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  1. Cranston PS
    Zootaxa, 2016 May 09;4109(3):315-31.
    PMID: 27394867 DOI: 10.11646/zootaxa.4109.3.3
    The presence of the Afro-Australian genus Conochironomus Freeman, 1961 (Diptera: Chironomidae) in Asia has been recognised only informally. An unpublished thesis included Conochironomus from Singapore, and the genus has been keyed from Malaysia without named species. Here, the Sumatran Conochironomus tobaterdecimus (Kikuchi & Sasa, 1980) comb. n. is recorded from Singapore and Thailand. The species is transferred from Sumatendipes Kikuchi & Sasa, 1980, rendering the latter a junior synonym (syn. n.) of Conochironomus Freeman. Conochironomus nuengthai sp. n. and Conochironomus sawngthai sp. n. are described as new to science, based on adult males from Chiang Mai, Thailand. All species conform to existing generic diagnoses for all life stages, with features from male and female genitalia, pupal cephalic tubercles and posterolateral 'spurs' of tergite VIII providing evidence for species distinction. Some larvae are linked to C. tobaterdecimus through molecular barcoding. Variation in other larvae, which clearly belong to Conochironomus and are common throughout Thailand, means that they cannot be segregated to species. Larval habitats include pools in river beds, urban storage reservoirs, drains with moderately high nutrient loadings, and peat swamps. Endochironomus effusus Dutta, 1994 from north-eastern India may be a congener but may differ in adult morphology, thereby precluding formal new combination until discrepancies can be reconciled. Many problems with vouchering taxonomic and molecular material are identified that need to be rectified in the future.
  2. Yeates DK, Cranston PS
    Zootaxa, 2013;3680:1-211.
    PMID: 26146692 DOI: 10.11646/zootaxa.3680.1.1
    Donald Henry Colless (24 August 1922–16 February 2012) was a taxonomist at the Australian National Insect Collection (ANIC) from 1960 until his retirement in 1987. He continued working in ANIC as an Honorary Fellow until his death in 2012. Don’s main scientific interests were in the taxonomy and biology of true flies, and in the theory of phylogenetic reconstruction and classification. Don was trained in entomology at the University of Sydney, and spent nearly two decades of his early career in Asia studying mosquitoes and disease transmission, first in the Army during the Second World War in New Guinea and Borneo (1942–45), then after the war in North Borneo (1947–1952) and as a lecturer in the Department of Parasitology at the University of Malaya (1952–1960) in Singapore. We list the 127 scientific papers and book chapters that Don published during his scientific career that spanned 64 years. Six of these papers were published in the prestigious international journal Nature, and he was Chief Curator of the ANIC from 1971–1977. Don had extremely broad taxonomic interests, publishing on the taxonomy of 18 families of Diptera that spanned the phylogenetic breadth of the order. He described as new to science the fly families Perissommatidae and Axiniidae, thirteen new genera and over 120 species and, with David McAlpine, authored the Diptera chapters in both editions of The Insects of Australia (Melbourne University Press, 1970 and 1991). He published a number of influential critiques of cladistic theory in the 1960's and 1970's, and advocated a phenetic approach to the discovery of taxonomic groups, and phylogenetic reconstruction.
  3. Plotkin JB, Chave J, Ashton PS
    Am Nat, 2002 Nov;160(5):629-44.
    PMID: 18707513 DOI: 10.1086/342823
    Tree species in tropical rain forests exhibit a rich panoply of spatial patterns that beg ecological explanation. The analysis of tropical census data typically relies on spatial statistics, which quantify the average aggregation tendency of a species. In this article we develop a cluster-based approach that complements traditional spatial statistics in the exploration and analysis of ecological hypotheses for spatial pattern. We apply this technique to six study species within a fully mapped 50-ha forest census in peninsular Malaysia. For each species we identify the scale(s) of spatial aggregation and the corresponding tree clusters. We study the correlation between cluster locations and abiotic variables such as topography. We find that the distribution of cluster sizes exhibits equilibrium and nonequilibrium behavior depending on species life history. The distribution of tree diameters within clusters also varies according to species life history. At different spatial scales, we find evidence for both niche-based and dispersal-limited processes producing spatial pattern. Our methodology for identifying scales of aggregation and clusters is general; we discuss the method's applicability to spatial problems outside of tropical plant ecology.
