Non-Skewed X-inactivation Results in NF-κB Essential Modulator (NEMO) Δ-exon 5-autoinflammatory Syndrome (NEMO-NDAS) in a Female with Incontinentia Pigmenti.

PURPOSE: Genetic hypomorphic defects in X chromosomal IKBKG coding for the NF-κB essential modulator (NEMO) lead to ectodermal dysplasia and immunodeficiency in males and the skin disorder incontinentia pigmenti (IP) in females, respectively. NF-κB essential modulator (NEMO) Δ-exon 5-autoinflammatory syndrome (NEMO-NDAS) is a systemic autoinflammatory disease caused by alternative splicing and increased proportion of NEMO-Δex5. We investigated a female carrier presenting with IP and NEMO-NDAS due to non-skewed X-inactivation. METHODS: IKBKG transcripts were quantified in peripheral blood mononuclear cells isolated from the patient, her mother, and healthy controls using RT-PCR and nanopore sequencing. Corresponding proteins were analyzed by western blotting and flow cytometry. Besides toll-like receptor (TLR) and tumor necrosis factor (TNF) signaling, the interferon signature, cytokine production and X-inactivation status were investigated. RESULTS: IP and autoinflammation with recurrent fever, oral ulcers, hepatitis, and neutropenia, but no immunodeficiency was observed in a female patient. Besides moderately reduced NEMO signaling function, type I interferonopathy, and elevated IL-18 and CXCL10 were found. She and her mother both carried the heterozygous variant c.613 C > T p.(Gln205*) in exon 5 of IKBKG previously reported in NEMO-deficient patients. However, X-inactivation was skewed in the mother, but not in the patient. Alternative splicing led to increased ratios of NEMO-Dex5 over full-length protein in peripheral blood cell subsets causing autoinflammation. Clinical symptoms partially resolved under treatment with TNF inhibitors. CONCLUSION: Non-skewed X-inactivation can lead to NEMO-NDAS in females with IP carrying hypomorphic IKBKG variants due to alternative splicing and increased proportions of NEMO-∆ex5.

Obstetric imaging practice characteristics associated with prenatal detection of critical congenital heart disease in a rural US region over 20 years.

OBJECTIVE: To identify clinical practice characteristics associated with the frequency of prenatal critical congenital heart disease (CCHD) detection (i.e., the number of liveborn infants with postnatally confirmed CCHD identified on prenatal sonography) over 20 years in a rural setting comprised of 11 primarily low-volume obstetric hospitals and the single tertiary academic hospital to which they refer. METHODS: This was a retrospective cohort study of all patients in the referral region with an initial prenatal and/or postnatal diagnosis of CCHD from 01/01/2002 to 12/31/2021. The frequency of prenatal CCHD detection at the time of an obstetric ultrasound was reported, as was the change in detection over time. Critical congenital heart disease detection was assessed as a function of cardiac lesion type, practice setting, and practice characteristics. RESULTS: There were 271 cases with a confirmed postnatal CCHD diagnosis, of which 49% were identified prenatally. The majority of community practices each averaged <10 CCHD cases in total over the study period. Prenatal detection at the tertiary academic hospital's obstetric ultrasound unit was 64%, compared to 22% at the combined referring community practices (p < 0.001), though CCHD detection improved over time in both settings. Professional accreditation by the American Institute of Ultrasound in Medicine, image interpretation by radiology or Maternal Fetal Medicine, and use of video clips of ventricular outflow tracts were associated with improved prenatal CCHD detection. CONCLUSIONS: Our data demonstrate the infrequency of CCHD cases at small-volume, rural hospitals and the substantial variation in prenatal CCHD detection across practice settings. Our methods allowed for the identification of practice characteristics associated with prenatal CCHD detection.

Verbatim theatre as a creative approach to health professions education research translation.

