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Biomedical subjects

Simon Jackson

Publications and source records attributed to Simon Jackson.

13 recordsLinked to original sources

Museum specimens reveal the genomic consequences of long-term population decline in an insect pollinator.

Global insect pollinator populations are under threat, with reported declines attributed to increasing habitat loss, pesticide use, and disease. Tracking how genetic diversity has changed over time could reveal the rate and extent of these declines, and the adaptive capacity of affected species-providing an important complement to habitat-based conservation efforts. However, few studies have been able to reconstruct suitable historical baselines to link genomic changes with population change. Here, we use whole genome data from 101 museum specimens of the declining moss carder bumblebee (Bombus muscorum) collected across Britain and Ireland between 1894 and 2019 to reveal a dramatic drop in genetic diversity over the last century. We find a substantial (∼24.6%) reduction in genome-wide heterozygosity across Britain during this period. In England and Wales, where habitat fragmentation is most pronounced, we observe a 2.86-fold increase in runs of homozygosity, commensurate with population fragmentation and isolation. Our results reveal the extent to which human-induced environmental change can lead to severe decadal-scale genomic erosion in a functionally important insect. Identified using DNA from historic museum collections, our approach has widespread applicability for insect conservation and understanding the evolutionary consequences of environmental change.

Animals↗

The early injected genomic region determines sensitivity to Type I restriction-modification defence against Autographiviridae phages.

Bacteriophages must evade bacterial defences to establish successful infections. Type I restriction-modification (RM) systems recognize specific DNA motifs and degrade unmethylated foreign DNA, restricting phage replication. In this study, we detected that Marinomonas mediterranea MMB-2 uses a Type I RM system (Mme2I) to protect against several new phages in the Murciavirus genus within the Autographiviridae family. Whole-genome sequencing and methylation analysis revealed a DNA sequence motif methylated in M. mediterranea MMB-2, which is also present in the phages. Phages lacking the motif within the leading, first injected, region of their genomes, either natural isolates or escape mutants of sensitive phages, successfully infect M. mediterranea MMB-2, despite the presence of the recognition motif elsewhere in their genomes. These results highlight the importance of considering RM motif locations when predicting avoidance of restriction sites as escape mechanisms from RM systems. Additionally, our findings indicate an important role for RM systems in specifically influencing the organization of the leading injected regions of phage genomes, which are highly variable and often encode diverse anti-defence systems.

Genome, Viral↗

Intentional urethral closure with a TVT (tension-free vaginal tape) for intractable urinary incontinence: a preliminary report of three cases.

Bladder neck and urethral closure with urinary diversion is offered as a last resort to patients with intractable urinary incontinence. Various techniques have been described to achieve bladder neck and urethral closure. Most of these are associated with either operative morbidity or long-term complications. A modification of the conventional tension-free vaginal tape (TVT) procedure is described. As the name suggests, during the conventional TVT procedure, the tape is inserted relatively without tension in such a manner that the urethra retains its function and post-operative voiding is possible. In the cases described in this short series, the aim was to achieve urethral and bladder neck closure with minimal operative morbidity. This was achieved by inserting the TVT exactly as in a conventional TVT procedure, but the tape was inserted under greater tension than is normally used to ensure continence. A long-term suprapubic catheter was used for urinary diversion. This procedure is simple to perform, is associated with low operative morbidity [Agostini et al., Eur J Obstet Gynecol Reprod Biol, 124(2):237-239, 2006] and results in functional urethral closure. Results suggest that it may be a useful alternative to other bladder neck and urethral closure procedures in selected patients.

Adult↗

Culture of skin cells in 3D rather than 2D improves their ability to survive exposure to cytotoxic agents.

