Репозиторий Университета

Copyright © 2018 Institute of Computer Science. The paper proposes a mathematical model for the therapy of glioma, taking into account the blood-brain barrier, radiotherapy and antibody therapy. The parameters were estimated from experimental data and the evaluation of the effect of parameter values on the effectiveness of treatment and the prognosis of the disease were obtained. The possible variants of sequential use of radiotherapy and the effect of antibodies have been explored. The combined use of radiotherapy with intravenous administration of mab Cx43 leads to a potentiation of the therapeutic effect in glioma. Radiotherapy must precede chemotherapy, as radio exposure reduces the barrier function of endothelial cells. Endothelial cells of the brain vessels fit tightly to each other. Between their walls are formed so-called tight contacts, whose role in the provision of BBB is that they prevent the penetration into the brain tissue of various undesirable substances from the bloodstream. Dense contacts between endothelial cells block the intercellular passive transport. The mathematical model consists of a continuous part and a discrete one. Experimental data on the volume of glioma show the following interesting dynamics: after cessation of radio exposure, tumor growth does not resume immediately, but there is some time interval during which glioma does not grow. Glioma cells are divided into two groups. The first group is living cells that divide as fast as possible. The second group is cells affected by radiation. As a measure of the health of the blood-brain barrier system, the ratios of the number of BBB cells at the current moment to the number of cells at rest, that is, on average healthy state, are chosen. The continuous part of the model includes a description of the division of both types of glioma cells, the recovery of BBB cells, and the dynamics of the drug. Reducing the number of well-functioning BBB cells facilitates the penetration of the drug to brain cells, that is, enhances the action of the drug. At the same time, the rate of division of glioma cells does not increase, since it is limited not by the deficiency of nutrients available to cells, but by the internal mechanisms of the cell. The discrete part of the mathematical model includes the operator of radio interaction, which is applied to the indicator of BBB and to glial cells. Within the framework of the mathematical model of treatment of a cancer tumor (glioma), the problem of optimal control with phase constraints is solved. The patient's condition is described by two variables: the volume of the tumor and the condition of the BBB. The phase constraints delineate a certain area in the space of these indicators, which we call the survival area. Our task is to find such treatment strategies that minimize the time of treatment, maximize the patient's rest time, and at the same time allow state indicators not to exceed the permitted limits. Since the task of survival is to maximize the patient's lifespan, it is precisely such treatment strategies that return the indicators to their original position (and we see periodic trajectories on the graphs). Periodic trajectories indicate that the deadly disease is translated into a chronic one.

© 2018 Media Sphera Publishing Group. All Rights Reserved. Surgical treatment of posterior cranial fossa and cerebellopontine angle tumors is associated with a risk of facial nerve dysfunction. The causes for facial muscle paresis include nerve compression by the tumor, destruction of the nerve structure by the tumor growing from nerve fibers, nerve injury during surgical removal of the tumor, etc. The first 3 months after facial nerve injury are a potential therapeutic window for the use of botulinum toxin type A (BTA). During this period, the drug is introduced both in the healthy side to improve the facial symmetry at rest and during mimetic movements and in the affected side to induce drug-induced ptosis. Post-paralytic syndrome develops 4-6 months after facial nerve injury. At this stage, administration of BTA is also an effective procedure; in this case, drug injections are performed on the affected side at small doses and symmetrically on the healthy side at doses doubling those for the affected side. BTA injections are mandatory in complex treatment of facial muscle paralysis.

© 2018 Russian Academy of Medical Sciences. All rights reserved. Phospholipase D (PLD) is one of the key enzymes that catalyzes the hydrolysis of cell membrane phospholipids. In this review current knowledge about six human PLD isoforms, their structure and role in physiological and pathological processes is summarized. Comparative analysis of PLD isoforms structure is presented. The mechanism of the hydrolysis and transphosphatidylation performed by PLD is described. The PLD1 and PLD2 role in the pathogenesis of some cancer, infectious, thrombotic and neurodegenerative diseases is analyzed. The prospects of PLD isoform-selective inhibitors development are shown in the context of the clinical usage and the already-existing inhibitors are characterized. Moreover, the formation of phosphatidylethanol (PEth), the alcohol abuse biomarker, as the result of PLD-catalyzed phospholipid transphosphatidylation is considered.

