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Heterogeneity in alpha-thalassemia interactions in Malays, Chinese and Indians in Malaysia

Wee YC, Tan KL, Chow TW, Yap SF, Tan JA

J Obstet Gynaecol Res, 2005 Dec;31(6):540-6.
PMID: 16343256 DOI: 10.1111/j.1447-0756.2005.00333.x

AIM: Interactions between different determinants of alpha-thalassemia raises considerable problems, particularly during pregnancies where antenatal diagnosis is necessary. This study aims to determine the different types of deletional alpha-thalassemia and Hemoglobin Constant Spring (HbCS), and their frequency in Malays, Chinese and Indians in Malaysia.
METHODS: DNA from 650 pregnant women from the Antenatal Clinic of the University of Malaya Medical Center in Kuala Lumpur, Malaysia who showed mean cell volume < or =89 fL and/or mean cell hemoglobin < or =28 pg were analyzed for the double alpha-globin gene South-East Asian deletion (--SEA), the -alpha3.7 and -alpha4.2 single alpha-globin gene deletions and HbCS.
RESULTS: One hundred and three (15.8%) of the pregnant women were confirmed as alpha-thalassemia carriers: 25 (3.8%) were alpha-thalassemia-1 carriers with the --SEA/alphaalpha genotype, 64 (9.8%) were heterozygous for the -alpha3.7 rightward deletion (-alpha3.7/alphaalpha), four (0.6%) were heterozygous for the -alpha4.2 leftward deletion (-alpha4.2/alphaalpha), nine (1.4%) were heterozygous for HbCS (alphaCSalpha/alphaalpha) and one (0.2%) was compound heterozygous with the -alpha3.7/alphaCSalpha genotype. The double alpha-globin gene --SEA deletion was significantly higher in the Chinese (15%) compared to the Malays (2.5%) and not detected in the Indians studied. The -alpha3.7 deletion was distributed equally in the three races. HbCS and -alpha4.2 was observed only in the Malays.
CONCLUSION: The data obtained gives a better understanding of the interactions of the different alpha-thalassemia determinants in the different ethnic groups, thus enabling more rapid and specific confirmation of alpha-thalassemia in affected pregnancies where antenatal diagnosis is necessary.
Study site: Antenatal clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
Fulltext Rapid and cost-effective antenatal diagnosis of haemoglobin Bart's hydrops foetalis syndrome using a duplex-polymerase chain reaction

Wee YC, Tan KL, Tan PC, Yap SF, Tan JAMA

Med J Malaysia, 2005 Oct;60(4):447-53.
PMID: 16570706

Haemoglobin Bart's hydrops foetalis syndrome (--SEA/--SEA) is not compatible with life and contributes to a majority of the hydropic foetuses in the Malaysian Chinese alpha-thalassaemia carriers who possess the 2-alpha-gene deletion in cis (--SEA/alphaalpha). A duplex-PCR which simultaneously amplifies a normal 136 bp sequence between the psialpha-alpha2-globin genes and a 730 bp Southeast Asian deletion-specific sequence (--SEA) between the psialpha2-theta1-globin genes was established. The duplex-PCR which detects the --SEA deletion in both chromosomes serves as a rapid and cost-effective confirmatory test in the antenatal diagnosis of Haemoglobin Bart's hydrops foetalis syndrome in Malaysia. In addition, the duplex-PCR is simple to perform as both the normal and deletion-specific alpha-globin gene sequences are amplified in the same PCR reaction.
Fulltext The use of the amplification refractory mutation system (arms) in the detection of rare beta-thalassemia mutations in the Malays and Chinese in Malaysia

Chan YF, Tan KL, Wong YC, Wee YC, Yap SF, Tan JAMA

Southeast Asian J. Trop. Med. Public Health, 2001 Dec;32(4):872-9.
PMID: 12041567

