Previous research has shown a positive relation between character strengths, well-being and health. The aim of this analysis was to identify relations between the application of signature character strengths (ASCS) at work, and well-being and health, among medical students (Study 1) and resident physicians (Study 2). We expected positive direct links between the constructs and indirect effects through emotional exhaustion. To test these hypotheses, 387 medical students in their first year and 136 resident physicians completed five scales measuring well-being, mental/physical health, character strengths, the application of their five individual signature strengths, and emotional exhaustion as an indicator of burnout. Partial correlations were examined, and mediation analyses performed. ASCS at work was positively linked with well-being and mental health but not with physical health. All links were mediated by emotional exhaustion in Study 1 and  also in Study 2. Future studies would therefore do well to investigate the promotion of ASCS at work of people operating in medical education and its potential in fostering well-being and preventing burnout from the outset. Positive psychology is a science that deals with three domains: (1) positive subjective experiences, (2) positive traits, and (3) positive institutions . PositivIn positive psychology the focus is not on health as the absence of illness, but on health as the “presence of the positive” , p. 99. This analysis emphasizes the first two domains of positive psychology (including well-being and character strengths), in particular as there is a clear research gap in the context of ASCS of medical students and resident physicians. Moreover this analysis takes additional variables of the third domain  into account, distinguishing it from mainstream research. This research is the first to analyze relations between ASCS, well-being and health of medical students in their first year (Study 1) and resident physicians working at two hospitals in Austria (Study 2).Well-being has been described in the theoretical and empirical literature to have several aspects: On the one hand, there is subjective well-being (SWB), which encompasses the presence of positive emotions, absence of negative emotions, and satisfaction with life as a whole. On the other, there is psychological well-being, which includes aspects such as engagement, relationships, meaning, mastery, and optimism . Well-beResearch has shown well-being, health and burnout to be important issues for medical students and (resident) physicians. Job Demands-Resources Model . The character strengths were grouped into six historically based universal human virtues . The es Model  is an ocApplicability of Character Strengths Rating Scales (ACS-RS) to “measure the extent to which each of the 24 character strengths of the VIA classification is applicable” in work or private life. Whereas the early years of character strengths research studied strengths possession , in the recent years an additional focus was placed on the applicability of character strengths in specific contexts. So far, there has rarely been research on character strengths and their applicability in the context of medical education. The alarming results of impaired health and well-being of health professionals show the need to address the issues surrounding the well-being, health and risk for burnout of medical students and physicians. The promotion of career satisfaction and the prevention of burnout, especially in the beginning of the career, should be aspired to . The preJob Demands-Resources model , mental health (Hypothesis 2b), and physical health (Hypothesis 3b), as well as indirect effects via emotional exhaustion .Additionally, following Study 1 was designed to examine Hypotheses 1a, 2a, 3a, 4a, 5a, and 6a in a sample of medical students. ASCS was investigated in relation to well-being, mental, and physical health. Furthermore, investigating emotional exhaustion as a possible mediator was a central focus of the study.N = 480). We found no significant differences between the three measurement times regarding the dependent variables. We collected complete data of 387 medical students at an Austrian medical university. Sixty-four percent were female with a mean age of 20.7 years (SD = 2.5). Most were Austrian (54%) nationals and single (67.4%). The students spent an average of 39 h per week studying . Twenty-four percent reported a secondary employment with an average of 8.7 h per week . Detailed demographics can be found in Table 1.We recruited three samples of medical students in their first year of studies  for an online survey and sent 1488 recruitment emails and two reminders. Incentives offered were direct feedback on participants’ individual five signature character strengths, medical education credits, and a raffle of medical books and vouchers. The response rate was 32% (Comprehensive Inventory of Thriving (CIT)   was usedreliable . The CITShort Form Health Survey (RAND-SF-12) (The German version of the D-SF-12)  measuresD-SF-12) .Values in Action Inventory of Strengths (VIA)  to α = 0.89  for the short version (The German 120 item version of the hs (VIA)  was used version . Sample  version , 2015.Applicability of Character Strengths Rating Scales (ASCS-RS) (The German ASCS-RS)  were useASCS-RS) , pp. 5–6never to 5 =  always. The items inquire whether the strength is encouraged, helps the individual, is important, and to which extent it is possible to act according to the strength in the respective context. A good internal consistency of the ASCS-RS with α = 0.84 was found in the present study.According to never to 7 = very often, and showed good reliability (α = 0.87). A sample item is “I feel burnt out from my work.”Emotional exhaustion, the key dimension of burnout, was measured using the adapted and modified German student version of the Maslach-Burnout-Inventory (MBI-SS-GV) by Data were analyzed using IBM SPSS Statistics 22. Frequencies, means, and SD were used to describe the sample characteristics. Correlations and regressions including mediations were designated. The latter were calculated with the SPSS macro PROCESS by Preacher and Hayes . The medN = 2; PWB: N = 1; SWB: N = 1; PCS: N = 3) could be identified and were deleted  resulting in a final N = 387. The PWB and ASCS-RS scores were normally distributed . SWB, PCS, MCS, and MBI-EE were non-normally distributed with the following values of skewness (SE = 0.12) and kurtosis (SE = 0.25) for SWB , PCS , MCS , and MBI-EE . This shows that students were relatively physically and mentally healthy, reported little emotional exhaustion and high SWB.First, in the preliminary analyses several outliers , older students had lower scores in ASCS , and marital status had no statistical effect. All subsequent analyses were controlled for the demographics of sex, age, and marital status.Second, means, SD, and internal consistencies of the measures were computed. Third, relations of the variables with demographics  were calculated, as proposed in several studies e.g., . Men shoTable 2).Partial correlation analyses showed significant relationships of ASCS with all variables except physical health. Effect sizes were moderate for well-being and small for mental health. Hypothesis 1a (well-being) and 2a  were confirmed; Hypothesis 3a  was not . Results showed a significant indirect effect of emotional exhaustion on SWB and PWB . Hypothesis 4a was thus confirmed for both well-being aspects.Based on these results, motional exhaustion on mental health was found (Table 3). Therefore, Hypotheses 5a was also confirmed.Moreover, a significant indirect effect of ephysical health was found in the previous correlational analyses. Nevertheless, a significant indirect effect through emotional exhaustion was found. Interpretation was based on No impact of ASCS on motional exhaustion on all three direct links.Results of Study 1 showed that ASCS was significantly related to the well-being and mental health but not the physical health of medical students. We found significant indirect effects of eAim of Study 2 was to replicate the findings of Study 1 in a sample of resident physicians working in hospitals. A further aim was to compare the results and the initial levels of well-being, ASCS, mental and physical health between the two samples to take the differences between the study and work context into account.At three time points (2015–2016) a total of 1266 recruitment emails and two reminders were sent to resident physicians. Resident physicians are physicians in training, having worked in a hospital between three and a half and six years. They have finished medical school, have a medical degree and are supervised during their work at the hospital. Out of 236 respondents (19%), datasets for 157 participants were complete. The resident physicians were 2 months’ minimum on the job. Nineteen had already finished their residency and were therefore excluded. Data was gathered through an online survey. Incentives offered were direct feedback of participants’ individual five signature character strengths, and vouchers for brunch. Again, no significant differences between the three measurement times regarding the dependent variables were found.Table 1). 65.4% of the resident physicians were female, with a mean age of 32.0 years . Most were Austrian (71.3%) nationals, most were in a partnership (75.7%), and 25% had children. Most of the resident physicians were living with their partner or family (65.4%). The resident physicians reported an average contractual working time of 39.94 h (SD = 7.94) and an actual working time of 48.76 h (SD = 10.00) per week.Complete data of 136 resident physicians were collected in two hospitals in Austria  to α = 0.90 . All other scales had satisfying reliabilities throughout (Table 2).Again, well-being was measured with the CIT , health n MBI-D; . The CroData were analyzed using IBM SPSS Statistics 22. Frequencies, means (M), and SD were used to describe the sample characteristics. Analyses of covariance (ANCOVAs) were used to compare the means between the samples. Correlations and regressions including mediators and covariates  were examined. The latter were calculated with the SPSS macro PROCESS by Preacher and Hayes .N = 1; PCS: N = 1) could be identified  and were deleted. The final dataset consisted of N = 136 resident physicians. MBI-EE, ASCS, and PWB were normally distributed . SWB, PCS, and MCS were non-normally distributed with the following values of skewness (SE = 0.21) and kurtosis (SE = 0.41) for SWB , PCS , and MCS . This shows that the resident physicians, too, were relatively healthy and had high SWB. Means, SD, and reliability of the instruments were computed. The means at t1 and t2 were then compared for statistical differences (ANCOVA). Lastly, possible covariates were analyzed. Sex, age, and marital status had no statistical effect. As in Study 1 all subsequent analyses were again controlled for demographics.In the preliminary analyses two outliers (SWB: p < 0.05) correlated with SWB, PWB, and mental health but not with physical health or burnout (Table 2). Effect sizes were moderate for PWB and small for SWB and mental health. Results confirmed Hypotheses 1b and 2b, but not 3b.Correlation analyses showed that ASCS was significantly  and 6b were confirmed; Hypothesis 5b was not (Table 4).emotional exhaustion on the links between ASCS and well-being and ASCS and physical health. We found no significant indirect effect on the ASCS-mental health link. All indirect effects were relatively small in Study 2.Results of Study 2 showed that ASCS was significantly related to well-being and mental health, but not to physical health of resident physicians. We identified significant indirect effects of Table 5). Thus, results showed that resident physicians had significantly higher means of ASCS and mental health compared with medical students. Both samples had similar means of SWB, PWB, and physical health.Several ANCOVAs were conducted to examine the differences between the two samples concerning their ASCS, well-being, and health. The ANCOVAs were computed with sample (sample 1 vs. sample 2) as between-subject factor, demographics  as covariates, and SWB, PWB, ASCS, MCS, and PCS as dependent variables. Results indicated significant differences between the two samples in the dependent variables of ASCS and mental health after controlling for demographics (z-transformation). In conclusion, Hypotheses 7, 8, 9, and 10 were not confirmed.In addition, we compared the differences between the correlation coefficients  between Studies 1 and 2 with each other. We