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  1. Fulltext HLA-Haploidentical Family Donors: The New Promise for Childhood Acute Lymphoblastic Leukaemia?
    Ab Rahman S, Matic T, Yordanova M, Ariffin H
    Front Pediatr, 2021;9:758680.
    PMID: 35127585 DOI: 10.3389/fped.2021.758680
    Allogeneic haematopoietic stem cell transplantation (HSCT) is indicated in children with high-risk, relapsed or refractory acute lymphoblastic leukaemia (ALL). HLA-matched grafts from cord blood and stem cell repositories have allowed patients without suitable sibling donors to undergo HSCT. However, challenges in procuring matched unrelated donor (MUD) grafts due to high cost, ethnic disparity and time constraints have led to the exponential rise in the use of stem cells from human leukocyte antigen (HLA)-haploidentical family donors. Whilst HLA-haploidentical HSCT (hHSCT) performed in adult patients with acute leukaemia has produced outcomes similar to MUD transplants, experience in children is limited. Over the last 5 years, more data have emerged on hHSCT in the childhood ALL setting, allowing comparisons with matched donor transplants. The feasibility of hHSCT using adult family donors in childhood ALL may also address the ethical issues related to selection of minor siblings in matched sibling donor transplants. Here, we review hHSCT in paediatric recipients with ALL and highlight the emergence of hHSCT as a promising therapeutic option for patients lacking a suitable matched donor. Recent issues related to conditioning regimens, donor selection and graft-vs.-host disease prophylaxis are discussed. We also identify areas for future research to address transplant-related complications and improve post-transplant disease-free survival.
  2. Improving the decolorization of glycerol by adsorption using activated carbon derived from oil palm biomass
    Ahmad Farid MA, Hassan MA, Roslan AM, Ariffin H, Norrrahim MNF, Othman MR, et al.
    Environ Sci Pollut Res Int, 2021 Jun;28(22):27976-27987.
    PMID: 33527241 DOI: 10.1007/s11356-021-12585-7
    This study provides insight into the decolorization strategy for crude glycerol obtained from biodiesel production using waste cooking oil as raw material. A sequential procedure that includes physico-chemical treatment and adsorption using activated carbon from oil palm biomass was investigated. The results evidenced decolorization and enrichment of glycerol go hand in hand during the treatment, achieving >89% color removal and > 98% increase in glycerol content, turning the glycerol into a clear (colorless) solution. This is attributed to the complete removal of methanol, free fatty acids, and triglycerides, as well as 85% removal of water, and 93% removal of potassium. Properties of the resultant glycerol met the quality standard of BS 2621:1979. The economic aspects of the proposed methods are examined to fully construct a predesign budgetary estimation according to chemical engineering principles. The starting capital is proportionate to the number of physical assets to acquire where both entail a considerable cost at USD 13,200. Having the benefit of sizeable scale production, it reasonably reduces the operating cost per unit product. As productivity sets at 33 m3 per annum, the annual operating costs amount to USD 79,902 in glycerol decolorization. This is translatable to USD 5.38 per liter glycerol, which is ~69% lower compared to using commercial activated carbon.
  3. Fulltext Subcritical Water-Carbon Dioxide Pretreatment of Oil Palm Mesocarp Fiber for Xylooligosaccharide and Glucose Production
    Ahmad N, Zakaria MR, Mohd Yusoff MZ, Fujimoto S, Inoue H, Ariffin H, et al.
    Molecules, 2018 May 30;23(6).
    PMID: 29848973 DOI: 10.3390/molecules23061310
    The present work aimed to investigate the pretreatment of oil palm mesocarp fiber (OPMF) in subcritical H₂O-CO₂ at a temperature range from 150⁻200 °C and 20⁻180 min with CO₂ pressure from 3⁻5 MPa. The pretreated solids and liquids from this process were separated by filtration and characterized. Xylooligosaccharides (XOs), sugar monomers, acids, furans and phenols in the pretreated liquids were analyzed by using HPLC. XOs with a degree of polymerization X2⁻X4 comprising xylobiose, xylotriose, xylotetraose were analyzed by using HPAEC-PAD. Enzymatic hydrolysis was performed on cellulose-rich pretreated solids to observe xylose and glucose production. An optimal condition for XOs production was achieved at 180 °C, 60 min, 3 MPa and the highest XOs obtained was 81.60 mg/g which corresponded to 36.59% of XOs yield from total xylan of OPMF. The highest xylose and glucose yields obtained from pretreated solids were 29.96% and 84.65%, respectively at cellulase loading of 10 FPU/g-substrate.
