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Disruption of predicted dengue virus type 3 major outbreak cycle coincided with switching of the dominant circulating virus genotype

Tan KK, Zulkifle NI, Abd-Jamil J, Sulaiman S, Yaacob CN, Azizan NS, et al.

Infect Genet Evol, 2017 Oct;54:271-275.
PMID: 28698156 DOI: 10.1016/j.meegid.2017.07.008

Dengue is hyperendemic in most of Southeast Asia. In this region, all four dengue virus serotypes are persistently present. Major dengue outbreak cycle occurs in a cyclical pattern involving the different dengue virus serotypes. In Malaysia, since the 1980s, the major outbreak cycles have involved dengue virus type 3 (DENV3), dengue virus type 1 (DENV1) and dengue virus type 2 (DENV2), occurring in that order (DENV3/DENV1/DENV2). Only limited information on the DENV3 cycles, however, have been described. In the current study, we examined the major outbreak cycle involving DENV3 using data from 1985 to 2016. We examined the genetic diversity of DENV3 isolates obtained during the period when DENV3 was the dominant serotype and during the inter-dominant transmission period. Results obtained suggest that the typical DENV3/DENV1/DENV2 cyclical outbreak cycle in Malaysia has recently been disrupted. The last recorded major outbreak cycle involving DENV3 occurred in 2002, and the expected major outbreak cycle involving DENV3 in 2006-2012 did not materialize. DENV genome analyses revealed that DENV3 genotype II (DENV3/II) was the predominant DENV3 genotype (67%-100%) recovered between 1987 and 2002. DENV3 genotype I (DENV3/I) emerged in 2002 followed by the introduction of DENV3 genotype III (DENV3/III) in 2008. These newly emerged DENV3 genotypes replaced DENV3/II, but there was no major upsurge of DENV3 cases that accompanied the emergence of these viruses. DENV3 remained in the background of DENV1 and DENV2 until now. Virus genome sequence analysis suggested that intrinsic differences within the different dengue virus genotypes could have influenced the transmission efficiency of DENV3. Further studies and continuous monitoring of the virus are needed for better understanding of the DENV transmission dynamics in hyperendemic regions.
Fulltext Survival predictors in paraquat intoxification and role of immunosuppression

Koh KH, Tan CH, Hii LW, Lee J, Ngu LL, Chai AJ, et al.

Toxicol Rep, 2014;1:490-495.
PMID: 28962262 DOI: 10.1016/j.toxrep.2014.06.010

Paraquat poisoning resulted in multiorgan failure and is associated with high mortality. We audited 83 historical cases of paraquat poisoning in past 2 years treated with conventional decontamination and supportive treatment, followed by enrolling 85 patients over a 2 year period into additional immunosuppression with intravenous (i.v.) methylprednisolone and i.v. cyclophosphamide. Our results showed that age, poor renal function and leucocytosis are the main predictors of fatal outcome. Immunosuppression regime rendered higher survival (6 out of 17 patients (35.3%)) versus historical control (1 out of 18 patients (5.6%)) (p = 0.041) in the cohort with admission eGFR < 50 ml/min/1.73 m(2) and WBC count > 11,000/μL. In contrast, there was no difference in survival with immunosuppression regime (38 out of 64 patients (59.4%)) compared to historical control (30 out of 52 patients (57.7%)) (p = 0.885) in those with eGFR > 50 ml/min/1.73 m(2) or WBC < 11,000/μL at presentation. Multivariable logistic regression showed survival probability = exp(logit)/(1 + exp(logit)), in which logit = 13.962 - (0.233 × ln(age (year))) - (1.344 × ln(creatinine (μmol/L))) - (1.602 × ln(rise in creatinine (μmol/day))) - (0.614 × ln(WBC (,000/μL))) + (2.021 × immunosuppression) and immunosuppression = 1 if given and 0 if not. Immunosuppression therapy yielded odds ratio of 0.132 (95% confidential interval: 0.029-0.603, p = 0.009). In conclusion, immunosuppression therapy with intravenous methylprednisolone and cyclophosphamide may counteract immune mediated inflammation after paraquat poisoning and improve survival of patients with admission eGFR < 50 ml/min/1.73 m(2) and WBC count > 11,000/μL.
Fulltext Striatin Gene Polymorphic Variants Are Associated With Salt Sensitive Blood Pressure in Normotensives and Hypertensives

Gupta T, Connors M, Tan JW, Manosroi W, Ahmed N, Ting PY, et al.

