Pathogenic homozygous mutation in the pleckstrin homology domain of RASA1 is responsible for familial tricuspid atresia in an Iranian consanguineous family

Objective: Tricuspid atresia [TA] is a rare life-threatening form of congenital heart defect [CHD]. The genetic mechanisms underlying TA are not clearly understood. According to previous studies, the endocardial cushioning event, as the primary sign of cardiac valvulogenesis, is governed by several overlapping signaling pathways including Ras/ ERK pathway. RASA1, a regulator of cardiovascular development, is involved in this pathway and its haploinsufficiency [due to heterozygous mutations] has been identified as the underlying etiology of the autosomal dominant capillary malformation/arteriovenous malformation [CM/AVM]

Materials and Methods: In this prospective study, we used whole exome sequencing [WES] followed by serial bioinformatics filtering steps for two siblings with TA and early onset CM. Their parents were consanguineous which had a history of recurrent abortions. Patients were carefully assessed to exclude extra-cardiac anomalies

Results: We identified a homozygous RASA1 germline mutation, c.1583A>G [p.Tyr528Cys] in the family. This mutation lies in the pleckstrin homology [PH] domain of the gene. The parents who were heterozygous for this variant displayed CM

Conclusion: This is the first study reporting an adverse phenotypic outcome of a RASA1 homozygous mutation. Here, we propose that the phenotypic consequence of the homozygous RASA1 p.Tyr528Cys mutation is more serious than the heterozygous type. This could be responsible for the TA pathogenesis in our patients. We strongly suggest that parents with CM/AVM should be investigated for RASA1 heterozygous mutations. Prenatal diagnosis and fetal echocardiography should also be carried out in the event of pregnancy in heterozygous parents

Differentiation of human scalp adipose-derived mesenchymal stem cells into mature neural cells on electrospun nanofibrous scaffolds for nerve tissue engineering applications

Objective: This study aimed to isolate and culture SADS cells, investigate their neurogenic capacity and evaluate their application for nerve tissue engineering

Materials and Methods: In this experimental study, SADS cells were isolated from human adipose tissue. After 7-day treatment of SADS cells with insulin, indomethacin and isobutylmethylxanthine, neurogenic differentiation of SADS cells was investigated. During this study, Poly [?-caprolactone] [PCL] and PCL/gelatin nanofibrous scaffolds were fabricated using electrospinning and subsequently nanofibrous scaffolds were coated with platelet-rich plasma [PRP]. SADS cells were also seeded on nanofibrous scaffolds and neurogentic differentiation of these cells on nanofibers was also evaluated. Effect of PRP on proliferation and differentiation of SADS cells on scaffolds was also studied

Results: Our results showed that after 7-day treatment of SADS cells with insulin, indomethacin and isobutylmethylxanthine, SADS cells expressed markers characteristic of neural cells such as nestin and neuron specific nuclear protein [NEUN] [as early neuronal markers] as well as microtubule-associated protein 2 [MAP2] and neuronal microtubule-associated [TAU] [as mature neuronal markers] while mature astrocyte maker [GFAP] was not expressed. MTT assay and SEM results showed that incorporation of gelatin and PRP into the structure of nanofibrous scaffolds has a significant positive influence on the bioactivity of scaffolds. Our results also showed neurogentic differentiation of SADS cells on scaffolds

Conclusion: Our results demonstrated that SADS cells have potential to differentiate into early and mature progenitor neurons, in vitro. PCL/gelatin/PRP was found to be a promising substrate for proliferation of SADS cells and differentiation of these cells into neural cells which make these scaffolds a candidate for further in vivo experiments and suggest their application for nerve tissue engineering

Sociological study on the transformation of fertility and childbearing concept in Iran

Fertility and childbearing, in addition to the biological aspects, has always been regarded as a social phenomenon and, therefore, to understand the incident, values and beliefs, norms, and in short, the culture of any society should be scrutinized. Since the concept, condition, and value of childbearing is associated with cultural, social, political and economic dimensions, it has undergone various transformations during passage of time from past to present. The sociological approach of the current study investigated the evolution of the concept and value of fertility and childbearing in light of historical, social, cultural and economic upheavals. This study shows that the methods of rationalizing and legitimizing decisions about fertility and childbearing are defined and specified in the context of society. The rational for selecting the decisions is intermingled with social, cultural, economic, and political evolutions of the society like modernization, urbanization and the level of development in human communities. Today, fertility, childbearing and the number of children are not only connected with the interpretations of the individuals about the conditions and micro and macro subjective and objective factors surrounding them, but they are also linked with factors such as family income, the amount of time parents allocate to their children, quality of child nurturing and other family variables

evaluation of the historical importance of fertility and its reflection in ancient mythology

