Dr. John Yahya I. Elshimali
Professor of Pathology and Oncology, UCLA School of Medicine & Charles R. Drew University of Medicine and Science, California, USA.

ISBN 978-93-90888-62-7 (Print)
ISBN 978-93-90888-70-2 (eBook)
DOI: 10.9734/bpi/hmmr/v10

This book covers key areas of medicine and medical research. The contributions by the authors include cardiovascular disease, physical inactivity, unhealthy diet, cardiac mechanics, ventricular function, end-systolic pressure-volume relation, intercept Vom of ESPVR, pump function of the heart, scoliosis, brace treatment, conservative management, brace treatment, delayed cord clamping, umbilical cord milking, very low birth weight, placental transfusion, traumatic ulcers, oral cavity, cultivar coratina, forensic dentistry, integrative oncology, oncological diseases, Insulin Potentiation Therapy, biomagnetic therapy,  stomach cancer, colon cancer, breast cancer, thymidine kinase, thymidine phosphorylase, adenosine deaminase, blood serum, lymphocytes, infertility, psychological and emotional trauma, involuntary childlessness, coping, craniorachischisis, neuroectoderm formation, neural tube defects, omphalocele, central nervous system, rehabilitating atrophied mandible, trichomoniasis, obesity, tumor markers, cytomorphometry, exfoliative cytology, cellular diameter, nuclear diameter, nuclear cytoplasmic ratio, esophageal cancer, adenocarcinoma, squamous cell carcinoma, personalized medicine, esophagus, adrenal medulla, adrenalin memorandum, mortality, spectrum analysis, public health. This book contains various materials suitable for students, researchers and academicians in the field of medicine and medical research.


Media Promotion:


While there has been measurable progress in the prevention of cardiovascular disease around the world, it has been inconsistent and insufficient, especially in low- and middle-income countries. Voluntary global targets have helped to focus attention, resources, and accountability on tobacco use, harmful alcohol use, unhealthy diets, and physical inactivity, all of which are major behavioural drivers of cardiovascular disease. The advancement in cardiovascular prevention continues to be hampered by many barriers and challenges. The inclusion of noncommunicable diseases as a specific priority in the Sustainable Development Agenda provides an unparalleled opportunity to accelerate global cardiovascular prevention progress. Such a strategy will need to provide leadership for intersectoral policy coherence, define successful ways to address commercial determinants of behavioural risk factors, employ rights-based arguments, increase public participation, and ensure transparency. The Sustainable Development Goals have a genuinely universal vision of common obligations for the entire world. It is a once-in-a-lifetime opportunity to boost everyone's health and well-being, particularly cardiovascular health.

Clinical Applications of the Areas under ESPVR: A Review

Rachad M. Shoucri

Highlights on Medicine and Medical Research Vol. 10, 11 May 2021, Page 10-15

Relations between the ejection fraction (EF), parameters describing the end-systolic pressure-volume relation (ESPVR) and the areas under the ESPVR are derived for a linear model of the ESPVR. The active pressure generated by the myocardium during an ejecting contraction (also called isovolumic pressure Piso by physiologists) is included in the mathematical formalism describing the ESPVR. The various areas under the ESPVR are sensitive indexes that reflect the state of the myocardium. Applications to clinical data published in the medical literature show the consistency of the mathematical formalism. Results indicate that using bivariate (or multivariate) analysis of data is superior to using one index (like EF) for the purpose of segregation between different clinical groups. When ratios of pressures are used, calculations can be carried out on data measured in a non-invasive way (ratio of pressures can be calculated by using the mathematical formalism introduced).

Bracing Scoliosis according to‚ Best Practice’ Standards

Maksym Borysov, Artem Borysov, Alexander Kleban, Hans-Rudolf Weiss

Highlights on Medicine and Medical Research Vol. 10, 11 May 2021, Page 16-23

Introduction: As has been demonstrated before bracing concepts in use today for the treatment of scoliosis include symmetric and asymmetric hard braces usually made of polyethylene (PE) and soft braces. The plaster cast method worldwide seems to be the most practiced technique for the construction of hard braces at the moment. CAD / CAM (Computer Aided Design / Computer Aided Manufacturing) systems are available which allow brace adjustments without plaster. As in the Ukraine the CAD / CAM technology is not affordable, we have tried to build our hand-made braces according to this standard via cast modelling. Aim of this study is to compare in-brace corrections of our brace built according to‚ Best Practice’ Chêneau standards by hand with the published results available in literature on Chêneau braces.

