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  1. Nor Azman NS, Hossan MS, Nissapatorn V, Uthaipibull C, Prommana P, Jin KT, et al.
    Exp Parasitol, 2018 Nov;194:67-78.
    PMID: 30268422 DOI: 10.1016/j.exppara.2018.09.020
    Treatment of drug resistant protozoa, bacteria, and viruses requires new drugs with alternative chemotypes. Such compounds could be found from Southeast Asian medicinal plants. The present study examines the cytotoxic, antileishmanial, and antiplasmodial effects of 11 ethnopharmacologically important plant species in Malaysia. Chloroform extracts were tested for their toxicity against MRC-5 cells and Leishmania donovani by MTT, and chloroquine-resistant Plasmodium falciparum K1 strain by Histidine-Rich Protein II ELISA assays. None of the extract tested was cytotoxic to MRC-5 cells. Extracts of Uvaria grandiflora, Chilocarpus costatus, Tabernaemontana peduncularis, and Leuconotis eugenifolius had good activities against L. donovani with IC50 
  2. Alhajj MN, Omar R, Khader Y, Celebić A, El Tantawi M, Folayan MO, et al.
    Int Dent J, 2020 Oct;70(5):328-339.
    PMID: 32501563 DOI: 10.1111/idj.12579
    OBJECTIVES: The extent to which dentists are happy with their profession and their life has not been well studied. The present study aimed to explore the level of happiness, satisfaction with life and psychological well-being among a sample of dental professionals from 21 countries.

    MATERIALS AND METHODS: The sample comprised 2,200 dentists from 21 countries. Three scales - Subjective Happiness Scale (SHS), Satisfaction With Life Scale (SWLS), and Affect Balance Scale (ABS) - were used to measure the subjective responses. Data related to demographic and social characteristics were recorded. Mann-Whitney and Kruskal-Wallis tests were used as appropriate. Scales were correlated, and multiple linear regression analyses were employed to identify the independent determinants of SHS, SWLS and ABS. Data were analysed using the SPSS software program; a value of P <0.05 was considered significant.

    RESULTS: The overall mean scores of SHS, SWLS and ABS were 18.53 ± 5.06, 23.06 ± 6.25 and 1.26 ± 2.40, respectively, with significant differences found across countries: dentists working in Croatia, Peru and Serbia recorded the highest scores, unlike dentists practicing in Yemen, Syria, and Iraq, who recorded the lowest scores. There were significant, moderately positive correlations between the various scales: SHS and SWLS: r = 0.535, P 

  3. Armas Rojas NB, Lacey B, Soni M, Charles S, Carter J, Varona-Pérez P, et al.
    BMC Public Health, 2021 05 27;21(1):963.
    PMID: 34039286 DOI: 10.1186/s12889-021-10911-9
    BACKGROUND: Cardiovascular disease accounts for about one-third of all premature deaths (ie, age =120 mmHg), diabetes, and BMI (>=22.5 kg/m2): 20 mmHg higher usual SBP about doubled cardiovascular mortality (RR 2.02, 95%CI 1.88-2.18]), as did diabetes (2.15, 1.95-2.37), and 10 kg/m2 higher usual BMI (1.92, 1.64-2.25). RR were similar in men and in women. The association with BMI and cardiovascular mortality was almost completely attenuated following adjustment for the mediating effect of SBP. Elevated SBP (>=120 mmHg), diabetes and raised BMI (>=22.5 kg/m2) accounted for 27%, 14%, and 16% of cardiovascular deaths, respectively.

    CONCLUSIONS: This large prospective study provides direct evidence for the effects of these major risk factors on cardiovascular mortality in Cuba. Despite comparatively low levels of these risk factors by international standards, the strength of their association with cardiovascular death means they nevertheless exert a substantial impact on premature mortality in Cuba.

