Background and objective: The increased participation in endurance sports such as marathon running has attracted scientific interest especially with regard to adult athletes. However, few studies have examined the impact of a marathon race on children and adolescents. Therefore, the aim of the present case study was two-fold: first, to describe pacing during a marathon race, and second, to examine acute responses of blood physiology and biochemistry parameters during the race  as well as five consecutive days after the race. Materials and Methods: Participant was a 15-year-old boy who completed a self-paced marathon attempt for the first time and finished in 5 h 19 m 53 s. Positive pacing  with a final end spurt was observed. Results: An increase in fluid intake across race was shown. Exercise-associated hyponatremia  was found post-race. C-reactive protein (CRP) did not correlate either with creatine kinase (CK)  or with lactate dehydrogenase (LDH) ; however, leukocytes correlated very largely with LDH  but not with CK . CK and LDH related almost perfectly with creatinine ; also, creatinine clearance correlated very largely with CK  but not with LDH . Leukocytes, aspartate aminotransferase, LDH, and CK deviated from physiological range post-race, but returned to normal values during the five-day recovery period. Conclusions: In summary, a male teenager at the age of 15 years was able to run a marathon in under 6 h without significant harmful effects on health. He developed mild and asymptomatic EAH and an increase in leucocytes, CRP, CK, and LDH as markers of inflammation and skeletal muscle damage. EAH after the marathon was resolved within one day of recovery. Marathon running has predominantly been a domain of elite runners ; howeverSeveral studies have demonstrated that marathon running below the official age of 18 years seems not to be harmful in terms of health ,11. Howewww.vikmotion.ch/wp-content/uploads/2016/06/VikMotion_Trainingsplan_Mara- thon.pdf). The marathon course was a long loop from Bad Ragaz to Buchs and back along the Rhine River, which forms the border between Switzerland and Austria in the eastern part of Switzerland.This case study was approved by the Institutional Review Board of EKOS (Ethikkommission Ostschweiz), Switzerland (EKOS 19/178). The runner and his parents provided their informed written consent for the case study. Our athlete is a 15-year-old boy  born 19 July 2003. On 10 November 2018, he performed a self-paced marathon attempt at the age of 15 years, 3 months, and 22 days. The athlete prepared for this event using the recommendations of his parents, his grandparents, and his teacher regarding training and equipment. No specific recommendations were followed regarding food and fluid intake before, during, and after the event. He trained for his attempt by using the recommendations of a former elite Swiss marathoner , the runner faced a tailwind; in the second half , he faced a strong headwind. The temperature rose from 12.5 °C at the start to 19 °C by the end of the run. During the run, the support crew provided food  and fluid  and recorded all details. In the first half of the run , two people acted as supporters. In the second half of the run , two additional people followed the athlete. The runner received liquid  and food  not according to a fixed scheme but according to his needs. Fluid intake was measured in deciliters; calorie intake was estimated using the consumer information on the product description. Sodium intake from the energy gels was 1010 mg and 195 mg from the energy bar. The athlete showed no signs of dehydration and/or hyponatremia.www.risch.ch). Creatinine clearance was estimated using the Cockcroft and Gault formula [During the run, the heart rate of the athlete was continuously measured using POLAR M400 . After each kilometer, the heart rate of the athlete was recorded. The day before, after the run, and then for five days during the recovery, venous blood samples were drawn for hematological analysis, including erythrocytes, hemoglobin, hematocrit, thrombocytes, mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), and leucocytes. Biochemical analyses were also conducted with regard to C-reactive protein (CRP), creatine kinase (CK), lactate dehydrogenase (LDH), glutamate pyruvate transaminase (GPT), aspartate aminotransferase (GOT), gamma-glutamyl transferase (γ-GT), creatinine, and sodium. All samples were drawn by a professional nurse and transferred for analyses to a professional laboratory of Labormedizinisches Zentrum Dr. Risch ( formula .2). The distance was divided into six 7 km splits, i.e., 1–7 km, 8–14 km, 15–21 km, 22–28 km, 29–35 km, and 36–42 km. For the purpose of this analysis, a split refers to distance interval rather than to a specific distance point. A repeated measures analysis of variance examined differences in speed and HR among splits. Confidence intervals (CI) of 95% were calculated for mean differences among splits. The magnitude of differences was estimated using an eta-square classified as small (0.010 < η2 ≤ 0.059), medium (0.059 < η2 ≤ 0.138), and large (η2 > 0.138). The abovementioned statistics should be considered with caution in terms of the interpretation of the findings, keeping in mind the general nature of the study .The variation of speed and heart rate (HR) by kilometer and split was examined using a linear or a fourth-degree polynomial regression analysis, depending on which one polynomial provided the best fit according to F test; the relationship between these variables was estimated by coefficient of determination , where the last split was slower than the first by 2.2 km/h . No main effect of the 7 km split on HR was shown . Speed  and HR correlated perfectly or very largely  with distance (7 km splits).As shown in p = 0.302) or with LDH ; however, leukocytes correlated very largely with LDH  but not with CK . CK and LDH related almost perfectly with creatinine ; also, creatinine clearance correlated very largely with CK  but not with LDH .The indices of blood physiology during the race and recovery are presented in It might be assumed that running a marathon at this age could be a health risk. However, several studies have found that running a marathon under the official age of 18 years poses no significant health