© 2018 Vitebsk State Medical University. All rights reserved. This clinical case demonstrates the development of severe streptococcal (Streptococcus pyogenes) necrotizing soft tissue infection as a result of perforation of the sigmoid neoplasm. The rapidly progressive necrotic process in the soft tissues of the lumbar and gluteal region as well as necrotic process in the left thigh (with the predominant lesion of the superficial fascia, subcutaneous fat and skin) led to the formation of an extensive postnecrectomic wound defect with an area of more than 1000 square centimeters. In addition to the severity of illness, the patient's belated treatment and the underestimation of the clinical situation by surgeons who provided emergency care contributed to such an extensive spread of the pathological process. The development of sepsis was accompanied by severe multiple organ failure. Because of the severity of the patient's condition, the surgical removal of the sigmoid neoplasm extended in the abdomen wall became possible only after its stabilization as a result of surgical focal sanation and complex intensive therapy in the conditions of the ICU. The most important point of the stage-by-stage surgical treatment was the choice of methods for the plastic closure of an extensive postnecrectomic wound that involved the entire left gluteal region, part of the lumbar and antero-inner surface of the left thigh. Taking into account the size and localization of the defect, the plastic reserves of the surrounding skin, the wound was closed in three stages with the help of combined plastic surgery techniques: with local tissues by the method of tissue expansion and a split-thickness skin graft.

© 2018 Vitebsk State Medical University. All rights reserved. Objective: To study the ultrastructural changes in the liver mitochondria in experimental diffuse purulent peritonitis against the background of the metabolic support. Methods: The morphometric evaluation of the rabbit liver mitochondria electron microscopic images (n=55) was performed in experimental diffuse purulent peritonitis. The obtained electron diffraction patterns were estimated using the ImageJ 1.45s program, in which the number of mitochondria sections, the number of intermithochondrial contacts and the number of damaged and intact mitochondria were counted. The average area, perimeter, and specific volume (measured in %) were calculated for the undamaged mitochondrial profiles. Metabolic agents with energotropic properties, phosphocreatine preparations containing creatine phosphate and preparations containing the succinic acid, niacinamide, inosine diphosphate and riboflavin were used. Results: Electron microscopic analysis of mitochondria of hepatocytes made it possible to reveal significant changes in their structure, caused by the development of purulent peritonitis. Morphometric evaluation of electron diffraction patterns showed changes in the quantitative and qualitative characteristics of mitochondria: the ratio of the damaged and intact mitochondria, their size, perimeter and specific volume of all groups. The use of metabolic support permitted to reduce the negative effect of purulent peritonitis in the postoperative period, which is exerted on the liver mitochondria, in comparison with the control group of animals that did not receive any metabolic support. Conducting a comparative analysis revealed a higher efficacy of the metabolic agent containing the succinic acid, niacinamide, inosine diphosphate and riboflavin, which resulted in more intensive restoration of the mitochondrial membrane structure. Conclusions: The development of purulent peritonitis is accompanied by a violation of the ultrastructural organization of the liver mitochondria in all studied groups. Metabolic correction allows restoring the membrane structure of mitochondria, and as the result improving the energy supply of cells to combat the negative consequences of endotoxicosis in peritonitis.

© 2018 Vitebsk State Medical University. All rights reserved. Objective: To study the functional activity and cytoarchitectonics of neutrophilic granulocytes by the atomic force microscopy technique in the patients with mechanical jaundice of benign genesis of varying severity. Methods: The subject of the study were 92 patients aged from 47 to 69 years undergoing the in-patient treatment in the surgical departments of medical institutions in Krasnoyarsk with the diagnosis of mechanical jaundice of benign genesis. The control group consisted of 60 donors, comparable in sex and age with the main group. Depending on the severity of mechanical jaundice, luminol-dependent chemiluminescence of neutrophils was investigated and atomic-force microscopy of neurophilic granulocytes was performed to determine the shape, membrane state, geometric dimensions and adhesion forces of the blood neutrophils. Results: In patients with mechanical jaundice, the intensity of spontaneous chemiluminescence depends on the severity of mechanical jaundice. The kinetics of the chemiluminescent response of the peripheral blood neutrophils indicates an increase in the compensatory functional capacity of this cell population in case of mild degree of mechanical jaundice severity with their depletion in parallel with the increase in the severity of mechanical jaundice. Atomic force microscopy revealed violations of the structural organization of the neutrophil granulocyte. With increasing severity of mechanical jaundice, neutrophil became convex in shape, the number of segments of the nucleus increased, the cell membrane became irregular, the neutrophil volume reached 62.20 + 5.94 m3. The magnitude of the adhesion forces of neutrophils decreased by 25% in patients with class B severity of mechanical jaundice and by 31% with class C severity of mechanical jaundice. Conclusions: Based on the analysis of the chemiluminescent activity of neutrophilic granulocytes and their cytoarchitectonics, we concluded that the functional capabilities of neutrophilic granulocytes in mechanical jaundice are depleted in parallel with the increase in the severity of mechanical jaundice. Dysfunctions of neutrophils in mechanical jaundice are caused by the change in its cytoarchitectonics and by the decrease in adhesion forces.

