Links between socio-demographic characteristics and body mass index to colorectal cancer in North Borneo, Malaysia: A case-control study.

INTRODUCTION: The fourth leading cause of cancer-related mortality and morbidity worldwide is colorectal cancer (CRC). Numerous reasons have contributed to the massive rise in CRC cases, for which Asian nations differ significantly in terms of risk incidence rates. The objectives of this study were to, first, identify the socio-demographic characteristics of those of North Borneo ethnicity and body mass index (BMI) and, second, determine the association of these factors with CRC. This research will contribute to preventing this form of cancer. MATERIALS AND METHODS: This study is an analysis of a matched case-control study with a ratio of 1:2. The case group contained 206 respondents, and the control group contained 412. All CRC cases were confirmed with the histological results. The control group was matched for links between age, sex and ethnicity with CRC. The Statistical Package for Social Sciences Statistics (SPSS) IBM version 28.0 was used to conduct descriptive analysis using chi-squared testing and simple logistic regression. The statistical significance was P < 0.05. RESULT: Overall, 618 respondents took part in this survey, of which 256 (41.4%) were female and 362 (58.6%) were male. The maximum age was 76, with a mean age ± SD of 53.17 ± 11.4. Those of Bajau ethnicity comprised 24.6% (152) of the population, followed by Dusun with 22.8% (141), Kadazan with 17.6% (109%), other North Borneo ethnic groups with 15.5% (96), Bugis with 9.7% (60), Brunei with 4.4% (27) and other predominant races with 5.3% (33). Regression analyses revealed that the incidence of CRC in North Borneo, Malaysia, was substantially correlated with income, occupation, other linked diseases and BMI. CONCLUSION: Various risk factors are linked to CRC, based on the findings related to socio-demographic characteristics and BMI. Therefore, to lower the nationwide prevalence of CRC, national public health campaigns should include collaboration with the regional authorities to highlight the incidence and risk factors of CRC based on ethnicity.

Development of the rural Palliative Care Services by the Kuala Lipis District Hospital.

In recognising the palliative care (PC) needs globally and in Malaysia, services were developed to serve the rural area of Kuala Lipis, Pahang. This communication describes the initial a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis, stages of development towards achieving a successful implementation. PC services were led by Kuala Lipis district hospital include inpatient referrals, outpatient and community care through home visits. These services involve multi-disciplinary team inclusive of representatives from health clinics and allied health. Referrals and opioid usage have demonstrated an increasing trend since its implementation in October 2018. Implementation of rural PC services is feasible; however, long-term sustainability needs to addressed.

Meis2 as a critical player in MN1-induced leukemia.

Meningioma 1 (MN1) is an independent prognostic marker for normal karyotype acute myeloid leukemia (AML), with high expression linked to all-trans retinoic acid resistance and poor survival. MN1 is also a potent and sufficient oncogene in murine leukemia models, strongly dependent on the MEIS1/AbdB-like HOX protein complex to transform common myeloid progenitors, block myeloid differentiation, and promote leukemic stem cell self-renewal. To identify key genes and pathways underlying leukemic activity, we functionally assessed MN1 cell phenotypic heterogeneity, revealing leukemic and non-leukemic subsets. Using gene expression profiling of these subsets combined with previously published comparisons of full-length MN1 and mutants with varying leukemogenic activity, we identified candidate genes critical to leukemia. Functional analysis identified Hlf and Hoxa9 as critical to MN1 in vitro proliferation, self-renewal and impaired myeloid differentiation. Although critical to transformation, Meis1 knockdown had little impact on these properties in vitro. However, we identified Meis2 as critical to MN1-induced leukemia, with essential roles in proliferation, self-renewal, impairment of differentiation and disease progression in vitro and in vivo. Here, we provide evidence of phenotypic and functional hierarchy in MN1-induced leukemic cells, characterise contributions of Hlf, Hoxa9 and Meis1 to in vitro leukemic properties, and reveal Meis2 as a novel player in MN1-induced leukemogenesis.