Am J Hypertens, 2017 Dec 08;31(1):124-131.
PMID: 28985281 DOI: 10.1093/ajh/hpx146

BACKGROUND: Understanding the interactions between genetics, sodium (Na+) intake, and blood pressure (BP) will help overcome the lack of individual specificity in our current treatment of hypertension. This study had 3 goals: expand on the relationship between striatin gene (STRN) status and salt-sensitivity of BP (SSBP); evaluate the status of Na+ and volume regulating systems by striatin risk allele status; evaluate potential SSBP mechanisms.
METHODS: We assessed the relationship between STRN status in humans (HyperPATH cohort) and SSBP and on volume regulated systems in humans and a striatin knockout mouse (STRN+/-).
RESULTS: The previously identified association between a striatin risk allele and systolic SSBP was demonstrated in a new cohort (P = 0.01). The STRN-SSBP association was significant for the combined cohort (P = 0.003; β = +5.35 mm Hg systolic BP/risk allele) and in the following subgroups: normotensives, hypertensives, men, and older subjects. Additionally, we observed a lower epinephrine level in risk allele carriers (P = 0.014) and decreased adrenal medulla phenylethanolamine N-methyltransferase (PNMT) in STRN+/- mice. No significant associations were observed with other volume regulated systems.
CONCLUSIONS: These results support the association between a variant of striatin and SSBP and extend the findings to normotensive individuals and other subsets. In contrast to most salt-sensitive hypertensives, striatin-associated SSBP is associated with normal plasma renin activity and reduced epinephrine levels. These data provide clues to the underlying cause and a potential pathway to achieve, specific, personalized treatment, and prevention.
Fulltext Plio-Pleistocene phylogeography of the Southeast Asian Blue Panchax killifish, Aplocheilus panchax

Beck SV, Carvalho GR, Barlow A, Rüber L, Hui Tan H, Nugroho E, et al.

PLoS One, 2017;12(7):e0179557.
PMID: 28742862 DOI: 10.1371/journal.pone.0179557

The complex climatic and geological history of Southeast Asia has shaped this region's high biodiversity. In particular, sea level fluctuations associated with repeated glacial cycles during the Pleistocene both facilitated, and limited, connectivity between populations. In this study, we used data from two mitochondrial and three anonymous nuclear markers to determine whether a fresh/brackish water killifish, Aplocheilus panchax, Hamilton, 1822, could be used to further understand how climatic oscillations and associated sea level fluctuations have shaped the distribution of biota within this region, and whether such patterns show evidence of isolation within palaeodrainage basins. Our analyses revealed three major mitochondrial clades within A. panchax. The basal divergence of A. panchax mitochondrial lineages was approximately 3.5 Ma, whilst the subsequent divergence timings of these clades occurred early Pleistocene (~2.6 Ma), proceeding through the Pleistocene. Continuous phylogeographic analysis showed a clear west-east dispersal followed by rapid radiation across Southeast Asia. Individuals from Krabi, just north of the Isthmus of Kra, were more closely related to the Indian lineages, providing further evidence for a freshwater faunal disjunction at the Isthmus of Kra biogeographic barrier. Our results suggest that Sulawesi, across the Wallace Line, was colonised relatively recently (~30 ka). Nuclear DNA is less geographically structured, although Mantel tests indicated that nuclear genetic distances were correlated with geographic proximity. Overall, these results imply that recent gene flow, as opposed to historical isolation, has been the key factor determining patterns of nuclear genetic variation in A. panchax, however, some evidence of historical isolation is retained within the mitochondrial genome. Our study further validates the existence of a major biogeographic boundary at the Kra Isthmus, and also demonstrates the use of widely distributed fresh/brackishwater species in phylogeographic studies, and their ability to disperse across major marine barriers in relatively recent time periods.
Fulltext Anti-obesity and anti-inflammatory effects of synthetic acetic acid vinegar and Nipa vinegar on high-fat-diet-induced obese mice

Beh BK, Mohamad NE, Yeap SK, Ky H, Boo SY, Chua JYH, et al.