  4. Barnett R, Westbury MV, Sandoval-Velasco M, Vieira FG, Jeon S, Zazula G, et al.
    Curr Biol, 2020 Dec 21;30(24):5018-5025.e5.
    PMID: 33065008 DOI: 10.1016/j.cub.2020.09.051
    Homotherium was a genus of large-bodied scimitar-toothed cats, morphologically distinct from any extant felid species, that went extinct at the end of the Pleistocene [1-4]. They possessed large, saber-form serrated canine teeth, powerful forelimbs, a sloping back, and an enlarged optic bulb, all of which were key characteristics for predation on Pleistocene megafauna [5]. Previous mitochondrial DNA phylogenies suggested that it was a highly divergent sister lineage to all extant cat species [6-8]. However, mitochondrial phylogenies can be misled by hybridization [9], incomplete lineage sorting (ILS), or sex-biased dispersal patterns [10], which might be especially relevant for Homotherium since widespread mito-nuclear discrepancies have been uncovered in modern cats [10]. To examine the evolutionary history of Homotherium, we generated a ∼7x nuclear genome and a ∼38x exome from H. latidens using shotgun and target-capture sequencing approaches. Phylogenetic analyses reveal Homotherium as highly divergent (∼22.5 Ma) from living cat species, with no detectable signs of gene flow. Comparative genomic analyses found signatures of positive selection in several genes, including those involved in vision, cognitive function, and energy consumption, putatively consistent with diurnal activity, well-developed social behavior, and cursorial hunting [5]. Finally, we uncover relatively high levels of genetic diversity, suggesting that Homotherium may have been more abundant than the limited fossil record suggests [3, 4, 11-14]. Our findings complement and extend previous inferences from both the fossil record and initial molecular studies, enhancing our understanding of the evolution and ecology of this remarkable lineage.
  5. Rickard CM, Marsh NM, Larsen EN, McGrail MR, Graves N, Runnegar N, et al.
    Lancet, 2021 04 17;397(10283):1447-1458.
    PMID: 33865494 DOI: 10.1016/S0140-6736(21)00351-2
    BACKGROUND: The optimal duration of infusion set use to prevent life-threatening catheter-related bloodstream infection (CRBSI) is unclear. We aimed to compare the effectiveness and costs of 7-day (intervention) versus 4-day (control) infusion set replacement to prevent CRBSI in patients with central venous access devices (tunnelled cuffed, non-tunnelled, peripherally inserted, and totally implanted) and peripheral arterial catheters.

    METHODS: We did a randomised, controlled, assessor-masked trial at ten Australian hospitals. Our hypothesis was CRBSI equivalence for central venous access devices and non-inferiority for peripheral arterial catheters (both 2% margin). Adults and children with expected greater than 24 h central venous access device-peripheral arterial catheter use were randomly assigned (1:1; stratified by hospital, catheter type, and intensive care unit or ward) by a centralised, web-based service (concealed before allocation) to infusion set replacement every 7 days, or 4 days. This included crystalloids, non-lipid parenteral nutrition, and medication infusions. Patients and clinicians were not masked, but the primary outcome (CRBSI) was adjudicated by masked infectious diseases physicians. The analysis was modified intention to treat (mITT). This study is registered with the Australian New Zealand Clinical Trials Registry ACTRN12610000505000 and is complete.

    FINDINGS: Between May 30, 2011, and Dec, 9, 2016, from 6007 patients assessed, we assigned 2944 patients to 7-day (n=1463) or 4-day (n=1481) infusion set replacement, with 2941 in the mITT analysis. For central venous access devices, 20 (1·78%) of 1124 patients (7-day group) and 16 (1·46%) of 1097 patients (4-day group) had CRBSI (absolute risk difference [ARD] 0·32%, 95% CI -0·73 to 1·37). For peripheral arterial catheters, one (0·28%) of 357 patients in the 7-day group and none of 363 patients in the 4-day group had CRBSI (ARD 0·28%, -0·27% to 0·83%). There were no treatment-related adverse events.

    INTERPRETATION: Infusion set use can be safely extended to 7 days with resultant cost and workload reductions.

    FUNDING: Australian National Health and Medical Research Council.

  6. Chellappan DK, Prasher P, Saravanan V, Vern Yee VS, Wen Chi WC, Wong JW, et al.
    Chem Biol Interact, 2022 Jan 05;351:109706.
    PMID: 34662570 DOI: 10.1016/j.cbi.2021.109706
    The challenges and difficulties associated with conventional drug delivery systems have led to the emergence of novel, advanced targeted drug delivery systems. Therapeutic drug delivery of proteins and peptides to the lungs is complicated owing to the large size and polar characteristics of the latter. Nevertheless, the pulmonary route has attracted great interest today among formulation scientists, as it has evolved into one of the important targeted drug delivery platforms for the delivery of peptides, and related compounds effectively to the lungs, primarily for the management and treatment of chronic lung diseases. In this review, we have discussed and summarized the current scenario and recent developments in targeted delivery of proteins and peptide-based drugs to the lungs. Moreover, we have also highlighted the advantages of pulmonary drug delivery over conventional drug delivery approaches for peptide-based drugs, in terms of efficacy, retention time and other important pharmacokinetic parameters. The review also highlights the future perspectives and the impact of targeted drug delivery on peptide-based drugs in the coming decade.
  7. Lorenzo JPP, Sollano MHMZ, Salido EO, Li-Yu J, Tankeh-Torres SA, Wulansari Manuaba IAR, et al.
    Int J Rheum Dis, 2022 Jan;25(1):7-20.
    PMID: 34931463 DOI: 10.1111/1756-185X.14266
    BACKGROUND: Gout is the most prevalent inflammatory arthritis in the Asia-Pacific region and worldwide. This clinical practice guideline (CPG) aims to provide recommendations based on systematically obtained evidence and values and preferences tailored to the unique needs of patients with gout and hyperuricemia in Asia, Australasia, and the Middle East. The target users of these guidelines are general practitioners and specialists, including rheumatologists, in these regions.

