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Article ; Online: RE: Complications and side effects of Wide-Awake Local Anaesthesia No Tourniquet (WALANT) in upper limb surgery: a systematic review and meta-analysis.

Clough, Richard / Jones, Samuel / Hamilton, Alex Euan

2024

Language	English
Publishing date	2024-04-23
Publishing country	Germany
Document type	Letter ; Comment
ZDB-ID	80384-4
ISSN	1432-5195 ; 0341-2695
ISSN (online)	1432-5195
ISSN	0341-2695
DOI	10.1007/s00264-024-06189-2
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Article: A 20-year misdiagnosis: a rare presentation of a basal cell carcinoma.

Liyanage, Dinithi / Clough, Richard / Pandit, Deepa / McKirdy, Stuart

Journal of surgical case reports

2024 Volume 2024, Issue 2, Page(s) rjae028

Abstract: Basal cell carcinoma (BCC) is the most common form of skin cancer. BCCs are seldom reported on the sole of the foot due to a lack of exposure to UV radiation which is the main risk factor. We present a brief literature review and case report of a 42-year- ...

Abstract	Basal cell carcinoma (BCC) is the most common form of skin cancer. BCCs are seldom reported on the sole of the foot due to a lack of exposure to UV radiation which is the main risk factor. We present a brief literature review and case report of a 42-year-old female with a non-resolving lesion on the mid-arch of her left foot over a 20-year period. Tissue diagnosis identified the lesion as a BCC. Disease-free control was achieved but the patient experienced significant morbidity resulting in three separate procedures to diagnose, excise and reconstruct the defect. When evaluating lesions on the sole clinicians should consider BCC as a differential, particularly in those which do not respond to initial treatment.
Language	English
Publishing date	2024-02-14
Publishing country	England
Document type	Case Reports
ZDB-ID	2580919-2
ISSN	2042-8812
ISSN	2042-8812
DOI	10.1093/jscr/rjae028
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Article ; Online: Major trauma among E-Scooter and bicycle users: a nationwide cohort study.

Clough, Richard Alexander / Platt, Esther / Cole, Elaine / Wilson, Mark / Aylwin, Christopher

Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention

2023 Volume 29, Issue 2, Page(s) 121–125

Abstract: Objectives: To determine the incidence, demographics and injury patterns involved in E-Scooter-related hospital admissions due to significant trauma compared with bicycle-related trauma within England and Wales. To compare morbidity and mortality ... ...

Abstract	Objectives: To determine the incidence, demographics and injury patterns involved in E-Scooter-related hospital admissions due to significant trauma compared with bicycle-related trauma within England and Wales. To compare morbidity and mortality between groups. Design: A retrospective cohort study based on data which has been prospectively collected and submitted to the UK Trauma Audit and Research Network (TARN) registry. Setting: Major trauma centres and trauma units within England and Wales. Participants: Patients of any age who were admitted to hospitals in England and Wales with injuries following E-Scooter or bicycle incidents between the dates 1 January 2021-31 December 2021. All patients must have met TARN database inclusion criteria. Outcomes: In-hospital mortality, critical care admission and length of stay (LoS), hospital LoS and discharge destination. Results: There were 293 E-Scooter trauma incidents compared with 2538 bicycle incidents. E-Scooter users were more likely to be admitted to a major trauma centre (p=0.019) or a critical care unit (p<0.001). Serious head and limb trauma (Abbreviated Injury Scale >2) occurred more frequently among the E-Scooter cohort (35.2% vs 19.7%, p<0.001 and 39.9% vs 27.2%, p<0.001, respectively) while serious chest and pelvic trauma were greater among bicycle users (p<0.001 and p=0.003, respectively). Over one-third of E-Scooter injuries were incurred outside the current legislation by patients who were intoxicated by alcohol and drugs (26%, 75/293) or under the age of 17 (14%, 41/293). Conclusions: These early results suggest a greater relative incidence of serious trauma and an alternative pattern of injury among E-Scooter users compared with bicycles. Trial registration number: TARN210101.
MeSH term(s)	Humans ; Cohort Studies ; Retrospective Studies ; Bicycling/injuries ; Head Protective Devices ; Hospitalization ; Accidents, Traffic/prevention & control
Language	English
Publishing date	2023-02-28
Publishing country	England
Document type	Journal Article
ZDB-ID	1433667-4
ISSN	1475-5785 ; 1353-8047
ISSN (online)	1475-5785
ISSN	1353-8047
DOI	10.1136/ip-2022-044722
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Article ; Online: RUNX1/RUNX1T1 mediates alternative splicing and reorganises the transcriptional landscape in leukemia.