Sci Rep, 2017 07 27;7(1):6664.
PMID: 28751642 DOI: 10.1038/s41598-017-06235-7

Recently, food-based bioactive ingredients, such as vinegar, have been proposed as a potential solution to overcome the global obesity epidemic. Although acetic acid has been identified as the main component in vinegar that contributes to its anti-obesity effect, reports have shown that vinegar produced from different starting materials possess different degrees of bioactivity. This study was performed to compare the anti-obesity and anti-inflammatory effects of synthetic acetic acid vinegar and Nipa vinegar in mice fed a high-fat diet. In this work, mice were fed a high-fat diet for 33 weeks. At the start of week 24, obese mice were orally fed synthetic acetic acid vinegar or Nipa vinegar (0.08 and 2 ml/kg BW) until the end of week 33. Mice fed a standard pellet diet served as a control. Although both synthetic acetic acid vinegar and Nipa vinegar effectively reduced food intake and body weight, a high dose of Nipa vinegar more effectively reduced lipid deposition, improved the serum lipid profile, increased adipokine expression and suppressed inflammation in the obese mice. Thus, a high dose of Nipa vinegar may potentially alleviate obesity by altering the lipid metabolism, inflammation and gut microbe composition in high-fat-diet-induced obese mice.
Shear wave elastography for characterization of breast lesions: Shearlet transform and local binary pattern histogram techniques

Acharya UR, Ng WL, Rahmat K, Sudarshan VK, Koh JEW, Tan JH, et al.

Comput Biol Med, 2017 12 01;91:13-20.
PMID: 29031099 DOI: 10.1016/j.compbiomed.2017.10.001

Shear wave elastography (SWE) examination using ultrasound elastography (USE) is a popular imaging procedure for obtaining elasticity information of breast lesions. Elasticity parameters obtained through SWE can be used as biomarkers that can distinguish malignant breast lesions from benign ones. Furthermore, the elasticity parameters extracted from SWE can speed up the diagnosis and possibly reduce human errors. In this paper, Shearlet transform and local binary pattern histograms (LBPH) are proposed as an original algorithm to differentiate malignant and benign breast lesions. First, Shearlet transform is applied on the SWE images to acquire low frequency, horizontal and vertical cone coefficients. Next, LBPH features are extracted from the Shearlet transform coefficients and subjected to dimensionality reduction using locality sensitivity discriminating analysis (LSDA). The reduced LSDA components are ranked and then fed to several classifiers for the automated classification of breast lesions. A probabilistic neural network classifier trained only with seven top ranked features performed best, and achieved 98.08% accuracy, 98.63% sensitivity, and 97.59% specificity in distinguishing malignant from benign breast lesions. The high sensitivity and specificity of our system indicates that it can be employed as a primary screening tool for faster diagnosis of breast malignancies, thereby possibly reducing the mortality rate due to breast cancer.
Proteins recovery from wet microalgae using liquid biphasic flotation (LBF)

Phong WN, Show PL, Teh WH, Teh TX, Lim HMY, Nazri NSB, et al.

Bioresour Technol, 2017 Nov;244(Pt 2):1329-1336.
PMID: 28602664 DOI: 10.1016/j.biortech.2017.05.165

In this work, the extraction of microalgal protein from wet Chlorella sorokiniana species using alcohol/salt liquid biphasic flotation (LBF) with the aid of ultrasonication for cell rupturing was proposed. The effect of varying crude feedstock concentration, flotation time, salt type, salt concentration, alcohol type, alcohol concentration, initial volumes of salt and alcohol were investigated. After the optimization process, the highest proportion of protein recovered in the top phase was achieved with 250g/L ammonium sulphate, 60% (v/v) 2-propanol, 1.0VR,initial, 20g/L crude biomass load, 4mm3/min air flowrate and 10min of flotation time. The recycling of phase components was introduced to minimize the use of alcohol and salt in the corresponding LBF. It was demonstrated that top phase (alcohol) recycling can achieve increasing performance for three consecutive recycling runs. Under optimized process conditions, the proportion of protein recovered in the top phase was 88.86% for the third recycle run.
Acanthamoebicidal activity of periglaucine A and betulinic acid from Pericampylus glaucus (Lam.) Merr. in vitro

Mahboob T, Azlan AM, Shipton FN, Boonroumkaew P, Nor Azman NS, Sekaran SD, et al.

