Background: In an ever-aging society, health care systems will be confronted with an increasing number of patients over 80 years (“the very old”). Currently, knowledge about and recommendations for delirium management are often based on studies in patients aged 60 to 65 years. It is not clear whether these findings apply to patients ≥80 years.Aim: Comparison of younger and older patients with delirium, especially regarding risk factors.Methods: In this prospective cohort study, within 1-year, 5,831 patients  with delirium were enrolled. The diagnosis of delirium was based on the Delirium Observation screening scale (DOS), Intensive Care Delirium Screening Checklist (ICDSC) and a DSM -5 construct of nursing instrument. Sociodemographic trajectories, as well as the relevant predisposing and precipitating factors for delirium, were assessed via a multiple regression analysis.Results: The very old were more commonly admitted as emergencies (OR 1.42), had a greater mortality risk (OR 1.56) and displayed fewer precipitating risk factors for the development of a delirium, although the number of diagnoses were not different (p = 0.325). Predisposing factors were sufficient almost alone for the development of delirium in patients ≥ 80 years of age; in 18–80 years of age, additional precipitating factors had to occur to make a delirium possible.Conclusion: When relevant predisposing factors for delirium are apparent, patients over 80 years of age require comparatively few or no precipitating factors to develop delirium. This finding should be taken into account at hospitalization and may allow better treatment of delirium in the future. Delirium is the most common, acute neuropsychiatric disorder manifesting in abrupt and fluctuating disorders of consciousness, attention or cognition  . The cauDespite the rise of life expectancy in industrialized countries, and as a consequence increase in health care demands of aging patients, there is a lack of evidence of the characteristics of delirium in very old patients . It is unclear to what extent the delirium of this increasing number of patients differs from that in “younger” patients (18–80 years). The short and long-term socioeconomic and medical consequences of delirium are vast : DeliriuIn addition to age, further risk factors for developing delirium can be divided into predisposing and precipitating factors –8. PrediTherefore, in this study we compared very old delirious patients, ≥80 years, with younger delirious patients between 18 and 80 years. The cut-off-value ≥80 years was chosen due to several aspects: Since in the literature a distinction is made between old and very old patients and this cut-off value is repeatedly given at 80 years of age, it seemed reasonable to follow this cut-off value. Furthermore, the rate of multimorbidity , frailtyDetect Evaluate Control Inpatient Risk factors, Prevent And Treat Hospital Acquired Deliriums, Between January 1st and December 31st 2014, a delirium detection initiative   Table 1Table 1, Since different delirium scales were used in normal wards and intensive care units, we used a set of three scales in total to measure delirium:1) The Delirium Observation Screening Scale  ,2) the Intensive Care Delirium Screening Checklist  , and3) a nursing instrument most recently validated by our group for the diagnosis of delirium, the Ergebnisorientiertes PflegeAssessment Acute-Care (ePA-AC) , 18 DSM-Given the circumstance that three different scales were used and the ePA-AC was not evaluated for delirium severity or subtype (hypoactive vs. hyperactive), we reduced the scales to whether delirium was present or not.The DOS is a 13-item scale validated to indicate delirium according to DSM-IV criteria. Items include disturbances of consciousness (1), attention (2–4), thought processes (5 and 6), orientation (7 and 8), memory (9), psychomotor behavior , and affect (12). Symptoms are rated on a scale (0–1) as not existent (0), sometimes to always existent (1), and unable to assess (-). The cut-off score for delirium is ≥3 and values were aggregated throughout recordings. This approach proved to be valid and correctly identified 91% of delirium diagnoses as determined by the consultation-liaison psychiatry service.The ICDSC is a screening instrument with eight items based on the DSM-IV criteria specifically designed for the intensive care setting with two points: Absent or present. This scale was designed for patients with limited communication abilities such as intubated patients. The items include the assessment of 1 - consciousness , 2 - orientation, 3 - hallucinations or delusions, 4 - psychomotor activity, 5 - inappropriate speech or mood, 6 - attentiveness, 7 - sleep-wake cycle disturbances and 8 - fluctuation of symptomatology. The maximum score is eight; scores of more than three indicate the presence of delirium. Each item is rated on the patient's behavior over the previous eight , 18.The ePA-AC is a nursing instrument administered daily assessing mobility, personal care and dressing, feeding, elimination, cognition and alertness, communication and interaction, sleeping, breathing, pain, pressure ulcers and wounds .On regular floors, patients ≥ 80 years were screened daily with DOS and ePA-AC. On intensive care units (ICU), ICDSC was conducted three times per day. Patients below 80 years were not routinely screened for delirium at hospital admission, but the delirium scales were applied in cases of clinical suspicion and a consultation psychiatry service was usually involved. DOS, ICDSC and ePA-AC were conducted by nursing staff and continued until remission of delirium was apparent. Nursing staff had been trained in a 4-h course with tests of achievement; In addition, literature research and eLearning were conducted. Further, the training was completed via case reports, lessons on epidemiology and characteristics of delirium, including the diagnostic criteria and approaches.p < 0.001).The chosen approach implementing the DOS, ICDSC and DSM-construct based on the ePA-AC was validated in the following manner: delirium diagnoses as determined by the gold-standard, the assessment by the consultation-liaison psychiatry service, were detected in 91%. Further, this construct was tested against the DOS and ICDSC and achieved perfect agreement . This study was approved by the ethics committee of the Canton of Zurich (KEK-ZH-Nr. 2012-0263). A waiver of informed consent was obtained from the committee. Our reporting is in line with the STROBE -statement .Data analysis, viewed in a highly simplified manner, involved two steps: (1) a descriptive description of sociodemographics and (2) a logistic regression of risk factors for delirium between the groups delirium 18–80 years vs. delirium ≥80 years. The analyses were performed with the Statistical Package for the Social Sciences (SPSS) version 25 and R statistical software version 3.5.0 for Windows.t-test and Mann-Whitney U-test, and Pearson's-χ2 test for categorical variables.Descriptive characteristics were summarized based on parametric properties using means and standard deviations or medians and interquartile ranges for continuous variables, and percentages for categorical variables. The data were tested with Shapiro-Wilk's test for distribution of normality. Inter-group differences for continuous variables were computed based on their parametric properties using Student's 2 by omitting non-contributory cluster.Then, simple logistic regressions were performed in order to determine the sociodemographic and clinical characteristics of delirium, as well as for the inclusion of medical clusters in the multiple regression analysis, with their respective odds ratios (OR) and corresponding confidence intervals (CIs). The multiple regression model was optimized with Cox-Snell's and Nagelkerke's rFor all inferential tests, two-tailed tests were chosen and the significance level alpha (α) was set at p<0.05. the delirium construct based on DSM-5 was tested on its agreement with the validated approach - with a DOS cut-off ≥3 or ICDSC≥4 - with Cohen's κ as measure of concordance. The agreement was defined as >0.80 as perfect .The sociodemographic and medical characteristics of the delirious patients as well as the corresponding differences between age groups are displayed in Table 2Sociodemographic and medical characteristics of delirious patients.The differences between groups are listed in The differences between groups are listed in p < 0.05.Only statistically significant results are reported. Factors frequently reported in the literature such as anemia, electrolyte disorder, or diabetes were analyzed, but did not reach the statistical significance level of By comparing very old patients with younger ones between 18 and 80 years we found that delirium in patients ≥80 years occurs more commonly and is characterized by a complicated course and worse prognosis . It is novel to compare delirious patients between age groups rather than non-delirious controls; hereby, the age factor can be better determined.p = 0.325), which might indicate a healthy survivor effect , which concurs with numbers reported in the literature –23. Betwr effect . Consequr effect . These wTo our knowledge, there are no studies to date that directly compare different age groups of delirium patients, especially not in patients ≥80 years.However, there are few comparative studies that have examined how the type and severity of delirium differ between children (0–17 years), adults (18–65 years) or elderly patients (66–91 years) –27. GrovFurthermore, there are studies comparing delirious patients of different specialties , but stuThe causes, manifestations and outcomes of delirium vary with age; although this may seem trivial, in this study of the very old, ≥ 80 years of age, admission mode, predisposing and precipitating factors for delirium and outcome were very different and not advantageous. The results of this study can be used as possible starting points for future management studies, as well as advanced care planning and, once again, illustrate that delirium is a common and potentially life-threatening condition.Clear strengths of this study are the overall (1) large group sizes and (2) prospective data collection and (3) extensive description of sociodemographic, medical and clinical characteristics of delirious patients. A novelty in this study is the comparison between two age groups of delirious patients, which leads to a better determination of the age factor. The differences in group sizes  can be considered problematic, potentially having led to disproportionate power in 18–80-year-olds; however, the different group sizes represent the natural demographic age distribution. In addition, the severity of diseases was not characterized, as this is difficult to statistically represent or operationalize. A major limitation of this study may represent the dichotomization of the variable age, which, while providing good contrast between groups, may also distort the results. Future studies on the variable age are necessary to further investigate this effect. The collected data is from 2014 and may not be fully generalizable due to improved delirium prevention in recent years. The administration of any medication  was not recorded, as this was not methodologically possible. Our patient population was representative for a tertiary care center, generalizability to other health care facilities is limited. Since patients > 80 years of age were routinely screened for delirium, but patients <80 years of age were not, there is a possibility that delirium is underdiagnosed in this age group, leading to biased results. Future studies are required to confirm these findings.Delirium in very old patients, i.e., those ≥ 80 years, is different from delirium in the general hospital population. The very old are at high risk for developing delirium. When relevant predisposing factors for delirium become apparent, the very old require only few or no precipitating factors for the development of delirium. This should be accounted for on admission and may allow better screening for and management of delirium in this age group in the future.Detect Evaluate Control Inpatient Risk factors, Prevent And Treat Hospital Acquired Deliriums, Between January 1st and December 31st 2014, a delirium detection initiative . The ethics committee waived the requirement of written informed consent for participation.JM analyzed clinical and diagnostic data and drafted and revised the manuscript. LB acquired clinical and diagnostic data and revised the manuscript. SF acquired clinical and diagnostic data and revised the manuscript. FH, JE, and RK analyzed clinical and diagnostic data and revised the manuscript. SB conceptualized the study, acquired and analyzed clinical and diagnostic data, and revised the manuscript. All authors contributed to the article and approved the submitted version.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.