    METHODS: Relevant clinical questions were formulated by the Steering Committee. Systematic reviews of evidence were done, and certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation methodology. A multi-sectoral consensus panel formulated the final recommendations.

    RESULTS: The Asia-Pacific League of Associations for Rheumatology Task Force developed this CPG for treatment of gout with 3 overarching principles and 22 recommendation statements that covered the treatment of asymptomatic hyperuricemia (2 statements), treatment of acute gout (4 statements), prophylaxis against gout flare when initiating urate-lowering therapy (3 statements), urate-lowering therapy (3 statements), treatment of chronic tophaceous gout (2 statements), treatment of complicated gout and non-responders (2 statements), treatment of gout with moderate to severe renal impairment (1 statement), and non-pharmacologic interventions (5 statements).

    CONCLUSION: Recommendations for clinically relevant scenarios in the management of gout were formulated to guide physicians in administering individualized care.

  8. Chang AB, Toombs M, Chatfield MD, Mitchell R, Fong SM, Binks MJ, et al.
    Front Pediatr, 2021;9:781168.
    PMID: 35111703 DOI: 10.3389/fped.2021.781168
    Background: Preventing and/or reducing acute lower respiratory infections (ALRIs) in young children will lead to substantial short and long-term clinical benefits. While immunisation with pneumococcal conjugate vaccines (PCV) reduces paediatric ALRIs, its efficacy for reducing infant ALRIs following maternal immunisation has not been studied. Compared to other PCVs, the 10-valent pneumococcal-Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) is unique as it includes target antigens from two common lower airway pathogens, pneumococcal capsular polysaccharides and protein D, which is a conserved H. influenzae outer membrane lipoprotein. Aims: The primary aim of this randomised controlled trial (RCT) is to determine whether vaccinating pregnant women with PHiD-CV (compared to controls) reduces ALRIs in their infants' first year of life. Our secondary aims are to evaluate the impact of maternal PHiD-CV vaccination on different ALRI definitions and, in a subgroup, the infants' nasopharyngeal carriage of pneumococci and H. influenzae, and their immune responses to pneumococcal vaccine type serotypes and protein D. Methods: We are undertaking a parallel, multicentre, superiority RCT (1:1 allocation) at four sites across two countries (Australia, Malaysia). Healthy pregnant Australian First Nation or Malaysian women aged 17-40 years with singleton pregnancies between 27+6 and 34+6 weeks gestation are randomly assigned to receive either a single dose of PHiD-CV or usual care. Treatment allocation is concealed. Study outcome assessors are blinded to treatment arms. Our primary outcome is the rate of medically attended ALRIs by 12-months of age. Blood and nasopharyngeal swabs are collected from infants at birth, and at ages 6- and 12-months (in a subset). Our planned sample size (n = 292) provides 88% power (includes 10% anticipated loss to follow-up). Discussion: Results from this RCT potentially leads to prevention of early and recurrent ALRIs and thus preservation of lung health during the infant's vulnerable period when lung growth is maximum. The multicentre nature of our study increases the generalisability of its future findings and is complemented by assessing the microbiological and immunological outcomes in a subset of infants. Clinical Trial Registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374381, identifier: ACTRN12618000150246.
  9. Ho LY, Chu PS, Consigliere DT, Zainuddin ZM, Bolong D, Chan CK, et al.
    World J Urol, 2018 Jan;36(1):79-86.
    PMID: 29051978 DOI: 10.1007/s00345-017-2097-2
    PURPOSE: The overall objective of the survey was to systematically examine patients' perspectives on lower urinary tract symptoms (LUTS) and their treatment in Southeast Asia.
    METHODS: A multinational cross-sectional survey involving adult men seeking consultation at urology outpatient clinics because of LUTS in Southeast Asia was conducted using convenience sampling. Self-reported prevalence, bother, treatment and treatment satisfaction of selected LUTS including urgency, nocturia, slow stream, and post-micturition dribble were evaluated.
