Displaying publications 1 - 20 of 39 in total

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  1. Utilization of breast cancer screening methods in a developing nation: results from a nationally representative sample of Malaysian households
    Dunn RA, Tan AK
    Breast J, 2011 Jul-Aug;17(4):399-402.
    PMID: 21615819 DOI: 10.1111/j.1524-4741.2011.01098.x
    As is the case in many developing nations, previous studies of breast cancer screening behavior in Malaysia have used relatively small samples that are not nationally representative, thereby limiting the generalizability of results. Therefore, this study uses nationally representative data from the Malaysia Non-Communicable Disease Surveillance-1 to investigate the role of socio-economic status on breast cancer screening behavior in Malaysia, particularly differences in screening behaviour between ethnic groups. The decisions of 816 women above age 40 in Malaysia to screen for breast cancer using mammography, clinical breast exams (CBE), and breast self-exams (BSE) are modeled using logistic regression. Results indicate that after adjusting for differences in age, education, household income, marital status, and residential location, Malay women are less likely than Chinese and Indian women to utilize mammography, but more likely to perform BSE. Education level and urban residence are positively associated with utilization of each method, but these relationships vary across ethnicity. Higher education levels are strongly related to using each screening method among Chinese women, but have no statistically significant relationship to screening among Malays.
  2. Cervical cancer screening in Malaysia: Are targeted interventions necessary?
    Dunn RA, Tan AKG
    Soc Sci Med, 2010 Sep;71(6):1089-93.
    PMID: 20685019 DOI: 10.1016/j.socscimed.2010.06.016
    This study examines the determinants of Papanicolaou Smear Test (PST) screening for cervical cancer among women in Malaysia. Attention is focused on the reasons different population subgroups give for non-screening. We find that Indian women are the least likely to have had a PST and also the least likely to know the reasons why one is screened. Malay women are less likely than Chinese women to have received a PST and are more likely to report embarrassment as the reason for not being tested. Urban women are less likely than rural women to have been tested and more likely to state lack of time as the reason. These results suggest targeted interventions may be necessary to increase screening rates in Malaysia.
    Study name: Malaysia Non-Communicable Disease Surveillance-1 (MyNCDS-1) survey
  3. Fulltext Conformational dynamics of dry lamellar crystals of sugar based lipids: an atomistic simulation study
    ManickamAchari V, Bryce RA, Hashim R
    PLoS One, 2014;9(6):e101110.
    PMID: 24978205 DOI: 10.1371/journal.pone.0101110
    The rational design of a glycolipid application (e.g. drug delivery) with a tailored property depends on the detailed understanding of its structure and dynamics. Because of the complexity of sugar stereochemistry, we have undertaken a simulation study on the conformational dynamics of a set of synthetic glycosides with different sugar groups and chain design, namely dodecyl β-maltoside, dodecyl β-cellobioside, dodecyl β-isomaltoside and a C12C10 branched β-maltoside under anhydrous conditions. We examined the chain structure in detail, including the chain packing, gauche/trans conformations and chain tilting. In addition, we also investigated the rotational dynamics of the headgroup and alkyl chains. Monoalkylated glycosides possess a small amount of gauche conformers (∼20%) in the hydrophobic region of the lamellar crystal (LC) phase. In contrast, the branched chain glycolipid in the fluid Lα phase has a high gauche population of up to ∼40%. Rotational diffusion analysis reveals that the carbons closest to the headgroup have the highest correlation times. Furthermore, its value depends on sugar type, where the rotational dynamics of an isomaltose was found to be 11-15% and more restrained near the sugar, possibly due to the chain disorder and partial inter-digitation compared to the other monoalkylated lipids. Intriguingly, the present simulation demonstrates the chain from the branched glycolipid bilayer has the ability to enter into the hydrophilic region. This interesting feature of the anhydrous glycolipid bilayer simulation appears to arise from a combination of lipid crowding and the amphoteric nature of the sugar headgroups.
