Supplemental Digital Content is available in the text Primary dysmenorrhea (PD), the most common gynecological diseases, seriously affects women's life and work; however, without more effective treatment. Chinese herbal medicine (CHM) has been widely used for relieving dysmenorrheic pain in patients with PD. To assess the effectiveness and safety of CHM in patients with PD, a systematic review and meta-analysis of current published evidence regarding CHM as treatment for PD would be conducted in this study.Literatures related to CHM for PD from the establishment of the database to June 2019 will be retrieved from the following databases: MEDLINE, EMBACE, Wed of Science and Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, and Wanfang Database. There are no language restrictions for retrieving literature. Eligible randomized clinical trials (RCTs) evaluating the effectiveness and safety of CHM in PD patients will be put in the study including outcomes of pain intensity, clinical effectiveness rate, quality of life, and adverse events. By scanning the titles, abstracts and full texts, 2 reviewers will independently select studies, extract data, and assess the quality of study. Meta-analysis of RCTs will be conducted using Review Manager 5.1 software. The results will be presented as risk ratio for dichotomous data, and standardized or weighted mean difference for continuous data.This study will provide high-quality available evidence for the treatment of PD with CHM based on pain, clinical efficacy, quality of life, and adverse events.The systematic review willto evaluate the efficacy of CHM in treating PD and provide evidence for clinicians.CRD42019121185. Dysmenorrhea is divided into primary dysmenorrhea (PD) and secondary dysmenorrhea (SD). PD is defined as the absence of organic pathologic changes in reproductive organs which occurs shortly after menarche, while SD is defined as menstrual pain caused by organic diseases of the genital system such as adenomyosis, uterine malformation, and pelvic inflammatory disease.Dysmenorrhea is a common gynecological disease characterized by abdominal pain before or during menstruation. 80% in Western Australia, 60% in Canada, while 48.4% in Mexico. In a number of studies of young women, absenteeism rates for PD ranged from 34% to 50%. About 10% of the patients with PD are so severe that they are unable to work for 1 to 3 days a month. In the United States, the economic losses caused by absence due to PD are about 600 million working hours and over 2 billion dollars per year. In addition, PD patients who still insist on working could easily lead to decreased productivity, increased possibility of accidents, and decreased work quality.The prevalence of dysmenorrhea seems to vary around the world, from 50% to 90%, PG could cause uterine smooth muscle contraction and spasm, resulting in decreased uterine blood flow, and at the same time increase the sensitivity of its peripheral nerves to pain, resulting in dysmenorrhea. In addition to PG, other factors may also be associated with PD. Interleukin could cause dysmenorrhea by constricting the smooth muscles of the uterus. In patients with dysmenorrhea, the content of oxytocin (OT) is much higher than that in women without dysmenorrhea. OT can directly act on uterine muscle cells to cause uterine contraction, and stimulate the release of PGs by endometrial cells at the same time, causing and aggravating dysmenorrhea. Researches have reported that mood, exercise, eating habits, and environment are correlated with dysmenorrhea.Currently, it has been recognized that increased prostaglandin (PG) is the main pathogenesis of PD. 17% to 95% (mean 67%) of women relieve pain with NSAIDs. At present, the main side effects of NSAIDs are the renal disturbances, gastrointestinal complications, and cardiovascular events. Oral contraceptives (OCs) are also recommended for the treatment of PD, which can relieve pain in up to 70% to 80% of the patients. However, OCs could cause nausea, vomiting, weight gain, or vaginal bleeding. Therefore, more and more patients with PD are seeking alternative therapies to relieve the discomfort caused by menstruation.The first line of therapy for PD is nonsteroidal anti-inflammatory drugs (NSAIDs).,20 moxibustion, massage and acupoint stimulation and massage in treating PD have been reviewed. According to the guidelines for gynecological practice in Japan, by the Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists (2011 edition), traditional Chinese medicine (TCM) could be used for PD. A quite number of clinical trials have shown that CHM is beneficial to the treatment of PD. Daily et al provided evidence for the effectiveness of Ginger in the treatment of PD. Jaafarpour et al found that Cinnamon markedly lighten the severity and duration of menstrual pain. Rehman et al confirmed Rheum Emodi is able to relieve the symptoms of PD. Sun et al indicated that Guizhi Fuling capsule possessed a remarkable spasmolytic effect on uterine tetanic contraction through in vivo and in vitro experiments. Ding et al found that Shaoyao Gancao decoction had obvious analgesic effect on dysmenorrhea model mice. Huang et al verified that Shaofu Zhuyu decoction in the treatment of Cold – Stagnation and Blood – Stasis PD in rats, the mechanism is closely related to the regulation of mitogen-activated protein kinase pathway.TCM has treated PD for more than 2000 years and its featured therapies include Chinese herbal medicine (CHM), acupuncture, moxibustion, massage, cupping, qigong, food therapy, and so on. The effectiveness of acupuncture, Another systematic review and meta-analysis provide evidence for the superiority of Danggui Shaoyao powder in the treatment of PD. However, the efficacy and safety of CHM in treating PD are still unclear due to the large number of TCM prescriptions. The purpose of this study is to systematically review the available literatures on the therapeutic effect of CHM on PD.In recent years, there have been a few systematic reviews on specific TCM prescriptions for treating PD. For instance, a systematic review and meta-analysis showed that Shaofu Zhuyu decoction was superior to the conventional drug group in the treatment of PD. In the past 10 years, there have been many new reports on the randomized controlled trials (RCTs) of CHM in treating PD. Therefore, we believe it is necessary to conduct a new systematic review to evaluate the efficacy of CHM in treating PD and provide evidence for clinicians.A related systematic review has been published on the topic. In 2007, Zhu systematic review provided evidence for the treatment of PD with CHM, proving that CHM can alleviate menstrual pain.22.1This study has been registered in the International prospective register of systematic reviews with the registration number of CRD42019121185. This protocol adheres to the preferred reporting items for systematic reviews and meta-analyses protocols 2015.2.2We will put all RCTs related to CHM for PD into the study of the effectiveness of CHM for PD.2.3 SD, such as endometriosis, uterine fibroids, and adenomyosis, was not taken in consideration in this study.This study will employ the diagnostic standards of the Clinical Guideline of PD by the Society of Obstetricians and Gynecologists of Canada.2.4Interventions of the including trials will be oral administration of CHM, which can be a decoction, granules, or CHM with other modern dosage forms. The dosage and treatment course are not limited. The intervention of CHM with traditional western medicine will make no difference.2.5The control group will include placebo, blank control, and conventional medicine (such as NSAIDs). If CHM is combined with western medicine (for instance CHM is administrated with the NSAIDs), the usage of western medicine in the control group should be consistent with that in the experimental group.2.6The primary outcomes include:(1)Pain: a reduction in pain  that occurs only during the intervention or as a result of the intervention, measured by a visual analog scale, other validated scales, or as a dichotomous outcome.(2)Clinical effectiveness rate: an overall relief on symptoms (other menstruation-related symptoms) that occurs only during the intervention or occurred as a result of the intervention, measured by changes in dysmenorrhea symptoms and treatment effectiveness, and either self-reported, observed, or reported by other similar measures.The secondary outcomes include:(1)Quality of life measured with valid questionnaires.(2)Adverse events.2.7http://links.lww.com/MD/D236.The databases reviewed to collect RCTS related to CHM for PD will be as follows: 4 English literature databases, which are Medline, Embase, Wed of Science and Cochrane Library, and 3 Chinese literature databases, which are Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, and Wanfang Database. There is no limit by language or publication status. Additional resources, such as relevant meeting minutes and qualified research references, will also be searched manually. File 1 shows the strategy for searching the database; 2.8Two reviewers independently run all literature search strategies, and records retrieved from the database are exported to the Endnote. According to the inclusion criteria, the titles and abstracts of references were determined by scanning literature retrieval, and irrelevant studies were excluded. Then the full text will be screened to determine eligible studies. Any differences between the reviewers will be resolved through discussion with a third reviewer. When the information is insufficient or unclear, we will contact the corresponding author via email or phone to ask for more information or clarification. Data extraction items included: first author, year of publication, diagnostic information, course of disease, sample size, age, intervention details, control and outcome, treatment time, follow-up time, and adverse events. The flow chart is shown in Figure 2.9Bias risk was assessed using the Cochrane Handbook 5.1.0 bias risk assessment tool, including random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other sources of bias. This review will take L, U, and H to represent the assessment results: L means low risk of bias, U means unclear risk of bias, and H means high risk of bias. Differences will be resolved through discussion among all authors.2.10Differences between the intervention group and the control group will be assessed. For continuous data, we will use the mean difference (MD) with 95% confidence intervals (CIs) to measure the therapeutic effect. We’re going to convert other forms of data into MDS. The standard MD of 95% CIs will be used for the outcome variables of different scales. We’re going to convert the other binary data into relative risk (RR) values. For binary data, we represent the processing effect as RRs with 95% CIs. All statistical analyses will be performed using the Cochrane Collaboration's software program Review Manager v. 5.3.5 for Windows. For research with insufficient data, we will contact relevant authors to obtain and verify data as far as possible.2.11χ2 test and evaluated quantitatively