    RESULTS: In total, 1535 eligible patients were enrolled in the survey. A majority of respondents were aged 56-75 years, not employed, and had not undergone prostate operation before. Overall, the self-reported prevalence of nocturia was 88% (95% CI 86-90%), slow stream 61% (95% CI 59-63%), post micturition dribble 55% (95% CI 52-58%), and urgency 52% (95% CI 49-55%). There were marked differences in the country specific prevalence of LUTS complaints. Frequently, symptoms coexisted and were combined with nocturia. More than half of patients felt at least some degree of bother from their symptoms: 61% for urgency, 57% for nocturia, 58% for slow stream, and 60% for post-micturition dribble. Before seeing the present urologists, nearly half of patients have received some form of prescribed treatment and more than 80% of patients indicated they would like to receive treatment.
    CONCLUSION: Men who sought urologist care for LUTS often presented with multiple symptoms. Nocturia emerged as the most common symptom amongst the four core symptoms studied.
    Study site in Malaysia: Urology clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
  10. Saunders JB, Hao W, Long J, King DL, Mann K, Fauth-Bühler M, et al.
    J Behav Addict, 2017 Sep 01;6(3):271-279.
    PMID: 28816494 DOI: 10.1556/2006.6.2017.039
    Online gaming has greatly increased in popularity in recent years, and with this has come a multiplicity of problems due to excessive involvement in gaming. Gaming disorder, both online and offline, has been defined for the first time in the draft of 11th revision of the International Classification of Diseases (ICD-11). National surveys have shown prevalence rates of gaming disorder/addiction of 10%-15% among young people in several Asian countries and of 1%-10% in their counterparts in some Western countries. Several diseases related to excessive gaming are now recognized, and clinics are being established to respond to individual, family, and community concerns, but many cases remain hidden. Gaming disorder shares many features with addictions due to psychoactive substances and with gambling disorder, and functional neuroimaging shows that similar areas of the brain are activated. Governments and health agencies worldwide are seeking for the effects of online gaming to be addressed, and for preventive approaches to be developed. Central to this effort is a need to delineate the nature of the problem, which is the purpose of the definitions in the draft of ICD-11.
  11. Elnaem MH, Mubarak N, K T MS, Barakat M, Abdelaziz DH, Mansour NO, et al.
    Front Public Health, 2022;10:1011376.
    PMID: 36388263 DOI: 10.3389/fpubh.2022.1011376
    BACKGROUND: Pharmacy students will assume future roles as frontline healthcare providers. Therefore, evaluating their current state of mental wellbeing and its associated factors is essential for better planning students' support initiatives. This study aimed to assess mental wellbeing and its associated factors among undergraduate pharmacy students from 14 countries during the pandemic.

    METHODS: A cross-sectional study was conducted among undergraduate pharmacy students in 14 countries in Asia and the Middle East. The validated Warwick-Edinburgh Mental Wellbeing Scale (the 14-item WEMWBS) was adopted to assess mental wellbeing. Data collection was performed online between February and April 2022. Descriptive and inferential statistics were used as appropriate.

    RESULTS: A total of 2,665 responses were received, mainly from females (68.7%) with a higher presence of private universities (59.1%). About 34.9% had low mental wellbeing levels, while 57 and 8.1% had medium, and high levels, respectively. Binary logistic regression showed that males (AOR: 1.34; CI 95%: 1.11-1.61; p < 0.01) and students with no chronic illnesses (AOR: 2.01; CI 95%: 1.45-2.80; p < 0.001) were more likely to have higher mental wellbeing. Also, participants who did not engage in any exercise (AOR: 0.71; CI 95%: 0.52-0.98; p = 0.04) and those in public universities (AOR: 0.82; CI 95%: 0.69-0.97; p = 0.02) were less likely to have higher mental wellbeing. Additionally, students who had interest/passion for pharmacy (AOR: 1.69; CI 95%: 1.07-2.68; p = 0.02), and those who known pharmacists inspired (AOR: 1.81; CI 95%: 1.06-3.12; p = 0.03), were more likely to have higher mental wellbeing compared with those who had no specific reason for their choice to study pharmacy. The participants with excellent (AOR: 1.87; CI 95%: 1.29-2.70; p = 0.001) or very good self-reported academic performance (AOR: 1.57; CI 95%: 1.12-2.22; p = 0.01) were more likely to have higher mental wellbeing compared to those with fair academic performance.