found no significant differences .Results of both studies showed that ASCS was directly linked to well-being and mental health, but not to physical health. Moreover, the mediation analyses showed significant indirect effects of emotional exhaustion on the links between ASCS, well-being and physical health. The results regarding ASCS and mental health were inconsistent  were relatively weak, perhaps due to the relatively small variance of physical health in these specific samples.In this analysis, as expected, the more ASCS participants reported in their studies (Study 1) and work (Study 2), the higher their levels of well-being and mental health. We found significant indirect effects between ASCS and well-being through emotional exhaustion on the link between ASCS and mental health. Whereas the link was clearly significant in Study 1, the effect was not significant in Study 2, albeit approaching nearly significance with a confidence interval near zero. This inconsistency seems to be mainly due to the smaller contribution of ASCS to emotional exhaustion in resident physicians than in medical students. Moreover, all indirect effects in Study 2 were relatively small. Other factors such as working conditions, stressors or other mental health restrictions may be more central for (the development of) burnout. The results were inconsistent regarding the significance of the indirect effect of In a further step, we compared the levels of well-being, ASCS, mental and physical health between the two samples across the studies to take into account differences between the study and work context. The results showed moderately higher means in ASCS and mental health for resident physicians compared to resident medical students, while all other variables were similar between both samples, with no statistically significant differences. Possible reasons for this could be differences in workflow or task related issues. Medical students may have lesser opportunities to use their character strengths during their studies  compared to the resident physicians, who are working in their field of expertise. Further study designs should take these possible causes for the observed differences in well-being into account.Harzer and Ruch have stated in 2013 that there is a lack of studies analyzing the specific role of character strengths in the context of work. In particular, they have recommended an investigation of specific jobs to look for the most appropriate character strengths and their application in the context of those jobs. We are not aware of any previous studies that have analyzed character strengths applicability in a sample of medical students and resident physicians, despite the particular risk for burnout, health problems, and reduced well-being for these groups in particular. Our research is a first step toward an understanding of whether fostering the application of character strengths may be a promising approach in medical education. Limitations of the present study were the different sample sizes and the cross-sectional study design using samples from only one medical university and hospitals from one state and country. Further research might aim to examine the links found in this study in the general population, at different workplaces and situations, or even in other life domains . Another limitation was that some of the indirect effects found were relatively small or not significant. A replication of this study design may potentially strengthen results. For all mediations it has to be considered that the cross-sectional design does not allow for any causal interpretations.Taking into account the described impact of ASCS, future research should address its potential of being a general predictor in longitudinal designs. Working climate or working conditions  are potential influencing factors. In addition, the connection between ASCS and work-related well-being should be investigated in more detail: Are individuals with higher ASCS at work likely to feel competent and self-confident more often in fulfilling their individual needs and, consequently, is their generalized expectation of self-efficacy  higher? A preventative approach including the concept of character strengths could help enhance well-being and health, and reduce the risk of burnout, for medical students and people in the medical field. Future (research) efforts to improve medical curricula may include the identification of character strengths that generally tend to be useful in the context of medical education. As a result, it could be investigated how these strengths may be promoted in medical students from the outset. Moreover, creating an awareness of (signature) character strengths (for the students themselves and for others) should be tested for its positive impact on students’ well-being and mental health as well as work engagement and zest for their profession. Teaching and fostering individual character strengths  in the educational and the working context could be a first step toward implementing this research in practice. Fostering character strengths through changing working and studying conditions toward a positive institution may be expected to increase well-being and health across the entire institution. Moreover, the potential advantages of a fit between individual character strengths and workplaces involving or fostering personal resources should specifically become a stronger focus in future research.The results of these studies have the following implications:Our analysis has shown that the ASCS is positively linked to well-being and mental health. Moreover, people who are able to use their signature character strengths at study or work are less likely to suffer from burnout (or vice versa).Our findings underline the potential of fostering the ASCS. As a result we recommend the experimental testing of an implementation of character strengths training for people studying or working in the context of medical education. Future research should analyze possible improvements of medical curricula by including the concept of character strengths in order to enhance the well-being and health of medical students and people operating in the medical field.This study was carried out in accordance with the recommendations of “The Board for Ethical Questions in Science of the University of Innsbruck” with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the “The Board for Ethical Questions in Science of the University of Innsbruck.”All authors were substantially involved in the planning of the study, the interpretation of data and revision of the article. MH and CS handled the data collection. MH conducted the data analysis and the writing of the article.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.


In both genders, this damage is associated with the imbalance of sex hormones and the modulation of the hypothalamic–pituitary–gonadal axis. Here, we report that OTs act as reproductive disruptors in vertebrate studies; among the compounds are tetrabutyltin, tributyltin chloride, tributyltin acetate, triphenyltin chloride, triphenyltin hydroxide, dibutyltin chloride, dibutyltin dichloride, diphenyltin dichloride, monobutyltin, and azocyclotin.Organotin (OTs) compounds are organometallic compounds that are widely used in industry, such as in the manufacture of plastics, pesticides, paints, and others. OTs are released into the environment by anthropogenic actions, leading to contact with aquatic and terrestrial organisms that occur in animal feeding. Although OTs are degraded environmentally, reports have shown the effects of this contamination over the years because it can affect organisms of different trophic levels. OTs act as endocrine-disrupting chemicals (EDCs), which can lead to several abnormalities in organisms. In male animals, OTs decrease the weights of the testis and epididymis and reduce the spermatid count, among other dysfunctions. In female animals, OTs alter the weights of the ovaries and uteri and induce damage to the ovaries. In addition, OTs prevent fetal implantation and reduce mammalian pregnancy rates. OTs cross the placental barrier and accumulate in the placental and fetal tissues. Exposure to OTs  Despx organs . For humx organs –11. OTs x organs –14. HereSeveral studies have evaluated OT exposure in male vertebrates, highlighting the dose-dependent impairment by OTs in different experimental models –19. MaleDanio rerio); when exposed to different doses of TBTCl from the first day of incubation of the eggs to PND 70, they exhibited effects such as reduced or completely lost sperm motility, absence of flagella, and the presence of only abnormal spermatozoa in semen (Sebastiscus marmoratus), and there was testicular vacuolization at 48 days of exposure  mRNA expression (Xenopus laevis) with 0.5 µg/L of azocyclotin  and in vitro , found impairment in oocyte development in vitro and a reduction in the number of secondary and mature ovarian follicles in vivo. In zebra fish treated with azocyclotin, the development of the oocyte was also impaired  exposed in utero to 2.5 and 3.8 mg/kg of DBTCl by the organogenesis period but with no effects on morphological development .–49.46–4950 value of 6.2 µM. The residual activity of TBTCl-saturated aromatase was 37%. DBTCl acted as a partial but less potent inhibitor of activity , whereas TeBT and MBT had no effect. By contrast, human 3β-HSD (3β-hydroxysteroid dehydrogenase) type I activity was only moderately inhibited by TBTCl   .−7 M for 48 h caused, through a cAMP-independent pathway, a dose-related increase in human chorionic gonadotrophin (hCG) secretion and an increase in aromatase activity; furthermore, this augmentation in enzymatic activity occurred concurrently with increases in mRNA expression and estrogen biosynthesis from androstenedione (In the human choriocarcinoma cell line (JAR cells) used as a placental experimental model, the findings on aromatase were contrary to those by Heidrich et al. . TBTCl aenedione . Otherwienedione . DBTCl2 enedione . Moreoveenedione .These placental factors are both induced by specific ligands of retinoid X receptors (RXRs) . The treExposure for 48 h to 100 nM of each OTs  caused an increase in 17β-HSD I activity in JAr cells. TBTCl and TPTCl metabolites also altered 17β-HSD I activity, but the level of activation decreased in proportion to the dealkylation or dearylation (mono- < di- < tri-) in JAr cells. The OTs that enhanced the catalytic activity of 17β-HSD I also increased its mRNA expression. However, the mRNA effects were much more pronounced than the changes in catalytic activity . Exposurvia the diet increased the proportion of females  of rats induced a reduction in the epididymis, prostate, and testis weights in a dose-dependent manner , demonstStudies have shown that testes can be a target organ for OTs action, as can be observed in the histological irregularities , 54, 55.via the diet, the spermatid and sperm counts were reduced, but no morphological changes or reduction in sperm motility were observed (In the parameters for sperm, OT–GP exposure has dose-dependent toxicological effects that vary according to the model of exposure used. In rats exposed to TBTCl observed . In miceobserved  was alsoRats exposed to TBTCl showed a dose-dependent increase in serum testosterone and LH levels as well as a reduction in the serum estrogen levels only in animals exposed to 125 ppm of TBTCl . MeanwhiThe effects of GP on OTs in the reproductive system of mammalian females have been underestimated until the present. Ogata et al.  reports Organotins induce endocrine-disrupting effects in vertebrates, including humans, mainly by the exposure to OT-contaminated seafood intake. The effects of OTs have been associated with gender-specific changes in the morphological functioning of reproductive organs, including gonadal cell dysfunction and weight variation in the sex organs. Moreover, OTs are capable of crossing the placental barrier and thus accumulate in the placenta and in fetal tissues, generating congenital abnormalities. The toxicity level of OTs in various species may be related to their concentration and the timing or period of life of exposure. Thus, toxicological and bioavailability studies are needed for regulatory agencies to make informed decisions about the safety of OTs in food and for the environment in general.The topics of the article were divided among the authors JA, PP, EM, IS, CC, ON, RF, LL, JG, who contributed with research and writing. In addition, JA and PP oversaw, assemble, and review the article. JA and PP contributed equally to the study.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.


