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  1. Vijayan K, Schroder HJ, Hameed A, Hitos K, Lo W, Laurence JM, et al.
    Transplantation, 2024 Feb 16.
    PMID: 38361237 DOI: 10.1097/TP.0000000000004937
    BACKGROUND: Uncontrolled donation after circulatory death (uDCD) is a potential additional source of donor kidneys. This study reviewed uDCD kidney transplant outcomes to determine if these are comparable to controlled donation after circulatory death (cDCD).

    METHODS: MEDLINE, Cochrane, and Embase databases were searched. Data on demographic information and transplant outcomes were extracted from included studies. Meta-analyses were performed, and risk ratios (RR) were estimated to compare transplant outcomes from uDCD to cDCD.

    RESULTS: Nine cohort studies were included, from 2178 uDCD kidney transplants. There was a moderate degree of bias, as 4 studies did not account for potential confounding factors. The median incidence of primary nonfunction in uDCD was 12.3% versus 5.7% for cDCD (RR, 1.85; 95% confidence intervals, 1.06-3.23; P = 0.03, I2 = 75). The median rate of delayed graft function was 65.1% for uDCD and 52.0% for cDCD. The median 1-y graft survival for uDCD was 82.7% compared with 87.5% for cDCD (RR, 1.43; 95% confidence intervals, 1.02-2.01; P = 0.04; I2 = 71%). The median 5-y graft survival for uDCD and cDCD was 70% each. Notably, the use of normothermic regional perfusion improved primary nonfunction rates in uDCD grafts.

    CONCLUSIONS: Although uDCD outcomes may be inferior in the short-term, the long-term outcomes are comparable to cDCD.

  2. Biria M, Banca P, Healy MP, Keser E, Sawiak SJ, Rodgers CT, et al.
    Nat Commun, 2023 Jun 27;14(1):3324.
    PMID: 37369695 DOI: 10.1038/s41467-023-38695-z
    There has been little analysis of neurochemical correlates of compulsive behaviour to illuminate its underlying neural mechanisms. We use 7-Tesla proton magnetic resonance spectroscopy (1H-MRS) to assess the balance of excitatory and inhibitory neurotransmission by measuring glutamate and GABA levels in anterior cingulate cortex (ACC) and supplementary motor area (SMA) of healthy volunteers and participants with Obsessive-Compulsive Disorder (OCD). Within the SMA, trait and clinical measures of compulsive behaviour are related to glutamate levels, whereas a behavioural index of habitual control correlates with the glutamate:GABA ratio. Participants with OCD also show the latter relationship in the ACC while exhibiting elevated glutamate and lower GABA levels in that region. This study highlights SMA mechanisms of habitual control relevant to compulsive behaviour, common to the healthy sub-clinical and OCD populations. The results also demonstrate additional involvement of anterior cingulate in the balance between goal-directed and habitual responding in OCD.
  3. Mohd Mydin FH, Mikton C, Choo WY, Shunmugam RH, Murray A, Yon Y, et al.
    Campbell Syst Rev, 2024 Sep;20(3):e1419.
    PMID: 39211334 DOI: 10.1002/cl2.1419
    BACKGROUND: The examination of psychometric properties in instruments measuring abuse of older people (AOP) is a crucial area of study that has, unfortunately, received relatively little attention. Poor psychometric properties in AOP measurement instruments can significantly contribute to inconsistencies in prevalence estimates, casting a shadow of uncertainty over the magnitude of the problem at national, regional, and global levels.

    OBJECTIVES: This review rigorously employed the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) guideline on the quality of outcome measures. It was designed to identify and review the instruments used to measure AOP, assess the instruments' measurement properties, and identify the definitions of AOP and abuse subtypes measured by these instruments, ensuring the reliability and validity of the findings.

    SEARCH METHODS: A comprehensive search was conducted up to May 2023 across various online databases, including AgeLine via EBSCOhost, ASSIA via ProQuest, CINAHL via EBSCOhost, EMBASE, LILACS, ProQuest Dissertation & Theses Global, PsycINFO via EBSCOhost, PubMed, SciELO, Scopus, Sociological Abstract via ProQuest, Chinese National Knowledge Infrastructure (CNKI), Google Scholar and WHO Global Index Medicus. Additionally, relevant studies were identified by thoroughly searching the grey literature from resources such as Campbell Collaboration, OpenAIRE, and GRAFT.

