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Fulltext Evaluation of dental arch dimensions in 12 year-old Vietnamese children - A cross-sectional study of 4565 subjects

Dung TM, Ngoc VTN, Hiep NH, Khoi TD, Xiem VV, Chu-Dinh T, et al.

Sci Rep, 2019 02 28;9(1):3101.
PMID: 30816230 DOI: 10.1038/s41598-019-39710-4

This study aimed to define the width and length of the dental arch in 12-year-old Vietnamese children, and to elucidate differences between genders and among ethnic groups. A cross-sectional study was conducted in 4565 12 years-old children from the 4 major ethnic groups in Vietnam (Kinh, Muong, Thai, and Tay), with a healthy and full set of 28 permanent teeth that had never had any orthodontic treatment and with no reconstructive materials at the measured points. The mean variables in all subjects were 36.39 mm for upper inter-canine width; 46.88 mm for upper inter-first molar width; 59.43 mm for upper inter-second molar width; 10.41 mm for upper anterior length; 32.15 mm for upper posterior length 1; 45.52 mm for upper posterior length 2; 28.31 mm for lower inter-canine width; 41.63 mm for lower inter-first molar width; 54.57 mm for lower inter-second molar width (LM2W); 7.06 mm for lower anterior length (LAL); 26.87 mm for lower posterior length 1 (LP1L); and 41.29 mm for lower posterior length 2. Significant differences in these parameters between genders were found in all ethnic groups, except for LAL in the Kinh and Thai groups, and LP1L in the Tay group. Significant ethnic differences were also found in almost all parameters except LM2W in both males and females. Taken together, the representative sizes of dental arches of 12-year-old Vietnamese children have been defined. Our data indicate that there are some variations in dental arch dimensions among ethnic groups and between genders.

Matched MeSH terms: Healthy Volunteers
Fulltext Small RNA Sequencing across Diverse Biofluids Identifies Optimal Methods for exRNA Isolation

Srinivasan S, Yeri A, Cheah PS, Chung A, Danielson K, De Hoff P, et al.

Cell, 2019 04 04;177(2):446-462.e16.
PMID: 30951671 DOI: 10.1016/j.cell.2019.03.024

Poor reproducibility within and across studies arising from lack of knowledge regarding the performance of extracellular RNA (exRNA) isolation methods has hindered progress in the exRNA field. A systematic comparison of 10 exRNA isolation methods across 5 biofluids revealed marked differences in the complexity and reproducibility of the resulting small RNA-seq profiles. The relative efficiency with which each method accessed different exRNA carrier subclasses was determined by estimating the proportions of extracellular vesicle (EV)-, ribonucleoprotein (RNP)-, and high-density lipoprotein (HDL)-specific miRNA signatures in each profile. An interactive web-based application (miRDaR) was developed to help investigators select the optimal exRNA isolation method for their studies. miRDar provides comparative statistics for all expressed miRNAs or a selected subset of miRNAs in the desired biofluid for each exRNA isolation method and returns a ranked list of exRNA isolation methods prioritized by complexity, expression level, and reproducibility. These results will improve reproducibility and stimulate further progress in exRNA biomarker development.

Matched MeSH terms: Healthy Volunteers
Association of IGF-1 and IGFBP-3 levels with gastric cancer: A systematic review and meta-analysis

Liu H, Gu H, Kutbi EH, Tan SC, Low TY, Zhang C

Int J Clin Pract, 2021 Nov;75(11):e14764.
PMID: 34469629 DOI: 10.1111/ijcp.14764

PURPOSE: Many studies have investigated the association between serum IGF-1 and IGFBP levels with gastric cancer (GC), but the results remained inconclusive. In this work, we performed a systematic review and meta-analysis to examine the precise association of serum levels of IGF-1 and IGFBP with GC.
METHODS: A comprehensive systematic search was carried out in PubMed/MEDLINE, SCOPUS, Web of Science, and EMBASE databases for (nested) case-control studies that reported the levels of IGF-1 and IGFBP in GC cases and healthy controls, from inception until October 2020. Weighted mean difference (WMD) was calculated for estimating combined effect size. Subgroup analysis was performed to identify the source of heterogeneity among studies.
RESULTS: We found eight and five eligible studies (with 1541 participants) which provided data for IGF-1 and IGFBP, respectively. All studies on IGFBP reported the IGFBP-3 isoform. The pooled results indicate that GC patients had significantly lower serum IGF-1 [WMD = -26.21 ng/mL (95% CI, -45.58 to -6.85; P = .008)] and IGFBP-3 [WMD = -0.41 ng/mL (95% CI, -0.80 to -0.01; P = .04; I2 = 89.9%; P

