Shiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071632420071201Independent Effect of Digoxin in Preventing Atrial Fibrillation in High Risk Patients after CABG Surgery19319739955ENM.H.NematiM.EskandariJournal Article20150525Background: Atrial fibrillation (AF) is one of the most common arrhythmias after coronary artery bypass graft (CABG) surgery. AF can result in hemodynamic instability, thromboembolic events, increase the perioperative myocardial infarction, congestive heart failure, stroke, more length of hospital stay (LOHS) and cost of treatment. The aim of this study was to evaluate the independent effect of digoxin in preventing AF after CABG in patients who had a predictor for AF and had already been on other anti-arrhythmic drugs. Methods: In a prospective randomized clinical trail, using alternate randomization, 239 patients categorized into three different groups. Group one consisted of 72 patients who had at least one predictor for developing AF after CABG. Group two consisted of 67 patients with the same predictors who received 0.5 mg intravenous digoxin after disconnecting from bypass pump followed by 0.25 mg intravenous digoxin one hour and four hours later. Oral daily digoxin (0.25 mg) was continued from the first post operation day to the 14th day with 2 days off per week. One hundred patients without those predictors for AF were randomly allocated in group three to confirm the impact of those predictors on developing AF. Results: AF occurred in 16 patients (22.2%) in group 1, six patients (8.8%) in group 2, and seven patients (7%) in group 3. The duration of AF was 6.43±4.23 min in group 1, 1.2±1.41min in group 2, and 47.18±67.29 min in group 3. Conclusion: Intraoperative digoxin can independently decrease the incidence of AF after CABG surgery in patients with high risk factors for AF.https://ijms.sums.ac.ir/article_39955_54b9140327de3a7599b0f9afc98b46b1.pdfShiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071632420071201Detection of Helicobacter Pylori Diagnostic Antigens in the Stool of Infected Patients19820439960ENAliSheikhianM.Hassan ZuhairA.MostafaieJournal Article20150525Background: Some antigens of H. pylori are excreted into the stool of infected people. These antigens can be used to detect the infection by immunoassays such as ELISA. Our aim was to identify these antigens by immunoblotting and affinity chromatography techniques. Methods: Four different antigenic preparations, namely, whole cell sonicate (WCS), outer membrane proteins (OMPs), cytoplasmic antigens (CAs) and cell surface-associated antigens (CSAAs) were obtained from H. pylori. Rabbit antiserum against these preparations was used to detect them in fecal antigenic extracts (FAEs) of infected patients. Results: By immunoblotting, we were able to detect a 26 kDa band in the positive stool samples. Anti-OMPs acted more specifically, so, it was used to isolate the Helicobacter pylori diagnostic antigens (HpDAs) from the stool. More antigens (at least 4 antigens with the molecular weights of about 14, 26, 55 and 57 kDa) were isolated by affinity chromatography. But, the 26 kDa antigen had a higher concentration and was seen in almost all positive samples. Conclusion: Since the 26 kDa antigen is detectable by these two techniques in all positive samples, we are confident that this antigen is one of the major antigens of H. pylori, which is released into the stool and can be considered as a candidate diagnostic antigen to be used in diagnostic kit development.https://ijms.sums.ac.ir/article_39960_84ae39f317f4fce9d36fdbe13b13eeae.pdfShiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071632420071201Accuracy of Impulse Oscillometry in Airway Dysfunction20521039962ENMostafaGhaneiF.DarvishzadehF.AlaeddiniI.AdibiJ.AslaniJournal Article20150525Background: The purpose of this study was to calculate and compare the specificity and sensitivity of impulse oscillometry (IOS) as a new technique in the detection of airways dysfunction by means of a simple pulmonary function test in chemical warfare injured cases suffering from respiratory diseases. Methods: The study was performed prospectively in 100 patients, who complained of dyspnea as a result of sulfur mustard gas exposure in the Iran-Iraq war, between 1981 and 1988. Following a physical examination, IOS and spirometery were performed for all the patients. Then, the specificity and sensitivity of IOS parameters were calculated and compared with those of spirometery. Results: With a routine cut-off point, R at 5Hz and R at 20Hz have a sensitivity and specificity of 48.9%, 