Improving the quality of medical images at pre- and post-surgery operations are necessary for beginning and speeding up the recovery process. Partial differential equations-based models have become a powerful and well-known tool in different areas of image processing such as denoising, multiscale image analysis, edge detection and other fields of image processing and computer vision. In this paper, an algorithm for medical image denoising using anisotropic diffusion filter with a convenient stopping criterion is presented. In this regard, the current paper introduces two strategies: utilizing the efficient explicit method due to its advantages with presenting impressive software technique to effectively solve the anisotropic diffusion filter which is mathematically unstable, proposing an automatic stopping criterion, that takes into consideration just input image, as opposed to other stopping criteria, besides the quality of denoised image, easiness and time. Various medical images are examined to confirm the claim.
Anisotropic diffusion filter; medical image denoising; stopping criterion
The purpose of this study was to examine the impacts of hinged and solid anklefoot orthoses (AFOs) on standing and walking abilities in children with spastic diplegia.
Materials & Methods
In a quasi-experimental design, 30 children with spastic diplegia, aged 4-6 years were recruited. They were matched in terms of age, IQ, and level of GMFCS E&R. Children were randomly assigned into 3 groups: a hinged AFO group (n=10) plus occupational therapy (OT), a solid AFO group (n=10) plus OT, a control group who used only OT for three months. Gross motor abilities were measured using Gross Motor Measure Function (GMFM).
We obtained statistically significant differences in the values between baseline and after treatment in all groups. The groups were also significantly different in total GMFM after intervention. Furthermore, there were differences between hinged AFOs and solid AFOs groups, and between hinged AFOs and control groups.
We concluded that gross motor function was improved in all groups; however, hinged AFOs group appears to improve the gross motor function better than solid AFOs and control groups.
Child; Cerebral palsy; Spastic diplegia; Equinus deformity; Orthosis; Rehabilitation
Objectives. To investigate the prevalence of tooth loss and different prosthetic rehabilitations among Iranian adults, as well as the potential determinants of tooth loss. Methods. In a cross-sectional community-based study conducted among 8094 Iranian adults living in Isfahan province, a self-administered questionnaire was used to assess epidemiologic features of tooth loss. Results. Thirty-two percent of subjects had all their teeth, 58.6% had lost less than 6, and 7.2% of participants had lost more than 6 teeth. One hundred and sixty-nine individuals (2.2%) were edentulous. Among participants, 2.3% had single jaw removable partial denture, 3.6% had complete removable denture in both jaws, and 4.6% had fixed prosthesis. Others reported no prosthetic rehabilitation (89.5%). In the age subgroup analysis (≤35 and >35 years old) tooth loss was more prevalent among men than women (OR = 2.8 and 1.9, resp., P < 0.01). Also, in both age groups, current and former smokers had higher levels of tooth loss than nonsmokers (P < 0.001 and P < 0.05, resp.). In addition, tooth loss was positively related to metabolic abnormality for age group >35 years (adjusted OR = 1.29, P < 0.01). Conclusions. Tooth loss is highly prevalent in Iranian adult population. Community programs promoting oral health for prevention of tooth loss should be considered taking into account its major determinants including lower educational level, male gender, smoking, and metabolic abnormality.
AIM: To explore the association between consumption of spicy foods and prevalence of irritable bowel syndrome (IBS) among Iranian adults.
METHODS: In this cross-sectional study, data from 4763 Iranian adult participants were used. Consumption of spicy foods was estimated using a dietary habits questionnaire that included a question on spicy foods consumption: “how frequently do you use spicy foods (pepper, curry, ginger, cinnamon and turmeric) during a week?” Participants could respond to the question by choosing one of these choices: never, 1-3 times, 4-6 times, 7-9 times, or more than 10 times per week. A modified Persian version of the Rome III questionnaire was used to determine the prevalence of IBS.
