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Periodic benchmarking of the epidemiology of COVID-19 in the Association of Southeast Asian Nations (ASEAN) countries is critical for the continuous understanding of the transmission and control of COVID-19 in the region. The incidence, mortality, testing and vaccination rates within the ASEAN region from 1 January 2020 to 15 October 2021 is analysed in this paper.COVID-19 data on cases, deaths, testing, and vaccinations were extracted from the Our World in Data (OWID) COVID-19 data repository for all the ten ASEAN countries. Comparative time-trends of the epidemiology of COVID-19 using the incidence rate, cumulative case fatality rate (CFR), delay-adjusted case fatality rate, cumulative mortality rate (MR), test positivity rate (TPR), cumulative testing rate (TR) and vaccination rate was carried out.Over the study period, a total of 12,720,661 cases and 271,475 deaths was reported within the ASEAN region. Trends of daily per capita cases were observed to peak between July and September 2021 for the ASEAN region. The cumulative case fatality rate (CFR) in Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Vietnam, was of 0.9% (N=68), 2.2% (N=2,610), 3.5% (N=142,889), 0.1% (N=36), 1.2% (N=27,700), 4.0% (N=18,297), 1.6% (N=40,424), 0.1% (N=215), 1.7% (N=18,123), and 2.6% (N=21,043), respectively. CFR was consistently highest between January-June 2020. The cumulative mortality rate (MR) was 9.5, 13.7, 51.4, 0.2, 80.3, 32.4, 34.5, 1.6, 23.9 and 19.7 per 100,000 population, respectively. The cumulative test positivity rate (TPR) was 8.4%, 16.9%, 4.6%, 7.5%, 11.1%, 12.9%, 0.5%, 11.7%, and 3.6%, with the cumulative testing rate (TR) at 25.0, 90.1, 27.4, 917.7, 75.8, 177.8, 3303.3, 195.2, and 224.9 tests per 1,000 population in Cambodia, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Vietnam, respectively. The percentage of population that completed vaccinations (VR) was 44.5%, 65.3%, 18.5%, 28.2%, 61.8%, 6.8%, 19.2%, 76.8%, 22.7%, and 10% in Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Vietnam, respectively.In 2020, most countries in ASEAN had higher case fatality rates but lower mortalities per population when compared to the third quarter of 2021 where higher mortalities per population were observed. Low testing rates have been one of the factors leading to high test positivity rates. Slow initiation of vaccination programs was found to be the key factor leading to high incidence and case fatality rate in most countries in ASEAN. Effective public health measures were able to interrupt the transmission of this novel virus to some extent. Increasing preparedness capacity within the ASEAN region is critical to ensure that any future similar outbreaks can be dealt with collectively.

The prevalence of urinary incontinence among pregnant women is high in Malaysia. However, healthcare providers appear to pay little attention to it along with a limited local intervention that addresses the continence health during pregnancy. This study aims to develop and validate intervention with pelvic floor muscle exercise (PFME) for pregnant women.The development of PFME intervention was guided by the Medical Research Council Framework for Developing and Evaluating Complex Intervention (MRC Framework). This involved four phases: identification of current research evidence, expert opinion, validation via focus group discussions with physiotherapists and pregnant women, and piloting the intervention using a single group pre-post design among 30 pregnant women at Maternity Hospital Kuala Lumpur to assess the feasibility of the intervention by evaluating changes in knowledge and attitude. The qualitative approach was used to analyse the first three phases, while non-parametric methods were used to analyse the pilot prepost test results.Based on research evidence and guidelines found during the literature review, a PFME intervention was developed using a new paradigm incorporating two theories, the Health Belief Model and Motivational Interviewing that have been shown to be important in continence promotion and exercise adherence. The contribution of the panel of experts in refining the intervention to meet the local context, endorses the achievement of the intervention's content validity. While, the focus group discussion with pregnant women and physiotherapists revealed the face-validity of the intervention. The findings of the pilot pre-testing showed that PFME knowledge (p0.001) and attitude (p=0.011) improved significantly immediately following the intervention.Evidently, this is a pioneer study that illustrates the development of a Malaysian context-adapting PFME intervention on the basis of recommended steps using the MRC Framework. Incorporating a theory-based and rigorous validation approach into the development of the PFME intervention brought novel perspectives to the intervention. Given the promising preliminary results of the pre-testing pilot study, the PFME intervention could be implemented in the planned randomised control trial to validate the robustness of the results.

No abstract provided.

Sharing of knowledge through Continuing Medical Education (CME) contribute immensely to professional development of skills in clinical medical practice. Thus, the writing of CME articles should adopt an approach that addresses the needs of the readers by attempting to fill gaps in their knowledge, skills, and ethics about clinical care. As such CME articles should be comprehensive and focused on specific areas. The specific learning outcomes should be well defined. In designing and development of such articles, pedagogic principles are to be borne in mind. In this article we outline a guide to writing a CME article, incorporating both the principles of instructional design and directed selflearning. The ideal CME articles will transit through multimedia-enhanced interactive online learning, with greater use of connectivity through the internet. Synchronous and asynchronous learning is in greater need, as distance and online learning are increasingly popular. Authors of CME articles will need to eventually design CME articles to be interactive, enriched with multimedia to engage their readers. Lesson plans employing instructional design principles should aim to promote both instructions for learning and formative assessment ensuring learning have taken place, and outcomes have been achieved. This article describes on how to write effective CME articles for medical journals.