  4. Sharma G, Ahmed HMA, Zilm PS, Rossi-Fedele G
    Aust Endod J, 2018 Apr;44(1):60-65.
    PMID: 29168274 DOI: 10.1111/aej.12216
    This review aims to evaluate the antimicrobial efficacy of calcium hydroxide against endodontic pathogens when used for 7 days or longer. A systematic electronic literature search was performed in the PubMed, Embase and EBSCO Dentistry & Oral Sciences Source databases using appropriate key words to identify investigations written in the English language that examined the association between the contact time of intracanal calcium hydroxide dressing and its antimicrobial properties. There were no exclusions based on study design. The search yielded 6993 publications. After duplicate removal, 5913 publications were identified and 11 studies met the inclusion criteria. Results showed that the antimicrobial effect of calcium hydroxide for contact times ranging between seven and 45 days is comparable. Two studies demonstrated contradictory findings when exposure was extended to more than 45 days. Future studies are warranted to investigate and optimise calcium hydroxide application for longer periods and identify the potential benefits of its use in clinical settings.
  5. Peter S, Abdul Rahman ZA, Pillai S
    Int J Oral Maxillofac Surg, 2019 Oct;48(10):1317-1322.
    PMID: 31014926 DOI: 10.1016/j.ijom.2019.03.896
    The aim of this study was to document differences in hypernasality during speaking and singing among children with cleft palate and to compare nasality score ratings of trained and untrained listeners. Twenty subjects with cleft palate aged between 7 and 12 years participated in this study. Audio recordings were made of the children reading a passage and singing a common local song, both in the Malay language. The degree of hypernasality was judged through perceptual assessment. Three trained listeners (a speech therapist, a classical singer, and a linguistic expert - all academicians) and two untrained listeners (a cleft volunteer worker and a national high school teacher) assessed the recordings using a visual analogue scale (VAS). Inter-rater and intra-rater reliability for hypernasality in both speaking and singing were verified using the intra-class correlation coefficient (ICC). A significant reduction in hypernasality was observed during singing as compared to speaking, indicating that hypernasality reduces when a child with cleft palate sings. The act of singing significantly reduces hypernasality. The outcome of this study suggests that children with cleft palate would benefit from singing exercises to ultimately reduce hypernasality. However, future research is needed to objectively measure nasality in singing compared to speaking.
  6. Kohyama TS, Potts MD, Kohyama TI, Kassim AR, Ashton PS
    Am Nat, 2015 Mar;185(3):367-79.
    PMID: 25674691 DOI: 10.1086/679664
    Different mechanisms have been proposed to explain how vertical and horizontal heterogeneity in light conditions enhances tree species coexistence in forest ecosystems. The foliage partitioning theory proposes that differentiation in vertical foliage distribution, caused by an interspecific variation in mortality-to-growth ratio, promotes stable coexistence. In contrast, successional niche theory posits that horizontal light heterogeneity, caused by gap dynamics, enhances species coexistence through an interspecific trade-off between growth rate and survival. To distinguish between these theories of species coexistence, we analyzed tree inventory data for 370 species from the 50-ha plot in Pasoh Forest Reserve, Malaysia. We used community-wide Bayesian models to quantify size-dependent growth rate and mortality of every species. We compared the observed size distributions and the projected distributions from size-dependent demographic rates. We found that the observed size distributions were not simply correlated with the rate of population increase but were related to demographic properties such as size growth rate and mortality. Species with low relative abundance of juveniles in size distribution showed high growth rate and low mortality at small tree sizes and low per-capita recruitment rate. Overall, our findings were in accordance with those predicted by foliage partitioning theory.
  7. Abdul-Razak S, Azzopardi PS, Patton GC, Mokdad AH, Sawyer SM
    J Adolesc Health, 2017 Oct;61(4):424-433.
    PMID: 28838752 DOI: 10.1016/j.jadohealth.2017.05.014
    PURPOSE: A rapid epidemiological transition in developing countries in Southeast Asia has been accompanied by major shifts in the health status of children and adolescents. In this article, mortality estimates in Malaysian children and adolescents from 1990 to 2013 are used to illustrate these changes.