risks ,11. DuriThe runner showed a positive pacing with a final end spurt. A decrease in running speed with a final end spurt is very common in marathon running. During the 2015 New York City Marathon, in 20,283 women and 28,282 men competed, women and men of all age groups exhibited a reduced running speed over the course of the marathon with a final spurt in the last segment . HoweverThe runner developed mild and asymptomatic EAH after the run with a plasma sodium concentration of 134 mmol/L. EAH is the most commonly reported electrolyte disorder associated with endurance performance ,16,17,18As time passed during the run, the athlete consumed more fluids but not more calories. Overall fluid intake during the run was 1.8 L. Fluid intake has been shown to be related to post-race plasma sodium levels. In marathoners competing in the 2006 Zürich Marathon, fluid intake correlated significantly and negatively with a change in plasma sodium between the start and finish of the race . It has After the run, we found elevated values for leukocytes, GOT, LDH, CK, and CRP. By the end of the five-day recovery period, all values turned into reference range. This confirms recent findings in a 17-year-old female teenager in a self-paced marathon attempt . An incrOne limitation of this case report was the inability to measure body mass and urinary parameters  to quantify hydration status and signs of dehydration. Weight loss and changes in hydration status might have had an effect on the biomarkers.In summary, in our study, a male teenager at the age of 15 years was able to run a marathon in under 6 h without significant harmful effects on health. He developed mild and asymptomatic EAH and an increase in leucocytes, CRP, CK, and LDH as markers of inflammation and skeletal muscle damage. After the marathon, EAH was resolved within one day of recovery. Given the lack of existing research and in light of the increased popularity of marathon running, this finding will be of practical value with regard to the acute physiological responses to a marathon race in adolescents. For instance, this case study can be used as an example in clinical practice when practitioners are questioned by the parents of young endurance runners about the safety of participating in a marathon race.


We assumed that perimenopausal women’s sense of quality of health (SQH) is a subjective evaluation of their psycho-physical health, and comprises three dimensions: sense of quality of life, menopausal symptoms, and the level of positive and negative affect.The aim of the study was to: 1) test a model about SQH, and 2) explore the role of personality traits, self-esteem, body self, and self-stereotype as predictors of SQH.The sample included 201 women aged between 45 and 55 (50.11±3.07). Participants filled out the Rosenberg Self-Esteem Scale, the Personality Inventory based on the Big Five Factor Model, the Body Self Questionnaire, and a survey querying perimenopausal women’s self-stereotype. To determine the individual SQH dimensions we used the Sense of Quality of Life Questionnaire, the Menopause Symptom List, and the Positive and Negative Affect Schedule. To verify the assumptions of the SQH model and look for SQH predictors we conducted a neural networks analysis with structure optimization via genetic algorithms .2 = 0.723, F = 133,232, p < 0.01). Moreover, we confirmed that SQH comprised three dimensions: quality of life, menopausal symptoms, and affect. SQH and menopausal symptoms were correlated. Similarly, positive and negative affect modified the women’s global sense of quality of life. SQH predictors included: personality traits, self-esteem, the body-self, and menopausal woman’s self-stereotype.The SQH model was verified in the course of several neural networks analyses with structure optimization via genetic algorithms (R = 0.849, RIn practical terms, our findings may help raise awareness among women and medical practitioners, calling for a holistic approach to the health of menopausal women. Our findings may also facilitate the creation of both prevention and therapeutic programs for women transitioning through menopause, for example, cognitive-behavioral therapy. Perimenopause is a neuroendocrine stage of woman’s life marked by changes affecting the somatic and psychosocial spheres of functioning, during which women confront social expectations about their health and vitality ,2.Menopausal women’s health has so far been analyzed in the context of experienced symptoms and occurring diseases ,4, womenWomen’s well-being depends on numerous factors, including experienced stress, bodily and physical changes, experienced affect, thoughts, beliefs, behavioral strategies, and social and cultural conditions ,6,14–23.Research confirms that menopausal experience is determined not only by biological factors (in particular those related to estrogen levels in the blood), but also social and cultural ones, including attitudes toward menopause held by society and the menopausal women themselves ,9,22–23.There are two models that emphasize the non-biological aspect of experiencing the menopausal period.The first, cognitive behavioral model of menopausal hot flushes proposed by Hunter and Rendall, is focused on the relationships between the experienced hot flushes and decreased levels of mood and self-esteem, which imply a negative perception of menopausal symptoms (stronger and more frequent flushes) ,14,16. TThe second model, by Veeninga and Kraaimaat, is multifactorial and refers to the development of bodily experiences and mood states during the climacteric, suggesting that the experience of menopause depends on the very process of perceiving and assessing menopausal symptoms . The proDespite the multiple research focused on the determinants of perimenopausal women’s health, there is a paucity of data on the predictors of the factors determining the sense of quality of health (SQH) in women around menopause.Going beyond the assumptions of the biomedical model, we posited that SQH is a cognitive-affective subjective evaluation of psycho-physical health, comprising three dimensions: sense of quality of life , comfort with closeness with others, and body protection, issues pertaining to the development, structure and way of defining the body self, as well as its importance