The first case of COVID-19 was reported in Malaysia on the 25 January 2020. By the 20 January 2021, the cumulative numbers reported confirmed cases of COVID-19 had reached 169,379 including 630 deaths. Malaysia has been hit by three waves of COVID-19. This article reports on the three waves, the current situation and some of the possible factors associated. It outlines the need to reassess the overall situation, re-strategize the approach in order to contain the spread. The first COVID-19 wave lasted from 25 January to 16 February 2020, the second wave occurred between the 27 February 2020 and the 30 June 2020. The current third wave began on 8th September 2020.The sudden surge of cases in the third wave was mainly due to the two largest contributors, namely the Benteng Lahad Datu cluster in Sabah state and Kedah's Tembok cluster. The current situation is critical. The daily confirmed cases of COVID-19 continue to soar. The challengers faced by healthcare workers and other front liners is tremendous. Non-communicable diseases such as cardiovascular diseases, diabetes and cancer are the leading cause of death in Malaysia. A paradigm shift in the approach is required to ensure the sustainability of the normal healthcare services provided by the government especially for the lower income groups. There is also a need to expedite the tabling of Tobacco Control Bill in coming parliament session which is long overdue. H.E. the King of Malaysia has called on all Malaysians to put aside political, racial and religious differences and show the spirit of loyalty, humanitarianism and steadfastness in fighting the COVID-19 pandemic.

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions. © Copyright.

No abstract provided.

The number of cancer cases in Malaysia has increased from 32,000 cases in 2008 with to 37,000 in 2012 (check figures in text). This number is expected to rise to 56,932 by 2025. Cancer patients undergoing chemotherapy experience low to moderate level of self-esteem.To determine the self-esteem among oncology patients receiving chemotherapy in selected government state hospitals, Peninsular Malaysia.A cross-sectional study was conducted using selfadministered questionnaires. 953 respondents were given questionnaires which included socio-demographic profile, physical effect, depression, anxiety, quality of life and self esteem. Inferential analysis was done by using Independent T-test or Pearson's Correlation and the level of significance was p0.05. Multivariate logistic regression was then used to determine the predictors using Statistical Package for Social Sciences software version 22.0 RESULTS: All 953 respondents selected participated in this study. The overall mean self-esteem in this study was 22.67, SD=4.98. The significant predictors of self-esteem where pvalue was0.05 were age; gender; marital status; working status; anxiety; depression; nausea; anemia; hair loss; skin and nail changes; overall quality of life and psychological domain of quality of life. The finding of this study indicates that predictors of selfesteem among patients undergoing chemotherapy should be taken into account to improve their quality of life. Guidelines on how to manage self-esteem in a chemotherapy patient can be done using this study as the baseline.

Poor sleep quality among adolescents is becoming a major worldwide concern and is widely recognized as a significant public health issue.To determine the prevalence and predictors of poor sleep quality among secondary school students in Gombak District, Selangor.A cross-sectional study was conducted in Gombak District. The sample size was 1,092 based on two group comparison formula. Students were selected using sampling with probability to proportionate to size. Selfadministered pretested questionnaires were used to collect the data. The data were analysed using the Statistical Package for Social Sciences (SPSS) version 22. Chi-square or Fisher's exact test was performed to determine the association between individual categorical variables and sleep quality. Variables with p-value0.25 were selected to be subjected into multivariate logistic regression to determine the predictors.The response rate was 93.0%. The prevalence of poor sleep quality was 24.0% (95% CI = 21.5, 26.6). Based on the analysis of simple logistic regression seven variables that were significantly associated with poor sleep quality were age, gender, marital status of parents, depression, anxiety, stress and academic performance found fit in the model. Multivariate logistic analysis showed that the significant predictors of poor sleep quality were age, marital status of parents, depression, anxiety, stress and academic performance. Factors that were not statistically significant were gender, religion, ethnicity, parent's educational level and family income.Prevalence of poor sleep quality among adolescents is high. The predictors of poor sleep quality are age, marital status of parents, depression, anxiety, stress and academic performance.

Pediculosis capitis infestation is endemic in both developing and developed countries leading to various physical, economical and psychological consequences. Our main objective was to determine the prevalence and predictors of pediculosis capitis among primary school children in Hulu Langat District, Malaysia.An analytic cross-sectional study using cluster random sampling method was carried out in Hulu Langat District, Malaysia. Self-administered pretested questionnaires were used to collect the data. Hair and scalp examination was also carried out. Multivariate logistic regression was used to control for potential confounding and determine the predictors.The overall mean age of the 1,336 respondents was 9.3 years. Majority were males (52.8%), Malays (79.5%) and 81.3% of the fathers had secondary or tertiary education as compared to 77.3% for the mothers. The overall prevalence of pediculosis capitis was 15.3%. The prevalence of pediculosis was significantly higher among females (28.4%) than males (3.7%, p=0.001). Multivariate logistic regression analysis showed that age 10 years or more (Odds Ratio (OR) = 2.34, 95% Confidence Interval (CI) = 1.673 to 3.272), female gender (OR = 10.26, 95% CI = 6.620 to 15.903), history of contact with an infested person (OR = 2.11, 95% CI = 1.506 to 2.960), Indian compared to Chinese (OR = 3.55, 95% CI = 1.282 to 9.860), Malay to Chinese (OR = 2.59, 95% CI = .994 to 6.774) were associated with pediculosis capitis.Prevalence of pediculosis capitis among children aged 7 - 12 years in Hulu Langat District was high. There is a need for screening and treatment of pediculosis capitis in primary schools.

