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Correlates of newly diagnosed HIV infection among cisgender women sex workers and transgender women sex workers in Greater Kuala Lumpur, Malaysia

Wang M, Lim SH, Gibson BA, Azwa I, Guadamuz TE, Altice FL, et al.

Int J STD AIDS, 2021 06;32(7):609-619.
PMID: 33752518 DOI: 10.1177/0956462420970417

Globally, cisgender women sex workers (CWSWs) and transgender women sex workers (TWSWs) experience increased vulnerabilities to HIV infection. Unfortunately, there is limited data on the drivers of HIV infection in these two understudied populations, particularly in Southeast Asia. To better understand factors associated with HIV infection, we evaluated correlates of newly diagnosed HIV infection in these two populations in Greater Kuala Lumpur, Malaysia. A total of 469 women (CWSW: n = 283; TWSW: n = 186) were included in this study. Most participants who tested HIV+ were unaware of their infection (59.6%; n = 34/57). Separate binary and multivariable logistic regressions were conducted to identify correlates of newly diagnosed HIV in CWSWs and TWSWs. Among CWSWs, Chlamydia trachomatis (aOR = 5.66; p = 0.007) and lifetime use of ecstasy/MDMA (aOR = 5.34; p = 0.03) were associated with newly diagnosed HIV, while condomless vaginal sex with clients was associated with lower likelihood of HIV infection (aOR = 0.98; p = 0.01). Among TWSWs, being single (aOR = 6.76; p = 0.03), using mobile application to solicit clients (aOR = 25.33; p = 0.006), and having C. trachomatis infection (aOR = 88.22, p = 0.02) were associated with newly diagnosed HIV. Expansion of HIV/sexually transmitted infection screening is needed to increase detection of HIV and linkage to care for sex workers. Interventions to reduce HIV infection among CWSWs and TWSWs should be tailored to these populations' unique vulnerabilities.
In vivo studies of nanostructure-based photosensitizers for photodynamic cancer therapy

Voon SH, Kiew LV, Lee HB, Lim SH, Noordin MI, Kamkaew A, et al.

Small, 2014 Dec 29;10(24):4993-5013.
PMID: 25164105 DOI: 10.1002/smll.201401416

Animal models, particularly rodents, are major translational models for evaluating novel anticancer therapeutics. In this review, different types of nanostructure-based photosensitizers that have advanced into the in vivo evaluation stage for the photodynamic therapy (PDT) of cancer are described. This article focuses on the in vivo efficacies of the nanostructures as delivery agents and as energy transducers for photosensitizers in animal models. These materials are useful in overcoming solubility issues, lack of tumor specificity, and access to tumors deep in healthy tissue. At the end of this article, the opportunities made possible by these multiplexed nanostructure-based systems are summarized, as well as the considerable challenges associated with obtaining regulatory approval for such materials. The following questions are also addressed: (1) Is there a pressing demand for more nanoparticle materials? (2) What is the prognosis for regulatory approval of nanoparticles to be used in the clinic?
Fulltext Post-caesarean septicaemia in Kandang Kerbau Hospital, Singapore, 1993-1995

Teo KP, Jacob SCM, Lim SH

Med J Malaysia, 1997 Dec;52(4):325-30.
PMID: 10968108

We reviewed all documented cases of septicaemia following caesarean deliveries in Kandang Kerbau Hospital between 1st January 1993 to 31st December 1995. There were 22 cases of septicaemia among 8201 caesarean births, and hence the incidence is 2.7:1000. There were 45,412 deliveries, and the overall caesarean section rate was 18.1%. Among the 22 documented cases of septicaemia which came under this study, the most common clinical conditions found were endomyometritis (7 cases), urinary tract infection (6 cases), and wound infection (3 cases). One of the three cases with wound infection also had pneumonia. There was one patient who had mild transient myocarditis. We could not determine with certainty any site of infection in five patients. The most common bloodstream bacterial isolates was Staphylococcus aureus (16), while the uncommon ones were Acinetobacter baumanii (2), Escherichia coli (1), Klebsiella sp. (1), Staphylococcus epidermidis (1), Streptococcus Group F (1), Peptostreptococcus species and Veillonella species (1). There was no mortality and prompt, vigorous treatment had led to uneventful recovery in all the cases.
Polyneurines A-H, iboga alkaloids from Tabernaemontana polyneura

Tang SY, Tan CH, Sim KS, Yong KT, Lim KH, Low YY, et al.

