Giardia Colonizes and Encysts in High-Density Foci in the Murine Small Intestine.

Giardia lamblia is a highly prevalent yet understudied protistan parasite causing significant diarrheal disease worldwide. Hosts ingest Giardia cysts from contaminated sources. In the gastrointestinal tract, cysts excyst to become motile trophozoites, colonizing and attaching to the gut epithelium. Trophozoites later differentiate into infectious cysts that are excreted and contaminate the environment. Due to the limited accessibility of the gut, the temporospatial dynamics of giardiasis in the host are largely inferred from laboratory culture and thus may not mirror Giardia physiology in the host. Here, we have developed bioluminescent imaging (BLI) to directly interrogate and quantify the in vivo temporospatial dynamics of Giardia infection, thereby providing an improved murine model to evaluate anti-Giardia drugs. Using BLI, we determined that parasites primarily colonize the proximal small intestine nonuniformly in high-density foci. By imaging encystation-specific bioreporters, we show that encystation initiates shortly after inoculation and continues throughout the duration of infection. Encystation also initiates in high-density foci in the proximal small intestine, and high density contributes to the initiation of encystation in laboratory culture. We suggest that these high-density in vivo foci of colonizing and encysting Giardia likely result in localized disruption to the epithelium. This more accurate visualization of giardiasis redefines the dynamics of the in vivo Giardia life cycle, paving the way for future mechanistic studies of density-dependent parasitic processes in the host. IMPORTANCEGiardia is a single-celled parasite causing significant diarrheal disease in several hundred million people worldwide. Due to limited access to the site of infection in the gastrointestinal tract, our understanding of the dynamics of Giardia infections in the host has remained limited and largely inferred from laboratory culture. To better understand Giardia physiology and colonization in the host, we developed imaging methods to quantify Giardia expressing bioluminescent physiological reporters in two relevant animal models. We discovered that parasites primarily colonize and encyst in the proximal small intestine in discrete, high-density foci. We also show that high parasite density contributes to encystation initiation

Identification of the domains of cauliflower mosaic virus protein P6 responsible for suppression of RNA silencing and salicylic acid signalling

Cauliflower mosaic virus (CaMV) encodes a 520 aa polypeptide, P6, which participates in several essential activities in the virus life cycle including suppressing RNA silencing and salicylic acid-responsive defence signalling. We infected Arabidopsis with CaMV mutants containing short in-frame deletions within the P6 ORF. A deletion in the distal end of domain D-I (the N-terminal 112 aa) of P6 did not affect virus replication but compromised symptom development and curtailed the ability to restore GFP fluorescence in a GFP-silenced transgenic Arabidopsis line. A deletion in the minimum transactivator domain was defective in virus replication but retained the capacity to suppress RNA silencing locally. Symptom expression in CaMV-infected plants is apparently linked to the ability to suppress RNA silencing. When transiently co-expressed with tomato bushy stunt virus P19, an elicitor of programmed cell death in Nicotiana tabacum, WT P6 suppressed the hypersensitive response, but three mutants, two with deletions within the distal end of domain D-I and one involving the N-terminal nuclear export signal (NES), were unable to do so. Deleting the N-terminal 20 aa also abolished the suppression of pathogen-associated molecular pattern-dependent PR1a expression following agroinfiltration. However, the two other deletions in domain D-I retained this activity, evidence that the mechanisms underlying these functions are not identical. The D-I domain of P6 when expressed alone failed to suppress either cell death or PR1a expression and is therefore necessary but not sufficient for all three defence suppression activities. Consequently, concerns about the biosafety of genetically modified crops carrying truncated ORFVI sequences appear unfounded

‘It's Skin Cancer’… a Rollercoaster of a Journey for Teenagers, Young People and Their Significant Other

Aim: To explore the lived experience of young people aged 16–24 years diagnosed with melanoma and that of their significant other in England. Design: Interpretive phenomenological analysis. Methods: Data were collected between August 2023 and January 2024 from one specialist cancer centre in England. Thirteen young people were approached, and 10 took part. Each young person was asked to nominate a significant other. Five nominated a significant other, and five nominated no one. Although interviews were offered face‐to‐face, virtual was the preferred method. In‐depth semi‐structured interviews were audio‐recorded with the participant's consent. Interview data were transcribed verbatim and analysed. Findings: The core conceptual thread woven throughout the findings was ‘It's like being on a rollercoaster,’ which is representative of the ups and downs of the treatment trajectory, often without the support of age‐appropriate specialist care. Four superordinate themes were identified: ‘Is something wrong?’, ‘Suddenly it's serious’, ‘Out on a limb’ and ‘Finding our place’. Conclusion: Although most young people were treated in a primary treatment centre for adults with cancer, their experience was challenging from route to diagnosis through their treatment and beyond. Few received age‐appropriate care to support their physical, emotional, and social wellbeing to help them navigate the experience. Impact: There is limited evidence exploring the experiences of teenagers and young adults living with melanoma or that of their significant other. This enriched understanding supports improvement of the care pathway and service delivery for these young people and their families. Patient and Public Involvement: One young person with lived experience was paid as a consultant to be part of the research team. He helped develop the grant application and research questions, data analysis, and writing this paper

Detection of neutralising antibodies to SARS-CoV-2 to determine population exposure in Scottish blood donors between March and May 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 in Hubei province, China as a cause of respiratory disease occasionally leading to coronavirus disease (COVID-19) [1,2]. Older age, male sex, smoking and comorbidities such as cardiac disease, hypertension and diabetes have been identified as risk factors for severe infections [3,4]. Symptomatic individuals typically exhibit fever, cough and shortness of breath 2–14 days after infection [5]. However, an unknown proportion of individuals experience no symptoms [6-8]. Antibody responses in both symptomatic and asymptomatic individuals are detectable in the blood 14–28 days after infection [9,10]. Subsequently, antibody levels drop and can become undetectable by some antibody assays in the early convalescent phase [9,11,12]. In this study, we used blood donors as a means of estimating population exposure from the start of the pandemic in March through to mid-May when PCR-detected cases in the United Kingdom (UK) had plateaued [13,14]. The detection frequency of neutralising antibodies in blood donors and a discussion of its applicability for estimating population level exposure are presented

Impact of policy for Children and Young People with Cancer

No abstract available

Widening Access; Developing an eLearning Resource for Health and Social Care Professionals Caring for Children and Young People with Cancer

Cancer is a key priority worldwide, and caring for children and young people with cancer requires a range of specific knowledge, skills and experience in order to deliver the complex care regimes both within the hospital or community environment. The aim of this paper is to disseminate work undertaken to design and develop pedagogical practice and innovation through an eLearning resource for health care professionals caring for children and young people with cancer across the globe. The work undertaken evaluated an existing cancer course (which has been withdrawn) that was developed and delivered through the Paediatric Oncology Nurses Forum, Royal College Nursing (Nurse Educators) and Warwick University. The evaluation consisted of 26 open and closed questions relating to the previous resource and was circulated to all health and social care professionals involved directly within specialist oncology services through the Children’s Cancer and Leukaemia Group. Questionnaires were sent out to a convenience sample of 773 health care professionals and the response rate was 14%. The findings identified that the course was predominantly accessed by nurses, but other health care professionals also found it useful. Participants highlighted several areas where they believed content could be developed or was lacking. This included areas such as palliative and end of life care, nutrition, sepsis and teenagers and young people. This feedback was then used to develop a site dedicated to the care of children and young people with cancer