    METHODS: All-cause and cause-specific mortality estimates were obtained from the 2013 Global Burden of Disease Study. Data were extracted from 1990 to 2013 for the developmental age range from 1 to 24 years, for both sexes. Trends in all-cause and cause-specific mortality for the major epidemiological causes were estimated.

    RESULTS: From 1990 to 2013, all-cause mortality decreased in all age groups. Reduction of all-cause mortality was greatest in 1- to 4-year-olds (2.4% per year reduction) and least in 20- to 24-year-olds (.9% per year reduction). Accordingly, in 2013, all-cause mortality was highest in 20- to 24-year-old males (129 per 100,000 per year). In 1990, the principal cause of death for 1- to 9-year boys and girls was vaccine preventable diseases. By 2013, neoplasms had become the major cause of death in 1-9 year olds of both sexes. The major cause of death in 10- to 24-year-old females was typhoid in 1990 and neoplasms in 2013, whereas the major cause of death in 10- to 24-year-old males remained road traffic injuries.

    CONCLUSIONS: The reduction in mortality across the epidemiological transition in Malaysia has been much less pronounced for adolescents than younger children. The contribution of injuries and noncommunicable diseases to adolescent mortality suggests where public health strategies should focus.

  8. Rayagiri SS, Ranaldi D, Raven A, Mohamad Azhar NIF, Lefebvre O, Zammit PS, et al.
    Nat Commun, 2018 03 14;9(1):1075.
    PMID: 29540680 DOI: 10.1038/s41467-018-03425-3
    A central question in stem cell biology is the relationship between stem cells and their niche. Although previous reports have uncovered how signaling molecules released by niche cells support stem cell function, the role of the extra-cellular matrix (ECM) within the niche is unclear. Here, we show that upon activation, skeletal muscle stem cells (satellite cells) induce local remodeling of the ECM and the deposition of laminin-α1 and laminin-α5 into the basal lamina of the satellite cell niche. Genetic ablation of laminin-α1, disruption of integrin-α6 signaling or blocking matrix metalloproteinase activity impairs satellite cell expansion and self-renewal. Collectively, our findings establish that remodeling of the ECM is an integral process of stem cell activity to support propagation and self-renewal, and may explain the effect laminin-α1-containing supports have on embryonic and adult stem cells, as well as the regenerative activity of exogenous laminin-111 therapy.
  9. Dong SX, Davies SJ, Ashton PS, Bunyavejchewin S, Supardi MN, Kassim AR, et al.
    Proc Biol Sci, 2012 Oct 7;279(1744):3923-31.
    PMID: 22833269
    The response of tropical forests to global climate variability and change remains poorly understood. Results from long-term studies of permanent forest plots have reported different, and in some cases opposing trends in tropical forest dynamics. In this study, we examined changes in tree growth rates at four long-term permanent tropical forest research plots in relation to variation in solar radiation, temperature and precipitation. Temporal variation in the stand-level growth rates measured at five-year intervals was found to be positively correlated with variation in incoming solar radiation and negatively related to temporal variation in night-time temperatures. Taken alone, neither solar radiation variability nor the effects of night-time temperatures can account for the observed temporal variation in tree growth rates across sites, but when considered together, these two climate variables account for most of the observed temporal variability in tree growth rates. Further analysis indicates that the stand-level response is primarily driven by the responses of smaller-sized trees (less than 20 cm in diameter). The combined temperature and radiation responses identified in this study provide a potential explanation for the conflicting patterns in tree growth rates found in previous studies.
  10. Feeley KJ, Davies SJ, Ashton PS, Bunyavejchewin S, Nur Supardi MN, Kassim AR, et al.
    Proc Biol Sci, 2007 Nov 22;274(1627):2857-64.
    PMID: 17785266
    The responses of tropical forests to global anthropogenic disturbances remain poorly understood. Above-ground woody biomass in some tropical forest plots has increased over the past several decades, potentially reflecting a widespread response to increased resource availability, for example, due to elevated atmospheric CO2 and/or nutrient deposition. However, previous studies of biomass dynamics have not accounted for natural patterns of disturbance and gap phase regeneration, making it difficult to quantify the importance of environmental changes. Using spatially explicit census data from large (50 ha) inventory plots, we investigated the influence of gap phase processes on the biomass dynamics of four 'old-growth' tropical forests (Barro Colorado Island (BCI), Panama; Pasoh and Lambir, Malaysia; and Huai Kha Khaeng (HKK), Thailand). We show that biomass increases were gradual and concentrated in earlier-phase forest patches, while biomass losses were generally of greater magnitude but concentrated in rarer later-phase patches. We then estimate the rate of biomass change at each site independent of gap phase dynamics using reduced major axis regressions and ANCOVA tests. Above-ground woody biomass increased significantly at Pasoh (+0.72% yr(-1)) and decreased at HKK (-0.56% yr(-1)) independent of changes in gap phase but remained stable at both BCI and Lambir. We conclude that gap phase processes play an important role in the biomass dynamics of tropical forests, and that quantifying the role of gap phase processes will help improve our understanding of the factors driving changes in forest biomass as well as their place in the global carbon budget.
  11. Goense L, van Rossum PS, Kandioler D, Ruurda JP, Goh KL, Luyer MD, et al.
    Ann N Y Acad Sci, 2016 10;1381(1):50-65.
    PMID: 27384385 DOI: 10.1111/nyas.13113
    Esophageal cancer is the eighth most common cancer worldwide, and the incidence of esophageal carcinoma is rapidly increasing. With the advent of new staging and treatment techniques, esophageal cancer can now be managed through various strategies. A good understanding of the advances and limitations of new staging techniques and how these can guide in individualizing treatment is important to improve outcomes for esophageal cancer patients. This paper outlines the recent progress in staging and treatment of esophageal cancer, with particularly attention to endoscopic techniques for early-stage esophageal cancer, multimodality treatment for locally advanced esophageal cancer, assessment of response to neoadjuvant treatment, and the role of cervical lymph node dissection. Furthermore, advances in robot-assisted surgical techniques and postoperative recovery protocols that may further improve outcomes after esophagectomy are discussed.
  12. van der Werf ET, Redmond NM, Turnbull S, Thornton H, Thompson M, Little P, et al.
    Br J Gen Pract, 2019 Apr;69(681):e236-e245.
    PMID: 30858333 DOI: 10.3399/bjgp19X701837
    BACKGROUND: Severity assessments of respiratory tract infection (RTI) in children are known to differ between parents and clinicians, but determinants of perceived severity are unknown.