RESULTS: IBS was prevalent in 21.7% (18.6% of men and 24.1% of women) of the study population. After controlling for potential confounders including dietary behaviors, those consuming spicy foods ≥ 10 times per week were 92% more likely to have IBS compared with those who never consumed spicy foods (OR = 1.92; 95%CI: 1.23-3.01, Ptrend < 0.01). The association remained significant even after taking lactose intolerance into account (OR = 1.85; 95%CI: 1.18-2.90, Ptrend < 0.01). Stratified analysis by gender revealed that the association between consumption of spicy foods and IBS was not significant in men; however, a significant association was found among women after taking potential cofounders, including meal regularity and lactose intolerance, into account. Women who consumed spicy foods ≥ 10 times per week were two times more likely to have IBS compared with those who never consumed spicy foods (OR = 2.03; 95%CI: 1.09-3.77, Ptrend = 0.02).
CONCLUSION: Consumption of spicy foods is directly associated with IBS, particularly in women. Further, prospective studies are warranted to (1) examine this association in other populations; and (2) evaluate whether dietary interventions, for example a reduction in spice consumption, would improve IBS symptoms.
Spice; Diet; Condiments; Red pepper; Irritable bowel syndrome; Functional gastrointestinal disorders
Regular exercise has been associated with improved quality of life (QoL) in patients with heart failure (HF). However, less is known on the theoretical framework, depicting how educational intervention on psychological, social, and cognitive variables affects physical activity (PA). The purpose of this study is to assess the effectiveness of a social cognitive theory-based (SCT-based) exercise intervention in patients with HF.
Materials and Methods:
This is a randomized controlled trial, with measurements at baseline, immediately following the intervention, and at 1, 3, and 6 months follow-up. Sixty patients who are referred to the cardiac rehabilitation (CR) unit and meet the inclusion criteria will be randomly allocated to either an intervention group or a usual-care control group. Data will be collected using various methods (i.e., questionnaires, physical tests, paraclinical tests, patients’ interviews, and focus groups). The patients in the intervention group will receive eight face-to-face counseling sessions, two focus groups, and six educational sessions over a 2-month period. The intervention will include watching videos, using book and pamphlets, and sending short massage services to the participants. The primary outcome measures are PA and QoL. The secondary outcome measures will be the components of SCT, heart rate and blood pressure at rest, body mass index, left ventricular ejection fraction, exercise capacity, and maximum heart rate.
The findings of this trial may assist with the development of a theoretical model for exercise intervention in CR. The intervention seems to be promising and has the potential to bridge the gap of the usually limited and incoherent provision of educational care in the CR setting.
Cardiac rehabilitation; exercise; heart failure; quality of life; randomized controlled trial; social cognitive theory
Quercetin has been distributed in a wide range of foods, but some of its known effects in vitro, are not proven in human studies. Therefore, the aim of this study was evaluation of the effects of quercetin intake on cardiovascular risk factors and inflammatory biomarkers in women with type 2 diabetes.
This double-blind randomized clinical trial was carried out on 72 women for 10 weeks. Subjects were assigned to quercetin and placebo groups using a permutated block randomization of size two. Quercetin was given to participants as a 500 mg capsule daily. Biochemical variables were measured at baseline and at the end of the study, and changes were compared using appropriate statistical methods.
Compared with placebo, quercetin intake decreased systolic blood pressure significantly (−8.8 ± 9.3 vs. −3.5 ± 11.7, P = 0.04). Although changes in diastolic blood pressure between the groups was not significant (P = 0.19), high-density lipoprotein cholesterol (HDL-C) was significantly decreased in both groups while changes in total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and ratio of TG/HDL-C and LDL-C/HDL-C were not significant between and within groups. Quercetin supplementation significantly reduced the serum concentration of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) (P = 0.01 and P < 0.0001, respectively); however, the mean changes in serum levels of IL-6, TNF-α, and high-sensitivity C-reactive protein were not significant between the groups.
Quercetin supplementation reduced systolic blood pressure significantly but had no effect on other cardiovascular risk factors and inflammatory biomarkers. Considering the biological effects of quercetin in vitro, we need more studies with a stronger design and sample size with different doses of quercetin.
Blood pressure; inflammatory biomarkers; lipids profile; quercetin
The aim of this study was to investigate eccentric torque production capacity of the ankle, knee and hip muscle groups in patients with unilateral chronic ankle instability (CAI) as compared to healthy matched controls.