  4. Fulltext Does performance of breast self-exams increase the probability of using mammography: evidence from Malaysia
    Dunn RA, Tan A, Samad I
    Asian Pac J Cancer Prev, 2010;11(2):417-21.
    PMID: 20843127
    OBJECTIVES: Breast self-examination (BSE) was evaluated to see if it is a significant predictor of mammography.

    METHODS: The decisions of females above age 40 in Malaysia to test for breast cancer using BSE and mammography are jointly modeled using a bivariate probit so that unobserved attributes affecting mammography usage are also allowed to affect BSE. Data come from the Malaysia Non-Communicable Disease Surveillance-1, which was collected between September 2005 and February 2006.

    RESULTS: Having ever performed BSE is positively associated with having ever undergone mammography among Malay (adjusted OR=7.343, CI=2.686, 20.079) and Chinese (adjusted OR=3.466, CI=1.330, 9.031) females after adjusting for household income, education, marital status and residential location. Neither relationship is affected by jointly modelling the decision problem. Although the association is also positive for Indian females when mammography is modelled separately (adjusted OR=5.959, CI=1.546 - 22.970), the relationship is reversed when both decisions are modelled separately.

    CONCLUSIONS: De-emphasizing BSE in Malaysia may reduce mammography screening among a large proportion of the population. Previous work on the issue in developed countries may not apply to nations with limited resources.
  5. Molecular dynamics simulation of monoalkyl glycoside micelles in aqueous solution: influence of carbohydrate headgroup stereochemistry
    Chong TT, Hashim R, Bryce RA
    J Phys Chem B, 2006 Mar 16;110(10):4978-84.
    PMID: 16526739
    Comparative molecular dynamics simulations of n-octyl-beta-D-galactopyranoside (beta-C8Gal) and n-octyl-beta-D-glucopyranoside (beta-C8Glc) micelles in aqueous solution have been performed to explore the influence of carbohydrate stereochemistry on glycolipid properties at the atomic level. In particular, we explore the hypothesis that differences in T(m) and T(c) for beta-C8Gal and beta-C8Glc in lyotropic systems arise from a more extensive hydrogen bonding network between beta-C8Gal headgroups relative to beta-C8Glc, due to the axial 4-OH group in beta-C8Gal. Good agreement of the 13 ns micelle-water simulations with available experimental information is found. The micelles exhibit a similar shape, size, and degree of exposed alkyl chain surface area. We find net inter- and intra-headgroup hydrogen bonding is also similar for beta-C8Gal and beta-C8Glc, although n-octyl-beta-D-galactopyranoside micelles do exhibit a slightly greater degree of inter- and intra-headgroup hydrogen bonding. However, the main distinction in the calculated microscopic behavior of beta-C8Glc and beta-C8Gal micelles lies in solvent interactions, where beta-d-glucosyl headgroups are considerably more solvated (mainly at the equatorial O4 oxygen). These results agree with preceding theoretical and experimental studies of monosaccharides in aqueous solution. A number of long water residence times are found for solvent surrounding both micelle types, the largest of which are associated with surface protrusions involving headgroup clusters. Our simulations, therefore, predict differences in hydrogen bonding for the two headgroup stereochemistries, including a small difference in inter-headgroup interactions, which may contribute to the higher T(m) and T(c) values of beta-C8Gal surfactants relative to beta-C8Glc in lyotropic systems.
  6. Multilocus sequence typing of historical Burkholderia pseudomallei isolates collected in Southeast Asia from 1964 to 1967 provides insight into the epidemiology of melioidosis
    McCombie RL, Finkelstein RA, Woods DE
    J Clin Microbiol, 2006 Aug;44(8):2951-62.