Grinev, Vasily V / Barneh, Farnaz / Ilyushonak, Ilya M / Nakjang, Sirintra / Smink, Job / van Oort, Anita / Clough, Richard / Seyani, Michael / McNeill, Hesta / Reza, Mojgan / Martinez-Soria, Natalia / Assi, Salam A / Ramanouskaya, Tatsiana V / Bonifer, Constanze / Heidenreich, Olaf

Nature communications

2021 Volume 12, Issue 1, Page(s) 520

Abstract: The fusion oncogene RUNX1/RUNX1T1 encodes an aberrant transcription factor, which plays a key role in the initiation and maintenance of acute myeloid leukemia. Here we show that the RUNX1/RUNX1T1 oncogene is a regulator of alternative RNA splicing in ... ...

Abstract	The fusion oncogene RUNX1/RUNX1T1 encodes an aberrant transcription factor, which plays a key role in the initiation and maintenance of acute myeloid leukemia. Here we show that the RUNX1/RUNX1T1 oncogene is a regulator of alternative RNA splicing in leukemic cells. The comprehensive analysis of RUNX1/RUNX1T1-associated splicing events identifies two principal mechanisms that underlie the differential production of RNA isoforms: (i) RUNX1/RUNX1T1-mediated regulation of alternative transcription start site selection, and (ii) direct or indirect control of the expression of genes encoding splicing factors. The first mechanism leads to the expression of RNA isoforms with alternative structure of the 5'-UTR regions. The second mechanism generates alternative transcripts with new junctions between internal cassettes and constitutive exons. We also show that RUNX1/RUNX1T1-mediated differential splicing affects several functional groups of genes and produces proteins with unique conserved domain structures. In summary, this study reveals alternative splicing as an important component of transcriptome re-organization in leukemia by an aberrant transcriptional regulator.
MeSH term(s)	Acute Disease ; Alternative Splicing ; Cell Line, Tumor ; Core Binding Factor Alpha 2 Subunit/genetics ; Core Binding Factor Alpha 2 Subunit/metabolism ; Gene Expression Profiling/methods ; Gene Expression Regulation, Leukemic ; Humans ; Leukemia, Myeloid/genetics ; Leukemia, Myeloid/pathology ; Models, Genetic ; Oncogene Proteins, Fusion/genetics ; Oncogene Proteins, Fusion/metabolism ; RNA Interference ; RNA Isoforms/genetics ; RNA Isoforms/metabolism ; RUNX1 Translocation Partner 1 Protein/genetics ; RUNX1 Translocation Partner 1 Protein/metabolism ; Transcription Initiation Site
Chemical Substances	Core Binding Factor Alpha 2 Subunit ; Oncogene Proteins, Fusion ; RNA Isoforms ; RUNX1 Translocation Partner 1 Protein ; RUNX1 protein, human
Language	English
Publishing date	2021-01-22
Publishing country	England
Document type	Journal Article ; 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/s41467-020-20848-z
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Article ; Online: Stearidonic acid: is there a role in the prevention and management of type 2 diabetes mellitus?