by I2. If there is no significant heterogeneity between studies (P > .1 and I2 ≤ 50%), a fixed-effect model is adopted for meta-analysis. If there is heterogeneity among studies , the sources of heterogeneity will be further analyzed. After excluding the effect of obvious clinical heterogeneity, a randomized effect model will be used for meta-analysis. Obvious clinical heterogeneity was treated by subgroup analysis, meta-analyst sensitivity analysis, or descriptive analysis.Heterogeneity of the including studies will be analyzed by 2.12If there are a plenty of subgroup studies, subgroup analysis will be analyzed to determine the heterogeneity between them. The subgroup analysis criteria are as follows:(1)treatment time or dose of CHM;(2)duration or severity of PD;(3)syndrome differentiation;(4)formulations.2.13Sensitivity analysis will be conducted to test the robustness of key decisions made during the review process. The main decision nodes include method quality, sample size, and the impact of missing data.2.14Reporting bias, such as the publication deviation will be evaluated by a funnel chart. When there are more than 10 trials in the analysis. If the visual examination shows asymmetry, we will use the Egger method for exploratory analysis.2.15Ethical approval is not required for this study because we did not use data related to individual patient. In addition, the findings will be disseminated through peer-reviewed publications or presentations at conferences.3PD is a common disease in women. In severe cases, it can affect patients’ life and work, bringing economic and social burdens. At present, the treatment of PD by western medicine mainly consists of analgesia, sedation, and spasmolysis. Although the pain can be postponed, there are many adverse reactions and the long-term effect is not good. More and more patients with PD are seeking alternative treatment. CHM has attracted more and more attentions in PD because of its small side effects. CHM has been used to treat PD for more than 2000 years. In recent years, CHM has been extensively used in the treatment of PD. Although there have been studied on the efficacy of individual formulations for dysmenorrhea, the relative differences between these formulations are still uncertain. This study will be a comprehensive review of CHM treatment and provide basis for clinical gynecologists to use CHM to treat PD.Conceptualization: Tao Shen.Formal analysis: Lu Xu, Tian Xie.Funding acquisition: Tao Shen.Investigation: Lu Xu, Tian Xie.Methodology: Lu Xu, Tian Xie.Project administration: Tao Shen.Supervision: Tianfeng Zhang.Validation: Tianfeng Zhang.Writing – original draft: Lu Xu.Writing – review & editing: Tao Shen.


Marsdenia tenacissima, is widely used in the adjuvant treatment of tumors in China. The present study aimed to evaluate the efficacy and safety of XAPI combined with chemotherapy for treating patients with advanced gastric cancer. Seven databases were searched for relevant studies published up to October 1, 2018, and Review Manager 5.3 software and Stata 12.0 software were used for meta-analysis. Fourteen studies, representing 1097 enrolled patients, were included in our analysis. Compared with chemotherapy alone, combination treatment with XAPI and the XELOX regimen  was found to improve the objective response rate (ORR) , disease control rate (DCR) , and Karnofsky Performance Status (KPS) improvement rate  and to reduce the incidence of leukopenia , liver damage , renal impairment , and hand-foot syndrome . However, median progression-free survival (PFS), 1-year survival rate, and median overall survival (OS) were not extended by XAPI plus XELOX. Combination treatment with XAPI and the SOX regimen  did not improve ORR or DCR, but it did enhance the KPS improvement rate  and reduce the incidence of nausea and vomiting . XAPI in combination with the FOLFOX regimen  enhanced only the KPS improvement rate  and had no significant effect on ORR or DCR or the incidence of adverse events. A single study reported that XAPI combined with the CPT-11 regimen (irinotecan) was superior to chemotherapy alone with respect to DCR and also reduced the incidence of leukopenia, liver damage, and hand-foot syndrome during chemotherapy, while prolonging PFS. Finally, one study reported that XAPI combined with the TP regimen  improved ORR and KPS improvement rate to a greater extent than TP alone. Although the present review has some limitations, the findings suggest that XAPI combined with chemotherapy may represent a beneficial treatment strategy, particularly the combination of XAPI and XELOX.Xiao Ai Ping injection (XAPI), extracted from the Chinese herbal medicine Gastric cancer is one of the most common malignancies, particularly in East Asia . AlthougIn recent years, the development and increasing popularity of Traditional Chinese Medicine (TCM) has resulted in its efficacy being increasingly recognized in China and abroad . TCM can Marsdenia tenacissima, primarily contains phenolic acids and steroidal glycosides, among other compounds , as shown in P=0.69, I2=0%), while the meta-analysis revealed that DCR in the experimental group was higher than that in the control group , as shown in The XELOX subgroup of 4 studies –26 reporP=0.57, I2=0%). The meta-analysis showed that ORR in the experimental group and the control group was comparable , and the difference between the two groups was not statistically significant (P=0.17), as shown in P=0.11, I2=55%), while the meta-analysis showed that DCR in the experimental group was similar to that in the control group , and the difference also was not statistically significant (P=0.20), as shown in The SOX subgroup of 4 studies –30 reporP=0.99, I2=0%). The meta-analysis showed that ORR in the experimental group was similar to that in the control group  and that any difference between the two groups was not statistically significant (P=0.11), as shown in P=0.01, I2=72%). The meta-analysis showed that DCR in the experimental group was similar to that in the control group , with no statistically significant difference between the groups (P=0.32), as shown in The FOLFOX subgroup of 4 studies –34 reporI 0.97,1.] and thaP<0.05).One study  in the CP<0.05).One study  in the TP=0.97, I2=0%), the SOX subgroup , and the FOLFOX subgroup . The meta-analysis showed that KPS improvement rates in the experimental groups of three subgroups were higher than those in the control groups. The effect values and 95% confidence intervals, respectively, were , , , with statistically significant difference between the experimental groups and control groups, as shown in P>0.05), while that in the control group did not change significantly (P<0.05). Moreover, one study , as shown in P>0.05). One study . The incidence of leukopenia in the experimental groups of the SOX subgroup  and the FOLFOX subgroup  was comparable with that in the control groups (P>0.05). These results are detailed in Supplementary P<0.05). One study . However, there was no significant difference in the incidence rate of nausea and vomiting between the experimental group and the control group of the XELOX and the FOLFOX subgroup, of which the effect values and 95% confidence intervals, respectively, were  and . These results are detailed in Supplementary In 2 studies , 25 in tP=0.98, I2=0%), 2 studies in the SOX subgroup , and 3 studies in the FOLFOX subgroup . The meta-analysis showed that the incidence rate of liver damage in the experimental group of the XELOX subgroup was lower than that in the control group . However, there was no significant difference in the incidence rate of liver damage between the experimental group and the control group of the SOX and the FOLFOX subgroup, of which the effect values and 95% confidence intervals, respectively, were  and . These results are detailed in Supplementary P<0.05). TP subgroup did not report relevant data.In 3 studies –25 in th 95%CI 0.,4.48; P>P=0.87, I2=0%). The meta-analysis showed that the incidence rate of renal impairment in the experimental group of the XELOX subgroup was lower than that in the control group . The results are detailed in Supplementary P>0.05). Other subgroups did not explicitly report the relevant data.Three studies –25 in thP=0.13, I2=50%). The meta-analysis showed that the incidence rate of hand-foot syndrome in the experimental group of the XELOX subgroup was lower than that in the control group . The results are detailed in Supplementary P<0.05). Other subgroups did not report the relevant data.Three studies –25 in th 95%CI 0.,0.90; P=t=1.44, P=0.15> 0.05) and the Egger test  indicated that there was no significant publication bias in this 12 studies, as shown in Figures Based on the ORR meta-analysis results, a funnel plot was used to assess publication bias and the impact of studies with small sample sizes. The results of the Begg test  induced p53-dependent mitochondrial pathway [Gastric cancer is one of the most common malignancies globally. In China, the incidence of gastric cancer is markedly higher than that in other countries, and the challenges of early detection mean that patients frequently present with advanced disease . Therefon in TCM , 43. TCMn in TCM , thus pon in TCM , but als pathway . These fThe 14 studies included in this systematic review were divided by chemotherapy regimen into XELOX, SOX, FOLFOX, CPT-11, and TP subgroup. The outcomes of the systemic review and meta-analysis can be summarized as follows:(i) XAPI combined with XELOX chemotherapy is superior to chemotherapy alone in terms of ORR, DCR, and KPS improvement rate. This combination can reduce the incidence of leukopenia, liver damage, renal impairment, and hand-foot syndrome during chemotherapy but cannot prolong median PFS or median OS in patients with gastric cancer.(ii) XAPI combined with SOX chemotherapy is superior to chemotherapy alone in terms of KPS improvement rate but cannot improve ORR or DCR. For adverse events, combination therapy can only reduce the incidence of nausea and vomiting during chemotherapy, but it cannot reduce the incidence of leukopenia and liver damage. Regarding the impact on patient survival, a single study reported that combination therapy prolonged median PFS and median OS in patients with gastric cancer.(iii) XAPI combined with FOLFOX chemotherapy is superior to chemotherapy alone in terms of KPS improvement rate. However, both regimens are comparable in terms of ORR and DCR. In addition, combination therapy cannot reduce the incidence of leukopenia, nausea and vomiting, liver damage, and renal impairment during chemotherapy.(iv) A single study reported that XAPI combined with CPT-11 chemotherapy is superior to chemotherapy alone with respect to DCR and median PFS. This combination can reduce the incidence of leukopenia, liver damage, and hand-foot syndrome during chemotherapy.