    PMID: 16891516
    A collection of 207 historically relevant Burkholderia pseudomallei isolates was analyzed by multilocus sequence typing (MLST). The strain collection contains environmental isolates obtained from a geographical distribution survey of B. pseudomallei isolates in Thailand (1964 to 1967), as well as stock cultures and colony variants from the U.S. Army Medical Research Unit (Malaysia), the Walter Reed Army Institute for Research, and the Pasteur Institute (Vietnam). The 207 isolates of the collection were resolved into 80 sequence types (STs); 56 of these were novel. eBURST diagrams predict that the historical-collection STs segregate into three complexes when analyzed separately. When added to the 760 isolates and 365 STs of the B. pseudomallei MLST database, the historical-collection STs cluster significantly within the main complex of the eBURST diagram in an ancestral pattern and alter the B. pseudomallei "population snapshot." Differences in colony morphology among reference isolates were found not to affect the STs assigned, which were consistent with the original isolates. Australian ST84 is likely characteristic of B. pseudomallei isolates of Southeast Asia rather than Australia, since multiple environmental isolates from Thailand and Malaysia share this ST with the single Australian clinical isolate in the MLST database. Phylogenetic evidence is also provided suggesting that Australian isolates may not be distinct from those of Thailand, since ST60 is common to environmental isolates from both countries. MLST and eBURST are useful tools for the study of population biology and epidemiology, since they provide methods to elucidate new genetic relationships among bacterial isolates.
  7. Fulltext Factors Contributing towards Loss to Follow Up among Tuberculosis Patients in Sabah
    Liaw, Y. C., Richard A., Mohammad Saffree J., Valentine J. G.
    Borneo Journal of Medical Sciences, 2019;2(101):9-10.
    MyJurnal
    Sabah is a high tuberculosis (TB) burden area with incidence rate of 120 – 138 per 100,000 population. Until now, TB is still unable to control due to high loss to follow up rates. Loss to follow up TB treatment can cause to increase notification rate, prolonged infection, recurrent TB infections, increase multiple drug-resistance, and increase morbidity and mortality rates. To know the factors that contribute towards loss to follow up will better understand the epidemiology of treatment outcome and guide for appropriate strategies planning to improve the situation. Previous study by Liew et al. indicated that, incidence rate for loss to follow up in 2012 in Malaysia was 10.5%.
  8. Obesity inequality in Malaysia: decomposing differences by gender and ethnicity using quantile regression
    Dunn RA, Tan AK, Nayga RM
    Ethn Health, 2012;17(5):493-511.
    PMID: 22360320 DOI: 10.1080/13557858.2012.661407
    OBJECTIVE: Obesity prevalence is unequally distributed across gender and ethnic group in Malaysia. In this paper, we examine the role of socioeconomic inequality in explaining these disparities.
    DESIGN: The body mass index (BMI) distributions of Malays and Chinese, the two largest ethnic groups in Malaysia, are estimated through the use of quantile regression. The differences in the BMI distributions are then decomposed into two parts: attributable to differences in socioeconomic endowments and attributable to differences in responses to endowments.
    RESULTS: For both males and females, the BMI distribution of Malays is shifted toward the right of the distribution of Chinese, i.e., Malays exhibit higher obesity rates. In the lower 75% of the distribution, differences in socioeconomic endowments explain none of this difference. At the 90th percentile, differences in socioeconomic endowments account for no more than 30% of the difference in BMI between ethnic groups.
    CONCLUSIONS: Our results demonstrate that the higher levels of income and education that accrue with economic development will likely not eliminate obesity inequality. This leads us to conclude that reduction of obesity inequality, as well the overall level of obesity, requires increased efforts to alter the lifestyle behaviors of Malaysians.
  9. Fulltext Ethnic disparities in metabolic syndrome in Malaysia: an analysis by risk factors
    Tan AKG, Dunn RA, Yen ST
    Metab Syndr Relat Disord, 2011 Dec;9(6):441-51.
    PMID: 21815810 DOI: 10.1089/met.2011.0031
    BACKGROUND: This study investigates ethnic disparities in metabolic syndrome in Malaysia.
