Hematological indices in prolonged menstruation: New roles for blood groups and coagulation factors

Background: Menorrhagia is the most common type of abnormal uterine bleeding, caused by disruption of hormonal regulation, uterine function or blood clotting. Developing an effective diagnostic strategy will improve patient's quality of life and management. Here we investigated the links between hematological characteristics and prolonged menstruation‎ to estimate the importance of the first line coagulation screening tests in young women ‎.Materials and Methods: In a case-control design and under supervision of a specialist, 43 cases and 104 age matched controls were selected. Menstrual characteristics were evaluated by a standardized questionnaire distributed to high school and university young students. Hematological indices including first line coagulation screening tests were performed for both groups and statistically assessed.Result: Statistical analysis showed that prolonged menstrual bleeding ‎is significantly correlated to prolonged bleeding time (p value, 0.01) as well as ‏ red blood cell count (p value, 0.04). The O blood group showed the greatest contribution to the bleeding periods longer than 7 days (53.4 %(. Additional coagulation tests revealed one coagulation factor VII deficiency patient.Conclusion: The results of the present study revealed the importance of menorrhagia management in young women and showed a significant correlation between prolonged menstrual bleeding ‎and blood types ‎. Our study findings also suggest a significant association between prolonged menstruation and bleeding time test, emphasizing on the role of blood coagulation traits in susceptibility to heavy menstrual bleeding

Distribution of Disease-Causing Mutations through Different Protein Domains in Patients with Severe Combined Immunodeficiency

Background and Aim: Severe combined immunodeficiency (SCID) has been described as the most severe form of primary immunodeficiency disorders (PID). The disease can be caused by mutations in more than 20 different genes with prevalence of 1 in 50000 to 100000 live births. In the present study, we described the protein domain position of variants in 14 main genes in patients with SCID. We also aimed to investigate the correlation between the variant distribution of protein domains and its pathogenicity and clinical outcome of the variant. Materials and Methods: Molecular genetic analysis including Sanger sequencing, targeted gene panel and whole exome sequencing were performed on 50 patients with SCID. Moreover, protein domains characteristics were extracted from different databases such as Uniprot and PDB and the reported mutations were obtained from HGMD and ENSEMBL databases. Results: Our results showed that the mortality rate had a significant correlation with severity of clinical manifestations in the patients (p-value=0.000). There was also a significant relationship between the protein type and mutation severity (p-value=0.001) and severity of clinical manifestations (p-value=0.025). However, there was no significant relationship between the mortality rate and occurrence of mutations in different domains of proteins (p-value=0.304) and the severity of mutations (p-value= 0.586). Conclusion: In severe genetic diseases such as SCID, mutations in related genes have affected the structure of the protein enough to cause severe symptoms. However, there are differences in the pathogenicity of the mutations based on their location on the protein domains. In order to determine these variations and predict the outcome of mutations, it is necessary to use in silico and laboratory methods along with statistical and data mining tools to track these minor differences

Follicular development and the expression of BAX and vascular endothelial growth factor in transplanted ovaries in uni- and bilateral ovariectomized mice: An experimental study

Background: Several conflicting results have been reported on the survival and function of transplanted ovaries. Objective: Evaluation of the follicular development and the expression of vascular endothelial growth factor (VEGF) and Bcl-2-associated X protein (BAX) in ovaries transplanted into uni- and bilaterally ovariectomized mice. Materials and Methods: In this experimental study, 40 female NMRI mice (21-days-old, 12-15 gr) were ovariectomized uni- and bilaterally (n = 20/ group), while the 8-wk-old mice were considered as intact control group (n = 6). 5 weeks after transplantation at the proestrus stage, the morphology of recovered transplanted ovaries and the proportion of follicles were studied at different developmental stages. The apoptosis cell death by pro-apoptotic protein BAX and the expression of VEGF were evaluated using immunohistochemistry. Results: In the bilaterally ovariectomized mice, among the 455 counted normal follicles, a lower rate of primordial and primary follicles and a higher rate of preantral and antral follicles were observed (p = 0.002). However, the percentages of preantral and antral follicles, and the corpus luteum were significantly lower in the intact control group (among the 508 counted normal follicles in this group) compared to other transplanted groups (p = 0.002). The number of BAX-positive cells in all groups was not significantly different. The VEGF expression was prominent in vessels of the corpus luteum, and also in the theca layer of large follicles of studied groups. Conclusion: Early discharge of ovarian reserve was prominent in the bilaterally ovariectomized group but the incidence of apoptotic cells and VEGF expression as angiogenic factor did not differ in both ovariectomized mice. Thus, unilaterally ovariectomy has less side effects on the ovarian reserve compared to bilateral ovariectomy. Key words: Autotransplantation, BAX protein, Vascular endothelial growth factor, Ovariectomy, Mice

Care of newborns born to mothers with COVID-19 infection; a review of existing evidence

