November - 2014 (Volume-4 ~ Issue-11)

Paper Type

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Research Paper

Title

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Steroid resistant nephrotic syndrome in children: Clinical presentation, renal histology, complications, treatment and outcome at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Country

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Bangladesh

Authors

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Roy RR || Haque SMS|| MamunAA|| MuinuddinG||Rahman MH

Page No.

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01-07

Paper Index

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DOI :10.9790/3013-040110107

ANED :: DDL :05.3013/040110107  

Steroid resistant nephrotic syndrome (SRNS) remains a challenge for pediatric nephrologists. The underlying histopathology usually affects the course of the disease and the response to treatment. This study was designed to determine clinical presentation, renal histology, complications, treatment and outcome in children presenting with SRNS. A prospective analysis was carried out among 32 steroid resistant nephrotic syndrome patients aged 1-18 year in the department of pediatric nephrology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh during the period of January 2011 to June 2014. Percutaneous renal biopsy were done in all patients. The histopathology slides were reviewed by competent pathologists. Patients with congenital nephrotic syndrome and nephrotic syndrome secondary to systemic diseases were excluded from the study. Thirty two children fulfilled the inclusion criteria, and included 19 boys and 13 girls, male to female ratio was 1.4:1. Their mean age of presentation was 9.2 year (range 16 month to 16 year). Nine patient(28.22) presented with typical presentation and 23 (71.88%) presented with atypical presentation which included hematuria (62.5%), very high cholesterol (>500mg/dl), persistent hypertension (40.63%), unfavorable age (28.13%), hypocomplementemia (21.88%) and azotemia. None had a positive family history or hepatitis B surface antigen. The renal histopathology was compatible with mesengioproliferative glomerulonephritis (MesPGN) in 40.63%% (n=17), membranoproliferative glomerulonephritis (MPGN) 21.88% (n=07), minimal change disease (MCD) 18.75% (n=06), focal and segmental glomerulosclerosis (FSGS) in 12.5% (n=4) and inadequate tissue was found in two cases. All patients were treated by intravenous methylprednisolone four to six pulses along with intravenous cyclophosphamide followed by oral prednisolone. Cyclosporine was added in patients who failed to achieve remission The outcome with steroid and cyclophosphamide-based treatment for iSRNS was further enhanced with addition of ACE inhibitor. Regarding outcome 21(65.63%) patient responded, five (15.63%) patients died, four (12.5%) reached end stage renal disease and two refused to take any treatment. This study revealed that MesPGN was the commonest histopathology in children presented with SRNS, IV methylprednisolone and IV cyclophosphamide are still agood option for treatment of SRNS with a response rate of sixty five percent.

 

Key Words: Management, Nephrotic syndrome, Outcome

[1]. Bagga A. Srivastava RN Nephrotic syndrome.In: Srivastava RN. Bagga A (eds). Pediatric Nephrology. 5th edition.Joypee Brothers Medical Publishers Ltd. New Delhi. 110002. 2011. 195-234.
[2]. Gargah T, Labessi A, Goucha- Louzir R, Ben Moussa F, Lakhoua MR. Histopathological spectrum of childhood idiopathic steroid-resistant nephrotic syndrome in Tunisia. Tunis Med.2011; 89(3):258-6.
[3]. Ehrich J. H., Geerlings C, Zivicnjak M., Franke D., Geerlings H., and Gellermann J., Steroid-resistant idiopathic childhood nephrosis: overdiagnosed and undertreated. Nephrology Dialysis Transplantation. 2007; 22: 2183–2193.
[4]. Indian Society of Pediatric Nephrology, Management of steroid resistant nephrotic syndrome. Indian Pediatrics. 2009; 46: 35–47.
[5]. Hamasaki Y., Yoshikawa N. and Hattori S. Cyclosporine and steroid therapy in children with steroid-resistant nephrotic syndrome. Pediatric Nephrology. 2009; 24: 2177–2185.
[6]. Habashy D., Hodson E. M., and Craig J. C. Interventions for steroid-resistant nephrotic syndrome: a systematic review. Pediatric Nephrology. 2003; 18:906–912.


Paper Type

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Research Paper

Title

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Patients' Perceptions of Community Pharmacy Practice in UAE: An Overview

Country

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United Arab Emirates

Authors

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Sarah Al Akshar|| Prof. Zakia Metwaly|| Dr Mohammed Shamssain

Page No.

