مجله علوم پزشکی رازی
سال بیست و هشتم شماره 1 (پیاپی 203، فروردین 1400)

Taking drugs (methamphetamines) increases free radicals and causes oxidative stress in the body. Addiction is a chronic disease that requires long-term treatment. To date, drugs that have been widely used to prevent relapse and reduce cravings in consumers have not been successful. Evidence also suggests that for better adaptation to the environment, a balance between physical fitness and physical composition is needed, and if individuals do not have favorable conditions in terms of physical condition and physical composition, they are usually isolated, pessimistic and isolated from mental balance. They will not have a good time. Basically, high levels of health, hygiene and physical fitness indicators can indicate the health and ability of a community and the term physical fitness can be used in connection with muscle strength, muscle strength, muscle endurance, cardiorespiratory endurance, flexibility and agility. Other factors affecting the diseases of addicted people include oxidative stress caused by the production of free radicals. Free radicals have negative effects such as cardiovascular disease. If the production of free radicals exceeds the ability of the antioxidant defense system to withstand, oxidative pressure is created. With increasing oxidative pressure, the balance between oxidative stress and antioxidant system disappears and by overcoming oxidative pressure on the antioxidant system, inflammatory responses are stimulated and organs are damaged and ultimately lead to various diseases and endanger the health of the individual. Sirt-1 is a basic protein for coping with oxidative stress and homeostasis control, also known as the elixir of youth and longevity factor. Sirt-1 is a basic protein for coping with oxidative stress and homeostasis control, also known as the elixir of youth and longevity factor. Sirt-1 destiles many target proteins, such as p53 and FoxO proteins, which provide protection against apoptosis and play an important role in the survival of many cell types. Recent studies have shown that Sirt-1 controls the transcription activities of FoxO. It is predicted that Sirt-1 is a suitable candidate that regulates the cells of the bodychr('39')s tissues against oxidative stresses. The use of non-pharmacological methods such as exercise training is important for the treatment of addiction. Among these exercises are Pilates exercises. Pilateschr('39') goal is to strengthen the physical strength, achieve and maintain a healthy body, as well as a healthy mind to perform good daily tasks and other physical activities. So The aim of the present study was to investigate the effect of eight weeks of Pilates training on serum levels of Sirt-1 and some physical fitness in methamphetamine-addicted men.

The present study was a semi-experimental study in which the study population of addicted men was quitting, 44 of whom were infected by random sampling method with at least three months of presence in addiction treatment camp in two groups (with inclusion criteria: a) duration of presence more than two months in Camp B) not taking certain drugs during the study period C) age range of 15-40 years d) history of drug use more than two years and addiction to methamphetamine And those with a history of orthopedic, cardiac and metabolic diseases with severe neurological symptoms were excluded from the study), exercise (21) and control group (23) were excluded. Seventy-two hours before the start of the training program, the subjects were familiar with the research conditions and the environment of the training hall in the briefing session and body indicators such as height and weight were measured. Also, in order to determine aerobic fitness and to evaluate the maximum oxygen consumption (VO2max), rockport one mile walking test was used and for muscular endurance was obtained through sitting test that the number of sittings per minute was measured for each person and for flexibility, sitting and reach test was used. Blood samples were performed 24 hours before the start of the exercises. The training group (Pilates) participated in 3 sessions of 60 Pilates precision training sessions each week. The control group continued their normal life until the end of the study without participating in any exercise program. Each Pilates training session consisted of 10 minutes of warm-up, 45 minutes of Pilates specialized training and 5 minutes of cooling. It should be noted that the training protocol based on the latest ACSM guidelines for inactive and unprovoked individuals and considered intensities also started from 40% and increased to 70% according to ACSM guidelines. Blood samples were taken from the braid vein in pre and post-test conditions of 5 cc. Sirt-1 concentration was measured using ZellBio GmbH ELISA kit, Germany. To detect the normal distribution of data, Kolmogrov-Smirnov test was used to investigate intragroup and intergroup changes of dependent and independent t-test. Data were analyzed using SPSS software version 20 at a significant level of 0.05.

Evaluations of dependent T-test after the intervention of eight seven Pilates exercises showed that sirt-1 serum values were significantly unchanged in the control group (p=0.814), but in the training group it was associated with a significant increase (p=0.001). Flexibility in the control group after 8 weeks was significantly unchanged (p=0.545), but in the training group after 8 weeks the intervention increased significantly (p=0.019) and muscle endurance in the control group after eight weeks was unchanged (p=0.496), but in the training group after eight weeks the intervention increased significantly (p=0.001).

The present study showed that after 8 weeks of Pilates training, serum levels of Sirt-1, muscular endurance and flexibility increased significantly. Considering the important role of Sirt-1 in different cellular processes and increasing its level after exercise and also strengthening physical fitness factors after exercises, it can be said that increasing these factors is one of the possible mechanisms that Pilates exercises can increase health and prevent risk factors and pathogenesis in addicts. Research has shown Sirt-1 plays its anti-oxidative role through SRT1720 activator, reducing oxidative stress caused by exposure to cigarette smoke in lung tissue. Sirt-1 does this by activating the Foxo3-dependent pathway and reducing oxidative stress caused by this pathway has a protective role against pulmonary inflammation in people with lung disease. Based on the present findings, Pilates training may be used as an important non-pharmacological agent to improve Sirt-1 and enhance muscle endurance and flexibility.

Osteoarthritis pain is a type of chronic pain. One of the reasons that make this pain one of the most problematic diseases of the present age is its coexistence with physical diseases and mental disorders. Studies show that anxiety and depression are commonly associated with chronic pain. Needless to say, due to its chronic, painful and debilitating nature, this disease has reduced the quality of life (1,2,3) and increase the prevalence of depression in these patients. Studies show that osteoarthritis pain, through its effect on fatigue and disability, causes a depressed mood. There is an extensive research literature today that shows that although behavioral and psychological factors may not play a significant role in the onset of pain, but these factors in the transformation of acute pain into chronic and its continuation and also in explaining the severity of pain and related problems, including Depression, disability and anxiety play a crucial role (4-7). Because depression is often undiagnosed in patients with chronic pain, this problem is often not treated, and on the other hand, depression is associated with reduced effectiveness of treatments methods (7,10). Studies have shown that osteoarthritis is a chronic inflammatory process with cellular and biochemical changes that justifies drug treatment (12). Accordingly, some studies support the efficacy and safety of ozone injection in the treatment of osteoarthritis (13,14), but there is no clear agreement on this, and ozone at high concentrations is likely to have different effects on osteoarthritis. Today, stem cells are used to treat many diseases, including osteoarthritis, and a recent study looked at their effect on depressive behaviors (15). In addition, exercise is a good way to achieve the desired mental state and improve states of depression, anxiety and self-confidence. Therefore, due to the few and sometimes contradictory studies in this regard and also due to the growing need for new therapies, we examined a new therapeutic approach for depressive disorders associated with osteoarthritis based on MSCs transplantation, ozone therapy and aerobic exercise in osteoarthritis rats.