(v) A single study reported that XAPI combined with TP chemotherapy is superior to chemotherapy alone with respect to ORR and KPS improvement rate and has no effect on the incidence of leukopenia.The present review had some limitations. First, despite a comprehensive search to reduce publication bias, only databases in Chinese or English were included, meaning that detection and language bias may have been present. Second, the methodological quality of the included studies was generally poor. Only three studies used an appropriate random grouping method, while the remaining studies did not describe the randomization method in detail. Unfortunately, one study used an inappropriate random allocation method. Third, not all studies had a double-blinded study design, which may have resulted in an expectation bias in the evaluation of efficacy. Fourth, not all studies implemented assignment hidden, which may lead to selective bias in determining the subjects. Fifth, all included studies were carried out in China among Chinese patients, so whether the results can be extrapolated to other populations requires further investigation. In addition, survival time is an important endpoint and an important indicator for evaluating the long-term efficacy of treatments for cancer. However, most of the included studies did not follow up on patients and report relevant data. Furthermore, different studies may have had potential differences in factors such as patient enrollment and treatment courses. Although these limitations may reduce the robustness of the present systematic review, the studies included were rigorously screened and were deemed relatively highly comparable.The findings of the present systematic review and meta-analysis indicate that XAPI combined with chemotherapy may represent a beneficial treatment strategy in patients with advanced gastric cancer, particularly the combination pf XAPI with XELOX. However, further high-quality randomized controlled trials of standardized design and following the principles of evidence-based medicine are needed to validate this conclusion.


As argued in the present paper, this (cap)ability may be important for providing patient-centred care that is culturally adequate and competent.Healthcare professionals and students of medical faculties in Poland increasingly encounter culturally diverse patients. It is necessary to support the development of cultural intelligence in order to improve the medical care provided to patients from different cultural backgrounds. At present there are no standardized tools in Poland that can accurately and reliably assess cultural intelligence, which is defined by Ang et al. as “The aim of the research was to show the multistage process of validation of the Polish version of The Cultural Intelligence Scale by Ang et al. and Van Dyne et. al.Across two studies we examined the psychometric properties of the Cultural Intelligence Scale, including reliability  and validity . In the first two-session study, 349 participants  completed the Polish version of the Cultural Intelligence Scale twice with an interval of at least 22 days. In addition, across two study sessions participants completed questionnaires constructed to measure (a) cultural competence, (b) need for cognitive closure, (c) emphatic sensitiveness, (d) emotional intelligence, (e) self-esteem, (f) social desirability, (g) personality, and (h) positive/negative attitudes towards culturally divergent people. Finally, to additionally examine the theoretical validity, 36 professional cross-cultural competence trainers completed the Cultural Intelligence Scale during a one-session study.The Cultural Intelligence Scale has been shown to have satisfactory psychometric properties. It has high reliability  and the factor structure seems to approach the postulated one. Theoretical and criterion accuracy are well proven; convergence is less straightforward, but it correlates well with tools that examine variables such as cultural competence, cognitive closure, empathy/emphatic sensitiveness, emotional intelligence, self-esteem, personality, and social desirability. The results suggest that these factors contribute to the development of the cultural intelligence.The Cultural Intelligence Scale can be successfully used in empirical research of cultural intelligence of medical professionals and students of medical majors and their education in Polish conditions. The concept of cultural intelligence is a relatively new construct from the early 21st century that is well described in English-language literature. The term ‘cultural intelligence’ is known in business and management of multicultural international teams and social psychology , 7, 8, 9Until recently, medical and nursing students in Poland were not trained in cultural competencies as these were not, unfortunately, considered essential for healthcare professionals in Poland due to the ethnically homogenous nature of Polish society. However, Poland’s accession to the EU in 2004 changed this situation dramatically and in recent years this country has observed a rapid growth of foreigners working or studying there . In 2011It is worth highlighting that training healthcare professionals in cultural competence is deemed necessary by the US Department of Health and Human Services . This USAccording to the patient-centred care model, an individual patient’s needs, values and preferences should be respected . Thus, hInitially, Earley and Ang  proposedBased on the works of Ang et al.  and Van According to Starosta , culturathe Cultural Intelligence Scale (CQS) by Ang et al.  Am always prepared.Conscientiousness . e.g. (I) Get stressed out easily).Emotional Stability . e.g. (I) Have a rich vocabulary.Intellect (creativity and level of openness to experience). e.g. ery inaccurate; 5 = very accurate). The IPIP-BFM-20 has sufficient and satisfactory reliability coefficients ranging from .61–.82 and the theoretical validity was confirmed.It consists of 20 items  rated on a 5-point scale (1 = vI am never late for school (work)). The reliability coefficients  of the questionnaire equalled 0.79–0.90. High coefficients of correlation (up to 0.82) with Marlowe-Crowne’s scale [The Social Desirability Scale  is a sel’s scale  were als’s scale . By usinery inaccurate; 5 = very accurate) measuring the concept of emotional intelligence introduced by Salovey and Mayer [The Emotional Intelligence Scale  is a selnd Mayer . It consI can almost always tell how my interlocutor feels.empathy and perception of emotions. 9 items relating to the ability to recognize, identify and empathize with emotional states expressed by others, e.g. I am usually very clear about my feelings.insight with emotional knowledge. 9 items relating to insight into one’s own emotions, e.g. I have my own ways of overcoming sadness and anger.mood managing. 7 items relating to the ability to manage negative emotions and states, e.g. The Emotional Intelligence Scale has sufficient and satisfactory reliability coefficients ranging from .63–.81 and the theoretical validity was confirmed.I feel that I have a number of good qualities) rated on a 4-point scale  and measures global self-esteem defined as attitude towards the self. The SES has sufficient and satisfactory reliability coefficients ranging from .81–.83 and the theoretical validity was confirmed.The Polish Rosenberg Self-Esteem Scale (SES)  consistsery inaccurate; 5 = very accurate). The IPIP-BFM-50 has sufficient and satisfactory reliability coefficients ranging from .77–.88 and the theoretical validity is confirmed. Please note that since the aforementioned IPIP-BFM-20 is a shortened version of the IPIP-BFM-50, it has slightly lower reliability coefficients compared to the full-length prototype. Therefore, in order to increase the precision of personality assessment, we additionally decided to use the IPIP-BFM-50 during the second experimental session.The International Personality Item Pool–Big Five Markers– 50 (IPIP-BFM-50)  is the PThe questionnaire consisted of 6 questions relating to the two main research areas: (1) the participant’s experience in interacting with and attitude towards people from diverse cultural backgrounds, and (2) attitude towards refugees. Regarding the former, participants were asked whether they: (a) have lived abroad for at least 1 month (Yes/No); (b) have close relationships with culturally diverse people (Yes/No); (c) would be willing (Yes/No) to marry a person from an ethnic minority , a different nation , or a religious minority community . In addition, they decided (Yes/No) whether European, Muslims, Romas and Afro-Americans should be granted the same free health care benefits as Polish citizens. As to the second area, participants were instructed to think about refugees coming to Poland and to answer (Yes/No) whether they should be accepted by the Polish government and whether the most promising students from war-torn countries  should be granted free medical university education. Please note that Study 1 was conducted after the European migrant crisis that occurred in 2015 when the European Commission decided to relocate Syria and Iraq refugees from south European countries to other the EU members. This matter started a long-lasting political discussion in Poland and divided the public as to the validity of the EC decision.The study was conducted between December 2017 and March 2018. The Research Ethics Committee at the Institute of Psychology at Jagiellonian University approved this study. Written consent for participation was obtained prior to data collection. No incentive was offered for participation in the study. The privacy and confidentiality of participants was strictly protected as follows: (1) all the information provided by each participant was coded by a number that does not directly identify any individual; (2) any identifying information was coded and removed from all non-numerical data so it is impossible for anyone but the experimenter to identify any individual; (3) any coded identifying information was kept separately from raw questionnaires and responses; (4) if an individual chose to stop participating in the study, any data already collected was removed from the study records.Participants from Jagiellonian University Medical College and The Medical University of Lodz were invited (either during participants’ classes or via email) by one of the two experimenters  to participate in the study. Importantly, the experimenters did not recruit students from the classes they themselves taught to avoid putting any pressure on students. Participants were informed that the goal of the study was the psychometric evaluation of the Polish adaptation of tool measuring cultural competencies and intelligence. They were also told that the study was for research purposes only. In addition, participants were informed that the study consisted of two experimental sessions, each lasting up to 1 hour. It was highly stressed that the study was entirely voluntary and they would not receive incentives for their participation or individual information about their results. They were also informed that they would be able to withdraw from the study at any point without any consequences. Finally, participants were informed of how their privacy and confidentiality would be protected.Volunteers willing to participate in the study were tested in groups by either AM  or PP  during scheduled sessions that took place at the