    SELECTION CRITERIA: All quantitative, qualitative (addressing face and content validity), and mixed-method empirical studies published in peer-reviewed journals or grey literature were included in this review. The included studies were primary studies that (1) evaluated one or more psychometric properties, (2) contained information on instrument development, or (3) examined the content validity of the instruments designed to measure AOP in community or institutional settings. The selected studies describe at least one psychometric property: reliability, validity, and responsiveness. Study participants represent the population of interest, including males and females aged 60 or older in community or institutional settings.

    DATA COLLECTION AND ANALYSIS: Two reviewers evaluated the screening of the selected studies' titles, abstracts, and full texts based on the preset selection criteria. Two reviewers assessed the quality of each study using the COSMIN Risk of Bias checklist and the overall quality of evidence for each psychometric property of the instrument against the updated COSMIN criteria of good measurement properties. Disagreements were resolved through consensus discussion or with assistance from a third reviewer. The overall quality of the measurement instrument was graded using a modified GRADE approach. Data extraction was performed using data extraction forms adapted from the COSMIN Guideline for Systematic Reviews of Outcome Measurement Instruments. The extracted data included information on the characteristics of included instruments (name, adaptation, language used, translation and country of origin), characteristics of the tested population, instrument development, psychometric properties listed in the COSMIN criteria, including details on content validity, structural validity, internal consistency, cross-cultural validity/measurement invariance, reliability, measurement error, criterion validity, hypotheses testing for construct validity, responsiveness, and interoperability. All data were synthesised and summarised qualitatively, and no meta-analysis was performed.

    MAIN RESULTS: We found 15,200 potentially relevant records, of which 382 were screened in full text. A total of 114 studies that met the inclusion criteria were included. Four studies reported on more than one instrument. The primary reasons for excluding studies were their focus on instruments used solely for screening and diagnostic purposes, those conducted in hospital settings, or those without evaluating psychometric properties. Eighty-seven studies reported on 46 original instruments and 29 studies on 22 modified versions of an original instrument. The majority of the studies were conducted in community settings (97 studies) from the perspective of older adults (90 studies) and were conducted in high-income countries (69 studies). Ninety-five studies assessed multiple forms of abuse, ranging from 2 to 13 different subscales; four studies measured overall abuse and neglect among older adults, and 14 studies measured one specific type of abuse. Approximately one-quarter of the included studies reported on the psychometric properties of the most frequently used measurement instruments: HS-EAST (assessed in 11 studies), VASS-12 items (in 9 studies), and CASE (in 9 studies). The instruments with the most evidence available in studies reporting on instrument development and content validity in all domains (relevance, comprehensiveness and comprehensibility) were the DEAQ, OAPAM, *RAAL-31 items, *ICNH (Norwegian) and OAFEM. For other psychometric properties, instruments with the most evidence available in terms of the number of studies were the HS-EAST (11 studies across 5 of 9 psychometric properties), CASE (9 studies across 6 of 9 psychometric properties), VASS-12 items (9 studies across 5 of 9 psychometric properties) and GMS (5 studies across 4 of 9 psychometric properties). Based on the overall rating and quality of evidence, the psychometric properties of the AOP measurement instruments used for prevalence measurement in community and institutional settings were insufficient and of low quality.

    AUTHORS' CONCLUSIONS: This review aimed to assess the overall rating and quality of evidence for instruments measuring AOP in the community and institutional settings. Our findings revealed various measurement instruments, with ratings and evidence quality predominantly indicating insufficiency and low quality. In summary, the psychometric properties of AOP measurement instruments have not been comprehensively investigated, and existing instruments lack sufficient evidence to support their validity and reliability.

