Displaying publications 21 - 40 of 116 in total

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  1. Campbell P, Schneider CJ, Adnan AM, Zubaid A, Kunz TH
    Mol Phylogenet Evol, 2004 Dec;33(3):764-81.
    PMID: 15522802
    Taxonomic relationships within the Old World fruit bat genus, Cynopterus, have been equivocal for the better part of a century. While nomenclature has been revised multiple times on the basis of phenotypic characters, evolutionary relationships among taxa representing the entire geographic range of the genus have not been determined. We used mitochondrial DNA sequence data to infer phylogenetic relationships among the three most broadly distributed members of the genus: C. brachyotis, C. horsfieldi, and C. sphinx, and to assess whether C. brachyotis represents a single widespread species, or a complex of distinct lineages. Results clearly indicate that C. brachyotis is a complex of lineages. C. sphinx and C. horsfieldi haplotypes formed monophyletic groups nested within the C. brachyotis species complex. We identified six divergent mitochondrial lineages that are currently referred to C. brachyotis. Lineages from India, Myanmar, Sulawesi, and the Philippines are geographically well-defined, while in Malaysia two lineages, designated Sunda and Forest, are broadly sympatric and may be ecologically distinct. Demographic analyses of the Sunda and Forest lineages suggest strikingly different population histories, including a recent and rapid range expansion in the Sunda lineage, possibly associated with changes in sea levels during the Pleistocene. The resolution of the taxonomic issues raised in this study awaits combined analysis of morphometric characters and molecular data. However, since both the Indian and Malaysian Forest C. brachyotis lineages are apparently ecologically restricted to increasingly fragmented forest habitat, we suggest that reevaluation of the conservation status of populations in these regions should be an immediate goal.
  2. Lappin DF, Robertson D, Hodge P, Treagus D, Awang RA, Ramage G, et al.
    J. Periodontol., 2015 Nov;86(11):1249-59.
    PMID: 26252750 DOI: 10.1902/jop.2015.150149
    BACKGROUND: Periodontal disease is a major complication of type 1 diabetes mellitus (T1DM). The aim of the present study is to investigate the relationship between glycated hemoglobin and circulating levels of interleukin (IL)-6, IL-8, and C-X-C motif chemokine ligand 5 (CXCL5) in non-smoking patients suffering from T1DM, with and without periodontitis. In addition, to determine the effect of advanced glycation end products (AGE) in the presence and absence of Porphyromonas gingivalis lipopolysaccharide (LPS) on IL-6, IL-8, and CXCL5 expression by THP-1 monocytes and OKF6/TERT-2 cells.

    METHODS: There were 104 participants in the study: 19 healthy volunteers, 23 patients with periodontitis, 28 patients with T1DM, and 34 patients with T1DM and periodontitis. Levels of blood glucose/glycated hemoglobin (International Federation of Clinical Chemistry [IFCC]) were determined by high-performance liquid chromatography. Levels of IL-6, IL-8, and CXCL5 in plasma were determined by enzyme-linked immunosorbent assay (ELISA). In vitro stimulation of OKF6/TERT-2 cells and THP-1 monocytes was performed with combinations of AGE and P. gingivalis LPS. Changes in expression of IL-6, IL-8, and CXCL5 were monitored by ELISA and real-time polymerase chain reaction.

    RESULTS: Patients with diabetes and periodontitis had higher plasma levels of IL-8 than patients with periodontitis alone. Plasma levels of IL-8 correlated significantly with IFCC units, clinical probing depth, and attachment loss. AGE and LPS, alone or in combination, stimulated IL-6, IL-8, and CXCL5 expression in both OKF6/TERT-2 cells and THP-1 monocytes.

    CONCLUSIONS: Elevated plasma levels of IL-8 potentially contribute to the cross-susceptibility between periodontitis and T1DM. P. gingivalis LPS and AGE in combination caused significantly greater expression of IL-6, IL-8, and CXCL5 from THP-1 monocytes and OKF6/TERT-2 cells than LPS alone.