Methods: In-brace correction and compliance clearly determine the outcome of bracing. Therefore, the in-brace correction is one of the most important parameters to estimate brace quality. We have been looking at the results achieved in our department after having been trained in the construction, adjustment and use of ‚Best Practice’ CAD / CAM Chêneau braces. All braces (of 207 patients) made between January 2009 and December 2010 have been reviewed for in-brace correction. As not all of the patients were in the normal range of brace indication, (Cobb 20 – 45°; age 10 – 14 years) we have been looking for the appropriate subset from our database fulfilling the following inclusion criteria: Girls only; diagnosis of an Adolescent Idiopathic Scoliosis (AIS); Cobb 20 – 45°; age 10 – 14 years).

Discussion: 92 Patients fulfilled the inclusion criteria (Cobb 20 – 45°; age 10 – 14 years). Average Cobb angle was 29.2° (SD 6), Average in-brace Cobb angle was 12.8° (SD 6.2).  In-brace correction in the whole sample was 56%.

Conclusion: After appropriate training the experienced CPO is able to provide a hand-made standard of braces comparable to the recent CAD / CAM standard of bracing. In principle the results may be repeatable. Further studies on our hand-made series of braces are necessary (1) to evaluate brace comfort and (2) effectiveness using the SRS inclusion criteria. Less experienced technicians are advised to use standardized, expert driven and well established, CAD / CAM services.

Health-Related Quality of Life (HRQL) of scoliosis patient’s has been investigated in numerous studies. The perception of health, self- and body image and participation in physical activities seems to be an issue for patient’s with spinal deformities. In previous studies it was concluded that adolescents with scoliosis have only “little stress” associated with their deformity. This study was performed to scientifically objectify the outcome of patient’s following brace treatment with respect to quality of life using the BSSQ-Deformity.

Materials and Methods: All 42 consecutive female patient’s returning to the office of the first author for a followup x-ray after brace weaning (February to December 2013) were asked to complete the BSSQ-Deformity. The average age of the patient’s was 15.8 years and the average treatment duration was 35.8 months. The patient’s average age at start of treatment was 12.8 years. In addition to the BSSQ we also evaluated the treatment results of this sample of patient’s with respect to Cobb angle (maximum angle in combined curvatures) and angle of trunk rotation (ATR) for thoracic and lumbar areas.

Results: The average BSSQ score was 22/24 with five patient’s scoring less than 20/24. The average Cobb angle at the start of treatment was 29.2° (range 15–69°) and after weaning it was 25.8°. None of the patient’s experienced a progression of > 5°, while 14 patient’s (33%) improved > 5° over the period of brace treatment.

Discussion: Patient’s with adolescent idiopathic scoliosis seem to be able to cope very well with their deformity. A BSSQ score of 22/24 indicates that cessation of brace treatment had very little impact on the patient’s quality of life.

Conclusions: Scoliosis-related stress is not necessarily a problem for patients with moderate angles of curvature after brace weaning when recent asymmetric bracing standards are applied. An improvement in the Cobb angle and trunk deformity is possible when recent asymmetric bracing standards are applied. Considering the small impact that AIS obviously has on patient’s participation in physical activities and quality of life, a general indication for surgery cannot be derived for treating this condition. Patient satisfaction after treatment in this cohort seems better than in the pilot investigation.

Effects of Placental Transfusion by Delayed Cord Clamping or Umbilical Cord Milking Versus Immediate Cord Clamping on Neonatal Outcomes in Very Low Birth Weight Neonates: A Recent Study

Swosti Joshi, Mopelola Akintorin, Alison Wiles, Annamarie Arias, Louis Fogg, Tuan Nguyen

