---

Background and Objective: The silent brain infarctions are common in first-ever stroke. Some recent studies show the possible role of silent brain infarction in ischemic stroke. The aim of this study was to evaluate the frequency of silent brain infarction in acute first-ever ischemic stroke and its association with stroke risk factors. Materials and Methods: This descriptive - analytical study was carried out on 203 (94 males, 109 females) patients with acute first-ever ischemic stroke in Shafa hospital in Kerman, Iran during 2010. The diagnosis of ischemic stroke was made by physical examination and was confirmed by MRI and CT Scan. A questionnaire containing demographic information and risk factors including hypertension, diabetes, hyperlipidemia, cigarette smoking, ischemic and non-ischemic heart disease for stroke as well as presence of silent stroke was completed for each patient. Data were analyzed using SPSS-16 and logistic regression test. Results: The mean age of patients was 62.56±17.35 years. Among our patients history of hypertension, hyperlipidemia, cigarette smoking, diabetes, history of ischemic heart disease, history of other cardiac disease and silent stroke were observed in 66 (32.5%), 26 (12.8%), 16 (7.9%), 40 (19.7%), 27 (13.3%), 16 (7.9%) and 31 (15.3%), respectively. The probability of silent stroke among patient with hyperlipidemia, was 3.7 times more than those without hyperlipidemia (95%CI: 1.556-12.780, P<0.05). There was no significant correlation between silent stroke and the above risk factors. Conclusion: Silent stroke was found in 15% of patients with ischemic stroke. Control of hyperlipidemia can have a vital role in the prevention of silent stroke.

---

Background and Objective: Many studies have showed malformation of low frequency of electromagnetic fields (EMF) on different tissues. This study was carried out to evaluate the effect of low frequency electromagnetic fields on the heart of white-leghorn chicken embryo. Materials and Methods: In this experimental study, 90 healthy, fresh and fertilized eggs were allocated into 6 groups including control, sham, and four preincubated experimental groups. Experimental groups I, II, III and IV (1.33, 2.66, 5.52 and 7.32 mT) were located in the electromagnetic device, sham group was located into the same coil with no exposure for 24h before incubation. Control, sham and experimental groups incubated (37±0.5 ºC, 60% humidity) for 14 days. Results: Disassembling cell regulation in experimental group I, dense nucleus of myocytes and increase of intercellular spaces in experimental group II, necrosis and bleeding in the heart tissue in experimental groups III and IV were seen in compare to control and sham groups. There was a significant increase in the level of activity of alkaline phosphatase in the heart of experimental groups in compare to control and sham groups. Conclusion: Low frequency of electromagnetic fields caused alternations in cardiac tissue and elevation of Alkaline phosphatase activity in chicken embryos.

---

Background and Objective: Free radical production andsubsqunt oxidative steress can be due to hyperglycemia and its oxidation. This study was done to evaluate the effect of swimming training test and Fenugreek seed extract on plasma glucose and antioxidant activity in heart tissue of streptozotocine – induced diabetic rats. Methods: In this experimental study, 50 male wistar rats were allocated into five groups diabetic (DC, n=10), healthy control (HC, n=10), swimming training (S, n=10), swimming training + Fenugreek seed extract (1.74 g/kg/bw) (SF1, n=10), and swimming training + Fenugreek seed extract (0.87 g/kg/bw) (SF2, n=10). Streptozotocine (60 mg/kg/bw) was used for induction of diabetes in DC, S, SF1 and SF2 groups. Serum glucose and the rat heart tissue antioxidant enzymes activities of superoxide dismutase, Catalase and Glutation peroxidase were determined. Results: Body weight in all groups were significantly reduced in comparsion with healthy control group (P<0.05). Plasma glucose level significantly reduced in SF1 and HC groups compared to diabetic group (P<0.05). Cardiac antioxidant enzymes in swimming training, SF1 and SF2 groups significantly increased in compare to diabetic group (P<0.05). Conclusion: The combination of endurance swimming training and fenugreek seed extract can reduce plasma glucose and increase cardiac antioxidant enzymes in streptozotocine – induced diabetic rats.

