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Fulltext Trace metals contamination potential and health risk assessment of commonly consumed fish of Perak River, Malaysia

Salam MA, Paul SC, Zain RAMM, Bhowmik S, Nath MR, Siddiqua SA, et al.

PLoS One, 2020;15(10):e0241320.
PMID: 33104734 DOI: 10.1371/journal.pone.0241320

The rapid growth of industrial and agricultural activities in Malaysia are leading to the impairment of most of the rivers in recent years through realising various trace metals. This leads to toxicity, particularly when the toxic has entered the food chain. Perak River is one of the most dynamic rivers for the Malaysian population. Therefore, in consideration of the safety issue, this study was conducted to assess the concentration of such metals (Cd, Cu, Zn, Fe, and Pb) in the muscles of most widely consumed fish species (Barbonymus schwanenfeldii, Puntius bulum, Puntius daruphani, Hexanematichthys sagor, Channa striatus, Mystacoleucus marginatus, and Devario regina) from different locations of Perak River, Malaysia by employing inductively coupled plasma optical emission spectroscopy (ICP-OES). Among the trace metals, Fe and Cd were found to be the highest (29.33-148.01 μg/g) and lowest (0.16-0.49 μg/g) concentration in all of the studied species, respectively. Although the estimated daily intakes (μg/kg/day) of Cd (0.65-0.85), Fe (79.27-352.00) and Pb (0.95-12.17) were higher than their reference, the total target hazard quotients values suggested that the local residents would not experience any adverse health effects from its consumption. In contrast, the target cancer risk value suggested that all fish species posed a potential cancer risk due to Cd and cumulative cancer risk values, strongly implying that continuous consumption of studied fish species would cause cancer development to its consumers.
Fulltext The genetic legacy of continental scale admixture in Indian Austroasiatic speakers

Tätte K, Pagani L, Pathak AK, Kõks S, Ho Duy B, Ho XD, et al.

Sci Rep, 2019 03 07;9(1):3818.
PMID: 30846778 DOI: 10.1038/s41598-019-40399-8

Surrounded by speakers of Indo-European, Dravidian and Tibeto-Burman languages, around 11 million Munda (a branch of Austroasiatic language family) speakers live in the densely populated and genetically diverse South Asia. Their genetic makeup holds components characteristic of South Asians as well as Southeast Asians. The admixture time between these components has been previously estimated on the basis of archaeology, linguistics and uniparental markers. Using genome-wide genotype data of 102 Munda speakers and contextual data from South and Southeast Asia, we retrieved admixture dates between 2000-3800 years ago for different populations of Munda. The best modern proxies for the source populations for the admixture with proportions 0.29/0.71 are Lao people from Laos and Dravidian speakers from Kerala in India. The South Asian population(s), with whom the incoming Southeast Asians intermixed, had a smaller proportion of West Eurasian genetic component than contemporary proxies. Somewhat surprisingly Malaysian Peninsular tribes rather than the geographically closer Austroasiatic languages speakers like Vietnamese and Cambodians show highest sharing of IBD segments with the Munda. In addition, we affirmed that the grouping of the Munda speakers into North and South Munda based on linguistics is in concordance with genome-wide data.
Treatment of chronic airway diseases using nutraceuticals: Mechanistic insight

Allam VSRR, Chellappan DK, Jha NK, Shastri MD, Gupta G, Shukla SD, et al.

Crit Rev Food Sci Nutr, 2021 May 12.
PMID: 33977840 DOI: 10.1080/10408398.2021.1915744

Respiratory diseases, both acute and chronic, are reported to be the leading cause of morbidity and mortality, affecting millions of people globally, leading to high socio-economic burden for the society in the recent decades. Chronic inflammation and decline in lung function are the common symptoms of respiratory diseases. The current treatment strategies revolve around using appropriate anti-inflammatory agents and bronchodilators. A range of anti-inflammatory agents and bronchodilators are currently available in the market; however, the usage of such medications is limited due to the potential for various adverse effects. To cope with this issue, researchers have been exploring various novel, alternative therapeutic strategies that are safe and effective to treat respiratory diseases. Several studies have been reported on the possible links between food and food-derived products in combating various chronic inflammatory diseases. Nutraceuticals are examples of such food-derived products which are gaining much interest in terms of its usage for the well-being and better human health. As a consequence, intensive research is currently aimed at identifying novel nutraceuticals, and there is an emerging notion that nutraceuticals can have a positive impact in various respiratory diseases. In this review, we discuss the efficacy of nutraceuticals in altering the various cellular and molecular mechanisms involved in mitigating the symptoms of respiratory diseases.
Responses of pro-inflammatory cytokines, acute phase proteins and cytological analysis in serum and cerebrospinal fluid during haemorrhagic septicaemia infection in buffaloes

Chung ELT, Jesse FFA, Marza AD, Ibrahim HH, Abba Y, Zamri-Saad M, et al.