Exp Parasitol, 2017 Dec;183:160-166.
PMID: 28916456 DOI: 10.1016/j.exppara.2017.09.002

Acanthamoeba species are pathogenic protozoa which account for amoebic keratitis, conjunctivitis and granulomatous amoebic encephalitis. These amoebae form cysts which resist drugs and more effective acanthamoebicidal agents are needed. Medicinal plants could be useful in improving the current treatment strategies for Acanthamoeba infections. In the present study, we examined the amoebicidal effects of Pericampylus glaucus (Lam.) Merr., a medicinal plant used for the treatment of conjunctivitis in Malaysia. Pathogenic Acanthamoeba triangularis were isolated from environmental water samples and treated with different concentrations of fractions obtained from Pericampylus glaucus (Lam.) Merr. as well as main constituents for 24-72 h. Chlorhexidine was used as a reference drug. Ethanol fraction of stem showed significant (p
Fulltext Phenotypic and microRNA transcriptomic profiling of the MDA-MB-231 spheroid-enriched CSCs with comparison of MCF-7 microRNA profiling dataset

Boo L, Ho WY, Mohd Ali N, Yeap SK, Ky H, Chan KG, et al.

PeerJ, 2017;5:e3551.
PMID: 28717596 DOI: 10.7717/peerj.3551

Breast cancer spheroids have been widely used as in vitro models of cancer stem cells (CSCs), yet little is known about their phenotypic characteristics and microRNAs (miRNAs) expression profiles. The objectives of this research were to evaluate the phenotypic characteristics of MDA-MB-231 spheroid-enriched cells for their CSCs properties and also to determine their miRNAs expression profile. Similar to our previously published MCF-7 spheroid, MDA-MB-231 spheroid also showed typical CSCs characteristics namely self-renewability, expression of putative CSCs-related surface markers and enhancement of drug resistance. From the miRNA profile, miR-15b, miR-34a, miR-148a, miR-628 and miR-196b were shown to be involved in CSCs-associated signalling pathways in both models of spheroids, which highlights the involvement of these miRNAs in maintaining the CSCs features. In addition, unique clusters of miRNAs namely miR-205, miR-181a and miR-204 were found in basal-like spheroid whereas miR-125, miR-760, miR-30c and miR-136 were identified in luminal-like spheroid. Our results highlight the roles of miRNAs as well as novel perspectives of the relevant pathways underlying spheroid-enriched CSCs in breast cancer.
Fulltext Contrasting evolutionary patterns between two haplogroups of Haematobia exigua (Diptera: Muscidae) from the mainland and islands of Southeast Asia

Low VL, Tan TK, Prakash BK, Vinnie-Siow WY, Tay ST, Masmeatathip R, et al.

Sci Rep, 2017 07 19;7(1):5871.
PMID: 28724923 DOI: 10.1038/s41598-017-05921-w

Uncovering the hidden diversity and evolutionary history of arthropods of medico-veterinary importance could have significant implications for vector-borne disease control and epidemiological intervention. The buffalo fly Haematobia exigua is an obligate bloodsucking ectoparasite of livestock. As an initial step towards understanding its population structures and biogeographic patterns, we characterized partial cytochrome c oxidase subunit I (COI) and cytochrome b (Cytb) sequences of H. exigua from three distinct geographic regions in Southeast Asia. We detected two distinct mitochondrial haplogroups of H. exigua in our surveyed geographic regions. Haplogroup I is widespread in the Southeast Asian mainland whereas haplogroup II is generally restricted to the type population Java Island. Both haplogroups were detected co-occurring on Borneo Island. Additionally, both haplogroups have undergone contrasting evolutionary histories, with haplogroup I exhibited a high level of mitochondrial diversity indicating a population expansion during the Pleistocene era dating back to 98,000 years ago. However, haplogroup II presented a low level of mitochondrial diversity which argues against the hypothesis of recent demographic expansion.
Application of the European quality indicators for psychosocial dementia care in long-term care facilities in the Asia-Pacific region: a pilot study

Jeon YH, Chien WT, Ha JY, Ibrahim R, Kirley B, Tan LL, et al.