Matched MeSH terms: Healthy Volunteers
The influence of type of visual image and gender on the perception of horizontality: a subjective visual horizontal (SVH) study

Zakaria MN, Tahir A, Zainun Z, Salim R, Mohd Sakeri NS, Abdul Wahat NH

Acta Otolaryngol, 2021 Jan;141(1):62-65.
PMID: 32957810 DOI: 10.1080/00016489.2020.1817552

BACKGROUND: The graviceptive otolith function can be measured using subjective visual horizontal (SVH) testing. Nevertheless, more research efforts are required to understand the essential variables affecting SVH.
OBJECTIVE: The aim of the present study was to determine the effects of type of visual image and gender on subjective visual horizontal (SVH) perception among healthy adults.
MATERIALS AND METHODS: In this comparative study, 50 healthy young adults were enrolled. While in an upright body position, they were required to report their perception of horizontality for two types of visual images (solid line and arrow pattern) using a computerized SVH device.
RESULTS: The arrow pattern produced significantly bigger SVH angles than the solid line (p < .001). In contrast, no significant influence of gender was found on SVH results (p = .743), Based on the statistical outcomes, the preliminary normative data for SVH were established.
CONCLUSIONS AND SIGNIFICANCE: The arrow pattern (a more complex visual image) produced bigger SVH deviations than the simple solid line image. In contrast, the horizontality perception does not appear to be affected by gender. The preliminary normative SVH data gathered from the present study can be beneficial for clinical and future research applications.

Matched MeSH terms: Healthy Volunteers
Fulltext Effects of stress associated with academic examination on the kynurenine pathway profile in healthy students

Myint K, Jacobs K, Myint AM, Lam SK, Henden L, Hoe SZ, et al.

PLoS One, 2021;16(6):e0252668.
PMID: 34081742 DOI: 10.1371/journal.pone.0252668

The effects of stress on the neuroendocrine, central nervous and immune systems are extremely complex. The kynurenine pathway (KP) of the tryptophan metabolism is recognised as a cross-link between the neuroendocrine- and immune systems. However, the effects of acute stress from everyday life on KP activation have not yet been studied. This study aims to investigate changes in the levels of the KP neuroactive metabolites and cytokines in response to stress triggered by academic examinations. Ninety-two healthy first year medical students benevolently participated in the study. Parameters were measured pre- examination, which is considered to be a high-stress period, and post-examination, as a low-stress period. Stress induced by academic examinations significantly increases the perceived stress scores (p<0.001), serum cortisol levels (p<0.001) and brain-derived neurotrophic factor (BDNF) levels (p<0.01). It decreased IL-10 levels (p<0.05) but had no effect on IL-6 and TNF-alpha levels. Only the KP neuroactive metabolite, 3-hydroxykynurenine (3-HK) significantly increased (p<0.01) in the post-examination period. In addition, the stress scores positively correlated with the levels of cortisol (r2 = 0.297, p<0.01) at post examination. Acute stress triggered by academic examinations increases cortisol and BDNF production and suppresses the anti-inflammatory cytokine, IL-10, but did not increase significantly the levels of other pro-inflammatory cytokines, tryptophan, kynurenine and downstream KP metabolites. The concomitant increased levels of BDNF under the duress of acute examination stress appear to limit the levels pro-inflammatory markers, which may attenuate the action of cortisol and the neuroinflammatory branch of the KP.

Matched MeSH terms: Healthy Volunteers
Fulltext Retinotopic effects of visual attention revealed by dichoptic multifocal pupillography

Rosli Y, Carle CF, Ho Y, James AC, Kolic M, Rohan EMF, et al.