Banz, William J / Davis, Jeremy E / Clough, Richard W / Cheatwood, Joseph L

The Journal of nutrition

2012 Volume 142, Issue 3, Page(s) 635S–640S

Abstract: Obesity and its related comorbidities are major public health concerns in the United States with over two-thirds of adults and one-third of children classified as overweight or obese. The prevalence of type 2 diabetes mellitus (T2DM) has similarly risen ... ...

Abstract	Obesity and its related comorbidities are major public health concerns in the United States with over two-thirds of adults and one-third of children classified as overweight or obese. The prevalence of type 2 diabetes mellitus (T2DM) has similarly risen to an estimated 25.8 million, which accounts for a staggering $174 billion in annual healthcare costs. Identification of dietary interventions that protect against the development of T2DM would markedly reduce the medical and economic consequences of the disease. Hence, we review current evidence supporting a role of (n-3) PUFA in T2DM and explore potential therapeutic implications of stearidonic acid (SDA). The low consumption of fish in the US along with a reduced efficiency to interconvert most plant (n-3) PUFA highlights a need to find alternative sources of (n-3) PUFA. The efficient biological conversion of SDA to EPA underscores the potential implications of SDA as a source of (n-3) PUFA. The full therapeutic efficacy of SDA remains to be further determined. However, recent data have suggested a protective role of SDA consumption on markers of dyslipidemia and inflammation. The AHA recommends that healthy individuals consume oily fish at least twice per week and individuals with a history of cardiovascular disease consume 1 g of EPA+DHA/d. These goals will likely not be met by the typical American diet. Therefore, SDA may represent a sustainable alternative to marine-based (n-3) PUFA and may have novel therapeutic efficacy regarding the development of T2DM.
MeSH term(s)	Diabetes Mellitus, Type 2/diet therapy ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/prevention & control ; Dietary Supplements ; Fatty Acids, Omega-3/administration & dosage ; Fish Oils/administration & dosage ; Humans ; Nutrition Policy ; Plant Oils/administration & dosage ; United States
Chemical Substances	Fatty Acids, Omega-3 ; Fish Oils ; Plant Oils ; stearidonic acid (P4CEK3495O)
Language	English
Publishing date	2012-01-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	218373-0
ISSN	1541-6100 ; 0022-3166
ISSN (online)	1541-6100
ISSN	0022-3166
DOI	10.3945/jn.111.146829
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Article ; Online: Functional dissection of the alpha-synuclein promoter: transcriptional regulation by ZSCAN21 and ZNF219.

Clough, Richard Lee / Dermentzaki, Georgia / Stefanis, Leonidas

Journal of neurochemistry

2009 Volume 110, Issue 5, Page(s) 1479–1490

Abstract: Alpha-synuclein (SNCA) is an abundant neuronal protein involved in synaptic neurotransmission. SNCA expression levels have been strongly implicated in Parkinson's disease pathogenesis. We have previously demonstrated that in the PC12 cell line elements ... ...

