Anorexia occurs in about half of cancer patients and is associated with high mortality rate. However, safe and long-term use of anorexia treatment is still an unmet need. The purpose of the present study was to examine the feasibility of Sipjeondaebo-tang  for cancer-related anorexia. A total of 32 participants with cancer anorexia were randomized to either Sipjeondaebo-tang group or placebo group. Participants were given 3 g of Sipjeondaebo-tang or placebo 3 times a day for 4 weeks. The primary outcome was a change in the Anorexia/Cachexia Subscale of Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The secondary outcomes included Visual Analogue Scale (VAS) of anorexia, FAACT scale, and laboratory tests. Anorexia and quality of life measured by FAACT and VAS were improved after 4 weeks of Sipjeondaebo-tang treatment. However, there was no significant difference between changes of Sipjeondaebo-tang group and placebo group. Sipjeondaebo-tang appears to have potential benefit for anorexia management in patients with cancer. Further large-scale studies are needed to ensure the efficacy.NCT02468141. This trial is registered with ClinicalTrials.gov  Anorexia is associated with high mortality rate in cancer patients, reduction in the effectiveness of anticancer therapy, reduced ability to perform activities of daily living, and lower quality of life in physical, mental, and social functions . It occuThere were case studies on the improvement of anorexia in cancer patients using acupuncture  and acupSipjeondaebo-tang , one of the most commonly used traditional herbal medicines in Korea, is prescribed for patients with deficiency syndrome, suffering from anemia, fatigue, and anorexia , 11. SJDThe purpose of this study was to evaluate the effect and safety of SJDBT for anorexia in cancer patients by comparing the experimental group to placebo group using the Functional Assessment of Anorexia and Cachexia Treatment , anorexia Visual Analogue Scale (VAS), weight, body mass index (BMI), adrenocorticotropic hormone (ACTH), and cortisol values.NCT02468141) prior to the completion of the clinical trial. We followed the methods of Cheon et al. 2016 [A randomized, double-blind, placebo-controlled trial was conducted at the Dunsan Korean Medicine Hospital of Daejeon University in Daejeon, Republic of Korea. The Institutional Review Board of the Dunsan Korean Medicine Hospital of Daejeon University approved the study (reference DJDSKH-15-03-2 (Ver. 2.0)). The study protocol of this study has already been published as a protocol paper and also registered in ClinicalTrials.gov NCT024681 prior tThis study was a pilot study that examines the feasibility for a full randomized clinical trial of SJDBT for treating cancer-related anorexia and determines the effect size for further large-scale studies. Thus, a total of 32 participants were recruited for the study. Sixteen participants were allocated to the SJDBT group and another sixteen to the placebo group. Cinnamomi Cortex (1.00 g), Paeoniae Radix (1.00 g), Atractylodis Rhizoma Alba (1.00 g), Ginseng Radix Alba (1.00 g), Cnidii Rhizoma (1.00 g), Astragali Radix (1.00 g), Poria Sclerotium (1.00 g), Rehmanniae Radix Preparata (1.00 g), Angelicae Gigantis Radix (1.00 g), and Glycyrrhizae Radix (0.5 g). These raw materials were extracted and concentrated to 3 grams for single dose. The placebo was made of lactose, corn starch, and caramel colouring, and it had similar appearance, shape, weight, taste, and colour to SJDBT. Investigational products were manufactured in accordance with the Korean herbal pharmacopoeia and the Korean pharmacopoeia [μm, and the filtrate is concentrated under reduced pressure at 60°C or lower and dried to obtain dried extract.SJDBT and placebo were produced and packaged by Hanpoong Pharm and Foods Co., Ltd., the pharmaceutical company, certified GMP (Good Manufacturing Practice) by the Ministry of Food and Drug Safety of Korea. SJDBT includesacopoeia , 16. BriThe participants received SJDBT or a placebo drug for four weeks. They orally took 3 grams of granules with water three times a day after meals for 4 weeks. The participants were required to return the remaining drug for calculating compliance at visit 3 and visit 4. During the trial, the participants were prohibited to receive other treatments for anorexia. All treatments were documented on the case report form (CRF), including the drug name, the daily dose, the purpose of the drug use, the route of administration, and the start date and stop date.Regardless of the type and stage of cancer, all patients with solid cancer complaining of anorexia have been subject to recruitment. Participants were recruited regardless of chemotherapy and radiotherapy. The inclusion and exclusion criteria are shown in Institute of Safety, Efficacy and Effectiveness Evaluation for Korean Medicine (ISEE) which was the Contract Research Organization (CRO) of the present study generated random numbers. Block randomization with block size of four was performed. The random numbers and randomization table were maintained by the ISEE during the research period in opaque and sealed envelopes. The opening procedure followed the Standard Operating Procedures (SOPs). A research assistant who was not involved in recruitment, intervention, or assessment of outcomes prepared the envelopes. Investigators responsible for recruitment and assessment were not allowed to take part in the group allocation. Therefore, all the investigators, monitors, and participants were blinded for assignment of the study drugs.The change in the ACS of FAACT between the baseline (visit 2) and end of the study (visit 4) was used as the primary outcome measurement . SecondaAt every visit, vital signs including blood pressure, pulse, respiration rate, and physical examination, haematologic test, biochemical test, and urine test related to safety assessment and any adverse events were documented in the CRFs.p value was considered statistically significant. ITT  data set was applied for data analysis. The continuous variables were displayed as mean ± SD, and the categorical variables were displayed as n (%). The baseline characteristics were compared to see whether there is a significant difference between SJDBT group and placebo group by either an independent t-test for continuous variables including age, height, weight, BMI, FAACT scale, anorexia VAS, SBP, DBP, pulse, ACTH, cortisol, ghrelin, interleukin 6, ESR, and CRP or the χ2 test for the categorical data including gender, cancer type, and anticancer therapy. For the efficacy variables, the mean differences between the baseline and the end of the treatment were compared using an independent t-test. Two-way repeated measured analysis of variance was also used to determine differences between the groups and over time. The normality assumption was tested using Shapiro-Wilk test.All statistical procedures were performed using the R statistical software . A two-sided, 5% or lower Of all the 32 randomized participants, 16 participants (50%) took SJDBT and 16 participants (50%) took placebo. There were 14 thyroid cancer, 7 breast cancer, 4 lung cancer, 2 breast cancer, 2 colon cancer, and 2 cervical cancer participants. Of the total 32 participants, 3 participants received both chemotherapy and radiation therapy, 7 participants received chemotherapy only, 9 participants received radiotherapy only, and 13 participants did not receive both chemotherapy and radiation therapy. In SJDBT group, there was one participant lost to follow-up for low compliance. In placebo group, there were two participants lost to follow-up who withdrew the informed consent. No one dropped out before receiving the intervention. Thus, 16 participants treated with SJDBT and 16 participants treated with placebo were included in the ITT analyses. After 4 weeks, 15 participants completed the trial in the SJDBT group and 14 participants completed the trial in the placebo group. Participants flow chart is shown in p > 0.05).The baseline characteristics of the two groups were shown in p = 0.245). In the within-group analysis, change in SJDBT group and placebo group showed significant difference . There was no statistically significant group-by-period interaction.The mean FAACT ACS score at each time point is shown in p = 0.124). In the within-group analysis, change in SJDBT group and placebo group showed significant difference . The changes in the anorexia VAS between baseline and the end of study were 25.78 in SJDBT group and 18.45 in placebo group, but the changes of anorexia VAS were not significantly different between the two groups (p = 0.346). In the within-group analysis, change in SJDBT group and placebo group showed significant difference . There were no statistically significant group-by-period interactions.The mean FAACT score and anorexia VAS at each time point are also shown in In between-group analysis, the change of ACTH, cortisol, ghrelin, IL-6, ESR, and CRP between baseline and the end of study did not show statistically significant difference . In withIn between-group analysis, the changes of qi deficiency scale and blood deficiency scale between baseline and end of the study did not show statistically significant difference . In withAt every visit, systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse, AST, ALT, blood urea nitrogen (BUN), and creatinine did not show significant difference between SJDBT group and placebo group . In withThe present study is double-blind, randomized, placebo-controlled trial that investigated whether SJDBT improves appetite loss measured by FAACT ACS score and anorexia VAS in cancer patients with anorexia after 4 weeks of treatment. However, there was no statistically significant difference between the SJDBT group and placebo group. In addition to appetite loss, general aspect in quality of life measured by FAACT was also assessed after 4 weeks of treatment. But, there was no statistically significant difference between two groups. Otherwise, changes of clinical laboratory tests including ACTH, cortisol, ghrelin, IL-6, ESR, and CRP were unremarkable.Although there was no statistically significant difference between SJDBT group and placebo group, the changes of FAACT and anorexia VAS in the SJDBT group imply the need for large-scale trial in further studies. Given that the aspect of change of total FAACT score is similar to that of FAACT ACS score, further studies need to focus on not only the anorexia but also overall status of cancer patients.There was a report that Rikkunshito which is often prescribed for the treatment of anorexia regulates ghrelin secretion and degradation, sensitizes ghrelin receptor, and antagonizes the 5-HT2b/c receptors . HoweverAlthough the present study did not show statistically significant difference between SJDBT and placebo, previous preclinical study reported that SJDBT improves cancer-induced weight loss and anorexia in mice . MoreoveQi deficiency leads to decreased visceral functions and lowered body resistance and blood deficiency is any pathological change characterized by deficiency of blood which fails to nourish organs, tissues, and meridians/channels . In the  Astragali Radix and ginsenoside Rg1 which is a major component of Ginseng Radix have a beneficial effect on anorexia [It has been reported thatanorexia , 32. Howanorexia . Likewisanorexia .There were some limitations of the present study. The sample size was too small to show statistically significant results. However, the results of the present pilot study will be used for designing the main study. The purpose of this study was to evaluate efficacy of SJDBT for anorexia; thus we only prohibited participants from taking medications that aim to improve appetite, not for other purposes; therefore many participants took herbal medicines which could affect the qi deficiency and blood deficiency for treatment of fatigue or pain, and so on. This has made it difficult to assess the effects of SJDBT on qi deficiency and blood deficiency. It was an inevitable choice for the needs of patients using Korean medicine hospital and for facilitating clinical trial recruitment. For a similar reason, all patients with solid cancer complaining of anorexia were recruited and the number of participants was too small to investigate the difference in the effect of SJDBT and the difference of anorexia according to cancer type. Another limitation of the present study is that the type of chemotherapy drugs was not confirmed and thus we could not confirm the difference of effect of SJDBT according to the type of chemotherapy. This is because the participants received primary treatment of cancer from other medical institutions, and then the study was conducted on participants who visited the trial institution for symptoms management. Although these limitations limit the interpretation of the study results, the present study is meaningful in that such pilot study results are necessary to conduct large-scale, rigorous study in the medical reality in Korea. Rigorous further studies which compensate these defects will be necessary to ascertain the efficacy of SJDBT for anorexia in cancer patient.The present pilot study showed the feasibility that SJDBT could be used for management of patients with cancer. Compared to baseline, 4 weeks of SJDBT treatment improved the quality of life assessed by the FAACT and anorexia in patients with cancer. However, there was no statistically significant difference between SJDBT group and placebo group. These findings could be used as preliminary data for further large-scale studies.


The aim of this study was to investigate the role of personal and collective work identity (including emotion and cognition components), in predicting work motivation  and organizational justice . Digitized questionnaires were distributed by e-mail to 2905 members, teachers, of a Swedish trade union. A total of 768 individuals answered the questionnaire and by that participated in this study. Personal- compared to collective work identity was shown to positively associate with self-determined motivation accounted for by the emotion component of personal work identity. Collective compared to personal work identity was reported to positively associate with organizational pay justice accounted for by the cognition component of collective work identity. All this suggests that both work-related motivation and organizational justice might be, to some extent, accounted for by the psychological mechanisms of work identity and that, as predicted, different types of work identity, play different significant roles in predicting motivation and justice at work. More precisely, the emotion component of work identity was more pronounced in personal work-bonding relationships, and the cognitive component, of work identity in contrast, was more pronounced in collective work-bonding relationships. We identify us with our work. A phenomenon labeled work identity, involving emotion and cognition processes, accounts for this type of bonding Knez, . Work idAnother important factor that guides our work-related behavior and engagement  is a higher order cognitive construct  and the organizational/workgroup level . This means that career/occupation at the former level “can be conceptualized as one of the life goals that we strive for and find meaning in Gini  and being cared for by, and caring for, others ; and (2) Collective work identity and Organizational pay justice (collective level of explanation).Despite the previous research on work-related motivation and justice no previous research has, as far as we know, investigated the role of personal and collective work identity in predicting these constructs. Accordingly, and in line with the general notion of foci of identification and its associated effects  and mean employment time within the organization was 14 years (SD = 10.2).Digitized questionnaires were distributed by e-mail to 2905 members of the Swedish trade union “The National Union of Teachers” (in Swedish “Lärarnas Riksförbund”) working in the south and middle part of Sweden, during April and May 2016. A total of 768 questionnaires were returned, with a response rate of 26%. Ninety-nine percent of the participants had an educational function, that is, they worked as teachers or similar. Also, the participants worked within the municipal sector (92.1%), had university studies as their highest level of education (68%), were in permanent employment (95.2%), had full-time jobs (80.5%) and were female (75.5%). Mean age was 46.3 , CFI = 0.95 and RMSEA = 0.08.In addition, we examined the construct validity of the personal work identity construct with a confirmatory factor analysis, including a second-order factor representing a general personal work identity construct, with cognitive and emotional components as first-order factors. According to Byrne  the modeCollective work identity was measured by the “Identification with a Psychological Group Scale” , CFI = 0.97 and RMSEA = 0.10  were reported in the present study: 0.87 for collective work identity, and 0.78 for emotional and 0.77 for cognitive component, indicating good internal consistency .In line with the four hypotheses, four types of multiple hierarchical regression analyses were performed in order to investigate the role of personal and collective work identity in predicting motivation and justice at work:Personal- and collective work identity (predictors) and work self-determined motivation (criterion variable)Emotion- and cognition component of personal work identity (predictors) and work self-determined motivation (criterion variable)Personal- and collective work identity (predictors) and organizational pay justice Emotion- and cognition component of collective work identity (predictors) and organizational pay justice monthly income; school sector (public vs. private); years of employment; and permanent employment (no vs. yes). These variables have previously been addressed as potential confounders, related to work self-determination motivation , personal compared to collective work-related identity was shown to positively associate with work self-determined motivation . In line with a general notion of focus of identification and its associated effects  in predicting motivation and justice at work, in a Swedish teacher sample  positively predicts all of the three psychological needs; competence, relatedness and autonomy, which may function as the basis of self-determined work motivation  work identity is more of a cognitive structure .ON collected the data, did the data analyses and wrote all manuscript sections together with IK.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.