    METHODS: Data were obtained from the Malaysia Non-Communicable Disease Surveillance-1 (2005/2006). Logistic regressions of metabolic syndrome health risks on sociodemographic and health-lifestyle factors were conducted using a multiracial (Malay, Chinese, and Indian and other ethnic groups) sample of 2,366 individuals.
    RESULTS: Among both males and females, the prevalence of metabolic syndrome amongst Indians was larger compared to both Malays and Chinese because Indians are more likely to exhibit central obesity, elevated fasting blood glucose, and low high-density lipoprotein cholesterol. We also found that Indians tend to engage in less physical activity and consume fewer fruits and vegetables than Malays and Chinese. Although education and family history of chronic disease are associated with metabolic syndrome status, differences in socioeconomic attributes do not explain ethnic disparities in metabolic syndrome incidence. The difference in metabolic syndrome prevalence between Chinese and Malays was not statistically significant. Whereas both groups exhibited similar obesity rates, ethnic Chinese were less likely to suffer from high fasting blood glucose.
    CONCLUSIONS: Metabolic syndrome disproportionately affects Indians in Malaysia. Additionally, fasting blood glucose rates differ dramatically amongst ethnic groups. Attempts to decrease health disparities among ethnic groups in Malaysia will require greater attention to improving the metabolic health of Malays, especially Indians, by encouraging healthful lifestyle changes.
    Study name: Malaysia Non-Communicable Disease Surveillance-1 (MyNCDS-1) survey
  10. Sociodemographic and health-lifestyle determinants of obesity risks in Malaysia
    Tan AK, Dunn RA, Samad MI, Feisul MI
    Asia Pac J Public Health, 2011 Apr;23(2):192-202.
    PMID: 20460299 DOI: 10.1177/1010539509359535
    The purpose of this study was to examine the sociodemographic and health-lifestyle factors that affect the likelihood of obesity among Malaysians. Data were obtained from the Malaysian Non-Communicable Disease Surveillance-1. The cross-sectional population-based survey consisted of 2447 observations, with an obesity prevalence rate of 17.2%. Based on logit regression analysis, the results suggest that obesity risks in Malaysia are affected by gender, education level, family history, health conditions, smoking status, and ethnic backgrounds. Specifically, Malaysians more likely to be obese are females (5.3%), lower educated (0.9%), those with history of family illnesses (4.8%), and nonsmokers (6.4%). However, Chinese (9.3%) and other (5.5%) ethnic groups are less likely to be obese when compared with Malays. Based on these results, several policy implications are discussed vis-à-vis obesity risks in Malaysia.
    Study name: Malaysia Non-Communicable Disease Surveillance-1 (MyNCDS-1) survey
  11. Fulltext Uncertainty in identifying local extinctions: the distribution of missing data and its effects on biodiversity measures
    Boakes EH, Fuller RA, McGowan PJ, Mace GM
    Biol Lett, 2016 Mar;12(3).
    PMID: 26961894 DOI: 10.1098/rsbl.2015.0824
    Identifying local extinctions is integral to estimating species richness and geographic range changes and informing extinction risk assessments. However, the species occurrence records underpinning these estimates are frequently compromised by a lack of recorded species absences making it impossible to distinguish between local extinction and lack of survey effort-for a rigorously compiled database of European and Asian Galliformes, approximately 40% of half-degree cells contain records from before but not after 1980. We investigate the distribution of these cells, finding differences between the Palaearctic (forests, low mean human influence index (HII), outside protected areas (PAs)) and Indo-Malaya (grassland, high mean HII, outside PAs). Such cells also occur more in less peaceful countries. We show that different interpretations of these cells can lead to large over/under-estimations of species richness and extent of occurrences, potentially misleading prioritization and extinction risk assessment schemes. To avoid mistakes, local extinctions inferred from sightings records need to account for the history of survey effort in a locality.