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08-14

Paper Index

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DOI :10.9790/3013-0401108014

ANED :: DDL :05.3013/041108014  

Only few pharmacists are viewed by the public as the preeminent health care professionals responsible for the use of medicines in the prevention and treatment of disease or rational medication.Study's objectives were to explore patients' perceptions of community pharmacists practice and roles and evaluation of the services provided by community pharmacists. In addition, investigate patients expectations of the community pharmacists in Ajman and Sharjah cities, as well as obstacles facing community pharmacy setting for the application of pharmaceutical care from patients perspectives. 500 cross sectional surveys distributed to patients visiting community pharmacies. Descriptive analysis was conducted using SPSS version 20. The response rate was 77% in which out of the 500 questionnaires distributed the total number of usable data was 385. 41 (10.6%), thought that pharmacists are primarily business people who are more concerned with making money. Forty nine percent (091) of patients thought that there is no privacy maintained concerning prescriptions and medications. 66(17.1%) of patients believed that the main barrier to approaching pharmacists is that doctors are more trusted. Improving perceptions and attitudes of patients, pharmacists and physicians towards the role of pharmaceutical care in improving patient overall health is essential. Community pharmacists roles must be expanded and they must look for new challenges in their profession in order to improve their experience and capabilities.

 

Key Words: community pharmacists, pharmaceutical care, attitudes, perceptions, obstacles)

[1] Burke, J. M., Miller, W. A., Spencer, A. P., Crank, C. W., Adkins, L., Bertch, K. E., & Valley, A. W. (2008). Clinical pharmacist competencies.Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy,28(6), 806-815.
[2] Good, M. L. (2003). Patient simulation for training basic and advanced clinical skills. Medical Education, 37(s1), 14-21
[3] Tinelli, M., Bond, C., Blenkinsopp, A., Jaffray, M., Watson, M., & Hannaford, P. (2007). Patient evaluation of a community pharmacy medications management service. The Annals of pharmacotherapy, 41(12), 1962-1970.
[4] Schommer, J. C. (1997). Patients' expectations and knowledge of patient counseling services that are available from pharmacists. American Journal of Pharmaceutical Education, 61(4), 402-406.
[5] Iversen, L., Mollison, J., & MacLeod, T. N. N. (2001). Attitudes of the general public to the expanding role of community pharmacists: a pilot study. Family practice, 18(5), 534-536.


Paper Type

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Research Paper

Title

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A Review Study on "Levo-Bupivacaine"

Country

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INDIA

Authors

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Meena Shyam C|| Dulara Suresh C|| Joshi Adhokshaj|| Daria Usha|| Singhal Manoj|| Khedia Chiranji || Meena Samta

Page No.

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15-18

Paper Index

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DOI :10.9790/3013-04011015018

ANED :: DDL :05.3013/0411015018  

--

 

Key Words: Levobupivacaine, regional anaesthesia, chemical properties of levobupivacaine

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Paper Type

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Research Paper

Title

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Role of Arterial catheters as a source of Hospital related Bacteremia

Country

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Malaysia

Authors

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MurtazaMustafa||SC.Shimmi||MTH.Parash||MDS.Rahman||SS.Husain

Page No.

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19-26

Paper Index

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DOI :10.9790/3013-04011019026

ANED :: DDL :05.3013/0411019026  

Central line-associated bloodstream infections (CLABSIs) are common in intensive care units(ICUs) and in the medical patients. In the United States approximately 250.000 cases of bloodstream infections (BSIs) reported annually, associated with increase in longer hospital stay, costs and mortality. Primary bacteremia without local infection elsewhere, Including intravascular catheter sources account for approximately one half of ICU related bacteremias. The incidence of CLABSIs in non-ICU, general medical patients compare able to the rate in ICU patients. Sources of BSIs include contaminated fluids, catheter hub and lumen, and contaminated skin at catheter insertion site. Pathogens gain access into to the blood stream through extraluminal or intraluminal surface of the device. Bacterial bioflm is thought to be a virtually universal phenomena following insertion of intravascular device. Gram positive organisms, gram negative organisms and fungi is the frequently isolated BSIs pathogens.Multi drug resistantpathogens,and extended spectrum βlactamase (ESBLs) producing organisms, and bacteremia in elderly has high mortality rate. Molecular methods play important role in the diagnostic laboratory techniques.CLABSIs can be prevented by following CDC's guidelines for the prevention of device- related infections.