Phytochemistry, 2023 Apr;208:113587.
PMID: 36646163 DOI: 10.1016/j.phytochem.2023.113587

Eight undescribed iboga alkaloids, polyneurines A-H, were isolated from the bark of Tabernaemontana polyneura. The structures of these alkaloids were established by interpretation of the MS and NMR data, while the configurations were determined using GIAO NMR calculations and DP4+ probability analysis, TDDFT-ECD method, or X-ray diffraction analysis. Polyneurine A possesses a γ-lactone unit embedded within the iboga skeleton, while polyneurines D and E incorporate a formylmethyl moiety at C-3 of the iboga skeleton. Biosynthetic pathways towards the formation of polyneurines A, C, D, and E were proposed.
A 5-year retrospective study of melioidosis cases treated in a district specialist hospital

Tang RY, Lim SH, Lam JE, Nurasykin S, Eileen T, Chan YW

Med J Malaysia, 2019 12;74(6):472-476.
PMID: 31929471

INTRODUCTION: Melioidosis is caused by Burkholderia pseudomallei, a gram-negative aerobic bacillus, found in the soil and surface water. Treating melioidosis has been a challenge in district hospitals due to high usage of broad spectrum antibiotics and prolonged hospitalisation. This study is to review the patients' demography, clinical presentations and microbiological data.
METHODS: A 5-year retrospective study was carried out on patients admitted with culture positive for melioidosis from year 2013 to 2017 in Hospital Teluk Intan, Perak.
RESULTS: There were a total of 46 confirmed cases of melioidosis. Majority of the patients were working in the agricultural and farming (28.6%), and factories (25.7%). Thirty-one patients had diabetes mellitus (71.1%). Presentations of patients with melioidosis included pneumonia (54.3%), skin and soft tissue infection (19.6%), deep abscesses (15.2%) and bone and joint infections (13%). An average of 5.8 days was needed to confirm the diagnosis of melioidosis via positive culture. However, only 39.4% of these patients were started on ceftazidime or carbapenem as the empirical therapy. The intensive care unit (ICU) admission rate for melioidosis was 46% and the mortality rate was 52%. Our microbial cultures showed good sensitivity towards cotrimoxazole (97.1%), ceftazidime (100%) and carbapenem (100%).
CONCLUSION: Melioidosis carries high mortality rate, especially with lung involvement and bacteremia. Physicians should have high clinical suspicion for melioidosis cases to give appropriate antimelioidosis therapy early.
Eugeniifoline, a Pentacyclic Indole Alkaloid from Leuconotis eugeniifolia, and Configurational Revision of Synthetic Eugeniifoline Isolated from a Diversity-Enhanced Extract

Tan YS, Wong SK, Yong KT, Lim KH, Lim SH, Low YY

J Nat Prod, 2023 Jan 27;86(1):232-236.
PMID: 36651825 DOI: 10.1021/acs.jnatprod.2c00731

Eugeniifoline (1), a pentacyclic indole alkaloid with a five-membered ring E, was isolated for the first time as a natural product from the stem-bark extract of Leuconotis eugeniifolia. Eugeniifoline (1) was previously reported as a synthetic product from a diversity-enhanced extract, but with the configuration at C-21 reported as S (1a). The configuration at C-21 was revised to R as shown in 1, based on the NOE data, GIAO NMR calculations, and DP4+ probability analysis, as well as the TDDFT-ECD method.
Quinoline, Indole, and Isogranatanine Alkaloids from Malayan Leuconotis eugeniifolia

Tan YS, Ng MP, Tan CH, Tang WK, Sim KS, Yong KT, et al.

