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Article: Engineering Pathways in Central Carbon Metabolism Help to Increase Glycan Production and Improve N-Type Glycosylation of Recombinant Proteins in E. coli

Jaffe, Stephen / Evans, Caroline / Fowler, Gregory

Bioengineering, 6(1):27

2019

Abstract: Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked ... ...

Abstract	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation. The addition of glycans to proteins remains a relatively inefficient process and here we aimed to combine genetic modifications within central carbon metabolic pathways in order to increase glycan precursor pools, prior to transfer onto polypeptide backbones. Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b. Unexpectedly, overexpression of a gene involved in the production of DXP from pyruvate (dxs), which was previously seen to have a positive impact on glycosylation, was detrimental to process efficiency and the possible reasons for this are discussed.
Keywords	Escherichia coli ; N-glycosylation ; cell engineering ; glycosylation efficiency ; recombinant protein production
Language	English
Document type	Article
Database	Repository for Life Sciences

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Article ; Online: The postnatal effects of perineal trauma on maternal psychological and emotional wellbeing: A longitudinal study.

Molyneux, Rebecca / Fowler, Gillian / Slade, Pauline

European journal of obstetrics, gynecology, and reproductive biology

2024 Volume 294, Page(s) 238–244

Abstract: Objective: To examine the postnatal psychological health and parenting adjustment of primiparous women experiencing perineal trauma.: Study design: Longitudinal cohort study assessing body image, perceptions of traumatic birth, psychological distress, ...

Abstract	Objective: To examine the postnatal psychological health and parenting adjustment of primiparous women experiencing perineal trauma. Study design: Longitudinal cohort study assessing body image, perceptions of traumatic birth, psychological distress, perineal pain, impact upon parental tasks and mother-infant bonding at 6-12 weeks (n = 103) and 6-10 months postnatally (n = 91). Primiparous women were recruited following vaginal birth and perineal suturing in a UK-based maternity hospital. al. Comparisons made according to the objective classification of perineal trauma experienced; 1st/2nd degree tear, episiotomy, and Obstetric Anal Sphincter Injuries (OASI). Results: At 6-12 weeks women with an episiotomy reported a more negative perception of their body image than those with OASI. Women with OASI or an episiotomy were more likely to have experienced birth as traumatic, and those with OASI reported more avoidance symptoms of post-traumatic stress and a greater negative impact on parenting tasks. At 6-10 months significantly more avoidance symptoms continued to be reported by those with OASI, whereas those with an episiotomy reported more anxiety related symptoms in general than those with OASI. Conclusions: OASI, whilst associated with traumatic birth and some early parenting impacts, may not be linked to general negative psychological outcomes when specialist routine follow-up care is provided. Psychological impacts for women with episiotomy may merit further input than currently provided. Consideration should be given with regards to widening the access to postnatal perineal care by extending the criteria for specialist follow up beyond those sustaining OASI.
MeSH term(s)	Pregnancy ; Female ; Humans ; Longitudinal Studies ; Episiotomy/adverse effects ; Episiotomy/methods ; Mothers ; Anal Canal/injuries ; Vagina ; Lacerations/etiology ; Birth Injuries ; Perineum/injuries ; Delivery, Obstetric/adverse effects ; Delivery, Obstetric/methods ; Risk Factors ; Obstetric Labor Complications/etiology
Language	English
Publishing date	2024-01-28
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	190605-7
ISSN	1872-7654 ; 0301-2115 ; 0028-2243
ISSN (online)	1872-7654
ISSN	0301-2115 ; 0028-2243
DOI	10.1016/j.ejogrb.2024.01.035
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Article ; Online: Follow up of women after obstetric anal sphincter injuries (OASI)-What is the role of anorectal testing?

Badri, Hawra / Fowler, Gillian / Lane, Steven

Neurourology and urodynamics

2023 Volume 42, Issue 6, Page(s) 1374–1380

Abstract: Aims: To evaluate the benefit of performing anorectal studies on all women following primary obstetric anal sphincter injury (OASI) repair over performing them on symptomatic women only.: Methods: Women who attended perineal clinic between 2007 and ... ...