In this experimental study, 40 two-month-old male Wistar rats were purchased from Pasteur Institute of Iran-Tehran, weighing about 230-250 g and transferred to the animal room. To prevent stress and change physiological conditions, they were kept under new conditions of temperature(22±2°C), humidity(%50±5) and light-dark cycle of 12:12 h for one week. Osteoarthritis was surgically treated (1). For this purpose, the animals were first anesthetized using a mixture of ketamine (50-50 mg/kg) and xylazine (3-5 mg/kg). Then, under sterile conditions, a vertical incision was made in the inner part of the knee of the right foot with a surgical blade and other surgical instruments on the skin that had been previously shaved. After removing the skin, the medial collateral ligament of the knee was removed to observe the internal meniscus. The osteoarthritis model was then induced by making an incision that incompletely resulted in rupture and injury to the meniscus, and the area was sutured again with a sterile method. All steps were performed in the least amount of pain to the animal according to the principles of working with laboratory animals. A three-week recovery period was considered after induction of the medial meniscus tear model. After induction of osteoarthritis, subjects were divided into eight groups of five, including 1) osteoarthritis patient control, 2) MSCs, 3) exercise, 4) ozone, 5) exercise+ozone, 6) Exercise+MSCs, 7) Ozone+MSCs, 8) Exercise+Ozone+MSCs were replaced. Also, to investigate the effects of osteoarthritis induction on the research variables, 5 rats were placed in a healthy control group. In order to get acquainted with the treadmill, were trained on the rodent treadmill for a week (3 times a week; for 10 minutes, without slope and at a speed of 5-8 m/min; 60%-70% VO2max). The main training program for 8 weeks in aerobic exercise groups, for three sessions per week and 30 minutes of running on a treadmill without slope at a speed of 16 m/min was initiated in the first week, which gradually reached 50 minutes in the eighth week (19). Also, 5 minutes at a speed of 8 m/min at the beginning and end of exercise were performed for Warm-up and cool-down the animals. In this study, bone marrow mesenchymal stem cells were obtained from the National Center for Genetic Resources and then transferred to an incubator under sterile conditions. After 2 days, the supernatant was removed and after washing with PBS,DMEM/F12 warm and fresh medium was gently added to it. The cells were qualitatively examined for morphology and growth process. The cell environment was changed every 2 to 3 days for about 2 weeks until the cells in each group reached the appropriate density. Then the first passage was performed, so that the cells was removed from the bottom of the cultivation dishes using Trypsin/EDTA 0.2% made by the German company Gibco and cultured in a ratio of 3:1. About 10-15 days after each passage, the next passage was done. After filling the bottom of the culture dish and reaching a density of 90%, these cells were frozen in the desired passage to be used for injection purposes in the next stage of research. Then, after complete anesthesia of the animal in the cell therapy groups and during the recovery period, 1×106 cells/kg were injected as a single injection at the model induction site (20). It also injects oxygen into the ozone generator and produced ozone there using electricity. Then a 10 ml syringe was connected to the generator output and 10 ml of the produced gas was used to obtain ozone with a concentration of 20μg/ml. In the ozone treatment groups, 20 μg/ml was injected into the knee tibia-femoral articular line in 3 weeks after surgery, in 3 repetitions, at different times and for 3 consecutive weeks before the start of the training program (21). In the ozone+MSCs group, after intra-articular injection of ozone and in the fourth week, MSCs were injected as a single injection at a dose of 1×106 cells/kg. At the end of the treatment period, open field test was performed to evaluate the level of anxiety and depression in osteoarthritis rats (22). This test was performed for one day at light time. To perform the test, we held the rats from the base of the tail and placed them in one of the four corners of the device, allowing the animal to freely explore the environment of the device for 5 minutes. In this test, the parameters of total travel distance, time spend in periphery and time spend in center were evaluated to assess the level of anxiety and depression in rats. To analyze the results, Shapiro-Wilk statistical tests, independent t-test and 3-way ANOVA were used (p≥0.05).

Induction of osteoarthritis led to anxiety and like depression behaviors (p≥0.05). However, exercise+MSCs significantly reduced circulation in the environment and significantly increased circulation in the center (p≥0.05); exercise, ozone, and MSCs each alone, exercise+ozone, and exercise+MSCs significantly increased the overall distance traveled (p≥0.05). Therefore, exercise, ozone, MScs, exercise+ozone interaction and exercise+MSCs had more favorable effects than the combination of MSCs+ozone and the interaction of all 3 interventions in increasing motor index and reducing depression.

Due to the discrepancy in the results of the reported studies, it is not possible to say with certainty, how chronic pain such as osteoarthritis is associated with the occurrence of behaviors related to depression and anxiety and the mechanism of effect of therapeutic interventions in the present study on osteoarthritis. However, exercise may reduce inflammatory factors, increase the activity of the serotonergic system, and reduce oxidative stress, which has anti-depressant effects, by increasing the expression and production of brain-derived neuronal growth factor (28). Also, injection of MSCs and ozone due to its anti-inflammatory properties and increase the oxygen content of the tissue improves the metabolism of cartilage tissue in the knee, which can reduce joint pain and stiffness by improving inflammatory factors, leading to improved function and quality of life in patients (32). On the other hand, ozone causes a feeling of well-being and happiness after ozone therapy by releasing endorphins and possibly increasing serotonin[33]. Overall, the results of this study showed that exercise, MSCs and MSCs+ozone have a protective effect in inducing the osteoarthritis model and modulate their anti-anxiety effects by increasing the circulation time in the center. Also, exercise, ozone, MSCs alone, and exercise+ozone and exercise+MSCs have more favorable effects in reducing depression due to osteoarthritis.

Type two diabetes mellitus (T2DM) is recognized as a metabolic disorder related to various complications such as heart disease, renal disease, and ischemic stroke. Type 2 diabetes is characterized by a defect in the insulin receptors on the cell membrane of the target cells, which in fact causes a kind of resistance or reduction of insulin sensitivity in the body. In recent years, various studies have been conducted on genes involved in diabetes, and research has revealed the fact that genes and gene interactions play an important role in pathogenesis as well as increasing the risk of diabetes. Given that type 2 diabetes accounts for about 25% to 25% in developed countries and even higher in developing countries, the prevention and care of this type of diabetes is of particular importance. The prevalence of type 2 diabetes has increased significantly in recent years in the world and in our country. In addition, unfortunately, we are witnessing a decrease in the age of onset of this disease. The ANGPTL4 is recognized as crucial protein that modulates glucose homeostasis and recent data suggest that ANGPTL4 may be correlated with the risk of type two diabetes. This protein is encoded in humans by the ANGPTL4 gene. This gene is a member of the angiopoietin family, which encodes a glycosylated secretory protein with an amino terminal domain containing compressed screws and a carboxyl end domain such as fibrinogen (11). This protein is expressed in mice and humans in a wide range of cells. In humans, it is more expressed in muscle, liver, kidney and intestine than other tissues, but the highest rate of expression is observed in humans in liver tissue. We sought to investigate ANGPTL4 expression in type 2 diabetic patients compared to healthy participants.

This study was a case-control study. Fifty patients with type 2 diabetes (15 males and 35 females) were included in the study group and 50 healthy individuals (18 males and 32 females) were included in the study. The subjects were gender matched. We recruited 50 patients with type 2 diabetes mellitus and 50 healthy individuals that referred to Shohadayeh Tajrish Hospital. FBS and insulin circulating levels were measured using Hitachi auto-analyzer and ELISA method respectively. We separated mononuclear leukocytes (PBMC) using a density gradient process following ficoll solution. Upon extraction of PBMC, we extracted RNA using Gene All kit. Then Real-time PCR method performed to assess the transcript levels of ANGPTL4. Written consent was obtained from all eligible individuals to agree to participate in the study, assuring them that the samples taken would only be used in this research project and that the results would be valid. This review will remain confidential. Quantitative data were analyzed using Kolmogorov-Smirnov test and if normal, using quantitative t test, quantitative data were compared between the two groups. Abnormal data were analyzed using Mann-Whitney test. Chi-square test was used to compare qualitative data between the two groups. Prism 6 software was used to analyze the data and data with p<0.05 were considered significant.

