المؤلفون: Barbara Bradbury, Helen Chester, Miriam Santer, Leanne Morrison, Mandy Fader, Jane Ward, Jill Manthorpe, Catherine Murphy

المصدر: BMC Geriatrics, Vol 24, Iss 1, Pp 1-9 (2024)

مصطلحات موضوعية: Dementia care, Urinary incontinence, Continence management, Primary healthcare professionals, Geriatrics, RC952-954.6

الوصف: Abstract Background People living with dementia at home and their family carers often feel unsupported by healthcare professionals in managing continence problems. In turn, primary and community-based healthcare professionals have reported lacking specific knowledge on dementia-continence. This study aimed to understand more about healthcare professionals’ experiences and views of supporting people living with dementia experiencing continence problems, as part of developing acceptable resources. Having a nuanced understanding of unmet need would facilitate the design of engaging resources that enable healthcare professionals to provide more effective continence support to people living with dementia at home. Methods Semi-structured interviews were conducted with a range of healthcare professionals (n = 31) working in primary and community care in the South of England in 2023. Transcribed interviews were uploaded to NVivo 12, then analysed inductively and deductively using a thematic framework. Results Continence-related conversations were avoided by many healthcare professionals due to lack of dementia-continence specific knowledge. Many considered that continence problems of people living with dementia were largely outside their remit once a physical cause had been ruled out. This contributed to a lack of priority and proactivity in raising the subject of continence in their consultations. Challenges to providing support included limited consultation time and lack of access to specialist services with availability to support individuals. Conclusion There is substantial scope to support primary and community-based healthcare professionals in their provision of continence-related support and advice to people living at home with dementia. This includes addressing knowledge deficits, enhancing confidence and instilling a sense of accomplishment.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2318Test

الوصول الحر: https://doaj.org/article/219408aa35294bffb9fdf57df329818cTest

المؤلفون: Catherine Murphy, Laura Devis-Jauregui, Ronja Struck, Ariadna Boloix, Ciara Gallagher, Cian Gavin, Federica Cottone, Aroa Soriano Fernandez, Stephen Madden, Josep Roma, Miguel F Segura, Olga Piskareva

المصدر: PLoS ONE, Vol 19, Iss 5, p e0303643 (2024)

مصطلحات موضوعية: Medicine, Science

الوصف: Neuroblastoma is the most common solid extracranial tumour in children. Despite major advances in available therapies, children with drug-resistant and/or recurrent neuroblastoma have a dismal outlook with 5-year survival rates of less than 20%. Therefore, tackling relapsed tumour biology by developing and characterising clinically relevant models is a priority in finding targetable vulnerability in neuroblastoma. Using matched cisplatin-sensitive KellyLuc and resistant KellyCis83Luc cell lines, we developed a cisplatin-resistant metastatic MYCN-amplified neuroblastoma model. The average number of metastases per mouse was significantly higher in the KellyCis83Luc group than in the KellyLuc group. The vast majority of sites were confirmed as having lymph node metastasis. Their stiffness characteristics of lymph node metastasis values were within the range reported for the patient samples. Targeted transcriptomic profiling of immuno-oncology genes identified tumour necrosis factor receptor superfamily member 4 (TNFRSF4) as a significantly dysregulated MYCN-independent gene. Importantly, differential TNFRSF4 expression was identified in tumour cells rather than lymphocytes. Low TNFRSF4 expression correlated with poor prognostic indicators in neuroblastoma, such as age at diagnosis, stage, and risk stratification and significantly associated with reduced probability of both event-free and overall survival in neuroblastoma. Therefore, TNFRSF4 Low expression is an independent prognostic factor of survival in neuroblastoma.

وصف الملف: electronic resource

العلاقة: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0303643&type=printableTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/b0fe2c271ed544baae45a1917975d15fTest

المؤلفون: Laura C Cappelli, Maria E Suarez-Almazor, Michelle Turner, Stephane Champiat, Caroline Robert, Julie R Brahmer, Jarushka Naidoo, Jeffrey Weber, Joanne Riemer, Elad Sharon, Michael B Atkins, M Catherine Pietanza, Karthik Suresh, Catherine Murphy, Javid Moslehi, David Feltquate, Lee M Krug