Abstract	Aims: To evaluate the benefit of performing anorectal studies on all women following primary obstetric anal sphincter injury (OASI) repair over performing them on symptomatic women only. Methods: Women who attended perineal clinic between 2007 and 2020 underwent symptom assessment and anorectal studies at 6 weeks and 6 months postpartum. Anorectal studies including endo anal ultrasound (EAUS) and anal manometry (AM) were performed. The anorectal studies of symptomatic women who were the case group, were compared with asymptomatic women who were the control group. Results: A total of 1348 women were seen in the perineal clinic over 13 years. A total of 454 (33.7%) women were symptomatic. A total of 894 (66.3%) women were asymptomatic. A total of 313 (35%) asymptomatic women had two abnormal anorectal studies, 274 (31%) had abnormal AM alone, and 86 (9.6%) had abnormal EAUS alone. A total of 221 (24.7%) asymptomatic women had normal anorectal studies. Conclusion: Almost 70% of women were asymptomatic 6 months following primary OASI repair. Most had at least one abnormal anorectal study result. Selectively performing anorectal tests on symptomatic women would not identify asymptomatic women at risk of future faecal incontinence following further vaginal birth. Without anorectal study results, women would not receive accurate counseling about the risks of vaginal birth. Anorectal studies should be offered to all women following OASI where resources allow.
MeSH term(s)	Pregnancy ; Female ; Humans ; Male ; Anal Canal/diagnostic imaging ; Anal Canal/injuries ; Delivery, Obstetric/adverse effects ; Delivery, Obstetric/methods ; Follow-Up Studies ; Parturition ; Fecal Incontinence/diagnostic imaging ; Fecal Incontinence/etiology
Language	English
Publishing date	2023-06-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	604904-7
ISSN	1520-6777 ; 0733-2467
ISSN (online)	1520-6777
ISSN	0733-2467
DOI	10.1002/nau.25220
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Article ; Online: Consecutive recovery of recovered carbon black and limonene from waste tyres by thermal pyrolysis in a rotary kiln

Bowles, A.J. / Nievas, Á / Fowler, G.D.

Sustainable Chemistry and Pharmacy. 2023 May, v. 32 p.100972-

2023

Abstract: End of life tyres are one of the most abundant and least recycled waste streams. Material recovery processes that accommodate for the complexity and heterogeneity of waste tyres, such as pyrolysis, require urgent development. Examples of recycled tyre ... ...

Abstract	End of life tyres are one of the most abundant and least recycled waste streams. Material recovery processes that accommodate for the complexity and heterogeneity of waste tyres, such as pyrolysis, require urgent development. Examples of recycled tyre pyrolysis products include recovered carbon black (RCb), a recycled filler, and limonene, a solvent, although investigations reporting the recovery of both are limited. In this study the pyrolysis of waste tyres was investigated in a batch rotary kiln under varying conditions (temperature, gas flow, sample mass). Characterisation analysis was then applied to selected samples of RCb (BET surface area, transmissibility of toluene extract, proximate analysis) and tyre pyrolysis oil (yield, limonene content, FTIR). The best RCb (77.7 m²/g, 0.2% volatile matter, 17.0% ash, 94.8% transmissibility of toluene extract) was produced at 550 °C with a high ratio of purge gas flow (2000 mL/min) to rubber sample mass pyrolysed (100 g), minimising the recondensation of tarry volatiles on the RCb. The highest oil and limonene yield (38.4% and 17.4 g/kg waste tyres respectively) was produced at a temperature of 550 °C with a low ratio of purge gas (400 mL/min) to rubber sample pyrolysed (200 g), as these conditions prevented the decomposition of limonene to less valuable products and improved the oil trap condensation efficiency. These findings demonstrate the importance of pyrolysis processing conditions when considering the consecutive production of RCb and solvents from waste tyre pyrolysis, which shows significant future potential to valorise waste tyres, incentivising recycling.
Keywords	green chemistry ; kilns ; limonene ; oils ; proximate composition ; pyrolysis ; pyrolysis oils ; rubber ; solvents ; soot ; surface area ; temperature ; tires ; toluene ; water reuse ; Waste tyre ; Recovered carbon black
Language	English
Dates of publication	2023-05
Publishing place	Elsevier B.V.
Document type	Article ; Online
ISSN	2352-5541
DOI	10.1016/j.scp.2023.100972
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Article ; Online: Long-term outcomes after amputation and sentinel node biopsy for subungual melanoma: A single-institution series.

Valenzuela, Cristian D / Fowler, Graham / Kozuma, Kaiya / Kusaka, Sonny / Vetto, John T

American journal of surgery

2024 Volume 231, Page(s) 79–85

Abstract: Background: Subungual melanoma (SUM) is a rare tumor with historically poor outcomes. Thus, the benefit of proximal versus distal amputation in SUM remains unclear.: Methods: We performed a retrospective review of our prospectively-maintained ... ...