---

Background and Objective: Imperforate anus is a common anorectal malformation, which is associated with other anomalies. This study was done to determine the associated malformations in newborns with imperforate anus in northern Iran. Methods: This descriptive study was carried out on 40 hospitalized newborns (24 boys and 16 girls) with imperforate anus in Taleghani teaching hospital in Gorgan, northern Iran during 2006-10. Results: From 40 newborns with imperforate anus, 23 newborns (57.5%) had associated anomalies. The commonest associated anomalies was genitourinary (65.2%) followed by heart (47.8%), gastrointestinal (13%) and musculoskeletal anomalies (8.7%). Conclusion: Associated anomalies in newborns with imperforate anus in northern Iran have a high prevalence in comparison with other reports.

---

Background and Objective: Fetal heart pattern is one of the most important criteria in non stress test. This study was done to compare the effect of two anxiety- reducing methods, maternal relaxation and fetal-maternal attachment skills training on the prevalence of sporadic fetal heart decelerations and heart beat variability. Methods: In this clinical trial study, 126 pregnant women were randomly divided into three groups including teaching relaxation, maternal-fetal attachment skills and controls. Training was done for four weeks. NST was performed 30 minutes before of traning and after 4th week of training in the interventional groups. In the control group, NST was done in the 4th week. Cranley scale was filled at the end of the study. Results: The prevalence of sporadic deceleration in attachment skills, relaxation and control groups before intervention was 23.8%, 19% and 21.4%, respectively. After the intervention, the prevalence of sporadic deceleration in attachment skills group non-significantly changed to 11.9%. After the intervention the prevalence of sporadic deceleration in the relaxation group significantly changed to 4.8% (P<0.05). Conclusion: Maternal relaxation training decreased the prevalence of sporadic fetal heart decelerations, and enhances fetal heart beat variability.

---

Background and Objective: A brief and short duration episode of ischemia is recorded in ischemic preconditioning (IPC). This latter condition provides a status in which large region of heart is protected when prolonged ischemia occurred. Levothyroxine play a protective role in IPC induction, and simultaneously with stress oxidative. This study was conducted to determine the protective effect of levothyroxine with oxidative stress reduction mechanism in ischemic preconditioning model in rat heart.
Methods: This experimental study was performed on 30 male Wistar rats in three groups of 10, as follows. In the reperfusion ischaemia group (IR), the heart of the animal was placed in a Langendorff apparatus. In the ischemic preconditioning group (IPC), prior to major ischemia, was exposed to 4 periods of 5-minute ischemia with reperfusion. In the intraperitoneally administered group, levothyroxine at a dose of 25 microgram per 100 g of body weight, the heart was exposed to reperfusion ischemia. The area of infarct and the level of malondialdehyde in the heart tissue were measured.
Results: The volume of Infarcted region in IR and IPC groups was 26.55 and 11.11 respectively. The same index for the Levothyroxine receiver was 12.56. Based on these findings it was demonstrated that Levothyroxine injection reduced the Infarcted region significantly similar with IPC (P<0.05). The MDA Levels in IR and IPC were 1328 and 777, respectively and in Levothyroxine group it was determined as 762. The size of Infarcted region in both IPC and treated with Levothyroxine groups significantly reduced in compared to IR group (P<0.05).
Conclusion: Injection of levothyroxine with ischemic preconditioning reduced the effect of reperfusion maladaptive ischemia in rat heart.

---

Background and Objective: Dyspnea is the main cause of hospitalization of patients with heart failure and it is often associated with anxiety. This study was conducted to determine the effect of Chamomile tea on the severity of dyspnea and anxiety in patients with chronic heart failure.
Methods: This randomized clinical trial study was conducted on 60 patients with chronic heart failure in an outpatient clinic of Jahrom University of Medical Sciences, Iran during 2014. Patients were randomly divided into intervention and control groups. Subjects in intervention group consumed Chamomile tea for 4 weeks. Oxygen cost diagram (OCD) and Beck anxiety inventory were recorded for each subject.
Results: The mean of severity of dyspnea in the intervention and control groups was 16.66±5.76 and 29.43±13.1, respectively (P<0.05). The mean anxiety severity in the intervention and control groups was 12.07±1.1 and 6.7±6.2, 20, respectively (P<0.05).
Conclusion: Chamomile tea can reduces the severity of dyspnea and anxiety in patients with chronic heart failure.