Background: Bone is the most common organ of involvement in patients with Langerhans cell histiocytosis (LCH), which is often painful and associated with significant morbidity from pathological fractures. Current first-line treatments include chemotherapy and steroids that are effective but often associated with adverse effects, whereas the disease may reactivate despite an initial response to first-line agents. Bisphosphonates are osteoclast inhibitors that have shown to be helpful in treating bone lesions of LCH. To date, there are no large international studies to describe their role in treating bone lesions of LCH. Method: We conducted a multicenter retrospective review of 13 patients with histologically proven LCH, who had received bisphosphonates either at diagnosis or at disease reactivation. Results: Ten patients (77%) had a single system bone disease, and 3 (23%) had bone lesions as part of multisystem disease. Median follow-up time post-bisphosphonate therapy was 4.6 years (range, 0.8 to 8.2 years). Treatment with bisphosphonates was associated with significant pain relief in almost all patients. Twelve (92%) achieved resolution of active bone lesions, and 10 out of them had no active disease for a median of 3.5 years (range, 0.8 to 5 years). One patient did not respond. No major adverse effects were reported in this series. Conclusion: Bisphosphonates are well-tolerated drugs that can significantly improve bone pain and induce remission in active bone LCH. Future prospective studies evaluating the role of bisphosphonates in LCH are warranted. © 2016.

Chemotherapy is the most common form of treatment among cancer patients. It is also known to cause many physical and psychological side-effects.This study developed, implemented and evaluated the outcome of a chemotherapy counseling module among oncology patients by pharmacists based on their psychological effects (depression, anxiety) and selfesteem.A randomized, single blind, placebo controlled study was conducted among 162 patients undergoing chemotherapy in a government hospital in Malaysia.Counseling sessions were conducted using the 'Managing Patients on Chemotherapy' module for oncology patients undergoing chemotherapy at each treatment cycle.The outcome of repetitive chemotherapy counseling using the module was determined at baseline, first follow-up, second follow-up and third follow-up.The findings revealed that there was significant improvement in the intervention group as compared to the control group with large effect size on depression (p = 0.001, partial η(2) = 0.394), anxiety (p = 0.001, partial η(2) = 0.232) and self-esteem (p = 0.001, partial η(2) = 0.541).Repetitive counseling using the 'Managing Patients on Chemotherapy' module was found to be effective in improving psychological effects and self-esteem among patients undergoing chemotherapy.

Undergraduate medical students have been the most distressed group among the student population. Depression and anxiety have been found to be more prevalent in this group of students compared to others.This study was conducted to determine the prevalence and predictors of suicidality among undergraduate medical students in a public university.This was an analytical cross-sectional study, conducted in a public university in Selangor, Malaysia. Data were collected using self-administered questionnaires from January to February 2013, and analysed using the Statistical Package for Social Sciences Software (version 21).Out of 625 undergraduate medical students, 537 (85.9%) participated in the study. The prevalence of the suicidality among undergraduate medical students was 7.0%. The significant predictors of suicidality based on multiple logistic regression were the respondent's lifetime suicide attempts (Adjusted Odds Ratio, AOR 10.4, 95% CI 2.7 to 40.9); depression (AOR 5.9, 95% CI 1.5 to 23.0); breaking off a steady love relationship (AOR 5.4, 95% CI 1.3 to 22.4); hopelessness (AOR 4.9, 95% CI 1.1 to 21.6); and something valued being lost or stolen (AOR 4.4, 95% CI 1.2 to 15.9).These findings indicate that mental health care services should be strengthened at university level. The results show a need for an intervention programme to reduce suicidality among the undergraduate medical students.

GLUT2, the major facilitative glucose transporter isoform expressed in hepatocytes, pancreatic β-cells, and absorptive epithelial cells, is unique not only with its low affinity and broad substrate specificity as a glucose transporter, but also with its implied function as a glucose-sensor. As a first essential step toward structural and biochemical elucidation of these unique, GLUT2 functions, we describe here the differential solubilization and DEAE-column chromatography of rat hepatocyte GLUT2 protein and its reconstitution into liposomes. The reconstituted GLUT2 bound cytochalasin B in a saturable manner with an apparent dissociation constant (Kd) of 2.3×10−6 M and a total binding capacity (BT) of 8.1 nmol per mg protein. The binding was completely abolished by 2% mercury chloride, but not affected by cytochalasin E. Significantly, the binding was also not affected by 500 mM D -glucose or 3-O-methyl D -glucose (3OMG). The purified GLUT2 catalyzed mercury chloride-sensitive 3OMG uptake, and cytochalasin B inhibited this 3OMG uptake. The inhibition was dose-dependent with respect to cytochalasin B, but was independent of 3OMG concentrations. These findings demonstrate that our solubilized GLUT2 reconstituted in liposomes is at least 60% pure and functional, and that GLUT2 is indeed unique in that its cytochalasin B binding is not affected by its substrate ( D -glucose) binding. Our partially purified GLUT2 reconstituted in vesicles will be useful in biochemical and structural elucidation of GLUT2 as a glucose transporter and as a possible glucose sensor.

We synthesized a transportable diazirine derivative of D-glucose, 3-deoxy-3,3-azi-D-glucopyranose (3-DAG), and studied its interaction with purified human erythrocyte facilitative glucose transporter, GLUT1. 3-DAG was rapidly transported into human erythrocytes and their resealed ghosts in the dark via a mercuric chloride-inhibitable mechanism and with a speed comparable with that of 3-O-methyl-D-glucose (3-OMG). The rate of 3-DAG transport in resealed ghosts was a saturable function of 3-DAG concentration with an apparent Km of 3.2 mM and the Vmax of 3.2 μmol/s/ml. D-Glucose inhibited the 3-DAG flux competitively with an apparent KI of 11 mM. Cytochalasin B inhibited this 3-DAG flux in a dose-dependent manner with an estimated KI of 2.4 × 10-7M. Cytochalasin E had no effect. These findings clearly establish that 3-DAG is a good substrate of GLUT1. UV irradiation of purified GLUT1 in liposomes in the presence of 3-DAG produced a significant covalent incorporation of 3-DAG into GLUT1, and 200 mMD-glucose abolished this 3-DAG incorporation. Analyses of trypsin and endoproteinase Lys-C digestion of 3-DAG-photolabeled GLUT1 revealed that the cleavage products corresponding to the residues 115-183, 256-300, and 301-451 of the GLUT1 sequence were labeled by 3-DAG, demonstrating that not only the C-terminal half but also the N-terminal half of the transmembrane domain participate in the putative substrate channel formation. 3-DAG may be useful in further identification of the amino acid residues that form the substrate channel of this and other members of the facilitative glucose transporter family.