Trop Anim Health Prod, 2019 Jul;51(6):1773-1782.
PMID: 30919320 DOI: 10.1007/s11250-019-01870-w

Sudden death is usually the main finding in field animals during haemorrhagic septicaemia outbreaks caused by Pasteurella multocida type B:2 that causes acute, fatal and septicaemic disease in cattle and buffaloes. This situation may be due to failure in early detection of the disease where early treatment of antibiotics may improve the prognosis of the animal and other surviving animals. Thus, there is a grey area on the knowledge on the potential usage of pro-inflammatory cytokines and acute phase proteins as early biomarkers in the diagnosis of haemorrhagic septicaemia. In addition, exploration of the cerebrospinal fluid during infection has never been studied before. Therefore, this study was designed to fill up the grey areas in haemorrhagic septicaemia research. Twenty-one buffalo calves were divided into seven treatment groups where group 1 was inoculated orally with 10 mL of sterile phosphate-buffered saline pH 7 which act as a negative control group. Groups 2 and 3 were inoculated orally and subcutaneously with 10 mL of 1012 colony-forming unit of P. multocida type B:2. Group 4 and 5 buffaloes were inoculated orally and intravenously with 10 mL of lipopolysaccharide broth. Groups 6 and 7 were administered orally and subcutaneously with 10 mL of outer membrane protein broth. During the post-infection period of 21 days, blood and cerebrospinal fluid were sampled for the analyses of pro-inflammatory cytokines, acute phase proteins and cytological examination. Buffalo calves infected with P. multocida and its immunogens via different routes of inoculation showed significant changes (p
Increasing complexity and interactions of oxidative stress in chronic respiratory diseases: An emerging need for novel drug delivery systems

Dua K, Malyla V, Singhvi G, Wadhwa R, Krishna RV, Shukla SD, et al.

Chem Biol Interact, 2019 Feb 01;299:168-178.
PMID: 30553721 DOI: 10.1016/j.cbi.2018.12.009

Oxidative stress is intensely involved in enhancing the severity of various chronic respiratory diseases (CRDs) including asthma, chronic obstructive pulmonary disease (COPD), infections and lung cancer. Even though there are various existing anti-inflammatory therapies, which are not enough to control the inflammation caused due to various contributing factors such as anti-inflammatory genes and antioxidant enzymes. This leads to an urgent need of novel drug delivery systems to combat the oxidative stress. This review gives a brief insight into the biological factors involved in causing oxidative stress, one of the emerging hallmark feature in CRDs and particularly, highlighting recent trends in various novel drug delivery carriers including microparticles, microemulsions, microspheres, nanoparticles, liposomes, dendrimers, solid lipid nanocarriers etc which can help in combating the oxidative stress in CRDs and ultimately reducing the disease burden and improving the quality of life with CRDs patients. These carriers improve the pharmacokinetics and bioavailability to the target site. However, there is an urgent need for translational studies to validate the drug delivery carriers for clinical administration in the pulmonary clinic.
Genomic diversity and genome-wide association analysis related to yield and fatty acid composition of wild American oil palm

Ithnin M, Vu WT, Shin MG, Suryawanshi V, Sherbina K, Zolkafli SH, et al.

Plant Sci, 2021 Mar;304:110731.
PMID: 33568284 DOI: 10.1016/j.plantsci.2020.110731

Existing Elaeis guineensis cultivars lack sufficient genetic diversity due to extensive breeding. Harnessing variation in wild crop relatives is necessary to expand the breadth of agronomically valuable traits. Using RAD sequencing, we examine the natural diversity of wild American oil palm populations (Elaeis oleifera), a sister species of the cultivated Elaeis guineensis oil palm. We genotyped 192 wild E. oleifera palms collected from seven Latin American countries along with four cultivated E. guineensis palms. Honduras, Costa Rica, Panama and Colombia palms are panmictic and genetically similar. Genomic patterns of diversity suggest that these populations likely originated from the Amazon Basin. Despite evidence of a genetic bottleneck and high inbreeding observed in these populations, there is considerable genetic and phenotypic variation for agronomically valuable traits. Genome-wide association revealed several candidate genes associated with fatty acid composition along with vegetative and yield-related traits. These observations provide valuable insight into the geographic distribution of diversity, phenotypic variation and its genetic architecture that will guide choices of wild genotypes for crop improvement.
Fulltext Circulating fatty acid profiles are associated with protein energy wasting in maintenance hemodialysis patients: a cross-sectional study

Khor BH, Sahathevan S, Sualeheen A, Ali MSM, Narayanan SS, Chinna K, et al.