Sci Rep, 2018 02 14;8(1):2991.
PMID: 29445236 DOI: 10.1038/s41598-018-21196-1

Multifocal pupillographic objective perimetry (mfPOP) has recently been shown to be able to measure cortical function. Here we assessed 44 regions of the central 60 degrees of the visual fields of each eye concurrently in 7 minutes/test. We examined how foveally- and peripherally-directed attention changed response sensitivity and delay across the 44 visual field locations/eye. Four experiments were completed comparing white, yellow and blue stimulus arrays. Experiments 1 to 4 tested 16, 23, 9 and 6 subjects, 49/54 being unique. Experiment 1, Experiments 2 and 3, and Experiment 4 used three variants of the mfPOP method that provided increasingly improved signal quality. Experiments 1 to 3 examined centrally directed attention, and Experiment 4 compared effects of attention directed to different peripheral targets. Attention reduced the sensitivity of the peripheral locations in Experiment 1, but only for the white stimuli not yellow. Experiment 2 confirmed that result. Experiment 3 showed that blue stimuli behaved like white. Peripheral attention showed increased sensitivity around the attentional targets. The results are discussed in terms of the cortical inputs to the pupillary system. The results agree with those from multifocal and other fMRI and VEP studies. mfPOP may be a useful adjunct to those methods.

Matched MeSH terms: Healthy Volunteers
Bilateral Motor Cortex Control for Left Thumb Movement: An Incidental Finding Through Functional MRI (fMRI)

Rashid A, Suppiah S, Hoo FK, Masiran R

BMJ Case Rep, 2018 Jan 04;2018.
PMID: 29301796 DOI: 10.1136/bcr-2017-221129

We report a case of a healthy, right-hand dominant young male who was a volunteer for a pilot run of a functional MRI (fMRI) study. The fMRI was performed with a 3.0 Tesla MRI scanner using a finger tapping task-based activity. The subjects were instructed to perform flexion of the right thumb and left thumb consecutively (activation task) and neuronal activation in bilateral primary motor cortex (PMC) were observed during each task. One particular subject demonstrated bilateral PMC activation during the left-thumb movement task, instead of the expected activation of the contralateral PMC alone.

Matched MeSH terms: Healthy Volunteers
Fulltext Normative data for hand grip strength and key pinch strength, stratified by age and gender for a multiethnic Asian population

Lam NW, Goh HT, Kamaruzzaman SB, Chin AV, Poi PJ, Tan MP

Singapore Med J, 2016 Oct;57(10):578-584.
PMID: 26768064 DOI: 10.11622/smedj.2015164

INTRODUCTION: Hand strength is a good indicator of physical fitness and frailty among the elderly. However, there are no published hand strength references for Malaysians aged > 65 years. This study aimed to establish normative data for hand grip strength (HGS) and key pinch strength (KPS) for Malaysians aged ≥ 60 years, and explore the relationship between hand strength and physical ability.
METHODS: Healthy participants aged ≥ 60 years with no neurological conditions were recruited from rural and urban locations in Malaysia. HGS and KPS were measured using hand grip and key pinch dynamometers. Basic demographic data, anthropometric measures, modified Barthel Index scores and results of the Functional Reach Test (FRT), Timed Up and Go (TUG) test and Jebsen-Taylor Hand Function Test (JTHFT) were recorded.
RESULTS: 362 subjects aged 60-93 years were recruited. The men were significantly stronger than the women in both HGS and KPS (p < 0.001). The hand strength of the study cohort was lower than that of elderly Western populations. Significant correlations were observed between hand strength, and residential area (p < 0.001), FRT (r = 0.236, p = 0.028), TUG (r = -0.227, p = 0.009) and JTHFT (r = -0.927, p < 0.001).
CONCLUSION: This study established reference ranges for the HGS and KPS of rural and urban elderly Malaysian subpopulations. These will aid the use of hand strength as a screening tool for frailty among elderly persons in Malaysia. Future studies are required to determine the modifiable factors for poor hand strength.

Matched MeSH terms: Healthy Volunteers
Fulltext Association of Environmental Uncertainty With Altered Decision-making and Learning Mechanisms in Youths With Obsessive-Compulsive Disorder

Marzuki AA, Tomic I, Ip SHY, Gottwald J, Kanen JW, Kaser M, et al.

