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Article ; Online: Planar Anchoring of C

Cui, Daling / MacLeod, Jennifer M / Rosei, Federico

Small (Weinheim an der Bergstrasse, Germany)

2019 Volume 15, Issue 45, Page(s) e1903294

Abstract: ... interface reveal that a 2D covalent organic framework (COF-1) can offer an anchoring effect to template C ...

Abstract	The surface-induced anchoring effect is a well-developed technique to control the growth of liquid crystals (LCs). Nevertheless, a defined nanometer-scale template has never been used to induce the anchored growth of LCs with molecular building units. Scanning tunneling microscopy results at the solid/liquid interface reveal that a 2D covalent organic framework (COF-1) can offer an anchoring effect to template C
Language	English
Publishing date	2019-09-12
Publishing country	Germany
Document type	Journal Article
ISSN	1613-6829
ISSN (online)	1613-6829
DOI	10.1002/smll.201903294
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Article: Ultrastructural analysis reveals mitochondrial placement independent of synapse placement in fine caliber C. elegans neurons.

Riboul, Danielle V / Crill, Sarah / Oliva, Carlos D / Restifo, Maria G / Joseph, Reggie / Joseph, Kerdes / Nguyen, Ken Cq / Hall, David H / Fily, Yaouen / Macleod, Gregory T

bioRxiv : the preprint server for biology

2024

Abstract: ... Therefore, beyond the capacity to disperse mitochondria throughout their length, at least in C. elegans, fine caliber neurons ...

Abstract	Neurons rely on mitochondria for an efficient supply of ATP and other metabolites. However, while neurons are highly elongated, mitochondria are discrete and limited in number. Due to the slow rates of diffusion over long distances it follows that neurons would benefit from an ability to control the distribution of mitochondria to sites of high metabolic activity, such as synapses. It is assumed that neurons' possess this capacity, but ultrastructural data over substantial portions of a neuron's extent that would allow for tests of such hypotheses are scarce. Here, we mined the Caenorhabditis elegans electron micrographs of John White and Sydney Brenner and found systematic differences in average mitochondrial length (ranging from 1.3 to 2.4 μm), volume density (3.7% to 6.5%) and diameter (0.18 to 0.24 μm) between neurons of different neurotransmitter type and function, but found limited differences in mitochondrial morphometrics between axons and dendrites of the same neurons. Analyses of distance intervals found mitochondria to be distributed randomly with respect to presynaptic specializations, and an indication that mitochondria were displaced from postsynaptic specializations. Presynaptic specializations were primarily localized to varicosities, but mitochondria were no more likely to be found in synaptic varicosities than non-synaptic varicosities. Consistently, mitochondrial volume density was no greater in varicosities with synapses. Therefore, beyond the capacity to disperse mitochondria throughout their length, at least in C. elegans, fine caliber neurons manifest limited sub-cellular control of mitochondrial size and distribution.
Language	English
Publishing date	2024-03-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.05.30.542959
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Article ; Online: Increasing uptake of hepatitis C virus infection case-finding, testing, and treatment in primary care: evaluation of the HepCATT (Hepatitis C Assessment Through to Treatment) trial.

Horwood, Jeremy / Clement, Clare / Roberts, Kirsty / Waldron, Cherry-Ann / Irving, William L / Macleod, John / Hickman, Mathew

The British journal of general practice : the journal of the Royal College of General Practitioners

2020 Volume 70, Issue 697, Page(s) e581–e588

Abstract: Background: Hepatitis C virus (HCV) infection is a key cause of liver disease but can be cured ... to be cost-effective; however, evidence of effective interventions is lacking. The Hepatitis C ...