Abstract	Background: Subungual melanoma (SUM) is a rare tumor with historically poor outcomes. Thus, the benefit of proximal versus distal amputation in SUM remains unclear. Methods: We performed a retrospective review of our prospectively-maintained institutional melanoma database, including SUM and non-subungual acral melanoma (AM) patients who underwent sentinel lymph node biopsy (SLNB) between 1999 and 2022. All SUMs had distal joint or proximal amputations. Primary endpoints were overall survival (OS) and recurrence free survival (RFS). Kaplan-Meier estimates, and Cox univariate and multivariate analyses were performed. Tests were repeated on propensity score matched (PSM) populations in a 2:1 ratio. Results: 123 patients underwent resection with SLNB for SUM (n = 27) and AM (n = 96). Median follow-up was 9.2 years. Unadjusted median OS was 149.1 months for AM and 198.1 months for SUM. In the PSM comparison, median OS and RFS remained comparable between SUM and AM (149.5 months versus 198.1 months; p = 0.612). Sentinel node positivity was associated with significantly worse overall survival outcome (Hazard Ratio 5.49; CI (1.59-18.97), p = 0.007). In the PSM population, male sex was also associated with a significant hazard of death (HR 3.00, CI (1.03-8.71), p = 0.043). Proximal amputations were associated with significantly worse OS (p < 0.002) and RFS (p < 0.01) compared to distal amputations in SUM. Conclusion: SUM was well-treated with distal amputations, and had better OS and RFS compared to SUM treated with proximal amputations. Sentinel lymph node status is an important prognostic factor for SUMs and AMs. SUMs can be treated similarly to AMs with comparably good long-term outcomes.
MeSH term(s)	Humans ; Male ; Melanoma/pathology ; Sentinel Lymph Node Biopsy ; Prognosis ; Survival Rate ; Skin Neoplasms/pathology ; Sentinel Lymph Node/pathology ; Retrospective Studies ; Nail Diseases/pathology ; Nail Diseases/surgery
Language	English
Publishing date	2024-02-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2953-1
ISSN	1879-1883 ; 0002-9610
ISSN (online)	1879-1883
ISSN	0002-9610
DOI	10.1016/j.amjsurg.2024.02.042
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Article ; Online: Maternal sepsis caused by

Dunphy, Louise / Polkampali, Mamatha / Simmons, William / Fowler, Grace

BMJ case reports

2022 Volume 15, Issue 10

Abstract: Improving maternal and child health is a global priority. Although infection ... ...

Abstract	Improving maternal and child health is a global priority. Although infection with
MeSH term(s)	Amoxicillin ; Child ; Female ; Humans ; Infant, Newborn ; Listeria monocytogenes ; Listeriosis/complications ; Listeriosis/diagnosis ; Listeriosis/drug therapy ; Obstetric Labor, Premature ; Penicillins ; Placenta ; Pre-Eclampsia ; Pregnancy ; Pregnancy Complications, Infectious/diagnosis ; Sepsis/complications
Chemical Substances	Penicillins ; Amoxicillin (804826J2HU)
Language	English
Publishing date	2022-10-03
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	1757-790X
ISSN (online)	1757-790X
DOI	10.1136/bcr-2022-249989
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Article ; Online: The role of anal manometry in the follow-up of women with obstetric anal sphincter injuries (OASI).

Badri, Hawra / Fowler, Gillian / Lane, Steven

International urogynecology journal

2022 Volume 34, Issue 2, Page(s) 399–404

Abstract: Introduction and hypothesis: Mode of birth (MOB) following OASI is determined by choice, symptoms and anorectal study results in asymptomatic women. Endoanal ultrasound (EAUS) is the gold-standard imaging modality. EAUS use in MOB counselling is ... ...

