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  1. Abdul-Razak S, Rahmat R, Mohd Kasim A, Rahman TA, Muid S, Nasir NM, et al.
    BMC Cardiovasc Disord, 2017 Oct 16;17(1):264.
    PMID: 29037163 DOI: 10.1186/s12872-017-0694-z
    BACKGROUND: Familial hypercholesterolaemia (FH) is a genetic disorder with a high risk of developing premature coronary artery disease that should be diagnosed as early as possible. Several clinical diagnostic criteria for FH are available, with the Dutch Lipid Clinic Criteria (DLCC) being widely used. Information regarding diagnostic performances of the other criteria against the DLCC is scarce. We aimed to examine the diagnostic performance of the Simon-Broom (SB) Register criteria, the US Make Early Diagnosis to Prevent Early Deaths (US MEDPED) and the Japanese FH Management Criteria (JFHMC) compared to the DLCC.

    METHODS: Seven hundered fifty five individuals from specialist clinics and community health screenings with LDL-c level ≥ 4.0 mmol/L were selected and diagnosed as FH using the DLCC, the SB Register criteria, the US MEDPED and the JFHMC. The sensitivity, specificity, efficiency, positive and negative predictive values of individuals screened with the SB register criteria, US MEDPED and JFHMC were assessed against the DLCC.

    RESULTS: We found the SB register criteria identified more individuals with FH compared to the US MEDPED and the JFHMC (212 vs. 105 vs. 195; p 

    Matched MeSH terms: Hyperlipoproteinemia Type II/blood*; Cholesterol, LDL/blood*
  2. Aleksandrova K, Jenab M, Leitzmann M, Bueno-de-Mesquita B, Kaaks R, Trichopoulou A, et al.
    Int J Epidemiol, 2017 Dec 01;46(6):1823-1835.
    PMID: 29025032 DOI: 10.1093/ije/dyx174
    BACKGROUND: There is convincing evidence that high physical activity lowers the risk of colon cancer; however, the underlying biological mechanisms remain largely unknown. We aimed to determine the extent to which body fatness and biomarkers of various biologically plausible pathways account for the association between physical activity and colon cancer.

    METHODS: We conducted a nested case-control study in a cohort of 519 978 men and women aged 25 to 70 years followed from 1992 to 2003. A total of 713 incident colon cancer cases were matched, using risk-set sampling, to 713 controls on age, sex, study centre, fasting status and hormonal therapy use. The amount of total physical activity during the past year was expressed in metabolic equivalent of task [MET]-h/week. Anthropometric measurements and blood samples were collected at study baseline.

    RESULTS: High physical activity was associated with a lower risk of colon cancer: relative risk ≥91 MET-h/week vs <91 MET-h/week = 0.75 [95% confidence interval (CI): 0.57 to 0.96]. In mediation analyses, this association was accounted for by waist circumference: proportion explained effect (PEE) = 17%; CI: 4% to 52%; and the biomarkers soluble leptin receptor (sOB-R): PEE = 15%; 95% CI: 1% to 50% and 5-hydroxyvitamin D (25[OH]D): PEE = 30%; 95% CI: 12% to 88%. In combination, these factors explained 45% (95% CI: 20% to 125%) of the association. Beyond waist circumference, sOB-R and 25[OH]D additionally explained 10% (95% CI: 1%; 56%) and 23% (95% CI: 6%; 111%) of the association, respectively.

    CONCLUSIONS: Promoting physical activity, particularly outdoors, and maintaining metabolic health and adequate vitamin D levels could represent a promising strategy for colon cancer prevention.

