Displaying publications 61 - 80 of 139 in total

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  1. Yang C, Guadamuz TE, Lim SH, Koe S, Wei C
    LGBT Health, 2016 Apr;3(2):168-74.
    PMID: 26789393 DOI: 10.1089/lgbt.2014.0041
    We explored factors associated with alcohol use before or during sex among a sample of 10,861 men who have sex with men (MSM) in Asia who were recruited online for the study. Multinomial logistic regression analysis indicated that having sex under the influence of alcohol was associated with having multiple male partners, seeking partners primarily through gay bar/gym/dance party/friends, selling sex and using multiple drugs during the past 6 months, and unprotected anal sex. More efforts are needed to better assess alcohol use and misuse among MSM in Asia and understand contextual influences on alcohol use and HIV-related behaviors in order to implement culturally-specific interventions.
  2. Pek JH, Lim SH, Ho HF, Ramakrishnan TV, Jamaluddin SF, Mesa-Gaerlan FJC, et al.
    Acute medicine & surgery, 2016 04;3(2):65-73.
    PMID: 29123755 DOI: 10.1002/ams2.154
    Aim: We aim to examine the similarities and differences in areas of EM development, workload, workforce, and capabilities and support in the Asia region. Emerging challenges faced by our EM community are also discussed.

    Methods: The National Societies for Emergency Medicine of Hong Kong, India, Japan, Malaysia, Philippines, Singapore, South Korea, Taiwan, Thailand and Turkey participated in the joint Japanese Association of Acute Medicine (JAAM) and Asian Conference of Emergency Medicine (ACEM) Special Symposium held in October 2013 at Tokyo, Japan. The findings are reviewed in this paper.

    Results: Emergency medicine (EM) has over the years evolved into a distinct and recognized medical discipline requiring a unique set of cognitive, administrative and technical skills for managing all types of patients with acute illness or injury. EM has contributed to healthcare by providing effective, safe, efficient and cost-effective patient care. Integrated systems have developed to allow continuity of emergency care from the community into emergency departments. Structured training curriculum for undergraduates, and specialty training programs for postgraduates are in place to equip trainees with the knowledge and skills required for the unique practice of EM.

    Conclusion: The practice of EM still varies among the Asian countries. However, as a region, we strive to continue in our efforts to develop the specialty and improve the delivery of EM.

