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1.  hERG1 channels drive tumour malignancy and may serve as prognostic factor in pancreatic ductal adenocarcinoma 
British Journal of Cancer  2015;112(6):1076-1087.
hERG1 channels are aberrantly expressed in human cancers. The expression, functional role and clinical significance of hERG1 channels in pancreatic ductal adenocarcinoma (PDAC) is lacking.
hERG1 expression was tested in PDAC primary samples assembled as tissue microarray by immunohistochemistry using an anti-hERG1 monoclonal antibody (α-hERG1-MoAb). The functional role of hERG1 was studied in PDAC cell lines and primary cultures. ERG1 expression during PDAC progression was studied in Pdx-1-Cre,LSL-KrasG12D/+,LSL-Trp53R175H/+ transgenic (KPC) mice. ERG1 expression in vivo was determined by optical imaging using Alexa-680-labelled α-hERG1-MoAb.
(i) hERG1 was expressed at high levels in 59% of primary PDAC; (ii) hERG1 blockade decreased PDAC cell growth and migration; (iii) hERG1 was physically and functionally linked to the Epidermal Growth Factor-Receptor pathway; (iv) in transgenic mice, ERG1 was expressed in PanIN lesions, reaching high expression levels in PDAC; (v) PDAC patients whose primary tumour showed high hERG1 expression had a worse prognosis; (vi) the α-hERG1-MoAb could detect PDAC in vivo.
hERG1 regulates PDAC malignancy and its expression, once validated in a larger cohort also comprising of late-stage, non-surgically resected cases, may be exploited for diagnostic and prognostic purposes in PDAC either ex vivo or in vivo.
PMCID: PMC4366888  PMID: 25719829
pancreatic ductal adenocarcinoma (PDAC); hERG1 potassium channels; EGF-R; prognosis; molecular-imaging
2.  The extended Theory of Planned Behavior in explaining exclusive breastfeeding intention and behavior among women in Kelantan, Malaysia 
The purpose of this study is to utilize an extended Theory of Planned Behavior in identifying predictors of exclusive breastfeeding intention and behavior among women in Kelantan, Malaysia.
A prospective cohort study was conducted, recruiting pregnant womenthrough two-stage cluster sampling. Their exclusive breastfeeding intention, attitude, perceived norm, perceived behavioral control and past behavior were obtained at baseline through interviewer-guided questionnaire. At one month after delivery, another interview was conducted to determine the two additional variables in the extended theory, which were their postpartum support and breastfeeding difficulty. The behavior, which was the actual duration of exclusive breastfeeding, was obtained from the second follow-up at six months. Pearson correlation and two hierarchical regression analyses were conducted.
A total of 200 women completed the study follow-up. Their median intended exclusive breastfeeding duration was 4.0 (IQR 5) months, and the median actual duration was 1.0 (IQR 4) month. The Theory of Planned Behavior explained 51.0% of the variance in intention, with perceived behavioral control and attitude were the significant predictors. It also explained 10.0% of the variance in behavior, but the addition of postpartum support and breastfeeding difficulty increased the amount of explained variance in behavior by 6.0%. The significant predictors of exclusive breastfeeding behavior were intention, postpartum support and breastfeeding difficulty.
The extended Theory of Planned Behaviorhad a good predictive ability in explaining exclusive breastfeedingintention and behavior. The women's intention to practice exclusive breastfeeding may be improved by improving their perceived behavioral control and attitude. Providing correct postpartum support and skills to handle breastfeeding difficulties after delivery will improve their exclusive breastfeeding behavior.
PMCID: PMC4742311  PMID: 26865916
Exclusive breastfeeding; Theory of Planned Behavior; postpartum support; breastfeeding difficulty
3.  Prognostic significance of K-Ras mutation rate in metastatic colorectal cancer patients 
Oncotarget  2015;6(31):31604-31612.
Introduction: Activating mutations of K-Ras gene have a well-established role as predictors of resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. Their prognostic value is controversial, and no data regarding the prognostic value of mutation rate, defined as the percentage of mutated alleles/tumor sample, are available. We aimed to evaluate the prognostic value of K-Rasmutation rate in a homogenous cohort of mCRC patients receiving first-line doublet plus bevacizumab.
Patients and Methods: This retrospective study enrolled 397 K-Ras mutant mCRC patients from 6 Italian centers, and 263 patients were fully evaluable for our analysis. K-Ras mutation rate was assessed by pyrosequencing. Patients with less than 60% of cancer cells in tumor tissue were excluded. No patients received anti-EGFR containing anticancer therapy, at any time. Median mutation rate was 40% and was adopted as cut-off. The primary and secondary endpoints were PFS and OS respectively.
