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  1. Article: Prosthetic femoral interposition arthroplasty with adult humeral implant, for children with cerebral palsy and symptomatic hips.

    Doyle, Finian / O'Sullivan, Michael D / Dawson, Peter / Murphy, Evelyn / Kelly, Paula / Cassidy, Noelle

    The surgeon : journal of the Royal Colleges of Surgeons of Edinburgh and Ireland

    2022  Volume 21, Issue 4, Page(s) e159–e163

    Abstract: Background: Immobile patients with cerebral palsy can suffer with painful dislocated hips. Decision-making and surgical management can prove challenging in this cohort of patients, with hips that cannot be reconstructed.: Methods: We conduced a ... ...

    Abstract Background: Immobile patients with cerebral palsy can suffer with painful dislocated hips. Decision-making and surgical management can prove challenging in this cohort of patients, with hips that cannot be reconstructed.
    Methods: We conduced a retrospective chart review of all patients who underwent prosthetic femoral interposition arthroplasty (PFIA) by two surgeons from 2013 to 2021, for unreconstructable hips. We compared pain and range of motion in preoperative period to the postoperative period. Caregiver reported outcomes were used to assess satisfaction post operatively. During the follow up, radiographs of the PFIA were obtained to assess for proximal migration, heterotopic ossification and loosening of implants.
    Results: Eleven index surgeries, which met the inclusion criteria, were included in this study. These were performed in eleven patients with an average follow up of 45 months. Regarding pain and range of motion post-operatively an excellent or good result was seen in nine cases. Two patients were classified as having a fair result with none having a poor result. Most caregivers reported being satisfied or very satisfied with the post-operative outcomes.
    Conclusion: A prescriptive operative solution to the painful dislocated hip in children with spastic cerebral palsy remains elusive. In this study, we have demonstrated both clinically and radiologically satisfactory results post proximal femoral interposition arthroplasty, for those patients with unreconstructable hips. Patient caregiver reported outcomes, show that the majority of caregivers were satisfied or very satisfied with the outcome of the surgery.
    MeSH term(s) Humans ; Adult ; Child ; Cerebral Palsy/complications ; Cerebral Palsy/surgery ; Treatment Outcome ; Retrospective Studies ; Arthroplasty/methods ; Hip Dislocation/etiology ; Hip Dislocation/surgery ; Pain/surgery ; Humerus/surgery ; Follow-Up Studies ; Arthroplasty, Replacement, Hip/methods
    Language English
    Publishing date 2022-10-26
    Publishing country Scotland
    Document type Journal Article
    ZDB-ID 2102927-1
    ISSN 1479-666X
    ISSN 1479-666X
    DOI 10.1016/j.surge.2022.09.006
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  2. Article ; Online: PPM1D suppresses p53-dependent transactivation and cell death by inhibiting the Integrated Stress Response.

    Andrysik, Zdenek / Sullivan, Kelly D / Kieft, Jeffrey S / Espinosa, Joaquin M

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 7400

    Abstract: The p53 transcription factor is a master regulator of cellular stress responses inhibited by repressors such as MDM2 and the phosphatase PPM1D. Activation of p53 with pharmacological inhibitors of its repressors is being tested in clinical trials for ... ...

    Abstract The p53 transcription factor is a master regulator of cellular stress responses inhibited by repressors such as MDM2 and the phosphatase PPM1D. Activation of p53 with pharmacological inhibitors of its repressors is being tested in clinical trials for cancer therapy, but efficacy has been limited by poor induction of tumor cell death. We demonstrate that dual inhibition of MDM2 and PPM1D induces apoptosis in multiple cancer cell types via amplification of the p53 transcriptional program through the eIF2α-ATF4 pathway. PPM1D inhibition induces phosphorylation of eIF2α, ATF4 accumulation, and ATF4-dependent enhancement of p53-dependent transactivation upon MDM2 inhibition. Dual inhibition of p53 repressors depletes heme and induces HRI-dependent eIF2α phosphorylation. Pharmacological induction of eIF2α phosphorylation synergizes with MDM2 inhibition to induce cell death and halt tumor growth in mice. These results demonstrate that PPM1D inhibits both the p53 network and the integrated stress response controlled by eIF2α-ATF4, with clear therapeutic implications.
    MeSH term(s) Animals ; Mice ; Apoptosis ; Cell Death ; Eukaryotic Initiation Factor-2/genetics ; Phosphorylation ; Transcription Factors ; Transcriptional Activation ; Tumor Suppressor Protein p53/genetics ; Protein Phosphatase 2C/metabolism ; Neoplasms
    Chemical Substances Eukaryotic Initiation Factor-2 ; Transcription Factors ; Tumor Suppressor Protein p53 ; Ppm1d protein, mouse (EC 3.1.3.16) ; Protein Phosphatase 2C (EC 3.1.3.16)
    Language English
    Publishing date 2022-12-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-35089-5
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  3. Article ; Online: Tibial rotation outcomes following hamstring lengthening as part of single event multilevel surgery in children with cerebral palsy.