70.4% and 40.0% and 85.2%, respectively. With a normal cut-off point of R at5Hz=-0.20 kpal/l/s, there is a 100% specificity (PPV=100%). Conclusion: While IOS is a new, cooperation independent technique and specific in the detection of airways dysfunction, it is less sensitive than spirometery in spotting small airways obstructions. IOS is a good diagnostic method in the detection of pulmonary involvements in uncooperative patients.https://ijms.sums.ac.ir/article_39962_1c08d420a132f633a8dc6f6bb72db6fb.pdfShiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071632420071201Status of Measles Elimination from the Reported Outbreaks: Fars Province, 2001–0321121639964ENG.A.ParhamJournal Article20150525Background: The status of measles elimination is best summarized by evaluation of the effective reproduction number R; maintaining R < 1 is necessary and sufficient to achieve elimination. In the present article, we estimated reproduction number for the measles data reported for the Fars province of Iran in 2001–03. Methods: We estimated by using sizes and durations of chains of measles transmission and the proportion of cases imported, when offspring distribution is either Poisson or geometric. In each case, we calculated the profile 95% confidence intervals. These comprised 575 cases, forming 191 chains of transmission, of which 79 had > 1 case. 128 cases were classified as importations. Results: The results using the Poisson and geometric distribution for offspring and the proportion of cases imported differed slightly, but all 3 methods gave an < 1. The results were not sensitive to the minimum size and duration of outbreak considered, as long as single-case chains were excluded, or to exclusion of chains without a known important source. Conclusion: These results demonstrated that susceptibility to measles was beneath the epidemic threshold and that endemic transmission was eliminated.https://ijms.sums.ac.ir/article_39964_83dd2d1927110ce9278922c309c85565.pdfShiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071632420071201Immediate Diagnosis of Early Onset Sepsis in Premature Newborns by Measurement of Cord C-Reactive Protein and Interleukin-621722139966ENM.M.GharehbaghiG.A.MaamuriA.PeirovifarH.BoskabadiJ.T.AfshariM.T.ShakeriJournal Article20150525Background: The purpose of this study was to determine the relationship between early onset sepsis and increased levels of C-reactive protein (CRP) and interleukin-6 (IL-6) in cord plasma. Methods: A prospective study was conducted in 141 premature infants delivered with gestational ages of 26-35 weeks. IL-6 and CPR were measured by enzyme-linked immunoassay in the cord plasma of the neonates. According to clinical, laboratory findings and blood culture results, newborn infants were allocated into four groups (A-D): documented early onset infection, clinical sepsis, possible infection, and control groups respectively. Results: Mean IL-6 levels in group A-D was 264, 212, 160, and 33.3 pg/ml respectively. Difference between groups was statistically significant (p=.002). With cut off point of 18 pg/ml, the sensitivity and specificity of IL-6 for diagnosis of early onset sepsis was 72% and 55% respectively. There was not significant difference between mean levels of CRP among groups (p=0.28). Conclusion: Having considered the relatively good sensitivity and moderate specificity of cord IL-6, using this test can be recommended as a useful detector of early onset sepsis and non-infected sick neonates.https://ijms.sums.ac.ir/article_39966_e6dd69a011bb1ea08598de99e8af7031.pdfShiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071632420071201The Effect of Hydroalcoholic Extract of Olive Leaves against Herpes Simplex Virus Type 122222639967ENM.MotamedifarA.A.NekooeianA.MoatariJournal Article20150525Background: It was shown that olive leave extract has antifungal, antibacterial and antiviral activities. The effects of OLE on herpes simplex virus-1 (HSV-1) have not been systematically investigated yet. The aim of this study was to examine the in vitro effect of olive leaf hydroalcoholic extract (OLHE) on HSV-1. Methods: Virucidal effect and viral replication in Vero cell line were studied in the presence of various concentrations of OLHE applied at different time intervals using a standard plaque assay method. The 50% cytotoxic concentration (CC50), 50% inhibitory concentration (IC50), and therapeutic index of OLHE were determined. Results: OLHE showed virucidal effect on HSV-1 in concentrations >1 mg/mL. The CC50 of OLHE for Vero cells and IC50 were 1.75 and 0.66 