Recent Submissions

  • Occupational Exposures to Organic Dust in Irish Bakeries and a Pizzeria Restaurant.

    Viegas, Carla; Fleming, Gerard T A; Kadir, Abdul; Almeida, Beatriz; Caetano, Liliana Aranha; Quintal Gomes, Anita; Twarużek, Magdalena; Kosicki, Robert; Viegas, Susana; Coggins, Ann Marie (2020-01-15)
    For decades, occupational exposure to flour dust has been linked to a range of respiratory diseases, including occupational asthma, thought to result from exposure to fungi present in the flour. Antifungal resistance is of increasing prevalence in clinical settings, and the role of occupational and environmental exposures, particularly for specific fungal species, is of concern. Occupational exposure to flour dust can occur in a range of occupational settings, however, few studies have focused on restaurant workers. The objective of this study was to measure occupational exposure to flour and microbial contamination, including azole resistance screening, in two small commercial bakeries and in a pizzeria. Personal full shift inhalable dust measurements were collected from workers, and were analyzed for inhalable dust and fungi, bacteria, azole resistance, and mycotoxins. Samples of settled dust were collected, and electrostatic dust cloths (EDC) were deployed and analyzed for microbial contamination, including azole resistance screening, and mycotoxins. Geometric mean exposures of 6.5 mg m-³ were calculated for inhalable dust, however, exposures of up to 18.30 mg m-³ were measured-70% of personal exposure measurements exceeded the occupational exposure limit for flour dust of 1.0 mg m-³. The air and EDC fungal counts were similar to those reported in previous studies for similar occupational environments. The fungi were dominated by Penicillium genera, however Aspergillus genera, including Fumigati and Flavi sections, were observed using culture-based methods, and the Fumigati section was also observed by molecular tools. Both Aspergillus sections were identified on the azole resistance screening. Mycotoxins were also detected in the settled dust samples, dominated by deoxynivalenol (DON). The role of environmental exposure in both the development of antimicrobial resistance and the total mycotoxin body burden is a growing concern; therefore, the presence of azole-resistant fungi and mycotoxin contamination, although low in magnitude, is of concern and warrants further investigation.
  • A core outcome set for studies of gestational diabetes mellitus prevention and treatment.

    Egan, Aoife M; Bogdanet, Delia; Griffin, Tomás P; Kgosidialwa, Oratile; Cervar-Zivkovic, Mila; Dempsey, Eugene; Allotey, John; Alvarado, Fernanda; Clarson, Cheril; Cooray, Shamil D; et al. (2020-03-20)
  • The impact of chronic kidney disease on developed countries from a health economics perspective: A systematic scoping review.

    Elshahat, Sarah; Cockwell, Paul; Maxwell, Alexander P; Griffin, Matthew; O'Brien, Timothy; O'Neill, Ciaran (2020-03-24)
  • The Development of a Consistent Europe-Wide Approach to Investigating the Economic Impact of Myalgic Encephalomyelitis (ME/CFS): A Report from the European Network on ME/CFS (EUROMENE).

    Pheby, Derek F H; Araja, Diana; Berkis, Uldis; Brenna, Elenka; Cullinan, John; de Korwin, Jean-Dominique; Gitto, Lara; Hughes, Dyfrig A; Hunter, Rachael M; Trepel, Dominic; et al. (2020-04-07)
  • Oncogenic Linear Collagen VI of Invasive Breast Cancer Is Induced by CCL5.

    Brett, Elizabeth; Sauter, Matthias; Timmins, Éadaoin; Azimzadeh, Omid; Rosemann, Michael; Merl-Pham, Juliane; Hauck, Stefanie M; Nelson, Peter J; Becker, Karl Friedrich; Schunn, Ilse; et al. (2020-04-02)
  • Correction to: One‑year clinical outcomes in patients with renal insuffciency after contemporary PCI: data from a multicenter registry.

    Scholz, Sean S; Lauder, Lucas; Ewen, Sebastian; Kulenthiran, Saarraaken; Marx, Nikolaus; Sakhov, Orazbek; Kauer, Floris; Witkowski, Adam; Vaglimigli, Marco; Wijns, William; et al. (2020-07)
  • Obesity-Associated Alterations of Natural Killer Cells and Immunosurveillance of Cancer.