J Nat Prod, 2024 Feb 23;87(2):286-296.
PMID: 38284153 DOI: 10.1021/acs.jnatprod.3c00960

Nine new alkaloids, eugeniinalines A-H (1-8) and (+)-eburnamenine N-oxide (9), comprising one quinoline, six indole, and two isogranatanine alkaloids, were isolated from the stem-bark extract of the Malayan Leuconotis eugeniifolia. The structures and absolute configurations of these alkaloids were established based on the analysis of the spectroscopic data, GIAO NMR calculations, DP4+ probability analysis, TDDFT-ECD method, and X-ray diffraction analysis. Eugeniinaline A (1) represents a new pentacyclic quinoline alkaloid with a 6/6/5/6/7 ring system. Eugeniinaline G (7) and its seco-derivative, eugeniinaline H (8), were the first isogranatanine alkaloids isolated as natural products. The known alkaloids leucolusine (10) and melokhanine A (11) were found to be the same compound, based on comparison of the spectroscopic data of both compounds, with the absolute configuration of (7R, 20R, 21S). Eugeniinalines A and G (1 and 7) showed cytotoxic activity against the HT-29 cancer cell line with IC50 values of 7.1 and 7.2 μM, respectively.
Pericardial abscess: The corollary of disseminated Methicillin-resistant Staphylococcus aureus following diabetic foot ulcer infection

Tan TL, Lim SH, Ruslan Mustapa M, Ganeswary R

Med J Malaysia, 2020 11;75(6):742-744.
PMID: 33219189

Methicillin-resistant Staphylococcus aureus (MRSA) purulent pericarditis, characterised by frank pus collection or microscopic pyogenic effusion in the pericardium represents the most serious form of pericardial infection. The route of MRSA acquisition in pericardial abscess commonly occurs via the blood stream infection and it is more commonly observed among immunocompromised individuals. To date, diabetic foot ulcer infection rarely disseminates and becomes a nidus for pericardial infection. Herein, we report an unusual case of MRSA pericardial abscess in a 44-year-old man who presented at Hospital Seri Manjung, Malaysia with cardiac tamponade. Past medical history indicated that he was recently treated for infected diabetic foot ulcer with MRSA bacteraemia one week earlier. Despite adequate pericardial drainage and extended parenteral vancomycin therapy, this case ended in fatality on day 42 of admission due to nosocomial infection. It is hoped that this report serves to increase the vigilance among clinicians that diabetic foot ulcer infections have the potential to progress to pericardial abscess in the presence of MRSA bacteraemia, although they may appear seemingly innocuous at presentation. Systemic vancomycin must be instituted promptly when MRSA bacteraemia is confirmed in order to circumvent the propagation of MRSA.
Sunitinib DDI with paracetamol, diclofenac, mefenamic acid and ibuprofen shows sex-divergent effects on the tissue uptake and distribution pattern of sunitinib in mice

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
Oxidized derivatives of macroline, sarpagine, and pleiocarpamine alkaloids from Alstonia angustifolia

Tan SJ, Lim JL, Low YY, Sim KS, Lim SH, Kam TS

J Nat Prod, 2014 Sep 26;77(9):2068-80.
PMID: 25211145 DOI: 10.1021/np500439u

A total of 20 new indole alkaloids comprising mainly oxidized derivatives of macroline- (including alstofonidine, a macroline indole incorporating a butyrolactone ring-F), pleiocarpamine-, and sarpagine-type alkaloids were isolated from the bark and leaf extracts of Alstonia angustifolia. The structures and relative configurations of these alkaloids were determined using NMR and MS analyses and in some instances confirmed by X-ray diffraction analyses. Alkaloids 3, 7, 35, and 41 showed moderate to weak activity, while 21 showed strong activity in reversing multidrug resistance in vincristine-resistant KB cells.
Fulltext An outbreak of methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit in Singapore: a 20-month study of clinical characteristics and control