    CONCLUSION: More than a third of the participants had low mental wellbeing. Various demographic, lifestyle, medical and academic factors appeared to affect students' mental wellbeing. Careful consideration of these factors and their integration into the pharmacy schools' plans for student support services and academic advising would be essential to improve students' mental wellbeing.

  12. Nadzir MSM, Ashfold MJ, Khan MF, Robinson AD, Bolas C, Latif MT, et al.
    Environ Sci Pollut Res Int, 2018 Jan;25(3):2194-2210.
    PMID: 29116536 DOI: 10.1007/s11356-017-0521-1
    The Antarctic continent is known to be an unpopulated region due to its extreme weather and climate conditions. However, the air quality over this continent can be affected by long-lived anthropogenic pollutants from the mainland. The Argentinian region of Ushuaia is often the main source area of accumulated hazardous gases over the Antarctic Peninsula. The main objective of this study is to report the first in situ observations yet known of surface ozone (O3) over Ushuaia, the Drake Passage, and Coastal Antarctic Peninsula (CAP) on board the RV Australis during the Malaysian Antarctic Scientific Expedition Cruise 2016 (MASEC'16). Hourly O3 data was measured continuously for 23 days using an EcoTech O3 analyzer. To understand more about the distribution of surface O3 over the Antarctic, we present the spatial and temporal of surface O3 of long-term data (2009-2015) obtained online from the World Meteorology Organization of World Data Centre for greenhouse gases (WMO WDCGG). Furthermore, surface O3 satellite data from the free online NOAA-Atmospheric Infrared Sounder (AIRS) database and online data assimilation from the European Centre for Medium-Range Weather Forecasts (ECMWF)-Monitoring Atmospheric Composition and Climate (MACC) were used. The data from both online products are compared to document the data sets and to give an indication of its quality towards in situ data. Finally, we used past carbon monoxide (CO) data as a proxy of surface O3 formation over Ushuaia and the Antarctic region. Our key findings were that the surface O3 mixing ratio during MASEC'16 increased from a minimum of 5 ppb to ~ 10-13 ppb approaching the Drake Passage and the Coastal Antarctic Peninsula (CAP) region. The anthropogenic and biogenic O3 precursors from Ushuaia and the marine region influenced the mixing ratio of surface O3 over the Drake Passage and CAP region. The past data from WDCGG showed that the annual O3 cycle has a maximum during the winter of 30 to 35 ppb between June and August and a minimum during the summer (January to February) of 10 to 20 ppb. The surface O3 mixing ratio during the summer was controlled by photochemical processes in the presence of sunlight, leading to the depletion process. During the winter, the photochemical production of surface O3 was more dominant. The NOAA-AIRS and ECMWF-MACC analysis agreed well with the MASEC'16 data but twice were higher during the expedition period. Finally, the CO past data showed the surface O3 mixing ratio was influenced by the CO mixing ratio over both the Ushuaia and Antarctic regions. Peak surface O3 and CO hourly mixing ratios reached up to ~ 38 ppb (O3) and ~ 500 ppb (CO) over Ushuaia. High CO over Ushuaia led to the depletion process of surface O3 over the region. Monthly CO mixing ratio over Antarctic (South Pole) were low, leading to the production of surface O3 over the Antarctic region.
  13. de Manuel M, Barnett R, Sandoval-Velasco M, Yamaguchi N, Garrett Vieira F, Zepeda Mendoza ML, et al.
    Proc Natl Acad Sci U S A, 2020 May 19;117(20):10927-10934.
    PMID: 32366643 DOI: 10.1073/pnas.1919423117
    Lions are one of the world's most iconic megafauna, yet little is known about their temporal and spatial demographic history and population differentiation. We analyzed a genomic dataset of 20 specimens: two ca. 30,000-y-old cave lions (Panthera leo spelaea), 12 historic lions (Panthera leo leo/Panthera leo melanochaita) that lived between the 15th and 20th centuries outside the current geographic distribution of lions, and 6 present-day lions from Africa and India. We found that cave and modern lions shared an ancestor ca. 500,000 y ago and that the 2 lineages likely did not hybridize following their divergence. Within modern lions, we found 2 main lineages that diverged ca. 70,000 y ago, with clear evidence of subsequent gene flow. Our data also reveal a nearly complete absence of genetic diversity within Indian lions, probably due to well-documented extremely low effective population sizes in the recent past. Our results contribute toward the understanding of the evolutionary history of lions and complement conservation efforts to protect the diversity of this vulnerable species.
  14. Xiao J, Ng CH, Chan KE, Fu C, Tay P, Yong JN, et al.
    J Clin Exp Hepatol, 2023;13(4):656-665.
    PMID: 37440949 DOI: 10.1016/j.jceh.2022.11.006
    BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease globally. While the prevalence, impact, and causes of mortality have been described in various meta-analyses, a systematic all-encompassing umbrella review has yet to be conducted to consolidate the evidence on outcomes associated with NAFLD.