JAMA Netw Open, 2021 Nov 01;4(11):e2136195.
PMID: 34842925 DOI: 10.1001/jamanetworkopen.2021.36195

IMPORTANCE: Adults with obsessive-compulsive disorder (OCD) display perseverative behavior in stable environments but exhibit vacillating choice when payoffs are uncertain. These findings may be associated with intolerance of uncertainty and compulsive behaviors; however, little is known about the mechanisms underlying learning and decision-making in youths with OCD because research into this population has been limited.
OBJECTIVE: To investigate cognitive mechanisms associated with decision-making in youths with OCD by using executive functioning tasks and computational modeling.
DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, 50 youths with OCD (patients) and 53 healthy participants (controls) completed a probabilistic reversal learning (PRL) task between January 2014 and March 2020. A separate sample of 27 patients and 46 controls completed the Wisconsin Card Sorting Task (WCST) between January 2018 and November 2020. The study took place at the University of Cambridge in the UK.
MAIN OUTCOMES AND MEASURES: Decision-making mechanisms were studied by fitting hierarchical bayesian reinforcement learning models to the 2 data sets and comparing model parameters between participant groups. Model parameters included reward and punishment learning rates (feedback sensitivity), reinforcement sensitivity and decision consistency (exploitation), and stickiness (perseveration). Associations of receipt of serotonergic medication with performance were assessed.
RESULTS: In total, 50 patients (29 female patients [58%]; median age, 16.6 years [IQR, 15.3-18.0 years]) and 53 controls (30 female participants [57%]; median age, 16.4 years [IQR, 14.8-18.0 years]) completed the PRL task. A total of 27 patients (18 female patients [67%]; median age, 16.1 years [IQR, 15.2-17.2 years]) and 46 controls (28 female participants [61%]; median age, 17.2 [IQR, 16.3-17.6 years]) completed the WCST. During the reversal phase of the PRL task, patients made fewer correct responses (mean [SD] proportion: 0.83 [0.16] for controls and 0.61 [0.31] for patients; 95% CI, -1.31 to -0.64) and switched choices more often following false-negative feedback (mean [SD] proportion: 0.09 [0.16] for controls vs 0.27 [0.34] for patients; 95% CI, 0.60-1.26) and true-positive feedback (mean [SD] proportion: 0.93 [0.17] for controls vs 0.73 [0.34] for patients; 95% CI, -2.17 to -1.31). Computational modeling revealed that patients displayed enhanced reward learning rates (mean difference [MD], 0.21; 95% highest density interval [HDI], 0.04-0.38) but decreased punishment learning rates (MD, -0.29; 95% HDI, -0.39 to -0.18), reinforcement sensitivity (MD, -4.91; 95% HDI, -9.38 to -1.12), and stickiness (MD, -0.35; 95% HDI, -0.57 to -0.11) compared with controls. There were no group differences on standard WCST measures and computational model parameters. However, patients who received serotonergic medication showed slower response times (mean [SD], 1420.49 [279.71] milliseconds for controls, 1471.42 [212.81] milliseconds for patients who were unmedicated, and 1738.25 [349.23] milliseconds for patients who were medicated) (control vs medicated MD, -320.26 [95% CI, -547.00 to -88.68]) and increased unique errors (mean [SD] proportion: 0.001 [0.004] for controls, 0.002 [0.004] for patients who were unmedicated, and 0.008 [0.01] for patients who were medicated) (control vs medicated MD, -0.007 [95% CI, -3.14 to -0.36]) on the WCST.
CONCLUSIONS AND RELEVANCE: The results of this cross-sectional study indicated that youths with OCD showed atypical probabilistic reversal learning but were generally unimpaired on the deterministic WCST, although unexpected results were observed for patients receiving serotonergic medication. These findings have implications for reframing the understanding of early-onset OCD as a disorder in which decision-making is associated with uncertainty in the environment, a potential target for therapeutic treatment. These results provide continuity with findings in adults with OCD.