Abstract	Alpha-synuclein (SNCA) is an abundant neuronal protein involved in synaptic neurotransmission. SNCA expression levels have been strongly implicated in Parkinson's disease pathogenesis. We have previously demonstrated that in the PC12 cell line elements in intron 1 may mediate SNCA transcriptional regulation in response to neurotrophins. We have now identified transcription factor (TF) binding sites in intron 1 and the 5'-promoter of SNCA. A binding site for the TF zinc finger and SCAN domain containing (ZSCAN)21 in the 5'-region of intron 1 is required for intron 1 transcriptional activity. Small interfering RNA against ZSCAN21 inhibits activation in the luciferase assay and diminishes SNCA protein levels in naïve and neurotrophin-treated PC12 cells and in primary cultured cortical neurons, demonstrating that ZSCAN21 is a novel transcriptional regulator of SNCA in neuronal cells. The 5'-promoter of SNCA has a complex architecture, including multiple binding sites for the TF zinc finger protein (ZNF)219, which functions as both an activator and a repressor. Targeting ZSCAN21 or other TFs controlling SNCA transcriptional activity may provide novel therapeutic avenues not only for Parkinson's disease but also for other synucleopathies.
MeSH term(s)	Animals ; Binding Sites/genetics ; Cells, Cultured ; DNA-Binding Proteins/physiology ; Gene Expression Regulation/physiology ; Humans ; Introns/genetics ; Kruppel-Like Transcription Factors/physiology ; Mice ; Nerve Growth Factors/physiology ; PC12 Cells ; Promoter Regions, Genetic/physiology ; RNA, Messenger/biosynthesis ; Rats ; Rats, Wistar ; Transcription, Genetic/physiology ; Zinc Fingers/genetics ; alpha-Synuclein/genetics ; alpha-Synuclein/metabolism
Chemical Substances	DNA-Binding Proteins ; Kruppel-Like Transcription Factors ; Nerve Growth Factors ; RNA, Messenger ; ZNF219 protein, human ; ZSCAN21 protein, human ; alpha-Synuclein
Language	English
Publishing date	2009-09
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/j.1471-4159.2009.06250.x
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Article: Functional dissection of the α-synuclein promoter: transcriptional regulation by ZSCAN21 and ZNF219

Clough, Richard Lee / Dermentzaki, Georgia / Stefanis, Leonidas

Journal of neurochemistry. 2009 Sept., v. 110, no. 5

2009

Abstract: Alpha-Synuclein (SNCA) is an abundant neuronal protein involved in synaptic neurotransmission. SNCA expression levels have been strongly implicated in Parkinson's disease pathogenesis. We have previously demonstrated that in the PC12 cell line elements ... ...

Abstract	Alpha-Synuclein (SNCA) is an abundant neuronal protein involved in synaptic neurotransmission. SNCA expression levels have been strongly implicated in Parkinson's disease pathogenesis. We have previously demonstrated that in the PC12 cell line elements in intron 1 may mediate SNCA transcriptional regulation in response to neurotrophins. We have now identified transcription factor (TF) binding sites in intron 1 and the 5'-promoter of SNCA. A binding site for the TF zinc finger and SCAN domain containing (ZSCAN)21 in the 5'-region of intron 1 is required for intron 1 transcriptional activity. Small interfering RNA against ZSCAN21 inhibits activation in the luciferase assay and diminishes SNCA protein levels in naïve and neurotrophin-treated PC12 cells and in primary cultured cortical neurons, demonstrating that ZSCAN21 is a novel transcriptional regulator of SNCA in neuronal cells. The 5'-promoter of SNCA has a complex architecture, including multiple binding sites for the TF zinc finger protein (ZNF)219, which functions as both an activator and a repressor. Targeting ZSCAN21 or other TFs controlling SNCA transcriptional activity may provide novel therapeutic avenues not only for Parkinson's disease but also for other synucleopathies.
Keywords	neurotrophins ; Parkinson disease
Language	English
Dates of publication	2009-09
Size	p. 1479-1490.
Publisher	Blackwell Publishing Ltd
Publishing place	Oxford, UK
Document type	Article
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/j.1471-4159.2009.06250.x
Database	NAL-Catalogue (AGRICOLA)

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Article: Stearidonic Acid: Is There a Role in the Prevention and Management of Type 2 Diabetes Mellitus?