    Matched MeSH terms: Vitamin D/blood*; Biomarkers/blood
  3. Nepal S, Kumar V, Makkar HPS, Stadtlander T, Romano N, Becker K
    Fish Physiol Biochem, 2018 Feb;44(1):143-162.
    PMID: 28900838 DOI: 10.1007/s10695-017-0420-x
    Jatropha seed cake (JSC) is an excellent source of protein but does contain some antinutritional factors (ANF) that can act as toxins and thus negatively affect the growth and health status of fish. While this can limit the use of JSC, detoxified Jatropha protein isolate (DJPI) may be a better option. An 8-week study was performed to evaluate dietary DJPI to common carp Cyprinus carpio. Five iso-nitrogenous diets (crude protein of 38%) were formulated that consisted of a C ontrol (fish meal (FM) based protein), J 50 or J 75 (50 and 75% of FM protein replaced by DJPI), and S 50 or S 75 (50 and 75% of FM protein replaced by soy protein isolate, SPI) and fed to triplicate groups of 75 carp fingerlings (75; av. wt. ± SD; 11.4 ± 0.25 g). The growth, feeding efficiencies, digestibility, plasma biochemistry, and intestinal enzymes were measured. Results showed that growth performance of fish fed the S 75- or DJPI-based diets were not significantly different from those fed the C ontrol diet, while carp fed the S 50 had significantly better growth than the J 75 diet. Fish fed the J 75 diet had significantly lower protein and lipid digestibility as well as significantly lower intestinal amylase and protease activities than all other groups. However, all plant protein-based diets led to significantly higher crude protein, crude lipid, and gross energy in the body of common carp compared to the control treatment. Plasma cholesterol and creatinine significantly decreased in the plant protein fed groups, although plasma triglyceride as well as the red blood cells count, hematocrit, albumin, globulin, total plasma protein, and lysozyme activity were higher in plant protein fed groups compared to FM fed group. White blood cells, hemoglobulin concentration, alkaline phosphatase and alanine transaminase activities, and glucose level in blood did not differ significantly among treatments. The results suggest that the DJPI is non-toxic to carp and can be used to replace FM in the diets of common carp up to 75%, but further research to potentially reduce some inherent ANF within this protein source, such as non-starch polysaccharides, may improve nutrient utilization.
    Matched MeSH terms: Cholesterol/blood; Triglycerides/blood
  4. Maherally Z, Fillmore HL, Tan SL, Tan SF, Jassam SA, Quack FI, et al.
    FASEB J, 2018 01;32(1):168-182.
    PMID: 28883042 DOI: 10.1096/fj.201700162R
    The blood-brain barrier (BBB) consists of endothelial cells, astrocytes, and pericytes embedded in basal lamina (BL). Most in vitro models use nonhuman, monolayer cultures for therapeutic-delivery studies, relying on transendothelial electrical resistance (TEER) measurements without other tight-junction (TJ) formation parameters. We aimed to develop reliable, reproducible, in vitro 3-dimensional (3D) models incorporating relevant human, in vivo cell types and BL proteins. The 3D BBB models were constructed with human brain endothelial cells, human astrocytes, and human brain pericytes in mono-, co-, and tricultures. TEER was measured in 3D models using a volt/ohmmeter and cellZscope. Influence of BL proteins-laminin, fibronectin, collagen type IV, agrin, and perlecan-on adhesion and TEER was assessed using an electric cell-substrate impedance-sensing system. TJ protein expression was assessed by Western blotting (WB) and immunocytochemistry (ICC). Perlecan (10 µg/ml) evoked unreportedly high, in vitro TEER values (1200 Ω) and the strongest adhesion. Coculturing endothelial cells with astrocytes yielded the greatest resistance over time. ICC and WB results correlated with resistance levels, with evidence of prominent occludin expression in cocultures. BL proteins exerted differential effects on TEER, whereas astrocytes in contact yielded higher TEER values and TJ expression.-Maherally, Z., Fillmore, H. L., Tan, S. L., Tan, S. F., Jassam, S. A., Quack, F. I., Hatherell, K. E., Pilkington, G. J. Real-time acquisition of transendothelial electrical resistance in an all-human, in vitro, 3-dimensional, blood-brain barrier model exemplifies tight-junction integrity.
    Matched MeSH terms: Blood-Brain Barrier/cytology; Blood-Brain Barrier/metabolism*
  5. Ma A, Wang Y, Liu XL, Zhang HM, Eamsobhana P, Yong HS, et al.
    J Helminthol, 2019 Jan;93(1):26-32.
    PMID: 29144215 DOI: 10.1017/S0022149X17001080
    Human gnathostomiasis is an emerging food-borne parasitic disease caused by nematodes of the genus Gnathostoma. Currently, serological tests are commonly applied to support clinical diagnosis. In the present study, a simple and rapid filtration-based test, dot immune-gold filtration assay (DIGFA) was developed using a partially purified antigen of Gnathostoma third-stage larvae (L3). A total of 180 serum samples were tested to evaluate the diagnostic potential of DIGFA for gnathostomiasis. The diagnostic sensitivity and specificity were 96.7% (29/30) and 100% (25/25), respectively. The cross-reactivity with sera from other helminthiasis patients ranged from 0 to 4%, with an average of 1.6% (2/125). DIGFA using a partially purified L3 antigen was not only simple and rapid, but also more accurate than standard assays for the diagnosis of human gnathostomiasis. DIGFA may represent a promising tool for application in laboratories or in the field, without requiring any instrumentation.
    Matched MeSH terms: Antibodies, Helminth/blood*; Gnathostomiasis/blood
  6. Yee A, Loh HS, Danaee M, Riahi S, Ng CG, Sulaiman AH
    J Sex Med, 2018 02;15(2):159-166.
    PMID: 29275046 DOI: 10.1016/j.jsxm.2017.12.004
    BACKGROUND: Methadone has been recognized as an effective maintenance treatment for opioid dependence. However, its use is associated with several complications, including sexual dysfunction in men.