Matched MeSH terms: Healthy Volunteers
Fulltext Effects of a Proprietary Freeze-Dried Water Extract of Eurycoma longifolia (Physta) and Polygonum minus on Sexual Performance and Well-Being in Men: A Randomized, Double-Blind, Placebo-Controlled Study

Udani JK, George AA, Musthapa M, Pakdaman MN, Abas A

Evid Based Complement Alternat Med, 2014;2014:179529.
PMID: 24550993 DOI: 10.1155/2014/179529

Background. Physta is a proprietary product containing a freeze-dried water extract of Eurycoma longifolia (tongkat ali), which is traditionally used as an energy enhancer and aphrodisiac. We aim to evaluate a 300 mg combination of Physta and Polygonum minus, an antioxidant, with regard to sexual performance and well-being in men. Methods. Men that aged 40-65 years were screened for this 12-week randomized, double-blind, placebo-controlled, parallel-group study. Outcome measures included validated questionnaires that aimed to evaluate erectile function, satisfaction with intervention, sexual intercourse performance, erectile hardness, mood, and overall quality of life. Results. 12 subjects in the active group and 14 in the placebo group completed the study. Significant improvements were noted in scores for the Sexual Intercourse Attempt diary, Erection Hardness Scale, Sexual Health Inventory of Men, and Aging Male Symptom scale (P < 0.05 for all). Three adverse events were reported in the active group and four in the placebo group, none of which were attributed to study product. Laboratory evaluations, including liver and kidney function testing, showed no clinically significant abnormality. Conclusion. Supplementation for twelve weeks with Polygonum minus and the proprietary Eurycoma longifolia extract, Physta, was well tolerated and more effective than placebo in enhancing sexual performance in healthy volunteers.

Matched MeSH terms: Healthy Volunteers
Fulltext Independent hospital dialysis in Brunei

Chin SS, Hart PL

Br Med J, 1971 Sep 11;3(5775):629-31.
PMID: 5569986

In establishing a chronic haemodialysis unit in Brunei the difficulties encountered were less insuperable than had been expected. Quite unsophisticated patients successfully dialysed unattended in some cases, or with minimal supervision in others.

Matched MeSH terms: Hospital Volunteers
Fulltext Leucocytic DNA Methylation of Interleukin-6 Promoter Reduction in Pre-Hypertensive Young Adults

Omar WFNW, Abdullah A, Talib NA, Shah ASM, Rahman JA

Malays J Med Sci, 2019 Nov;26(6):46-54.
PMID: 31908586 MyJurnal DOI: 10.21315/mjms2019.26.6.5

Background: Pre-hypertension is associated with increased risk of cardiovascular disease. Chronic inflammation plays an important role in the pathophysiology of essential hypertension, with epigenetic dysregulation involvement. Nevertheless, the role of DNA methylation in prehypertensive state is unknown. The aim of this study was to investigate the association between DNA methylation level of interleukin-6 (IL-6) promoter in pre-hypertensive (PreHT) and normotensive (NT) young adults.
Methods: A total of 80 NT and 80 PreHT healthy subjects aged between 18-45 years were recruited in Kuantan, Pahang, Malaysia using an observational cross-sectional study approach. DNA methylation level of IL-6 promoter in peripheral leukocytes were measured using bisulphite conversion and MethyLight assay.
Results: There was no significant difference in age between NT and PreHT (P = 0.655). The mean blood pressure was 110(8)/73(5) mmHg in NT and 125(7)/82(5) mmHg in PreHT subjects. The IL-6 promoter methylation level was significantly lower in PreHT compared to NT subjects (P < 0.001).
Conclusion: The current study demonstrates that hypomethylation of IL-6 promoter was associated with pre-hypertension in young adults. Thus, IL-6 methylation could be used as an early indicator for predicting hypertension and related risk of cardiovascular diseases in prehypertensive subjects. Gene expression and longitudinal studies are warranted to examine the methylation effect on IL-6 expression over time.

Matched MeSH terms: Healthy Volunteers
Adopting the primary health care approach in malaria control in Malaysia: lessons in community participation

Riji HM

Southeast Asian J Trop Med Public Health, 1992;23 Suppl 1:18-22.
PMID: 1341838

The Primary Health Care approach in Malaysia was first tried out in Sarawak, East Malaysia in 1982. In 1984, the Vector Borne Disease Control Program, Kelantan decided to adopt the Primary Health Care approach as an additional strategy in its effort to control malaria in the state, which then experienced an increase in malaria cases. Much effort was directed at creating the awareness and stimulating the interest of health staff and communities to adopt the strategy. Kelantan was made the model state. The paper gives an outline of the process involved and some characteristics of PHC workers. A study was carried out among health workers, community members and health staff on their knowledge and involvement in PHC in three states, including Kelantan. In view of the overall success of this approach, and the weaknesses which have been identified possible solutions have been suggested and should be acted upon.