Highlights on Medicine and Medical Research Vol. 10, 11 May 2021, Page 34-41

Background: Delayed cord clamping (DCC) and umbilical cord milking (UCM) are two recently advocated interventions to enhance placental trans-fusion at birth. DCC and UCM might increase blood volume and help neo-nates to transition from fetal to neonatal circulation. Objective: To evaluate the effects of delayed cord clamping (DCC), umbilical cord milking (UCM), and immediate cord clamping (ICC) on very low birth weight (VLBW) neo-nates. Methods: At our institution, ICC was routinely done until December, 2012 when it was replaced by DCC. UCM was implemented in March, 2015. Neonatal outcomes were compared among ICC, DCC, and UCM. Results: A total of 94 neonates met inclusion criteria. Comparing with ICC neonates, DCC and UCM neonates had higher hematocrits, fewer blood transfusions, and lower incidence of chronic lung disease at 36 completed weeks of gestation. All groups were similar in APGAR scores, vasopressor use, intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC). Conclusion: Compared to ICC, DCC and UCM appear to be more beneficial to VLBW neonates without apparent adverse risks. The use of either method to enhance placental transfusion appears to be superior to ICC and may be considered as an option in the delivery of VLBW neonates to optimize outcomes.

Use of Extra Virgin Olive Oil (EVOO) in the Treatment of Traumatic Ulcers Case Report

Antonia Sinesi, Cinzia Casu, Savino Cefola, Ruggiero Damato, Germano Orrù

Highlights on Medicine and Medical Research Vol. 10, 11 May 2021, Page 42-48

In Southern Italy, precisely in all the countryside of northern Bari in Puglia, is produced a particular type of extra virgin olive oil (EVOO) from the cultivar called "Coratina". It is characterized by the presence of a high content of polyphenols and other biocoumponds, the highest compared to other cultivars.

The EVOO is an essential food in the Mediterranean diet. Moreover for the ancient populations of southern Italy the oil was use it to treat various diseases: burns, trauma, hematomas, dermatitis etc. Although numerous studies on EVOO have shown its remarkable effectiveness in wound healing, no scientific studies have been proposed for the treatment of traumatic ulcers in the oral cavity.

In this clinical case, we propose the use of EVOO as a therapy in therapeutic treatment as a valid alternative to drug treatment

Integrative Oncology at the Clinicist's Look Chronology for the Formation and Progress of the IPT & BMP Method for Treatment of Oncological Diseases

Christo Damyanov, Ivan Maslev, Vladimir Pavlov, Alexander Todorov

Highlights on Medicine and Medical Research Vol. 10, 11 May 2021, Page 54-62

The current presentation displays chronologically our summarized and updated results of more than 12 years of the accumulated experience of integrative oncology application in our medical practice. Based on our concept of systemic approach, we have created treatment protocol for cancer patients with leading method of administering Insulin Potentiation Therapy (IPT). For the past 12 years period we treated more than 1100 cancer patients, greater part of which (94%) were patients with advanced metastatic tumors (?2-?4) and more than 80% of them experienced failure of previous conventional treatment for cancer with chemo- and radiotherapy. The achieved treatment results demonstrated remission in about 80% of the patients, and were presented in our earlier publications. In search for new opportunities of improvement of our treatment efficiency since April 2018, we created treatment method which includes combination of IPT with Biomagnetic therapy with magnetic pairs. (IPT & BMP). Until August 2019 this specific treatment has been applied to 33 cancer patients with advanced metastatic tumors (?2-?4) in which 19 out of 23 (82%) experienced failure of previous standard treatment. Twenty-three patients have completed their treatment and were followed up by us. Out of them, 5 patients (21%) have achieved complete remission, and 17 patients (74%) have achieved stabilization. The average remission period is 10 months up till now. Registered failed treatment is present in only one case. Illustrating the opportunities of the new method, we present herewith two new cases with the results of complete clinical remission. In our opinion, the results are an illustration of the opportunities of the Integrative oncology, and the need for change in the concept for cancer patients’ treatment. The first successful results of the treatment with combined IPT & BMP method open new therapeutic possibilities. Our achieved results give us firm ground for developing our activities in optimization of our medical practice and methodology.