for human personality, can be defined using Krueger’s description –40.Self-stereotype can be defined as the simplified and evaluative image of reality that functions in the popular awareness of perimenopausal women –44. It pIn sum, we propose that the sense of the quality of health should not be limited to the symptoms of menopause but also include the sense of quality of life and positive and negative affect .Thus, the aims of the study were as follows:To verify whether SQH comprises three dimensions: sense of the quality of life, symptoms of menopause, and positive and negative affect;To identify the predictors of SQH among: personality traits, self-esteem, body self, and self-stereotype.We decided to verify the following hypotheses:H1: SQH comprises three dimensions: sense of the quality of life, frequency and intensity of menopausal symptoms, and positive and negative affect.H2: Higher level of the sense of quality of life  is associated with higher levels of extraversion, openness, agreeableness, conscientiousness, and self-esteem, lower levels of neuroticism and a lesser dysfunction of the body-self (lower score), and a positive self-stereotype of the menopausal woman.H3: Less frequent and less intense psychological, vasomotor and somatic symptoms of menopause are associated with higher levels of extraversion, openness, agreeableness, conscientiousness, and self-esteem, lower levels of neuroticism and a lesser dysfunction of the body-self (lower score), and a positive self-stereotype of the menopausal woman.H4: Higher positive affect is associated with higher levels of extraversion, openness, agreeableness, conscientiousness, and self-esteem, lower levels of neuroticism and a lesser dysfunction of the body-self (lower score), and a positive self-stereotype of the menopausal woman.H5: Higher negative affect is associated with lower levels of extraversion, openness, agreeableness, conscientiousness, and self-esteem, higher levels of neuroticism and a greater dysfunction of the body-self (lower score), and a negative self-stereotype of the menopausal womanParticipants were 201 married women aged 45–55 with a university degree in pedagogy, working as teachers in several schools in Wrocław, Poland. The main criterion for choosing this group was participants’ availability. Women using hormonal replacement therapy and those who underwent ovariectomy/hysterectomy leading to artificial menopause were excluded from the study. This information was obtained based on a survey attached to the questionnaires  .Inclusion criteria: regularity and duration of the menstrual cycle, as well as the time and cause why menstruation ceased.Exclusion criteria: women using hormonal replacement therapy and those whose medical treatment led to artificial menopause were excluded from the study.This research project received approval of the Research Ethics Committee at the Psychology Institute, University of Wrocław. Participants were informed about the voluntary participation, the anonymous character of study (data was collected in a way that made it impossible to associate questionnaire answers with a specific participant), the aim and scope of the study, as well as the possibility of withdrawing at any stage. Before the questionnaires were distributed, we made sure that each participant was aware of what areas were covered by their consent to the study and understood the scope of information to be obtained and the intended use of the data to be collected. To minimize the negative impact the study could have on participant’s mental state, we offered the women psychological consultation after the completion of the study. Oral consent to the study was obtained from 201 participants.We administered six questionnaires and two surveys: self-stereotype and a survey determining participants’ menopausal status and the time and cause why menstruation ceased. Participants filled them out in any given order.1.1. Measurement of sense of quality of lifeWe used the Sense of Quality of Life Questionnaire in the Polish adaptation by Straś-Romanowska, Oleszkowicz, and Frąckowiak to measure participants’ level of this variable, a choice we made for two reasons –28. Firsα = 0.70; for the psycho-physical sphere–α = 0.77; for the psychosocial sphere–α = 0.71; for the subjective sphere–α = 0.72; and for the metaphysical sphere–α = 0.65. The higher the score, the higher the sense of quality of life –not even once in the past 3 months; Rarely (1)–once or twice in the past 3 months; Sometimes (2)–up to 4 times in the past 3 months; Often (3)–between 5 and 10 times; Very often (4)–more than 10 times in the past 3 months; Almost always (5)–almost every day in the past 3 months. In turn, the following 6-point scale is used to rate symptom intensity: (0)–the sensation did not occur; Slight (1)–a barely noticeable change or sensation; Low (2)–a small change, a weak sensation; Moderate (3)–a noticeable change / sensation; High (4)–a clearly noticeable change and an intense sensation; Very high (5)–a radical change and an extremely intense sensation. The raw scores are converted into sten scores.Participants rate each of the symptoms on a 6-point scale, taking account of the frequency and intensity with which the symptom has occurred in the past three months. When rating symptom frequency, participants use the following scale: p < 0.01 or p < 0.05, was determined based on correlations with the results of Green’s Climacteric Symptom Rating Scale. The higher the score, the higher the frequency and intensity of menopausal symptoms. Reliability of the Polish questionnaire was calculated using the test-retest method and by comparing parts of the test (Spearman-Brown coefficient). Cronbach’s alphas for the 3 subscales fell into the range between 0.70 and 0.87. In turn, correlation coefficients for test-retest ranged between 0.69 and 0.90, and were statistically significant (p < 0.01). High Cronbach’s alphas suggest satisfactory internal consistency of the instrument’s subscales, its high reliability additionally demonstrated by the Spearman-Brown coefficient   [slight or none) to 5 (very strong). The raw scores were then converted into sten scores. The instrument’s reliability  ranged between 0.73 and 0.95, depending on the version and type of sample. The higher the score, the