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Fulltext Visualising functional 5-HT3 receptors containing A and C subunits at or near the cell surface

Abad IPL, Fam RL, Nguyen DT, Nowell CJ, Trinh PNH, Manallack DT, et al.

Biomed Pharmacother, 2020 Dec;132:110860.
PMID: 33059258 DOI: 10.1016/j.biopha.2020.110860

Five different subunits of the human serotonin 3 (5-hydroxytrptamine 3; 5-HT3) receptor exist and these are present in both central and peripheral systems. Different subunits alter the efficacy of 5-HT3 receptor antagonists used to treat diarrhoea predominant-irritable bowel syndrome, chemotherapy induced nausea and vomiting and depression. Cell surface arrangement of 5-HT3 receptor complexes and the contribution of C, D and E subunits to receptor function is poorly understood. Here, we examine interactions of A and C subunits using 5-HT3 receptor subunits containing fluorescent protein inserts between the 3rd and 4th transmembrane spanning region. HEK293T cells that do not normally express 5-HT3 receptor subunits, were transiently transfected with A or C or both subunits. Patch clamp experiments show that cells transfected with either fluorescent protein tagged A or A and C subunits generate whole cell currents in response to 5-HT. These findings correlate with the apparent distribution of fluorescent protein tagged A and C subunits at or near cell surfaces detected using TIRF microscopy. In co-transfected cells, the A and C subunits are associated forming AC heteromer complexes at or near the cell surface and a proportion can also form A or C homomers. In conclusion, it is likely that both A homomers and AC heteromers contribute to whole cell currents in response to 5-HT with minimal contribution from C homomers.
Photoprotection awareness and practices among patients with systemic lupus erythematosus and its association with disease activity and severity

Abdul Kadir WD, Jamil A, Shaharir SS, Md Nor N, Abdul Gafor AH

Lupus, 2018 Jul;27(8):1287-1295.
PMID: 29665756 DOI: 10.1177/0961203318770016

Objective The objective of this paper is to determine photoprotection awareness, knowledge, practices, and its relationship with disease activity and damage in patients with systemic lupus erythematosus (SLE).
Methods A cross-sectional study was performed. Data were acquired from in-person interviews and medical records.
Results A total of 199 (89.6%) females and 23 (10.4%) males were recruited. Median age was 39.00 (interquartile range (IQR) 18) years, disease duration 12.12 (IQR 8) years, Fitzpatrick skin phototype III 119 (53.6%) and IV 81 (36.5%). Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) was 2.95 (IQR 4) while Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC-ACR DI) was 1.20 (IQR 2). The majority 205 (92.3%) were aware of sun exposure effects on SLE. Photoprotection methods were shade seeking 209 (94.1%), sun avoidance 212 (95.5%), long pants 168 (75.7%), long sleeves 155 (69.8%), sunscreen 116 (52.3%), sunglasses 114 (51.4%) and head cover 103 (46.4%). Significantly higher photoprotection practice scores (PPS) were observed in females, Malays, and individuals with higher education level and internet accessibility. PPS were not significantly correlated with SLICC-ACR DI and SLEDAI-2 K. Independent predictors for good photoprotection practice (GPP) were ethnicity (OR = 3.66, 95% CI 1.78-7.53), awareness (OR = 3.77, 95% CI 1.09-13.08) and cutaneous involvement (OR = 2.43, 95% CI 1.11-5.28). Photoprotection methods and GPP were not predictors for disease activity or damage.
Conclusion Photoprotection awareness and knowledge was good. Shade seeking and sun avoidance were the common photoprotection methods practised. The use of sunscreen requires improvement. Photoprotection awareness and cutaneous manifestation were predictors for GPP. Neither photoprotection methods nor GPP were associated with disease activity or damage.
Study site: Nephrology, Rheumatology and Dermatology clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
Fulltext Evaluation of antidiabetic and antioxidant properties of Brucea javanica seed

Ablat A, Mohamad J, Awang K, Shilpi JA, Arya A

ScientificWorldJournal, 2014;2014:786130.
PMID: 24688431 DOI: 10.1155/2014/786130