Spices have exhibited numerous health benefits in preventing and treating a wide variety of diseases such as cancer, aging, metabolic, neurological, cardiovascular, and inflammatory diseases. The present review aims to provide a comprehensive summary of the most relevant and recent findings on spices and their active compounds in terms of targets and mode of action; in particular, their potential use in food preservation and enhancement of shelf life as a natural bioingredient.Spices have been used since ancient times. Although they have been employed mainly as flavoring and coloring agents, their role in food safety and preservation have also been studied  Plant, animal, and microbes represent an unlimited source of compounds with medicinal properties  for rituals, cosmetics and perfumery, their flavoring, coloring and, especially, preservative properties have founded wide applications both in the traditional food preparations and in the food industry. In fact, many compounds isolated from spices Table  have shoSpices have been important to mankind since the beginning of history. Several mythological evidence including “Epic of Gilgamaesh,” and the “Bagavad Gita,” suggest their use for several purposes. Because of their strong preservative quality, spices were also used for embalming. According to Ayurveda, they help to maintain the balance of the body humors . Eugenol, the main component of pimento essential oil, limited the formation of acrylamide by 50%  and/or biological . Despite the current technologies available in the production chain , it seems impossible to eliminate completely the risk of food spoilage , and by inhibiting/regulating the growth of those pathogenic  have been tested against microbes  as compared to E. coli  and P. aeruginosa , different bacteria can react in different ways , human respiratory syncytial virus (HRSV), and human rotavirus) has been reported  reduced markedly the amount of citral needed for the same effect (from around 150 to 50 mg/L). However, Tejeswini et al.  while lower pH favored the antimicrobial power of linalool  against S. cerevisae. Some other hurdle technologies were also used for the enhancement of antimicrobial potential of essential oils. Tyagi and Malik , bay oil was effective against Alternaria alternata infection , and butylated hydroxyanisole  status provided by the regulatory agencies of U.S. However, its application is sometimes limited because of its poor aqueous solubility, instability at high temperature, and susceptibility to degradation by nucleophilic molecules , a bioactive organosulfur compound found in cruciferous, plants, such as mustard, is known for its anticarcenogenic properties. It has been tested for effectiveness in preservation of fresh beef, sliced raw tuna and cheese. It possesses a strong antimicrobial activity against in vivo studies ended up with products acceptable for the consumers, the sensory aspect represents a critical point in the use of spices and their active compounds in food. In fact, sometimes MIC values were three or four times higher than those estimated in vitro, have been applied to have a measurable or stable antimicrobial effect in vivo. This aspect can dramatically affect the physical characteristics and organoleptic properties of the food products. To overcome these issues, several strategies have been exploited for the enhancement of antimicrobial potential of spices in vivo.Although some E. coli O157:H7 in young coconut liquid endosperm. They found that the combined effect was most significant only at concentrations above 250 and 210 mg/L, respectively for vanillin and LRE. The efficacy of thymol (0.1% w/w) in combination with sodium lactate (1 and 2% v/w) was evaluated in fish patty samples stored at 4°C for 5 days. The presence of thymol plus 2% of sodium lactate had a synergetic effect against S. enterica ser. Typhimurium . On the contrary, this effect was inhibited when SHMP was combined.The synergistic effect of spices together with their constituents or other natural products has been tested. Water extracts of clove, cinnamon, and oregano were applied, alone (10 mg/L) or in combination (3.3 g/L each), in raw chicken meat and several characteristics were followed during storage for 15 days at 4°C. The mixture of the three extracts had the strongest impact on the bacterial load due to the synergistic actions of antimicrobial compounds present in the mixed spices  cinnamon. The maximum inactivation level (1.97 log10 cycles) was achieved at 30 kV/cm–700 μs plus 5% cinnamon. Patrignani et al.  and human pathogens (food safety) due to the antimicrobial and antifugal activity of their natural constituents. Spices are provided from natural herbs and plants and generally recognized as safe (GRAS) by the American Food and Drug Administration (FDA). However, the need of high amount of natural compounds represent the main limitation for effective performance against microorganisms. Mostly, their organoleptic characteristics may impact the results of DG: Data compilation, manuscript writing, DB: Data compilation, table formation, SP: Data compilation, manuscript writing, and formating, AT: Data compilation, manuscript writing, editing and formatting, and final approval.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.


Patients with schizophrenia suffer from symptoms such as hallucination and delusion. There are currently a number of publications that discuss the treatment, diagnosis, prognosis, and damage in schizophrenia. This study utilized joint independent component analysis to process the images of GMV and WMV and incorporated the Wisconsin card sorting test (WCST) and the positive and negative syndrome scale (PANSS) to examine the correlation of obtained brain characteristics. We also used PANSS score to classify schizophrenic patients into acute and subacute cases, to analyze the brain structure differences. Finally, we used brain structure images and the error rate of the WCST as eigenvalues in support vector machine learning and classification. The results of this study showed that the frontal and temporal lobes of a normal brain are more apparent than those of a schizophrenia brain. The highest level of classification recognition reached 91.575%, indicating that the WCST error rate and characteristic changes in brain structure volume can be used to effectively distinguish schizophrenia and normal brains. Similarly, this result confirmed that the WCST and brain structure volume are correlated with the differences between schizophrenia and normal participants. Typical schizophrenia tends to occur in young adults, in whom the disability can last for life, and obstruct social functions such as personal relationship, job, and self-care. The social function impairments of patients with late-stage schizophrenia can result in substantial cost burden to the patients, their families, and the healthcare system , 2. In tIn the earlier days, Brief Psychiatric Rating Scale was widely used for the evaluation of psychological symptoms and their severity . In receIn 1976, Johnstone et al.  discoverT1-weighted images are a type of high-resolution three-dimensional images. In this study, we used VBM for accurate observation of changes in brain tissue morphology –23. SarrIn order to discuss whether the changes in brain structure volume obtained by the WCST are correlated to the differences between patients with schizophrenia and normal participants, we adopted the classification algorithms for learning and classification in this study. If the classification recognition rate based on these eigenvalues was good, then these eigenvalues strongly correlated to the classification of patients with schizophrenia and normal participants. It is also possible to build models for predicting unknown classification and to use the result in research. The currently known classification algorithms include Neural Network, support vector machine (SVM), and Learning Vector Quantization. The primary strength of SVM is that, with relatively small sample size, it has great classification ability in terms of identification in high-dimensional space and relatively accurate classification. SVM is a learning algorithm based on statistical theories. It was first proposed by Vapnik and can be applied to the classification of linear and nonlinear data . In brieIn this study, we investigated the difference in brain structure between normal subjects and patients with schizophrenia using T1-weighted images and analyzed the differences with voxel-based morphometry (VBM) and joint independent component analysis (jICA). The WCST error rate and results of data analysis such as eigenvalues were applied to the SVM classification.The study included 19 schizophrenic patients  and 16 normal control subjects  . The 19 3, and number of slices = 120.The morphological sequence we use is T1-weighted image. All participants received a whole-brain MR scan  with the following image parameters: field strength = 1.5 T, repetition time (TR) = 10.428 ms, echo time (TE) = 3.128 ms, inversion time (TI) = 400 ms, slice thickness = 1.5 mm, matrix = 256 × 256, voxel size = 1.5 × 1.5 × 1.5 mmImages Preprocessing. VBM was used for the pretreatment of MRI. As an analysis technique of neurological images, VBM is widely used for the detection of changes in the brain GMV and WMV. Every image was processed using the default settings for the VBM8 Toolbox (http://dbm.neuro.uni-jena.de/) for the MATLAB  Statistical Parametric Mapping 8 . First, the anterior commissure was set as the center of all T1-weighted images. The voxel intensities in the images were plotted as a histogram. Mixture Gaussian filter removed the curve that could affect the intensity, to avoid the issue of partial volume. These steps segmented T1-weighted images into GMV, WMV, and cerebrospinal fluid (CSF). In addition, the affine registration was carried out to the tissue probability maps during native space tissue segmentation and was aligned to 1 × 1 × 1 mm2 standard anatomical space coordinate axis provided by MNI 152. By using SPM8 DARTEL Toolbox, the images at the same location were aligned to known anatomical coordinate axes [ate axes . FinallyJoint Independent Component Analysis. Fusion ICA Toolbox (FIT) in MATLAB  was used in this study [is study . All imais study . These cVisualization. Each joint-source was converted into Z-score (unit standard deviation) and into three-dimensional images. The illustration was then converted into MNI brain model to be displayed in the normalized coordinate space, with threshold of Z > 3.5. The significant areas in all joint-sources were converted into standard Talairach space from the MNI normalized template.p < 0.05 familywise error rate threshold was used for adjustment. Two-tailed t-test was used for jICA, to verify the significant differences between patients with schizophrenia and normal participants.The statistical software used in this study was SPSS. First, age and sex covariances of patients with schizophrenia and normal controls were controlled. Then, VBM was used to carry out subsequent brain structure analysis. Because the observed voxels did not independently exist in neighboring voxels, SVM is a type of supervised learning structure and processes data for classification. In brief, SVM builds a hyperplane and moves it, until an appropriate boundary is found. Apart from keeping the correct classification of the hyperplane, SVM also maximizes the empty space on the side of the hyperplane . The LIBIn this study, not only the jICA was used to analyze normal and schizophrenia patients but also the brain differences based on PANSS scores were divided