Abstract	Background: Hepatitis C virus (HCV) infection is a key cause of liver disease but can be cured in more than 95% of patients. Around 70 000 people in England may have undiagnosed HCV infection and many more will not have been treated. Interventions to increase case-finding in primary care are likely to be cost-effective; however, evidence of effective interventions is lacking. The Hepatitis C Assessment Through to Treatment (HepCATT) trial assessed whether a complex intervention in primary care could increase case-finding, testing, and treatment of HCV. Aim: To investigate the feasibility and acceptability of the HepCATT intervention. Design and setting: A qualitative study with primary care practice staff from practices in the south west of England taking part in the HepCATT trial. Method: Semi-structured interviews were carried out with GPs, nurses, and practice staff to ascertain their views of the HepCATT intervention at least 1 month after implementing the intervention in their practice. Normalisation process theory, which outlines the social processes involved in intervention implementation, informed thematic data analysis. Results: Participants appreciated the HepCATT intervention for increasing knowledge and awareness of HCV. Although some initial technical difficulties were reported, participants saw the benefits of using the audit tool to systematically identify patients with HCV infection risk factors and found it straightforward to use. Participants valued the opportunity to discuss HCV testing with patients, especially those who may not have been previously aware of HCV risk. Future implementation should consider fully integrating software systems and additional resources to screen patient lists and conduct tests. Conclusion: When supported by a complex intervention, primary care can play a crucial role in identifying and caring for patients with HCV infection, to help stem the HCV epidemic, and prevent HCV-related illness.
MeSH term(s)	Cost-Benefit Analysis ; England ; Hepacivirus ; Hepatitis C/diagnosis ; Hepatitis C/drug therapy ; Hepatitis C/epidemiology ; Humans ; Primary Health Care
Language	English
Publishing date	2020-07-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1043148-2
ISSN	1478-5242 ; 0035-8797 ; 0960-1643
ISSN (online)	1478-5242
ISSN	0035-8797 ; 0960-1643
DOI	10.3399/bjgp20X708785
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Article ; Online: GLOBAL REACH 2018: intra-arterial vitamin C improves endothelial-dependent vasodilatory function in humans at high altitude.

Stone, Rachel M / Ainslie, Philip N / Tremblay, Joshua C / Akins, John D / MacLeod, David B / Tymko, Michael M / DeSouza, Christopher A / Bain, Anthony R

The Journal of physiology

2021 Volume 600, Issue 6, Page(s) 1373–1383

Abstract: ... infusion of ACh with the antioxidant vitamin C (ACh+VitC). The total FBF response to ACh ...

Abstract	High altitude-induced hypoxaemia is often associated with peripheral vascular dysfunction. However, the basic mechanism(s) underlying high-altitude vascular impairments remains unclear. This study tested the hypothesis that oxidative stress contributes to the impairments in endothelial function during early acclimatization to high altitude. Ten young healthy lowlanders were tested at sea level (344 m) and following 4-6 days at high altitude (4300 m). Vascular endothelial function was determined using the isolated perfused forearm technique with forearm blood flow (FBF) measured by strain-gauge venous occlusion plethysmography. FBF was quantified in response to acetylcholine (ACh), sodium nitroprusside (SNP) and a co-infusion of ACh with the antioxidant vitamin C (ACh+VitC). The total FBF response to ACh (area under the curve) was ∼30% lower at high altitude than at sea level (P = 0.048). There was no difference in the response to SNP at high altitude (P = 0.860). At sea level, the co-infusion of ACh+VitC had no influence on the FBF dose response (P = 0.268); however, at high altitude ACh+VitC resulted in an average increase in the FBF dose response by ∼20% (P = 0.019). At high altitude, the decreased FBF response to ACh, and the increase in FBF in response to ACh+VitC, were associated with the magnitude of arterial hypoxaemia (R
MeSH term(s)	Acetylcholine/pharmacology ; Altitude ; Antioxidants/pharmacology ; Ascorbic Acid/pharmacology ; Endothelium, Vascular/physiology ; Forearm/blood supply ; Humans ; Hypoxia ; Nitroprusside/pharmacology ; Regional Blood Flow ; Vasodilation ; Vasodilator Agents/pharmacology
Chemical Substances	Antioxidants ; Vasodilator Agents ; Nitroprusside (169D1260KM) ; Acetylcholine (N9YNS0M02X) ; Ascorbic Acid (PQ6CK8PD0R)
Language	English
Publishing date	2021-11-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP282281
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Article ; Online: A cluster randomised trial of a Needs Assessment Tool for adult Cancer patients and their carers (NAT-C) in primary care: A feasibility study.

Clark, Joseph / Amoakwa, Elvis / Wright-Hughes, Alexandra / Blenkinsopp, John / Currow, David C / Meads, David / Farrin, Amanda / Allgar, Victoria / Macleod, Una / Johnson, Miriam

PloS one

2021 Volume 16, Issue 1, Page(s) e0245647

Abstract: ... The Needs Assessment Tool-Cancer (NAT-C) is a validated, structured method of assessing patient/carer concerns and ... armed cluster randomised trial of NAT-C in primary care by evaluating: recruitment of GP practices ... patients and carers; most effective approach of ensuring NAT-C appointments, acceptability of study ...

