address heterogeneity where appropriate [One author entered related data into the meta-analysis software package  and little heterogeneity was indicated . Three trials reported the effect on hospital LOS with a total of 410 patients , although minor heterogeneity was indicated . Three trials reported data on postoperative mortality [P = 0.62). The risk of postoperative adverse events was higher in the combination of magnesium and beta-blocker group than beta-blocker alone group .The OR used for estimating the combination of magnesium and beta-blocker versus beta-blocker alone to prevent postoperative AA is shown in Figure ortality ,21,23, wP = 0.72). There was no statistically significant heterogeneity across the studies .We used subgroup analysis to explore the effect of POAT, including AF in Figure P = 0.38) (Table P = 0.21)  and high (> =50 mmol) dosages of magnesium. In the 2 trials with low dose magnesium (243 patients) ,20, the P = 0.92) (Table P = 0.38)  Table . In anot8) Table .AF is a common complication of CABG, especially in the elderly ,27. AlthAA is a common complication of CABG and beta-blockers have been shown to decrease the incidence of postoperative AA. Although magnesium has proven effective in reducing ventricular tachyarrhythmias and early mortality in acute myocardial infarction , its rolAlthough the meta-analysis by Miller et al.  concludeOne issue with the use of antiarrhythmic agents to prevent postoperative AA is that the majority of patients does not develop postoperative AA after cardiac surgery but would still be exposed to potential side effects of prophylactic intervention. From our meta-analysis, the risk of postoperative adverse events was higher in the combination of magnesium and beta-blocker group than beta-blocker alone group. The majority of adverse events were bradycardia and hypotension. An explanation for this phenomenon could be that intravenous administration of magnesium prolongs sinoatrial node conduction time, atrioventricular nodal refractory period, and PR and atrial-His intervals, as shown in electrophysiologic studies in healthy human subjects . It is aIt has been reported that sotalol is not only a beta-blocker but also a potent potassium channel blocker. Therefore, we conducted a subgroup analysis and subdivided trials into sotalol group and other beta-blockers group. Both sotalol group and other beta-blockers group showed the same result that magnesium in addition to beta-blocker could not significantly decrease the incidence of postoperative AA. At the same time, trials were subdivided into low and high dosages of magnesium, and showed the same result. Because there was no use of amiodarone in all the included trials, so we can exclude the impact of amiodarone on the results of this meta-analysis.Since postoperative AA has been associated with LOS extended, greater risk of major morbidity and accompanying increases in hospital costs, we conducted subgroup analyses about LOS and mortality. From this meta-analysis, magnesium in addition to beta-blocker did not significantly reduce the LOS in this meta-analysis. Since only 3 studies provided data on LOS, additional studies or data are warranted. Three trials reported data on mortality, and the result showed that the overall mortality was not affected by magnesium administration in addition to beta-blocker.This meta-analysis is limited by the lack of studies and complete availability of relevant data, particularly for LOS, mortality and adverse effects. Each included trial had different categories of adverse events. For example, the trial by Bert et al.  demonstrBased on this meta-analysis of RCTs, we can conclude that magnesium administration isn’t significantly effective for reducing postoperative AA, hospital LOS and mortality. Moreover, we observed an association with more adverse events in those people who received magnesium and beta-blocker. The combination of magnesium and beta-blocker does not appear to offer incremental benefit over beta-blocker alone in the prevention of AA. Considering the higher adverse effects, the combination of magnesium and beta-blocker should be contraindicated in patients undergoing CABG. Beta-blockers or amiodarone should be used for the prevention of postoperative AA. Therefore, we believe that this meta-analysis offers the more definitive evidence against the prophylactic administration of intravenous magnesium for prevention of AA after CABG when beta-blockers are routinely administered. In addition, considering limitations of this meta-analysis, more RCTs are needed to analyze and do more subgroups analysis in order to get much more accurate data. Larger studies to further confirm these clinical benefits and evaluate their cost-effectiveness would be worthwhile.The authors declare that they have no competing interests.XW conceived the study, participated in the design, collected the data, and drafted the manuscript. CW conceived the study, participated in the design, and helped to draft the manuscript. JZ collected the data, and drafted the manuscript. CZ and YZ collected the data, and performed statistical analyses. YG helped to draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/13/5/prepub


We describe a very rare case of outflow cannula obstruction with fungal infectious thrombus formation. Discussion includes the etiology, diagnosis, and management of fungal infection complications related with long-term mechanical circulatory support. Left ventricular assist devices (LVADs) are increasingly used as bridge to transplant and permanent long-term therapy in the population with end-stage heart failure. Even though better clinical outcomes have been achieved with the newer-generation continuous-flow devices, infection complications are still a major risk for patients with continuous-flow LVAD implantation in long-term follow-up . Device-related infections can be categorized as driveline infections, pump-pocket infections, and LVAD-associated endocarditis . The microbiological profile is very heterogeneous; the most common pathogens are Staphylococcus, Pseudomonas, Streptococcus species, and Candida. Severe