Publications by authors named "Christopher Harding"

Background: Almost half of all women will have at least one symptomatic urinary tract infection (UTI) in their lifetime. Although usually self-remitting, 74% of women contacting a health professional are prescribed an antibiotic, and in rare instances, they may progress to more severe infections. Therefore, the standard of care for the treatment of symptomatic uncomplicated UTIs is oral antibiotic therapy, which aims to achieve symptom resolution and prevent the development of complications such as pyelonephritis.

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Article Synopsis
  • Sacral neuromodulation (SNM) and percutaneous tibial nerve stimulation (PTNS) are recommended treatments for complex lower urinary tract issues, but they often face challenges like treatment failure and limited long-term effectiveness, necessitating better follow-up strategies.
  • A recent consensus report from a 2024 meeting highlighted the importance of "rescue programming" to enhance patient outcomes and device use, alongside exploring alternative stimulation sites for better results.
  • Current SNM techniques have not evolved significantly, and while there's little evidence for PTNS rescue programming, advancements in implantable devices and neurostimulation targeting the pudendal nerve show promise for improving treatment adherence and effectiveness.
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Nucleosides are ubiquitous to life and are required for the synthesis of DNA, RNA, and other molecules crucial for cell survival. Despite the notoriously difficult organic synthesis of nucleosides, 2'-deoxynucleoside analogues can interfere with natural DNA replication and repair and are successfully employed as anticancer, antiviral, and antimicrobial compounds. Nucleoside 2'-deoxyribosyltransferase (dNDT) enzymes catalyze transglycosylation via a covalent 2'-deoxyribosylated enzyme intermediate with retention of configuration, having applications in the biocatalytic synthesis of 2'-deoxynucleoside analogues in a single step.

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Intracellular leucine aminopeptidases (PepA) are metalloproteases from the family M17. These enzymes catalyze peptide bond cleavage, removing N-terminal residues from peptide and protein substrates, with consequences for protein homeostasis and quality control. While general mechanistic studies using model substrates have been conducted on PepA enzymes from various organisms, specific information about their substrate preferences and promiscuity, choice of metal, activation mechanisms, and the steps that limit steady-state turnover remain unexplored.

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Pseudomonas aeruginosa is an opportunistic pathogen that causes serious illness, especially in immunocompromised individuals. P. aeruginosa forms biofilms that contribute to growth and persistence in a wide range of environments.

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Context: Overactive bladder syndrome (OAB) is highly prevalent among women and has a negative impact on their quality of life. The current available treatments for OAB symptoms include conservative, pharmacological, or surgical modalities.

Objective: To provide an updated contemporary evidence document regarding OAB treatment options and determine the short-term effectiveness, safety, and potential harms of the available treatment modalities for women with OAB syndrome.

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Uropathogenic is a major cause of urinary tract infections. Analysis of the innate immune response in immortalized urothelial cells suggests that the bacterial flagellar subunit, flagellin, is key in inducing host defenses. A panel of 48 clinical uro-associated .

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Cyclodipeptide synthases (CDPSs) generate a wide range of cyclic dipeptides using aminoacylated tRNAs as substrates. Histidine-containing cyclic dipeptides have important biological activities as anticancer and neuroprotective molecules. Out of the 120 experimentally validated CDPS members, only two are known to accept histidine as a substrate yielding cyclo(His-Phe) and cyclo(His-Pro) as products.

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Background: Overactive bladder is a common, long-term symptom complex, which includes frequency of micturition, urgency with or without associated incontinence and nocturia. Around 11% of the population have symptoms, with this figure increasing with age. Symptoms can be linked to social anxiety and adaptive behavioural change.

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Aims: The basic evaluation or percutaneous nerve evaluation (PNE) is a method to assess pre-implantation therapeutic response in patients considering sacral neuromodulation for the treatment of refractory overactive bladder. A new PNE lead with a more robust design and greater distensibility designed to reduce the possibility of lead migration has recently been introduced to the market. The aim of this prospective, multicenter, global, postmarket study was to evaluate the clinical performance and safety of the new InterStim PNE lead with the foramen needle.

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Background: The AnTIC trial linked continuous low-dose antibiotic prophylaxis treatments to a lower incidence of symptomatic urinary tract infections (UTIs) among individuals performing clean intermittent self-catheterisation (CISC).

Objective: To explore potential mechanisms underlying the protective effects of low-dose antibiotic prophylaxis treatments, blood and urine samples and uro-associated isolates from AnTIC participants were analysed.