  4. Fulltext Mechanical Strength, Thermal Conductivity and Electrical Breakdown of Kenaf Core Fiber/Lignin/Polypropylene Biocomposite
    Ahmad Saffian H, Talib MA, Lee SH, Md Tahir P, Lee CH, Ariffin H, et al.
    Polymers (Basel), 2020 Aug 15;12(8).
    PMID: 32824275 DOI: 10.3390/polym12081833
    Mechanical strength, thermal conductivity and electrical breakdown of polypropylene/lignin/kenaf core fiber (PP/L/KCF) composite were studied. PP/L, PP/KCF and PP/L/KCF composites with different fiber and lignin loading was prepared using a compounding process. Pure PP was served as control. The results revealed that tensile and flexural properties of the PP/L/KCF was retained after addition of lignin and kenaf core fibers. Thermal stability of the PP composites improved compared to pure PP polymer. As for thermal conductivity, no significant difference was observed between PP composites and pure PP. However, PP/L/KCF composite has higher thermal diffusivity. All the PP composites produced are good insulating materials that are suitable for building. All PP composites passed withstand voltage test in air and oil state as stipulated in IEC 60641-3 except PP/L in oil state. SEM micrograph showed that better interaction and adhesion between polymer matrix, lignin and kenaf core fibers was observed and reflected on the better tensile strength recorded in PP/L/KCF composite. This study has successfully filled the gap of knowledge on using lignin and kenaf fibers as PP insulator composite materials. Therefore, it can be concluded that PP/Lignin/KCF has high potential as an insulating material.
  5. Fulltext Malaysian child infected with Plasmodium vivax via blood transfusion: a case report
    Anthony CN, Lau YL, Sum JS, Fong MY, Ariffin H, Zaw WL, et al.
    Malar J, 2013;12:308.
    PMID: 24007496 DOI: 10.1186/1475-2875-12-308
    Malaria may be a serious complication of blood transfusion due to the asymptomatic persistence of parasites in some donors. This case report highlights the transfusion-transmitted malaria of Plasmodium vivax in a child diagnosed with germ cell tumour. This child had received blood transfusion from three donors and a week later started developing malaria like symptoms. Nested PCR and sequencing confirmed that one of the three donors was infected with P. vivax and this was transmitted to the 12-year-old child. To the best of the authors' knowledge, this is the first reported transfusion-transmitted malaria case in Malaysia.
  6. Fulltext Griscelli syndrome
    Ariffin H, Geikowski A, Chin TF, Chau D, Arshad A, Abu Bakar K, et al.
    Med J Malaysia, 2014 Aug;69(4):193-4.
    PMID: 25500851 MyJurnal
    We report a case of Griscelli Syndrome (GS). Our patient initially presented with a diagnosis of haemophagocytic lymphistiocytosis (HLH). Subsequent microscopic analysis of the patient's hair follicle revealed abnormal distribution of melanosomes in the shaft, which is a hallmark for GS. Analysis of RAB27A gene in this patient revealed a homozygous mutation in exon 6, c.550C>T, p.R184X . This nonsense mutation causes premature truncation of the protein resulting in a dysfunctional RAB27A. Recognition of GS allows appropriate institution of therapy namely chemotherapy for HLH and curative haemotopoeitic stem cell transplantation.
  7. Chemical recycling of polyhydroxyalkanoates as a method towards sustainable development
    Ariffin H, Nishida H, Hassan MA, Shirai Y
    Biotechnol J, 2010 May;5(5):484-92.
    PMID: 20408140 DOI: 10.1002/biot.200900293
    Chemical recycling of bio-based polymers polyhydroxyalkanoates (PHAs) by thermal degradation was investigated from the viewpoint of biorefinery. The thermal degradation resulted in successful transformation of PHAs into vinyl monomers using alkali earth compound (AEC) catalysts. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)s (PHBVs) were smoothly and selectively depolymerized into crotonic (CA) and 2-pentenoic (2-PA) acids at lower degradation temperatures in the presence of CaO and Mg(OH)(2) as catalysts. Obtained CA from 3-hydroxybutyrate sequences in PHBV was copolymerized with acrylic acid to produce useful water-soluble copolymers, poly(crotonic acid-co-acrylic acid) that have high glass-transition temperatures. The copolymerization of CA derived from PHA pyrolysis is an example of cascade utilization of PHAs, which meets the idea of sustainable development.
