MyMedR

Displaying publications 541 - 560 of 1053 in total

Abstract:

Sort:

Fulltext A data-driven machine learning approach for discovering potent LasR inhibitors

Koh CMM, Ping LSY, Xuan CHH, Theng LB, San HS, Palombo EA, et al.

Bioengineered, 2023 Dec;14(1):2243416.
PMID: 37552115 DOI: 10.1080/21655979.2023.2243416

The rampant spread of multidrug-resistant Pseudomonas aeruginosa strains severely threatens global health. This severity is compounded against the backdrop of a stagnating antibiotics development pipeline. Moreover, with many promising therapeutics falling short of expectations in clinical trials, targeting the las quorum sensing (QS) system remains an attractive therapeutic strategy to combat P. aeruginosa infection. Thus, our primary goal was to develop a drug prediction algorithm using machine learning to identify potent LasR inhibitors. In this work, we demonstrated using a Multilayer Perceptron (MLP) algorithm boosted with AdaBoostM1 to discriminate between active and inactive LasR inhibitors. The optimal model performance was evaluated using 5-fold cross-validation and test sets. Our best model achieved a 90.7% accuracy in distinguishing active from inactive LasR inhibitors, an area under the Receiver Operating Characteristic Curve value of 0.95, and a Matthews correlation coefficient value of 0.81 when evaluated using test sets. Subsequently, we deployed the model against the Enamine database. The top-ranked compounds were further evaluated for their target engagement activity using molecular docking studies, Molecular Dynamics simulations, MM-GBSA analysis, and Free Energy Landscape analysis. Our data indicate that several of our chosen top hits showed better ligand-binding affinities than naringenin, a competitive LasR inhibitor. Among the six top hits, five of these compounds were predicted to be LasR inhibitors that could be used to treat P. aeruginosa-associated infections. To our knowledge, this study provides the first assessment of using an MLP-based QSAR model for discovering potent LasR inhibitors to attenuate P. aeruginosa infections.
Fulltext Vector competence of Aedes aegypti, Culex tarsalis, and Culex quinquefasciatus from California for Zika virus

Main BJ, Nicholson J, Winokur OC, Steiner C, Riemersma KK, Stuart J, et al.

PLoS Negl Trop Dis, 2018 Jun;12(6):e0006524.
PMID: 29927940 DOI: 10.1371/journal.pntd.0006524

Zika virus (ZIKV) has emerged since 2013 as a significant global human health threat following outbreaks in the Pacific Islands and rapid spread throughout South and Central America. Severe congenital and neurological sequelae have been linked to ZIKV infections. Assessing the ability of common mosquito species to transmit ZIKV and characterizing variation in mosquito transmission of different ZIKV strains is important for estimating regional outbreak potential and for prioritizing local mosquito control strategies for Aedes and Culex species. In this study, we evaluated the laboratory vector competence of Aedes aegypti, Culex quinquefasciatus, and Culex tarsalis that originated in areas of California where ZIKV cases in travelers since 2015 were frequent. We compared infection, dissemination, and transmission rates by measuring ZIKV RNA levels in cohorts of mosquitoes that ingested blood meals from type I interferon-deficient mice infected with either a Puerto Rican ZIKV strain from 2015 (PR15), a Brazilian ZIKV strain from 2015 (BR15), or an ancestral Asian-lineage Malaysian ZIKV strain from 1966 (MA66). With PR15, Cx. quinquefasciatus was refractory to infection (0%, N = 42) and Cx. tarsalis was infected at 4% (N = 46). No ZIKV RNA was detected in saliva from either Culex species 14 or 21 days post feeding (dpf). In contrast, Ae. aegypti developed infection rates of 85% (PR15; N = 46), 90% (BR15; N = 20), and 81% (MA66; N = 85) 14 or 15 dpf. Although MA66-infected Ae. aegypti showed higher levels of ZIKV RNA in mosquito bodies and legs, transmission rates were not significantly different across virus strains (P = 0.13, Fisher's exact test). To confirm infectivity and measure the transmitted ZIKV dose, we enumerated infectious ZIKV in Ae. aegypti saliva using Vero cell plaque assays. The expectorated plaque forming units PFU varied by viral strain: MA66-infected expectorated 13±4 PFU (mean±SE, N = 13) compared to 29±6 PFU for PR15-infected (N = 13) and 35±8 PFU for BR15-infected (N = 6; ANOVA, df = 2, F = 3.8, P = 0.035). These laboratory vector competence results support an emerging consensus that Cx. tarsalis and Cx. quinquefasciatus are not vectors of ZIKV. These results also indicate that Ae. aegypti from California are efficient laboratory vectors of ancestral and contemporary Asian lineage ZIKV.
Virtual patient with temporal evolution for mechanical ventilation trial studies: A stochastic model approach

Ang CYS, Chiew YS, Wang X, Ooi EH, Nor MBM, Cove ME, et al.

Comput Methods Programs Biomed, 2023 Oct;240:107728.
PMID: 37531693 DOI: 10.1016/j.cmpb.2023.107728

BACKGROUND AND OBJECTIVE: Healthcare datasets are plagued by issues of data scarcity and class imbalance. Clinically validated virtual patient (VP) models can provide accurate in-silico representations of real patients and thus a means for synthetic data generation in hospital critical care settings. This research presents a realistic, time-varying mechanically ventilated respiratory failure VP profile synthesised using a stochastic model.
METHODS: A stochastic model was developed using respiratory elastance (Ers) data from two clinical cohorts and averaged over 30-minute time intervals. The stochastic model was used to generate future Ers data based on current Ers values with added normally distributed random noise. Self-validation of the VPs was performed via Monte Carlo simulation and retrospective Ers profile fitting. A stochastic VP cohort of temporal Ers evolution was synthesised and then compared to an independent retrospective patient cohort data in a virtual trial across several measured patient responses, where similarity of profiles validates the realism of stochastic model generated VP profiles.
RESULTS: A total of 120,000 3-hour VPs for pressure control (PC) and volume control (VC) ventilation modes are generated using stochastic simulation. Optimisation of the stochastic simulation process yields an ideal noise percentage of 5-10% and simulation iteration of 200,000 iterations, allowing the simulation of a realistic and diverse set of Ers profiles. Results of self-validation show the retrospective Ers profiles were able to be recreated accurately with a mean squared error of only 0.099 [0.009-0.790]% for the PC cohort and 0.051 [0.030-0.126]% for the VC cohort. A virtual trial demonstrates the ability of the stochastic VP cohort to capture Ers trends within and beyond the retrospective patient cohort providing cohort-level validation.
CONCLUSION: VPs capable of temporal evolution demonstrate feasibility for use in designing, developing, and optimising bedside MV guidance protocols through in-silico simulation and validation. Overall, the temporal VPs developed using stochastic simulation alleviate the need for lengthy, resource intensive, high cost clinical trials, while facilitating statistically robust virtual trials, ultimately leading to improved patient care and outcomes in mechanical ventilation.
Development and physicochemical characterization of a biodegradable microspheres formulation loaded with samarium-153 and doxorubicin for chemo-radioembolization of liver tumours

Alregib AH, Tan HY, Wong YH, Kasbollah A, Wong EH, Abdullah BJJ, et al.

J Labelled Comp Radiopharm, 2023 Aug;66(10):308-320.
PMID: 37287213 DOI: 10.1002/jlcr.4046

Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are promising treatments for unresectable liver tumours. Some recent studies suggested that combining TACE and TARE in one treatment course might improve treatment efficacy through synergistic cytotoxicity effects. Nonetheless, current formulations do not facilitate a combination of chemo- and radio-embolic agents in one delivery system. Therefore, this study aimed to synthesise a hybrid biodegradable microsphere loaded with both radioactive agent, samarium-153 (153 Sm) and chemotherapeutic drug, doxorubicin (Dox) for potential radio-chemoembolization of advanced liver tumours. 152 Sm and Dox-loaded polyhydroxybutyrate-co-3-hydroxyvalerate (PHBV) microspheres were prepared using water-in-oil-in-water solvent evaporation method. The microspheres were then sent for neutron activation in a neutron flux of 2 × 1012 n/cm2 /s. The physicochemical properties, radioactivity, radionuclide purity, 153 Sm retention efficiency, and Dox release profile of the Dox-153 Sm-PHBV microspheres were analysed. In addition, in vitro cytotoxicity of the formulation was tested using MTT assay on HepG2 cell line at 24 and 72 h. The mean diameter of the Dox-153 Sm-PHBV microspheres was 30.08 ± 2.79 μm. The specific radioactivity was 8.68 ± 0.17 GBq/g, or 177.69 Bq per microsphere. The 153 Sm retention efficiency was more than 99%, tested in phosphate-buffered saline (PBS) and human blood plasma over 26 days. The cumulative release of Dox from the microspheres after 41 days was 65.21 ± 1.96% and 29.96 ± 0.03% in PBS solution of pH 7.4 and pH 5.5, respectively. The Dox-153 Sm-PHBV microspheres achieved a greater in vitro cytotoxicity effect on HepG2 cells (85.73 ± 3.63%) than 153 Sm-PHBV (70.03 ± 5.61%) and Dox-PHBV (74.06 ± 0.78%) microspheres at 300 μg/mL at 72 h. In conclusion, a novel biodegradable microspheres formulation loaded with chemotherapeutic drug (Dox) and radioactive agent (153 Sm) was successfully developed in this study. The formulation fulfilled all the desired physicochemical properties of a chemo-radioembolic agent and achieved better in vitro cytotoxicity on HepG2 cells. Further investigations are needed to evaluate the biosafety, radiation dosimetry, and synergetic anticancer properties of the formulation.
Incidence and prevalence of generalized pustular psoriasis in multiethnic Johor Bahru, Malaysia: a population-based cohort study using routinely captured electronic health records in the Teleprimary Care (TPC®) clinical information system from 2010 to 2020