Traditional risk factors for chronic kidney disease (CKD) include diabetes mellitus (DM), hypertension (HTN), and metabolic syndrome, which are health conditions related to obesity. We aimed to investigate which of the three obesity indices has the strongest association with CKD and to explore whether there are gender differences in these relationships in the middle-aged and elderly Taiwanese population.2. We used a multiple logistic regression model to evaluate the association between each obesity index and CKD for both genders. Further, we used the area under the receiver operating characteristic (ROC) curve (AUC) to examine the best obesity indices to predict CKD in different genders.This was a cross-sectional, community-based study. It included 400 residents  residing in a community in northern Taiwan. Each participant was asked to fill a questionnaire that collected personal information, medical history, medication use, and anthropometric measurements. The laboratory data were obtained by testing the blood and urine samples. The baseline characteristics were compared, and the obesity indices included body mass index (BMI), waist circumference (WC), and visceral adiposity index (VAI). CKD was defined as the presence of renal dysfunction  or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73mThe average age of the subjects was 64.47 ± 8.45 years, and men were significantly older. CKD was found in 31 (22.0%) males and 50 (19.3%) females. In men, there was no significant difference between the CKD and non-CKD groups among the three obesity indices. However, in women, only VAI was significantly higher in subjects with CKD  than in subjects without CKD  . The multivariate logistic regression revealed that even after adjusting for possible confounding factors, VAI was found to be an independent risk factor for CKD in women , but not in men . The AUC of VAI had a significant ability to predict CKD in women but not in men.Our results showed that among the three obesity indices, VAI had the strongest association with CKD compared to BMI and WC in women. In addition, VAI in women should be given more importance in the screening for CKD among the middle-aged and elderly Taiwanese population. Obesity is associated with several metabolic disorders and might result in increased risks of adverse health outcomes. Globally, the proportion of adults with a body mass index (BMI) of 25 or above increased from 28.8% in 1980 to 36.9% in 2013 for men and from 29.8% to 38.0% for women. The increase was observed in both developed and developing countries. The proportion of adults with overweight and obesity in Taiwan is significantly higher than that in Japan, South Korea, and other neighboring Asian countries, especially in females . AccordiThe relationship between obesity and CKD is complex and not yet fully understood. There is no consensus about which index is a better predictor for CKD. Previous studies showed BMI, as a representative of obesity, was associated with an increased risk of CKD –15. HoweFurthermore, a newer obesity index, the visceral adiposity index (VAI), was proposed by Amato and his research group in 2009. VAI is a novel sex-specific index based on WC, BMI, triglycerides, and high-density lipoprotein (HDL) and can estimate the visceral adiposity dysfunction associated with cardiometabolic risk . HoweverTherefore, this study aimed to investigate which of the three obesity indices has the strongest association with CKD and to explore whether there are gender differences in these relationships in the middle-aged and elderly Taiwanese population.2 for other confounding factors = 0.5  subjects aged 50 years of age or above and (2) subjects residing in Guishan District for half one year or more. Participants were excluded if they (1) had functional disability, (2) declined to participate or could not complete all examinations and the interview, (3) had recent cardiovascular diseases Figure 12). WC was measured at the mid-point between the lower border of the rib cage and the upper iliac crest on the mid-axillary line. Systolic BP (SBP), diastolic BP (DBP), and heart rate was checked at least twice after 5 minutes of rest on a chair. Laboratory tests included blood urea nitrogen (BUN), serum creatinine, fasting blood glucose, total cholesterol, high-density lipo-protein-cholesterol (HDL-C), low-density lipo-protein-cholesterol (LDL-C), TG, and urine albumin to creatinine ratio. Venous blood samples were collected after overnight fasting for at least 12 hours, and serum samples were used for biochemistry analysis. Urine specimens were obtained in the morning and scheduled to avoid the menstrual periods. A standardized biochemistry analyzer  was used for determination of laboratory tests. Personal history was collected by a standard interview, and the information in the structured questionnaires included smoking/drinking habits, past medical history and current medication use. Obesity was defined as a BMI ≥ 27 kg/m2 or WC ≥ 90 cm for males and ≥ 80 cm for females, according to the criteria of the Department of Health in Taiwan. HTN was defined as SBP ≧ 140 mmHg or DBP ≧ 90 mmHg, current use of antihypertensive medications, or history of HTN. The definition of HTN was based on the 2015 guidelines of the Taiwan Society of Cardiology and the Taiwan Hypertension Society for the Management of Hypertension , and heart rate were recorded. BMI was calculated as weight (kg) divided by height squared , according to the 2005 guidelines of Kidney Disease: Improving Global Outcomes (KDIGO) (2) = 175 × Creatinine (mg/dl)-1.234 × Age-0.179× 0.79 (for women)  <60 mL/min/1.73m (KDIGO) . The eGFr women) .The sample size determination was based on the G*power 3.1 software. General characteristics were expressed as mean ± standard deviation (SD) and median with inter-quartile range (IQR) for continuous variables and number (%) for categorical variables. P-values were derived from Mann-Whitney U test for continuous variables and chi-square test for categorical variables. Multivariate logistic regression models were developed to investigate the independence of obesity indices associated with CKD. We used the area under the receiver-operating characteristic curve (AUC) and 95% confidence intervals (CI) to assess the discriminatory power of each obesity index to predict the risk for CKD. All statistical analyses were performed using SPSS version 22.0 software . A p-value <0.05 was considered significant.2, while the median eGFR among men was significantly lower (p < 0.001). In addition, the proportion of subjects who were current smokers and consumed alcohol was significantly higher in men than in women. However, there was no significant difference between the two groups in terms of the past medical history, such as presence of HTN, DM, hyperlipidemia and CKD and current medication use including Chinese herb and analgesics use.A total of 400 participants aged 50 years and above were enrolled in this study. The general characteristics of the study population divided by gender are shown in Multivariate logistic regression analysis of the three obesity indices associated with the risk of CKD in men and women is shown in The main finding of this cross-sectional study was that among three different obesity indices, only VAI was significantly associated with CKD in the middle-aged and elderly female Taiwanese population. Few studies have compared the association between obesity indices and CKD, and the gender differences in this relationship. And, the predictive power of traditional measurements for chronic diseases is still debatable. To our knowledge, our study has found for the first time that among the middle-aged and elderly population, VAI had a better capability for predicting CKD compared to the traditional indices, only in women, and BMI and WC did not effectively identify the risk of CKD in both genders.Obesity is closely associated with HTN, DM, and hyperlipidemia, all of which are unfavorable factors to renal function , 11, 25.Many methods can be used to assess visceral adiposity. Electronic methods used as the gold standard, include, densitometry , magnetic resonance imaging, and computed tomography, which provide the assessment of body and visceral fat with high precision . These mAn interesting finding of our study was a gender difference in the association between CKD and obesity indices. A significant association between CKD and VAI was seen only in women by multiple logistic regression and AUC analyses. A similar finding was presented by Dai et al., who reported that VAI and lipid accumulation product index was superior to BMI, WC, and waist-to-height ratio for predicting CKD only in women in the Northeast Chinese rural population . The reaOur study had several limitations. First, the prevalence of CKD in our study was higher than that reported in a Taiwanese national sample survey 11.93%) (% (3), anIn conclusion, our analysis found that among the three obesity indices, VAI was significantly associated with the risk of CKD in women after adjusting for confounding factors. In addition, we also found that VAI showed the strongest ability for predicting CKD compared to BMI and WC only in women.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by Institutional Review Board of Chang-Gung Medical Foundation. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.J-YC planned and conceptualized the work. Data collection and analysis was performed by J-YC. I-JC wrote the original draft, and J-YC revised the draft. J-YC, L-TH, M-CL, Y-JC, and M-TT supervised the work. All authors contributed to the article and approved the submitted version.This study was supported by Chang Gung Memorial Hospital .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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


P = 0.004). Faster achievement of postoperative knee flexion to 90 degrees  and first ambulation , reduced number of postoperative complications such as postoperative orthostatic intolerance  and constipation , and reduced length of hospital stay  in the intervention group in comparison to the control group were noted. Emotional exhaustion and burnout of nurses were reduced significantly in the intervention group than in the control group . Reduced personal accomplishments in nurses were improved significantly in the intervention group when compared with the control group . We concluded that video-assisted health education may promote TKA patient recovery and reduce burnout and stress in nurses when compared with oral education. Video-assisted health education could be helpful in situation where manpower of nurse is in shortage.Emerging evidence suggests video-assisted health education being an effective way in promoting rehabilitation. The present study was aimed at evaluating the effectiveness of video-assisted health education in promoting rehabilitation training in postoperative OA patients and at comparing it with oral education. This study was a noncontemporaneous control study involving 179 patients who underwent TKA. For the intervention group, a bedside interactive system that recorded a series of educational videos showing a rehabilitation training program was established. For the control group, oral education having the same content as that in the videos for the intervention group was provided. After education, clinical outcomes such as occurrence of complications, circulating biomarkers of inflammation, and rehabilitation progress of the patients were obtained. Furthermore, job stress and burnout in nurses who participated in the present study were assessed. Results showed that C-reactive protein levels of patients were significantly lower in the intervention group than in the control group (84.54 ± 36.09 vs. 99.45 ± 31.73 mg/L,  Knee osteoarthritis (KOA) is a chronic, progressive, and recurrent joint disorder that leads to joint instability and physical disability . KOA is Elevated immune response was observed