  3. Ahmad B, Friar EP, Vohra MS, Garrett MD, Serpell CJ, Fong IL, et al.
    Phytochemistry, 2020 Dec;180:112513.
    PMID: 33010536 DOI: 10.1016/j.phytochem.2020.112513
    The prevalence of obesity is increasing rapidly globally and has recently reached pandemic proportions. It is a multifactorial disorder linked to a number of non-communicable diseases such as type-2 diabetes, cardiovascular disease, and cancer. Over-nutrition and a sedentary lifestyle are considered the most significant causes of obesity; a healthy lifestyle and behavioural interventions are the most powerful ways to achieve successful weight loss, but to maintain this in the long term can prove difficult for many individuals, without medical intervention. Various pharmacological anti-obesogenic drugs have been tested and marketed in the past and have been moderately successful in the management of obesity, but their adverse effects on human health often outweigh the benefits. Natural products from plants, either in the form of crude extracts or purified phytochemicals, have been shown to have anti-obesogenic properties and are generally considered as nontoxic and cost-effective compared to synthetic alternatives. These plant products combat obesity by targeting the various pathways and/or regulatory functions intricately linked to obesity. Their mechanisms of action include inhibition of pancreatic lipase activities, an increase in energy expenditure, appetite regulation, lipolytic effects, and inhibition of white adipose tissue development. In this review, we discuss the distinct anti-obesogenic properties of recently reported plant extracts and specific bioactive compounds, along with their molecular mechanisms of action. This review will provide a common platform for understanding the different causes of obesity and the possible approaches to using plant products in tackling this worldwide health issue.
  4. Barberio B, Mahadeva S, Black CJ, Savarino EV, Ford AC
    Aliment Pharmacol Ther, 2020 09;52(5):762-773.
    PMID: 32852839 DOI: 10.1111/apt.16006
    BACKGROUND: Prevalence of uninvestigated dyspepsia varies across cross-sectional surveys. This may be due to differences in definitions used or study methodology, rather than global variability.

    AIM: To determine the global prevalence of uninvestigated dyspepsia according to Rome criteria.

    METHODS: MEDLINE and EMBASE were searched to identify population-based studies reporting prevalence of uninvestigated dyspepsia in adults (≥18 years old) according to Rome I, II, III or IV criteria. Prevalence of uninvestigated dyspepsia was extracted, according to criteria used to define it. Pooled prevalence, according to study location and certain other characteristics, odds ratios (OR), and 95% confidence intervals (CIs) were calculated.

    RESULTS: Of 2133 citations evaluated, 67 studies fulfilled eligibility criteria, representing 98 separate populations, comprising 338 383 subjects. Pooled prevalence ranged from 17.6% (95% CI 9.8%-27.1%) in studies defining uninvestigated dyspepsia according to Rome I criteria, to 6.9% (95% CI 5.7%-8.2%) in those using Rome IV criteria. Postprandial distress syndrome was the commonest subtype, occurring in 46.2% of participants using Rome III criteria, and 62.8% with Rome IV. Prevalence of uninvestigated dyspepsia was up to 1.5-fold higher in women, irrespective of the definition used. There was significant heterogeneity between studies in all our analyses, which persisted even when the same criteria were applied and similar methodology was used.

    CONCLUSIONS: Even when uniform symptom-based criteria are used to define the presence of uninvestigated dyspepsia, prevalence varies between countries. This suggests that there are environmental, cultural, ethnic, dietary or genetic influences determining symptoms.