Choon SE, Wright AK, Griffiths CEM, Wong KW, Tey KE, Lim YT, et al.

Br J Dermatol, 2023 Sep 15;189(4):410-418.
PMID: 37162007 DOI: 10.1093/bjd/ljad158

BACKGROUND: There is limited understanding of the epidemiology of generalized pustular psoriasis (GPP) internationally, with no population-based estimates of GPP in South East Asia.
OBJECTIVES: To determine the incidence and prevalence of GPP in the Malaysian population and characterize its flares and trigger factors.
METHODS: We conducted a population-based cohort study using the Teleprimary Care database between January 2010 and December 2020. We identified 230 dermatologist-confirmed GPP cases using International Classification of Diseases, 10th revision, diagnostic codes. Annual prevalence and incidence rates were stratified by age, sex and ethnicity. We compared data regarding flares and trigger factors for patients with GPP who had associated psoriasis vulgaris (PV) with those who did not have associated PV.
RESULTS: The prevalence of GPP was 198 per million (267 women, 127 men) and incidence was 27.2 per million person-years [95% confidence interval (CI) 22.8-31.6]; 35.3 (28.4-42.2) per million person-years for women and 18.3 (13.1-23.5) per million person-years for men. Rates were higher in Chinese individuals [prevalence 271 per million; incidence 41.6 per million person-years (28.9-54.3)] than in the Malay population [prevalence 186; incidence 24.6 (19.4-29.7)] or the Indian ethnic group [prevalence 179; incidence 25.0 (13.8-36.3)]. Annual prevalence was consistently higher in women than in men and highest among the Chinese population, followed by the Indian and Malay populations. Overall, 67% of patients with GPP had associated PV. The prevalence and incidence of GPP without PV were lower than GPP with PV at 66 vs. 132 per million and 19.3 (95% CI 15.6-23.0) vs. 8.0 (95% CI 5.6-10.3) per million person-years, respectively. The mean age at GPP onset was 42.7 years (SD 18.4). A bimodal trend in the age of GPP onset was observed, with first and second peaks at age 20-29 years and age 50-59 years, respectively. Disease onset was significantly earlier in patients with GPP without PV than in those with PV [mean age 37.5 years (SD 20.7) vs. 44.9 years (SD 17.0), P = 0.026]. Flares occurred more frequently in patients without PV than in those with PV [mean number of flares per patient per year was 1.35 (SD 0.77) vs. 1.25 (SD 0.58), P = 0.039]. Common triggers of flares in patients with GPP who did not have PV were infections, pregnancy, menstruation and stress, whereas withdrawal of therapy, particularly systemic corticosteroids, was a more frequent trigger in patients with GPP who also had PV.
CONCLUSIONS: Our findings contribute to the global mapping of GPP, which will help inform the management of this rare condition.
Fulltext Testing the validity of a new scale designed to assess beliefs and perceptions about colorectal cancer and colorectal cancer screening in Malaysia: a principal component analysis

Su TT, Adekunjo FO, Schliemann D, Cardwell CR, Htay MNN, Dahlui M, et al.