Molecular characterization and prenatal diagnosis for beta-thalassemia can be carried out using the Amplification Refractory Mutation System (ARMS). The ARMS is a rapid and direct molecular technique in which beta-thalassemia mutations are visualized immediately after DNA amplification by gel electrophoresis. In the University of Malaya Medical Center, molecular characterization and prenatal diagnosis for beta-thalassemia is carried out using ARMS for about 96% of the Chinese and 84.6% of the Malay patients. The remaining 4% and 15.4% of the uncharacterized mutations in the Chinese and Malay patients respectively are detected using DNA sequencing. DNA sequencing is an accurate technique but it is more time-consuming and expensive compared with the ARMS. The ARMS for the rare Chinese beta-mutations at position -29 (A-->G) and the ATG-->AGG base substitution at the initiator codon for translation in the beta-gene was developed. In the Malays, ARMS was optimized for the beta-mutations at codon 8/9 (+G), Cap (+1) (A-->C) and the AATAAA-->AATAGA base substitution in the polyadenylation region of the beta-gene. The ARMS protocols were developed by optimization of the parameters for DNA amplification to ensure sensitivity, specificity and reproducibility. ARMS primers (sequences and concentration), magnesium chloride concentration, Taq DNA polymerase and PCR cycling parameters were optimized for the specific amplification of each rare beta-thalassemia mutation. The newly-developed ARMS for the 5 rare beta-thalassemia mutations in the Chinese and Malays in Malaysia will allow for more rapid and cost-effective molecular characterization and prenatal diagnosis for beta-thalassemia in Malaysia.
Mild beta-thalassemia intermedia caused by compound heterozygosity for (G)gamma((A)gammadeltabeta)(o)/beta-thalassemia and molecular characterization of the defect in four Chinese families

Tan JAMA, Yap SF, Tan KL, Wong YC, Wee YC, Kok JL

Acta Haematol., 2003;109(4):169-75.
PMID: 12853688 DOI: 10.1159/000070965

Molecular characterization of the compound heterozygous condition - (G)gamma((A)gammadeltabeta)(o)/beta-thalassemia - in four families showing mild beta-thalassemia intermedia was carried out using DNA amplification techniques. Using the Amplification Refractory Mutation System (ARMS) to confirm the beta-mutations and DNA amplification to detect the 100-kb Chinese-specific (G)gamma((A)gammadeltabeta)(o)-deletion, ()two families were confirmed to possess (G)gamma((A)gammadeltabeta)(o)/beta-thalassemia with the IVSII No. 654 beta(+)-allele. In the third family, the (G)gamma((A)gammadeltabeta)(o)-deletion was confirmed in the father and the mother was a beta-thalassemia carrier with the cd 41-42 beta(o)-allele. Their affected child with (G)gamma((A)gammadeltabeta)(o)/beta-thalassemia was found to be transfusion dependent. The same (G)gamma((A)gammadeltabeta)(o)-deletion and beta-thalassemia (cd 41-42) was also confirmed in a fourth family. In addition, the mother was also diagnosed with Hb H disease (genotype -alpha(3.7)/-(SEA)). Both the children were found to possess (G)gamma((A)gammadeltabeta)(o)/beta-thalassemia but they were not transfusion dependent and this could be due to co-inheritance of alpha-thalassemia-2 (genotype-alpha(3.7)/alphaalpha) in the children together with their compound heterozygous condition.
Combine-ARMS: a rapid and cost-effective protocol for molecular characterization of beta-thalassemia in Malaysia

