University College Cork
http://hdl.handle.net/10147/627173
2024-03-27T16:31:00ZMetagenomic assembled plasmids of the human microbiome vary across disease cohorts.
http://hdl.handle.net/10147/641315
Metagenomic assembled plasmids of the human microbiome vary across disease cohorts.
Harrington, R S; Khokhlova, E V; Daly, K M; McDonnell, S A; O'Reagan, O; Nolan, J A; Sheehan, D; Lavelle, A; Draper, L A; Ross, R P; Stockdale, Stephen; Hill, Colin; Shanahan, Fergus; Shkoporov, Andrey
We compiled a human metagenome assembled plasmid (MAP) database and interrogated differences across multiple studies that were originally designed to investigate the composition of the human microbiome across various lifestyles, life stages and events. This was performed as plasmids enable bacteria to rapidly expand their functional capacity through mobilisation, yet their contribution to human health and disease is poorly understood. We observed that inter-sample β-diversity differences of plasmid content (plasmidome) could distinguish cohorts across a multitude of conditions. We also show that reduced intra-sample plasmidome α-diversity is consistent amongst patients with inflammatory bowel disease (IBD) and Clostridioides difficile infections. We also show that faecal microbiota transplants can restore plasmidome diversity. Overall plasmidome diversity, specific plasmids, and plasmid-encoded functions can all potentially act as biomarkers of IBD or its severity. The human plasmidome is an overlooked facet of the microbiome and should be integrated into investigations regarding the role of the microbiome in promoting health or disease. Including MAP databases in analyses will enable a greater understanding of the roles of plasmid-encoded functions within the gut microbiome and will inform future human metagenome analyses.
2022-06-02T00:00:00ZmiRNA signatures associated with vulnerability to food addiction in mice and humans.
http://hdl.handle.net/10147/641282
miRNA signatures associated with vulnerability to food addiction in mice and humans.
Fernández-Castillo, Noèlia; Pineda-Cirera, Laura; Mayneris-Perxachs, Jordi; Burokas, Aurelijus; Espinosa-Carrasco, Jose; Arboleya, Silvia; Latorre, Jessica; Cormand, Bru; Fernández-Real, Jose-Manuel; Martín-García, Elena; Maldonado, Rafael; García-Blanco, Alejandra; Domingo Rodriguez, Laura; STANTON, CATHERINE; Cabana-Dominguez, Judit
Food addiction is characterized by a loss of behavioral control over food intake and is associated with obesity and other eating disorders. The mechanisms underlying this behavioral disorder are largely unknown. We aimed to investigate the changes in miRNA expression promoted by food addiction in animals and humans and their involvement in the mechanisms underlying the behavioral hallmarks of this disorder. We found sharp similitudes between miRNA signatures in the medial prefrontal cortex (mPFC) of our animal cohort and circulating miRNA levels in our human cohort, which allowed us to identify several miRNAs of potential interest in the development of this disorder. Tough decoy (TuD) inhibition of miRNA-29c-3p in the mouse mPFC promoted persistence of the response and enhanced vulnerability to developing food addiction, whereas miRNA-665-3p inhibition promoted compulsion-like behavior and also enhanced food addiction vulnerability. In contrast, we found that miRNA-137-3p inhibition in the mPFC did not lead to the development of food addiction. Therefore, miRNA-29c-3p and miRNA-665-3p could be acting as protective factors with regard to food addiction. We believe the elucidation of these epigenetic mechanisms will lead to advances toward identifying innovative biomarkers and possible future interventions for food addiction and related disorders based on the strategies now available to modify miRNA activity and expression.
2022-05-16T00:00:00ZNo Effect of Levothyroxine on Hemoglobin in Older Adults With Subclinical Hypothyroidism: Pooled Results From 2 Randomized Controlled Trials.
http://hdl.handle.net/10147/641266
No Effect of Levothyroxine on Hemoglobin in Older Adults With Subclinical Hypothyroidism: Pooled Results From 2 Randomized Controlled Trials.
McCarthy, Vera J C; Byrne, Stephen; Baretella, Oliver; van Heemst, Diana; Dekkers, Olaf M; Jukema, J WOUTER; Smit, Johannes W A; Gussekloo, Jacobijn; den Elzen, Wendy P J; Du Puy, Robert; Poortvliet, Rosalinde; Sattar, Naveed; Mooijaart, Simon; Collet, Tinh-Hai; Rodondi, Nicolas; Stott, David J.; Quinn, Terry; westendorp, rudi; Kearney, Patricia
Context: Subclinical thyroid dysfunction and anemia are common disorders, and both have increasing prevalence with advancing age.