Age-Specific Features of the Enzymatic Proliferation Markers upon the Cancer of Different Localisations

Berta G. Borzenko, Elena M. Bakurova, Kseniia A. Mironova, Ulia D. Tursunova

Highlights on Medicine and Medical Research Vol. 10, 11 May 2021, Page 63-71

A comparative study of enzyme activity features of thymidilate "salvage pathway" synthesis and adenosine catabolism in blood serum and cancer tissues from solid adjacent tumors of different localizations was carried out. Aim: To evaluate both the diagnostic relevance of thymidilate metabolism enzymes and adenosine deaminase (ADA) activity and their association with tumor growth. Methods: The determinations of enzymes activity were examined blood serum and lymphocytes of 169 patients by the radioisotope method and spectrophotometrically. Results: We revealed that in case of cancer development the thymidine phosphorylase activity in blood serum is lower as compared to healthy persons. It was accompanied by of thymidine kinase (TK) and adenosine deaminase (ADA) activity increasing. It was shown that enzymes activity features were correlated with age and stage of disease. The enzymes activity changes depended on the efficacy of chemotherapy and eradication of the tumor. The lymphocytes ADA activity features can be the useful marker of its dysfunction. Conclusion: Our findings suggest that study of individual dynamics of the enzymes activity in blood serum may be used as informative tests for disease recurrence diagnostic and drug treatment optimization.

The expectation of getting married and having children is for many individuals a natural part of adult life. Many young people anticipate the prospect of becoming biological mothers and fathers. This expectation of parenthood emanates as individuals and couples are socially groomed to aspire to this social norm. Therefore, infertility can be a very traumatic and tormenting time for many men and women who aspire to conform to these socio-cultural conventions of normative parenthood and who believe that childbearing is central to their lives. Infertility is medically defined as the inability to achieve a pregnancy after a period of at least twelve months of regular sexual intercourse without contraception. For both men and women infertility may present pervasive feelings of incompleteness, a sense of failure and inadequacy. However, infertile women tend to endure a myriad of feeling losses and high levels of suffering and sorrow as a result of their inability to have children. This study explored a sample of South Africa women’s experiences of coping with infertility. Utilising a qualitative methodology, a diverse group of 21 married women who were diagnosed with primary infertility were recruited. Semi-structured, in-depth individual interviews were conducted and the data were analysed using thematic analysis. The results of the study indicated that the women reported emotional turmoil characterised by emotions such as disappointment and shock, anger and frustration, a deep sense of sadness and then progressed to experience a sense of acknowledgement that a problem existed. The findings of this study suggest that severe psychological and emotional strain accompany infertility. The coping strategies employed by these women in the study included social withdrawal and women isolating themselves from social events and social gatherings, avoiding pregnant women and women with children, engaging in escapism strategies on both a psychological level and a physical level. Employing an escapism strategy on a psychological level would involve deliberately thinking about strategies to avoid thinking about infertility, pregnancy or babies. Escapism on the physical level would include engaging in activities like shopping, working longer hours, sleeping more than usual, engaging in activities that would occupy an individual to the extent that they cannot think about anything else except the activities they are currently engaged in. This study has revealed that in-fertility is not an easy journey and coping with infertility requires the infertile couple to possess a strong sense of resilience and to surround themselves with solid social support that is supportive rather than obtrusive.

Study of Craniorachischisis, with Emphasis on Prenatal Diagnosis and Prevention

Gayathri Pandurangam, S. Saritha, D. Nagajyothi, T. V. Ramani, N. Himabindu

Highlights on Medicine and Medical Research Vol. 10, 11 May 2021, Page 85-95

Introduction: Central nervous system (CNS) malformations account for a sizable proportion of all congenital malformations, second only to cardiac malformations. Failure of fusion of cephalic part of neural tube is known as Exencephaly and caudal part of neural tube is Spina bifida.

Aim: The purpose of this study was to provide a comprehensive understanding of Craniorachischisis, which is characterised by anencephaly and open spina bifida. It was also linked to congenital fissures in the skull and spinal column. This is the most severe form of NTDs, and recent evidence shows that taking folic acid periconceptionally reduces the occurrence of NTDs by 50-70%. Therefore emphasis was based on prenatal diagnosis and prevention.

Methods and Results: The current study includes 1000 live births as well as 100 stillborn foetuses and abortuses in order to better understand Craniorachischisis.The two unclaimed foetuses, one with Craniorachischisis totalis and the other with Craniorachischisis with omphalocele, were sent from the Obstetrics and Gynecology department. There was no information available about the patient's family and obstetric history.