 

Key Words: Device associated bacteremia , Blood stream infections, Diagnosis, Prevention

[1]. Maki D.Sepsis arising from Extrinsic Contamination of the infusion and measures for control.Lancaster,UK:MTP Press;1977.
[2]. 0'Grady NP,AlexanderM,DellingerEP,etal.Guidelines for the prevention of intravascular catheter-related infections.Infect Control Hosp Epidemiol.2002;23:759-69.
[3]. WisplinghoffH,BischoffT,TallentSM,etal.Noscomial bloodstream infections in US hospitals:analysis of24,179 cases from prospective nationwide surveillance study. Clin Infect Dis.2004;39:309-17.
[4]. Edwards JR,PetersonKD,AndrusMI,etal.National Healthcare Safety Network (NHSN) Report,data summary for 2006,issued June 2007.Am J InfetControl.2007;35:290-301.


Paper Type

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Research Paper

Title

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Analysis of used disinfectants and antiseptics correlated with the occurrence of nosocomial infections – Clinical hospital Stip, Republic of Macedonia in period of 2007 – 2011

Country

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Brazil

Authors

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Sofija Petkovska || Biljana Gjorgjeska

Page No.

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27-36

Paper Index

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DOI :10.9790/3013-04011027036

ANED :: DDL :05.3013/0411027036  

Intra-hospital or nosocomial hospital infections are caused by microorganisms acquired during the hospitalization of the patient, and clinically are manifested from 48 to 72 hours after admission at earliest. The procedures for disinfection and the type and quantity of disinfectants used are directly related to the effects. The control of intra-hospital infections is performed by intra-hospital infections Commission which is responsible for taking swabs of sediments and air for proving none/presence of bacteria, as well as taking measures if contamination occurs and timely detection of intra-hospital infections. This research's aim is to review and select appropriate ways in order to prevent intra-hospital infections. Statistical processing of data received from Clinical Centre in Stip, Republic of Macedonia in the period 2009 to 2013 gives a complete insight into the connection between the use of disinfectants with occurrence and absence of intra-hospital infections. Prevention of intra-hospital infections is possible only by implementing standard processes and procedures that enable optimal use of properly selected disinfectants in all departments in hospitals. Special attention should be given to the procedures for preparing and delivering food to patients and the procedures for disinfection and control of space and food preparation, store and distribute food.

 

 

[1]. Dr. Stefan Gartiser, Ismene Jäger, Efficiency and practicability of risk mitigation measures for biocidal products with focus on disinfectants, ENVIRONMENTAL RESEARCH OF THE FEDERAL MINISTRY OF THE ENVIRONMENT, NATURE CONSERVATION AND NUCLEAR SAFETY, pp 17
[2]. Gerald McDonnell, A. Denver Russell, Аntiseptics and Disinfectants: Activity, Action, and Resistance, Clin. Microbiol. Rev. January 1999 vol. 12 no.1
[3]. Prevention of hospital-acquired infections, A practical guide, 2nd edition, 2002, World Health Organization, Department of Communicable Disease, Surveillance and Response
[4]. I. B. R. DUNCAN, M.D., F.R.C.P. [C], M.C.Path., London, Ont. And R. D. COMTOIS, M.Sc.,f Ottawa, Ont. Hospital Infections Caused by a Group of Recently Recognized Strains of Staphylococcus Aureus, THE CANADIAN MEDICAL ASSOCIATION, Le JOURNAL de L`ASSOCIATON MEDICALE CANADIENNE, APRIL 23, 1966 . VOL. 94, NO. 17
[5]. Thale Cathrine Berg, Knut E. Kjørstad, Per Espen Akselsen, Bjørn Edvard Seim, Hege Line Løwer, Maryann Nesset Stenvik, Nina Kristine Sorknes, Hanne-Merete Eriksen, National surveillance of surgical site infections after coronary artery bypass grafting in Norway: incidence and risk factors, Oxford Journals, Medicine & Health, European Journal Cardio-Thoracic Surgery, Volume 40, Issue 6, Pp. 1291-1297


Paper Type

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Research Paper

Title

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Sensitivity and specificity of 99mTc-UBI29-41 and 67Ga-Citrate
scintigraphy imaging to discriminate infection lesion induced by
Staphylococcus aureus and sterile inflammation lesion induced by
Carrageenan in foot's rat

Country

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Iran

Authors

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A. Doroudi ||M. Erfani || K. Damavandi Kamali|| S.M. Saadati || F. Ahmadi
||A.Kiasat || M.J. Khodayar || H. Meghdadi

Page No.