The ethanol extract of B. javanica seed was fractionated with solvents of different polarities and tested for antioxidant activities by several assays including DPPH radical scavenging activity, ferric reducing antioxidant power (FRAP), ferrous ion chelating activity (FCA), and nitric oxide radical scavenging activity (NORSA) along with their polyphenolic contents. Antidiabetic activity was evaluated both in vitro and in vivo using a glycogen phosphorylase α (GPα) inhibition assay and oral glucose tolerance test (OGTT) in nondiabetic rats. The ethyl acetate fraction (EAF), rich in tannin, exhibited the strongest antioxidant activities to DPPH, FRAP, and NORSA, except for FCA. The EAF also exerted a dose-depended inhibition of GPα (IC50 = 0.75 mg/ml). Further evaluation of hypoglycemic effect on OGGT indicated that rats treated with EAF (125 mg/kg bw) showed a 39.91% decrease (P < 0.05) in blood glucose levels at 30 min, and continuous fall (P < 0.05) of 28.89% and 20.29% was observed in the following hours (60 and 90 min) compared to the normal control during OGTT. The EAF was applied to polyamide column chromatography, and the resulting tannin-free fraction was tested for both GPα inhibition and antioxidant (DPPH only) activity. The GP α inhibitory activity was retained, while antioxidant activity was lost (4.6-fold) after tannin removal. These results concluded that the GPα inhibitory activity initially detected was primarily due to the compounds other than tannins, whereas antioxidant activity was mainly due to the tannins.
Antidiabetic effects of Brucea javanica seeds in type 2 diabetic rats

Ablat A, Halabi MF, Mohamad J, Hasnan MH, Hazni H, Teh SH, et al.

BMC Complement Altern Med, 2017 Feb 06;17(1):94.
PMID: 28166749 DOI: 10.1186/s12906-017-1610-x

Brucea javanica (B. javanica) seeds, also known as "Melada pahit" in Indo-Malay region are traditionally used to treat diabetes. The objective of this study was to determine antidiabetic, antioxidant and anti-inflammatory effects of B. javanica seeds on nicotinamide (NA)-streptozotocin (STZ) induced type 2 diabetic (T2D) rats and to analyze its chemical composition that correlate with their pharmacological activities.
Lymphocutaneous sporotrichosis of the abdominal wall: A lesson in lymphatic drainage

Arumugam M, Leelavathi M, Harun NL, Jamil A

Med J Malaysia, 2021 07;76(4):583-584.
PMID: 34305124

Cutaneous sporotrichosis (CS) presents as asymptomatic lesions of varied morphology. The most common variant is the lymphocutaneous type which typically progresses from a papule to an ulcer and then forms nodules along the superficial lymphatic channels. Diagnosis CS may be challenging when the lesion presents at an uncommon site where the superficial lymphatic drainage is unfamiliar. We present here a case of sporotrichosis of the abdominal wall which was initially misdiagnosed as an abscess but later confirmed by culture and managed successfully.
Merkel cell carcinoma: Preparing to go the distance

Arumugam M, Jamil A, Amiseno RA, Rosli N, Abdul Shukor N

Malays J Pathol, 2020 Aug;42(2):277-281.
PMID: 32860382

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare and aggressive malignancy of the skin, with poor clinical outcomes. Typical conditions include a rapidly growing, solitary dome-shaped, violaceous nodule. Several root causes have been identified - sun exposure, age, lighter skin, immunocompromised state, and polyomavirus infection. Wide local excision is the best treatment. The tumour is radiotherapy-responsive. However, the success rate of the treatment with chemotherapy is rather limited. Immunotherapy has shown promising results. Early detection is important to prevent morbidity and mortality.
CASE REPORT: In this literature work, we reported on a particular case of MCC, as exhibited by an 84-year-old Chinese woman, and discussed the clinical features and management of MCC.
DISCUSSION: We highlighted that MCC cases have a link to the polyomavirus 5. Patients who were identified with the Polyomavirus 5, and underwent immunotherapy, were seen to depict much better prognosis.
Effects of Malaysian thermal spring water as adjunct therapy for mild to moderate acne vulgaris - a prospective, randomised, controlled, split face study