higher the positive and negative affect (see To assess participants’ levels of positive (PA) and negative affect (NA), we used Watson and Clark’s (1988) Positive and Negative Affect Schedule (PANAS) in its Polish adaptation by Brzozowski  . In this2.1. Measurement of personality traitsStrongly disagree, and E for Strongly agree. To obtain raw scores, the scores for particular factors are summed and converted into sten scores. The instrument’s studies yielded a high degree of internal consistency for each of the five scales, ranging between α = 0.81 and 0.86. Factorial validity was also assessed, confirming that the subscales’ factor structure confirmed theoretical expectations, although some deviations from these assumptions were also found. The higher the score, the higher the level of each individual personality trait.To assess participants’ personality traits, we used Costa and McCrae’s NEO Personality Inventory (NEO PI-R) in the Polish adaptation by Siuta . The too2.2. Measurement of self-esteemStrongly agree) to 4 (Strongly disagree). The result is the sum of points representing global self-esteem level. The raw scores are converted into sten scores. The scale’s reliability ranged between α = 0.81 and 0.83 for different age groups. The higher the score, the higher the participant’s self-esteem.Participants’ self-esteem levels were determined using the Rosenberg Self-Esteem Scale (RSES) in the Polish adaptation by Lachowicz-Tabaczek, Dzwonkowska, and Łaguna . Designe2.3. Measurement of the body selfIntegrating body self and psychological self. Creating a new story in psychoanalysis and psychotherapy [Never; 2 –Very rarely (once or twice in a lifetime); 3 –Sometimes; 4 –Quite often; and 5 –Very often. The measure of the above mentioned scales is the sum of scores obtained on a given scale, which are then averaged so that the participant’s score falls within the range <1,5> [To measure the body self, we used the Body Self Questionnaire developed by Sakson-Obada . Createdotherapy , which oge <1,5> . The higα = 0.62 and 0.89  that participants presented in connection to the onset of menopause in their lives;stage versus non-stage in their personal development; andsecond, we took account of whether participants perceived menopause as a third, we identified the traits that participants attributed to the menopausal woman.This permitted us to distinguish two types of the self-stereotype presented by menopausal women: positive self-stereotype, demonstrated by 44 women (22% of the sample), and negative self-stereotype, shown by 157 women (78% of the sample).The study type was cross-sectional. The recruitment process was as follows. First, we looked for participants in schools, subsequently visiting the schools and asking the women to take part in the study. We also made an attempt to recruit nurses in local hospitals. Unfortunately, an insufficient number of only 12 women agreed to participate, although the questionnaires they filled out proved a useful resource for further analyses. Having consented to the study, the school teachers were informed about the anonymous character of the study and their being allowed to withdraw at any time.Participation was voluntary, anonymous and individual, and the women were informed about being able to drop out at any time. The study took place between May 2011 and July 2013 in Wrocław. The study was carried out individually. Participants were instructed on how to fill out the questionnaire, which they did individually at school or at home. We held an information meeting in a school for teachers, where we described the study in detail, as well as explaining the scope of data we needed to acquire, how the data would be stored, and how we would protect the data against unauthorized access. The average questionnaire completion time was two hours. The questionnaires were filled out in any order. Participants were given a week’s time to fill out the questionnaires. Once a week, on days previously agreed on with the respondents, we visited the schools and collected the completed questionnaires. Of the 211 teachers we talked to, 210 expressed a wish to participate in the study. Eventually, we collected valid questionnaires from 201 women, as 9 of the teachers dropped out in the process. They only filled out the questionnaires on menopausal symptoms and quality of life, making their documents unsuitable for analysis on account of providing insufficient data.Statistica 10 software and performed a structural analysis by using neural networks with structure optimization via genetic algorithms (GAS) [training algorithm, which then leads to the necessary data structure being automatically created in the network’s memory. The network relies on that data structure to utilize the newly-created model.We used ms (GAS) . Using tms (GAS) . Neural Importantly, using artificial neuro-fuzzy networks permits model optimization in order to turn imprecise and uncertain data into sharp and consistent output data .An additional advantage of using neural networks over other statistical methods is that they allow for reducing statistical problems related to non-linearity when analyzing multiple variables (as was the case in this study). It is also worth emphasizing that when numerous variables are involved, relying on path analysis may generate erroneous and overly complicated models.Neural networks may be used when there exists an actual relationship between dependent and independent variables, one that is non-expressible via correlations or inter-group differences. A good example of statistical analyses based on neural networks were those used to create the structure of 120 psychopathological symptoms of the twelve DSM-IV diagnostic categories. It has been concluded that complicated network models better demonstrate the complex phenomenon of psychopathological symptoms than do traditional methods of statistical analysis . AnotherFuzzy sets were used in the inference block and each trait was initially subject to fuzzification by use of three triangular membership functions.New basic distribution was obtained for variables following the optimization via genetic algorithms of the shape and distribution of function of membership to fuzzy sets . Apart fFirst, we divided the set of 201 data into three sets (A (N = 67), B (N = 