into two groups of schizophrenia patients. Therefore, the components of jICA, volume of brain structure, and WCST error rate were subjected to further analysis and discussion.p value should be lower than 0.05/15 = 0.003333. Only Component 15 (p = 0.000) and Component 11 (p = 0.002) were within this range. Thus, we discussed Component 15 and Component 11. The loading parameters of Component 15 and Component 11  and control group  data were decomposed using jICA. The result showed 15 component sources. After Bonferroni correction, onent 11  showed iR square value is 0.453, and the higher loading parameters correspond to lower WCST score. When using separation analysis, R square value is 0.635 for normal controls only as shown in We used partial correlations to control sex and age for Component 15  and WCST . In p scale) in PANSS, with a threshold of 24. The significant regions are the postcentral gyrus, precentral gyrus, insula, inferior parietal lobule, transverse temporal gyrus, superior temporal gyrus, and inferior semilunar lobule in the grey matter and the postcentral gyrus, inferior parietal lobule, precentral gyrus, subgyrus, middle temporal gyrus, lingual gyrus, cuneus, and middle occipital gyrus in the white matter  located anteriorly to the striate visual area, which was reduced in the cohort (BA 17). Both Ananth et al. and Antonova et al. discovered the WMV reduction in the visual cortex , 73. TheThe superior temporal gyrus GMV reduction has 100% replicability with the region of interest approach, particularly anteriorly, and voxel-based morphometry concentration studies have repeatedly observed temporal lobe reduction –78, whicp scale correlated with general psychopathology, suggesting the severity of illness. In the future, our efforts will be to determine how to apply the loading parameter to demonstrate the severity of illness, antipsychotic efficacy, and outcome. Finally, some parietal and temporal lobe changes were also found in only schizophrenia. p scale in the PANSS was a positive phenomenon score, and, hence, finding changes in the auditory cortex was reasonable in this study. Moreover, we used a t-test to analyze the hallucinatory behaviour on p scale, with the result yielding p = 0.059. Although p value is not significant enough, the result might tend to be significant if the sample size could be larger. Therefore, we think that p scale was controlled by the structural covariance as seen in The PANSS is now well established in clinical evaluation of patients with schizophrenia. Bell et al.  further R square, indicating that the reduction in this parameter resulted in more errors, while there was no significant correlation in patients only. Therefore, the correlation is more obvious in normal brains. The reason that the correlation is not so obvious in schizophrenia brains could be the strong disease effect. The PANSS is one of the important clinical parameters for schizophrenia. Schizophrenia can be classified as acute and subacute based on PANSS score, and the differences could be observed by the differences in the analysis of brain structure. Apart from statistical methods, SVM classification was also used in this study to observe the differences between schizophrenia and normal participants. The classification success rate was as high as 91.575%. The results showed that alterations in brain structure and clinical scoring could indeed effectively distinguish the two types of brains. In the future, we hope that there is great potential in the development of methods based on fMRI as a biologically based marker for medical diagnosis.Our study results demonstrate that there are clear differences between the schizophrenia and normal brain structures. In addition, this study also observed that a correlation existed between the error rate of WCST and PANSS and brain structure images loaded from jICA component. The WCST is related to logic and thinking evaluation. The result showed that a higher WCST error rate represented more mistakes. The corresponding component decreased with the corresponding loading parameter, displaying reduced brain network strength and, thus, higher error rate. Apart from this, a correlation test on the WCST error rates of patients with schizophrenia and normal participants showed that normal people had higher


Creativity is a multidimensional phenomenon and an important component of human capacities. This ability is characterized by the involvement of several cognitive functions particularly linked to the prefrontal cortex. We compared divergent thinking, a measure of creativity, in patients affected by progressive supranuclear palsy (PSP), other parkinsonian syndromes, and healthy controls (HCs).Creativity features were evaluated using the Abbreviated Torrance Test for Adults (ATTA). Consecutive PSP outpatients were screened for inclusion. Then, patients with multiple system atrophy (MSA) and Parkinson’s disease (PD) and a group of HC were studied. All groups have preserved cognitive functions and were matched for gender, education, disease duration, and age at onset with exception of PD patients who were matched by disease severity rather than disease duration.PSP patients were characterized by lower values in total ATTA and all subscales than HC and both MSA and PD patients. No differences were found comparing HC versus both MSA and PD patients. PSP patients were characterized by more impaired frontal functioning [assessed by means of Frontal Assessment Battery (FAB)] than HC and both PD and MSA patients.In the present study, ATTA was significantly lower in PSP patients than in the other study groups. The worst performance in ATTA-total score and the lower score in FAB in PSP patients support the role of frontal function in creative processes. Creative skills and creative process are still a fascinating, but unresolved topic up for debate as regards a variety of brain diseases . It is known as the ability “to understand, develop and express in a systematic, novel orderly relationship” and also “to generate ideas that are both novel and useful in a particular social setting” , 2. GuilMeasurement of creativity is crucial in order to be able to study and understand the phenomenon. One approach is to measure DT, which includes a number of aspects, such as fluency, flexibility, originality, and elaboration . AlthougNevertheless, inconclusive results link executive functions and creativity. Miller et al.  have stuIn addition, DT—which is affected by mesolimbic dopamine—may be influenced or triggered by the use of psychotropic substances. This has recently been studied in Parkinson’s disease (PD) patients –12, in wThere are also other neurodegenerative diseases that are characterized by different types of cortical and subcortical dysfunction, dysregulation of dopamine circuitries, and response to dopaminergic therapy. Progressive supranuclear palsy (PSP), a predominant 4-repeat tauopathy, is characterized by midbrain atrophy, as well as atrophy of the internal pallidum, subthalamic nucleus, thalamus, and frontal cortex resulting in rigid-akinetic syndrome, ocular motor dysfunction, postural instability and falls, frontal signs, and bulbar dysfunction . No therWe conducted a prospective case–control study at the outpatient clinic of the Parkinson Institute . First, consecutive PSP patients were included according to the criteria of the National Institute of Neurological Disorders and Stroke/Society for the diagnosis of Progressive Supranuclear Palsy (NINDS/SPSP) . Then, wProbable MSA was diagnosed according to the criteria provided in the second consensus statement on the diagnosis of MSA idiopathic PD was diagnosed in agreement with the UK PD Society Brain Bank criteria . All patDementia (as assessed by MMSE score > 24/30 points) , 39 was Flexibility , Fluency , Originality , and Elaboration (the ability to further develop a concept by adding new elements).The Abbreviated Torrance Test for Adults (ATTA)  was usedA visuospatial task [Clock Drawing Test (CDT)]  and a frOn the same day, clinical work-up included the evaluation of disease severity and motor functions (in worst “OFF” conditions) by means of the Hoehn and Yahr (H&Y) staging system  and the Sample size was calculated on the difference in primary outcome variable  between PSP patients and HCs. Considering a meaningful difference in total ATTA score of at least 20 points and a common SD of 18 points , the samt-test for paired data with exception of the comparison with CBS patients (test for unpaired data). Specifically, we compared PSP patients to HC and other parkinsonian syndromes. The comparison between HC and other types of parkinsonian syndromes was also investigated. Categorical variables were presented as count and percentage. Finally, correlations between test scores were analyzed using Kendall’s tau test.Continuous variables were reported as mean and SD and compared between groups using the Student’s P-value of <0.05.All data were analyzed using MedCalc Statistical Software version 16.8.4 , setting the level of significance at a two-tailed The study was performed in agreement with the principles of the Declaration of Helsinki and the protocol was approved by the local Ethics Committee (Protocol 272-2010). We obtain written informed consent from every patient and control subject recruited.P < 0.05) in FAB were observed in MSA patients compared to controls. MSA patients showed also lower CDT score than HC (P < 0.05). Data regarding creativity, as assessed by ATTA, are reported in Table P = 0.034) and MMSE-design copy .Demographic and clinical characteristics of the study groups are shown in Table In the present study, DT, measured by means of ATTA, was significantly lower in PSP patients than in the other study groups. The worst performance in terms of ATTA-total, along with the lower score in FAB, found in PSP patients suggests that frontal function has an important role in creative processes.The role of the frontal cortex in DT has been pointed out in previous studies in HC. Regional cerebral blood flow measurements were used in control subjects with high and low scores in creative tests to study the functional organization of the cortex. Highly creative subjects showed bilateral frontal activation during DT tasks . Fink etClock Drawing Test was significantly worse than MSA when compared to HC, likely due to more impaired visual-spatial abilities –57. PD aAlthough the results are interesting, we are aware that our study has some limitations. First, our sample size was relatively small due to the rare nature of parkinsonisms and the inclusion criteria. Therefore, the study groups included are not fully representative of the patient populations. Particularly, it is known that cognitive deficits are frequent in these patients  and we iEthics Committee: ASST-G Pini, Centro Specialistico Ortopedico Traumatologico, Milano, Italy. The study was performed in agreement with the principles of the Declaration of Helsinki and the protocol was approved by the local Ethics Committee (Protocol 272-2010). We obtain written informed consent from every patient and control subject recruited.All the authors significantly contributed to the work, read, and approved the final version of the manuscript. MC, MR, AR, and VC contributed to study design. MC, AR, VC, and FM; contributed to data collection. MC, MR, EC, AR, VC, and FM contributed to data analyses and interpretation; contributed to manuscript drafting. MC, MR, EC, AR, VC, and GP contributed to critical revision of the manuscript.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. The reviewer SM and handling Editor declared their shared affiliation.