Results: At univariate analysis, K-Ras mutation rate higher than 40% was significantly associated with lower PFS (7.3 vs 9.1 months; P < 0.0001) and OS (21 vs 31 months; P = 0.004). A multivariate model adjusted for age at diagnosis, site of origin of tumor tissue (primary vs metastases), referral center, number of metastatic sites, and first-line chemotherapy backbone, showed that K-Ras mutation rate remained a significant predictor of PFS and OS in the whole population.
Discussion: Our data demonstrate an association between K-Ras mutation rate and prognosis in mCRC patients treated with bevacizumab-containing first-line therapy. These data deserve to be verified in an independent validation set.
PMCID: PMC4741627  PMID: 26384309
K-Ras; mutation rate; colorectal cancer; bevacizumab; prognosis
4.  Neuroscience Club in SKKK3 and SMSTMFP: The Brain Apprentice Project 
Sekolah Menengah Sains Tengku Muhammad Faris Petra (SMSTMFP) and Sekolah Kebangsaan Kubang Kerian (3) (SKKK3) were selected by the Department of Neurosciences, Universiti Sains Malaysia (USM), in 2011 to be a ‘school-based Neuroscience Club’ via the ‘Knowledge Transfer Programme (KTP) – Community’ project. This community project was known as “The Brain Apprentice Project”. The objectives of this project were to promote science and the neurosciences beyond conventional classroom teachings whilst guiding creativity and innovation as well as to assist in the delivery of neuroscience knowledge through graduate interns as part of the cultivation of neuroscience as a fruitful future career option. All of the planned club activities moulded the students to be knowledgeable individuals with admirable leadership skills, which will help the schools produce more scientists, technocrats and professionals who can fulfil the requirements of our religion, race and nation in the future. Some of the activities carried out over the years include the “My Brain Invention Competition”, “Mini Brain Bee Contest”, “Recycled Melody” and “Brain Dissection”. These activities educated the students well and improved their confidence levels in their communication and soft skills. The participation of the students in international-level competition, such as the “International Brain Bee”, was one of the ways future professionals were created for the nation. The implementation of Neuroscience Club as one of the organisations in the school’s cocurriculum was an appropriate step in transferring science and neuroscience knowledge and skills from a higher education institution, namely USM, to both of the schools, SMSTMFP and SKKK3. The club members showed great interest in all of the club’s activities and their performance on the Ujian Pencapaian Sekolah Rendah (UPSR) or Primary School Achievement Test and Sijil Pelajaran Malaysia (SPM) or Malaysian Certificate of Education examinations improved tremendously.
PMCID: PMC4683850  PMID: 26715909
neurosciences; knowledge; creativity; society
5.  Application of an Effective Statistical Technique for an Accurate and Powerful Mining of Quantitative Trait Loci for Rice Aroma Trait 
PLoS ONE  2015;10(6):e0129069.
When a phenotype of interest is associated with an external/internal covariate, covariate inclusion in quantitative trait loci (QTL) analyses can diminish residual variation and subsequently enhance the ability of QTL detection. In the in vitro synthesis of 2-acetyl-1-pyrroline (2AP), the main fragrance compound in rice, the thermal processing during the Maillard-type reaction between proline and carbohydrate reduction produces a roasted, popcorn-like aroma. Hence, for the first time, we included the proline amino acid, an important precursor of 2AP, as a covariate in our QTL mapping analyses to precisely explore the genetic factors affecting natural variation for rice scent. Consequently, two QTLs were traced on chromosomes 4 and 8. They explained from 20% to 49% of the total aroma phenotypic variance. Additionally, by saturating the interval harboring the major QTL using gene-based primers, a putative allele of fgr (major genetic determinant of fragrance) was mapped in the QTL on the 8th chromosome in the interval RM223-SCU015RM (1.63 cM). These loci supported previous studies of different accessions. Such QTLs can be widely used by breeders in crop improvement programs and for further fine mapping. Moreover, no previous studies and findings were found on simultaneous assessment of the relationship among 2AP, proline and fragrance QTLs. Therefore, our findings can help further our understanding of the metabolomic and genetic basis of 2AP biosynthesis in aromatic rice.
PMCID: PMC4464510  PMID: 26061689
6.  Tetrapleura tetraptera spice attenuates high-carbohydrate, high-fat diet-induced obese and type 2 diabetic rats with metabolic syndrome features 
Tetrapleura tetraptera, a seasoning and nutritive spice is also used in western African folk medicine in the management of wide variety of diseases including diabetes, inflammation and hypertension. Flavonoids and saponins are some abundant secondary metabolic constituents in the fruits of this plant. This study aimed at evaluating the potential therapeutic action of the polyphenol-rich hydroethanolic extract (HET) of this fruit in experimentally induced obese and type 2 diabetic rats (T2DM) with characteristic metabolic syndrome (MetS).
MetS was induced in rats by high-carbohydrate, high-fat diet and administration of low-dose streptozotocin. Then different oral doses of HET (200 and 400 mg/kg) were administered to T2DM rats for 28 days. A standard antidiabetic drug, metformin (300 mg/kg), was used for comparison. The body weight, systolic blood pressure, oxidative stress and metabolic parameters were then assessed to evaluate the effect of HET on MetS.