67), C (N = 66)). In the neuro-fuzzy network learning cycle, sets A and B were learning, and set C was testing. Then sets A and C were learning and set B was testing. Finally, sets B and C were learning and set A was testing. The learning of the regression model, and the change in learning and network parameters (including the shape and distribution of function of membership to fuzzy sets) continued until comparable models were obtained in each of the three attempts. This yielded a model that is neither overlearned nor does it overfit the data. Instead, it reflects the variable interactions occurring in the sample under examination.The results obtained by participants on all the questionnaires had normal distribution. The questionnaire-derived raw scores were converted into sten scores, with the exception of the sense of quality of life questionnaire, in which case T-scale scores were used.The neural networks analysis was preceded by a determination of the basic parameters of the variables analyzed. Mean age was 50.11±3.07. Of the 201 women taking part in the study, 49 were in the early and 152 in the late stage of perimenopause. The level of participants’ life satisfaction was average, as was the frequency and intensity of their menopausal symptoms. The women additionally demonstrated a low level of positive affect (27.78±6.97) and a high level of negative affect (24.83±8.18).With regard to the analyzed personality traits: the level of neuroticism was high (107.60±27.05), of extraversion–moderate (97.26±22.32), of openness–high (106.41±21.57), of agreeableness–low (108.04±24.27), of conscientiousness–moderate (110.27 ±24.59), and of self-esteem–moderate (28.66±4.63).With respect to the analyzed dimensions of the body-self: no or little dysfunction related to perceiving stimuli generating too weak a sensation or no sensation at all (1.46±0.52), no or little dysfunction related to perceiving stimuli generating excessively strong sensations (1.74±0.74), no dysfunction related to the interpretation of sensations in terms of physical states (2.49±0.73), difficulty in interpreting bodily sensations in terms of emotions (2.95±0.71), no or little difficulty in interpreting bodily sensations in terms of a distorted sense of physical identity (1.96±0.87), difficulty in regulation of emotions (2.95±0.71), difficulty in regulation of physical states (2.72±0.66), negative attitude toward the body (2.78±0.88), lack of comfort with closeness with others (3.10±0.53), body protection (2.18±0.55), and a moderate level of the body-self (2.39±0.49). Positive self-stereotype of the menopausal woman was displayed by 44 of the 157 women under examination see .β values suggest that the higher women score on sense of quality of life and its spheres, the less frequently they experience psychological , vasomotor , and somatic  symptoms of menopause (We have confirmed that SQH comprises three dimensions (H1): sense of quality of life, menopausal symptoms, and positive and negative affect. In addition, structural analysis also revealed relationships between the proposed SQH dimensions. With respect to the entire model, a relationship of interaction  was observed between sense of quality of life, and frequency and intensity of menopausal symptoms. enopause .Moreover, sense of quality of life had the strongest influence on experiencing menopausal symptoms with respect to their frequency, with the influence related to their intensity being slightly weaker see .β = 0.435; Z = 6.322; p < 0.01), the higher the level of global sense of quality of life and its spheres. At the same time, we observed a decrease in the level of negative affect . In this light, we concluded that the level of positive and negative affect was a modifier of participants’ global sense of quality of life.Interesting to note, our analyses showed that the third SQH dimension, that is, experiencing positive and negative affect, only had an impact on the sense of quality of life (and its spheres). As it turned out, the higher the level of positive affect  and revealed multiple relationships existing between the variables under study, that is, causal structures, including the influence of the independent on dependent variables, which were also found to be related with each other. A detailed graph is presented in The model, which was also used to verify the remaining hypotheses, was significant  is associated with higher levels of extraversion, openness, agreeableness, conscientiousness, and self-esteem, lower levels of neuroticism and less dysfunction of the body-self functioning, and a positive self-stereotype of the menopausal woman (as suggested within H2). Detailed data about the strength and direction of revealed relations is included in In the model, variables are described by three parameters: Chi2 = 5.343; p = 0.004) and, at the same time, the lower the probability of the participant showing a negative self-stereotype ((negative self-stereotype)*< 0.334 Chi2 = 5.890; p = 0.008), the greater the decrease in both frequency and intensity of psychological, vasomotor, and somatic symptoms of menopause. In the context of our third hypothesis (H3), we have shown that less frequent and less intense psychological, vasomotor and somatic symptoms of menopause are associated with higher levels of extraversion, openness, agreeableness, conscientiousness, and self-esteem, lower levels of neuroticism and less dysfunction of the body-self functioning (lower score), and a positive self-stereotype of the menopausal woman. Through its direct impact on the global sense of quality of life and its spheres, the menopausal woman’s self-stereotype is an indirect predictor of the frequency and intensity of menopausal symptoms. This is because the higher the probability of a participant showing a positive self-stereotype of the menopausal woman ((positive self-stereotype)*> 0.676 We also demonstrated that higher positive affect is associated with higher levels of extraversion, openness, agreeableness, conscientiousness, and self-esteem, lower levels of neuroticism and less dysfunction of the body-self functioning, and a positive self-stereotype of the menopausal woman (as suggested within H4).A the same time, higher negative affect is associated with lower levels of extraversion, openness, agreeableness, conscientiousness, and