CONTEXT: Traditionally, the impact and outcomes from health professions education research (HPER) have focused on academic outputs, whereas in the humanities, research translation is conceptualised more broadly and creatively, including research-based performances like verbatim theatre. Translating HPER findings through the emotive and embodied nature of a verbatim theatre performance provides a unique opportunity to translate research data and create alternative learning spaces for rich and valuable insights that aligns with transformative pedagogy. APPROACH: In this paper, we describe the background of verbatim theatre, a form of performance, which draws on a research participants' testimony and lived experience and how we used this creative approach to translate HPER findings. We discuss the experiential process of bringing an interdisciplinary team together, health professions academics and an academic playwright to craft a verbatim theatre script that provided space to honour the breadth, depth and diversity of participant voices from a large (n = 100) qualitative research study exploring professionalism and sociocultural factors in health professions education (HPE). Furthermore, we discuss the powerful potential of drawing on research-based performance to create alternative, safe and non-threatening learning spaces to resonate with and experience HPER in new and transformative ways. Finally, we offer reflexive insights on the key opportunities and challenges we encountered in translating HPER into a verbatim theatre performance. CONCLUSIONS: Verbatim theatre presents an innovative and creative way to communicate and translate HPER. This paper offers research and pedagogical insights in translating research into verbatim theatre to support transformative pedagogy and practice in HPE. In conclusion, we encourage other health professions researchers to consider this dynamic and creative approach to transforming HPE.

Healthcare professionals' experiences of caring for women with false-positive screening test results in the National Health Service Breast Screening Programme.

BACKGROUND: Understanding healthcare professionals' (HCPs) experiences of caring for women with false-positive screening test results in the National Health Service Breast Screening Programme (NHSBSP) is important for reducing the impact of such results. METHODS: Interviews were undertaken with 12 HCPs from a single NHSBSP unit, including advanced radiographer practitioners, breast radiographers, breast radiologists, clinical nurse specialists (CNSs), and a radiology healthcare assistant. Data were analysed thematically using Template Analysis. RESULTS: Two themes were produced: (1) Gauging and navigating women's anxiety during screening assessment was an inevitable and necessary task for all participants. CNSs were perceived as particularly adept at this, while breast radiographers reported a lack of adequate formal training. (2) Controlling the delivery of information to women (including amount, type and timing of information). HCPs reported various communication strategies to facilitate women's information processing and retention during a distressing time. CONCLUSIONS: Women's anxiety could be reduced through dedicated CNS support, but this should not replace support from other HCPs. Breast radiographers may benefit from more training to emotionally support recalled women. While HCPs emphasised taking a patient-centred communication approach, the use of other strategies (e.g., standardised scripts) and the constraints of the 'one-stop shop' model pose challenges to such an approach. PATIENT AND PUBLIC CONTRIBUTION: During the study design, two Patient and Public Involvement members (women with false-positive-breast screening test results) were consulted to gain an understanding of patient perspectives and experiences of being recalled specifically in the NHSBSP. Their feedback informed the formulations of the research aim, objectives and the direction of the interview guide.

Lost in translation: a national cross-sectional study on medical interpreter use by pediatric residents.

BACKGROUND: Lack of communication in a family's preferred language is inequitable and results in inferior care. Pediatric residents provide care to many families with non-English or French language preferences (NEFLP). There is no data available about how Canadian pediatric residents use interpreters, making it difficult to develop targeted interventions to improve patient experience. OBJECTIVES: Our purpose was to assess translation services in pediatric training centers and evaluate resident perception of their clinical skills when working with NEFLP patients and families. This survey represents the first collection of data from Canadian pediatric residents about interpreter services. METHODS: Eligible participants included all pediatric residents enrolled in an accredited Canadian pediatric training program. An anonymous survey was developed in REDCap© and distributed via email to all pediatric residents across Canada. Descriptive statistics were performed in STATA v15.1. RESULTS: 122 residents responded. Interpreter services were widely available but underused in a variety of clinical situations. Most (85%) residents felt they provided better care to patients who shared their primary language (English or French), compared with families who preferred other languages-even when an interpreter was present. This finding was consistent across four self-assessed clinical skills. CONCLUSIONS: Residents are more confident in their clinical and communication skills when working with families who share their primary language. Our findings suggest that residents lack the training and confidence to provide equal care to families with varying language preferences. Pediatric training programs should develop curriculum content that targets safe and effective interpreter use while reviewing non-spoken aspects of cultural awareness and safety.

Impaired Tertiary Dentin Secretion after Shallow Injury in Tgfbr2-Deficient Dental Pulp Cells Is Rescued by Extended CGRP Signaling.