  3. Sim DS, Teoh WY, Sim KS, Lim SH, Thomas NF, Low YY, et al.
    J Nat Prod, 2016 Apr 22;79(4):1048-55.
    PMID: 26918761 DOI: 10.1021/acs.jnatprod.5b01117
    Six new bisindole alkaloids of the iboga-vobasine type, vobatensines A-F (1-6), in addition to four known bisindoles (8-11), were isolated from a stem bark extract of a Malayan Tabernaemontana corymbosa. The structures of these alkaloids were determined based on analysis of the spectroscopic data and in the case of vobatensines A (1), B (2), and 16'-decarbomethoxyvoacamine (8) also confirmed by partial syntheses. Nine of these alkaloids (1-5, 8-11) showed pronounced in vitro growth inhibitory activity against human KB, PC-3, LNCaP, HCT 116, HT-29, MCF7, MDA-MB-231, and A549 cancer cells.
  4. Wong CC, Lim SH, Sagineedu SR, Lajis NH, Stanslas J
    Pharmacol Res, 2016 05;107:66-78.
    PMID: 26940565 DOI: 10.1016/j.phrs.2016.02.024
    SRJ09 (3,19-(2-bromobenzylidene)andrographolide), a semisynthetic andrographolide (AGP) derivative, was shown to induce G1 cell cycle arrest and eventually apoptosis in breast and colon cancer cell lines. The present investigation was carried out to elucidate the mechanisms cell cycle arrest and apoptosis and evaluate the in vivo antitumor activity of SRJ09. The in vitro growth inhibitory properties of compounds were assessed in colon (HCT-116) and breast (MCF-7) cancer cell lines. Immunoblotting was utilized to quantitate the protein levels in cells. The gene expressions were determined using reverse transcriptase PCR (RT-PCR). Pharmacokinetic investigation was carried out by determining SRJ09 levels in plasma of Balb/C mice using HPLC. In vivo antitumor activity was evaluated in athymic mice carrying HCT-116 colon tumor xenografts. SRJ09 displayed improved in vitro activity when compared with AGP by producing rapid cell killing effect in vitro. Its activity was not compromised in MES-SA/Dx5 multidrug resistant (MDR) cells expressing p-glycoprotein. Cells treated with SRJ09 (0.1-10μM) displayed increased p21 protein level, which corresponded with gene expression. Whereas CDK4 protein level and gene expression was suppressed. The treatment did not affect cyclin D1. Changes of these proteins paralleled G1 cell cycle arrest in both cell lines as determined by flow cytometry. Induction of apoptosis by SRJ09 in HCT-116 cells which occurred independent of p53 and bcl-2 was inhibited in the presence of caspase 8 inhibitor, implicating the extrinsic apoptotic pathway. A single dose (100mg/kg, i.p) of SRJ09 produced a plasma concentration range of 12-30.4μM. At 400mg/kg (q4dX3), it significantly retarded growth of tumor xenografts. The antitumor activity of SRJ09 is suggested mediated via the induction of p21 expression and suppression of CDK-4 expression without affecting cyclin D1 to trigger G1 arrest leading to apoptosis.
  5. Nge CE, Chong KW, Thomas NF, Lim SH, Low YY, Kam TS
    J Nat Prod, 2016 05 27;79(5):1388-99.
    PMID: 27077800 DOI: 10.1021/acs.jnatprod.6b00129
    Ten new indole alkaloids (1-10) comprising five ibogan, two aspidosperman, one vincamine, and two bisindole alkaloids, in addition to 32 known alkaloids, were isolated from the stem-bark extract of a Malayan Tabernaemontana corymbosa. The structures of these alkaloids were determined based on analysis of the NMR and MS data and, in five instances (1, 3, 5, 6, 8), confirmed by X-ray diffraction analysis. Two of the iboga alkaloids, conodusines B (2) and C (3), and the iboga-containing bisindole tabernamidine B (10) are notable for the presence of an α-substituted acetyl group at C-20 of the iboga carbon skeleton. The iboga alkaloid (+)-conodusine E (5) had MS and NMR data that were identical to those of (-)-ervatamine I, recently isolated from Ervatamia hainanensis. Establishment of the absolute configuration of (+)-conodusine E (5) was based on analysis of the ECD data, correlation with (-)-heyneanine, and X-ray analysis, which showed that (+)-5 belongs to the same enantiomeric series as exemplified by (-)-coronaridine. The configuration at C-20' of the previously reported Tabernaemontana bisindole alkaloid 19'-oxotabernamine (renamed tabernamidine B) required revision based on the present results. Several of the bisindoles showed pronounced in vitro growth inhibitory activity against drug-sensitive and vincristine-resistant KB cells.
  6. Tan SY, Wong MM, Tiew AL, Choo YW, Lim SH, Ooi IH, et al.
    Cancer Chemother Pharmacol, 2016 10;78(4):709-18.
    PMID: 27495788 DOI: 10.1007/s00280-016-3120-9
    PURPOSE: Pharmacokinetic interaction of sunitinib with diclofenac, paracetamol, mefenamic acid and ibuprofen was evaluated due to their P450 mediated metabolism and OATP1B1, OATP1B3, ABCB1, ABCG2 transporters overlapping features.

    METHODS: Male and female mice were administered 6 sunitinib doses (60 mg/kg) PO every 12 h and 30 min before the last dose were administered vehicle (control groups), 250 mg/kg paracetamol, 30 mg/kg diclofenac, 50 mg/kg mefenamic acid or 30 mg/kg ibuprofen (study groups), euthanized 6 h post last administration and sunitinib plasma, liver, kidney, brain concentrations analyzed.