self-esteem, higher levels of neuroticism and more dysfunction of the body-self functioning, and a negative self-stereotype of the menopausal woman (as stated within H5). Additional detailed results are included in The aim of the study was, first, to confirm that SQH comprises the three dimensions of sense of quality of life, menopausal symptoms, and positive and negative affect, and, second, to identify the predictors of SQH.The findings of the neutral networks analysis allow for the conclusion that SQH does, indeed, comprise the three postulated dimensions.Perimenopausal women’s SQH is largely dependent upon personality traits, self-esteem, the body self, and self-stereotype. These findings corroborated the results of previous studies, especially those emphasizing the role of internal variables for women’s health ,52–67.Among predictors of SQH, we found that higher level of the sense of quality of life  is associated with higher levels of extraversion, openness, agreeableness, conscientiousness, and self-esteem, lower levels of neuroticism and less dysfunction of the body-self functioning (lower score), and a positive self-stereotype of the menopausal woman.Sense of quality of life and all its dimensions  are primarily determined by self-esteem and personality traits. This is in line with the data reported in the literature. For example, a positive correlation has been found between high self-esteem and life satisfaction . With rePerceiving one’s life in negative or positive terms is associated with two affective mechanisms that determine the predispositions to experiencing a sense of happiness . These aMoreover, both personality traits have a bearing on the general activity of individuals and their relations with others. Extraversion may play a dual role by serving as a buffer to the negative impact of stressors on the volume of experienced tension and by decreasing the intensity of experienced stress, thereby increasing the level of life satisfaction. In addition, extraversion is conducive to establishing and maintaining social relations, thus boosting life satisfaction, as well as facilitating good relations with others, providing the individual with a sense of happiness . ConversWe also confirmed the third hypothesis, according to which less frequent and less intense psychological, vasomotor and somatic symptoms of menopause are associated with higher levels of extraversion, openness, agreeableness, conscientiousness, and self-esteem, lower levels of neuroticism and less dysfunction of the body-self functioning (lower score), and a positive self-stereotype of the menopausal woman.Our findings showed that frequency and intensity of menopausal symptoms depends on the following: personality traits, including neuroticism, agreeableness and self-esteem, sense of quality of life, and women’s functioning on the particular dimensions of the body self, namely, strength of the body self, interpretation of sensations in terms of a distorted sense of physical identity, emotional attitude toward the body, regulation of emotions and physical states, as well as lowered and raised sensation thresholds.We found that the way women experience the symptoms of menopause is related to all the parameters of the body self. A decreased intensity and frequency of the symptoms is associated with a tendency to depreciate the strength of one’s arousal and noticing few changes in the body, both of which are characteristic of persons with a strong body self. In contrast, an increased intensity and frequency of experienced symptoms can be associated with a tendency to take overt notice of the sensations coming from the body and to exaggerate the strength of arousal. Given the unpleasant bodily sensations they produce, intense and frequent symptoms of menopause may have women adopt negative attitudes toward their bodies. These, according to McKinley and Lyon, may in turn lead to experiencing negative affect and decreased well-being .The importance of individual factors in perceiving and interpreting bodily sensations as well as moderating their intensity is emphasized by conceptions that describe the mechanisms linking personality and state of health . For insThis mechanism is described in great detail by the Multifactorial model as applied to the development of bodily experiences and mood states during the climacteric . The modOther studies have also demonstrated that cultural context serves as a basis for women’s interpreting the changes affecting their bodies in terms of symptoms of menopause ,62. At tAnother hypothesis we managed to confirm was hypothesis four, which assumed that higher positive affect is associated with higher levels of extraversion, openness, agreeableness, conscientiousness, and self-esteem, lower levels of neuroticism and less dysfunction of the body-self functioning (lower score), and a positive self-stereotype of the menopausal woman.Moreover, we also confirmed the final hypothesis, according to which higher negative affect should be associated with lower levels of extraversion, openness, agreeableness, conscientiousness, and self-esteem, higher levels of neuroticism and more dysfunction of the body-self functioning (lower score), and a negative self-stereotype of the menopausal woman.There is plenty of research on the menopausal woman stereotypes –26,42–44Consistent with studies by Costa and McCrae, extraversion and neuroticism have been revealed as the strongest determinants of experiencing positive and negative affect ,64. IndiThere are several reasons why the findings presented above must be interpreted with a degree of caution. First, the sample was confined to married women with higher education living in a large Polish city, while SQH determinants may differ for women enjoying different socio-economic status. This may likely impact on the generalizability of our findings. Second, the sample was fairly small relative to the number of variables studied. Third, the questionnaires measuring sense of quality of life and the body self have only been statistically evaluated in Poland and are yet to be used abroad. Fourth, the study made no use of variables concerning experienced stress, a factor that is often cited as impacting on the experience of menopause .In practical terms, our findings may help