This review evaluates the literature examining the association between MRI measures of neurodegeneration derived from T1-weighted images and disability in MS patients.Multiple sclerosis (MS) is characterised by the accumulation of permanent neurological disability secondary to irreversible tissue loss (neurodegeneration) in the brain and spinal cord. MRI measures derived from T1-weighted image analysis  are correlated with pathological measures of irreversible tissue loss. Quantifying the degree of neurodegeneration A systematic PubMed search was conducted in January 2017 to identify MRI studies in MS patients investigating the relationship between “black holes” and/or atrophy in the brain and spinal cord, and disability. Results were limited to human studies published in English in the previous 10 years.A large number of studies have evaluated the association between the previous MRI measures and disability. These vary considerably in terms of study design, duration of follow-up, size, and phenotype of the patient population. Most, although not all, have shown that there is a significant correlation between disability and black holes in the brain, as well as atrophy of the whole brain and grey matter. The results for brain white matter atrophy are less consistently positive, whereas studies evaluating spinal cord atrophy consistently showed a significant correlation with disability. Newer ways of measuring atrophy, thanks to the development of segmentation and voxel-wise methods, have allowed us to assess the involvement of strategic regions of the CNS  and to map the regional distribution of damage. This has resulted in better correlations between MRI measures and disability and in the identification of the critical role played by some CNS structures for MS clinical manifestations.The evaluation of MRI measures of atrophy as predictive markers of disability in MS is a highly active area of research. At present, measurement of atrophy remains within the realm of clinical studies, but its utility in clinical practice has been recognized and barriers to its implementation are starting to be addressed. The application of magnetic resonance imaging (MRI) techniques is integral to our understanding of the pathogenesis of multiple sclerosis (MS). Historically, MS was considered to be an autoimmune-driven inflammatory disease characterised by focal white matter (WM) demyelination , visualiTwo major advances in our understanding of MS are helping to resolve this paradox. First, the pathological substrates of MS extend well beyond focal WM lesions. Advanced MRI techniques, as well as postmortem histopathological findings, have shown that MS is also characterised by more widespread damage to the so-called “normal-appearing” WM (NAWM), as well as focal and diffuse damage to the grey matter (GM) of the brain and spinal cord , 4. SecoIt is well accepted that neurodegenerative changes, irrespective of their aetiology, underlie the accumulation of permanent neurological disability that characterises MS –13. As aThe aim of this review was to discuss the literature examining the association between MRI measures of neurodegeneration derived from the analysis of T1-weighted images (black holes and atrophy) and disability in patients with MS. Black holes represent areas of focal axonal damage and irreversible tissue destruction , while aAtrophy is most commonly quantified as the loss of overall brain tissue from T1-weighted images. Some methods for atrophy quantification also work on T2 and FLAIR images. Advances in the methods of analysis have made it possible to measure atrophy of spinal cord, GM, WM, and specific regions and structures of the brain . A number of techniques are used to quantify atrophy, ranging from manual bi-dimensional assessment to automated or semi-automated volumetric measurement. Methods for the quantification of atrophy are continuously evolving, improving not only image acquisition and analysis strategies but also in terms of increased understanding of the technical , physiological , lifestyle , genetics , and other factors  that may affect brain volume results. For instance, it is now established that WM lesions affect atrophy calculations, since they influence the detection of GM/WM/cerebrospinal fluid intensity differences. Different techniques, that can be applied in a wide range of atrophy tools, have been proposed to fill in the signal from these lesions and alleviate this problem. For a review of these techniques and factors, the reader is referred to review articles on this topic –20. WithA systematic PubMed search was conducted in January 2017 to identify studies investigating the relationship between disability and black holes and/or atrophy in the brain and spinal cord. Results were limited to human studies published in English in the previous 10 years. Studies that examined the effect of disease-modifying treatments on measures of neurodegeneration were excluded, as this was outside the scope of this review. The search terminology is summarized in the Table S1 in Supplementary Material.Results are presented first for studies that assessed black holes/atrophy in the brain, followed by studies that assessed these measures in the spinal cord. Studies that assessed both brain and spinal cord atrophy in relation to disability are presented in a separate section.n = 35), while 10 focused on relapsing-remitting multiple sclerosis (RRMS), four on primary progressive multiple sclerosis (PPMS), three on relapsing MS, two on clinically isolated syndrome (CIS), and one on relapsing onset  MS. The remaining four studies compared MS subtypes. In the majority of studies, the EDSS score was used to assess disability; other disability measures included the MSFC, the Multiple Sclerosis Severity Score (MSSS), the 9HPT, and the T25FW. Most of the studies evaluated whole brain atrophy as a measure of neurodegeneration; other measures included black holes and atrophy of the global GM, global WM, regional GM, and/or GM of specific structures.Overall, 59 key studies evaluating the association between MRI measures of brain neurodegeneration and disability were identified Table . Of thesHistorically, black holes were introduced as the first MRI measure of neurodegeneration and prevention of the evolution of newly formed lesions into persistent black holes is currently being evaluated as a possible measure of neuroprotection in several treatment trials in patients with MS.p < 0.001 for both). Over the 10-year follow-up, there was a modest correlation between the increase in EDSS score and black hole volume (p < 0.001). In a stepwise multiple regression analysis, EDSS score worsening over 10 years was best associated with the combination of baseline black hole numbers and increasing black hole volume (p < 0.001)   , 86, 87.) Figure . In cont) Figure . In a cr < 0.01) .Several strategies have been proposed to increase black hole detection and improve the correlation with disability, including the restriction of black hole measurements according to their intensity  or relaxp < 0.05 for all; see Table p-values) (p = 0.001)  evaluated the association between whole brain atrophy and disability; most included patients with mixed disease phenotype. Five of the cross-sectional studies reported a significant correlation between whole brain atrophy and EDSS  , 56, 58.= 0.001) .p < 0.001), while at 10 years, there was a trend for greater decrease in whole brain volume in patients with disability progression   .p < 0.0001). In addition, brain volume was significantly lower in patients with progression vs those with stable or improved disability (p < 0.05). However, baseline brain volume was not related to the change in EDSS score during the follow-up period (p = 0.01)  (p period . Pichler = 0.01) .p < 0.01); this correlation was not observed for those with a high baseline lesion burden ] demonstrated a significant correlation with EDSS score (p < 0.05), but not the T25FW (p = 0.0008)  evaluated the correlation between global GM loss and disability. Of the six cross-sectional studies that assessed disability using the EDSS, three studies  and the ratio of the T1:T2 lesion volume . AlthougIn most of the studies in which it was evaluated, there was a correlation between black holes and disability outcome measures. This supports the concept that focal, irreversible tissue loss, as well as more diffuse loss of tissue, has an impact on disability in MS. A number of the studies assessing black holes also evaluated T2 lesion load, which represents focal WM lesions. In the largest of these studies , conductWhen considering the results of the studies included in this review, it should be borne in mind that correlation does not prove causality, and multivariate analysis, to control for confounding variables, was not applied in all studies. It is also clear from the information presented Tables –3 that sEstablishing a definitive link between MRI measures of neurodegeneration and disability progression would allow such measures to be used as objective surrogate markers of disease progression, with the potential to predict future disability. They could also be used to evaluate response to treatment, which will become increasingly important as research becomes more focused on developing treatments for progressive stages/forms of MS.Brain atrophy is already being used as an outcome measure in clinical trials of disease-modifying therapies for MS. Indeed, in a meta-analysis of data from 13 trials , treatment effects on disability progression were correlated with treatment effects both on brain atrophy and on active MRI lesions . At a reThe evaluation of MRI measures of neurodegeneration as predictive markers of disability in MS is a highly active area of research. Over the last 10 years, a large number of MRI studies have added to the existing literature on this subject, confirming that in general, MRI measures of atrophy correlate with disability. These efforts have culminated in the use of brain atrophy measurements to assess the effects of disease-modifying therapies. Although currently limited to clinical trials, discussions are beginning on how brain atrophy measurement can be applied in clinical practice. The next 10 years promises to be equally fruitful; as MRI techniques evolve, so the pathological substrates of disability will become more clearly delineated. As we work toward this goal, we should not lose sight of the challenges, both technological and financial, of introducing these techniques into everyday clinical practice.All the authors were responsible for defining the scope and content of the article. All the authors reviewed each draft and provided approval of the final version.MR has received speaker honoraria from Biogen Idec, Novartis, Teva Neurosciences, and Genzyme and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla. GC has received compensation for consulting services for Novartis, Teva, Sanofi, Genzyme, Merck, Biogen, Excemed, Roche, Almirall, Chugai, Receptos and Forward Pharma, and compensation for speaking activities for Novartis, Teva, Sanofi, Genzyme, Merck, Biogen, Excemed, and Roche. MF is Editor-in-Chief of the Journal of Neurology; serves on a scientific advisory board for Teva Pharmaceutical Industries; has received compensation for consulting services and/or speaking activities from Biogen Idec, Merk-Serono, Novartis, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Teva Pharmaceutical Industries, Novartis, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, Cure PSP, Alzheimer’s Drug Discovery Foundation (ADDF), the Jacques and Gloria Gossweiler Foundation (Switzerland), and ARiSLA .