    RESULTS: Ibuprofen halved sunitinib plasma concentration in female mice (p 

  7. Nge CE, Sim KS, Lim SH, Thomas NF, Low YY, Kam TS
    J Nat Prod, 2016 10 28;79(10):2709-2717.
    PMID: 27759387
    Examination of the EtOH extract of the Malayan Tabernaemontana corymbosa resulted in the isolation of three new alkaloids, viz., cononuridine (1), an unusual hexacyclic, iboga-derived, monoterpenoid indole characterized by contraction of the tetrahydroazepine C-ring and incorporation of an additional isoxazolidine ring, taberisidine (2), a seco-corynanthean alkaloid, and conofolidine (3), an Aspidosperma-Aspidosperma bisindole that showed pronounced in vitro growth inhibitory activity against an array of human cancer cell lines, including KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, HT-29, and HCT 116 cells. The structures and absolute configurations of 1 and 3 and the absolute configuration of the novel pyridopyrimidine indole alkaloid vernavosine (4) were confirmed by X-ray diffraction analysis. A reasonable biosynthesis route to cononuridine starting from an iboga precursor is presented.
  8. Jin H, Friedman MR, Lim SH, Guadamuz TE, Wei C
    LGBT Health, 2016 Dec;3(6):465-471.
    PMID: 26982598
    PURPOSE: Men who have sex with men and are sex workers (MSMSW) are disproportionately affected by the growing and emerging HIV epidemic. As sex work and same-sex behavior are heavily stigmatized and often illegal in most Asian countries, HIV research focusing on MSMSW has been limited. The goal of this analysis is to examine HIV testing practices and identify correlates of HIV testing among MSMSW in Asia.

    METHODS: The Asia Internet MSM Sex Survey, an online cross-sectional survey of 10,861 men who have sex with men (MSM), was conducted in 2010. Data on sociodemographic characteristics, HIV testing behaviors, and sexual behaviors were collected. Five hundred and seventy-four HIV-negative/unknown respondents reported receiving payment for sex with men at least once in the past 6 months and were included in this analysis. Multivariable logistic regression was conducted to identify independent correlates of HIV testing in the past year.

    RESULTS: About half (48.6%) of the participants had been tested for HIV at least once within the past year, and 30.5% had never been tested. We also found that MSMSW participants who engaged in risky behaviors were less likely to be tested.

    CONCLUSION: While one might expect a high HIV testing rate among MSMSW due to the risks associated with engaging in sex work, we found that HIV testing uptake is suboptimal among MSMSW in Asia. These results suggest that targeted HIV prevention and testing promotion among MSMSW are needed.

  9. Lim LY, Miao H, Lim JS, Lee SC, Bhoo-Pathy N, Yip CH, et al.
    Cancer Med, 2017 Jan;6(1):173-185.
    PMID: 28000426 DOI: 10.1002/cam4.985
    We aim to identify clinicopathologic predictors for response to neoadjuvant chemotherapy and to evaluate the prognostic value of pathologic complete response (pCR) on survival in Asia. This study included 915 breast cancer patients who underwent neoadjuvant chemotherapy at five public hospitals in Singapore and Malaysia. pCR following neoadjuvant chemotherapy was defined as 1) no residual invasive tumor cells in the breast (ypT0/is) and 2) no residual invasive tumor cells in the breast and axillary lymph nodes (ypT0/is ypN0). Association between pCR and clinicopathologic characteristics and treatment were evaluated using chi-square test and multivariable logistic regression. Kaplan-Meier analysis and log-rank test, stratified by other prognostic factors, were conducted to compare overall survival between patients who achieved pCR and patients who did not. Overall, 4.4% of nonmetastatic patients received neoadjuvant chemotherapy. The median age of preoperatively treated patients was 50 years. pCR rates were 18.1% (pCR ypT0/is) and 14.4% (pCR ypT0/is ypN0), respectively. pCR rate was the highest among women who had higher grade, smaller size, estrogen receptor negative, human epidermal growth factor receptor 2-positive disease or receiving taxane-based neoadjuvant chemotherapy. Patients who achieved pCR had better overall survival than those who did not. In subgroup analysis, the survival advantage was only significant among women with estrogen receptor-negative tumors. Patients with poor prognostic profile are more likely to achieve pCR and particularly when receiving taxane-containing chemotherapy. pCR is a significant prognostic factor for overall survival especially in estrogen receptor-negative breast cancers.
  10. Alcantara VS, Lim GH, Lim SH, Sultana R, Lee JA
    J Surg Oncol, 2017 Apr;115(5):523-537.
    PMID: 28168712 DOI: 10.1002/jso.24559
    BACKGROUND AND OBJECTIVES: Triple negative breast cancer (TNBC) carries a worse prognosis compared to the other subtypes. There have been conflicting studies that race may impact the prognosis of TNBC patients. We aim to determine the incidence and prognosis of TNBC among the different ethnic races in Singapore, and to determine its associated risk factors for prognosis.

