Within-host dynamics and evolution

Infections typically spread from a primary site to target organs. Rapid early defences are critical to contain an infection. However, recognition is not error-free and shows a trade-off between specificity and sensitivity. The within-host dynamics of an infection can be studied in various ways, e.g. with target cell-limited models. The disease space can trace within-host infection trajectories and predict the eventual outcome. Also, computational and systems immunology identify important defence elements and predict the course of an infection. Infecting populations evolve within their hosts. Horizontal transfer of genetic elements, recombination, and mutations thereby allow pathogens to escape host defences; examples are escape mutants or antigenic variation. The evolution of antimicrobial resistance is of special concern. Co-infecting parasites, such as bacteria, can cooperate to exploit a host (e.g. by production of siderophores) or compete for access (e.g. by releasing bacteriocins). Multiscale models combine within- and between-host episodes.

P–385 The relationship between systemic oestradiol and vaginal microbiota composition in miscarriage and normal pregnancy

Study question Is there an association between serum oestradiol, vaginal microbial composition and pregnancy outcome in the early first trimester? Summary answer In women with a vaginal microbiome deplete of Lactobacillus species at the time of Pregnancy of Uncertain Viability (IPUV), higher serum oestradiol associates with livebirth. What is known already During pregnancy, oestradiol mediates vaginal mucosal properties and increases glycogen deposition in epithelial cells which is thought to support colonisation of Lactobacillus species. Low levels of Lactobacillus associates with adverse outcomes such as miscarriage and preterm birth. The direct relationship between systemic oestradiol and the vaginal microbiome has never been studied in pregnancy. However studies have shown a positive correlation between serum oestrone, vaginal glycogen and Lactobacillus abundance in menopausal women. Study design, size, duration This was a prospective cohort study where one-hundred women were recruited in early pregnancy at the time of IPUV and donated paired blood and vaginal samples. 40 women had an eventual miscarriage, 58 had a livebirth and two pregnancies were terminated. All 100 women donated one paired serum and vaginal sample at this time point, and 22 women with Lactobacillus depletion at the time of IPUV donated further longitudinal vaginal samples. Participants/materials, setting, methods Participants were recruited from an Early Pregnancy Unit and underwent transvaginal ultrasound assessment of their pregnancy. Serum samples were analysed with an immunoassay on a ROCHE COBAS E411 analyser for Oestradiol (pg/ml) and Progesterone (ng/ml). Bacterial DNA was extracted from paired vaginal swabs and sequenced using Illumina MiSeq sequencing of 16S rRNA gene amplicons. Main results and the role of chance Lactobacillus dominance of the vagina was associated with higher serum levels of E2 and progesterone compared to depletion (E2=398pg/ml vs 302pg/ml(p = 0.02), P4=23.1ng/ml vs 17ng/ml(p = 0.02)). E2 and P4 were positively correlated (r = 0.6, p < 0.05). At species level, L. crispatus dominance associated with significantly higher levels of E2 compared to high-diversity communities (468pg/ml vs 302pg/ml(p = 0.03) but no such relationship was observed for P4. Both E2 and P4 levels were lower in women who eventually miscarried. However there was no significant difference in the vaginal bacterial composition at genera or species level at this early gestational age (P = 0.08) regardless of per vaginal bleeding. However in women with Lactobacillus depleted microbiota, livebirth was associated with significantly higher E2 levels compared to women suffering miscarriage (212pg/ml in miscarriage vs 395pg/ml in livebirth, p = 0.003) (OR = 22.4 P = 0.004). In 22 women who had Lactobacillus depletion at the time of IPUV (7 with an eventual outcome of miscarriage, and 15 with an eventual outcome of livebirth), longitudinal vaginal bacterial DNA sequencing was performed. In 7/15 women with livebirth, and higher E2 levels, the microbial composition changed to become more Lactobacillus dominant during pregnancy, whereas in those with miscarriage, only 1/7 changed to become Lactobacillus dominant. Limitations, reasons for caution In this study, serum oestradiol levels were compared to the local vaginal bacterial environment. The ideal would be to study local vaginal oestradiol, glycogen and the bacterial composition. Wider implications of the findings: In contrast to previous studies in menopause where low oestrogen levels associate with the vaginal microbial composition, this study uses the high oestradiol environment of early pregnancy to study the mechanistic relationship between oestradiol and vaginal Lactobacillus abundance. Trial registration number NA

Qualitative study: learning from recovery: what do people who have recovered from alcohol dependence have to teach those who are still struggling?