Abstract	Background: People with cancer often have unidentified symptoms and social care needs. The Needs Assessment Tool-Cancer (NAT-C) is a validated, structured method of assessing patient/carer concerns and prompting action, to address unmet need. Aims: Assess feasibility and acceptability of a definitive two-armed cluster randomised trial of NAT-C in primary care by evaluating: recruitment of GP practices, patients and carers; most effective approach of ensuring NAT-C appointments, acceptability of study measures and follow-up. Methods: Non-blinded, feasibility study in four General Practices, with cluster randomisation to method of NAT-C appointment delivery, and process evaluation. Adults with active cancer were invited to participate with or without carer. Practices cluster randomised (1:1) to Arm I: promotion and use of NAT-C with a NAT-C trained clinician or Arm II: clinician of choice irrespective of training status. Participants completed study questionnaires at: baseline, 1, 3 and 6 months. Patients booked a 20 minute needs-assessment appointment post-baseline. Patients, carers and GP practice staff views regarding the study sought through interviews/focus groups. Quantitative data were analysed descriptively. Qualitative data were analysed thematically, informed by Normalisation Process Theory. Progression to a definitive trial was assessed against feasibility outcomes, relating to: recruitment rate, uptake and delivery of the NAT-C, data collection and quality. Results: Five GP practices approached, four recruited and trained to use the NAT-C. Forty-seven participants and 17 carers recruited. At baseline, 34/47 (72%) participants reported at least one moderate-severe unmet need, confirming study rationale. 32/47 (68%) participants received a NAT-C-guided consultation, 19 of which on Arm I. Study attrition at one month (n = 44 (94%), n = 16 (94%)), three months (n = 38 (81%), n = 14 (82%)) and six months (n = 32 (68%), n = 10 (59%)). Fifteen patient interviews conducted across the whole study and one focus group at each GP practice. Participants supported a definitive study and found measures acceptable. Conclusion: The feasibility trial indicated that recruitment rate, intervention uptake and data collection were appropriate, with refinements, for a definitive multi-centre cluster randomised controlled trial. Feasibility outcomes informed the design of a 2-armed cluster randomised controlled trial to test the effectiveness and cost-effectiveness of the NAT-C compared with usual care.
MeSH term(s)	Aged ; Aged, 80 and over ; Caregivers ; Feasibility Studies ; Female ; Humans ; Male ; Middle Aged ; Needs Assessment ; Neoplasms/therapy ; Primary Health Care ; Quality of Life
Language	English
Publishing date	2021-01-28
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0245647
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Article ; Online: Disruptive lysosomal-metabolic signaling and neurodevelopmental deficits that precede Purkinje cell loss in a mouse model of Niemann-Pick Type-C disease.

Kim, Sarah / Ochoa, Kathleen / Melli, Sierra E / Yousufzai, Fawad A K / Barrera, Zerian D / Williams, Aela A / McIntyre, Gianna / Delgado, Esteban / Bolish, James N / Macleod, Collin M / Boghos, Mary / Lens, Hayden P / Ramos, Alex G / Wilson, Vincent B / Maloney, Kelly / Padron, Zachary M / Khan, Amaal H / Blanco, Rosa E / Soto, Ileana

Scientific reports

2023 Volume 13, Issue 1, Page(s) 5665

Abstract: Purkinje cell (PC) loss occurs at an early age in patients and animal models of Niemann-Pick Type C ...

Abstract	Purkinje cell (PC) loss occurs at an early age in patients and animal models of Niemann-Pick Type C (NPC), a lysosomal storage disease caused by mutations in the Npc1 or Npc2 genes. Although degeneration of PCs occurs early in NPC, little is known about how NPC1 deficiency affects the postnatal development of PCs. Using the Npc1
MeSH term(s)	Mice ; Animals ; Purkinje Cells/metabolism ; Niemann-Pick Disease, Type C/genetics ; Niemann-Pick Disease, Type C/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Disease Models, Animal ; Lysosomes/metabolism
Chemical Substances	Intracellular Signaling Peptides and Proteins
Language	English
Publishing date	2023-04-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-32971-0
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Article ; Online: Tenascin-C expression controls the maturation of articular cartilage in mice.