Tan KL, Tan JA, Wong YC, Wee YC, Thong MK, Yap SF

Genet. Test., 2001;5(1):17-22.
PMID: 11336396 DOI: 10.1089/109065701750168626

Beta-thalassemia major patients have chronic anemia and are dependent on blood transfusions to sustain life. Molecular characterization and prenatal diagnosis of beta3-thalassemia is essential in Malaysia because about 4.5% of the population are heterozygous carriers for beta-thalassemia. The high percentage of compound heterozygosity (47.62%) found in beta-thalassemia major patients in the Thalassaemia Registry, University of Malaya Medical Centre (UMMC), Malaysia, also supports a need for rapid, economical, and sensitive protocols for the detection of beta-thalassemia mutations. Molecular characterization of beta-thalassemia mutations in Malaysia is currently carried out using ARMS, which detects a single beta-thalassemia mutation per PCR reaction. We developed and evaluated Combine amplification refractory mutation system (C-ARMS) techniques for efficient molecular detection of two to three beta-thalassemia mutations in a single PCR reaction. Three C-ARMS protocols were evaluated and established for molecular characterization of common beta-thalassemia mutations in the Malay and Chinese ethnic groups in Malaysia. Two C-ARMS protocols (cd 41-42/IVSII #654 and -29/cd 71-72) detected the beta-thalassemia mutations in 74.98% of the Chinese patients studied. The CARMS for cd 41-42/IVSII #654 detected beta-thalassemia mutations in 72% of the Chinese families. C-ARMS for cd 41-42/IVSI #5/cd 17 allowed detection of beta-thalassemia mutations in 36.53% of beta-thalassemia in the Malay patients. C-ARMS for cd 41-42/IVSI #5/cd 17 detected beta-thalassemia in 45.54% of the Chinese patients. We conclude that C-ARMS with the ability to detect two to three mutations in a single reaction provides more rapid and cost-effective protocols for beta-thalassemia prenatal diagnosis and molecular analysis programs in Malaysia.
Interaction of Hb South Florida (codon 1; GTG-->ATG) and HbE, with beta-thalassemia (IVS1-1; G-->A): expression of different clinical phenotypes

Tan JA, Tan KL, Omar KZ, Chan LL, Wee YC, George E

Eur J Pediatr, 2009 Sep;168(9):1049-54.
PMID: 19034506 DOI: 10.1007/s00431-008-0877-9

INTRODUCTION: Interactions of different hemoglobin variants with thalassemia alleles can result in various clinical phenotypes. HbE-beta-thalassemia generally manifests with severe anemia where individuals exhibit beta-thalassemia major with regular blood transfusions or beta-thalassemia intermedia with periodic blood transfusions. This study presents a unique Malay family with three beta-globin gene defects-HbE, Hb South Florida, and IVS1-1 (G-->A).
MATERIALS AND METHODS: HbE activates a cryptic splice site that produces non-functional mRNAs. Hb South Florida is a rare beta-hemoglobin variant, and its interactions with other beta-thalassemia alleles have not been reported. IVS1-1 is a Mediterranean mutation that affects mRNA processing giving rise to beta(o)-thalassemia.
RESULTS AND DISCUSSION: Fifteen mutations along the beta-globin gene complex were analyzed using the amplification refractory mutation system. Hb South Florida was identified by direct sequencing using genomic DNA.
CONCLUSION: The affected child with HbE/IVS1-1 produced a beta-thalassemia major phenotype. Compound heterozygosity for Hb South Florida/IVS1-1 produced a beta-thalassemia carrier phenotype in the mother.
Fulltext Enhanced Contextual Fear Memory and Elevated Astroglial Glutamate Synthase Activity in Hippocampal CA1 BChE shRNA Knockdown Mice

Chen S, Lin Z, Tan KL, Chen R, Su W, Zhao H, et al.

Front Psychiatry, 2020;11:564843.
PMID: 33061920 DOI: 10.3389/fpsyt.2020.564843

Butyrylcholinesterase (BChE) efficiently hydrolyzes acetylcholine (ACh) at high concentrations when acetylcholinesterase (AChE) is substrate-inhibited. Recent studies have shown that BChE also has a function that is independent of ACh, but it has not been fully explored. Low BChE expression is accompanied with higher stress-induced aggression and ghrelin levels in stress models, and BChE knockout mice exhibit cognitive and memory impairments. However, the role of BChE in posttraumatic stress disorder (PTSD) remains unclear. In the present study, we investigated the role of BChE in contextual fear memory and its regulatory effect on the expression of factors related to the glutamate (Glu)-glutamine (Gln) cycle via knockdown studies. We used AAVs and lentiviruses to knockdown BChE expression in the mouse hippocampal CA1 region and C8D1A astrocytes. Our behavioral data from those mice injected with AAV-shBChE in the hippocampal CA1 region showed strengthened fear memory and increased dendritic spine density. Elevated Glu levels and glutamine synthetase (GS) enzyme activity were detected in contextual fear conditioned-BChE knockdown animals and astrocytes. We observed that an AAV-shBChE induced lowering of BChE expression in the hippocampus CA1 region enhanced contextual fear memory expression and promoted the astrocytic Glu-Gln cycle but did not elevate ACh-hydrolyzing activity. This study provides new insight into the regulatory role of BChE in cognition and suggests potential target for stress-related psychiatric disorder such as PTSD where patients experience fear after exposure to severe life-threatening traumatic events.
Fulltext Brachytherapy of tongue carcinoma in a patient with difficult airway: anesthetic considerations

Ghaffar ZA, Chong SE, Tan KL, Appalanaido GK, Musa MY, Hussin HB, et al.