AimsThe aim is to tap into user experience in the UK and to analyse what lessons can be learnt from those who have recovered from alcohol dependence to help those who are struggling including to inform the delivery of alcohol services.MethodThe study was conducted in London, UK. 20 males in the age group 30–45 years were recruited. 10 of these participants had recovered from alcohol dependence and the other 10 were in treatment for alcohol dependency and diagnosed as dependent according to ICD-10 or DSM 5 criteria. In the former group, each participant had at least 2 years of complete sobriety. A semi structured questionnaire was developed and used to interview all the subjects.Males 30-45 years were eligible as alcohol dependence is more common in this age group and purposive sampling drove the selection (i.e. if early analysis suggests the importance of a particular factor, subjects likely not to show that factor would be sampled for comparison).Grounded analysis was the qualitative analysis method of choice and constant comparison was used, i.e., data were collected and analysed concurrently.ResultThe main “families” that arose grouped around relationships in both the recovered alcoholics (RA) and continued alcoholics (CA). A successful shift required a change in the relationship to self, from feeling empty or critical towards acceptance and this shift was facilitated by being accepted and respected by others.Relationship as motivator to stop drinking24% people had the insight to self-refer to voluntary organisations such as AA but 76% did so because of fear of losing either their relationship or their job.Although 80% of recovered alcoholics had been ambivalent about coming off alcohol, the shift happened when they had a nurturing relationship elsewhere such as a key worker at the Alcoholics Anonymous.Insight and PerceptionAwareness of alcohol as an obstacle rather than a solution was key for change to occur. Although 75% people with insight into their difficulties were more successful in maintaining sobriety, insight alone without action was insufficient. Moreover, action was possible without insight. Fear of death alone was a sufficient motivator.ConclusionDifference between support systemsAs a result of comparing those patients with alcohol dependence who responded well to treatment compared to those who were very recalcitrant to treatment important characteristics of an effective service have been identified. It was clear that the quality of services offered to those with alcohol dependence who attended A&E departments could be improved by offering more time for the initial assessments and adopting a more individualistic approach for each patient.Training sessions to the A&E staff about the differences required in management between those with alcohol dependence who are motivated to abstain compared to those who will only be able to reduce consumption should be offered rather than mere blanket exhortations to abstain from alcohol consumption. The importance of behavioural avoidance of situations where alcohol is excessively consumed is more helpful in terms of eventual outcome.The A&E staff should be encouraged to employ individuals from Alcoholics Anonymous in their department as early involvement with AA improves engagement and outcome can greatly improve engagement with treatment programs subsequently and lead to significantly better outcomes.

Three pre-vaccine responses to Covid-like epidemics

This paper contains a theoretical study of epidemic control. It is inspired by current events but not intended to be an accurate depiction of the SARS-CoV-2 pandemic. We consider the emergence of a highly transmissible pathogen, focusing on metropolitan areas. To ensure some degree of realism, we present a conceptual model of the outbreak and early attempts to stave off the onslaught, including the use of lockdowns. Model outputs show strong qualitative—in some respects even quantitative—resemblance to the events of Spring 2020 in many cities worldwide. We then use this model to project forward in time to examine different paths in epidemic control after the initial surge is tamed and before the arrival of vaccines. Three very different control strategies are analyzed, leading to vastly different outcomes in terms of economic recovery and total infected population (or progress toward herd immunity). Our model, which is a version of the SEIQR model, is a time-dependent dynamical system with feedback-control. One of the main conclusions of this analysis is that the course of the epidemic is not entirely dictated by the virus: how the population responds to it can play an equally important role in determining the eventual outcome.