  8. GATA1 mutations in patients with down syndrome and acute megakaryoblastic leukaemia do not always confer a good prognosis
    Ariffin H, Garcia JC, Daud SS, Ibrahim K, Aizah N, Ong GB, et al.
    Pediatr Blood Cancer, 2009 Jul;53(1):108-11.
    PMID: 19260099 DOI: 10.1002/pbc.21983
    Children with Down syndrome and acute megakaryoblastic leukemia (DS-AMKL) have been shown to have increased sensitivity to cytarabine based chemotherapy. The excellent prognosis in patients with DS-AMKL may be due to mutations in the GATA1 gene leading to reduced expression of the enzyme cytidine deaminase. This leads to a decreased ability to convert cytarabine into its inactive metabolite, resulting in high intracellular concentration of this cytotoxic agent. We report two cases of DS-AMKL with GATA1 mutations who had poor outcome. These patients had high expression levels of cytidine deaminase mRNA transcripts. We speculate that other factors can affect overall outcome in patients with DS-AMKL irrespective of the presence of GATA1 mutations.
  9. Production of bacterial endoglucanase from pretreated oil palm empty fruit bunch by bacillus pumilus EB3
    Ariffin H, Hassan MA, Shah UK, Abdullah N, Ghazali FM, Shirai Y
    J Biosci Bioeng, 2008 Sep;106(3):231-6.
    PMID: 18929997 DOI: 10.1263/jbb.106.231
    In this study, endoglucanase was produced from oil palm empty fruit bunch (OPEFB) by a locally isolated aerobic bacterium, Bacillus pumilus EB3. The effects of the fermentation parameters such as initial pH, temperature, and nitrogen source on the endoglucanase production were studied using carboxymethyl cellulose (CMC) as the carbon source. Endoglucanase from B. pumilus EB3 was maximally secreted at 37 degrees C, initial pH 7.0 with 10 g/l of CMC as carbon source, and 2 g/l of yeast extract as organic nitrogen source. The activity recorded during the fermentation was 0.076 U/ml. The productivity of the enzyme increased twofold when 2 g/l of yeast extract was used as the organic nitrogen supplement as compared to the non-supplemented medium. An interesting finding from this study is that pretreated OPEFB medium showed comparable results to CMC medium in terms of enzyme production with an activity of 0.063 U/ml. As OPEFB is an abundant solid waste at palm oil mills, it has the potential of acting as a substrate in cellulase production.
  10. Li-Fraumeni syndrome in a Malaysian kindred
    Ariffin H, Martel-Planche G, Daud SS, Ibrahim K, Hainaut P
    Cancer Genet. Cytogenet., 2008 Oct;186(1):49-53.
    PMID: 18786442 DOI: 10.1016/j.cancergencyto.2008.06.004
    We report on a Malaysian kindred with Li-Fraumeni syndrome. The proband was an 8-year-old girl who presented with embryonal rhabdomyosarcoma of the trunk at the age of 8 months and developed a brain recurrence at the age of 7 years, which was 5 years after remission. A younger sister later developed adrenocortical carcinoma at the age of 6 months. Their mother and maternal grandmother were diagnosed with breast cancer at the ages of 26 and 38 years, respectively. TP53 mutation detection in this family revealed a duplication of a GGCGTG motif starting at nucleotide 17579 in exon 10, resulting in an in-frame insertion of two amino acids between residues 334 and 336 in the tetramerization domain of the p53 protein. This mutation was found in the proband and her affected sister as well as her mother. In addition, the mutation was detected in two other siblings (a brother aged 3 years and a sister aged 18 months) who have not yet developed any malignancy. Sequencing of TP53 in the father and two other asymptomatic siblings revealed wild-type TP53. To our knowledge, this is a first report of a Li-Fraumeni syndrome family in Southeast Asia.