following TKA procedures. Increased immune response, systematic or localized, to acute oxidative stress and levels of cytokines after surgery was reported , 8. PostRecently, video-assisted health education, a fast and intuitive educational method, has been reported to be helpful for patients to understand health information and thus improve their acceptance and promote their rehabilitation . StudiesThe present study was conducted after approval by the Research Ethics Committee of Shandong Provincial Hospital affiliated to Shandong First Medical University (no. 2017-055) and was reported in accordance with the CONSORT 2010 statement. Written consent was obtained from each patient who participated in the study.The present study was a noncontemporaneous control study. A convenience sampling method was used for the recruitment of subjects from January 2018 to October 2019. Subjects who met the following inclusion criteria were included: (1) 18 years of age or older and (2) subjects who were diagnosed as having degenerative osteoarthritis and underwent primary TKA. The exclusion criteria were as follows: (1) having any diagnosed hip or ankle disorders, (2) having any balance disorders or ligament instability, (3) severe osteoporosis or severe cardiopulmonary diseases, or (4) ankylosing spondylitis, hemophilic arthritis, and severe deformities of the knee joint due to diseases other than KOA that could affect the results. Subjects who underwent TKA from January 2018 to December 2018 were assigned to the control group, and the patients from January 2019 to October 2019 who underwent TKA were assigned to the intervention group.Baseline information including age, gender, marital status, and education level, comorbidities, and osteoarthritis history were obtained on the day of admission. The Numerical Rating Scale (NRS) was used to evaluate pain, and the Barthel index (BI) was used to evaluate the ability of daily living.A standardized exercise plan for TKA patients was developed by the rehabilitation team in our hospital. The content of the exercise plan included ankle pump, isometric contraction, straight leg raising, and flexion knee exercises . A 3-minThe patients in the control group were provided with oral education by the trained nurses about the exercise plan shown in The time to achieve first ambulation, straight leg elevation, and knee flexion to 90 degrees was evaluated at 8:00 am, 12:00 pm, 16:00 pm, and 22:00 pm every day. Occurrence of the following postoperative complications was recorded if they were diagnosed following the criteria reported elsewhere –19: (1) Job burnout in nurses was assessed using the Maslach Burnout Inventory (MBI) before and after the intervention. MBI was compiled by Maslach and Jackson in 1986 , 21 and Job stress in nurses was evaluated using the China Nurses' Job Stressors Scale (CNSS) before and after intervention, which was compiled by Li in 1999 . Brieflyt-test and chi-squared test for continuous data and discrete data, respectively. Fisher's exact test was used in the analysis of contingency tables. A P value less than 0.05 was considered statistically significant.G∗Power 3.1 software was used for sample size estimation. Based on our pilot results, a minimal sample size of 82 was suggested to reach a power of 0.80% and a significance of 0.05. Statistical analysis was performed using IBM SPSS Statistics software . Numerical variables are expressed as the means and standard deviations (SDs) if data were normally distributed. Discrete data were expressed as frequencies or percentages. Differences between two groups were tested using the independent A total of 185 patients participated in the study. Six patients were transferred to the intensive care unit due to severe postoperative cardiopulmonary disease and thus were excluded. The mean age of the participants was 63.6 years . The ratio for female and for married was 76.5% and 96.6 %, respectively. Demographic and disease-related data of the participants are summarized in The hospitalization time and time to first ambulation, straight leg raising, and knee flexion to 90 degrees after the intervention in the video-assisted health education group were significantly shortened compared to those in the oral education group with data summarized in P = 0.243).After the intervention, constipation and postoperative orthostatic intolerance were significantly reduced. Comparisons of postoperative complications are summarized in P = 0.004 and P = 0.016, respectively).Levels of biomarkers are summarized in P = 0.002, P = 0.004, and P < 0.001, respectively).Job burnout and job stress in nurses are summarized in In this study, video-assisted health education was shown to be more useful than oral education in promoting postoperative recovery on TKA patients and reducing job burnout and job stress in nurses.Manpower shortage of nurse in the public healthcare system remains challenging, and thus, the registered nurses are under a heavy workload, which probably affects the quality of healthcare service. For example, in one survey, 51.6% of nurses believed that the main factor affecting nurses' performance of health education duties was time tension . FurtherThe condition of heavy workload increases the pressure of nurses. The application of video-assisted health education in the rehabilitation training on patients after TKA reduces repetitive explanation for questions that were commonly raised and for the inconsistent oral expressions. In this way, video-assisted health education can improve work efficiency of nurses and thus reduce their work pressure and job burnout. Besides, application of video-assisted health education can be extended to community care services, home care services, and other fields to promote rehabilitation training . Health α, IL-1β, and IL-6 and promoted the recovery of joint function. The present study enhanced the evidence for the benefits of rehabilitation training and further suggested an advantage of video-assisted health education over oral education in the training provided by nurses who had heavy workload.Oxidative stress can cause oxidative damage to various macromolecules, and it has been considered to be one of the causative factors in the pathogenesis of KOA , 3. TKA This study has some limitations. First, confounding information about KOA classification and evaluation of knee function was not obtained, which may have led to bias in the results. Second, compliance of patients was not assessed, and it probably caused response bias, which may limit the generalizability of the study results. Therefore, further studies with confounding factors better controlled and with larger sample size are warranted.Video-assisted health education may promote the recovery after total knee arthroplasty and reduce job burnout and job stress in nurses when compared with classical oral education. Video-assisted health education could be helpful in situation where manpower of nurse is in shortage.


Frequent communication with their own community, higher levels of school education, and having a job were determinants of higher self-esteem in persons with disabilities. We suggest the importance of an active inclusive reconstruction program to support persons with disabilities in local municipalities affected by armed conflict in developing countries.This cross-sectional study explored the association between self-esteem and social participation of persons with disabilities living in two municipalities affected by armed conflict in Colombia. We studied the socioeconomic status, communication level, social participation, and self-esteem of the participants. The Rosenberg Self-Esteem Scale (RSES) was used to evaluate the level of self-esteem. We performed bivariate analysis and multiple regression analysis to identify the determinants of higher self-esteem in the target populations. In total, there were 579 participants in the study. The mean RSES score was 28.8 (SD = 4.5). Self-esteem was associated with monthly household income (β = 0.45,  Since World War II, the world has faced many types of armed conflict, colonial wars, wars for national liberation, cold war-related struggles, religious conflicts, political conflicts, and more . BetweenThe Republic of Colombia (Colombia) is known as one of the countries affected by armed conflict, which has continued over five decades between the government armed forces, anti-government guerrillas, and paramilitaries . The intThe government has estimated that approximately 6.4% of the total population in Colombia are persons with disabilities . FurtherRosenberg defined that self-esteem is a positive or negative attitude an individual has toward themselves . A previThe purposes of this study were as follows: (1) describe the socioeconomic status, social participation, and self-esteem of persons with disabilities affected by armed conflict in rural Colombia and (2) identify the determinants of higher self-esteem.Colombian Government Unit for comprehensive attention and reparation to victims of internal conflict and Japan International Cooperation Agency (JICA) implemented the Project for Social Inclusion of Conflict Victims with Disabilities (hereinafter referred to as “the Project”) in two local municipalities; Granada, Antioquia and El Carmen de Chucurí, Santander were the first pilot sites . The ProThe baseline survey included information on the current life conditions, socioeconomic status, activities of daily living, and level of participation in society for victims and non-victims with disabilities. The survey was conducted from September to November 2015.The participants in the Project’s baseline survey were all persons with disabilities aged 0–80 years residing in the two Project sites. They were chosen from the list of persons with disabilities that the local governments had and from the information of the people in the local district. Staff from the Project and local government contacted participants by mobile phone to schedule a date for administering the questionnaire in a face-to-face interview. A total of 925 persons with disabilities  participated in the survey after obtaining informed consent. We excluded 142 persons with disabilities aged 0–17 years from the analyses because a family member participated in the interview on behalf of the child. Consequently, the responses to the items would not be those of the child. In addition, we excluded 204 participants aged 18 and older who did not respond to items about self-esteem. The final sample consisted of 579 persons with disabilities aged 18–80 years .This was a cross-sectional study using a structured questionnaire with face-to-face interviews conducted by trained local interviewers. The project implemented data collection in two local municipalities affected by armed conflict.To measure the level of self-esteem, we used the Rosenberg Self-Esteem Scale (RSES). The RSES was developed by Rosenberg  to assesRegarding socioeconomic status, we selected 10 items from the responses to the structured questionnaire: age, sex, monthly household income, education level, reading ability (Yes/No), writing ability (Yes/No), residential area , current work (Yes/No), type of disability, and victim of armed conflict (Yes/No). Type of disability was self-reported because there was no documentation or certification of a medical diagnosis indicating type of disability. Participants chose from six options on the questionnaire: physical disability, hearing disability, visual disability, intellectual disability, psychosocial disability, and do not know. If they chose multiple options, they were considered as multiple disabilities. There were five options for monthly household income: none, low, lower middle, upper middle, and high. High income was more than the minimum wage in 2015 in Colombia  ,28. EducTo analyze social participation, we chose four items from the responses to the structured questionnaire: frequency of communication with family