J Contemp Brachytherapy, 2018 Dec;10(6):573-576.
PMID: 30662482 DOI: 10.5114/jcb.2018.79856

The practice of brachytherapy in unresectable tongue carcinoma is gaining popularity. However, this procedure poses specific anesthetic challenges, particularly challenges of airway sharing and a higher rate of difficult airway. We report a 74-year-old chronic smoker, chronic alcoholic with history of stroke, who had undergone brachytherapy for tongue carcinoma. Apart from a huge tongue tumor, he had an epiglottic mass but refused elective tracheostomy. This had led to a few critical states throughout the process of treatment, including a metabolic crisis due to thiamine deficiency and difficult airway crisis. To our best knowledge, there have been no reported case on a patient with vocal cord mass undergoing tongue brachytherapy. We hope sharing of this experience may aid the management of similar patients in future.
Fulltext Prevalence and Factors Associated with Suicidal Ideation in Institutionalized Patients with Schizophrenia

Chong BTW, Wahab S, Muthukrishnan A, Tan KL, Ch'ng ML, Yoong MT

Psychol Res Behav Manag, 2020;13:949-962.
PMID: 33204188 DOI: 10.2147/PRBM.S266976

Purpose: The shorter life expectancy and increased risk of suicide in patients with schizophrenia have been well documented. However, study outcomes on suicidality in this special population have been few to date. This study investigated the prevalence and factors associated with suicidal ideation in a population of institutionalized patients with schizophrenia.
Methods: Two hundred fifty-six patients with schizophrenia between the age of 18 and 65 years were randomly recruited. This cross-sectional study utilised the Calgary Depression Scale for Schizophrenia (CDSS), the Positive and Negative Syndrome Scale (PANSS) and the Psychotic Symptom Rating Scale (PSYRATS-AH). Univariate analysis was performed using an independent t-test or chi-square test, followed by binary logistic regression to determine the factors associated with increased suicidal risks.
Results: The socio-demographic factors associated with suicidal ideation included level of education (p=0.039); secondary-level education (OR=5.76, 95% CI:1.49, 22.34, p=0.011) and tertiary-level education (OR=9.30, 95% CI: 1.80, 48.12, p=0.008) posed a greater risk. A history of attempted suicide (OR=2.09, 95% CI: 1.01, 4.36, p=0.049) and the presence of co-morbid physical illnesses (OR=2.07, 95% CI: 1.02, 4.21, p=0.044) were also found to be associated with a suicidal ideation. Other significant factors associated with suicidal thoughts were concurrent depression (OR=9.68, 95% CI: 3.74, 25.05, p<0.001) and a higher PSYRATS score in emotional characteristics of auditory hallucinations (OR=1.13, 95% CI: 1.06, 1.21, p<0.001).
Conclusion: Suicide in schizophrenia appears to be more closely associated with certain socio-demographic factors and affective symptoms. Appropriate screening and treatment addressing these challenges must be emphasized if suicidal thoughts and actions are to be reduced.
Characterisation and confirmation of rare beta-thalassaemia mutations in the Malay, Chinese and Indian ethnic groups in Malaysia

Tan JA, Chin PS, Wong YC, Tan KL, Chan LL, George E

Pathology, 2006 Oct;38(5):437-41.
PMID: 17008283

In Malaysia, about 4.5% of the Malay and Chinese populations are heterozygous carriers of beta-thalassaemia. The initial identification of rare beta-globin gene mutations by genomic sequencing will allow the development of simpler and cost-effective PCR-based techniques to complement the existing amplification refractory mutation system (ARMS) and gap-PCR used for the identification of beta-thalassaemia mutations.
Compliance with WHO IYCF Indicators and Dietary Intake Adequacy in a Sample of Malaysian Infants Aged 6-23 Months