---

Background and Objective: Patients experience full stress condition after open heart surgery. Foot reflexology massage has a potential impact on the comfort of patients with special care. This study was done to evaluate the effect of soles of feet reflexology massage on feeling of comfort in open heart surgery patients.
Methods: This clinical trial study was done on 70 patients who were divided into intervention and control groups using permutable blocking method. 35 patients in interventional group were received Soles of feet Reflexology Massage after mesearment of vital sigins for six days. 35 patients in the control group did not receive any intervention received routine care. Data gathering tools were demographic items and HCQ questionnaire, which was completed in two stages, 24 hours after surgery, before massage and the 6th day after massage.
Results: The mean total comfort score in the intervention group was 103.1±9.04 and 110.63±7.6 before and after the intervention, respectively. This differnce was not significant. The mean total comfort score in control group was 105.14±10.37 and 111.29±7.56 perior and the end of study, respectively, this difernce was not significant. Also, there was no significant difference between considering the mean scors of comfort between the tow in the intervention and control groups.
Conclusion: Reflexotherapy massage had no effect on feeling of comfort in open heart surgery patients.

---

Background and Objective: Gestational diabetes mellitus (GDM) is usually a disease caused by inadequate insulin production in pregnant women. GDM induces abnormal fetal growth.This study was done to evaluate the BMP2 and BMP4 genes expression in the development of the embryos heart in induced gestational diabetes of C57BL/6 mice.
Methods: In this experimental study, 8-week old adult C57BL/6 mice were randomly divided into diabetic and control groups. After mating of animals, the dams in diabetic group were received a single dose of 150 mg/kg/bw of streptozotocin on gestational day 1 of pregnancy, intrapereatonally. After 11.5 days of pregnancy, the embryos of both groups were extracted and heart tissue was extracted. RNA total tissue of the heart was extracted by trazole. After extracting RNA, expression of BMP2 and BMP4 genes in the heart of both groups was estimated by Real-time PCR.
Results: There was no singnificant diference in expression of BMP2 and BMP4 genes in the heart of 11.5 days of embryos in gestational diabetes mellitus group and control group.
Conclusion: Gestational diabetes mellitus had no effect on the expression of BMP2 and BMP4 genes in the development of the embryos heart.

---

Background and Objective: Gestational diabetes (GDM) is a metabolic disorder which is caused by insufficient secretion of insulin. GDM is a risk factor for embryo during pregnancy and it is possible leads to congenital heart defects (CHD). Some of these defects may be due to a change in the expression of some of the important structural genes in the heart. Desmocollin 2 and collagen structural genes have important role in the cell adhesion of the cardiomyocytes.This study was done to determine the effect of gestational diabetes on expersion of desmocollin 2 and col5a2 structural genes in C57BL mouse embryo heart.
Methods: In this experimental study, 12 adult female and six adult male C57BL mice were used.After mating of the animals and observation of the vaginal plug, the female mice with vaginal plug were randomly divided into diabetic and control groups. At the first day of pregnancy, Induction of gestational diabetes mellitus in dams in the diabetic group was performed by the intraperitoneal (IP) injection of Streptozotocin with a dose of 150 mg / kg body weight per day in GD1. While in the control group, only citrate buffer was injected.Cesarean Surgery was done at E11.5 and embryo's heart was extracted from the body.Extraction of RNA, cDNA, and quantitative measurements of the amount of RNA were performed using Real -Time PCR.
Results: Induction of gestational diabetes increased the expersion of desmocollin 2 and col5a2 structural genes in compared to controls, althought only the expersion of desmocollin 2 gene was significant (P<0.05).
Conclusion: We suggest that the induction of DM lead to upregulation of structural genes primarily including desmocollin 2 and col5a2 in embryos heart development.