The transforming growth factor ß (TGFß) superfamily is a master regulator of development, adult homeostasis, and wound repair. Dysregulated TGFß signaling can lead to cancer, fibrosis, and musculoskeletal malformations. We previously demonstrated that TGFß receptor 2 (Tgfbr2) signaling regulates odontoblast differentiation, dentin mineralization, root elongation, and sensory innervation during tooth development. Sensory innervation also modulates the homeostasis and repair response in adult teeth. We hypothesized that Tgfbr2 regulates the neuro-pulpal responses to dentin injury. To test this, we performed a shallow dentin injury with a timed deletion of Tgfbr2 in the dental pulp mesenchyme of mice and analyzed the levels of tertiary dentin and calcitonin gene-related peptide (CGRP) axon sprouting. Microcomputed tomography imaging and histology indicated lower dentin volume in Tgfbr2cko M1s compared to WT M1s 21 days post-injury, but the volume was comparable by day 56. Immunofluorescent imaging of peptidergic afferents demonstrated that the duration of axon sprouting was longer in injured Tgfbr2cko compared to WT M1s. Thus, CGRP+ sensory afferents may provide Tgfbr2-deficient odontoblasts with compensatory signals for healing. Harnessing these neuro-pulpal signals has the potential to guide the development of treatments for enhanced dental healing and to help patients with TGFß-related diseases.

Supporting post-pandemic recovery: a qualitative study of the capabilities, opportunities and motivations to deliver oral health behaviour change messages to parents of young children in community settings.

BACKGROUND: The COVID-19 pandemic exacerbated vulnerabilities and inequalities in children's oral health, and treatment activity virtually ceased during periods of lockdown. Primary care dentistry is still in the post-pandemic recovery phase, and it may be some years before normal service is resumed in NHS dentistry. However, opportunities to support the dental workforce through offering some preventative care in outreach settings may exist. This has the additional benefit of potentially reaching children who do not routinely see a dentist. The aim of this research was therefore to explore views around upskilling practitioners working in early years educational and care settings to support families of pre-school aged children to adopt and maintain preventative oral health behaviours. METHODS: Using the Capability, Opportunity and Motivation model of behaviour (COM-B) to structure our data collection and analysis, we conducted semi-structured interviews with 16 practitioners (dental and non-dental) and analysed the data using deductive framework analysis. RESULTS: The data were a good fit with the COM-B model, and further themes were developed within each construct, representing insights from the data. CONCLUSION: Early years practitioners can reach vulnerable children who are not usually brought to see a dentist, and have the capability, opportunity and motivation to support the oral health behaviours of families of children in their care. Further research is needed to identify training needs (oral health and behaviour change knowledge and skills), acceptability to parents, and supporting dental practice teams to work in partnership with early years settings.

Outcomes of Children Discharged Prior to Absolute Neutrophil Count Recovery After Admission for Febrile Neutropenia.

Febrile neutropenia (FN) management in pediatric oncology patients traditionally necessitates inpatient admission until evidence of bone marrow recovery. Discharge before count recovery may be a way to safely reduce the length of hospitalizations for select patients. A chart review was conducted of patients admitted for FN at one tertiary care children's hospital, where the standard is to discharge well-appearing patients after 48 hours of negative cultures if afebrile for at least 24 hours, irrespective of absolute neutrophil count (ANC). Patients with ANC <500 at discharge were identified as early discharges, and data were collected with respect to rates of readmission and infectious complications in this cohort. Among 1230 FN encounters, 765 (62%) were early discharges. 122 patients (15.9%) were readmitted within 7 days. Patients with acute myeloid leukemia and ANC <100 at discharge were more likely to be readmitted. Of the early discharges, only 10 (1.31%) were readmitted with positive blood cultures and 5 (0.7%) were admitted to the pediatric intensive care unit within 24 hours of readmission. Routine discharge before ANC recovery allows for short hospital stays with low rates of readmission, infectious complications, and critical illness for pediatric oncology patients. This safe and beneficial policy should be considered at other institutions.

The interplay between suicidal experiences, psychotic experiences and interpersonal relationships: a qualitative study.