Tan KW, Tay L, Lim SH

Singapore Med J, 1994 Jun;35(3):277-82.
PMID: 7997904

Methicillin resistant Staphylococcus aureus (MRSA) is a major infection control problem in many countries. There have been many reports of outbreaks in neonatal nurseries including, in our part of the world, Australia, Hong Kong and Malaysia. A recent outbreak of MRSA in the neonatal intensive care unit in the Kandang Kerbau Hospital, Singapore, presented us with the opportunity to study the clinical characteristics of the outbreak and the effects of infection control measures. Neonates admitted to the neonatal intensive care unit were studied over a 20-month period. They were all screened for nasal colonisation on admission and weekly thereafter. Infections were documented. Over this period there were altogether 2,576 admissions of which 85 infants had nasal colonisation with MRSA (3.3%) and 28 developed infections (1%). Although the majority of infants colonised by MRSA suffered no ill effects, 3 had septicaemia and 2 had septicaemia with osteomyelitis. There were no deaths. Standard infection control measures with barrier nursing and the use of mupirocin nasal ointment were ineffective, and control was achieved only after strict cohorting together with the use of mupirocin was instituted. This was done without additional costs to the department and without additional nurses or doctors.
Tuberculosis (TB)-associated immune reconstitution inflammatory syndrome in TB-HIV co-infected patients in Malaysia: prevalence, risk factors, and treatment outcomes

Tan HY, Yong YK, Lim SH, Ponnampalavanar S, Omar SF, Pang YK, et al.

Sex Health, 2014 Dec;11(6):532-9.
PMID: 25200957 DOI: 10.1071/SH14093

Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an important early complication of antiretroviral therapy (ART) in countries with high rates of endemic TB, but data from South-East Asia are incomplete. Identification of prevalence, risk factors and treatment outcomes of TB-IRIS in Malaysia was sought.
METHODS: A 3-year retrospective study was conducted among TB-HIV co-infected patients treated at the University of Malaya Medical Centre. Simple and adjusted logistic regressions were used to identify the predictors for TB-IRIS while Cox regression was used to assess the influence of TB-IRIS on long-term CD4 T-cell recovery.
RESULTS: One hundred and fifty-three TB-HIV patients were enrolled, of whom 106 had received both anti-TB treatment (ATT) and ART. The median (IQR) baseline CD4 T-cell count was 52 cells μL(-1) (13-130 cells μL(-1)). Nine of 96 patients (9.4%) developed paradoxical TB-IRIS and eight developed unmasking TB-IRIS, at a median (IQR) time of 27 (12-64) and 19 (14-65) days, respectively. In adjusted logistic regression analysis, only disseminated TB was predictive of TB-IRIS [OR: 10.7 (95% CI: 1.2-94.3), P=0.032]. Mortality rates were similar for TB-IRIS (n=1, 5.9%) and non-TB-IRIS (n=5, 5.7%) patients and CD4 T-cell recovery post-ART was not different between the two groups (P=0.363).
CONCLUSION: Disseminated TB was a strong independent predictor of TB-IRIS in Malaysian HIV-TB patients after commencing ART. This finding underscores the role of a high pathogen load in the pathogenesis of TB-IRIS; so interventions that reduce pathogen load before ART may benefit HIV patients with disseminated TB.
The Bisindole Alkaloids Angustilongines M and A from Alstonia penangiana Induce Mitochondrial Apoptosis and G0/G1 Cell Cycle Arrest in HT-29 Cells through Promotion of Tubulin Polymerization

Tan CH, Yeap JS, Lim SH, Low YY, Sim KS, Kam TS

J Nat Prod, 2021 05 28;84(5):1524-1533.
PMID: 33872002 DOI: 10.1021/acs.jnatprod.1c00013