BMJ Open, 2023 Aug 31;13(8):e072166.
PMID: 37652591 DOI: 10.1136/bmjopen-2023-072166

OBJECTIVE: To conduct a cultural adaptation and validation of the Champion Health Belief Model Scale (CHBMS) for colorectal cancer (CRC) screening (CHBMS-CRC-M) in order to assess and investigate perceptions and beliefs about CRC screening in Malaysia.
DESIGNS AND PARTICIPANTS: The results from an evidence synthesis and the outcomes from an expert panel discussion were used to shape CHBMS scale content into an assessment of beliefs about CRC screening (CHBMS-CRC). This questionnaire assessment was translated into the official language of Malaysia. An initial study tested the face validity of the new scale or questionnaire with 30 men and women from various ethnic groups. Factorial or structural validity was investigated in a community sample of 954 multiethnic Malaysians.
SETTING: Selangor state, Malaysia.
RESULTS: The new scale was culturally acceptable to the three main ethnic groups in Malaysia and achieved good face validity. Cronbach's alpha coefficients ranged from 0.66 to 0.93, indicating moderate to good internal consistency. Items relating to perceived susceptibility to CRC 'loaded' on Factor 1 (with loadings scoring above 0.90); perceived benefits of CRC screening items loaded on factor 2 and were correlated strongly (loadings ranged between 0.63 and 0.83) and perceived barriers (PBA) to CRC screening (PBA) items loaded on factor 3 (range 0.30-0.72).
CONCLUSION: The newly developed CHBMS-CRC-M fills an important gap by providing a robust scale with which to investigate and assess CRC screening beliefs and contribute to efforts to enhance CRC screening uptake and early detection of CRC in Malaysia and in other Malay-speaking communities in the region.
Fulltext Methylation profiling and evaluation of demethylating therapy in renal cell carcinoma

Ricketts CJ, Morris MR, Gentle D, Shuib S, Brown M, Clarke N, et al.

Clin Epigenetics, 2013 Sep 13;5(1):16.
PMID: 24034811 DOI: 10.1186/1868-7083-5-16

BACKGROUND: Despite therapeutic advances in targeted therapy, metastatic renal cell carcinoma (RCC) remains incurable for the vast majority of patients. Key molecular events in the pathogenesis of RCC include inactivation of the VHL tumour suppressor gene (TSG), inactivation of chromosome 3p TSGs implicated in chromatin modification and remodelling and de novo tumour-specific promoter methylation of renal TSGs. In the light of these observations it can be proposed that, as in some haematological malignancies, demethylating agents such as azacitidine might be beneficial for the treatment of advanced RCC.
RESULTS: Here we report that the treatment of RCC cell lines with azacitidine suppressed cell proliferation in all 15 lines tested. A marked response to azacitidine therapy (>50% reduction in colony formation assay) was detected in the three cell lines with VHL promoter methylation but some RCC cell lines without VHL TSG methylation also demonstrated a similar response suggesting that multiple methylated TSGs might determine the response to demethylating therapies. To identify novel candidate methylated TSGs implicated in RCC we undertook a combined analysis of copy number and CpG methylation array data. Candidate novel epigenetically inactivated TSGs were further prioritised by expression analysis of RCC cell lines pre and post-azacitidine therapy and comparative expression analysis of tumour/normal pairs. Thus, with subsequent investigation two candidate genes were found to be methylated in more than 25% of our series and in the TCGA methylation dataset for 199 RCC samples: RGS7 (25.6% and 35.2% of tumours respectively) and NEFM in (25.6% and 30.2%). In addition three candidate genes were methylated in >10% of both datasets (TMEM74 (15.4% and 14.6%), GCM2 (41.0% and 14.6%) and AEBP1 (30.8% and 13.1%)). Methylation of GCM2 (P = 0.0324), NEFM (P = 0.0024) and RGS7 (P = 0.0067) was associated with prognosis.
CONCLUSIONS: These findings provide preclinical evidence that treatment with demethylating agents such as azacitidine might be useful for the treatment of advanced RCC and further insights into the role of epigenetic changes in the pathogenesis of RCC.
Fulltext A prospective comparison of UK and Malaysian patients with irritable bowel syndrome in secondary care

Chuah KH, Black CJ, Tee V, Lim SZ, Hian WX, Sahran NF, et al.