fungal infection may lead to dysfunction of the LVAD due to obstructive mass formation within the device. Due to the only anecdotal reports in the current literature, we present a very rare case of outflow fungal infectious thrombus formation leading to outflow cannula obstruction in patient with LVAD. Left ventricular assist devices (LVADs) are increasingly used as bridge to transplant and permanent long-term therapy in the population with end-stage heart failure. Even though better clinical outcomes have been achieved with the newer-generation continuous-flow devices, infection complications are still a major risk for patients with continuous-flow LVAD implantation in long-term follow-up . Device-A 56-year-old caucasian male with dilated cardiomyopathy was previously treated with an implantable cardiac defibrillator (ICD) as secondary prevention therapy (2002) and with a combined system of cardiac resynchronization therapy (CRT) and ICD—CRT/ICD therapy (2009) with several infectious complications, which led to explantation of the system and reimplantation of the CRT/ICD .The patient was admitted to our institution (12/2010) from a referral hospital in cardiogenic shock with arrhythmic storm triggered with incessant monomorphic ventricular arrhythmia. Radiofrequency (RF) ablation was unsuccessful, so urgent implantation of an LVAD—HeartMate II  was indicated. The procedure was performed in a standard fashion under transesophageal echocardiogram (TEE) guidance together with De Vega tricuspid valve annuloplasty and cryodestruction of arrhythmogenic substrate.During the entire postoperative period, repeated life-threatening septic complications were observed. The patient was treated gradually with antibiotics to 02/2011 . Computed tomography (CT) scans showed signs of pulmonary interstitial pneumonia in both lungs from 12/2010 to 2/2011. During this period, it was necessary to intubate the patient several times because of respiratory insufficiency. Clinical signs of infection disappeared after prolonged treatment with broad-spectrum antibiotics. In early 2/2011 CT scans, bronchoscopy with lavage, and blood cultures were negative.The patient also had repeated gastrointestinal bleeding that required blood transfusion. Colonoscopy showed no clear source of bleeding—inflammation and small surface ulceration of the colon, two small sores in rectal ampulla, and normal gastric fibroscopy. Parenteral nutrition and intermittent nasogastric tube were used.Following the gradual rehabilitation and education of the patient about operating the LVAD equipment and dressing the driveline exit site, he was discharged to home. Calculated LVAD flow ranged between 5.0 and 6.0 L/min. During the entire duration of circulatory support, no LVAD suction events were detected, pump power consumption remained in the normal range , and the patient was listed for heart transplantation. We did not observe any signs of hemolysis; anticoagulation levels remained stable, and the bilirubin levels throughout postoperative follow-up were within normal range. The patient had no signs of active systemic infection.The patient was rehospitalized in 3/2011 due to worsening of his condition. He was afebrile, fatigued, had a dry cough and brown discoloration of urine. Hemoglobinuria, an increase of inflammatory markers, and mild alteration in hepatic and renal function were detected. Initial blood cultures were negative. Transthoracic echocardiogram (TTE) and TEE imaging showed no obstruction of the inflow or outflow cannulas, but there was a decrease in flow velocities . The left ventricle was severely dilated and hypokinetic. The aortic valve was opening at 1:1. Even at high-speed operation , the left ventricle could not be unloaded with closure of the aortic valve. Systemic thrombolysis was considered, but a donor heart became available (patient was listed as an urgent candidate) and heart transplantation was performed in 4/2011. Examination of the explanted LVAD revealed thrombotic-like obstruction of the outflow cannula (Figures ® Therapy. Candida albicans was culture-confirmed in multiple samples. Therefore, the patient was aggressively treated with antifungal therapy in the first three months with intrakonazol and then treated for the next nine months with fluconazol. Lower-dose corticosteroid protocol with 5 mg of prednisone daily was administered. After one year, conversion from sirolimus to everolimus was made because of early signs of coronary artery disease in the donor heart. During the two years follow-up, the patient was monitored according to our institutional protocol with regular cardiac biopsies and echocardiogram examinations, without any signs of serious complications.The patient was discharged from the hospital eight weeks after the transplantation. During the first 12 months, patient was repeatedly hospitalized due to soft tissue wound infections. Treatment consisted of soft tissue debridement and V.A.C.With increasing durations of LVAD support, the accurate diagnosis of device malfunction is crucial . DiagnosCandida infection prophylaxis to all LVAD paints, during high-risk periods. Aspergillosis prophylaxis is not routinely recommended. In case of proved fungal infection the early initiation of effective should be critical. Patients afflicted by Candida endocarditis should be immediately treated with echinocandin. In patients with suspected invasive aspergillosis voriconazole is administered as the first choice therapy [According to the recent guidelines, in our institution, we administer fluconazol as a  therapy . Here shIn our case, the major pathogen was Aspergillus species, which was identified through histopathological methods. Clinical manifestation of Aspergillus infection is uncommon. When it does occur, it is almost always in the setting with an immunocompromised patient. Filamentous fungi as a pathogen are infrequently associated with device infection. In earlier presented case series of Aspergillus infections in LVAD patients, there was clinical evidence of outflow-tract obstruction related to overwhelming device infection similar to our case. Current imaging