A new linearly fused macroline-sarpagine bisindole, angustilongine M (1), was isolated from the methanolic extract of Alstonia penangiana. The structure of the alkaloid was elucidated based on analysis of the spectroscopic data, and its biological activity was evaluated together with another previously reported macroline-akuammiline bisindole from the same plant, angustilongine A (2). Compounds 1 and 2 showed pronounced in vitro growth inhibitory activity against a wide panel of human cancer cell lines. In particular, the two compounds showed potent and selective antiproliferative activity against HT-29 cells, as well as strong growth inhibitory effects against HT-29 spheroids. Cell death mechanistic studies revealed that the compounds induced mitochondrial apoptosis and G0/G1 cell cycle arrest in HT-29 cells in a time-dependent manner, while in vitro tubulin polymerization assays and molecular docking analysis showed that the compounds are microtubule-stabilizing agents, which are predicted to bind at the β-tubulin subunit at the Taxol-binding site.
Antiproliferative and Microtubule-stabilizing Activities of Two Iboga-vobasine Bisindoles Alkaloids from Tabernaemontana corymbosa in Colorectal Adenocarcinoma HT-29 Cells

Tan CH, Sim DSY, Lim SH, Mohd Mohidin TB, Mohan G, Low YY, et al.

Planta Med, 2022 Nov;88(14):1325-1340.
PMID: 35100653 DOI: 10.1055/a-1755-5605

Two iboga-vobasine bisindoles, 16'-decarbomethoxyvoacamine (1: ) and its 19,20-dihydro derivative, 16'-decarbomethoxydihydrovoacamine (2: ) from Tabernaemontana corymbosa exhibited potent cytotoxicity against the human colorectal adenocarcinoma HT-29 cells in our previous studies. Bisindoles 1: and 2: selectively inhibited the growth of HT-29 cells without significant cytotoxicity to normal human colon fibroblasts CCD-18Co. Treatment with bisindoles 1: and 2: suppressed the formation of HT-29 colonies via G0/G1 cell cycle arrest and induction of mitochondrial apoptosis. Owing to its higher antiproliferative activity, bisindole 2: was chosen for the subsequent studies. Bisindole 2: inhibited the formation of HT-29 spheroids (tumor-like cell aggregates) in 3D experiments in a dose-dependent manner, while an in vitro tubulin polymerization assay and molecular docking analysis showed that bisindole 2: is a microtubule-stabilizing agent which is predicted to bind at the β-tubulin subunit at the taxol-binding site. The binding resulted in the generation of ROS, which consequently activated the oxidative stress-related cell cycle arrest and apoptotic pathways, viz., JNK/p38, p21Cip1/Chk1, and p21Cip1/Rb/E2F, as shown by microarray profiling.
Fulltext Malaysian macroalga Padina australis Hauck attenuates high dose corticosterone-mediated oxidative damage in PC12 cells mimicking the effects of depression

Subermaniam K, Yow YY, Lim SH, Koh OH, Wong KH

Saudi J Biol Sci, 2020 Jun;27(6):1435-1445.
PMID: 32489279 DOI: 10.1016/j.sjbs.2020.04.042

Oxidative damage has been associated with the pathophysiology of depression. Macroalgae are equipped with antioxidant defense system to counteract the effects of free radicals. We explored the use of Malaysian Padina australis to attenuate high dose corticosterone-mediated oxidative damage in a cellular model mimicking depression. Fresh specimen of P. australis was freeze-dried and extracted sequentially with hexanes, ethyl acetate and ethanol. The extracts were screened for their phytochemical contents and antioxidant activities. Ethanol extract demonstrated the most potent antioxidant capacity and was selected for subsequent assays against high dose corticosterone of 600 µM-mediated oxidative damage in the rat pheochromocytoma (PC12) cells. The corticosterone reduced the cell viability, glutathione (GSH) level, aconitase activity, and mitochondrial membrane potential (MMP); and increased the lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) level and apoptosis. However, the extent of oxidative damage was reversed by 0.25-0.5 mg/mL ethanol extract suggesting a possible role of P. australis-based antioxidants in the mitochondrial defense against constant ROS generation and regulation of antioxidant pathway. The effects were similar to that of desipramine, a tricyclic antidepressant. Our findings indicate that P. australis can be developed as a mitochondria-targeted antioxidant to mitigate antidepressant-like effects.
Fulltext Malaysian brown macroalga Padina australis mitigates lipopolysaccharide-stimulated neuroinflammation in BV2 microglial cells