    METHODS: Search was conducted on Medline and Embase for meta-analysis investigating associated complications and causes of mortality in NAFLD patients. Summary estimates were presented with original units, sample size, and I2 for heterogeneity. The Assessment of Multiple Systematic Reviews 2 was employed for article selection.

    RESULTS: 25 meta-analyses were included in the present review. NAFLD increased the risks of systemic complications, including cardiovascular diseases, systemic malignancies, diabetes, and chronic kidney disease. Regarding hepatic outcomes, the incidence of hepatocellular carcinoma in NAFLD was 2.39 per 100 person years (CI: 1.40 to 4.08). Individuals with NAFLD were also found to have an increased likelihood of cholangiocarcinoma (OR: 1.88, CI: 1.25 to 2.83) and gallstone disease (OR: 1.55, CI: 1.31 to 1.82) compared to individuals without NAFLD. NAFLD was associated with a higher risk of fatal and non-fatal CVD events (HR: 1.45, CI: 1.31 to 1.61) compared to individuals without NAFLD. Coronary heart disease and subclinical and clinical coronary heart disease were also significantly elevated in NAFLD individuals compared to individuals without NAFLD. Additionally, NAFLD was associated with an increased risk of all-cause mortality (HR: 1.34, CI: 1.17 to 1.54) and cardiovascular (HR: 1.30, CI: 1.08 to 1.56) but not cancer-related mortality.

    CONCLUSION: The study summarizes high-level evidence from published meta-analyses to provide a much-needed update on the outcomes in patients with NAFLD. The significant systemic burden associated with NAFLD and impending fatty liver epidemic requires prompt action from multidisciplinary providers, policy providers, and stakeholders to reduce the burden of NAFLD.

  15. Chang AB, Yerkovich ST, Baines KJ, Burr L, Champion A, Chatfield MD, et al.
    BMJ Open Respir Res, 2024 May 07;11(1).
    PMID: 38719503 DOI: 10.1136/bmjresp-2023-002216
    INTRODUCTION: Bronchiectasis is a worldwide chronic lung disorder where exacerbations are common. It affects people of all ages, but especially Indigenous populations in high-income nations. Despite being a major contributor to chronic lung disease, there are no licensed therapies for bronchiectasis and there remain relatively few randomised controlled trials (RCTs) conducted in children and adults. Our RCT will address some of these unmet needs by evaluating whether the novel mucoactive agent, erdosteine, has a therapeutic role in children and adults with bronchiectasis.Our primary aim is to determine in children and adults aged 2-49 years with bronchiectasis whether regular erdosteine over a 12-month period reduces acute respiratory exacerbations compared with placebo. Our primary hypothesis is that people with bronchiectasis who regularly use erdosteine will have fewer exacerbations than those receiving placebo.Our secondary aims are to determine the effect of the trial medications on quality of life (QoL) and other clinical outcomes (exacerbation duration, time-to-next exacerbation, hospitalisations, lung function, adverse events). We will also assess the cost-effectiveness of the intervention.

    METHODS AND ANALYSIS: We are undertaking an international multicentre, double-blind, placebo-RCT to evaluate whether 12 months of erdosteine is beneficial for children and adults with bronchiectasis. We will recruit 194 children and adults with bronchiectasis to a parallel, superiority RCT at eight sites across Australia, Malaysia and Philippines. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, exacerbation duration, time-to-next exacerbation, hospitalisations and lung function.

    ETHICS AND DISSEMINATION: The Human Research Ethics Committees (HREC) of Children's Health Queensland (for all Australian sites), University of Malaya Medical Centre (Malaysia) and St. Luke's Medical Centre (Philippines) approved the study. We will publish the results and share the outcomes with the academic and medical community, funding and relevant patient organisations.