    AIM: To assess plasma testosterone and sexual function in Southeast Asian men on methadone maintenance treatment (MMT) or buprenorphine maintenance treatment (BMT).

    METHODS: 76 sexually active men on MMT (mean age = 43.30 ± 10.32 years) and 31 men on BMT (mean age = 41.87 ± 9.76 years) from a Southeast Asian community were evaluated using plasma total testosterone (TT) and prolactin levels, body mass index, social demographics, substance use measures, and depression severity scale.

    OUTCOMES: Prevalence and associated factors of TT level lower than the reference range in men on MMT or BMT.

    RESULTS: More than 1 third of men (40.8%, n = 31) on MMT had TT levels lower than the reference range, whereas 1 fourth of men (22.6%, n = 7) on BMT did. At univariate analysis, MMT vs BMT (β = 0.298, adjusted R2 = 0.08, P = .02) and body mass index (β = -0.23, adjusted R2 = 0.12, P = .02) were associated with changes in TT after stepwise regression. There were no significant associations with age; Opiate Treatment Index Q scores for alcohol, heroin, stimulant, tobacco, or cannabis use and social functioning domain; education levels; hepatitis C status; and severity of depression. Prolactin level did not differ between the MMT and BMT groups.

    CLINICAL IMPLICATIONS: The sex hormonal assay should be used regularly to check men on MMT.

    STRENGTHS AND LIMITATIONS: This is the first study conducted in the Southeast Asian community. Our study was limited by the lack of a healthy group as the reference for serum levels of testosterone and prolactin.

    CONCLUSIONS: The findings showed that plasma testosterone levels are lower in MMT than in BMT users. Hence, men who are receiving MMT should be screened for hypogonadism routinely in the clinical setting. Yee A, Loh HS, Danaee M, et al. Plasma Testosterone and Sexual Function in Southeast Asian Men Receiving Methadone and Buprenorphine Maintenance Treatment. J Sex Med 2018;15:159-166.

    Matched MeSH terms: Prolactin/blood; Testosterone/blood*
  7. Nour El Huda AR, Norsidah KZ, Nabil Fikri MR, Hanisah MN, Kartini A, Norlelawati AT
    Psychiatry Clin Neurosci, 2018 Apr;72(4):266-279.
    PMID: 29160620 DOI: 10.1111/pcn.12622
    AIM: This study examined catechol-O-methyltransferase (COMT) DNA methylation in the peripheral blood of schizophrenia patients and also in healthy controls to investigate its potential use as a peripheral biomarker of schizophrenia and its relations with the clinical variables of schizophrenia patients.

    METHODS: We examined the DNA methylation levels of COMT using genomic DNA from the peripheral blood of schizophrenia patients (n = 138) and healthy control participants (n = 132); all were Malaysian Malays. The extracted DNA was bisulfite converted, and the percentage methylation ratio value was calculated based on the results following a MethyLight protocol analysis.

    RESULTS: The percentage methylation ratio of COMT was lower in schizophrenia than it was in the healthy controls (P blood could be a potential peripheral biomarker of schizophrenia.

    Matched MeSH terms: Schizophrenia/blood*; Biomarkers/blood
  8. Badrasawi M, Shahar S, Zahara AM, Nor Fadilah R, Singh DK
    Clin Interv Aging, 2016;11:1675-1686.
    PMID: 27895474
    BACKGROUND: Frailty is a biological syndrome of decreased reserve and resistance to stressors due to decline in multiple physiological systems. Amino acid deficiency, including L-carnitine, has been proposed to be associated with its pathophysiology. Nevertheless, the efficacy of L-carnitine supplementation on frailty status has not been documented. Thus, this study aimed to determine the effect of 10-week L-carnitine supplement (1.5 g/day) on frailty status and its biomarkers and also physical function, cognition, and nutritional status among prefrail older adults in Klang Valley, Malaysia.

    METHODOLOGY: This study is a randomized, double-blind, placebo-controlled clinical trial conducted among 50 prefrail subjects randomized into two groups (26 in L-carnitine group and 24 in placebo group). Outcome measures include frailty status using Fried criteria and Frailty Index accumulation of deficit, selected frailty biomarkers (interleukin-6, tumor necrosis factor-alpha, and insulin-like growth factor-1), physical function, cognitive function, nutritional status and biochemical profile.

    RESULTS: The results indicated that the mean scores of Frailty Index score and hand grip test were significantly improved in subjects supplemented with L-carnitine (P<0.05 for both parameters) as compared to no change in the placebo group. Based on Fried criteria, four subjects (three from the L-carnitine group and one from the control group) transited from prefrail status to robust after the intervention.