Khor GL, Tan SY, Tan KL, Chan PS, Amarra MS

Nutrients, 2016 Dec 01;8(12).
PMID: 27916932

BACKGROUND: The 2010 World Health Organisation (WHO) Infant and Young Child Feeding (IYCF) indicators are useful for monitoring feeding practices.
METHODS: A total sample of 300 subjects aged 6 to 23 months was recruited from urban suburbs of Kuala Lumpur and Putrajaya. Compliance with each IYCF indicator was computed according to WHO recommendations. Dietary intake based on two-day weighed food records was obtained from a sub-group (N = 119) of the total sample. The mean adequacy ratio (MAR) value was computed as an overall measure of dietary intake adequacy. Contributions of core IYCF indicators to MAR were determined by multinomial logistic regression.
RESULTS: Generally, the subjects showed high compliance for (i) timely introduction of complementary foods at 6 to 8 months (97.9%); (ii) minimum meal frequency among non-breastfed children aged 6 to 23 months (95.2%); (iii) consumption of iron-rich foods at 6 to 23 months (92.3%); and minimum dietary diversity (78.0%). While relatively high proportions achieved the recommended intake levels for protein (87.4%) and iron (71.4%), lower proportions attained the recommendations for calcium (56.3%) and energy (56.3%). The intake of micronutrients was generally poor. The minimum dietary diversity had the greatest contribution to MAR (95% CI: 3.09, 39.87) (p = 0.000) among the core IYCF indicators.
CONCLUSION: Malaysian urban infants and toddlers showed moderate to high compliance with WHO IYCF indicators. The robustness of the analytical approach in this study in quantifying contributions of IYCF indicators to MAR should be further investigated.
Total percutaneous endovascular aneurysm repair (pEVAR): the initial experience in Hospital Kuala Lumpur

Leong BDK, Govindarajanthran N, Hafizan TM, Tan KL, Hanif H, Zainal AA

Med J Malaysia, 2017 04;72(2):91-93.
PMID: 28473670 MyJurnal

INTRODUCTION: There has been a paradigm shift in the treatment of AAA with the advent of endovascular aneurysm repair (EVAR). Rapid progress and evolution of endovascular technology has brought forth smaller profile devices and closure devices. Total percutaneous endovascular aneurysm repair (pEVAR) involves the usage of suture-mediated closure devices (SMCDs) at vascular access sites to avoid a traditional surgical cutdown.
MATERIALS AND METHODS: We retrospectively reviewed our experience of pEVAR between April 2013 and July 2014. Primary success of the procedure was defined as closure of a common femoral artery (CFA) arteriotomy without the need for any secondary surgical or endovascular procedure within 30 days.
RESULTS: In total there were 10 pEVAR cases performed in the study period, one case in Queen Elizabeth Hospital during visiting vascular service. Patients have a mean age of 73.4 year old (66-77 year old) The mean abdominal aortic size was 7.2 cm (5.6-10.0cm). Mean femoral artery diameter was 9.0 mm on the right and 8.9 mm on the left. Mean duration of surgery was 119 minutes (98- 153 minutes). 50% of patients were discharged at post-operative day one, 30%- day two and 20%- day three. Primary success was achieved in 9 patients (90%) or in 19 CFA closures (95%). No major complication was reported.
DISCUSSION: We believe that with proper selection of patients undergoing EVAR, pEVAR offers a better option of vascular access with shorter operative time, less post- operative pain, shorter hospital stay and minimises the potential complications of a conventional femoral cutdown.
Fulltext Effect of chlorhexidine pretreatment on bacterial contamination at rhinoplasty field

Kim SH, Tan KL, Lee SY, Kim DW, Shin S, Jin HR

Springerplus, 2016;5(1):2116.
PMID: 28090430 DOI: 10.1186/s40064-016-3679-y

This study investigated on bacterial contamination of the rhinoplasty field. The effect of preoperative chlorhexidine treatment on decreasing bacterial contamination in the rhinoplasty field is examined.
Fulltext Comparing quality of life and treatment satisfaction between patients on warfarin and direct oral anticoagulants: a cross-sectional study

Ng DL, Gan GG, Chai CS, Chee KH, Tan KL, Tan SB, et al.