In this study, we asked the question of whether cells in 3D culture cope more effectively with cytotoxic agents than cells in 2D. The sensitivities of human skin cells (keratinocytes, dermal fibroblasts and endothelial cells) to oxidative stress (hydrogen peroxide) and to a potentially toxic heavy metal (silver) when cultured under 2D and 3D conditions were investigated. The results show a marked resistance of cells to a given dose of hydrogen peroxide or silver nitrate causing a 50% loss of viability in 3D cultures, when compared to the same cells grown in 2D. There was also an improvement in the ability of cells to withstand both stresses when cells were in co-culture rather than in mono-culture. Foetal calf serum was found to have a mild protective effect in 2D culture but this was not extended to findings in 3D culture. This study suggests that dermatotoxicity testing using 3D co-cultures might be more likely to reflect true physiological responses to xenobiotic materials than existing models that rely on 2D mono-cultures.

Cell Culture Techniques↗

Free radical production and quenching in honeys with wound healing potential.

OBJECTIVES: Honey-impregnated wound dressings are now available on drug tariff in the UK, though the modes of action of honeys with antibacterial and wound healing properties are not entirely clear. The action of some but not all of these honeys is linked to the production of hydrogen peroxide on dilution of the honey with wound exudate. The present study investigates both free radical production and the antioxidant potential of some honeys, properties which may have a role to play in wound healing. METHODS: Free radical production and quenching of three honey types (manuka, antibacterial but non-peroxide-producing; pasture, antibacterial peroxide-producing; commercial heat processed, non-antibacterial) was investigated by electron paramagnetic resonance (EPR) spectroscopy; quenching was also examined using a superoxide quenching assay. RESULTS: All honeys tested had antioxidant potential, with manuka able to completely quench added radicals within 5 min of spiking. Only the peroxide-producing honey (pasture PS9) was found to form radicals on dilution. CONCLUSIONS: The ability to modulate production and quenching of free radicals may contribute to the demonstrated ability of some honeys to help in resolving the state of inflammation typifying chronic wounds.

Antioxidants↗

Non-surgical treatment for detrusor overactivity.

Urinary incontinence is a common but under-reported condition. Approximately 17% of women are affected by detrusor overactivity at some time in their lives. Pharmacological treatment of this condition used to be severely limited by the side-effects of the drugs and the associated poor patient compliance. Recently, however, the tolerability and effectiveness of pharmacotherapy have been improved by the introduction of new drugs and alternative methods of drug delivery. This review assesses the effectiveness and tolerability of these new treatments. Anticholinergic agents, botulinum toxin and neuromodulation are also discussed.

Botulinum Toxins, Type A↗

Stress urinary incontinence: new management options.

Stress urinary incontinence is the most prevalent form of urinary incontinence. In spite of its significant negative impact on quality of life less than one-third of patients in the UK present with symptoms to their GP. The current mainstay treatment is pelvic floor exercises. Previously, the only option available to patients for whom conservative treatments were not effective has been surgical intervention. However, recent developments have led to the first selective serotonin and noradrenaline reuptake inhibitor that has proved effective in the treatment inhibitor of stress urinary incontinence. This article profiles current treatments and the place of an oral agent in stress urinary incontinence. This review article includes papers that were retrieved through PubMed using search criteria 'stress urinary incontinence', 'management' and the specific therapy area, e.g. tension-free vaginal tape. The main guidance of the Department of Health (London, UK) and associated bodies was also used.

Adrenergic alpha-Agonists↗

A scored form of the Bristol Female Lower Urinary Tract Symptoms questionnaire: data from a randomized controlled trial of surgery for women with stress incontinence.

OBJECTIVE: Lower urinary tract symptoms are common among older women. The Bristol Female Lower Urinary Tract Symptoms (BFLUTS) questionnaire was designed to assess a wide range of symptoms, including incontinence, and impact on sexual function and quality of life. This paper describes development and validation of a scored form BFLUTS questionnaire. STUDY DESIGN: Baseline and 6-month follow-up data from a randomized trial compared tension-free vaginal tape with colposuspension for 344 women with urodynamically proven stress incontinence. Problematic and responsive items were identified and subjected to factor analysis to develop a scoring system. RESULTS: Three domains were identified to assess symptoms: incontinence (5 items); voiding (3 items); and filling (4 items); with additional subscales for sexual function (2 items) and quality of life (5 items). All scales have simple additive scores. CONCLUSION: A scored form of the BFLUTS questionnaire is now available and should be useful in research and clinical practice in urology and gynecology.