HET reduced weight gain, fasting blood glucose and plasma insulin levels as well as homeostasis model assessment of insulin resistance (HOMA-IR) and alleviated obesity and T2DM associated oxidative stress and hypertension in rats. Moreover, a significantly hypolipidemic property and an attenuation of liver injury and tissue steatosis was observed after HET administration. HET further demonstrated its anti-inflammation effect via down regulation of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), leptin and an increase in adiponectin. The HET exhibited dose-dependent effects which were comparable to that of metformin.
The present study thereby demonstrates the anti-insulin resistance, antilipidemic, anti-obesity, hypotensive and anti-inflammatory properties of HET; hence it has the potential to be further developed for the management of MetS such as obesity, T2DM and hypertension.
PMCID: PMC4448292  PMID: 26003803
Obesity; Type 2 diabetes; High-carbohydrate high-fat diet; Metabolic syndrome; Inflammation; Tetrapleura tetraptera
7.  Deregulation of dicer and mir-155 expression in liposarcoma 
Oncotarget  2015;6(12):10586-10591.
Liposarcoma (LPS) is the most common soft tissue sarcoma. It has been demonstrated that mir-155 was the most overexpressed miRNA in well-differentiated LPS(WDLPS)/dedifferentiated LPS (DDLPS). The aim of this study is to evaluate the involvement of Dicer, Drosha and mir-155 in development of LPS and their possible role in stratification of different histological subtypes. Dicer, Drosha and mir-155 mRNA levels were analyzed in formalin-fixed paraffin-embedded specimens from patients diagnosed with 62 LPS and compared with samples of adipose tissues of healthy donors. The experimental data were obtained using qRT-PCR comparing Dicer, Drosha and mir-155 expression levels in tumor samples versus normal fat. The tumor samples from LPS patients showed a significantly lower Dicer expression versus normal adipose tissue, while Drosha levels did not differ. Concerning mir155 expression levels, our results demonstrated a significant mir-155 up-regulation in all LPS subtypes versus normal adipose tissue except for WDLS. These findings demonstrate for the first time that Dicer is deregulated in LPS and show that mir-155 is differentially expressed in LPS subgroups and it could be a promising tool to improve LPS disease stratification and differential diagnosis.
PMCID: PMC4496377  PMID: 25888631
Dicer; Drosha; mir-155; liposarcoma
8.  Anemia among children aged 2–5 years in the Gaza Strip- Palestinian: a cross sectional study 
BMC Public Health  2015;15:319.
Anemia is a major public health problem worldwide, with adverse consequences on child growth, development, and survival. This deficiency has affected approximately a quarter of the world population. This study aimed to determine the prevalence of anemia and the associated factors among preschool children in the Gaza Strip.
A cross-sectional study was conducted between May and September 2012. A total of 357 preschool children were selected using multistage sampling method from Jabalya refugee camp, El Remal urban area, and Al Qarara rural area. Hemoglobin level was measured, and anemia diagnosis was confirmed at a level <11.0 g/dL. In this study, we utilized a pretested questionnaire for face to face interview with mothers. Anthropometric indicators for children were measured using the WHO guideline. Descriptive and multivariate analyses were conducted to determine the prevalence and associated factors of anemia.
The overall prevalence of anemia was 59.7% among preschool children in the Gaza Strip, 46.5% and 13.5% of which are mild and moderate, respectively. The mean hemoglobin level was 10.83 ± 0.86 g/dl. Children living in Jabalya refugee camp have a high risk of anemia [adjusted b= −0.55; 95% confidence interval (CI;-0.72,-0.39); p < 0.001]. Boys were more susceptible to this deficiency than girls [adjusted b = 0.17; 95% CI (0.0.01, 0.33); p = 0.031]. Hemoglobin level increased with age [adjusted b = 0.02; 95% CI (0.01, 0.03); p < 0.001]. Hemoglobin level decreased in children living in poor households [adjusted b = −0.24; 95%CI (−0.41,-0.06); p = 0.006]. Underweight children were more susceptible to anemia than normal weight children [adjusted b = − 0.22; 95% CI (−0.41, −0.03); p = 0.025].
The prevalence of anemia among preschool children in the Gaza Strip was higher than those reported in previous local studies, indicating that anemia is a major public health problem. In this study, we also observed mild and moderate cases among children, whereas severe anemia was not observed. Independent predictors of anemia were geographic location, sex, age, monthly income, and malnutrition. Results provided the baseline information on anemia, therefore, especial attention should be given on intervention of anemia.
PMCID: PMC4391478  PMID: 25879619
Anemia; Hemoglobin; Prevalence; Associated factors
9.  Ipilimumab and immune-mediated adverse events: a case report of anti-CTLA4 induced ileitis 
BMC Cancer  2015;15:87.