    AIM: To investigate the (dis)agreement between, and compare the determinants of, parent and clinician severity scores.

    DESIGN AND SETTING: Secondary analysis of data from a prospective cohort study of 8394 children presenting to primary care with acute (≤28 days) cough and RTI.

    METHOD: Data on sociodemographic factors, parent-reported symptoms, clinician-reported findings, and severity assessments were used. Kappa (κ)-statistics were used to investigate (dis) agreement, whereas multivariable logistic regression was used to identify the factors associated with illness severity.

    RESULTS: Parents reported higher illness severity (mean 5.2 [standard deviation (SD) 1.8], median 5 [interquartile range (IQR) 4-7]), than clinicians (mean 3.1 [SD 1.7], median 3 [IQR 2-4], P<0.0001). There was low positive correlation between these scores (+0.43) and poor inter-rater agreement between parents and clinicians (κ 0.049). The number of clinical signs was highly correlated with clinician scores (+0.71). Parent-reported symptoms (in the previous 24 hours) that were independently associated with higher illness severity scores, in order of importance, were: severe fever, severe cough, rapid breathing, severe reduced eating, moderate-to-severe reduced fluid intake, severe disturbed sleep, and change in cry. Three of these symptoms (severe fever, rapid breathing, and change in cry) along with inter/subcostal recession, crackles/crepitations, nasal flaring, wheeze, and drowsiness/irritability were associated with higher clinician scores.

    CONCLUSION: Clinicians and parents use different factors and make different judgements about the severity of children's RTI. Improved understanding of the factors that concern parents could improve parent-clinician communication and consultation outcomes.