Faisal UA, Jamil A, Jaafar H, Aqma WS, Arumugam M

Med J Malaysia, 2024 Mar;79(2):157-164.
PMID: 38553920

INTRODUCTION: Acne is a common skin disease with a high psychosocial burden, affecting mostly adolescents and youth worldwide. Management of acne is often challenged by cutaneous side effects that leads to therapeutic intolerance, poor compliance and impaired efficacy.
MATERIALS AND METHODS: This was a single-centre, evaluatorblinded, split-face, randomised study investigating the effects of thermal spring water (TSW) in improving efficacy and tolerability of standard acne therapy. Total of 31 participants with mild-to-moderate acne were recruited and subjected to TSW spray to one side of the face 4 times daily for 6 weeks in addition to standard therapy. The other side received standard therapy only.
RESULTS: Six (19.4%) males and 25 (80.6%) female with mean age 25.1±6.13 participated, 15 (48.4%) had mild acne while 16 (51.6%) had moderate acne. Seven (22.6%) were on oral antibiotics, 25 (80.6%) used adapalene, 6 (19.4%) tretinoin and 21 (67.7%) benzoyl peroxide. Skin hydration improved and better on spring water treated side with mean difference12.41±30.31, p = 0.04 at the forehead, 39.52±65.14, p < 0.01 at the cheek and 42.172±71.71, p < 0.01 at the jaw at week 6. Participants also report significant reduction in dryness at the treated side at week 6, mean difference 0.93±0.10, p < 0.001. TEWL, sebum and pH were comparable on both sides with no significant differences. Tolerability towards standard therapy improved as early week 2 with reduction of stinging following application of topical therapy (mean difference 0.62±1.43, p = 0.03), increase in skin feeling good (-1.79±1.70, p < 0.001) and skin suppleness (0.62±1.43, p < 0.001). These improvements were significantly maintained till week 6. Cardiff acne disability index significantly improved at week 6 (p<0.001) despite no significant changes in Comprehensive Acne Severity Scale score before and after treatment.
CONCLUSION: TSW may have a role as an adjunct to standard acne therapy by improving hydration, acne disability index and tolerability towards standard topical treatment.
Fulltext A randomized half-body, double blind, controlled trial on the effects of a pH-modified moisturizer vs. standard moisturizer in mild to moderate atopic dermatitis

Goh SW, Jamil A, Safian N, Md Nor N, Muhammad N, Saharudin NL

An Bras Dermatol, 2020 03 21;95(3):320-325.
PMID: 32291095 DOI: 10.1016/j.abd.2019.11.007

BACKGROUND: Higher skin pH in atopic dermatitis contributes to impaired epidermal barrier. A moisturizer compatible with physiological pH could improve atopic dermatitis.
OBJECTIVE: To determine the effect of a physiologically compatible pH moisturizer in atopic dermatitis.
METHODS: A randomized half body, double blind, controlled trial involving patients with stable atopic dermatitis was performed. pH-modified moisturizer and standard moisturizer were applied to half body for 6 weeks.
RESULTS: A total of 6 (16.7%) males and 30 (83.3%) females participated. Skin pH reductions from week 0, week 2 and 6 were significant at the forearms (5.315 [0.98] to 4.85 [0.54] to 5.04 [0.78], p=0.02) and abdomen (5.25 [1.01], 4.82 [0.64], 5.01 [0.59], p=0.00) but not at the shins (5.01 [0.80], 4.76 [0.49], 4.85 [0.79], p=0.09) with pH-modified moisturizer. Transepidermal water loss (TEWL) at the forearms decreased (4.60 [2.55] to 3.70 [3.10] to 3.00 [3.55], p=0.00), abdomen (3.90 [2.90] to 2.40 [3.45] to 2.70 [2.25], p=0.046). SCORAD improved from 14.1±12.75 to 10.5±13.25 to 7±12.25, p=0.00. In standard moisturizer group, pH reductions were significant at the forearms (5.29 [0.94] to 4.84 [0.55] to 5.02 [0.70], p=0.00) and abdomen (5.25 [1.09], 4.91 [0.63], 5.12 [0.66], p=0.00). TEWL at the forearm were (4.80 [2.95], 4.10 [2.15], 4.60 [3.40], p=0.67), shins (3.80 [1.40], 3.50 [2.35], 4.00 [2.50], p=0.91) and abdomen (3.70 [2.45], 4.10 [3.60], 3.40 [2.95], p=0.80). SCORAD improved from 14.2±9.1 to 10.9±10.65 to 10.5±11, p=0.00. Reduction in pH was observed with both moisturizers while TEWL significantly improved with pH-modified moisturizer. pH-modified moisturizer resulted in greater pH, TEWL and SCORAD improvements however the differences were not significant from standard moisturizer.
STUDY LIMITATION: Skin hydration was not evaluated.
CONCLUSION: Moisturization is beneficial for atopic dermatitis; use of physiologically compatible pH moisturizer is promising.
Fulltext Exacerbation of systemic lupus erythematosus in a patient with concomitant chronic plaque psoriasis treated with ustekinumab