members, frequency of communication with neighbors or friends, going out from home (Yes/No), and level of participation in community organization activities (Yes/No). Frequency of communication with family members and with neighbors or friends had three answers: every day, some days a week, occasionally or not communicate  was used for all statistical analyses.First, we calculated descriptive statistics for all the variables of interest in the study. Descriptive statistics included means and standard deviations for continuous variables, and frequencies and percentages for categorical variables. Second, means and standard deviations of the RSES scores were calculated for each independent variable category. Age was divided into three categories: under 40 years, 40–60 years, and over 60 years. To examine the raw associations of socioeconomic status and other possible factors with self-esteem, we conducted a univariate regression analysis. Then, we performed multiple regression analysis including all socioeconomic and social participation variables to identify determinants of the higher RSES scores using the stepwise variable selection method (inclusion criteria ≤ 0.20 and exclusion criteria > 0.20). Statistical significance was tested with a two-tailed test of significance at This study analyzed the data from the reports published by the Project for Social Inclusion of Conflict Victims with Disabilities, Colombia . We adop= 4.5) for all participants. The variables related to monthly income (p = 0.002), education level (p < 0.001), including reading ability (p = 0.008) and writing ability (p = 0.002), living in urban areas (p = 0.011), and social participation, such as having a job (p = 0.009), frequent communication with neighbors or friends (p < 0.001), frequently going outside (p < 0.001), and participation in community organization activities in the last six months (p = 0.002) were significantly associated with the RSES scores. This revealed that persons with disabilities with a higher education level and frequency of communication with neighbors or friends were more likely to have higher self-esteem.2 = 0.110): sex, monthly household income, education level, living area, currently working, victim of armed conflict, type of disability, frequency of communication with neighbors or friends, and usual participation in community organization activities.The results of the stepwise multiple regression analysis are shown in p = 0.028), education level , currently working , type of disability , frequency of communication with neighbors or friends , and participation in community organization activities .The significant variables were monthly household income . This result coincided with a previous study showing that persons with disabilities have lower self-esteem than peers without disabilities [A previous study reported that the mean RSES of the general Colombian population without any disabilities was 34.2 . In the bilities . RSES scbilities . Comparebilities . Furtherbilities . A largeIn the present study, self-esteem was also associated with the following factors: more communication with neighbors and friends, active participation in the community organization, having a job, and monthly household income. These findings are similar to those of previous studies ,16,20,22Despite these limitations, the present study findings are worthy and valuable for the following reasons. In Colombia, there have been no full surveys focusing on persons with disabilities in rural areas, especially in conflict-affected areas. Moreover, no study has directly interviewed a large number of persons with disabilities. This study focused on a normally hidden population that is hard to access. In particular, people with disabilities living in local municipalities affected by armed conflict are difficult to invite to field-based studies. Furthermore, the data were collected from persons with various types of disability who could answer the questionnaire by themselves. We believe that these findings from Colombia could contribute to disseminating useful information that social participation is important to improve the self-esteem of persons with disabilities living in similar conditions. Furthermore, the findings suggest the importance of promoting a national reconstruction program for social inclusion (involving persons with disabilities) in Colombia, emphasized in the Goal 16 of the Sustainable Development Goals (SDGs), which is to promote a just, peaceful, and inclusive society .This study focused on persons with various types of disability living in local municipalities affected by armed conflict in Colombia. Frequent communication in one’s own community, higher education, and having a job were identified as determinants of higher self-esteem in persons with disabilities in local municipalities affected by armed conflict. Promoting inclusive reconstruction programs to support persons with disabilities affected by armed conflict is extremely crucial in global health issues. In particular, this study strongly exhibited that more social inclusion of people with disabilities may promote global development, global peace, and order. This is consistent with Goal 16 of the SDGs, which is to promote a just, peaceful, and inclusive society. As a next step, it would be important to evaluate the effectiveness of programs and activities developed as a result of the findings and the extent to which Goal 16 is being achieved.


To assess the psychometric properties of the Dutch-Flemish Patient-Reported Outcome Measurement Information System Scale v1.2 – Global Health (PROMIS-GH).p < 0.001), internal consistency , precision , measurement invariance , and cross-cultural validity  of its subscales, composed of four items each, Global Mental Health (GMH) and Global Physical Health (GPH), were assessed.The PROMIS-GH  was administered to 4370 persons from the Dutch general population. Unidimensionality , local independence , monotonicity (H > 0.30), model fit with the Graded Response Model  and GPH . Local independence, monotonicity, GRM model fit, internal consistency, precision and cross-cultural validity were supported. However, Global10  showed misfit on the GMH subscale, while Global08 (fatigue) presented DIF for age.The psychometric properties of the PROMIS-GH in the Dutch population were considered acceptable. Sufficient local independence, monotonicity, GRM fit, internal consistency, measurement invariance and cross-cultural validity were found. If future studies find similar results, structural validity of the GMH could be enhanced by improving or replacing Global10 .The online version contains supplementary material available at 10.1186/s12955-021-01855-0. Health-related quality of life (HRQoL) refers to the ‘‘physical, psychological, and social domains of health, seen as distinct areas that are influenced by a person’s experiences, beliefs, expectations, and perceptions’’ . HRQoL mThe Patient-Reported Outcomes Measurement Information System (PROMIS®) initiative  was estaTo our knowledge, no studies assessed the psychometric properties of the PROMIS-GH in a general population sample outside the US . Also, nParticipants were recruited from an existing internet panel of the Dutch general population by a data collection company . The panel was provided by Global Market Insite (GMI). Panellists were recruited mainly through telephone and ads and banners on websites. Informed consent to become a panellist is ensured by GMI. For this particular study, panellists were recruited in 4 waves by an invitation from the panel host. Panelists receive “panel points” by participating in studies, which they can collect at regular intervals to receive a small amount of money, or—more often—a web voucher. For our study, panelists were recruited by an invitation from the panel host. The invitation mentioned the topic and length of the survey. By voluntarily responding to the invitation for this survey, panelists provided informed consent to participate in the study. All data collected were strictly anonymous, as the data collection company did not know the identity of the respondents, and the panel provider did not know what panelists responded to the survey.www.cbs.nl) (maximum of 2.5% deviation) with respect to distribution of age , gender, education , region , and ethnicity .No information was collected about the response rate. The Medical Ethics Review Committee of VU University Medical Center confirmed that the Medical Research Involving Human Subjects Act (WMO) does not apply to this study and that an official approval of this study by the committee was not required; the reason for this is that the test subjects are not subjected to any action and they are not imposed a mode of conduct, as laid down in the WMO.The sample needed to be representative of the Dutch general population, according to data from Statistics Netherlands in 2016 (www.polimetrix.com).In addition, we used data from the US PROMIS Wave 1 sample, obtained from the Health Measures Dataverse , 18, to This study was part of a larger initiative to assess the psychometric properties of eight full Dutch-Flemish PROMIS item banks and the PROMIS-GH in the Dutch general population , 20. Fouwww.healthmeasures.net [The v1.2 PROMIS-GH consists of ten items . Each itures.net , after aDescriptive statistics were used to describe the socio-demographic characteristics of the sample and the distributions of the items. Table It is legitimate to calculate IRT-based scores. This requires, from a psychometric perspective, that items meet the assumptions of an IRT-model , and fit the underlying IRT-model . To stuFrom a user perspective, it is also important that the measure:Is able to discriminate between different levels of the construct (or latent variable or trait) and, as a consequence, is able to measure differences between persons or change within persons over time. This requires, from a psychometric perspective, that all item discrimination indexes, assessed using IRT modeling, are satisfactory.Covers the relevant range of the construct, that is the range where future respondents  are supposed to be located with respect to their health status. This requires, from a psychometric perspective, that the range of the item difficulties is acceptable. The range of item difficulties was assessed using IRT-modeling.Is able to measure the total sample of respondents and respondents with different health states  reliably (or precisely). This requires, from a psychometric perspective, good internal consistency and precision. Internal consistency was studied within the Classical Theory Test framework and precision was assessed by plotting Test Information Curves (TICs), Item Information Curves (IICs) and Standard Error Curves.Functions in the same way in different (sub)groups.This requires, from a psychometric perspective, measurement invariance  between relevant (sub)groups.In this study, we explored DIF for sex , age , region , educational level , and ethnicity . DIF analyses were performed using an ordinal logistic regression framework.Can be used, for international studies, to compare cultural/language groups.This requires, from a psychometric perspective, cross-cultural validity (or absence of DIF) between these groups. In this study, we compared the language groups Dutch and US English, using data from the US PROMIS Wave 1 sample , 18. TheFrom a user perspective, for an IRT-derived measure, it is crucial to know whether:The PROMIS-GH was completed by 4370 Dutch adults from the general population (in 4 samples). Table Table Dimensionality. The CFA on the entire PROMIS-GH highlighted some departure from the two-factor structure . The Exploratory Bifactor Analysis did not converge for GMH without restricting the number of group factors since loadings > 1 were present. After fixing the number of group factors to 2 and, consequently, constraining the general factor loadings to avoid specifying an under-identified model, the