Objective: The aim of this study was to assess whether levothyroxine treatment leads to a rise in hemoglobin levels in older persons with subclinical hypothyroidism.
Methods: This preplanned combined analysis of 2 randomized controlled trials included community-dwelling persons aged 65 years and older with subclinical hypothyroidism who were randomly assigned to levothyroxine or placebo treatment. The levothyroxine dose was periodically titrated aiming at thyroid stimulating hormone (TSH) level within the reference range, with mock titrations in the placebo group. The main outcome measure was the change in hemoglobin level after 12 months.
Results: Analyses included 669 participants (placebo n = 337, levothyroxine n = 332) with a median age of 75 years (range, 65-97) and mean baseline hemoglobin of 13.8 ± 1.3 g/dL. Although levothyroxine treatment resulted in a reduction in TSH from baseline after 12 months of follow-up compared with placebo, the change in hemoglobin level was not different between the levothyroxine and the placebo groups (-0.03 g/dL [95% CI, -0.16 to 0.11]). Similar results were found in stratified analyses including sex, age, or TSH levels. No difference in change of hemoglobin levels after 12 months was identified in 69 participants with anemia at baseline (-0.33 g/dL [95% CI, -0.87 to 0.21]).
Conclusion: In persons aged 65 years and older with subclinical hypothyroidism, treatment with levothyroxine does not lead to a rise in hemoglobin levels, regardless of the presence of anemia.
2022-02-26T00:00:00ZDeveloping Clinically Relevant Dissolution Specifications (CRDSs) for Oral Drug Products: Virtual Webinar Series.
http://hdl.handle.net/10147/641264
Developing Clinically Relevant Dissolution Specifications (CRDSs) for Oral Drug Products: Virtual Webinar Series.
Cole, Susan; Kotzagiorgis, Evangelos; Limberg, Jobst; Moir, Andrea; Anand, Om; Turner, David B; Darwich, Adam; Dressman, Jennifer; Mackie, Claire; Mangas Sanjuan, Victor; Dickinson, Paul; Zhou, Diansong; Dokoumetzidis, Aristides; Griffin, Brendan; McAllister, Mark; Flanagan, Talia; Le Merdy, Maxime; pepin, xavier; Mead, Heather; Abend, Andreas; Tistaert, Christophe
A webinar series that was organised by the Academy of Pharmaceutical Sciences Biopharmaceutics focus group in 2021 focused on the challenges of developing clinically relevant dissolution specifications (CRDSs) for oral drug products. Industrial scientists, together with regulatory and academic scientists, came together through a series of six webinars, to discuss progress in the field, emerging trends, and areas for continued collaboration and harmonisation. Each webinar also hosted a Q&A session where participants could discuss the shared topic and information. Although it was clear from the presentations and Q&A sessions that we continue to make progress in the field of CRDSs and the utility/success of PBBM, there is also a need to continue the momentum and dialogue between the industry and regulators. Five key areas were identified which require further discussion and harmonisation.
2022-05-07T00:00:00ZTolerating bad health research: the continuing scandal.
http://hdl.handle.net/10147/641263
Tolerating bad health research: the continuing scandal.
Pirosca, Stefania; Treweek, Shaun; Shiely, Frances; Clarke, Mike
Background: At the 2015 REWARD/EQUATOR conference on research waste, the late Doug Altman revealed that his only regret about his 1994 BMJ paper 'The scandal of poor medical research' was that he used the word 'poor' rather than 'bad'. But how much research is bad? And what would improve things?
Main text: We focus on randomised trials and look at scale, participants and cost. We randomly selected up to two quantitative intervention reviews published by all clinical Cochrane Review Groups between May 2020 and April 2021. Data including the risk of bias, number of participants, intervention type and country were extracted for all trials included in selected reviews. High risk of bias trials was classed as bad. The cost of high risk of bias trials was estimated using published estimates of trial cost per participant. We identified 96 reviews authored by 546 reviewers from 49 clinical Cochrane Review Groups that included 1659 trials done in 84 countries. Of the 1640 trials providing risk of bias information, 1013 (62%) were high risk of bias (bad), 494 (30%) unclear and 133 (8%) low risk of bias. Bad trials were spread across all clinical areas and all countries. Well over 220,000 participants (or 56% of all participants) were in bad trials. The low estimate of the cost of bad trials was £726 million; our high estimate was over £8 billion. We have five recommendations: trials should be neither funded (1) nor given ethical approval (2) unless they have a statistician and methodologist; trialists should use a risk of bias tool at design (3); more statisticians and methodologists should be trained and supported (4); there should be more funding into applied methodology research and infrastructure (5).