Background:The novel Coronavirus disease 2019 (COVID-19) pandemic is already wreaking havoc on families and communities\u27 welfare. It is critical to discuss newborn care of infected mothers with COVID-19 based on the latest international guidelines and national guidelines of countries with the highest incidence of COVID-19 cases. Objective:We discuss how to care for a newborn of a suspected or infected mother with COVID-19 using existing evidence. Method:As of 16 April 2020, we reviewed articles and guidelines related to COVID-19 in the reproductive health field, mother, and newborn health. Our review yielded in 10 categories (i) the risk of diagnostic procedures in suspected mothers on fetus/infant health, (ii) the risk of intrauterine or postpartum transmission to the fetus/infant, (iii) appropriate method and delivery time in women with confirmed COVID-19, (iv) umbilical cord clamping and skin to skin contact, (v) clinical manifestations of infected infants, (vi) confirmation of infection in a suspected neonate/infant, (vii) instructions for infant\u27s care and how to feed her/him, (viii) bathing the baby, (ix) the criteria of discharging baby from the hospital, (x) the impact of isolation on the maternal mental health. Results:Our findings showed that the possibility of intrauterine or perinatal transmission of COVID-19 is still questionable and ambiguous. However, what has been agreed upon in the existing texts and guidelines is that the close contact of mother and infant after birth can transmit the virus to the baby through droplets or micro-droplets. Conclusions:Based on our findings, it is recommended to separate the baby from the mother with confirmed (or suspected) COVID-19 infection for at least 2 weeks. Since the motivation and stable situation of mothers allow breastfeeding during the isolation, infected mothers should be taught about breast expression skills, common breast problems, the symptoms of their baby\u27s infection, and the principles of personal hygiene to protect the infant against COVID-19 infection

The current applications of cell-free fetal DNA in prenatal diagnosis of single-gene diseases: A review

Prenatal diagnosis of hereditary diseases has substantially altered the way medical geneticists are helping families affected by genetic disorders. However, the risk of miscarriage and fear of invasive diagnostic procedures may discourage many couples from seeking prenatal diagnosis. With the discovery of maternal plasma cell-free fetal DNA, prenatal diagnosis has entered a new era of progress. Cell-free DNA is released during normal physiological functions as well as through the cell death programs of apoptosis and necrosis. It can be found in the plasma and other body fluids. Although this method has the advantage of being noninvasive, it is still rather expensive and requires advanced hardware and comprehensive data analysis. Promising implications of noninvasive prenatal diagnosis methods for the diagnosis of common trisomy disorders have paved the way for the development of more complicated assays of single-gene disorders. Relative mutation dosage and relative haplotype dosage are the most widely implemented assays for noninvasive prenatal diagnosis of single-gene disorders. However, each assay has its own advantages and disadvantages. Relative mutation dosage is based on the droplet digital polymerase chain reaction (PCR) technique which includes quantification features of real-time PCR assays. Relative haplotype dosage is based on next-generation sequencing that includes analysis of the maternal and paternal genome followed by sequencing of maternal plasma cell-free DNA. Co-amplification at a lower denaturation temperature PCR is another approach that is based on forming heteroduplexes between alleles to selectively amplify paternal mutations. In this review, we have described the most common noninvasive prenatal diagnosis approaches and compared their applications in genetic disorder diagnosis with different inheritance patterns. Key words: Cell-free nucleic acids, Prenatal diagnosis, Noninvasive prenatal testing, Single-gene diseases, Non-invasive techniques

Explaining Mothers’ Experiences from Breastfeeding Education

Introduction: The aims of this study were describing mothers’ experiences from breastfeeding education and identifying the problems related to breastfeeding in order to submit a suggestion to policymakers who work in field of mother and child health promotion. Method: This descriptive qualitative study was conducted in Tehran, Iran, from May 2012 to June 2015. Participants were 9 women undergoing cesarean and one breastfeeding teacher who were selected purposefully. The method of data collection was an in-depth semi-structured interview. Obtained data were analyzed through conventional content analysis. Results: The codes derived from analysis of interviews were labeled in four categories: amount and conditions of breastfeeding education before and after childbirth, content and method of breastfeeding education before and after childbirth, barriers to effectiveness of education before and after childbirth, and suggestion about the most appropriate time and method for breastfeeding education. Conclusion: Most of the mothers do not have suitable conditions to learn how to breastfeed after baby delivery. Thus, the best time for initiation of breastfeeding education is during pregnancy, especially in the last weeks and days. After baby delivery and during the postpartum period, breastfeeding education has to be continued. Group-based breastfeeding education decreases the quality of education while the most appropriate way for breastfeeding education is individual education on mother’s bedside. Keywords: Breastfeeding, Hospitals, Cesarean section, Qualitative research, Educatio

