Journal of Medical Hypotheses and Ideas5Stress perimetry: An Alternative for Early Detection of Open Angle Glaucoma in High Risk Population9090AlirezaGhaffariyehNazafarinHonarpishehFuadAbasovMohammad HosseinHeidari20151005Glaucoma is a significant public health problem worldwide, defined by a typical appearance of the optic nerve head and visual field defects. The most common type of glaucoma is Primary Open Angle Glaucoma (POAG). Glaucoma has been reported to be the second most common cause of visual loss in the world, and a worldwide upsurge in POAG prevalence is expected by 2012. According to numerous population-based studies, the rate of undiagnosed cases of glaucoma is more than 50%. The current unsatisfactory situation with early diagnosis and protection against glaucoma has motivated us to look for new solutions. Our method can rapidly detect suspected glaucoma. Any increase in perimetry threshold after stress test would be considered positive and high risk for glaucoma.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/90https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/90/90Journal of Medical Hypotheses and Ideas5Consumption of ”Stressed milk” resulting in”Stressful child”9191NSSatish KumarRAswini duttPPJagadish Rao20151005Various factors lead to stress in human beings which have a physical component and psychological component. These factors can be from the environment or from within the body. We propose a hypothesis that there is a third element where the stress factors can be transmitted from stressed lactating mother to their babies through breast milk. The babies thus exposed to high levels of stress hormones viz., cortisol display symptoms of stress. Chronic exposure to such abnormal levels of cortisol also lead to defective brain growth and the whole body overreacts to normal levels of stress hormones later in their life.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/91https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/91/91Journal of Medical Hypotheses and Ideas5Diode Laser 810 nm as a potential treatment to improve visual function in Nonarteritic Anterior Ischemic Optic Neuropathy (NAION)9292AlirezaGhaffariyehNazafarinHonarpishehMohammadrezaGhorbani KhebrehFuadAbasovMohammad HosseinHeidari20151005Nonarteritic anterior ischemic optic neuropathy (NAION) is one of the most widespread visually disabling diseases in the middle-aged and elderly population. The optic nerve damage appears to result from a perfusion insufficiency in the short posterior ciliary arteries leading to infarction of the retrolaminar portion of the optic disc. Induced Heat shock protein (Hsp) is known to have neuroprotective effects against ischemic injury of the central nervous system in mammals. Transpupillary thermotherapy (TTT) application to the optic nerve head induces Hsp70 expression. We hypothesize that Transpupillary thermotherapy (TTT) could be a novel method for improving and preserving the function of the optic nerve fibers in the eye with NAION. An 810-nm diode laser beam is focused to the center of the optic nerve head to induce Hsp. Controlled prospective and randomized clinical trial is necessary to confirm conclusively the effectiveness of this method.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/92https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/92/92Journal of Medical Hypotheses and Ideas5Letter to the editor: “Stressed milk might result in stressful child” but “Stressful adult”9393VirojWiwanitkit20151005https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/93https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/93/93Journal of Medical Hypotheses and Ideas5Letter to the editor: Usage of U7 snRNA in gene therapy of hemoglobin J Iran disorder: why it is not applicable?9494VirojWiwanitkit20151005https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/94https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/94/94Journal of Medical Hypotheses and Ideas5The Rationale behind wearing strings of Jasmine flower by the lactating South Indian Women9595AswiniRNSKumarSandhyaHemraj20151005Jasmine flower belonging to Oleaceae family is cultivated in temperate places across the globe which has more than 200 species. This flower has traditional, religious, social, spiritual and medicinal benefits. It is considered as symbol of beauty, deep affection, happiness and elegance. It is the National flower of many countries. Due to its charming fragrance, it is extensively used in perfume industry. The vital ingredient of jasmine aroma is due to the amalgamation of phytochemicals and alcoholic compounds. In India these flower strings have special importance among the fairer gender. In South India, strings of Jasmine flower are worn by lactating women. It is believed to produce increased lactopoiesis and prolong the lactational amenorrhoea. The mechanisms can be the activation of olfactory area by olfactory nerve or stimulants crossing blood brain barrier triggering a neuroendocrine responsehttps://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/95https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/95/95Journal of Medical Hypotheses and Ideas5Novel material to quantify sharpness and traction of vitreous cutters9696AlirezaGhaffariyehNazafarinHonarpishehAkbarKarkhanehFuadAbasov20151005There is no available method for evaluating cutting quality of vitreotomes. The available methods of assessment allow only indirect judgment of their quality and are difficult to apply in clinical practice. We propose using a collagen film with maximum thickness of 1-2 micron to test the sharpness of instruments under conditions resembling clinical ones. The collagen film is fixed by a special device, then place in physiological saline, and then cut under the operation microscope. It shows whether the cutting edges are sharp enough, and the collagen film is cut smoothly. We also use an Electroforce 3100 machine and Dynamic Mechanical Analysis software to quantify the vitreoretinal force applied to the retina during vitrectomy.