model converged. The Explained Common Variance (ECV) revealed the presence of a strong general factor (ECV = 0.80) whereas the Omega-Hierarchical (ωH) did not met the criterion (ωH = 0.75). Similarly, the Exploratory Bifactor Analysis performed on the GPH revealed that the general factor explained most of the common variance (ECV = 0.71) whereas the ωH did not met the criterion (ωH = 0.65) (Table p < 0.001) for GMH and GPH, respectively, and Pearson’s correlation coefficients between the GMH and GPH were 0.561 and 0.562 (p < 0.001) for raw and IRT-based scores, respectively.Local dependence. No local dependence was detected  (Table 0) Table .Monotonicity. The scalability coefficients for the scales were high  (Table i > 0.30) (Table H) Table . The sca0) Table . Global0IRT-model fit. Both subscales fitted the GRM model . However, all items displayed misfit to the GRM model (p < 0.0001) . The ten IRT-analyses showed satisfactory item fit statistics for all items (p ≥ 0.001) except for Global02 , Global04 , and Global05   and Global10   for GMH, and Global07 (pain intensity) (p < 0.001 in Sample#5) for GPH , and GPH (0.78). Alpha values after item deletion decreased for all items, except forGlobal10 . Finally, corrected item-to-total correlations were satisfactory for all items of both subscales (rs > 0.40) , with younger participants being more likely to endorse lower response categories than older participants at the same level of fatigue. However, after visual inspection of the Test Characteristic Curves per group, it was concluded that the impact of DIF on the total score was negligible  showed misfit to the IRT-model in six out of 10 (60%) subsamples. Moreover Global10  had the lowest item-scale correlation, was the only item that would increase Cronbach’s alpha if deleted, had the lowest discrimination parameter and lowest information value. Sufficient internal consistency, measurement invariance  and cross-cultural validity were found.The analysis of the dimensionality of the PROMIS-GH showed that considering the GMH and the GPH as unidimensional scales might be the most appropriate strategy. The use of a multidimensional model was ruled out by our 2-factor model, the results of which are comparable to the 2-factor model results of Hays et al.  and KatzAlthough the global fit to the GRM model was adequate, some items displayed lack of fit after adjusting for Type I errors. The misfit of items Global07, Global02, Global04 and Global05, however, was present in no more than 3 random subsamples, and visual inspection of their empirical plots revealed only slight deviations from the expected item response functions. On the contrary, item-level misfit of Global10 was apparent in most of the random subsamples and by visual inspection of its empirical plot. Lack of fit to the GRM model might result in biased ability and item parameters estimates . TherefoIt is possible that these subscales do not perfectly fit the IRT-model, because they do not measure a real psychometric construct . This has an impact on the requirement of unidimensionality and calculation and interpretation of scores. A formative model means that measured variables are considered to be the cause of the construct ; on the other hand, in the reflective model, the indicators are considered to be caused by that construct  , 36. In i = 0.525). Therefore, in light of these results, we do not suggest a modification of the Global06 response categories.The results of the monotonicity analysis showed that no items presented disordered thresholds. Upon a visual inspection of the ICCs, only the Global06 showed a short interval in the thresholds between 3 (Moderately) and 4 (Mostly) scores, and between 4 (Mostly) and 5 (Completely) scores. This result may be due to the content of the response options; indeed, Global06 is the only item that has these response categories. Our subjects may had difficulty discriminating the fine differences between these three categories. However, the findings of the Mokken scale analysis confirmed that Global06 presented monotonicity (HOur results show that the item slope parameters (discriminative ability) of each item is higher than the cut-off of 1.0; this means that each item is able to distinguish different levels of latent traits that it intends to measure. On the other hand, there is no range of interpretations for the difficulties of the items; the range should be as wide as possible; our results showed a wide range for both GMH and GPH which suggests that each subscale is able to measure a large range of the latent variable it intends to measure.Most of PROMIS-GH items function in the same way across different groups, as indicated by measurement invariance, which means that the same IRT-model can be applied to compare different groups of patients in terms of gender, educational level and ethnicity and to compare US versus Dutch patients. Our results are similar to those of the previous literature. A recent study  found noOur results showed that Global10  showed problems with item fit and precision,. Similar results were reported by Hays et al.  who founThe strength of this study concerns the large number of enrolled participants answering the PROMIS-GH. However, this study also has limitations that deserve to be discussed. Unfortunately, response rate information is not available. Moreover, we studied subjects from the general population that may include not many patients seen in daily clinical practice, although it seems fair to assume that the general population also includes people with different diseases. Also, our analyses were conducted using a convenience sample of Dutch–speaking adults; this issue could limit the generalizability of the results to other contexts. Since this is one of the most commonly used PROMIS measures, recommended by ICHOM to be used in clinical practice, future studies in clinical populations and other countries are recommended. Finally, in order to study the item ability to discriminate between different levels of the construct, and, consequently, its ability to measure change within person over time, we assessed the item discrimination; test–retest reliability and responsiveness are more relevant to measure change over time; therefore, future researches should assess these psychometric properties.Our results and those of other articles , 14 dispOur findings showed that the psychometric properties of the PROMIS-GH in a large Dutch sample are acceptable. Sufficient local independence, monotonicity, GRM fit, internal consistency, measurement invariance and cross-cultural validity were found. However, that Global10 , showed problems with item fit and precision. If future studies confirm our results, the measurement properties of GMH could be improved by modifying or replacing Global10.Additional file 1: Figure S1. Detail of the Item Characteristics Curve for Global 06.Additional file 1: Figure S2-S3. Empirical plot of items display misfit to the IRT model in at least one subsample.


A detailed community-level understanding of socioeconomic status (SES) and sociocultural status (SCS) of suicides and suicide attempters (SAs) in a prospective design could have significant implications for policymakers at the local prevention and treatment levels. The effect of SCS and SES on SAs is poorly understood and investigated in Iran. The present study aimed to investigate the incidence, trend, and role of SES and SCS on suicide and SAs.A longitudinal study was conducted based on the registry for SAs in Malekan County, Iran, from 2015 to 2018. Demographic characteristics, SES, SCS, incidence rates, and predictors of suicidal behaviors were measured via structured instruments. Simple and multiple logistic regressions were used to estimate crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs).A total of 853 SAs (32 suicides and 821 attempts) were identified during the study. Trend analysis revealed that the suicide rate significantly decreased from 2014 (10.28) to 2018 (1.75) per 100,000. In the final multiple variable models, age (26–40), male sex, unemployment, antisocial activities, history of SA, hanging method, and season (spring) increased the suicide risk while religious commitment had protective effects on suicide.Our findings indicated that demographic characteristics, low SES, and SCS are associated with suicide. In this county, trend of suicide and SA were decreased from 2014 to 2018. This study findings highlight the need to consider a wide range of contextual variables, socio-demographic, SES, and SCS in suicide prevention strategies. Improving inter-sectoral collaborations and policymakers’ attitudes are imperative for SA reduction. Suicide has been defined as death caused by self-directed injurious behavior with any intent to die due to this behavior. A suicide attempt (SA) is a nonfatal self-directed, potentially injurious behavior with any intent to die due to the behavior . SuicideIn Iran, a 20-year trend indicates increased suicidal deaths with an estimated average rate of 9.9 per 100,000 persons per year. It is estimated that 200 years of life lost (YLL) per 100,000 persons are attributed to suicidal behaviors (SBs) and self-inflicted violence in Iran , 6.Suicide is a complex and multifactorial issue determined by several demographic and low socioeconomic status (SES), mental illness, sociocultural status (SCS), history of SBs, and health systems’ performance concerning suicide prevention , 7. SES Prior to this study, a health community assessment indicated that SBs are the most important health priorities in Malekan County. The Primary Health Care (PHC) system of Malekan County implemented a suicide prevention program to reduce suicide and SBs and re-attempts during 2014–2018 . The CouA detailed community-level understanding of SES, SCS, and predictors of SBs in a prospective design could have significant implications for policymakers and health system managers at the local prevention and treatment level, especially the effect of SCS and SES on SBs that are poorly understood and investigated in Iran . LikewisSuicide and SBs are affected strongly by SCS compared to other diseases. Culture might provide a support system for an individual’s vulnerability and defenses related to ego-functioning; on the other hand, it might perpetuate an ecologically unhealthy environment. Cultural factors cannot be ignored as they significantly correlate with the global incidence of death by suicide .The main objective of this temporal study was to identify the incidence rate, predictors, and SES of SBs in Malekan County, Iran. Another aim was to determine the role of SCS in SBs based on the registry for SBs from 2015 to 2018.This study was conducted and extracted from a community-based suicide prevention and follow-up program   study (as a part of this project), the incidence rate, SES, SCS, and the main risk factors of suicides and SAs were measured in Malekan County from 2015 to 2018.The study population and participants (sampling frame) included all SAs, and suicides, and the involved individuals in the County during 2015–2018 and registered in the registry for suicide system. The study samples were included all 821 SAs and 32 suicide cases of the native population in Malekan County during 2015–2018. This study involved also SAs and suicide cases of Malekan County who registered in the neighborhood areas or counties. Malekan County is located in northwestern Iran with a population of 111,319 people  according to the 2015 national census. The native language of all the people of this County is Turkish, and all of them are Muslims. Almost 70% of the County population lives in rural areas. Their main occupation is farming or farming-related .In this study, SBs were collected via both hospital (emergency ward) and non-hospital sources  Community Health Workers (CHWs) who have face-to-face contact with large numbers of community members as part of their routine performance , and heaBehvarz in