Matched MeSH terms: Volunteers
Fulltext Infant feeding concerns in times of natural disaster: lessons learned from the 2014 flood in Kelantan, Malaysia

Sulaiman Z, Mohamad N, Ismail TA, Johari N, Hussain NH

Asia Pac J Clin Nutr, 2016;25(3):625-30.
PMID: 27440698 DOI: 10.6133/apjcn.092015.08

The flood that hit Kelantan in December 2014 was the worst in Malaysian history. Women and their infants accounted for a large proportion of the people at risk who were badly affected, as almost half of the population in Kelantan was in the reproductive age group. This report serves to raise awareness that breastfeeding mothers and infants are a special population with unique needs during a disaster. Four of their concerns were identified during this massive flood: first, the negative impact of flood on infant nutritional status and their health; second, open space and lack of privacy for the mothers to breastfeed their babies comfortably at temporary shelters for flood victims; third, uncontrolled donations of infant formula, teats, and feeding bottles that are often received from many sources to promote formula feeding; and lastly, misconceptions related to breastfeeding production and quality that may be affected by the disaster. The susceptibility of women and their infant in a natural disaster enhances the benefits of promoting the breastfeeding rights of women. Women have the right to be supported which enables them to breastfeed. These can be achieved through monitoring the distribution of formula feeding, providing water, electricity and medical care for breastfeeding mothers and their infants. A multifaceted rescue mission team involving various agencies comprising of local government, including the health and nutrition departments, private or non-governmental organizations and individual volunteers have the potential to improve a satisfactory condition of women and infants affected by floods and other potential natural disasters.

Matched MeSH terms: Volunteers
P450 (Cytochrome) Oxidoreductase Gene (POR) Common Variant (POR*28) Significantly Alters CYP2C9 Activity in Swedish, But Not in Korean Healthy Subjects

Hatta FH, Aklillu E

OMICS, 2015 Dec;19(12):777-81.
PMID: 26669712 DOI: 10.1089/omi.2015.0159

CYP2C9 enzyme contributes to the metabolism of several pharmaceuticals and xenobiotics and yet displays large person-to-person and interethnic variation. Understanding the mechanisms of CYP2C9 variation is thus of immense importance for personalized medicine and rational therapeutics. A genetic variant of P450 (cytochrome) oxidoreductase (POR), a CYP450 redox partner, is reported to influence CYP2C9 metabolic activity in vitro. We investigated the impact of a common variant, POR*28, on CYP2C9 metabolic activity in humans. 148 healthy Swedish and 146 healthy Korean volunteers were genotyped for known CYP2C9 defective variant alleles (CYP2C9*2, *3). The CYP2C9 phenotype was determined using a single oral dose of 50 mg losartan. Excluding oral contraceptive (OC) users and carriers of 2C9*2 and *3 alleles, 117 Korean and 65 Swedish were genotyped for POR*5, *13 and *28 using Taqman assays. The urinary losartan to its metabolite E-3174 metabolic ratio (MR) was used as an index of CYP2C9 metabolic activity. The allele frequency of the POR*28 variant allele in Swedes and Koreans was 29% and 44%, respectively. POR*5 and *13 were absent in both study populations. Considering the CYP2C9*1/*1 genotypes only, the CYP2C9 metabolic activity was 1.40-fold higher in carriers of POR*28 allele than non-carriers among Swedes (p = 0.02). By contrast, no influence of the POR*28 on CYP2C9 activity was found in Koreans (p = 0.68). The multivariate analysis showed that ethnicity, POR genotype, and smoking were strong predictors of CYP2C9 MR (p < 0.05). This is the first report to implicate the importance of POR*28 genetic variation for CYP2C9 metabolic activity in humans. These findings contribute to current efforts for global personalized medicine and using medicines by taking into account pharmacogenetic and phenotypic variations.