    TRIAL REGISTRATION NUMBER: ACTRN12621000315819.

  16. Lazarev VN, Levitskii SA, Basovskii YI, Chukin MM, Akopian TA, Vereshchagin VV, et al.
    J Bacteriol, 2011 Sep;193(18):4943-53.
    PMID: 21784942 DOI: 10.1128/JB.05059-11
    We present the complete genome sequence and proteogenomic map for Acholeplasma laidlawii PG-8A (class Mollicutes, order Acholeplasmatales, family Acholeplasmataceae). The genome of A. laidlawii is represented by a single 1,496,992-bp circular chromosome with an average G+C content of 31 mol%. This is the longest genome among the Mollicutes with a known nucleotide sequence. It contains genes of polymerase type I, SOS response, and signal transduction systems, as well as RNA regulatory elements, riboswitches, and T boxes. This demonstrates a significant capability for the regulation of gene expression and mutagenic response to stress. Acholeplasma laidlawii and phytoplasmas are the only Mollicutes known to use the universal genetic code, in which UGA is a stop codon. Within the Mollicutes group, only the sterol-nonrequiring Acholeplasma has the capacity to synthesize saturated fatty acids de novo. Proteomic data were used in the primary annotation of the genome, validating expression of many predicted proteins. We also detected posttranslational modifications of A. laidlawii proteins: phosphorylation and acylation. Seventy-four candidate phosphorylated proteins were found: 16 candidates are proteins unique to A. laidlawii, and 11 of them are surface-anchored or integral membrane proteins, which implies the presence of active signaling pathways. Among 20 acylated proteins, 14 contained palmitic chains, and six contained stearic chains. No residue of linoleic or oleic acid was observed. Acylated proteins were components of mainly sugar and inorganic ion transport systems and were surface-anchored proteins with unknown functions.
  17. Brunton LA, Desbois AP, Garza M, Wieland B, Mohan CV, Häsler B, et al.
    Sci Total Environ, 2019 Oct 15;687:1344-1356.
    PMID: 31412468 DOI: 10.1016/j.scitotenv.2019.06.134
    Aquaculture systems are highly complex, dynamic and interconnected systems influenced by environmental, biological, cultural, socio-economic and human behavioural factors. Intensification of aquaculture production is likely to drive indiscriminate use of antibiotics to treat or prevent disease and increase productivity, often to compensate for management and husbandry deficiencies. Surveillance or monitoring of antibiotic usage (ABU) and antibiotic resistance (ABR) is often lacking or absent. Consequently, there are knowledge gaps for the risk of ABR emergence and human exposure to ABR in these systems and the wider environment. The aim of this study was to use a systems-thinking approach to map two aquaculture systems in Vietnam - striped catfish and white-leg shrimp - to identify hotspots for emergence and selection of resistance, and human exposure to antibiotics and antibiotic-resistant bacteria. System mapping was conducted by stakeholders at an interdisciplinary workshop in Hanoi, Vietnam during January 2018, and the maps generated were refined until consensus. Thereafter, literature was reviewed to complement and cross-reference information and to validate the final maps. The maps and component interactions with the environment revealed the grow-out phase, where juveniles are cultured to harvest size, to be a key hotspot for emergence of ABR in both systems due to direct and indirect ABU, exposure to water contaminated with antibiotics and antibiotic-resistant bacteria, and duration of this stage. The pathways for human exposure to antibiotics and ABR were characterised as: occupational (on-farm and at different handling points along the value chain), through consumption (bacterial contamination and residues) and by environmental routes. By using systems thinking and mapping by stakeholders to identify hotspots we demonstrate the applicability of an integrated, interdisciplinary approach to characterising ABU in aquaculture. This work provides a foundation to quantify risks at different points, understand interactions between components, and identify stakeholders who can lead and implement change.
  18. Li K, Anderson G, Viallon V, Arveux P, Kvaskoff M, Fournier A, et al.
    Breast Cancer Res, 2018 12 03;20(1):147.
    PMID: 30509329 DOI: 10.1186/s13058-018-1073-0
    BACKGROUND: Few published breast cancer (BC) risk prediction models consider the heterogeneity of predictor variables between estrogen-receptor positive (ER+) and negative (ER-) tumors. Using data from two large cohorts, we examined whether modeling this heterogeneity could improve prediction.