Patient Prefer Adherence, 2019;13:1363-1373.
PMID: 31616136 DOI: 10.2147/PPA.S204246

Introduction and aim: Patient quality of life (QOL) while on long-term oral anticoagulant therapy has been receiving greater attention in recent years due to the increase in life expectancy brought about by advances in medical care. This study aimed to compare the QOL, treatment satisfaction, hospitalization and bleeding rate in patients on long-term warfarin versus direct oral anticoagulants (DOAC).
Methods: This was a cross-sectional study of patients with non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE) on long-term anticoagulant therapy attending the cardiology clinic and anticoagulation clinic of the University Malaya Medical Centre from July 1, 2016, to June 30, 2018. Patient QOL was assessed by using the Short Form 12 Health Survey (SF12), while treatment satisfaction was assessed by using the Perception of Anticoagulation Treatment Questionnaire 2 (PACT-Q2).
Results: A total of 208 patients were recruited; 52.4% received warfarin and 47.6% received DOAC. There was no significant difference in QOL between warfarin and DOAC based on SF12 (physical QOL, P=0.083; mental QOL, P=0.665). Nevertheless, patients in the DOAC group were significantly more satisfied with their treatment compared to the warfarin group based on PACT-Q2 (P=0.004). The hospitalisation rate was significantly higher in the warfarin group than the DOAC group (15.6% versus 3.0%, P=0.002). Clinically relevant minor bleeds and severe bleeding events were non-significantly higher in the warfarin group than the DOAC group (66.7% versus 40.0%, P=0.069).
Conclusion: Compared to warfarin, treatment of NVAF and VTE with DOAC showed comparable QOL, higher treatment satisfaction, lesser hospitalization, and a non-significant trend toward fewer bleeding episodes.
Fulltext Lipid profile of regular kratom (Mitragyna speciosa Korth.) users in the community setting

Leong Bin Abdullah MFI, Tan KL, Mohd Isa S, Yusoff NS, Chear NJY, Singh D

PLoS One, 2020;15(6):e0234639.
PMID: 32525924 DOI: 10.1371/journal.pone.0234639

BACKGROUND AND AIM: Kratom, or Mitragyna speciosa Korth., is a tropical plant that has been reported to exhibit opioid-like effects. Although opioids have been demonstrated to alter the lipid profile of regular users, data on the lipid-altering effects of kratom are scarce. This study aimed to compare the fasting lipid profile of regular kratom users to that of healthy subjects who do not use kratom. It also determined the association between various characteristics of kratom users and the serum triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels of regular kratom users.
METHODS: A total of 200 participants (n = 100 kratom users and n = 100 healthy subjects who do not use kratom) were recruited for this analytical cross-sectional study. Data on sociodemographic status, kratom use characteristics, cigarette smoking, physical activity, body mass index (BMI), fasting serum lipid profile, and liver function were collected from all participants.
RESULTS: The liver parameters of the study participants were within normal range. The serum total cholesterol and LDL of kratom users were significantly lower than those of healthy subjects who do not use kratom. There were no significant differences in the serum triglyceride and HDL levels. However, higher average daily frequency of kratom use and increasing age were associated with increased serum total cholesterol among kratom users. Other kratom use characteristics such as age of first kratom intake, duration of kratom use, and quantity of daily kratom intake were not associated with increased serum triglyceride, total cholesterol, LDL, and HDL levels.
CONCLUSIONS: Our findings suggest regular kratom consumption was not linked to elevated serum lipids, except when there is a higher frequency of daily kratom intake. However, the study was limited by the small sample size, and hence a more comprehensive study with larger sample size is warranted to confirm the findings.
Fulltext Prevalence and Predictors of Left Ventricular Diastolic Dysfunction in Malaysian Patients With Type 2 Diabetes Mellitus Without Prior Known Cardiovascular Disease

Chee KH, Tan KL, Luqman I, Saiful SS, Chew YY, Chinna K, et al.