Ipilimumab is a fully human monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4 , a key negative regulator of T-cell activation approved by the Food and Drug Administration as of March 2011 for the treatment of metastatic melanoma. As a result of the up-regulation of the immune system, several immune-mediated adverse effects have been reported including colitis, dermatitis, hepatitis and rarely hypophysitis. The most frequent immune-mediated adverse effects described in literature include gastrointestinal toxicity such as diarrhea, colitis and case of colitis and ileitis.
Case presentation
In this paper we report an interesting case of immune-mediate ileitis without colitis in a 54 years old woman with metastatic melanoma treated with ipilimumab. We also discuss about case management and the possible pathological mechanisms considering also previous reports.
The aim of this article is to support further investigations concerning epigenetic and genetic analysis in order to personalize biological therapy and to reduce immune related adverse events observed after ipilimumab administration.
PMCID: PMC4350587  PMID: 25885696
Melanoma; Ipilimumab; Immune-mediated adverse events; Ileitis
10.  Self-perception and quality of life among overweight and obese rural housewives in Kelantan, Malaysia 
Obesity, in the past was perceived to be the problem of the rich, but recent studies have reported that the problem of obesity is a worldwide problem and rural population is no less affected. Self-perceived health and weight appropriateness is an important component of weight-loss and eating behaviors and may be mediated by local, social and cultural patterning. In addition to the quality of life assessment, it should therefore be an important focal point for the design and implementation of clinical and public health policies.
The present study was carried out to assess the self-perception of weight appropriateness as well as the quality of life of overweight and obese individual among the rural population particularly among housewives. A total of 421 respondents participated in the study which consisted of 36.6% in the overweight and 63.4% in the obese categories.
the analysis of the survey revealed that self-perception regarding obesity among respondents show common similarities, particularly in self reporting on health, dietary habit and also the concept of beauty and a beautiful body. Character and behavior are highly regarded in evaluating a person’s self-worth in society. The results on the quality of life using the ORWELL 97 instrument show that the quality of life of respondents was moderate. Most of the respondents were aware of their body weight and indicated an intention to lose weight but also reported themselves as healthy or very healthy.
The results of the survey indicated that perception on obesity did not differed very much between respondents, in fact there existed a lot of similarities in their perception about health, quality of life, personal health and self-satisfaction with own body. However, their quality of life was within the normal or moderate level based on the ORWELL 97 assessment. Even though most of the respondents were aware of their body weight and indicated an intention to lose weight they also reported themselves as healthy or very healthy, suggesting that public health messages intended for rural housewives need to be more tailored to health-related consequences of fatness.
PMCID: PMC4328071  PMID: 25879187
Overweight; Obesity; Quality of life; Self-perception; Rural housewives
11.  The Frequency of Anti-Aquaporin-4 Ig G Antibody in Neuromyelitis Optica and Its Spectrum Disorders at a Single Tertiary Referral Center in Malaysia 
Background. In the past the occurrence of neuromyelitis optica in Malaysia was thought to be uncommon and the frequency of anti-aquaporin-4 Ig G antibody was unknown. Objective. To evaluate the frequency of anti-aquaporin-4 Ig G antibody (Anti-AQP4 antibody) amongst patients with neuromyelitis optica (NMO) and its spectrum disorders (NMOSD) and the differences between the seropositive and seronegative groups. Methods. Retrospectively, 96 patients with NMO/high risk syndromes for NMOSD (HRS-NMOSD) were identified out of 266 patients with idiopathic inflammatory demyelinating disease from a single center hospital based registry. Anti-AQP4 seropositivity was found in 38/48 (79.2%) with NMO, 12/21 (57.1%) with brain involvement at high risk for NMOSD, 12/15 (80%) with transverse myelitis (i.e., 11/15 with relapsing transverse myelitis and one with monophasic transverse myelitis), and 3/7 (42.8%) with relapsing optic neuritis. Sixty-five out of 96 patients, that is, 67.7%, with NMO/HRS for NMOSD were seropositive. Seropositivity was significantly associated with female gender, a higher number of mean relapses, that is, 5.15 ± 4.42 versus 2.10 ± 1.68, longer length of spinal cord lesions, that is, 6.6 ± 4.9 versus 2.9 ± 2.5, vertebral bodies, higher EDSS, 4.5 ± 2.4 versus 2.4 ± 2.6, presence of paroxysmal tonic spasms, and blindness (unilateral/bilateral); P < 0.001. Longitudinally extensive cord lesions (contiguous or linear), presence of lesions in the cervical and thoracic regions, and involvement of the central gray matter or holocord regions on axial scans, were also significantly associated with seropositivity; P < 0.001. Conclusion. NMO and HRS for NMOSD are present in larger numbers than previously thought in Malaysia. More than 2/3rds are seropositive. Seropositive and seronegative NMO/NMOSD have differences that are useful in clinical practice.