  13. Muria-Gonzalez MJ, Yeng Y, Breen S, Mead O, Wang C, Chooi YH, et al.
    Front Microbiol, 2020;11:466.
    PMID: 32269554 DOI: 10.3389/fmicb.2020.00466
    Septoria nodorum blotch is a major disease of wheat caused by the fungus Parastagonospora nodorum. Recent studies have demonstrated that secondary metabolites, including polyketides and non-ribosomal peptides, produced by the pathogen play important roles in disease and development. However, there is currently no knowledge on the composition or biological activity of the volatile organic compounds (VOCs) secreted by P. nodorum. To address this, we undertook a series of growth and phytotoxicity assays and demonstrated that P. nodorum VOCs inhibited bacterial growth, were phytotoxic and suppressed self-growth. Mass spectrometry analysis revealed that 3-methyl-1-butanol, 2-methyl-1-butanol, 2-methyl-1-propanol, and 2-phenylethanol were dominant in the VOC mixture and phenotypic assays using these short chain alcohols confirmed that they were phytotoxic. Further analysis of the VOCs also identified the presence of multiple sesquiterpenes of which four were identified via mass spectrometry and nuclear magnetic resonance as β-elemene, α-cyperone, eudesma-4,11-diene and acora-4,9-diene. Subsequent reverse genetics studies were able to link these molecules to corresponding sesquiterpene synthases in the P. nodorum genome. However, despite extensive testing, these molecules were not involved in either of the growth inhibition or phytotoxicity phenotypes previously observed. Plant assays using mutants of the pathogen lacking the synthetic genes revealed that the identified sesquiterpenes were not required for disease formation on wheat leaves. Collectively, these data have significantly extended our knowledge of the VOCs in fungi and provided the basis for further dissecting the roles of sesquiterpenes in plant disease.
  14. Janib SM, Gustafson JA, Minea RO, Swenson SD, Liu S, Pastuszka MK, et al.
    Biomacromolecules, 2014 Jul 14;15(7):2347-58.
    PMID: 24871936 DOI: 10.1021/bm401622y
    Recombinant protein therapeutics have increased in number and frequency since the introduction of human insulin, 25 years ago. Presently, proteins and peptides are commonly used in the clinic. However, the incorporation of peptides into clinically approved nanomedicines has been limited. Reasons for this include the challenges of decorating pharmaceutical-grade nanoparticles with proteins by a process that is robust, scalable, and cost-effective. As an alternative to covalent bioconjugation between a protein and nanoparticle, we report that biologically active proteins may themselves mediate the formation of small multimers through steric stabilization by large protein polymers. Unlike multistep purification and bioconjugation, this approach is completed during biosynthesis. As proof-of-principle, the disintegrin protein called vicrostatin (VCN) was fused to an elastin-like polypeptide (A192). A significant fraction of fusion proteins self-assembled into multimers with a hydrodynamic radius of 15.9 nm. The A192-VCN fusion proteins compete specifically for cell-surface integrins on human umbilical vein endothelial cells (HUVECs) and two breast cancer cell lines, MDA-MB-231 and MDA-MB-435. Confocal microscopy revealed that, unlike linear RGD-containing protein polymers, the disintegrin fusion protein undergoes rapid cellular internalization. To explore their potential clinical applications, fusion proteins were characterized using small animal positron emission tomography (microPET). Passive tumor accumulation was observed for control protein polymers; however, the tumor accumulation of A192-VCN was saturable, which is consistent with integrin-mediated binding. The fusion of a protein polymer and disintegrin results in a higher intratumoral contrast compared to free VCN or A192 alone. Given the diversity of disintegrin proteins with specificity for various cell-surface integrins, disintegrin fusions are a new source of biomaterials with potential diagnostic and therapeutic applications.
  15. Léger A, Lambraki I, Graells T, Cousins M, Henriksson PJG, Harbarth S, et al.
    J Antimicrob Chemother, 2021 01 01;76(1):1-21.
    PMID: 33057678 DOI: 10.1093/jac/dkaa394
    The global threat of antimicrobial resistance (AMR) requires coordinated actions by and across different sectors. Increasing attention at the global and national levels has led to different strategies to tackle the challenge. The diversity of possible actions to address AMR is currently not well understood from a One Health perspective. AMR-Intervene, an interdisciplinary social-ecological framework, describes interventions to tackle AMR in terms of six components: (i) core information about the publication; (ii) social system; (iii) bio-ecological system; (iv) triggers and goals; (v) implementation and governance; and (vi) assessment. AMR-Intervene provides a broadly applicable framework, which can inform the design, implementation, assessment and reporting of interventions to tackle AMR and, in turn, enable faster uptake of successful interventions to build societal resilience to AMR.
  16. Léger A, Lambraki I, Graells T, Cousins M, Henriksson PJG, Harbarth S, et al.
    BMC Infect Dis, 2021 Aug 26;21(1):873.
    PMID: 34445962 DOI: 10.1186/s12879-021-06483-z
    BACKGROUND: Antimicrobial resistance (AMR) is among the most pressing One Health issues. While interventions and policies with various targets and goals have been implemented, evidence about factors underpinning success and failure of interventions in different sectors is lacking. The objective of this study is to identify characteristics of AMR interventions that increase their capacity to impact AMR. This study focuses on AMR interventions targeting E. coli.