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/96https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/96/96Journal of Medical Hypotheses and Ideas5Old fathers and long-telomered offspring: elongation of telomeres in the testes of older men versus transgenerational erosion of germline telomeres9797ReinhardStindl20151005There have been several reports of a significant positive correlation between paternal age and chromosome telomere length in offspring. Moreover, the telomeres in sperm cells of older men tend to be longer than in young men, and it has been concluded that telomeres lengthen in the testes during adulthood. This would be the first evidence of an increasing biological advantage with age, and therefore contradicts current models in which telomere shortening is a biomarker of aging. Instead, an alternative model of telomere erosion between human generations is discussed in which longer germ cell telomeres in old men result from their being members of a previous generation. Based on the well-known correlation between maternal age and the incidence of aneuploid pregnancies, it is hypothesized that telomere erosion predominantly operates in the female germline, leading to a carry-over effect for both sexes into the next generation. This theory fits well with experimental results that maternal age does not correlate with longer telomeres in offspring. An experimental design is presented to distinguish between the two possible scenarios leading to old fathers with long-telomered offspring - namely lifetime lengthening in the testis versus transgenerational germline erosion. Consideration of net loss of telomeric DNA between human generations is supported by recent findings of a large difference in blood telomere length between different European populations of the same age, and is likely to have profound consequences for species evolution.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/97https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/97/97Journal of Medical Hypotheses and Ideas5Is dissection a must for better knowledge among future doctors?9898TabindaHasanMohamed SalihMahfouzDeeba HasanBarkat IrfanShaanMohamed Husain20151005While the importance of anatomy education in contemporary medicine remains undisputable, the medium used to deliver anatomy information to medical learners is rapidly changing .The traditional dissection lies in the midst of a downward spiral as modern technological teaching alternatives rapidly substitute the cadaver. In this climate of pedagogical metamorphosis, the long-term cognitive impact of a ‘cadaver less' curriculum in the assimilation of core knowledge among our future physicians and surgeons remains an issue of fervent debate.The authors propose the hypothesis that active cadaveric dissection directly enhances the ‘long term learning outcomes' among students and is indispensible to the creation and retention of anatomy memory in the minds of learners. This retention of core concepts is not attainable through other instructional aids and might go a long way in framing the professional character of our medical community and the fate of our patients.To prove the same, this study provides objective evidence based on measurable data regarding the medical student's pedagogic preferences in anatomy education and their superior academic performance with the aid of dissection, thereby indicating the pivotal role of the cadaver in enhancing cognitive outcomes.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/98https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/98/98Journal of Medical Hypotheses and Ideas5Micro-holistic body model: reconciliation of Traditional Chinese Medicine with modern biomedicine?9999AihuaXie20151005Development of molecular biology reveals that multicellular organism could be considered as a cell community. By scrutinizing constitution and activities of a single cell under context of the whole community, I got a micro-holistic body model constituted of two aspects and seven compartments. The two inseparable aspects are the extracellular signalling molecules and the cells that communicate with each other using extracellular signalling molecules. The seven compartments include three universal sub-cellular compartments running within every cell in the body and four specific systems comprised of specific cell groups and molecules providing particular services needed generally by cells in the body. The constitution and internal relationship of the model match the fundamentals of traditional Chinese medicine (TCM) perfectly, thus can philosophically bridge the understanding between traditional Chinese medicine and western medicine, provide research hypotheses, and connect molecular level research with clinical diagnosis and treatment of complex diseases more directly, and may cause profound revolution in human healthcare technology.