المصدر: Journal for ImmunoTherapy of Cancer, Vol 11, Iss 3 (2023)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) therapy may vary substantially in their clinical presentation, including natural history, outcomes to treatment, and patterns. The application of clinical guidelines for irAE management can be challenging for practitioners due to a lack of common or consistently applied terminology. Furthermore, given the growing body of clinical experience and published data on irAEs, there is a greater appreciation for the heterogeneous natural histories, responses to treatment, and patterns of these toxicities, which is not currently reflected in irAE guidelines. Furthermore, there are no prospective trial data to inform the management of the distinct presentations of irAEs. Recognizing a need for uniform terminology for the natural history, response to treatment, and patterns of irAEs, the Society for Immunotherapy of Cancer (SITC) convened a consensus panel composed of leading international experts from academic medicine, industry, and regulatory agencies. Using a modified Delphi consensus process, the expert panel developed clinical definitions for irAE terminology used in the literature, encompassing terms related to irAE natural history (ie, re-emergent, chronic active, chronic inactive, delayed/late onset), response to treatment (ie, steroid unresponsive, steroid dependent), and patterns (ie, multisystem irAEs). SITC developed these definitions to support the adoption of a standardized vocabulary for irAEs, which will have implications for the uniform application of irAE clinical practice guidelines and to enable future irAE clinical trials.

وصف الملف: electronic resource

العلاقة: https://jitc.bmj.com/content/11/3/e006398.fullTest; https://doaj.org/toc/2051-1426Test

الوصول الحر: https://doaj.org/article/ce3651e8e8104a2ca8905bdbc8dd0dd4Test

المؤلفون: Susan Tuddenham, Pawel Gajer, Anne E. Burke, Catherine Murphy, Sabra L. Klein, Christina A. Stennett, Barbara Wilgus, Jacques Ravel, Khalil G. Ghanem, Rebecca M. Brotman

المصدر: EBioMedicine, Vol 87, Iss , Pp 104407- (2023)

مصطلحات موضوعية: Hormonal contraception, Vaginal microbiome, Reproductive health, Stability, Obstetrics and gynecology, Medicine, Medicine (General), R5-920

الوصف: Summary: Background: Bacterial vaginosis (BV), a condition in which vaginal Lactobacillus spp. are in low abundance, is associated with vulvovaginal symptoms, obstetric outcomes and urogenital infections. Recurrent BV is difficult to manage, and emerging data indicate a reduced risk of BV with the use of hormonal contraception (HC). Despite widespread use, little longitudinal data is available on whether, and in what timeframe, combined oral contraceptive pills (COCs) may act to affect vaginal microbiota stability and Lactobacillus dominance. Methods: We compared the vaginal microbiota of reproductive-age cisgender women during intervals on combined estrogen and progestin COCs with non-use intervals in a 2-year observational study. Vaginal microbiota were characterized by 16S rRNA gene amplicon sequencing. Findings: COC users were more likely to have Lactobacillus-dominated microbiota and more stable microbiota over time. Stability increased and then plateaued four weeks after COC initiation. The associations between COCs and Lactobacillus spp. dominance, and microbiota stability, were statistically significant for White, but not African American women; however sample size was limited for African American participants. Findings were similar for other forms of HC and when excluding samples collected during menses. Interpretation: Our study provides a methodologic framework to evaluate observational longitudinal microbiota data with exposure crossovers. We found COCs are associated with vaginal microbiota stability and a Lactobacillus-dominated state. COCs appear to impact stability within a month of initiation. Our findings have clinical implications for how soon benefits can be expected in (at least White) patients initiating COCs, and support the need for larger prospective trials to verify our results in ethnically diverse populations. Funding: R01-AI089878.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2352396422005898Test; https://doaj.org/toc/2352-3964Test