Gruber, Bastian L / Mienaltowski, Michael J / MacLeod, James N / Schittny, Johannes / Kasper, Stephanie / Flück, Martin

BMC research notes

2020 Volume 13, Issue 1, Page(s) 78

Abstract: Objective: Expression of the de-adhesive extracellular matrix protein tenascin-C (TNC) is ... of tenascin-C in the post-natal maturation of the extracellular matrix in articular cartilage. This might be ...

Abstract	Objective: Expression of the de-adhesive extracellular matrix protein tenascin-C (TNC) is associated with the early postnatal development of articular cartilage which is both load-dependent and associated with chondrocyte differentiation. We assessed morphological changes in the articular cartilage of TNC deficient mice at postnatal ages of 1, 4 and 8 weeks compared to age-matched wildtype mice. Results: Cartilage integrity was assessed based on hematoxylin and eosin stained-sections from the tibial bone using a modified Mankin score. Chondrocyte density and cartilage thickness were assessed morphometrically. TNC expression was localized based on immunostaining. At 8 weeks of age, the formed tangential/transitional zone of the articular cartilage was 27% thicker and the density of chondrocytes in the articular cartilage was 55% lower in wildtype than the TNC-deficient mice. TNC protein expression was associated with chondrocytes. No relevant changes were found in mice at 1 and 4 weeks of age. The findings indicate a role of tenascin-C in the post-natal maturation of the extracellular matrix in articular cartilage. This might be a compensatory mechanism to strengthen resilience against mechanical stress.
MeSH term(s)	Aging/pathology ; Animals ; Cartilage, Articular/metabolism ; Cartilage, Articular/pathology ; Cell Count ; Genotype ; Mice ; Tenascin/deficiency ; Tenascin/metabolism
Chemical Substances	Tenascin
Language	English
Publishing date	2020-02-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2413336-X
ISSN	1756-0500 ; 1756-0500
ISSN (online)	1756-0500
ISSN	1756-0500
DOI	10.1186/s13104-020-4906-8
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Article: Cases shown at F.R.C.S. Demonstration.

Macleod, C

Postgraduate medical journal

2011 Volume 15, Issue 169, Page(s) 374.2–382

Language	English
Publishing date	2011-01-06
Publishing country	England
Document type	Journal Article
ZDB-ID	80325-x
ISSN	1469-0756 ; 0032-5473
ISSN (online)	1469-0756
ISSN	0032-5473
DOI	10.1136/pgmj.15.169.374-a
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Article ; Online: A cluster randomised trial of a Needs Assessment Tool for adult Cancer patients and their carers (NAT-C) in primary care

Joseph Clark / Elvis Amoakwa / Alexandra Wright-Hughes / John Blenkinsopp / David C Currow / David Meads / Amanda Farrin / Victoria Allgar / Una Macleod / Miriam Johnson

PLoS ONE, Vol 16, Iss 1, p e

A feasibility study.

2021 Volume 0245647

Abstract: ... The Needs Assessment Tool-Cancer (NAT-C) is a validated, structured method of assessing patient/carer concerns and ... cluster randomised trial of NAT-C in primary care by evaluating: recruitment of GP practices, patients and ... carers; most effective approach of ensuring NAT-C appointments, acceptability of study measures and ...