    Bähr, Ina; Spielmann, Julia; Quandt, Dagmar; Kielstein, Heike (2020-03-13)
    Obesity is accompanied by a systemic chronic low-grade inflammation as well as dysfunctions of several innate and adaptive immune cells. Recent findings emphasize an impaired functionality and phenotype of natural killer (NK) cells under obese conditions. This review provides a detailed overview on research related to overweight and obesity with a particular focus on NK cells. We discuss obesity-associated alterations in subsets, distribution, phenotype, cytotoxicity, cytokine secretion, and signaling cascades of NK cells investigated in vitro as well as in animal and human studies. In addition, we provide recent insights into the effects of physical activity and obesity-associated nutritional factors as well as the reduction of body weight and fat mass on NK cell functions of obese individuals. Finally, we highlight the impact of impaired NK cell physiology on obesity-associated diseases, focusing on the elevated susceptibility for viral infections and increased risk for cancer development and impaired treatment response.
  • Trial Forge Guidance 2: how to decide if a further Study Within A Trial (SWAT) is needed.

    Treweek, Shaun; Bevan, Simon; Bower, Peter; Briel, Matthias; Campbell, Marion; Christie, Jacquie; Collett, Clive; Cotton, Seonaidh; Devane, Declan; El Feky, Adel; et al. (2020-01-07)
  • A comparison, for older people with diabetes, of health and health care utilisation in two different health systems on the island of Ireland.

    Pierse, Tom; Barry, Luke; Glynn, Liam; Murphy, Andrew W; Cruise, Sharon; O'Neill, Ciaran; Health Economic and Policy Analysis Centre, National University of Ireland Galway, Galway, Ireland. (2020-09-24)
  • An Engineered Pathway for Production of Terminally Sialylated -glycoproteins in the Periplasm of .

    Zhu, Jing; Ruan, Yao; Fu, Xin; Zhang, Lichao; Ge, Gaoshun; Wall, J Gerard; Zou, Teng; Zheng, Yang; Ding, Ning; Hu, Xuejun (2020-04-15)
    Terminally sialylated N-glycoproteins are of great interest in therapeutic applications. Due to the inability of prokaryotes to carry out this post-translational modification, they are currently predominantly produced in eukaryotic host cells. In this study, we report a synthetic pathway to produce a terminally sialylated N-glycoprotein in the periplasm of Escherichia coli, mimicking the sialylated moiety (Neu5Ac-α-2,6-Gal-β-1,4-GlcNAc-) of human glycans. A sialylated pentasaccharide, Neu5Ac-α-2,6-Gal-β-1,4-GlcNAc-β-1,3-Gal-β-1,3-GlcNAc-, was synthesized through the activity of co-expressed glycosyltransferases LsgCDEF from Haemophilus influenzae, Campylobacter jejuni NeuBCA enzymes, and Photobacterium leiognathi α-2,6-sialyltransferase in an engineered E. coli strain which produces CMP-Neu5Ac. C. jejuni oligosaccharyltransferase PglB was used to transfer the terminally sialylated glycan onto a glyco-recognition sequence in the tenth type III cell adhesion module of human fibronectin. Sialylation of the target protein was confirmed by lectin blotting and mass spectrometry. This proof-of-concept study demonstrates the successful production of terminally sialylated, homogeneous N-glycoproteins with α-2,6-linkages in the periplasm of E. coli and will facilitate the construction of E. coli strains capable of producing terminally sialylated N-glycoproteins in high yield.
  • The Epidemiology of Traumatic Brain Injury Due to Traffic Accidents in Latin America: A Narrative Review.