University. During each experimental session, participants were told the same information as during the recruiting phase. Importantly, they were explicitly informed that they were free to withdraw from the study at any point. The experimenter assured them that their responses would be confidential and they could refrain from reporting particularly sensitive information by marking “X” as an answer.Since we wanted to study the relationship between cultural intelligence and the wide variety of different variables , it was unfeasible (due to time constraints and participants’ capacity) to ask participants to fill in all the questionnaires during one session. For this reason, participants were provided with different sets of tools during the first and second sessions (but the CQS was filled in during each session). The first and second sessions lasted up to 1 hour. Below we more precisely describe the sets of tools used.First session. During the first session, participants completed the following questionnaires: CQS, CCCI, The Positive/Negative Attitude Towards Culturally Divergent People Questionnaire, Emphatic Sensitiveness Scale, The Need for Closure Scale, International Personality Item Pool–Big Five Markers 20, The Social Desirability Scale.Second session. During the second session they completed CQS, The Emotional Intelligence Scale, The Rosenberg Self-Esteem Scale, IPIP-BFM-50.Finally, a new group of professional cross-cultural trainers completed only the CQS and CCCI tools during one study session.d with small, medium, and large effects defined as 0.2, 0.5, and 0.8, respectively [The software STATISTICA  and IBM SPSS AMOS (version 25.00) were used for statistical analysis. The licences were obtained by and granted to Jagiellonian University for research purposes and were used in accordance with the terms of use by the first author only (KB). In the descriptive statistics we used means and standard deviations. To analyse the reliability of the CQS we utilized (a) Cronbach’s alpha  to assesectively .r(349) = .77, p < .001 and it ranged between .62 and .80 across subscales.The overall means for the CQS are provided in χ2), normed chi-square (χ2/df), goodness-of-fit index (GFI), the adjusted goodness-of-fit index (AGFI), normed fit index (NFI), root mean square error of approximation (RMSEA), comparative fit index (CFI), non-normed fit index (NNFI), and standardized root mean square residual (SRMR). The results indicated that while the four-factor CQS model postulated by the authors did not perfectly fit the data, it was satisfactory and acceptable: χ2(164) = 482.56, p < .001, χ2/df = 2.94, GFI = .88, AGFI = .84, NFI = .90, RMSEA = .08, 90% CI , CFI = .93, NNFI = .92, SRMR = .04. For example, models with the following values indicate an acceptable fit: CFI values between .80 and .90 (or higher); RMSEA and SRMR values close to (or lower than) .06 and .08, respectively, and up to .10; χ2/df values should be less than 3; GFI, AGFI and NFI higher than .90, .95, and .90, respectively .Next, we performed confirmatory factor analysis to further examine the factorial structure of the CQS. In particular, we verified the postulated a four-factor structure of the CQS . Importaly e.g. , 68, 69), 69χ2), In order to further examine the CQS’s criterion validity we correlated the total score of the CQS with another tool constructed to measure a similar concept; namely, the Cross-Cultural Competence Scale (CCCI) , 30. Pler(303) = .66, p < .001 and r(31) = .76, p < .001 in the non-professional group and professional trainers, respectively.As presented in As demonstrated in α = .05, the critical value q was .043.To analyse the CQS’s validity we verified whether participants who demonstrated positive relationships with and/or attitudes towards foreign-born populations, minorities and migrants performed higher on the CQS scale, as it may be theoretically expected. For example, we would expect that an individual who has a close and positive relationship with the Roma minority would perform higher on the cultural intelligence scale compared to someone who has no such experience. To fulfil this goal, we conducted a series of independent t-tests for differences in the total score of CQS between participants with positive and negative attitudes that were operationalized as agreeing (positive attitude) or disagreeing (negative attitude) with statements such as, for example, “Refugees from Syria or Iraq should be provided with free university education”. In total, we performed 15 t-tests. To control for multiple comparisons we chose the False Discovery Rate correction . With α As can be seen in t-test. With α = .05, the critical corrected value q was .050. As can be seen in Finally, to test the differences between professionals and non-professionals in the CQS, the overall means for the CQS total score as well as for the CQS’s subscales were entered into an independent The present study examined the psychometric properties of the Polish version of the Cultural Intelligence Scale (CQS), developed originally by Ang et al. . More prThe first goal of our study was to analyse the reliability of the CQS. For this reason, participants completed the CQS twice, which additionally allowed us to verify the test-retest reliability. Our findings provide strong evidence that CQS has satisfactory internal consistency  and is quite stable over time (i.e. the test-retest correlations ranged between .62 and .80).internalized cultural knowledge intelligence’, and motivational and behavioural items are combined into second single dimension called ‘effective cultural flexibility intelligence’. As suggested by Bücker et al. [per se, the latter reflects the self-conscious adjustment that comprises both the self-efficacy and the ability to (non-)verbally adjust to culturally divergent situations and contexts.At the same time, although the original version of the CQS was assumed to have a 4-dimensional factor structure , confirmr et al. , while tIn summary, while there is a need to further investigate the factorial structure of the CQS, since all items were significantly and strongly related to the general latent trait, we argue that the CQS can be successfully used to measure the general concept of cultural intelligence. Put differently, we highly recommend the usage of the total score of the CQS.The second overriding goal of the present study was to examine the validity of the CQS. To fulfil this aim, we examined theoretical validity, criterion validity and convergent validity.Regarding criterion validity, it was expected that CQS would correlate highly with another tool constructed to measure the theoretically similar concept of cross-cultural competencies. Our results were in line with this expectation; namely, we observed a statistically significant high positive correlation with the Cross-cultural Competence Inventory (CCCI) , 30. TheNext, we examined the theoretical validity of the CQS in two ways: Firstly, we compared the group of non-professionals with the group of cross-cultural-trainers in terms of their mean total score in the CQS. As expected, we observed higher cultural intelligence scores for professionals compared to non-professionals. Secondly, participants who demonstrated a positive attitude to culturally diverse national and religious groups of people scored significantly higher on the CQS. These findings together provide strong empirical support for the theoretical validity of the CQS.Finally, we also assessed the convergent validity of the CQS by examining the correlations between CQS and the following variables: (1) personality–extraversion, agreeableness, conscientiousness, intellect (positive correlation); (2) empathic sensitiveness–perspective taking and empathic concern (positive correlation), personal distress (negative correlation); (3) the need for cognitive closure–decisiveness (positive correlation), closed mindedness (negative correlation); (4) emotional intelligence–perception of emotion and empathy, insight with emotional knowledge and mood managing (positive correlation); (5) social desirability (positive correlations). As expected and argued in the present study section, variables such as personality, emotional intelligence and empathy (i.e. empathic concern and perspective taking) correlated positively with cultural intelligence, while closed mindedness and personal distress were negatively correlated. In general, these findings suggest that the development of cultural intelligence and efficient and appropriate interaction with culturally diverse individuals may be supported by (a) being open to new and novel situations and experiences; (b) the ability to recognize and feel the emotions expressed by others; (c) the ability to communicate with people who have different ways of functioning and emotional expression; (d) the ability to take different perspectives and points of view; (e) the ability to empathize with others; (f) being resistant to anxiety or discomfort when observing others’ negative experiences; (g) having positive attitudes towards other people; (h) having a high level of sociability.Importantly, these results are in line with findings reported in the literature , 73, 74 While, it can be argued that the development of cultural intelligence is an important developmental task for every person who has contact with foreigners, in the present paper we placed the focus of our attention mainly on healthcare professionals. In the present form of the education of medical professionals, students of medical majors are more focused on the development of social skills. However, a current challenge for medicine and nursing is to develop cross-cultural intelligence and competencies in order to meet the demands and needs of the global community. If there were to be a significant increase in the number of culturally diverse patients, difficulties could arise that are related to different ways of communication , approach to time, problem solving, decision making or other interpersonal relations. Therefore, cultural intelligence should become an important attribute of all employees, including healthcare professionals who take up jobs in culturally diverse environments that allow cultural differences to be overcome. Cultural Intelligence is a “signpost” to understanding the norms adopted in a different culture–it helps when applying culturally specific rules of behaviour to situations that require them. It is not about forcing oneself into an artificial imitation of behaviours and attitudes; it is about adjusting one’s behaviour towards culturally diverse patients/co-workers so that they do not feel discomfort in our presence. It seems that CQS can be widely used as a tool for studying cultural intelligence. For example, CQS allows predictions to be made related to vulnerability to cultural shock and labour productivity , culturaWhen considering the findings of the present study, some limitations should be taken into account. For instance, since the CFA acceptably but not perfectly confirmed the 4-dimensional structure of the CQS (but it still bears a resemblance to this postulated structure), future studies should further