Hypertension and obesity are established and independent risk factors for cardiovascular diseases. There are important inter-relationships between these two factors that may explain the aetiology of coronary heart disease. To determine the prevalence of hypertension and obesity in a rural community setting in Malaysia, and to identify their associated factors, a cross-sectional study was conducted among residents aged 15 years and above in Mukim Dengkil, Selangor from June to October 1999. Sample size was 570, giving a response rate of 86.7%. Prevalence of hypertension was 26.8%, with the highest prevalence among those aged 60 years and above (57.3%), and 50 to 59 years old (53.3%). Factors found to be significantly associated with hypertension were male (χ²=4.71, df=1, p0.05) and age (t=10.7, df=568, p0.01). Prevalence of obesity was 11.4%, with the highest prevalence among those aged 40 to 49 years (22.7%) and 30 to 39 years (14.4%). The factors associated with obesity were age (p0.01), female (χ²=12.45, df=1, p0.05) and ethnicity (Fisher's Exact probability, p0.05) with Chinese and Malays having a higher prevalence compared to other ethnic groups. However, there was no significant association between hypertension and obesity (OR=1.14, 95% CI=0.65, 2.02). The prevalence of hypertension and obesity in this study is high. There is a need for prevention programs for these risk factors in rural communities in Malaysia.

We labeled rat adipocyte cell surface glucose transporters with an impermeable, photoreactive glucose analogue, 1,3-bis-(3-deoxy-D-glucopyranose-3-yloxy)-2-propyl 4-benzoylbenzoate (B3GL) and its radioactive tracer [3H]B3GL. The labeling did not affect glucose transporter subcellular distribution in basal and insulin-stimulated adipocytes. When basal or insulin-stimulated adipocytes were labeled with [3H]B3GL and incubated at 37 degrees C in steady state, labeled GLUT4 was rapidly reduced at the cell surface and stoichiometrically recovered in microsomes without any change in GLUT4 protein levels in either pool. The labeled GLUT4 equilibrium exchange was found to be a simple first order process describable by two first order rate constants, one for internalization (k(in)) and the other for externalization (kex). Insulin affected both rate constants, reducing k(in) by 2.8-fold and increasing kex by 3.3-fold. It is concluded that GLUT4 constantly and rapidly recycles in adipocytes between the cell surface and its storage pool, and insulin increases the cell surface GLUT4 level in rat adipocytes by modulating both the internalization and the externalization steps of constitutively recycling GLUT4.

Self-esteem is an important determinant of psychological well-being that is particularly problematic during adolescent life stage. There is a correlation between low self-esteem and other social problems among today's adolescents. This study was conducted to determine the mean self-esteem score, and to determine the association between self-esteem and age, sex, race, religion, number of siblings, ranking among siblings, family function, parental marital status and smoking among adolescents aged 12 to 20-years-old. A cross sectional study design using random cluster sampling method was done. Four out of a total of 35 secondary schools in Klang District, Selangor were selected. Respondents consisted of individual students in selected classes from the four selected schools. Data was collected using a self-administered, structured, pre-tested questionnaire and was analyzed using the SPSS version 12.0. Out of 1089 respondents, 793 completed the questionnaire (response rate 73.82%). The overall mean self-esteem score was 27.65. The mean self-esteem score for males (27.99) was slightly higher than females (27.31). The differences in the mean scores by race were statistically significant. There was a statistically significant relationship between mean self-esteem scores and sex, age, race, religion, number of siblings, smoking and family function. There was no statistically significant difference between mean self-esteem score with parental marital status and with ranking among siblings. The overall mean self-esteem score was 27.65. Self-esteem was associated with sex, age, race, religion, number of siblings, smoking and family function.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and its diagnosis on routine stains is usually straightforward, except in some cases where there may be difficulty in distinguishing HCCs from metastatic carcinomas (MC) and cholangiocarcinomas (CC). Hepatocyte Paraffin 1 antibody (Hep Par 1) is a new monoclonal antibody which reacts with normal and neoplastic hepatocytes, and this study aims to determine its specificity and sensitivity in distinguishing hepatocellular carcinoma (HCC) from cholangiocarcinoma (CC) and metastatic carcinomas (MC). Hep Par 1 antibody was applied to 28 cases of HCC, 22 cases of MC from varying sites and 8 CCs, and produced a strong, diffuse, granular, cytoplasmic staining of all benign hepatocytes. 23 out of 28 cases of HCC showed heterogeneously positive staining for Hep Par 1 irrespective of their degree of differentiation, while 2 out of 8 cases of cholangiocarcinoma were positive for Hep Par 1, and all 22 cases of metastatic carcinoma were negative. The sensitivity and specificity of Hep Par 1 for HCC was 82.1% and 93.3% respectively; whereby the antibody was noted to show occasional false positivity in cases of cholangiocarcinoma and non-neoplastic bowel mucosa, while its variable staining in HCC produced false negative results in some small biopsies. Thus, Hep Par 1 should be used in a panel with other antibodies to obtain useful information in distinguishing HCC from CC and MC.