Aging Ment Health, 2018 10;22(10):1279-1286.
PMID: 28714742 DOI: 10.1080/13607863.2017.1351521

OBJECTIVES: An Asia-Pacific regional collaboration group conducted its first multi-country research project to determine whether or not European quality indicators (QIs) for psychosocial care in dementia could be implemented as a valid tool in residential aged care across seven Asia-Pacific sites (Australia, Hong Kong Special Administrative Region, Mainland China, Malaysia, Singapore, South Korea, and Thailand).
METHOD: Following the European QI protocol, auditing and data extraction of medical records of consenting residents with dementia were conducted by trained auditors with relevant health care backgrounds. Detailed field notes by the auditors were also obtained to describe the characteristics of the participating care facilities, as well as key issues and challenges encountered, for each of the 12 QIs.
RESULTS: Sixteen residential care facilities in the seven Asia-Pacific sites participated in this study. Data from 275 residents' records revealed each of the 12 Qis' endorsement varied widely within and between the study sites (0%-100%). Quality of the medical records, family and cultural differences, definitions and scoring of certain indicators, and time-consuming nature of the QI administration were main concerns for implementation.
CONCLUSION: Several items in the European QIs in the current format were deemed problematic when used to measure the quality of psychosocial care in the residential aged care settings in participating Asia-Pacific countries. We propose refinements of the European QIs for the Asian-Pacific context, taking into account multiple factors identified in this study. Our findings provide crucial insights for future research and implementation of psychosocial dementia care QIs in this region.
Experience of a rapid access falls and syncope service at a teaching hospital in Kuala Lumpur

Gan SY, Saedon NI, Sukanya S, Fairuz NHA, Sakinah SMN, Fatin NIAH, et al.

Med J Malaysia, 2017 08;72(4):203-208.
PMID: 28889130 MyJurnal

No abstract available.
Nanotechnology based approaches for anti-diabetic drugs delivery

Kesharwani P, Gorain B, Low SY, Tan SA, Ling ECS, Lim YK, et al.

Diabetes Res Clin Pract, 2018 Feb;136:52-77.
PMID: 29196152 DOI: 10.1016/j.diabres.2017.11.018

Nanotechnology science has been diverged its application in several fields with the advantages to operate with nanometric range of objects. Emerging field of nanotechnology has been also being approached and applied in medical biology for improved efficacy and safety. Increased success in therapeutic field has focused several approaches in the treatment of the common metabolic disorder, diabetes. The development of nanocarriers for improved delivery of different oral hypoglycemic agents compared to conventional therapies includes nanoparticles (NPs), liposomes, dendrimer, niosomes and micelles, which produces great control over the increased blood glucose level and thus becoming an eye catching and most promising technology now-a-days. Besides, embellishment of nanocarriers with several ligands makes it more targeted delivery with the protection of entrapped hypoglycaemic agents against degradation, thereby optimizing prolonged blood glucose lowering effect. Thus, nanocarriers of hypoglycemic agents provide the aim towards improved diabetes management with minimized risk of acute and chronic complications. In this review, we provide an overview on distinctive features of each nano-based drug delivery system for diabetic treatment and current NPs applications in diabetes management.
Sleep Quality and Nocturnal Sleep Duration in Pregnancy and Risk of Gestational Diabetes Mellitus

Cai S, Tan S, Gluckman PD, Godfrey KM, Saw SM, Teoh OH, et al.