This study was performed as a case-control study on 50 patients with type 2 diabetes and 50 healthy individuals as a control group. The demographic and clinical characteristics of the subjects are shown in Table 1. Due to the abnormal distribution of data, the data using the median and IQR, as well as to compare the differences between the two groups, the Mann-Whitney test was used. As shown in the table, the age range was 57 (43-69) in the diabetic group and 55 (49-64) in the healthy group (p=0.058).The ANGPTL4 gene expression in type 2 diabetic group was decreased compared with the healthy participants, but it was not statistically significant (p<0.065). Overall, our results demonstrate that there is a positive correlation between FBS and ANGPTL4 expression (r= 0.214, p<0.0067). The average body mass index in the diabetic group was 27.9 (29-24) Kg / m2 and in the healthy group was 26 (28-23) Kg / m2. The results also showed that the mean blood sugar in the diabetic group was 139 (125.3-180) and in the healthy group was 91 (99-84). Statistical analysis showed that there was a significant difference between the blood sugar results of the two groups (p=0.001).

Recent studies have shown that ANGPTL4 plays an important role in glucose homeostasis, pathogenesis of diabetes as well as metabolic syndrome. However, studies have not been sufficient and in some studies, contradictory results are observed. Therefore, the present study was designed to evaluate and compare the expression of ANGPTL4 gene with indices associated with people with type 2 diabetes compared with healthy individuals. In this study, it was found that serum levels of FBS (P value <0.001) and HOMA-IR in the diabetic group increased compared to the control group. While no significant difference was observed between other parameters such as BMI. Also, due to matching the control and patient groups in terms of age and selection from both male and female groups, no significant difference in terms of age and sex was observed between the two groups. The level of expression of ANGPTL4 in participants with type 2 diabetes has diminished. The results of the present study showed that the expression level of ANGPTL4 gene in diabetic individuals decreases compared to healthy individuals. In addition, the expression of this gene is positively correlated with fasting blood sugar. However, the association of this molecule with glucose metabolism as well as the pathogenesis of diabetes has not been fully investigated. It seems that despite the studies on the relationship between ANGPTL4 and type 2 diabetes, our understanding of this relationship and mechanism is still incomplete and more studies are needed in this field. It is suggested that in future studies, the level of ANGPTL4 in the serum of individuals Diabetes and its relationship with biochemical parameters such as HDL-c and LDL-c as well as the enzyme lipoprotein lipase should be examined. It seems that despite studies on the relationship between ANGPTL4 and type 2 diabetes, we unable to describe the possible relationship and mechanism of ANGPTL4 in metabolic pathways. Further studies are needed to investigate this notion.

Walking as a form of transportation, is the basis for competitive sports as well as health and fitness. However, in connection with the common style of walking forward much research has been done, however, walking backward has not been noticed and is new to most people (11). Walking backward can have potentially beneficial benefits for rehabilitating a physical injury and be equally important for a sedentary one (14). Electromyographic activity of the lower limb muscles while walking backward is higher than forwards, resulting in more energy consumption (15). Other benefits of walking backward include producing more muscle activity due to the personchr('39')s effort compared to walking forward. This consumes more energy while walking backward. Also, walking back requires more oxygen, metabolic and cardiorespiratory responses than walking forward (16, 17). The researches done in this regard have shortcomings so that in none of the researches, a certain speed has been used and the subjects have practiced at the desired speed and the intensity of the exercises is not known in much researches. On the other hand, in this researches, exercises have been performed on a flat surface without slopes and on the ground, and most of the tests performed have been reported in the field using formulas and mathematical calculations, and laboratory and accurate studies are rarely seen among them. Therefore, according to the above, it is possible to observe different effects in training responses by manipulating the components and training methods. Therefore, the aim of the present study was to compare the effect of four weeks of walking back and forth on a treadmill on the components of body composition and physical fitness in sedentary and overweight girls.

The present study was conducted in a quasi-experimental design with two measurement steps and in two groups (walking forward and walking backward). The statistical population of this study was female students of the Ferdowsi University of Mashhad and the statistical sample of the study was 30 female students who were selected voluntarily through available sampling and based on research criteria. Before the start of the study, all subjects attended a coordination session and in this session, after a complete description of the objectives, research method, and possible risks arising from the research, all subjects completed the informed consent form, relevant questionnaires and randomly in two The group of 15 people was divided into walking forward and walking backward. Subjects in both groups performed back and forth walking protocols for four weeks. Measurement of variables from subjects (fat mass weight, lean mass weight, hamstring flexibility, quadriceps flexibility, cardiorespiratory endurance, hamstring muscle strength, quadriceps strength, hamstring endurance, quadriceps endurance- Thigh, static balance) was performed in two stages 24 hours before the first training session and 48 hours after the last training session in the fourth week. The training protocol consisted of four weeks of walking forward on a treadmill (for the forward walking group) and four weeks of walking backward on the treadmill (for the backward walking group), which was performed 3 sessions per week (4). Each session included 5 minutes of warm-up and 5 minutes of cooling with a treadmill at the desired speed. The training speed for 4 weeks was 1.1 m / s equal to 4 km / h and the treadmill slope was equal to 5%. To increase the load, the training time was increased by 5 minutes per week and reached 25 minutes in the last week (4). To measure body composition variables (weight, fat mass, and lean mass) from body composition analyzer with Inbody720 brand made in South Korea, the flexibility of hamstring and quadriceps muscle using a goniometer (9). Maximum oxygen consumption using Bruce test (12), lower body muscle strength using forward thigh movements with the machine and back movement with a supine device (10), muscular endurance using repetition to fatigue test with 70% of maximum repetition The person was moving in front of the thigh and behind the thigh with the device (12) and the balance was measured with the help of the Biodex balance device (13). SPSS statistical software (version 16) was used to analyze the data. Also, to compare intra-group and inter-group changes, the dependent and independent therapeutic methods were used, respectively. P-value of less than 0.05 was considered significant.

The results showed that between the two groups walking forward and walking backwards in the values of fat mass weight (p = 0.315), lean mass weight (p=0.872), general balance score (p=0.571), There is no significant difference between posterior anterior balance score (p=0.675), lateral balance score (p=0.987) and maximum oxygen consumption (p=0.053). But between the two groups in terms of superior hamstring muscle flexibility (p=0.001), non-superior hamstring muscle flexibility (p=0.015), superior quadriceps muscle flexibility (p=0.012), muscle flexibility Non-superior quadriceps (p=0.001), hamstring muscle strength (p=0.002), quadriceps muscle strength (p=0.001), hamstring muscle endurance (p=0.003) and endurance There is a significant difference in the quadriceps muscle (p=0.001) in favor of the backward walking group.

The results of the present study showed that walking forward during a four-week training period has a positive effect on improving cardiorespiratory endurance, muscle strength, muscle endurance, muscle flexibility and static balance, however, it has no effect on body composition indicators. The results also showed that walking backwards during a four-week training period has a positive effect on improving muscle strength, muscle endurance, and muscle flexibility and is more effective than walking forward. It also improves cardiorespiratory endurance index and static balance, although it did not show a significant difference with the way of walking forward, however, it had no effect on body composition indices. Therefore, using this method can play an important role in improving physical fitness indicators in sedentary people. Sedentary and overweight girls can use a four-week back-and-forth workout to improve cardiorespiratory endurance, muscular strength, muscular endurance, muscle flexibility, and static balance. Back, this method is recommended.