Sci Rep, 2021 01 14;11(1):1416.
PMID: 33446880 DOI: 10.1038/s41598-020-80812-1

The metabolic impact of circulating fatty acids (FAs) in patients requiring hemodialysis (HD) is unknown. We investigated the associations between plasma triglyceride (TG) FAs and markers of inflammation, insulin resistance, nutritional status and body composition. Plasma TG-FAs were measured using gas chromatography in 341 patients on HD (age = 55.2 ± 14.0 years and 54.3% males). Cross-sectional associations of TG-FAs with 13 markers were examined using multivariate linear regression adjusted for potential confounders. Higher levels of TG saturated fatty acids were associated with greater body mass index (BMI, r = 0.230), waist circumference (r = 0.203), triceps skinfold (r = 0.197), fat tissue index (r = 0.150), serum insulin (r = 0.280), and homeostatic model assessment of insulin resistance (r = 0.276), but lower malnutrition inflammation score (MIS, r = - 0.160). Greater TG monounsaturated fatty acid levels were associated with lower lean tissue index (r = - 0.197) and serum albumin (r = - 0.188), but higher MIS (r = 0.176). Higher levels of TG n-3 polyunsaturated fatty acids (PUFAs) were associated with lower MIS (r = - 0.168) and interleukin-6 concentrations (r = - 0.115). Higher levels of TG n-6 PUFAs were associated with lower BMI (r = - 0.149) but greater serum albumin (r = 0.112). In conclusion, TG monounsaturated fatty acids were associated with poor nutritional status, while TG n-3 PUFAs were associated with good nutritional status. On the other hand, TG saturated fatty acids and TG n-6 PUFAs had both favorable and unfavorable associations with nutritional parameters.
Fulltext Associations between the indoor microbiome, environmental characteristics and respiratory infections in junior high school students of Johor Bahru, Malaysia

Fu X, Yuan Q, Zhu X, Li Y, Meng Y, Hashim JH, et al.

Environ Sci Process Impacts, 2021 Aug 01;23(8):1171-1181.
PMID: 34278392 DOI: 10.1039/d1em00115a

Pathogens are commonly present in the human respiratory tract, but symptoms are varied among individuals. The interactions between pathogens, commensal microorganisms and host immune systems are important in shaping the susceptibility, development and severity of respiratory diseases. Compared to the extensive studies on the human microbiota, few studies reported the association between indoor microbiome exposure and respiratory infections. In this study, 308 students from 21 classrooms were randomly selected to survey the occurrence of respiratory infections in junior high schools of Johor Bahru, Malaysia. Vacuum dust was collected from the floor, chairs and desks of these classrooms, and high-throughput amplicon sequencing (16S rRNA and ITS) and quantitative PCR were conducted to characterize the absolute concentration of the indoor microorganisms. Fifteen bacterial genera in the classes Actinobacteria, Alphaproteobacteria, and Cyanobacteria were protectively associated with respiratory infections (p < 0.01), and these bacteria were mainly derived from the outdoor environment. Previous studies also reported that outdoor environmental bacteria were protectively associated with chronic respiratory diseases, such as asthma, but the genera identified were different between acute and chronic respiratory diseases. Four fungal genera from Ascomycota, including Devriesia, Endocarpon, Sarcinomyces and an unclassified genus from Herpotrichillaceae, were protectively associated with respiratory infections (p < 0.01). House dust mite (HDM) allergens and outdoor NO2 concentration were associated with respiratory infections and infection-related microorganisms. A causal mediation analysis revealed that the health effects of HDM and NO2 were partially or fully mediated by the indoor microorganisms. This is the first study to explore the association between environmental characteristics, microbiome exposure and respiratory infections in a public indoor environment, expanding our understanding of the complex interactions among these factors.
Fulltext Discovery of New Genes Involved in Curli Production by a Uropathogenic Escherichia coli Strain from the Highly Virulent O45:K1:H7 Lineage

Nhu NTK, Phan MD, Peters KM, Lo AW, Forde BM, Min Chong T, et al.