Discussion: Neural tube defects (NTDs) are embryonic induction disorders that result from the failure of mesoderm and neuroectoderm formation. The reduction of 50-70 percent of NTDs after periconceptional folic acid administration prompted a number of authors to conduct a series of clinical studies.

Conclusion: Finally, most NTDs are sporadic, with both genetic and non-genetic environmental factors playing a role in their aetiology.

Early Loaded Single Implant Reinforced Mandibular Overdenture: A Case Report

K. Nischal, R. Chowdhary

Highlights on Medicine and Medical Research Vol. 10, 11 May 2021, Page 96-102

Rehabilitating atrophied mandible with two-implant supported denture is a common treatment modality for implant retained removable overdenture in mandible. This paper aims to design a treatment modality where single implant reinforced overdenture is fabricated for a severely atrophied mandibular ridge with early loading protocol. Single implant overdenture can be an alternative treatment modality, as it is cost effective and less invasive than 2-implant retained overdenture.  Results of studies have shown that a single implant mandibular overdenture significantly increases the satisfaction and quality of life of patients with edentulism. Midline fracture of the prosthesis is the most common complication related to single implant and two-implant retained mandibular overdentures. To manage such complication, a thin metal mesh is used to reinforce the overdenture and also to make the prostheses lighter and cost effective as compared to conventional cast metal framework.

Management and Control of Trichomonas vaginalis Infection: A Recent Study

Padmalaya Das

Highlights on Medicine and Medical Research Vol. 10, 11 May 2021, Page 103-106

Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease (STD) in the world. The infection occurs in the female and male urogenital tract and humans are the only natural host for the parasite. In this chapter, the Management of Trichomonas vaginalis Infection as well as prevention are well described. Multidose metronidazole has been found to be superior to single-dose metronidazole for the treatment of trichomoniasis. The drug is well tolerated with minimal adverse reactions. The authors suggested that treating trichomoniasis in women with a 7-day dose of metronidazole should be the first line of treatment.

Tumor Markers and Cortisol Metabolism in Obesity

Moses O. Akiibinu, Bob O. Soile, Ajibola M. U. Amzat, Oyetunji T. Kolawole

Highlights on Medicine and Medical Research Vol. 10, 11 May 2021, Page 107-113

Obesity is a medical condition characterized by an excessive accumulation of body fat with consequent metabolic syndrome. In obesity, modulation of metabolic pathways plays critical roles in the pathogenesis of many diseases. Our study linked obesity, metabolic stress and tumor by evaluating the levels of tumor markers and cortisol (a stress-induced hormone) in obese individuals. Thirty-three obese (18 males, 15 females, body mass index=34 ± 3.8 Kg/M2) and 37 apparently non-obese (19 males, 18 females, body mass index=22 ± 1.4 Kg/M2) individuals (controls) volunteered to participate in this study. All participants were not on drugs (i.e. alcohol, cigarette or steroids) and were healthy adults without apparent medical problems. Every participant had his/her body weight and height taken, and the body mass index (BMI) calculated before inclusion in the study. Obesity was defined by using the body mass index (BMI; Kg/M2), where a BMI higher than 25 Kg/M2 was used as an index of overweight, while a BMI higher than 30 Kg/M2 was used as a cut-off point to indicate obesity. Plasma levels of carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), alpha fetoprotein (AFP) and cortisol were determined in these subjects using enzyme linked immunosorbent assay methods. In the obese subjects, plasma levels of CA125 and cortisol increased significantly (p<0.05), while plasma levels of CEA and AFP did not show significant (p>0.05) changes compared with controls. Metabolic changes could account for the increased rate of synthesis of cortisol and CA125 in obesity.

A Cytomorphometric Analysis of Oral Mucosal Changes in Tobacco Users

Anju Mathew

Highlights on Medicine and Medical Research Vol. 10, 11 May 2021, Page 114-122

Aim: To investigate the effect of tobacco smoking and chewing on the buccal mucosa using cytomorphometry.

Materials and Methodology: Oral mucosal cells were collected from 45 subjects divided into three groups: smokers, chewers, and nonsmokers.The cells were stained with Papanicolaou stain and examined under a high magnification microscope.

Image J analysis software was used to perform cytomorphometric analyses on the cells in the captured image to determine the Cellular Diameter, Nuclear Diameter, and Nuclear Cytoplasmic Ratio. The statistical test used was ANOVA and p<0.05 was considered significant.