Goh SW, Jamil A, Nor NM, Cader RA, Shaharir SS

Indian J Dermatol Venereol Leprol, 2019 12 12;86(1):68-70.
PMID: 31823905 DOI: 10.4103/ijdvl.IJDVL_961_18
Fulltext Spectrofluorometric and molecular docking studies on the binding of curcumenol and curcumenone to human serum albumin

Hamdi OA, Feroz SR, Shilpi JA, Anouar el H, Mukarram AK, Mohamad SB, et al.

Int J Mol Sci, 2015;16(3):5180-93.
PMID: 25756376 DOI: 10.3390/ijms16035180

Curcumenol and curcumenone are two major constituents of the plants of medicinally important genus of Curcuma, and often govern the pharmacological effect of these plant extracts. These two compounds, isolated from C. zedoaria rhizomes were studied for their binding to human serum albumin (HSA) using the fluorescence quench titration method. Molecular docking was also performed to get a more detailed insight into their interaction with HSA at the binding site. Additions of these sesquiterpenes to HSA produced significant fluorescence quenching and blue shifts in the emission spectra of HSA. Analysis of the fluorescence data pointed toward moderate binding affinity between the ligands and HSA, with curcumenone showing a relatively higher binding constant (2.46 × 105 M-1) in comparison to curcumenol (1.97 × 104 M-1). Cluster analyses revealed that site I is the preferred binding site for both molecules with a minimum binding energy of -6.77 kcal·mol-1. However, binding of these two molecules to site II cannot be ruled out as the binding energies were found to be -5.72 and -5.74 kcal·mol-1 for curcumenol and curcumenone, respectively. The interactions of both ligands with HSA involved hydrophobic interactions as well as hydrogen bonding.
Fulltext A Quantum Chemical and Statistical Study of Cytotoxic Activity of Compounds Isolated from Curcuma zedoaria

Hamdi OA, Anouar el H, Shilpi JA, Trabolsy ZB, Zain SB, Zakaria NS, et al.

Int J Mol Sci, 2015 Apr 27;16(5):9450-68.
PMID: 25923077 DOI: 10.3390/ijms16059450

A series of 21 compounds isolated from Curcuma zedoaria was subjected to cytotoxicity test against MCF7; Ca Ski; PC3 and HT-29 cancer cell lines; and a normal HUVEC cell line. To rationalize the structure-activity relationships of the isolated compounds; a set of electronic; steric and hydrophobic descriptors were calculated using density functional theory (DFT) method. Statistical analyses were carried out using simple and multiple linear regressions (SLR; MLR); principal component analysis (PCA); and hierarchical cluster analysis (HCA). SLR analyses showed that the cytotoxicity of the isolated compounds against a given cell line depend on certain descriptors; and the corresponding correlation coefficients (R2) vary from 0%-55%. MLR results revealed that the best models can be achieved with a limited number of specific descriptors applicable for compounds having a similar basic skeleton. Based on PCA; HCA and MLR analyses; active compounds were classified into subgroups; which was in agreement with the cell based cytotoxicity assay.
Fulltext Chilaiditi's syndrome presenting as acute abdomen

Hisham AN, Gunn A, Jamil AA

Med J Malaysia, 1995 Sep;50(3):281-3.
PMID: 8926911
Fulltext Antinociceptive and antioxidant activity of Zanthoxylum budrunga wall (Rutaceae) seeds

Islam MK, Biswas NN, Saha S, Hossain H, Jahan IA, Khan TA, et al.