Matched MeSH terms: Healthy Volunteers
Fulltext Modafinil increases the latency of response in the Hayling Sentence Completion Test in healthy volunteers: a randomised controlled trial

Mohamed AD, Lewis CR

PLoS One, 2014;9(11):e110639.
PMID: 25391155 DOI: 10.1371/journal.pone.0110639

BACKGROUND: Modafinil is a medication licensed for the treatment of narcolepsy. However, it has been reported that healthy individuals without wakefulness disorders are using modafinil off-label to enhance cognitive functioning. Although some studies have reported that modafinil improves cognitive task performance in healthy volunteers, numerous other studies have failed to detect cognitive enhancing effects of modafinil on several well-established neuropsychological tasks. Interestingly, several clinical and preclinical studies have found that improved cognitive task performance by modafinil is accompanied by slower response times. This observation raises the question as to whether this slowing of response time in healthy volunteers is a necessary and sufficient condition for cognitive enhancement with modafinil. The aim of the current experiment was to explore this question by investigating the effects of modafinil on the Hayling Sentence Completion Test (HSCT).
METHODOLOGY: Sixty-four healthy volunteers received either a single dose (200 mg) of modafinil (n = 32) or placebo (n = 32) in a randomized, double-blind, placebo-controlled, parallel group study in which the principal outcome measures were response latencies on the response initiation and response inhibition sections of the HSCT.
PRINCIPAL FINDINGS: Participants dosed with modafinil had significantly longer mean response latencies on the HSCT for both the response initiation and response inhibition compared to participants dosed with placebo. However, participants in both groups made a similar number of errors on each of these measures, indicating that modafinil did not enhance the accuracy of performance of the task relative to placebo.
CONCLUSIONS: This study demonstrated that administration of single 200 mg doses of modafinil to healthy individuals increased the latency of responses in the performance of the HSCT, a task that is highly sensitive to prefrontal executive function, without enhancing accuracy of performance. This finding may provide important clues to defining the limitations of modafinil as a putative cognitive enhancer.
TRIAL REGISTRATION: ClinicalTrials.gov NCT02051153.

Matched MeSH terms: Healthy Volunteers
Population pharmacokinetics of orally administered mefloquine in healthy volunteers and patients with uncomplicated Plasmodium falciparum malaria

Reuter SE, Upton RN, Evans AM, Navaratnam V, Olliaro PL

J Antimicrob Chemother, 2015 Mar;70(3):868-76.
PMID: 25377567 DOI: 10.1093/jac/dku430

BACKGROUND: The determination of dosing regimens for the treatment of malaria is largely empirical and thus a better understanding of the pharmacokinetic/pharmacodynamic properties of antimalarial agents is required to assess the adequacy of current treatment regimens and identify sources of suboptimal dosing that could select for drug-resistant parasites. Mefloquine is a widely used antimalarial, commonly given in combination with artesunate.
PATIENTS AND METHODS: Mefloquine pharmacokinetics was assessed in 24 healthy adults and 43 patients with Plasmodium falciparum malaria administered mefloquine in combination with artesunate. Population pharmacokinetic modelling was conducted using NONMEM.
RESULTS: A two-compartment model with a single transit compartment and first-order elimination from the central compartment most adequately described mefloquine concentration-time data. The model incorporated population parameter variability for clearance (CL/F), central volume of distribution (VC/F) and absorption rate constant (KA) and identified, in addition to body weight, malaria infection as a covariate for VC/F (but not CL/F). Monte Carlo simulations predict that falciparum malaria infection is associated with a shorter elimination half-life (407 versus 566 h) and T>MIC (766 versus 893 h).
CONCLUSIONS: This is the first known population pharmacokinetic study to show falciparum malaria to influence mefloquine disposition. Protein binding, anaemia and other factors may contribute to differences between healthy individuals and patients. As VC/F is related to the earlier portion of the concentration-time profiles, which occurs during acute malaria, and CL/F is more related to the terminal phase during convalescence after treatment, this may explain why malaria was found to be a covariate for VC/F but not CL/F.

Matched MeSH terms: Healthy Volunteers
Significant genotype difference in the CYP2E1 PstI polymorphism of indigenous groups in Sabah, Malaysia with Asian and non-Asian populations