DEAE-column-purified band 4.5 polypeptides of human erythrocyte membranes are mostly glucose transporters with nucleoside transporters as a minor component. The purpose of the present work was to differentially identify and isolate the nucleoside transporters in band 4.5 free from glucose transporters. Equilibrium binding studies demonstrated that the band 4.5 preparation binds nibrobenzylthioinosine (NBTI), a potent nucleoside transport inhibitor, at two distinct sites, one with a high affinity (dissociation constant, KD of 1 nM) with a small capacity, BT (0.4 nmol/mg protein), and the other with a low affinity (KD of 15 microM) with a large BT (14-16 nmol/mg protein). The BT of the low-affinity site was equal to that of the cytochalasin B binding site in the preparation. A gel-filtration chromatography of band 4.5 photolabeled with [3H]NBTI and [3H]cytochalasin B identified three polypeptides of apparent Mr 55,000, 50,000 and 40,000. Of these, the 55 kDa polypeptide was specifically labeled by cytochalasin B (p55GT), indicating that it is a glucose transporter. Both the 50 and 40 kDa polypeptides were labeled with NBTI at low ligand concentrations (less than 0.1 microM), which was abolished by an excess (20 microM) of nitrobenzylthioguanosine, indicating that they are two forms (p50NT and p40NT, respectively) of the high affinity NBTI binding protein or nucleoside transporter. At higher (not less than 10 microM) NBTI concentrations, however, p55GT was also labeled with NBTI, indicating that the low-affinity NBTI binding is due to a glucose transporter. Treatment of band 4.5 with trypsin reduced the p50NT labeling with a concomitant and stoichiometric increase in the p40NT NBTI labeling without affecting the high-affinity NBTI binding of the preparation. These findings indicate that the nucleoside transporter is slightly smaller in mass than the glucose transporter and that trypsin digestion produces a truncated nucleoside transporter of apparent Mr 40,000 which retains the high-affinity NBTI binding activity of intact nucleoside transporter. Both p55GT and p50 NT were coeluted in a major protein fraction, P1 in the chromatography, while p40NT was eluted separately as a minor protein fraction, P1a. All three polypeptides formed mixed dimers, which were eluted in a fraction PO. We have purified and partially characterized the truncated nucleoside transporter, p40NT. The purified p40NT may be useful for biochemical characterization of the nucleoside transporter.

The diagnosis of prostatic carcinoma (Pca) on routine biopsies may be challenging, and to date the commonly used marker to distinguish prostate carcinoma from benign prostatic lesions has been High Molecular Weight-Cytokeratin (HMW-CK). However, the antigen of HMW-CK is susceptible to the effect of formalin fixation and causes frequent loss or patchy staining in the obviously benign glands. More recently, antibodies to p63 have been reported to be more sensitive than HMW-CK for the detection of prostatic basal cells. p63, a homologue of tumour suppressor gene p53, is essential for prostate development and is selectively expressed in the nuclei of basal cells of normal prostate glands. The objective of this study is to compare the sensitivity and specificity of HMW-CK and p63 in distinguishing prostatic carcinomas from benign prostatic lesions, as well as determining their positive predictive values. Seventy-two cases from HUKM (comprising 29 prostatic carcinomas and 43 benign prostatic hyperplasias) were stained for both HMW-CK and p63. The sensitivity of p63 and HMW-CK in identifying basal cells in benign glands was 88.37% and 90.70% respectively. The specificity of both reagents was 100%, and the positive predictive value for both reagents was also 100%. Thus, p63 is a useful complementary basal cell specific stain to HMW-CK, and would be very helpful to practicing pathologists in dealing with difficult cases.

Depression is characterized by symptoms like disturbance in behavior, cognition and mood. This is commonly known to affect people aged 60 years and above especially those who are also afflicted with illnesses. The objectives of this study were to determine the prevalence of depression and its associated factors among the elderly in a tertiary care centre in Wilayah Persekutuan. A cross sectional study design was done. Stratified cluster sampling method was used to select the respondents. All elderly patients were selected from the orthopaedic, surgical, gynaecology and medical wards in a government hospital in Wilayah Persekutuan. A 30-item Geriatric Depression Scale questionnaire was used as a screening instrument. Out of the 246 elderly subjects, 198 were interviewed giving a response rate of 80.5%. The results showed that 54% of the elderly respondents were found to have depressive symptoms. Age (p=0.022), sex (p=0.008), ethnicity (p=0.022) and functional disabilities in bathing (p=0.001), grooming (p=0.007), dressing (p= 0.007), using the toilet (p=0.002), transferring from bed to chair and back (p=0.000), mobility (p=0.000) and climbing stairs (p=0.000) were all found to be significantly associated with depression among the elderly respondents. The outcome of this study will have an important impact on the implementation of the health policy for the elderly patients admitted to hospitals.

A community based cross-sectional study was carried out to determine the prevalence and causes of visual impairment and blindness in residents aged forty years and above in kampung Jenderam Hilir of Sepang district, Selangor state. A total of 311 out of 341 (91.3%) respondents participated in this study. The prevalence of visual impairment and blindness observed was 18.9% and 2.9% respectively. The prevalence of visual impairment and blindness increased significantly with age. Amongst the 159 respondents who agreed for eye checkup, refractive errors (56%), cataract (20.1%), glaucoma (4.4%) and diabetic retinopathy (1.3%) were found to be causing visual impairment and blindness.

The aim of this study was to determine the prevalence of psychological stress among medical students and to identify its symptoms and association with depression. A cross-sectional study design was used. Three-hundred and ninety-six medical students at a university in Malaysia were included in the study. Tools similar to the General Health Questionnaire (GHQ-12) and Beck Depression Inventory (BDI) were used to screen for psychological stress and depression, respectively. 41.9% of the medical students were found to have psychological stress, which was significantly associated with depression (chi2=4.636, df=1, p0.05). Psychological stress is common among medical students and is associated with depression.