    CONCLUSION: L-carnitine supplementation has a favorable effect on the functional status and fatigue in prefrail older adults.

    Matched MeSH terms: Tumor Necrosis Factor-alpha/blood; Interleukin-6/blood
  9. Khor CS, Mohd-Rahim NF, Hassan H, Chandren JR, Nore SS, Johari J, et al.
    Vector Borne Zoonotic Dis, 2018 03;18(3):131-137.
    PMID: 29336685 DOI: 10.1089/vbz.2017.2153
    Q fever is a disease caused by Coxiella burnetii. It is a disease of public health concern in many parts of the world. In this study, we described the seroprevalence of Q fever among selected populations of Orang Asli (OA), indigenous people, many of whom live within the forest fringe areas of Peninsular Malaysia. Serum samples were obtained from 887 OA participants from selected villages. Samples were analyzed for the presence of IgG antibodies reactive against C. burnetii by enzyme-linked immunosorbent assay. Statistical methods were used to identify possible associations between seropositivity for C. burnetii and a number of demographic variables obtained from the questionnaires. In total, 9.6% (n = 85/887) of the serum samples were reactive to C. burnetii. Statistical results suggest that elderly male OA residing in OA village, Bukit Payung, were most likely to be tested seropositive for C. burnetii. This study suggests that OA are at a significant risk of contracting C. burnetii infection, and both demographic and geographic factors are important contributors to this risk. Further prospective studies are needed to establish the true burden of C. burnetii infection within the indigenous population as well as within Peninsular Malaysia as a whole.
    Matched MeSH terms: Antibodies, Bacterial/blood*; Q Fever/blood
  10. Amzar N, Iqbal M
    J Environ Pathol Toxicol Oncol, 2017;36(4):293-307.
    PMID: 29431062 DOI: 10.1615/JEnvironPatholToxicolOncol.2017019824
    Liver diseases still represents a major health burden worldwide. Moreover, medicinal plants have gained popularity in the treatment of several diseases, including liver disease. Clidemia hirta possesses many medicinal properties for healing several diseases and for health maintenance. However, the hepatoprotective effects and antioxidative potential of C. hirta have not been fully investigated. In the present study, we evaluated the hepatoprotective and antioxidative potential of C. hirta against carbon tetrachloride (CCl4)-induced liver injuries and oxidative damage in a murine model. Various biochemical changes associated with liver damage and oxidative stress were measured. The mice were pretreated for 14 consecutive days with aqueous extract of C. hirta at selected doses (150 mg/kg body weight [b.w.], 300 mg/kg b.w. and 600 mg/kg b.w.) followed by two doses of CCl4 (1.0 mL/kg b.w.) orally on days 14 and 15. All animals were sacrificed 24 hours after the last dose of CCl4 or saline. Blood and liver tissues were taken quickly for biochemical and histopathological studies to assess the derangement in the functioning of liver. The development of oxidative stress was observed through the escalation of hepatic lipid peroxidation, depletion of glutathione, and reduced antioxidant enzymes (glutathione peroxidase, glutathione reductase, catalase, glutathione S-transferase and quinone reductase). Hepatic damage was evaluated by measuring serum transaminase (ALT and AST). In addition, CCl4-induced hepatic damage was further evaluated using histopathological assessments. However, most of these changes were dependently ameliorated by the pretreatment of mice with a C. hirta dose. These results indicate that the hepatoprotective effect of C. hirta might be due to its antioxidant and free-radical scavenging properties.
    Matched MeSH terms: Alanine Transaminase/blood; Aspartate Aminotransferases/blood
  11. Kalid N, Zaidan AA, Zaidan BB, Salman OH, Hashim M, Albahri OS, et al.
    J Med Syst, 2018 Mar 02;42(4):69.
    PMID: 29500683 DOI: 10.1007/s10916-018-0916-7
    This paper presents a new approach to prioritize "Large-scale Data" of patients with chronic heart diseases by using body sensors and communication technology during disasters and peak seasons. An evaluation matrix is used for emergency evaluation and large-scale data scoring of patients with chronic heart diseases in telemedicine environment. However, one major problem in the emergency evaluation of these patients is establishing a reasonable threshold for patients with the most and least critical conditions. This threshold can be used to detect the highest and lowest priority levels when all the scores of patients are identical during disasters and peak seasons. A practical study was performed on 500 patients with chronic heart diseases and different symptoms, and their emergency levels were evaluated based on four main measurements: electrocardiogram, oxygen saturation sensor, blood pressure monitoring, and non-sensory measurement tool, namely, text frame. Data alignment was conducted for the raw data and decision-making matrix by converting each extracted feature into an integer. This integer represents their state in the triage level based on medical guidelines to determine the features from different sources in a platform. The patients were then scored based on a decision matrix by using multi-criteria decision-making techniques, namely, integrated multi-layer for analytic hierarchy process (MLAHP) and technique for order performance by similarity to ideal solution (TOPSIS). For subjective validation, cardiologists were consulted to confirm the ranking results. For objective validation, mean ± standard deviation was computed to check the accuracy of the systematic ranking. This study provides scenarios and checklist benchmarking to evaluate the proposed and existing prioritization methods. Experimental results revealed the following. (1) The integration of TOPSIS and MLAHP effectively and systematically solved the patient settings on triage and prioritization problems. (2) In subjective validation, the first five patients assigned to the doctors were the most urgent cases that required the highest priority, whereas the last five patients were the least urgent cases and were given the lowest priority. In objective validation, scores significantly differed between the groups, indicating that the ranking results were identical. (3) For the first, second, and third scenarios, the proposed method exhibited an advantage over the benchmark method with percentages of 40%, 60%, and 100%, respectively. In conclusion, patients with the most and least urgent cases received the highest and lowest priority levels, respectively.