Front Cardiovasc Med, 2021;8:676862.
PMID: 34646868 DOI: 10.3389/fcvm.2021.676862

Objective: Existing data showed that left ventricular diastolic dysfunction is common in individuals with type 2 diabetes mellitus (T2DM). However, most of the studies included diabetic patients who have prior cardiovascular disease, which might be the compounding factor for ventricular dysfunction. This study aimed to determine the prevalence and predictors of left ventricular diastolic dysfunction in an Asian population with T2DM without prior cardiovascular disease using the latest recommended echocardiographic assessment for left ventricular diastolic dysfunction. Design and Participants: This is a cross-sectional study in which eligible patients with T2DM without history of coronary artery disease, heart failure, or valvular heart disease were recruited. Demographic data, diabetic control, comorbidities, microvascular/macrovascular complications, and medications prescribed were recorded. Venous blood was sent to test for B-type natriuretic peptide, and transthoracic echocardiography was performed to assess left ventricular dysfunction. Setting: This study was performed in a tertiary healthcare center located in Kuala Lumpur, Malaysia. Results: Of the 301 patients, 83.1% have had T2DM for >10 years, with 45.8% being poorly controlled. Comorbidities include hypertension (77.1%), hyperlipidemia (91.0%), and pre-obesity/obesity (72.9%). Majority had absence of microvascular (albuminuria, retinopathy, and neuropathy) and macrovascular (peripheral vascular disease and stroke) complications. None had raised B-type natriuretic peptide levels, and 93.7% had no symptoms of heart failure. On echocardiographic assessment, 70.1% had left ventricular diastolic dysfunction, and 90.5% had Grade 1/mild severity. Age, ethnicity, insulin therapy, presence of hypertension, and hyperlipidemia were significantly associated with left ventricular diastolic dysfunction. Older T2DM patients of Chinese ethnicity and on insulin are about two times more likely to develop left ventricular diastolic dysfunction. Conclusion: There was a high prevalence of asymptomatic left ventricular diastolic dysfunction among patients with T2DM without prior known cardiovascular disease. Older age, insulin therapy, and Chinese ethnicity were risk factors for left ventricular diastolic dysfunction in T2DM.
Pharmacokinetics and Bioequivalence Study of a New Branded Generic Moxifloxacin Tablet Among Healthy Volunteers

Amran A, Tan CY, Tan KL, Ho RM, Anand AK, Leong CW

Clin Pharmacol Drug Dev, 2021 12;10(12):1514-1518.
PMID: 34107173 DOI: 10.1002/cpdd.964

A newly developed branded generic of a moxifloxacin (MOX) 400-mg tablet formulation was manufactured prior to this study. A bioequivalence (BE) study was done to assess the pharmacokinetics of the formulation using a randomized, open-label, 2-period crossover, 2-sequence, and single-dose experiment. Thirty healthy male volunteers were recruited. The test formulation, Flonoxin 400 mg, was compared with the reference formulation, Avelox 400 mg. The pharmacokinetic parameters of MOX were calculated based on the plasma drug concentration-time profile. Noncompartmental analysis was performed to determine its safety and tolerability. The 90% confidence intervals (CIs) were 88.5%-104.6%, 96.1%-101.1%, and 96.8%-100.7% for Cmax , AUC0-t , and AUC0-inf , respectively. All CIs were within the 80.0%-125.0% boundary, thus fulfilling the acceptable BE criteria according to the ASEAN guidelines.
Fulltext NUB1 and FAT10 Proteins as Potential Novel Biomarkers in Cancer: A Translational Perspective

Arshad M, Abdul Hamid N, Chan MC, Ismail F, Tan GC, Pezzella F, et al.