Myths are reflective of human concerns and needs during ancient times. By reviewing them, it turns out that many human problems today, have a historical background. Among the main themes of ancient mythologies, fertility and reproduction have various representations in ancient civilizations. The purpose of this paper was to review myths and common symbols of fertility and reproduction in ancient civilizations and evaluate the reasons of their continuous importance in different cultures. The data in this review study was obtained by scrutinizing the related literature. The gathered data indicated the multiplicity and variety of fertility symbols in ancient myths. Most ancient fertility symbols were inspired by the nature and some of them like earth and water were common in mythology of different civilizations. Therefore, the symbols consolidate the concept of conformity between human reproductive concerns and the nature's necessities

Embryo donation in Iranian legal system: a critical review

Recent developments and newly-discovered methods for infertility treatment including in vitro fertilization and third party reproduction raise many questions and challenges with different ethical, legal, sociological and psychological dimensions. In Islamic countries, despite great developments in using this technology, the questions concerned with recognition of IVF methods and third party reproduction and legalization of this method are still the challenging ones. The approach of a few Shiite clerics to this issue has facilitated the legalisation of infertility treatment in Iran. The Iranian Parliament, with reference to Shiite clerics' opinions [Fatwa], enacted the Act concerning Embryo Donation to Infertile Couples and its bylaw which can be considered as a successful example of legalization of third party reproduction in an Islamic country. The aforementioned Act permits embryo donation through artificial insemination from legally married couples to infertile couples. However, many of the legal aspects of this event are not specified in this Act and in many cases it added several uncertainties. This uncertainty, especially regarding the rights and duties of recipients and the child, causes important problems which generate more concerns. This article aimed to review the advantages and flaws of the Act. It is believed that the enactment of the aforementioned Act is an important step but an insufficient measure in this field. Important issues have been left unanswered and unclear in this Act which should be considered by legislators in any future revision of it

Attitudes about sex selection and sex preference in Iranian couples referred for sex selection technology

Gender preference is prevalent in some communities and using medical techniques to choose the baby's sex may cause the gender discrimination and gender imbalance in communities. Therefore, evaluating the gender preferences and attitudes towards using sex selection technologies seems to be necessary. This cross-sectional study was conducted in Avicenna Fertility Center. Participants were 100 women with one child who were referred for sex selection. Data were collected through self-developed questionnaires. The questions were designed by the researchers at the experts' panel. To determine the validity of the questionnaire, the viewpoints of professors specialized in these issues were obtained. The statistical analysis of the data was performed using SPSS software [Version 11.5], and p<0.05 was considered significant. Tendency toward the male was more than female sex [55.5% male, 15.5% female and 28.5% no tendency]. Majority of participants agreed with sex selection with medical reason and sex selection in order to balance the family. Women's level of education had positive effect on agreements to fetal sex selection with medical and non-medical reasons [p<0.001]. Although gender preferences were toward the male sex but this preference was not very strong. Most participants agreed with non-medical sex selection for balancing the sex composition of their children. It doesn't seem that non-medical sex selection for family balancing causes severe sex imbalance in Iran

Phenotypical characterization of 13q deletion syndrome: Report of two cases.

Patients with 13q deletion syndrome are characterized with different phenotypical features depending on the size and location of the deleted region on chromosome 13. These patients fall into three groups: In Group 1, deleted region is in the proximal and does not extend into q32; in Group 2, deleted region involves proximal to the q32 and in Group 3 q33‑q34 is deleted. We present two cases with 13q syndrome with two different deleted region and different severity on clinical features: One case with interstitial deletion belongs to the Group 1 with mild mental retardation and minor malformations and the other case with terminal deletion belongs to Group 3 with moderate to severe mental retardation and major malformations.