One of the clinically relevant problems of Internet use is the phenomenon of Internet addiction. Considering the fact that there is ample evidence for the relationship between attachment style and substance abuse, it stands to reason that attachment theory can also make an important contribution to the understanding of the pathogenesis of Internet addiction.The aim of this study was to examine people’s tendency toward pathological Internet usage in relation to their attachment style.An online survey was conducted. Sociodemographic data, attachment style (Bielefeld questionnaire partnership expectations), symptoms of Internet addiction , used Web-based services, and online relationship motives  were assessed. In order to confirm the findings, a study using the Rorschach test was also conducted.In total, 245 subjects were recruited. Participants with insecure attachment style showed a higher tendency to pathological Internet usage compared with securely attached participants. An ambivalent attachment style was particularly associated with pathological Internet usage. Escapist and social-compensatory motives played an important role for insecurely attached subjects. However, there were no significant effects with respect to Web-based services and apps used. Results of the analysis of the Rorschach protocol with 16 subjects corroborated these results. Users with pathological Internet use frequently showed signs of infantile relationship structures in the context of social groups. This refers to the results of the Web-based survey, in which interpersonal relationships were the result of an insecure attachment style.Pathological Internet use was a function of insecure attachment and limited interpersonal relationships. Nowadays the Internet is a central aspect of everyday life. There are many opportunities for online dating, problems can be discussed in thematically appropriate forums, and doctors can be consulted ,2. Even One of the clinically relevant problems Internet use may yield is Internet addiction. Even though most people use the Internet every day without problems, recent figures highlight that excessive Internet use is a significant problem . As a unWith regard to the many behaviors associated with the Internet, the question arises as to whether “Internet addiction” concerns a singular disorder, or whether the only commonality among various Internet-related behavior disorders is the use of the same medium . AccordAnother question relating to the independence of the disorder “Internet addiction” has been discussed for many years : Is “IntBehavioral addiction is a relatively new term for excessive behavior, which depicts characteristics of psychological dependence ,21. The The inclusion in Section III of DSM-5 outlines the importance of Internet-related addictions, emphasizing the need for further research in this area. Thus, further studies investigating the etiology and pathogenesis are necessary. Furthermore, it is crucial to identify variables and dispositions that determine the etiology of Internet addiction in order to develop effective therapeutic measures.In line with integrative explanations for substance use disorders, complex etiopathogenic models are also employed for Internet addiction. For instance, Wölfling et al  developeOn the basis of the discussed findings, the aim of this study was to investigate the relationship between attachment style, motives for use, used services, and Internet addiction. It was hypothesized that, in comparison with securely attached users, significantly more insecurely attached users would display an Internet addiction. Furthermore, it was assumed that users with an insecure attachment style would differ in their motives for use compared with users with a secure attachment style. It was also hypothesized that users with an Internet addiction would report different motives for use compared with users without an Internet addiction. Finally, it was assumed that users with an insecure attachment style would use Web-based services more often than users with a secure attachment style.A Web-based survey was carried out. The Web-based questionnaire was distributed both on Facebook and on 15 thematically different forums  to obtain the most heterogeneous sample possible. The survey period lasted for 6 weeks. For descriptive inferential data analysis and hypothesis testing, SPSS version 20  was used.To rule out methodological artifacts in the first quantitative self-assessment study, a second qualitative study was conducted. In light of the limitations given in any self-evaluation study, the prior aim of this methodological triangulation study was to gain data that for sure could not be influenced by intentional or unintentional bias. Therapists in Austrian clinics as well as the University Clinic of Mainz were contacted to recruit possible participants for the Rorschach study.Age, gender, relationship status, and the duration of the existing partnership, highest level of education as well as current job situation were assessed. Furthermore, information about duration and frequency of Internet usage was collected.completely disagree) to 4 (completely agree).The Bielefelder partnership expectations questionnaire was used to assess the attachment style of participants. This inventory consists of 31 items that are rated on a 5-point Likert scale ranging from 0  is satisfactory.The questionnaire evaluates the following five attachment styles: The Bielefeld questionnaire is different from others in two ways: (1) attachment style is operationalized as configurations of scale scores, which allow qualitative distinctions in terms of functioning and (2) five empirically identified attachment styles are distinguished. Nonetheless validation of the classifications with a German translation of the “Adult Attachment Scale (AAS)” yielded good results .normal (<7 points), problematic (>7 points and <13 points), and pathological (>13 points).The online addiction scale is a diagnostic tool consisting of 14 items about Internet addiction that are rated on a 5-point Likert scale with a maximum possible total score of 27 points. Cutoff values differentiate three different user types: never) to 3 (very often).In addition, the questionnaire assesses how frequently participants used the following 8 different Web-based services: Web-based games, shopping, chatting in forums, writing emails, Web-based sex services, Web-based gambling, Web-based communities, and information retrieval. The frequency of use is reported on a 4-point scale ranging from 0  to 4 (strongly disagree): anonymity, opportunity to meet new people, simple communication, curiosity, emotional support, social contact, escape from the real-world, finding love or a sexual partner.The Cyber Relationship Motive Scale is a self-evaluation of user’s relationship motives for going online. Survey respondents are prompted to rate how well each of the 27 possible items applied to their motives for Internet usage on a 5-point scale ranging from 0  had provoked numerous discussions about its reliability, validity, and utility, it has received a maybe more intensive level of scrutiny than any other personality test, summarized in a meta-analysis and reproved in an independent blue ribbon panel. Taken together, studies on reliability and validity of the RIM showed the same or even more valid results for the RIM as for other well-validated inventories ,37.During the survey period, the Web-based questionnaire was accessed N=1009 times. Around 39,74% (401/1009) of participants did not proceed past the start page, another 28.35% (286/1009) had dropped out by page 3. However, as only a further few participants dropped out at later stages of the survey, the dropout rate can be deemed acceptable .Overall, the questionnaire was completed 249 times, constituting 24.86% of total page views. After checking for plausibility of answers, 4 records were removed, resulting in a total sample of 245 participants  aged 16-61 years .At the time of the survey, 78.8% (193/245) were in a partnership, with an average relationship duration of mean 77.2 months (SD 101.21). Less than half (40.81%) of subjects (100/245) were employed full-time or part-time, one-quarter of the sample consisted of students , a further 5.71% (14/245) were also working in addition to studying, a small fraction of the total sample were unemployed , few participants  were self-employed, and 2.86% were trainees (7/245). In total, 30 subjects (12.2%) reported “other” in terms of employment.The Rorschach Inkblot Test was conducted with a small sample of 16 voluntary male subjects. Although 8 participants showed abusive Internet usage and 3 of them met the criteria for Internet addiction, a control group of 8 subjects with nonabusive Internet usage was recruited. Participants were aged between 18 and 47 years (mean 31 years). Subjects were primarily students, full-time employees, or self-employed.On average, study participants had used the Internet for over 10 years . The daily use of the Internet for private purpose amounted to an average of mean 4.35 h (SD 4.27), ranging from a minimum of 0.1 h up to 21 h a day. A majority of the sample  used the Internet daily, only 6.9% (17/245) went online 2-3 times per week. None of the subjects stated that they used the Internet once a week, once a month, or less.Subjects used the Internet mainly for online shopping . Other popular services included online research  and social platforms , emails , as well as chats and forums . In contrast, games , sexual content , and gambling  were less popular.Simple communication  and the opportunity to find new friends  were the dominant motives for Internet use. Emotional support , anonymity , and escapism  appear to be motives of medium importance. The lowest, sexual , and social-compensatory motives , were less frequently reported as online relationship motives.ambivalent-closed, ambivalent-clingy, and avoidant-closed), whereas almost as many subjects showed a secure attachment style . Therefore, secure and insecure attachment style was equally represented in the sample  of participants showed an insecure attachment style  of users showed normal Internet use.Only 1.2% of subjects (3/245) could be classified as addicted Internet users. To allow for appropriate statistical analysis, the categories “pathological” and “problematic use” were merged to the variable It was hypothesized that, in comparison with securely attached users, significantly more insecurely attached users would display an Internet addiction. Descriptive data revealed that the majority of participants with a tendency for Internet addiction (n=24) were categorized as insecurely attached, and only a few (n=6) were securely attached. An opposite trend can be detected when considering subjects without Internet addiction tendencies. More subjects categorized as securely attached (n=115) showed no tendencies for an Internet addiction than insecurely attached subjects (n=99).1=12.0, P=.003). Furthermore, differences regarding Internet addiction tendencies between the five attachment categories were significant . Most strikingly, an ambivalent attachment style was associated with Internet addiction. More than two-third (n=21) of all subjects, who showed Internet addiction tendencies (n=30), could be allocated to this category, although occupation of this category was generally rather low (n=52).A chi-square test was conducted. Unsurprisingly, it was found that insecurely attached subjects differ significantly from securely attached subjects in their tendency for Internet addiction  and emotional support . For subjects with an insecure attachment, the