Aliment Pharmacol Ther, 2023 Jul;58(2):168-174.
PMID: 37259882 DOI: 10.1111/apt.17567

BACKGROUND: The prevalence of irritable bowel syndrome (IBS) is now known to be similar in various geographical regions, but there has been no study directly comparing characteristics of patients with IBS between populations.
AIMS: To evaluate clinical and psychological differences between adults with IBS seen in secondary care in the United Kingdom (UK) and Malaysia.
METHODS: Age- and sex-matched patients with IBS from a single centre in the UK (Leeds) and two centres in Malaysia (Kuala Lumpur and Kota Bharu), who fulfilled Rome III criteria, were recruited prospectively. Demographic characteristics and gastrointestinal and psychological symptoms were compared between both groups.
RESULTS: A total of 266 (133 UK and 133 Malaysian) age- and sex-matched patients with Rome III IBS were recruited (mean age: 45.1 years Malaysia, vs. 46.5 years UK; 57.9% female). UK patients were more likely to consume alcohol than Malaysian patients (54.1% vs. 10.5%, p
Editorial: Recognising the regional variations in profile of irritable bowel syndrome-better late than never! Authors' reply

Chuah KH, Black CJ, Tee V, Lim SZ, Hian WX, Sahran NF, et al.

Aliment Pharmacol Ther, 2023 Aug;58(4):476-477.
PMID: 37499105 DOI: 10.1111/apt.17634
Fulltext Human adipose tissue derived stem cells as a source of smooth muscle cells in the regeneration of muscular layer of urinary bladder wall

Salem SA, Hwie AN, Saim A, Chee Kong CH, Sagap I, Singh R, et al.

Malays J Med Sci, 2013 Jul;20(4):80-7.
PMID: 24044001 MyJurnal

Adipose tissue provides an abundant source of multipotent cells, which represent a source of cell-based regeneration strategies for urinary bladder smooth muscle repair. Our objective was to confirm that adipose-derived stem cells (ADSCs) can be differentiated into smooth muscle cells.
Fulltext Seroprevalence of Sparganosis in Rural Communities of Northern Tanzania

Kavana N, Sonaimuthu P, Kasanga C, Kassuku A, Al-Mekhlafi HM, Fong MY, et al.

Am J Trop Med Hyg, 2016 Oct 05;95(4):874-876.
PMID: 27481059 DOI: 10.4269/ajtmh.16-0211

In this study, the seroprevalence of sparganosis and its relationship with sociodemographic factors in northern Tanzania have been assessed. A total of 216 serum samples from two rural districts, Monduli and Babati, were tested for sparganosis using an enzyme-linked immunosorbent assay. The seroprevalence of anti-sparganum IgG antibodies was 62.5% (95% confidence interval [CI] = 56.1-68.9) in all age groups. There were significant associations between district (relative risk [RR] = 1.95, 95% CI = 1.42-2.69), education (RR = 1.40, 95% CI = 1.15-1.70), and pet ownership with seropositivity (RR = 1.48, 95% CI = 1.02-2.16) based on univariate analysis. However, only the district was significantly associated with seropositivity (odds ratio = 4.20, 95% CI = 1.89-9.32) in binary logistic regression analysis. Providing health education to people residing in sparganosis-endemic areas is likely to improve the efficacy of preventative measures and reduce human disease burden.
Investigating serum concentration profiles of orally ingested short-chain fatty acid supplements

Green CG, Ong MLY, Rowland SN, Bongiovanni T, James LJ, Clifford T, et al.

Food Funct, 2024 Nov 25;15(23):11525-11536.
PMID: 39498577 DOI: 10.1039/d4fo04028g

Acetate, propionate, and butyrate are naturally-occurring short-chain fatty acids (SCFAs) derived from bacterial metabolism of dietary fibre and have been associated with numerous positive health outcomes. All three acids have been shown to offer unique physiological and metabolic effects and, therefore, could be targeted for co-ingestion as part of a nutritional/medicinal plan. However, a better understanding of the outcomes of supplementing in combination on circulating concentration profiles is necessary to confirm uptake efficacy. This study sought to investigate the acute circulating concentration profiles of acetate, propionate, and butyrate following oral supplementation. Three experimental trials were conducted including investigations to understand the impact of capsule coating on circulating concentration profiles, the effect of supplementation dose on uptake kinetics, and the outcome of a short, repeated, supplementation routine on circulating levels. Serum samples were analysed for SCFA content using a quantitative GC-MS assay. It was observed that an acid-resistant coated capsule caused a delayed and blunted blood concentration response, with the non-acid resistant trial displaying earlier and more intense peak serum concentrations. For dose comparison investigations, all SCFAs peaked within 60 min and returned to baseline concentrations by 120 min post-supplementation. A graded dose relationship was present for propionate and butyrate when considering the total circulating exposure across a 240 min monitoring period. In addition, a one-week, twice-daily, repeated supplementation protocol resulted in no changes in basal serum SCFA concentrations. Overall, these data indicate that acetate, propionate, and butyrate display relatively similar circulating concentration profiles following oral co-ingestion, adding knowledge to help inform supplementation strategies for future outcomes where acute elevation of circulating SCFAs is desired.
The future of food from the sea