© Rational Pharmacotherapy in Cardiology 2018. The immediate and remote benefits of smoking cessation are considered. Within one year after quitting smoking the ischemic heart disease (IHD) risk will be 2 folds lower than the risk in smoking patient. Within 15 years the IHD risk declines to non-smoking population level. After 5-15 years after quitting smoking the risk of stroke also declines to non-smoker risk. Smoking cessation prior to cardio surgical intervention leads to reduction of complications incidence by 41%. Smoking cessation significantly reduces the risk of developing stable and unstable angina, acute myocardial infarction, cardiovascular death, transient ischemic attack, ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, peripheral arterial diseases, abdominal aortic aneurysm at any age, in both sexes in comparison to patients who continue to smoke. Smoking cessation is the most cost-effective strategy of cardiovascular disease prevention. Today, the most effective smoking cessation strategy is the identification of smokers and continuous advice on smoking cessation, and offer of the appropriate medication, primarily varenicline. The article contains data from a number of studies showing that varenicline is an effective and safe drug for tobacco dependence treatment, in particular, in patients with acute and chronic cardiovascular disease.

© Rational Pharmacotherapy in Cardiology 2018. Background. Carriership of CYP4F2*3 (rs2108622, Val433Met) allelic variant can affect antiplatelet effect of clopidogrel, thus changing efficacy and safety of its standard dose. Aim. To study the impact of carriership of at least one CYP4F2*3 allele on the risk of resistance to clopidogrel in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). Material and methods. The study enrolled 81 patients with ACS and PCI: 64 males and 17 females, mean age 63.9±10.9 years. CYP4F2 allelic variants were detected by the method of real-time polymerase chain reaction. Platelet functional activity was evaluated by a portative aggregometer - the VerifyNow P2Y12 assay. Results. Pharmacogenetic testing showed that 40 (49.4%) of ACS patients had normal genotype (CC), 38 (46.9%) patients were carriers of one associated with reduced drug metabolism allele (CT genotype), and 3 (3.7%) patients were homozygotes for T (TT genotype). Genotype and allele distribution was in the Hardy-Weinberg equilibrium (χ2=2.79; p=0.095). There were no statistically significant differences in CYP4F2*3 allele frequency between patients that are resistant to clopidogrel (PRU > 208) and in patients with a normal response to clopidogrel (PRU < 208): 36.8% vs 54.8% (p=0.17). Average platelet reactivity units (PRU) and average platelet inhibition (%) in patients with and without T allelic variant of CYP4F2 also were not significantly different: 165.34±51.03 PRU vs 174.8±51.06 PRU (p=0.407), respectively, and 29.51±21.59% vs 27.72±18.35%, respectively (p=0.69). Conclusion. Carriership of CYP4F2*3 allelic variant does not affect antiplatelet effect of clopidogrel in ACS patients. Further research on larger samples is needed to determine the role of CYP4F2 polymorphisms in personalization of clopidogrel antiplatelet therapy.