To determine the prevalence of depression among the elderly and to identify its associated factors.A cross sectional study design was used. Stratified proportionate cluster sampling method was used to select the respondents. A 30 item Geriatric Depression Scale questionnaire was used as a screening instrument.7.6% of the elderly were found to have depression. Only employment status was found to be significantly associated with depression.The prevalence of depression in the elderly was 7.6%. Primary Care providers need to be vigilant when treating elderly patients as depression is commonly found in this age group.

Insulin-responsive aminopeptidase (IRAP) colocalizes with glucose transporter type 4 (GLUT4) in adipocytes and is recruited to the plasma membrane in response to insulin. Microinjection of peptides corresponding to the IRAP cytoplasmic domain sequences causes GLUT4 recruitment in adipocytes. Inhibitors of protein kinase C-ζ (PKC-ζ) abolish the insulin-induced GLUT4 recruitment in rat adipocytes. These findings suggest an interesting possibility that PKC-ζ may phosphorylate IRAP, playing a key role in GLUT4/IRAP recruitment. To test this possibility, here we studied the 32 P incorporation into IRAP catalyzed by PKC-ζ in insulin-stimulated cells. There was a small but significant 32 P incorporation into IRAP in rat adipocytes, which was partly abolished upon addition of a PKC-ζ pseudosubstrate, suggesting that PKC-ζ may be responsible in part for the IRAP phosphorylation in adipocytes. PKC-ζ also catalyzed the incorporation of 32 P not only into IRAP in GLUT4 vesicles isolated from rat adipocytes but also into the IRAP cytoplasmic domain inserts in glutathione S-transferase-fusion proteins, demonstrating direct IRAP phosphorylation by PKC-ζ. Reversed-phase HPLC, matrix-assisted laser desorption ionization mass spectrometry, and radiosequencing of the tryptic digests of the 32 P -labeled IRAP fusion proteins identified Ser-80 and Ser-91 as major phosphorylation sites. In GLUT4 vesicles, the 32 P incorporation into IRAP was exclusively localized at a 6.9-kDa tryptic fragment identified as IRAP76–138 and the 32 P labeling at Ser-80 accounted for 80–90% of the total IRAP labeling, suggesting that Ser-80 is the major phosphorylation site in intact IRAP. These findings are consistent with the possibility that the IRAP cytoplasmic domain phosphorylation by PKC-ζ plays a key role in insulin-induced IRAP or GLUT4 recruitment in adipocytes.

The yeast-based two-hybrid screening of a human cardiac myocyte cDNA library revealed a peptide, C109 that interacted with the C-terminal cytoplasmic domain of GLUT4 (GLUT4C). cDNA-duced amino acid sequence of C109 was identical to the human cardiac muscle myosin heavy chain β isoform sequence 1469-1909. GST-fusion protein of C109 (GST-C109) bound synthetic GLUT4C-peptide in vitro, but not GLUT1C-peptide. GST-C109 avidly bound to the GLUT4-vesicles isolated from basal rat adipocytes but not those isolated from insulin treated adipocytes. Furthermore, the incorporation of C109 into rat adipocytes greatly reduced the plasma membrane GLUT4 level and the 3-O-methyl D glucose flux in host cells without affecting total cellular GLUT4 content. These findings suggest that myosin or a myosin-like protein plays a key role in insulin-regulated movement of GLUT4 to the plasma membrane in rat adipocytes.

GLUT4, the major insulin-responsive glucose transporter isoform in rat adipocytes, rapidly recycles between the cell surface and an intracellular pool with two first order rate constants, one for internalization (kin) and the other for externalization (kex). Insulin decreases kin by 2.8-fold and increases kex by 3.3-fold, thus increasing the steady-state cell surface GLUT4 level by approximately 8-fold (Jhun, B. H., Rampal, A. L., Liu, H., Lachaal, M., and Jung, C. (1992) J. Biol. Chem. 267, 17710-17715). To gain an insight into the biochemical mechanisms that modulate these rate constants, we studied the effects upon them of okadaic acid (OKA), a phosphatase inhibitor that exerts a insulin-like effect on glucose transport in adipocytes. OKA stimulated 3-O-methylglucose transport maximally 3.1-fold and increased the cell surface GLUT4 level 3.4-fold. When adipocytes were pulse-labeled with an impermeant, covalently reactive glucose analog, [3H]1,3-bis-(3-deoxy-D-glucopyranose-3-yloxy)-2-propyl 4-benzoylbenzoate, and the time course of labeled GLUT4 recycling was followed, the kex was found to increase 2.8-fold upon maximal stimulation by OKA, whereas the kin remained unchanged within experimental error. These findings demonstrate that OKA mimics the insulin effect on only GLUT4 externalization and suggest that insulin stimulates GLUT4 externalization by increasing the phosphorylation state of a serine/threonine phosphoprotein, probably by inhibiting protein phosphatase 1 or 2A.

We labeled rat adipocyte cell surface glucose transporters with an impermeable, photoreactive glucose analogue, 1,3-bis-(3-deoxy-D-glucopyranose-3-yloxy)-2-propyl 4-benzoylbenzoate (B3GL) and its radioactive tracer [3H]B3GL. The labeling did not affect glucose transporter subcellular distribution in basal and insulin-stimulated adipocytes. When basal or insulin-stimulated adipocytes were labeled with [3H]B3GL and incubated at 37 degrees C in steady state, labeled GLUT4 was rapidly reduced at the cell surface and stoichiometrically recovered in microsomes without any change in GLUT4 protein levels in either pool. The labeled GLUT4 equilibrium exchange was found to be a simple first order process describable by two first order rate constants, one for internalization (k(in)) and the other for externalization (kex). Insulin affected both rate constants, reducing k(in) by 2.8-fold and increasing kex by 3.3-fold. It is concluded that GLUT4 constantly and rapidly recycles in adipocytes between the cell surface and its storage pool, and insulin increases the cell surface GLUT4 level in rat adipocytes by modulating both the internalization and the externalization steps of constitutively recycling GLUT4.