mBio, 2018 08 21;9(4).
PMID: 30131362 DOI: 10.1128/mBio.01462-18

Curli are bacterial surface-associated amyloid fibers that bind to the dye Congo red (CR) and facilitate uropathogenic Escherichia coli (UPEC) biofilm formation and protection against host innate defenses. Here we sequenced the genome of the curli-producing UPEC pyelonephritis strain MS7163 and showed it belongs to the highly virulent O45:K1:H7 neonatal meningitis-associated clone. MS7163 produced curli at human physiological temperature, and this correlated with biofilm growth, resistance of sessile cells to the human cationic peptide cathelicidin, and enhanced colonization of the mouse bladder. We devised a forward genetic screen using CR staining as a proxy for curli production and identified 41 genes that were required for optimal CR binding, of which 19 genes were essential for curli synthesis. Ten of these genes were novel or poorly characterized with respect to curli synthesis and included genes involved in purine de novo biosynthesis, a regulator that controls the Rcs phosphorelay system, and a novel repressor of curli production (referred to as rcpA). The involvement of these genes in curli production was confirmed by the construction of defined mutants and their complementation. The mutants did not express the curli major subunit CsgA and failed to produce curli based on CR binding. Mutation of purF (the first gene in the purine biosynthesis pathway) and rcpA also led to attenuated colonization of the mouse bladder. Overall, this work has provided new insight into the regulation of curli and the role of these amyloid fibers in UPEC biofilm formation and pathogenesis.IMPORTANCE Uropathogenic Escherichia coli (UPEC) strains are the most common cause of urinary tract infection, a disease increasingly associated with escalating antibiotic resistance. UPEC strains possess multiple surface-associated factors that enable their colonization of the urinary tract, including fimbriae, curli, and autotransporters. Curli are extracellular amyloid fibers that enhance UPEC virulence and promote biofilm formation. Here we examined the function and regulation of curli in a UPEC pyelonephritis strain belonging to the highly virulent O45:K1:H7 neonatal meningitis-associated clone. Curli expression at human physiological temperature led to increased biofilm formation, resistance of sessile cells to the human cationic peptide LL-37, and enhanced bladder colonization. Using a comprehensive genetic screen, we identified multiple genes involved in curli production, including several that were novel or poorly characterized with respect to curli synthesis. In total, this study demonstrates an important role for curli as a UPEC virulence factor that promotes biofilm formation, resistance, and pathogenesis.
Quantification of blue carbon in seagrass ecosystems of Southeast Asia and their potential for climate change mitigation

Stankovic M, Ambo-Rappe R, Carly F, Dangan-Galon F, Fortes MD, Hossain MS, et al.

Sci Total Environ, 2021 Aug 20;783:146858.
PMID: 34088119 DOI: 10.1016/j.scitotenv.2021.146858

Seagrasses have the ability to contribute towards climate change mitigation, through large organic carbon (Corg) sinks within their ecosystems. Although the importance of blue carbon within these ecosystems has been addressed in some countries of Southeast Asia, the regional and national inventories with the application of nature-based solutions are lacking. In this study, we aim to estimate national coastal blue carbon stocks in the seagrass ecosystems in the countries of Southeast Asia including the Andaman and Nicobar Islands of India. This study further assesses the potential of conservation and restoration practices and highlights the seagrass meadows as nature-based solution for climate change mitigation. The average value of the total carbon storage within seagrass meadows of this region is 121.95 ± 76.11 Mg ha-1 (average ± SD) and the total Corg stock of the seagrass meadows of this region was 429.11 ± 111.88 Tg, with the highest Corg stock in the Philippines (78%). The seagrass meadows of this region have the capacity to accumulate 5.85-6.80 Tg C year-1, which accounts for $214.6-249.4 million USD. Under the current rate of decline of 2.82%, the seagrass meadows are emitting 1.65-2.08 Tg of CO2 year-1 and the economic value of these losses accounts for $21.42-24.96 million USD. The potential of the seagrass meadows to the offset current CO2 emissions varies across the region, with the highest contribution to offset is in the seagrass meadows of the Philippines (11.71%). Current national policies and commitments of nationally determined contributions do not include blue carbon ecosystems as climate mitigation measures, even though these ecosystems can contribute up to 7.03% of the countries' reduction goal of CO2 emissions by 2030. The results of this study highlight and promote the potential of the southeast Asian seagrass meadows to national and international agencies as a practical scheme for nature-based solutions for climate change mitigation.
Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial

Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im SA, Yusof MM, et al.

Lancet, 2020 12 05;396(10265):1817-1828.
PMID: 33278935 DOI: 10.1016/S0140-6736(20)32531-9