الوصول الحر: https://doaj.org/article/d8f2603361c7469084dd44a679065aa4Test

المؤلفون: Natasha Kekre, Kevin A. Hay, John R. Webb, Ranjeeta Mallick, Miruna Balasundaram, Mhairi K. Sigrist, Anne-Marie Clement, Julie S. Nielsen, Jennifer Quizi, Eric Yung, Scott D. Brown, Lisa Dreolini, Daniel D. Waller, Julian Smazynski, Nicole S. Gierc, Bianca C. Loveless, Kayla Clark, Tyler Dyer, Richard Hogg, Leah McCormick, Michael Gignac, Shanti Bell, D. Maria Chapman, David Bond, Siao Yong, Rachel Fung, Heather M. Lockyer, Victoria Hodgson, Catherine Murphy, Ana Subramanian, Evelyn Wiebe, Piriya Yoganathan, Liana Medynski, Dominique C. Vaillan, Alice Black, Sheryl McDiarmid, Michael Kennah, Linda Hamelin, Kevin Song, Sujaatha Narayanan, Judith A. Rodrigo, Stefany Dupont, Terry Hawrysh, Justin Presseau, Kednapa Thavorn, Manoj M. Lalu, Dean A. Fergusson, John C. Bell, Harold Atkins, Brad H. Nelson, Robert A. Holt

المصدر: Frontiers in Immunology, Vol 13 (2022)

مصطلحات موضوعية: CAR-T cells, hematologic malignancies, immune effector cells, point-of-care manufacturing, prodigy, in-house manufacturing, Immunologic diseases. Allergy, RC581-607

الوصف: Access to commercial CD19 CAR-T cells remains limited even in wealthy countries like Canada due to clinical, logistical, and financial barriers related to centrally manufactured products. We created a non-commercial academic platform for end-to-end manufacturing of CAR-T cells within Canada’s publicly funded healthcare system. We report initial results from a single-arm, open-label study to determine the safety and efficacy of in-house manufactured CD19 CAR-T cells (entitled CLIC-1901) in participants with relapsed/refractory CD19 positive hematologic malignancies. Using a GMP compliant semi-automated, closed process on the Miltenyi Prodigy, T cells were transduced with lentiviral vector bearing a 4-1BB anti-CD19 CAR transgene and expanded. Participants underwent lymphodepletion with fludarabine and cyclophosphamide, followed by infusion of non-cryopreserved CAR-T cells. Thirty participants with non-Hodgkin’s lymphoma (n=25) or acute lymphoblastic leukemia (n=5) were infused with CLIC-1901: 21 males (70%), median age 66 (range 18-75). Time from enrollment to CLIC-1901 infusion was a median of 20 days (range 15-48). The median CLIC-1901 dose infused was 2.3 × 106 CAR-T cells/kg (range 0.13-3.6 × 106/kg). Toxicity included ≥ grade 3 cytokine release syndrome (n=2) and neurotoxicity (n=1). Median follow-up was 6.5 months. Overall response rate at day 28 was 76.7%. Median progression-free and overall survival was 6 months (95%CI 3-not estimable) and 11 months (95% 6.6-not estimable), respectively. This is the first trial of in-house manufactured CAR-T cells in Canada and demonstrates that administering fresh CLIC-1901 product is fast, safe, and efficacious. Our experience may provide helpful guidance for other jurisdictions seeking to create feasible and sustainable CAR-T cell programs in research-oriented yet resource-constrained settings.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03765177, identifier NCT03765177.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2022.1074740/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/ba9bb5ccb69a4646aee78f29aa8e0137Test

المؤلفون: Catherine Murphy, Noirin Noonan, Eilis O’Toole, Patrick Plunkett, Mary Paula Colgan, Caitriona Canning, Zenia Martin, Martina Hennessy

المصدر: Clinical Case Reports, Vol 9, Iss 4, Pp 1876-1881 (2021)

مصطلحات موضوعية: COVID‐19, healthcare worker, prolonged course, rehabilitation program, return to work, Medicine, Medicine (General), R5-920

الوصف: Abstract We highlight the need for planning for mass workforce absentees as we prepare for subsequent surges. We suggest a multicomponent intervention including guiding return dates more by symptomatology and fitness for work rather than infectivity status.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2050-0904Test

الوصول الحر: https://doaj.org/article/a6cb91994d1547eea26011f76c546e93Test

المؤلفون: Susan Tuddenham, Khalil G. Ghanem, Laura E. Caulfield, Alisha J. Rovner, Courtney Robinson, Rupak Shivakoti, Ryan Miller, Anne Burke, Catherine Murphy, Jacques Ravel, Rebecca M. Brotman

المصدر: Reproductive Health, Vol 16, Iss 1, Pp 1-8 (2019)

مصطلحات موضوعية: Bacterial Vaginosis, Vaginal microbiome, Betaine, Food frequency questionnaire, Gynecology and obstetrics, RG1-991