    METHODS: Patients diagnosed with invasive breast cancer (BC) from 2005 to 2013 at our tertiary institution were included and divided according to race and subtypes. Demographic and clinical information of non-metastatic TNBC patients were analyzed. Log-rank test, univariate and multivariate Cox proportional hazard regression models were used to find associated risk factors related with overall survival (OS) and disease-free survival (DFS).

    RESULTS: Among 1227 BC patients, 129 (10.5%) had TNBC. TNBC patients had the worst OS (P: 0.0005) and DFS (P: 0.0016) among the subtypes. However, variations in race did not have any difference in OS or DFS among TNBC patients. Axillary lymph node involvement, invasive lobular histology, larger tumor size, and the presence of lymphovascular invasion (LVI) were factors associated with both poor DFS and OS among TNBC patients.

    CONCLUSIONS: Racial variation did not have any impact on the prognosis of the TNBC.

  11. Bourne A, Cassolato M, Thuan Wei CK, Wang B, Pang J, Lim SH, et al.
    J Int AIDS Soc, 2017 08 02;20(1):21899.
    PMID: 28782336 DOI: 10.7448/IAS.20.1.21899
    BACKGROUND: Men who have sex with men (MSM) continue to be disproportionately affected by HIV in Malaysia. Recent success has been observed within demonstration projects examining the efficacy of HIV pre-exposure prophylaxis (PrEP), an antiretroviral -based medication taken by HIV-negative men to prevent sero-conversion. In order for such promising findings to be translated in real-world settings, it is important to understand the acceptability of PrEP, including perceived barriers to access or uptake.

    METHODS: As part of a larger mixed-methods study exploring acceptability and willingness to use PrEP among MSM in Malaysia, 19 men took part in audio-recorded focus group discussions hosted by a community-based HIV organization and facilitated by a trained researcher. Discussions focussed on awareness and potential information management, general perceptions of PrEP and potential motivations or barriers to the use of PrEP, including those at the personal, social, health system or structural level. Data were transcribed verbatim and underwent a detailed thematic analysis.

    RESULTS: Rather than perceiving PrEP as a replacement for condoms in terms of having safer sex, many participants viewed it as an additional layer protection, serving as a crucial barrier to infection on occasions where condom use was intended, but did not occur. It was also perceived as more valuable to "at-risk" men, such as those in HIV sero-discordant relationships or those with a higher number of sexual partners. Elements of discussion tended to suggest that some men taking PrEP may be subject to stigma from others, on the assumption they may be promiscuous or engage in high-risk sexual behaviours.

    CONCLUSIONS: This qualitative study indicates that, broadly speaking, PrEP may be acceptable to MSM in Malaysia. However, in order for its potential to be realized, and uptake achieved, educative interventions are required to inform the target population as to the efficacy and potential, positive impact of PrEP. Given concerns for how those taking it may be stigmatized, it is crucial that the use of PrEP is presented as a responsible course of action, and one of a range of strategies that men can use to keep themselves safe from HIV.