Persian) to obtain valid information. CHWs created a medical file for those attempting suicide in the community health center to record demographic and healthcare services and invite and coordinate interviews with participants.All SAs were followed up and interviewed after SA during the study period 2015–2018. The basic and primary information included name, age, sex, telephone number, residence, and attempted method collected by the emergency ward or community health centers. Attempts were made to increase the coverage of suicide and SA registry in the county, including 1) fast-collecting of SAs from the emergency ward by a simple and rapid checklist, 2) collecting lists of SAs referred to neighboring counties, such as Miyandowab, Bonab, and Maragheh, and 3) using native CHWs , to obtain valid and reliable information. Furthermore, we used CHWs, who had face-to-face contact with large numbers of community members, to evaluate the reliability of previous interviews with the closest member and accurate information about suicide cases.Demographic variables included sex, age, marital status, residence, living alone, and family size. Age was measured continuously and grouped as 10–25, 26–40, and ≥ 41 years. Marital status was measured as single, married/cohabiting, widowed and/or divorced.SES was measured by a valid and reliable questionnaire previously developed and validated among Iranian samples in this province . SocioecThe trend of SAs included incidence rates of suicide and SA by year, sex, and season. Incidence rates were measured via the number of SAs occurring based on registry system × 100,000/the number of County population in the specific time/year. Methods of SA, seasons, place, and the history of attempts were measured via the registry system and face-to-face interviews.A valid social participation questionnaire among Iranian samples was used for measuring SCS. This questionnaire (Persian version) was used and validated by Rashedi et al.  and DarvSCS, as an individual social characteristic and participation, included “social/teamwork collaborations and/or participation,” “faith and/or religious commitment,” “individual assistance and helpfulness,” and “conflict/antisocial status” .Social/teamwork collaborations were defined as the strength of constructive relationships within groups in developing a common goal and/or membership in cultural and social associations in the community. Faith and religious commitment were defined as performing the religious duties and obligations of Muslims, including prayers, fasting, enjoining the good, forbidding the evil, etc. Individual assistance and helpfulness character was defined as a person who provides service to the people  and shares their grief. Also, conflict/antisocial status was defined as a long-term pattern of manipulating, exploiting, or violating the rights of others without any remorse , 20.P-value< 0.05 was considered significant.The SPSS 21.0  was used for data analysis. Kolmogorov-Smirnov test was used to check data normality. Descriptive statistics, including charts and figures, were used to display SBs distribution by sex and seasons. Chi-squared (χ2) test was used to assess the relationship between SB and dichotomous variables. Simple and multiple logistic regressions were used to estimate the crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of suicide in the presence of variables. In all the tests, the confidence interval was considered 95%, and P = 0.001). Moreover, the 26–40 age group had the highest frequency of suicide and SAs, and a significant association was found between age groups and suicide (P = 0.001). Regarding another demographic status, family size, living alone, and marital status were not associated with suicide risk (P > 0.05).Table r = − 0.92, P = 0.001). Likewise, the trend of the SA rate also significantly reduced during the study from 2014 to 2018. Moreover, suicide rates among males in all the years were higher than females. In contrast, SA rates among males in all the years were lower than females (P = 0.036), r = 0.903) . Furthermore, the findings revealed that high family income was a risk factor for successful suicide (P = 0.001). Moreover, some behavior characteristics, including alcohol, substance abuse, and current smoking, were associated with suicide risk (P < 0.05).Table P = 0.028). Regarding the place of SAs, the majority of both suicide  and SAs  had occurred in residential buildings.Table P = 0.001).Fig. Table P = 0.001). Likewise, having social and teamwork activities and a state of helpfulness and assistance were associated with suicide and SAs prevention. However, there was no significant evidence in the final analysis that these reduced the suicide risk (P > 0.05). Moreover, our results demonstrated a positive association between antisocial activities and the suicide risk .Table This registry-based prospective study was conducted on individuals with SAs (suicide and SAs) in Malekan County from 2015 to 2018. Face-to-face interviews were performed to measure the role of SCS, SES, demographic status, and trend of incidence rates of suicide and SA in terms of sex and the main predictors of suicide. The study outcome refers to whole community (population) of Malekan County, but not for a group of individuals of community.In this community-based and health system research study, suicide and SA data were collected from various hospital and non-hospital sources. We used the regional  health system data and resources, as well as the health system of neighborhood areas, and community healthcare providers to achieve valid findings in a prospective design with psychological interviews and followed up of attempters.Since suicide cases are similar to the tip of the iceberg, community-based methods and efforts that used for collecting suicide and SA statistics and risk factors in this study can present a valid suicide and suicidal behaviors situation in this area and Iranian context. Moreover, the finding of this study highlights the importance role of this study and suicide research, and prevention strategies for policymakers and health managers by considering that the incidence rate of suicide has increased in Iran over the past decades which there are limited studies on suicide . In thisRegarding the demographic characteristics and SES, the final analysis showed that male sex, the age range of 26–40, low educational level, low occupational status (unemployed or self-employed), income , and rural area were risk factors for suicide. Aschan et al. in South East London found that low SES was directly associated with SAs . ConsistIn this study, suicide deaths were prevalent in high-income households, while SA was prevalent in low-income households. A review study found that low economic status, weakened wealth, and unemployment were associated with SBs, but they reported insufficient data to draw clear conclusions at the country level .Our trend analysis showed that the incidence of suicide and SA decreased in the County from 2015 to 2018. Also, in all the years, the incidence of suicide in males was higher than in females, while SA had quite the opposite situation compared to suicide. The reason for the decrease in suicide and SA rates during the study was the implementation of a community-based suicide prevention program in the County health system from 2014 to 2018. However, long term period is needed for evaluating the effectiveness of the interventions.In this study, there was a protective relationship between faith and religious commitment and suicide, while a negative association was found between antisocial activities and suicide risk. Consistent with our results, a study from 25 nations found a negative association between religious commitment and suicide rates . BesidesHowever, there was no significant association between individuals with teamwork activities and helpfulness or assistance characteristics and suicide prevention in the present study. However, in the present study, the teamwork and helpfulness aspects as individual social characteristics were poorly associated with suicide prevention; nevertheless, there was no decrease in successful suicide in the final analysis. Nonetheless, comparing these aspects with controls from the general population might reveal additional information. Consistent with our findings, Martikianen et al. and a study in Denmark did not find a significant relationship between individual social characteristics and suicide mortality , 31.Another finding of this study was that suicidal individuals mostly selected the hanging method for death, so that a very strong association was found between the hanging method and the risk of suicide. Consistent with the present study, Kolves et al. analyzed 8140 suicides and found a significant increase in hanging in both sexes and poisoning with drugs in females . A studyMost studies from both the Northern and the Southern hemispheres have confirmed a seasonal pattern and variation for suicide . The preThe present study showed the high prevalence of suicide mortality among non-academic, unemployed and/or self-employed individuals. Consistent with the present study, a study indicated that educational level, sex, and age were critical risk factors for suicide in Iran . SimilarMoreover, the present study showed that committing suicide at home or residential buildings was more prevalent than in outdoor settings. Consistent with the findings of this study, Kposowa et al. reported that suicide is prevalent at home . A studyTo the best of our knowledge, this prospective study, unlike other studies that focused on a single subject or were individual-based, is one of the rare population- and register-based studies that measured various aspects of suicide and SA, including SCS, demographics, and SES, and the trend of suicide and SAs in a longitudinal design.This prospective study revealed interesting and important results about SES, social and cultural aspects of SAs, and incidence rates of SAs based on a population registry-based system. However, there were some limitations. This study was a non-control prospective study and might do not allow for causal inferences. Comparison of suicides with controls without a history of SB can ascertain high strength of association. To diminish this problem, we used multiple logistic regression analyses to estimate the adjusted measures of associations and compared its findings with systematic reviews and population-based studies. On the other hand, death by suicide imposes a huge emotional and financial burden on health systems and communities. Our main objective was to identify predictors, trends, and prevention of suicide in the county, not SA, and the study achieved its objectives.N = 32) in comparison with SAs (N = 821) to explore associated risk factors. However, this study was used multiple logistic regression analysis to estimate the adjusted measure of associations (odds ratios) for suicide risk.Another concern was several large 95% CIs due to the low sample size of suicide cases , male sex, low educational level, unemployment, antisocial activities, history of SA, hanging method, and season (spring) increased suicide risk while religious commitment and having social participation were associated against suicide. Furthermore, suicide and SA rates decreased from 2014 to 2018 in the county.The practical framework that emerged in this research will provide a basis for developing an evidence-based suicide prevention strategies in Iranian and other contexts. This study findings challenge the personal-based risk-factor models of suicide prevention and highlight the need to consider a wide range of contextual, socio-demographic, and economic characteristics, and socio-cultural status (SCS) when developing and implementing strategies and programs against suicide and SA. Likewise, improving inter-sectoral collaborations and support from policymakers concerning SCS and SES are imperative for SA reduction.