Bilateral secondary testicular, epididymal and spermatic cords carcinoma of prostatic origin: a case report and review of the literature

Background Prostatic carcinoma is emerging as the most common male malignancy in Nigeria and the second most common male cancer worldwide. Patients often present with locally advances stages, and common sites of metastasis are the spine, pelvis, chest, and long bones. Metastases to the testes and spermatic cords are reputed to be rare and may be indicative of a worse outcome, when they occur. We recently encountered a clinical case of bilateral testicular, epididymal and spermatic cords prostatic cancer metastases. Case presentation A 71-year-old Nigerian man, who presented at our hospital with 1-month-old complaints of inability to walk together with low back and bilateral thigh pains. This presentation had been preceded by a 5-month history of lower urinary tract symptoms. On examination, the prostate was hard and nodular as were the left testis and spermatic cord. On histological assessment of a needle biopsy, prostatic adenocarcinoma (Gleason score 5 + 5 = 10) was diagnosed. A subsequent therapeutic bilateral total orchidectomy specimen was found to contain metastatic prostatic carcinoma deposits, in the testes, epididymides, and spermatic cords. Although our patient is currently doing well postoperatively on zoledronic acid, ketoconazole, bicalutamide, and tamsulosin, he is being re-evaluated periodically for any feature of recurrence. Conclusion Since it has implications for eventual outcome, every clinically suspicious therapeutic orchidectomy specimen should be subjected to a detailed histopathological examination in order to exclude secondaries from the primary prostatic malignancy.

Rhinoplasty Dissection Planes (Subcutaneous, Sub-SMAS, Supra-perichondral, and Sub-perichondral) and Soft Tissues Management

Rhinoplasty as an operation is akin to a game of chess, where every maneuver will influence the eventual outcome. Undoubtedly, more than one approach to the nasal soft tissues envelop can produce beautiful and safe results as will be described in the paper namely, the subcutaneous, sub-superficial musculoaponeurotic system, supra- and sub-perichondral planes. For different justifiable reasons surgeons have their preferences, regarding dissection planes on the tip, middle and upper thirds, and regarding the manipulation of the soft tissue layers and nasal ligaments. The concept of the nasal layers and the presence of relevant ligamentous structures and how to restore them in an anatomical fashion, will help to understand the logic behind various approaches.

It’s Just Not Cricket!

The world of cricket was stunned by the ‘spot-fixing’ allegations against three Pakistani cricket team players during one of the most important games in the cricket calendar for the nation in the summer of 2010. News of the World, a British tabloid, conducted a sting operation against Pakistani players, trapping them into deliberately bowling no-balls during a match against England, an illegal practice known as spot-fixing. The ‘bookies’ take bets for such events happening during a game, and gamblers can make substantial sums of money if they have foreknowledge. The players were offered payments for these actions to be performed during the game, which may or may not impact the eventual outcome of the game but can entail serious monetary benefits for the bookies and their allies. The discovery of these events raised several questions regarding the governance and ethics of the sport. The ICC and British courts subsequently found the trio guilty of corruption and were banned and imprisoned. This case aims to analyse theories and concepts in ethics using this well-known incident in cricket as the context.

The Importance of Morocco in the Spanish Civil War

This paper addresses the pivotal yet forgotten role that Morocco played in the Spanish Civil War. Other histories and analyses of the Civil War limit discussion to the Spanish side of the conflict without recognizing the colonialist holdings that Spain had and the ways that those lands and people impacted the war. This leads to an incomplete history that denies the Civil War its full historical context and the foundational context for the Nationalist side of the conflict. This paper analyzes the war as well as the ideological creations behind Spanish Fascism and the ways in which Morocco was tied to the creation of the Spanish Civil War, how it was important to the fighting of the conflict, and how it was pivotal to the war's eventual outcome. This will be argued by looking at the racist and eurocentric views of the Spanish Republic and how those views lead directly to its failure in the Civil War. This article will analyze first hand accounts of people directly involved in the war and the factors that led to the involvement of Moroccans on the Nationalist side.