  12. Chong KW, Yeap JS, Lim SH, Weber JF, Low YY, Kam TS
    J Nat Prod, 2017 11 22;80(11):3014-3024.
    PMID: 29087707 DOI: 10.1021/acs.jnatprod.7b00621
    Reexamination of the absolute configuration of recently isolated eburnane alkaloids from Malaysian Kopsia and Leuconotis species by X-ray diffraction analysis and ECD/TDDFT has revealed the existence of biosynthetic enantiodivergence. Three different scenarios are discerned with respect to the composition of the enantiomeric eburnane alkaloids in these plants: first, where the new eburnane congeners possess the same C-20, C-21 absolute configurations as the common eburnane alkaloids (eburnamonine, eburnamine, isoeburnamine, eburnamenine) occurring in the same plant; second, where the new eburnane congeners possess opposite or enantiomeric C-20, C-21 absolute configurations compared to the common eburnane alkaloids found in the same plant; and, third, where the four common eburnane alkaloids were isolated as racemic or scalemic mixtures, while the new eburnane congeners were isolated as pure enantiomers with a common C-20, C-21 configuration (20α, 21α). Additionally, the same Kopsia species (K. pauciflora) found in two different geographical locations (Peninsular Malaysia and Malaysian Borneo) showed different patterns in the composition of the enantiomeric eburnane alkaloids. Revision of the absolute configurations of a number of new eburnane congeners (previously assigned based on the assumption of a common biogenetic origin to that of the known eburnane alkaloids co-occurring in the same plant) is required based on the present results.
  13. Lim SH, Mburu G, Bourne A, Pang J, Wickersham JA, Wei CKT, et al.
    PLoS One, 2017;12(9):e0182838.
    PMID: 28902857 DOI: 10.1371/journal.pone.0182838
    OBJECTIVE: We examined willingness to use pre-exposure prophylaxis (PrEP) for HIV prevention among men who have sex with men (MSM) in Malaysia.

    METHODS: An online survey of 990 MSM was conducted between March and April 2016. Eligibility criteria included being biological male, Malaysian citizen, 18 years of age or above, identifying as MSM, and being HIV negative or unknown status. Participants' demographics, sexual and drug use behaviors, attitudes towards PrEP, and preferences regarding future access to PrEP were collected. Bivariate analysis and logistic regression were performed to determine factors associated with willingness to use PrEP.

    RESULTS: Fewer than half of participants (44%) knew about PrEP before completing the survey. Overall, 39% of the sample were willing to take PrEP. Multivariate logistic regression indicated that Malay men (AOR: 1.73, 95% CI:1.12, 2.70), having 2 or more male anal sex partners in the past 6 months (AOR: 1.98, 95% CI: 1.29, 3.05), previous knowledge of PrEP (AOR: 1.40, 95%CI: 1.06, 1.86), lack of confidence in practising safer sex (AOR: 1.36, 95% CI: 1.02, 1.81), and having ever paid for sex with a male partner (AOR: 1.39, 95% CI: 1.01, 1.91) were independently associated with greater willingness to use PrEP, while men who identified as heterosexual were less willing to use PrEP (AOR, 0.36, 95% CI: 0.13, 0.97). Majority of participants preferred to access PrEP at affordable cost below 100 Malaysian Ringgit (USD25) per month from community based organisations followed by private or government hospitals.

    CONCLUSIONS: Overall, MSM in Malaysia reported a relatively low level of willingness to use PrEP, although willingness was higher among those previously aware of PrEP. There is a need to provide PrEP at affordable cost, increase demand and awareness of PrEP, and to provide access to this preventative medication via diverse, integrated and tailored sexual health services.

  14. Khan F, Krishnan A, Ghani MA, Wickersham JA, Fu JJ, Lim SH, et al.
    Subst Use Misuse, 2018 01 28;53(2):249-259.
    PMID: 28635521 DOI: 10.1080/10826084.2016.1267217
    BACKGROUND: As part of an ongoing initiative by the Malaysian government to implement alternative approaches to involuntary detention of people who use drugs, the National Anti-Drug Agency has created new voluntary drug treatment programs known as Cure and Care (C&C) Centers that provide free access to addiction treatment services, including methadone maintenance therapy, integrated with social and health services.

    OBJECTIVES: We evaluated early treatment outcomes and client satisfaction among patients accessing C&C treatment and ancillary services at Malaysia's second C&C Center located in Kota Bharu, Kelantan.

    METHODS: In June-July 2012, a cross-sectional convenience survey of 96 C&C inpatients and outpatients who entered treatment >30 days previously was conducted to assess drug use, criminal justice experience, medical co-morbidities, motivation for seeking treatment, and attitudes towards the C&C. Drug use was compared for the 30-day-period before C&C entry and the 30-day-period before the interview.