In this case-control study, 40 participants (20 with CAI and 20 controls) were recruited based on convenient non-probability sampling. The average peak torque to body weight (APT/BW) ratio of reciprocal eccentric contraction of ankle dorsi flexor/plantar flexor, ankle evertor/invertor, knee flexor/extensor, hip flexor/extensor and hip abductor/adductor was determined using an isokinetic dynamometer. All subjects participated in two separate sessions with a rest interval of 48 to 72 hours. In each testing session, the torque production capacity of the ankle, knee, and hip muscle groups of only one lower limb was measured. At first, 3 repetitions of maximal eccentric-eccentric contraction were performed for the reciprocal muscles of a joint in a given movement direction. Then, the same procedure of practice and testing trials was repeated for the next randomly-ordered muscle group or joint of the same limb.
There was no significant interaction of group (CAI and healthy controls) by limb (injured and non-injured) for any muscle groups. Main effect of limb was not significant. Main effect of group was only significant for eccentric torque production capacity of ankle dorsi flexor and hip flexor muscle groups. The APT/BW ratio of these muscles was significantly lower in the CAI group than the healthy controls (P<0.05).
CAI is associated with eccentric strength deficit of ankle dorsi flexor and hip flexor muscles as indicated by reduction in torque production capacity of these muscles compared to healthy controls. This strength deficit appeared to exist in both the injured and non-injured limbs of the patients.
Eccentric Strength; Lower Limb; Chronic Ankle Instability
Placental abruption is one of the most common causes of bleeding during pregnancy. Multiple factors are known to be associated with increase of risk of placental abruption such as alcohol, cocaine use and cigarette smoking. The objective of this study was to identify risk factors for placental abruption in an Iranian women population.
Materials and Methods:
In a retrospective case – control study birth records included 78 cases with placental abruption and 780 randomly selected controls were investigated. Statistical analysis for comparing the studied risk factors between groups was performed using Pearson's Chi-square test along with presenting relevant odds ratio (OR).
From 7301 deliveries included in the study, 78 (1%) was complicated placental abruption. Women aged 35 or more likely for experiencing (OR = 3.650, 95% confidence interval [CL] = 1.57-6.83) and those who had a previous cesarean section (OR = 2.65, 95% CL = 3.91- 33.41) were in higher risk for placental abruption ([50 cases] 64% vs. [28 cases] 36% P < 0.01).
The results indicate that among the placental abruption is one of the most common causes of bleeding during the pregnancy and one of the major obstetrical emergency.
Iran; placental abruption; pregnancy; risk factors
Ginger rhizomes (rich in gingerols, shogaols, paradols and zingerone) have been used in Asia for the treatment of asthma, diabetes, and pain, and have shown potent anti-inflammatory attributes. Common spices such as Cinnamon (including cinnamic aldehyde and cinnamyl aldehydeis) are used in food and many studies have focused on its anti-inflammatory components. Intense exercise can result in an inflammatory response to cell damage and also muscle soreness. The efficacy of dietary ginger and cinnamon as anti-inflammatory agents and their effectiveness in reducing muscle soreness has been investigated in limited studies on humans. Therefore, we have studied the effects of dietary ginger and cinnamon on inflammation and muscle soreness in Iranian female taekwondo players.
Sixty healthy, trained women, aged 13-25 years, were enrolled in the six-week investigation and randomly categorized into three groups (cinnamon, ginger or placebo) and received 3 g of ginger, cinnamon or placebo powder each day, depending on the group they belonged to. The IL-6 level and Likert Scale of Muscle Soreness were evaluated at the beginning and the end of the study and compared among the groups.
Forty-nine of the participants completed the six-week intervention. There were no significant changes in the IL-6 cinnamon and ginger group when compared with the placebo group, whereas, there was a significant fall in muscle soreness in the cinnamon group and placebo (P < 0.1) and ginger group and placebo (P < 0.01).
Administration of ginger and cinnamon in athlete women for six weeks did not show any significant change in the IL-6 level, but showed a decrease in muscle soreness in the cinnamon and ginger groups.
Athletes; cinnamon; ginger; inflammation; muscle soreness
The need for energy in strenuous exercises necessitates an increase in oxygen consumption and production of reactive oxygen species. It seems that supplementation of vitamins C and E reduces exercise-induced oxidative stress. Therefore, this study aims to investigate the effects of vitamin C and E supplementation on muscle damage and oxidative stress in female athletes.