BACKGROUND: Pembrolizumab monotherapy showed durable antitumour activity and manageable safety in patients with metastatic triple-negative breast cancer. We aimed to examine whether the addition of pembrolizumab would enhance the antitumour activity of chemotherapy in patients with metastatic triple-negative breast cancer.
METHODS: In this randomised, placebo-controlled, double-blind, phase 3 trial, done in 209 sites in 29 countries, we randomly assigned patients 2:1 with untreated locally recurrent inoperable or metastatic triple-negative breast cancer using a block method (block size of six) and an interactive voice-response system with integrated web-response to pembrolizumab (200 mg) every 3 weeks plus chemotherapy (nab-paclitaxel; paclitaxel; or gemcitabine plus carboplatin) or placebo plus chemotherapy. Randomisation was stratified by type of on-study chemotherapy (taxane or gemcitabine-carboplatin), PD-L1 expression at baseline (combined positive score [CPS] ≥1 or <1), and previous treatment with the same class of chemotherapy in the neoadjuvant or adjuvant setting (yes or no). Eligibility criteria included age at least 18 years, centrally confirmed triple-negative breast cancer; at least one measurable lesion; provision of a newly obtained tumour sample for determination of triple-negative breast cancer status and PD-L1 status by immunohistochemistry at a central laboratory; an Eastern Cooperative Oncology Group performance status score 0 or 1; and adequate organ function. The sponsor, investigators, other study site staff (except for the unmasked pharmacist), and patients were masked to pembrolizumab versus saline placebo administration. In addition, the sponsor, the investigators, other study site staff, and patients were masked to patient-level tumour PD-L1 biomarker results. Dual primary efficacy endpoints were progression-free survival and overall survival assessed in the PD-L1 CPS of 10 or more, CPS of 1 or more, and intention-to-treat populations. The definitive assessment of progression-free survival was done at this interim analysis; follow-up to assess overall survival is continuing. For progression-free survival, a hierarchical testing strategy was used, such that testing was done first in patients with CPS of 10 or more (prespecified statistical criterion was α=0·00411 at this interim analysis), then in patients with CPS of 1 or more (α=0·00111 at this interim analysis, with partial alpha from progression-free survival in patients with CPS of 10 or more passed over), and finally in the intention-to-treat population (α=0·00111 at this interim analysis). This study is registered with ClinicalTrials.gov, NCT02819518, and is ongoing.
FINDINGS: Between Jan 9, 2017, and June 12, 2018, of 1372 patients screened, 847 were randomly assigned to treatment, with 566 patients in the pembrolizumab-chemotherapy group and 281 patients in the placebo-chemotherapy group. At the second interim analysis (data cutoff, Dec 11, 2019), median follow-up was 25·9 months (IQR 22·8-29·9) in the pembrolizumab-chemotherapy group and 26·3 months (22·7-29·7) in the placebo-chemotherapy group. Among patients with CPS of 10 or more, median progression-free survival was 9·7 months with pembrolizumab-chemotherapy and 5·6 months with placebo-chemotherapy (hazard ratio [HR] for progression or death, 0·65, 95% CI 0·49-0·86; one-sided p=0·0012 [primary objective met]). Median progression-free survival was 7·6 and 5·6 months (HR, 0·74, 0·61-0·90; one-sided p=0·0014 [not significant]) among patients with CPS of 1 or more and 7·5 and 5·6 months (HR, 0·82, 0·69-0·97 [not tested]) among the intention-to-treat population. The pembrolizumab treatment effect increased with PD-L1 enrichment. Grade 3-5 treatment-related adverse event rates were 68% in the pembrolizumab-chemotherapy group and 67% in the placebo-chemotherapy group, including death in <1% in the pembrolizumab-chemotherapy group and 0% in the placebo-chemotherapy group.
INTERPRETATION: Pembrolizumab-chemotherapy showed a significant and clinically meaningful improvement in progression-free survival versus placebo-chemotherapy among patients with metastatic triple-negative breast cancer with CPS of 10 or more. These findings suggest a role for the addition of pembrolizumab to standard chemotherapy for the first-line treatment of metastatic triple-negative breast cancer.
FUNDING: Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc.
Fulltext Prevalence, reasons, and determinants of dietary supplements use among undergraduate female students of health and non-health colleges in a Saudi public university

Islam MA, Al-Karasneh AF, Rizvi M, Nisa ZU, Albakheet AM, Alshagawi MA, et al.

PLoS One, 2021;16(3):e0247295.
PMID: 33657129 DOI: 10.1371/journal.pone.0247295

PURPOSE: The aim of this study was to gather data from female students studying in both health and non-health colleges at Imam Abdulrahman Bin Faisal University and report the prevalence, reasons, and determinants of dietary supplements use.
METHODS: A month-long cross-sectional study was conducted in health and non-health colleges affiliated to Imam Abdulrahman Bin Faisal University in Dammam, Saudi Arabia. Convenient sampling was employed, and the data was gathered through an online survey using the English and Arabic versions of the Dietary Supplement Questionnaire (DSQ). The data was analyzed using SPSS version 23 and Medcalc. The study was approved by an ethics committee.
RESULTS: Data from 545 participants was collected. The overall prevalence of dietary supplement use was 32.7% (95% CI: 29.06%- 36.51%). The prevalence was 29.77% (95% CI: 25.29%- 34.56%) among students at all health colleges combined and, it was 37.50% (95% CI: 31.36%- 43.96%) among students at all non-health colleges. Most students used a brand product, spent a monthly cost of SAR 286 (USD 76.3) on supplements and agreed that supplements were good for health (N = 392, 71.9%). Students from non-health- colleges agreed that dietary supplements are good for health in greater numbers as compared to non-health college students (p < 0.001). Students aged ≥ 20 years, studying in a non-health college and up to 3rd year of study, were more 2 times more likely to agree that dietary supplements are good for health.
CONCLUSION: Supplements were commonly used among female students at this university however, it was quite low as compared to students from other local and regional universities. Prevalence was higher in non-health colleges as compared to health colleges and the most commonly used supplements were brand products and, multivitamins, used for general health and well-being. This highlights the inclination of students towards supplement use.
Fulltext Assessment of quality of work life (QWL) among healthcare staff of intensive care unit (ICU) and emergency unit during COVID-19 outbreak using WHOQoL-BREF

Bilal Maqsood M, Ashraful Islam M, Zeb-Un-Nisa, Abbas Naqvi A, Al Qarni A, Fuad Al-Karasneh A, et al.

