Understanding the role of sexual transmission in the spread of ZIKA virus using an individual-based interconnected population model

Citation: Tanver, F., Lee, C., Mcvey, D., & Scoglio, S. (2018). Understanding the role of sexual transmission in the spread of ZIKA virus using an individual-based interconnected population model. Pre-Print, Unpublished Manuscript.Zika virus has affected the world as a long-term threat. Modeling its transmission is important in order to facilitate forecasts and control measures. We propose a novel node-based interconnected population model to simulate both vectored and sexual transmission of Zika virus. Using a sexual contact network, we incorporate heterogeneous mixing in the host population with stochastic transmission for realistic predictions. We also incorporate climatic variations in our model, which affect the mosquito vector population and consequently the arbovirus transmission. We perform extensive simulations to understand the effects of sexual transmission rate and network topology on the spreading of infections. Sexual transmission contributes to the epidemic spread and under certain conditions, can sustain it up to several months without vectors. This can potentially lead to recurrences once the mosquitoes overwinter. We also find that sexual transmission can have a stronger effect when vectored transmission is relatively weaker due to climatic conditions. Our results show that vectored and sexual transmission affect the disease dynamics differently

Variation in National Clinical Audit Data Capture:Is Using Routine Data the Answer?

National Clinical Audit (NCA) data are collected from all National Health Service providers in the UK, to measure the quality of care and stimulate quality improvement initatives. As part of a larger study we explored how NHS providers currently collect NCA data and the resources involved. Study results highlight a dependence on manual data entry and use of professional resources, which could be improved by exploring how routine clinical data could be captured more effectively

Understanding the survival of Zika virus in a vector interconnected sexual contact network

Citation: Ferdousi, T., Cohnstaedt, L. W., McVey, D. S., & Scoglio, C. M. (2019). Understanding the survival of Zika virus in a vector interconnected sexual contact network. Scientific Reports, 9(1), 7253. https://doi.org/10.1038/s41598-019-43651-3The recent outbreaks of the insect-vectored Zika virus have demonstrated its potential to be sexually transmitted, which complicates modeling and our understanding of disease dynamics. Autochthonous outbreaks in the US mainland may be a consequence of both modes of transmission, which affect the outbreak size, duration, and virus persistence. We propose a novel individual-based interconnected network model that incorporates both insect-vectored and sexual transmission of this pathogen. This model interconnects a homogeneous mosquito vector population with a heterogeneous human host contact network. The model incorporates the seasonal variation of mosquito abundance and characterizes host dynamics based on age group and gender in order to produce realistic projections. We use a sexual contact network which is generated on the basis of real world sexual behavior data. Our findings suggest that for a high relative transmissibility of asymptomatic hosts, Zika virus shows a high probability of sustaining in the human population for up to 3 months without the presence of mosquito vectors. Zika outbreaks are strongly affected by the large proportion of asymptomatic individuals and their relative transmissibility. The outbreak size is also affected by the time of the year when the pathogen is introduced. Although sexual transmission has a relatively low contribution in determining the epidemic size, it plays a role in sustaining the epidemic and creating potential endemic scenarios

Going places

Journeys. We all make them. Often they take us to exotic places. Sometimes they take us even further. They might take us through time. Or they might take us into a new way of life. There are times too, when we go all over the world and back again only to find that home is, after all, where it’s all happening. This book contains stories about many different types of journey. We hope you will enjoy travelling into it and finding a world that suits you

The impact of obesity and bariatric surgery on the immune microenvironment of the endometrium

BACKGROUND: The incidence of endometrial cancer is rising in parallel with the obesity epidemic. Obesity increases endometrial cancer risk and weight loss is protective, but the underlying mechanisms are incompletely understood. We hypothesise that the immune microenvironment may influence susceptibility to malignant transformation in the endometrium. The aim of this study was to measure the impact of obesity and weight loss on the immunological landscape of the endometrium. METHODS: We conducted a prospective cohort study of women with class III obesity (body mass index, BMI ≥ 40 kg/m(2)) undergoing bariatric surgery or medically-supervised low-calorie diet. We collected blood and endometrial samples at baseline, and two and 12 months after weight loss intervention. Serum was analysed for inflammatory markers CRP, IL-6 and TNF-α. Multiplex immunofluorescence was used to simultaneously identify cells positive for immune markers CD68, CD56, CD3, CD8, FOXP3 and PD-1 in formalin-fixed paraffin-embedded endometrial tissue sections. Kruskal–Wallis tests were used to determine whether changes in inflammatory and immune biomarkers were associated with weight loss. RESULTS: Forty-three women with matched serum and tissue samples at all three time points were included in the analysis. Their median age and BMI were 44 years and 52 kg/m(2), respectively. Weight loss at 12 months was greater in women who received bariatric surgery (n = 37, median 63.3 kg) than low-calorie diet (n = 6, median 12.8 kg). There were significant reductions in serum CRP (p = 3.62 × 10(−6), r = 0.570) and IL-6 (p = 0.0003, r = 0.459), but not TNF-α levels, with weight loss. Tissue immune cell densities were unchanged except for CD8+ cells, which increased significantly with weight loss (p = 0.0097, r = −0.323). Tissue CD3+ cell density correlated negatively with systemic IL-6 levels (p = 0.0376; r = −0.318). CONCLUSION: Weight loss is associated with reduced systemic inflammation and a recruitment of protective immune cell types to the endometrium, supporting the concept that immune surveillance may play a role in endometrial cancer prevention

An online breathing and wellbeing programme (ENO Breathe) for people with persistent symptoms following COVID-19: a parallel-group, single-blind, randomised controlled trial