    METHODS: We used the AMR-Intervene framework to extract descriptions of the social and ecological systems of interventions to determine factors contributing to their success.

    RESULTS: We identified 52 scientific publications referring to 42 unique E. coli AMR interventions. We mainly identified interventions implemented in high-income countries (36/42), at the national level (16/42), targeting primarily one sector of society (37/42) that was mainly the human sector (25/42). Interventions were primarily funded by governments (38/42). Most intervention targeted a low leverage point in the AMR system, (36/42), and aimed to change the epidemiology of AMR (14/42). Among all included publications, 55% (29/52) described at least one success factor or obstacle (29/52) and 19% (10/52) identified at least one success factor and one obstacle. Most reported success factors related to communication between the actors and stakeholders and the role of media, and stressed the importance of collaboration between disciplines and external partners. Described obstacles covered data quality, access to data and statistical analyses, and the validity of the results.

    CONCLUSIONS: Overall, we identified a lack of diversity regarding interventions. In addition, most published E. coli interventions were poorly described with limited evidence of the factors that contributed to the intervention success or failure. Design and reporting guidelines would help to improve reporting quality and provide a valuable tool for improving the science of AMR interventions.

  17. Yap HY, Muria-Gonzalez MJ, Kong BH, Stubbs KA, Tan CS, Ng ST, et al.
    Microb Cell Fact, 2017 Jun 12;16(1):103.
    PMID: 28606152 DOI: 10.1186/s12934-017-0713-x
    BACKGROUND: Genome mining facilitated by heterologous systems is an emerging approach to access the chemical diversity encoded in basidiomycete genomes. In this study, three sesquiterpene synthase genes, GME3634, GME3638, and GME9210, which were highly expressed in the sclerotium of the medicinal mushroom Lignosus rhinocerotis, were cloned and heterologously expressed in a yeast system.

    RESULTS: Metabolite profile analysis of the yeast culture extracts by GC-MS showed the production of several sesquiterpene alcohols (C15H26O), including cadinols and germacrene D-4-ol as major products. Other detected sesquiterpenes include selina-6-en-4-ol, β-elemene, β-cubebene, and cedrene. Two purified major compounds namely (+)-torreyol and α-cadinol synthesised by GME3638 and GME3634 respectively, are stereoisomers and their chemical structures were confirmed by 1H and 13C NMR. Phylogenetic analysis revealed that GME3638 and GME3634 are a pair of orthologues, and are grouped together with terpene synthases that synthesise cadinenes and related sesquiterpenes. (+)-Torreyol and α-cadinol were tested against a panel of human cancer cell lines and the latter was found to exhibit selective potent cytotoxicity in breast adenocarcinoma cells (MCF7) with IC50 value of 3.5 ± 0.58 μg/ml while α-cadinol is less active (IC50 = 18.0 ± 3.27 μg/ml).

    CONCLUSIONS: This demonstrates that yeast-based genome mining, guided by transcriptomics, is a promising approach for uncovering bioactive compounds from medicinal mushrooms.

  18. McCallum GB, Singleton RJ, Redding GJ, Grimwood K, Byrnes CA, Valery PC, et al.
    Pediatr Pulmonol, 2020 04;55(4):975-985.
    PMID: 32096916 DOI: 10.1002/ppul.24696
    OBJECTIVE: The sole prospective longitudinal study of children with either chronic suppurative lung disease (CSLD) or bronchiectasis published in the current era was limited to a single center. We sought to extend this study by evaluating the longer-term clinical and lung function outcomes and their associated risk factors in Indigenous children of adolescents from Australia, Alaska, and New Zealand who participated in our previous CSLD or bronchiectasis studies during 2004-2010.

    METHODS: Between 2015 and 2018, we evaluated 131 out of 180 (72.8%) children of adolescents from the original studies at a single follow-up visit. We administered standardized questionnaires, reviewed medical records, undertook clinical examinations, performed spirometry, and scored available chest computed tomography scans.