---

Background and Objective: Aging reduces cardiac autonomic function parameters such as heart rate response to exercise and heart rate recovery after physical activity. This study aimed to determine the parasympathetic nerves reactivation after upper body exercise among young and middle-aged men.
Methods: In this quasi-experimental study 24 active men based on their age were divided into two groups including 30-35 (young) and 55-60 years old men (middle-aged). Participants performed upper body exercise on a Monark arm ergometer. During the test, heart rate was recorded continuously by electrocardiogram. Also, participants' heart rate was recorded for 10 minutes after completion of the test. In order to measure the time domain parameters of heart rate variability (PNN50 and RMSSD), one-minute successive RR waves intervals collected in 5 minutes and 10 minutes after the completion of the test and then were transmitted to the heart rate variability software for analysis. Also, heart rate recovery was measured in one minute and two minutes after the test by the difference between the maximum heart rate during the test with heart rate in one and two minutes after the completion of the test.
Results: There was a significant difference between PNN50 in minutes 5 and 10 after the test in young men (P<0.05). Young men also had higher values of RMSSD in minutes 5 and 10 compared to middle-aged men. The heart rate recovery in the 2 minutes after test was significantly higher than 1 minute after test in both groups (P<0.05). Heart rate recovery was higher in young people than in middle-aged people at 5 and 10 minutes after high-intensity exercise due to faster withdrawal of sympathetic nerves.
Conclusion: Changes in the autonomic nervous system is dependent on the type, duration of activity, and the age of the participants.
 

---

Background and Objective: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic hepatic diseases which may be associated with cardiovascular disease. This study aimed to consider the effect of combined therapy with resveratrol supplementation and interval exercise training on heart cells apoptosis in rats with NAFLD using TUNEL assay.
Methods: This experimental study was done on 35 Wistar rats. Animals were randomly allocated into five groups including control (healthy) and four NAFLD groups, including patient, resveratrol, interval exercise, and resveratrol + interval exercise. A TUNEL assay kit was applied for the detection of apoptosis in heart tissue.
Results: The patient group had significantly higher percentage of heart apoptotic cells (24.38±0.69%) compared to the other groups (P<0.05), while the resveratrol + interval exercise (9.02±0.49%) and resveratrol (9.47±0.83%) groups showed significantly lower mean levels of heart apoptotic cells compared to the patient and interval exercise (P<0.05) groups. There was no significant difference in mean of apoptotic cells between resveratrol and resveratrol + interval exercise groups. The mean of apoptotic cells in interval exercise group was 11.39±0.28%.
Conclusion: Nonalcoholic fatty liver disease is considerably associated with heart cells apoptosis. Resveratrol supplementation especially combined with interval exercise significantly reduces apoptotic cells in heart tissue.

---

Background and Objective: Diabetes mellitus is one of the most common metabolic and global health threats. The gene needed for the development of the TBX20 gene is the fusion of the gene, and the defect in the sequence and expression of this gene also causes heart defects. Due to significant prevalence of gestational diabetes mellitus in human population, this study was done to evaluate the effect of TBX20-induced gestational diabetes mellitus in the heart of the mice embryo at 11.5 days.
Methods: This experimental study was done on induced diabetic C57BL/6 female mice. Gestational diabetes induced by interaperitoneal injection of sterptozotocin at GD1. On the day of pregnancy 11.5, embryonic heart samples from these mice were isolated. After extraction of RNA, cDNA synthesis of RNA was performed. The Real Time-PCR technique was used to determine the expression of TBX20 gene. Expression level   of TBX20 gene in experimental and control was calculated using the 2^–∆∆CT method.
Results: Expression of TBX20 gene in diabetic specimens was twice as high as the control samples, which was statistically significant (P<0.05).
Conclusion: It seems, increasing TBX20 gene expression in embryonic heart tissue may be one of the complications of gestational diabetes mellitus and can lead to abnormalities in the heart embryo.

---

Background and Objective: Congenital anomalies are one of the major causes of neonatal mortality. Congenital heart disease (CHD) is the most common birth defect world wide, and recent studies about CHD have reported congenital heart disease approximately is about one percent of all live births. This study was done to determine the frequency of congenital heart disease using ecocardiography in patients with extra-cardiac anomalies in Gorgan peadiatric center in north of Iran.
Methods: In this descriptive study, 55 girls, 84 boys a total of 139 patients were in the age range of birth to 12 years of age whom have referred to Taleghani Teaching and Medical Center in Gorgan during 2012-17. 139 cases of congenital heart disorders with echocardiographic report sheet in their medical record were evaluated. Information of patients including age, sex, ethnicity, type of extra-cardiac, anomalies, cardiac anomalies (simple, complex and ductal anomalies), cardiac murmur status, and clinical symptoms were extracted from their medical records.
Results: From of total of echocardiography, 139 patients (88.5%) were affected by congenital heart disease. The anomalies were included of 88 cases (56.05%), 48 cases (31.21%), 2 cases (1.27%) simple, complex anomaly and ductal dependent anomaly respectively. The other disorders accompanied with congenital heart diseases were 17 cases (12.2%) with cleft palate, 4 cases (2.9%) with congenital diaphragmatic hernia, 8 cases (5.8%) with closed anus, 52 cases (37.4%) with Down syndrome, 4 cases (2.9%) with Turner syndrome, 4 cases (2.9%) with ileum atresia, 11 cases (7.9%) with Esophageal atresia, 7 cases (5%) with Hirschsprung's disease, 6 cases (4.3%) with urogenital anomalies and 26 cases (18.7%) with other extra-cardiac abnormalities.
Conclusion: Down syndrome and cleft palate are among the highest prevalant anomalies with congenital heart diseases.