Banz, William J / Davis, Jeremy E / Clough, Richard W / Cheatwood, Joseph L

journal of nutrition. 2012 Mar., v. 142, no. 3

2012

Abstract	Obesity and its related comorbidities are major public health concerns in the United States with over two-thirds of adults and one-third of children classified as overweight or obese. The prevalence of type 2 diabetes mellitus (T2DM) has similarly risen to an estimated 25.8 million, which accounts for a staggering $174 billion in annual healthcare costs. Identification of dietary interventions that protect against the development of T2DM would markedly reduce the medical and economic consequences of the disease. Hence, we review current evidence supporting a role of (n-3) PUFA in T2DM and explore potential therapeutic implications of stearidonic acid (SDA). The low consumption of fish in the US along with a reduced efficiency to interconvert most plant (n-3) PUFA highlights a need to find alternative sources of (n-3) PUFA. The efficient biological conversion of SDA to EPA underscores the potential implications of SDA as a source of (n-3) PUFA. The full therapeutic efficacy of SDA remains to be further determined. However, recent data have suggested a protective role of SDA consumption on markers of dyslipidemia and inflammation. The AHA recommends that healthy individuals consume oily fish at least twice per week and individuals with a history of cardiovascular disease consume 1 g of EPA+DHA/d. These goals will likely not be met by the typical American diet. Therefore, SDA may represent a sustainable alternative to marine-based (n-3) PUFA and may have novel therapeutic efficacy regarding the development of T2DM.
Keywords	cardiovascular diseases ; childhood obesity ; economics ; fatty fish ; fish consumption ; health services ; hyperlipidemia ; inflammation ; noninsulin-dependent diabetes mellitus ; polyunsaturated fatty acids ; public health ; United States
Language	English
Dates of publication	2012-03
Size	p. 635S-640S.
Publishing place	American Society for Nutrition
Document type	Article
ZDB-ID	218373-0
ISSN	1541-6100 ; 0022-3166
ISSN (online)	1541-6100
ISSN	0022-3166
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Regulation of α-synuclein expression in cultured cortical neurons.

Clough, Richard Lee / Dermentzaki, Georgia / Haritou, Maria / Petsakou, Afroditi / Stefanis, Leonidas

Journal of neurochemistry

2011 Volume 117, Issue 2, Page(s) 275–285

Abstract: Alpha-synuclein (SNCA) is a predominantly neuronal protein involved in the control of neurotransmitter release. The levels of SNCA expression are closely linked to the pathogenesis of Parkinson's disease; however, the biochemical pathways and ... ...

Abstract	Alpha-synuclein (SNCA) is a predominantly neuronal protein involved in the control of neurotransmitter release. The levels of SNCA expression are closely linked to the pathogenesis of Parkinson's disease; however, the biochemical pathways and transcriptional elements that control SNCA expression are not well understood. We previously used the model system of neurotrophin-mediated PC12 cell neuronal differentiation to examine these phenomena. Although these studies were informative, they were limited to the use of a cell line; therefore, in the current work, we have turned our attention to cultured primary rat cortical neurons. In these cultures, SNCA expression increased with time in culture, as the neurons mature. Luciferase assays based on transient transfections of fusion constructs encoding components of the transcriptional control region of SNCA identified various promoter areas that have a positive or negative effect on SNCA transcription. Intron 1, previously identified by us as an important regulatory region in the PC12 cell model, cooperates with regions 5' to exon 1 to mediate gene transcription. Using selective pharmacological tools, we find that tyrosine kinase receptors and the phosphatidyl-inositol 3 kinase signaling pathway are involved in mediating these effects. The exogenous application of the neurotrophin brain-derived neurotrophic factor (BDNF) is sufficient on its own to promote the transcriptional activation of SNCA through this pathway, but a neutralizing antibody against BDNF failed to affect SNCA transcription in maturing cultures, suggesting that BDNF is not the main factor involved in maturation-induced SNCA transcription in this model. Further in vivo studies are needed to establish the role of neurotrophin signaling in the control of SNCA transcription.
MeSH term(s)	Analysis of Variance ; Animals ; Antibodies/pharmacology ; Brain-Derived Neurotrophic Factor/immunology ; Brain-Derived Neurotrophic Factor/pharmacology ; Cells, Cultured ; Cerebral Cortex/cytology ; Drug Administration Schedule ; Drug Interactions ; Embryo, Mammalian ; Enzyme Inhibitors/pharmacology ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/physiology ; Neurons/drug effects ; Neurons/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Promoter Regions, Genetic/drug effects ; Promoter Regions, Genetic/genetics ; Rats ; Rats, Wistar ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Time Factors ; Transfection/methods ; alpha-Synuclein/genetics ; alpha-Synuclein/metabolism
Chemical Substances	Antibodies ; Brain-Derived Neurotrophic Factor ; Enzyme Inhibitors ; alpha-Synuclein ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-)
Language	English
Publishing date	2011-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/j.1471-4159.2011.07199.x
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Article ; Online: Piroplasms of New Zealand seabirds.