    Dunne, Jack; Quiñones-Ossa, Gabriel Alexander; Still, Ethne Grey; Suarez, María N; González-Soto, José A; Vera, David S; Rubiano, Andrés M (2020-05-02)
    Objective  Traumatic brain injuries (TBIs) are devastating injuries and represent a major cause of morbidity and mortality worldwide. Traffic accidents are one of the main causes, especially in low- and middle-income countries. The epidemiology of TBI due to road traffic in Latin America is not clearly documented. Methods  A narrative review was conducted using PubMed, SCOPUS, and Google Scholar, looking for TBI studies in Latin America published between 2000 and 2018. Seventeen studies were found that met the inclusion and exclusion criteria. Results   It was found that TBI due to road traffic accidents (RTAs) is more frequent in males between the ages of 15 and 35 years, and patients in motor vehicles accounted for most cases, followed by pedestrians, motorcyclists, and cyclists. Conclusion  Road traffic accidents is a common cause of TBI in Latin America. More studies and registries are needed to properly document the epidemiological profiles of TBI related to RTAs.
  • A Novel 3D Osteoblast and Osteocyte Model Revealing Changes in Mineralization and Pro-osteoclastogenic Paracrine Signaling During Estrogen Deficiency.

    Naqvi, Syeda Masooma; Panadero Pérez, Juan Alberto; Kumar, Vatsal; Verbruggen, Anneke S K; McNamara, Laoise M (2020-06-10)
    Recent in vitro studies have revealed that the mechanobiological responses of osteoblasts and osteocytes are fundamentally impaired during estrogen deficiency. However, these two-dimensional (2D) cell culture studies do not account for in vivo biophysical cues. Thus, the objectives of this study are to (1) develop a three-dimensional (3D) osteoblast and osteocyte model integrated into a bioreactor and (2) apply this model to investigate whether estrogen deficiency leads to changes in osteoblast to osteocyte transition, mechanosensation, mineralization, and paracrine signaling associated with bone resorption by osteoclasts. MC3T3-E1s were expanded in media supplemented with estrogen (17β-estradiol). These cells were encapsulated in gelatin-mtgase before culture in (1) continued estrogen (E) or (2) no further estrogen supplementation. Constructs were placed in gas permeable and water impermeable cell culture bags and maintained at 5% CO2 and 37°C. These bags were either mechanically stimulated in a custom hydrostatic pressure (HP) bioreactor or maintained under static conditions (control). We report that osteocyte differentiation, characterized by the presence of dendrites and staining for osteocyte marker dentin matrix acidic phosphoprotein 1 (DMP1), was significantly greater under estrogen withdrawal (EW) compared to under continuous estrogen treatment (day 21). Mineralization [bone sialoprotein (BSP), osteopontin (OPN), alkaline phosphatase (ALP), calcium] and gene expression associated with paracrine signaling for osteoclastogenesis [receptor activator of nuclear factor kappa-β ligand (RANKL)/osteoprotegerin OPG ratio] were significantly increased in estrogen deficient and mechanically stimulated cells. Interestingly, BSP and DMP-1 were also increased at day 1 and day 21, respectively, which play a role in regulation of biomineralization. Furthermore, the increase in pro-osteoclastogenic signaling may be explained by altered mechanoresponsiveness of osteoblasts or osteocytes during EW. These findings highlight the impact of estrogen deficiency on bone cell function and provide a novel in vitro model to investigate the mechanisms underpinning changes in bone cells after estrogen deficiency.
  • Challenges in pain assessment and management among individuals with intellectual and developmental disabilities.

    Barney, Chantel C; Andersen, Randi D; Defrin, Ruth; Genik, Lara M; McGuire, Brian E; Symons, Frank J (2020-06-16)
  • Understanding the Attitudes of Communities to the Social, Economic, and Cultural Importance of Working Donkeys in Rural, Peri-urban, and Urban Areas of Ethiopia.