    METHODS: We built two models, for ER+ (ModelER+) and ER- tumors (ModelER-), respectively, in 281,330 women (51% postmenopausal at recruitment) from the European Prospective Investigation into Cancer and Nutrition cohort. Discrimination (C-statistic) and calibration (the agreement between predicted and observed tumor risks) were assessed both internally and externally in 82,319 postmenopausal women from the Women's Health Initiative study. We performed decision curve analysis to compare ModelER+ and the Gail model (ModelGail) regarding their applicability in risk assessment for chemoprevention.

    RESULTS: Parity, number of full-term pregnancies, age at first full-term pregnancy and body height were only associated with ER+ tumors. Menopausal status, age at menarche and at menopause, hormone replacement therapy, postmenopausal body mass index, and alcohol intake were homogeneously associated with ER+ and ER- tumors. Internal validation yielded a C-statistic of 0.64 for ModelER+ and 0.59 for ModelER-. External validation reduced the C-statistic of ModelER+ (0.59) and ModelGail (0.57). In external evaluation of calibration, ModelER+ outperformed the ModelGail: the former led to a 9% overestimation of the risk of ER+ tumors, while the latter yielded a 22% underestimation of the overall BC risk. Compared with the treat-all strategy, ModelER+ produced equal or higher net benefits irrespective of the benefit-to-harm ratio of chemoprevention, while ModelGail did not produce higher net benefits unless the benefit-to-harm ratio was below 50. The clinical applicability, i.e. the area defined by the net benefit curve and the treat-all and treat-none strategies, was 12.7 × 10- 6 for ModelER+ and 3.0 × 10- 6 for ModelGail.

    CONCLUSIONS: Modeling heterogeneous epidemiological risk factors might yield little improvement in BC risk prediction. Nevertheless, a model specifically predictive of ER+ tumor risk could be more applicable than an omnibus model in risk assessment for chemoprevention.

  19. Matejcic M, de Batlle J, Ricci C, Biessy C, Perrier F, Huybrechts I, et al.
    Int J Cancer, 2017 Mar 15;140(6):1246-1259.
    PMID: 27905104 DOI: 10.1002/ijc.30536
    Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1  = 1.26; 95% CI 1.00-1.58; Ptrend  = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1  = 1.29; 95% CI 1.02-1.62; Ptrend  = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.
  20. Matejcic M, Lesueur F, Biessy C, Renault AL, Mebirouk N, Yammine S, et al.
    Int J Cancer, 2018 Nov 15;143(10):2437-2448.
    PMID: 30110135 DOI: 10.1002/ijc.31797
    There are both limited and conflicting data on the role of dietary fat and specific fatty acids in the development of pancreatic cancer. In this study, we investigated the association between plasma phospholipid fatty acids and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The fatty acid composition was measured by gas chromatography in plasma samples collected at recruitment from375 incident pancreatic cancer cases and375 matched controls. Associations of specific fatty acids with pancreatic cancer risk were evaluated using multivariable conditional logistic regression models with adjustment for established pancreatic cancer risk factors. Statistically significant inverse associations were found between pancreatic cancer incidence and levels of heptadecanoic acid (ORT3-T1 [odds ratio for highest versus lowest tertile] =0.63; 95%CI[confidence interval] = 0.41-0.98; ptrend = 0.036), n-3 polyunsaturated α-linolenic acid (ORT3-T1 = 0.60; 95%CI = 0.39-0.92; ptrend = 0.02) and docosapentaenoic acid (ORT3-T1 = 0.52; 95%CI = 0.32-0.85; ptrend = 0.008). Industrial trans-fatty acids were positively associated with pancreatic cancer risk among men (ORT3-T1 = 3.00; 95%CI = 1.13-7.99; ptrend = 0.029), while conjugated linoleic acids were inversely related to pancreatic cancer among women only (ORT3-T1 = 0.37; 95%CI = 0.17-0.81; ptrend = 0.008). Among current smokers, the long-chain n-6/n-3 polyunsaturated fatty acids ratio was positively associated with pancreatic cancer risk (ORT3-T1 = 3.40; 95%CI = 1.39-8.34; ptrend = 0.007). Results were robust to a range of sensitivity analyses. Our findings suggest that higher circulating levels of saturated fatty acids with an odd number of carbon atoms and n-3 polyunsaturated fatty acids may be related to lower risk of pancreatic cancer. The influence of some fatty acids on the development of pancreatic cancer may be sex-specific and modulated by smoking.
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