The prevalence of Enterobius vermicularis in four groups of adults, all trainee public health inspectors or public health nurses, aged 18-35 years and all living in hostels on campus was studied. The modified scotch tape technique was used and the subjects were taught to do the examination on themselves to detect the presence of eggs over a period of 6 successive mornings. Each was given an elaborately illustrated diagram on how and when to take the samples and given demonstration in groups. The samples were examined by trained people. Most of the subjects took samples on 6 consecutive days. Of the 119 subjects who returned samples, the overall prevalence of E. vermicularis was 9.2% and this was thought to be high for this particular age group. This was due to the higher prevalence (19.4%) in one group, whereas in the others the range was 3.5-8.0%. Based on the samples returned on the first day none of the subjects were detected as having the infection. After examination on 3 successive days (109 subjects) 10.1% were found to be infected (chi 2 = 10.704; d. f. = 1) and after examination on 6 successive days (72 subjects) 13.9% were found to be infected (chi 2 = 3.026; d. f. = 1). There was no significance between examination over 3 successive days and 6 consecutive days (chi 2 = 0.296; d. f. = 1). There was no difference in the prevalence between males and females.(ABSTRACT TRUNCATED AT 250 WORDS)

1. The human erythrocyte glucose transporter was phosphorylated in vitro by protein kinase C. 2. Tryptic cleavage of phosphorylated native transporter produced two major unphosphorylated membrane-embedded fragments weighing 23 and 19 kDa and released numerous water-soluble peptides. 3. Ion-exchange FPLC of the soluble tryptic peptides resolved the mixture into two phosphopeptide peaks. 4. Tryptic digestion of glucose transporter that was phosphorylated in vivo in response to phorbol esters produced soluble phosphopeptides that eluted at identical salt concentrations. 5. Proteolytic digestion and peptide mapping of the transporter revealed that the site(s) of phosphorylation lie within the large cytoplasmic domain that bisects the molecule.

On the basis of details of the three-dimensional structures of beta-D-glucose and of cytochalasins, either previously published or reported here (cytochalasin A), we propose a model to explain the observed difference in activity of cytochalasins in the inhibition of glucose transport. In our model cytochalasin B binds to the glucose carrier through hydrogen bonds at N2 (donates), O7 (accepts), and O23 (accepts) analogous to O6, O3, and O1, respectively, on beta-D-glucose. The hydrophobic region from C13 to C19 is also essential in binding and appears to act as an anchor in a hydrophobic domain of the glucose carrier. The presence of hydrophilic groups in this essential hydrophobic region accounts, at least in part, for the inactivity of the other cytochalasins in the series.

Chemical and functional purity of the human erythrocyte glucose transporter preparation obtained by DEAE column chromatography after octyl glucoside solubilization was assessed. The cytochalasin B binding capacity of the preparation indicates that the preparation is 60–85% functional glucose transporter. Gel filtration chromatography on TSK 250 column separates this preparation into at least three major peptide fractions, namely, P0, P1 and P2, with apparent Mr of approx. 80 000, 43 000 and 17 000, respectively. When the preparation is photolabelled with [3H]cytochalasin B prior to the separation only P0 and P1 are labelled. Exposure of the preparation to octyl glucoside or to ultraviolet light irradiation results in an increase in P0 in a time-dependent manner with a concomitant and proportional reduction in P1, without affecting P2 appreciably. For individual preparations, relative abundance of P0 and P1 vary widely in a reciprocal fashion, while that of P2 is practically fixed at approx. 10% of the total protein. The specific activity of cytochalasin B binding of each preparation correlates linearly with the relative abundance of P1 of the preparation, which gives a calculated specific binding activity of 22 nmol/mg protein for this fraction. These results indicate that P1 and P0 are native and denatured transporter, respectively, while P2 is contaminating protein impurities. These results demonstrate that the glucose transporter preparation contains approx. 10% of nontransporter protein impurities, with a varying amount (up to 30%) of denatured transporter, and that the transporter free of the chemical impurities and the denatured transporter can be obtained by a gel filtration chromatography of this preparation.

A family of structurally related intrinsic membrane proteins (facilitative glucose transporters) catalyzes the movement of glucose across the plasma membrane of animal cells. Evidence indicates that these proteins show a common structural motif where approximately 50% of the mass is embedded in lipid bilayer (transmembrane domain) in 12 alpha-helices (transmembrane helices; TMHs) and accommodates a water-filled channel for substrate passage (glucose channel) whose tertiary structure is currently unknown. Using recent advances in protein structure prediction algorithms we proposed here two three-dimensional structural models for the transmembrane glucose channel of GLUT1 glucose transporter. Our models emphasize the physical dimension and water accessibility of the channel, loop lengths between TMHs, the macrodipole orientation in four-helix bundle motif, and helix packing energy. Our models predict that five TMHs, either TMHs 3, 4, 7, 8, 11 (Model 1) or TMHs 2, 5, 11, 8, 7 (Model 2), line the channel, and the remaining TMHs surround these channel-lining TMHs. We discuss how our models are compatible with the experimental data obtained with this protein, and how they can be used in designing new biochemical and molecular biological experiments in elucidation of the structural basis of this important protein function.