    RESULTS: Self-reported drug use levels decreased significantly among both inpatient and outpatient clients after enrolling in C&C treatment. Higher levels of past drug use, lower levels of social support, and more severe mental health issues were reported by participants who were previously imprisoned. Self-reported satisfaction with C&C treatment services was high. Conclusions/Importance: Preliminary evidence of reduced drug use and high levels of client satisfaction among C&C clients provide support for Malaysia's ongoing transition from compulsory drug detention centers (CDDCs) to these voluntary drug treatment centers. If C&C centers are successful, Malaysia plans to gradually transition away from CDDCs entirely.
  15. Ezeoke MC, Krishnan P, Sim DS, Lim SH, Low YY, Chong KW, et al.
    Phytochemistry, 2018 Feb;146:75-81.
    PMID: 29247894 DOI: 10.1016/j.phytochem.2017.12.003
    From the leaves of Elaeocarpus tectorius (Lour.) Poir. four previously undescribed phenethylamine-containing alkaloids were isolated, namely, tectoricine, possessing an unprecedented isoquinuclidinone ring system incorporating a phenethylamine moiety, tectoraline, representing a rare alkamide incorporating two phenethylamine moieties, and tectoramidines A and B, representing the first naturally occurring trimeric and dimeric phenethylamine alkaloids incorporating an amidine function. The structures of these alkaloids were established by detailed spectroscopic analysis. The absolute configuration of tectoricine was determined by comparison of the experimental and calculated ECD spectra. Plausible biosynthetic pathways to the four alkaloids are proposed.
  16. Burch WJ, Hart GJ, Lim SH
    AIDS Educ Prev, 2018 04;30(2):85-95.
    PMID: 29688771 DOI: 10.1521/aeap.2018.30.2.85
    Young men who have sex with men (YMSM) are a group at high risk for HIV infection, yet no research has been conducted to understand this population in Malaysia. Semistructured interviews from a combination of YMSM aged 18-25 (n = 20) and local service providers of sexual health services (n = 4) were conducted from May to June 2015. Thematic analysis was used to identify common themes in participant responses from transcripts. Participants reported societal and internalized homophobia, an absence of sex education and difficulty accessing confidential HIV testing. This study provides insights into how homophobia in Malaysian society influences individual risk behavior for HIV in Malaysian YMSM, and makes practical suggestions for more effective HIV prevention in this population.
  17. Lim SH, Akbar M, Wickersham JA, Kamarulzaman A, Altice FL
    Int J Drug Policy, 2018 05;55:256-262.
    PMID: 29605540 DOI: 10.1016/j.drugpo.2018.02.019
    BACKGROUND: The intentional use of illicit drugs for sexual purposes (also known as 'chemsex') is well known within the MSM communities in Malaysia although research in this population is scarce primarily because both drug use and homosexuality are illegal and stigmatised in Malaysia.

    METHODS: From April to December 2014, interviews were conducted with twenty men (age range 21-43) living in Greater Kuala Lumpur who had sexual intercourse with other men in the past 6 months and who used illicit drugs at least monthly in the past 3 months. Fourteen men were recruited via gay social networking smartphone applications or websites while six were referred by the participants. Data were analsed using thematic analytic approach.

    FINDINGS: The average duration of illicit drug use was 6.4 years (range 1-21) and all participants were using methamphetamine ("ice" or crystal meth) with frequency of use ranged from daily to once a month. Participants came from diverse ethnic, economic, and occupational backgrounds. Most participants used an inhalation apparatus ("bong") to consume methamphetamine and injection was rare in the sample. The primary motivation of methamphetamine use was to increase sexual capacity, heighten sexual pleasure and enhance sexual exploration and adventurism. Socializing with friends ("chilling"), and increased energy for work were secondary motivations. Participants emphasized the need to control the use of methamphetamine and some have established rules to control the amount and duration of use and a minority of men have maintained condom use during anal sex while under the influence of methamphetamine. Participants who professed to be in control of their drug use characterized themselves as functional users regardless of the health and social consequences from continuing use. Overall, participants perceived themselves differently from the traditional opioid users and reported limited access to sexual health and substance use treatment services.