BACKGROUND: Suicidal thoughts, acts, plans and deaths are considerably more prevalent in people with non-affective psychosis, including schizophrenia, compared to the general population. Social isolation and interpersonal difficulties have been implicated in pathways which underpin suicidal experiences in people with severe mental health problems. However, the interactions between psychotic experiences, such as hallucinations and paranoia, suicidal experiences, and the presence, and indeed, absence of interpersonal relationships is poorly understood and insufficiently explored. The current study sought to contribute to this understanding. METHODS: An inductive thematic analysis was conducted on transcripts of 22, individual, semi-structured interviews with adult participants who had both non-affective psychosis and recent suicidal experiences. A purposive sampling strategy was used. Trustworthiness of the analysis was assured with researcher triangulation. RESULTS: Participants relayed both positive and negative experiences of interpersonal relationships. A novel conceptual model is presented reflecting a highly complex interplay between a range of different suicidal experiences, psychosis, and aspects of interpersonal relationships. Three themes fed into this interplay, depicting dynamics between perceptions of i. not mattering and mattering, ii. becoming disconnected from other people, and iii. constraints versus freedom associated with sharing suicidal and psychotic experiences with others. CONCLUSION: This study revealed a detailed insight into ways in which interpersonal relationships are perceived to interact with psychotic and suicidal experiences in ways that can be both beneficial and challenging. This is important from scientific and clinical perspectives for understanding the complex pathways involved in suicidal experiences. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03114917), 14th April 2017. ISRCTN (reference ISRCTN17776666 .); 5th June 2017). Registration was recorded prior to participant recruitment commencing.

A qualitative exploration of influences on eating behaviour throughout pregnancy.

BACKGROUND: Pregnancy is often conceptualised as a 'teachable moment' for health behaviour change. However, it is likely that different stages of pregnancy, and individual antenatal events, provide multiple distinct teachable moments to prompt behaviour change. Whilst previous quantitative research supports this argument, it is unable to provide a full understanding of the nuanced factors influencing eating behaviour. The aim of this study was to explore influences on women's eating behaviour throughout pregnancy. METHODS: In-depth interviews were conducted online with 25 women who were less than six-months postpartum. Interviews were audio-recorded and transcribed verbatim. Data were analysed thematically. RESULTS: Five themes were generated from the data that capture influences on women's eating behaviour throughout pregnancy: 'The preconceptual self', 'A desire for good health', 'Retaining control', 'Relaxing into pregnancy', and 'The lived environment'. CONCLUSION: Mid-pregnancy may provide a more salient opportunity for eating behaviour change than other stages of pregnancy. Individual antenatal events, such as the glucose test, can also prompt change. In clinical practice, it will be important to consider the changing barriers and facilitators operating throughout pregnancy, and to match health advice to stages of pregnancy, where possible. Existing models of teachable moments may be improved by considering the dynamic nature of pregnancy, along with the influence of the lived environment, pregnancy symptoms, and past behaviour. These findings provide an enhanced understanding of the diverse influences on women's eating behaviour throughout pregnancy and provide a direction for how to adapt existing theories to the context of pregnancy.

Enhancing community weight loss groups in a low socioeconomic status area: Application of the COM-B model and Behaviour Change Wheel.

BACKGROUND: Obesity rates are higher among people of lower socioeconomic status. While numerous health behaviour interventions targeting obesity exist, they are more successful at engaging higher socioeconomic status populations, leaving those in less affluent circumstances with poorer outcomes. This highlights a need for more tailored interventions. The aim of this study was to enhance an existing weight loss course for adults living in low socioeconomic communities. METHODS: The Behaviour Change Wheel approach was followed to design an add-on intervention to an existing local authority-run weight loss group, informed by mixed-methods research and stakeholder engagement. RESULTS: The COM-B analysis of qualitative data revealed that changes were required to psychological capability, physical and social opportunity and reflective motivation to enable dietary goal-setting behaviours. The resulting SMART-C booklet included 6 weeks of dietary goal setting, with weekly behavioural contract and review. CONCLUSION: This paper details the development of the theory- and evidence-informed SMART-C intervention. This is the first report of the Behaviour Change Wheel being used to design an add-on tool to enhance existing weight loss services. The process benefitted from a further checking stage with stakeholders.

Educators' experiences and perspectives of child weight discussions with parents in primary school settings.

BACKGROUND: The role of schools in addressing rising childhood obesity levels has been acknowledged, and numerous diet- and physical activity-related interventions exist. Aside from formal interventions, opportunistic parent-educator conversations about child weight can arise, particularly in primary school settings, yet little is known about how useful these are. This study aimed to understand the utility of child weight related conversations with parents through exploring educators' experiences and perspectives. METHODS: This qualitative study consisted of semi-structured interviews conducted with primary school teaching staff in the United Kingdom (N = 23), recruited through purposive and subsequent snowball sampling. Interviews were audio-recorded, transcribed, and analysed using thematic analysis. RESULTS: Participants identified opportunities and need for child weight discussions in schools. However, conversations were prevented by the indirect and sensitive nature of conversations, and educators' professional identity beliefs. Using pre-existing face-to-face opportunities, good parent-teacher relationships and holistic approaches to child health and wellbeing were reported as important in optimising these conversations. CONCLUSIONS: Whilst educator-parent child weight discussions are necessary, discussions are highly challenging, with contradictory views on responsibility sometimes resulting in avoidance. Educators' roles should be clarified, and communication training tailored to increase teacher confidence and skills. Current social distancing will likely reduce opportunistic encounters, highlighting a need to further improve communication routes.