© Rational Pharmacotherapy in Cardiology 2018. Aim. To study serum level of leptin in patients with the metabolic syndrome (MS), including in patients with MS in combination with left ventricular hypertrophy (LVH) to determine the diagnostic significance of this marker in MS. Material and methods. The study involved 43 patients with MS, 33 of them with signs of LVH, and 33 patients without MS comparable age, including 10 patients with LVH. The average age of patients in the MS group at the time of inclusion into the study was 62.7±10.3 years, in the control group (without MS) - 60±14.7 years. All patients underwent a comprehensive examination that included the collection of complaints, study of history, physical examination, anthropometric measurements, laboratory and instrumental examination, including study of the serum level of leptin. Results. Patients of both groups had statistically significant differences in the size of the heart chambers, the presence of LVH signs, left ventricle contractile function, the thickness of the epicardial fat layer. Thus, enlargement of the heart, thickness of the interventricular septum, posterior wall of the left ventricle, thickness of epicardial fat, reduction of ejection fraction of the left ventricle and characteristics of aortic atherosclerosis were observed significantly more often in patients with MS compared with the group without MS (p < 0.05).The average serum level of leptin in the MS group (41.89±33.28 ng/ml) was significantly higher compared to the group without MS (17.64±16.87 ng/ml), p < 0.001. At that women had significantly higher levels of serum leptin (38.65±29.23 ng/ml) compared to males (19.54±27.23 ng/ml), p=0.006. A positive correlation between leptin levels and symptoms of LVH (r=0.294, p < 0.001) was revealed: in the absence of LVH average level of leptin was 21.7±4.1 ng/ml, in the presence of signs of LVH - 39.2±4.95 ng/ml. Conclusions. Leptin levels in MS patients is higher than in patients without MS, and in patients with MS associated with LVH is higher than in MS patients without LVH. As the leptin level increases, the risk of LVH increases.

© 2017, Morozov D.A., Pimenova E.S., Tarasova D.S., Yakovenko D.D., © 2017, Russian Open Medical Journal. 6-year-old girl with first revealed anorectal malformation with perineal fistula was investigate. She did not have any complaints or history of constipation/soiling. Resting and squeeze anal pressure by anorectal manometry was normal. Recto-anal inhibitory reflex registered. There was no signs of dyssynergic defecation. The diameter of the colon by contrast enema was normal, megarectum did not detect, barium all came out after defecation. Muscles electro-identification confirmed external anal sphincter located posterior to the anus. After examination, council for Pediatric Surgery decided not to perform the surgery. Monitoring of the patient continued.

C1q glomerulopathy is a rare variety of chronic glomerulonephritis manifested as C1q deposition revealed by immunofluorescence microscopy. The pathogenesis and etiology of the disease have not been studied. The paper deals with the results of clinical, morphological, immunofluorescence, and electron microscopic examinations in 13 patients with C1q glomerulopathy. Light microscopy more commonly revealed membranous nephropathy, mesangioproliferative glomerulonephritis, and nephrosclerosis. Immunofluorescence microscopy detected a C1q fraction in association with other deposits, more frequently IgM and IgG ones. A correlation was found between the clinical presentation and morphological form of chronic glomerulonephritis.

© 2018 Media Sphera Publishing Group. All rights reserved. The objective of the present study was to elucidate the peculiar morphological features of the blood stains on the snow over of different density. We have undertaken the modeling and investigation of the blood stains on the loose snow cover (ρ=0.35±0.03 g/cm3) and at the areas of snow compacted by a motor-vehicle wheel (ρ=0.96±0.03 g/cm3) with the use of the visual, metric, descriptive, and statistical methods. The analysis of the blood stain patterns on the loose snow showed that a blood drop tends to form a depressed cylindrical canal at the bottom of which an irregularly shaped spherical element can be seen; it is composed of small snow crystals soaked with blood. The upper end of the canal has the fine-scalloped edge tending to shed unevenly. The morphological picture of the blood stains at the compacted snow cover is similar to that on the hard wettable rough surfaces; they have the oval shape and the unevenly serrated edge with the well apparent signs of sputtering.at the periphery.