motives “emotional support” (mean 2.66) and “anonymity” (mean 2.36) were significantly more important than for subjects with secure attachment . To check for significant differences between the three attachment styles, post hoc single comparisons were performed. Bonferroni correction was used to adjust the significance threshold for multiple comparisons. There were significant differences between users with the attachment style ambivalent-closed and conditionally secure (P <.001) and secure (P=.02) with respect to the motives anonymity and emotional support. Ambivalent-closed participants showed significantly higher values in the motives anonymity (mean 2.84) and emotional support (mean 2.56) than conditionally secure  or secure users .A univariate test of between-subjects effects  was conducted to investigate the relationships between attachment style and motives for Internet use. A significant result was found for two motives, that is, anonymity , simplified communication , emotional support , social compensation , and escapism .It was checked whether people with Internet addiction tendencies differed significantly in their online relationship motives compared with normal Internet users. A comparison of means revealed significant differences in the online relationship motives For all motives, participants with Internet addiction tendencies had higher mean values see .A multivariate analysis of variance (MANOVA) was performed to examine the relationship between attachment style and Web-based services. Using the conservative Pillai trace, no significant main effect for the factor attachment style could be found. Thus, the hypothesis that the use of various Web-based services and apps is associated with different binding styles can be rejected.t32.219=−3.20, P=.002, d=0.84) and the use of chats and forums . The comparison of means showed that both services were more frequently used by subjects with Internet addiction tendencies  than by modest users .There were significant differences between groups with and without Internet addiction tendencies with regard to the use of Web-based sex services , whereas a higher level of accuracy of perception  occurred in the control group of patients who denied a tendency to pathological Internet use. Examination of the homogeneity of variance using Levene test proved the parameters of the percentage of intermediate figure responses (“S-responses”) that are seen as an indicator for the potential of aggression, as significant (P<.001). In the group of abusive patients, the minimum percentage of S-responses was at 0% and the maximum at 38.6%, whereas in the group of inconspicuous Internet users, the minimum was at 10.64% and the maximum was at 25%. Therefore, the group of abusive Internet users can be regarded not only as particularly aggression-inhibited, but also as aggressive patients. Of particular interest in this context is the common assumption that the online world can both dissipate and fuel aggression.The analysis of the Rorschach protocols gave the following results: patients who reported a tendency to pathological Internet use showed a significantly lower degree of sociability (as measured by H% [percentage of human figures], Although a growing body of scientific literature highlights that Internet addiction is a serious health problem, there have been no etiopathological studies to support this claim. Since an association between secure or insecure attachment and substance dependence is well-documented, the aim of this study was to examine whether people differ in their Internet addiction tendencies in regards to their attachment style.anonymity and social support were significantly more important than for secure and conditionally secure users. Furthermore, participants with Internet addiction tendencies usage identified anonymity, emotional support, escapism, and social compensation as important relationship motives for Internet use.The assumption that insecure attached people show higher Internet addiction tendencies could be confirmed. Ambivalent attachment styles were particularly associated with pathological Internet usage tendencies. For ambivalent-closed attached people, the motives However, attachment styles were not associated with the Web-based services used. Nonetheless, there was a difference in the use of Web-based services with regards to the Internet addiction tendencies. In particular, participants with Internet addiction tendencies engaged significantly more in Web-based chats and forums than normal users. Thus, the possibility of Web-based communication seems to play a prevalent role in the context of pathological Internet use.It appears therefore that, in comparison with Web-based services used, motivational factors relating to online relationships can best explain this finding. In contrast, the relationship between the Web-based services used and the tendency toward Internet addiction can be attributed to the individual addictive potential of the particular Web-based service in question.Overall, the findings of the Rorschach Inkblot Test are in line with the results of the Web-based survey, in which abusive Internet use presents itself as a function of insecure attachment and impaired interpersonal relationships, that is, the preference for chats and forums by study participants with tendencies toward Internet addiction as a result of an infantile relationship that has not reached the level of group compatibility. Chats and forums offer fictional contact with a group, while communication between users remains in virtual space, which in turn significantly weakens the experience of group presence. Thus, communication in chat-rooms or forums is within the framework of a group constellation, however, always experienced at the level of primary intersubjectivity, that is, within the relationship between I and You. Considering interpersonal skills as an expression of attachment capability , it is sThese results illustrate the escapist and social-compensatory function associated with pathological Internet usage. Although ambivalent-closed users demonstrate difficulties with acceptance and opening up to others, a parallel desire to connect with others also exists . The medThe satisfaction of these motives is in line with the needs relevant in the context of media usage postulated in Schramm and Hasebrink . Above aOverall, this study allows for important conclusions about the background of pathological Internet usage to be made. As a consequence, the presented findings are indicatory for future research regarding the etiopathology of Internet addiction.Methodological issues limit the validity of the research results. For example, the lack of participants classified as “addicted” marks a key problem of this study. Therefore, conclusions can only be drawn for problematic, subclinical Internet use. In light of the generally low prevalence of the disorder of only 3-5% , it is rIn all Web-based surveys, the sample composition constitutes another issue limiting the value of the found results . It may For the Rorschach test, it has to be taken into account that projective techniques are differing from structured tests in stimulus and response and therefore remain “problematic instruments from a psychometric standpoint” . In projA tendency to pathological Internet use was associated with an insecure attachment style and limited interpersonal relationships; it therefore seems plausible to take therapeutic measures to help patients address real-life deficits, that is, this can be achieved by a therapeutic relationship with the therapist as a “substitute attachment figure” , or in a


Studies that examined geographic variation in heart failure (HF) and its association with risk factors at county and state levels were limited. This study aimed to test a hypothesis that HF mortality is disproportionately distributed across the United States, and this variation is significantly associated with the county- and state-level prevalence of high blood pressure (HBP), diabetes, obesity and physical inactivity.Data from 1,723 counties in 51 states (including District of Columbia as a state) on the age-adjusted prevalence of obesity, physical inactivity, HBP and diabetes in 2010, and age-adjusted HF mortality in 2013–2015 are examined. Geographic variations in risk factors and HF mortality are analyzed using spatial autocorrelation analysis and mapped using Geographic Information System techniques. The associations between county-level HF mortality and risk factors (level 1) are examined using multilevel hierarchical regression models, taking into consideration of their variations accounted for by states (level 2).p < 0.0001), HBP , obesity , and physical inactivity  after controlling for gender, race/ethnicity, and poverty index. After further controlling obesity and physical inactivity in diabetes and HBP models, the effects of diabetes  and HBP  on HF mortality had a considerable reduction.There are significant variations in HF mortality, ranging from the lowest 11.7 (the state of Vermont) to highest 85.0 (Mississippi) per 100,000 population among the 51 states. Age-adjusted prevalence of obesity, physical inactivity, HBP, and diabetes are positively and significantly associated with HF mortality. Multilevel analysis indicates that county-level HF mortality rates remain significantly associated with diabetes (β = 2.7, 95% CI: 1.7–3.7, HF mortality disproportionately affects the counties and states across the nation. The geographic variations in HF morality are significantly explained by the variations in the prevalence of obesity, physical inactivity, diabetes, and HBP. Heart failure (HF), one of the major forms of cardiovascular diseases, is a complex clinical syndrome that results in the impairment of heart’s ability to fill or to pump out blood , 2. HF hTo address the geographic variations in risk factors and HF mortality, we applied spatial and ecological analyses approaches. The current knowledge suggests that one of the biological pathways by which behavior risk factors increase the risk of heart diseases may go through an increased risk for diabetes and HBP , 13–15. In the study, we collected data from 51 states (including the District of Columbia as a state) in the U.S. County-level sex-specific and age-adjusted HF mortality rates were collected from the U.S. CDC WONDER (Wide-ranging Online Data for Epidemiologic Research) . Data foCounty- and state-level age-adjusted HF mortality rates were estimated in residents aged 35 and older for the period 2013–2015 using direct standardization method. The U.S. 2000 standard population was used in the direct standardization . We incl2]. Physical inactivity is defined as a “no” response to the question, “During the past month, other than your regular job, did you participate in any physical activities or exercises such as running, calisthenics, golf, gardening, or walking for exercise?” (We focus on two groups of exposures: (1) Behavior-related factors, including county- and state-level age-adjusted prevalence of obesity and physical inactivity. Obesity is defined as body mass index [weight (kg)/height (m)*height (m) ≥ 30 kg/mercise?”  (2) Healercise?” . Howeverercise?” , 19. Thiercise?” .is) between BP (SBP and DBP) and predictors  using these measured variables in NHANES . We then applied the estimated β1–4 by using data from NHANES to estimate SBP and DBP using data from BFRSS.We first estimated the state-level prevalence of HBP as BRFSS has the most data for the measures of HBP at the state level, but it has no exact measures of systolic and diastolic blood pressure (SBP and DBP). If we estimated the prevalence of HBP using the data from BRFSS only, we would miss cases for those who did not know whether they had HBP due to without exact measures of SBP and DBP. To estimate SBP and DBP, we applied multi-stage regression analysis approach . We firsi) of state-level HBP (estimated from the above section) with state-level obesity, diabetes and physical inactivity using data from BRFSS , where XBR represents data from BRFSS. HBPBR-NHANES_S represents the estimated HBP from both BRFSS and NHANES (see the above section), XBR_SO, XBR_SDM, and XBR_SPIA represent the state-level prevalence of obesity, diabetes, and physical inactivity from BRFSS. The estimated regression coefficients of obesity (βBR_SO), diabetes (βBR_SDM), and physical inactivity (βBR_SPIA) were then applied to estimate county-level HBP using country-level obesity (XCDC_CO), diabetes (XCDC_CDM), and physical inactivity (XCDC_CPIA) represent data from CDC County Data system , where HBPES_C represents the estimated county-level prevalence of HBP.Behavior Risk Factor Surveillance System has personal health behavior and health condition data by states, but not by county. Therefore, we further estimated the county-level prevalence of HBP using the estimated state-level prevalence of HBP and using data on the prevalence of obesity, physical inactivity, and diabetes from the CDC County Data system. In the first step, we calculated the associations , and socioeconomic status (assessed by poverty rate in adults aged 18 and older), because these factors are the strongest confounders in the study of the associations between the predictors and outcomes of the study .I, and Geary’s C  are used to evaluate the spatial correlation. Moran’s I ranges from −1 to +1, where values between 0 and +1 indicate a positive association between variables, and values between 0 and −1 indicate a negative association and 0 indicates there is no correlation between variables. Geary’s C is always positive and usually ranges from 0 to (+2), where a positive autocorrelation is less than 1, and a negative autocorrelation is greater than 1. SAS procedure of variogram was used to test spatial autocorrelation  and tested the difference in the characteristics using analysis of variance for continuous variables, and chi-square test for categorical variables. Geographic variations in the study variables of interest were examined using spatial autocorrelation and mapped using the Geographic Information System technique  . The sparelation –25.In the second group analysis, we examined associations of age-adjusted HF mortality with age-adjusted prevalence of hypertension, diabetes, physical inactivity, and obesity using correlation analysis  .R2 to test the proportional reduction in residual variance between two nested models when adding additional predictors and covariates  on the age-adjusted HF mortality (level 1) with adjusting covariates  and considering the variations accounted for by states (level 2) using multilevel hierarchical linear regression analysis techniques –29. We evariates , 31.z-scores to use data with standardized normal distributions  to present a summary finding. In the study, we were unable to calculate county-level age-sex-adjusted mortality rates, because we had no individual-level data by age and sex. We used ArcGIS  and SAS  in mapping and statistical analyses. A two-sided Table Significant variations in age-adjusted HF mortality across the 51 states were observed in men and women . Of the 51 states, the top three states that had the highest HF mortality rates  were Mississippi (85.0), Alabama (84.7), and Louisiana (71.2), the three states that had the lowest HF mortality were Vermont (11.7), Arizona (13.0), and Washington (15.9), respectively. Figure I > 0, and Geary’s C > 0 and <1, which suggest that the variations in age-adjusted HF mortality, age-adjusted prevalence of obesity, physical inactivity, HBP, and diabetes by counties were positively and geographically clustered.Figure p < 0.0001). Of the four risk factors, HBP shows to have the strongest correlation with the risk of HF mortality. The correlation coefficients are 0.46  in both sexes, 0.51  in men, and 0.50  in women.Table Figure Figure p < 0.001), 3.80 , 1.20 , and 1.47  for diabetes, HBP, obesity, and physical inactivity, respectively. Model 3 shows that the effects of the four risk factors on HF mortality were attenuated after adjustment for demographic and socioeconomic variables . With a further adjustment for obesity and physical inactivity, Model 4 shows that the effects of diabetes on HF mortality become non-statistically significant (p = 0.121). The effect of HBP on HF mortality decreased as well , but it remains statistically significant (p = 0.003). It suggests that for an estimated every 1% increase in the prevalence of HBP, HF mortality increases by 2.41 units. The values of AIC  and Pseudo R2  suggest that the models with adjusting covariates have a better fitness of the regression between the risk factors and HF mortality than the other models  it is one of the first studies that maps the burden of HF mortality and examines the associations between four preventable risk factors and the risk of HF mortality across the counties and states of the U.S. It highlights that an estimate of 42.8% of the variations in HF mortality is accounted for by the differences across 50 states. (2) The study further highlights that the geographic disparity in HF mortality is significantly associated with the disproportionate distributions of the prevalent obesity, physical inactivity, diabetes and HBP across the counties and states. These associations are independent of gender, race/ethnicity and socioeconomic status (assessed by poverty rate). (3) After controlling for obesity and physical inactivity, the effects of diabetes and HBP on HF mortality are hugely attenuated, which further confirms the importance of changes in behavior risk factors in disease control.An increasing burden of HF has been reported by several studies, including our own reports , 33–36. In the multilevel hierarchal regression analysis, findings from Model 3 highlight the significant independent effects of each risk factor on the risk of HF mortality. In Model 4, the association between diabetes and HF mortality became non-significant after further adjusting for obesity and physical inactivity. Given a high correlation of obesity and physical inactivity with diabetes (data not shown), it is very likely that this non-significant result is largely explained by the adjustment for a possible pathway of these two factors for the risk of diabetes, then subsequently to the risk of HF. It should be noted that although this study does not necessary to interpret any cause inference relationship due to the nature of the ecological study design, the pathway of obesity and physical inactivity with the risk of diabetes and HBP, and diabetes and HBP as independent risk factors for cardiovascular diseases are well established . Given aThe mechanisms by which the behavioral-related and disease risk factors cause the development of HF and risk of HF mortality have been established at personal levels. For example, the associations of obesity and physical inactivity with an increased risk of HF may go through their effects on an increased risk for HBP and diabetes. However, at a population level, the geographic variations in HF mortality may indicate an even wider range of risk factors, including tobacco control and health-care support systems. Presently, we did not examine the associations between these factors and risk of HF mortality because of the lack of the relevant and valid data. Further studies are needed to confirm the current findings and extend the current work.There are several advantages of this study. First, to the best of our knowledge, the study using a spatial and ecological study design in HF mortality study at the county-level, has the largest sample size , and the key measures of the study variables of interest (exposures and outcomes) are defined and examined using standard approaches by the U.S. CDC. Second, the study addresses two important components of risk factors for HF mortality, one related to the health behaviors, and the other related to the common diseases controlled by the primary health-care settings. Third, we applied multilevel regression analysis technique, which addresses the variations accounted for by states and we can further precisely test the associations between county-level exposures and HF mortality withholding the hierarchical effect due to the variation accounted for by the states.It should be noticed that there are several limitations when interpreting the results of the study. First, potential ecologic bias may have occurred when we analyzed the data across the county- and state levels. The risk of HF mortality and the prevalent risk factors of interest at county- and state levels is not necessary to represent an individual risk of HF. In the study, we applied an ecologic analysis approach with aims to addressing geographic health disparity in HF mortality and its possible reduction or elimination by examining its associations with four most common and preventable risk factors across the county- and state levels. Meanwhile, we were unable to address race/ethnicity differences across the counties in the study, because most counties had a small proportion of minority populations, except for people living in the southern regions. Certainly, further studies are needed to focus on race/ethnicity disparities in HF. Second, several other risk factors for HF, such as cigarette smoking, dietary patterns, and health-care services indicators are not included because of the lack of age-specific and county-level data in detail. Therefore, findings from the study are subjected to represent the involved study factors of interest only. Like any other studies, the magnitudes of the associations between risk factors and outcomes of interest largely depend on what variables are included in multivariable and multilevel models. Therefore, findings of the study are not necessary to be generalized for a study that contains different study variables. However, a basic trend of these associations is expected in most studies. Last, but not least, age- and sex-adjusted rates were not available in the study because age-specific outcomes (HF) and risk factors  were reported in groups by sex and county  in the CDC WONDER and CDC County Data system. To keep the limitation in mind, we test and present our results by sex whenever it is possible. In our multilevel regression models, to examine and present the sex-combined analysis, we adjusted county-level male-to-female ratio and percent of African Americas in Models 3 and 4.Although several limitations may exist, the present analysis is one of the first large-scale studies across the counties that address the geographic health disparities in HF mortality and its associations with risk factors across the nation. Findings from the study emphasize that the four most common and preventable risk factors both related to health behaviors and the health-care system at county-level significantly predict age-adjusted mortality from HF. These geographic differences need to be paid specific attention in HF prevention and control.LL: did the study design, conducted data analysis, and drafted the manuscript. XY: participated in the study design, assisted in doing visualization and spatial analysis using GIS and SAS, and gave comments on the draft manuscript. MC, HJ, HE and AH: participated in the study design and gave comments on the draft 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.