address the factor structure of the CQS. At the same time, as argued above, usage of the total CQS score is still highly recommended. Importantly, the next step that needs to be taken is to examine the factor structure of the Polish version of the CQS using exploratory factorial analysis (i.e. EFA). While this exceeds the scope of the present paper, we argue that this is already one of the most important and urgent issues that need to be addressed in future studies.Second, the possible relationship between cultural intelligence and other variables  still needs to be thoroughly examined. More precisely, since cultural intelligence may be considered as an important factor for maintaining efficient social interactions with culturally and ethnically diverse people, it may also influence the labour productivity of nurses and other medical professionals; however, this assumption still needs empirical verification. There is also a need for studies that more thoroughly examine discriminant (i.e. divergent) validity by establishing the relationships between CQS scores and other tests measuring variables that should not directly affect cultural intelligence, such as general cognitive capability .Third, it is worth highlighting that all measures discussed in the present study were based on self-report, which may put some constraints on our data. As pointed out elsewhere , it may Next, while the sample of the population of healthcare professionals, medical students and student nurses were recruited from two large Universities in Poland, we are aware that there is still a need for further studies including larger sample sizes of such participants from different Universities in general, and from different regions in particular. It might also be useful to control participants’ clinical experience with and without culturally divergent clients to additionally evaluate the role of previous clinical experience in the development of cultural intelligence. What is more, cultural intelligence might also be further evaluated among different groups of professionals . Finally, one may argue that analysing the differences in the CQS between the professional cross-cultural trainers group and the non-professional participant group may not be very informative, mainly due to the small sample size of the cross-cultural trainers. Ideally, future studies should further examine the theoretical validity by using a comparable sample size of both professional cross-cultural trainers and non-professionals.Taking all these together, as is evident from the foregoing discussion, our results open up a set of intriguing questions for future research.Due to the fact that until recently Poland was a relatively homogeneous country, its inhabitants did not have to work in a culturally diverse milieu. Developing skills such as cultural intelligence was a neglected area in education, including medical education and research. Despite the possible limitations of the presented CQS research tool, it should be considered important and reliable and it can be used to assess cultural intelligence among medical professionals and students of medical majors in Poland. Importantly, it has been shown in the described studies that CQS has satisfactory psychometric properties. It has high reliability and the factor structure seems to approach the postulated one. Theoretical and criterion accuracy has been well proven; although convergence is less straightforward, it correlates well with research tools and variables such as cultural competence, cognitive closure, empathy/emphatic sensitiveness, emotional intelligence, self-esteem, personality, social desirability. Therefore, it may be argued that these factors contribute to the development of cultural intelligence. Finally, this tool can be used, e.g. before and after intercultural training of medical students, doctors, nursing educators and clinical managers, and it helps to identify areas of professional competence in which development of cultural intelligence is necessary to improve the quality of care.S1 Appendix(PDF)Click here for additional data file.S2 Appendix(XLSX)Click here for additional data file.


Cancer may influence personality in patients and survivors. However, the possible relations between the treatments that the patients have undergone and the personality in survivors are not clear. This study aimed to establish the differences in personality between a group of breast cancer survivors and a control group, and to test the predictive utility of the treatments on the personality traits in survivors. Thirty breast cancer survivors and thirty participants from the general population completed the Eysenck personality questionnaire-revised (EPQ-R) and a socio-demographic questionnaire. Survivors had lower scores on extraversion and higher scores on neuroticism than the control group, but these differences were not significant. However, differences in psychoticism were significant, with higher scores in the survivor group. Breast-conserving therapy predicted extraversion while breast reconstruction predicted psychoticism. These results suggest that the physical consequences of surgery may lead to social and psychological impairments in this group of patients. Personality is described as a way of perceiving, relating, and thinking about the environment and oneself. The concept of personality includes different traits, which can be described as relevant aspects of personality that are present in a wide range of situations and contexts, and these traits are relatively stable over time ,2, but mIn this line of research, previous data suggests that cancer patients have higher levels of neuroticism and psychoticism when compared with the general population one year after completion of treatment, probably due to work changes and high distress levels ,11. As fThe participants of this study consisted of sixty-two women who were divided into two groups. Thirty-two breast cancer survivors were invited to join the study based on the condition that they had completed their treatment. Most of the patients had received more than one treatment: mastectomy (80%), chemotherapy (73%), radiotherapy (43%), hormonal therapy (33%), breast-conserving therapy (16%), and breast reconstruction (15%). The time from the end of treatment was between one and 21 years, with an average of 8.90 years (SD = 5.89). All patients were in stages I–III and free of metastases or relapse. The average age was 58.70 years (SD = 7.77). Ultimately, thirty breast cancer survivors agreed to participate in the study. For the control group, thirty women were chosen who had not experienced any type of cancer; their average age was 54.96 years (SD = 11.92).T scores, from which the results are interpreted. T scores are classified as follows: 1–35 Very Low, 36–45 Low, 46–55 Average, 56–65 High, and 66–99 Very High. High scores indicate a tendency to possess the personality trait represented by each subscale. Extraversion represents sociability and liveliness; neuroticism represents emotional instability and anxiety; psychoticism indicates aggressiveness, coldness, and egocentricity, and sincerity/compliance is represented by acceptance of social norms. The reliability of the different scales is adequate in the Spanish population: Extraversion (α = 0.80), Neuroticism (α = 0.86), Psychoticism (α = 0.71), Sincerity/Compliance (α = 0.77) [The participants completed the full Spanish version of the Eysenck Personality Questionnaire-Revised (EPQ-R) . This qu = 0.77) . FurtherWe contacted the association against cancer in Cordoba (Spain) asking for permission to conduct the study. After receiving the ethical committee’s approval, professionals of the association were asked to provide participants meeting the criteria. When interested participants were identified, the association provided our contact number so that they could make an appointment. Thirty-two patients were invited to participate. Two declined the invitation; the reason cited in both cases was: “I don’t want to remember the cancer”. Thirty volunteers from the same association were invited to participate as controls and all of them agreed to participate. Both groups were provided with a written informed consent form which provided information regarding the objectives of the study and outlined the confidentiality of the results. All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of the Spanish Association Against Cancer.χ2 and independent samples t-test. Furthermore, we tried to find differences between the groups in personality scores using t-test. Finally, a hierarchical multiple regression analysis was performed for neuroticism and extraversion dimensions, with age in the first block using forced entry and the treatments in the second block using a stepwise method, as these personality dimensions are sensitive to change over time [p < 0.05.To test the differences between the groups in sociodemographic variables, we applied ver time . Concernχ2  = 10.72, p = 0.005). Extraversion and neuroticism scores were at average levels in both groups; survivors showed lower levels of extraversion and higher levels of neuroticism but with no significant differences. Psychoticism and sincerity/compliance were in the high category in the survivors group, and sincerity/compliance was in the high category in the control group. For the remaining dimensions, all scores were in the average range in both groups. Statistical differences were only observed in psychoticism , breast-conserving therapy explains more than 30% of the variance on extraversion (ΔR2 = 0.312). Additionally, breast reconstruction explained 29% of the variance of psychoticism scores  on the personality dimensions assessed. Our results showed that, after controlling for age (ores see . Concernr(30) = 0.57, p < 0.001).Finally, in the socio-demographic variables, only age was correlated with sincerity/compliance in survivors (Personality in cancer survivors has been related to key aspects of survival such as depression, quality of life, and fatigue ,6,7,8. HThere were several limitations of this research. Firstly, some patients received more than one type of medical treatment and there may have been an interaction effect between them, which might hamper the interpretation of the results. Future research should consider this limitation and try to obtain a sample of participants who have been subjected to a single treatment condition. Secondly, the sample size needs to be expanded to ensure the generalization of results in this group of patients. Finally, the results obtained must be confirmed using longitudinal studies and with a baseline evaluation of personality scores in patients.Our study, according to previous data, confirms that the differences between personality traits of survivors and the general population are significant. However, the way in which cancer diagnosis and treatment can affect personality traits remains unclear. Further research explaining these problems are needed. These results can be helpful in preventing personality and behavioral changes in cancer survivors by helping them to implement preventive psychosocial strategies.