Design Setting And Participants: Blood samples ( = 204) were analysed for gene polymorphisms associated with UTI susceptibility and multiple urine samples ( = 558) were analysed for host urogenital responses.

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Context: Female lower urinary tract symptoms (LUTS) are a common presentation in urological practice. Thus far, only a limited number of female LUTS conditions have been included in the European Association of Urology (EAU) guidelines compendium. The new non-neurogenic female LUTS guideline expands the remit to include these symptoms and conditions.

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Context: Female lower urinary tract symptoms (LUTS) are a common presentation in urological practice. Thus far, only a limited number of female LUTS conditions have been included in the European Association of Urology (EAU) guidelines compendium. The new non-neurogenic female LUTS guidelines expand the remit to include these symptoms and conditions.

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Context: Female bladder outlet obstruction (fBOO) is a relatively uncommon condition compared with its male counterpart. Several criteria have been proposed to define fBOO, but the comparative diagnostic accuracy of these remains uncertain.

Objective: To identify and compare different tests to diagnose fBOO through a systematic review process.

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Context: Urethral stricture disease (USD) is initially managed with minimally invasive techniques such as urethrotomy and urethral dilatation. Minimally invasive techniques are associated with a high recurrence rate, especially in recurrent USD. Adjunctive measures, such as local drug injection, have been used in an attempt to reduce recurrence rates.

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Cyclodipeptide synthases (CDPSs) produce a variety of cyclic dipeptide products by utilising two aminoacylated tRNA substrates. We sought to investigate the minimal requirements for substrate usage in this class of enzymes as the relationship between CDPSs and their substrates remains elusive. Here, we investigated the enzyme, BtCDPS, which synthesises cyclo(l-Leu-l-Leu).

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Injuries to the bladder and ureter are uncommon but usually require prompt urological management. Due to their infrequent nature, Urologists maybe unfamiliar with managing these acute problems and may not work in specialist centres with readily available expertise in open and abdominal surgery. We aim to provide advice in the form of a consensus statement led by the Female, Neurological and Urodynamic Urology (FNUU) Section of the British Association of Urological Surgeons (BAUS), in consultation with BAUS members and consultants working in units throughout the UK, to create a comprehensive management pathway and a series of statements to aid clinicians.

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Bacterial hybrid malic enzymes (MaeB grouping, multidomain) catalyse the transformation of malate to pyruvate, and are a major contributor to cellular reducing power and carbon flux. Distinct from other malic enzyme subtypes, the hybrid enzymes are regulated by acetyl-CoA, a molecular indicator of the metabolic state of the cell. Here we solve the structure of a MaeB protein, which reveals hybrid enzymes use the appended phosphotransacetylase (PTA) domain to form a hexameric sensor that communicates acetyl-CoA occupancy to the malic enzyme active site, 60 Å away.

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Objective: In view of changing landscape of surgical treatment for LUTS secondary to BPE, this audit was undertaken to assess key aspects of the processes and outcomes of the current interventional treatments for BPE, across different units in the UK.

Materials And Method: A multi-institutional snapshot audit was conducted for patients undergoing interventions for LUTS/BPE over 8-week period. Using Delphi process two-part proforma was designed to capture data.

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Objective: To provide an update on the literature regarding the management of complications secondary to synthetic mesh placed to treat stress urinary incontinence (SUI).

Methods: We performed a systematic review of the literature using a multi-database structured search within OVID, the Medical Literature Analysis and Retrieval System Online (MEDLINE), the Excerpta Medica dataBASE (EMBASE) and Cochrane library databases; using the keywords: urology, incontinence, mesh and surgery.

Results: Several million synthetic polypropylene meshes have been inserted into women worldwide to manage SUI.

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Aims: Mitochondrial diseases present with a spectrum of clinical features, usually with multiorgan involvement and are often characterized by a loss of smooth muscle function. Hence, we hypothesized that mitochondrial dysfunction may contribute to lower urinary tract (LUT) dysfunction.

Methods: We performed a prospective cohort study at a single, quaternary, mitochondrial disease referral center, enrolling consecutive adult patients with genetically confirmed mitochondrial disease.

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Lysozymes are among the best-characterized enzymes, acting upon the cell wall substrate peptidoglycan. Here, examining the invasive bacterial periplasmic predator Bdellovibrio bacteriovorus, we report a diversified lysozyme, DslA, which acts, unusually, upon (GlcNAc-) deacetylated peptidoglycan. B.

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One complication of malaria is increased susceptibility to invasive bacterial infections. infections impair host immunity to non-Typhoid (NTS) through heme-oxygenase I (HO-I)-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS.

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