  12. Fulltext The globalization of addiction research: capacity-building mechanisms and selected examples
    Rawson RA, Woody G, Kresina TF, Gust S
    Harv Rev Psychiatry, 2015;23(2):147-56.
    PMID: 25747927 DOI: 10.1097/HRP.0000000000000067
    Over the past decade, the amount and variety of addiction research around the world has increased substantially. Researchers in Australia, Canada, United Kingdom, United States, and western Europe have significantly contributed to knowledge about addiction and its treatment. However, the nature and context of substance use disorders and the populations using drugs are far more diverse than is reflected in studies done in Western cultures. To stimulate new research from a diverse set of cultural perspectives, the National Institute on Drug Abuse (NIDA) has promoted the development of addiction research capacity and skills around the world for over 25 years. This review will describe the programs NIDA has developed to sponsor international research and research fellows and will provide some examples of the work NIDA has supported. NIDA fellowships have allowed 496 individuals from 96 countries to be trained in addiction research. The United Arab Emirates and Saudi Arabia have recently developed funding to support addiction research to study, with advice from NIDA, the substance use disorder problems that affect their societies. Examples from Malaysia, Tanzania, Brazil, Russian Federation, Ukraine, Republic of Georgia, Iceland, China, and Vietnam are used to illustrate research being conducted with NIDA support. Health services research, collaboratively funded by the U.S. National Institutes of Health and Department of State, addresses a range of addiction service development questions in low- and middle-income countries. Findings have expanded the understanding of addiction and its treatment, and are enhancing the ability of practitioners and policy makers to address substance use disorders.
  13. Molecular dynamics study of anhydrous lamellar structures of synthetic glycolipids: effects of chain branching and disaccharide headgroup
    Achari VM, Nguan HS, Heidelberg T, Bryce RA, Hashim R
    J Phys Chem B, 2012 Sep 27;116(38):11626-34.
    PMID: 22967067
    Glycolipids form materials of considerable potential for a wide range of surfactant and thin film applications. Understanding the effect of glycolipid covalent structure on the properties of their thermotropic and lyotropic assemblies is a key step toward rational design of new glycolipid-based materials. Here, we perform molecular dynamics simulations of anhydrous bilayers of dodecyl β-maltoside, dodecyl β-cellobioside, dodecyl β-isomaltoside, and a C(12)C(10) branched β-maltoside. Specifically, we examine the consequences of chain branching and headgroup identity on the structure and dynamics of the lamellar assemblies. Chain branching of the glycolipid leads to measurable differences in the dimensions and interactions of the lamellar assembly, as well as a more fluid-like hydrophobic chain region. Substitution of the maltosyl headgroup of βMal-C(12) by an isomaltosyl moiety leads to a significant decrease in bilayer spacing as well as a markedly altered pattern of inter-headgroup hydrogen bonding. The distinctive simulated structures of the two regioisomers provide insight into the difference of ~90 °C in their observed clearing temperatures. For all four simulated glycolipid systems, with the exception of the sn-2 chain of the branched maltoside, the alkyl chains are ordered and exhibit a distinct tilt, consistent with recent crystallographic analysis of a branched chain Guerbet glycoside. These insights into structure-property relationships from simulation provide an important molecular basis for future design of synthetic glycolipid materials.
  14. The Morphological and Molecular Description of Acanthogyrus (Acanthosentis) fusiformis n. sp. (Acanthocephala: Quadrigyridae) from the Catfish Arius sp. (Ariidae) in the Pacific Ocean off Vietnam, with Notes on Zoogeography
    Amin OM, Chaudhary A, Heckmann RA, Ha NV, Singh HS
    Acta Parasitol, 2019 Dec;64(4):779-796.
    PMID: 31332657 DOI: 10.2478/s11686-019-00102-3
    BACKGROUND: Most (82%) of the 46 recognized species of Acanthogyrus (Acanthosentis) Verma and Datta, 1929 are known from Asian freshwater fishes. Only three species of Acanthosentis are known from marine or brackish water fishes from India and Pakistan. We have discovered another marine species of Acanthosentis in the Pacific Ocean, off Vietnam.