techniques, either CT scan or echocardiography, were limited in their ability to exactly detect LVAD-associated endocarditis in our patient. Definitive diagnosis was established from species identification of the obstructive mass in the internal surface of the outflow cannula following explantation of the device. It should be stressed that tissue specimens from the device must always undergo histopathological examination.Current data are limited, but it is confirmed that combined medical and surgical therapy generally should be the preferred treatment for fungal endocarditis. Although there are no currently available evidence-based guidelines regarding LVAD endocarditis, we believe that clinical decision-making in patients with signs of ongoing sepsis and end-organ dysfunction together with any signs of LVAD malfunction should be very straightforward in terms of device exchange or explantation. In patients with VADs and severe fungal infection who cannot be explanted electively, an urgent transplant listing plays key role. Due to organ donors shortage VAD exchange via left subcostal incision is increasingly used.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.LVAD: Left ventricular assist device; ICD: Implantable cardiac defibrillator; CRT: Cardiac resynchronization therapy; RF: Radio-frequency; TEE: Transesophageal echocardiogram; TTE: Transthoracic echocardiogram; CT: Computer tomography.The authors whose names are listed immediately below certify that they have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript. Authors: Jiri Maly, MD, PhD; Ondrej Szarszoi, MD, PhD; Zora Dorazilova, MD; Josef Besik MD, PhD; Martin Pokorny, MD; Tomas Kotulak MD; Ivan Netuka MD, PhD.JM Operated on the patient, main author. OS Operated on the patient, co-author. ZD the patient was followed-up in her cardiological ambulance after LVAD implantation, co-author. JB the patient was followed-up in his surgical ambulance after LVAD implantation, co-author. MP took care of the patient on ICU, co-author and drafted the manuscript. TK Anaesthetist, co-author. IN Operated on the patient, co-author. All authors read and approved the final manuscript.


Yoga is one of the most common forms of complementary and alternative therapies utilized for weight loss. This mixed methods study included quantitative surveys and interviews of participants of a 10-week, bi-weekly yoga and Ayurveda-based weight loss program designed for overweight and obese women. The program involved training in yoga poses, breathing, and philosophy as well as eating mindfully, cultivating relaxation, and compassion.This analysis focuses on the subject interviews which occurred both pre and post program and covered the topics of: (1) hopes and found benefits of the program, (2) anticipated challenges and lessons learned, (3) subjects’ relationships with food pre and post program. Analysis was directed by a grounded theory approach. The interview notes were double coded independently by the two authors. Any disagreements in coding were addressed in discussion. Coding consisted of searching for sought themes and emergent themes in each transcript as well as condensing responses to each topic across the sample.Thirty-seven overweight and obese participants were enrolled  with mean age of 48.3 years. Most were yoga naïve and had tried weight loss programs in the past. The qualitative findings support the trial’s quantitative findings of statistically significant improvements baseline to post program in BMI (p<0.05), and a number of psychosocial variables. Pre-program, subjects reported that they were drawn to the yoga-based program to achieve greater clarity, structure, and security in their lives in addition to losing weight. Post program, subjects reported greater sense of security, self-confidence, self-compassion, and insight into their behavioral motivations. Useful program tools mentioned are: breath work, mindful eating, focus on self-care, relaxation.Our data suggests that participation in a 10-week yoga and Ayurveda-based weight loss program is associated with improvements in reported psychosocial health immediately following program completion.


DES) are associated with desminopathy; a myofibrillar myopathy mainly characterized by muscle weakness, conduction block, and dilated cardiomyopathy. To date, only ~50 disease-associated variants have been described, and the majority of these lead to dominant-negative effects. However, the complete genotypic spectrum of desminopathy is not well established.Variants in the desmin gene (DES variants, both of which are predicted to lead to a loss-of-function. Consistent with recessive inheritance, each variant was identified in an unaffected parent.Next-generation sequencing was performed on 51 cardiac disease genes in a proband with profound skeletal myopathy, dilated cardiomyopathy, and respiratory dysfunction. Our analyses revealed compound heterozygous This case report serves to broaden the variant spectrum of desminopathies and provides insight into the molecular mechanisms of desminopathy, supporting distinct dominant-negative and loss-of-function etiologies. DES) encodes an intermediate filament protein important for maintaining cytoskeletal architecture in skeletal, smooth, and cardiac muscles [DES variants described thus far are missense variants inherited in a dominant fashion. These variants commonly result in a dominant-negative effect on wild-type proteins, leading to destabilization of desmin intermediate filament networks, accumulation of mutant desmin aggregates, and ultimately, myofibrillar disorganization and toxicity [The desmin gene . Variant calls were generated using the Burrows-Wheeler Aligner (BWA) followed by GATK analysis. Sanger sequencing was used to confirm variants and to perform familial sequencing. Variants are reported according to HGVS nomenclature (http://www.hgvs.org/mutnomen) using NCBI Reference Sequence NM_001927.3.SureSelect oligonucleotide-based target enrichment  followed by next generation sequencing on the Illumina HiSeq2000 platform was used to sequence the coding regions and splice sites of 51 cardiomyopathy genes (for a list of genes see: DES gene: c.600delG which is predicted to result in a frameshift and subsequent premature termination codon (p. Lys201ArgfsX20), and c.1285C > T which is predicted to result in a premature termination codon (p. Arg429X) . However, this does not conflict with a pathogenic role, as this individual may be presymptomatic . Both variants lead to premature termination codons and are predicted to result in truncated or absent proteins. Based on the presentation in this family, these variants are likely to be pathogenic when present in combination, and unlikely to cause disease in isolation. Although the segregation of DES variants in this family supports a recessive inheritance, dominant effects with reduced penetrance or a milder presentation leading to late-onset disease cannot be ruled out.The Lys201ArgfsX20 variant in DES variants. Together, these data suggest that recessive desminopathies may lead to a severe, early-onset form of disease.The majority of desminopathies described to date are dominant; however, three cases exhibiting a recessive mode of inheritance have been reported including compound heterozygosity for two missense variants (p. Ala360Pro and p. Asn393Ile) in a family with severe, childhood-onset desminopathy, homozygosity for an in-frame deletion (p. Arg173_Glu179del) in a family with early-onset desminopathy and congenital sensory deafness, and recently, compound heterozygosity for loss-of-function variants (p. Thr76fsX21 and p. Glu108X) in a family with early-onset proximal muscle fatigue and weakness . The famDES variants have been previously reported in the literature [DES variants result in impaired intermediate filament formation and aberrant desmin aggregation, suggesting that these variants do not result in a complete loss-of-function and instead lead to mRNAs that escape NMD and are translated in heterozygous individuals, resulting in a dominant-negative effect on the wild-type protein [Nine predicted loss-of-function terature -11. It iterature . Howeverterature . Functio protein ,7.The three heterozygous family members of our index case carry predicted loss-of-function variants yet are currently unaffected, suggesting that these variants may lead to genuine loss-of-function, as the presence of truncated protein would be expected to lead to a phenotype in heterozygous individuals. It is predicted then, that the affected individuals in this family lack any functional desmin protein. While we were unable to analyze a muscle biopsy from our current case for desmin staining, a recent report of an additional family with recessive desminopathy caused by loss-of-function DES variants revealed a complete lack of desmin staining in a muscle biopsy from an affected individual in that family . InteresDES variants in two siblings with desminopathy. This study broadens the variant spectrum of desminopathy and provides evidence that both dominant-negative and loss-of-function effects play a role in the molecular pathogenesis of desminopathy.We present compound heterozygous, predicted loss-of-function The patient has read and approved the manuscript and written informed consent was obtained.The authors declare that they have no competing interests.HMM performed variant analysis and interpretation and drafted the manuscript. MAK performed variant analysis and interpretation and edited the manuscript. PPH provided genetic counseling to the family and assisted in clinical evaluation of the proband. BTD performed the neurological examination of the proband. BF performed variant analysis and interpretation and edited the manuscript. JP performed clinical evaluation of the proband and assisted in drafting of the manuscript. All authors have read and approved the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/14/68/prepub


To improve quality of life (QOL) in patients with multiple sclerosis (MS), it is important to decrease disability and prevent relapse. The aim of this study was to examine the causal and mutual relationships contributing to QOL in Japanese patients with MS, develop path diagrams, and explore interventions with the potential to improve patient QOL.Data of 163 Japanese MS patients were obtained using the Functional Assessment of MS (FAMS) and Nottingham Adjustment Scale-Japanese version (NAS-J) tests, as well as four additional factors that affect QOL . Data were then used in structural equation modeling to develop path diagrams for factors contributing to QOL.The Expanded Disability Status Scale (EDSS) score had a significant effect on the total FAMS score. Although EDSS negatively affected the FAMS symptom score, NAS-J subscale scores of anxiety/depression and acceptance were positively related to the FAMS symptom score. Changes in employment status after MS onset negatively affected all NAS-J scores. Knowledge of disease information improved the total NAS-J score, which in turn improved many FAMS subscale scores. Communication with doctors and nurses directly and positively affected some FAMS subscale scores.Disability and change in employment status decrease patient QOL. However, the present findings suggest that other factors, such as acquiring information on MS and communicating with medical staff, can compensate for the worsening of QOL. Multiple sclerosis (MS) is a chronic disease of the central nervous system that manifests as inflammation, demyelination, axonal degeneration, and gliosis. To date, however, no known cure for the disease exists, and patients with MS may experience a number of neurological disabilities despite receiving adequate disease-modifying therapies. The disabling nature of the disease has multiple consequences which not only affect physical activity, psychological aspects, and social interplay, but also create burdens for family members . Role liWe previously reported the first evaluation of the entire QOL spectrum in Japanese MS patients by using the Functional Assessment of MS (FAMS), which consists of an MS-specific QOL scale with a self-reported questionnaire and the Nottingham Adjustment Scale-Japanese version (NAS-J), which is a self-reported questionnaire for