Data protection, information governance and the potential erosion of ethnographic methods in health care?

With the most recent developments to the European General Data Protection Regulations (GDPR) introduced in May 2018, the resulting legislation meant a new set of considerations for study approvers and health-care researchers. Compared with previous legislation in the UK (The Data Protection Act, 1998), it introduced more extensive and directive principles, requiring anybody 'processing' personal data to specifically define how this data will be obtained, stored, used and destroyed. Importantly, it also emphasised the principle of accountability, which meant that data controllers and processors could no longer just state that they planned to adhere to lawful data protection principles, they also had to demonstrate compliance. New questions and concerns around accountability now appear to have increased levels of scrutiny in all areas of information governance (IG), especially with regards to processing confidential patient information. This article explores our experiences of gaining required ethical and regulatory approvals for an ethnographic study in a UK health-care setting, the implications that the common law duty of confidentiality had for this research, and the ways in which IG challenges were overcome. The purpose of this article was to equip researchers embarking on similar projects to be able to navigate the potentially problematic and complex journey to approval.

Predictors of Out-of-Class Mindfulness Practice Adherence During and After a Mindfulness-Based Intervention.

OBJECTIVE: Out-of-class mindfulness meditation practice is a health behavior that is considered to be a crucial ingredient in mindfulness-based interventions (MBIs), yet participant adherence to practice recommendations is often inconsistent. Furthermore, MBIs may enhance factors that lead to greater adherence to medical regimens in other contexts. This study examined baseline factors previously found to relate to adherence to medical regimen, MBI-related changes in these baseline factors, and treatment-related factors as predictors of meditation adherence in an 8-week MBI. METHODS: Baseline traits (personality, depressive symptoms, and executive function) were entered into regression models (n = 96) to predict intervention and postintervention out-of-class meditation adherence. Trait changes and treatment-related factors were entered into models to predict postintervention meditation adherence. RESULTS: Baseline conscientiousness (ß = 0.33, p = .002), openness (ß = 0.23, p = .019), and depressive symptoms (ß = 0.19, p = .042) predicted intervention meditation adherence, whereas conscientiousness (ß = 0.21, p = .044) and depressive symptoms (ß = 0.22, p = .020) predicted postintervention meditation adherence. Although all trait variables except for agreeableness changed significantly pre-to-post intervention, these changes did not predict postintervention meditation adherence. Retreat attendance (ß = 0.38, p = .029) and instructor/group-related therapeutic factors collectively predicted postintervention meditation adherence (R2 = 0.21, p = .019). CONCLUSIONS: The identified baseline trait factors could be used to increase adherence in these interventions as a method of increasing their effectiveness. An emphasis on the MBI retreat and social factors during the intervention may be important for participant out-of-class practice postintervention.Trial Registration:ClinicalTrials.govNCT01831362.

Psychometric properties of the Suicidal Ideation Attributes Scale (SIDAS) in a longitudinal sample of people experiencing non-affective psychosis.

BACKGROUND: Suicidal ideation is a key precursor for suicide attempts and suicide deaths. Performing routine screening of suicide precursors can help identify people who are at high risk of death by suicide. This is, arguably, an important suicide prevention effort. The aim of this study was to assess the validity, reliability, and factor structure of the Suicidal Ideation Attributes Scale (SIDAS) in a three-month longitudinal study with people with a diagnosis of schizophrenia or non-affective psychosis and experiences of suicidal ideation and/or behaviours. It was predicted that the SIDAS would have high internal consistency, test-retest reliability, convergent, discriminant and construct validity. METHODS: Ninety-nine participants experiencing psychosis completed the SIDAS at baseline and 89 participants completed it 3 months later. Additionally, participants completed a demographic questionnaire, the Beck Scale for Suicide Ideation, the Beck Hopelessness Scale, and the Defeat and Entrapment Scales. The internal consistency, test-retest reliability, convergent validity, and discriminant validity of the SIDAS were investigated in comparison to other constructs. Factor analysis was performed to examine the factor structure of the scale. RESULTS: Principal component analysis yielded a theoretically coherent one-dimensional factor structure of SIDAS, suggesting good construct validity (PCA = .71). The SIDAS had high internal consistency (α = .89) and good test-retest reliability (α = .73). It was highly correlated with other self-report measures, including the Beck Scale for Suicide Ideation, Beck Hopelessness Scale, Defeat and Entrapment scales, indicating excellent construct validity. CONCLUSION: The SIDAS is a valid and reliable self-report instrument for assessing the severity of suicidal ideation in a population of people with a diagnosis of schizophrenia or non-affective psychosis. Further research should test the psychometric properties of the scale in individuals experiencing different mental health problems in cross-cultural settings, in order to establish its broader validity, reliability, and clinical utility.