Saudi Pharm J, 2021 Sep 20.
PMID: 34566456 DOI: 10.1016/j.jsps.2021.09.002

Objective: The study aimed to document the quality of work life (QWL) among healthcare staff of intensive care unit (ICU) and emergency unit during COVID-19 outbreak using WHOQoL-BREF.
Methods: A multicenter cross-sectional study was conducted for two months (May - June 2020) among healthcare staff working in intensive care units (ICUs) and emergency units of the hospitals under National Guard Health Authority (NGHA) across five cities of Saudi Arabia. The study used the WHOQoL-BREF instrument to document the QWL through an electronic institutional survey. The data was analyzed through IBM SPSS version 23. The study was approved by an ethics committee.
Results: A total of 290 healthcare professionals responded to the survey. The mean overall quality of life score was 3.37 ± 0.97, general health = 3.66 ± 0.88, domains, i.e., physical = 11.67 ± 2.16, psychological = 13.08 ± 2.14, social = 13.22 ± 3.31 and environment = 12.38 ± 2.59. Respondents aged > 40 years, male gender, married status, being a physician and, having a work experience > 15 years and no extra working hours, had higher mean scores for several domains of Quality of life (QoL), overall QoL and general health (p < 0.05).
Conclusion: The QWL among healthcare staff during COVID-19 pandemic was low. Demographic factors were mainly the determinants for a higher QWL while extra working hours was determinant of lower QWL. Despite the pandemic, no COVID-19 related variable affected the work life of healthcare staff.
Fulltext Reproductive hormonal variations and adenohypophyseal lesions in pre-pubertal buffalo heifers inoculated with Pasteurella multocida type B: 2 and its immunogens

Jesse FF, Ibrahim HH, Abba Y, Chung EL, Marza AD, Mazlan M, et al.

BMC Vet Res, 2017 Apr 05;13(1):88.
PMID: 28381248 DOI: 10.1186/s12917-017-1010-y

BACKGROUND: Hemorrhagic septicemia is a fatal disease of cattle and buffaloes caused by P. multocida. Although the pathogenesis of the bacteria has been well established in literature, there is a paucity of information on the possible role of the bacteria and its immunogens; lipopolysaccharide (LPS) and outer membrane proteins (OMPs) on the reproductive capacity of buffalo heifers.
METHODS: In this study, twenty one healthy prepubertal female buffaloes aged 8 months were divided into seven groups of 3 buffaloes each (G1-G7). Group 1 (G1) served as the negative control group and were inoculated orally with 10 mL sterile Phosphate Buffer Saline (PBS), groups 2 (G2) and 3 (G3) were inoculated orally and subcutaneously with 10 mL of 10(12) colony forming unit (cfu) of P.multocida type B: 2, while groups 4 (G4) and 5 (G5) received 10 mL of bacterial LPS orally and intravenously, respectively. Lastly, groups 6 (G6) and 7 (G7) were orally and subcutaneously inoculated with 10 mL of bacterial OMPs. Whole blood was collected in EDTA vials at stipulated time points (0, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, 360, 408, 456 and 504 h), while tissue sections of the pituitary glands were collected and transported to the histopathology laboratory in 10% buffered formalin for processing and Hematoxylin and eosin staining. Plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), progesterone (PG), estradiol (EST) and gonadotrophin releasing hormone (GnRH) were determined.
RESULTS: The histopathological lesions observed in the pituitary gland included hemorrhage, congestion, inflammatory cell infiltration, hydropic degeneration, necrosis and edema. These changes were higher (p
Fulltext Genotype-guided versus traditional clinical dosing of warfarin in patients of Asian ancestry: a randomized controlled trial

Syn NL, Wong AL, Lee SC, Teoh HL, Yip JWL, Seet RC, et al.