PMCID: PMC4274866  PMID: 25548676
12.  Evaluation of microRNA-10b prognostic significance in a prospective cohort of breast cancer patients 
Molecular Cancer  2014;13:142.
MicroRNA-10b (miR-10b) has a prominent role in regulating tumor invasion and metastasis by targeting the HOXD10 transcriptional repressor and has been found up-regulated in several tumor types.
We evaluated the expression of miR-10b in paired tumor and normal specimens obtained from a prospective cohort of breast cancer patients with at least 36 months follow-up enrolled according to the REMARK guidelines (n = 150). RNA quality was measured and only samples with RNA Integrity Number (RIN) ≥7.0 were analyzed.
The relative expression of miR-10b in tumor as compared to its normal counterpart (RER) was determined by RT-qPCR. miR-10b RERs were higher in the subgroup of patients with synchronous metastases (n = 11, Median 0.25; IQR 0.11-1.02) as compared with patients without metastases (n = 90, Median 0.09; IQR 0.04-0.29) (p = 0.028). In the subgroup of patients without synchronous metastases (n = 90), higher miR-10b RERs were associated with increased risk of disease progression and death in both univariable (HR 1.16, p = 0.021 and HR 1.20, p = 0.015 respectively for 0.10 unitary increase of miR-10b RERs levels) and multivariable (HR1.30, p < 0.001, and HR 1.31, p = 0.003 respectively for 0.10 unitary increase of miR-10b RERs levels) Cox regression models. The addition of miR-10b RERs to the Nottingham Prognostic Index (NPI) provided an improvement in discrimination power and risk reclassification abilities for the clinical outcomes at 36 months. Survival C-indices significantly increased from 0.849 to 0.889 (p = 0.009) for OS and from 0.735 to 0.767 (p = 0.050) for DFS.
Our results provide evidences that the addition of miR-10b RERs to the prognostic factors used in clinical routine could improve the prediction abilities for both overall mortality and disease progression in breast cancer patients.
PMCID: PMC4055397  PMID: 24897960
Breast cancer; microRNA; Metastasis; RT-qPCR
13.  Association between household food insecurity and nutritional outcomes among children in Northeastern of Peninsular Malaysia 
Nutrition Research and Practice  2014;8(3):304-311.
The purpose of the study was to investigate the relationship between household food insecurity and nutritional status of children in low-income households. A cross sectional study involved a survey of households (n = 223) receiving the financial assistance.
Eligible mothers that fulfilled the inclusion criteria such as non-pregnant, non-lactating mothers, aged 18 to 55 years with their youngest children aged 2 to 12 years, were purposively selected. The Radimer/Cornell hunger and food-insecurity instrument was administered and children's height and weight were measured.
About 16.1% of the households were food secure, while 83.9% experienced some kind of food insecurity. Out of food insecure category, 29.6% households were food insecure, 19.3% women were individual food insecure and 35.0% fell into the child hunger category. Education of the mother (P = 0.047), household size (P = 0.024), number of children (P = 0.024), number of children going to school (P = 0.048), total monthly income (P < 0.001), income per capital (P < 0.001), number of household members contributing to the income (P = 0.018) and food expenditure (P = 0.006) were significant risk factors for household food insecurity. The prevalence of underweight, stunting and wasting in children were 61.0%, 61.4% and 30.6% respectively. Based on multinomial logistic regression, children in food-insecure households were 2.15 times more likely to be underweight and three times to be stunted than children in the food-secure households.
The findings suggest that household food insecurity is associated with the nutritional status of the children in the rural area of Northeastern Peninsular Malaysia.
PMCID: PMC4058565  PMID: 24944776
Northeastern Peninsular Malaysia; child hunger; household food insecurity; nutritional status
14.  Obesity and overweight: prevalence and associated socio demographic factors among mothers in three different areas in the Gaza Strip-Palestine: a cross-sectional study 
BMC obesity  2014;1:7.
The increasing number of obesity and overweight cases in developing countries, especially among women, requires serious attention because of its effects on the health care system and the quality of life. Few studies have been conducted in the Gaza Strip to determine obesity and overweight prevalence and the associated factors. This study aimed at determining the prevalence of obesity and overweight cases in relation to socio-demographic factors among mothers aged 18–50 years in the Gaza Strip-Palestine from June 2012 to September 2012.
Mothers childbearing age 18–50 years (n = 357) were selected using a cross-sectional multistage sampling methodology from three different geographical locations, namely, El Remal urban area, Jabalia refugee camp, and Al Qarrara rural area.
The weight and height of the mothers were measured, and their body mass indexes (BMI) were computed. The mothers were categorized according to the criteria of World Health Organization (WHO) for BMI. The criteria categorize mothers as overweight if they have a BMI 25–29.9 kg/m2 and obese if their BMI ≥ 30.0 kg/m2.