    Matched MeSH terms: Oxygen/blood; Blood Pressure Monitoring, Ambulatory
  12. Mahmood S, Mandal UK, Chatterjee B
    Int J Pharm, 2018 May 05;542(1-2):36-46.
    PMID: 29501737 DOI: 10.1016/j.ijpharm.2018.02.044
    Raloxifene HCl belongs to a class of selective estrogen receptor modulators (SERMs) which is used for the management of breast cancer. The major problem reported with raloxifene is its poor bioavailability which is only up to 2%. The main objective of the present work was to formulate raloxifene loaded ethosomal preparation for transdermal application and compare it with an oral formulation of the drug. Five ethosomal formulations with different concentrations of ethanol and a conventional liposomes formulation were prepared by rotary evaporation method. The prepared systems were characterised by high resolution transmission electron microscopy (HRTEM), force emission electron microscopy (FESEM), atomic force microscopy (AFM), X-ray diffraction (XRD) and 31P NMR study. All these advanced characterization study established that the ethosome formulation was well defined by its size, shape and its bilayer formation. Transdermal flux of the optimized ethosome formulation was 22.14 ± 0.83 µg/ml/cm2 which was 21 times higher when compared to the conventional liposomes. Confocal microscopy study revealed an enhanced permeation of coumarin-6 dye loaded ethosomes to much deeper layers of skin when compared with conventional liposomes. The gel was found to be pseudoplastic with elastic behaviour. In-vivo studies on rats showed a higher bioavailability of RXL (157% times) for ethosomal formulation when compared with the oral formulation. In conclusion, RXL loaded ethosomal formulation via transdermal route showed superior drug delivery properties as compared to oral formulation.
    Matched MeSH terms: Selective Estrogen Receptor Modulators/blood; Raloxifene Hydrochloride/blood
  13. Mamat-Noorhidayah, Yazawa K, Numata K, Norma-Rashid Y
    PLoS One, 2018;13(3):e0193147.
    PMID: 29513694 DOI: 10.1371/journal.pone.0193147
    Resilin functions as an elastic spring that demonstrates extraordinary extensibility and elasticity. Here we use combined techniques, laser scanning confocal microscopy (LSCM) and scanning electron microscopy (SEM) to illuminate the structure and study the function of wing flexibility in damselflies, focusing on the genus Rhinocypha. Morphological studies using LSCM and SEM revealed that resilin patches and cuticular spikes were widespread along the longitudinal veins on both dorsal and ventral wing surfaces. Nanoindentation was performed by using atomic force microscopy (AFM), where the wing samples were divided into three sections (membrane of the wing, mobile and immobile joints). The resulting topographic images revealed the presence of various sizes of nanostructures for all sample sections. The elasticity range values were: membrane (0.04 to 0.16 GPa), mobile joint (1.1 to 2.0 GPa) and immobile joint (1.8 to 6.0 GPa). The elastomeric and glycine-rich biopolymer, resilin was shown to be an important protein responsible for the elasticity and wing flexibility.
    Matched MeSH terms: Forelimb/blood supply; Wings, Animal/blood supply
  14. Abubakar MB, Gan SH
    Niger J Physiol Sci, 2017 Dec 30;32(2):219-225.
    PMID: 29485645
    Although anastrozole (Anas) plays a key role in the management of endocrine sensitive post-menopausal (PM) breast cancer (BC), there is much variability in its efficacy and tolerability. Anas-associated musculoskeletal symptoms (MS) and other adverse reactions, such as hot flashes (HF) and vaginal dryness/dyspareunia (VDD), are common and can affect the quality of life of BC patients, even sometimes leading to treatment withdrawal. The aim of this study was to determine the clinical and demographic factors associated with these adverse events. This is a cross-sectional study in estrogen receptor (ER) positive PM women (n = 92) with stages I to III BC receiving Anas. Multivariate analyses were performed to investigate the factors associated with Anas-induced adverse effects such as MS, HF and VDD. A serum estradiol concentration was undetectable (< 36.7 pmol/L) in 68.1% of patients but was detectable within a normal range (>36.7-88.1 pmol/L) in the other 31.9% of patients, and this group was found to have a lower odds of having at least one adverse effect (AE) compared to those with undetectable levels [adjusted odds ratio (AOR) 0.12, 95% confidence interval (CI) 0.02 to 0.64, p = 0.013]. Women with grades II and III tumors and a family history of BC had a higher odds of AE (grade II: AOR 12.22, CI 1.48 to 100.80, p = 0.020; grade III: AOR 12.95, CI 1.25 to 134.33, p = 0.032) and VDD (AOR 5.99, CI 1.30 to 27.52, p = 0.021), respectively. Patients who received Anas treatment for more than one year had a higher odds of VDD (one to three years: AOR 34.57, CI 3.86, 309.50, p = 0.002; more than 3 years: AOR 27.90, CI 2.21 to 351.84, p = 0.010). Advanced age also lowered the odds of HF (AOR 0.90, CI 0.83 to 1.00, p = 0.049). In conclusion, patients' hormonal environments and durations of Anas treatment may play a role in developing Anas-induced adverse effects.
    Matched MeSH terms: Breast Neoplasms/blood*; Estradiol/blood*
  15. Manosroi W, Tan JW, Rariy CM, Sun B, Goodarzi MO, Saxena AR, et al.
    J Clin Endocrinol Metab, 2017 11 01;102(11):4124-4135.
    PMID: 28938457 DOI: 10.1210/jc.2017-00957
    Context: Hypertension in young women is uncommon compared with young men and older women. Estrogen appears to protect most women against hypertension, with incidence increasing after menopause. Because some premenopausal women develop hypertension, estrogen may play a different role in these women. Genetic variations in the estrogen receptor (ER) are associated with cardiovascular disease. ER-β, encoded by ESR2, is the ER predominantly expressed in vascular smooth muscle.