Role of local anesthetics on pain relief in endometrial biopsy: randomized clinical trial

Endometrial biopsy is necessary for diagnosing the reason of abnormal uterine bleeding in perimenopausal women. Currently outpatient endometrial biopsy is used for evaluation of abnormal uterine bleeding which is associated with moderate to severe pain. Using lidocaine is one of the procedures which is used for pain relief while biopsy. This study is aimed at comparing the effect of different local anesthesia procedures on pain relief during endometrial biopsy. In this randomized clinical trial, 160 multiparous 40-55 years old women with AUB [Abnormal Uterine Bleeding], candidates for endometrial biopsy, were randomly assigned into four equal groups, to receive: 1-intrauterine lidocaine; 2-cervical spray lidocaine;3- intrauterine lidocaine plus cervical spray lidocaine; or 4-intrauterine distilled water. Pain relief was measured at 3 different times: during endometrial biopsy, just after and 15 minutes after biopsy. Pain intensity was reduced significantly at different times in intrauterine lidocaine and intrauterine lidocaine with cervical spray lidocaine receivers in compare with the groups which received cervical spray lidocaine and distilled water. The mean of difference pain relief during biopsy and 15 minutes after that was reduced significantly in the group which received intrauterine lidocaine and intrauterine lidocaine with cervical spray lidocaine in comparison with the other two groups. Intrauterine lidocaine was effective during endometrial biopsy, and using it with cervical spray lidocaine had no more beneficial effect

Genomic characterization of some Iranian children with idiopathic mental retardation using array comparative genomic hybridization.

BACKGROUND: Mental retardation (MR) has a prevalence of 1‑3% and genetic causes are present in more than 50% of patients. Chromosomal abnormalities are one of the most common genetic causes of MR and are responsible for 4‑28% of mental retardation. However, the smallest loss or gain of material visible by standard cytogenetic is about 4 Mb and for smaller abnormalities, molecular cytogenetic techniques such as array comparative genomic hybridization (array CGH) should be used. It has been shown that 15‑25% of idiopathic MR (IMR) has submicroscopic rearrangements detectable by array CGH. In this project, the genomic abnormalities were investigated in 32 MR patients using this technique. MATERIALS AND METHODS: Patients with IMR with dysmorphism were investigated in this study. Karyotype analysis, fragile X and metabolic tests were first carried out on the patients. The copy number variation was then assessed in a total of 32 patients with normal results for the mentioned tests using whole genome oligo array CGH. Multiple ligation probe amplification was carried out as a confirmation test. RESULTS: In total, 19% of the patients showed genomic abnormalities. This is reduced to 12.5% once the two patients with abnormal karyotypes (upon re‑evaluation) are removed. CONCLUSION: The array CGH technique increased the detection rate of genomic imbalances in our patients by 12.5%. It is an accurate and reliable method for the determination of genomic imbalances in patients with IMR and dysmorphism.

Long-term results of transcatheter closure of patent ductus arteriosus in infants using amplatzer duct occluder

Patent ductus arteriosus [PDA] is one of the most frequently seen congenital heart diseases. Its closure is recommended because of the risk of infective endocardis, as well as morbidity and mortality in the long. The aim of this study was to assess the long term results of the transcatheter closure of PDA in infants using amplatzer duct occlude [ADO]. From May 2004 to September 2011, forty eight infants underwent transcatheter closure of PDA. A lateral or right anterior oblique view aortogram was done to locate PDA and to measure its size. Before discharge, repeat aortogram was performed to evaluate eventual residual shunt and to confirm the appropriate deployment of the ADO. Follow up evaluations were done with transthoracic echocardiography at discharge, 1 month, 6 months, 12 months and yearly thereafter. Findings: The mean age of patients at procedure was 9.18 +/- 2.32 [range 3 to 12] months, mean weight 6.73 +/- 1.16 [range 4.5 to 10.1] kg. The PDA occluded completely in 20 out of the 48 patients. Twenty four patients had trivial or mild shunt and two patients had moderate residual shunt which disappeared in one patient within 24 hours and other patient with moderate shunt in 1 month. One patient [age 8 months] had mild LPA stenosis. The device emobolization occurred in two patients, immediately after the procedure in one and during night in the other patient The long term results suggested that transcatheter closure of PDA using Amplatzer duct occluder is a safe and effective treatment in infants less than 1 year of age with minimal complications