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37-43

Paper Index

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DOI :10.9790/3013-04011037043

ANED :: DDL :05.3013/0411037043  

This study was launched to evaluate the efficacy and efficiency of 99mTc-UBI29-41scintigraphy
imaging to visualize the infection foci induced by staphylococcus aureus and inflammation lesions induced by carrageenan in the foot's rat in comparison with 67Ga-Citrate radioisotope scintigraphy imaging. The labeling and quality control of 99mTc-UBI29-41have been performed according to the manufacturer's instructions. A total number thirty six adult, male NMRI rats were chosen. The animals were randomly divided into two equal group's .One group for 99mTc-UBI29-41 scintigraphy imaging and the other group for 67Ga-Citrate scintigraphy imaging respectively. Every group subdivided into two groups equally. Septic lesion was induced by Staphylococcus aureus due to inoculation of bacteria suspension in the foot's rat in one group. The aseptic inflammation lesion was induced by Carrageenan in the foot's rat in the other group. The 99mTc-UBI29-41 and 67Ga-Citrate radiotracer scintigraphy imaging studies have been performed to evaluate the sensitivity and specificity 99mTc-UBI29-41radiopharmaceutical for preferentially diagnosis between infection and sterile inflammation lesions. The images have been shown the uptake 67Ga at the infection and inflammation sites. The labeling of UBI by technetium can provide images with good quality and a shorter investigation time in comparison to 67Ga radioisotope imaging. The infection foci could be visualized by 99mTc-UBI29- 41scintigraphy imaging due to selective bonding UBI 29-41 to the negatively charged groups present on the microbial membrane due to electrostatic interaction. The inflammation sites have been observed by non-specific uptake of 99mTc-UBI29-41. Both scintigraphy imaging studies have not demonstrated preferentially diagnosis septic and aseptic inflammation lesions. The sensitivity, specificity and positive predictive value of both scintigraphy imaging techniques were 100%, 50% and 50% respectively. In spite of high sensitive of the 99mTc- UBI 29-41 scintigraphy imaging to localize the lesions, but it could not demonstrate to discriminate between septic and aseptic inflammation lesions. The other modalities must be considered for interpretation of images has obtained by 99mTc-UBI 29-41 scintigraphy imaging study.

 

Key Words: Carrageenan, 67Ga, Staphylococcus aureus, 99mTc, 99mTc-UBI 29-41 scintigraphy imaging

[1] G . Ferro-Flores , F.M Ramirez, L. Melendez-Alafort , C.A. Murphy , M. Pedra-Lopez .Molecular recognition and stability of 99mTC-UBI 29-41 based on experimental and semiemprical results. Appl Radiat Isot 61,2004,1261-1268

[2] L. Melendez-Alafort , F.M. Ramirez , G. Ferro-Flores G, C.A. Murphy , M. Pedra-Lopez , D.J. Hnatowich. Lys and Arg in UBI.A specific site for a stable Tc-99m complex. Nucl Med Biol 30, 2003,605-615

[3] M. Gandomkar, R. Najafi , M. Mazidi, M. Goudarzi, S.H. Mirfallah. New peptide based Freeze-Dried kit [99m Tc-HYNIC]-UBI 29-41 as a human specific infection imaging agent. Iran J Nucl Med 16, 2008,25-30

[4] M. Gandomkar , R. Najafi, M. Mazidi, S.H. Mirfallah , M. Goudarzi. Three different procedures in labeling of Uniquicidin with technetium 99m:a comparative study.Iran J Radiat Res 7,2009,97-104

[5] M. Gandomkar , R. Najafi , M. Shafiei, M. Mazid , M. Goudarzi , S.H. Mirfallah. Clinical evaluation of antimicrobial peptide [99m Tc/Tricine/HYNIC]ubiquicidin 29-41 as a human-specific infection imaging agent.Nucl Med and Biol 36,2009,199-205