raise awareness among women and medical practitioners, calling for a holistic approach to the health of menopausal women. Rather than limiting one’s perspective to the experienced symptoms, account should also been taken of life satisfaction, personality traits, self-esteem and experienced emotions, among other factors.Such therapeutic action could be focused on working with the body, as the body self is suggested to be an important determinant of health .The present study has also demonstrated that self-esteem plays a vital role for menopausal women’s sense of quality of life and its spheres and negative affect. Therefore, health promotion may benefit from action directed at building and strengthening self-esteem.By undertaking a range of specific intervention techniques, which take account of the present results, for example, in cognitive-behavioral therapy (CBT), practitioners could prevent the creation of a negative self-stereotype of the menopausal woman, thus reducing the risk of severe symptoms of menopause and depression.Further research could benefit from a thorough analysis testing the SQH model on a group of women enjoying a differential menopausal status and diverse education. For instance, it is worth checking whether intervention based on the findings presented here does indeed help women transition through menopause. Another interesting contribution could come from testing the role that sexual functioning plays on perimenopausal women’s SQH.In the present paper we have proven that SQH comprises three dimensions: sense of quality of life, menopausal symptoms, and positive and negative affect. Moreover, we showed that SQH is significantly predicted by the strength of the body self, regulation of emotions, regulation of physical states, interpretation of sensations in terms of emotions, interpretation of sensations in terms of a distorted sense of physical identity, attitudes toward the body, and raised and lowered sensation thresholds. We additionally demonstrated an interactive relationship between sense of quality of life and frequency and intensity of menopausal symptoms. Apart from the purely scientific value, our findings may have significant practical implications, as they may facilitate the creation of both prevention and therapeutic programs for women transitioning through menopause.S1 File(DOCX)Click here for additional data file.S2 File(DOC)Click here for additional data file.S3 File(DOC)Click here for additional data file.S4 File(DOCX)Click here for additional data file.S5 File(DOCX)Click here for additional data file.S6 File(DOC)Click here for additional data file.S7 File(XLSX)Click here for additional data file.S8 File(PDF)Click here for additional data file.S9 File(DOCX)Click here for additional data file.


Background: Although gemcitabine plus cisplatin (GP) is considered as standard chemotherapy for patients with advanced biliary tract cancer (BTC), the optimal regimen remains unknown.Methods: Using Network meta-analysis (NMA), a systematic review was conducted to find the most effective chemotherapy regimen for advanced BTC. We searched PubMed, Web of Science, Embase, Scopus and the Cochrane Library for articles published before October 6, 2018. Articles about chemotherapeutic comparisons were included. Hazard ratios (HRs) for overall survival (OS) and progression free survival (PFS) were estimated while odd ratios (ORs) was assessed for objective response rate (ORR).Results: The NMA included 25 studies and 3,312 individuals. Among all the regimens, Folfox-4 regimen obtained a superior difference in OS . XP was slightly better than GP in OS and GS approximately obtained the same efficacy to GP . Most of the targeted therapies included in this study tend to achieve better results in PFS and ORR but failed to improve OS, in which E-GEMOX achieved the best ORR when compared to BSC .Conclusions: Folfox-4 regimen is likely to be the optimal chemotherapy for patients with advanced BTC and the predominant targeted therapy hasn't achieved significant success currently. XP and GS can be considered as alternatives for advanced BTC. Biliary tract cancer (BTC) is a heterogeneous group of malignancies with features of biliary tract differentiation arising from distinct anatomical locations of the biliary tree. BTC is generally classified as intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder carcinoma, and ampullary cancer. Biliary tract cancer is a rare tumor in some European countries and the United State, but with a higher incidence in Latin America and Asia –4. BTC iTherefore, we used NMA of randomized controlled trials and retrospective studies in this study to find the optimal regimen for advanced BTC.This NMA was conducted and reported on the recommendations of the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines .A literature search was conducted for all articles published before October 6, 2018 using PubMed, Web of Science, Embase, Scopus and the Cochrane Library. The following search terms were used separately or in combination:  AND . Additionally, we manually searched bibliographies and added related references. Two investigators (YY Zhou and YL Hong) independently reviewed the titles and abstracts. Any disagreements were resolved by discussion and consultation.The selection criteria and exclusion criteria were predefined. Articles were included if they met the following inclusion criteria: (1) randomized controlled trials or retrospective studies; (2) patients with advanced biliary tract cancer who received chemotherapy; (3) reported outcome values . The exclusion criteria were as followed: (1) letter, commentaries, case reports, reviews, non-human studies and articles that did not provide raw data; (2) non-English articles; (3) articles that were not randomized or retrospective studies; (4) studies that did not include chemotherapeutic comparison; (5) studies included chemotherapeutic comparison concerning adjuvant therapy or new-adjuvant therapy. If multiple publications from the same study were available, we included the publication with the largest number of cases and the most applicable information.Two investigators (YY Zhou and YL Hong) independently reviewed the full text and extracted the following information: (1) publication data: first author name, publication