determining psychological adaptation . Out invTo improve QOL in MS, it is important to decrease disability and prevent relapse. Therefore, in this study we used structural equation modeling for the following purposes: 1) to examine the causal and mutual relationships that contribute to QOL in Japanese MS patients; and 2) to develop path diagrams for determining the interventions that are useful for targeting the environmental factors with the potential to improve QOL.The study population of the present study is the same as that of our previous study . BrieflyThe study protocol was approved by the Ethics Committee of Hokkaido University, and written consent was obtained from all patients.The measures completed by the MS patients as a means to assess QOL are described in detail in our previous paper . In thisUsing SPSS® Amos, structural equation modeling was performed to develop path diagrams of the factors that contribute to QOL. Models were constructed with the additional four factors as independent variables, FAMS subscales as dependent variables, and NAS-J subscales as mediator variables between the independent and dependent variables.When analyzing the total FAMS score as well as each FAMS subscale, the mean score of all FAMS subscales was taken to be the dependent variable, and the mean score of all NAS-J subscales was taken to be the mediator variable. Finally, the mediating effects of the NAS-J subscales were investigated by examining latent variables to determine whether any of the relationships among the measures had been incorrectly assumed during the modeling process.2, p), comparative fit index (CFI), and root mean square error of approximation (RMSEA). When parameters with a high goodness-of-fit were determined such that several models had high fitness indices, the most parsimonious model was selected based on the Akaike’s Information Criterion.Maximum likelihood estimation was used to estimate model parameters. During this process, we used the following three goodness-of-fit indices: results of a Chi-squared test (χ2 (5) = 2.656, p = 0.753, CFI = 1.000, RMSEA = 0.000. The EDSS score affected the total FAMS score directly, and the direct negative influence of the EDSS score on the total FAMS score had the largest path coefficient compared with other factors. Changes in household income positively and directly affected the total FAMS score. Increases in the number of sources of disease information and self-evaluation of knowledge of disease information positively affected the total NAS-J score, while changes in employment status negatively affected the total NAS-J score. The total NAS-J score positively influenced the total FAMS score, and its influence was 1.5-fold greater than that of EDSS.Goodness-of-fit values were as follows: χ2 (7) = 7.129, p = 0.416, CFI = 1.000, RMSEA = 0.011. The EDSS score and changes in employment status decreased the scores of the latent variable comprising NAS-J anxiety/depression and acceptance. In contrast, self-evaluation of knowledge on MS positively affected these NAS-J subscales. A reduced EDSS score had a direct negative effect on the FAMS mobility score, and the path coefficient related to this influence was more negative than that for the effect of the EDSS score on the NAS-J anxiety/depression and acceptance scores. Finally, NAS-J anxiety/depression and acceptance scores positively affected FAMS mobility, although this positive effect was weak compared with the negative effect of increases on the EDSS score.Goodness-of-fit values were as follows: χ2 (6) = 5.167, p = 0.523, CFI = 1.000, RMSEA = 0.000. Increased EDSS scores and changes in employment status reduced the scores of the latent variables comprising NAS-J anxiety/depression and acceptance, whereas the knowledge of disease information score increased these scores. However, knowledge of disease information negatively affected FAMS symptoms. Communication with doctors had a direct positive influence on the FAMS symptom score. The NAS-J anxiety/depression and acceptance scores had a positive effect on the FAMS symptom score, and its influence was 1.5-fold greater than that of EDSS. These data suggest that a decrease in patient anxiety/depression and acceptance of the disease (and its severity) can improve MS symptoms compared with an evaluation of patient disability using the EDSS.Goodness-of-fit values were as follows: χ2 (24) = 28.870, p = 0.225, CFI = 0.990, RMSEA = 0.035. Changes in employment status and EDSS scores negatively affected the NAS-J anxiety/depression, self-esteem, acceptance, and attitude scores. In contrast, these NAS-J subscales positively affected scores for the number of sources of disease information and self-evaluation of knowledge of disease information. Latent variables comprising the NAS-J anxiety/depression, self-esteem, acceptance, and attitude scores had a significant positive effect on the FAMS emotional well-being score. The personal income score also influenced the FAMS emotional well-being score, although the effect was weak.Goodness-of-fit values were as follows: χ2 (23) = 22.968, p = 0.463, CFI = 1.000, RMSEA = 0.000. All NAS-J subscale scores, except for attitude, positively affected the FAMS general contentment score. EDSS and changes in employment status scores negatively affected latent variables comprising NAS-J anxiety/depression, acceptance, and self-esteem scores, whereas increases in the self-evaluation of knowledge of disease information score positively affected these NAS-J subscale scores. Furthermore, increases in the score for the number of sources of disease information increased latent variables comprising NAS-J locus of control and self-efficacy scores. Here, the first set of the NAS-J latent variables comprising anxiety/depression, acceptance, and self-esteem scores produced a greater positive effect on the FAMS general contentment score compared with the second set which comprised the locus of control and self-efficacy scores.Goodness-of-fit values were as follows: χ2 (13) = 18.104, p = 0.154, CFI = 0.981, RMSEA = 0.049. NAS-J anxiety/depression, attitude, and acceptance scores positively affected