[6] A.W. Thomson, E.F. Fowler . Carrageenan:a review of its effects on the immune system. Agents and Actions 11,1981,265-273

[7] S. Crerand, M. Dolan, P. Laing , M. Bird , L.M. Smith, L. Klerman.Diagnosis of osteomyelitis in neuropathic foot ulcers. J Bone and Joint Surg 78, 996,51-55


Paper Type

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Research Paper

Title

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Antioxidative effect of Capsicum oleoresins compared with pure capsaicin

Country

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Europe

Authors

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Maksimova Viktorija|| Koleva G. Liljana|| Ruskovska Tatjana|| Cvetanovska Ana|| Gulaboski Rubin

Page No.

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44-48

Paper Index

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DOI :10.9790/3013-04011044048

ANED :: DDL :05.3013/0411044048  

Capsicum annum L, or hot peppers are unique among the plant species, because of their ability to synthesize capsaicin. Capsaicin is an alkaloid which has been known for its analgesic, antireumatic, antiseptic, antidiabetic and few more pharmacological properties. Its antioxidative potential is also a subject of many experiments, in the last few years. The aim of this study is to examine the antioxidant potential of capsaicin and capsicum oleoresins produced from Capsicum sp. cultivated in R. of Macedonia. This experiment comprises four different genotypes of Capsicum annuum L., which were used for obtaining ethanolic oleoresins. Their antioxidant potential was measured and compared to the antioxidative potential of the pure capsaicin standards. As a method for measuring the total antioxidant capacity was used FRAP (Ferric reducing antioxidant potential) method. This is a simple photometric method for estimation of in vitro antioxidative potential which is expressed as μmol/L Fe2+. The results from this study are showing a very good correlation between antioxidant potential of capsaicin and capsicum oleoresins. This confirms that antioxidative potential of hot peppers does not come only from the vitamins and phenolic compounds in them, but capsaicinoids are also included.

 

Key Words: antioxidants, capsaicin, FRAP, fruit, hot peppers

[1]. M. Malgorzata, P. J. Andriena, P., J. Antioxidant Activity of the Main Phenolic Compounds Isolated from Hot Pepper Fruit (Capsicum annuum L.), Agric. Food Chem, 53, 2005, 1750−1756
[2]. M. Peusch, E. Müller-Seitz, M. Petz, A. Müller, E. Anklam, Extraction of capsaicinoids from chillies (Capsicum frutescens L.) and paprika (Capsicum annuum L.) using supercritical fluids and organic solvents, European food research and technology, 1997, 204, 5, 1997, 351-355
[3]. D. Palevitch, L. E. Cracker, Nutritional and medicinal importance of red pepper (Capsicum spp.), J. Herbs Spices Med. Plants, 3, 1995, 55-83
[4]. H.G. Daood, M. Vinkler, F. Markus, E. A. Hebshi, P. A. Biacs, Antioxidant vitamin content of spice red pepper (paprika) asaffected by technological and varietal factors, Food Chem., 55, 1996, 365-372


Paper Type

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Research Paper

Title

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Pharmacognostical and Phytochemical Studies of Kukutnakhi- Aspidium Cicutarium - A Folklore Plant

Country

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India

Authors

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Dr. Manasi Deshpande ||Dr. Shobha Khilari ||Dr. Ankush Mahajan

Page No.

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49-52

Paper Index

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DOI :10.9790/3013-04011049052

ANED :: DDL :05.3013/0411049052  

Aspidium cicutarium L. from Dryopteridaceae family is a folk medicinal plant used in the treatment of shotha (inflammation). The rhizomes of this herb are said to be successful in managing Inflammation. This study is aimed at assessing the scientific evaluation of Aspidium cicutarium in the course of pharmacognostical and phytochemical analysis, which mainly covered the macroscopic and microscopic features of the rhizomes including powder microscopy and Phytochemical parameters such as pH, total ash value, water-soluble extract values were assessed in the preliminary physicochemical screening. Qualitative analysis revealed the existence of certain chemical constituents such as flavonoids, tannins, organic acids and saponin glycosides. The ethanol extract of rhizomes was subjected to TLC for the separation of components.