Sleep, 2017 Feb 01;40(2).
PMID: 28364489 DOI: 10.1093/sleep/zsw058

STUDY OBJECTIVES: To examine the influence of maternal sleep quality and nocturnal sleep duration on risk of gestational diabetes mellitus (GDM) in a multiethnic Asian population.
METHODS: A cohort of 686 women (376 Chinese, 186 Malay, and 124 Indian) with a singleton pregnancy attended a clinic visit at 26-28 weeks of gestation as part of the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort study. Self-reported sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index (PSQI). GDM was diagnosed based on a 75-g oral glucose tolerance test administered after an overnight fast (1999 WHO criteria). Multiple logistic regression was used to model separately the associations of poor sleep quality (PSQI score > 5) and short nocturnal sleep duration (<6 h) with GDM, adjusting for age, ethnicity, maternal education, body mass index, previous history of GDM, and anxiety (State-Trait Anxiety Inventory score).
RESULTS: In the cohort 296 women (43.1%) had poor sleep quality and 77 women (11.2%) were categorized as short sleepers; 131 women (19.1%) were diagnosed with GDM. Poor sleep quality and short nocturnal sleep duration were independently associated with increased risk of GDM (poor sleep, adjusted odds ratio [OR] = 1.75, 95% confidence interval [CI] 1.11 to 2.76; short sleep, adjusted OR = 1.96, 95% CI 1.05 to 3.66).
CONCLUSIONS: During pregnancy, Asian women with poor sleep quality or short nocturnal sleep duration exhibited abnormal glucose regulation. Treating sleep problems and improving sleep behavior in pregnancy could potentially reduce the risk and burden of GDM.
Genome-wide methylation analysis identifies genes silenced in non-seminoma cell lines

Noor DAM, Jeyapalan JN, Alhazmi S, Carr M, Squibb B, Wallace C, et al.

NPJ Genom Med, 2016;1:15009.
PMID: 29263807 DOI: 10.1038/npjgenmed.2015.9

Silencing of genes by DNA methylation is a common phenomenon in many types of cancer. However, the genome-wide effect of DNA methylation on gene expression has been analysed in relatively few cancers. Germ cell tumours (GCTs) are a complex group of malignancies. They are unique in developing from a pluripotent progenitor cell. Previous analyses have suggested that non-seminomas exhibit much higher levels of DNA methylation than seminomas. The genomic targets that are methylated, the extent to which this results in gene silencing and the identity of the silenced genes most likely to play a role in the tumours' biology have not yet been established. In this study, genome-wide methylation and expression analysis of GCT cell lines was combined with gene expression data from primary tumours to address this question. Genome methylation was analysed using the Illumina infinium HumanMethylome450 bead chip system and gene expression was analysed using Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. Regulation by methylation was confirmed by demethylation using 5-aza-2-deoxycytidine and reverse transcription-quantitative PCR. Large differences in the level of methylation of the CpG islands of individual genes between tumour cell lines correlated well with differential gene expression. Treatment of non-seminoma cells with 5-aza-2-deoxycytidine verified that methylation of all genes tested played a role in their silencing in yolk sac tumour cells and many of these genes were also differentially expressed in primary tumours. Genes silenced by methylation in the various GCT cell lines were identified. Several pluripotency-associated genes were identified as a major functional group of silenced genes.
Assessment of sarcopenia in virally suppressed HIV-infected Asians receiving treatment

Abdul Aziz SA, Mcstea M, Ahmad Bashah NS, Chong ML, Ponnampalavanar S, Syed Omar SF, et al.