P-nonlinearity = 0.0378). The present evidence suggests that height is positively associated with increased risk of hip fracture. Further well-designed cohort studies are needed to confirm the present findings in other ethnicities.The association between height and risk of hip fracture has been investigated in several studies, but the evidence is inconclusive. We therefore conducted this meta-analysis of prospective cohort studies to explore whether an association exists between height and risk of hip fracture. We searched PubMed and EMBASE, Web of Science, and the Cochrane Library for studies of height and risk of hip fracture up to February 16, 2016. The random-effects model was used to combine results from individual studies. Seven prospective cohort studies, with 7,478 incident hip fracture cases and 907,913 participants, were included for analysis. The pooled relative risk (RR) was 1.65 : 1.26–2.16) comparing the highest with the lowest category of height. Result from dose-response analysis suggested a linear association between height and hip fracture risk ( Hip fracture is the femoral fracture that occurs between the articular of hip joint and 5 cm below the distal point of the lesser trochanter . As a maPrevious studies have shown that smoking, physical inactivity, and low body mass index were associated with increased risk of hip fracture –8. OtherWe conducted this meta-analysis according to the checklist of the Meta-Analysis of Observational Studies in Epidemiology . A literStudies were included for analysis if they met the following criteria: (1) having a prospective cohort design, (2) considering the association between height and risk of hip fracture, (3) reporting risk estimates with 95% confidence intervals (CIs) for at least three quantitative height categories . Animal studies, reviews, conference abstracts, editorials, and letters were excluded. If a study was reported in more than one article, only the result with the longest follow-up years was used.Two reviewers (W. F. and Y. C.) independently carried out the data extraction. The following data were extracted from each included study: name of the first author, publication year, study name, study location, follow-up years, characteristics of participants (sex and age), number of cases and participants, fracture ascertainment, variables adjusted for in the analysis, and the relative risks (RRs) or hazard ratios (HRs) or odds ratios (ORs) of hip fracture and corresponding 95% CIs for all categories of height.The Newcastle-Ottawa Scale  was usedTo take into account heterogeneity between studies, a random-effects model  was usedP value for nonlinearity was calculated by testing the null hypothesis that the coefficient of the second spline was equal to zero [We assigned the median or mean height in each category to the corresponding RR for each study. When the median or mean height per category was not reported, the midpoint of the upper and lower boundaries was considered the height of each category. If the lower or upper boundaries for the lowest and highest category were not available, we assumed the length of these categories to be the same as the closest category. We examined a potential nonlinear relationship between height and hip fracture risk by using restricted cubic splines with 3 knots at percentiles  of the distribution . A P val to zero .Q statistics (significance level of P≦0.10) and I2 statistics [I2 values of 25%, 50%, and 75% were considered to be low, moderate, and high degrees of heterogeneity, respectively [P values were two-sided and P < 0.05 was considered statistically significant unless where otherwise stated.Heterogeneity between studies was assessed by using atistics . I2 valectively . Subgrouectively , 28. Theectively . This mehttp://dx.doi.org/10.1155/2016/2480693).I2 = 76.2%, P-heterogeneity < 0.05).P-nonlinearity = 0.0378). As compared with individuals who were in the lowest height, the RR of hip fracture for each 10 cm increment was 1.007 (95% CI: 1.002–1.012).P values < 0.05). However, the trim and fill method identified 3 hypothetical missing studies, and the repooled results incorporating the hypothetical studies continued to show a statistically significant association between height and risk of hip fracture .Publication bias was found across the included studies indicated by Begg's and Egger's test  than in men . However, because the CIs for HR of hip fracture are overlapping for women and men, and meanwhile the lower limit of the CI for men includes 1, whether there is a gender difference of association between body height and risk of hip fracture should be further explored.Due to the aging of the population, the number of hip fractures continues to increase , 36. AltOur meta-analysis had several strengths. Because this meta-analysis only included prospective cohort studies, we minimized the potential effect of recall bias on our findings. In addition, each included study had a follow-up period long enough to observe potential association between height and risk of hip fracture. Another strength was that the studies involved a large number of participants; it was therefore possible to detect moderate reductions in risk.Our study also had some limitations that deserve consideration. First, because our meta-analysis was based on observational studies, we could not rule out potential confounding from other fracture risk factors. Although the included studies adjusted for several potential confounders, for example, all studies adjusted for age, three studies adjusted for alcohol intake, and three studies adjusted for smoking, the association between height and risk of hip fracture could potentially be due to residual confounding from other factors related to tall people.Second, although it has been shown that self-report was relatively accurate for hip fracture in adults , 39, howThird, the potential publication bias existed across the included studies indicated that studies reporting positive association between height and risk of hip fracture were more easily published, as indicated by Egger's test and Begg's test. However, when we performed the trim and fill method, the result continued to suggest statistically significant association between height and hip fracture, although the pooled RR was attenuated by the hypothesized missing studies.Fourth, high statistical heterogeneity was found across the studies. One potential source of heterogeneity might be the difference of the number of hip fracture cases between studies, as suggested by the subgroup analysis. Although the heterogeneity may weaken the strength of our findings, the subgroup analysis and sensitivity analysis showed that results from our meta-analysis were robust.Finally, the results of our meta-analysis were based on studies that only involved participants from Europe or the United States. However, the genetic factors and environmental factors with respect to height varied among different ethnicities, especially between east and west. Therefore, the findings of this study should be interpreted with caution among the population from the east.In summary, the results from this meta-analysis of prospective studies indicate that height is positively associated with risk of hip fracture. However, due to residual confounding from other fracture risk factors related to height, the findings from this meta-analysis need to be confirmed by well-designed prospective studies, especially among other ethnicities.Table S1 presented the methodological quality score of included studies assessed by the Newcastle-Ottawa Scale (NOS). Studies that scored 0–3, 4–6, and 7–9 were considered as low, moderate, and high quality, respectively. 5 studies were in high quality while the other 2 studies were in moderate quality.