the FAMS thinking and fatigue score. Conversely, increases in the EDSS and self-evaluation of knowledge of disease information scores decreased the FAMS thinking and fatigue score directly. Changes in household income and self-evaluation of knowledge of disease information scores related positively to the NAS-J anxiety/depression, attitude, and acceptance scores. However, the influence of the NAS-J anxiety/depression, attitude, and acceptance scores on the FAMS thinking and fatigue score was more than 2-fold that of EDSS.Goodness-of-fit values were as follows: χ2 (24) = 25.634, p = 0.372, CFI = 0.994, RMSEA = 0.021. Anxiety/depression, self-esteem, attitude, and acceptance scores all positively affected the FAMS family/social well-being score, and these NAS-J subscales were in turn negatively affected by changes in employment status and EDSS scores. Moreover, self-evaluation of knowledge of disease information scores positively influenced these NAS-J subscales. Scores for communication with nurses and the number of sources of disease information had a positive effect on the FAMS family/social well-being score. However, EDSS scores did not affect the family/social well-being score directly.Goodness-of-fit values were as follows: χThe EDSS score had the most prominent affect on the NAS-J subscale scores as well as on all the FAMS subscale scores both directly and indirectly. Worsening of disability negatively affected psychological status, which was followed by worsening of FAMS scores. Furthermore, the EDSS score directly affected mobility, symptoms, emotional well-being, and thinking and fatigue. Taken together, the EDSS score is an important reflection of the QOL of MS patients, which means that, for example, prevention of relapse and improvement of disability through rehabilitation could improve patient QOL ,15. ConvChanges in employment status after being diagnosed with MS reduced all NAS-J scores, and changes in employment status worsened patient anxiety, depression, acceptance of disability, and self-esteem scores. In contrast, obtaining more information on the disease compensated for worsening of the NAS-J scores in response to a change in employment status. We previously reported that 62% of patients experienced some kind of change in employment status, such as quitting a job or reducing their working hours, after the onset of MS . The ageet al.[Obtaining information on MS improved the total NAS-J score, which was followed by improvement of many of the FAMS subscale scores. Increasing the number of sources of disease information also improved the scores for several NAS-J subscales. These findings indicate that acquiring information on MS is useful for psychological adjustment in MS patients and that awareness and coping may be associated with this improvement, as pointed out by Patti et al.. In contThe effect of communication with medical staff differs between communication with doctors and that with nurses. Good communication with doctors improved the total FAMS score and FAMS symptom score directly, not through the total NAS-J score. Good communication with nurses also improved the FAMS family/social well-being score. The data suggest that good communication with medical staff can improve the QOL of MS patients while compensating for worsening disability. Moreover, it may be more effective for doctors to talk about symptoms and therapies with patients and for nurses to talk about daily life activities and self-care.The findings of the present study, which are in agreement with those of previous studies, indicate that the progression of disability and changes in employment status are major factors that decrease QOL for MS patients. While progression of disability may not be avoidable even in patients receiving adequate treatment, our findings suggest that other factors such as acquiring adequate information on MS and communication with medical staff can compensate for the decrease in QOL. Interventions that target these factors have the potential to improve QOL in Japanese MS patients.MS: Multiple sclerosis; QOL: Quality of life; FAMS: The functional assessment of multiple sclerosis; NAS-J: The Nottingham adjustment scale-Japanese version; EDSS: The expanded disability status scale; CFI: The comparative fit index; RMSEA: The root mean square error of approximation.The authors declare that they have no competing interests.HK designed the study and wrote manuscript. NM performed statistical analysis. MN assisted with writing the manuscript and reviewed the manuscript. JK, TK, KO, MT, HO, and SN contributed to data collection. SK assisted in study design and reviewed the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2377/13/10/prepub


Trial design and conduct is informed by systematic reviews and meta-analyses (MAs). For time-to-event outcomes, they are typically based on hazard ratios (HRs). Ideally, these are calculated from individual patient data (IPD). Alternatively, they can be extracted from published aggregate data (AD) or estimated from other statistics or from Kaplan-Meier (KM) curves. As reporting and the reliability of each estimation method is likely variable, we investigate how HRs from AD and IPD compare.We used 18 of our published IPD systematic reviews and MAs. For our primary outcome of overall survival, we extracted or estimated logHRs and standard errors (SEs) from eligible trials wherever possible. We compared HRs from AD and IPD at the trial and meta-analysis level, using Bland-Altman methods to assess agreement.Of 245 unique trials eligible for the meta-analyses, HRs were available from IPD for 199 (81%), and from AD for 155 (63%) including 75 (48%) based on KM curves. Trial logHRs from AD were biased towards benefit compared to IPD , and SEs were inflated . Bias was not influenced by estimation method (p=0.84). Similar bias was seen in MA logHRs from AD , and again inflated SEs . The level of bias varied by meta-analysis.Although MAs of AD-derived HRs can be biased, their use is widespread and needed when the IPD approach is infeasible. We will present results on causes of these biases and guidance on overcoming them.