    Marron, A / O'Sullivan, R / Kelly, E / Kiernan, D

    Gait & posture

    2020  Volume 79, Page(s) 126–132

    Abstract: Background: Hamstring lengthening remains the most common surgical procedure in the treatment of crouch gait for children with cerebral palsy (CP). While sagittal plane knee kinematics have been shown to improve post-surgery, the effects on transverse ... ...

    Abstract Background: Hamstring lengthening remains the most common surgical procedure in the treatment of crouch gait for children with cerebral palsy (CP). While sagittal plane knee kinematics have been shown to improve post-surgery, the effects on transverse plane kinematics have not been reported. Given the differing actions of the medial and lateral hamstring muscles there is potential for change in tibial rotation post hamstring lengthening.
    Research question: What is the effect of medial only versus combined medial and lateral hamstring lengthening on tibial rotation during gait in children with CP?
    Methods: A retrospective analysis of children with a diagnosis of CP who underwent a hamstring lengthening procedure. These children were divided into 2 groups: G1 (n = 18) had isolated medial hamstring lengthening while G2 (n = 30) had combined medial and lateral hamstring lengthening. A matched non-surgical control group (n = 15) was also included. Kinematic data were analysed pre and post-operatively. Pre-operative to post-operative outcomes for G1 and G2, a comparison at baseline for both groups and the difference in outcomes between the groups were analysed. Baseline to follow-up outcomes for the control group were also analysed.
    Results: External tibial rotation increased significantly within groups (G1: -10°, p < 0.01; G2: -11°, p < 0.001, control: -7.7, p < 0.01), with no significant difference in the change between the intervention groups. Foot progression angles became more external in both intervention groups (G1: -15°, p < 0.001; G2: -15°, p < 0.0001) and did not change in the control group.
    Significance: Results demonstrated similar increases in external tibial rotation, regardless of whether an isolated medial or combined medial and lateral surgery was performed. The control group demonstrated a similar change in external tibial rotation suggesting that hamstring lengthening surgery does not contribute to increased external tibial rotation in children with CP compared to what would be expected due to natural progression.
    MeSH term(s) Adolescent ; Case-Control Studies ; Cerebral Palsy/physiopathology ; Cerebral Palsy/surgery ; Child ; Female ; Gait ; Hamstring Muscles/surgery ; Humans ; Male ; Retrospective Studies ; Rotation ; Tenotomy/methods ; Tibia/physiopathology ; Treatment Outcome
    Language English
    Publishing date 2020-05-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 1162323-8
    ISSN 1879-2219 ; 0966-6362
    ISSN (online) 1879-2219
    ISSN 0966-6362
    DOI 10.1016/j.gaitpost.2020.04.026
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  4. Article ; Online: Global Analyses to Identify Direct Transcriptional Targets of p53.

    Galbraith, Matthew D / Andrysik, Zdenek / Sullivan, Kelly D / Espinosa, Joaquín M

    Methods in molecular biology (Clifton, N.J.)

    2021  Volume 2267, Page(s) 19–56

    Abstract: The transcription factor p53 controls a gene expression program with pleiotropic effects on cell biology including cell cycle arrest and apoptosis. Identifying direct p53 target genes within this network and determining how they influence cell fate ... ...