year, country, and period of recruitment; (2) characteristics of each study population: number of patients, median age, and gender; (3) tumor stage and the ECOG performance status of patients; (4) treatment characteristics: regimen, dosage, cycles and median follow-up period; (5) outcome: PFS, OS, and ORR. When HRs was not reported in the articles, digitizing software (Digitizeit) was used to extract the HRs from the survival curve with a high degree of accuracy following established methods .2 test and the I2 statistic. The P-value > 0.10 for the Chi2 test or I2 >50% implied heterogeneity, thus a random effects method was required, or else a fixed effects method was needed. In this study, heterogeneity was found in the direct comparison of two articles and a random effects method was used.Data was entered and analyzed using Review Manager Version 5.3 . Time-related endpoints (PFS and OS) were reported as hazard ratios (HRs) with 95% confidence intervals (95% CI) which were used to calculate the efficacy of different chemotherapy for BTC. HRs was obtained directly from the articles or used Kaplan-Meier survival curves to estimate, while ORR and odd ratios (ORs) were used to assess the pharmacological effects. Pairwise comparisons were made by combining studies that compared the same intervention. Statistical heterogeneity from the eligible studies was assessed with the ChiA Bayesian framework and Markov chain Monte Carlo methods were used for a random-effects model in indirect comparison meta-analysis . The NMA2 with the combination of cisplatin at a dose of 25 mg/m2, which was considered as a standard GP regimen. The dose of oxaliplatin was commonly 100 mg/m2 while the other drugs differed. The regimens' cycles differed and Most of the studies got outcomes of OS and PFS. However, clinical stage was not explained clearly in most of the including studies  articles were reviews, letters, meetings, and case reports; (2) the research object was not human; (3) articles did not concern chemotherapeutic comparison. Full-texts of the 958 articles were assessed and 933 articles were excluded as they were not available, contained no eligible data, contained duplication of data, and/or were not suitable for analysis. Therefore, 25 RCTs and retrospective articles were included in this NMA . 3,312 p studies .p < 0.0001) while no significant difference was observed when cetuximab plus GEMOX (C-GEMOX) was compared to GEMOX, gemcitabine plus S-1 (GS) to GEM and GS to S-1. The pooled analysis of PFS was based on six studies enrolling 941 patients. p < 0.00001). Seven studies were included for pooled analysis of ORR with 980 patients. From A total of seven studies including 1,003 patients were available for the meta-analysis for OS. As shown in 7).The evidence network of eligible comparisons for OS, PFS and ORR in this NMA is shown in . CalculaHRs for overall survival was presented in For progression free survival , statistAs for objective response rate , when coValues of SUCRA were shown in P = 0.0031)  . Oxalipl 0.0031) , 17 that 0.0031)  came to  0.0031) , 31 and Recently, there are several clinical trials on going. A study conducted by Kobayashi et al. in Japan revealed that GP plus S-1 had a promising survival benefit  and a raThis NMA does have some limitations. In order to make indirect comparison available, this analysis included not only RCTs but also retrospective studies which increased the heterogeneity in design. Because of the lack of enough evidence, it was an inevitable problem that the reliability of the result in our study had greatly reduced. Also, most of the studies included did not provide detail information, so a stratified or subgroup analysis in our study was not accomplished. There were variations in the definition of advanced biliary tract cancer which included not only locally advanced or metastasis but also recurrence in this systematic review and some of the studies also could not give a specific illustration of the clinical stage. In this analysis, treatment outcomes of the four tumor types could not be extracted, respectively, and proportion of cancers based on the anatomy location was not balanced. Detailed analysis was hard to perform and we draw the above conclusions on the premise of ignoring the heterogeneity produced by different types' characteristics. And in our study, we assumed that patients with biliary tract cancer in different countries react to the same chemotherapeutic regimen similar. Additional, populations, gender ratio, and patients' age of these studies were assumed similar though they differed among the studies enrolled. For example, some studies got a large sample of up to 410 people while some studies got a small sample like 43 people. The ratio of men and women was approximately equal in only a few studies and the proportion of men was larger than women in all. Patient' age in the majority of our studies was about 65 years old, so attention can be taken away from the heterogeneity produced by age. Publication bias and selective reporting biases cannot be excluded which might affect some comparisons. Also, some treatments could not be included due to failing for obtaining full-text or connecting to other treatments. In addition, articles not published in English were not included which might lead to a language bias. Lastly, direct comparisons were scant in some comparisons which might affect the result of the analysis. Therefore, it seemed that the optimal treatment still remained uncertain and more RCTs are required.In addition, a meta-analysis conducted by Zhuang  has discFrom this NMA, we can conclude that targeted therapy currently achieved little success in prolonging OS but is still a promising treatment. The Folfox-4 regimen may be a new replacement for the previous GP regimen as it achieves a lot in OS. XP and GS can be considered as convenient alternatives for advanced biliary tract cancer.The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.YL, YZ, YH, MH, DZ, and FL designed the study. YZ and YH screened studies and collected data. YZ and CY did the statistical analyses. YZ, YH, MH, and SW prepared the figures and reviewed the results. YL, YH, and MH interpreted data. YL and YH wrote the manuscript. YL, CY, DZ, and FL revised 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.