Subermaniam K, Lew SY, Yow YY, Lim SH, Yu WS, Lim LW, et al.

Iran J Basic Med Sci, 2023;26(6):669-679.
PMID: 37275754 DOI: 10.22038/IJBMS.2023.67835.14842

OBJECTIVES: Neuroinflammation and microglial activation are pathological features in central nervous system disorders. Excess levels of reactive oxygen species (ROS) and pro-inflammatory cytokines have been implicated in exacerbation of neuronal damage during chronic activation of microglial cells. Padina australis, a brown macroalga, has been demonstrated to have various pharmacological properties such as anti-neuroinflammatory activity. However, the underlying mechanism mediating the anti-neuroinflammatory potential of P. australis remains poorly understood. We explored the use of Malaysian P. australis in attenuating lipopolysaccharide (LPS)-stimulated neuroinflammation in BV2 microglial cells.
MATERIALS AND METHODS: Fresh specimens of P. australis were freeze-dried and subjected to ethanol extraction. The ethanol extract (PAEE) was evaluated for its protective effects against 1 µg/ml LPS-stimulated neuroinflammation in BV2 microglial cells.
RESULTS: LPS reduced the viability of BV2 microglia cells and increased the levels of nitric oxide (NO), prostaglandin E2 (PGE2), intracellular reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). However, the neuroinflammatory response was reversed by 0.5-2.0 mg/ml PAEE in a dose-dependent manner. Analysis of liquid chromatography-mass spectrometry (LC-MS) of PAEE subfractions revealed five compounds; methyl α-eleostearate, ethyl α-eleostearate, niacinamide, stearamide, and linoleic acid.
CONCLUSION: The protective effects of PAEE against LPS-stimulated neuroinflammation in BV2 microglial cells were found to be mediated by the suppression of excess levels of intracellular ROS and pro-inflammatory mediators and cytokines, denoting the protective role of P. australis in combating continuous neuroinflammation. Our findings support the use of P. australis as a possible therapeutic for neuroinflammatory and neurodegenerative diseases.
Vobatensines A-F, Cytotoxic Iboga-Vobasine Bisindoles from Tabernaemontana corymbosa

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.
Conolodinines A-D, Aspidosperma- Aspidosperma Bisindole Alkaloids with Antiproliferative Activity from Tabernaemontana corymbosa

Sim DS, Navanesan S, Sim KS, Gurusamy S, Lim SH, Low YY, et al.

J Nat Prod, 2019 04 26;82(4):850-858.
PMID: 30869890 DOI: 10.1021/acs.jnatprod.8b00919

Examination of the EtOH extract of the leaves of the Malayan Tabernaemontana corymbosa resulted in the isolation of four new (1-4) and two known bisindole alkaloids (5, 6) of the Aspidosperma- Aspidosperma type. The structures of these alkaloids were determined based on analysis of the spectroscopic data (NMR and HRESIMS). X-ray diffraction analyses of the related bisindole alkaloids conophylline (5) and conophyllinine (6) established the absolute configurations. Treatment of the bisindole alkaloid conophylline (5) with benzeneselenic anhydride gave, in addition to the known bisindole polyervinine (7) previously isolated from another Malayan Tabernaemontana, another bisindole product, 8, an isolable tautomer of 7. X-ray diffraction analyses yielded the absolute configurations of both bisindoles and in addition showed that polyervinine (7) exists primarily as the neutral dione structure. The bisindoles (1-8) and the related conophylline-type bisindoles (9-13) 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, A549, HT-29, and HCT 116 cells, with IC50 values for the active compounds in the 0.01-5 μM range.
Fulltext Use of Smartphone to Seek Sexual Health Information Online Among Malaysian Men Who Have Sex with Men (MSM): Implications for mHealth Intervention to Increase HIV Testing and Reduce HIV Risks

Shrestha R, Lim SH, Altice FL, Copenhaver M, Wickersham JA, Saifi R, et al.