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/99https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/99/99Journal of Medical Hypotheses and Ideas5The low-frequency oscillation model of hallucinations in neurodegenerative disorders and in delirium100100GrzegorzJuszczak20151005Electroencephalography (EEG) found in dementia with Lewy bodies, Parkinson's disease, Alzheimer's disease and delirium, is characterized by increased power of delta and theta frequencies with the degree of EEG slowing parallel to the frequency of hallucinations occurrence. According to the proposed model of hallucination, pathological low-frequency oscillations may interfere with information processing in two different ways leading to hallucinations. First, pathological low-frequency oscillations may be a source of signal noise, which is next transformed into emotionally charged signal. The filtering of the signal noise may depend on differences in synaptic weights between networks storing representations of emotionally charged and neutral objects. Initially filtered signal can be next reinforced by attention leading to hallucinations. Second, there is growing body of evidence that theta oscillations in distributed cortical networks participate in mechanism of working memory. Therefore, pathological low-frequency oscillations may interfere with the mechanisms of working memory leading to excessive activation of memory traces and to the intrusion of memories into consciousness. The assumption that neuronal representations of emotionally relevant and neutral objects differ in synaptic strengths is supported by studies showing enhanced memory for emotional stimuli. The model is also supported by experiments showing that perception of feared object is facilitated by stimulus-driven, involuntary and automatic recruitment of attention. Consistently with the model, hallucinations are most often unpleasant and emotionally irrelevant objects are rarely hallucinated in neurodegenerative disorders. Proposed disturbances of visual working memory are consistent with the high incidence of palinopsia (perseveration of previously viewed objects after a certain time) in demented patients. The significance of the model for understanding hallucinations that occur in schizophrenia is also discussed. The proposed model predicts that we should search for treatments decreasing the power of cortical delta and theta oscillations or reshaping synaptic plasticity in order to prevent the occurrence of hallucinations.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/100https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/100/100Journal of Medical Hypotheses and Ideas5Letter to the editor: Stokes’ law, infection and changes in erythrocyte sedimentation rate101101SimonBrown20151005https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/101https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/101/101Journal of Medical Hypotheses and Ideas5Intraocular interleukin-7 injection can be an effective strategy for prevention and treatment of proliferative vitreoretinopathy102102Sayed ShahabuddinHoseiniNasrinShoarSaeedShoar20151005Proliferative vitreoretinopathy (PVR) is one of the ocular diseases caused by excessive production of fibrotic tissues in both surfaces of retina and vitreous humour and is considered as the most common cause of failure in retinal reattachment surgery. Such fibrosis may occur as a result of excessive profibrotic molecule production in the body. Ocular level of transforming growth factor-β (TGF-β) and fibronectin has been reported to be elevated in affected eyes by PVR and hence administration of these two molecules could result in ocular fibrosis as well as traction retinal detachments. Some studies have shown the antagonistic function of interleukin-7 (IL-7) on profibrotic effects of TGF-β in human subconjunctival fibroblasts and modulating extracellular matrix (ECM) production. Such excessive production of ECM and subsequent fibrosis has been shown to be responsible for PVR pathology. In this article we hypothesize that IL-7 via its inhibitory effects on pathogenic activity of TGF-β in ECM production could lead to a decrease in collagen production and fibronectin synthesis in retina and vitreous humour; hence its local application as an eye drop or its intraocular administration can be exploited to prevent and treat patients at higher risk of or affected by PVR.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/102https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/102/102Journal of Medical Hypotheses and Ideas5Letter to the editor: Jasmine and lactation103103VirojWiwanitkit20151005https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/103https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/103/103Journal of Medical Hypotheses and Ideas5Erythrocyte sedimentation rate, simple hematological test but interesting in fluid dynamics104104VirojWiwanitkit20151005https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/104https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/104/104Journal of Medical Hypotheses and Ideas5Inducing of angiogenesis is the net effect of the amniotic membrane without epithelial cells105105GhodsiehPaeini-VayghanHabibollahPeiroviHassanNiknejad20151005Amniotic membrane (AM), the nearest layer of placenta to the fetus, has some biological properties important for the experimental and clinical applications including anti-microbial, anti-fibrosis, anti-scarring, as well as low immunogenicity. The basement membrane of the AM contains several extracellular matrix components such as types І, III, IV, V collagen, laminin, fibronectin and perlecan which can induce proliferation of endothelial cells. The stormal side of the AM consists of mesenchymal cells which have capability to differentiate into endothelial cells. Moreover, several angiogenic factors such as interleukin (IL)-6, IL-8, growth-related oncogene (GRO), monocyte chemoattractant protein-1 (MCP-1) and intravascular adhesion molecule (ICAM) are secreted by the amniotic mesenchymal cells. Since the majority of anti-angiogenic factors are released by amniotic epithelial cells and due to the advantages of basement membrane and stromal side for inducing of angiogenesis, we have suggested here that the AM without epithelial layer would promote angiogenesis, an effect that would be a beneficial therapeutic approach for ischemic vascular diseases. To evaluate the hypothesis, the AM with or without epithelial cells will be implanted onto the striated muscle tissue of rats. The dorsal skinfold chamber model will be employed for intravital microscopic observation of the angiogenic host tissue response to implanted biomaterials throughout a time period of 7-14 days.