to investigate the myocardial expression of some structural proteins and markers of cellular proliferation and innate immunity for assessing their possible diagnostic and prognostic role in patients with chronic myocarditis. Subjects and methods. The investigation enrolled 23 patients (16 men; mean age, 52.0±12.4 years (range, 27 to 73) with various forms of noncoronarogenic myocardial injury who underwent right ventricular endomyocardial biopsy (n=4), intraoperative left ventricular biopsy (n=17) or autopsy (n=2). Prior to their morphological examination, the patients were divided into two groups: 1) 10 patients with dilated cardiomyopathy and presumptive myocarditis; 2) 13 patients with valvular heart disease, hypertrophic cardiomyopathy, myxoma, and chronic pulmonary thromboembolism, presumptively without myocarditis. Along with myocardial histological and immunohistochemical (IHC) examinations, the expression of vimentin, desmin, c-kit, Ki-67, and Toll-like receptors (TLR) 2 and 9 was determined. Polymerase chain reaction was used to identify whether herpes viruses of and parvovirus B19 genomes were present in the blood and myocardial samples; indirect ELISA was applied to estimate the blood level of antibodies against various cardiac antigens. Results. According to the histological findings, active/borderline lymphocytic myocarditis was diagnosed in all the patients (Group 1) and in 6 patients (Group 2) in conjunction with the underlying disease (only in 9 and 7 patients, respectively), viral genome was detected in the myocardium of 15 patients, including in 5 without morphological signs of myocarditis (parvovirus B19 (n=11), herpesvirus 6 (n=4), herpes simplex virus types 1 and 2 (n=1), Epstein-Barr virus (n=2), and cytomegalovirus (n=1)), and in the blood (n=4). A marked correlation was found between TLR2 and TLR9 expressions and the morphological pattern of active myocarditis in the absence of this correlation with the expression level of other studied markers. The expression level of TLR2 in patients with and without borderline myocarditis was 0 [0; 0,75] and in those with active myocarditis was 1.5 [1; 1,5] points; that of TLR9 was 2 [2; 2] and 4 [3; 4] points, respectively (p0.001). The expression of TLR2 and TLR9 in patients with borderline myocarditis was lower than in those without myocarditis (0 [0; 0] versus 0 [0; 1] and 2 [1,5; 2] versus 2 [2; 3] points), which can reflect cardiomyocyte destruction/depletion at later stages of the disease. There was also a close correlation between the expression level of TLR2 and that of TLR9 (r=0.824; p0.001) and with Ki-67 levels (r=-0.531 and r=-0.702; p0.01). There was also a correlation of the expression of the studied markers with viral persistence (desmin), the degree of myocardial dysfunction and cardiosclerosis (c-kit), which calls for further investigations. Conclusion. Determination of the myocardial expression level of TLR2 and TLR9 may serve as an immunohistochemical marker for myocarditis and preservation of its activity, which is especially valuable in patients with borderline forms. The marked expression of these markers for innate immunity may reflect both one of the mechanisms of genetic predisposition to myocarditis and its severe course and their secondary activation in the pathogenesis of the disease and is a potential target of therapy.

Scleromyxedema is regarded as a rare cutaneous mucinosis from a group of lichen myxedematosus characterized by diffuse mucin deposition, sclerosis, and lichenoid eruptions in the absence of thyroid disease. The paper discusses the pathogenesis of the disease and histological changes in tissues. It underlines the need for using histochemical tests to identify acidic and neutral glycosaminoglycans and gives a differential diagnosis of this disease.

© 2018 Media Sphera Publishing Group. All rights reserved. The objective of the present study was to elucidate the specific morphological features of the imprints of blood-soaked straight and wavy head hair. The contact imprints of straight and wavy head hair dirtied with blood were obtained experimentally. The imprints of straight hair were shown to exhibit the elements in the form of the rectilinear and bow-shaped slightly bent stripes. The imprints of wavy hair were shaped as the arches, waves, circles, and a large number of various small elements, such as dashes and commas.

© 2018 Media Sphera Publishing Group. All rights reserved. Russia joined the Bologna process in 2003 and since that time has become integrated into the unified European educational space. The key element of the new form of the higher education process is the self-guided unsupervised work of the students. Motivation is needed to promote the involvement of the students in the educational process which implies the necessity of the goal-oriented initiative for the acquisition of professional knowledge and practical experience in the field of forensic medicine. To achieve this goal, the Department of Forensic Medicine of I.M. Sechenov First Moscow State Medical University places special emphasis on the experience with carrying out student competitions. Each such competition consists of several contests focused on the solution of a specific problem, e.g. the inspection of the place of occurrence under investigation with a gunshot or punctured-and-incised wound, forensic medical autopsy, problem studies, and intelligence tests. All the contests and problem studies are held in the form of an interactive game. The experience gained in the course of the student competitions gives practical evidence that the interdepartmental intelligence contests contribute to raising the interest of students in forensic medicine. The open competition provides a highly efficient tool for the popularization of scientific knowledge and the promotion of interest in the participation in the forensic medical research activities. Moreover, the student competitions facilitate formation of the earlier professional skills indispensable for team working and the development of abilities for making decisions under the extreme conditions. In addition, the contests teach the participants the art of public appearance. They improve the quality of vocational training in forensic medicine and help to establish the first professional contacts at the interinstitutional (including international) level.