ScientificWorldJournal, 2014;2014:869537.
PMID: 24707219 DOI: 10.1155/2014/869537

Different parts of the medicinal plant Zanthoxylum budrunga Wall enjoy a variety of uses in ethnobotanical practice in Bangladesh. In the present study, a number of phytochemical and pharmacological investigations were done on the ethanol extract of Z. budrunga seeds (ZBSE) to evaluate its antinociceptive and antioxidant potential. ZBSE was also subjected to HPLC analysis to detect the presence of some common antioxidants. In acetic acid induced writhing test in mice, ZBSE showed 65.28 and 74.30% inhibition of writhing at the doses of 250 and 500 mg/kg and the results were statistically significant (P < 0.001). In hot-plate test, ZBSE raised the pain threshold significantly (P < 0.001) throughout the entire observation period. In DPPH scavenging assay, the IC50 of ZBSE was observed at 82.60 μg/mL. The phenolic content was found to be 338.77 mg GAE/100 g of dried plant material. In reducing power assay, ZBSE showed a concentration dependent reducing ability. HPLC analysis indicated the presence of caffeic acid with a concentration of 75.45 mg/100 g ZBSE. Present investigation supported the use of Zanthoxylum budrunga seed in traditional medicine for pain management. Constituents including caffeic acid and other phenolics might have some role in the observed activity.
An ethnobotanical study of medicinal plants used by tribal and native people of Madhupur forest area, Bangladesh

Islam MK, Saha S, Mahmud I, Mohamad K, Awang K, Jamal Uddin S, et al.

J Ethnopharmacol, 2014 Feb 3;151(2):921-30.
PMID: 24342778 DOI: 10.1016/j.jep.2013.11.056

Madhupur forest area, Tangail is one of early human settlements in Bangladesh. Having abode in the vicinity of the forest, a strong ethnobotanical practice has prevailed in this area since ancient time. Due to the rapid deforestation during the last few decades, many plants have already disappeared or are facing extinction. Thus we attempted to document the medicinal plant use of Madhupur forest area with a view to preserve the ethnobotanical knowledge and in order to protect the biodiversity of this area.
Kiwi Omnicup versus Malmstrom metal cup in vacuum assisted delivery: a randomized comparative trial

Ismail NA, Saharan WS, Zaleha MA, Jaafar R, Muhammad JA, Razi ZR

J Obstet Gynaecol Res, 2008 Jun;34(3):350-3.
PMID: 18686348

AIM: To compare the success, clinical outcomes, and maternal and neonatal complications between the Kiwi Omnicup and the Malmstrom metal cup in vacuum assisted delivery.
METHODS: This was a prospective randomized comparative trial. Women who required vacuum assisted vaginal delivery were randomized into the Kiwi Omnicup (KO) group and the Malmstrom metal cup (MM) group. The vacuum assisted deliveries were conducted according to hospital protocol. Details of the procedure and delivery outcomes including success and complications were analyzed.
RESULTS: One hundred and sixty-four women were recruited - 85 were assigned to vacuum assisted delivery using the KO and 79 the MM. One hundred percent delivery success was achieved with no significant differences between the two instruments in terms of maternal morbidity (P = 0.66). Six women in the MM group sustained post delivery complications in comparison to five in the KO group. Three babies were diagnosed with birth asphyxia in each group. More babies in the MM group were admitted to the Neonatal Intensive Care Unit (NICU) (10 babies versus 5 babies) and suffered complications (14 versus 12 babies), compared to the KO group, although the difference was not statistically significant. There were no intrapartum or neonatal deaths and of those admitted to the NICU, all were discharged within a week without any serious consequences.
CONCLUSION: Kiwi Omnicup is an effective alternative to the currently available Malmstrom metal cup for vacuum assisted delivery with no increase in maternal or neonatal morbidity or mortality.
Fulltext Frequency and Association of Stress Levels with Modes of Commuting Among Medical Students of a Developing Country

Jahangeer SMA, Hasnain N, Tariq MT, Jamil A, Zia SY, Amir W

Malays J Med Sci, 2021 Aug;28(4):113-122.
PMID: 34512136 DOI: 10.21315/mjms2021.28.4.12