Goh LP, Chong ET, Chua KH, Chuah JA, Lee PC

Asian Pac J Cancer Prev, 2014;15(17):7377-81.
PMID: 25227845

CYP2E1 PstI polymorphism G-1259C (rs3813867) genotype distributions vary significantly among different populations and are associated with both diseases, like cancer, and adverse drug effects. To date, there have been limited genotype distributions and allele frequencies of this polymorphism reported in the three major indigenous ethnic groups (KadazanDusun, Bajau, and Rungus) in Sabah, also known as North Borneo. The aim of this study was to investigate the genotype distributions and allele frequencies of the CYP2E1 PstI polymorphism G-1259C in these three major indigenous peoples in Sabah. A total of 640 healthy individuals from the three dominant indigenous groups were recruited for this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) at G-1259C polymorphic site of CYP2E1 gene was performed using the Pst I restriction enzyme. Fragments were analyzed using agarose gel electrophoresis and confirmed by direct sequencing. Overall, the allele frequencies were 90.3% for c1 allele and 9.7% for c2 allele. The genotype frequencies for c1/c1, c1/c2 and c2/c2 were observed as 80.9%, 18.8%, and 0.3%, respectively. A highly statistical significant difference (p<0.001) was observed in the genotype distributions between indigenous groups in Sabah with all Asian and non-Asian populations. However, among these three indigenous groups, there was no statistical significant difference (p>0.001) in their genotype distributions. The three major indigenous ethnic groups in Sabah show unique genotype distributions when compared with other populations. This finding indicates the importance of establishing the genotype distributions of CYP2E1 PstI polymorphism in the indigenous populations.

Matched MeSH terms: Healthy Volunteers
Fulltext Real-time PCR assay in differentiating Entamoeba histolytica, Entamoeba dispar, and Entamoeba moshkovskii infections in Orang Asli settlements in Malaysia

Lau YL, Anthony C, Fakhrurrazi SA, Ibrahim J, Ithoi I, Mahmud R

Parasit Vectors, 2013;6(1):250.
PMID: 23985047 DOI: 10.1186/1756-3305-6-250

Amebiasis caused by Entamoeba histolytica is the third leading cause of death worldwide. This pathogenic amoeba is morphologically indistinguishable from E. dispar and E. moshkovskii, the non-pathogenic species. Polymerase chain reaction is the current method of choice approved by World Health Organization. Real-time PCR is another attractive molecular method for diagnosis of infectious diseases as post-PCR analyses are eliminated and turnaround times are shorter. The present work aimed to compare the results of Entamoeba species identification using the real-time assay against the established nested PCR method.

Matched MeSH terms: Healthy Volunteers
Obesity can predict and promote systemic inflammation in healthy adults

Ellulu MS, Khaza'ai H, Rahmat A, Patimah I, Abed Y

Int J Cardiol, 2016 Jul 15;215:318-24.
PMID: 27128554 DOI: 10.1016/j.ijcard.2016.04.089

BACKGROUND: To find out the differences on biomedical data between obese and non-obese participants, and to identify risk factors associated with systemic inflammation in healthy Palestinian adults.
METHODOLOGY: A cross-sectional study involved 105 apparently healthy adults. Interview questionnaire was used to collect personal information. Participants were excluded if they suffered from acute or chronic inflammatory diseases, or continued using medicines, which might affect the biomedical results.
RESULTS: In association with increased Body Mass Index (BMI), the obese group displayed significant higher markers including: interleukin 6 (IL-6), high sensitivity C reactive protein (hs-CRP), total cholesterol (TC), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Obese group in association with increased waist circumference (WC) was higher significantly in inflammatory markers (IL-6, hs-CRP), lipid profile (TC) and triglyceride (TG), and blood pressure (SBP, DBP). A tertile of a feature of systemic inflammation (hs-CRP) was created, by Ordinal Logistic Regression, after adjusting for the age, gender, smoking habits, physical activity pattern, father and mother's health history; risk factors were the increased BMI [OR: 1.24] (95% CI: 1.005-1.548, P=0.050), IL-6 [OR: 3.35] (95% CI: 1.341-8.398, P=0.010), DBP [OR: 1.19] (95% CI: 1.034-1.367, P=0.015), and reduced Adiponectin [OR: 0.59] (95% CI: 0.435-0.820, P=0.001). Finally, BMI correlated with IL-6 and hs-CRP (r=0.326, P=0.005; r=0.347, P<0.001; respectively), and hs-CRP correlated with IL-6 (r=0.303, P=0.010), and inversely with Adiponectin (r=-0.342, P=0.001).
CONCLUSION: The increased level of IL-6 and reduced Adiponectin, which strongly associated with obesity, indicated that having high BMI is a useful marker in association with IL-6 and further developed systemic inflammation.

Matched MeSH terms: Healthy Volunteers

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