Violence against women is one of the worldwide issues, the most common type of this issue is domestic violence; Domestic violence or violence by a close partner is violence perpetrated by a partner against women. According to the World Health Organization (WHO), any act of husband against his spouse that results in emotional, psychological, physical, or sexual harm to her or may result in, affecting her health, covertly or overtly is called spouse abuse. Spouse abuse with this modern definitions includes four types of abuse: physically, sexually, psychologically and financially and is not a new phenomenon that has just emerged in modern times, women have been physically, mentally, sexually and financially abused throughout the history and spouse abuse has existed since the formation of the family in traditional societies. Despite a long history of spousal abuse, this phenomenon, like other social maltreats, seems to have been neglected for a long time until now in modern times due to the influence of The widespread participation of women in the First and Second World Wars, the increase in womenchr('39')s self-awareness and the efforts of humanitarian associations and institutions have led to an increase in public awareness of the abuses committed against women. To guide the construct of the family towards equal rights, and humanitarian construct, emphasizing the role of preventing spousal abuse in the mental and moral health of society, have made a redoubled effort to establish equal rights for men and women. As a subject of this study, spouse abuse is one of the main types of violence against women and aim of this study is estimating the prevalence of spouse abuse in urban and rural areas of Delphan, Lorestan province, Iran.

In this study 69 married women aged 15-48 living in urban and rural areas of Nourabad city of Delphan, Lorestan province who had married at least for one year and have been referred to Nurabad Forensic Medicine Organization, Delfan Social Welfare Emergency Center and Family Court due to physical injury and violence by their spouse, have participated. They have been selected through the available sampling method from forensic, social emergency, welfare and family cour. After explaining and obtaining informed consent, the confidentiality of information was explained to all participants in the study and after that, they have completed the Haj Yahya questionnaire, if the participants are illiterate, the forms have been read and completed by the researcher and entered into the study after completing the personal consent. Data have been analyzed using descriptive statistics and by IBM SPSS v24.

Results show that the sexual abuse with the frequency, mean, percentage and standard deviation respectively equal to 19, 2.69, 26 and 0.192 has the highest average among the dimensions that have been assessed, at the county level. Financial abuse with frequency, mean, percentage and standard deviation respectively equal to 15, 2.40, 24 and 0.362 has the lowest average and psychological abuse with the frequency, mean, percentage and standard deviation respectively equal to 18, 2.58, 25.5 and 0.108 and physical abuse with frequency, mean, percentage and standard deviation respectively equal to 17, 2.52, 24.5 and 0.132 are other dimensions of the abuse that have been studied.

According to the results prevalence of spouse abuse relatively high in all dimensions, especially in Delphan , thus the need to pay attention to this issue at the county level has been felt. These results can help conduct more specific studies on the different factors of spouse abuse in the counties, the results of this research can be studied and analyzed in two different ways; From the perspective of modern societies, It is based on the teachings of the modern family the results indicate spousal abuse in Delfan city and need serious attention and education because this view considers men and women completely independent of each other who live together under a contract called marriage and this contract may end at any time. From another perspective, which is based on the religious and traditional teachings of Muslims and Iranians, the results are considered very desirable because, in this perspective, men and women are considered interdependent. In this perspective, the woman has given up some of her husbandchr('39')s abuse and may tolerate some of her husbandchr('39')s abuse. Now, according to the two types of perspectives that were proposed, the analysis of spousal abuse from the perspective of each of these two approaches will be different and distinct; The first approach condemns spousal abuse, and the second approach considers spousal abuse to be somewhat acceptable and originates from the status of women and The man evaluates in the family. By combining the above two views, we can reach an average view and attitude about spousal abuse.

Colon cancer is among the four most prevalent cancers and the second lethal cancer in the world. After proposing of cancer stem cell hypothesis in recent years numerous studies have been done on various tumor markers with the aim of finding a molecule characterizing the cancer stem cell having prognostic and probably therapeutic value. Cancer stem cell model is well known nowadays which emphasize only small number of tumor cells could initiate tumor growth and maintain its own population.Multiple stem cell markers such as CD44, CD24, SOX2, OCT4, are introduced,among which CD133 has more or less shown this property in different kinds of cancers. CD133 is a glycoprotein which is produced by hematopoietic cells, glial cells and colorectal cancers. Tumor cells with expression of CD133 on their surface lose their special character but have strong epithelial adhesion molecule, recent studies have shown that CD133-positive colorectal cancer cells are a major trigger for this type of cancer; but the results are contradictory as to whether these cells are the same cancer stem cells. The expression of this marker may be associated with a poor prognosis, but its association with metastasis is unknown. The aim of this study was to determine the relationship between this tumor marker and clinical pathological findings, to clarify its role in tumor formation, spread and metastasis. In addition, this marker can be used as a potential pharmacological target in the treatment of cancer patients.

First, the pathology archive of Rasoul Akram Hospital was investigated and the clinical and pathological information related to the pathology files and reports of patients with colorectal cancer who underwent colon resection surgery in this hospital from 1390 to 1396 were extracted. The aim of this study was to evaluate the expression of CD133 marker in NOS adenocarcinoma. Therefore, in order to standardize the test conditions of patients with non-epithelial tumors, mucinous and ring cell carcinoma tumors were excluded from the study. Also, patients with rectosigmoid carcinoma who underwent neoadjuvant chemotherapy before surgery were excluded from the study due to its effect on the nature of cancer cells. Tumor location in patients was divided into two groups. Tumors located in the proximal to the middle of the transverse colon were called right colon tumors and distal tumors were called left colon tumors. Tumor size was entered as the largest tumor diameter in centimeters. Since pathology reports were prepared by three other pathologists during the mentioned years, in order to standardize the study conditions of patientschr('39') slides in terms of depth of tumor invasion, lymph node involvement, degree of tumor differentiation, vascular invasion and perineural invasion was reviewed by a pathologist and, if necessary, slides were prepared from the relevant paraffin blocks. During the examination of the slides, an area with an approximate area of one square centimeter was identified with a marker in the part of the tumor that was located in the invasive front. Human retina was placed on a slide as a positive control. Then, according to the instructions of the marker manufacturer and standard immunohistochemical staining methods, IHC slides were prepared. In the light microscopy, the entire surface of the slides was examined for the color of the marker. According to previous studies, a 5% cut offwas used for this purpose, so that if more than 5% of tumor cells were positive for the above marker, the patient was positive, and if less than this amount was positive, or if no cells were positive, the tumor was reported negative.

Among the 137 patients surveyed, 28 patients (20.4%) were positive for CD133 and 109 patients (79.4%) were negative. In this study, the staining of this marker was luminal and membrane, and as a result, no tumor with poor differentiation was positive. The mean age of patients with CD133 positive tumor was 61.2 16 16.2 years and in negative tumors was 57.2 16 16.3 years. There was no significant relationship. P-value: 0.28: In this study, 76 male patients And 61 were women. Among men, 15 were positive for markers and 61 were negative, and among women, 13 were positive and 48 were negative. There was no statistically significant relationship between patientschr('39') sex and the incidence of 133 CDs (= 0.83). The mean of the largest tumor diameter was 4.7 2 1.2 cm in CD133 positive tumors and 5.2 2 2.2 cm in CD133 negative tumors. Among the tumors located on the left, 22 were positive for CD133 and the remaining 83 were negative. Also, among the tumors located on the right colon, 6 tumors were positive for CD133 and 26 were negative, and in general, there was not significant relationship between the tumor site and marker. Apart from the degree of histological differentiation, no statistically significant relationship was found between any of the other clinical-pathological findings and the expression of this marker.