Conclusions: Most randomised trials are bad and most trial participants will be in one. The research community has tolerated this for decades. This has to stop: we need to put rigour and methodology where it belongs - at the centre of our science.
2022-06-02T00:00:00ZInterlaboratory study on SbS interplay between structure, dielectric function, and amorphous-to-crystalline phase change for photonics.
http://hdl.handle.net/10147/641261
Interlaboratory study on SbS interplay between structure, dielectric function, and amorphous-to-crystalline phase change for photonics.
Rosales, Saul A; García-Fernández, Pablo; Dicorato, Stefano; Giangregorio, Maria M; Palumbo, Fabio; Ishchenko, Olga; Garry, Guy; Jonuzi, Tigers; Georghe, Marin; Cobianu, Cornel; Cobet, Christoph; Moreno, Fernando; Pernice, Wolfram H P; Gutierrez Vela, Yael; Ovvyan, Anna; LOSURDO, MARIA; Santos, Gonzalo; Dilonardo, Elena; Junquera, Javier; Modreanu, Mircea Gabriel; Resl, Josef; Hingerl, Kurt; Juan, Dilson
Antimony sulfide, Sb2S3, is interesting as the phase-change material for applications requiring high transmission from the visible to telecom wavelengths, with its band gap tunable from 2.2 to 1.6 eV, depending on the amorphous and crystalline phase. Here we present results from an interlaboratory study on the interplay between the structural change and resulting optical contrast during the amorphous-to-crystalline transformation triggered both thermally and optically. By statistical analysis of Raman and ellipsometric spectroscopic data, we have identified two regimes of crystallization, namely 250°C ≤ T < 300°C, resulting in Type-I spherulitic crystallization yielding an optical contrast Δn ∼ 0.4, and 300 ≤ T < 350°C, yielding Type-II crystallization bended spherulitic structure with different dielectric function and optical contrast Δn ∼ 0.2 below 1.5 eV. Based on our findings, applications of on-chip reconfigurable nanophotonic phase modulators and of a reconfigurable high-refractive-index core/phase-change shell nanoantenna are designed and proposed.
Antimony sulfide, Sb2S3, is interesting as the phase-change material for applications requiring high transmission from the visible to telecom wavelengths, with its band gap tunable from 2.2 to 1.6 eV, depending on the amorphous and crystalline phase. Here we present results from an interlaboratory study on the interplay between the structural change and resulting optical contrast during the amorphous-to-crystalline transformation triggered both thermally and optically. By statistical analysis of Raman and ellipsometric spectroscopic data, we have identified two regimes of crystallization, namely 250°C ≤ T < 300°C, resulting in Type-I spherulitic crystallization yielding an optical contrast Δn ∼ 0.4, and 300 ≤ T < 350°C, yielding Type-II crystallization bended spherulitic structure with different dielectric function and optical contrast Δn ∼ 0.2 below 1.5 eV. Based on our findings, applications of on-chip reconfigurable nanophotonic phase modulators and of a reconfigurable high-refractive-index core/phase-change shell nanoantenna are designed and proposed.
2022-05-10T00:00:00ZThe experiences of men following recurrent miscarriage in an Irish tertiary hospital: A qualitative analysis.
http://hdl.handle.net/10147/641245
The experiences of men following recurrent miscarriage in an Irish tertiary hospital: A qualitative analysis.
Trench, Maria; Harty, Tommy; Keegan, Orla; O'Donoghue, Keelin; Nuzum, Daniel
Introduction: Miscarriage is one of the most common complications of pregnancy, and recurrent miscarriage affects approximately 1% of couples. The psychological impact of early pregnancy loss on women has been well documented in the literature; however, the burden of miscarriage on men remains largely unexplored.
Methods: This qualitative research involved semi-structured interviews with five men whose partners had experienced at least two consecutive miscarriages. Participants were recruited through an early pregnancy loss clinic in a large, tertiary maternity hospital. Interviews were recorded and transcribed verbatim and analysed thematically.
Results: Recurrent miscarriage had a pronounced psychological impact on all the men interviewed, which worsened with each successive miscarriage. Three primary themes were developed from the data: (1) the deeply emotional experiences of men following recurrent miscarriage; (2) frustrations experienced during the provision of support following recurrent miscarriage; and (3) a sense of feeling unimportant. Lack of timely provision of information about miscarriage as well as lack of access to services were highlighted as deficiencies in the quality of care provided after recurrent miscarriage.
