Microevolution during the emergence of a monophasic Salmonella Typhimurium epidemic in the United Kingdom

Microevolutionary events associated with the emergence and clonal expansion of new 27 epidemic clones of bacterial pathogens hold the key to understanding the drivers of 28 epidemiological success. We describe a comparative whole genome sequence and 29 phylogenomic analysis of monophasic Salmonella Typhimurium isolates from the UK 30 and Italy from 2005-2012. Monophasic isolates from this time formed a single clade 31 distinct from recent monophasic epidemic clones described previously from North 32 America and Spain. The current UK monophasic epidemic clones encode a novel 33 genomic island encoding resistance to heavy metals (SGI-3), and composite transposon 34 encoding antibiotic resistance genes not present in other Typhimurium isolates, that 35 may have contributed to the epidemiological success. We also report a remarkable 36 degree of genotypic variation that accumulated during clonal expansion of a UK 37 epidemic including multiple independent acquisitions of a novel prophage carrying the 38 sopE gene and multiple deletion events affecting the phase II flagellin locus

The genomic basis of adaptive evolution in threespine sticklebacks

Marine stickleback fish have colonized and adapted to thousands of streams and lakes formed since the last ice age, providing an exceptional opportunity to characterize genomic mechanisms underlying repeated ecological adaptation in nature. Here we develop a high-quality reference genome assembly for threespine sticklebacks. By sequencing the genomes of twenty additional individuals from a global set of marine and freshwater populations, we identify a genome-wide set of loci that are consistently associated with marine–freshwater divergence. Our results indicate that reuse of globally shared standing genetic variation, including chromosomal inversions, has an important role in repeated evolution of distinct marine and freshwater sticklebacks, and in the maintenance of divergent ecotypes during early stages of reproductive isolation. Both coding and regulatory changes occur in the set of loci underlying marine–freshwater evolution, but regulatory changes appear to predominate in this well known example of repeated adaptive evolution in nature.National Human Genome Research Institute (U.S.)National Human Genome Research Institute (U.S.) (NHGRI CEGS Grant P50-HG002568

The Sound/Image Cinema Lab, Long Way Back (dir. Brett Harvey): developing working principles for crewing feature film production with higher education students

Since the release of the feature film Weekend Retreat (Dir. Brett Harvey 2011 and produced by Simon Harvey), students and graduates at Falmouth University have worked on over a dozen feature film and high-end TV projects as part of direct opportunities presented by staff, through directly produced, co-produced or partnered projects via the Sound/Image Cinema Lab, a research centre based at Falmouth University. Using our three most recent projects – the feature films Enys Men (Dir. Mark Jenkin 2022), which premiered in Cannes as part of Director’s Fortnight in 2022 and is was released in January 2023 through the BFI and Long Way Back (Dir. Brett Harvey 2021) that was released in cinemas in 2022, together with a coproduction of the short film The Birdwatcher (Dir. Ryan Mackfall 2022) as case studies, we apply a production studies approach in the vein of those highlighted by Banks, Conor & Mayer (2016). Through interviews with participants, we contextualise placements through a research overview that “take[s] the lived realities of people involved in media production as the subjects for theorizing production culture” (Mayer, Banks & Caldwell, 2009, 4). We consider how these projects have served as a catalyst for both learning gain, provided confidence in seeking out other opportunities, and have helped industrial partners and production companies reconsider their approaches to entry-level talent

The invasome of Salmonella Dublin as revealed by whole genome sequencing

Background Salmonella enterica serovar Dublin is a zoonotic infection that can be transmitted from cattle to humans through consumption of contaminated milk and milk products. Outbreaks of human infections by S. Dublin have been reported in several countries including high-income countries. A high proportion of S. Dublin cases in humans are associated with invasive disease and systemic illness. The genetic basis of virulence in S. Dublin is not well characterized. Methods Whole genome sequencing was applied to a set of clinical invasive and non-invasive S. Dublin isolates from different countries in order to characterize the putative genetic determinants involved in the virulence and invasiveness of S. Dublin in humans. Results We identified several virulence factors that form the bacterial invasome and may contribute to increasing bacterial virulence and pathogenicity including mainly Gifsy-2 prophage, two different type 6 secretion systems (T6SSs) harbored by Salmonella pathogenicity islands; SPI-6 and SPI-19 respectively and virulence genes; ggt and PagN. Although Vi antigen and the virulence plasmid have been reported previously to contribute to the virulence of S. Dublin we did not detect them in all invasive isolates indicating that they are not the main virulence determinants in S. Dublin. Conclusion Several virulence factors within the genome of S. Dublin might contribute to the ability of S. Dublin to invade humans’ blood but there were no genomic markers that differentiate invasive from non-invasive isolates suggesting that host immune response play a crucial role in the clinical outcome of S. Dublin infection