Immediate, short, intermediate and long-term results of balloon valvuloplasty in congenital pulmonary valve stenosis

Transluminal balloon valvuloplasty is an alternative to surgical valvotomy for congenital pulmonary valve stenosis. The aim of this study was to evaluate the long term results [to 13.5 years] of balloon pulmonary valvuloplasty. From June 1998 to January 2012, percutaneous balloon pulmonary valvuloplasty for congenital pulmonary valve stenosis was performed in 98 patients [50 males, 48 females, with a median age of 6.75 years] underwent balloon valvuloplasty of pulmonary valve stenosis. Follow-up was performed based on the Doppler echocardiographic data and clinical findings. Forty three of ninety eight patients were 10 years of age or older. The mean peak to peak pressure gradient across pulmonary valve before and immediately after balloon pulmonary valvuloplasty [BPV] was 88.7 +/- 36.4 mmHg and 21.8 +/- 15.9 mmHg [P<0.001] respectively. Doppler pressure gradient across pulmonary valve before BPV, at 3 month [short term], at 1 year [intermediate term] and long term follow-up were 93.2 +/- 41.3 mmHg, 18.7 +/- 15.8 mmHg [P<0.001], 15.8 +/- 13.1 mmHg [P0.001] and 13.6 +/- 7.4 mmHg [P<0.017] respectively. Mild pulmonary regurgitation [PR] was observed in 55 [57%] patients immediately after BPV and 30 [31%] patients at late follow up. Rupture of the right ventricular outflow tract was the major complication in two patients with fatal event. Short, intermediate and long-term results of BPV for typical valvular pulmonary stenosis are excellent. Therefore, it can be considered as treatment of choice for patients with typical valvular pulmonary stenosis

Acute poisoning in children; a population study in Isfahan, Iran, 2008-2010

Acute accidental poisoning in children is still an important public health problem. The epidemiological investigation specific for each country is necessary to determine the extent and characteristics of the problem. The aim of our study was to elucidate the current pattern of acute poisoning among children. The present retrospective study describes the epidemiology of acute accidental poisoning in children [less than 10 years old] admitted to the Emergency Department of two teaching hospitals during a period of two years. Three hundred and forty four children under 10 years old were admitted to emergency department of two teaching hospitals due to acute accidental poisoning. Drugs were the most common agents causing the poisoning [58.1%], followed by Hydrocarbons [13.1%], and opioids [9.3%]. Common signs were neurological [42.6%] with lethargy being the most common [39.1%]. 50.6% of cases were discharged from hospital within 6-12 hours, 91.6% of them without any complication. Accidental poisonings are still a significant cause of morbidity among children in developing countries. Regarding the high prevalence of pharmaceutical drug poisoning and because lethargic was the most frequent neurological sign, comprehensive toxicology screen tests should be included as part of the routine evaluation of children presenting to an ED with an apparent life-threatening event

Aspects of psychosocial development in infertile versus fertile men

Infertility is one of the most difficult life experiences that a couple might encounter. Infertility as a bio-psycho-social phenomenon, could influence all aspects of life. While paying special attention to the psychological aspects of infertility in couples; many studies have investigated the non-clinical aspects of infertility, however, they rarely have evaluated the psychosocial development of infertile versus fertile men. We aimed to study the effects of infertility on psychosocial development in men. In fact, we designed the study based on "Erikson's theory of psychosocial development". We focused on the relationship between psychosocial development and some self-conceived indices. For this purpose, we divided the participants volunteers into two groups of cases [80 infertile men] and controls [40 fertile men] and asked them to complete a 112 [questions questionnaire based on "self description"]. The statistical analysis was performed by SPSS [version 13] using independent t-test, Pearson correlation coefficient and analysis of covariance. A p-value <0.05 was considered significant. Data analysis showed significant inter and intra group differences. Infertile and fertile groups showed significant differences in trust, autonomy, generativity and integrity stages [p<0.05]. Infertile intergroup analysis represents us to higher scores in positive than negative stages. Infertility as a phenomenon had its own effects on the psychosocial development of infertile men. However, good coping skills are powerful tools to manage these myriad of feelings surrounding infertile men