الوصف: Abstract Objectives Bacterial vaginosis (BV), a clinical condition characterized by decreased vaginal Lactobacillus spp., is difficult to treat. We examined associations between micronutrient intake and a low-Lactobacillus vaginal microbiota as assessed by molecular methods (termed “molecular-BV”). Methods This cross-sectional analysis utilized data collected at the baseline visit of the Hormonal Contraception Longitudinal Study, a cohort of reproductive-aged women followed over 2 years while initiating or ceasing hormonal contraception (HC). The Block Brief 2000 Food Frequency Questionnaire was administered and micronutrient intakes were ranked. Vaginal microbiota composition was assessed using 16S rRNA gene amplicon sequencing and clustered into community state types (CSTs) based on the types and relative abundance of bacteria detected. Associations between the lowest estimated quartile intake of nutrients and having a low-Lactobacillus CST (molecular-BV) were evaluated by logistic regression. Separate models were built for each nutrient controlling for age, body mass index, behavioral factors, HC use and total energy intake. We also conducted a literature review of existing data on associations between micronutrient intakes and BV. Results Samples from 104 women were included in this analysis. Their mean age was 25.8 years (SD 4.3), 29.8% were African American, 48.1% were using HC, and 25% had molecular-BV. In adjusted multivariable analyses, the lowest quartile of betaine intake was associated with an increased odds of molecular-BV (aOR 9.2, p value

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s12978-019-0814-6Test; https://doaj.org/toc/1742-4755Test

الوصول الحر: https://doaj.org/article/bcdb8490698e4d8198e89328473b00a7Test

المؤلفون: Debora Collotta, William Hull, Raffaella Mastrocola, Fausto Chiazza, Alessia Sofia Cento, Catherine Murphy, Roberta Verta, Gustavo Ferreira Alves, Giulia Gaudioso, Francesca Fava, Magdi Yaqoob, Manuela Aragno, Kieran Tuohy, Christoph Thiemermann, Massimo Collino

المصدر: Molecular Metabolism, Vol 39, Iss , Pp - (2020)

مصطلحات موضوعية: Metaflammation, Baricitinib, High-fat-high sugar diet, JAK2-STAT2 pathway, Insulin resistance, Internal medicine, RC31-1245

الوصف: Objective: Recent evidence suggests the substantial pathogenic role of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway in the development of low-grade chronic inflammatory response, known as “metaflammation,” which contributes to obesity and type 2 diabetes. In this study, we investigated the effects of the JAK1/2 inhibitor baricitinib, recently approved for the treatment of rheumatoid arthritis, in a murine high-fat-high sugar diet model. Methods: Male C57BL/6 mice were fed with a control normal diet (ND) or a high-fat-high sugar diet (HD) for 22 weeks. A sub-group of HD fed mice was treated with baricitinib (10 mg/kg die, p.o.) for the last 16 weeks (HD + Bar). Results: HD feeding resulted in obesity, insulin-resistance, hypercholesterolemia and alterations in gut microbial composition. The metabolic abnormalities were dramatically reduced by chronic baricitinib administration. Treatment of HD mice with baricitinib did not change the diet-induced alterations in the gut, but restored insulin signaling in the liver and skeletal muscle, resulting in improvements of diet-induced myosteatosis, mesangial expansion and associated proteinuria. The skeletal muscle and renal protection were due to inhibition of the local JAK2-STAT2 pathway by baricitinib. We also demonstrated that restored tissue levels of JAK2-STAT2 activity were associated with a significant reduction in cytokine levels in the blood. Conclusions: In summary, our data suggest that the JAK2-STAT2 pathway may represent a novel candidate for the treatment of diet-related metabolic derangements, with the potential for EMA- and FDA-approved JAK inhibitors to be repurposed for the treatment of type 2 diabetes and/or its complications.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2212877820300831Test; https://doaj.org/toc/2212-8778Test