  5. Chen JE, Barbrook AC, Cui G, Howe CJ, Aranda M
    PLoS One, 2019;14(2):e0211936.
    PMID: 30779749 DOI: 10.1371/journal.pone.0211936
    Modern transformation and genome editing techniques have shown great success across a broad variety of organisms. However, no study of successfully applied genome editing has been reported in a dinoflagellate despite the first genetic transformation of Symbiodinium being published about 20 years ago. Using an array of different available transformation techniques, we attempted to transform Symbiodinium microadriaticum (CCMP2467), a dinoflagellate symbiont of reef-building corals, with the view to performing subsequent CRISPR-Cas9 mediated genome editing. Plasmid vectors designed for nuclear transformation containing the chloramphenicol resistance gene under the control of the CaMV p35S promoter as well as several putative endogenous promoters were used to test a variety of transformation techniques including biolistics, electroporation and agitation with silicon carbide whiskers. Chloroplast-targeted transformation was attempted using an engineered Symbiodinium chloroplast minicircle encoding a modified PsbA protein expected to confer atrazine resistance. We report that we have been unable to confer chloramphenicol or atrazine resistance on Symbiodinium microadriaticum strain CCMP2467.
  6. Vohra MS, Ahmad B, Serpell CJ, Parhar IS, Wong EH
    Differentiation, 2020 08 23;115:62-84.
    PMID: 32891960 DOI: 10.1016/j.diff.2020.08.003
    Adipogenesis has been extensively studied using in vitro models of cellular differentiation, enabling long-term regulation of fat cell metabolism in human adipose tissue (AT) material. Many studies promote the idea that manipulation of this process could potentially reduce the prevalence of obesity and its related diseases. It has now become essential to understand the molecular basis of fat cell development to tackle this pandemic disease, by identifying therapeutic targets and new biomarkers. This review explores murine cell models and their applications for study of the adipogenic differentiation process in vitro. We focus on the benefits and limitations of different cell line models to aid in interpreting data and selecting a good cell line model for successful understanding of adipose biology.
  7. Ahmad B, Vohra MS, Saleemi MA, Serpell CJ, Fong IL, Wong EH
    Biochimie, 2021 May;184:26-39.
    PMID: 33548390 DOI: 10.1016/j.biochi.2021.01.015
    Brown and beige adipose tissues are the primary sites for adaptive non-shivering thermogenesis. Although they have been known principally for their thermogenic effects, in recent years, it has emerged that, just like white adipose tissue (WAT), brown and beige adipose tissues also play an important role in the regulation of metabolic health through secretion of various brown adipokines (batokines) in response to various physiological cues. These secreted batokines target distant organs and tissues such as the liver, heart, skeletal muscles, brain, WAT, and perform various local and systemic functions in an autocrine, paracrine, or endocrine manner. Brown and beige adipose tissues are therefore now receiving increasing levels of attention with respect to their effects on various other organs and tissues. Identification of novel secreted factors by these tissues may help in the discovery of drug candidates for the treatment of various metabolic disorders such as obesity, type-2 diabetes, skeletal deformities, cardiovascular diseases, dyslipidemia. In this review, we comprehensively describe the emerging secretory role of brown/beige adipose tissues and the metabolic effects of various brown/beige adipose tissues secreted factors on other organs and tissues in endocrine/paracrine manners, and as well as on brown/beige adipose tissue itself in an autocrine manner. This will provide insights into understanding the potential secretory role of brown/beige adipose tissues in improving metabolic health.
  8. Ismail AH, Munro KJ, Armitage CJ, Marsden A, Dawes PD
    Trends Hear, 2021 6 1;25:2331216520969472.
    PMID: 34057373 DOI: 10.1177/2331216520969472
    Suboptimal hearing aid use negatively impacts health and well-being. The aim of this study was to conduct a controlled trial of a behavior change intervention to promote hearing aid use. This study was a quasi-randomized controlled trial with two arms. A total of 160 first-time hearing aid users were recruited at their hearing aid fitting appointments. The control arm received standard care. In addition to standard care, the intervention arm received I-PLAN, which comprised (a) information about the consequences of hearing aid use/nonuse, (b) reminder prompt to use the hearing aids, and (c) an action plan. The primary outcome, measured at 6 weeks, was self-reported proportion of time the hearing aid was used in situations that caused hearing difficulty. Secondary outcomes were data-logged hearing aid use, self-reported hearing aid benefit, self-regulation, and habit formation. The results showed that the proportion of time the hearing aids were used in situations that caused hearing difficulty was similar in both groups. There were no statistically significant differences between groups in any outcome measure including data-logged hearing aid use. The relatively high levels of hearing aid use across research participants may have limited the potential for the intervention to impact on hearing aid use. Although the intervention materials proved acceptable and deliverable, future intervention trials should target suboptimal hearing aid users.
  9. Razali A, Fullerton CJ, Turci F, Hallett JE, Jack RL, Royall CP
    Soft Matter, 2017 May 03;13(17):3230-3239.
    PMID: 28401216 DOI: 10.1039/c6sm02221a