J Community Health, 2020 02;45(1):10-19.
PMID: 31375976 DOI: 10.1007/s10900-019-00713-x

In settings where stigma and discrimination toward men who have sex with men (MSM) are high or illegal, like in Malaysia, innovative methods to anonymously reach them are urgently needed. The near ubiquitous availability of mobile technology, including smartphones, has the potential to open new frontiers (such as mHealth) to prevent HIV and other sexually transmitted infections (STIs). The extent to which MSM use mHealth tools for HIV and STI prevention in the Malaysia context, however, is unknown. A cross-sectional online survey in 622 Malaysian MSM was conducted between July and November 2017. Participants were recruited via advertisements on mobile apps frequently used by MSM. In addition to demographic, smartphone access and utilization, and other information were assessed using logistic regression to determine factors associated with the use of a smartphone to search for online sexual health information. Nearly all (99.2%) participants owned a smartphone, with 63% reported having used one to seek sexual health information, including HIV/STIs. Overall, 96% used smartphones to find sexual partners, with high levels of HIV risk behavior reported. Independent correlates of smartphone use to seek online sexual health information included older age (aOR 0.943, p = 0.005), higher education (aOR 2.14, p = 027), recent (past year) HIV testing (aOR 3.91, p = 0.026), and seeking sexual partners using geosocial networking apps (aOR 5.58, p = 0.006). These findings suggest high smartphone use by high-risk MSM to seek sexual health information and suggests that mHealth strategies may be an effective strategy to engage MSM in HIV prevention activities.
Fulltext Willingness to Use HIV Self-Testing and Associated Factors Among Transgender Women in Malaysia

Shrestha R, Galka JM, Azwa I, Lim SH, Guadamuz TE, Altice FL, et al.

Transgend Health, 2020;5(3):182-190.
PMID: 32923668 DOI: 10.1089/trgh.2019.0085

Background: While global research on the implementation of HIV self-testing (HIVST) has increased exponentially, few studies have assessed information on HIVST uptake factors (i.e., willingness, preferences) in transgender women (TW) and none in the Malaysian context. We therefore sought to assess willingness to use HIVST among this understudied key population. Methods: A cross-sectional survey was conducted among 361 HIV-negative Malaysian TW in 2017. Participants were recruited using flyers, announcements through social media, and direct referral from staff members of the community-based organizations serving the TW communities. Multivariable logistic regression was used to identify correlates of willingness to use HIVST. Results: Nearly half of the participants (47.6%) reported that they would be willing to use HIVST. Multivariable analysis showed that willingness to use HIVST was positively associated with having experienced sexual assault in childhood (adjusted odds ratio [aOR]=3.239, p<0.001), having ever used mobile phone or apps to find sex work clients (aOR=1.677, p=0.040), and having engaged in condomless sex in the past 6 months (aOR=1.886, p=0.018). In contrast, living in Kuala Lumpur (aOR=0.559, p=0.032), having higher number of sex work clients per day (aOR=0.927, p=0.004), and current depressive symptoms (aOR=0.576, p=0.026) were negatively associated with willingness to use HIVST. Conclusions: Findings in this study suggest that TW in our sample were moderately willing to use HIVST. Especially important here is the increased interest in HIVST among TW who are at higher risk for HIV infection. Overall, our findings underscore the need for additional research on how to most effectively implement HIVST for key populations, including TW, such that uptake and retention in regular HIV screening is sustained.

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