Cells, 2021 08 24;10(9).
PMID: 34571823 DOI: 10.3390/cells10092176

Cancer increases the global disease burden substantially, but it remains a challenge to manage it. The search for novel biomarkers is essential for risk assessment, diagnosis, prognosis, prediction of treatment response, and cancer monitoring. This paper examined NEDD8 ultimate buster-1 (NUB1) and F-adjacent transcript 10 (FAT10) proteins as novel biomarkers in cancer. This literature review is based on the search of the electronic database, PubMed. NUB1 is an interferon-inducible protein that mediates apoptotic and anti-proliferative actions in cancer, while FAT10 is a ubiquitin-like modifier that promotes cancer. The upregulated expression of both NUB1 and FAT10 has been observed in various cancers. NUB1 protein binds to FAT10 non-covalently to promote FAT10 degradation. An overexpressed FAT10 stimulates nuclear factor-kappa β, activates the inflammatory pathways, and induces the proliferation of cancer. The FAT10 protein interacts with the mitotic arrest deficient 2 protein, causing chromosomal instability and breast tumourigenesis. FAT10 binds to the proliferating cell nuclear antigen protein and inhibits the DNA damage repair response. In addition, FAT10 involves epithelial-mesenchymal transition, invasion, apoptosis, and multiplication in hepatocellular carcinoma. Our knowledge about them is still limited. There is a need to further develop NUB1 and FAT10 as novel biomarkers.
Thalassemia intermedia in HbH-CS disease with compound heterozygosity for beta-thalassemia: challenges in hemoglobin analysis and clinical diagnosis

Tan JA, Kok JL, Tan KL, Wee YC, George E

Genes Genet Syst, 2009 Feb;84(1):67-71.
PMID: 19420802

Co-inheritance of alpha-thalassemia with homozygosity or compound heterozygosity for beta-thalassemia may ameliorate beta-thalassemia major. A wide range of clinical phenotypes is produced depending on the number of alpha-thalassemia alleles (-alpha/alphaalpha --/alphaalpha, --/-alpha). The co-inheritance of beta-thalassemia with alpha-thalassemia with a single gene deletion (-alpha/alphaalpha) is usually associated with thalassemia major. In contrast, the co-inheritance of beta-thalassemia with two alpha-genes deleted in cis or trans (--/alphaalpha or -alpha/-alpha) generally produces beta-thalassemia intermedia. In Southeast Asia, the most common defect responsible for alpha-thalassemia is the Southeast Asian (SEA) deletion of 20.5 kilobases. The presence of the SEA deletion with Hb Constant Spring (HbCS) produces HbH-CS disease. Co-inheritance of HbH-CS with compound heterozygosity for beta-thalassemia is very rare. This study presents a Malay patient with HbH-CS disorder and beta degrees/beta+-thalassemia. The SEA deletion was confirmed in the patient using a duplex-PCR. A Combine-Amplification Refractory Mutation System (C-ARMS) technique to simultaneously detect HbCS and Hb Quong Sze confirmed HbCS in the patient. Compound heterozygosity for CD41/42 and Poly A was confirmed using the ARMS. This is a unique case as the SEA alpha-gene deletion in cis (--SEA/alphaalpha) is generally not present in the Malays, who more commonly possess the two alpha-gene deletion in trans (-alpha/-alpha). In addition, the beta-globin gene mutation at CD41/42 is a common mutation in the Chinese and not in the Malays. The presence of both the SEA deletion and CD41/42 in the mother of the patient suggests the possible introduction of these two defects into the family by marriage with a Chinese.
A Multigroup Analysis of Bidirectional Work-Family Enrichment on Family Satisfaction of Hospitality Employees during the Pandemic: Where Religiosity and Marital Status Matter

Tan KL, Sim AKS, Hii ISH, Pidani R, Donohue T

J Psychol, 2023;157(1):48-70.
PMID: 36328776 DOI: 10.1080/00223980.2022.2134278

The COVID-19 pandemic has changed our lives. As many industries face a complete stand-still, it also highlights the need to maintain family satisfaction (FS) during this challenging time, empirical research on achieving this remains scant. This study elucidates how marital status influences employees' religiosity, work-family enrichment (WFE) and FS. Data from 295 employees was examined using the analyzed using the partial least squares method structural equation modeling (PLS-SEM) multigroup analysis. Results suggest that religiosity has a positive significant relationship on the bidirectionality of WFE. The multigroup analysis indicates a significant difference in how single and married employees interpret work-family experience. We extend family-work interfaces by incorporating both the construct of marital status and religiosity. It advances the body of knowledge in understanding work-family interfaces, especially in times of the pandemic.

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