Introduction: This study aimed at determining the frequency and association of stress levels with modes of transportation and was likely to reveal the contributing transportation-related factors for stress in medical students.
Methods: This was a questionnaire-based, cross-sectional study that included undergraduate medical students of a public sector medical university in Karachi, Pakistan. A total of 573 students participated voluntarily, of which 300 were provided a manual questionnaire and 273 filled it online. The reliability of the questionnaire was assessed using Cronbach's alpha at 0.791. The collected data were analysed using IBM SPSS Statistics for Windows, version 21.0.
Results: Out of 573 participants, 99.3% (n = 298) of students filled the questionnaire manually, whereas 100% of students filled the questionnaire online. Almost two-thirds of students used university transport; more than 90% lived more than 5 km from the university and 56% had a traveling time of more than an hour. Approximately 15.4% of students reported physical trauma and some form of harassment. Sheldon Cohen's stress scale surprisingly revealed 90% of students to be within the moderate-to-high stress category. Risk factors were associated with stress levels and significant associations were observed with noise exposure (P = 0.023) and sleep quality (P = 0.001). The most common reported stressors associated with commuting included overcrowding, long travel, and air and noise pollution. Noise pollution was the main predictor of stress among commuters.
Conclusion: Poor transportation has adverse effects on health and academic performance. Administration in their respective jurisdictions is needed to investigate this matter to make commuting a routine rather than a hassle.
Vesicles and erosions in a patient with chronic eczema: is it just eczema?

Jamil A, Muthupalaniappen L

Ann Acad Med Singap, 2014 Feb;43(2):130-1.
PMID: 24652437
Fulltext Primary dapsone resistant Mycobacterium leprae in a non endemic country

Jamil A, Noor NM, Osman AS, Baseri MM, Muthupalaniappen L

Indian J Dermatol Venereol Leprol, 2013 Jul-Aug;79(4):527-9.
PMID: 23760326 DOI: 10.4103/0378-6323.113096
Invasive squamous cell carcinoma arising from chromoblastomycosis

Jamil A, Lee YY, Thevarajah S

Med Mycol, 2012 Jan;50(1):99-102.
PMID: 21449695 DOI: 10.3109/13693786.2011.571295

Chromoblastomycosis is a chronic subcutaneous mycosis seen mainly in tropical regions. While malignant transformation rarely occurs, the present report describes a 69-year-old man with a 21-year history of chromoblastomycosis complicated by invasive squamous cell carcinoma requiring amputation of the affected limb. A review of previous reported cases shows malignancy arising after 20-30 years of infection in ≥60-year-old males who have received inadequate treatment of chromoblastomycosis and have had relapses. An immunocompromised state is not an associated feature of such cases. The extremities are commonly affected as carcinomas occur from the most chronic lesions which are generally found on these limbs.
Development of an extended model for the permeation of environmentally hazardous CO2 gas across asymmetric hollow fiber composite membranes

Jamil A, Ching OP, Iqbal T, Rafiq S, Zia-Ul-Haq M, Shahid MZ, et al.

J Hazard Mater, 2021 Sep 05;417:126000.
PMID: 33992016 DOI: 10.1016/j.jhazmat.2021.126000

This study presents an extended thermodynamic and phenomenological combined model to mitigate the environmental hazardous acid gas over composite membranes. The model has been applied to an acid gas such as carbon dioxide (CO2) for its permeation through polyetherimide incorporated montmorillonite (Mt) nanoparticles hollow fiber asymmetric composite membranes. The well-established non-equilibrium lattice fluid (NELF) model for penetrating low molecular weight penetrant in a glassy polyetherimide (PEI) was extended to incorporate the other important polymer/filler system features such as tortuosity in acid gas diffusion pathways resulted from layered filler aspect ratio and concentration. The model mentioned above predicts the behavior of acid gas in PEI-Mt composite membranes based on thermodynamic characteristics of CO2 and PEI and tortuosity due to Mt. The calculated results are compared to experimentally determined values of CO2 permeability through PEI-Mt composite asymmetric hollow fiber membranes at varying transmembrane pressures and Mt concentrations. A reasonable agreement was found between the model predicted behavior and experimentally determined data in terms of CO2 solubility, Mt concentration and aspect ratio were calculated based on average absolute relative error (%AARE). The proposed modified model efficiently predicts the CO2 permeance across MMMs up to 3 wt% Mt loadings and 6 bar pressure with ± 10%AARE.

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