Costello C, Cao L, Gelcich S, Cisneros-Mata MÁ, Free CM, Froehlich HE, et al.

Nature, 2020 12;588(7836):95-100.
PMID: 32814903 DOI: 10.1038/s41586-020-2616-y

Global food demand is rising, and serious questions remain about whether supply can increase sustainably1. Land-based expansion is possible but may exacerbate climate change and biodiversity loss, and compromise the delivery of other ecosystem services2-6. As food from the sea represents only 17% of the current production of edible meat, we ask how much food we can expect the ocean to sustainably produce by 2050. Here we examine the main food-producing sectors in the ocean-wild fisheries, finfish mariculture and bivalve mariculture-to estimate 'sustainable supply curves' that account for ecological, economic, regulatory and technological constraints. We overlay these supply curves with demand scenarios to estimate future seafood production. We find that under our estimated demand shifts and supply scenarios (which account for policy reform and technology improvements), edible food from the sea could increase by 21-44 million tonnes by 2050, a 36-74% increase compared to current yields. This represents 12-25% of the estimated increase in all meat needed to feed 9.8 billion people by 2050. Increases in all three sectors are likely, but are most pronounced for mariculture. Whether these production potentials are realized sustainably will depend on factors such as policy reforms, technological innovation and the extent of future shifts in demand.
Improving the diagnosis of endometriosis in Asia-Pacific: Consensus from the Asia-Pacific Endometriosis Expert Panel for Endometriosis

Yen CF, Hamdan M, Hengrasmee P, Huang Z, Jeong K, Dao LA, et al.

Int J Gynaecol Obstet, 2023 Dec;163(3):720-732.
PMID: 37837343 DOI: 10.1002/ijgo.15142

Endometriosis should be diagnosed as early as possible in the continuum of care; but substantial delays of approximately 6-8 years between symptom onset and endometriosis diagnosis have been widely reported. With the purpose of improving the prompt diagnosis of endometriosis, the Asia-Pacific Endometriosis Expert Panel (APEX) sought to address the reasons for diagnostic delays across the region, and formulate a multi-pronged approach to overcoming these challenges. In the first instance, clinical diagnosis is preferable to surgical diagnosis, in order to facilitate earlier empirical treatment and minimize the negative sequelae of undiagnosed/untreated disease. There should be a high clinical index of suspicion in women presenting with cyclical symptoms, including those involving extrapelvic organs. Diagnostic delays in Asia-Pacific countries are attributable to a variety of patient, physician, and healthcare factors, including poor awareness, normalization/trivialization of pain, individual/cultural attitudes toward menstruation, default use of symptom-suppressing treatments, misdiagnosis, and a lack of diagnostic resourcing or adequate referral pathways in some areas. Suggested initiatives to reduce diagnostic delays are geared toward improving public awareness, improving clinical diagnostic skills, streamlining multidisciplinary care pathways for timely referral, updating and implementing diagnostic guidelines, lobbying policymakers and insurance companies for endometriosis support, and increasing efforts to bridge data gaps and perform further research in this field. Formulating specific action plans and gathering traction are the responsibility of individual countries within local parameters. The APEX group advocates for any initiatives and policies that support the unmet needs of women with endometriosis, to improve patient experience and outcomes.
Fulltext Artesunate-mefloquine versus chloroquine for treatment of uncomplicated Plasmodium knowlesi malaria in Malaysia (ACT KNOW): an open-label, randomised controlled trial

Grigg MJ, William T, Menon J, Dhanaraj P, Barber BE, Wilkes CS, et al.