  4. Winter AJ, de Courcy-Ireland F, Phillips AP, Barker JM, Bakar NA, Akter N, et al.
    Angew Chem Int Ed Engl, 2024 Dec 02;63(49):e202410502.
    PMID: 39105412 DOI: 10.1002/anie.202410502
    The delineation of the complex biosynthesis of the potent antibiotic mupirocin, which consists of a mixture of pseudomonic acids (PAs) isolated from Pseudomonas fluorescens NCIMB 10586, presents significant challenges, and the timing and mechanisms of several key transformations remain elusive. Particularly intriguing are the steps that process the linear backbone from the initial polyketide assembly phase to generate the first cyclic intermediate PA-B. These include epoxidation as well as incorporation of the tetrahydropyran (THP) ring and fatty acid side chain required for biological activity. Herein, we show that the mini-module MmpE performs a rare online (ACP-substrate) epoxidation and is integrated ('in-cis') into the polyketide synthase via a docking domain. A linear polyketide fragment with six asymmetric centres was synthesised using a convergent approach and used to demonstrate substrate flux via an atypical KS0 and a previously unannotated ACP (MmpE_ACP). MmpE_ACP-bound synthetic substrates were critical in demonstrating successful epoxidation in vitro by the purified MmpE oxidoreductase domain. Alongside feeding studies, these results confirm the timing as well as chain length dependence of this selective epoxidation. These mechanistic studies pinpoint the location and nature of the polyketide substrate prior to the key formation of the THP ring and esterification that generate PA-B.
  5. Jolly TA, Cooper PS, Badwi SA, Phillips NA, Rennie JL, Levi CR, et al.
    Psychophysiology, 2016 Feb;53(2):258-67.
    PMID: 26511789 DOI: 10.1111/psyp.12565
    Although the relationship between aging and cognitive decline is well established, there is substantial individual variability in the degree of cognitive decline in older adults. The present study investigates whether variability in cognitive performance in community-dwelling older adults is related to the presence of whole brain or tract-specific changes in white matter microstructure. Specifically, we examine whether age-related decline in performance on the Montreal Cognitive Assessment (MoCA), a cognitive screening tool, is mediated by the white matter microstructural decline. We also examine if this relationship is driven by the presence of cardiovascular risk factors or variability in cerebral arterial pulsatility, an index of cardiovascular risk. Sixty-nine participants (aged 43-87) completed behavioral and MRI testing including T1 structural, T2-weighted FLAIR, and diffusion-weighted imaging (DWI) sequences. Measures of white matter microstructure were calculated using diffusion tensor imaging analyses on the DWI sequence. Multiple linear regression revealed that MoCA scores were predicted by radial diffusivity (RaD) of white matter beyond age or other cerebral measures. While increasing age and arterial pulsatility were associated with increasing RaD, these factors did not mediate the relationship between total white matter RaD and MoCA. Further, the relationship between MoCA and RaD was specific to participants who reported at least one cardiovascular risk factor. These findings highlight the importance of cardiovascular risk factors in the presentation of cognitive decline in old age. Further work is needed to establish whether medical or lifestyle management of these risk factors can prevent or reverse cognitive decline in old age.
  6. Grigg MJ, William T, Clemens EG, Patel K, Chandna A, Wilkes CS, et al.
    Emerg Infect Dis, 2020 Jul;26(7):1409-19.
    PMID: 32568664 DOI: 10.3201/eid2607.191722
    Orientia tsutsugamushi, spotted fever group rickettsioses, and typhus group rickettsioses (TGR) are reemerging causes of acute febrile illness (AFI) in Southeast Asia. To further delineate extent, we enrolled patients >4 weeks of age with nonmalarial AFI in Sabah, Malaysia, during 2013-2015. We confirmed rickettsioses (past or acute, IgG titer >160) in 126/354 (36%) patients. We confirmed acute rickettsioses (paired 4-fold IgG titer rise to >160) in 38/145 (26%) patients: 23 O. tsutsugamushi, 9 spotted fever group, 4 TGR, 1 O. tsutsugamushi/spotted fever group, and 1 O. tsutsugamushi/TGR. PCR results were positive in 11/319 (3%) patients. Confirmed rickettsioses were more common in male adults; agricultural/plantation work and recent forest exposure were risk factors. Dizziness and acute hearing loss but not eschars were reported more often with acute rickettsioses. Only 2 patients were treated with doxycycline. Acute rickettsioses are common (>26%), underrecognized, and untreated etiologies of AFI in East Malaysia; empirical doxycycline treatment should be considered.
  7. Ning F, Luo L, Ahmad S, Valli H, Jeevaratnam K, Wang T, et al.
    Pflugers Arch, 2016 Apr;468(4):655-65.
    PMID: 26545784 DOI: 10.1007/s00424-015-1750-0
    Catecholaminergic polymorphic ventricular tachycardia (CPVT) predisposes to ventricular arrhythmia due to altered Ca(2+) homeostasis and can arise from ryanodine receptor (RyR2) mutations including RyR2-P2328S. Previous reports established that homozygotic murine RyR2-P2328S (RyR2 (S/S)) hearts show an atrial arrhythmic phenotype associated with reduced action potential (AP) conduction velocity and sodium channel (Nav1.5) expression. We now relate ventricular arrhythmogenicity and slowed AP conduction in RyR2 (S/S) hearts to connexin-43 (Cx43) and Nav1.5 expression and Na(+) current (I Na). Stimulation protocols applying extrasystolic S2 stimulation following 8 Hz S1 pacing at progressively decremented S1S2 intervals confirmed an arrhythmic tendency despite unchanged ventricular effective refractory periods (VERPs) in Langendorff-perfused RyR2 (S/S) hearts. Dynamic pacing imposing S1 stimuli then demonstrated that progressive reductions of basic cycle lengths (BCLs) produced greater reductions in conduction velocity at equivalent BCLs and diastolic intervals in RyR2 (S/S) than WT, but comparable changes in AP durations (APD90) and their alternans. Western blot analyses demonstrated that Cx43 protein expression in whole ventricles was similar, but Nav1.5 expression in both whole tissue and membrane fractions were significantly reduced in RyR2 (S/S) compared to wild-type (WT). Loose patch-clamp studies similarly demonstrated reduced I Na in RyR2 (S/S) ventricles. We thus attribute arrhythmogenesis in RyR2 (S/S) ventricles resulting from arrhythmic substrate produced by reduced conduction velocity to downregulated Nav1.5 reducing I Na, despite normal determinants of repolarization and passive conduction. The measured changes were quantitatively compatible with earlier predictions of linear relationships between conduction velocity and the peak I Na of the AP but nonlinear relationships between peak I Na and maximum Na(+) permeability.
  8. Burahee AS, Duraku LS, Hundepool CA, Eberlin KR, Moore A, Dy CJ, et al.
    Plast Reconstr Surg Glob Open, 2024 Jan;12(1):e5559.
    PMID: 38264442 DOI: 10.1097/GOX.0000000000005559
    BACKGROUND: This study aimed to evaluate a novel, multi-site, technology-facilitated education and training course in peripheral nerve surgery. The program was developed to address the training gaps in this specialized field by integrating a structured curriculum, high-fidelity cadaveric dissection, and surgical simulation with real-time expert guidance.

