A case study of long-term CCA preservative leaching from treated hardwood poles in a humid tropical condition

Chromated copper arsenate (CCA)-treated Malaysian hardwoods have long been used as utility poles, posts, construction piles and motorway fencing in soil contact exposed to the threats of decay fungi and termites. Despite global concerns citing predominantly temperate conditions of long-term leaching of CCA toxic heavy metals from wood into surrounding soils and groundwater since the 1990’s, the preservative leaching severity in the tropics has been far less appreciated due to dearth of work in this area. In 2013 (after 30 years exposure), levels of total copper, chromium and arsenic within 20 treated hardwood poles of Sarawak and in soils surrounding these poles, installed in 1980 and 1981 at a plot located in Timber Research and Technical Training Centre, Kuching, Sarawak, Malaysia, were sampled. The ground is waterlogged after heavy rainfall. It is shown that there is insignificant variations of CCA salt retention in wood between 1300 cm above ground and 0-20 cm below ground (P<0.05). Nevertheless levels of these elements are significantly (P<0.05) elevated in soils surrounding, especially up to 25 mm away from, the poles than at distant sampling points (150 – 300 mm) from poles as well as at sites well away from the poles containing very low levels (<6 – 13.4 ppm) of such heavy metals. Metal levels were also highest at the soil surface directly in contact with the poles (0 – 50 mm soil depth position) and decreased with remaining 2 soil depth positions 150 – 200 mm and 300 – 350 mm. Mean extractable arsenic levels ranged from 14.5 to 100.1 ppm, chromium levels from 23.3 to 148.3 ppm and copper from 21.8 to 104.7 ppm. Results, rather than indicating relatively higher CCA leaching, concurred with that reported temperate experience and showed that soil closest to the treated poles are most contaminated, albeit slightly, after 30 years of in-ground exposure

A Macromolecular Approach to Eradicate Multidrug Resistant Bacterial Infections while Mitigating Drug Resistance Onset

Polymyxins remain the last line treatment for multidrug-resistant (MDR) infections. As polymyxins resistance emerges, there is an urgent need to develop effective antimicrobial agents capable of mitigating MDR. Here, we report biodegradable guanidinium-functionalized polycarbonates with a distinctive mechanism that does not induce drug resistance. Unlike conventional antibiotics, repeated use of the polymers does not lead to drug resistance. Transcriptomic analysis of bacteria further supports development of resistance to antibiotics but not to the macromolecules after 30 treatments. Importantly, high in vivo treatment efficacy of the macromolecules is achieved in MDR A. baumannii-, E. coli-, K. pneumoniae-, methicillin-resistant S. aureus-, cecal ligation and puncture-induced polymicrobial peritonitis, and P. aeruginosa lung infection mouse models while remaining non-toxic (e.g., therapeutic index—ED50/LD50: 1473 for A. baumannii infection). These biodegradable synthetic macromolecules have been demonstrated to have broad spectrum in vivo antimicrobial activity, and have excellent potential as systemic antimicrobials against MDR infections

Health promotion activity in Kampung Rosob, Pitas

We, group 3 members which consist of 9 medical students, 8 who recently finished 1st year Medical program and 1 who recently finished 2nd year Medical program and 5 nursing students went to Kg Rosob, Pitas for health promotion from 24th August 2015 to 2nd September 2015. During our visit in the village, we started with opening ceremony once we reached the village as we have already planned with the head of the village to do opening ceremony before any activities in the village. The next day, we started our rapid rural appraisal (RRA) to get overview of the village and health problems and then we planned activities according to information from RRA to promote the health of villagers by various actions such as 1. RRA which indudes direct or field observation, secondary data resources, key informant Interview, individual interview, group meeting or interview and discussion, house-house visit, and social mapping. 2. Health education by means of talk such as breast and cervix cancer , demonstration , exhibitions , and health screening . 3. Life style and behavioral changes; for example: talk for high blood pressure , personal hygiene practice, school activities ,mini sports day and aerobic exercise. 4. Nutritional education; for example: talk on balanced diet, proper way to take medicine and good eating habits. 5. Education ; fun learning for year 5 students as a preparation for them to sit for next year UPSR examination. And involved in motivation camp for year 6 students as a preparation for their UPSR examination in August. 6.Voluntary works ; such as gotong royong to clean the compound of the village for the benefits of their health, and also killing the hair louse for the infected girls in the dorm

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation

A functional genetic screen using loss-of-function and gain-of-function alleles was performed to identify modifiers of tau-induced neurotoxicity using the 2N/4R (full-length) isoform of wild-type human tau expressed in the fly retina. We previously reported eye pigment mutations, which create dysfunctional lysosomes, as potent modifiers; here, we report 37 additional genes identified from ∼1900 genes screened, including the kinases shaggy/GSK-3beta, par-1/MARK, CamKI and Mekk1. Tau acts synergistically with Mekk1 and p38 to down-regulate extracellular regulated kinase activity, with a corresponding decrease in AT8 immunoreactivity (pS202/T205), suggesting that tau can participate in signaling pathways to regulate its own kinases. Modifiers showed poor correlation with tau phosphorylation (using the AT8, 12E8 and AT270 epitopes); moreover, tested suppressors of wild-type tau were equally effective in suppressing toxicity of a phosphorylation-resistant S11A tau construct, demonstrating that changes in tau phosphorylation state are not required to suppress or enhance its toxicity. Genes related to autophagy, the cell cycle, RNA-associated proteins and chromatin-binding proteins constitute a large percentage of identified modifiers. Other functional categories identified include mitochondrial proteins, lipid trafficking, Golgi proteins, kinesins and dynein and the Hsp70/Hsp90-organizing protein (Hop). Network analysis uncovered several other genes highly associated with the functional modifiers, including genes related to the PI3K, Notch, BMP/TGF-β and Hedgehog pathways, and nuclear trafficking. Activity of GSK-3β is strongly upregulated due to TDP-43 expression, and reduced GSK-3β dosage is also a common suppressor of Aβ42 and TDP-43 toxicity. These findings suggest therapeutic targets other than mitigation of tau phosphorylation

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

DESIGN & SYNTHESIS OF BIODEGRADABLE POLYCARBONATES AS MACROMOLECULAR ANTI-MICROBIALS

Ph.DDOCTOR OF PHILOSOPH

Preservative leaching from chromated copper arsenate (CCA) treated timber to the soil enviroment

Wood has been used for centuries as building materials and the concern of le~ching of toxic elements into the soils and groundwater arise when Chromated Copper Arsenate (CCA) wood preservatives were used to extend the service life of timbers in soil contact against decay and termites infestation. In this study, the levels of total copper, chromium and arsenic within CCAtreated poles and in soils surrounding the poles in service at a plot in Timber Research and Technical Training Centre, Kuching, Sarawak, Malaysia since 1980 or 1981, were investigated There are significant decreases of CCA salt retention in poles after 30 years of weathering (p0.05) between retention of CCA salt in wood 1300 mm above ground level and 0-20 mm below ground level. The levels of these elements were found to be significantly elevated compared to control sites (background level) in soils immediately adjacent to the treated poles. The metal levels were highest at the soil surface in contact with the poles but decreased with distance and depth. Mean extractable arsenic levels ranged from 14.53 up to 100.06 mg/kg, chromium levels from 23.31 to 148.32 mg/kg and mean copper levels from 21.83 to 104.72 mg/kg. The results show that the soil is contaminated, albeit slightly, after 30 years exposure of CCA treated wood in ground contact