Factor Analysis, Statistical↗

National survey for intrapartum and postpartum bladder care: assessing the need for guidelines.

Variation in the practice of intrapartum and postpartum bladder care reported by 189 maternity units in England and Wales hospitals was evaluated by analysing the data obtained from a postal questionnaire completed by labour ward managers or heads of midwifery. The survey revealed that there was no consensus of opinion about the diagnostic criteria for postpartum urinary retention and therefore the optimum management for voiding dysfunction remains controversial. In spite of the increasing awareness of the risk management issues involved, the majority of the units were found to be non-compliant with the limited RCOG recommendations currently available. Although further research is needed to develop evidence-based guidelines, all units should be timing and measuring the voided volume and ideally checking the first post-void residual volume to ensure that retention does not go unrecognised.

Catheters, Indwelling↗

Hormone replacement therapy and the bladder.

Lower urinary tract symptoms are a common, distressing and embarrassing problem for women of all ages, but become increasingly more common with advancing age. Oestrogen preparations have been used for many years to manage urinary symptoms, but there is still controversy over the efficacy of these preparations. The purpose of this review is to provide a critical overview of the epidemiological evidence when considering hormone replacement therapy for treatment of urinary symptoms in women. Various studies have demonstrated that oestrogen replacement can improve, or even cure, urinary stress and urge incontinence. High dose oestrogen can reduce the total number of voids in 24 hours, including nocturnal voids. Vaginal oestriol significantly reduces the risk of recurrent infections in postmenopausal women with a history of recurrent urinary tract infections. Data on combining oestrogen with a progestogen are limited, but suggest it may negate the benefit and more research is still required in this area to clarify their role.

Epidemiologic Studies↗

The effect of oestradiol on vaginal collagen metabolism in postmenopausal women with genuine stress incontinence.

OBJECTIVE: To determine whether oestrogen replacement will produce an improvement in the quantity, or quality, of pelvic collagen in postmenopausal women. DESIGN: A prospective double-blind placebo controlled trial of oestrogen therapy. SETTING: Southmead Hospital, Bristol, UK. POPULATION: Fifty-five postmenopausal women with a urodynamic diagnosis of genuine urinary stress incontinence. METHODS: Randomisation to a six-month, double-blind, placebo-controlled, trial of oestradiol valerate 2mg once daily. A 10mg-30mg periurethral biopsy was taken from the vaginal epithelium before and after treatment. Tissue was analysed for total collagen content, intermolecular cross-links, advanced glycation end-products, collagen type ratios and matrix metalloproteinase (MMP) activity. RESULTS: Forty-nine women completed the trial of whom 26 received oestrogen and 23 received placebo. When compared with placebo, oestrogen treatment resulted in significant decreases in total collagen (P = 0.0054), the mature cross-link HHL (P = 0.0009) and the advanced glycation end-product NFC-1 (P = 0.0009). There was a significant rise in the immature cross-link HLKNL (P = 0.0191). Oestrogen produced a significant increase in MMP-2 expression (Pro MMP-2, P = 0.0017). CONCLUSIONS: Six months treatment with oestrogen has profound effects upon pelvic collagen metabolism, stimulating collagen degradation via increased proteinase activity. While aged collagen is being lost, new collagen is synthesised as witnessed by the increase in the immature cross-links and the decrease in both mature cross-links and advanced glycation end-products. Collagen loss contradicts previous reports; perhaps aged collagen degradation is merely an early response to oestrogen stimulation. We have evidence of new collagen synthesis, and it may be that a longer treatment interval would show total collagen content increasing. Further studies within this field are warranted.

Aged↗