BACKGROUND: There are few evidence-based interventions for long COVID; however, holistic approaches supporting recovery are advocated. We assessed whether an online breathing and wellbeing programme improves health related quality-of-life (HRQoL) in people with persisting breathlessness following COVID-19. METHODS: We conducted a parallel-group, single-blind, randomised controlled trial in patients who had been referred from one of 51 UK-based collaborating long COVID clinics. Eligible participants were aged 18 years or older; were recovering from COVID-19 with ongoing breathlessness, with or without anxiety, at least 4 weeks after symptom onset; had internet access with an appropriate device; and were deemed clinically suitable for participation by one of the collaborating COVID-19 clinics. Following clinical assessment, potential participants were given a unique online portal code. Participants were randomly assigned (1:1) to either immediate participation in the English National Opera (ENO) Breathe programme or to usual care. Randomisation was done by the research team using computer-generated block randomisation lists, with block size 10. The researcher responsible for randomisation was masked to responses. Participants in the ENO Breathe group participated in a 6-week online breathing and wellbeing programme, developed for people with long COVID experiencing breathlessness, focusing on breathing retraining using singing techniques. Those in the deferred group received usual care until they exited the trial. The primary outcome, assessed in the intention-to-treat population, was change in HRQoL, assessed using the RAND 36-item short form survey instrument mental health composite (MHC) and physical health composite (PHC) scores. Secondary outcome measures were the chronic obstructive pulmonary disease assessment test score, visual analogue scales (VAS) for breathlessness, and scores on the dyspnoea-12, the generalised anxiety disorder 7-item scale, and the short form-6D. A thematic analysis exploring participant experience was also conducted using qualitative data from focus groups, survey responses, and email correspondence. This trial is registered with ClinicalTrials.gov, NCT04830033. FINDINGS: Between April 22 and May 25, 2021, 158 participants were recruited and randomly assigned. Of these, eight (5%) individuals were excluded and 150 participants were allocated to a treatment group (74 in the ENO Breathe group and 76 in the usual care group). Compared with usual care, ENO Breathe was associated with an improvement in MHC score (regression coefficient 2·42 [95% CI 0·03 to 4·80]; p=0·047), but not PHC score (0·60 [-1·33 to 2·52]; p=0·54). VAS for breathlessness (running) favoured ENO Breathe participation (-10·48 [-17·23 to -3·73]; p=0·0026). No other statistically significant between-group differences in secondary outcomes were observed. One minor self-limiting adverse event was reported by a participant in the ENO Breathe group who felt dizzy using a computer for extended periods. Thematic analysis of ENO Breathe participant experience identified three key themes: (1) improvements in symptoms; (2) feeling that the programme was complementary to standard care; and (3) the particular suitability of singing and music to address their needs. INTERPRETATION: Our findings suggest that an online breathing and wellbeing programme can improve the mental component of HRQoL and elements of breathlessness in people with persisting symptoms after COVID-19. Mind-body and music-based approaches, including practical, enjoyable, symptom-management techniques might have a role supporting recovery. FUNDING: Imperial College London

"They're Really PD Today": An Exploration of Mental Health Nursing Students' Perceptions of Developing a Therapeutic Relationship With Patients With a Diagnosis of Antisocial Personality Disorder

The therapeutic relationship is of particular importance when working with patients with antisocial personality disorder, but despite this, there is a paucity of literature exploring student nurses’ perceptions of developing a therapeutic relationship with such patients. Hence, this qualitative study explored the perceptions of second-year mental health nursing students of developing a therapeutic relationship with this patient group. Student nurses from a University in the Northwest of England participated in two focus groups, to compare the perceptions of a group of student nurses who had experience in secure settings (forensic hospital) with those who had not. Four key themes emerged: diagnosis, safety, engagement, and finally environmental influences. Both groups commented on looking beyond the diagnosis and seeing the person. The student nurses cited other staff in their clinical placement areas as hugely influential in terms of the development of their perceptions of patients with antisocial personality disorder and how to relate to them

Drosophila DNA polymerase theta utilizes both helicase-like and polymerase domains during microhomology-mediated end joining and interstrand crosslink repair

Double strand breaks (DSBs) and interstrand crosslinks (ICLs) are toxic DNA lesions that can be repaired through multiple pathways, some of which involve shared proteins. One of these proteins, DNA Polymerase theta (Pol theta), coordinates a mutagenic DSB repair pathway named microhomology-mediated end joining (MMEJ) and is also a critical component for bypass or repair of ICLs in several organisms. Pol theta contains both polymerase and helicase-like domains that are tethered by an unstructured central region. While the role of the polymerase domain in promoting MMEJ has been studied extensively both in vitro and in vivo, a function for the helicase-like domain, which possesses DNA-dependent ATPase activity, remains unclear. Here, we utilize genetic and biochemical analyses to examine the roles of the helicase-like and polymerase domains of Drosophila Pol theta. We demonstrate an absolute requirement for both polymerase and ATPase activities during ICL repair in vivo. However, similar to mammalian systems, polymerase activity, but not ATPase activity, is required for ionizing radiation-induced DSB repair. Using a site-specific break repair assay, we show that overall end-joining efficiency is not affected in ATPase-dead mutants, but there is a significant decrease in templated insertion events. In vitro, Pol theta can efficiently bypass a model unhooked nitrogen mustard crosslink and promote DNA synthesis following microhomology annealing, although ATPase activity is not required for these functions. Together, our data illustrate the functional importance of the helicase-like domain of Pol theta and suggest that its tethering to the polymerase domain is important for its multiple functions in DNA repair and damage tolerance