Lancet Infect Dis, 2016 Feb;16(2):180-188.
PMID: 26603174 DOI: 10.1016/S1473-3099(15)00415-6

BACKGROUND: The zoonotic parasite Plasmodium knowlesi has become the most common cause of human malaria in Malaysia and is present throughout much of southeast Asia. No randomised controlled trials have been done to identify the optimum treatment for this emerging infection. We aimed to compare artesunate-mefloquine with chloroquine to define the optimum treatment for uncomplicated P knowlesi malaria in adults and children.
METHODS: We did this open-label, randomised controlled trial at three district hospitals in Sabah, Malaysia. Patients aged 1 year or older with uncomplicated P knowlesi malaria were randomly assigned, via computer-generated block randomisation (block sizes of 20), to receive oral artesunate-mefloquine (target dose 12 mg/kg artesunate and 25 mg/kg mefloquine) or chloroquine (target dose 25 mg/kg). Research nursing staff were aware of group allocation, but allocation was concealed from the microscopists responsible for determination of the primary endpoint, and study participants were not aware of drug allocation. The primary endpoint was parasite clearance at 24 h. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01708876.
FINDINGS: Between Oct 16, 2012, and Dec 13, 2014, we randomly assigned 252 patients to receive either artesunate-mefloquine (n=127) or chloroquine (n=125); 226 (90%) patients comprised the modified intention-to-treat population. 24 h after treatment, we recorded parasite clearance in 97 (84% [95% CI 76-91]) of 115 patients in the artesunate-mefloquine group versus 61 (55% [45-64]) of 111 patients in the chloroquine group (difference in proportion 29% [95% CI 18·0-40·8]; p<0·0001). Parasite clearance was faster in patients given artesunate-mefloquine than in those given chloroquine (18·0 h [range 6·0-48·0] vs 24·0 h [6·0-60·0]; p<0·0001), with faster clearance of ring stages in the artesunate-mefloquine group (mean time to 50% clearance of baseline parasites 8·6 h [95% CI 7·9-9·4] vs 13·8 h [12·1-15·4]; p<0·0001). Risk of anaemia within 28 days was lower in patients in the artesunate-mefloquine group (71 [62%; 95% CI 52·2-70·6]) than in those in the chloroquine group (83 [75%; 65·6-82·5]; p=0·035). Gametocytaemia as detected by PCR for pks25 was present in 44 (86%) of 51 patients in the artesunate-mefloquine group and 41 (84%) of 49 patients in the chloroquine group at baseline, and in three (6%) of 49 patients and two (4%) of 48 patients, respectively, at day 7. Fever clearance was faster in the artesunate-mefloquine group (mean 11·5 h [95% CI 8·3-14·6]) than in the chloroquine group (14·8 h [11·7-17·8]; p=0·034). Bed occupancy was 2426 days per 1000 patients in the artesunate-mefloquine group versus 2828 days per 1000 patients in the chloroquine group (incidence rate ratio 0·858 [95% CI 0·812-0·906]; p<0·0001). One (<1%) patient in the artesunate-mefloquine group had a serious neuropsychiatric event regarded as probably related to study drug.
INTERPRETATION: Artesunate-mefloquine is highly efficacious for treatment of uncomplicated P knowlesi malaria. The rapid therapeutic response of the drug offers significant advantages compared with chloroquine monotherapy and supports a unified treatment policy for artemisinin-based combination therapy for all Plasmodium species in co-endemic areas.
FUNDING: Malaysian Ministry of Health, Australian National Health and Medical Research Council, and Asia Pacific Malaria Elimination Network.
Fulltext Serological evidence of henipavirus exposure in cattle, goats and pigs in Bangladesh

Chowdhury S, Khan SU, Crameri G, Epstein JH, Broder CC, Islam A, et al.

PLoS Negl Trop Dis, 2014 Nov;8(11):e3302.
PMID: 25412358 DOI: 10.1371/journal.pntd.0003302

BACKGROUND: Nipah virus (NiV) is an emerging disease that causes severe encephalitis and respiratory illness in humans. Pigs were identified as an intermediate host for NiV transmission in Malaysia. In Bangladesh, NiV has caused recognized human outbreaks since 2001 and three outbreak investigations identified an epidemiological association between close contact with sick or dead animals and human illness.
METHODOLOGY: We examined cattle and goats reared around Pteropus bat roosts in human NiV outbreak areas. We also tested pig sera collected under another study focused on Japanese encephalitis.
PRINCIPAL FINDINGS: We detected antibodies against NiV glycoprotein in 26 (6.5%) cattle, 17 (4.3%) goats and 138 (44.2%) pigs by a Luminex-based multiplexed microsphere assay; however, these antibodies did not neutralize NiV. Cattle and goats with NiVsG antibodies were more likely to have a history of feeding on fruits partially eaten by bats or birds (PR=3.1, 95% CI 1.6-5.7) and drinking palmyra palm juice (PR=3.9, 95% CI 1.5-10.2).
CONCLUSIONS: This difference in test results may be due to the exposure of animals to one or more novel viruses with antigenic similarity to NiV. Further research may identify a novel organism of public health importance.
Fulltext The kiss/kissr systems are dispensable for zebrafish reproduction: evidence from gene knockout studies