In our study, like some other researchers, but not all tumors with poor differentiation were negative in terms of the expression of markers, which could be explained by the low frequency of glandular structures and lumen formation in such tumors. Our study in comparison with other studies on the relationship between CD133 and clinical-pathological findings of colorectal cancer can show similarities and differences, four studies have found a significant relationship between tumor depth and the expression of this marker. In our study, if we compare T1 + T2 tumors with T3 + t4 tumors, the p-value for this relationship will be 0.07. It seems that if the samples in this study had a larger volume in each group, this relationship would be significant. In other words, the presence of small samples in the group of tumors with low invasive depth and also the presence of small samples in the group with high invasion Due to the lack of surgery in this group, the number of samples in each group was not enough and may be the cause of lack of relationship with some clinical pathological findings.

Coronary heart disease is the most common type of cardiovascular disease (1) and a coronary artery bypass graft (CABG) is the first surgical procedure used to treat coronary heart disease (2).  (CABG). Powell et al (2017) reported that more than one third of patients (36%) had moderate to severe symptoms of depression based on Beck questionnaire (6). Various indicators have been used to evaluate heart disease. In recent years, new indicators called cardiac troponin I and cardiac creatine kinase isoenzyme (CK-MB) have been used to study myocardial cell damage (7). Cardiac troponin I is a regulatory protein that forms part of the contractile system of cardiac cells (8). The cardiac isoenzyme creatine kinase is responsible for the transfer of the phosphate group to creatine in heart cells (7). Clinical studies have shown that troponin I and creatine kinase increase after CABG surgery and return to baseline after a few days (9), there may be an increase in troponin I levels for several days in these patients. The primary increase in cardiac troponin I is associated with the release of cytosolic troponin I and its secondary increase is related to the release of troponin I from myofibrils that rehabilitate the heart. Long-term increase in troponin has been observed in patients with angina pectoris (8). Creatine kinase index is also used to diagnose the severity of heart disease, and since this isozyme is not significantly concentrated in extracellular tissues, it is considered as a relatively special cardiac index. It is possible to determine the severity of possible injuries as well as the appropriate treatment method by testing these indicators (7). Another method used to treat these patients is potent and selective serotonin reuptake inhibitors (16). Studies have illustrated that selective serotonin reuptake inhibitors (SSRI), such as sertraline can be used to treat tissue damage, inflammation, anxiety, and depression in heart patients because they are safe and well tolerated)17). Research has determined that SSRIs can be profitable for the cardiovascular system and also reduce the risk of cardiovascular disease (18). Andrew et al (2016) claimed that aerobic exercise with a dose of 50-200 mg of sertraline per day decreased the level of depression and increased the quality of life in cardiovascular patients (19).

The present study is a randemized double-blind clinical trial that was performed by availability sampling method in the cardiopulmonary rehabilitation ward of Fatemeh Zahra Heart Hospital in Sari. The permission was obtained from the hospital management. The necessary ethical license was received from the Medical Ethics Committee of Mazandaran University of Medical Sciences (ethics code 1398.1167) and was registered in the clinical trial system with the code IRCT20191125045496N1. Ultimately, patients were randomly divided into 4 groups: 1- aerobic exercise+sertraline, (n = 9) 2- aerobic exercise+placebo (n = 8), 3- sertraline (n = 8) 4- control (placebo) (n = 8). The studied variables including age, physical characteristics (height, weight, body mass index), psychological characteristics (anxiety and depression) and quality of life were measured before and after the exercise rehabilitation program. In addition to routine care, intervention groups (aerobic exercise and aerobic exercise with medication) participated in an 8-week aerobic program. The aerobic exercise group with the drug and the drug group took sertraline at a minimum dose of 25 mg and a maximum dose of 50 mg once daily (in the evening) based on the therapistchr('39')s prescription for 2 months (19). The aerobic and control training group used a placebo with the same dose and duration, as well as the same shape and color as the original medicine made by Hakim Daroo Company. In this study, Kolmogorov-Smirnov test was used to determine the normal distribution of data, and descriptive statistics were used to arrange and describe the data. Analysis of Covariance (ANOVA), correlated t-test and Bonferroni post hoc test were also used in inferential statistics. It should be noted that statistical tests were analyzed using SPSS software version 22 at a significance level of P <0.05.

The results of statistical analysis of the data showed that there is no significant difference between the four groups including exercise + placebo, exercise + drug, drug and placebo in the pre-test values. Based on Table 2, the result of analysis of covariance (ANOVA) illustrated that there is a significant diference between the groups in the levels of CK-MB and quality of life in post-test values (p <0.05 between groups). The results of correlated t-test demonstrated that there is a significant difference between the levels of troponin I and CK-MB in the exercise + drug groups, and also the quality of life index in the exercise + placebo, exercise + drug, drug and placebo groups was before the intervention (p <0.05 within the group).The results of post hoc test in Table 3 showed that there is a significant difference between the group of  exercise + drug  and placebo in the level of  CK-MB and there is also a significant difference between exercise + placebo, exercise + drug, drug and placebo groups in quality of life index (p <0.05).

This study was aimed to evaluate the interaction effect of cardiac rehabilitation and sertraline on troponin I, creatine kinase and quality of life in CABG patients undergoing chronic depression. The results illustrated that aerobic exercise with sertraline decreased troponin I, CK-MB and increased quality of life during 8 weeks. The findings demonstrated that cardiac rehabilitation with sertraline was able to reduce cardiac tissue damage and improve quality of life CABG patients undergoing chronic depression. Therefore, moderate intensity aerobic exercise with sertraline can be used as an effective factor to improve the indicators of heart tissue damage and quality of life in patients after coronary artery bypass graft surgery.

reast milk is the best food and the most valuable gift that any mother can give to her infant. After breastfeeding, 19 digestive hormones are released in the mother and neonate. Some of these hormones stimulate the growth of intestinal villi and cause more nutrients to be absorbed. Exclusive breastfeeding is the best nutrition for infants up to 6 months of age, in addition to providing physical and biological needs, it completes the psychological needs of infants and also mothers. This has been one of the most important recommendations of the World Health Organization and UNICEF in recent years. In recent years, malnutrition, respiratory infections and diarrhea have been the leading causes of child mortality. In this regard, there are reports that breastfeeding significantly reduces the incidence of these diseases. Exclusive breastfeeding in addition to the beneficial effects on the infant and mother, has obvious economic effects on family and society, due to lack of consumption of formula. Also, among the intervention programs that have been carried out in order to continue breastfeeding in developing countries, few studies have used an appropriate theoretical framework for breastfeeding continuity, therefore, in order to increase the effectiveness of educational programs, by understanding the mechanism responsible for change, it is necessary to design and evaluate interventions focusing on the mediating psychological variables. Success in breastfeeding requires several steps: Sufficient awareness - Comprehensive support for the mother - Acquiring the necessary skills.Education of benefits of breastfeeding should begin in the second half of pregnancy and continue immediately after delivery with the help and training of how to properly place the neonate on the motherchr('39')s breast and support the mother. In recent years, many studies have been conducted on the effect of skin-to-skin contact in premature neonates and significant results have been obtained. advantages of skin-to-skin contact between mother and infant include: Improving infantchr('39')s weight gain, improving infantchr('39')s sleep quality, reducing motherchr('39')s stress and anxiety, reducing infantchr('39')s crying rates, improving brain development, increasing maternal confidence in the ability of taking care of infant and reducing postpartum depression symptoms in mother. Considering the numerous benefits of skin-to-skin contact between mother and infant and the failure to find a study that examined the relationship between teaching this type of contact with exclusive breastfeeding in healthy non- hospitalized term neonate, this study aimed to investigate the effect of skin-to-skin contact education to mothers on rate of exclusive breastfeeding in the first two months of life.