Background and Objectives: Relative energy deficiency in sport (RED-S) has been introduced as a broad-spectrum syndrome leading to possible dysfunction in numerous physiological systems, driven primarily by low energy availability (EA). Research in females has identified specific EA cut-points indicative of risk level for developing physiological and performance disturbances. Cut-points in males have yet to be evaluated. This study examined the prevalence of low EA in competitive (non-elite), recreationally trained (CRT) male endurance athletes. Materials and Methods: Subjects were 108 CRT  male endurance athletes  who completed a descriptive survey online via Qualtrics® and returned 3 day diet and exercise training records. EA was calculated from returned surveys and training records. Resting metabolic rate (RMR) and lean body mass (LBM) were estimated from self-reported survey data. Prevalence of risk group was categorized based on the female cut-points: At risk (AR) ≤30 kcal/kg LBM, moderate risk (MR) = 30–45 kcal/kg LBM, or no risk (NR) ≥45 kcal/kg LBM. Results: In this sample, 47.2% (n = 51) were classified as AR, 33.3% (n = 36) as MR, and 19.4% (n = 21) as NR for low EA. Cyclists had lower EA  than runners  and all other sport categories . Conclusions: The findings indicate this sample had a high prevalence of risk for low EA, at 47.2%. Only 19.4% of participants were at no risk, meaning ~80% of participants were at some degree of risk of experiencing low EA. Cyclists were at greater risk in this cohort of low EA, although why this occurred was unclear and is in need of further investigation. Future research should address whether the current female cut-points for low EA are appropriate for use in male populations. Relative energy deficiency in sport (RED-S) was identified in 2014 as a broad-spectrum syndrome leading to possible dysfunction in numerous physiological systems, driven primarily by the development of low energy availability (EA) , but theLow EA risk is thought to be greater in aesthetic , weight-sensitive  and endurance-based  sports than in team or ball-based sports  . The ratExtensive research in females has identified low EA cut-points indicative of risk level for the development of physiological and performance disturbances. These cut-points are: at risk (AR) ≤30 kcal/kg lean body mass (LBM), moderate risk (MR) 30–45 kcal/kg LBM, and no risk (NR) ≥45 kcal/kg LBM . WhetherMost individuals participating in sport are not at an elite level, but tend to be more health-focused and recreationally inclined with their exercise ,13. To tTherefore, the purpose of this study was to investigate the prevalence of low EA in competitive (non-elite), recreationally trained male endurance athletes using an epidemiological survey approach. The survey was distributed to competitive, recreational exercise training groups in North America who were registered members of USA Track and Field, USA Cycling, and USA Triathlon, as well as comparable sport collegiate clubs.To investigate the prevalence of low EA by risk category  a cross-sectional design including an online survey with diet and exercise training logs was implemented. This study was reviewed for all methods, procedures, and recruitment techniques by the Office of Human Research Ethics at the University of North Carolina, which granted approval for its implementation . The purpose was explained to and informed consent was obtained from the participants as they completed the initial two pages of the survey, which also notified them of the inclusion/exclusion criteria and the total study requirements and expectations.The population for this study consisted of competitive, recreationally trained male endurance athletes. Participants were recruited from active running, cycling, and triathlon clubs across the United States. Inclusion criteria included exercise training for at least 10 h per week and currently training for a specific endurance event . Individ® with an anonymous weblink. At the end of the survey, participants were able to request that an individualized report be emailed to them.The current survey was adapted from the previously validated Community Health Activities Model Program for Seniors (CHAMPS) physical activity questionnaire with guidance from a content expert . Consult® page was also created to share the link, along with dissemination through Twitter®. Confirmation of distribution to club team members was rare, and subsequent emails from the researchers requesting the number of team members provided few responses. While some response was received regarding roster numbers from organizations, it is impossible to accurately extrapolate the few numbers received to the potential number of overall participates contacted. Confirmed team numbers ranged from 6 to over 400 members. The recruitment email detailed the purpose of the study and included expectations of participants and link to the survey. Participants were made aware they would need to provide a personal email to receive the diet and exercise training logs. They could either return the logs through the Qualtrics® survey platform or email the principal investigator (PI) directly.Emails were sent to 22 cycling, 116 triathlon, 158 running, and 118 club teams registered with USA Track & Field, USA Cycling, and USA Triathlon, as well as similar sports collegiate clubs across the United States . Team/club contacts were asked to send the information and link to their club membership, specifically the males. A Facebookn = 219) of consented participants completed the survey and subsequently received the diet and training record information. Of these, 49.3% (n = 108) of participants who completed the survey also completed the additional study activities by returning the requested diet and training records (see the following section). Only participants completing the entire survey  and returning the diet and training records were included in the analysis for this study.A total of 396 individuals responded, with consent provided by 285 (72.0%) participants. Of these, 76.8%  and decrease the respondent burden. The most questions a respondent would have encountered was 38 of the 49 total questions. The survey included 15 pages with no more than four questions per page. The average time to complete the survey was approximately 16 min. Upon completion of the survey, participants were sent the diet and exercise training record forms that had been introduced before consent.The descriptive survey was open from 1 February 2017, to 1 February 2018, and could be accessed through the QualtricsUpon completion of the survey, participants received an automatic email providing further details on how to record their three days (one weekend day and two weekdays) of dietary intake and exercise training, used by investigators to assess EI and EEE, respectively. Directions for measurement and recording food along with guidance on portion size was provided  along with the diet record forms to complete. Food items on records were analyzed using a nutritional analysis system  to determine total macronutrient (not reported herein) and subsequent EI per day .Instructions for quantifying exercise training sessions were included along with the forms to record on. Relative to exercise sessions, assessment variables captured included: Exercise mode , duration (minutes per day), and intensity of daily exercise (ratings of perceived exertion (RPE); guidance was provided on how to use the RPE scale), heart rate (applicable to those participants that used heart rate monitors) and type of training session . Exercise energy expenditure (EEE) was calculated using the Compendium of Physical Activity , using tParticipants were encouraged to contact the PI by email or in person if they had questions about how to provide proper diet/training information. Furthermore, once submitted, all diet/training records were reviewed by the PI and if any anomalies were noted, the participant was contacted to clarify issues.Information collected from the diet and exercise training records was utilized to estimate measures of EA. Energy availability was calculated as ,9:EA =  provided the details used to calculate eLBM  and estiOnly fully completed, questionnaires were included in this analysis. Prevalence, the primary outcome of the study, was determined by the percentage of participants in each EA risk category. Additionally, ANOVA and, where appropriate, t-tests were conducted as secondary analysis to investigate mean (±SD) differences in physical and training characteristics, modes of exercise training, and effect of injury-induced exercise training breaks between EA risk groups  . If significant F-ratios were detected in the ANOVAs, Tukey’s post hoc procedures were utilized to determine specific mean differences. Alpha level for statistical significance was set a priori at ≤0.05.In total, 219 individuals completed the survey; however, only 108 participants completed all aspects of the study . Chi-square analyses were conducted to determine whether any variable might explain why some individuals did not return all study components. There were no meaningful differences to explain the lack of completion, and these data have not been reported.F2.105 = 3.181, p = 0.023).A summary of the physical and training characteristics for participants is presented in n = 51; 95% CI ) were classified AR, 33.3% ) as MR, and 19.4% ) as NR for low EA. Actual mean (± standard deviation (SD)) EA values  are shown in F2.105 = 152.443, p < 0.001; all differing from one another).As noted, prevalence for this study is categorized by EA risk status: (1) AR: EA ≤ 30 kcal/kg eLBM; (2) MR: EA 30—45 kcal/kg eLBM; and (3) NR: EA ≥ 45 kcal/kg eLBM. Based upon these criteria, within this sample of competitive, recreationally trained male endurance athletes, 47.2% ; exercise energy expenditure (EEE)) and estimated (lean body mass (eLBM) and resting metabolic rate (eRMR)) for the total sample can be found in F2.105 = 4.089, p = 0.019). Post hoc analysis indicated that cyclists demonstrated significantly lower EA  compared to runners  and the others category .Energy availability risk status differed significantly by primary training mode . However, and most importantly, within each specific risk category, the EA was unaffected by the injury-induced training breaks .Relative to exercise training, the risk groups did not differ for hours per week and years of training (n = 47). Categories of supplements consumed are shown in F1.106 = 1.586, p = 0.211).At least one nutritional supplement was consumed by 43.5% of participants  and MR (33.3%) groups, approximately 80% of the participants in this study were at some level of risk for low EA. This finding implies that low EA may have a greater prevalence among male competitive, recreational endurance athletes than previously considered. That is, low EA is not restricted only to elite male athletes engaged in exercise training.The majority of EA research has been