Abstract	Background People with cancer often have unidentified symptoms and social care needs. The Needs Assessment Tool-Cancer (NAT-C) is a validated, structured method of assessing patient/carer concerns and prompting action, to address unmet need. Aims Assess feasibility and acceptability of a definitive two-armed cluster randomised trial of NAT-C in primary care by evaluating: recruitment of GP practices, patients and carers; most effective approach of ensuring NAT-C appointments, acceptability of study measures and follow-up. Methods Non-blinded, feasibility study in four General Practices, with cluster randomisation to method of NAT-C appointment delivery, and process evaluation. Adults with active cancer were invited to participate with or without carer. Practices cluster randomised (1:1) to Arm I: promotion and use of NAT-C with a NAT-C trained clinician or Arm II: clinician of choice irrespective of training status. Participants completed study questionnaires at: baseline, 1, 3 and 6 months. Patients booked a 20 minute needs-assessment appointment post-baseline. Patients, carers and GP practice staff views regarding the study sought through interviews/focus groups. Quantitative data were analysed descriptively. Qualitative data were analysed thematically, informed by Normalisation Process Theory. Progression to a definitive trial was assessed against feasibility outcomes, relating to: recruitment rate, uptake and delivery of the NAT-C, data collection and quality. Results Five GP practices approached, four recruited and trained to use the NAT-C. Forty-seven participants and 17 carers recruited. At baseline, 34/47 (72%) participants reported at least one moderate-severe unmet need, confirming study rationale. 32/47 (68%) participants received a NAT-C-guided consultation, 19 of which on Arm I. Study attrition at one month (n = 44 (94%), n = 16 (94%)), three months (n = 38 (81%), n = 14 (82%)) and six months (n = 32 (68%), n = 10 (59%)). Fifteen patient interviews conducted across the whole study and one focus ...
Keywords	Medicine ; R ; Science ; Q
Subject code	420
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cost effectiveness of an intervention to increase uptake of hepatitis C virus testing and treatment (HepCATT): cluster randomised controlled trial in primary care.

Roberts, Kirsty / Macleod, John / Metcalfe, Chris / Hollingworth, Will / Williams, Jack / Muir, Peter / Vickerman, Peter / Clement, Clare / Gordon, Fiona / Irving, Will / Waldron, Cherry-Ann / North, Paul / Moore, Philippa / Simmons, Ruth / Miners, Alec / Horwood, Jeremy / Hickman, Matthew

BMJ (Clinical research ed.)

2020 Volume 368, Page(s) m322

Abstract: ... in primary care that aims to increase uptake of hepatitis C virus (HCV) case finding and treatment.: Design ...

Abstract	Objective: To evaluate the effectiveness and cost effectiveness of a complex intervention in primary care that aims to increase uptake of hepatitis C virus (HCV) case finding and treatment. Design: Pragmatic, two armed, practice level, cluster randomised controlled trial and economic evaluation. Setting and participants: 45 general practices in South West England (22 randomised to intervention and 23 to control arm). Outcome data were collected from all intervention practices and 21/23 control practices. Total number of flagged patients was 24 473 (about 5% of practice list). Intervention: Electronic algorithm and flag on practice systems identifying patients with HCV risk markers (such as history of opioid dependence or HCV tests with no evidence of referral to hepatology), staff educational training in HCV, and practice posters/leaflets to increase patients' awareness. Flagged patients were invited by letter for an HCV test (with one follow-up) and had on-screen pop-ups to encourage opportunistic testing. The intervention lasted one year, with practices recruited April to December 2016. Main outcome measures: Primary outcome: uptake of HCV testing. Secondary outcomes: number of positive HCV tests and yield (proportion HCV positive); HCV treatment assessment at hepatology; cost effectiveness. Results: Baseline HCV testing of flagged patients (six months before study start) was 608/13 097 (4.6%) in intervention practices and 380/11 376 (3.3%) in control practices. During the study 2071 (16%) of flagged patients in the intervention practices and 1163 (10%) in control practices were tested for HCV: overall intervention effect as an adjusted rate ratio of 1.59 (95% confidence interval 1.21 to 2.08; P<0.001). HCV antibodies were detected in 129 patients from intervention practices and 51 patients from control practices (adjusted rate ratio 2.24, 1.47 to 3.42) with weak evidence of an increase in yield (6.2% Conclusion: HepCATT had a modest impact but is a low cost intervention that merits optimisation and implementation as part of an NHS strategy to increase HCV testing and treatment. Trial registration: ISRCTN61788850.
MeSH term(s)	Antiviral Agents/therapeutic use ; Cost-Benefit Analysis ; England ; Hepacivirus/isolation & purification ; Hepatitis C/diagnosis ; Hepatitis C/drug therapy ; Hepatitis C/economics ; Hepatitis C/virology ; Humans ; Outcome and Process Assessment, Health Care ; Primary Health Care/economics ; Reagent Kits, Diagnostic/economics ; Reagent Kits, Diagnostic/supply & distribution ; State Medicine
Chemical Substances	Antiviral Agents ; Reagent Kits, Diagnostic
Language	English
Publishing date	2020-02-26
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1362901-3
ISSN	1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
ISSN (online)	1756-1833
ISSN	0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
DOI	10.1136/bmj.m322
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