Pancreas transplantation is considered a therapeutic option for patients with complicated diabetes mellitus. In this study, we compared survival rate between patients on the waiting list for pancreas transplant alone(PTA), simultaneous pancreas–kidney(SPK) transplant, and pancreas after kidney(PAK) transplant and transplant recipients. A total of 503 patients  and 280 PT recipients  were retrospectively analyzed at our center between February 2000 and December 2015; 11.9%(60/503) of the patients on the waiting list and 4.3%(12/280) of the PT recipients died. The overall survival rate was higher in the waiting list group for the first year (99.3% vs. 97.8%), after which it was significantly higher in PT group (p = 0.039). The overall relative risk of all-cause mortality for transplant recipients was 2.145(p = 0.285) for PTA, 0.688(p = 0.735) for PAK, however,0.361 (p = 0.012) for SPK compared with that for the waiting list patients. SPK transplant recipients had considerable higher survival benefits, despite the relatively long waiting period, especially after 1 year. In addition, PTA and PAK can also be considered as a treatment option as patient survival was not poor. It has been well established that the worldwide prevalence of diabetes mellitus (DM) has steadily increased,2. MoreoPancreas transplantation (PT) is considered an acceptable therapeutic option for restoring normoglycemia by supplying sufficient β cells. This was made possible by improvement in both patient and graft survival and postoperative management as well as decrease in postoperative morbidity due to technological progress and development of immunosuppressants,6. HowevDelaying the progression of diabetes complications and increasing life expectancy are the ultimate goals for the treatment of DM. However, it is poorly understood whether PT has a beneficial effect on life expectancy compared with established insulin therapies. There are some large population studies which access the beneficial effect of pancreas transplantation,8. HowevIn the present study, we compared the survival rate of PT recipients with that of patients on the waiting list for PT at a single institution.In this study, we enrolled patients who underwent PT and those on the KONOS waiting list. The acceptance onto the waiting list for PT was decided by the KONOS criteria.From February 2000 to December 2015, 890 patients registered our institution for pancreas transplantation. Among them, 504 patients were still on the waiting list for PT and 280 patients underwent PT. We excluded one patient who was listed for multi-organ (other than simultaneous pancreas–kidney) transplantation. Six patients were excluded because we couldn’t follow-up their medical records. As a result, the waiting group consisted of 503 patients and the PT group of 280 patients. In each group, the patients were subdivided according to the transplant type . In the SPK group, simultaneous pancreas and kidney from a deceased donor and a cadaveric pancreas and kidney from a living donor (SPLK) were included .The study was approved by Institutional Review Board (S2015-1965) of Asan Medical Center. And the need for informed consent was waived due to the retrospective study. The study was conducted in accordance with the 2008 Declaration of HelsinkiThe endpoint was the death of the patients in the two groups. Patient survival was calculated from the time when the patients were diagnosed as diabetes to death or latest follow-up in the waiting list and PT groups. The overall mortality rate and cause were analyzed. To compare patient survival according to the follow-up period, we divided the periods into <1 year and ≥1 year. Patient survival and relative risk of mortality were analyzed according to each period.The clinical characteristics of the patients at the time when they registered to KONOS for pancreas transplantation were also analyzed according to their group and transplant type. The demographics, duration, and history of DM, amount of insulin, complications of DM, and history of cardiovascular diseases were included.2 test. Quantitative variables were analyzed using mean and standard deviation. Differences between the means were analyzed using a Student’s t-test or Mann–Whitney U test. Patient survival was analyzed using Kaplan–Meier estimator and log-rank tests. And the relative risks of patient survival according to their surgery or waiting were analyzed by Cox-regression test. The confounding factors were adjusted. Statistical calculations were performed using SPSS version 21.0 statistical software  and p < 0.05 was considered statistically significant.The categorical variables were analyzed using absolute and relative frequencies with XBetween February 2000 and December 2015, 116 (23.1%), 303 (60.2%), and 84 (16.7%) patients were on the waiting list for PTA, SPK, and PAK transplants, respectively. During the same period, 89 (n = 31.8%), 155 (55.4%), and 36 (12.9) patients underwent PTA, SPK, and PAK, respectively .The demographics and clinical characteristics of the two groups are shown in The cause of mortality in the waiting rand PT groups was analyzed  and was We compared patients in the waiting group and those in the PT group according to their transplant type  . We alsoFor PTA, the mean age of the waiting group was significantly older than that of the PT group . There was more male patients in the waiting group , and BMI and age at DM onset were also higher . The overall patient survival was not significantly different between the two groups (p = 0.644) .For SPK, patient’s age, age at DM onset, BMI, prevalence of neuropathy, DM foot, hypertension, coronary artery disease, and cerebrovascular accidents were significantly higher in the waiting group. Patient survival rate was higher in the waiting group for the first year, after which it was significantly higher in the PT group (p = 0.001) .For PAK, age at DM onset, BMI, prevalence of neuropathy and hypertension, and rate of type II DM were significantly higher in the waiting group. Patient survival did not significantly differ between the two groups (p = 0.658) .The relative risk of death among the patients on the waiting list was compared with that among transplant recipients for equal follow-up periods (<1 year and ≥1 year) for the same procedure .For PTA, the overall relative risk of death following transplantation was 2.145 [95% confidence interval (CI): 0.531–8.684; p = 0.285). Until the first year, PTA recipients had a 1.86-fold higher risk of death than patients on the waiting list for the same period . After the first year, they had a relative risk of 2.069 ; however, this association was not statistically significant.SPK recipients exhibited a relative risk of 0.361  for the follow-up period. For the first year after transplantation, SPK recipients had a 1.306-fold higher risk of death compared with those on the waiting list; however, this was not statistically significant . After the first year, the relative risk was 0.183 .For PAK recipients, the overall relative risk of death following transplantation was 0.688 . For the first year, there were no deaths in the PT group. After the first year, PAK had a relative risk of 0.949 ; however, this was not statistically significant.Since PT was introduced in 1966 at the University of Minnesota, it has been considered an acceptable treatment based on the improvement in surgical techniques, immunosuppressants, and graft outcomes,6. At ou4. For the first year, patient survival of the waiting group was higher than that of the PT group. However, after the first year, the patient survival of the PT group was higher.Thus, we attempted to analyze and compare the survival rate between patients with DM on the waiting list and PT recipients. Van Dillen et al. previousIn this study, we included SPLK group in SPK group for analyzing patient survival. In general, SPLK and SPK are different procedure. In the surgical procedure, SPLK are from two different donors and have a shorter waiting time relatively because they registered on waiting list of solitary pancreas transplantation (PTA or PAK). However, SPK received the organ from one donor and longer waiting time (average 5–6 years in Korea). However, we focused our primary outcome, patient survival. We focused on the patient survival from the time of DM diagnosis. We thought that SPLK and SPK can be considered the same group in that the patients have DM with ESRD as underlying disease and DM with ESRD is corrected after transplantation. Before the transplantation, they had to control DM and do renal replacement therapy such as hemodialysis or peritoneal dialysis. During these periods, DM and its various complications can progress and effect on the patient survival. After transplantation, they don’t need to control DM using exogenous insulin do HD or PD. However, the patients who are on the waiting list have to receive the treatment continuously, and during this period, the disease can progress more and increase the mortality of these patients. For this reason, we considered that the two surgeries (SPLK and SPK) showed the same course of death progression in the disease progression of DM and ESRD patients, and classified into the same group.The causes of death in each group were significantly different . In the When we analyzed each group according to their transplant type, we were able to identify that these characteristics were accentuated for SPK. The relative risk associated with SPK was also higher in the PT group than in the waiting group over time. This is reflective of cardiovascular or other complications associated with DM functioning as a major cause of increasing the mortality rate of DM patients. Moreover, the need for life-long immunosuppression can increase the mortality rate following transplantation due to secondary complications  despite improvements in operative techniques and graft outcome. In both PTA and PAK, our data revealed a lower mortality rate in the PT group than in the waiting group. This low mortality rate reveals the survival benefits of PT in patients with DM and normal renal function, and these findings are comparable with those of previous reports,4,7,8. DIn Venstrom et al.’s study, PTA wasBut, there are some points that we need to caution for our results. Our data showed that patient survival for SPK and PAK are nearly similar . And, in PAK, patient survival was not significantly different between patients on waiting list and patients underwent PAK. However, the numbers of patients who listed to waiting list for PAK and underwent PAK are relatively small and it can be one of the limitations for presenting the patient survival correctly. When we reviewed the waiting periods from listing to surgery, solitary pancreas transplantation is performed with 1 year on the average, and many data showed that PAK tend to perform quicker than SPK and better patient survival compared those of patients with diabetes with renal dysfunction. Therefore, for more accurate comparison, the large number of patients should be enrolled and other confounding factors should be also considered carefully.This study has several limitations. It was a single center retrospective analysis and we collected data from 2000; thus, any changes and improvements in immunosuppressants might have an effect on the postoperative mortality regardless of DM. However, our institution is a large volume center which is performed PT and the number of PT is continuously increasing annually. So, we tried to analyze and evaluate the benefit or disadvantage of PT in a single center population.Our data suggest that SPK can offer considerable survival benefits despite the associated surgical or immunological complications, particularly in patients with obvious renal impairment. In addition, PTA and PAK can also be considered as a treatment option as patient survival was not poor. However, if renal function is preserved, greater caution should be taken for selecting and determining PT candidates. The actual risks, benefits and perioperative mortality, and morbidity associated with PT and other medical treatments deserve careful consideration.S1 Data(XLS)Click here for additional data file.