    METHODS: A collaboration between the Global Nerve Foundation and Esser Masterclass facilitated the program, which was conducted across three international sites. The curriculum was developed by a panel of experienced peripheral nerve surgeons and included both text-based and multimedia resources. Participants' knowledge and skills were assessed using pre- and postcourse questionnaires.

    RESULTS: A total of 73 participants from 26 countries enrolled and consented for data usage for research purposes. The professional background was diverse, including hand surgeons, plastic surgeons, orthopedic surgeons, and neurosurgeons. Participants reported significant improvements in knowledge and skills across all covered topics (p < 0.001). The course received a 100% recommendation rate, and 88% confirmed that it met their educational objectives.

    CONCLUSIONS: This study underscores the potential of technology-enabled, collaborative expert-led training programs in overcoming geographical and logistical barriers, setting a new standard for globally accessible, high-quality surgical training. It highlights the practical and logistical challenges of multi-site training, such as time zone differences and participant fatigue. It also provides practical insights for future medical educational endeavors, particularly those that aim to be comprehensive, international, and technologically facilitated.

  9. Mohd Mydin FH, Mikton C, Choo WY, Shanmugam RH, Murray A, Yon Y, et al.
    Campbell Syst Rev, 2023 Sep;19(3):e1342.
    PMID: 37383829 DOI: 10.1002/cl2.1342
    BACKGROUND: The psychometric properties of elder abuse measurement instruments have not been well-studied. Poor psychometric properties of elder abuse measurement instruments may contribute to the inconsistency of elder abuse prevalence estimates and uncertainty about the magnitude of the problem at the national, regional, and global levels.