    Abstract The transcription factor p53 controls a gene expression program with pleiotropic effects on cell biology including cell cycle arrest and apoptosis. Identifying direct p53 target genes within this network and determining how they influence cell fate decisions downstream of p53 activation is a prerequisite for designing therapeutic approaches that target p53 to effectively kill cancer cells. Here we describe a comprehensive multi-omics approach for identifying genes that are direct transcriptional targets of p53. We provide detailed procedures for measuring global RNA polymerase activity, defining p53 binding sites across the genome, and quantifying changes in steady-state mRNA in response to p53 activation.
    MeSH term(s) Animals ; Cell Line ; Chromatin Immunoprecipitation Sequencing/methods ; Genomics/methods ; Humans ; RNA-Seq/methods ; Transcriptional Activation ; Transcriptome ; Tumor Suppressor Protein p53/metabolism
    Chemical Substances Tumor Suppressor Protein p53
    Language English
    Publishing date 2021-03-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1217-0_3
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  5. Article ; Online: PPM1D suppresses p53-dependent transactivation and cell death by inhibiting the Integrated Stress Response

    Zdenek Andrysik / Kelly D. Sullivan / Jeffrey S. Kieft / Joaquin M. Espinosa

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 16

    Abstract: The authors describe a functional crosstalk between the p53 network and the integrated stress response through the p53 repressor PPM1D. Inhibition of PPM1D potentiates p53-dependent transactivation and apoptosis via induction of the HRI-eIF2α-ATF4 ... ...

    Abstract The authors describe a functional crosstalk between the p53 network and the integrated stress response through the p53 repressor PPM1D. Inhibition of PPM1D potentiates p53-dependent transactivation and apoptosis via induction of the HRI-eIF2α-ATF4 pathway.
    Keywords Science ; Q
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Prognostic value of pre-operative mean corpuscular volume (MCV) in colorectal cancer.

    Shokuhi, Poorya / O'Sullivan, Niall J / Temperley, Hugo C / Russell, Thomas / McEntee, Philip D / Mehigan, Brian J / McCormick, Paul H / Gallagher, David / Gillham, Charles / Kennedy, John / Kelly, Michael E / Larkin, John O

    Irish journal of medical science

    2023  

    Abstract: Background: Mean corpuscular volume (MCV) has been shown to have some correlation to oncological outcomes in oesophageal cancer, with high pre-operative MCV associated with disease recurrence. A similar association has previously been reported in ... ...

    Abstract Background: Mean corpuscular volume (MCV) has been shown to have some correlation to oncological outcomes in oesophageal cancer, with high pre-operative MCV associated with disease recurrence. A similar association has previously been reported in colorectal cancer.
    Aims: This study is aimed at investigating whether high MCV bears similar relation to post-operative outcome and disease recurrence in colorectal cancer (CRC).
    Methods: Patients undergoing elective CRC resection with curative intent between January 2008 and December 2019 were identified from our prospective database. Review of patient demographic details, American Society of Anaesthesiologists (ASA) grade, smoking and alcohol intake were performed. In addition, tumour location and staging, operation performed, pre-operative laboratory data and oncological management of each patient were noted. Post-operative morbidity (Clavien-Dindo (CD) score > 2), 30-day mortality, in-hospital mortality and cancer recurrence were examined and multivariable regression analysis was performed to predict these outcomes.
    Results: A total of 1,293 CRCs were resected, with 1,159 patients (89.7%) experiencing a hospital course without major morbidity (CD < 3). 30-day mortality rate was less than 1% (12/1293). There were 176 patients (13.6%) with recurrence at follow-up. When multivariable regression analysis was performed, high pre-operative MCV did not predict negative post-operative or oncological outcomes.
    Conclusion: MCV does not appear to be an independent prognostic factor for outcomes following elective CRC resection.
    Language English
    Publishing date 2023-11-09
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 390895-1
    ISSN 1863-4362 ; 0021-1265
    ISSN (online) 1863-4362
    ISSN 0021-1265
    DOI 10.1007/s11845-023-03571-8
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  7. Article ; Online: Public Health Emergency Preparedness Practices and the Management of Frontline Communicable Disease Response.