الوصول الحر: https://doaj.org/article/0bd346f6d49542e6a6efd0bfa718368aTest

المؤلفون: Cynthia J. Burrows, Shu Wang, Hyun Jae Kim, Gerald J. Meyer, Kirk Schanze, T. Randall Lee, Jodie L. Lutkenhaus, David Kaplan, Christopher Jones, Carolyn Bertozzi, Laura Kiessling, Mary Beth Mulcahy, Craig W. Lindsley, M. G. Finn, Joel D. Blum, Prashant Kamat, Courtney C. Aldrich, Stuart Rowan, Bin Liu, Dennis Liotta, Paul S. Weiss, Deqing Zhang, Krishna N. Ganesh, Patrick Sexton, Harry A. Atwater, J. Justin Gooding, David T. Allen, Christopher A. Voigt, Jonathan Sweedler, Alanna Schepartz, Vincent Rotello, Sébastien Lecommandoux, Shana J. Sturla, Sharon Hammes-Schiffer, Jillian Buriak, Jonathan W. Steed, Hongwei Wu, Julie Zimmerman, Bryan Brooks, Phillip Savage, William Tolman, Thomas F. Hofmann, Joan F. Brennecke, Thomas A. Holme, Kenneth M. Merz, Gustavo Scuseria, William Jorgensen, Gunda I. Georg, Shaomeng Wang, Philip Proteau, John R. Yates, Peter Stang, Gilbert C. Walker, Marc Hillmyer, Lynne S. Taylor, Teri W. Odom, Erick Carreira, Kai Rossen, Paul Chirik, Scott J. Miller, Anne McCoy, Joan-Emma Shea, Martin Zanni, Catherine Murphy, Gregory Scholes, Joseph A. Loo

المصدر: ACS Omega, Vol 5, Iss 17, Pp 9624-9625 (2020)

مصطلحات موضوعية: Chemistry, QD1-999

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2470-1343Test

الوصول الحر: https://doaj.org/article/713071e57aeb46bfb7c588a1fe575afaTest

المؤلفون: Sura Al Zoubi, Jianmin Chen, Catherine Murphy, Lukas Martin, Fausto Chiazza, Debora Collotta, Muhammad M. Yaqoob, Massimo Collino, Christoph Thiemermann

المصدر: Frontiers in Immunology, Vol 9 (2018)

مصطلحات موضوعية: sepsis, septic cardiomyopathy, NF-κB, IKK-16, DPP-4, linagliptin, Immunologic diseases. Allergy, RC581-607

الوصف: The mortality rate of patients who develop sepsis-related cardiac dysfunction is high. Many disease conditions (e.g., diabetes) increase the susceptibility to infections and subsequently sepsis. Activation of the NF-κB pathway plays a crucial role in the pathophysiology of sepsis-associated cardiac dysfunction and diabetic cardiomyopathy. The effect of diabetes on outcomes in patients with sepsis is still highly controversial. We here hypothesized that type 2 diabetes (T2DM) augments the cardiac (organ) dysfunction associated with sepsis, and that inhibition of the NF-κB pathway with linagliptin attenuates the cardiac (organ) dysfunction in mice with T2DM/sepsis. To investigate this, 10-week old male C57BL/6 mice were randomized to receive normal chow or high fat diet (HFD), 60% of calories derived from fat). After 12 weeks, mice were subjected to sham surgery or cecal ligation and puncture (CLP) for 24 h. At 1 hour after surgery, mice were treated with linagliptin (10 mg/kg, i.v.), IKK-16 (1 mg/kg, i.v.), or vehicle (2% DMSO, 3 ml/kg, i.v.). Mice also received analgesia, fluids and antibiotics at 6 and 18 h after surgery. Mice that received HFD showed a significant increase in body weight, impairment in glucose tolerance, reduction in ejection fraction (%EF), and increase in alanine aminotransferase (ALT). Mice on HFD subjected to CLP showed further reduction in %EF, increase in ALT, developed acute kidney dysfunction and lung injury. They also showed significant increase in NF-κB pathway, iNOS expression, and serum inflammatory cytokines compared to sham surgery group. Treatment of HFD-CLP mice with linagliptin or IKK-16 resulted in significant reductions in (i) cardiac, liver, kidney, and lung injury associated with CLP-sepsis, (ii) NF-κB activation and iNOS expression in the heart, and (iii) serum inflammatory cytokine levels compared to HFD-CLP mice treated with vehicle. Our data show that pre-existing type 2 diabetes phenotype worsens the organ dysfunction/injury associated with CLP-sepsis in mice. Most notably, inhibition of NF-κB reduces the organ dysfunction/injury associated with sepsis in mice with pre-existing T2DM.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fimmu.2018.02996/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/20d66ce58a844c66a2415a7c76025e12Test