    RESULTS: Participants were seen at a mean age of 12.3 years (standard deviation: 2.6) and a median of 9.0 years (range: 5.0-13.0) after their original recruitment. With increasing age, rates of acute lower respiratory infections (ALRI) declined, while lung function was mostly within population norms (median forced expiry volume in one-second = 90% predicted, interquartile range [IQR]: 81-105; forced vital capacity [FVC] = 98% predicted, IQR: 85-114). However, 43 out of 111 (38.7%) reported chronic cough episodes. Their overall global rating judged by symptoms, including ALRI frequency, examination findings, and spirometry was well (20.3%), stable (43.9%), or improved (35.8%). Multivariable regression identified household tobacco exposure and age at first ALRI-episode as independent risk factors associated with lower FVC% predicted values.

    CONCLUSION: Under our clinical care, the respiratory outcomes in late childhood or early adolescence are encouraging for these patient populations at high-risk of premature mortality. Prospective studies to further inform management throughout the life course into adulthood are now needed.

  19. Kim Y, Griffin JM, Nor MNM, Zhang J, Freestone PS, Danesh-Meyer HV, et al.
    Neurotherapeutics, 2017 Oct;14(4):1148-1165.
    PMID: 28560708 DOI: 10.1007/s13311-017-0536-9
    The cis benzopyran compound tonabersat (SB-220453) has previously been reported to inhibit connexin26 expression in the brain by attenuating the p38-mitogen-activated protein kinase pathway. We show here that tonabersat directly inhibits connexin43 hemichannel opening. Connexin43 hemichannels have been called "pathological pores" based upon their role in secondary lesion spread, edema, inflammation, and neuronal loss following central nervous system injuries, as well as in chronic inflammatory disease. Both connexin43 hemichannels and pannexin channels released adenosine triphosphate (ATP) during ischemia in an in vitro ischemia model, but only connexin43 hemichannels contributed to ATP release during reperfusion. Tonabersat inhibited connexin43 hemichannel-mediated ATP release during both ischemia and reperfusion phases, with direct channel block confirmed using electrophysiology. Tonabersat also reduced connexin43 gap junction coupling in vitro, but only at higher concentrations, with junctional plaques internalized and degraded via the lysosomal pathway. Systemic delivery of tonabersat in a rat bright-light retinal damage model (a model for dry age-related macular degeneration) resulted in significantly improved functional outcomes assessed using electroretinography. Tonabersat also prevented thinning of the retina, especially the outer nuclear layer and choroid, assessed using optical coherence tomography. We conclude that tonabersat, already given orally to over 1000 humans in clinical trials (as a potential treatment for, and prophylactic treatment of, migraine because it was thought to inhibit cortical spreading depression), is a connexin hemichannel inhibitor and may have the potential to be a novel treatment of central nervous system injury and chronic neuroinflammatory disease.
  20. Fong MWK, Stephens E, Brockington A, Jayabal J, Scott S, Zhang T, et al.
    Epilepsia, 2024 Apr 18.
    PMID: 38634858 DOI: 10.1111/epi.17975
    OBJECTIVE: Determination of the real-world performance of a health care system in the treatment of status epilepticus (SE).

    METHODS: Prospective, multicenter population-based study of SE in Auckland, New Zealand (NZ) over 1 year, with data recorded in the EpiNet database. Focus on treatment patterns and determinants of SE duration and 30-day mortality. The incidence, etiology, ethnic discrepancies, and seizure characteristics of this cohort have been published previously.

    RESULTS: A total of 365 patients were included in this treatment cohort; 326 patients (89.3%) were brought to hospital because of SE, whereas 39 patients (10.7%) developed SE during a hospital admission for another reason. Overall, 190 (52.1%) had a known history of epilepsy and 254 (70.0%) presented with SE with prominent motor activity. The mean Status Epilepticus Severity Score (STESS) was 2.15 and the mean SE duration of all patients was 44 min. SE self-terminated without any treatment in 84 patients (22.7%). Earlier administration of appropriately dosed benzodiazepine in the pre-hospital setting was a major determinant of SE duration. Univariate analysis demonstrated that mortality was significantly higher in older patients, patients with longer durations of SE, higher STESS, and patients who developed SE in hospital, but these did not maintain significance with multivariate analysis. There was no difference in the performance of the health care system in the treatment of SE across ethnic groups.

    SIGNIFICANCE: When SE was defined as 10 continuous minutes of seizure, overall mortality was lower than expected and many patients had self-limited presentations for which no treatment was required. Although there were disparities in the incidence of SE across ethnic groups there was no difference in treatment or outcome. The finding highlights the benefit of a health care system designed to deliver universal health care.

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