    Sullivan, Amy D / Strickland, Colten J / Howard, Kelly M

    Journal of public health management and practice : JPHMP

    2019  Volume 26, Issue 2, Page(s) 180–183

    MeSH term(s) Civil Defense/methods ; Civil Defense/standards ; Civil Defense/statistics & numerical data ; Communicable Diseases/epidemiology ; Communicable Diseases/therapy ; Disaster Planning/methods ; Disaster Planning/organization & administration ; Humans ; Oregon ; Public Health/methods ; Public Health/standards ; Public Health/trends
    Language English
    Publishing date 2019-02-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2027860-3
    ISSN 1550-5022 ; 1078-4659
    ISSN (online) 1550-5022
    ISSN 1078-4659
    DOI 10.1097/PHH.0000000000000963
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  8. Article ; Online: Prophylactic antireflux procedures are not necessary in neurologically impaired children undergoing gastrostomy placement.

    Williams, Michael D / Skertich, Nicholas / Sullivan, Gwyneth A / Harmon, Kelly / Madonna, Mary Beth / Pillai, Srikumar / Shah, Ami N / Gulack, Brian C

    Pediatric surgery international

    2023  Volume 39, Issue 1, Page(s) 122

    Abstract: Purpose: Fundoplication is frequently used in children with neurologic impairment even in the absence of reflux due to concerns for future gastric feeding intolerance, but supporting data are lacking. We aimed to determine the incidence of secondary ... ...

    Abstract Purpose: Fundoplication is frequently used in children with neurologic impairment even in the absence of reflux due to concerns for future gastric feeding intolerance, but supporting data are lacking. We aimed to determine the incidence of secondary antireflux procedures (fundoplication or gastrojejunostomy (GJ)) post gastrostomy tube (GT) placement in children with and without neurologic impairment.
    Methods: Children under 18 undergoing a GT placement without fundoplication between 2010 and 2020 were identified utilizing the PearlDiver Mariner national patient claims database. Children with a diagnosis of cerebral palsy or a degenerative neurologic disease were identified and compared to children without these diagnoses. The incidence of delayed fundoplication or conversion to GJ were compared utilizing Kaplan-Meier and Cox proportional hazards regression analyses.
    Results: A total of 14,965 children underwent GT placement, of which 3712 (24.8%) had a diagnosis of neurologic impairment. The rate of concomitant fundoplication was significantly higher among children with a diagnosis of neurologic impairment as compared to those without (9.3% vs 6.4%, p < 0.001). While children with neurologic impairment had a significantly higher rate of fundoplication or GJ conversion at 5 years compared to children without (12.6% [95% confidence interval (CI): 11.4%-13.8%] vs 8.6% [95% CI 8.0%-9.2%], p < 0.001), the overall incidence remained low.
    Conclusion: Although children with neurologic impairment have a higher rate of requiring an antireflux procedure or GJ conversion than other children, the overall rate remains less than 15%. Fundoplication should not be utilized in children without clinical reflux on the basis of neurologic impairment alone.
    MeSH term(s) Child ; Humans ; Infant, Newborn ; Infant ; Gastrostomy/methods ; Gastroesophageal Reflux/complications ; Gastroesophageal Reflux/surgery ; Gastroesophageal Reflux/epidemiology ; Fundoplication/methods ; Enteral Nutrition ; Nervous System Diseases/complications ; Nervous System Diseases/surgery ; Retrospective Studies
    Language English
    Publishing date 2023-02-14
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 632773-4
    ISSN 1437-9813 ; 0179-0358
    ISSN (online) 1437-9813
    ISSN 0179-0358
    DOI 10.1007/s00383-023-05398-x
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    Zs.A 2138: Show issues Location:
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  9. Article ; Online: Research priorities in HIV, aging and rehabilitation: building on a framework with the Canada-International HIV and Rehabilitation Research Collaborative.

    O'Brien, Kelly K / Ibáñez-Carrasco, Francisco / Birtwell, Kelly / Donald, Graeme / Brown, Darren A / Eaton, Andrew D / Kasadha, Bakita / Stanmore, Emma / St Clair-Sullivan, Natalie / Townsend, Liam / Vera, Jaime H / Solomon, Patricia

    AIDS research and therapy

    2023  Volume 20, Issue 1, Page(s) 86

    Abstract: Background: In 2016, the Canada-International HIV and Rehabilitation Research Collaborative established a framework of research priorities in HIV, aging and rehabilitation. Our aim was to review and identify any new emerging priorities from the ... ...