This study is a randomized clinical trial. The study population included mothers with 3 to 5-day-old neonate and referred them for receiving usual care to Valfajr Clinic in West Tehran Health Center (University Center affiliated to Iran University of Medical Sciences) in the year 2019.Inclusion criteria: term infant born NVD or cesarean section whose mother wanted to participate in the study and collaborate, she was literate, and did not have any contraindication for breastfeeding. These mothers should breastfeed infants often until day 3 to 5. Data collection tools included demographic and midwifery information form and postpartum information form and breastfeeding nutrition evaluation and 12 Question of Quality of Life Questionnaire, the shortened form of Quality of Life Questionnaire is 36 questions that are widely used in various studies. Eligible mothers were taught in a session how to breastfeed properly, and it was recommended that they should exclusively be breastfed for two months. The source of the education was a "Maternal Guide for Breastfeeding" developed by UNICEF and the Ministry of Health. After a half-hour education session on how to properly breastfeed for all participating in the study, the intervention group was trained about the benefits and methods of doing skin-to-skin contact for at least 60 minutes a day and was recommended to do it after ending breastfeeding at 21-26°C. The procedure was that the mother should place her naked infant (only with a diaper cover) between her two bare breasts. The intervention group additionally was trained how to complete the forms, how to complete the daily skin-to-skin contact form was also added to the motherschr('39') training, so that mothers should have registered daily skin-to-skin contact time, daily sleep and a crying period during these two months. The control group included mothers who was not receive any training on the benefits of skin-to-skin contact, but were taught how to breastfeed properly, and was appointed to check their infantchr('39')s daily sleep and crying for two months and register at the checklist. At the end of the training session, both groups completed the demographic and midwifery information forms, the postpartum information form and the breastfeeding nutrition evaluation form, and a 12-question questionnaire on the quality of life. Mothers randomly entered the study to reach the required number of samples.Two months after the first visit, when the mother and infant were referred to receive usual care in both groups, weight, height, and head circumference were measured and recorded, Completed forms were collected and a questionnaire of 12 Questions on Quality of Life and 24-hours nutrition reminder form were filled out by the researcher with a question from the mother to evaluate the amount of exclusive breastfeeding.Data were analyzed by SPSS 18th edition software. Exclusive breastfeeding amount, height, head circumference, infant sleep and crying, and maternal quality of life scores at baseline and two months later were compared. The main variable, which was exclusive breastfeeding, was evaluated by questioning (self-declaration) and completing a checklist. The significance level for all tests on this study was 0.05 and 95% confidence interval was considered.

The study included 250 mothers and their infants. Demographic information was compared between the two groups. The results showed that there were no significant differences between the two groups in terms of motherchr('39')s age, education, employment, underlying disease, maternity and quality of life scores of the mother, education of the father, sex of the neonate, weight, height and head circumference of the neonate at the birth time.After the conducted training at the beginning of the study, exclusive breastfeeding in the intervention group was significantly higher than the control group (p=0.0001). Study on the variables of infant crying and sleeping showed that these variables had a significant change in skin-to-skin contact group so that the amount of crying decreased (p=0.018) and the amount of sleep increased (p=0.025). Furthermore, the mean score of maternal quality of life in the intervention group was significantly higher than the control group (p=0.013). The variables of weight, height and head circumference of the infant after two months were not significantly different between the two groups.

Education of skin-to-skin contact to mothers and doing it during the first two months of life by them has a significant effect on increasing exclusive breastfeeding, improving the quality of life of mothers scores, increasing sleep and reducing the infants crying rates in the first two months of life. The results of this clinical trial support health policies that recommend facilitating breastfeeding as soon as possible after birth, while recommending persistent skin-to-skin contact after birth and during the first two months of life. Skin-to-skin contact has protected infants against a wide range of negative outcomes. This safe and cost-effective intervention can prevent many of the complications associated with preterm delivery and can also bring benefits to term neonates

The moral culture of the students of medical universities reflects the respected values of the educational system of these universities. This kind of culture will affect the way these students work after graduation. The aim of this study was to determine the effect of medical ethics education on the moral culture of medical students. One of the important strategic priorities of education and research of medical universities is education and observance of medical ethics, and in this regard, it is very important to pay attention to education and implementation of ethical culture. On the other hand, teaching the principles of medical ethics should be active and appropriate. And considering that in most medical universities, traditional methods are used to teach medical ethics and research has shown that these methods do not have much effect on changing the moral culture of medical students, so in this study based on the component Medical Ethics in Medical Education, while designing a new educational package, tried to measure and study the impact of medical ethics education on the moral culture of medical students.Ethical culture is an important factor in creating public value and credibility among employees, and if supervisors and field managers are morally influenced, they will eventually create an ethical culture in their organization, which will have a positive effect on the behavior of their subordinates. The existence and implementation of a proper ethical culture in medical universities causes medical students to receive a good model and after graduation, to use this type of culture in society. In our research, we sought to find the answer to this question. Is there a significant difference between the pre-test and post-test scores of the two control groups (the group that was taught medical ethics by the old and traditional methods) and the experimental group (the group that was taught medical ethics with the new training package)? There are selected training courses, in other words, does the new training package have a greater impact on the moral culture of medical students?

The research method was a quasi-experimental pretest-posttest with a control group. The study sample consisted of four classrooms consisting of 99 students who were selected by cluster random sampling method from nursing students of Shiraz University of Medical Sciences who were taking a course in professional ethics (medical ethics) and by random arrangement, two classes were selected experimentally and two classes as evidence. For the experimental group, a new medical ethics training package was used and for the control group, an old and traditional medical ethics training package was used for teaching. Old and traditional ethics education package. Medicine included pure lectures and in rare cases, PowerPoint presentation, but in the new medical ethics training package, new content and teaching methods that include lectures, PowerPoint presentations, videos, WhatsApp group, texting, CD or flash, photos, PDF and was used, in other words, students participated in an active combination and multimedia educational program.Data collection in the present study was done by referring to research samples by presenting researcher-made questionnaires. Questionnaires were designed in two parts. The first part was related to individual questions and demographic information of the samples and the second part was questions designed in line with the research objectives. The researcher-made questionnaire on moral culture included 24 items and 6 dimensions.Before the intervention, a pre-test was performed to compare the information of the two groups in the selected courses and after the intervention, ie applying an independent variable (new training package), a post-test was performed to compare the final information of the two groups in the selected courses. Finally, based on quantitative results, discussions and conclusions were made.

The mean of pre-test scores in the experimental group is 67.06 and the standard deviation is 8.94. These values in the post-test for the experimental group with an average of 72.15 and standard deviation are 7.41. Therefore, considering that the mean of the post-test in the experimental group was higher than the mean of the control group and based on the obtained t -6.46 in the degree of freedom of 57, there was a significant difference at the level of p <0.01 in the two groups of experiments and controls.