Nasopharyngeal non-intestinal-type adenocarcinoma: a case report and updated review of the literature.

BACKGROUND: Non-intestinal-type adenocarcinoma is a malignancy traditionally found in the sinonasal cavity. To our knowledge, this case is the first reported of this rare condition originating in the nasopharynx. CASE PRESENTATION: A 67-year-old woman with nasopharyngeal non-intestinal-type adenocarcinoma, with an accompanying parapharyngeal mass received primary radiation treatment for both lesions. Her tumour subsequently persisted, with a concomitant conversion in pathology from a low- to a high-grade malignancy. RESULTS: Non-intestinal-type and intestinal-type adenocarcinomas of the nasopharynx are extremely rare tumours and do not appear in the World Health Organization classification system. We review the pathophysiologic features of these malignancies and propose modifications to the current classification system. CONCLUSIONS: Non-intestinal-type adenocarcinoma should be included in the differential diagnosis of nasopharyngeal masses. In our experience, this tumour in this location showed a partial response to primary radiation but later converted from a low- to a high-grade adenocarcinoma.

Constitutive IRF8 expression inhibits AML by activation of repressed immune response signaling.

Myeloid differentiation is blocked in acute myeloid leukemia (AML), but the molecular mechanisms are not well characterized. Meningioma 1 (MN1) is overexpressed in AML patients and confers resistance to all-trans retinoic acid-induced differentiation. To understand the role of MN1 as a transcriptional regulator in myeloid differentiation, we fused transcriptional activation (VP16) or repression (M33) domains with MN1 and characterized these cells in vivo. Transcriptional activation of MN1 target genes induced myeloproliferative disease with long latency and differentiation potential to mature neutrophils. A large proportion of differentially expressed genes between leukemic MN1 and differentiation-permissive MN1VP16 cells belonged to the immune response pathway like interferon-response factor (Irf) 8 and Ccl9. As MN1 is a cofactor of MEIS1 and retinoic acid receptor alpha (RARA), we compared chromatin occupancy between these genes. Immune response genes that were upregulated in MN1VP16 cells were co-targeted by MN1 and MEIS1, but not RARA, suggesting that myeloid differentiation is blocked through transcriptional repression of shared target genes of MN1 and MEIS1. Constitutive expression of Irf8 or its target gene Ccl9 identified these genes as potent inhibitors of murine and human leukemias in vivo. Our data show that MN1 prevents activation of the immune response pathway, and suggest restoration of IRF8 signaling as therapeutic target in AML.

Worldwide burden of COPD in high- and low-income countries. Part III. Asia-Pacific studies.

Chronic obstructive pulmonary disease (COPD) is a global health problem that poses a heavy burden on most countries in the Asia-Pacific region. When compared to industrialised Western countries, the COPD burden in the Asia-Pacific region is higher in terms of the number of deaths, years spent living with disability and years of life lost. Given the high prevalence of tobacco smoking, poor indoor and outdoor air quality and the aging population in many Asian countries, urgent actions need to be taken to reduce the development, morbidity and mortality of this disease.

Bacillus licheniformis proteases as high value added products from fermentation of wastewater sludge: pre-treatment of sludge to increase the performance of the process.

Wastewater sludge is a complex raw material that can support growth and protease production by Bacillus licheniformis. In this study, sludge was treated by different thermo-alkaline pre-treatment methods and subjected to Bacillus licheniformis fermentation in bench scale fermentors under controlled conditions. Thermo-alkaline treatment was found to be an effective pre-treatment process in order to enhance the proteolytic activity. Among the different pre-treated sludges tested, a mixture of raw and hydrolysed sludge caused an increase of 15% in the protease activity, as compared to the untreated sludge. The benefit of hydrolysis has been attributed to a better oxygen transfer due to decrease in media viscosity and to an increase in nutrient availability. Foam formation was a major concern during fermentation with hydrolysed sludge. The studies showed that addition of a chemical anti-foaming agent (polypropylene glycol) during fermentation to control foam could negatively influence the protease production by increasing the viscosity of sludge.