Cytochalasin B inhibits phytomitogen-induced human lymphocyte proliferation with a Ki of approximately 6 X 10(-6) M. Cytochalasins A, C, D, E, and H are also inhibitory with varying degrees of potency, whereas cytochalasin G and chaetoglobosins A, B, C, E, F, and J are not at concentrations as high as 15 microM. Cytochalasin B also competitively inhibits carrier-mediated equilibrium exchange of hexose (Ki of approximately 7 X 10(-7) M), but cytochalasin E is ineffective. Cytochalasin B binds reversibly to the lymphocyte at three distinct sites: L, M, and H. The ligand binding at L site shows the apparent dissociation constant (Kd) of 1 to 3 X 10(-6) M and total binding sites (Bt) of 6 to 8 X 10(7)/cell, represents approximately 85% of the total saturable binding, displays a broad specificity interacting with cytochalasins C, D, and E, is not displaceable by D-glucose, is located mostly in a cytosol fraction, and exists in intimate relation to cytoskeletal actin. M site shows a Kd of 2 to 4 X 10(-7) M and Bt of 5 to 8 X 10(6)/cell, represents about 8% of the total saturable binding, shows stringent specificity not being displaced by cytochalasins C, D, and E, is competitively displaced by D-glucose and phloretin, and is quantitatively recoverable in the plasma membrane fraction. The binding to H site shows a Kd of 0.5 to 1.0 X 10(-7) M and Bt of 4 to 5 X 10(6)/cell, representing approximately 7% of the total saturable binding, shows a broad specificity, is insensitive to D-glucose, and is membrane bound. It is proposed that L site is actin and is involved in the inhibition of lymphocyte mitogenesis, whereas M site is associated with the hexose transport carrier. Structure-activity relationships of cytochalasin effects are also discussed.

This report highlights some of the educational aspects on nutrition and tropical diseases. Health conditions in most of the countries in this region has improved but not at the same pace as the progress in medical sciences. The slow progress in tackling this problem has been partly due to the failure of understanding psycho-social, cultural and economic patterns. Many of the health workers and educators who are involved in the control of tropical diseases emphasize on practice rather than research. Due emphasis should be given to training and research in health education involving not only the professionals and auxiliary staff but also political leaders, policy makers and community leaders at grassroot level.

We have previously described three different cytochalasin B binding sites in human erythrocyte membranes, a D-glucose-sensitive site (Site I), a cytochalasin E-sensitive site (Site II), and a site (Site III) insensitive to both D-glucose and cytochalasin E. Ligand bindings to each of these sites were considered to be independent (Jung, C., and Rampal, A. (1977) J. Biol. Chem. 252, 5456-5463). However, we have obtained subsequently the following evidence which indicated that an interaction occurs between Sites II and III, and this modulates sensitivity of Site III to the sugar. The displacement of cytochalasin E greatly exceeds the sum of their independent displacements. This ghosts extracted with EDTA or 2,3-dimethylmaleic anhydride at low ionic strength lack Site II activity but retain Site I and III activities, and both of these activities are displaceable by D-glucose alone. This indicated that the removal of Site II from the membrane confers glucose sensitivity to Site III. These observations are consistent with a model that Sites II and III in the membrane exist in a close association through which unliganded Site II maintains the glucose insensitivity of Site III, and once site II is liganded or removed by extraction this association is disrupted and Site III becomes glucose-sensitive. The ghosts extracted with Triton X-100 retain a cytochalasin B binding activity similar to that of site II (Kd = 1.8 X 10(-7) M, cytochalasin E-sensitive, glucose-insensitive), whereas a binding activity similar to that of Site I (Kd = 4 X 10(-7) M, cytochalasin E-insensitive, glucose-sensitive) is recovered in the Triton extract. A cytochalasin B binding activity similar to that of Site II is solubilized by EDTA at low ionic strength.

Twenty cytochalasins were tested for binding to and for inhibition of glucose transport in human erythrocyte membrane. In this membrane three cytochalasin B (CB) binding sites have been identified. All but three of the cytochalasins bind at site II. On the other hand, only nine of them, which are structurally closely related, bind at site I and inhibit glucose transport. For site I (and site III) binding and glucose transport inhibitory activities (a) the macrocyclic ring in the cytochalasin molecule must be at least 13-membered, (b) the nature of the aromatic ring at C-10 is not important, (c) the C-20-C-23 region makes a major contribution, and (d) the C-5-C-7 segment has a relatively minor influence. These findings do not support a proposed mechanism which involves 24, C-23, C-20, and C-1 oxygen atoms for interaction of CB with glucose carrier. The structural requirements for site II activity are less stringent. The size and the structure of the macrocyclic ring and the nature of the aromatic residue at C-10 modulate this activity only slightly, if at all. Modifications in the C-5-C-7 region of the molecule, however, result in substantial changes in this activity.

Nasopharyngeal carcinoma (NPC) is one of the highly malignant tumours of the head and neck, affecting most commonly the ethnic Chinese, living in the Southeast Asian countries—South China, Taiwan and Hong Kong. It is reputed for delayed diagnosis and as such poor prognosis (1). Not infrequently NPC patients with obvious clinical features, at times with extensive disease, are not diagnosed early due to inability on the part of cliniciansto obtain representative biopsy specimens for histopathological confirmation. Over a period of time this problem of late diagnosis has partly been resolved due to increased awareness on the part of the patients and the doctors in these regions, utilization of modern facilities to visualise the nasopharynx [in particular the fossa of Rosenmuller (FOR)] and by the detection of elevated titres of IgA anti Epstein Barr virus capsid antigen (IgA/VCA test).

A survey was conducted to investigate the prevalence of Enterobius vermicularis in 1352 Chinese children between the ages of 6-12 years from the three National Type Chinese Primary Schools in Pulau Ketam in 1988, using the scotch-tape technique on three successive days. The overall prevalence was high (56.88%). The prevalence in Sin Bin School was significantly lower (50.86%) compared to the other two schools (56.60% and 61.04%). Prevalence was significantly higher amongst the 6-7 years age group (61.61%-70.18%) compared to other age groups (47.9%-59.29%). There was no difference in the prevalence between the boys and girls being 56.15% and 57.55% respectively.