  11. Ethnic differences in the frequency of subtypes of childhood acute lymphoblastic leukemia: results of the Malaysia-Singapore Leukemia Study Group
    Ariffin H, Chen SP, Kwok CS, Quah TC, Lin HP, Yeoh AE
    J Pediatr Hematol Oncol, 2007 Jan;29(1):27-31.
    PMID: 17230064
    Childhood acute lymphoblastic leukemia (ALL) is clinically heterogeneous with prognostically and biologically distinct subtypes. Although racial differences in frequency of different types of childhood ALL have been reported, many are confounded by selected or limited population samples. The Malaysia-Singapore (MA-SPORE) Leukemia Study Group provided a unique platform for the study of the frequency of major subgroups of childhood ALL in a large cohort of unselected multiethnic Asian children. Screening for the prognostically important chromosome abnormalities (TEL-AML1, BCR-ABL, E2A-PBX1, and MLL) using multiplex reverse-transcription polymerase chain reaction was performed on 299 consecutive patients with ALL at 3 study centers (236 de novo, 63 at relapse), with the ethnic composition predominantly Chinese (51.8%) and Malay (34.8%). Reverse-transcription polymerase chain reaction was successful in 278 (93%) of cases screened. The commonest fusion transcript was TEL-AML1 (19.1%) followed by BCR-ABL (7.8%), MLL rearrangements (4.2%), and E2A-PBX1 (3.1%). Chinese have a significantly lower frequency of TEL-AML1 (13.3% in de novo patients) compared with Malays (22.2%) and Indians (21.7%) (P=0.04). Malays have a lower frequency of T-ALL (6.2%) compared with the Chinese and Indians (9.8%). Both Malays (7.4%) and Chinese (5.0%) have significantly higher frequency of BCR-ABL compared with the Indian population (P<0.05) despite a similar median age at presentation. Our study suggests that there are indeed significant and important racial differences in the frequency of subtypes of childhood ALL. Comprehensive subgrouping of childhood ALL may reveal interesting population frequency differences of the various subtypes, their risk factors and hopefully, its etiology.
  12. Cefepime monotherapy for treatment of febrile neutropenia in children
    Ariffin H, Ai CL, Lee CL, Abdullah WA
    J Paediatr Child Health, 2006 Dec;42(12):781-4.
    PMID: 17096713
    Empirical therapy for children with febrile neutropenia has traditionally consisted of combination antibiotics, usually a beta-lactam and an aminoglycoside. However, recent trends and international guidelines have now made monotherapy a feasible option in the management of this group of patients. We prospectively evaluated the efficacy and safety of cefepime monotherapy in our population of paediatric cancer patients with febrile neutropenia.
  13. Haemophagocytic lymphohistiocytosis in Malaysian children
    Ariffin H, Lum SH, Cheok SA, Shekhar K, Ariffin WA, Chan LL, et al.
    J Paediatr Child Health, 2005 Mar;41(3):136-9.
    PMID: 15790325
    To study the clinical presentation, therapy and outcome of children diagnosed with both primary and secondary haemophagocytic lymphohistiocytosis (HLH) at the University of Malaya Medical Centre.
  14. Surveillance blood counts for early detection of relapse in acute lymphoblastic leukemia
    Ariffin H, Lim HL
    Pediatr Blood Cancer, 2005 Aug;45(2):229.
    PMID: 15768379
  15. Prenatal exclusion of severe factor VII deficiency
    Ariffin H, Millar DS, Cooper DN, Chow T, Lin HP
    J Pediatr Hematol Oncol, 2003 May;25(5):418-20.
    PMID: 12759632
    A nonconsanguineous asymptomatic couple, were identified as carriers of factor VII (FVII) deficiency when two of their newborn children died of massive intracranial hemorrhage secondary to severe congenital FVII deficiency. Complete sequence analysis of the factor VII (F7) gene in this couple indicated that the mother was heterozygous for an A to G transition at position -2 of the exon 5 acceptor splice site, and the father was heterozygous for a G to T transversion at position +1 of the exon 6 donor splice site. This information allowed us to exclude a compound heterozygous deficiency state in a subsequent pregnancy using PCR/direct sequencing of the F7 gene using DNA obtained from chorionic villi at 10 weeks' gestation. Our experience with the family reported here further supports the conclusion that mutation-specific detection is reliable in the prenatal exclusion of severe bleeding disorders.