    Objective: To determine an association of single nucleotide polymorphisms in ESR2 with salt sensitivity of blood pressure (SSBP) and estrogen status in women.

    Methods: Candidate gene association study with ESR2 and SSBP conducted in normotensive and hypertensive women and men in two cohorts: International Hypertensive Pathotype (HyperPATH) (n = 584) (discovery) and Mexican American Hypertension-Insulin Resistance Study (n = 662) (validation). Single nucleotide polymorphisms in ESR1 (ER-α) were also analyzed. Analysis conducted in younger (<51 years, premenopausal, "estrogen-replete") and older women (≥51 years, postmenopausal, "estrogen-deplete"). Men were analyzed to control for aging.

    Results: Multivariate analyses of HyperPATH data between variants of ESR2 and SSBP documented that ESR2 rs10144225 minor (risk) allele carriers had a significantly positive association with SSBP driven by estrogen-replete women (β = +4.4 mm Hg per risk allele, P = 0.004). Findings were confirmed in Hypertension Insulin-Resistance Study premenopausal women. HyperPATH cohort analyses revealed risk allele carriers vs noncarriers had increased aldosterone/renin ratios. No associations were detected with ESR1.

    Conclusions: The variation at rs10144225 in ESR2 was associated with SSBP in premenopausal women (estrogen-replete) and not in men or postmenopausal women (estrogen-deplete). Inappropriate aldosterone levels on a liberal salt diet may mediate the SSBP.

    Matched MeSH terms: Blood Pressure/drug effects; Blood Pressure/genetics
  16. Kongkaew C, Scholfield NC, Dhippayom T, Dilokthornsakul P, Saokaew S, Chaiyakunapruk N
    J Ethnopharmacol, 2018 Apr 24;216:162-174.
    PMID: 29409850 DOI: 10.1016/j.jep.2018.01.028
    ETHNOPHARMACOLOGICAL RELEVANCE: Pueraria candollei var. mirifica (Airy Shaw & Suvat.) Niyomdham (commonly termed P. mirifica, PM) growing in upland Thailand has a long history as a postmenopausal rejuvenant therapy for indigenants. Its amelioration of menopause symptoms in clinical trials was assessed.

    MATERIALS AND METHODS: International and Thai databases were searched from inception to February 2017. Clinical trials investigating effects of PM menopausal or postmenopausal women were included. Outcomes were self-reported menopausal symptoms, serum reproductive hormones, urino-genital tract function, and bone surrogates. Methodological quality was assessed by Cochrane risk-of-bias v2.0, and a 22-parameter quality score based on the CONSORT checklist for herbal medicines.