    OBJECTIVES: The present review will utilise the COSMIN taxonomy on the quality of outcome measures to identify and review the instruments used in measuring elder abuse, assess the instrument's measurement properties, and identify the definitions of elder abuse and abuse subtypes measured by the instrument.

    SEARCH METHODS: Searches will be conducted in the following online databases: Ageline, ASSIA, CINAHL, CNKI, EMBASE, Google Scholar, LILACS, Proquest Dissertation & Theses Global, PsycINFO, PubMed, SciELO, Scopus, Sociological Abstract and WHO Index Medicus. Relevant studies will also be identified by searching the grey literature from several resources such as OpenAIRE, BASE, OISter and Age Concern NZPotential studies by searching the references of related reviews. We will contact experts who have conducted similar work or are currently conducting ongoing studies. Enquiries will also be sent to the relevant authors if any important data is missing, incomplete or unclear.

    SELECTION CRITERIA: All quantitative, qualitative (that address face and content validity), and mixed-method empirical studies published in peer-reviewed journals or the grey literature will be included in this review. Studies will be included if they are primary studies that (1) evaluate one or more psychometric properties; (2) contain information on instrument development, or (3) perform content validity of the instruments designed to measure elder abuse in the community or institutional settings. Studies should describe at least one of the psychometric properties, such as reliability, validity and responsiveness. Study participants represent the population of interest, including males and females aged 60 or older in community or institutional settings (i.e., nursing homes, long-term care facilities, assisted living, residential care institutions, and residential facilities).

    DATA COLLECTION AND ANALYSIS: Screening of titles, abstracts, and full texts of the selected studies will be evaluated based on the preset inclusion criteria by two reviewers. Two reviewers will be assessing the quality appraisal of each study using the COSMIN Risk of Bias checklist and the overall quality of evidence of each psychometric property of the instrument against the updated criteria of good measurement properties. Any dispute between the two reviewers will be resolved through discussions or consensus with a third reviewer. The overall quality of the measurement instrument will be graded using a modified GRADE approach. Data extraction will be performed using the data extraction forms adapted from the COSMIN Guideline for Systematic Reviews of Outcome Measurement Instruments. The information includes the characteristic of included instruments (name, adaptation, language used, translation and country of origin), characteristics of the tested population, psychometric properties listed in the COSMIN criteria, including details on the instrument development, content validity, structural validity, internal consistency, cross-cultural validity/measurement invariance, reliability, measurement error, criterion validity, hypotheses testing for construct validity, responsiveness and interoperability. We will perform a meta-analysis to pool psychometric properties parameters (where possible) or summarise qualitatively.