In the present study, participants in the experimental and control groups were not significantly different in terms of demographic information such as age, marital status, field of study, degree and were similar to each other. According to the research questions and based on the obtained results, according to the means in the control and experimental groups based on the obtained t value (-1.63) in the degree of freedom 97, there is a significant difference between the mean scores of the two groups in the pre-test. It is not observed. Also, the mean of pre-test scores in the experimental group is 67.06 and the standard deviation is 8.97. These values in the post-test for the experimental group are 72.15 and the standard deviation is 7.41. Therefore, considering that the mean of the post-test in the experimental group was higher than the mean of the control group and based on the obtained t -6.46 in the degree of freedom of 57, there was a significant difference at the level of p <0.01 There are two groups of experiments and controls. According to the results of this research, it is possible to promote the moral culture in medical students by changing the method and content of medical ethics courses. One of the limitations of the research, which fortunately became an opportunity, is the limitation of face-to-face classes due to the prevalence of coronary heart disease, which caused two-thirds of face-to-face classes to be held virtually, which fortunately was in line with the research hypothesis.In this study and based on the findings, it was found that teaching medical ethics with a new educational package compared to the old method, has a greater impact on the moral culture of medical students and it is suggested that medical education centers use this package in their training. Also, more attention of educational planners to combined education is very important in teaching medical ethics, and educational planners should pay more attention to this point, especially in clinical settings.

After its occurrence in December 2019 in Wuhan, China, the corona virus disease 2019 (COVID-19) rapidly became a pandemic, but there is still no effective treatment for the disease. The novel coronavirus known as SARS-CoV2 Destroying destroys the lung epithelial cells and due to the attack of a novel coronavirus known as SARS-CoV2 results in acute respiratory problems. Besides, overactivation of immune cells due to the virus infection induces a cytokine storm that its outcomes along with the acute respiratory distress are the major causes of adverse conditions and patient’s hospitalization in the intensive care units. Despite using antiviral and anti-inflammatory drugs for patients, at least in some cases, the medical efforts are not effective and the disease leads to death. A growing body of research has recently been published in favor of preventive effects of vitamin D against COVID-19 and also the therapeutic effects of the vitamin in the patients. This study aimed to review the factors involved in vitamin D production, the role and mechanisms of action of this vitamin in preventing COVID-19, and decreasing the adverse effects of the disease in the patients.Vitamin D in addition to being involved in calcium homeostasis and bone metabolism has an important role in boosting and regulating the immune system. Various studies have reported a positive role for vitamin D in the prevention of COVID-19 and reduction of the adverse effects of the virus infection. According to different studies, a sufficient amount of serum levels of vitamin D should be more than 30 ng/ml and the optimal amount is between 40 and 60 ng/ml (11, 18). Vitamin D is synthesized in the skin under the influence of the sunlight UV radiation (23, 25). However, due to the special climatic conditions and religious and cultural beliefs, most of the population especially women in Iran are at a higher risk of vitamin D deficiency. Considering the current COVID-19 pandemic condition, it can be suggested that measuring the serum level of vitamin D, and compensating for the possible deficiencies via dietary and drug supplementation can be effective in preventing COVID-19. Iranchr('39')s geographical location is between 25- and 40-degrees north latitude of the equator, and therefore the northern half of Iran is faced with a lack of sunlight needed to produce a sufficient amount of vitamin D in most seasons (37). Also, in large urban areas with high levels of nitrogen dioxide, people receive less UV radiation that is not enough for adequate vitamin D synthesis in the skin (37). The seasonal prevalence of viral diseases such as influenza as well as decreased serum levels of vitamin D in the winter season can also indicate an association between the vitamin D deficiency and the increased risk of respiratory diseases (44). Vitamin D besides the involvement in calcium homeostasis and bone metabolism has an important role in boosting and regulating the immune system (11,12). Therefore, vitamin D via improving the immune system and production of antioxidants and anti-microbial factors could also have a potential role in preventing COVID-19. The active form of vitamin D is produced by an enzyme known as 1-alpha hydroxylase, which along with vitamin D receptors are present in all cells of the innate immune system. By activation of macrophages, the enzyme 1-alpha hydroxylase is activated in these cells and produces the active form of vitamin D. The increased production of vitamin D in macrophages leads to the release of a large number of antimicrobial agents such as cathelicidin and defensin, which in turn enhance the microbicidal effects of macrophages and monocytes (12). Inactive B and T lymphocytes lack vitamin D receptors but upon activation, they will express vitamin D receptors. Therefore, the release of vitamin D from macrophages also affects the function of surrounding lymphocytes, which will be effective in defense against viruses (12). Vitamin D also exerts its anti-inflammatory effects through various mechanisms. First, vitamin D inhibits prostaglandins production by inhibiting the enzyme cyclooxygenase 2, and therefore, exerts an anti-inflammatory effect.  Prostaglandins facilitate the migration of immune cells into the tissue and increases the symptoms of inflammation by increasing the permeability of postcapillary venules. Second, vitamin D through activating the enzyme phosphatase-5 inhibits the phosphorylation and activation of p38 mitogen-activated protein kinase (MAPK) signaling pathway, which is a specific pathway for the production of inflammatory cytokines. Further, vitamin D reduces the transcription of inflammatory cytokines genes by inhibiting the nuclear factor kappa B (NFκB) (13).  Besides, the antioxidant role of vitamin D is attributed to the increased expression of enzymes producing antioxidants such as superoxide dismutase 1 and 2, thioredoxin reductases, and glutathione (13). Taken together, vitamin D via modulating and improving the function of innate and adaptive immune cells, and also reducing the inflammation caused by the overactivation of the immune cells could decrease the COVID-19 symptoms.