Background: Adult height, weight, and adiposity measures have been suggested by some studies to be predictors of depression, cognitive impairment, and dementia. However, the presence of confounding factors and the lack of a thorough neuropsychological evaluation in many of these studies have precluded a definitive conclusion about the influence of anthropometric measures in cognition and depression. In this study we aimed to assess the value of height, weight, and abdominal perimeter to predict cognitive impairment and depressive symptoms in aged individuals.Methods and Findings: Cross-sectional study performed between 2010 and 2012 in the Portuguese general community. A total of 1050 participants were included in the study and randomly selected from local area health authority registries. The cohort was representative of the general Portuguese population with respect to age (above 50 years of age) and gender. Cognitive function was assessed using a battery of tests grouped in two dimensions: general executive function and memory. Two-step hierarchical multiple linear regression models were conducted to determine the predictive value of anthropometric measures in cognitive performance and mood before and after correction for possible confounding factors . We found single associations of weight, height, body mass index, abdominal perimeter, and age with executive function, memory and depressive symptoms. However, when included in a predictive model adjusted for gender, age, school years, and lifestyle factors only height prevailed as a significant predictor of general executive function  and memory . No relation was found between mood and any of the anthropometric measures studied.Conclusions and Relevance: Height is an independent predictor of cognitive function in late-life and its effects on the general and executive function and memory are independent of age, weight, education level, gender, and lifestyle factors. Altogether, our data suggests that modulators of adult height during childhood may irreversibly contribute to cognitive function in adult life and that height should be used in models to predict cognitive performance. Cognitive impairment and depressive symptoms have a significant impact on the quality of life of the elderly  were shown to be associated with cognitive impairment  and depressive symptoms in adult life. This analysis was controlled for factors previously shown to influence cognition and mood such as age, gender, alcohol consumption, physical activity, and smoking  and was approved by the national ethical committee  and by the local ethics review boards . The study goals and the neurocognitive/psychological and clinical assessments were explained to all participants, who all gave informed consent.n = 560; 53.3%) and age . All the participants were community-dwellers. The majority of them was retired  and located in the medium socio-economic stratum in the Graffar scale . The percentage of the cohort that attended school for [1–2], [3–4], [5–8], [9–12], and ≥13 years was 9.8, 61.0, 6.9, 7.5, and 1.5%, respectively. On socio-demographic measures, Portugal ranks close to the OECD  average. These data are detailed in Table The cohort was composed by 1051 participants randomly selected from two cities in the north of Portugal (Guimarγes and Vizela) using the local area health authority registries as described elsewhere , height (m), and abdominal perimeter (cm). For lifestyle, alcohol consumption , physical activity status , and smoking habits  were considered. Alcohol consumption was calculated and recorded as total grams/day, taking as reference the estimations of grams of alcohol per glass for each consumed beverage. Physical activity included any planned activities  that comprised a continuous 30 min effort  above the everyday living activities such as the case of regular short walk to the grocery store. Activity quantity rather than intensity was considered due to the mixed clinical profiles and age range of the study population. Alcohol consumption and smoking habits consumption were self-reported by the participants during the clinical interview, and were referent to the current habits.z scores to express all variables in the same scale and then grouped in two different categories: general and executive function (GENEXEC) and memory (MEM) based on a factorial analysis as described elsewhere  or were unable/unwilling to complete the test (n = 7) were excluded from further analysis. The Geriatric Depression Scale  was used to assess depressive mood, which was considered a single dimension.Tests were selected to provide cognitive profiles . A team of trained psychologists conducted the neurocognitive/ psychological evaluations as described elsewhere  are also presented. All the statistical analyses were conducted using the software SPSS 22.0 .Pearson correlations were calculated to measure the strength of the association between the studied quantitative variables. Afterwards, a Multiple Linear Regression Model (MLRM) was performed for each of the composite scores previously calculated  using two blocks of variables as predictors. In block 1 we aimed to understand the value of height, weight, and abdominal perimeter to predict cognition and depression and therefore, these parameters were included in the model together with gender and age. In the second block possible confounding variables previously shown to be involved in cognition such as school years, smoking status, alcohol consumption, and physical activity, were added to the model. Besides regression coefficients , betas and measures of model fit  and MEM  and, negatively correlated with GDS . This means that superior height values are associated with better executive performance, better memory, and less depressive symptoms. Weight was also significantly and positively correlated with GENEXEC  and negatively correlated with GDS  meaning that higher weight scores are associated with higher executive performance and better mood. Both BMI and abdominal perimeter were significantly and negatively correlated with GENEXEC  and MEM  and positively correlated with GDS  meaning that higher adiposity, estimated by abdominal perimeter and BMI, is associated with lower performance on both cognitive dimensions and more depressive symptoms. Abdominal perimeter showed a strong positive correlation with weight and BMI and a less significant, but yet positive, correlation with height meaning that abdominal perimeter is higher in heavier and taller individuals. Older age was associated with worst performance in both cognitive dimensions  and was not associated with depressive symptoms. Elder individuals also displayed higher abdominal perimeter  and shorter stature .Table Two-step hierarchical multiple linear regression models were conducted to determine the predictive value of anthropometric measures in cognitive performance and mood (depressive symptoms) before and after correction for possible confounding factors .F = 30.67; p < 0.001], 25.9% of the variance of GENEXEC , and 17.1% of the variance of MEM . Concerning GDS, only gender was significantly correlated with depressive symptoms, which were more prevalent in women . Age, height, weight, and abdominal perimeters lost significance in predicting GDS when used in this model. For cognitive function, age and height were significant predictors of both GENEXEC and MEM. Specifically, older age was associated with a worst performance in both general and executive function  and memory . Higher height was associated with a better performance in both general executive function  and memory . Abdominal perimeter was negatively associated with general executive function . Interestingly, weight lost significance when used in this model.Table F = 18.51; R2 = 0.186; ΔR2 = 0.051; p < 0.001], 43.8% of the variance of GENEXEC , and 27.1% of the variance of MEM . Males , higher education , alcohol consumption , and physical activity more than 3 times a week  were significantly associated with a lower score in GDS. Younger age , higher height , higher education , former smoking , moderate alcohol consumption , and physical activity <3 times a week  were associated with a better performance in the composite score for general executive function. Female gender , younger age , higher height , higher education  moderate alcohol consumption , and physical activity <3 times  were positively associated with a better performance on memory tests. Adding lifestyle variables into the model showed that height is not a predictor of mood but is a significant predictor of general executive function and memory.In the second block Figure  variableIn this study, we investigated whether height and other anthropometric measures are predictors of cognitive function and mood in community-dwellers older than 50-years. Our results showed that adult body height is a good predictor of cognitive performance independently of gender, age, weight, abdominal perimeter, smoking status, alcohol consumption, and physical activity.Compared with other studies reporting similar findings  and worst cognitive performance, others failed to demonstrate this association , were all associated with less depressive symptoms. The “protective effect” of alcohol consumption is remarkable and had already been found in different cohorts  “SwitchBox” (Contract HEALTH-F2-2010-259772) project and co-financed by the Portuguese North Regional Operational Program (ON.2—O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER), and by Fundação Calouste Gulbenkian—Inovar em Saúde . NCS is supported by a SwitchBox post-doctoral fellowship.