    CONCLUSION: There is a need to increase access to HIV prevention services such as PrEP and PEP, professional support, and substance abuse treatment for drug-using MSM. A more open and friendly environment towards drug-using MSM may help them access and engage with the health services.

  18. Ng KT, Oong XY, Lim SH, Chook JB, Takebe Y, Chan YF, et al.
    Clin Infect Dis, 2018 07 02;67(2):261-268.
    PMID: 29385423 DOI: 10.1093/cid/ciy063
    Background: Rhinovirus (RV) is one of the main viral etiologic agents of acute respiratory illnesses. Despite the heightened disease burden caused by RV, the viral factors that increase the severity of RV infection, the transmission pattern, and seasonality of RV infections remain unclear.

    Methods: An observational study was conducted among 3935 patients presenting with acute upper respiratory illnesses in the ambulatory settings between 2012 and 2014.

    Results: The VP4/VP2 gene was genotyped from all 976 RV-positive specimens, where the predominance of RV-A (49%) was observed, followed by RV-C (38%) and RV-B (13%). A significant regression in median nasopharyngeal viral load (VL) (P < .001) was observed, from 883 viral copies/µL at 1-2 days after symptom onset to 312 viral copies/µL at 3-4 days and 158 viral copies/µL at 5-7 days, before declining to 35 viral copies/µL at ≥8 days. In comparison with RV-A (median VL, 217 copies/µL) and RV-B (median VL, 275 copies/µL), RV-C-infected subjects produced higher VL (505 copies/µL; P < .001). Importantly, higher RV VL (median, 348 copies/µL) was associated with more severe respiratory symptoms (Total Symptom Severity Score ≥17, P = .017). A total of 83 phylogenetic-based transmission clusters were identified in the population. It was observed that the relative humidity was the strongest environmental predictor of RV seasonality in the tropical climate.

    Conclusions: Our findings underline the role of VL in increasing disease severity attributed to RV-C infection, and unravel the factors that fuel the population transmission dynamics of RV.

  19. Krishnan P, Lee FK, Chong KW, Mai CW, Muhamad A, Lim SH, et al.
    Org. Lett., 2018 12 21;20(24):8014-8018.
    PMID: 30543301 DOI: 10.1021/acs.orglett.8b03592
    Two new monoterpenoid indole alkaloids, alstoscholactine (1) and alstolaxepine (2), were isolated from Alstonia scholaris. Compound 1 represents a rearranged stemmadenine alkaloid with an unprecedented C-6-C-19 connectivity, whereas compound 2 represents a 6,7- seco-angustilobine B-type alkaloid incorporating a rare γ-lactone-bridged oxepane ring system. Their structures and absolute configurations were determined by spectroscopic analyses. Compound 1 was successfully semisynthesized from 19 E-vallesamine. Compound 2 induced marked vasorelaxation in rat isolated aortic rings precontracted with phenylephrine.
  20. Yap YY, Law KB, Sathar J, Lau NS, Goh AS, Chew TK, et al.
    Exp Hematol Oncol, 2018;7:31.
    PMID: 30564475 DOI: 10.1186/s40164-018-0124-7
    Background: The evolution of molecular studies in myeloproliferative neoplasms (MPN) has enlightened us the understanding of this complex disease consisting of polycythaemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The epidemiology is well described in the western world but not in Asian countries like Malaysia.

    Materials and methods: This retrospective national registry of MPN was conducted from year 2009 to 2015 in Malaysia.

    Results: A total of 1010 patients were registered over a period of 5 years. The mean age was 54 years with male predominance. The ethnic distribution revealed that Chinese had a relatively high weighted incidence proportion (43.2%), followed by Indian (23.8%), Malay (15.8%) and other ethnic groups (17.2%). The types of MPN reported were 40.4% of ET (n = 408), 38.1% of PV (n = 385), 9.2% of PMF (n = 93), 3.1% of hypereosinophilic syndrome (HES) (n = 31) and 7.9% of unclassifiable MPN (MPN-U) (n = 80). Splenomegaly was only palpable clinically in 32.2% of patients. The positive JAK2 V617F mutation was present in 644 patients with 46.6% in PV, 36.0% in ET, 9.0% in PMF, and 7.4% in MPN-U, and had significantly lower haemoglobin (p 

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