  16. Ceftazidime-resistant Klebsiella pneumoniae bloodstream infection in children with febrile neutropenia
    Ariffin H, Navaratnam P, Mohamed M, Arasu A, Abdullah WA, Lee CL, et al.
    Int J Infect Dis, 2000;4(1):21-5.
    PMID: 10689210
    OBJECTIVES: To evaluate prevalence of ceftazidime-resistant Klebsiella pneumoniae (CRKP) in the pediatric oncology unit of University Hospital, Kuala, Lumpur, and to identify differences between febrile neutropenic pediatric patients with CRKP and ceftazidime-sensitive K. pneumoniae (CSKP) bacteremia.

    MATERIALS AND METHODS: Febrile neutropenic patients treated between January 1996 and December 1997 at the pediatric oncology unit of University Hospital, Kuala Lumpur, were prospectively studied. Empirical antibiotic therapy consisted of ceftazidime and amikacin. Those who developed K. pneumoniae bacteremia were identified, and clinical features analyzed. Ceftazidime-resistance was documented via disk-diffusion testing. Production of extended-spectrum beta-lactamase (ESBL) was inferred on the basis of synergy between ceftazidime and amoxicillin-clavulanic acid. The different features between the two groups and variables associated with the development of CRKP bacteremia were analyzed using chi-square and t-tests and calculation of odds ratios. A multivariate analysis was used to identify independent factors for CRKP development.

    RESULTS: Ceftazidime-resistance was seen in 51.6% of all K. pneumoniae isolates, and all these isolates were inferred to be ESBL producers. All isolates were sensitive to imipenem. Susceptibility to gentamicin was 90.5%. The mean continuous hospital stay prior to the detection of bacteremia was 13.7 days overall, but significantly longer in the CRKP group (21.9 d) compared to the CSKP group (4.3 d) (P = 0.003). Children with CRKP were more likely to have received antibiotics in the 2 weeks prior to detection of bacteremia (87.5% of cases) than the CSKP group (20.0% of cases) (P = 0.0008). Sepsis-related mortality was higher in those with CRKP (50.0%) than in the CSKP group (13.3%) (P = 0.02). Patients who did not receive CRKP-directed antibiotics within 48 hours of admission were more likely to have a fatal outcome than those who did (P = 0.009). Logistic regression analysis identified use of third-generation cephalosporins 2 weeks prior to presentation and a hospital stay of 2 weeks or more as independent risk factors for development of CRKP.

    CONCLUSIONS: More than half of total K. pneumoniae isolated from blood cultures in the unit were ceftazidime-resistant. Children with febrile neutropenia with prolonged hospital stay and recent prior antibiotic exposure are at high risk of developing CRKP bacteremia. Mortality was significantly higher in this group. Early commencement of appropriate antibiotics (e.g., imipenem with or without gentamicin), according to susceptibility study results, may be beneficial in such circumstances.

  17. Single-daily ceftriaxone plus amikacin versus thrice-daily ceftazidime plus amikacin as empirical treatment of febrile neutropenia in children with cancer
    Ariffin H, Arasu A, Mahfuzah M, Ariffin WA, Chan LL, Lin HP
    J Paediatr Child Health, 2001 Feb;37(1):38-43.
    PMID: 11168867
    OBJECTIVE: Empirical antibiotic treatment for febrile neutropenic patients has been the mainstay of treatment for many years. Beta-lactam antibiotics and aminoglycosides have been the most frequently used drug combination. The purpose of this study was to evaluate the efficacy, safety, tolerance and costs of single-daily ceftriaxone plus amikacin versus thrice-daily dose of ceftazidime plus amikacin.

    METHODOLOGY: One hundred and ninety-one episodes of fever and neutropenia in 128 patients from October 1997 to December 1998 were included in a prospective, open-label, single-centre study. Patients were randomly assigned to either treatment group and evaluated as successes or failures according to defined criteria. Daily assessments were made on all patients and all adverse events recorded. Univariate and multivariate analysis of outcomes and a cost analysis were carried out.