The study was a four-week randomized, double-blind clinical trial, conducted on 64 trained female athletes recruited in the Isfahan sports club. They were randomly assigned to one of the following four groups: (a) vitamin C (250 mg/day), (b) vitamin E (400 IU), (c) vitamin C + vitamin E, and the control (placebo). Aspartate transaminase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH) for assessing muscle damage, and malondialdehyde, were measured before and after the intervention.
In the between-groups comparison, only creatine kinase significantly changed at the end of the period (P = 0.03). However, in the intergroup comparison creatine kinase was significantly decreased in group 1 (P = 0.002). As for Aspartate aminotransferase, no significant difference was spotted in any of the comparisons. Lactate dehydrogenase was significantly decreased in group 2 (P = 0.02). Finally, this study revealed a significant decrease in oxidative stress markers in groups 1, 3, and 4 (P < 0.05).
It is induced from the results that vitamin C and E supplementation plays a role in reducing muscle damage markers of aerobic exercises.
Vitamin E; female athlete; oxidative stress; muscle damage; vitamin C
Due to the special training conditions and lifestyle athletes require an antioxidant system that is more efficient than others. To keep this system optimal, many of them use antioxidant supplements. This study aimed to investigate the effects of vitamins C and E supplementation on muscle damage, performance, and body composition in athlete women.
The study was a 4-week randomized, double-blind clinical trial conducted on 64 trained female athletes recruited in Isfahan sports club. They were randomly assigned to one of the following four groups; A: vitamin C (250 mg/day), B: vitamin E (400 IU), C: vitamin C + vitamin E and control (placebo). Harvard Step Test was used to measure maximal oxygen consumption for performance, body composition, and damage marker (myoglobin) were measured before and after the intervention.
Comparing the result of the test in performance of sport, there was no significant difference between groups in VO2 max. Also, vitamin supplements had no significant effect on subcutaneous fat between the groups, however, in the intergroup comparison, were significantly increased in group control (P = 0.03). But, there were no significant differences, change in myoglobin between the groups. There was a significant increase in group A (P = 0.04).
Vitamins C and E supplementation had no significant effect on any of the studied parameters.
Body composition; clinical trial; vitamin supplementation; female athlete; muscle damage; performance; vitamin C; vitamin E
Ginger (rich in gingerols and shogaols) rhizomes have been widely used as dietary spices and to treat different diseases in Asia. Cinnamon (containing cinnamic aldehyde and cinnamyl aldehyde) is used as spices and as a pharmacological agent in ancient medicine. Intense exercise can result in oxidative damage to cellular compounds and also muscle soreness. Efficacy of dietary ginger and cinnamon as antioxidant agents and their effectiveness in exercise performance and reducing muscle soreness have been investigated in limited studies on humans. So we studied the effects of dietary ginger and cinnamon on oxidative stress and exercise performance and body composition in Iranian female taekwondo players.
Sixty healthy trained women, aged 13-25 years, were enrolled in the 6 week investigation and randomly categorized in three groups (cinnamon, ginger, or placebo) and received three grams of ginger, cinnamon, or placebo powder each day depending on the group they belonged. Human malondialdehyde (MDA) level, exercise performance, and body composition were evaluated in the beginning and at the end of the study and compared among the groups.
Forty-nine of the participants completed the 6 weeks intervention. There was minor decrease in MDA in cinnamon and ginger group compared with the placebo group and significant increase in exercise performance in ginger group (P < 0.01), and considerable increase in skin fold in cinnamon groups (P < 0.01), whereas there were significant accretion in BMI for ginger group (P < 0.1) and cinnamon group (P < 0.05). No significant changes in MDA, EP, and BMI were observed between groups over time. But there were specific changes in skin fold between cinnamon and placebo group (P < 0.05) and cinnamon and ginger groups (P < 0.05).
Six weeks administration of ginger and cinnamon in athlete women did not show any significant change in MDA level, body composition, and exercise performance as compared with the placebo group.
Cinnamon; exercise; ginger
Asymmetric dimethylarginine (ADMA) has a predominant role in progression of some cardiovascular diseases, including diabetes. It interferes with L-arginine in production of nitric oxide (NO) by inhibition of NO synthase. The purpose of this study was to evaluate the effect of resistance training on plasma NO and ADMA concentrations in type 1 diabetic male rats.