Increasing COPD awareness.

Early diagnosis and smoking cessation are the only available methods to stop the progression of chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the effects of early detection of airflow limitation (AL) in a population with high risk for COPD, using spirometric screening. Smokers aged 40 yrs with a smoking history of 10 pack-yrs were invited to visit a local outpatient chest clinic for simple spirometry (forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)). Smoking history was recorded, followed by smoking cessation advice relating the results of spirometry to the smoking behaviour. Subjects who did not fulfil the above criteria (younger and/or nonsmokers) were also screened. A total 110,355 subjects were investigated; they were aged 53.5+/-11.5 yrs and 58.2% were males. Of the total amount of subjects, 64% were current smokers, 25.1% were former smokers and 10.9% were lifelong nonsmokers. Spirometry tests were within normal values for 70.3%, and 20.3% showed signs of AL: this was mild in 7.6%, moderate in 6.7% and severe in 5.9%. The remaining 8.3% of subjects presented with a restrictive pattern of ventilatory impairment. Airflow limitation was found in 23% of smokers aged 40 yrs with a history of 10 pack-yrs. This study concluded that large-scale voluntary spirometry screening of the population with high risk for COPD detects a large number of subjects with AL.

Exhaled breath condensate levels of eotaxin and macrophage-derived chemokine in stable adult asthma patients.

BACKGROUND: Asthma is associated with esoinophilic airway inflammation and overproduction of T-helper type 2 (Th2) lymphocyte-related cytokines. OBJECTIVE: This study assessed the eosinophil chemoattractant eotaxin and Th2-specific macrophage-derived chemokine (MDC) in the adult asthmatic airway. Eotaxin and MDC levels were determined in exhaled breath condensate (EBC) obtained from adult patients with asthma. METHODS: Fifty-four asthmatics (20 male, mean (SD) age 40 (12) years and percentage predicted forced expiratory volume in 1 s (FEV(1)) 81.7 (20.8)) and 20 age- and sex-matched controls were studied. EBC was collected using EcoScreen by 10 min of tidal breathing with a nose clip. Concentrations of eotaxin and MDC were measured by ELISA. RESULTS: Asthma patients on inhaled corticosteroid (ICS) had a higher median interquartile range (IQR) level of eotaxin than the steroid-naïve asthmatics (18.5 (17.7-20.1) vs. 17.9 (17.0-18.6) pg/mL, P=0.02) and controls (18.5 (17.7-20.1) pg/mL vs 17.4 (16.3-18.0) pg/mL, P=0.001). Eotaxin level in EBC had a significant negative correlation with the FEV(1)/forced vital capacity ratio (r=-0.43, P=0.03) in steroid-naïve asthmatics. EBC MDC level was higher in subjects on ICS than the steroid naïve asthmatics (120 (118-125) vs. 117 (116-119) pg/mL, P=0.01) and the controls (120 (118-125) vs. 117 (116-120) pg/mL, P=0.02). CONCLUSIONS: Eotaxin and MDC could be measured in EBC of adults with asthma. EBC eotaxin and MDC levels were higher in asthmatics on ICS than the steroid-naïve asthmatics or controls. Exhaled chemokines may be potential non-invasive markers for assessing airway inflammation in asthmatics.

Heterogeneous mutations in the SLC3A1 and SLC7A9 genes in Chinese patients with cystinuria.