    RESULTS: There were 176 evaluable patient-episodes with 51.1% in the single-daily ceftriaxone-amikacin group and 48.9% in the ceftazidime-amikacin group. There were 50 positive blood cultures: 12 Gram-positive bacteria, 33 Gram-negative bacteria and five fungi. Pseudomonas aeruginosa (P. aeruginosa) accounted for 14% of total isolates. The overall success rate was 55.5% in the ceftriaxone group compared to 51.2% in the ceftazidime group (P = 0.56). Mean time to defervescence was 4.2 days in the single-daily group and 4.3 days in the thrice-daily group. There were nine infection-related deaths; five in the single-daily ceftriaxone group. The daily cost of the once-daily regime was 42 Malaysian Ringgit less than the thrice-daily regime. There was a low incidence of adverse effects in both groups, although ototoxicity was not evaluable.

    CONCLUSIONS: The once-daily regime of ceftriaxone plus amikacin was as effective as the 'standard' combination of thrice-daily ceftazidime and amikacin with no significant adverse effects in either group. The convenience and substantial cost benefit of the once-daily regime will be particularly useful in developing countries with limited health resources and in centres with a low prevalence of P. aeruginosa.

  18. Surveillance study of bacteraemic episodes in febrile neutropenic children
    Ariffin H, Navaratnam P, Lin HP
    Int J Clin Pract, 2002 May;56(4):237-40.
    PMID: 12074201
    We prospectively studied the type, frequency and outcome of infections in 513 patients with 762 consecutive episodes of febrile neutropenia (FN) over a five-year period between 1995 and 1999 in a single paediatric oncology unit. The findings were then compared with a similar study carried out in our unit between 1990 and 1994. The types of bacterial isolates and sensitivity patterns were also studied to identify trends and to gauge the suitability of antibiotics chosen for empirical therapy. Bacteraemia was documented in 35.4% of FN episodes, although 70% of patients did not have an obvious site of sepsis. The majority of isolates (61.9%) were gram-negative bacteria, a consistent finding throughout the study period. Resistance to ceftazidime, amikacin and imipenem among gram-negative bacteria was 26.3%, 21.2% and 0.7%, respectively. Methicillin resistance among gram-positive bacteria was 26.3%, while no vancomycin-resistant bacteria were encountered. There were 36 sepsis-related deaths. Factors associated with a fatal outome were prolonged capillary refill time, hypotension, fever above 39 degrees C and pneumonia. Rapid neutrophil recovery was associated with a good prognosis. A change to our current choice of empirical antibiotics for FN, comprising ceftazidime/ceftriaxone and amikacin appears necessary because of the relatively high resistance rates found.
  19. Fulltext Infantile myofibromatosis
    Ariffin H, Teh KH, Looi LM, Ariffin WA, Lin HP
    Med J Malaysia, 2001 Dec;56(4):497-9.
    PMID: 12014771
    Infantile myofibromatosis (IMF) is a rare tumour with a wide spectrum of disease activity ranging from a solitary cutaneous nodule through to a multicentric form with widespread visceral involvement. It is characterised by its unique ability to spontaneously regress and has a typical histological appearance of actin-positive fibroblasts arranged in whorls or fascicles and vessels in a pericytomatous pattern. A male infant with multiple lesions involving the subcutaneous tissue and bone from birth is described and followed-up for two years. Treatment of IMF is dependent on the location of the tumour/s with surgery or chemotherapy reserved for rapidly progressive or symptomatic disease. However, due to the low rate of recurrence and the possibility of spontaneous tumoral regression, therapeutic abstention, as practised in our patient, is justified.
  20. Fulltext Second malignant neoplasms: an increasingly recognized complication of childhood cancer
    Ariffin H, Ariffin WA, Chan LL, Lam SK, Lin HP
    Med J Malaysia, 1997 Jun;52(2):174-7.
    PMID: 10968078
    Second malignant neoplasms (SMN) are an increasingly recognized late complication seen in childhood cancer survivors. A total of 3 cases of SMN have been found in the Department of Paediatrics, University Hospital Kuala Lumpur after a 15-year experience of treating childhood malignancies. Two cases are described here. The first developed abdominal non-Hodgkin's lymphoma 3 years after undergoing an allogeneic bone marrow transplant for second relapse of acute lymphoblastic leukaemia, while the second child developed myeloid leukaemia two years after completing treatment for acute lymphoblastic leukaemia. Progress in the management of childhood cancer in Malaysia and the availability of bone marrow transplantation facilities have increased the number of childhood cancer survivors; leading to increased incidence of SMN.
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