Abstract	Introduction and hypothesis: Mode of birth (MOB) following OASI is determined by choice, symptoms and anorectal study results in asymptomatic women. Endoanal ultrasound (EAUS) is the gold-standard imaging modality. EAUS use in MOB counselling is supported by strong evidence. Less is understood about how anal manometry (AM) influences MOB counselling. Methods: A retrospective observational study was conducted from 2007 to 2020. Women underwent symptom assessment using validated ePAQ and St Mark's incontinence score (SMIS). Anorectal studies using EAUS and AM were performed. The case group was the normal ultrasound group and the control group was the abnormal ultrasound group. Both groups were compared with normal and abnormal AM result groups. Results: A total of 1348 women were included over 13 years. Among these, 454 women were symptomatic, 894 were asymptomatic; 274 (31%) asymptomatic women had isolated abnormal AM results, 313 (35%) had two abnormal anorectal results and 221 (24.7%) had normal anorectal results. Eighty-six asymptomatic women (10.4%) had isolated abnormal EAUS results, 138 (30.4%) symptomatic women had isolated abnormal AM, 221 (48.7%) had two abnormal anorectal results and 57 (12.6%) had normal anorectal results. Thirty-eight symptomatic women (8.4%) had an isolated abnormal EAUS result. Conclusions: AM identifies more women with sphincter function impairment than EAUS alone. Without AM, almost one third of asymptomatic women would not have been identified and could have been inadequately counselled. Performing AM and EAUS together captured most women with compromised anal sphincter function. We conclude that AM should be performed in all women with OASI alongside EAUS to enable accurate MOB counselling.
MeSH term(s)	Pregnancy ; Humans ; Female ; Anal Canal/injuries ; Fecal Incontinence ; Follow-Up Studies ; Endosonography/methods ; Manometry/methods ; Delivery, Obstetric/methods
Language	English
Publishing date	2022-10-24
Publishing country	England
Document type	Observational Study ; Journal Article
ZDB-ID	1050631-7
ISSN	1433-3023 ; 0937-3462
ISSN (online)	1433-3023
ISSN	0937-3462
DOI	10.1007/s00192-022-05380-6
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Article: Assessing the impacts of feedstock and process control on pyrolysis outputs for tyre recycling

Bowles, A.J. / Fowler, G.D.

Resources, conservation, and recycling. 2022 Mar. 04,

2022

Abstract: Tyres are a problematic waste stream which are associated with low recycling rates; most are dumped or incinerated, offering poor value return from this material-rich and energy intensive waste. Pyrolysis offers the potential for 30% of a tyre to be ... ...

Abstract	Tyres are a problematic waste stream which are associated with low recycling rates; most are dumped or incinerated, offering poor value return from this material-rich and energy intensive waste. Pyrolysis offers the potential for 30% of a tyre to be directly recyclable as ‘recovered carbon black’ (RCb), potentiating tyre-to-tyre recycling. However, most attempts to exploit the process have failed to produce consistent, high quality RCb on a commercially viable scale. Current consensus implies that RCb quality can only be improved by expensive post-processing, such as demineralisation using chemical solvents. Here it is shown that the quality (ash and volatile matter content) and consistency of RCb can be improved significantly by careful application of feedstock and process control during pyrolysis. This was achieved via the analysis of peer reviewed data from 31 waste tyres and yields from 161 runs in 37 pyrolysis reactors. A statistical bootstrapping regime showed that by selective exclusion of high ash tyres, and mixing the remainder thoroughly, RCb ash content could be reduced from 49% (upper 99% CI) to 14%. By utilising a unique reactor classification, it was found that fixed beds performed inconsistently, whilst rotary kilns and conical spouted beds produced high quality RCb and a high oil yield, even at lower pyrolysis temperatures. Due to their higher throughput, this work therefore suggests that application of rotary kilns with feedstock control are best mechanisms to produce consistent high-quality products from pyrolysis, increasing the recyclability of automotive tyres.
Keywords	ash content ; energy ; feedstocks ; oils ; process control ; pyrolysis ; soot ; tires ; wastes
Language	English
Dates of publication	2022-0304
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ZDB-ID	1498716-8
ISSN	0921-3449
ISSN	0921-3449
DOI	10.1016/j.resconrec.2022.106277
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Article ; Online: Comment on: Randomized controlled trial of plain English and visual abstracts for disseminating surgical research via social media.

Pringle, H / Bennett, M / Fowler, G / Bethune, R M

The British journal of surgery

2020 Volume 107, Issue 3, Page(s) 316

Language	English
Publishing date	2020-01-23
Publishing country	England
Document type	Letter
ZDB-ID	2985-3
ISSN	1365-2168 ; 0263-1202 ; 0007-1323 ; 1355-7688
ISSN (online)	1365-2168
ISSN	0263-1202 ; 0007-1323 ; 1355-7688
DOI	10.1002/bjs.11467
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Article ; Online: The case for neutrality on assisted dying - a personal view.

Fowler, Godfrey

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

2013 Volume 63, Issue 607, Page(s) 69

MeSH term(s)	Humans ; Suicide, Assisted/ethics
Language	English
Publishing date	2013-04-08
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	1043148-2
ISSN	1478-5242 ; 0035-8797 ; 0960-1643
ISSN (online)	1478-5242
ISSN	0035-8797 ; 0960-1643
DOI	10.3399/bjgp13X662920
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Zs.MO 100: Show issues

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