    We consider the sedimentation of a colloidal gel under confinement in the direction of gravity. The confinement allows us to compare directly experiments and computer simulations, for the same system size in the vertical direction. The confinement also leads to qualitatively different behaviour compared to bulk systems: in large systems gelation suppresses sedimentation, but for small systems sedimentation is enhanced relative to non-gelling suspensions, although the rate of sedimentation is reduced when the strength of the attraction between the colloids is strong. We map interaction parameters between a model experimental system (observed in real space) and computer simulations. Remarkably, we find that when simulating the system using Brownian dynamics in which hydrodynamic interactions between the particles are neglected, we find that sedimentation occurs on the same timescale as the experiments. An analysis of local structure in the simulations showed similar behaviour to gelation in the absence of gravity.
  10. Ling I, Kumari H, Mirzamani M, Sobolev AN, Garvey CJ, Atwood JL, et al.
    Chem Commun (Camb), 2018 Sep 25;54(77):10824-10827.
    PMID: 30140821 DOI: 10.1039/c8cc05650a
    We report on the assembly of three-fold axially compressed icosahedral arrays of the bowl shaped p-sulfonatocalix[4]arene molecules in the solid-state, intricately bound to dipicolinate and yttrium(iii) ions, with the compression reflected in Hirshfeld surface analyses. Solution studies show dissolution of the icosahedra intact, but with a geometrical rearrangement to regular icosahedra.
  11. Abdullah NA, Inman M, Moody CJ, Storr SJ, Martin SG
    Invest New Drugs, 2021 10;39(5):1232-1241.
    PMID: 33768386 DOI: 10.1007/s10637-021-01106-5
    Radiotherapy is an effective treatment modality for breast cancer but, unfortunately, not all patients respond fully with a significant number experiencing local recurrences. Overexpression of thioredoxin and thioredoxin reductase has been reported to cause multidrug and radiation resistance - their inhibition may therefore improve therapeutic efficacy. Novel indolequinone compounds have been shown, in pancreatic cancer models, to inhibit thioredoxin reductase activity and exhibit potent anticancer activity. The present study evaluates, using in vitro breast cancer models, the efficacy of a novel indolequinone compound (IQ9) as a single agent and in combination with ionising radiation using a variety of endpoint assays including cell proliferation, clonogenic survival, enzyme activity, and western blotting. Three triple-negative breast cancer (MDA-MB-231, MDA-MB-468, and MDA-MB-436) and two luminal (MCF-7 and T47D) breast cancer cell lines were used. Results show that treatment with IQ9 significantly inhibited thioredoxin reductase activity, and inhibited cell growth and colony formation of breast cancer cells with IC50 values in the low micromolar ranges. Enhanced radiosensitivity of triple-negative breast cancer cells was observed, with sensitiser enhancement ratios of 1.20-1.43, but with no evident radiosensitisation of luminal breast cancer cell lines. IQ9 upregulated protein expression of thioredoxin reductase in luminal but not in triple-negative breast cancer cells which may explain the observed differential radiosensitisation. This study provides important evidence of the roles of the thioredoxin system as an exploitable radiobiological target in breast cancer cells and highlights the potential therapeutic value of indolequinones as radiosensitisers.***This study was not part of a clinical trial. Clinical trial registration number: N/A.
  12. Guest H, Dewey RS, Plack CJ, Couth S, Prendergast G, Bakay W, et al.
    Trends Hear, 2018;22:2331216518803213.
    PMID: 30295145 DOI: 10.1177/2331216518803213
    Lifetime noise exposure is generally quantified by self-report. The accuracy of retrospective self-report is limited by respondent recall but is also bound to be influenced by reporting procedures. Such procedures are of variable quality in current measures of lifetime noise exposure, and off-the-shelf instruments are not readily available. The Noise Exposure Structured Interview (NESI) represents an attempt to draw together some of the stronger elements of existing procedures and to provide solutions to their outstanding limitations. Reporting is not restricted to prespecified exposure activities and instead encompasses all activities that the respondent has experienced as noisy (defined based on sound level estimated from vocal effort). Changing exposure habits over time are reported by dividing the lifespan into discrete periods in which exposure habits were approximately stable, with life milestones used to aid recall. Exposure duration, sound level, and use of hearing protection are reported for each life period separately. Simple-to-follow methods are provided for the estimation of free-field sound level, the sound level emitted by personal listening devices, and the attenuation provided by hearing protective equipment. An energy-based means of combining the resulting data is supplied, along with a primarily energy-based method for incorporating firearm-noise exposure. Finally, the NESI acknowledges the need of some users to tailor the procedures; this flexibility is afforded, and reasonable modifications are described. Competency needs of new users are addressed through detailed interview instructions (including troubleshooting tips) and a demonstration video. Limited evaluation data are available, and future efforts at evaluation are proposed.
  13. Ismail AH, Armitage CJ, Munro KJ, Marsden A, Dawes PD
    Ear Hear, 2022 01 06;43(4):1103-1113.
    PMID: 34999593 DOI: 10.1097/AUD.0000000000001195
    OBJECTIVE: Provision of information is already part of standard care and may not be sufficient to promote hearing aid use. The I-PLAN is a behavior change intervention that is designed to promote hearing aid use in adults. It consists of a prompt, an action plan and provision of information. The objective was to test the effectiveness of the I-PLAN prompt and plan components in promoting hearing aid use and benefit. Hypotheses were: there would be greater hearing aid use, benefit, self-regulation, and hearing aid use habit among participants who received the prompt or plan component, compared with no prompt or no plan component, and the effect would be the greatest in participants who received both prompt and plan; and self-regulation and habit would mediate the effect of prompt and/or plan components on hearing aid use and benefit.