mg/mL, respectively. When applied to cell culture infected with the HSV-1, one hour earlier, OLHE showed no antiviral activities. When applied to the cells followed by the virus infection one hour later, or to the media containing the virus and the combination was added to cell culture one hour later, OLHE showed anti-HSV-1 activities at concentrations >1 mg/mL. Conclusion: OLHE has anti-HSV-1 activity likely due to the prevention of virus entry into the cells.https://ijms.sums.ac.ir/article_39967_166ee0bda401238eff59cf74812476fd.pdfShiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071632420071201The Effect of Verapamil Administred before the Reperfusion Insult in Isolated Preconditioned Rat Heart on the Microsomal ATPase and Mitochondrial Enzyme Activities22723339968ENGino A.KurianJ.PaddikkalaJournal Article20150525Background: Calcium overload and free radical mediated damage in the mitochondria is the most important pathological changes associated with myocardial ischemic-reperfusion injury. The verapamil post-treatment has been previously reported to prevent reperfusion-induced myocardial injury but functional recovery may be delayed due to the drug's inherent direct myocardial depression effect. In the present study the effect of verapamil on mitochondrial enzymes and sarcoplasmic ATPase system was examined during the myocardial preconditioning and ischemic reperfusion in rat heart. Methods: Four groups of isolated rat hearts were perfused with KH buffer in a retrograde manner by Lagendroff apparatus. A time controlled ischemia, ischemic reperfusion and classical precondition was produced by restoring the flow of KH buffer in ischemic rat heart. The hearts were then processed to isolate the mitochondria and sarcoplasmic reticulum for the biochemical estimation. Results: Mitochondrial enzyme and sarcoplasmic ATPase activities were diminished in the ischemic period and further decreased during reperfusion. However, preconditioning the rat heart before the insult of ischemia and reperfusion improved the enzyme activities. The preconditioning procedure consisted of 4 cycles of 4 min. short ischemic periods followed by 4 min. KH buffer perfusion applied before 30 min. global ischemia and reperfusion caused an improvement in the mitochondrial enzyme activities. On the other hand, sarcoplasmic ATPase enzymes required a precondition procedure of 7 cycles of 2 min. short ischemic periods followed by 2 min. reperfusion. The activities of the above enzymes were improved further when verapamil was administered before the insult of ischemic reperfusion. Conclusion: This study shows the beneficial effect of classical preconditioning with verapamil.https://ijms.sums.ac.ir/article_39968_d1d7c9cfbd09ed03b81c2fe25f48cc0f.pdfShiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071632420071201Level of Hemoglobin F and Gg Gene Expression in Sickle Cell Disease and Their Association with Haplotype and XmnI Polymorphic Site in South of Iran23423939969ENZohrehRahimiDepartment of Clinical Biochemistry, Medical School, Daneshgah Avenue, Kermanshah, IranA.Vaisi-RayganiA.MeratM.HaghshenassM.RezaeiJournal Article20150525Background: Molecular genetic factors regulating hemoglobin F (Hb F) expression are important modifiers of the severity of sickle cell anemia (SS). Methods: The prevalence of XmnI polymorphic site, the Gg:Ag ratio and the Hb F level were determined using PCR-RFLP procedure, HPLC and alkaline denaturation method, respectively, in various haplotypes of 52 patients with SS, 18 patients with sickle/β-thalassemia (S/Thal), 17 with sickle cell trait (AS) and 53 normal subjects from Fars and Khuzestan provinces who attended the Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran during 2002–03. Results: The prevalence of XmnI (+/+) site in patients with SS was 53.8% which was higher than that for S/Thal (23.5%), AS (22.2%) and normal individuals (7.5%). There was a correlation between the presence of XmnI site and high Gg:Ag ratio in SS and S/Thal patients with Arab-Indian homozygous or heterozygous haplotypes (contingency coefficient=0.43, P=0.002). In the present study, the Hb F level was significantly higher in SS patients with one or two Arab-Indian haplotypes as compared to Bantu, Benin and Cameroon haplotypes. However, the Hb F level was significantly higher in patients with S/Thal having two XmnI sites carrying Arab-Indian and Senegal haplotypes as compared to Bantu, Benin and Cameroon haplotypes. The increasing effect of presence XmnI site on Hb F level appears only when hemolytic stress is present as in SS and S/Thal