A Review on the Role of Mitochondrial DNA Mutations in Cancer

Mitochondria implement various cellular functions, including energy production through the electron transport chain by oxidative phosphorylation mechanism. These respiratory chains consist of several complexes and protein subunits which are encoded by nuclear and mitochondrial genes. Due to mutation susceptibility and repair limitation, more aberrations have occurred in mitochondrial DNA in comparison to nuclear DNA. Given the fact that mitochondrial DNA lacks introns, mutations almost occur in the coding sequence, which comprises a direct impact on its functions. Emerging evidence indicates that mutations in the mitochondrial DNA led to the production of reactive oxygen species, disrupted apoptosis, and tumor development. Studies reported various somatic and germline variants in mitochondrial DNA related to tumorigenesis. The D-loop region which is the starting point for replication and transcription of mitochondrial DNA is the most prevalent site of somatic mutations in solid tumors. The D-loop mutations also cause copy number variations which are gaining interest in studies of solid tumors including breast cancer, colon cancer, hepatocellular carcinomas, and prostate cancer. Most studies have reported a mitochondrial DNA reduction which subsequently prevents apoptosis and promotes metastasis. The mitochondrial DNA region-specific haplogroups are also involved in the sequence variations due to processes such as genetic drift and adaptive selection. This review article discusses the biology and function of mitochondria and related genes. By explanation of mitochondrial dysfunction caused by different kinds of alterations, we attempt to elucidate the role of mitochondria in tumorigenesis. Prominently published articles in this field were reviewed and the role of germline and somatic mutations of mitochondrial DNA have been investigated in common cancers. *Corresponding Author: Shirin Shahbazi; Email: [email protected]; ORCID iD: 0000-0002-7634-5350 Please cite this article as: Dahi F, Mortezanejad S, Nakhaee S, Geranpayeh L, Shahbazi S. A Review on the Role of Mitochondrial DNA Mutations in Cancer. Arch Med Lab Sci. 2021;7:1-12 (e18). https://doi.org/10.22037/amls.v7.3473

Effects of Maternal Coagulation disorder on Birth Weight and Post-Natal Non-Coagulation Problems of Neonates

Background: To evaluate the birth weight and post-natal non-coagulation problems of infants of mothers with coagulopathies versus normal mothers. Materials and Methods: In a retrospective cohort study, 100 women with coagulation problems attended the Iranian Haemophilia Comprehensive Care Center, and 200 normal women attending two health centers in Tehran and Karaj, with a history of at least one pregnancy were studied. A questionnaire about mothers’ and neonates’ condition was filled out by an interview, and the data were analyzed using SPSS software, version 16. Results: Using linear regression, the maternal coagulation problem had a negative effect on birth weight (p<0.001, β= -0.31). The prevalence of early and prolonged jaundice in newborns of mothers with coagulopathy was higher than that in newborns of normal mothers (12% vs. 2%, and 7% vs. 3%, respectively), the difference between the two groups in terms of incidence of early jaundice was statistically significant (chi square-p<0.001). The frequency of using phototherapy and blood exchange for treating neonatal jaundice, in neonates of mothers with coagulopathy was higher than in neonates of normal mothers (31% vs. 21% and 8% vs. 21%, respectively) (p<0.001). Furthermore, the duration of hospitalization, hospitalization in NICU, and re-hospitalization during the first month of life in neonates of mothers with coagulation problems was higher than in neonates of normal mothers (p<0.001). Conclusion: Considering the high prevalence of neonatal problems in newborns of mothers with coagulation problems and their lower birth weight, further care measures should be provided for them. &nbsp

Tendon reattachment to bone in an ovine tendon defect model of retraction using allogenic and xenogenic demineralised bone matrix incorporated with mesenchymal stem cells

BACKGROUND: Tendon-bone healing following rotator cuff repairs is mainly impaired by poor tissue quality. Demineralised bone matrix promotes healing of the tendon-bone interface but its role in the treatment of tendon tears with retraction has not been investigated. We hypothesized that cortical demineralised bone matrix used with minimally manipulated mesenchymal stem cells will result in improved function and restoration of the tendon-bone interface with no difference between xenogenic and allogenic scaffolds. MATERIALS AND METHODS: In an ovine model, the patellar tendon was detached from the tibial tuberosity and a complete distal tendon transverse defect measuring 1 cm was created. Suture anchors were used to reattach the tendon and xenogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5), or allogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5) were used to bridge the defect. Graft incorporation into the tendon and its effect on regeneration of the enthesis was assessed using histomorphometry. Force plate analysis was used to assess functional recovery. RESULTS: Compared to the xenograft, the allograft was associated with significantly higher functional weight bearing at 6 (P = 0.047), 9 (P = 0.028), and 12 weeks (P = 0.009). In the allogenic group this was accompanied by greater remodeling of the demineralised bone matrix into tendon-like tissue in the region of the defect (p = 0.015), and a more direct type of enthesis characterized by significantly more fibrocartilage (p = 0.039). No failures of tendon-bone healing were noted in either group. CONCLUSION: Demineralised bone matrix used with minimally manipulated mesenchymal stem cells promotes healing of the tendon-bone interface in an ovine model of acute tendon retraction, with superior mechanical and histological results associated with use of an allograft