Background: Emerging evidence suggests that inflammatory response biomarkers are predictive factors that can improve the accuracy of colorectal cancer (CRC) prognoses. We aimed to evaluate the prognostic significance of C-reactive protein (CRP), the Glasgow Prognostic Score (GPS), and the CRP-to-albumin ratio (CAR) in CRC.Methods: Overall, 307 stage I–III CRC patients and 72 colorectal liver metastases (CRLM) patients were enrolled between October 2013 and September 2019. We investigated the correlation between the pretreatment CRP, GPS, and CAR and the clinicopathological characteristics. The Cox proportional hazards model was used for univariate or multivariate analysis to assess potential prognostic factors. A receiver operating characteristic (ROC) curve was constructed to evaluate the predictive value of each prognostic score. We established CRC survival nomograms based on the prognostic scores of inflammation.Results: The optimal cutoff levels for the CAR for overall survival (OS) in all CRC patients, stage I–III CRC patients, and CRLM patients were 0.16, 0.14, and 0.25, respectively. Kaplan–Meier analysis and log-rank tests demonstrated that patients with high CRP, CAR, and GPS had poorer OS in CRC, both in the cohorts of stage I–III patients and CRLM patients. In the different cohorts of CRC patients, the area under the ROC curve (AUC) of these three markers were all high. Multivariate analysis indicated that the location of the primary tumor, pathological differentiation, and pretreatment carcinoembryonic antigen (CEA), CRP, GPS, and CAR were independent prognostic factors for OS in stage I–III patients and that CRP, GPS, and CAR were independent prognostic factors for OS in CRLM patients. The predictors in the prediction nomograms included the pretreatment CRP, GPS, and CAR.Conclusions: CRP, GPS, and CAR have independent prognostic values in patients with CRC. Furthermore, the survival nomograms based on CRP, GPS, and CAR can provide more valuable clinical significance. Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer-related death worldwide. CRC is one of the most common gastrointestinal malignancies . The livSince Virchow first reported the association between inflammation and cancer in 1863, various studies have analyzed this relationship . InflammTherefore, the present study aimed to assess the relationship between CRP, GPS, and CAR and the prognosis and clinicopathology of patients with CRC and to compare the prognostic value of these indicators in patients undergoing treatment for CRC.The data of 1,286 patients with CRC who were admitted to the Gastrointestinal Surgery Department of the Guangxi Medical University Cancer Hospital between October 2013 and September 2019 were retrospectively analyzed. Of these, 379 were included in this study and 907 were excluded because of incomplete medical information or lack of follow-up, the details of which are presented in This study was approved by the Local Ethics Committee of the Guangxi Medical University Cancer Hospital, and it was conducted in accordance with the ethical guidelines of the 2008 Declaration of Helsinki and of the current hospital. All patients provided written informed consent.CRP was detected with the latex enhanced immunoturbidimetric method. Albumin was detected using the bromocresol green method. The levels of serum CEA and CA19-9 were measured with a chemiluminescence microparticle immunoassay using the Arhcitect i2000SR analyzer and the corresponding reagent kits, which were purchased from Architect Diagnostics . All operations followed the manufacturer’s instructions. Systemic inflammatory response was assessed using CRP, GPS, and CAR. GPS is a cumulative score and was calculated as described previously . PatientC-index). The larger the C-index, the more accurate the prognostic prediction. The calibration ability of the nomogram was evaluated by a calibration plot. The closer the calibration curve is to the reference line, the more perfect the calibration. All statistical tests were two-sided, and when the associated probability was less than 0.05, p-values were considered statistically significant.Statistical analyses were conducted using SPSS (version 21.0) and R (version 3.5.1). Data are expressed as the mean ± standard deviation (SD). The optimal cutoff values were assessed by using receiver operating characteristic (ROC) curves based on the Youden index (YI = sensitivity + specificity - 1) and by X-tile software. The end point of survival analysis is OS. Spearman’s or Pearson’s correlation analysis was used to determine the association between CRP, GPS, and CAR and the other clinicopathological features. Kaplan–Meier analysis and log-rank test were used to determine the differences in the survival curves between the two groups. The ROC curve was constructed to evaluate the discriminative ability of each prognostic score, and the area under the ROC curve (AUC) was measured and compared with that obtained by the method established by Overall, 379 patients were enrolled , including 307 stage I–III patients and 72 CRLM patients. The optimal cutoff level for CAR was 0.16  for OS in all recruited CRC patients . For subThe correlation analysis in all CRC patients revealed that pretreatment CRP was positively correlated with sex, location of the primary tumor, pretreatment CEA and CA19-9, lymphatic invasion, and stage and negatively correlated with pathological differentiation. Pretreatment GPS was also revealed to be positively correlated with age, location of the primary tumor, pretreatment CEA and CA19-9, and stage and negatively correlated with pathological differentiation in CRC patients. In addition, pretreatment CAR was positively correlated with sex, location of the primary tumor, pretreatment CEA and CA19-9, and stage and negatively correlated with pathological differentiation in CRC patients . In stagp < 0.05)  , 3.p < 0.05)  .p < 0.05)  .ROC curves were used to analyze patient survival at the 24-, 36-, and 48-month follow-up periods, and the AUC assessed the discriminative ability of each inflammation-based prognostic score in CRC patients, stage I–III CRC patients, and CRLM patients . Each prp < 0.05). Multivariate analysis indicated that the location of the primary tumor , pathological differentiation , pretreatment CEA , and pretreatment CAR  were independent prognostic factors for OS. Because CRP, CAR, and GPS contained the same data, three tables were made to consider them separately when performing a multifactor analysis. The HR of CAR was the highest; therefore, the table containing CAR was included in the main manuscript . Multivariate analysis indicated that pretreatment CAR  was an independent prognostic factor for OS. The HR of CAR was the highest; therefore, the table containing CAR was included in the main manuscript . Multivariate analysis indicated that the location of the primary tumor , lymphatic invasion , pretreatment CEA , stage , and pretreatment CAR  were independent prognostic factors for OS. The HR of CAR was the highest; the table containing CAR, CRP, GPS are presented as The correlations between OS and the clinicopathological factors in CRC patients are shown in C-index for OS prediction was 0.85 (95% CI = 0.80–0.91). C-index for OS prediction of 0.81 (95% CI = 0.73–0.88). For the CRLM cohort, the prognostic nomogram for OS is shown in C-index for OS prediction was 0.81 (95% CI = 0.70–0.93). The values of the C-index suggest that the nomograms based on the prognostic scores of inflammation were useful predictors for survival of CRC patients. The calibration plot demonstrated a favorable agreement between the predicted and the observed values  of CRC patients undergoing surgery had normal preoperative serum CEA levels . The aboPrevious studies have reported that the peripheral inflammation markers, including the levels of CRP, GPS, and CAR, are related to the prognosis of CRC patients , and thiPresently, the commonly used methods to determine the optimal cutoff values included the median value method, ROC analysis, and the X-tile software. In this study, in addition to obtaining the optimal cutoff value of CAR through ROC analysis for subsequent analysis, we also used X-tile software to obtain the optimal cutoff value. Kaplan–Meier analysis and the log-rank tests showed that, patients with high CAR values obtained by the two methods have worse OS than those with low values, which scientifically reveals the significance of CAR in the prognosis of CRC patients, both in the stage I–III and CRLM patient cohorts. However, the optimal cutoff value obtained using the X-tile software for stage I–III CRC patients was higher than that for CRLM patients, which is not conducive to clinical application. This may be because there are not enough CRLM patients included.C-index  and the calibration plot.In this study, CAR was able to accurately divide CRC patients into two independent groups, similarly to CRP and GPS. Because CAR and GPS are based on only two measured parameters and have high AUC values, they can be conventionally available, simple, and inexpensive. Some studies have found that inflammation markers were related to tumor progression . We alsoThere are some potential limitations to this study. Firstly, this is a retrospective single-center study. Secondly, the same variables  were included in the analysis of CRP, GPS, and CAR in our multivariate analysis. Thirdly, the best cutoff value for pretreatment CAR is unknown. Therefore, a large-scale, multicenter prospective study is still necessary in the future.In summary, CRC patients with high CRP, GPS and CAR values have worse OS than those with corresponding low values. The three markers have independent prognostic values in patients with CRC, both in the cohorts of stage I–III patients and CRLM patients. Furthermore, we have developed survival nomograms based on the three markers, which might increase the clinical significance of the study.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/JZ designed the study, performed the statistical analysis, and prepared the manuscript. JZ, WW, SN, and BH acquired the data. JL helped with quality control of data and algorithms. JZ and JL analyzed and interpreted the data. KL and LZ edited the manuscript. All authors reviewed the manuscript and approved the final version.