    PURPOSE: The purpose is to describe the new species morphologically and molecularly and provide new information of its evolutionally relationships with other species of the subgenus.

    METHODS: Standard methods of collection and examination of marine hosts, processing and illustrating of specimens, and taxonomic identification of parasites using the extensive collection of the lead author were used. Specimens were further studied using energy-dispersive X-ray analysis and ion sectioning of hooks, SEM analysis, and molecular sequencing. Type specimens were deposited at the Harold W. Manter Lab. collection, Lincoln, Nebraska.

    RESULTS: Acanthogyrus (Acanthosentis) fusiformis n. sp. is described from the catfish, Arius sp. (Ariidae: Siluriformes) off the Pacific Coast of Vietnam at Bac Lieu in the Gulf of Thailand. The three other marine Indian species include A. (A.) arii Bilqees, 1971 which is also described from a similar catfish, Arius serratus Day off the Karachi coast in the Arabian Sea, Indian Ocean. Our new species from Vietnam is distinguished from the other 46 species by a combination of characters including a small fusiform trunk, complete circles of small hollow spines covering the entire trunk, prominent double apical organs often extending posteriorly past posterior hooks, middle and posterior hooks of equal size slightly smaller than anterior hooks, large neck continuous with the outline of the proboscis without distinct separation, big drop-shaped cephalic ganglion, extension of the proboscis receptacle anteriorly past the base of the proboscis up to the insertion point of the posterior hooks, presence of two para-receptacle structures (PRSs), free unattached thick lemnisci, short female reproductive system with filamentous attachment of the distal end of the uterine bell to the ventral body wall, and small narrowly ellipsoid eggs with thickened polar ends. Partial sequences of the 18S and internal transcribed spacers (ITS1-5.8S-ITS2) of ribosomal RNA were generated and used for phylogenetic analyses to confirm the taxonomic identity of Acanthogyrus (Acanthosentis) fusiformis n. sp.

    CONCLUSIONS: We describe unique morphological features of A. fusiformis never before known in the subgenus Acanthosentis. The uniqueness of A. fusiformis is further demonstrated by its EDXA fingerprint characterized by high levels of calcium and phosphorous in hooks. The zoogeography of species of Acanthosentis is elucidated in the Indian subcontinent, the Caribbean, China, and Africa. Molecular data have been available only in few species of Acanthogyrus (Acanthosentis) to date on GenBank database. For 18S, only two sequences from unknown Acanthosentis sp. from India are available, while for the ITS1-5.8S-ITS2 region, only sequences of A. cheni from China and of two unidentified species from Malaysia are available. Additional studies of species of Acanthosentis based on morphological and molecular genetic data will be needed to reconstruct the evolutionary history and phylogenetic affinities of this group of acanthocephalans.

  15. Non-native mangroves support carbon storage, sediment carbon burial, and accretion of coastal ecosystems
    Soper FM, MacKenzie RA, Sharma S, Cole TG, Litton CM, Sparks JP
    Glob Chang Biol, 2019 Aug 29.