Jude Medical Regent valve in a large series of patients, and to determine if these effects are influenced by patient confounding variables.The study was designed to evaluate the effects of moderate prosthesis-patient mismatch .The prevalence of moderate prosthesis-patient mismatch was documented in 46 patients (43.4%) at discharge. During the follow-up period, no difference in the regression of left ventricular mass, decrease of transvalvular pressure gradients, mortality and prosthesis-related complications was observed between patients with and without moderate prosthesis-patient mismatch. After adjustment for several risk factors, moderate prosthesis-patient mismatch was associated with increased midterm mortality in patients with baseline left ventricular ejection fraction < 50% , but with normal prognosis in those with preserved LV function. Younger age  was not an independent predictor of increased midterm mortality and valve-related complications in patients with moderate prosthesis-patient mismatch.Moderate prosthesis-patient mismatch after aortic valve replacement with a small mechanical prosthesis is associated with increased mortality and adverse events in patients with pre-existing left ventricular dysfunction. Selected patients with small aortic annulus can experience satisfactory clinical improvements and midterm survival after aortic valve replacement with a 17-mm Regent valve. The measured EOAi, a valid parameter for quantification of the severity of P-PtM, was calculated by dividing the EOA by the BSA. Also, the projected EOAi was derived from the published normal in vivo EOA values for the 17 mm SJMR valve and indexed to BSA , and therefore a “quick and simple” procedure was required to reduce myocardial ischemic time. It is clinically evident that a prolonged aortic cross-clamp time is one of the most important risk factors for post-AVR adverse events [4.9%], an.5%, NYHAAn important finding of this study is that moderate P-PtM is associated with increased postoperative mortality in patients with LVEF < 50%, but with normal prognosis in those with preserved ventricular function. Since patients with impaired LV function are more vulnerable to the excessive afterload imposed by P-PtM, it is reasonable to find in our series that the follow-up mortality are significantly increased in patients with a combination of moderate P-PtM and impaired LV systolic function. Studies from several groups also clearly indicated that the influential role of moderate P-PtM on late survival is more important in patients with reduced ventricular reserve than in those with preserved LV function ,13. On tPrevious studies have demonstrated that the influence of P-PtM on postoperative outcomes is an age-dependent phenomenon. As reported by Mohty et al.  and MoonSome could argue that the use of mechanical prostheses in AVR may potentially increase mortality and morbidity compared with the use of bioprosthesis, particularly due to anticoagulation–related complications . HoweverThis study was subject to the limitations inherent to a retrospective, nonrandomized comparison of clinical data, so it is likely that a selection bias or unidentified confounders might have influenced the results. In the present study, moderate P-PtM was determined by echocardiographic-measured EOAi. As suggested by other studies ,26, the 2. Hence, the observed effects of the moderate P-PtM on midterm outcomes after AVR with a 17-mm Regent valve cannot be generalized to obese patients. In addition, the small number of patients with severe P-PtM in our series prevented our further investigation of the long-term safety and effectiveness of the 17-mm Regent valve.The improvement of a patient’s physical capacity was not quantified in the present study (eg. the use of the SF-36 questionnaire), and the impact of the moderate P-PtM on patients’ quality of life is thereby questionable. Beyond the preoperative LVEF and age, body mass index is also an important factor that may have a significant impact on postoperative outcomes. However, in our series, only a small proportion of patients (11 patients) have a body mass index above 25 kg/mModerate P-PtM after implantation of a small mechanical prosthesis at aortic position is associated with increased midterm mortality and valve-related complications in patients with pre-existing LV dysfunction. Selected patients with small aortic annulus can experience satisfactory clinical results and midterm survival after isolated AVR with a 17-mm SJMR valve.AVR: Aortic valve replacement; BSA: Body surface area; EOA(i): Effective orifice area (index); LV: Left ventricle; LVM(i): Left ventricular mass (index); LVEF: Left ventricular ejection fraction; NYHA: New York Heart Association; P-PtM: Prosthesis-patient mismatch; PT-INR: International normalized ratio of prothrombin time; SJMR: St. Jude Medical Regent.The authors declare that they have no competing interests.JH designed the protocol, analyzed data, contributed to the discussion and wrote the manuscript. HQ, YL and JG collected, researched data, contributed to the discussion. JJZ analyzed and researched data. EZ contributed to the discussion and reviewed/edited the manuscript. All authors read and approved the final manuscript.