Tang H, Liu Y, Luo D, Ogawa S, Yin Y, Li S, et al.

Endocrinology, 2015 Feb;156(2):589-99.
PMID: 25406015 DOI: 10.1210/en.2014-1204

The kiss1/gpr54 signaling system is considered to be a critical regulator of reproduction in most vertebrates. However, this presumption has not been tested vigorously in nonmammalian vertebrates. Distinct from mammals, multiple kiss1/gpr54 paralogous genes (kiss/kissr) have been identified in nonmammalian vertebrates, raising the possibility of functional redundancy among these genes. In this study, we have systematically generated the zebrafish kiss1(-/-), kiss2(-/-), and kiss1(-/-);kiss2(-/-) mutant lines as well as the kissr1(-/-), kissr2(-/-), and kissr1(-/-);kissr2(-/-) mutant lines using transcription activator-like effector nucleases. We have demonstrated that spermatogenesis and folliculogenesis as well as reproductive capability are not impaired in all of these 6 mutant lines. Collectively, our results indicate that kiss/kissr signaling is not absolutely required for zebrafish reproduction, suggesting that the kiss/kissr systems play nonessential roles for reproduction in certain nonmammalian vertebrates. These findings also demonstrated that fish and mammals have evolved different strategies for neuroendocrine control of reproduction.
Fulltext The high-affinity human IgG receptor Fc gamma receptor I (FcγRI) is not associated with vascular leakage of dengue

Mohamad Zamberi Z, Zakaria Z, Abdul Aziz AT, Heng BS, Zaid M, Chong CL, et al.

J Negat Results Biomed, 2015;14:1.
PMID: 25566870 DOI: 10.1186/s12952-014-0020-6

Dengue is a major public health problem in many tropical and sub-tropical countries. Vascular leakage and shock are identified as the major causes of deaths in patients with severe dengue. Studies have suggested the potential role of Fc gamma receptors I (FcγRI) in the pathogenesis of dengue. We hypothesized that the circulating level of Fcγ receptor I could potentially be used as an indicator in assisting early diagnosis of severe dengue.
Fulltext Antibiotic management of complicated intra-abdominal infections in adults: The Asian perspective

Kurup A, Liau KH, Ren J, Lu MC, Navarro NS, Farooka MW, et al.

Ann Med Surg (Lond), 2014 Sep;3(3):85-91.
PMID: 25568794 DOI: 10.1016/j.amsu.2014.06.005

Regional epidemiological data and resistance profiles are essential for selecting appropriate antibiotic therapy for intra-abdominal infections (IAIs). However, such information may not be readily available in many areas of Asia and current international guidelines on antibiotic therapy for IAIs are for Western countries, with the most recent guidance for the Asian region dating from 2007. Therefore, the Asian Consensus Taskforce on Complicated Intra-Abdominal Infections (ACT-cIAI) was convened to develop updated recommendations for antibiotic management of complicated IAIs (cIAIs) in Asia. This review article is based on a thorough literature review of Asian and international publications related to clinical management, epidemiology, microbiology, and bacterial resistance patterns in cIAIs, combined with the expert consensus of the Taskforce members. The microbiological profiles of IAIs in the Asian region are outlined and compared with Western data, and the latest available data on antimicrobial resistance in key pathogens causing IAIs in Asia is presented. From this information, antimicrobial therapies suitable for treating cIAIs in patients in Asian settings are proposed in the hope that guidance relevant to Asian practices will prove beneficial to local physicians managing IAIs.
Fulltext HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia

Jiamsakul A, Sungkanuparph S, Law M, Kantor R, Praparattanapan J, Li PC, et al.

J Int AIDS Soc, 2014;17:19053.
PMID: 25141905 DOI: 10.7448/IAS.17.1.19053

First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART.

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links