    PMID: 31465581 DOI: 10.1111/gcb.14813
    Mangrove forests play an important role in climate change adaptation and mitigation by maintaining coastline elevations relative to sea level rise, protecting coastal infrastructure from storm damage and storing substantial quantities of carbon (C) in live and detrital pools. Determining the efficacy of mangroves in achieving climate goals can be complicated by difficulty in quantifying C inputs (i.e., differentiating newer inputs from younger trees from older residual C pools), and mitigation assessments rarely consider potential offsets to CO2 storage by methane (CH4 ) production in mangrove sediments. The establishment of non-native Rhizophora mangle along Hawaiian coastlines over the last century offers an opportunity to examine the role mangroves play in climate mitigation and adaptation both globally and locally as novel ecosystems. We quantified total ecosystem C storage, sedimentation, accretion, sediment organic C burial and CH4 emissions from ~70 year old R. mangle stands and adjacent uninvaded mudflats. Ecosystem C stocks of mangrove stands exceeded mudflats by 434 ± 33 Mg C ha-1 , and mangrove establishment increased average coastal accretion by 460%. Sediment organic C burial increased 10-fold (to 4.5 Mg C ha-1 yr-1 ), double the global mean for old growth mangrove forests, suggesting that C accumulation from younger trees may occur faster than previously thought, with implications for mangrove restoration. Simulations indicate that increased CH4 emissions from sediments offset ecosystem CO2 storage by only 2-4%, equivalent to 30-60 Mg CO2 -eq ha-1 over mangrove lifetime (100-year sustained global warming potential). Results highlight the importance of mangroves as novel systems that can rapidly accumulate C, have a net positive atmospheric greenhouse gas removal effect, and support shoreline accretion rates that outpace current sea level rise. Sequestration potential of novel mangrove forests should be taken into account when considering their removal or management, especially in the context of climate mitigation goals.
  16. Pd local structure and size correlations to the activity of Pd/TiO2 for photocatalytic reforming of methanol
    Abdullah N, Bahruji H, Rogers SM, Wells PP, Catlow CRA, Bowker M
    Phys Chem Chem Phys, 2019 Jul 24;21(29):16154-16160.
    PMID: 31294427 DOI: 10.1039/c9cp00826h
    The interaction between Pd and TiO2 for promoting photocatalytic activity was investigated by tailoring the size of Pd nanoparticles and monitoring the photocatalytic activity of methanol photo-reforming reaction for hydrogen gas production. We show that at 0.6 wt% Pd loading, the catalyst with highly dispersed nanoparticles obtained at 1 °C temperature exhibits superior photocatalytic activity for hydrogen gas production. At different weights of Pd loading, tailoring two sets of catalysts with different structural properties provides correlation between the changes in the Pd local structures and the rate of hydrogen production. The impact of controlling the structural properties of metal nanoparticles on influencing H2 production outweighs the effect of metal loading variation. The differences of Pd/TiO2 activity at the different metal loadings were correlated with the changes in the Pd local structure consequently affecting the electronic transfer and photocatalytic efficiency.
  17. Fulltext Pharmacologically antagonizing the CXCR4-CXCL12 chemokine pathway with AMD3100 inhibits sunlight-induced skin cancer
    Sarchio SNE, Scolyer RA, Beaugie C, McDonald D, Marsh-Wakefield F, Halliday GM, et al.
    J Invest Dermatol, 2014 Apr;134(4):1091-1100.
    PMID: 24226205 DOI: 10.1038/jid.2013.424
    One way sunlight causes skin cancer is by suppressing anti-tumor immunity. A major mechanism involves altering mast cell migration via the C-X-C motif chemokine receptor 4-C-X-C motif chemokine ligand 12 (CXCR4-CXCL12) chemokine pathway. We have discovered that pharmacologically blocking this pathway with the CXCR4 antagonist AMD3100 prevents both UV radiation-induced immune suppression and skin cancer. The majority of control mice receiving UV-only developed histopathologically confirmed squamous cell carcinomas. In contrast, skin tumor incidence and burden was significantly lower in AMD3100-treated mice. Perhaps most striking was that AMD3100 completely prevented the outgrowth of latent tumors that occurred once UV irradiation ceased. AMD3100 protection from UV immunosuppression and skin cancer was associated with reduced mast cell infiltration into the skin, draining lymph nodes, and the tumor itself. Thus a major target of CXCR4 antagonism was the mast cell. Our results indicate that interfering with UV-induced CXCL12 by antagonizing CXCR4 significantly inhibits skin tumor development by blocking UV-induced effects on mast cells. Hence, the CXCR4-CXCL12 chemokine pathway is a novel therapeutic target in the prevention of UV-induced skin cancer.