---

Background and Objective: Bisphenol A (BPA) is the monometer of epoxy resins and polycarbonate plastics that plays an important role in the pathogenesis of cardiovascular diseases. This study was done to evaluate the effect of aerobic exercises on oxidative stress indices in heart tissue of male Wistar rats after poisoning with Bisphenol A.
Methods: In this experimental study, 20 adult male Wistar rats were allocated into four groups including control, aerobic exercise, BPA and BPA + aerobic exercise. Animals in control and aerobic exercise groups were receieved olive oil and the BPA (100 μg/kg) intraperitoneally, respectively. Animals in BPA + aerobic training group were treated with BPA (100 μg/kg) intraperitoneally for 30 days. Exercise program consisted of 25-64 minutes of running with 57-75% oxygen consumption, 5 sessions per week for two months. Indicators of oxidative stress in heart tissue including Gpx, SOD, TAC, MDA, CAT and AOPP were evaluated.
Results: BPA intoxication induced a significant increase in the activity of SOD , GPX enzymes, AOPP and MDA levels and  reduction  in CAT enzyme activity and TAC level in compared to control group (P<0.05). While aerobic exercise could diminish the oxidative stress due to BPA intoxication. Aerobic exercise reduced the activity of the GPX, SOD and increased catalase activity in rats with BPA intoxication (P<0.05). Also, level of MDA and AOPP significantly reduced in in aerobic exercise group in comparison with with BPA intoxication (P<0.05).
Conclusion: Aerobic exercise activity has moderating effects on BPA intoxication in cardiac oxidative stress. Aerobic exercise can increase the amount of antioxidant enzymes that play an important role in modulating oxidative stress induced by BPA.

---

Background and Objective: Having a proper diet is very important. Many risk factors are involved in the development of cardiovascular disease that by changing them, the incidence of this disease can be reduced. This study was performed to determine the relationship between nutritional knowledge and level of physical activity with the prevalence of metabolic syndrome and some cardiovascular risk factors in militaries men.
Methods: This descriptive-analytical study was performed on 97 athletes and non-athletes militaries men. The standard Parmenter and Wardle Nutrition Knowledge Questionnaire of 1999 and Baecke Physical Activity Questionnaire were completed. Subjects' fitness scores and physical indicators were measured. Prevalence of metabolic syndrome, based on revised ATP ш and IDF was calculated.
Results: The mean nutritional knowledge of the subjects was moderate to low. There was a significant correlation between the nutritional knowledge, level of physical activity and fitness score and cardiovascular risk factors (P<0.05). Also there was a significant correlation between the nutritional knowledge, level of physical activity and fitness score with preventing metabolic syndrome (P<0.05).
Conclusion: With increasing nutritional knowledge, physical activity and fitness scores the risk of cardiovascular factors reduces and the possibility of metabolic syndrome prevention increase.
 

---

Myocardial infarction is characterized by the interruption of blood supply to part of the myocardium, leading to tissue damage. Acute myocardial infarction rarely affects young adults. However, considering the possibility of its occurrence, particularly in the presence of risk factors such as obesity and smoking, can help provide appropriate and timely diagnostic and therapeutic measures. Herein, were present a case of acute myocardial infarction in a young adult male.
 