Obesity and overweight rates in urban area, refugee camp, and rural area were found to be 57.0%, 66.8%, and 67.5%, respectively. Moreover, BMI increased with age, adjusted b = 0.39; 95% CI (0.31, 0.48); p = < 0.001, whereas BMI was lower in low-income subjects, adjusted b = −1.59, 95% CI (−2.74,-0.44), p = 0.007. Housewives were more susceptible to obesity than employed woman, adjusted b = −2.76, 95% CI (−5.33,-0.19), p = 0.036. However, the study found no association among BMI level and household size, geographical location, educational level, and family assistance.
The results showed that obesity and being overweight are highly prevalent among women in the Gaza Strip. Independent predictors of obesity in the population studied were increasing age, high income, and housewives. This finding is an important baseline for the monitoring of obesity and overweight cases in the future and highlights the need for community-based programs to combat this problem in Palestine.
PMCID: PMC4510884  PMID: 26217499
Overweight; Obesity; Prevalence; Socio-demographic factors
15.  Multiple Sclerosis in Malaysia: Demographics, Clinical Features, and Neuroimaging Characteristics 
Background. Multiple sclerosis (MS) is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country. Objectives. To investigate the spectrum of multiple sclerosis in Malaysia. Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia. Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald's criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders. Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here.
PMCID: PMC3888747  PMID: 24455266
16.  Tumor associated macrophages polarization dictates the efficacy of BCG instillation in non-muscle invasive urothelial bladder cancer 
To evaluate the prognostic role of TAMs in patients affected by non-muscle invasive bladder cancer (NMIBC), undergone Trans Urethral Resection of Bladder (TURB) and Bacillus Calmette-Guerin (BCG) therapy.
Data from 40 patients (36 men, 4 women), mean age 69 years (40-83 years), treated for NMIBC with TURB and BCG instillation were collected. Two different groups were considered: group with and group without bladder cancer recurrence. Correlations between immunofluorescence measured Mtot, M1 and M2 infiltration and clinicopathological parameters were evaluated using Spearman and Mann–Whitney methods. The recurrence-free survival rate was calculated using the Kaplan-Meier method.
CD68 positive cells (Mtot) were observed in all specimens tested. High Mtot, M1 and M2 infiltration was observed in patients with disease recurrence, even before endovescical BCG instillation. Significant value for M2 infiltration (p = 0,042) was found calculating significativity between two group medians before BCG therapy. p = 0,072 and p = 0,180 were observed correlating median of Mtot and M1 between two groups of patients respectively. Values of p = 0,44, p = 0,23 and p = 0,64 from correlation between DFS and Mtot, M1 and M2 median in patients before endovescical BCG instillation, were calculated respectively. Comparing DFS and Mtot, M1 and M2 median in patients group after endovescical BCG instillation significant values were obtained (p = 0,020; p = 0,02; and p = 0,029 respectively).
M2 tumor infiltration could be a prognostic value of recurrence in patients with NMIBC.
PMCID: PMC4029537  PMID: 24423367
Bladder cancer; Endovescical instillation; Tumor-associated macrophages; Macrophages polarization; Prognosis
17.  The role of macrophages polarization in predicting prognosis of radically resected gastric cancer patients 
Tumour-associated Macrophages (TAM) present two different polarizations: classical (M1) characterized by immunostimulation activity and tumour suppression; alternative (M2) characterized by tumour promotion and immune suppression. In this retrospective study, we evaluated the correlation between the two forms of TAM with survival time in radically resected gastric cancer patients. A total of 52 chemo- and radio-naive patients were included. Two slides were prepared for each patient and double-stained for CD68/NOS2 (M1) or CD68/CD163 (M2) and five representative high-power fields per slide were evaluated for TAM count. The median value of the two macrophage populations density and the median value of M1/M2 ratio were used as cut-off. Twenty-seven patients with M1 density above-the-median had a significantly higher survival compared to those below the median. Twenty-six patients with M1/M2 ratio above the median showed median OS of 27.2 months compared to 15.5 months of the patients below the median. No association between M2 macrophage density and patient's outcome was found. In multivariate analysis, M1/M2 was a positive independent predictor of survival. The M1 macrophage density and M1/M2 ratio, as confirmed in multivariate analysis, are factors that can help in predicting patients survival time after radical surgery for gastric cancer.
PMCID: PMC4117554  PMID: 24283947
tumour associated macrophages; M1 polarization; M2 polarization; prognostic factor; gastric cancer
18.  Necrotizing Fasciitis on the Right Side of the Neck with Internal Jugular Vein Thrombophlebitis and Septic Emboli: A Case of Lemierre’s-Like Syndrome 
Lemierre’s syndrome (LS) is a rare life-threatening infective condition typically starting with an oropharyngeal infection causing thrombophlebitis and metastatic abscesses. The most common aetiology of LS is Fusobacterium necrophorum; however, it can also occur after infection with other organisms. LS mainly affects young healthy adults. The initial infection site can be in the head and neck or in the abdomen. The morbidity rate of this disease is high despite aggressive treatments. In this article, we report a 63-year-old male patient with uncontrolled diabetes mellitus, presenting with Klebsiella pneumoniae infection-induced necrotizing fasciitis on the right side of the neck, leading to LS.