AIDS, 2018 05 15;32(8):1025-1034.
PMID: 29547442 DOI: 10.1097/QAD.0000000000001798

OBJECTIVES: In a clinic-based, treated HIV-infected cohort, we identified individuals with sarcopenia and compared with age, sex and ethnically matched controls; and investigated associated risk factors and health outcomes.
DESIGN: Sarcopenia (age-related muscle loss) causes significant morbidity to the elderly, leading to frequent hospitalizations, disability and death. Few have characterized sarcopenia in the HIV-infected who experience accelerated aging.
METHODS: Sarcopenia was defined as low muscle mass with weak grip strength and/or slow gait speed using lower 20th percentiles of controls. Multivariate logistic and linear regression analyses were used to explore risk factors and health-related outcomes associated with sarcopenia among HIV-infected individuals.
RESULTS: We recruited 315 HIV-infected individuals aged at least 25 years with at least 1-year history of undetectable viral load on treatment (HIV RNA <50 copies/ml). Percentage of sarcopenia in 315 HIV-infected was 8%. Subsequently, 153 of the 315 were paired with age, sex and ethnically matched HIV-uninfected. The percentage of sarcopenia in the HIV-infected (n = 153) compared with uninfected (n = 153) were 10 vs. 6% (P = 0.193) respectively, whereas of those at least 50 years of age among them were 17% vs. 4% (P = 0.049), respectively. Associated risk factors among the HIV-infected include education level, employment status, BMI, baseline CD4 cell count, duration on NRTIs and GGT levels. Identified negative outcomes include mortality risk scores [5.42; 95% CI 1.46-9.37; P = 0.007) and functional disability (3.95; 95% CI 1.57-9.97; P = 0.004).
CONCLUSION: Sarcopenia is more prevalent in HIV-infected at least 50 years old compared with matched controls. Our findings highlight associations between sarcopenia with loss of independence and greater healthcare burden among treated HIV-infected individuals necessitating early recognition and intervention.
Fulltext Discovery of indolylpiperazinylpyrimidines with dual-target profiles at adenosine A2A and dopamine D2 receptors for Parkinson's disease treatment

Shao YM, Ma X, Paira P, Tan A, Herr DR, Lim KL, et al.

PLoS One, 2018;13(1):e0188212.
PMID: 29304113 DOI: 10.1371/journal.pone.0188212

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra of the human brain, leading to depletion of dopamine production. Dopamine replacement therapy remains the mainstay for attenuation of PD symptoms. Nonetheless, the potential benefit of current pharmacotherapies is mostly limited by adverse side effects, such as drug-induced dyskinesia, motor fluctuations and psychosis. Non-dopaminergic receptors, such as human A2A adenosine receptors, have emerged as important therapeutic targets in potentiating therapeutic effects and reducing the unwanted side effects. In this study, new chemical entities targeting both human A2A adenosine receptor and dopamine D2 receptor were designed and evaluated. Two computational methods, namely support vector machine (SVM) models and Tanimoto similarity-based clustering analysis, were integrated for the identification of compounds containing indole-piperazine-pyrimidine (IPP) scaffold. Subsequent synthesis and testing resulted in compounds 5 and 6, which acted as human A2A adenosine receptor binders in the radioligand competition assay (Ki = 8.7-11.2 μM) as well as human dopamine D2 receptor binders in the artificial cell membrane assay (EC50 = 22.5-40.2 μM). Moreover, compound 5 showed improvement in movement and mitigation of the loss of dopaminergic neurons in Drosophila models of PD. Furthermore, in vitro toxicity studies on compounds 5 and 6 did not reveal any mutagenicity (up to 100 μM), hepatotoxicity (up to 30 μM) or cardiotoxicity (up to 30 μM).
Vitamin D deficiency is associated with ethnicity and knee pain in a multi-ethnic South-East Asian nation: Results from Malaysian Elders Longitudinal Research (MELoR)

Mat S, Jaafar MH, Sockalingam S, Raja J, Kamaruzzaman SB, Chin AV, et al.

Int J Rheum Dis, 2018 May;21(5):930-936.
PMID: 29611292 DOI: 10.1111/1756-185X.13279

AIM: To determine the association between vitamin D and knee pain among participants of the Malaysian Elders Longitudinal Research (MELoR) study.

METHOD: This was a cross-sectional study from the MELoR study consisting of a representative group of 1011 community-dwelling older persons (57% female), mean age 86.5 (54-94) years; 313 were Malays, 367 Chinese and 330 Indians. Participants were asked if they had knee pain. Levels of serum 25-hydroxy cholecalciferol (25-[OH]D), an indicator of vitamin D status, were measured using routine laboratory techniques.

RESULTS: In unadjusted analysis, presence of knee pain was significantly associated with vitamin D deficiency (odds ratio [OR] 1.42; 95% confidence interval (CI) 1.08-1.85, P 0.011). Vitamin D levels were significantly associated with ethnicity differences where Malays (OR 7.08; 95% CI 4.94-10.15) and Indians (OR 6.10; 95% CI 4.28-9.71) have lower levels of vitamin D compared to Chinese. Subsequent multivariate analysis revealed that the association between vitamin D deficiency and knee pain was confounded by ethnic differences.