---

Background and Objective: Considering the role of diet and the use of natural antioxidants in addition to exercise, the attention of researchers has been drawn to take further advantage of the effects of exercise to improve cellular metabolism. Despite the favorable role of exercise and antioxidants on heart health, the simultaneous effect of exercise and consumption of propolis (prepared by bees) is not yet known. This study aimed to investigate the effects of endurance training and propolis against oxidative and myocardial stress in diabetic ovariectomized rats.
Methods: This experimental study was conducted on 36 female Sprague Dawley rats aged 12-16 weeks and weighing 220-250 grams. Six rats were included in the healthy control group. Diabetes was induced in 30 overiectomized rats by intraperitoneal injection of streptozotocin (40 mg/kg). Then, the diabetic animals were divided into five groups of six including diabetic ovariectomized control, sham, propolis, endurance training, and endurance training + propolis. Rats in the training groups trained for eight weeks, five sessions per week, with 55-75% VO2 max. Moreover, propolis was administered 100 mg/kg/day by peritoneal injection. The level of Pro-oxidant-antioxidant balance (PAB) and expression of HSP72 and NF-κB genes were measured.
Results: HSP72 expression was significantly higher in the propolis, endurance training, and endurance training + propolis groups. The levels of NF-kB and malonaldehyde were significantly decreased in the ovariectomized diabetic rats (P<0.05). Expression of HSP72 in the endurance training and endurance training + propolis groups were significantly higher than in the propolis group. Moreover, NF-kB in the endurance training and endurance training + propolis groups were significantly lower than in the propolis group (P<0.05). The value of PAB in the propolis and endurance training + propolis groups were significantly lower than in the ovariectomized diabetic rats (P<0.05).
Conclusion: Exercise and consumption of propolis seem to synergistically improve the protective HSP72 pathway and reduce oxidative stress in heart tissue following estrogen dysfunction and diabetes. However, the interaction of the two depends on endurance training.
 

---

Background and Objective: With the increase in the spread of COVID-19, mental health consequences such as fear, anxiety, and depression have become prevalent. This study aimed to investigate the predictive role of fear of COVID-19 and quarantine fatigue on depression in congenital heart disease patients during the pandemic.
Methods: This descriptive-analytical study was conducted on 105 patients with congenital heart disease (6 men and 99 women) who were referred to Shahid Rajaee Hospitals and Tehran Heart Center during 2021-22. Data were collected using a depression scale, a fear scale for COVID-19, and a quarantine fatigue questionnaire.
Results: The results showed that 28.6% of patients with congenital heart disease experienced mild depression, while 7.6% had severe depression. Quarantine fatigue was found to be mild in 43.8% of patients. Additionally, fear of COVID-19 (r=0.195, P=0.001) and quarantine fatigue (r=0.617, P=0.001) were significantly correlated with depression in congenital heart patients.
Conclusion: Fear of COVID-19 is related to depression caused by coronavirus and quarantine fatigue in patients with congenital heart disease.
 

---

Background and Objective: In recent years, studies have been conducted to determine the prevalence rate of congenital abnormalities in different regions of Iran, most of which were conducted on live births. This study was conducted to determine fetal abnormalities in pregnancies leading to legal abortion in Golestan province.
Methods: This descriptive-analytical study was conducted on 199 pregnant women with a gestational age of less than 20 weeks with abortion licenses from the Forensic Medicine Center of Golestan province over 9 months during 2018-19. Demographic characteristics, including parents’ age, ethnicity, and family relationship, and the type of fetal abnormalities were recorded.
Results: Given 29,460 births in Golestan province over a 9-month period, the prevalence of fetal abnormalities was determined to be 6.75 per thousand births. The incidence rates of fetal abnormalities were determined to be 6.78, 6.68, 7.69, and 5.65 per thousand births in native Fars (80 cases), Turkmen (65 cases), Sistani (34 cases), and other (20 cases) ethnic groups, respectively. Since the gender of 80 fetuses was unknown, the incidence rates of abnormality were determined to be 4.36 and 3.72 per thousand births in female (63 cases) and male (56 cases) fetuses, respectively. The most common fetal abnormalities included central nervous system (n=49, 24.62%), chromosomal abnormalities (n=47, 23.61%), and cardiovascular impairments (n=26, 13.06%). The incidence of fetal abnormalities was not found to have a statistically significant relationship with parents' age, ethnicity, and family relationship.
Conclusion: The most prevalent fetal abnormality was related to central nervous system disorders. The incidence of fetal abnormalities had no relationship with the parents’ age, ethnicity, and family relationship.