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/105https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/105/105Journal of Medical Hypotheses and Ideas5Flux change, electrolyte and infection106106VirojWiwanitkit20151005https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/106https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/106/106Journal of Medical Hypotheses and Ideas5Change of blood cell morphology, a cause of change in its characteristic in clinical pathology107107VirojWiwanitkit20151005https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/107https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/107/107Journal of Medical Hypotheses and Ideas5An electric method for Qualifying Cytogenetic Slides108108MasumehZamanluSaeedKhamnei20151005Cytogenetics is a branch of genetics that involves critical applications in medical decisions. The procedures involved take cells with chromosomes and rupture them on the slide to release their chromosomes in metaphase spreadings. Usually the slide contains few metaphase spreadings and plenty of intact cells, so finding and analyzing metaphase spreadings are difficult. It is for this reason that many investigations search for innovations that optimize chromosome spreading and facilitate cytogenetic studies. To aid rupturing cells in cytogenetic slide preparation, Pulsed Electric Fields (PEFs) could be used. PEFs are a kind of electric fields, which affect the cell membrane in a way that can lead to cell lysis. These effects are currently the basis of applications such as nonthermal pasteurization. Therefore, applying PEFs to cell suspension of the cytogenetic experiments would probably lyse all the cells, yielding a clear slide with many metaphase spreadings.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/108https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/108/108Journal of Medical Hypotheses and Ideas5A New Candidate for Guided Tissue Regeneration: Biomimetic Eggshell Membrane109109JunJiaZhaoxiaGuoJianYuYuanyuanDuan20151005Periodontal disease that involves the deterioration of tooth supporting structures is the primary cause of tooth loss among adults. Guided tissue regeneration (GTR) technique is a commonly used surgical procedure for the treatment of periodontal diseases by using a barrier membrane. Natural eggshell membrane (ESM) is a semi-permeable membrane consisting of two individual layers with fibrous meshwork structures. With the aid of successful preparation of soluble eggshell membrane proteins (SEP) from natural ESM in the previous study, we hypothesized that one new type of biomimetic nanofibrous eggshell membrane could be successfully constructed by sequential electrospinning method. This proposed membrane is composed of two interconnected nanofibrous layers with different density and porosity which can mimic the composition, morphology and structure of natural ESM. It is expected to greatly enhance the periodontal tissue regeneration as well as physically maintain the space for tissue repair, thus to be a promising and cost-effective GTR membrane candidate.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/109https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/109/109Journal of Medical Hypotheses and Ideas5Fundamental fluid mechanics and erythrocyte sedimentation110110SimonBrown20151005https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/110https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/110/110Journal of Medical Hypotheses and Ideas5Enhance tissue flap survival by intracellular delivery of hypoxia-inducible factor-1α111111DaweiLiPinDong20151005Tissue flap has been widely applied in head and neck surgery to repair tissue defects resulting from focal or organ resection. Ischemic necrosis usually becomes the main complication in the hypoxic grafts. Hypoxia-inducible factor 1α (HIF-1α) could be obvi-ously activated and rapidly accumulated under hypoxic conditions. Recent studies have indicated that HIF-1α could accelerate revascularization and attenuate cellular ische-mia/reperfusion injury in the grafted tissue via activating the HIF-1α dependent signal transduction pathways. Moreover, HIF-1α plays a pivotal role in hypoxic/ischemic pre-conditioning for elevating cellular tolerability to a subsequent lethal hypoxic/ischemic injury. Therefore, we postulate that intracellular delivery of adeno-associated viral human HIF-1α gene (lacking ODD domain) will offer potential as a novel means to en-hance tissue flap survival.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/111https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/111/111Journal of Medical Hypotheses and Ideas5Ischemia Reperfusion May Be a New Approach in Cancer Interventional Therapy112112QiongDuanTianlunYang20151005Cancer is a leading course of death worldwide. Interventional cancer therapy made huge progress in the past decades, however, traditional interventional therapy, e.g. transarterial embolization and transarterial chemoembolization remain to be developed for its potential limitations. Numerous studies in the past half century demonstrated that tissue injury accelerated after ischemia reperfusion. Reactive Oxygen Species (ROS) production, cell death, inflammatory factors involved in the development of ischemia reperfusion injury. As outline above, we hypothesize that reperfusing the tumor lesion with high oxygen, high calcium and high pH fluid together with ROS-generating agents and/or inhibitor of antioxidant system, with or without traditional chemotherapeutic agents after short time arterial embolization can effectively induce cancer cells death, and it might be a new attempt in cancer interventional therapy.