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 the subsequent resting periods, HF means showed increases over time in the RHS , but not in PHS nurses. LF means did not show any substantial increases in the resting periods, in the PHS group with geometric means lower when compared to SLS, in the non-working and resting periods. Our study evidences that both prolonged and recent perceived high work stress were associated with a reduction of HF and LF powers during work. In addition, prolonged stress was associated with a lack of recovery during not-working and resting periods. The deregulation of the autonomic nervous system assessed through the heart rate variability (HRV) analysis is a promising pathway linking work stress and cardiovascular diseases. We aim to investigate the associations between HRV High Frequency (HF) and Low Frequency (LF) powers and work stress in a sample of 36 healthy nurses. Perceived work stress was assessed twice one year apart, using the Job Content and Effort Reward Imbalance questionnaires. This allows to classify nurses in three exposure groups: “prolonged high stress” (PHS), “recent high stress” (RHS) and “stable low stress” (SLS). A 24-h ECG monitoring was later performed during a working day (WD) and a subsequent resting day (RD). Statistically significantly lower ( Psychological work stress has been associated with the development of coronary heart disease ,2,3. TwoHRV variations characterise the early effects on the heart of the imbalance between the sympathetic and the vagal systems . HRV modPerceived work stress has repeatedly been shown to be associated with the incidence of coronary heart disease, when characterised either by the demand-control ,16,17 orSeveral studies have investigated the association between work stress and the decrease of the time domain HRV parameters in apparently healthy employees ,25,26,27The studies that have explored the association between work stress and the frequency domain (FD) HRV parameters report contradictory results ,30,31,32A sample of nurses and nurse assistants, employed full-time (36 h per week) since at least one year in a Northern Italian university hospital, were invited to participate in a survey on working conditions and work stress, as elsewhere further described . The surThe perceived work stress conditions were assessed using both the Job Content Questionnaire (JCQ) ,27 and tBased on available clinical records, some subjects were excluded for ECG monitoring due to being affected by conditions altering the autonomic nervous system (ANS), like established diagnoses of cardiovascular diseases, hypertension, neurological disorders, diabetes and other metabolic diseases or endocrinal disorders, pregnancy and lactation. Similarly, we excluded subjects taking drugs with effects on the ANS, like antihypertensive, antiarrhythmic, neuroleptic, antidepressant medications. The flow-chart in All enrolled subjects underwent a twenty-four-hour ECG monitoring, repeated twice in a working day (WD) and a subsequent resting day (RD), within 1 month following the second survey. Working time covers the periods from 7 a.m. to 2 p.m. or from 2 p.m. to 9 p.m.2). The LF and HF ratio was also computed.The ECG monitoring was carried out at least 72 h apart from a night shift to reduce the effect of sleep deprivation. Holter ECG recording was applied in the morning, between 7:00 and 8:00 a.m. and it was removed the following morning. All subjects were instructed to fill in a diary, indicating the starting and the ending times of each relevant activity  occurred during the ECG recordings. ECG Holter monitoring placement was performed by professional nurses, on workers in a semi-upright sitting position. Twelve channels were used in order to better detect rate and location of any abnormal repolarization . ECG segFor each subject, we registered 24-h ECG recordings for each day (WD and RD) . For WD,We summarized major demographic, clinical and psychological characteristics in the three work stress exposure categories  using either mean and standard deviation, or frequencies, for quantitative and qualitative variables, respectively. Differences across groups were tested through the ANOVA for quantitative variables and the chi-square test for qualitative variables. To reduce the influence of extreme values, HRV parameters were log-transformed , and we report the geometric mean. As in previous analyses , we inclWe estimated the age- and smoking status-adjusted geometric means for the HRV frequency domain parameters across the SLS, RHS and PHS groups from ANCOVA linear regression models, for registrations in the working day  and in the subsequent resting day (morning and night). We tested the differences across groups using a 2-df Wald chi-square test, while pairwise comparisons between groups were tested adjusting for multiplicity with the Tukey-Kramer method. Finally, we estimated within each exposure group, changes in HF and LF parameters using repeated-measures regression models, adjusted for age and smoking status, across a conceptual recovery time scale ranked from working periods of WDs, to non-working periods of a WDs and then to subsequent mornings of RDs. Separate beta-coefficients over time were estimated and the null hypothesis of no change (beta = 0) was tested using a Wald chi-square test. A two-sided α equal to 0.05 was the level of significance for all statistical tests. Statistical analyses were performed with SAS Version. 9.4 , while the figure was drawn using R .n = 26, 72.2%) and nurse assistants  who gave their written consent to participate, of which 19, 7 and 10 in the SLS, RHS and PHS groups, respectively , with a higher prevalence in the PHS group. Even if the mean age was not statistically different among the groups, the SLS groups was younger by three and almost four years in comparison to the RHS and PHS, respectively.Eligible and recruited nurses did not show statistically significant differences in major demographic and clinical characteristics (data not shown). Eligible and enrolled nurses were characterized by a high proportion of women (above 80%), to be mostly professional nurses (more than 70%) and with a mean age around 39 years and an average job tenure of about 11 years. As reported in p = 0.08). In the remaining analyzed periods of the WD , as well as in the two periods of the RD, there were no statistically significant differences in HF, although the lowest values were consistently observed among the PHS category.p-value = 0.02) and in NWP , as well as in the subsequent resting morning . In particular, the geometric mean values were constantly halved in the PHS as compared to the SLS groups . Conversely, sleeping LF did not show alterations across stress groups, neither during the working nor in the resting days. Finally, we did not observe any difference in the LF/HF ratio across groups. This finding is consistent with the observed consensual changes of LF and HF values. Statistically significant differences were observed among work stress groups for LF values in the working day, in WP (p = 0.06) almost half of to one observed in the RHS. Such trends indicate that HF reduces during the working time in stressed nurses, but while the RHS group shows a clear tendency to increase back HF variability starting from the non-working period and continuing in the following rest day morning, this trend is attenuated for nurses in the PHS group, indicating that recovery is reduced.p = 0.08), but the small sample size should be take into account (n = 7). In comparison with the trends registered for HF, LF shows an absent recovery in the PHS group and a similar tendency to recover for the RHS subjects. Finally, the LF/HF ratio decreased over time in all the three stress categories  and in the PHS group  is associated with consistent reductions of both HF and LF powers. Moreover, under persistent stressful working conditions, recovery to higher HF and LF values during not-working and resting periods is reduced or even absent. These alterations of the two major HRV power components under prolonged work stress conditions are in accordance with a recent review of autonomic cardiovascular regulation studies indicating that HF and LF are both determined by the parasympathetic system.