PMCID: PMC3957351  PMID: 24643401
necrotizing fasciitis; Lemierre syndrome; Fusobacterium necrophorum; Klebsiella pneumoniae
19.  Mesenchymal Chondrosarcoma: A Case Report 
Mesenchymal chondrosarcoma is a rare disease with poor prognosis. Treatment including wide or radical excision is very important. Radiotherapy and chemotherapy are additional treatment options, but no conclusive results for their efficacy have been shown until date. Imaging modalities can give important clues for diagnosis and management planning. Angioembolization before surgery could be useful as prophylaxis to control intraoperative bleeding, increasing the likelihood of complete resection.
PMCID: PMC3743986  PMID: 23966829
mesenchymal chondrosarcoma; extraskeletal; therapeutic embolization
20.  Image-guided chemoport insertion by interventional radiologists: A single-center experience on periprocedural complications 
To report our early experience in image-guided chemoport insertions by interventional radiologists.
Materials and Methods:
This was a cross-sectional study conducted in a tertiary center with 161 chemoport insertions done from June 2008 to June 2010. The chemoports were inserted either at the angiography suite or at the mobile operation theater unit. Ninety percent of the chemoports had right internal jugular vein (IJV) as the entry site. Other entry sites included the left IJV, subclavian veins and the inferior vena cava. Immediate and early complications were recorded. All insertions were performed under image guidance with the aid of ultrasound and fluoroscopy.
The technical success rate was 99.4%. In terms of immediate complications, there were only two cases of arterial puncture that resolved with local compression. No pneumothorax or air embolism was documented. Twenty-six early complications were recorded. The most common early complication was catheter blockage (12/161; 7.4%), followed by catheter-related infection (9/161; 5.6%). Other complications were catheter malposition, venous thrombosis and catheter dislodgement or leak. A total of 11 (6.8%) chemoports had to be removed within 30 days; most of them were due to infections that failed to respond to systemic antibiotic therapy. In terms of place of procedure, there were no significant differences in complication rates between the angiography suite and the mobile operation theater unit.
Image-guided chemoport insertion by interventional radiologist gives low periprocedural complication rates. Using right IJV as the entry site, the image guidance gives good success rate with least complication.
PMCID: PMC3777320  PMID: 24082475
Central venous catheterization; complications; interventional radiology; vascular access ports
21.  Percutaneous Catheter-Based Rheolytic Thrombectomy for Massive Pulmonary Embolism: A Case Report 
Pulmonary thromboembolism is a life-threatening cardiovascular condition. The mortality rate is high in its current management. Besides supportive treatments, systemic thrombolysis and surgical thrombectomy play important roles in the comprehensive management of pulmonary embolism (PE). The percutaneous catheter-based rheolytic thrombectomy is a promising alternative for management of massive pulmonary emboli, particularly, when patients have contraindication with systemic thrombolysis or are not suitable for surgery.
We present the case of a 36-year-old Somalian man who came to our center for a total knee replacement (TKR). Three days after TKR, he developed sudden shortness of breath and decreased oxygen saturation. Computed tomography of pulmonary arteriogram showed extensive thrombi within the main pulmonary trunk, right and left pulmonary arteries, bilateral ascending and bilateral descending pulmonary arteries in keeping with massive PE. Because the patient was contraindicated for systemic thrombolysis, percutaneous, catheter-based rheolytic thrombectomy was chosen as the alternative treatment. His clinical symptoms improved immediately post-treatment. In conclusion, catheter-based rheolytic thrombectomy can serve as an alternative treatment for massive PE with a good clinical outcome.
PMCID: PMC3744003  PMID: 23983581
thrombectomy; thrombolysis; pulmonary embolism
22.  Better Rooting Procedure to Enhance Survival Rate of Field Grown Malaysian Eksotika Papaya Transformed with 1-Aminocyclopropane-1-Carboxylic Acid Oxidase Gene 
ISRN biotechnology  2012;2013:958945.
A high survival rate for transformed papaya plants when transferred to the field is useful in the quest for improving the commercial quality traits. We report in this paper an improved rooting method for the production of transformed Malaysian Eksotika papaya with high survival rate when transferred to the field. Shoots were regenerated from embryogenic calli transformed with antisense and RNAi constructs of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) genes using the Agrobacterium tumefaciens-mediated transformation method. Regenerated transformed shoots, each measuring approximately 3-4 cm in height, were cultured in liquid half-strength Murashige and Skoog (MS) medium or sterile distilled water, and with either perlite or vermiculite supplementation. All the culturing processes were conducted either under sterile or nonsterile condition. The results showed that rooting under sterile condition was better. Shoots cultured in half-strength MS medium supplemented with vermiculite exhibited a 92.5% rooting efficiency while perlite showed 77.5%. The survival rate of the vermiculite-grown transformed papaya plantlets after transfer into soil, contained in polybags, was 94%, and the rate after transfer into the ground was 92%. Morpho-histological analyses revealed that the tap roots were more compact, which might have contributed to the high survival rates of the plantlets.