 

Key Words: Aspidium cicutarium, pharmacognosy, phytochemistry, TLC

[1] Late Vd. Shankar Daji Padeshatri, Vanaspati Gunadarsh, vol IV, 142, Published by Ramesh Raghuvanshi, pp 103
[2] The ferns of Bombay, Bombay, D. B. Taraporevala Sons & Co., 1922
[3] The ferns of Bombay, by E. Blatter & J. F. d'Almeida. With 2 coloured and 15 black and white plates and 43 text figures. Bombay: D.
[4] B. Taraporevala Sons & Co., 1922. url , p. 132,
[5] Wikipedia. website available at http/www.org/wiki/User:Nonenmac/Aspidium#not_placed_elsewhere,cited on 1st October 2014
[6] The Ayurvedic Pharmacopoeia of India. 3rd edition, Govt. Of India, Ministry of Health and Welfare, Published by the controller of Publications, Delhi, 1985.
[7] Khandelwal KR. Techniques and Experiments, Practical Pharmacognosy. Ed 17th, Nirali Prakashan, Pune, 2007, 149-156
[8] Wagener H, Bladt S. Plant drug analysis – A thin layer chromatography atlas. Berlin: Springer; 1996. P. 230-1.


Paper Type

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Research Paper

Title

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Clinical, pharmacokinetic and technological aspects of the hydroxychloroquine sulfate

Country

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Brazil

Authors

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Leslie Raphael de Moura Ferraz|| Fabiana Lícia Araújo dos Santos|| Pablo de Ataíde Ferreira|| Ricardo Tadeu Lourenço Maia Junior|| Talita Atanazio Rosa || Larissa Araújo Rolim|| Pedro José Rolim-Neto

Page No.

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53-64

Paper Index

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DOI :10.9790/3013-04011053064

ANED :: DDL :05.3013/0411053064  

Developed originally as an antimalarial agent, hydroxychloroquine sulfate (HCQS) is often used as a slow-acting drug in treating disorders of connective tissue. Over the past two decades, several data have been accumulated on the systemic effects of HCQS, expanding the potential uses of this drug in different therapeutic classes. The purpose of this article was to conduct a narrative review with qualitative approach on clinical, pharmacokinetic and technological aspects of HCQS, aiming to gather relevant pieces of information for the development of new therapeutic approaches to this drug. A search of the literature of scientific experimental and theoretical studies in the period 1980-2013 was performed. According to the data collected, among the activities HCQS, there are the indications for the treatment of autoimmune diseases such as lupus erythematosus and rheumatoid arthritis. Reports also indicate that HCQS improves insulin sensitivity, ability to reduce thromboembolic events, reduction of lipid levels and treatment for infection by human immunodeficiency virus. The evidence found out ocular and cutaneous adverse effects and the formation of three chiral active metabolites, what encourages studies to evaluate the kinetic behavior of HCQS and the intrinsic physicochemical characteristics of the drug, which is yet poorly described in the literature.

 

Key Words: Autoimmune Diseases, Chiral Drugs, HIV, Hydroxychloroquine Sulfate.

[1] N.J. Olsen, M.A. Schleich and D.R. Karp, Multifaceted effects of hydroxychloroquine in human disease, Semin Arthritis Rheum., 43(2), 2013, 264-72.
[2] A.J. McLachlan, S.E. Tett, D.J. Cutler and R.O. Day, Disposition of the enantiomers of hydroxychloroquine in patients with rheumatoid arthritis following multiple doses of the racemate, Br J Clin Pharmacol., 36(1), 1993, 78-81.
[3] S.E. Tett, D.J. Cutler, R.O. Day and K.F. Brown. Bioavailability of hydroxychloroquine tablets in healthy volunteers, Br J Clin Pharmacol., 27(6), 1989, 771-79.
[4] A. Semeniuk, A. Niedospial, J. Kalinowska-Tluscik, W. Nitek and B. J. Oleksyn, Molecular geometry of antimalarial amodiaquine in different crystalline environments, J Mol Struct., 875(1–3), 2008, 32–41.
[5] T.A. Shapiro and D.D. Goldberg, Quimioterapia das infecções por protozoários, In: L.S. Goodman; A. Gilman, As Bases Farmacológicas da Terapêutica, (Rio de Janeiro: McGraw-Hill; 2006) 927-9.