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/112https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/112/112Journal of Medical Hypotheses and Ideas5Can a research map help organizing interdisciplinary studies of relation between medical disorders and school performance? A framework for development of pediatric school psychology113113AtaPourabbasiMahbubehEbrahimnegad ShirvaniPatriciaKhashayar20151005School psychologists try to prepare ideal conditions for students in order to learn better because education is the most important tool in achieving sustainable development in human societies. Pediatric school psychology is a new area of interest concerned with the impacts of medical disorders on the students' school performance and education. This area, previously known as educational medicine, focuses on medical aspects of school psychology.Pediatric school psychology includes pediatric medical concept and psychology and education. According to this fact, developing a conceptual model to integrate these concepts, organize previous studies, translate them into protocols and guidelines and understand its pitfalls for further studies is necessary. The present research map aims to clarify the process through which the guidelines and protocols needed for evaluating, diagnosis and management of the illnesses affecting learning, education and school performance. The present roadmap highlights the diseases believed to affect learning and school performance based on previous studies. The resulted array would show different aspects of learning influenced by the disorder, paving the way for further studies based on which policymakers would detect the gaps and develop clinical guidelines. In other words, the roadmap not only provides a map for further studies in this field but also helps translate research into practice.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/113https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/113/113Journal of Medical Hypotheses and Ideas5Physical stress may result in growth suppression and pubertal delay in working boys114114MuhammadIrfanGhazalaKaukab RajaShahnazMurtazaRubinaMansoorMazharQayyumSyed ShakeelRaza Rizvi20151005Child labor is an immense problem of Pakistan. As labor boys stay under persistent/severe physical stress, we hypothesized, that it may result in higher levels of cortisol and exhaust glycogen, fats and proteins. Depletion of fats may result in lower body weight, and insufficient leptin concentrations to excite gonadotropic releasing hormone (GnRH) at the normal time of puberty in working boys. Moreover, lower testosterone levels in working boys, due to delayed puberty, may result in suppression of somatotropic axis. The Short/weak stature and failure of the onset of puberty may cause poor performance, the inferiority complex and psychological disorders. Therefore, present study is designed to find out timing of onset of the puberty in working boys. The study will include 10-18 years of working boys as a case and non-working boys of same age groups as control. Working boys will be labor boys while the control group will not be involved in physical work. A questionnaire will be used to record socioeconomic status, major diseases, nutritional status, type, and duration of work and family history of puberty, growth and obesity of subjects. Boys with familial history of pubertal delay, obesity, malnutrition, mental disorders, hematological diseases and severe/chronic diseases will be excluded. The intensity of physical working stress will be determined by a grading scale. The anthropometric data including height, weight, body mass index (BMI), bone age, tests of adiposity will be collected from subjects. The stages of pubertal onset will be determined by Tanner staging. Serum concentrations of hormones of growth, thyroid, adrenal, brain-gut and gonadal axis will be determined in nonworking and working boys. Physical and hormonal tests of the working boys and comparison with non-working boys are sufficient to test the idea.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/114https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/114/114Journal of Medical Hypotheses and Ideas5Targeting CD44 by hyaluronic acid-based nano drug delivery systems may eradicate cancer stem cells in human breast cancer115115NavidGoodarziMohammad HosseinGhahremaniRassoulDinarvand20151005Despite the significant progress in cancer diagnosis and therapy, still invasion and metastasis of cancer cells, development of drug resistance and cancer recurrence are the main causes of mortality in cancer patients. Recent researches on cancer stem cells (CSCs) along with the role of CD44 marker in drug resistance and as the main marker of breast CSCs, highlight the importance of CD44 in cancer targeted therapy. Additionally, co-localization of MDR1 and CD44 in cancer cell population showed that one protein directly influences the expression of the other and disruption of interaction has significant effects on drug resistance, cell migration and in vitro invasion. Based on the above information, using nanotechnology-derived CD44 targeted drug delivery systems will be able to address recurrence of the disease and other major obstacles in cancer chemotherapy. Therefore, we hypotheses that using combination of cytotoxic agents and CSC specific agents anchored in hyaluronic acid (as the endogenous substrate of CD44), have the potential to develop novel drug delivery systems to eradicate breast cancer.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/115https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/115/115