    Abstract Background: In 2016, the Canada-International HIV and Rehabilitation Research Collaborative established a framework of research priorities in HIV, aging and rehabilitation. Our aim was to review and identify any new emerging priorities from the perspectives of people living with HIV, clinicians, researchers, and representatives from community organizations.
    Methods: We conducted a multi-stakeholder international consultation with people living with HIV, researchers, clinicians and representatives of community-based organizations. Stakeholders convened for a one-day Forum in Manchester, United Kingdom (UK) to discuss research priorities via a web-based questionnaire and facilitated discussions. We analyzed data using conventional content analytical techniques and mapped emerging priorities onto the foundational framework.
    Results: Thirty-five stakeholders from the UK(n = 29), Canada(n = 5) and Ireland(n = 1) attended the Forum, representing persons living with HIV or representatives from community-based organizations(n = 12;34%), researchers or academics(n = 10;28%), service providers(n = 6;17%), clinicians(n = 4;11%); and trainees(n = 4;11%). Five priorities mapped onto the Framework of Research Priorities across three content areas: A-Episodic Health and Disability Aging with HIV (disability, frailty, social participation), B-Rehabilitation Interventions for Healthy Aging across the Lifespan (role, implementation and impact of digital and web-based rehabilitation interventions) and C-Outcome Measurement in HIV and Aging (digital and web-based rehabilitation health technology to measure physical activity). Stakeholders indicated methodological considerations for implementing digital and web-based rehabilitation interventions into research and practice and the importance of knowledge transfer and exchange among the broader community.
    Conclusion: Results highlight the sustained importance of the Framework of Research Priorities and provide further depth and areas of inquiry related to digital and web-based rehabilitation interventions and technology aging with HIV.
    MeSH term(s) Humans ; Rehabilitation Research ; HIV Infections ; Aging ; Surveys and Questionnaires ; Canada
    Language English
    Publishing date 2023-12-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2173450-1
    ISSN 1742-6405 ; 1742-6405
    ISSN (online) 1742-6405
    ISSN 1742-6405
    DOI 10.1186/s12981-023-00582-4
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  10. Article ; Online: Culturomics and the history of psychiatry: testing the Google Ngram method.

    O'Sullivan, O P / Duffy, R M / Kelly, B D

    Irish journal of psychological medicine

    2019  Volume 36, Issue 1, Page(s) 23–27

    Abstract: Objectives: Culturomics is the study of behaviour and culture through quantitative analysis of digitised text. We aimed to apply a modern technique in this field to examine trends related to the history of psychiatry. In doing so, we aimed to explore ... ...

    Abstract Objectives: Culturomics is the study of behaviour and culture through quantitative analysis of digitised text. We aimed to apply a modern technique in this field to examine trends related to the history of psychiatry. In doing so, we aimed to explore the nature of the Google Ngram methodology.
    Methods: Using Google Ngram Viewer, we studied Google's corpus of over 4% of all published books and explored relevant trends in word usage.
    Results: An exponential growth in the use of 'psychiatry' between 1890 and 1984 was identified. 'Sigmund Freud' was mentioned more frequently than all other prominent figures in the history of psychiatry combined. Mentions of 'suicide' increased since 1820. The impact of several DSM editions is discussed.
    Conclusion: This study demonstrated the potential application of the Ngram methodology to the study of the history of psychiatry. The role of textual analysis in this field merits careful, constructive consideration and is likely to expand with technological advances.
    MeSH term(s) Culture ; Databases, Factual ; History, 19th Century ; History, 20th Century ; Humans ; Internet ; Literature, Modern ; Psychiatry/history ; Search Engine
    Language English
    Publishing date 2019-03-31
    Publishing country England
    Document type Historical Article ; Journal Article
    ZDB-ID 227751-7
    ISSN 2051-6967 ; 0790-9667
    ISSN (online) 2051-6967
    ISSN 0790-9667
    DOI 10.1017/ipm.2017.37
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