Mycobacterium tuberculosis (Mtb) in the pathogenesis of infection and disease, as well their potential for use as diagnostic reagents and vaccine antigens, are unknown.The role of the surface capsular polysaccharides (CPs) of Serum antibody to two CPs of Mtb, arabinomannan (AM) and glucan (Glu), were studied in samples from 52 18–74 year-old HIV-seronegative, immunocompetent individuals in Houston Texas. The effects of Mtb exposure, infection and disease upon the levels of antibodies to these CPs were assessed. Subjects were grouped according to the standard international classification.IgA anti-Glu levels were significantly higher in the active and treated TB compared to a group that was PPD-negative without TB exposure history (p<0.05). Antibodies against AM demonstrated a similar pattern, with the exception that IgG anti-AM was higher in groups who had active TB or previously documented active TB, and IgA anti-AM was higher in subjects with previously documented active TB compared to the level in an unexposed, PPD-negative group (p<0.05). Serum IgG anti-Glu levels were higher in subjects with active TB or previously documented active TB than in the unexposed PPD-negative group, but the differences were not significant.These data suggest that the evaluation of antibody responses to the CP of Mtb may have utility for TB serodiagnosis, and that vaccines designed to induce humoral responses to TB CPs should be tested for their capacity to evoke anti-tuberculosis protective immunity. Despite the availability of chemotherapeutic agents and a vaccine (BCG), Mtb remains the number one cause of death due to bacterial infectious diseases worldwide. In 2011, 8.7 million people developed clinical disease and 1.4 million died from TB [Haemophilus influenzae type b, Streptococcus pneumoniae, Neisseria meningitidis and Salmonella typhi have been shown to inhibit complement-mediated and phagocytic actions, thereby preventing initial control of infection [Mtb is an encapsulated organism and its capsule is composed of lipid derivatives of arabinomann (AM) and glucan (Glu) -6. The rnfection ,8. AntibMale and female subjects ≥ 18 years old ;Group I Exposed to TB but no evidence of infection ;Group 2 TB infection (positive PPD) but no disease ;Group 3 Active TB;Group 4 History of active TB with no current disease (previously documented active TB).2O, freeze dried and passed through a CL-6B Sepharose column. The single peak in this eluate, composed of AM, was dialyzed and freeze-dried. Both CPs contained <1% protein and nucleic acids [The two polysaccharides were purified from a 70% ethanol precipitate of a liquid culture of Mtb strain MT29248. The precipitates were suspended in 0.02 M potassium phosphate, pH 7.4, stirred 2 hours, spun down and the supernatant passed through a DEAE column equilibrated in the same buffer. The non-retarded fraction was concentrated, passed through a CL-4B Sepharose column and the major peak, composed of Glu, freeze-dried. The later eluant fractions were dialyzed against Hic acids .nd antibody . A patient’s plasma obtained by plasmapheresis was used as the standard for the 3 isotypes The isotype-specific concentrations of anti GLU and anti AM in that plasma were assigned by ELISA in comparison to purified IgG, IgM and IgA of known concentrations, as described [Serum anti-Glu or anti-AM levels were measured by ELISA during year 2000 . Nunc plescribed .Unexposed, PPD-negative subjects (group 0) were considered the reference control group for statistical evaluations of serum antibody levels against the two polysaccharides. Data were not normally distributed, so non-parametric statistical analyses were performed. Median antibody levels between groups were compared using a Kruskall-Wallis (KW) test, and when significant differences were identified, post- hoc comparisons of other groups to group 0 were performed using Dunn’s post hoc test corrected for multiple comparisons. P values ≤ 0.05 were considered significant.Fifty-two eligible subjects were enrolled Table . The meaAntibodies to both polysaccharides were detectable in all groups Table . There wSerum antibodies of the three major isotypes to two CPs of Mtb in HIV-negative adults stratified according to their tuberculosis status were measured by ELISA with purified antigens. Antibodies to both polysaccharides were detectable in all groups. Importantly, the Ig A anti-Glu levels were significantly higher in the active and treated TB groups compared to unexposed subjects who were PPD-negative. Antibodies against AM demonstrated a similar pattern, with the exception that IgG anti-AM was higher in subjects with active TB or previously documented active TB, and the IgA anti-AM was higher in subjects with previously documented active TB when compared with unexposed, PPD-negative subjects. Serum IgG anti-Glu levels were higher in groups with active TB or previously documented active TB than in a group of unexposed, PPD-negative subjects, but the differences were not significant. Thus, with this small number of subjects, groups of patients who had active or treated disease could be identified by the level of antibodies to these two CPs. These data suggest that assays based on antibody responses to the CPs of Mtb may be of value for the serodiagnosis of TB.Mycobacterium avium sonic extracts and mycobacterial LAM in children correlates with increasing age, and by 18 years of age many individuals were seroreactive to mycobacterial antigens [What could be the origin of CP antibodies in unexposed, PPD-negative people? Similar to other capsulated pathogens, cross-reactive anti-polysaccharide antibodies were probably generated by exposure to environmental mycobacteria or non-pathogenic enteric or pulmonary bacteria -15. In fantigens . This coThe role of antibodies in the pathogenesis of tuberculosis and protection against Mtb infections is controversial. Further, the impact of specific antibody isotypes on TB infections is uncertain. The role of serum anti-CPs is under study, but there are accumulating data that this immune component may be protective ,17-22. TIn summary, serum antibody levels against surface CPs were shown to be higher among subjects with active or treated tuberculosis. Similar results showing higher AM IgG antibody levels in TB patients than in controls, and higher in TB-HIV negative than in TB-HIV positive patients, were published recently . Our datNone of the living authors have competing interests; no competing interests are known for RWA.WAK: Study design; data acquisition, analyses and interpretation; manuscript preparation and revision. ZDD: Antibody purification and detection assay; study design; manuscript preparation and revision. RWA: Study design; data acquisition. RLA: Data analyses and interpretation; manuscript preparation and revision. SM: Antigen preparation; manuscript review . RS: Supervision of antibody purification and detection assay; study conception and design; data interpretation; manuscript preparation, revision and approval. JBR: Supervision of antibody purification and detection assay; study conception and design; data interpretation; manuscript pr eparation, revision and approval. All authors (with the exception of Dr. Awe) read and approved the final manuscript.Dr. Rachel Schneerson, Dr. John Robbins and Dr. ZhongDong Dai these authors are retired.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/13/276/prepub