MC supplementation (24 mg daily) yielded significant improvement in MPOD, overall sleep quality, headache frequency, eye strain, eye fatigue, and all visual performance measures, versus placebo . Increased MPOD significantly improves visual performance and, in turn, improves several undesirable physical outcomes associated with excessive ST. The improvement in sleep quality was not directly related to increases in MPOD, and may be due to systemic reduction in oxidative stress and inflammation.The dramatic rise in the use of smartphones, tablets, and laptop computers over the past decade has raised concerns about potentially deleterious health effects of increased “screen time” (ST) and associated short-wavelength (blue) light exposure. We determined baseline associations and effects of 6 months’ supplementation with the macular carotenoids (MC) lutein, zeaxanthin, and mesozeaxanthin on the blue-absorbing macular pigment (MP) and measures of sleep quality, visual performance, and physical indicators of excessive ST. Forty-eight healthy young adults with at least 6 h of daily near-field ST exposure participated in this placebo-controlled trial. Visual performance measures included contrast sensitivity, critical flicker fusion, disability glare, and photostress recovery. Physical indicators of excessive screen time and sleep quality were assessed via questionnaire. MP optical density (MPOD) was assessed via heterochromatic flicker photometry. At baseline, MPOD was correlated significantly with all visual performance measures ( Prior to the advent of artificial lighting, the sun was the primary source of light. When the sun sets today, however, one is hard-pressed to find darkness—illumination from light-emitting diodes (LEDs), and incandescent, fluorescent, and xenon-arc sources (among others) provide indoor and outdoor illumination. The effects of exposure to this seemingly unnatural technological adaptation are starting to become evident, with several studies indicating undesirable associations between exposure to artificial light at night and both reduced sleep quality ,2 and diThe potential for damage from blue light in the retina has been met with a favorable adaptation in the eye: a diet-derived, blue-absorbing pigment composed of the dietary carotenoids lutein (L) and zeaxanthin (Z). L and Z are found in relatively high concentrations in leafy-green vegetables , and aloThe present study was motivated not only by the potential deleterious effects of the precipitous recent increase in the use of near-field technological devices , but also the fact that the optical density (OD) of MP (MPOD) is (given its source in the diet) notoriously variable among people, ranging from 0 to well over 1 logarithmic unit of OD . If therThis study was reviewed and approved by the University of Georgia Institutional Review Board. Informed consent was obtained for each subject, and the study adhered to the tenets of the Declaration of Helsinki. Forty-eight subjects, recruited from the population of students at the University of Georgia in Athens, Georgia, participated in this 6-month, double-blind, randomized, placebo-controlled supplementation trial. Subjects were healthy, college-aged  non-smokers with a body mass index (BMI) <27. The concern with BMI involves not only good general health, but also the possibility that, being lipid-soluble, supplemented macular carotenoids may be deposited in adipose tissue, thus reducing the fraction deposited in the retina. A BMI of 27 is higher than “normal” (18.5–24.9) but falls well below “obese” (BMI = 30 or greater). We had seven participants who approached 27, and five of them were athletes (whose muscle structure accounted for the relatively high BMI). Subjects were instructed to maintain their current diet; those that were planning on changing their diet (for whatever reason) were excluded from consideration for the trial. For those subjects enrolled in the trial, stability of diet was evaluated via questionnaire at each visit. In consideration of vision testing, all subjects had uncorrected or contact lens-corrected visual acuity of 20/20 or better in the test (right) eye, and had no current or previous history of ocular pathology. Subjects wearing spectacles for vision correction were not considered for the study, due primarily to potential reflection and coating-mediated light absorption issues with glare testing. Subjects were also screened to ensure that they spent at least 6 h daily viewing screens at a distance of 3 feet or less. Items specific to smartphones, tablets, computers, and television viewing were included on the questionnaire. Measures of all visual and physical parameters (detailed below) were taken at baseline, 3 months and 6 months.n = 13) or MC supplement (n = 35) groups. Pills for each group were identical, brown-colored, soft gelatin capsules. Placebos contained no L, Z, or MZ, but only safflower oil. Independent analysis indicated that the active supplement pills (Lutemax 2020 formulation) contained 24 mg of L, Z, and MZ suspended in safflower oil at a ratio of 83%:10%:7%, respectively. All reported values were within +/−5% sum total variability. A previous investigation [Subjects were randomly assigned to either placebo . A densitometer  described by Wooten et al.  was usedSubjects were presented with a 550 nm narrow-band , 1-degree disc of light that was alternated on and off in square-wave counterphase. Thresholds for flicker fusion (when the light was flickering at a rate such that there was no longer any flickering or pulsing evident) were obtained for both ascending and descending trials. For ascending trials, the rate of flicker was set well below the critical flicker fusion frequency (CFF) threshold, and at a rate of roughly 1 Hz/second, the flicker rate was increased by the experimenter until the participant indicated complete flicker fusion. On descending trials, the rate of flicker was set well above the CFF threshold, and then decreased roughly 1 Hz/second until the participant just noticed minimal pulsing or flicker. The overall threshold for the CFF task was calculated as the average of two ascending and two descending thresholds; the task took 1 min for subjects to complete.During each visit, participants completed a short questionnaire regarding the weekly frequency of occurrence of five outcome variables typically associated with excessive ST: headache, blurry vision, neck strain, eye strain, and eye fatigue. If a specific item occurred less frequently than once/week, but still occurred on a monthly basis , participants were instructed to write down the monthly frequency next to the item. For calculation purposes, a month was considered four weeks; monthly frequency was therefore simply divided by four to yield a weekly value. The questionnaire took approximately 5 min to complete.Sleep quality was evaluated with the Pittsburgh Sleep Quality index , a 19-iLmax and Lmin represent the maximum and minimum luminance in a grating, respectively. Twenty-five stimulus presentations were used to determine a threshold, and trials always started with the Gabor set to maximum contrast (90% Michelson contrast). On correct responses, the contrast of the Gabor was decreased by 27% of its previous value. Incorrect responses resulted in an increase of 21% of the previous Gabor’s contrast value. Based on the results of an ideal observer model, these values most accurately predicted actual contrast thresholds for a trial consisting of 25 stimulus presentations, averaging the last three reversals. The subjects typically produced five or more reversals; actual thresholds were determined by computing the average of the last three reversals. Two thresholds were determined at each visit; the average of the two thresholds was taken as the true threshold, and used for statistical analysis. A 1-min rest period was allowed between each trial. Total time spent on contrast sensitivity testing was roughly 10 min.Contrast sensitivity (CS) testing was conducted on the same computer/monitor as described above. A subject’s threshold for detection of a Gabor patch’s orientation  was determined for a single stimulus, a 6 cycle/degree target subtending 2 degrees of visual angle. A two-alternative, forced-choice staircase procedure was implemented to determine a subject’s contrast threshold. If there was no response, it was recorded as incorrect. Contrast was specified as Michelson contrast:A custom apparatus for assessing disability glare (DG) and photostress recovery (PSR) time was created to provide sufficient intensity of light and a uniform spatial distribution with minimal reliance on optics. A microcontroller, coupled to high-intensity cool-white LEDs, provided a pulse-width modulated signal, which permitted the glare and photostress sources to be held at an adjustable intensity for any needed duration, while maintaining a high degree of linearity and stability in adjustment. The LEDs appear white by virtue of the phosphor emitting a strong blue component and a broad yellow–orange component. For human vision, a mix of blue and yellow sources will result in a range of whites, denoted “cool” to “warm” . For th2, and appeared medium-gray to subjects. For the PSR experiment, subjects were aligned to the optical system via an adjustable chin and forehead rest. Once comfortable, subjects were instructed to direct their gaze at the center of the monitor. The photostress light  was then presented for 8 s. Subjects were asked to look directly at the light, and try to refrain from blinking or closing their eyes. After the exposure was complete, subjects were advised to blink and look in the center of the monitor for the Gabor target, which was tilted 45 degrees left or right from vertical. Once the target was detected, subjects pressed either the left or right arrow key on a keyboard to indicate which direction the target was leaning. If correct, subjects were again presented with the photostress light for 8 s. This procedure was repeated until a total of 5 recovery thresholds were obtained. To control for any possible interocular effects (however unlikely), only the right eye was used for all vision testing. For both DG and PSR experiments, the target was a 6 cycle/degree, 15% Michelson contrast Gabor patch that subtended 2 degrees of visual angle. The Gabor patch was presented centrally on an LCD monitor. The background luminance was 20 cd/mFor DG testing, subjects viewed the Gabor patch target through the ring of LEDs. To guard against visual adaptation effects or potential subject bias, the Gabor patch was made to vertically tilt back and forth 45 degrees every second. The experimenter adjusted the intensity of the LED ring to the point at which the veiling glare was sufficient to prevent a subject from detecting the tilting of the Gabor patch. Four thresholds were obtained: two approaching from below, and two approaching from above the visibility threshold. The four thresholds were averaged to form the overall DG threshold. Total time per session for these tasks was roughly 15 min.n = 12, the power calculation determined that the treatment group required 30 subjects to detect effects (if present). We recruited additional subjects for the study, assuming some attrition.The statistical and graphing program OriginPro 9.3  was used to conduct repeated-measures ANOVA, Pearson product–moment correlations, and generate figures for the manuscript. Levene’s test for homogeneity of variance was used and determined to be non-significant. In consideration of the unequal N for the two groups, a power analysis was conducted to determine adequate sample sizes in order to detect effects of supplementation on all of the outcome measures. The statistical power rate 1−β was set at 0.80; a 20% change in visual performance or physical indicator status in treatment groups, a standard deviation of 20%, and α = 0.05 were parameters used for calculation. With the placebo group set at r = −0.48; p < 0.001), DG , CFF , and CS . CFF