patients (contingency coefficient=0.35, P=0.01). Conclusion: The presence of XmnI polymorphic site in haplotype backgrounds of Arab-Indian and Senegal in sickle cell anemia is correlated with high level of Hb F and Gg:Ag ratio.https://ijms.sums.ac.ir/article_39969_a6023355cc48445fd9546a589610c1e7.pdfShiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071632420071201Monitoring of Airborne Fungi in Two General Hospitals in Shiraz, Southern Iran24024439956ENKeyvanPakshirG.ShekarkharS.MostagnieB.SabayanA.VaghefikiaJournal Article20150525Hospitalized patients have a potential risk for nosocomial infections. Airborne fungi are one of the main causes of fungal infections in this group. The objective of this study was to investigate the concentrations and species of airborne fungi in two general hospitals in Shiraz, southern Iran. Air samples were collected from high-risk wards, using settle plate method. Fungal colonies were identified, enumerated, and reported. A total of 1075 microbial colonies were detected, 419 of which were fungi. Fungal isolates from two hospitals, belonged to 15 genera. 4.25% of rooms in hospital A and 16% in hospital B were clean rooms. Cladosporium followed by Aspergillus spp were the predominant genus in two hospitals studied. The highest fungal deposition rates were 1016 and 1797 CFU/m2 in Emergency and Surgery rooms. Monitoring airborne fungi is one of the best ways for prevention and control of these infections. Caring for high-risk patients in hospital rooms has lead to reduced rates of nosocomial fungal infections.https://ijms.sums.ac.ir/article_39956_74a4ec4e805cdd21d7b57a195e92d0ab.pdfShiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071632420071201Actinomycetoma in a 60-Year-Old Woman for 20 Years24524739957ENA.Zarei MahmoudabadiR.YaghoobiJournal Article20150525Mycetoma is a chronic and pustular infection usually involves foot. Mycetoma in Iran is not common and most cases have been reported from the South and North of Iran. The objective of present study was to review the mycetoma and the distribution of its etiologic agents in Iran. Moreover, a 60-year-old woman with actinomycetoma lesions in her left foot was presented. Direct smear of the grains showed positive, non-acid fast and branching filaments of actinomycetes. Negative result was obtained from the cultures of grains.https://ijms.sums.ac.ir/article_39957_17bd1c2a644e965d62b5ba12248d951a.pdfShiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071632420071201Pulmonary Actinomycosis Mimicking Lung Cancer24825039961ENVahidMontazeriM.SokoutiA.FakhrjuJournal Article20150525Herein, we reported on a case of solid type of pulmonary actinomycosis in a 10-year-old boy. He had productive cough for 40 days. Bronchoscopy was normal. Cmputed tomography revealed a solid large mass in the upper lobe of his left lung with mimicking malignant leisions. He was referred for surgery and underwent left upper lobectomy. Macroscopically, the specimen measured 13×9×5 cm and was creamy to whitish on cut section. Microscopic findings included a large number of inflammatory cells and colonies of actinomyces. Pulmonary actinomycosis should be included in the differential diagnoses of pulmonary mass lesions, especially in the young adults.https://ijms.sums.ac.ir/article_39961_ef385517156f17c8759a8b87c0050b2f.pdfShiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071632420071201Blueberry Muffin Rash in a Patient with Hemolytic Disease of the Newborn Due to Anti-Cw25125339963ENMalilehKadivarH.SamaeeA.Arab HoseiniSh.NourbakhshJournal Article20150525Blueberry muffin rash is a characteristic multiple bluish skin nodules associated with perinatal infection, severe and chronic anemia, and neoplastic infiltrative diseases. We present an unusually severe case of hemolytic disease of the newborn. He required exchange transfusions for several times. The complete work up led to the diagnosis of anti-Cw. The skin lesion regressed spontaneously within one month.https://ijms.sums.ac.ir/article_39963_ec6cbb8f9c6d97d64587b47c8981a1c6.pdfShiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071632420071201Two Sewing Needles in the Brain: A Case Re-port25425539965ENHamidAshrafiR.BoostaniS.NazarbaghiJournal Article20150525Brain foreign bodies and penetrating missile injuries of the brain are familiar topics for Iranian physicians, especially after Iran and Iraq war. But it’s not easily plausible that there is a couple of sewing needles in the cranium of a patient who has not any history of head trauma or penetrating injury. The patient was a 42-year-old man