    Geiger, Martha; Hockenhull, Jo; Buller, Henry; Tefera Engida, Gebre; Getachew, Mulugeta; Burden, Faith Adelaide; Whay, Helen Rebecca (2020-02-14)
    Working donkeys (Equus africanus asinus) are vital to the development and support of people's livelihoods in rural, peri-urban, and urban areas of Ethiopia. However, despite their critical role in providing transport, food security, and income generation to some of the poorest and most marginalized households, donkey contributions to human livelihoods have been largely unexplored. Donkey users, veterinary surgeons, business owners, and civil servants were interviewed to investigate the role humans play in shaping donkey lives while furthering our understanding of the social and economic impacts of working donkeys to human lives. Findings are discussed through seven guiding themes; donkeys as generators of income, the relationship between donkeys and social status, donkeys and affect, empowerment through donkeys, the role of donkeys in reducing vulnerability and encouraging resilience, donkey husbandry, and gender dynamics all of which gave a broader and richer insight into the value of donkeys. Donkeys are an important support in rural, peri-urban, and urban settings through the creation of economic security, independence, and participation in local saving schemes. In addition, donkeys provide social status, empowerment to marginalized groups such as women and the very poor and provide a sense of companionship. Whether the interviewee was a donkey user or a key informant appeared to influence their views on donkeys and their welfare, as did their location. The variations in views and practices between urban and rural settings suggests that assessing the socioeconomic value of donkeys in different locations within the same area or country is critical, rather than assuming that similar views are held between compatriots. Despite their centrality to many people's lives in Ethiopia, working donkeys often hold lowly status, are misunderstood, and given little husbandry and healthcare.
  • A worm gel-based 3D model to elucidate the paracrine interaction between multiple myeloma and mesenchymal stem cells.

    Spelat, Renza; Ferro, Federico; Contessotto, Paolo; Warren, Nicholas J; Marsico, Grazia; Armes, Steven P; Pandit, Abhay (2020-01-07)
    Multiple myeloma (MM) is a malignancy of terminally-differentiated plasma cells that develops mainly inside the bone marrow (BM) microenvironment. It is well known that autocrine and paracrine signals are responsible for the progression of this disease but the precise mechanism and contributions from single cell remain largely unknown. Mesenchymal stem cells (MSC) are an important cellular component of the BM: they support MM growth by increasing its survival and chemo-resistance, but little is known about the paracrine signaling pathways. Three-dimensional (3D) models of MM-MSC paracrine interactions are much more biologically-relevant than simple 2D models and are considered essential for detailed studies of MM pathogenesis. Herein we present a novel 3D co-culture model designed to mimic the paracrine interaction between MSC and MM cells. MSC were embedded within a previously characterized thermoresponsive block copolymer worm gel that can induce stasis in human pluripotent stem cells (hPSC) and then co-cultured with MM cells. Transcriptional phenotyping of co-cultured cells indicated the dysregulation of genes that code for known disease-relevant factors, and also revealed IL-6 and IL-10 as upstream regulators. Importantly, we have identified a synergistic paracrine signaling pathway between IL-6 and IL-10 that plays a critical role in sustaining MM cell proliferation. Our findings indicate that this 3D co-culture system is a useful model to investigate the paracrine interaction between MM cells and the BM microenvironment in vitro. This approach has revealed a new mechanism that promotes the proliferation of MM cells and suggested a new therapeutic target.
  • The Secretome Derived From Mesenchymal Stromal Cells Cultured in a Xeno-Free Medium Promotes Human Cartilage Recovery .

    Palamà, Maria Elisabetta Federica; Shaw, Georgina Margaret; Carluccio, Simonetta; Reverberi, Daniele; Sercia, Laura; Persano, Luana; Pisignano, Dario; Cortese, Katia; Barry, Francis Peter; Murphy, Josephine Mary; et al. (2020-02-14)
    Osteoarthritis (OA) is a disabling joint disorder causing articular cartilage degeneration. Currently, the treatments are mainly aimed to pain and symptoms relief, rather than disease amelioration. Human bone marrow stromal cells (hBMSCs) have emerged as a promising paracrine mechanism-based tool for OA treatment. Here, we investigate the therapeutic potential of conditioned media (CM) and extracellular vesicles (EVs) isolated from hBMSC and grown in a xeno-free culture system (XFS) compared to the conventional fetal bovine serum-culture system (FBS) in an in vitro model of OA. First, we observed that XFS promoted growth and viability of hBMSCs compared to FBS-containing medium while preserving their typical phenotype. The biological effects of the CM derived from hBMSC cultivated in XFS- and FBS-based medium were tested on IL-1α treated human chondrocytes, to mimic the OA enviroment. Treatment with CM derived from XFS-cultured hBMSC inhibited IL-1α-induced expression of IL-6, IL-8, and COX-2 by hACs compared to FBS-based condition. Furthermore, we observed that hBMSCs grown in XFS produced a higher amount of EVs compared to FBS-culture. The hBMSC-EVs not only inhibit the adverse effects of IL-1α-induced inflammation, but play a significant in vitro chondroprotective effect. In conclusion, the XFS medium was found to be suitable for isolation and expansion of hBMSCs with increased safety profile and intended for ready-to-use clinical therapies.
  • Iron, Zinc and Phytic Acid Retention of Biofortified, Low Phytic Acid, and Conventional Bean Varieties When Preparing Common Household Recipes.