  18. Examining the relationship between local extinction risk and position in range
    Boakes EH, Isaac NJB, Fuller RA, Mace GM, McGowan PJK
    Conserv Biol, 2018 02;32(1):229-239.
    PMID: 28678438 DOI: 10.1111/cobi.12979
    Over half of globally threatened animal species have experienced rapid geographic range loss. Identifying the parts of species' distributions most vulnerable to local extinction would benefit conservation planning. However, previous studies give little consensus on whether ranges decline to the core or edge. We built on previous work by using empirical data to examine the position of recent local extinctions within species' geographic ranges, address range position as a continuum, and explore the influence of environmental factors. We aggregated point-locality data for 125 Galliform species from across the Palearctic and Indo-Malaya into equal-area half-degree grid cells and used a multispecies dynamic Bayesian occupancy model to estimate rates of local extinctions. Our model provides a novel approach to identify loss of populations from within species ranges. We investigated the relationship between extinction rates and distance from range edge by examining whether patterns were consistent across biogeographic realm and different categories of land use. In the Palearctic, local extinctions occurred closer to the range edge than range core in both unconverted and human-dominated landscapes. In Indo-Malaya, no pattern was found for unconverted landscapes, but in human-dominated landscapes extinctions tended to occur closer to the core than the edge. Our results suggest that local and regional factors override general spatial patterns of recent local extinction within species' ranges and highlight the difficulty of predicting the parts of a species' distribution most vulnerable to threat.
  19. Platelet accumulation in brain microvessels in fatal pediatric cerebral malaria
    Grau GE, Mackenzie CD, Carr RA, Redard M, Pizzolato G, Allasia C, et al.
    J Infect Dis, 2003 Feb 1;187(3):461-6.
    PMID: 12552430
    The pathogenesis of fatal cerebral malaria (CM) is not well understood, in part because data from patients in whom a clinical diagnosis was established prior to death are rare. In a murine CM model, platelets accumulate in brain microvasculature, and antiplatelet therapy can improve outcome. We determined whether platelets are also found in cerebral vessels in human CM, and we performed immunohistopathology for platelet-specific glycoprotein, GPIIb-IIIa, on tissue from multiple brain sites in Malawian children whose fatal illness was severe malarial anemia, CM, or nonmalarial encephalopathy. Platelets were observed in 3 locations within microvessels: between malaria pigment and leukocytes, associated with malaria pigment, or alone. The mean surface area of platelet staining and the proportion of vessels showing platelet accumulation were significantly higher in patients with CM than in those without it. Platelet accumulation occurs in the microvasculature of patients with CM and may play a role in the pathogenesis of the disease.
  20. Fulltext Helminth infection promotes colonization resistance via type 2 immunity
    Ramanan D, Bowcutt R, Lee SC, Tang MS, Kurtz ZD, Ding Y, et al.
    Science, 2016 Apr 29;352(6285):608-12.
    PMID: 27080105 DOI: 10.1126/science.aaf3229
    Increasing incidence of inflammatory bowel diseases, such as Crohn's disease, in developed nations is associated with changes to the microbial environment, such as decreased prevalence of helminth colonization and alterations to the gut microbiota. We find that helminth infection protects mice deficient in the Crohn's disease susceptibility gene Nod2 from intestinal abnormalities by inhibiting colonization by an inflammatory Bacteroides species. Resistance to Bacteroides colonization was dependent on type 2 immunity, which promoted the establishment of a protective microbiota enriched in Clostridiales. Additionally, we show that individuals from helminth-endemic regions harbor a similar protective microbiota and that deworming treatment reduced levels of Clostridiales and increased Bacteroidales. These results support a model of the hygiene hypothesis in which certain individuals are genetically susceptible to the consequences of a changing microbial environment.
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