    DESIGN: A 2 x 2 factorial randomized controlled trial design. Two hundred forty new adult patients (60 in each group) were randomized to: information (info) only; info + prompt; info + plan; or info + prompt + plan. All participants received treatment as usual in addition to I-PLAN components, which were provided in a sealed envelope at the end of the hearing aid fitting consultation. Participants in the prompt group were instructed to use their hearing aid box as a physical prompt to remind them to use the device. Participants in the plan group were instructed to write an action plan to encourage them to turn their intentions into action. Participants, audiologists, and researchers were blinded to group allocation. The primary outcome was self-reported proportion of time hearing aids were used in situations where they had listening difficulties. Secondary outcomes were hearing aid use derived from data logging, self-reported hearing aid benefit, self-reported self-regulation, and habit. Outcomes were measured at 6-week post-fitting.

    RESULTS: Contrary to predictions, participants who received the prompt component reported using their hearing aid less than participants without the prompt (p = 0.03; d = 0.24). The mean proportion of time hearing aid were used was 73.4% of the time in the prompt group compared with 79.9% of the time in the no prompt group. Participants who received the plan component reported using their hearing aids more frequently than those who did not receive the plan (Meanplan = 81.0% vs Meannoplan = 71.8% of the time; p = 0.01; d = 0.34). Receiving both prompt and plan components did not change self-reported proportion of time hearing aids were used but data-logging use was significantly reduced. The prompt reduced self-regulation of hearing aid use compared with the no prompt (p = 0.04; d = 0.28), while the plan promoted stronger hearing aid use habits than the no plan group (p = 0.02; d = 0.30).

    CONCLUSIONS: Audiologists should consider using action plans to promote hearing aid use. Despite the decrease in hearing aid use when using the hearing aid box as a physical prompt, hearing aid use was still high (≈70% of the time). The hearing aid box may have slightly reduced hearing aid use by undermining self-regulation. Participants may have delegated responsibility for hearing aid use to the prompt. Subsequent studies should evaluate different prompts and test the long-term benefit of the plan on hearing aid use via habit formation.

  14. Mensah GA, Fuster V, Murray CJL, Roth GA, Global Burden of Cardiovascular Diseases and Risks Collaborators
    J Am Coll Cardiol, 2023 Dec 19;82(25):2350-2473.
    PMID: 38092509 DOI: 10.1016/j.jacc.2023.11.007
  15. Longo CJ, Fitch MI, Banfield L, Hanly P, Yabroff KR, Sharp L
    Support Care Cancer, 2020 Oct;28(10):4645-4665.
    PMID: 32653957 DOI: 10.1007/s00520-020-05620-9
    PURPOSE: Financial toxicity related to cancer diagnosis and treatment is a common issue in developed countries. We seek to systematically summarize the extent of the issue in very high development index countries with publicly funded healthcare.

    METHODS: We identified articles published Jan 1, 2005, to March 7, 2019, describing financial burden/toxicity experienced by cancer patients and/or informal caregivers using OVID Medline Embase and PsychInfo, CINAHL, Business Source Complete, and EconLit databases. Only English language peer-reviewed full papers describing studies conducted in very high development index countries with predominantly publicly funded healthcare were eligible (excluded the USA). All stages of the review were evaluated in teams of two researchers excepting the final data extraction (CJL only).

    RESULTS: The searches identified 7117 unique articles, 32 of which were eligible. Studies were undertaken in Canada, Australia, Ireland, UK, Germany, Denmark, Malaysia, Finland, France, South Korea, and the Netherlands. Eighteen studies reported patient/caregiver out-of-pocket costs (range US$17-US$506/month), 18 studies reported patient/caregiver lost income (range 17.6-67.3%), 14 studies reported patient/caregiver travel and accommodation costs (range US$8-US$393/month), and 6 studies reported financial stress (range 41-48%), strain (range 7-39%), or financial burden/distress/toxicity among patients/caregivers (range 22-27%). The majority of studies focused on patients, with some including caregivers. Financial toxicity was greater in those with early disease and/or more severe cancers.

    CONCLUSIONS: Despite government-funded universal public healthcare, financial toxicity is an issue for cancer patients and their families. Although levels of toxicity vary between countries, the findings suggest financial protection appears to be inadequate in many countries.