Cystinuria is a recessively inherited aminoaciduria that leads to recurrent urolithiasis. It is caused by the defective transport of cystine and dibasic amino acids in the proximal renal tubules and intestinal epithelium. Two genes responsible for this, SLC3A1 and SLC7A9, are known. Patients with two SLC3A1 mutations are classified as type A cystinuria, whereas patients with two SLC7A9 mutations are classified as type B cystinuria. Few clinical and molecular data have been reported for Asian cystinuria patients. In this study, we determined the molecular basis of cystinuria in eight unrelated Chinese subjects. Coding exons and flanking introns of the SLC3A1 and SLC7A9 genes were directly sequenced after amplification by polymerase chain reaction. Five different SLC3A1 mutations were found. Two missense mutations, D210G and S547L, were novel. The other three SLC3A1 mutations (IVS6+2T>C, R181Q and R365W) have been described previously. In addition, four novel SLC7A9 mutations, C137R, c.730delG, IVS10+2_3delTG and IVS12+3insT, together with two previously reported mutations (A70V and G195R) were found. All patients except one carried compound heterozygous mutations. IVS12+3insT was detected in patients from two families. This is the first molecular genetic study on Chinese cystinuria patients. Three patients with type A cystinuria, two with type B cystinuria, and three carriers of type B cystinuria were identified. Our results suggest that the molecular basis of cystinuria is heterogeneous in our local population.

Granulocytic sarcoma of the small bowel causing intestinal obstruction.

Granulocytic sarcomas of the small bowel are rare. They are discrete tumours of leukaemic myeloblasts and partially matured granulocytes that form in any part of the body. This disease is infrequently seen in patients with acute myeloid leukaemia, and rarely seen in patients without leukaemia. Here we report a case of small bowel obstruction due to granulocytic sarcoma of mid-ileum in a non-leukaemic patient. We also review the literature on treatment and prognosis of this condition.

Candidate genetic polymorphisms for asthma in Chinese schoolchildren from Hong Kong.

BACKGROUND: Polymorphisms in several genes have been associated with asthma, atopy and bronchial hyperresponsiveness in white and Japanese populations. In this study we tested for associations of 11 polymorphisms with wheeze and asthma in 10-year-old Chinese schoolchildren. METHODS: The subjects were 107 children who had wheeze in the last 12 months and 118 without wheeze in the last 12 months. They were randomly selected from 3110 children who took part in Phase II of the International Study of Asthma and Allergies in Childhood. These schoolchildren underwent questionnaire, spirometry and methacholine challenge testing. RESULTS: The A allele of the tumor necrosis factor-alpha (TNFA) G-308A polymorphism was significantly associated with wheeze in the last 12 months (odds ratio [OR] 2.1, P = 0.04) and current asthma (OR 2.6, P = 0.006). When stratified by gender, these associations were only seen in the female study participants. In girls, the OR for the TNFA-308A allele and wheeze in the last 12 months was 3.6 (P = 0.01) and for current asthma it was 6.0 (P = 0.0006). CONCLUSION: The A allele of the TNFA G-308A polymorphism was a risk factor for asthma-related phenotypes in girls but not boys.

Infantile isolated sulphite oxidase deficiency in a Chinese family: a rare neurodegenerative disorder.

We report the clinical, biochemical, neuroradiological, and neurophysiological findings of a 4-year-old Chinese girl with infantile isolated sulphite oxidase deficiency. This is the first reported case in our locality. She presented at the age of 5 months with refractory seizures and developmental regression, and progressed rapidly to profound psychomotor retardation, spasticity, dystonia, microcephaly, and blindness. At the age of 3.5 years, she was admitted to the intensive care unit with septic shock. Ophthalmologic examination at this time revealed bilateral dislocation of the lens. Diagnosis of this very rare disorder was made on the basis of increased levels of urinary sulphite, thiosulphate, and sulphocysteine; normal urine xanthine and hypoxanthine; normal plasma uric acid; and low plasma cystine levels. The diagnosis was confirmed by the absence of sulphite oxidase activities in skin fibroblasts. Isolated sulphite oxidase deficiency is a rare inborn error of sulphur metabolism that is difficult to diagnose on clinical features and routine metabolic tests. The presence of ectopia lentis, seizures, and progressive neurological abnormalities should alert clinicians to the diagnosis.