who admitted in neurology ward of Mottahari Hospital in Urmia city with a complaint of headache. Brain computed tomography revealed some hyperdense foci with artifact shadows adjacent to them in frontoparietal region of the brain. Skull plain radiography indicated two sewing needles in his cranium. Probably these needles were inserted in cranial fossa at infancy when the fontanels were steel patent.https://ijms.sums.ac.ir/article_39965_7bbaddad2fcc0e18ee5ff698dd2e009f.pdfShiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071632420071201The Role of Mathematics on Human Structure25625739959ENSwapanKumar AdhikariJournal Article20150525This book explores the mathematical view of selected body systems and organs and as claimed by its author, “it has an objective to facilitate modern treatment with mathematical precision.”The author, Dr. Adhikari has PhD in mathematics and is the Head of the Institution and Department of Mathematics, Ghusuri Uchcha Madhyamic Vidyalaya, West Bengal, India. The motivation of the author in writing this book has been the mathematical views and ideas of Leonardo DaVinci and Rene Descartes on structural anatomy and physiological principles, respectively. He expects the physicians, medical surgeons and research workers to use his book in calculating physiological movements.The book comprises of 14 chapters, which shall be approached as follows: The first chapter is the preface and the second devotes to the introduction of Leonardo Da Vinci as the “anatomist of great ability.” The third chapter is devoted to “physiological concepts of Rene Descartes” on human physiology, followed by detailed mathematical explanation of his concept of pineal gland throughout the fourth chapter. The fifth chapter focuses on "the mechanism of movements of heart.” In this chapter, the author introduces the thermo-dynamical movement as the cause of contraction and expansion due to the variation of heat carried by blood into the heart. In the sixth chapter, the author expresses the causes of cervical and cartilage deformations on a mathematical basis. The traction weights for different injury levels are tabulated at the end of this chapter. Throughout the seventh chapter, he analyzes the structure and mechanism involving in the skeletal shoulder-joint and its efficiency through mathematical processes.The effectiveness of vertebral column, causes of secondary curvatures in skeleton and the application of forces of the upper part of body on different parts of pelvis and its distribution are explained briefly in the eighth and ninth chapters, again by mathematical deductions. In the tenth chapter, the author tries to find the applied forces on the femur and shows the related capacity of absorbing stress and strain by the shaft of femur due to its spiral or helical formations; the role of spiralic grains of lateral and medial condyles of femur on transition of body weight to the tibial condyles is discussed throughout the eleventh chapter. The twelfth chapter locates and represents the point of concentration of weight within the head of femur through the acetabulum and the next chapter expresses the structure of acetabular-joint and the mathematical deduction of the role of ligaments in different forms of movements of the femur at the hip-joint. The last chapter is just an alphabetical index to the pages of the previous chapters.The author expects physicians, medical surgeons and research workers to follow the precise mathematical deductions used to model the human anatomy and physiology in this book, while the least necessity was to have two introductory chapters explaining mathematical and biomechanical terms and principles. This book seems to be more suitable for biomechanical and rehabilitation engineers in obtaining initial ideas to model and design the implants. Pathologists and physiotherapists could also benefit from the book in realizing the cause of fractures and applying suitable treatment methods.Leonardo’s ideas stated in combined Latin and English phrases are confusing and useless in chapter 2. The utilized fonts, inappropriate capitalization and low tone illustrations need more attentions. Lengthy complimentary data and information in parenthesis could have been substituted by footnotes.It was expected that concepts of bioelectricity, especially those of ion movement across the cell membrane, the Hodgkin and Huxley formulas and the muscle contraction in defining the heart movement, be covered in chapter 5. The book also lacks the solution of appropriate selected numerical examples for the derived mathematical