Long-term results of balloon pulmonary valvuloplasty in children with congenital pulmonary valve stenosis

Immediate, short and midterm outcome of balloon pulmonary valvuloplasty are well known, but there is limited information on long term results. We report long term results of 2-13. 5 years follow up of balloon pulmonary valvuloplasty in children. From June 1998 to January 2012 sixty consecutive patients [33 females, 27 males] with moderate to severe valvar pulmonary stenosis [right ventricular to pulmonary artery pressure gradient greater than 50 mmHg] were considered for balloon valvuloplasty. The gradient was measured pre and immediately post-valvuloplasty at catheterization, and then by echocardiography at follow up. Follow up studies were performed 2-13.5 years [mean +/- SD; 7.1 +/- 2.5 years, median: 5.5 years] after procedure, by Doppler echocardiography in all patients and catheterization and angiography in two patients. Balloon pulmonary valvuloplasty BPV was successful in 53 of 60 [88.3%] patients whereas surgical valvotomy was necessary in 6 to 60 [10%]. There was one immediate death due to perforation of the right ventricular outflow tract. Pulmonary valve systolic pressure gradient decreased from 83.3 +/- 32.1 to 19.3 +/- 14.2 mmHg immediately after BPV and to 12.3 +/- 6.6 mmHg at late follow up [P<0.001]. Pulmonary insufficiency was noted in 20 [38%] patient at short-term, but it was demonstrated in 17 [32%] at late follow up. A second valvuloplasty was performed in two [3.8%] patients presenting with re-stenosis. The short, intermediate and long-term outcomes of pulmonary balloon valvuloplasty in children are excellent. Therefore it can be considered as the treatment of choice for children with pulmonary valve stenosis

Long-term follow-up of patent ductus arteriosus closure with the Amplatzer Duct Occluder in children

Transcatheter closure of patent ductus arteriosus [PDA] has become an alternative treatment to surgery. We evaluated the long-term results of the transcatheter closure of PDA with the Amplatzer Duct Occluder [ADO] in children. Between May 2004 and October 2012, 138 children with PDA [43 males and 95 females] underwent transcatheter PDA closure. Clinical, electrocardiographic, echocardiographic, and hemodynamic data were assessed pre and postprocedurally and at follow-up. The mean age of the patients at procedure was 3.53 +/- 2.43 years [range = 1.1 to 9.5 years], mean weight was 11.9 +/- 4.6 kg [range = 6 to 29 kg], median pulmonary end diameter of the PDA was 5 mm [range = 4 to 15 mm], and median diameter of the ADO was 8 mm [range = 6 to 16 mm]. The mean follow-up time was 43.4 +/- 23.5 months [range = 13.5 to 98 months]. The devices were successfully deployed in 136 [98.5%] patients. Device embolization occurred in 2 patients, immediately in one patient and during the first postprocedural night in the other patient. The first patient had percutaneous device retrieval, followed by implantation of a larger device. The second patient had surgical device removal and PDA ligation. Immediately after device implantation, trivial to mild residual shunts were detected in 112 [80%] patients; all the shunts, however, disappeared 24 hours after the procedure. One patient had left pulmonary artery stenosis with a gradient of 25 mm Hg at 24 hours', 40 mmHg at one month's, and 64 mmHg at 6 months' follow-up. There were no cases of late embolization, aortic obstruction, late hemolysis, infective endocarditis, or death. Transcatheter PDA closure with the ADO was safe and effective, with a high success rate at long-term follow-up

Prevalence of primary infertility in Iran in 2010

Infertility is one of the most significant medical, as well as social problems that affect psychological health of families and societies. Determining the prevalence of infertility is important for evaluating the potential of fertility. There are different reports on the prevalence of infertility in Iran, but the current research employs fertility history in order to provide an unbiased estimation of primary infertility. Data from a national survey of Iranian women aged 20-40 years was used in this study in year 2011. Totally, 1011 clusters were randomly selected according to post office codes, proportional to the population of the province. We evaluated the history of fertility as the basis for gathering information. Accordingly, we designed a questionnaire. Subsequently, we recruited and trained nurses and obstetricians to call on married women to fill the questionnaires. Primary infertility refers to a condition in which couples have not been able to conceive a child after one year of unprotected intercourse. In this research, we questioned 17187 women in 1011 clusters. The mean age of the women at the time of their marriage was 20.1, and that of their husbands was 25.4 years. The mean age of women at the time of their first pregnancy was 21.1. This research revealed the prevalence of primary infertility to be 20.2% in Iran. The prevalence of primary infertility in Iran seems to be higher than the world average. Therefore, it is crucially important to support the large number of couples who face this problem