Prevalence of wheeze, bronchial hyper-responsiveness and asthma in the elderly Chinese.

BACKGROUND: Asthma is a common health problem affecting patients of all ages. Because of the ease of sampling, epidemiological studies have concentrated mainly on the paediatric and general population. OBJECTIVE: This study aimed to determine the prevalence of wheeze, bronchial hyper-responsiveness and asthma amongst our elderly population and deduce any clinical and laboratory risk factors that might identify elderly asthmatics at an earlier stage. METHODS: Two thousand and thirty-two elderly Chinese aged > or = 70 years, randomly selected from a registered list of all recipients of Old Age and Disability Allowances in Hong Kong, were administered a questionnaire on lung health. Two hundred and fifty subjects were invited to attend our laboratory for skin tests and pulmonary function tests and 179 agreed. Of these, 173 (96.6%) and 176 (98.3%) had eosinophil count and serum IgE levels measured, respectively. Two definitions of asthma were used: (1) bronchial hyper-responsiveness (BHR) plus current wheeze, and (2) history of wheezing without previous diagnostic labels of emphysema or chronic bronchitis. RESULTS: Fifteen patients (out of 179: 8.4%) reported wheezing over the past 1 year. Fifty-one patients (28.5%) demonstrated BHR on spirometry or histamine challenge tests. Seven patients had both symptoms of wheezing and evidence of BHR. The prevalence of asthma using this definition is therefore 3.9% (95% CI 1.6-7.9%). Nine patients had symptoms of wheezing without previous diagnostic labels of chronic bronchitis or emphysema and, using this definition, the prevalence is 5.0% (95% CI 2.3-9.3%). Using multiple logistic regression studies, sex, social class, age, smoking habits, serum IgE levels and eosinophil counts did not predict a diagnosis of asthma using either definition. We found no association between a positive skin test and any respiratory symptoms or illnesses including asthma. CONCLUSION: Wheeze, bronchial hyper-responsiveness and asthma are prevalent amongst our elderly population. However, there were no identifiable demographic and laboratory risk factors in this study that may help us predict a diagnosis of asthma.

Absorption of lidocaine during aspiration anesthesia of the airway.

STUDY OBJECTIVE: To determine the optimal solution to use when anesthetizing the airway by aspiration of lidocaine. DESIGN: Randomized, double-blind clinical study. SETTING: University hospital. PATIENTS: 96 adult ASA physical status 1,II, and III patients, scheduled for diagnostic flexible bronchoscopy. INTERVENTIONS: Patients were randomized to receive one of 5 solutions of lidocaine: Group A (n = 16): 1% lidocaine, 0.2 mL. kg(-1); Group B (n = 16): 1.5% 0.2 mL. kg(-1); Group C (n = 32): 2% 0.2 mL. kg(-1); Group D (n = 16): 1% 0.3 mL. kg(-1), and Group E (n = 16): 2% 0.3 mL. kg(-1). Fiberoptic bronchoscopy was performed after the airway was anesthetized with this aspiration technique, using the assigned lidocaine solution. The scope was manipulated in the trachea to test for anesthesia. MEASUREMENTS AND MAIN RESULTS: Successful airway anesthesia was determined by tolerance to bronchoscopy without sustained coughing, and also by the number of lidocaine supplements, if any, that were given via the bronchoscope. Arterial plasma concentrations of lidocaine were measured in 33 patients from Groups C, D, and E. All solutions provided equally effective anesthesia of the airway. All patients tolerated endoscopy through the vocal cords, and 94 patients required no supplementary anesthesia, or only one dose of lidocaine, during bronchoscopy to the carina. The highest peak plasma concentrations of lidocaine were 5.02 and 6.28 microg. mL. No patient had signs of toxicity. CONCLUSIONS: This technique produced anesthesia of the airway to the carina, safely, suitable for awake intubation, in 94 of 95 patients. The use of 1% lidocaine, 0.2 to 0.3 mL. kg(-1), so that the volume is 10 to 20 mL, is recommended.