CONCLUSION: A previous study suggested that vitamin D deficiency was associated with knee pain. This relationship was reproduced in our study, but we further established that the association was explained by ethnic variations. As vitamin D status is dependent on skin tone, diet and sunlight exposure, which are all effected by ethnicity, future studies are now required to determine whether a true relationship exists between vitamin D and knee pain.
Natural Organochlorines as Precursors of 3-Monochloropropanediol Esters in Vegetable Oils

Tiong SH, Saparin N, Teh HF, Ng TLM, Md Zain MZB, Neoh BK, et al.

J Agric Food Chem, 2018 Jan 31;66(4):999-1007.
PMID: 29260544 DOI: 10.1021/acs.jafc.7b04995

During high-temperature refining of vegetable oils, 3-monochloropropanediol (3-MCPD) esters, possible carcinogens, are formed from acylglycerol in the presence of a chlorine source. To investigate organochlorine compounds in vegetable oils as possible precursors for 3-MCPD esters, we tested crude palm, soybean, rapeseed, sunflower, corn, coconut, and olive oils for the presence of organochlorine compounds. Having found them in all vegetable oils tested, we focused subsequent study on oil palm products. Analysis of the chlorine isotope mass pattern exhibited in high-resolution mass spectrometry enabled organochlorine compound identification in crude palm oils as constituents of wax esters, fatty acid, diacylglycerols, and sphingolipids, which are produced endogenously in oil palm mesocarp throughout ripening. Analysis of thermal decomposition and changes during refining suggested that these naturally present organochlorine compounds in palm oils and perhaps in other vegetable oils are precursors of 3-MCPD esters. Enrichment and dose-response showed a linear relationship to 3-MCPD ester formation and indicated that the sphingolipid-based organochlorine compounds are the most active precursors of 3-MCPD esters.
Fulltext Alterations of haemodynamic parameters in spontaneously hypertensive rats by Aristolochia ringens Vahl. (Aristolochiaceae)

Aigbe FR, Munavvar ASZ, Rathore H, Eseyin O, Pei YP, Akhtar S, et al.

J Tradit Complement Med, 2018 Jan;8(1):72-80.
PMID: 29321992 DOI: 10.1016/j.jtcme.2017.02.006

Aristolochia ringens Vahl. (Aristolochiaceae (AR); mǎ dōu líng) is used traditionally in Nigeria for the management of various disorders including oedema. Preliminary investigation revealed its modulatory effect on the cardiovascular system. This study was aimed at investigating the effect of the aqueous root extract of A. ringens (AR) on haemodynamic parameters of spontaneously hypertensive rats (SHRs). The effect of oral subacute (21 days) and intravenous acute exposure of SHRs to the extract were assessed using tail cuff and carotid artery canulation methods respectively. In the latter, the effect of chloroform, butanol and aqueous fractions of AR were also evaluated. The extract significantly reduced systolic and diastolic blood pressures in SHRs, with peak reductions of 20.3% and 26.7% respectively at 50 mg/kg by the 21st day of oral subacute exposure. Upon intravenous exposure, AR (50 mg/kg) reduced systolic and diastolic blood pressure by as much as 53.4 ± 2.2 and 49.2 ± 2.8 mmHg respectively. A dose-dependent reduction in heart rate, significant at 25 and 50 mg/kg was also observed. Hexamethonium (20 mg/kg) and atropine (1 mg/kg) inhibited the extract's reduction of systolic blood pressure, diastolic blood pressure and heart rate significantly. The extract's butanol fraction produced the greatest systolic and diastolic blood pressures reduction of 67.0 ± 3.8 and 68.4 mmHg respectively at 25 mg/kg and heart rate reduction of 40 ± 7 beats per minute at 50 mg/kg. HPLC analysis revealed the presence of 4-hydroxybenzoic acid and quercetin in AR. The extract's alterations of haemodynamic parameters in this study show that it has hypotensive effect on spontaneously hypertensive rats.

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