  10. Blyth CC, Foo H, van Hal SJ, Hurt AC, Barr IG, McPhie K, et al.
    Emerg Infect Dis, 2010 May;16(5):809-15.
    PMID: 20409371 DOI: 10.3201/eid1605.091136
    Influenza outbreaks during mass gatherings have been rarely described, and detailed virologic assessment is lacking. An influenza outbreak occurred during World Youth Day in Sydney, Australia, July 2008 (WYD2008). We assessed epidemiologic data and respiratory samples collected from attendees who sought treatment for influenza-like illness at emergency clinics in Sydney during this outbreak. Isolated influenza viruses were compared with seasonal influenza viruses from the 2008 influenza season. From 100 infected attendees, numerous strains were identified: oseltamivir-resistant influenza A (H1N1) viruses, oseltamivir-sensitive influenza A (H1N1) viruses, influenza A (H3N2) viruses, and strains from both influenza B lineages (B/Florida/4/2006-like and B/Malaysia/2506/2004-like). Novel viruses were introduced, and pre-WYD2008 seasonal viruses were amplified. Viruses isolated at mass gatherings can have substantial, complex, and unpredictable effects on community influenza activity. Greater flexibility by public health authorities and hospitals is required to appropriately manage and contain these outbreaks.
  11. Vimalanathan K, Palmer T, Gardner Z, Ling I, Rahpeima S, Elmas S, et al.
    Nanoscale Adv, 2021 Oct 12;3(20):5785-5792.
    PMID: 36132680 DOI: 10.1039/d1na00598g
    A diversity of two-dimensional nanomaterials has recently emerged with recent attention turning to the post-transition metal elements, in particular material derived from liquid metals and eutectic melts below 330 °C where processing is more flexible and in the temperature regime suitable for industry. This has been explored for liquid gallium using an angled vortex fluidic device (VFD) to fabricate ultrathin gallium oxide (Ga2O3) sheets under continuous flow conditions. We have established the nanosheets to form highly insulating material and have electrocatalytic activity for hydrogen evolution, with a Tafel slope of 39 mV dec-1 revealing promoting effects of the surface oxidation (passivation layer).
  12. Mellone M, Hanley CJ, Thirdborough S, Mellows T, Garcia E, Woo J, et al.
    Aging (Albany NY), 2016 12 15;9(1):114-132.
    PMID: 27992856 DOI: 10.18632/aging.101127
    Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two. Analysis of CAF cultured ex vivo, showed that senescent CAF are predominantly SMA-positive; this was confirmed by immunochemistry in head & neck (HNSCC) and esophageal (EAC) cancers. In vitro, we found that fibroblasts induced to senesce develop molecular, ultrastructural and contractile features typical of myofibroblasts and this is dependent on canonical TGF-β signaling. Similar to TGF-β1-generated myofibroblasts, these cells secrete soluble factors that promote tumor cell motility. However, RNA-sequencing revealed significant transcriptomic differences between the two SMA-positive CAF groups, particularly in genes associated with extracellular matrix (ECM) deposition and organization, which differentially promote tumor cell invasion. Notably, second harmonic generation imaging and bioinformatic analysis of SMA-positive human HNSCC and EAC showed that collagen fiber organization correlates with poor prognosis, indicating that heterogeneity within the SMA-positive CAF population differentially impacts on survival. These results show that non-fibrogenic, SMA-positive myofibroblasts can be directly generated through induction of fibroblast senescence and suggest that senescence and myofibroblast differentiation are closely linked processes.
  13. Harun A, Kan A, Schwabenbauer K, Gilgado F, Perdomo H, Firacative C, et al.
    PMID: 35024355 DOI: 10.3389/fcimb.2021.761596
    Scedosporium spp. are the second most prevalent filamentous fungi after Aspergillus spp. recovered from cystic fibrosis (CF) patients in various regions of the world. Although invasive infection is uncommon prior to lung transplantation, fungal colonization may be a risk factor for invasive disease with attendant high mortality post-transplantation. Abundant in the environment, Scedosporium aurantiacum has emerged as an important fungal pathogen in a range of clinical settings. To investigate the population genetic structure of S. aurantiacum, a MultiLocus Sequence Typing (MLST) scheme was developed, screening 24 genetic loci for polymorphisms on a tester strain set. The six most polymorphic loci were selected to form the S. aurantiacum MLST scheme: actin (ACT), calmodulin (CAL), elongation factor-1α (EF1α), RNA polymerase subunit II (RPB2), manganese superoxide dismutase (SOD2), and β-tubulin (TUB). Among 188 global clinical, veterinary, and environmental strains, 5 to 18 variable sites per locus were revealed, resulting in 8 to 23 alleles per locus. MLST analysis observed a markedly high genetic diversity, reflected by 159 unique sequence types. Network analysis revealed a separation between Australian and non-Australian strains. Phylogenetic analysis showed two major clusters, indicating correlation with geographic origin. Linkage disequilibrium analysis revealed evidence of recombination. There was no clustering according to the source of the strains: clinical, veterinary, or environmental. The high diversity, especially amongst the Australian strains, suggests that S. aurantiacum may have originated within the Australian continent and was subsequently dispersed to other regions, as shown by the close phylogenetic relationships between some of the Australian sequence types and those found in other parts of the world. The MLST data are accessible at http://mlst.mycologylab.org. This is a joined publication of the ISHAM/ECMM working groups on "Scedosporium/Pseudallescheria Infections" and "Fungal Respiratory Infections in Cystic Fibrosis".