BMC Med, 2018 07 10;16(1):104.
PMID: 29986700 DOI: 10.1186/s12916-018-1093-8

BACKGROUND: Genotype-guided warfarin dosing has been shown in some randomized trials to improve anticoagulation outcomes in individuals of European ancestry, yet its utility in Asian patients remains unresolved.
METHODS: An open-label, non-inferiority, 1:1 randomized trial was conducted at three academic hospitals in South East Asia, involving 322 ethnically diverse patients newly indicated for warfarin (NCT00700895). Clinical follow-up was 90 days. The primary efficacy measure was the number of dose titrations within the first 2 weeks of therapy, with a mean non-inferiority margin of 0.5 over the first 14 days of therapy.
RESULTS: Among 322 randomized patients, 269 were evaluable for the primary endpoint. Compared with traditional dosing, the genotype-guided group required fewer dose titrations during the first 2 weeks (1.77 vs. 2.93, difference -1.16, 90% CI -1.48 to -0.84, P
The ability of lipopolysaccharide (LPS) of Pasteurella multocida B:2 to induce clinical and pathological lesions in the nervous system of buffalo calves following experimental inoculation

Marza AD, Jesse Abdullah FF, Ahmed IM, Teik Chung EL, Ibrahim HH, Zamri-Saad M, et al.

Microb Pathog, 2017 Mar;104:340-347.
PMID: 28126667 DOI: 10.1016/j.micpath.2017.01.031

Lipopolysaccharide (LPS) of P. multocida B:2, a causative agent of haemorrhagic septicaemia (HS) in cattle and buffaloes, is considered as the main virulence factor and contribute in the pathogenesis of the disease. Recent studies provided evidences about the involvement of the nervous system in pathogenesis of HS. However, the role of P. multocida B:2 immunogens, especially the LPS is still uncovered. Therefore, this study was designed to investigate the role of P. multocida B:2 LPS to induce pathological changes in the nervous system. Nine eight-month-old, clinically healthy buffalo calves were used and distributed into three groups. Calves of Group 1 and 2 were inoculated orally and intravenously with 10 ml of LPS broth extract represent 1 × 10(12) cfu/ml of P. multocida B:2, respectively, while calves of Group 3 were inoculated orally with 10 ml of phosphate buffer saline as a control. Significant differences were found in the mean scores for clinical signs, post mortem and histopathological changes especially in Group 2, which mainly affect different anatomic regions of the nervous system, mainly the brain. On the other hand, lower scores have been recorded for clinical signs, gross and histopathological changes in Group 1. These results provide for the first time strong evidence about the ability of P. multocida B:2 LPS to cross the blood brain barrier and induce pathological changes in the nervous system of the affected buffalo calves.
Fulltext Genomic structure and insertion sites of Helicobacter pylori prophages from various geographical origins

Vale FF, Nunes A, Oleastro M, Gomes JP, Sampaio DA, Rocha R, et al.

Sci Rep, 2017 02 16;7:42471.
PMID: 28205536 DOI: 10.1038/srep42471

Helicobacter pylori genetic diversity is known to be influenced by mobile genomic elements. Here we focused on prophages, the least characterized mobile elements of H. pylori. We present the full genomic sequences, insertion sites and phylogenetic analysis of 28 prophages found in H. pylori isolates from patients of distinct disease types, ranging from gastritis to gastric cancer, and geographic origins, covering most continents. The genome sizes of these prophages range from 22.6-33.0 Kbp, consisting of 27-39 open reading frames. A 36.6% GC was found in prophages in contrast to 39% in H. pylori genome. Remarkably a conserved integration site was found in over 50% of the cases. Nearly 40% of the prophages harbored insertion sequences (IS) previously described in H. pylori. Tandem repeats were frequently found in the intergenic region between the prophage at the 3' end and the bacterial gene. Furthermore, prophage genomes present a robust phylogeographic pattern, revealing four distinct clusters: one African, one Asian and two European prophage populations. Evidence of recombination was detected within the genome of some prophages, resulting in genome mosaics composed by different populations, which may yield additional H. pylori phenotypes.
DNA damage and protein oxidation associated with ageing correlate with cognitive dysfunction in a Malaysian population

Abdul Sani NF, Ahmad Damanhuri MH, Amir Hamzah AIZ, Abu Bakar ZH, Tan JK, Nor Aripin KN, et al.

Free Radic Res, 2018 Sep;52(9):1000-1009.
PMID: 30079776 DOI: 10.1080/10715762.2018.1506877

Ageing is associated with increased oxidative stress accompanied by cognitive decline. The aim of this study was to evaluate oxidative stress biomarkers and their possible relationship with cognitive performances during ageing among the Malay population. Approximately 160 healthy Malay adults aged between 28 and 79 years were recruited around Selangor and Klang Valley. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA), forward digit span (FDS), backward digit span (BDS), digit symbol, Rey Auditory Verbal Learning Test immediate recalled [RAVLT(I)] and delayed recalled [RAVLT(D)], and visual reproduction immediate recalled (VR-I) and delayed recalled (VR-II). DNA damage, plasma protein carbonyl and malondialdehyde (MDA) levels were also determined. Cognitive function test showed significant lower scores of MoCA, BDS, RAVLT(I), RAVLT(D), digit symbol, VR-I, and VR-II in the older age group (60 years old) compared with the 30-, 40-, and 50-year-old group. The extent of DNA damage was sequential with age: 60 > 50 > 40 > 30, whereas protein carbonyl was higher in 40-, 50-, and 60-year-old groups compared with the youngest group (30 years old). However, the MDA level was observed unchanged in all age groups. Approximately 21.88% of the participants had cognitive impairment. Multiple logistic regression analysis revealed that DNA damage and protein carbonyl levels are predictors for cognitive impairment in healthy Malays. In conclusion, cognitive decline occurred in healthy adult Malay population at an early age of 30 years old with corresponding higher DNA damage and protein oxidation.
Fulltext Analgesic Activity, Chemical Profiling and Computational Study on Chrysopogon aciculatus