Autism Spectrum Disorders (ASD) refers to a group of neurodevelopmental abnormalities characterized by impairment in communication, social skills and eye contacts with restrictive interests and repetitive behaviors. Individuals with autism show variable reactions in sensitive situations. Some children have normal intelligence and some have intellectual disability, macrocephaly, microcephaly, developmental delay and/or epilepsy. The symptoms appear in infancy and early childhood and affect daily functioning. Recent studies suggest that approximately 1 in 54 children are affected by an autism spectrum disorder. Autism spectrum disorder is notably four times more common in boys than in girls. Many types of research have revealed that genetic and environmental factors are linked to ASD. Major susceptibility factors can play a critical role in the development of autistic behaviors. It is well accepted that ASD have a strong genetic predisposition; however, genes that cause neuropsychiatric disorders are unknown and more than 100 genes are involved in ASD patients. Several genetic factors, such as mitochondrial DNA (mtDNA) variations, have been linked to autistic behaviors. We searched the PubMed, Science Direct, Elsevier, SID, HGMD, SFARI and AUTDB databases for mitochondrial dysfunction associated with the development of autistic behaviors published between 2010 and 2020. The purpose of the search strategy was to obtain relevant studies that provided appropriate information. In 1985, Coleman and Blass made the first hypothesis associating ASD with high levels of lactate in the plasma of individuals with autistic behaviors. Studies showed that various biomarkers of mitochondrial disruption (alanine-to-lysine ratio, acylcarnitine) are altered in some cases with ASD. So far, a great deal of research has been carried out in the field of genetics, perinatal factors, immune and environmental factors affecting autistic behaviors, so that in the latest update of genes involved in human and animal models of autism (on AutDB and SFARI.GENE databases), about 2000 genes involved in the etiology of autism and autistic behaviors have been classified. This list contains many genes including mTOR, MECP2 and genes involved in mitochondrial function or responsible for mtDNA maintenance. Several pathogenic variations that cause defects in mitochondrial metabolic pathways can lead to alterations in neuronal circuits and neurotransmitter systems. Protein coding genes of the mitochondria are components of the respiratory oxidative phosphorylation chain. Oxidative phosphorylation is vital to the growing nerve cells. Studies show that the capacity of oxidative phosphorylation in granulocytes is significantly lower in autistic children, in comparison with normal children. There is evidence of modified immune function in neural systems. The antigen-antibody complexes can induce immune cell migration and stimulate neuro-inflammation. Several investigations revealed that an immune abnormality during pregnancy or postnatal environment results in psychiatric disorders. Immune system irregularities, including defects in T cell responses or Th1/Th2 cytokines, have been reported in individuals with psychiatric disorders, proposing that unusual immune functions in the brain may play an important role in a significant subset of children with autism. Furthermore, Interferons can also induce the expression of more than 300 genes, some of which are mitochondrial genes and some are nuclear genes involved in regulating mitochondrial function. Glucocorticoids can inhibit the production of certain cytokines, such as TNF-α, IL-2, IL-6, IL1β and IL-8, and also can alter the production of anti-inflammatory cytokines, such as IL-10, IL-4, and growth factor-β. Besides, nuclear- or mitochondrial-encoded oxidative phosphorylation subunits (OXPHOS) are regulated by glucocorticoids that their receptors have been identified in the mitochondria. In summary, immune system disorders can impair prenatal brain development or postnatal brain function, so that they can create causality with the ASD phenotype. Also, some maternal allergies during pregnancy, such as exposure to infections, can cause persistent and long-term changes in mitochondrial functions that can lead to autism-like behaviors. This study focused on some clinical aspects of mitochondrial dysfunction in ASD. Most children with autistic behaviors indicate mitochondrial dysfunction and enhanced oxidative stress. Published findings have revealed broad alterations in the immune and nervous systems of children with autistic behaviors. Detection of dependent factors related to ASD can help in the early intervention of these children to address psychological requirements. This article tries to give a useful summary of critical pathways involved in mitochondrial dysfunction in autistic behaviors. Data of this review will give a wide perspective to genetic factors in autism.

Prenatal diagnose (PND) in carrier β-Thalassemia couples is very important. PND of Thalassemia, is a part of national prevention program. In all over the world, conventional prenatal diagnosis of Thalassemia is CVS or AC. These methods are invasive, we want to experience the new NIPD for β-Thalassemia with this hypothesis that 50% of invasive PND removed.Non invasive prenatal diagnose of Thalassemia is possible via detection of paternally mutation in maternal plasma. The history of fetal DNA (fDNA) in maternal circulation dates back to the 1948 by Mandel and Metais. The discovery of fDNA in maternal plasma and serum has opened up new opportunities in non invasive prenatal diagnosis (NIPD). This method has been shown to be potentially useful for prenatal diagnosis of certain neurological disorders, fetal sex determination, sex – linked disease, RhD genotyping, and aneuploidies. Fetal DNA originated from trophoblast cells in the placenta, and it detectable very soon during pregnancy, it only comprised about 3 to 6% (although up to 10% has been reported). Fetal DNA fragments are small in size (< 313 bp). It present during pregnancy until birth. They are rapidly cleared within 2 hours after delivery.Taq- Man is one of the first methods introduced for Real-time sequence detection. A Taq-Man reaction involves 2 specific primers and probes. Each probe is complimentary to one of the alleles of a mutation and each of them is labeled with a different fluorophore. This method exploits the 5chr('39') endonucleolytic activity of Taq DNA polymerase to slice an oligonucleotide probe through PCR amplification thus generating a detectable signal.The aim of this study was non invasive prenatal diagnosis of β-Thalassemia and determination the sensitivity and specificity of this technique for detection paternally inherited IVS II-I (GA) mutation in fetus.

Subjects were selected following ethical approval of study protocol from the ethical committee of Mazandaran University of Medical Science, Iran. The sample size of this study calculated according the related studies . Fifty Iranian pregnant women enrolled in this study, they were at risk of having fetuses with β-Thalassemia major. They attended in prenatal diagnosis of Thalassemia center (at 11-14 weeks of pregnancy, before performance of CVS), between May 2014 and Feb 2015, in Sari, Iran. All women assigned informed consent form. We focused exclusively on couples in which the father was carrier for IVS II-I GàA mutation and the mother had been genotyped to carry another β-globin gene mutation, (Of course, the mutation in each subject had been determined previously by conventional PCR and ARMS method, and followed by agarose gel electrophoresis). Also, 10 milliliters of maternal blood from each pregnant woman were collected into EDTA-containing tube. Maternal plasma was separated from cells by high –speed centrifugation (1900 g or 3000 rpm), and it stored at – 80 0 c until analysis. We were masked as to the identity the samples with numerical coding system, so, these were examined in a blinded manner. We designed two specific primers for IVSII-1(GàA) mutation (Accession No.141900) (www.hgvs.org), on the HBB DNA sequences (NCBI Reference Sequence: NG_000007.3 3 (Homo sapiens beta globin region (HBB)), the oligonucleotid primers of this study were; forward primer: 5chr('39')TCACCTGGACAACCTCAAG3chr('39'), and reverse primer: 5chr('39')CCCATTCTAAACTGTACCC3chr('39'). The primers pair was optimized to particularly amplify a 200-bp segment of exon 2 of the human β-globin gene. Of course we consider the locus of maternal mutation in β-globin gene that doesnchr('39')t interfere to our PCR product. Also, for design the Taq-Man probes, we refer in Taq- Man design site (primer digital.com/fast PCR/m15.html FAST PCR manual). The characterics of probes were; GC content 45-65%, no dimer with primer, high Tm 60-65 oc, probe length 18-30 bp, and Tm of primer was 8-10 oc higher than Tm primer. Also, the kind of quencher and reporter were matched with kind of quencher and reporter in the kit. Probe for wild allele was; FAM-AGAACTTCAGGGTGAGTCTATGGG-BHQ1, and the Probe for mutant allele was; VIC-AGAACTTCAGGATGAGTCTATGGG-BHQ1. Circulatory DNA was extracted from 200 µl of peripheral blood plasma with QIAamp DNA mini and blood kit according to the manufacturerchr('39')s instructions. DNA was eluted in a final volume of 200 µl AE buffer and stored at -20 0 c until used for additional analyzing. Also, the genomic DNA concentration was measured by NanoDrope system and electrophoresis. For detection of paternally inherited mutation Taq-Man Real time PCR was used and the result of Taq- man method compared with result of chorionic vilus sampling method (CVS) as a gold standard.

The clinical performance of Taq-Man test was assayed by comparing with routine test. Included in this study were 50 pregnant mothers. In Taq-Man method 38 samples cited in scatter analysis graph as a negative control, because the concentration of DNA was very low and this method didn’t have enough sensitivity and specificity for detection, so, the final analysis for assessment of this method was done on 12 samples. We reported 5 cases true positive, 4 cases true negative, 2 cases false negative and 1 cases false positive. Also the sensitivity of Taq-Man was 71.43% with CI95% (60%-83.43%), and specificity 66.67% with CI 95% (54.67%-78.67%). LR+ and LR- were 2.15 and 0.5 respectively. Also NPV and PPN of Taq-Man test were 66.67%, 83.4% respectively.

Non invasive prenatal diagnose can be detect paternally inherited mutation of thalassemia.