© 2018 Media Sphera Publishing Group. All rights reserved. The present article was designed to summarize the results of the 20 year scientific, practical, and educational activities of the Department of Forensic Medicine, I.M. Sechenov First Moscow State Medical University (Sechenovsky University). The main directions of the research work and achievements of the Department's staff are described, and the prospects for its further development are highlighted. The new approaches to and technologies for the teaching and training specialists in forensic medicine are introduced to meet the novel requirements imposed in the framework of the ongoing reform of higher medical education in accordance with the main principles of the Bologna declaration.

© 2018 Media Sphera Publishing Group. All rights reserved. The objective of the present study was the development of the diagnostic model for determining the human age based on the results of the comprehensive examination of the 230 thyroid cartilages (TC) obtained from the corpses of men and women of different age. TC were examined with the use of the anthropometric, X-ray, and histological methods. The anthropometric investigations confirmed the gender-related differences in the structure of human TC. Various characteristics of TC were shown to correlate with the age but these relationships were rather weak even if formally significant. The X-ray studies of TC have revealed the significant correlation of the relative amount of the bone tissue on the images with the age (r=0.8). Of the 27 parameters subjected to the morphometric evaluation, the following ones were shown to significantly correlates with the age: percentage of the bony (r=0,82) and cartilaginous (r=-0.8) tissue areas, average density of the adipose (r=0.76) and reticular (r=0.7) tissues, the maximum length of trabeculae (r=0.67), the width of the mature cartilage zone (r=0.54), the cortical plate thickness (r=0.5), and the mean number of immature chondrocytes in the field of vision (r=0.5). The comprehensive investigation into the structure of the human thyroid cartilage provided a basis for the development of the method for determining the human age with the use of the linear regression equations. It is concluded that the proposed method can be employed as an additional diagnostic tool for determining the human age for the purposes of forensic medical expertise and personality identification.

© 2018 Media Sphera Publishing Group. All rights reserved. The objective of the present study was to evaluate the possibilities for the use of the changes in the AgNOR staining patterns in the neurons of the dorsal raphe nucleus (DRN) for the purposes of the medical differential diagnostics of the cases of death from chronic alcohol intoxication. We elucidated the characteristics of the activity of protein biosynthesis including the number and the area of the nucleoli in the nuclei of the neurons of the individuals who had died from chronic alcohol intoxication (n=20) in comparison with the subjects of the control group (n=13). To reveal the morphological structures associated with protein biosynthesis in the nucleoli of the serotoninergic neurons of the dorsal raphe nucleus in the brain, the histological preparations were stained with the use of the silver-staining technique for nucleolar organizer regions (AgNOR). The comparative statistical analysis of the results thus obtained with the calculated confidence coefficients was carried out. The aggregated analysis of all the dorsal raphe subnuclei revealed the impairment of the AgNOR staining characteristics in the neurons of the subjects who had died from chronic alcohol intoxication in comparison with those of the subjects comprising the control group. It is concluded that the results of the study can be used for differential diagnostics of deaths from chronic alcohol intoxication and other causes.

© Bionika Media Ltd. Objective. To systematize the current medical knowledge and experience in the management of pregnancy and delivery in patients with mesenchymal dysplasias (Marfan syndrome, Ehlers-Danlos syndrome, Rendu-Osler syndrome). Material and methods. The paper includes the data of foreign investigations and medical guidelines for this problem, which have been published in the past 5 years. Results. The paper describes the molecular bases of each syndrome, diagnostic criteria, and their clinical manifestations in various organs and systems: musculoskeletal and cardiovascular systems, the organ of vision, etc. Such patients during pregnancy are at extremely high risk for life-threatening complications. Conclusion. A successful outcome of pregnancy requires early diagnosis and a multidisciplinary approach throughout during pregnancy and delivery.