PMCID: PMC4403608  PMID: 25969786
23.  In Situ Identification of CD44+/CD24− Cancer Cells in Primary Human Breast Carcinomas 
PLoS ONE  2012;7(9):e43110.
Breast cancer cells with the CD44+/CD24− phenotype have been reported to be tumourigenic due to their enhanced capacity for cancer development and their self-renewal potential. The identification of human tumourigenic breast cancer cells in surgical samples has recently received increased attention due to the implications for prognosis and treatment, although limitations exist in the interpretation of these studies. To better identify the CD44+/CD24− cells in routine surgical specimens, 56 primary breast carcinoma cases were analysed by immunofluorescence and confocal microscopy, and the results were compared using flow cytometry analysis to correlate the amount and distribution of the CD44+/CD24− population with clinicopathological features. Using these methods, we showed that the breast carcinoma cells displayed four distinct sub-populations based on the expression pattern of CD44 and CD24. The CD44+/CD24− cells were found in 91% of breast tumours and constituted an average of 6.12% (range, 0.11%–21.23%) of the tumour. A strong correlation was found between the percentage of CD44+/CD24− cells in primary tumours and distant metastasis development (p = 0.0001); in addition, there was an inverse significant association with ER and PGR status (p = 0.002 and p = 0.001, respectively). No relationship was evident with tumour size (T) and regional lymph node (N) status, differentiation grade, proliferative index or HER2 status. In a multivariate analysis, the percentage of CD44+/CD24− cancer cells was an independent factor related to metastasis development (p = 0.004). Our results indicate that confocal analysis of fluorescence-labelled breast cancer samples obtained at surgery is a reliable method to identify the CD44+/CD24− tumourigenic cell population, allowing for the stratification of breast cancer patients into two groups with substantially different relapse rates on the basis of CD44+/CD24− cell percentage.
PMCID: PMC3441535  PMID: 23028444
24.  Breast milk expression among formally employed women in urban and rural Malaysia: A qualitative study 
Many women are unable to practice exclusive breastfeeding because they are separated from their infants while working. Expressing their breast milk helps them to continue breastfeeding. This study explores the perception and experiences related to the feasibility, acceptability and safety of breast milk expression among formally employed women in Kelantan, Malaysia.
A qualitative method using in-depth interviews was conducted from December 2008 to December 2009 among Malay women from urban and rural areas. A snowball sampling method was used to recruit the informants, and the interviews, which were facilitated by an interview guide, were audio-recorded and transcribed verbatim. Thematic analysis was conducted, with construction of codes and themes from each interview.
Analysis of the interviews with 20 informants identified three themes related to breast milk expression. The themes were as follows: (i) lack of feasibility of expressing breast milk, (ii) negative feelings about expressing breast milk, and (iii) doubts about the safety and hygiene of expressed breast milk. The informants who did not practice exclusive breastfeeding believed that expressing their breast milk was not feasible, commonly because they felt there were not enough facilities for them. They also had negative feelings such as embarrassment. The safety and hygiene of the expressed breast milk was also their main concern.
More practical and focused education, as well as provision of facilities, is needed for women to effectively and safely express and store their breast milk. The issue of inadequate milk production should be emphasized, especially by encouraging them to express their breast milk as a way to improve milk production.
PMCID: PMC3453522  PMID: 22929649
Breast milk expression; Pumping; Exclusive breastfeeding; Employed; In-depth interview
25.  Fatal mediastinal biopsy: How interventional radiology saves the day 
Annals of Thoracic Medicine  2012;7(2):107-109.
This was a case of a 35-year-old man with mediastinal mass requiring computed tomography (CT)-guided biopsy for tissue diagnosis. A posterior approach with an 18-gauge biopsy needle was used to obtain tissue sample. Post biopsy, patient condition deteriorated and multiphase CT study detected active bleeding in arterial phase at the biopsy site with massive hemothorax. Subsequent angiography showed arterial bleeder arising from the apical branch of the right pulmonary artery. Selective endovascular embolization with NBCA (n-Butyl cyanoacrylate) was successful. Patient survived the complication. The case highlighted a rare complication in a common radiology procedure and the value of the interventional radiology unit in avoiding a fatal outcome.
PMCID: PMC3339201  PMID: 22558017
Biopsy; complications; computed tomography; guidance; mediastinum; therapeutic embolization

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