conducted in female populations. As RED-S gains attention in the scientific community, more research is now addressing male athletes and the need to determine the severity of this issue and how best to prevent health and performance detriments. However, the number of male-based studies is limited, and, for that reason, findings from both sexes are addressed here.n = 49) of participants were categorized as being at risk of low EA. It is important to point out some differences between this and the current study. The female participants were not competitively training, with eligibility requiring they meet the American College of Sports Medicine exercise guidelines [The current study’s findings are in line with the first study of prevalence for low EA in female recreational athletes, conducted by Slater et al. . These iidelines , classifidelines . The EA idelines , insteadidelines ,27, giveidelines . Heikuran = 10) in female runners and triathletes found that all of them had EA < 30 kcal/kg LBM, regardless of eumenorrheic  or amenorrheic  status [In a study comparing elite endurance females with and without menstrual dysfunction, both groups identified a majority of athletes with EA < 30 kcal/kg LBM, 67% and 56%, respectively . Similarn = 167) had EA < 30 kcal/kg LBM. When separated by sport, the male (n = 22) and female (n = 18) endurance athletes had average EA levels of 26.9 ± 11.4 kcal/kg LBM and 36.2 ± 14 kcal/kg LBM, respectively. An investigation into the nutritional behaviors of professional jockeys, a unique population, identified an EA of 0.8 ± 12 kcal/kg LBM on race days. With an average of at least three race days per week, the authors thought it is unlikely the jockeys could make up the caloric deficit on rest days to remain in a balanced state, but rest day EA was not measured [While this was one of the first studies to focus exclusively on a male population  and prevalence of risk for low EA, several studies have included both females and males. For example, Viner et al. studied cyclists  who had their EA measured during pre-season, competition, and off-season. During each of the time points, the prevalence of low EA was never below 70% and, interestingly, was highest, at 90%, during the off-season [However, not all studies have agreed with such a high prevalence of low EA occurrence. Hoch et al.  found coThe differences in EA risk prevalence might be explained by several factors. For example, the prevalence for low EA could be dependent on age, sex, sport category, level of expertise , and perhaps the measurement of low EA. Unfortunately, the lowest prevalence in the reviewed studies was still 25% of participants. That is, at least one in four athletes is at some level of risk for low EA. This finding indicates a need to educate athletes about energy availability and the importance of maintaining adequate levels of food intake.To remain consistent with the majority of current literature, the recognized female cut-points of <30 kcal/kg LBM, 30–45 kcal/kg LBM, and ≥45 kcal/kg LBM were utilized in this study. In doing this, we were aware that there is a lack of literature confirming the use of the female cut-points as appropriate in male populations. However, to our knowledge, no literature has identified appropriate EA level cut-points that should be utilized in males.Some researchers have suggested that cut-points should be lower in men due to reduced energy demand in the reproductive systems of males versus females . Still, Factors such as nutritional supplementation use breaks in training due to injury and mode of training all have the potential to moderate the current prevalence findings. This was not the case, however, which suggests that long-term exercise training and dietary behavior were driving factors in the energy availability of the participants. These lacks of effect also support the notion that, even though the duration of observation of the participants was relatively short in this study, the findings seem reflective of their real-life practices.n = 109) can be been found in the female EA literature [As a prevalence study, the present sample size was relatively small. However, the demands of 3 day diet and training records in addition to the online survey likely caused substantial participant burden. Comparable prevalence size . We feel, however, since the actual physical characteristics from which BMI is calculated were not significantly different in and of themselves, this points to the BMI differences perhaps being a statistical anomaly. Furthermore, in the energy calculations body weight (mass) was utilized and not BMI; as such we did not consider this occurrence of the BMI difference to be a critical issue.We recognize these prior points are limitations in our data; however, this project was designed as a medical epidemiology study employing a survey questionnaire. Our approach is commonly used by practitioners in the field , and this real-world pragmatic aspect to our study is a strength that increases the utility of our findings . Nonetheless, all questionnaires used in research have issues of validity and precision in the measurements, and our study was no different. We encourage researchers who pursue this topic moving forward to incorporate laboratory-based assessments to more accurately address parameters and eliminate some of these limitations, and in so doing, corroborate or refute our findings.Finally, it should be noted that the participants in this study were competitive, recreational athletes, not elite, national-level athletes. While they were competitive in their sport, it was not their livelihood, but rather an important aspect of their lives. The generalizability of this sample, therefore, is quite broad when compared to the public-at-large, as the majority of individuals exercising are at a recreational level  and are Participants in this study had a relatively high prevalence of being at risk for low EA. Nearly one half (47.2%) of the participants were in the AR group. Only 19.4% of participants were found to have no risk of displaying low EA. This is an alarming finding, as it indicates 80% of participants were at some degree of risk of experiencing low EA. Our prevalence of participants with low EA  was in agreement with much of the literature available in women and men, although the total number of available studies on men is spare. Cyclists, in particular, were at greater risk in this cohort of low EA; why this occurred is unclear and in need of further investigation. Finally, we do note that the methodological limitations of our study design and approach necessitate that caution be used in the interpretation and translation of our results to practical application.Future research is also needed to address whether the current female cut-points are appropriate for use in male populations. Additionally, educational programs informing women and men participating in competitive, recreational endurance activities about the potential risks and warning signs of low EA are important and need to be implemented.


Introduction: Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders with complex multifactorial etiologies. Medical comorbidities are common in ASD and include functional gastrointestinal disorders (fGID), which are reported in 30–70% of patients. In this research study, we aimed to systematically assess the prevalence of gastrointestinal problems in ASD and describe their clinical correlates.Methods: In this retrospective study, we reviewed the medical records of all patients admitted to the Comprehensive Medical Program for ASD (AMITEA) at Gregorio Marañón University General Hospital from January 2012 to December 2015. All patients fulfilled the clinical criteria for ASD (DSM-IV-TR). In addition to fGID, epidemiological and clinical variables were collected at intake. Clinical and demographic features were compared among subjects with and without comorbid gastrointestinal problems.Results: The analyses included all patients with documented information about presence/absence of fGID . Ages ranged from 1 to 53 years . At least one fGID was present in 30.5% of patients, constipation being the most prevalent (47.4% of fGID patients); fGID were significantly associated with intellectual disability (ID) (p = 0.017), sleep disorders (p = 0.012), and prescription of psychopharmacological treatment (p = 0.019).Conclusions: Almost one-third of ASD patients in our sample had at least one fGID. The presence of fGID was associated with ID, sleep problems and with behavioral problems (as measured by the prescription of psychotropic drugs). This subsample of ASD patients with fGID deserves particular attention in future research projects, focusing on specific phenotypic characteristics and overlapping biological markers that may underlie both pathologies. Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterized by impairments in social communication and restricted, repetitive patterns of behavior, interests, or activities . The neuIt is widely reported that children with ASD are more likely to experience unmet medical needs compared with typically developing children . AccordiAfter years of debate about the presence of gastrointestinal (GI) symptoms in autism, there is currently a consensus to describe GI symptoms as a common comorbidity in patients with ASD even though the underlying mechanisms are largely unknown . A revieThe GI problems, most commonly reported in autism, are chronic constipation, abdominal pain with or without diarrhea, and encopresis as a consequence of constipation . FurtherBased on Roma Foundation working team, functional gastrointestinal disorders (fGIDs) are described as gut-brain interaction disorders, defined as a resulting on combination of symptoms affecting motility, hypersensitivity, immunity, and other alterations in mucose, causing an illness experience in patient's body; which are not caused by a anatomic or motility disorder .A high prevalence of sleeping problems has been found in children with ASD –22, withThere are common pathophysiological mechanisms that account for both autism and epilepsy . ASD andIt has been suggested that high medical comorbidity in ASD subjects may be due to common etiopathological factors or shared intermediate mechanisms, such as inflammation, immunity, redox status, etc. . HoweverAgainst this background, the purpose of this work was to explore fGID and associated conditions in a large sample of patients consecutively seen in a medical program for ASD subjects over a representative period of time.In this study, we specifically evaluated (1) the prevalence of fGID in a large sample of individuals with ASD quasi-representative of the population of ASD patients in the Community of Madrid and (2) the sociodemographic and clinical characteristics and comorbidities in the subgroup of ASD patients with fGID.We conducted a retrospective study reviewing clinical records of all patients admitted to the Comprehensive Medical Program for ASD (AMITEA)  at GregoAll participants fulfilled DSM-IV-TR criteria for ASD. Diagnoses were made by Child and Adolescent Psychiatrists, after a full psychiatric and developmental history, previous reports' review and observation of the child/adolescent. The Autistic Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule-Generic ADOS-G were used to support the diagnosis when clinicians deemed it necessary. When needed, ADI-R clinically trained and ADOS research trained child psychiatrists or psychologists did conduct these evaluations. All data was introduced in the electronic medical history of the Hospital at the time of intake, and electronically signed. In order to organize the information from the hospital medical history and report the data herein presented, we built a database in which patients' data were de-identified.All data were collected as part of routine care, according to a protocol completed for every new participant registered in AMITEA. Sociodemographic and clinical variables were collected systematically by attending physicians (Child and Adolescent Psychiatrists). Data collected included age, sex, ASD diagnosis, type of ASD, and presence of fGID . Specifics of the fGID, if present, were manually extracted from the electronic medical record and entered verbatim in the study database. Within variables deemed interesting with respect to gastrointestinal comorbidity, we only analyzed data that was included in the initial intake clinical history template. In this way, the data we report herein were available for all patients. GI information was categorized according to the domains in the ROME-III-R questionnaire for fGID . Other comorbidities such as epilepsy, estimated intellectual disability (ID), and sleep disorders were also compiled. Behavioral and emotional problems were recorded as part of the psychiatric history, with no standard questionnaire; therefore, prescription of psychotropic treatment was gathered as a proxy for the behavioral problems . Estimated ID was recorded as a dichotomous (yes/no) clinical variable after reviewing all the information in the medical record including psychometric tests, adaptive functioning questionnaires, and school placement and performance. The Institutional Review Board (IRB) of Gregorio Marañón University General Hospital approved the study.We used descriptive statistics to characterize the study population including demographic variables and clinical characteristics. These were compared between patients groups with and without comorbid GI problems. A logistic regression model was then used to estimate odds ratios (ORs) and explore how factors differentially distributed between patients with and without fGID in the bivariate analyses contributed to the association with fGID. Therefore, we included age, sex, intellectual disability and sleep disorder as covariates in the multivariate analysis. Statistical analyses were performed with SPSS 21 for Windows software (IBM).n = 845; 95.6%) of a total sample of 879 persons admitted in the AMITEA program during 4 years; therefore, 34 patients were excluded from analysis since data of interest were not fully completed in clinical records. Ages ranged from 1 to 53 years, with a mean age of 10.52 (SD 8.92), and 19.6% were female. Children under 5 years of age comprised 25.2% of the sample (n = 213), 43% (n = 363) were ages 5–12, 15.9% (n = 134) were adolescents ages 13–17, and 16% (n = 135) were 18 or older. Four children aged 21–23 months were included in the program (following criteria as in the moderate-to-severe concern in Toddler module of the ADOS). Per DSM-IV criteria, all patients had a diagnosis of Pervasive Developmental Disorder; most patients  had a diagnosis of Autistic Disorder, 210 (24.9%) had a diagnosis of Pervasive Developmental Disorder Not Otherwise Specified, 116 (13.7%) Asperger's Disorder, 2 patients (0.2%) had Rett's Disorder; and a small group  did not had an specified subtype in the clinical record.Our analyses included all patients with available information about presence/absence of fGID  had an fGID, constipation being the most prevalent, occurring in almost half  of the sub-sample with fGID; other symptoms identified were functional diarrhea , gastrointestinal reflux , functional abdominal pain , aerophagia , cyclic vomiting , and other fGID not specifically reported . Eighty-four patients (9.9%) of total sample were referred to a gastroenterologist for assessment, in this subgroup 75% presented fGID .Thirty percent of subjects (2 = 79.184 p = 0.015), with a similar frequency in adolescents (79.9%) and adults (79.5%).With respect to the other comorbidities explored, 34.9% of the patients had a sleep disorder, 9.2% epilepsy, and 44.3% intellectual disability. More than half of the patients in the sample (55%) were prescribed psychopharmacological treatment. Psychotropic medication was more frequently used in patients over 12 years of age (χp = 0.017).In contrast to the 30.5% of fGID in total sample, within the subsample of patients with ID, fGID was present in 34.8%, while in patients without ID, fGID was present in 65.2% (p = 0.017), as was in the sleep disorder group (p = 0.012), and the group with prescription of psychotropic drugs (p = 0.019). Other clinical variables did not differ in both groups. No differences concerning age and gender were found between groups with and without fGID.With respect to the differential sociodemographic and clinical characteristics of patients with and without fGID see . The per2 = 31.732, p < 0.001).Most patients with sleep disorders (71.8%) were on psychopharmacological treatment, while only 28.2% of patients with sleep disorders were receiving no psychotropic medication (χp = 0.015) and sleep disorder  were significantly associated with fGID. Result remained significant in the multivariate analysis when OR was adjusted for age, sex, and sleep problems; and also when OR for sleep problems when covariated by age, sex, and intellectual disability. Due to the high association between sleep disorder and psychopharmacological treatment, this last variable was not included in the regression.Exploring eventual predictors of fGID, we examined the variables associated with functional Gastrointestinal Disorders see , logistiIn this sample of 845 patients with ASD seen in a specialty care program for ASD patients in a tertiary hospital, almost a third had an fGID, constipation being the most prevalent (47%). The presence of fGID was associated with ID, sleep problems and with behavioral problems (as measured by the higher percentage of children in the ASD group with fGID treated with psychotropic drugs), but it was intellectual disability and sleep problems that stood out as the most significant associations with fGID once other variables were considered. No differences were detected in the prevalence of fGID among age groups or ASD diagnosis category.p = 0.017), the percentage could well be higher, taking into account the difficulties that ASD+ID patients may have communicating symptoms, especially if those include subjective perceptions such as pain or discomfort.In this large ASD sample, relatively representative of ASD subjects in a general population of around 6,000,000, there emerges a subgroup of patients (around 25% of the sample) characterized by GID and ID. This group of patients has concomitant associated health problems such as sleep and behavioral problems. Although parents with ID report fGID only a bit more frequently than parents of children without ID  . In sampAlthough the direction of the causal relationship between sleep problems and fGID is not known in many of the cases, early identification and treatment of GI disorders could improve sleep and help increase functionality and well-being in patients with ASD. In some cases, sleep problems clearly seem to arise from abdominal discomfort. As an example, a high percentage (40%) of some monogenic forms of autism, such as Phelan-McDermid syndrome, present a specific gastrointestinal disorder, namely gastroesophageal reflux . This isGI problems have been described in the literature in association with behavioral problems in patients with ASD , 22 and Identifying clinical phenotypes in ASD via medical comorbidities may be a promising approach for improving our understanding of the pathophysiology of subgroups of patients and optimizing therapeutic interventions . WasilewThere is considerable evidence that the gut-brain axis is involved in the etiology of autism. This is based on a number of studies focusing on permeability of the intestinal mucosa, abnormal gut development, leaky gut, and others, with different mechanisms involving different systemic processes and the intermediate mechanism, many of those pointing toward a systemic chronic pro-inflammatory status. Furthermore, for the last several years, there has been an escalating number of studies showing changes of gut microbiota in patients with ASD .We are aware that this study is subject to some limitations. Above all, it is a retrospective study, based on data recorded in medical records with only part of the clinical data potentially relevant to the topic of this study and systematically gathered. Since this is a transversal study, no data is available concerning how treatment of functional gastrointestinal symptoms could change patients' behavior. In addition, some clinical data potentially relevant for interpreting our results was not systematically recorded and could not therefore be analyzed.Despite the above limitation, our study has important strengths. The major strength is the large sample size and its particularities, making it a sample quite representative of a population of children and adults with ASD.In conclusion, a large sample of ASD patients from a tertiary hospital shows a subgroup of patients with fGID, half of them with intellectual disability and frequently with comorbid sleep problems and/or behavioral problems. This is a subgroup of patients with greater medical needs that need to be addressed, on top of their autistic core symptoms, in order to improve their well-being and consequently their adjustment.This study was conducted following the recommendations of the IRB of our institution and the Spanish Agency of Medicines and Medical Devices (AEMPS). Waiver of individual informed consent was approved by the IRB.MJP and MP were responsible for conception and design of the study. MJP, GS, CL, PH, CM, MD, and MP were responsible for the clinical interview with patients and recorded data from clinical records. MJP and GS conducted the database generation and drafted the article. MJP and MP performed statistical analysis and data interpretation. MJP, GS, CL, PH, CM, MD, and MP reviewed the manuscript, made substantial contributions to conception and data acquisition and interpretation, making modifications as appropriate to the work in progress. All authors agree with the final content of this work.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.