Thyroid Hormones and Pregnant Women

Background: Thyroid illness is a group of disorders affecting the thyroid gland. The thyroid is a small, butterfly-shaped gland at the front of your neck that produces thyroid hormones, since thyroid hormones regulate how our bodies use energy; they have an impact on practically every physical organ, including the pulse. The hormones thyroid creates play a key role in regulating our metabolism the way our body uses energy along with temperature, weight, cholesterol levels and other key body functions. Thyroid disorders may be present before pregnancy, or they may develop during pregnancy. Being pregnant does not change the symptoms of thyroid disorders. How the fetus is affected depends on which thyroid disorder present and which medications are used for treatment. Because thyroid hormones are essential for the healthy development of the baby\u27s brain and nervous system, babies who are dependent on other sources for their thyroid hormones during the first trimester may be born with neurological development issues. Objectives: the purpose of the study of thyroid hormone and pregnancy are to emphasis on the relationship between thyroid hormone and pregnancy, and the impacts of thyroid dysfunction on maternal and fetal health during pregnancy. Method: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review (PRISMA-ScR) guidelines. Using search keywords like prostate cancer, risk factors, screening, and preventative approaches, scholarly papers published in electronic databases including PubMed, Scopus, and Google Scholar from 2004-2025 were obtained for the review Conclusion: thyroid dysfunction during pregnancy is a key area of focus in clinical endocrinology. For babys brains and neurological system to develop normally, thyroid hormones are essential, they depends on thyroid hormone supply, which is delivered by the placenta during the first trimester. Healthy women can develop slightly high thyroid hormone during pregnancy.  Thyroid problems can be hard to diagnose in pregnancy due to higher levels of thyroid hormones and other symptoms that occur in both pregnancy and thyroid disorders. Thyroid hormones that are high can harm the mother’s health and the baby’s.&nbsp

Global, regional, and national burden of tuberculosis, 1990–2016: results from the Global Burden of Diseases, Injuries, and Risk Factors 2016 Study

Background Although a preventable and treatable disease, tuberculosis causes more than a million deaths each year. As countries work towards achieving the Sustainable Development Goal (SDG) target to end the tuberculosis epidemic by 2030, robust assessments of the levels and trends of the burden of tuberculosis are crucial to inform policy and programme decision making. We assessed the levels and trends in the fatal and non-fatal burden of tuberculosis by drug resistance and HIV status for 195 countries and territories from 1990 to 2016. Methods We analysed 15 943 site-years of vital registration data, 1710 site-years of verbal autopsy data, 764 site-years of sample-based vital registration data, and 361 site-years of mortality surveillance data to estimate mortality due to tuberculosis using the Cause of Death Ensemble model. We analysed all available data sources, including annual case notifications, prevalence surveys, population-based tuberculin surveys, and estimated tuberculosis cause-specific mortality to generate internally consistent estimates of incidence, prevalence, and mortality using DisMod-MR 2.1, a Bayesian meta-regression tool. We assessed how the burden of tuberculosis differed from the burden predicted by the Socio-demographic Index (SDI), a composite indicator of income per capita, average years of schooling, and total fertility rate. Findings Globally in 2016, among HIV-negative individuals, the number of incident cases of tuberculosis was 9·02 million (95% uncertainty interval [UI] 8·05–10·16) and the number of tuberculosis deaths was 1·21 million (1·16–1·27). Among HIV-positive individuals, the number of incident cases was 1·40 million (1·01–1·89) and the number of tuberculosis deaths was 0·24 million (0·16–0·31). Globally, among HIV-negative individuals the age-standardised incidence of tuberculosis decreased annually at a slower rate (–1·3% [–1·5 to −1·2]) than mortality did (–4·5% [–5·0 to −4·1]) from 2006 to 2016. Among HIV-positive individuals during the same period, the rate of change in annualised age-standardised incidence was −4·0% (–4·5 to −3·7) and mortality was −8·9% (–9·5 to −8·4). Several regions had higher rates of age-standardised incidence and mortality than expected on the basis of their SDI levels in 2016. For drug-susceptible tuberculosis, the highest observed-to-expected ratios were in southern sub-Saharan Africa (13·7 for incidence and 14·9 for mortality), and the lowest ratios were in high-income North America (0·4 for incidence) and Oceania (0·3 for mortality). For multidrug-resistant tuberculosis, eastern Europe had the highest observed-to-expected ratios (67·3 for incidence and 73·0 for mortality), and high-income North America had the lowest ratios (0·4 for incidence and 0·5 for mortality). Interpretation If current trends in tuberculosis incidence continue, few countries are likely to meet the SDG target to end the tuberculosis epidemic by 2030. Progress needs to be accelerated by improving the quality of and access to tuberculosis diagnosis and care, by developing new tools, scaling up interventions to prevent risk factors for tuberculosis, and integrating control programmes for tuberculosis and HIV

A missed diagnosis of ovarian torsion in a patient with multiple degenerating uterine fibroids: a case report

The presentation of ovarian torsion can be dramatic with most patients presenting with acute or severe nonspecific lower abdominal and pelvic pain, either intermittent or continuous, with nausea and vomiting. The diverse clinical presentation is one major reason the diagnosis of ovarian torsion is frequently missed. The incidence of ovarian torsion ranges from 3-10% and ovarian cyst accidents constitutes about 3-5% of gynaecological emergencies. The aim was to document a case of acute abdomen suspected to be acute red degeneration of fibroids and/or acute appendicitis with incidental finding of ovarian cyst accident with consequent loss of the ovary. Our patient is a 35-year-old lady who presented with lower abdominal swelling, right sided abdominal pain and vomiting, suspected to be acute appendicitis and/or red degeneration of uterine fibroids but subsequently had exploratory laparotomy with right salpingo-oophorectomy due to right ovarian torsion, alongside myomectomy and appendectomy. Ovarian torsion is a preventable incident if early diagnosis and intervention is made. There is therefore need to consider ovarian torsion as a differential diagnosis of acute abdomen in young females to avoid loss of ovary and its function

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes