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1,3-Dipolar cycloadditions of 2-thio-3-chloroacrylamides with diazoalkanes
(RSC Publishing, 2010-06-21) Kissane, Marie; Lawrence, Simon E.; Maguire, Anita R.; Irish Research Council for Science Engineering and Technology
2-Thio-3-chloroacrylamides undergo 1,3-dipolar cycloadditions with diazoalkanes leading to a series of novel pyrazolines and pyrazoles. The mechanistic and synthetic features of the cycloadditions to the 2-thio-3-chloroacrylamides at both the sulfide and sulfoxide levels of oxidation are rationalised on the basis of the nature of the substituents.
1,3-Dipolar cycloadditions of 2-thio-3-chloroacrylamides with nitrile oxides and nitrones
(Elsevier, 2010-06-19) Kissane, Marie; Lawrence, Simon E.; Maguire, Anita R.; Irish Research Council for Science Engineering and Technology
1,3-Dipolar cycloadditions of 2-thio-3-chloroacrylamides with nitrile oxides and nitrones is described. A series of novel isoxazolines are isolated from the nitrile oxide cycloadditions, whilst the isoxazolines generated from the nitrone cycloadditions undergo further ring opening to yield piperidines.
18-Fluorodeoxyglucose positron emission tomography/computed tomography in the management of aggressive non-Hodgkin's B-cell lymphoma
(Hindawi Publishing Corporation, 2012) Shelly, M. J.; McDermott, S.; O'Connor, Owen J.; Blake, M. A.
18-Fluorodeoxyglucose (FDG-PET/CT) is an established imaging modality that has been proven to be of benefit in the management of aggressive B-cell non-Hodgkin's lymphoma, such as diffuse large B-cell lymphoma and advanced stage follicular lymphoma. The combination of anatomic and functional imaging afforded by FDG-PET/CT has led to superior sensitivity and specificity in the primary staging, restaging, and assessment of response to treatment of hematological malignancies when compared to FDG-PET and CT alone. The use of FDG-PET/CT for post treatment surveillance imaging remains controversial, and further study is needed to ascertain whether this modality is cost effective and appropriate for use in this setting.
The 2019-20 Irish National Drug and Alcohol Survey: Main findings
(Health Research Board, 2021) Mongan, Deirdre; Millar, Seán R.; Galvin, Brian; Department of Health, Ireland
The 5-HT1F receptor as the target of ditans in migraine - from bench to bedside
(Springer Nature Ltd., 2023-07-12) Mitsikostas, Dimos D.; Waeber, Christian; Sanchez-del-Rio, Margarita; Raffaelli, Bianca; Ashina, Håkan; Maassen van den Brink, Antoinette; Andreou, Anna; Pozo-Rosich, Patricia; Rapoport, Alan; Ashina, Messoud; Moskowitz, Michael A.
Migraine is a leading cause of disability in more than one billion people worldwide, yet it remains universally underappreciated, even by individuals with the condition. Among other shortcomings, current treatments (often repurposed agents) have limited efficacy and potential adverse effects, leading to low treatment adherence. After the introduction of agents that target the calcitonin gene-related peptide pathway, another new drug class, the ditans — a group of selective serotonin 5-HT1F receptor agonists — has just reached the international market. Here, we review preclinical studies from the late 1990s and more recent clinical research that contributed to the development of the ditans and led to their approval for acute migraine treatment by the US Food and Drug Administration and the European Medicines Agency.
A microbiota-targeted strategy to attenuate antipsychotic-induced weight gain
(University College Cork, 2023) Lipuma, Timothy; Schellekens, Harriet; English, Jane
Background: Atypical antipsychotics such as olanzapine are an essential treatment for psychotic-spectrum disorders, but their use is associated with significant weight gain and increased cardiometabolic disease risk. Attenuating these side effects could improve the tolerability and adherence to antipsychotic medications. Evidence suggests that the microbiome plays a role in antipsychotic-induced weight gain, thus targeting the microbiome may be a viable therapeutic strategy to attenuate the side effect profile of antipsychotics like olanzapine. Furthermore, metabolomics approaches are being increasingly employed to elucidate disease pathophysiology and potential therapeutic targets, but these strategies have not yet been applied to the problem of antipsychotic-induced obesity and hyperphagia. Aims: The primary aims of this study are to (1) investigate if combined microbiome-targeted treatments (probiotic [APC1472], prebiotic [xanthohumol], and their combination) with olanzapine attenuate antipsychotic-induced obesity, metabolic dysfunction, and hyperphagia in female Sprague-Dawley rats, and (2) analyse blood plasma using discovery metabolomics to generate potential mechanistic and therapeutic targets related to the side effects of olanzapine. Methods: Animals were treated with olanzapine (2 mg/kg body weight) alone (n=12), olanzapine with probiotic (n=11), olanzapine with prebiotic (n=11), olanzapine with probiotic and prebiotic (n=12) or control vehicle (n=12) twice a day via intraperitoneal injection for 31 days. Changes in body weight, adiposity, glucose metabolism, dietary intake, anxiety-like behaviour, plasma biomarkers (corticosterone, insulin, ghrelin), and hypothalamic and hepatic gene expression were examined. Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) and subsequent metabolomic analysis using Progensis QI and Metaboanalyst were used to characterise plasma differences between the olanzapine treatment group and controls. Results: After the study conclusion, quality control issues with the probiotic formulation were discovered, limiting the interpretability of the data from those treatment groups. However, the olanzapine treatment displayed increased weight gain, dietary intake, and hypothalamic genes related to ghrelinergic signalling. Olanzapine did not increase adiposity, change hepatic gene expression, plasma biomarkers, or hypothalamic genes related to anorexigenic signalling. No treatments attenuated olanzapine-induced weight gain. There were no observed differences in anxiety-like behaviour between any groups. Lastly, the metabolomics investigation revealed several highly differentially expressed metabolites; two androstanoids and one endocannabinoid (oleamide). Conclusion: These findings indicate that olanzapine-associated increases in hypothalamic ghrelinergic signalling can occur before or without the onset of peripheral changes in metabolic health. Although the attenuation of olanzapine-associated increases in hypothalamic ghrelinergic signalling could not be assessed due to the quality control issues with the probiotic, targeting ghrelinergic signalling via microbiome-targeted approaches warrants further research. Additionally, the metabolomics analyses highlight oleamide as a novel metabolite that is potentially at the intersection of the endocannabinoid system, the microbiota, and olanzapine treatment, but further research is needed to clarify if the observed increase in oleamide is due to changes in host and/or microbial metabolism.
Ability of early neurological assessment and continuous EEG to predict long term neurodevelopmental outcome at 5 years in infants following hypoxic-ischaemic encephalopathy
(University College Cork, 2018) O'Connor, Catherine M.; Murray, Deirdre M.; Boylan, Geraldine B.; Health Research Board
Hypoxic-ischaemic encephalopathy (HIE) symptoms evolve during the first days of life and their monitoring is critical for treatment decisions and long-term outcome predictions. This thesis aims to report the five-year outcome of a HIE cohort born in the pre-therapeutic hypothermia era and to evaluate the predictive value of (a) neonatal neurological and EEG markers and (b) development in the first 24 months, for outcome. Methods: Participants were recruited at age five from two birth cohorts; HIE and Comparison. Repeated neonatal neurological assessments using the Amiel-TisonNeurological-Assessment-at-Term, continuous video EEG monitoring in the first 72 hours, and Sarnat grading at 24 hours were recorded. EEG severity grades were assigned at 6, 12 and 24 hours. Development was assessed in the HIE cohort at 6, 12 and 24 months using the Griffiths Mental Development (0-2) Revised Scales. At age five, intellectual (WPPSI-IIIUK scale), neuropsychological (NEPSY-II scales), neurological and ophthalmic testing was completed. Results: 5-year outcomes were available for 81.5% (n=53) of HIE and 71.4% (n=30) of Comparison cohorts. In HIE, 47.2% (27% mild, 47% moderate, 83% severe Sarnat), had non-intact outcome vs. 3.3% of the Comparison cohort. Non-intact outcome rates by 6-hour EEG-grade were: grade0=3%, grade1=25%, grade2=54%, grade3/4=79%. In HIE, processing speed (p=0.01) and verbal short-term memory (p=0.005) were below test norms. No significant differences were found in IQ, NEPSY-II or ocular biometry scores between children following mild and moderate HIE. Median IQ scores for mild (99(94-112),p=grade 2) at 24hours had superior positive predictive value (74%; AUROC(95%CI)=0.70(0.55-0.85) for non-intact 5-year outcome than abnormal EEG at 6 hours (68%; AUROC(95%CI)=0.71(0.56-0.87). Within-child development scores were inconsistent across the first 24 months. Although all children with intact 24-month Griffiths quotient (n=30) had intact 5-year IQ, 8/30 had non-intact overall outcome. Conclusion: Predictive value of neonatal neurological assessments and an EEG grading system for outcome was confirmed. Intact early childhood outcomes post-HIE may mask subtle adverse neuropsychological sequelae into the school years. This thesis supports emerging evidence that mild-grade HIE is not a benign condition and its inclusion in studies of neuroprotective treatments for HIE is warranted.
The ability of Listeria monocytogenes to form biofilm on surfaces relevant to the mushroom production environment
(Elsevier, 2019-10-22) Dygico, Lionel Kenneth; Gahan, Cormac G.; Grogan, Helen; Burgess, Catherine M.; Department of Agriculture, Food and the Marine, Ireland; Food Institutional Research Measure
Due to its ubiquitous nature, Listeria monocytogenes is a threat to all fresh fruits and vegetables, including mushrooms, which are Ireland's largest horticultural crop. Although fresh cultivated mushrooms (Agaricus bisporus) have not been previously linked with listeriosis outbreaks, the pathogen still poses a threat to the industry, particularly due to its ability to form biofilms. This threat is highlighted by the multiple recalls of mushroom products caused by L. monocytogenes contamination and by previous studies demonstrating that L. monocytogenes is present in the mushroom production environment. In this study, the biofilm formation potential of L. monocytogenes strains isolated from the mushroom production environment was investigated on materials and at temperatures relevant to mushroom production. A preliminary assessment of biofilm formation of 73 mushroom industry isolates was undertaken using a crystal violet assay on polystyrene microtitre plates. The biofilm formation of a subset (n = 7) of these strains was then assessed on twelve different materials, including materials that are representative of the materials commonly found in the mushroom production environments, using the CDC biofilm reactor. Vertical scanning interferometry was used to determine the surface roughness of the chosen materials. All the strains tested using the CDC biofilm reactor were able to form biofilms on the different surfaces tested but material type was found to be a key determining factor on the levels of biofilm formed. Stainless steel, aluminium, rubber, polypropylene and polycarbonate were all able to support biofilm levels in the range of 4–4.9 log10 CFU/cm2, for seven different L. monocytogenes strains. Mushroom industry-specific materials, including growing nets and tarpaulins, were found to support biofilms levels between 4.7 and 6.7 log10 CFU/cm2. Concrete was found to be of concern as it supported 7.7 log10 CFU/cm2 of biofilm for the same strains; however, sealing the concrete resulted in an approximately 2-log reduction in biofilm levels. The surface roughness of the materials varied greatly between the materials (0.7–3.5 log10 Ra) and was found to have a positive correlation with biofilm formation (rs = 0.573) although marginally significant (P = 0.051). The results of this study indicate that L. monocytogenes can readily form biofilms on mushroom industry relevant surfaces, and additionally identifies surfaces of specific concern, where rigorous cleaning and disinfection is required.
Abnormal patterns of tongue-palate contact in the speech of individuals with cleft palate
(Informa Healthcare, 2004-08) Gibbon, Fiona E.; Scottish Office Department of Health; Lloyds TSB Foundation for Scotland; MacRobert Trust, Scotland
Individuals with cleft palate, even those with adequate velopharyngeal function, are at high risk for disordered lingual articulation. This article attempts to summarize current knowledge of abnormal tongue-palate contact patterns derived from electropalatographic (EPG) data in speakers with cleft palate. These data, which have been reported in 23 articles published over the past 20 years, have added significantly to our knowledge about cleft palate speech. Eight abnormal patterns of tongue-palate contact are described and illustrated with data from children and adults with repaired cleft palate. The paper also discusses some of the problems in interpreting EPG data from speakers with abnormal craniofacial anatomy and emphasizes the importance of quantifying relevant aspects of tongue-palate contact data. Areas of research requiring further investigation are outlined.
Abnormal placental cord insertion and adverse pregnancy outcomes: a systematic review and meta-analysis
(BioMed Central Ltd., 2017) Ismail, Khadijah Irfah; Hannigan, Ailish; O'Donoghue, Keelin; Cotter, Amanda
Background: Abnormal placental cord insertion (PCI) includes marginal cord insertion (MCI) and velamentous cord insertion (VCI). VCI has been shown to be associated with adverse pregnancy outcomes. This systematic review and meta-analysis aims to determine the association of abnormal PCI and adverse pregnancy outcomes. Methods: Embase, Medline, CINAHL, Scopus, Web of Science, ClinicalTrials.gov, and Cochrane Databases were searched in December 2016 (from inception to December 2016). The reference lists of eligible studies were scrutinized to identify further studies. Potentially eligible studies were reviewed by two authors independently using the following inclusion criteria: singleton pregnancies, velamentous cord insertion, marginal cord insertion, and pregnancy outcomes. Case reports and series were excluded. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Outcomes for meta-analysis were dichotomous and results are presented as summary risk ratios with 95% confidence intervals. Results: Seventeen studies were included in the systematic review, all of which were assessed as good quality. Normal PCI and MCI were grouped together as non-VCI and compared with VCI in seven studies. Four studies compared MCI, VCI, and normal PCI separately. Two other studies compared MCI with normal PCI, and VCI was excluded from their analysis. Studies in this systematic review reported an association between abnormal PCI, defined differently across studies, with preterm birth, small for gestational age (SGA), low birthweight (< 2500 g), emergency cesarean delivery, and intrauterine fetal death. Four cohort studies comparing MCI, VCI, and normal PCI separately were included in a meta-analysis resulting in a statistically significant increased risk of emergency cesarean delivery for VCI (pooled RR 2.86, 95% CI 1.56–5.22, P = 0.0006) and abnormal PCI (pooled RR 1.77, 95% CI 1.33–2.36, P < 0.0001) compared to normal PCI. Conclusions: The available evidence suggests an association between abnormal PCI and emergency cesarean delivery. However, the number of studies with comparable definitions of abnormal PCI was small, limiting the analysis of other adverse pregnancy outcomes, and further research is required.
Acceptability of microneedle-patch vaccines: A qualitative analysis of the opinions of parents
(Elsevier Ltd., 2017-08-02) Marshall, Sarah; Fleming, Aoife; Moore, Anne C.; Sahm, Laura J.; Health Research Board
Vaccines incorporated into microneedle-based patch platforms offer advantages over conventional hypodermic injections. However, the success and clinical utility of these platforms will depend on its acceptance among stakeholders. Minimal focus has been placed on determining parents' acceptability of microneedle-patch vaccines intended for paediatric use. This qualitative study probes the perceived acceptability of microneedle technology for paediatric vaccination in a parent population. Focus groups (n=6) were convened through purposive sampling of Cork city primary schools. Discussions were audio-recorded, transcribed verbatim, anonymised, independently verified and analysed by thematic analysis, with constant comparison method applied throughout. The opinions of 32 parents were included. All participants declared that their children were fully vaccinated. Five core themes were identified and defined as: (i) concern, (ii) suitability for paediatric use, (iii) potential for parental administration, (iv) the role of the healthcare professional and (v) special populations. Drivers for acceptance include; concerns with current vaccines and vaccination programmes; attributes of microneedle-patch (reduced pain, bleeding, fear and increased convenience) and endorsement by a healthcare professional. Barriers to acceptance include; lack of familiarity, concerns regarding feasibility and suitability in paediatrics, allergic potential, inability to confirm delivery and potential reduction in vaccine coverage. This is the first study to explore parental acceptance of microneedle-patch vaccines. Capturing the opinions of parents, the ultimate decision makers in paediatric vaccination, is crucial in the understanding of the eventual uptake of microneedle technology and therefore adds to literature currently available. This study has revealed that even "vaccine-acceptors"; parents who agree with, or do not question vaccination, will question the safety and efficacy of this novel method. Participants in this study remained tentative. However, the study has also revealed that endorsement by healthcare professionals could reduce this tentativeness, thereby identifying the role of healthcare professionals in disseminating information and providing support to parents. An increased awareness of developments in microneedle technology is needed to permit informed decision-making by parents.
Accommodating interruptions: a grounded theory of young people with asthma
(University College Cork, 2014) Hughes, Mary; Savage, Eileen; Andrews, Tom
Background: Accommodating Interruptions is a theory that emerged in the context of young people who have asthma. A background to the prevalence and management of asthma in Ireland is given to situate the theory. Ireland has the fourth highest incidence of asthma in the world, with almost one in five Irish young people having asthma. Although national and international asthma management guidelines exist it is accepted that the symptom control of asthma among the young people population is poor. Aim: The aim of this research is to investigate the lives of young people who have asthma, to allow for a deeper understanding of the issues affecting them. Methods: This research was undertaken using a Classic Grounded Theory approach. It is a systematic approach to allowing conceptual emergence from data in generating a theory that explains behaviour in resolving the participant’s main concern. The data were collected through in-depth interviews with young people aged 11-16 years who had asthma for over one year. Data were also collected from participant diaries. Constant comparative analysis, theoretical coding and memo writing were used to develop the theory. Results: The theory explains how young people resolve their main concern of being restricted, by maximizing their participation and inclusion in activities, events and relationships in spite of their asthma. They achieve this by accommodating interruptions in their lives in minimizing the effects of asthma on their everyday lives. Conclusion: The theory of accommodating interruptions explains young people’s asthma management behaviours in a new way. It allows us to understand how and why young people behave the way they do in order minimise the effect of asthma on their lives. The theory adds to the body of knowledge on young people with asthma and challenges some viewpoints regarding their behaviours.
Accuracy of computer-aided design/computer-assisted manufacture (CAD/CAM) fabricated dental restorations: a comparative study
(University College Cork, 2015) Nasruddin, Mohd Faiz; Burke, Francis M.; Ray, Noel J.; Theocharopoulos, Antonios; Universiti Teknologi MARA, Malaysia
Introduction: Computer-Aided-Design (CAD) and Computer-Aided-Manufacture (CAM) has been developed to fabricate fixed dental restorations accurately, faster and improve cost effectiveness of manufacture when compared to the conventional method. Two main methods exist in dental CAD/CAM technology: the subtractive and additive methods. While fitting accuracy of both methods has been explored, no study yet has compared the fabricated restoration (CAM output) to its CAD in terms of accuracy. The aim of this present study was to compare the output of various dental CAM routes to a sole initial CAD and establish the accuracy of fabrication. The internal fit of the various CAM routes were also investigated. The null hypotheses tested were: 1) no significant differences observed between the CAM output to the CAD and 2) no significant differences observed between the various CAM routes. Methods: An aluminium master model of a standard premolar preparation was scanned with a contact dental scanner (Incise, Renishaw, UK). A single CAD was created on the scanned master model (InciseCAD software, V2.5.0.140, UK). Twenty copings were then fabricated by sending the single CAD to a multitude of CAM routes. The copings were grouped (n=5) as: Laser sintered CoCrMo (LS), 5-axis milled CoCrMo (MCoCrMo), 3-axis milled zirconia (ZAx3) and 4-axis milled zirconia (ZAx4). All copings were micro-CT scanned (Phoenix X-Ray, Nanotom-S, Germany, power: 155kV, current: 60µA, 3600 projections) to produce 3-Dimensional (3D) models. A novel methodology was created to superimpose the micro-CT scans with the CAD (GOM Inspect software, V7.5SR2, Germany) to indicate inaccuracies in manufacturing. The accuracy in terms of coping volume was explored. The distances from the surfaces of the micro-CT 3D models to the surfaces of the CAD model (CAD Deviation) were investigated after creating surface colour deviation maps. Localised digital sections of the deviations (Occlusal, Axial and Cervical) and selected focussed areas were then quantitatively measured using software (GOM Inspect software, Germany). A novel methodology was also explored to digitally align (Rhino software, V5, USA) the micro-CT scans with the master model to investigate internal fit. Fifty digital cross sections of the aligned scans were created. Point-to-point distances were measured at 5 levels at each cross section. The five levels were: Vertical Marginal Fit (VF), Absolute Marginal Fit (AM), Axio-margin Fit (AMF), Axial Fit (AF) and Occlusal Fit (OF). Results: The results of the volume measurement were summarised as: VM-CoCrMo (62.8mm3 ) > VZax3 (59.4mm3 ) > VCAD (57mm3 ) > VZax4 (56.1mm3 ) > VLS (52.5mm3 ) and were all significantly different (p presented as areas with different colour. No significant differences were observed at the internal aspect of the cervical aspect between all groups of copings. Significant differences (p< M-CoCrMo Internal Occlusal, Internal Axial and External Axial 2 ZAx3 > ZAx4 External Occlusal, External Cervical 3 ZAx3 < ZAx4 Internal Occlusal 4 M-CoCrMo > ZAx4 Internal Occlusal and Internal Axial The mean values of AMF and AF were significantly (p M-CoCrMo and CAD > ZAx4. Only VF of M-CoCrMo was comparable with the CAD Internal Fit. All VF and AM values were within the clinically acceptable fit (120µm). Conclusion: The investigated CAM methods reproduced the CAD accurately at the internal cervical aspect of the copings. However, localised deviations at axial and occlusal aspects of the copings may suggest the need for modifications in these areas prior to fitting and veneering with porcelain. The CAM groups evaluated also showed different levels of Internal Fit thus rejecting the null hypotheses. The novel non-destructive methodologies for CAD/CAM accuracy and internal fit testing presented in this thesis may be a useful evaluation tool for similar applications.
Acetylated microtubules are essential for touch sensation in mice
(University College Cork, 2016) Morley, Shane J.; Heppenstall, Paul; Rae, Mark
The sense of touch depends upon the transformation of mechanical energy into electrical signals by peripheral sensory neurons and associated cells in the skin. This conversion is thought to be mediated by a complex of proteins in which ion channels such as Piezo2 function as mechanotransducers. However, how mechanical energy is transmitted into mechanosensitive ion channel opening, and how cellular components such as the cytoskeleton influence this process, is largely unknown. Here we show that mice lacking the tubulin acetyltransferase, Atat1, in sensory neurons display profound deficits in their ability to detect mechanical touch and pain. In the absence of Atat1, behavioural responses to innocuous and noxious mechanical stimuli are strongly reduced in multiple assays while sensitivity of mice to thermal stimuli is unaltered. In ex vivo skin-nerve preparations, the mechanosensitivity of all low- and high- threshold mechanoreceptor subtypes innervating the skin is substantially decreased in Atat1 conditional knockout mice. In cultured dorsal root ganglion neurons, both slowly- and rapidly- adapting mechanically- activated currents are absent or reduced upon Atat1 deletion with no effect on other neuronal functions. We establish that this broad loss of mechanosensitivity is dependent upon the acetyltransferase activity of Atat1, and that by mimicking α-tubulin acetylation genetically by substituting the lysine amino acid for a structurally similar glutamine, mechanosensitivity can be restored in Atat1- deficient sensory neurons. Finally, we demonstrate that acetylated microtubules localize to a prominent band under the membrane of sensory neuron cell bodies and axons, and in the absence of Atat1 and acetylated α-tubulin, cultured sensory neurons display significant reductions in their membrane elasticity. Our results indicate that the microtubule cytoskeleton is an essential component of the mammalian mechanotransduction complex and that by influencing cellular stiffness, α-tubulin acetylation can tune mechanical sensitivity across the full range of mechanoreceptor subtypes.
Acknowledging the resilience of student nurses during COVID-19
(Elsevier Inc., 2021-06-17) Goodwin, John
Activation of a TLR9 mediated innate immune response in preeclampsia
(Nature Publishing Group, 2019-04-11) Williamson, Rachel D.; McCarthy, Fergus P.; Kenny, Louise C.; McCarthy, Cathal M.; Science Foundation Ireland; Health Research Board
Preeclampsia is a multisystemic disorder leading to the development of a placental ischemic microenvironment with a resultant increase in oxidative stress. There is evidence that mitochondrial dysfunction and the innate immune system both play a role in the pathophysiology of this disease. Mitochondrial DAMPs such as mtDNA bind specific pattern recognition receptors such as Toll-like receptor 9 (TLR9) on the endosomal surface of immune cells, in particular neutrophils, subsequently activating them and triggering an innate response. We hypothesised that the exaggerated innate immune response seen in preeclampsia is provoked by dysfunctional mitochondria. Here we provide evidence that TLR9 activity is significantly increased at time of disease in women with preeclampsia. Furthermore, we show activation of neutrophil markers, Calprotectin, Myeloperoxidase (MPO), and IL-8 are significantly increased at time of disease compared to uncomplicated pregnancies. This research supports a potential role of TLR9 activation of an innate immune response evident in preeclampsia which may possibly be initially triggered by dysfunctional mitochondria.
Activation of both TLR and NOD signaling confers host innate immunity-mediated protection against microbial infection
(Frontiers Media, 2019-01-14) Zhou, Huiting; Coveney, Andrew P.; Wu, Ming; Huang, Jie; Blankson, Siobhan; Zhao, He; O'Leary, D. Peter; Bai, Zhenjiang; Li, Yiping; Redmond, H. Paul; Wang, Jiang Huai; Wang, Jian; National Natural Science Foundation of China; Natural Science Foundation of Jiangsu Province; Science and Technology Program of Suzhou; Pediatric Solid Tumor Multidisciplinary Team; Pediatric Precise Surgical Clinical Medical Center of Suzhou
The detection of microbial pathogens relies on the recognition of highly conserved microbial structures by the membrane sensor Toll-like receptors (TLRs) and cytosolic sensor NOD-like receptors (NLRs). Upon detection, these sensors trigger innate immune responses to eradicate the invaded microbial pathogens. However, it is unclear whether TLR and NOD signaling are both critical for innate immunity to initiate inflammatory and antimicrobial responses against microbial infection. Here we report that activation of both TLR and NOD signaling resulted in an augmented inflammatory response and the crosstalk between TLR and NOD led to an amplified downstream NF-kB activation with increased nuclear transactivation of p65 at TNF-a and IL-6 promoters. Furthermore, co-stimulation of macrophages with TLR and NOD agonists maximized antimicrobial activity with accelerated phagosome maturation. Importantly, administration of both TLR and NOD agonists protected mice against polymicrobial sepsis-associated lethality with increased serum levels of inflammatory cytokines and accelerated bacterial clearance from the circulation and visceral organs. These results demonstrate that activation of both TLR and NOD signaling synergizes to induce efficient inflammatory and antimicrobial responses, thus conferring protection against microbial infection.
Active and healthy ageing and independent living 2016
(Hindawi Publishing Corporation, 2016-08) Illario, Maddalena; Vollenbroek-Hutten, Miriam M. R.; Molloy, D. William; Menditto, Enrica; Iaccarino, Guido; Eklund, Patrik
Active peer-mentored learning can improve student understanding of physiological concepts in an undergraduate journal club
(American Physiological Society, 2019-07-15) Drumm, Bernard T.; Rae, Mark G.; Ward, Sean M.; National Institute of Diabetes and Digestive and Kidney Diseases
One of the most ubiquitous active learning modalities in the biological sciences at third level is the journal club. Journal club can promote several beneficial learning outcomes for students such as gaining critical reading skills to evaluate the scientific literature, improving scientific literacy, serving as an introduction to new concepts and techniques and improving communication skills. However, it can be difficult for instructors who facilitate journal club to gauge student audiences' understanding of topics being related by presenters. At the University of Nevada, Reno School of Medicine, international life sciences undergraduate students enrolled in our research program undergo a 12-month placement in selected research laboratories within the medical school in order to develop an understanding of basic medical scientific research and physiological concepts. As such, an integral component of this program is participation in regular journal club sessions which we had assumed helped students to develop such an understanding. However as we had never empirically assessed if this was the case or not, the aim of the current study was to determine if student understanding could be improved by complementing the standard journal club with peer-mentored workshop presentations. Data from this case study suggest that by allowing students to undergo peer-mentored learning in conjunction with journal club, student understanding of physiological concepts, as well as student confidence in presenting and communication, increases.
Acute hospital dementia care: results from a national audit
(BioMed Central, 2016-05-31) Timmons, Suzanne; O'Shea, Emma; O'Neill, Desmond; Gallagher, Paul F.; de Siún, Anna; McArdle, Denise; Gibbons, Patricia; Kennelly, Sean; Atlantic Philanthropies
Background: Admission to an acute hospital can be distressing and disorientating for a person with dementia, and is associated with decline in cognitive and functional ability. The objective of this audit was to assess the quality of dementia care in acute hospitals in the Republic of Ireland. Methods: Across all 35 acute public hospitals, data was collected on care from admission through discharge using a retrospective chart review (n = 660), hospital organisation interview with senior management (n = 35), and ward level organisation interview with ward managers (n = 76). Inclusion criteria included a diagnosis of dementia, and a length of stay greater than 5 days. Results: Most patients received physical assessments, including mobility (89 %), continence (84 %) and pressure sore risk (87 %); however assessment of pain (75 %), and particularly functioning (36 %) was poor. Assessment for cognition (43 %) and delirium (30 %) was inadequate. Most wards have access at least 5 days per week to Liaison Psychiatry (93 %), Geriatric Medicine (84 %), Occupational Therapy (79 %), Speech & Language (81 %), Physiotherapy (99 %), and Palliative Care (89 %) Access to Psychology (9 %), Social Work (53 %), and Continence services (34 %) is limited. Dementia awareness training is provided on induction in only 2 hospitals, and almost half of hospitals did not offer dementia training to doctors (45 %) or nurses (48 %) in the previous 12 months. Staff cover could not be provided on 62 % of wards for attending dementia training. Most wards (84 %) had no dementia champion to guide best practice in care. Discharge planning was not initiated within 24 h of admission in 72 % of cases, less than 40 % had a single plan for discharge recorded, and 33 % of carers received no needs assessment prior to discharge. Length of stay was significantly greater for new discharges to residential care (p < .001). Conclusion: Dementia care relating to assessment, access to certain specialist services, staffing levels, training and support, and discharge planning is sub-optimal, which may increase the risk of adverse patient outcomes and the cost of acute care. Areas of good practice are also highlighted.

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