Thirty-six male wistar rats were randomly divided into four groups: (1) control; (2) diabetic; (3) diabetic trained, and (4) control trained (n = 9 each). In the trained groups, the animals undertook one training session per day, 3 days/week, for 4 weeks. At the end of experiment, blood samples were taken and the concentrations of plasma glucose, insulin, lipid profile, NO and ADMA concentrations were determined.
plasma ADMA concentration showed a significant increase in diabetic rats compare to control group (0.73 ± 0.07 vs. 0.62 ± 0.04 μmol/l; P < 0.05). The plasma ADMA level in the trained diabetic and control were lower than the sedentary groups, although it was not statistically significant. Plasma NO concentration in diabetic group was lower than control (P < 0.05). Resistance training significantly increased plasma NO concentration in diabetic animals (P < 0.05).
Elevated ADMA level in diabetic animals can normalize during resistance exercise. Reduced ADMA level and increased NO level following resistance training might improve cardiovascular risk in diabetic subjects.
Asymmetric dimethylarginine; diabetes; nitric oxide; resistance training
Objectives. The aim of the current study was to investigate the growth status of CH, generate specialized growth charts of CH infants, and compare them with their counterparts of regional normal infants. Methods. In this prospective cohort study, 760 (345 girls and 415 boys) neonates born in 2002–2009 diagnosed by neonatal CH screening program in Isfahan were followed up from the time of diagnosis. 552 healthy children were recruited as a control group. The empirical 3rd, 15th, 50th, 85th, and 97th percentiles for height, weight, and head circumference of both sexes were determined and compared with their counterpart values of the control group. The relative frequency of patients with impaired growth for each studied variable was determined. Also, specialized growth charts of CH patients were generated. Results. The percentiles of weight, height, and head circumference of studied patients are significantly different from regional healthy children (P < 0.001). The relative frequency of impaired head circumference was decreased to less than 3% at the 3rd year of age and for height it reached gradually 3% and 9% at the 5th year of age for boys and girls, respectively (P < 0.05); however for weight still it was statistically more than 3% in both sexes. Conclusion. CH patients had impaired growth development which was improved during follow up, but the catch-up time was earlier for head circumference and later for weight.
Flavonoids comprise a large group of plant metabolites, 6,000 of which have been identified to date. Some studies have shown the increased aerobic performance and maximal oxygen consumption (VO2max) and therefore fitness following quercetin intake as a result of elevated number of intracellular mitochondria caused by the flavonoid.
This double-blind clinical trial comprised 60 male students having an athletic history of at least 3 years. Body composition, exercise performance, and some blood biomarkers were analyzed. The individuals were selected by convenient sampling, and then were assigned into four groups of equal number by using permuted block randomization. The first to fourth groups received a 500 mg supplemental quercetin capsule plus a 250 mg vitamin C pill, a 500 mg supplemental quercetin capsule plus a 250 mg placebo vitamin C pill, a 500 mg placebo quercetin capsule plus a 250 mg vitamin C pill, and a 500 mg placebo quercetin capsule plus a 250 mg placebo vitamin C pill, respectively, daily for 8 weeks. The participants were asked to continue their routine diet and physical activity during the study and they were monitored through phone calls or text messages.
Lean body mass, total body water, basal metabolic rate, and total energy expenditure increased significantly in the quercetin group after intervention. On the other hand, VO2max increased in the “quercetin” and “quercetin + vitamin C” groups following the intervention, non-significantly.
Our findings suggest that supplementation with quercetin in athletes may improve some indices of performance.
Athletes; quercetin; body composition; exercise performance; muscle damage
Objective. The present paper aimed at investigating the association between perceived stress and major life events stressors in Iranian general population. Methods. In a cross-sectional large-scale community-based study, 4583 people aged 19 and older, living in Isfahan, Iran, were investigated. Logistic quantile regression was used for modeling perceived stress, measured by GHQ questionnaire, as the bounded outcome (dependent), variable, and as a function of most important stressful life events, as the predictor variables, controlling for major lifestyle and sociodemographic factors. This model provides empirical evidence of the predictors' effects heterogeneity depending on individual location on the distribution of perceived stress. Results. The results showed that among four stressful life events, family conflicts and social problems were more correlated with level of perceived stress. Higher levels of education were negatively associated with perceived stress and its coefficients monotonically decrease beyond the 30th percentile. Also, higher levels of physical activity were associated with perception of low levels of stress. The pattern of gender's coefficient over the majority of quantiles implied that females are more affected by stressors. Also high perceived stress was associated with low or middle levels of income. Conclusions. The results of current research suggested that in a developing society with high prevalence of stress, interventions targeted toward promoting financial and social equalities, social skills training, and healthy lifestyle may have the potential benefits for large parts of the population, most notably female and lower educated people.