Conclusion: The experiences of men after recurrent miscarriage are based largely on their assumed role as the protector and supporter of their partner, which often results in neglect of their own psychological needs. The support required by men is similar to that required by women, and greater access to information and services is needed to improve the experiences of men following recurrent miscarriage.
Patient contribution: Participants were recruited through the Pregnancy Loss Clinic at Cork University Maternity Hospital and were identified by specialist midwives. Participants were approached and interviewed by one of the researchers. Participation was voluntary and the men received no financial contribution for their time.
2022-03-03T00:00:00ZPrimary healthcare professionals' perspectives on patient help-seeking for lung cancer warning signs and symptoms: a qualitative study.
http://hdl.handle.net/10147/641221
Primary healthcare professionals' perspectives on patient help-seeking for lung cancer warning signs and symptoms: a qualitative study.
Hegarty, Josephine; Saab, Mohamad; O’Driscoll, Michelle; FitzGerald, Serena; Sahm, Laura; Leahy-Warren, Patricia; Noonan, Brendan; Kilty, Caroline; Lyons , Noreen; Burns, Heather; Kennedy, Una; Lyng, Aine
Background: Lung cancer is the leading cause of cancer incidence and mortality worldwide. Prompt patient help-seeking for signs and symptoms suggestive of lung cancer is crucial for early referral, diagnosis, and survivorship. However, individuals with potential lung cancer symptoms tend to delay help-seeking. This qualitative study explored perceived barriers to patient help-seeking and strategies to enhance help-seeking for lung cancer warning signs and symptoms from the perspective of primary healthcare professionals.
Methods: Semi-structured focus groups and individual interviews were conducted with 36 primary healthcare professionals. Data were collected via videoconferencing. Inductive thematic analysis was conducted.
Results: The following two themes were created from the data: (i) perceived barriers to patient help-seeking for signs and symptoms of concern and (ii) facilitating early patient presentation for signs and symptoms of concern. Some participants believed that the high cost of a general practitioner visit, long waiting times, and previous bad experiences with the healthcare system would deter patients from seeking help for symptoms of lung cancer. Perceived patient-related barriers to help-seeking related to the different emotions associated with a potential cancer diagnosis as well as stigma, embarrassment, and guilt felt by smokers. Sociodemographic factors such as drug use, homelessness, living in rural areas, and being male and older were also perceived to impede patient help-seeking. The negative impact of the COVID-19 pandemic on cancer help-seeking also featured strongly. Participants recommended several strategies to enable patients to seek help for symptoms of concern including targeted educational campaigns focussing on symptoms (e.g., cough) rather than behaviours (e.g., smoking), accessible and free health services, and using patients' support networks.
Conclusions: Patient-related and healthcare system-related barriers to help-seeking for lung cancer warning signs and symptoms include cost of healthcare, cancer fear, and various sociodemographic factors. Participants suggested that increased awareness and early patient help-seeking for symptoms of concern could be achieved through targeted patient education, national campaigns, the use of community support networks, and free and accessible targeted screening services.
2022-05-18T00:00:00ZThe blood-brain barrier in aging and neurodegeneration.
http://hdl.handle.net/10147/641220
The blood-brain barrier in aging and neurodegeneration.
Knox, Emily; aburto, MARIA; CLARKE, GERARD; Cryan, John; O'Driscoll, Caitriona
The blood-brain barrier (BBB) is vital for maintaining brain homeostasis by enabling an exquisite control of exchange of compounds between the blood and the brain parenchyma. Moreover, the BBB prevents unwanted toxins and pathogens from entering the brain. This barrier, however, breaks down with age and further disruption is a hallmark of many age-related disorders. Several drugs have been explored, thus far, to protect or restore BBB function. With the recent connection between the BBB and gut microbiota, microbial-derived metabolites have been explored for their capabilities to protect and restore BBB physiology. This review, will focus on the vital components that make up the BBB, dissect levels of disruption of the barrier, and discuss current drugs and therapeutics that maintain barrier integrity and the recent discoveries of effects microbial-derived metabolites have on BBB physiology.
2022-03-31T00:00:00ZProtocol for the Birth Asphyxia in African Newborns (Baby BRAiN) Study: a Neonatal Encephalopathy Feasibility Cohort Study.
http://hdl.handle.net/10147/641211
Protocol for the Birth Asphyxia in African Newborns (Baby BRAiN) Study: a Neonatal Encephalopathy Feasibility Cohort Study.