Transcription repression of human hepatitis B virus genes by negative regulatory element-binding protein/SON.

A negative regulatory element (NRE) is located immediately upstream of the upstream regulatory sequence of core promoter and second enhancer of human hepatitis B virus (HBV). NRE represses the transcription activation function of the upstream regulatory sequence of core promoter and the second enhancer. In this study, we described the cloning and characterization of an NRE-binding protein (NREBP) through expression cloning. NREBP cDNA is 8266 nucleotides in size and encodes a protein of 2386 amino acids with a predicted molecular mass of 262 kDa. Three previously described cDNAs, DBP-5, SONB, and SONA, are partial sequence and/or alternatively spliced forms of NREBP. The genomic locus of the NREBP/SON gene is composed of 13 exons and 12 introns. The endogenous NREBP protein is localized in the nucleus of human hepatoma HuH-7 cells. Antibody against NREBP protein can specifically block the NRE binding activity present in fractionated nuclear extracts in gel shifting assays, indicating that NREBP is the endogenous nuclear protein that binds to NRE sequence. By polymerase chain reaction-assisted binding site selection assay, we determined that the consensus sequence for NREBP binding is GA(G/T)AN(C/G)(A/G)CC. Overexpression of NREBP enhances the repression of the HBV core promoter activity via NRE. Overexpression of NREBP can also repress the transcription of HBV genes and the production of HBV virions in a transient transfection system that mimics the viral infection in vivo.

Obstructive sleep apnoea syndrome: treatment update.

Obstructive sleep apnoea syndrome is a common but underrecognised disorder with associated substantial morbidity and mortality. Excessive daytime sleepiness caused by the disorder leads to poor work performance and increases the risk of an individual having an automobile accident. The main objective of treatment for sleep apnoea is the relief of disabling daytime sleepiness and the improvement of quality of life. Conservative measures such as weight reduction and the avoidance of alcohol should be initiated when appropriate. Nasal continuous positive airway pressure devices have remained the standard treatment since it was first introduced in 1981. Oral appliances provide an alternative treatment choice in mild-to-moderate cases, whereas surgery is useful in selected cases.

Transcriptional repression of human hepatitis B virus genes by a bZIP family member, E4BP4.

Box alpha is an essential element of both the upstream regulatory sequence of the core promoter and the second enhancer, which positively regulate the transcription of human hepatitis B virus (HBV) genes. In this paper, we describe the cloning and characterization of a box alpha binding protein, E4BP4. E4BP4 is a bZIP type of transcription factor. Overexpression of E4BP4 represses the stimulating activity of box alpha in the upstream regulatory sequence of the core promoter and the second enhancer in differentiated human hepatoma cell lines. E4BP4 can also suppress the transcription of HBV genes and the production of HBV virions in a transient-transfection system that mimics the viral infection in vivo. Expression of an E4BP4 antisense transcript can, instead, elevate the transcription of the core promoter. A low abundance of E4BP4 protein and mRNA in differentiated human hepatoma cell lines is detected, and E4BP4 is not a major component of box alpha binding proteins in untransfected differentiated human hepatoma cell lines. C/EBPalpha and C/EBPbeta, in contrast, are major components of the box alpha binding activity present in nuclear extracts. E4BP4 has a stronger binding affinity towards box alpha than the endogenous box alpha binding activity present in nuclear extracts. Structure and function analysis of E4BP4 reveals that DNA binding activity is sufficient to confer the negative regulatory function of E4BP4. These results indicate that binding site occlusion is the mechanism whereby E4BP4 suppresses transcription in HBV.