Athletes use flavonoids as antioxidant to enhance endurance and physical performance. In vitro data indicate flavonoids have antioxidative and antiinflammatory functions but data in human studies are limited. The aim of this study was to determine the effects of a 2-month flavonoid quercetin supplementation on oxidative stress and inflammatory biomarkers in nonprofessional athletes with regular exercise.
Materials and Methods:
The randomized double-blind clinical trial was done among subjects with systematic and regular exercise for 8 weeks in four groups, each containing 15 individuals: 500 mg quercetin + 250 mg vitamin C as pro-oxidant (Q+C), 500 mg of quercetin alone (Q), 250 mg of vitamin C alone (C), and placebo (Control). IL-6, CRP, E-selectin and F2-isoprostane were measured before and after intervention.
In 60 participants with mean (±SD) age of 21.0 ± 1.6 years, statistically significant within group differences were observed in IL-6 (P<0.1), CRP (P<0.01) and F2-isoprostane for group 1 and pre- and postchanges in E-selectin was marginally significant for all study groups (P<0.1). Group 1 had marginally smaller F2-isoprostane (P<0.1) and interleukin 6 than control group (P<0.05) and there were marginally differences in CRP between respondents in group 1 and 2 with the control group (P<0.1).
Eight-week supplementation with quercein-vitamin C was effective in reducing oxidative stress and reducing inflammatory biomarkers including CRP and IL-6 with little effect on E-selectin in healthy subjects.
CRP; E-selectin; F2-isoprostane; interleukin 6; Quercetin; ROS production; vitamin C
Quercetin is a bioflavonoid occurs in many food items. Some previous studies on quercetin showed the inconsistent results on exercise performance and muscle damage in athletes. The aim of this study was to determine the effects of 8 weeks of quercetin supplementation on exercise performance and muscle damage indices in student athletes.
This placebo-controlled, double-blind clinical trial was conducted on 60 male students for 8 weeks. The subjects were randomly assigned to one of the four groups: a) quercetin (500 mg/day quercetin + 200 mg/day placebo), b) quercetin+ vitamin C (500 mg/day quercetin + 200 mg/day vitamin C), vitamin C (500 mg/day placebo + 200 mg/day vitamin C), and placebo (500 mg/day placebo + 200 mg/day placebo). Time to exhaustion (TTE) for measuring performance, aspartate transaminase (AST), and creatine kinase (CK) for measuring muscle damage and body fat percent (BFP) were measured before and after intervention.
CK levels reduced in group 1 significantly (P=0.045) and BFP reduced in group 1, 3, and 4, significantly, too (P=0.018, P=0.013, and P=0.043, respectively). Whereas statistically significant changes between groups were not observed for TTE, AST, CK, and BFP after 8 weeks of intervention.
Supplementation with quercetin and vitamin C for 8 weeks did not improve exercise performance but reduced muscle damage and body fat percent in healthy subjects.
body composition; muscle damage; performance; Quercetin; vitamin C
The present study was aimed at investigating the awareness level about warning signs of cancer and its determinants in an Iranian general population. This cross-sectional interview-based survey investigated 2,500 people aged 18 years and over, as a representative sample of Tehran population. Latent class regression was applied for analyzing data. A small (18.8%) proportion of the respondents had high level of knowledge, and 54.5% had moderate awareness, and 26.7% had low level of awareness. Most effective predictors for awareness were educational attainment, sex, and marital status. The findings suggest that the overall level of knowledge about warning signs of cancer among the public is low, particularly about some specific signs. Accordingly, educational and intervention programmes, with special attention placed on particular at-risk populations, to increase awareness about the disease leading to its early diagnosis are needed.
Awareness; Cancer; Cross-sectional studies; Health education; Neoplasms; Public education; Signs and symptoms; Iran