    RESULTS: Eight studies (9 articles) used data from 309 menopausal patients. Five-studies demonstrated that PM was associated with climacteric scores reduced by ~50% compared to baseline. Other PM studies using limited numbers of placebo participants suggested improved vaginal and other urogenital tract symptoms. Bone alkaline phosphatase halved (suggesting lowered bone turnover). Variable serum reproductive hormone levels suggested menopausal status differed between studies. PM active ingredients and sources were not defined. Adverse event rates (mastodynia, vaginal spotting, dizziness) were similar in all groups (PM, conjugated equine estrogen, and placebos) but serum C-reactive protein doubled. These studies had design and reporting deficiencies, high risks of biases, and low quality scores.

    CONCLUSIONS: The efficacy of PM on menopausal symptoms remains inconclusive because of methodological short-comings especially placebo effects inherent in self-assessment/recall questionnaires and no PM standardization. PM efficacy and safety need a fundamental re-appraisal by: (i) cohort (retro- and prospective) studies on current users to define its traditional use for rejuvenation; (ii) tightly coupling long-term efficacy to safety of well-defined PM and multiple end-points; (iii) using study design related to current understanding of menopause progression and estrogen pharmacology (iv) robust pharmacovigilance.

    Matched MeSH terms: Menopause/blood; Biomarkers/blood
  17. Eng CSY, Bhowruth D, Mayes M, Stronach L, Blaauw M, Barber A, et al.
    Nephrol Dial Transplant, 2018 05 01;33(5):847-855.
    PMID: 29136192 DOI: 10.1093/ndt/gfx287
    Background: Fluid balance is pivotal in the management of children with chronic kidney disease (CKD) and on dialysis. Although many techniques are available to assess fluid status, there are only a few studies for children, of which none have been comparable against cardiovascular outcome measures.

    Methods: We performed a longitudinal study in 30 children with CKD5-5D and 13 age-matched healthy controls (71 measurements) to determine a correlation between optimal weight by bioimpedance spectroscopy (Wt-BIS) and clinical assessment (Wt-CA). The accuracy of Wt-BIS [relative overhydration (Rel-OH)] was compared against indicators of fluid status and cardiovascular measures.

    Results: There was poor agreement between Wt-CA and Wt-BIS in children on dialysis (P = 0.01), but not in CKD5 or control subjects. We developed a modified chart to plot Rel-OH against systolic blood pressure (SBP) z-score for the appropriate representation of volume status and blood pressure (BP) in children. In total, 25% of measurements showed SBP >90th percentile but not with concurrent overhydration. Rel-OH correlated with peripheral pulse pressure (P = 0.03; R = 0.3), higher N-terminal pro-brain natriuretic peptide (P = 0.02; R = 0.33) and left ventricular end-diastolic diameter (P = 0.05; R = 0.38). Central aortic mean and pulse pressure significantly associated with the left ventricular end-diastolic diameter (P = 0.03; R = 0.47 and P = 0.01; R = 0.50, respectively), but not with Rel-OH. SBP was positively associated with pulse wave velocity z-score (P = 0.04). In total, 40% of children on haemodialysis and 30% on peritoneal dialysis had increased left ventricular mass index.

    Conclusions: BIS provides an objective method for the assessment of hydration status in children on dialysis. We noted a marked discrepancy between BP and hydration status in children on dialysis that warrants further investigation.

    Matched MeSH terms: Blood Pressure*; Blood Pressure Determination
  18. Htet AS, Kjøllesdal MK, Aung WP, Moe Myint AN, Aye WT, Wai MM, et al.
    BMJ Open, 2017 Nov 15;7(11):e017465.
    PMID: 29146640 DOI: 10.1136/bmjopen-2017-017465
    OBJECTIVE: The first is to estimate the prevalence of dyslipidaemia (hypercholesterolaemia, hypertriglyceridaemia, high low-density lipoprotein (LDL) level and low high-density lipoprotein (HDL) level), as well as the mean levels of total cholesterol, triglyceride, LDL and HDL, in the urban and rural Yangon Region, Myanmar. The second is to investigate the association between urban-rural location and total cholesterol.

    DESIGN: Two cross-sectional studies using the WHO STEPS methodology.

    SETTING: Both the urban and rural areas of the Yangon Region, Myanmar.

    PARTICIPANTS: A total of 1370 men and women aged 25-74 years participated based on a multistage cluster sampling. Physically and mentally ill people, monks, nuns, soldiers and institutionalised people were excluded.