  14. Golden CD, Koehn JZ, Shepon A, Passarelli S, Free CM, Viana DF, et al.
    Nature, 2021 Oct;598(7880):315-320.
    PMID: 34526720 DOI: 10.1038/s41586-021-03917-1
    Despite contributing to healthy diets for billions of people, aquatic foods are often undervalued as a nutritional solution because their diversity is often reduced to the protein and energy value of a single food type ('seafood' or 'fish')1-4. Here we create a cohesive model that unites terrestrial foods with nearly 3,000 taxa of aquatic foods to understand the future impact of aquatic foods on human nutrition. We project two plausible futures to 2030: a baseline scenario with moderate growth in aquatic animal-source food (AASF) production, and a high-production scenario with a 15-million-tonne increased supply of AASFs over the business-as-usual scenario in 2030, driven largely by investment and innovation in aquaculture production. By comparing changes in AASF consumption between the scenarios, we elucidate geographic and demographic vulnerabilities and estimate health impacts from diet-related causes. Globally, we find that a high-production scenario will decrease AASF prices by 26% and increase their consumption, thereby reducing the consumption of red and processed meats that can lead to diet-related non-communicable diseases5,6 while also preventing approximately 166 million cases of inadequate micronutrient intake. This finding provides a broad evidentiary basis for policy makers and development stakeholders to capitalize on the potential of aquatic foods to reduce food and nutrition insecurity and tackle malnutrition in all its forms.
  15. Cysique LA, Levin J, Howard C, Taylor J, Rule J, Costello J, et al.
    Lancet HIV, 2025 Jan;12(1):e71-e80.
    PMID: 39615509 DOI: 10.1016/S2352-3018(24)00248-0
    Prevalence and incidence of HIV among people aged 50 years and older continue to rise worldwide, generating increasing awareness among care providers, scientists, and the HIV community about the importance of brain health in older adults with HIV. Many age-related factors that adversely affect brain health can occur earlier and more often among people with HIV, including epigenetic ageing, chronic medical conditions (eg, cardiovascular disease), and age-related syndromes (eg, frailty). Extensive dialogue between HIV community leaders, health-care providers, and scientists has led to the development of a multidimensional response strategy to protect and enhance brain health in people ageing with HIV that spans across public health, clinical spaces, and research spaces. This response strategy was informed by integrated ageing care frameworks and is centred on prevention, early detection, and management of brain health issues associated with HIV (eg, neurocognitive disorders), with specific considerations for low-resource or middle-resource countries. A collaborative, international, and data-informed update of the diagnostic criteria for HIV-associated neurocognitive disorders is a cornerstone of the proposed response strategy. The proposed response strategy includes a dynamic, international, online knowledge hub that will provide a crucial community resource for emerging evidence on the brain health of people ageing with HIV.
  16. Haridan US, Mokhtar U, Machado LR, Abdul Aziz AT, Shueb RH, Zaid M, et al.
    PLoS One, 2015;10(1):e0116791.
    PMID: 25594501 DOI: 10.1371/journal.pone.0116791
    The FCGR3 locus encoding the low affinity activating receptor FcγRIII, plays a vital role in immunity triggered by cellular effector and regulatory functions. Copy number of the genes FCGR3A and FCGR3B has previously been reported to affect susceptibility to several autoimmune diseases and chronic inflammatory conditions. However, such genetic association studies often yield inconsistent results; hence require assays that are robust with low error rate. We investigated the accuracy and efficiency in estimating FCGR3 CNV by comparing Sequenom MassARRAY and paralogue ratio test-restriction enzyme digest variant ratio (PRT-REDVR). In addition, since many genetic association studies of FCGR3B CNV were carried out using real-time quantitative PCR, we have also included the evaluation of that method's performance in estimating the multi-allelic CNV of FCGR3B. The qPCR assay exhibited a considerably broader distribution of signal intensity, potentially introducing error in estimation of copy number and higher false positive rates. Both Sequenom and PRT-REDVR showed lesser systematic bias, but Sequenom skewed towards copy number normal (CN = 2). The discrepancy between Sequenom and PRT-REDVR might be attributed either to batch effects noise in individual measurements. Our study suggests that PRT-REDVR is more robust and accurate in genotyping the CNV of FCGR3, but highlights the needs of multiple independent assays for extensive validation when performing a genetic association study with multi-allelic CNVs.