expressions which would result in a more practical advantage.But in all, the author has successfully correlated some body structures and physiological movements with mathematical deductions for an audience with a good command of mathematics throughout his book; although he does not furnish solved numerical examples quite enough. Rather than orthopedic surgeons, artificial organ designers could benefit from the derived formulas. It would be even more logical to summarize and replace long historical reviews by introductory chapters on principles of mathematics and biomechanics. At last, the book benefits “facilitating modern treatment with mathematical precision.” https://ijms.sums.ac.ir/article_39959_eb49cf8ae4bda933567b0f05510fca2c.pdfShiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071632420071201Behçet's Disease Long Time after Sulfur Mustard Poisoning25825939958ENAfshinBorhani HaghighiJournal Article20150525Dear Editor, A 35-year-old man presented with severe headache and left sided hemiparesis since one day prior to admission. He reported frequent bouts of oral and genital aphthous ulcers, an attack of deep venous thrombosis of left lower extremity, one episode of right knee arthritis, and several attacks of headache, neck rigidity, and fever. He had been a victim of mustard-gas poisoning at the time of Iran-Iraq war (14 years before). The symptoms of poisoning were tearing, photophobia, dyspnea, nausea, vomiting, anorexia, and papules and pustules on legs that were the sites of exposure to the gas. These symptoms had improved after about 2 months but he experienced reactivation of skin symptoms in the same parts of the body in the following years.In physical examination, he was afebrile. He had multiple oral aphthous ulcers and two scrotal ulcers. In neurological examination, he was drowsy and confused. He had neck rigidity and weakness of muscles in the left side of face, arm, and leg associated with Hoffman and Babinski signs in the same side. Deep tendon reflexes were ½ in both sides.Routine laboratories and vasculitic profiles were all negative but pathergy skin reaction was positive. The brain magnetic resonance imaging (MRI) showed an area of increased signal intensity in the right basal ganglia and right cerebral peduncle in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. Smaller similar changes were also seen in the left basal ganglia. Some patches of enhancement were demonstrated after gadolinium administration in the right basal ganglia. Cerebrospinal fluid analysis showed mononuclear pleocytosis but normal protein and glucose.The patient revealed a dramatic response to pulse dose (1000 mg) of intravenous methylprednisolone and discharged with oral prednisolone, azathioprine, colchicines and aspirin. Ten months later, he presented with confusion, spastic quadriparesis and urinary incontinence. New MRI revealed new large confluent hyper-signal lesions in thalami, basal ganglia, and midbrain of both sides. Intravenous and oral corticosteroids and monthly intravenous cyclophosphamide were prescribed with unsatisfactory response. Two months later, he passed away with a fatal pneumonia.In autopsy, major microscopic pathologic findings in cerebral structures were moderate brain edema and margination and permeation of capillaries and venules by mononuclear inflammatory cells (mainly mature lymphocytes) most prominently in basal ganglia, midbrain, and thalamic regions (figure). Informed consent was taken from his family for this report. The patient fulfilled ISG criteria for Behçet's disease and his histopathological findings were consistent with main pathological finding of neuro-Behçet's disease.1Immunological effects of mustard poisoning long time after exposure have been previously reported in several studies.2 Diminishment of natural killer cells after exposure to sulphur mustard has been reported in two Iranian studies.3,4 It was also shown that exposure to sulphur mustard resulted in impairment of natural killer cells function in Japanese sulphur mustard gas workers.5 Meanwhile, it was demonstrated that natural killer cell activity in the clinically active stage of Behçet's disease was significantly lower than that of healthy controls and patients in the convalescent stage.6In summary, although we cannot consider this case with pathologically confirmed Behçet's disease and legally proved sulphur mustard poisoning more than a coincidence but we can justify this association with the role of natural killer cells.https://ijms.sums.ac.ir/article_39958_dbefdf74e4316c5775aef986335a1b61.pdf