Results: From controls to smokers and chewers, cellular diameter decreases while nuclear diameter and nuclear cytoplasmic ratio increase.

Conclusion: The findings indicated that chewing tobacco changed the cytomorphology of normal buccal mucosa, and that the degree of change was greater in chewers than in smokers.Oral smears can be analysed cytomorphometrically on a regular basis to detect changes in cellular and nuclear dimensions, particularly among tobacco users.

A Current and Evolving Treatment Landscape on Esophageal Cancer

Nicole B. Balmaceda, Joaquina C. Baranda, Peter DiPasco, Weijing Sun, John Ashcraft, Joseph Valentino, Mazin Al-Kasspooles

Highlights on Medicine and Medical Research Vol. 10, 11 May 2021, Page 123-136

With advances in state-of-the-art technology, trendy diagnostic and prognostic molecular markers, and cutting-edge surgical techniques, the overall survival for patients with many types of cancers has improved. However, there is a disconnect between esophageal cancer and the acceleration in cancer care seen in other malignancies.  Based on data reported by Surveillance, Epidemiology, and End Results Program (SEER), the 5-year survival rate for patients with esophageal cancer is only 19.9% [1]. Poor prognosis is likely due to an overwhelming number of patients with advanced disease during the time of diagnosis, and is also reflective of the unsatisfactory outcomes from current treatments.

In this article, we will review the epidemiology and the recently revised staging of esophageal and esophagogastric junction cancers. We will discuss the current roles of endoscopic resection, surgery, radiation therapy, and systemic therapy used individually, or as components of multimodality treatment. We will describe the changes in treatment landscape with targeted therapy and immunotherapy. The focus of clinical investigations continues to shift from the traditional empiric chemotherapy to more individualized treatments based on molecular oncology and use of immunotherapy. Further identification of prognostic values may help clarify the optimal approach to treatment and management for patients with esophageal cancer, and hopefully improve survival. Clinical trials investigating strategies in prevention, early diagnosis, and treatment of early and advanced disease are guided by lessons learned in epidemiology, molecular genetics, pharmacogenomics, and precision medicine.

Adrenaline Hunters: Past, Present and Future at 1900

Tetsumori Yamashima

Highlights on Medicine and Medical Research Vol. 10, 11 May 2021, Page 137-165

Adrenal gland was first described by the Italian anatomist Eustachio in 1564, but its physiologic role remained unknown for three centuries. Even after the report of Addison’s disease in 1855, nobody knew its function. Oliver and Schäfer first discovered the blood pressure-raising property of adrenal extracts in 1894. Accordingly, in the late 1890’s, highly motivated scientists had directed their attention to isolate active principle for the therapeutic utilization, but all failed. For instance, Abel’s preparation ‘epinephrine’ was an inactive benzoylated derivative. In August 5, 1900 the Japanese industrial chemist Takamine and his young associate Uenaka settled in New York, succeeded to crystallize the adrenal extract by a procedure different from any yet employed. The active principle was isolated in the vacuum pan, crystallized with ammonia, and confirmed by the Vulpian reaction. ‘Uenaka’s Experimental Memorandum’ describes that the novel crystal was coined ‘adrenalin’ (no “e”) on November 7, 1900. Simultaneously, Takamine applied the US patent which was approved on June 2, 1903, and Parke, Davis & Company trademarked the name ‘Adrenalin’ to market worldwide. As a hemostatic during surgery and for treating heart failure, adrenaline has saved numerous lives. There are historical, etymological and practical justifications for using the term ‘adrenaline’.

Commentary on Maternal and Perinatal Mortality in Nigeria: Establishment of Obstetric Waiting Units and Targeting Uterine Rupture

S. F. Eli, D. S. Abam, D. G. B. Kalio, J. Ikimalo

Highlights on Medicine and Medical Research Vol. 10, 11 May 2021, Page 166-170

Transportation is a challenge to women especially in rural settings where there are little or no means of transportation or access to health facilities where basic obstetric care could be given; hence, patients with ruptured uterus may end up losing both their babies and their lives. Government, non-governmental organizations, religious groups, community heads, multinationals, international organizations must support the crusade in averting maternal and perinatal mortality by reducing risk factors of ruptured uterus.