Webb, Emily L; Mugalu, J; Robertson, Nicola J; Nabawanuka, A; Gilbert, Guillaume; Bwambale, J; Bainbridge, Alan; Lubowa, Samson; Srinivasan, Latha; Ssebombo, H; Morgan, Cathy; Hagmann, Cornelia; Cowan, Frances M; Boylan, Geraldine B; Nakimuli, Annettee; Tann, Cally J; Wintermark, Pia; le doare, kirsty; Kawooya, Michael; Martinello, Kathryn; sadoo, Samantha; Nanyunja, Carol; Mambule, Ivan Kiggundu; mathieson, sean; Nyirenda, Moffat
BACKGROUND: Neonatal encephalopathy (NE) is a leading cause of child mortality worldwide and contributes substantially to stillbirths and long-term disability. Ninety-nine percent of deaths from NE occur in low-and-middle-income countries (LMICs). Whilst therapeutic hypothermia significantly improves outcomes in high-income countries, its safety and effectiveness in diverse LMIC contexts remains debated. Important differences in the aetiology, nature and timing of neonatal brain injury likely influence the effectiveness of postnatal interventions, including therapeutic hypothermia. METHODS: This is a prospective pilot feasibility cohort study of neonates with NE conducted at Kawempe National Referral Hospital, Kampala, Uganda. Neurological investigations include continuous video electroencephalography (EEG) (days 1-4), serial cranial ultrasound imaging, and neonatal brain Magnetic Resonance Imaging and Spectroscopy (MRI/ MRS) (day 10-14). Neurodevelopmental follow-up will be continued to 18-24 months of age including Prechtl's Assessment of General Movements, Bayley Scales of Infant Development, and a formal scored neurological examination. The primary outcome will be death and moderate-severe neurodevelopmental impairment at 18-24 months. Findings will be used to inform explorative science and larger trials, aiming to develop urgently needed neuroprotective and neurorestorative interventions for NE applicable for use in diverse settings. DISCUSSION: The primary aims of the study are to assess the feasibility of establishing a facility-based cohort of children with NE in Uganda, to enhance our understanding of NE in a low-resource sub-Saharan African setting and provide infrastructure to conduct high-quality research on neuroprotective/ neurorestorative strategies to reduce death and disability from NE. Specific objectives are to establish a NE cohort, in order to 1) investigate the clinical course, aetiology, nature and timing of perinatal brain injury; 2) describe electrographic activity and quantify seizure burden and the relationship with adverse outcomes, and; 3) develop capacity for neonatal brain MRI/S and examine associations with early neurodevelopmental outcomes.
BACKGROUND: Neonatal encephalopathy (NE) is a leading cause of child mortality worldwide and contributes substantially to stillbirths and long-term disability. Ninety-nine percent of deaths from NE occur in low-and-middle-income countries (LMICs). Whilst therapeutic hypothermia significantly improves outcomes in high-income countries, its safety and effectiveness in diverse LMIC contexts remains debated. Important differences in the aetiology, nature and timing of neonatal brain injury likely influence the effectiveness of postnatal interventions, including therapeutic hypothermia. METHODS: This is a prospective pilot feasibility cohort study of neonates with NE conducted at Kawempe National Referral Hospital, Kampala, Uganda. Neurological investigations include continuous video electroencephalography (EEG) (days 1-4), serial cranial ultrasound imaging, and neonatal brain Magnetic Resonance Imaging and Spectroscopy (MRI/ MRS) (day 10-14). Neurodevelopmental follow-up will be continued to 18-24 months of age including Prechtl's Assessment of General Movements, Bayley Scales of Infant Development, and a formal scored neurological examination. The primary outcome will be death and moderate-severe neurodevelopmental impairment at 18-24 months. Findings will be used to inform explorative science and larger trials, aiming to develop urgently needed neuroprotective and neurorestorative interventions for NE applicable for use in diverse settings. DISCUSSION: The primary aims of the study are to assess the feasibility of establishing a facility-based cohort of children with NE in Uganda, to enhance our understanding of NE in a low-resource sub-Saharan African setting and provide infrastructure to conduct high-quality research on neuroprotective/ neurorestorative strategies to reduce death and disability from NE. Specific objectives are to establish a NE cohort, in order to 1) investigate the clinical course, aetiology, nature and timing of perinatal brain injury; 2) describe electrographic activity and quantify seizure burden and the relationship with adverse outcomes, and; 3) develop capacity for neonatal brain MRI/S and examine associations with early neurodevelopmental outcomes.
2022-03-03T00:00:00Z