  16. Bhubalan K, Chuah JA, Shozui F, Brigham CJ, Taguchi S, Sinskey AJ, et al.
    Appl Environ Microbiol, 2011 May;77(9):2926-33.
    PMID: 21398494 DOI: 10.1128/AEM.01997-10
    The synthesis of bacterial polyhydroxyalkanoates (PHA) is very much dependent on the expression and activity of a key enzyme, PHA synthase (PhaC). Many efforts are being pursued to enhance the activity and broaden the substrate specificity of PhaC. Here, we report the identification of a highly active wild-type PhaC belonging to the recently isolated Chromobacterium sp. USM2 (PhaC(Cs)). PhaC(Cs) showed the ability to utilize 3-hydroxybutyrate (3HB), 3-hydroxyvalerate (3HV), and 3-hydroxyhexanoate (3HHx) monomers in PHA biosynthesis. An in vitro assay of recombinant PhaC(Cs) expressed in Escherichia coli showed that its polymerization of 3-hydroxybutyryl-coenzyme A activity was nearly 8-fold higher (2,462 ± 80 U/g) than that of the synthase from the model strain C. necator (307 ± 24 U/g). Specific activity using a Strep2-tagged, purified PhaC(Cs) was 238 ± 98 U/mg, almost 5-fold higher than findings of previous studies using purified PhaC from C. necator. Efficient poly(3-hydroxybutyrate) [P(3HB)] accumulation in Escherichia coli expressing PhaC(Cs) of up to 76 ± 2 weight percent was observed within 24 h of cultivation. To date, this is the highest activity reported for a purified PHA synthase. PhaC(Cs) is a naturally occurring, highly active PHA synthase with superior polymerizing ability.
  17. Dewey RS, Francis ST, Guest H, Prendergast G, Millman RE, Plack CJ, et al.
    Neuroimage, 2020 Jan 01;204:116239.
    PMID: 31586673 DOI: 10.1016/j.neuroimage.2019.116239
    In animal models, exposure to high noise levels can cause permanent damage to hair-cell synapses (cochlear synaptopathy) for high-threshold auditory nerve fibers without affecting sensitivity to quiet sounds. This has been confirmed in several mammalian species, but the hypothesis that lifetime noise exposure affects auditory function in humans with normal audiometric thresholds remains unconfirmed and current evidence from human electrophysiology is contradictory. Here we report the auditory brainstem response (ABR), and both transient (stimulus onset and offset) and sustained functional magnetic resonance imaging (fMRI) responses throughout the human central auditory pathway across lifetime noise exposure. Healthy young individuals aged 25-40 years were recruited into high (n = 32) and low (n = 30) lifetime noise exposure groups, stratified for age, and balanced for audiometric threshold up to 16 kHz fMRI demonstrated robust broadband noise-related activity throughout the auditory pathway (cochlear nucleus, superior olivary complex, nucleus of the lateral lemniscus, inferior colliculus, medial geniculate body and auditory cortex). fMRI responses in the auditory pathway to broadband noise onset were significantly enhanced in the high noise exposure group relative to the low exposure group, differences in sustained fMRI responses did not reach significance, and no significant group differences were found in the click-evoked ABR. Exploratory analyses found no significant relationships between the neural responses and self-reported tinnitus or reduced sound-level tolerance (symptoms associated with synaptopathy). In summary, although a small effect, these fMRI results suggest that lifetime noise exposure may be associated with central hyperactivity in young adults with normal hearing thresholds.
  18. Heim A, Grimm C, Müller U, Häußler S, Mackeen MM, Merl J, et al.
    Nucleic Acids Res, 2014 Jul;42(12):7833-50.
    PMID: 24914048 DOI: 10.1093/nar/gku488
    The Fe(II) and 2-oxoglutarate dependent oxygenase Jmjd6 has been shown to hydroxylate lysine residues in the essential splice factor U2 auxiliary factor 65 kDa subunit (U2AF65) and to act as a modulator of alternative splicing. We describe further evidence for the role of Jmjd6 in the regulation of pre-mRNA processing including interactions of Jmjd6 with multiple arginine-serine-rich (RS)-domains of SR- and SR-related proteins including U2AF65, Luc7-like protein 3 (Luc7L3), SRSF11 and Acinus S', but not with the bona fide RS-domain of SRSF1. The identified Jmjd6 target proteins are involved in different mRNA processing steps and play roles in exon dependent alternative splicing and exon definition. Moreover, we show that Jmjd6 modifies splicing of a constitutive splice reporter, binds RNA derived from the reporter plasmid and punctually co-localises with nascent RNA. We propose that Jmjd6 exerts its splice modulatory function by interacting with specific SR-related proteins during splicing in a RNA dependent manner.
  19. Mirsafian H, Manda SS, Mitchell CJ, Sreenivasamurthy S, Ripen AM, Mohamad SB, et al.
    Genomics, 2016 07;108(1):37-45.
    PMID: 26778813 DOI: 10.1016/j.ygeno.2016.01.002
    Long non-coding RNAs (lncRNAs) have been shown to possess a wide range of functions in both cellular and developmental processes including cancers. Although some of the lncRNAs have been implicated in the regulation of the immune response, the exact function of the large majority of lncRNAs still remains unknown. In this study, we characterized the lncRNAs in human primary monocytes, an essential component of the innate immune system. We performed RNA sequencing of monocytes from four individuals and combined our data with eleven other publicly available datasets. Our analysis led to identification of ~8000 lncRNAs of which >1000 have not been previously reported in monocytes. PCR-based validation of a subset of the identified novel long intergenic noncoding RNAs (lincRNAs) revealed distinct expression patterns. Our study provides a landscape of lncRNAs in monocytes, which could facilitate future experimental studies to characterize the functions of these molecules in the innate immune system.
  20. Ford AC, Moayyedi P, Black CJ, Yuan Y, Veettil SK, Mahadeva S, et al.
    Aliment Pharmacol Ther, 2021 01;53(1):8-21.
    PMID: 32936964 DOI: 10.1111/apt.16072
    BACKGROUND: Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy is unknown.

    AIM: To perform a systematic review with network meta-analysis to resolve this uncertainty.

    METHODS: We searched the medical literature through July 2020 for randomised controlled trials (RCTs) assessing efficacy of drugs for adults with FD, compared with each other, or placebo. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic with a 95% confidence interval (CI) to summarise efficacy of each comparison tested. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities.

    RESULTS: We identified 71 eligible RCTs (19 243 participants). Tricyclic antidepressants (TCAs) were ranked second for efficacy (RR of remaining symptomatic = 0.71; 95% CI 0.58-0.87, SUCRA 0.87), and first when only low risk of bias trials were included. Most RCTs that used TCAs recruited patients who were refractory to other drugs included in the network. Although sulpiride or levosulpiride were ranked first for efficacy (RR = 0.49; 95% CI 0.36-0.69, SUCRA 0.99), trial quality was low and only 86 patients received active therapy. TCAs were more likely to cause adverse events than placebo.

    CONCLUSIONS: TCAs, histamine-2 receptor antagonists, standard- and low-dose proton pump inhibitors, sulpiride or levosulpiride, itopride and acotiamide were all more efficacious than placebo for FD.

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