    RESULTS: Compared with rural counterparts, urban dwellers had a significantly higher age-standardised prevalence of hypercholesterolaemia (50.7% vs 41.6%; p=0.042) and a low HDL level (60.6% vs 44.4%; p=0.001). No urban-rural differences were found in the prevalence of hypertriglyceridaemia and high LDL. Men had a higher age-standardised prevalence of hypertriglyceridaemia than women (25.1% vs 14.8%; p<0.001), while the opposite pattern was found in the prevalence of a high LDL (11.3% vs 16.3%; p=0.018) and low HDL level (35.3% vs 70.1%; p<0.001).Compared with rural inhabitants, urban dwellers had higher age-standardised mean levels of total cholesterol (5.31 mmol/L, SE: 0.044 vs 5.05 mmol/L, 0.068; p=0.009), triglyceride (1.65 mmol/L, 0.049 vs 1.38 mmol/L, 0.078; p=0.017), LDL (3.44 mmol/L, 0.019 vs 3.16 mmol/L, 0.058; p=0.001) and lower age-standardised mean levels of HDL (1.11 mmol/L, 0.010 vs 1.25 mmol/L, 0.012; p<0.001). In linear regression, the total cholesterol was significantly associated with an urban location among men, but not among women.

    CONCLUSION: The mean level of total cholesterol and the prevalence of hypercholesterolaemia were alarmingly high in men and women in both the urban and rural areas of Yangon Region, Myanmar. Preventive measures to reduce cholesterol levels in the population are therefore needed.

    Matched MeSH terms: Cholesterol/blood*; Triglycerides/blood*
  19. Md Ralib A, Mat Nor MB
    Asia Pac J Clin Nutr, 2018 2 1;27(2):329-335.
    PMID: 29384319 DOI: 10.6133/apjcn.062017.09
    BACKGROUND AND OBJECTIVES: Refeeding hypophosphataemia (RH) is characterized by an acute electrolyte derangement following nutrition therapy. Complications associated include heart failure, respiratory failure, paraesthesia, seizure and death. We aim to assess its incidence, risk factors, and outcome in our local intensive care unit (ICU).

    METHODS AND STUDY DESIGN: A prospective observational cohort study was conducted at the mixed medical- surgical of a tertiary ICU in Kuantan, Malaysia. The study was registered under the National Medical Research Register (NMRR-14-803-19813) and has received ethical approval. Inclusion criteria include adult admission longer than 48 hours who were started on enteral feeding. Chronic renal failure patients and those receiving dialysis were excluded. RH was defined as plasma phosphate less than 0.65 mmol/L and a drop of more than 0.16 mmol/L following feeding.

    RESULTS: A total of 109 patients were recruited, of which 44 (42.6%) had RH. Patients with RH had higher SOFA score compared to those without (p=0.04). There were no differences in the APACHE II and NUTRIC scores. Serum albumin was lower in those with RH (p=0.04). After refeeding, patients with RH had lower serum phosphate, magnesium and albumin, and higher supplementation of phosphate, potassium and calcium. There were no differences in mortality, length of hospital or ICU stay.

    CONCLUSIONS: Refeeding hypophosphataemia occurs in almost half of ICU admission. Risk factors for refeeding include high organ failure score and low albumin. Refeeding was associated with imbalances in phosphate, magnesium, potassium and calcium. Future larger study may further investigate these risk factors and long-term outcomes.

    Matched MeSH terms: Electrolytes/blood; Phosphates/blood*
  20. Ravishankar D, Salamah M, Akimbaev A, Williams HF, Albadawi DAI, Vaiyapuri R, et al.
    Sci Rep, 2018 Jun 22;8(1):9528.
    PMID: 29934595 DOI: 10.1038/s41598-018-27809-z
    Flavonoids exert innumerable beneficial effects on cardiovascular health including the reduction of platelet activation, and thereby, thrombosis. Hence, flavonoids are deemed to be a molecular template for the design of novel therapeutic agents for various diseases including thrombotic conditions. However, the structure-activity relationships of flavonoids with platelets is not fully understood. Therefore, this study aims to advance the current knowledge on structure-activity relationships of flavonoids through a systematic analysis of structurally-related flavones. Here, we investigated a panel of 16 synthetic flavones containing hydroxy or methoxy groups at C-7,8 positions on the A-ring, with a phenyl group or its bioisosteres as the B-ring, along with their thio analogues possessing a sulfur molecule at the 4th carbon position of the C-ring. The antiplatelet efficacies of these compounds were analysed using human isolated platelets upon activation with cross-linked collagen-related peptide by optical aggregometry. The results demonstrate that the hydroxyl groups in flavonoids are important for optimum platelet inhibitory activities. In addition, the 4-C=O and B ring phenyl groups are less critical for the antiplatelet activity of these flavonoids. This structure-activity relationship of flavonoids with the modulation of platelet function may guide the design, optimisation and development of flavonoid scaffolds as antiplatelet agents.
    Matched MeSH terms: Blood Platelets/drug effects; Blood Platelets/physiology
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