Paparini, Andrea / McInnes, Linda M / Di Placido, Daniela / Mackereth, Graham / Tompkins, Daniel M / Clough, Richard / Ryan, Una M / Irwin, Peter J

Parasitology research

2014 Volume 113, Issue 12, Page(s) 4407–4414

Abstract: Blood and ectoparasitic ticks were collected from migratory seabirds in New Zealand, including Australasian gannets (n = 13) from two sites and red-billed gulls (n = 9) and white-fronted terns (n = 2) from a third location. Blood smears were screened for ...

Abstract	Blood and ectoparasitic ticks were collected from migratory seabirds in New Zealand, including Australasian gannets (n = 13) from two sites and red-billed gulls (n = 9) and white-fronted terns (n = 2) from a third location. Blood smears were screened for parasite presence by microscopy, while DNA from blood samples was subjected to PCR for the presence of tick-transmitted protozoan haemoparasites belonging to the order Piroplasmida. Parasites were identified by comparing small subunit ribosomal RNA (18S rDNA) gene sequences to related sequences on GenBank. Analyses indicated that nine birds were infected with unknown variants of a Babesia poelea-like parasite (recorded as genotypes I and II), while four harboured a piroplasm that was genetically similar to Babesia kiwiensis. There was no parasite stratification by bird species; both the gannets and gulls were positive for all three parasites, while the terns were positive for the B. kiwiensis-like and the B. poelea-like (genotype I) parasites. The B. kiwiensis-like parasite found in the birds was also found in two species of ticks: Carios capensis and Ixodes eudyptidis. This represents the first report of Babesia-positive ticks parasitising seabirds in New Zealand. The lack of host specificity and evidence of wide ranging distributions of the three piroplasm genotypes suggests there is a high degree of haemoparasite transmission occurring naturally between New Zealand seabird populations and species.
MeSH term(s)	Animal Migration ; Animals ; Arachnid Vectors/parasitology ; Argasidae/parasitology ; Babesia/classification ; Babesia/genetics ; Babesiosis/epidemiology ; Babesiosis/parasitology ; Bird Diseases/epidemiology ; Bird Diseases/parasitology ; Birds ; Charadriiformes/parasitology ; Cytochromes b/genetics ; DNA, Protozoan/blood ; DNA, Protozoan/chemistry ; DNA, Ribosomal/blood ; DNA, Ribosomal/chemistry ; Female ; Genotype ; Ixodes/parasitology ; Male ; New Zealand/epidemiology ; Phylogeny ; Polymerase Chain Reaction/veterinary ; RNA, Ribosomal, 18S/genetics ; Sequence Analysis, DNA/veterinary ; Tick Infestations/parasitology ; Tick Infestations/veterinary
Chemical Substances	DNA, Protozoan ; DNA, Ribosomal ; RNA, Ribosomal, 18S ; Cytochromes b (9035-37-4)
Language	English
Publishing date	2014-09-10
Publishing country	Germany
Document type	Journal Article
ZDB-ID	284966-5
ISSN	1432-1955 ; 0932-0113 ; 0044-3255
ISSN (online)	1432-1955
ISSN	0932-0113 ; 0044-3255
DOI	10.1007/s00436-014-4118-z
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