Fraccaro syndrome: report of two Iranian casesþ:þ an infant and an adult in a family

49,XXXXY is rare chromosomal pattern and these patients have mental retardation, small penis,cryptorchidism and skeletal anomalies. We reported a 10 month-old boy who has hypotonia, microcephaly, hypertelorism, depressed nasal bridge, epicanthic folds and bilateral multiple ear tags, high arched palate, down set ears, micrognathia and congenital heart disease such as patent ductus arteriosus [PDA], Atrial septaldefect [ASD], mild pulmonary stenosis. Among the skeletal anomalies, he has kyphoscoliosis, clinodactyly of the fourth and fifth fingers of both hands, and bilateral club foot and unilateral dysplasia of the hip. Karyotype was found as 49,XXXXY[44]/48,XXXY[6] and this cytogenetic analysis was help to establish clinical diagnosis Fraccaro syndrome

Cytogenetic abnormalities in 222 infertile men with azoospermia and oligospermia in Iran: Report and review.

Background: Infertility affects approximately 10%-15% of couples in reproductive age. In half of the couples, causes are male-related, associated with impaired spermatogenesis. There is a complex correlation between genetics and infertility. Several factors affect on gametogenesis, from which factors that lead to chromosomal abnormalities are one of the best known. The aim of this study was to determine type and rate of chromosomal abnormalities in infertile azoospermic and oligospermic males in Iranian population. Materials and Methods: The records of a total of 222 participants were evaluated retrospectively. Results: As a whole we observed 13.96% chromosomal abnormality, from which 12.15% showed numerical and 1.8% showed structural abnormalities. Conclusion: Comparison of our results with the review of the literature shows a higher incidence (4- fold) of gonosomal, in particular, numerical gonosomal, chromosomal anomalies. Cytogenetic analysis is strongly suggested for infertile men, particularly in those who suffer from azoospermia.

Mutational screening of ARX gene in Iranian families with X-linked intellectual disability

Mutations in the human aristaless-related homeobox [ARX] gene are amongst the major causes of developmental and neurological disorders. They are responsible for a wide spectrum of phenotypes, including nonsyndromic X-linked intellectual disability [NS-XLID], and syndromic [XLIDS] forms such as X-linked lissencephaly with abnormal genitalia [XLAG], Partington syndrome [PRTS], and X-linked infantile spasm syndrome [ISSX]. The recurrent 24 bp duplication mutation, c.428_451dup[24 bp], is the most frequent ARX mutation, which accounts for 40% of all cases reported to date. We have screened the entire coding sequences of the ARX gene in 65 Iranian families with intellectual disabilities in order to obtain the relative prevalence of ARX mutations. At first these families were screened for the most recurrent mutation, the c.428_451dup[24 bp]. For samples with negative results, single strand conformation polymorphism [SSCP] analysis was performed. We identified one family with the c.428_451dup[24 bp] duplication. Three shifts [one shift in exon 5 and two shifts in exon 4] were also identified among the total families. According to the results of the sequencing analysis, two shifts were not associated with any mutation and the other one was a c.1347C>T [p.G449G] substitution in exon 4. Hence, we suggest that molecular analysis of ARX mutations as a second cause of XLID should be considered as routine diagnostic procedure in any male who presents with either NS-XLID or XLIDS

Combined transcatheter closure of atrial septal defect and pulmonary valve balloon dilation

Critical pulmonary valve stenosis [CPVS] and atrial septal defect [ASD] is an uncommon form of congenital heart disease. Concurrent transcatheter pulmonary valvuplasty and closure of secundum atrial septal defect appears to be an interesting alternative to surgical correction. We present the simultaneous balloon valvuloplasty of critical pulmonary stenosis [PS] with supra systemic right ventricular pressure and medium sized secundum ASD with right to left shunt