Zihad SMNK, Bhowmick N, Uddin SJ, Sifat N, Rahman MS, Rouf R, et al.

Front Pharmacol, 2018;9:1164.
PMID: 30374304 DOI: 10.3389/fphar.2018.01164

Present study was undertaken to evaluate the analgesic activity of the ethanol extract of Chrysopogon aciculatus. In addition to bioassays in mice, chemical profiling was done by LC-MS and GC-MS to identify phytochemicals, which were further docked on the catalytic site of COX-2 enzymes with a view to suggest the possible role of such phytoconstituents in the observed analgesic activity. Analgesic activity of C. aciculatus was evaluated by acetic acid induced writhing reflex method and hot plate technique. Phytochemical profiling was conducted using liquid chromatography mass spectrometry (LC-MS) and gas chromatography mass spectrometry (GC-MS). In docking studies, homology model of human COX-2 enzyme was prepared using Easy Modeler 4.0 and the identified phytoconstituents were docked using Autodock Vina. Preliminary acute toxicity test of the ethanol extract of C. aciculatus showed no sign of mortality at the highest dose of 4,000 mg/kg. The whole plant extract significantly (p < 0.05) inhibited acetic acid induced writhing in mice at the doses of 500 and 750 mg/kg. The extract delayed the response time in hot plate test in a dose dependent manner. LC-MS analysis of the plant extract revealed the presence of aciculatin, nudaphantin and 5α,8α-epidioxyergosta-6,22-diene-3β-ol. Three compounds namely citronellylisobutyrate; 2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one and nudaphantin were identified in the n-hexane fraction by GC-MS. Among these compounds, six were found to be interacting with the binding site for arachidonic acid in COX-2 enzyme. Present study strongly supports the traditional use of C. aciculatus in the management of pain. In conclusion, compounds (tricin, campesterol, gamma oryzanol, and citronellyl isobutyrate) showing promising binding affinity in docking studies, along with previously known anti-inflammatory compound aciculatin can be held responsible for the observed activity.
Fulltext Diversified lineages and drug-resistance profiles of clinical isolates of Mycobacterium tuberculosis complex in Malaysia

Noorizhab Fakhruzzaman MN, Abidin NZ, Aziz ZA, Lim WF, Richard JJ, Noorliza MN, et al.

Int J Mycobacteriol, 2019 12 4;8(4):320-328.
PMID: 31793500 DOI: 10.4103/ijmy.ijmy_144_19

Background: Tuberculosis (TB) is still a major health problem in Malaysia with thousands of cases reported yearly. This is further burdened with the emergence of multidrug-resistant TB (MDR-TB). Whole-genome sequencing (WGS) provides high-resolution molecular epidemiological data for the accurate determination of Mycobacterium tuberculosis complex (MTBC) lineages and prediction of the drug-resistance patterns. This study aimed to investigate the diversity of MTBC in Malaysia in terms of lineage and drug-resistance patterns of the clinical MTBC isolates using WGS approach.
Methods: The genomes of 24 MTBC isolated from sputum and pus samples were sequenced. The phenotypic drug susceptibility testing (DST) of the isolates was determined for ten anti-TB drugs. Bioinformatic analysis comprising genome assembly and annotation and single-nucleotide polymorphism (SNP) analysis in genes associated with resistance to the ten anti-TB drugs were done on each sequenced genome.
Results: The draft assemblies covered an average of 97% of the expected genome size. Eleven isolates were aligned to the Indo-Oceanic lineage, eight were East-Asian lineage, three were East African-Indian lineage, and one was of Euro-American and Bovis lineages, respectively. Twelve of the 24 MTBC isolates were phenotypically MDR M. tuberculosis: one is polyresistance and another one is monoresistance. Twenty-six SNPs across nine genes associated with resistance toward ten anti-TB drugs were detected where some of the mutations were found in isolates that were previously reported as pan-susceptible using DST. A haplotype consisting of 65 variants was also found among the MTBC isolates with drug-resistance traits.
Conclusions: This study is the first effort done in Malaysia to utilize 24 genomes of the local clinical MTBC isolates. The high-resolution molecular epidemiological data obtained provide valuable insights into the mechanistic and epidemiological qualities of TB within the vicinity of Southeast Asia.

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