and CS were also significantly correlated , as were DG and PSR . Lastly, a marginally significant correlation was found for PSR and CFF . One significant correlation was determined between visual measures and physical indicators of excessive ST: PSR and eye fatigue . Several marginal correlations were determined at baseline for the measures of physical indicators of excessive ST, including MPOD and eye fatigue , eye strain , and headache frequency . Additionally, there were marginal correlations found between headache frequency and both eye strain  and neck strain ; frequency of neck strain and eye strain were also marginally correlated . At baseline, several measures were found to be significantly correlated. For the visual measures, MPOD was correlated with PSR (p = 0.023) and overall sleep quality (p = 0.025) changed significantly after 3 months of supplementation. At 6 months, several additional variables were found to have changed significantly versus placebo. These included MPOD (p = 0.015), CFF (p < 0.001), sleep quality (p = 0.01), CS (p = 0.002), DG (p = 0.021), PSR (p = 0.011), headache frequency (p = 0.029), eye strain (p = 0.046), and eye fatigue (p = 0.016). Frequency of blurry vision and neck strain were not found to change appreciably throughout the study in either the placebo or treatment group. Subjects’ consumption of foods that contain L and Z did not change throughout the study period (p = 0.53), and neither did their estimates of ST (p = 0.62).Compared to the placebo group, those in the MC supplementation group changed significantly for several of the variables measured in the study. See There are two major points to take away from the results of this study. First, baseline data suggest that MPOD is associated with several visual and physical benefits for those who view near-field screens for at least 6 h daily. At baseline, MPOD was significantly related to each of the visual performance measures, and marginally related to frequency of headaches, eye strain, and eye fatigue. Second, 6 months of supplementation with 24 mg of MCs led to significant improvements in each of the visual measures (including a significant increase in MPOD), a significant improvement in sleep quality, and a significant reduction in the frequency of headaches, eye strain, and eye fatigue see .Given the rich deposition of the MCs in the foveal retina, the most parsimonious explanation of the effects determined in our study would seem to involve the deposition of the MCs in the retina as MP. Certainly this is the most plausible explanation for the visual performance results—baseline relationships and changes with MPOD augmentation for these measures have also been shown in previous studies . The results of the physical indicators of excessive ST portion of the study are somewhat unexpected. MPOD is (by definition) located in the eye, and by extension expected to have its effects on vision. Marginal associations and significant improvements were seen, however, in a few of the physical indicator variables. The question that arises from this seeming discrepancy involves the link between the two—how can something with such a specific location have its effects elsewhere in the body? With regard to the significant improvement in eye fatigue with supplementation, a plausible explanation could involve the aforementioned increased efficiency of the visual cycle seen with increased MPOD. Although light from smartphone, tablet or computer screens is not typically very intense, there is nevertheless prodigious demand for metabolic resources when viewing any light source continually. If the visual system is able to regenerate photopigment more efficiently, it may keep the state of visual adaptation at a level that serves to increase visual sensitivity, which may manifest as an increase in CS  is the root of several of the negative outcomes of excessive ST. The effects of ST on children are just starting to be appreciated, and they represent another population of interest. Accommodative ability is typically not an issue in children, but there may be other, less obvious issues and effects in this population. For example, children younger than 10 years old are known to have exceptionally clear crystalline lenses , and may


In this study, first time attempt has been made to predict cell-penetrating property of peptides containing natural and modified residues. The dataset used to develop prediction models, include structure and sequence of 732 chemically modified cell-penetrating peptides and an equal number of non-cell penetrating peptides. We analyzed the structure of both class of peptides and observed that positive charge groups, atoms, and residues are preferred in cell-penetrating peptides. In this study, models were developed to predict cell-penetrating peptides from its tertiary structure using a wide range of descriptors . Random Forest model developed by using PaDEL descriptors  achieved maximum accuracy of 95.10%, MCC of 0.90 and AUROC of 0.99 on the main dataset. The performance of model was also evaluated on validation/independent dataset which achieved AUROC of 0.98. In order to assist the scientific community, we have developed a web server “CellPPDMod” for predicting the cell-penetrating property of modified peptides (http://webs.iiitd.edu.in/raghava/cellppdmod/).Designing drug delivery vehicles using cell-penetrating peptides is a hot area of research in the field of medicine. In the past, number of  Candida albicans, Staphylococcus aureus as well as Mycobacterium smegmatis  and validation dataset  is one out of 8 atoms.Where atom  of the peptide, and used to convert the variable length of modified peptides to fixed length feature vectors. The diatomic composition provided the fixed length of 64 (8 × 8) vectors.a) is one out of 64 diatoms.Where diatom  is the percent composition of amino acid (a); Ra is the numbers of residues of type a, and N represents the total number of peptide's residues.Here, We also calculated dipeptide composition of the peptides since it provides global information of the peptide. The dipeptide composition was calculated using the formula 4, and it generated the vector of 400 (20 × 20).a) is one out of 400 dipeptides.Where dipeptide , Specificity (Spc), Accuracy (Acc), and Matthews's correlation coefficient (MCC), where Sensitivity is true positive rate, Specificity is true negative rate, accuracy is ability to differentiate true positive and true negative and MCC is a correlation coefficient between observed and predicted. These can be calculated using the following equations.TP represents correctly predicted positive, TN represents the correctly predicted negative examples, PS represents total sequences in positive set, NS represents total sequences in negative set, FP represents actual negative examples which have been wrongly predicted as positive and FN represents wrongly predicted positive examples. This is a well-established method of measuring performance and has been used earlier in many studies  curve is drawn between false positive and false negative rates. In order to measure performance, Area Under Curve ROC curve is computed called AUROC.We compute percent average composition of atoms in CPPs and non-CPPs to understand the preference of certain types of atoms present in the CPPs and non-CPPs. Overall, the profile is more or less same in both CPPs and non-CPPs.CPPs are slightly rich in H and N atoms whereas non-CPPs are slightly rich in C, O, and S Figure . We analIn addition to compositional preference, we also computed preference of different types of residues in CPPs. It was revealed that some specific type of residues was preferred in the positive dataset contain CPPs as compared to the negative dataset contain non-CPPs. Residues like Rand K are highly preferred at various positions CPPs particularly at N terminal Figure . SimilarWe used various machine-learning approaches like SVM, Random Forest, Naive Bayes, J48 and SMO for developing the prediction model. These models utilize different features or descriptors to discriminate or classify CPPs and non-CPPs. The results are explained in details in the following sections.Tertiary structure of a peptide can present all type of modifications. Thus structure of peptide is used to predict cell penetration ability of modified peptide. In this study, we got structure of peptides from databases CPPsite 2.0 and SATPdb. The models were developed using various features of peptide structures. First, we developed model using atomic composition of peptides. In order to obtain atomic composition of peptides from its structure, we convert structure from sdf format to SMILES. The atomic composition of peptides was calculated from SMILES of peptide. Prediction models were developed using different classifiers like SVM, RF, Naive Bayes, SMO and J48 using atomic composition as an input feature. Random Forest based classification model provided the highest accuracy of 84.02%, MCC of 0.68 and AUROC of 0.91 on the training dataset. On validation dataset, we achieved maximum accuracy of 78.33%, MCC of 0.57 and AUROC of 0.88. Performance of different classifiers given in Table N = 5 and lookup size D = 1). In case of 2D descriptors, total 144 descriptors were calculated initially and were reduced to 17 after feature selection. List of the selected features is provided in Table We developed models individually for 2D descriptors, 3D descriptors, and Fingerprints as well as the single model by combining 2D, 3D descriptors, and Fingerprints. The descriptors were computed using PaDEL software from tertiary structure of peptides (sdf format). The models were developed on the features, selected after performing feature selection, by attribute evaluator named, “CfsSubsetEval” with search method of “BestFirst” at default parameters in the forward direction  of the modified peptide as an input and does the prediction. If a user has no structural information, he/she can generate PDB structure of their peptide up to 25 residues in length using server “PEPstrMOD”  developed by our group specifically for predicting the structure of the modified peptide. In case of natural peptide user can also use following servers PEP-FOLD  and QUARK  for predicting structure of peptides. Multiple modification options are provided there, and the user can choose the desired modification. After generating the structure, user can do the prediction on “PREDICTION” module, whether the given modified PDB structure is CPP or non-CPP. Beside the main model, we have also implemented model based on peptide sequence (Subsidiary model). We have also provided a “DOWNLOAD” module from where the user can download the dataset used in this study.To assist the scientific community, the best models are provided freely at CPPs has shown a promising impact in the field of therapeutics or for targeting a specific disease  as well as fingerprint with accuracy 92.33% and AUROC 0.98 on validation dataset. As fingerprint alone will be computationally more feasible as compared to the combined method, so we have implemented this model on webserver.We believe this work will prove a great assist to the researchers aim to design cell penetrating peptide, as well as incorporate different modification and to check their effect on cell penetration ability. In future, we can improve this method, if better art of structure prediction will be developed, as right now PEPstrMOD could tackle only 7–25 amino acid length and other best model I-TASSER only deals with natural residues. So, in conclusion this field must grow simultaneously with the betterment of art-of-structure prediction.VK and PA generated the dataset. VK, PA, RK, and SB performed the experiments. VK, PA, and RK performed data analysis and prepared the tables and figures. VK, PA, RK, SB, and SU developed the web interface. VK, RK, PA, SU, and GR write the manuscript. GR and GV conceived the idea and coordinated the project.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.