  17. Yap LF, Velapasamy S, Lee HM, Thavaraj S, Rajadurai P, Wei W, et al.
    J Pathol, 2015 Feb;235(3):456-65.
    PMID: 25294670 DOI: 10.1002/path.4460
    Undifferentiated nasopharyngeal carcinoma (NPC) is a highly metastatic disease that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the contribution of lysophosphatidic acid (LPA) signalling to the pathogenesis of NPC. Here we demonstrate two distinct functional roles for LPA in NPC. First, we show that LPA enhances the migration of NPC cells and second, that it can inhibit the activity of EBV-specific cytotoxic T cells. Focusing on the first of these phenotypes, we show that one of the LPA receptors, LPA receptor 5 (LPAR5), is down-regulated in primary NPC tissues and that this down-regulation promotes the LPA-induced migration of NPC cell lines. Furthermore, we found that EBV infection or ectopic expression of the EBV-encoded LMP2A was sufficient to down-regulate LPAR5 in NPC cell lines. Our data point to a central role for EBV in mediating the oncogenic effects of LPA in NPC and identify LPA signalling as a potential therapeutic target in this disease.
  18. Zakaria Z, Zainordin NA, Sim BL, Zaid M, Haridan US, Aziz AT, et al.
    J Infect Dev Ctries, 2014 Jul;8(7):869-75.
    PMID: 25022297 DOI: 10.3855/jidc.4283
    INTRODUCTION: The latest revised version of the World Health Organization's dengue classification was released in 2009. A handful of studies have taken initiatives to evaluate the old and revised guidelines to determine early signs and symptoms of severe dengue. This retrospective study aimed to compare the classification of dengue using both the 1997 and 2009 guidelines in a selected cohort of dengue patients from Peninsular Malaysia between 2008 and 2012.
    METHODOLOGY: Adult dengue patients were recruited from tertiary hospitals in two different states, Selangor and Kelantan, in Peninsular Malaysia. Their clinical manifestations were assessed.
    RESULTS: A total of 281 confirmed dengue patients were enrolled; the mean duration of illness at admission was five days. Of these, 88.6%, 10.7%, and 0.7% were classified according to the 1997 guidelines as having dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS), respectively. When the WHO 2009 guidelines were applied, 17.1%, 78.3%, and 4.6% were classified as dengue without warning signs, dengue with warning signs, and severe dengue, respectively.
    CONCLUSIONS: Our data suggests that the revised WHO 2009 guidelines stratify a much larger proportion of patients into a category that requires a higher level of medical and nursing care.
  19. Kim HS, Mukhopadhyay R, Rothbart SB, Silva AC, Vanoosthuyse V, Radovani E, et al.
    Cell Rep, 2014 Mar 13;6(5):892-905.
    PMID: 24565511 DOI: 10.1016/j.celrep.2014.01.029
    Condensin is a central regulator of mitotic genome structure with mutants showing poorly condensed chromosomes and profound segregation defects. Here, we identify NCT, a complex comprising the Nrc1 BET-family tandem bromodomain protein (SPAC631.02), casein kinase II (CKII), and several TAFs, as a regulator of condensin function. We show that NCT and condensin bind similar genomic regions but only briefly colocalize during the periods of chromosome condensation and decondensation. This pattern of NCT binding at the core centromere, the region of maximal condensin enrichment, tracks the abundance of acetylated histone H4, as regulated by the Hat1-Mis16 acetyltransferase complex and recognized by the first Nrc1 bromodomain. Strikingly, mutants in NCT or Hat1-Mis16 restore the formation of segregation-competent chromosomes in cells containing defective condensin. These results are consistent with a model where NCT targets CKII to chromatin in a cell-cycle-directed manner in order to modulate the activity of condensin during chromosome condensation and decondensation.
  20. Oxford J, Berezin EN, Courvalin P, Dwyer DE, Exner M, Jana LA, et al.
    Am J Infect Control, 2014 Apr;42(4):423-5.
    PMID: 24679569 DOI: 10.1016/j.ajic.2013.10.016
    We investigated the survival of a pandemic strain of influenza A H1N1 on a variety of common household surfaces where multiple samples were taken from 4 types of common household fomite at 7 time points. Results showed that influenza A H1N1sw virus particles remained infectious for 48 hours on a wooden surface, for 24 hours on stainless steel and plastic surfaces, and for 8 hours on a cloth surface, although virus recovery from the cloth may have been suboptimal. Our results suggest that pandemic influenza A H1N1 can survive on common household fomites for extended periods of time, and that good hand hygiene and regular disinfection of commonly touched surfaces should be practiced during the influenza season to help reduce transmission.
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