    Hummel, Marijke; Talsma, Elise F; Taleon, Victor; Londoño, Luis; Brychkova, Galina; Gallego, Sonia; Raatz, Bodo; Spillane, Charles (2020-02-28)
    Biofortification is an effective method to improve the nutritional content of crops and nutritional intake. Breeding for higher micronutrient mineral content in beans is correlated with an increase in phytic acid, a main inhibitor of mineral absorption in humans. Low phytic acid (lpa) beans have a 90% lower phytic acid content compared to conventional beans. This is the first study to investigate mineral and total phytic acid retention after preparing common household recipes from conventional, biofortified and lpa beans. Mineral retention was determined for two conventional, three biofortified and two lpa bean genotypes. Treatments included soaking, boiling (boiled beans) and refrying (bean paste). The average true retention of iron after boiling was 77.2-91.3%; for zinc 41.2-84.0%; and for phytic acid 49.9-85.9%. Soaking led to a significant decrease in zinc and total phytic acid after boiling and refrying, whereas for iron no significant differences were found. lpa beans did not exhibit a consistent pattern of difference in iron and phytic acid retention compared to the other groups of beans. However, lpa beans had a significantly lower retention of zinc compared to conventional and biofortified varieties (p < 0.05). More research is needed to understand the underlying factors responsible for the differences in retention between the groups of beans, especially the low retention of zinc. Combining the lpa and biofortification traits could further improve the nutritional benefits of biofortified beans, by decreasing the phytic acid:iron and zinc ratio in beans.
  • Primary Human Osteoblasts Cultured in a 3D Microenvironment Create a Unique Representative Model of Their Differentiation Into Osteocytes.

    Nasello, Gabriele; Alamán-Díez, Pilar; Schiavi, Jessica; Pérez, María Ángeles; McNamara, Laoise; García-Aznar, José Manuel (2020-04-24)
    Microengineered systems provide an in vitro strategy to explore the variability of individual patient response to tissue engineering products, since they prefer the use of primary cell sources representing the phenotype variability. Traditional in vitro systems already showed that primary human osteoblasts embedded in a 3D fibrous collagen matrix differentiate into osteocytes under specific conditions. Here, we hypothesized that translating this environment to the organ-on-a-chip scale creates a minimal functional unit to recapitulate osteoblast maturation toward osteocytes and matrix mineralization. Primary human osteoblasts were seeded in a type I collagen hydrogel, to establish the role of lower (2.5 × 105 cells/ml) and higher (1 × 106 cells/ml) cell density on their differentiation into osteocytes. A custom semi-automatic image analysis software was used to extract quantitative data on cellular morphology from brightfield images. The results are showing that cells cultured at a high density increase dendrite length over time, stop proliferating, exhibit dendritic morphology, upregulate alkaline phosphatase (ALP) activity, and express the osteocyte marker dental matrix protein 1 (DMP1). On the contrary, cells cultured at lower density proliferate over time, do not upregulate ALP and express the osteoblast marker bone sialoprotein 2 (BSP2) at all timepoints. Our work reveals that microengineered systems create unique conditions to capture the major aspects of osteoblast differentiation into osteocytes with a limited number of cells. We propose that the microengineered approach is a functional strategy to create a patient-specific bone tissue model and investigate the individual osteogenic potential of the patient bone cells.

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