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Allium essential oils. This organosulfur molecule can be used as a feed additive to decrease the appearance of bacterial resistances caused by the residues of antibiotics. In previous in vitro genotoxicity studies, contradictory results were reported for PTS. In this work, the in vivo genotoxicity of PTS in male and female rats was assessed for the first time, following OECD (Organisation for Economic Co-operation and Development) guidelines. After oral administration , a combination of the micronucleus (MN) assay (OECD 474) in bone marrow and the standard and enzyme-modified comet assay (OECD 489) was performed. After necropsy, histopathological studies were also carried out. The results did not show the in vivo genotoxicity of PTS at any doses assayed, revealed by the absence of increased MN, and DNA strand breaks or oxidative DNA damage in the standard and enzyme-modified comet assays. The histopathological study revealed that only the highest dose tested (55.0 mg/kg) in the liver and all dose groups in the stomach presented minimal pathological lesions in the organs studied. Consequently, the present work confirms that PTS is not genotoxic at the doses assayed, and it is a promising natural alternative to synthetic preservatives and antibiotics in animal feed.Propyl-propanethiosulfinate (PTS) is a component of  Allium species and their essential oils have been extensively used for medical applications and as a flavoring agent. Vegetables of the genus Allium  are well known for their antioxidant and anticancer properties in humans [n humans . In addin humans ,3,4,5,6.Allium genus  with biological activity, and they have a characteristic aroma. These molecules are generated when tissues of these plants are damaged. If so, alliinase degrades the initial compounds into new ones exerting biological activity [® , which is composed of a mixture of several compounds, mainly propyl thiosulfinate oxide (PTSO) and, in a lower proportion, of propyl-propanethiosulfinate (PTS). ProAllium® has been successfully incorporated into films to produce active packaging, able to expand the shelf life of ready-to-eat food and to control their spoilage [Organosulfur compounds (OSCs) are secondary metabolites of plants from the activity   panel on Food Contact Materials, Enzymes, Flavorings, and Processing Aids (CEF) has published the “Recent developments in the risk assessment of chemicals in food and their potentials impact on the safety assessment of substances used in food contact materials” . AdditioAllium extracts and essential oil are still scarce, especially in vivo. However, subchronic toxicity has been studied through a 90-day oral assay of Proallium [Toxicological data about roallium , whose mroallium .Previous in vitro genotoxicity and mutagenicity studies for PTS carried out in our laboratory reported contradictory results . NegativConsidering all these facts, in order to clarify the contradictory results obtained in in vitro genotoxicity studies with PTS, the present study aimed to carry out the in vivo genotoxic assessment for PTS by using the combined MN-comet assay in rats for the first time. The tissues selected were bone marrow for the MN assay , and sto4EDTA), HEPES, Giemsa, and Trizma® base were purchased from Sigma Aldrich . Bovine serum was purchased from Gibco . Endonuclease III and formamidopyrimidine DNA Glycosylase were purchased from Biolabs Inc. Sybr Gold was purchased from Invitrogen.PTS  was developed, chemically isolated, and provided by DMC RC . Sodium chloride (NaCl), potassium chloride (KCl), ethylenediaminetetraacetic acid (EDTA), sodium ethylenediaminetetraacetate . Animals were humanely cared for in compliance with the guidelines for the protection of animals used for scientific purposes (Directive 2010/63 UE).Eight-week-old Wistar female and male rats, strain RjHan:WI (type outbred rats), were obtained from the Centre for Animal Production and Experimentation of the University of Sevilla (Spain). Upon arrival, animals were weighted and then accommodated into polycarbonate cages with stainless steel covers. Later, the animals were acclimatized to the environmental conditions with a 12 h dark/light cycle, temperature of 23 ± 1 °C, and relative humidity of 55 ± 10% for 1 week before the experiment. During this time, the animals were provided certified pellet food  and tap water ad libitum, free from any type of chemical contamination.The selection of PTS doses was calculated while taking into account a preceding acute toxicity study carried out by our research group, in which rats (8–10 weeks old) were administrated decreasing doses of PTS to establish the maximum tolerated dose (MTD). According to the OECD guidelines for testing chemicals , the iniAfter acclimation time, 28 male and 28 female rats were randomly divided into control or treatment groups: the negative control (C−) , the solvent control (C sol)  treated with water with 0.3% Tween 80, and the positive control (C+)  treated with 200 mg/kg b.w. of ethylmethanesulfonate (EMS). The three PTS-treated groups  were exposed to 55.0, 17.4, and 5.5 mg of PTS/kg b.w. The number of animals was selected according to OECD 474  and OECDDoses were dissolved in water with Tween 80  in a final volume of 1.5 mL. Tween 80 was previously used in genotoxicity in vivo studies by Mellado-Garcia et al.  with theAfter treatment, each rat was observed twice daily for clinical signs such as changes in the eye, fur, or skin, changes in gait and posture, and secretions.® sodium Heparin Tubes . Furthermore, samples from the bone marrow of both femurs of each animal were gathered for the MN assay and were rapidly used to prepare smears  among total erythrocytes (polychromatic and normochromic erythrocytes (NCE)) ratio and PCE for every NCE ratio were calculated by counting 500 erythrocytes per rat. The number of micronuclei found in immature erythrocytes was calculated by counting a total of 5000 micronucleated immature erythrocytes (MNPCE) per rat, and it was expressed as %MN.4EDTA, and 9.9 µM of Trizma® base) at 4 °C for at least 1 h. After this step, microscope slides intended for enzyme treatment were washed 3 times for 5 min with an enzyme buffer (buffer F)  Afterward, the agarose gels in slides were exposed to 30 µL of lysis buffer, buffer F, and buffer F comprising Endo III or FPG, and they were incubated in a metal box for 30 min at 37 °C. All microscope slides were subjected to electrophoresis for 20 min, at 0.81 V/cm up to 400 mA. The DNA released from the nucleus of the cells was immersed in PBS, water, 70% ethanol, and absolute before being stained with SYBR Gold . The %DNA in the tail, automatically acquired by the software, were used to define each of the comets analyzed. Endo III and Fpg sensitive sites were established by deducting the % of DNA in the tail after repair enzymes incubation. The medians of the scored comets were taken to describe each animal, and the means of each group of doses and controls are represented in Liver and stomach samples were processed and observed under the microscope according to Diez-Quijada et al. . A semiqp values < 0.05 were considered statistically significant. Analyses were carried out using Graph-Pad Prism software .The results of the MN test are presented as the mean ± standard deviation (SD) for each group of animals, and a statistical analysis was performed using the analysis of variance (ANOVA) followed by Dunnett’s multiple comparison test. The results of the standard and enzyme-modified comet assays were calculated for each group as the mean ±SD of the medians. The distribution of the results was checked for normality utilizing the Kolmogorov–Smirnov test, and the total scores of the different groups were compared using the nonparametric Kruskal–Wallis test followed by Dunn’s multiple comparison test. For the histopathological study, the Kolmogorov–Smirnov test was used to assess if distributions were parametric. Groups were compared by applying the nonparametric Kruskal–Wallis test followed by Dunn’s multiple comparison test. No clinical signs were observed during the entire course of the study after treating the rats with all levels of doses of PTS, water, or water with added Tween 80. However, rats treated with EMS presented piloerection and an attenuation in their normal physical activity.The results obtained in the positive and negative control groups in others and recent studies  were simp < 0.05). Considering the PCE/Total ratio, a significant reduction was also observed in males and females at 55 mg/kg (p < 0.05), and in females at 17.4 mg/kg (p < 0.05). Moreover, the % of MN in immature erythrocytes was not significantly changed in any groups of either sex. Rats exposed to 200 mg/kg of EMS showed remarkable reductions in PCE/NCE and PCE/total ratios, and a significant increase in the frequency of MN (positive control).In The %DNA in the tail results found in the standard and enzyme-modified comet assays are represented in The histopathological study of the stomach and liver did not show differences between males and females (data not shown). The scores obtained after the pathological evaluation of both the stomach and liver are shown in p < 0.05) in the damage recorded in comparison to the negative and solvent control group (p < 0.05) compared to the negative and solvent controls  in comparison to negative and solvent controls (p < 0.05) compared to the negative and solvent controls . Genotoxicity studies are one of the basic sets of toxicological studies included in the guidelines on the safety of feed additives, or substances employed in food contact materials, required by EFSA ,32,33,34As it has been mentioned before, previous PTS in vitro genotoxicity studies provided divergent results about its genotoxic potential . Thus, PIn this sense, the in vivo results reported in the present work confirm that PTS is not genotoxic in male and female rats orally exposed , according to the negative results observed for the MN and comet assays. Furthermore, no DNA oxidative damage was induced by PTS in any of the tissues investigated  when the enzyme-modified comet assays were applied. In case of negative results in the in vivo genotoxicity studies, EFSA  indicateRegarding the experimental procedure performed in the present work, the combination of the in vivo MN and comet assays into a single rodent study is recommended by EFSA  and OECDHistopathological examination of the most related tissues, the liver and stomach, was carried out in order to provide additional relevant evidence for the global toxicological profile and support to identify the possible target organs for PTS. Generally, rats treated with PTS  showed very mild histopathological changes, and, generally, only minimal inflammatory processes in the liver and stomach were detected at the highest dose (55 mg/kg b.w.) in the liver and in all dose groups in the stomach. These results agree with the histopathological damage observed in the in vivo genotoxicity study performed with PTSO , in whic®, showed contradictory responses after the application of a battery of four in vitro genotoxicity assays [To better understand the safety of PTS in vivo, the in vitro genotoxicity studies and our in vivo results need to be compared. Regarding the concentrations assayed previously by Mellado-García et al. , PTS hady assays , and laty assays .Allium sp. such as DADS  by oxidation (cytochrome P450) to produce diallyl sulfoxide (DASO) and allyl sulfone (DASO2). Moreover, various in vivo studies have found that DAS  and DADS can modulate the phase I and phase II metabolizing enzymes [These contradictory results between the genotoxicity test in mammalian cell lines in vitro showing positive results, when compared to the negative findings in the in vivo assays of both OSC compounds, PTS and PTSO, could be due to several reasons ,39. The  enzymes ,41. Acco enzymes  reportedFurther research focused on metabolism processes and toxicokinetic aspects of PTS are necessary to define metabolic derivates of this organosulfur compound and to assess its safety to be applied as a feed additive. In addition, following the guidance of EFSA for feed additives, the subchronic toxicity test should be performed through a 90-day assay.The combined in vivo MN-comet assay protocol showed that PTS did not produce genotoxic effects in the stomach, liver, blood cells, and bone marrow of male and female rats orally (gavage) exposed to 5.5, 17.4, and 55.0 mg/kg b.w. In addition, no oxidative DNA damage was induced by PTS when the enzymes FPG and Endo III were applied in the nucleus isolated from the cells of the liver, stomach, and blood. The histopathological study revealed only minimal hypertrophy of the mucus cells and flaking epithelium in the stomach and slight lesions in the liver, and occasionally, minimal inflammatory infiltrates in rats exposed to the highest dose (55.0 mg of PTS/kg). Consequently, the absence of in vivo genotoxic effects of PTS supports its approval as a feed additive or active agent in food contact materials, although more studies are needed to obtain a global picture of its safety profile.