AMEE Consensus Statement: Planetary health and education for sustainable healthcare.

The purpose of this Consensus Statement is to provide a global, collaborative, representative and inclusive vision for educating an interprofessional healthcare workforce that can deliver sustainable healthcare and promote planetary health. It is intended to inform national and global accreditation standards, planning and action at the institutional level as well as highlight the role of individuals in transforming health professions education. Many countries have agreed to 'rapid, far-reaching and unprecedented changes' to reduce greenhouse gas emissions by 45% within 10 years and achieve carbon neutrality by 2050, including in healthcare. Currently, however, health professions graduates are not prepared for their roles in achieving these changes. Thus, to reduce emissions and meet the 2030 Sustainable Development Goals (SDGs), health professions education must equip undergraduates, and those already qualified, with the knowledge, skills, values, competence and confidence they need to sustainably promote the health, human rights and well-being of current and future generations, while protecting the health of the planet.The current imperative for action on environmental issues such as climate change requires health professionals to mobilize politically as they have before, becoming strong advocates for major environmental, social and economic change. A truly ethical relationship with people and the planet that we inhabit so precariously, and to guarantee a future for the generations which follow, demands nothing less of all health professionals.This Consensus Statement outlines the changes required in health professions education, approaches to achieve these changes and a timeline for action linked to the internationally agreed SDGs. It represents the collective vision of health professionals, educators and students from various health professions, geographic locations and cultures. 'Consensus' implies broad agreement amongst all individuals engaged in discussion on a specific issue, which in this instance, is agreement by all signatories of this Statement developed under the auspices of the Association for Medical Education in Europe (AMEE).To ensure a shared understanding and to accurately convey information, we outline key terms in a glossary which accompanies this Consensus Statement (Supplementary Appendix 1). We acknowledge, however, that terms evolve and that different terms resonate variably depending on factors such as setting and audience. We define education for sustainable healthcare as the process of equipping current and future health professionals with the knowledge, values, confidence and capacity to provide environmentally sustainable services through health professions education. We define a health professional as a person who has gained a professional qualification for work in the health system, whether in healthcare delivery, public health or a management or supporting role and education as 'the system comprising structures, curricula, faculty and activities contributing to a learning process'. This Statement is relevant to the full continuum of training - from undergraduate to postgraduate and continuing professional development.

Generation and Evaluation of a Glaesserella (Haemophilus) parasuis Capsular Mutant.

Glaesserella (Haemophilus) parasuis is a commensal bacterium of the upper respiratory tract in pigs and also the causative agent of Glässer's disease, which causes significant morbidity and mortality in pigs worldwide. Isolates are characterized into 15 serovars by their capsular polysaccharide, which has shown a correlation with isolate pathogenicity. To investigate the role the capsule plays in G. parasuis virulence and host interaction, a capsule mutant of the serovar 5 strain HS069 was generated (HS069Δcap) through allelic exchange following natural transformation. HS069Δcap was unable to cause signs of systemic disease during a pig challenge study and had increased sensitivity to complement killing and phagocytosis by alveolar macrophages. Compared with the parent strain, HS069Δcap produced more robust biofilm and adhered equivalently to 3D4/31 cells; however, it was unable to persistently colonize the nasal cavity of inoculated pigs, with all pigs clearing HS069Δcap by 5 days postchallenge. Our results indicate the importance of the capsular polysaccharide to G. parasuis virulence as well as nasal colonization in pigs.

Altering access to autobiographical episodes with prior semantic knowledge.

Within autobiographical knowledge, semantic and episodic memory are traditionally considered separate, but newer models place them along a continuum, which raises the possibility of an intermediate form of knowledge - personal semantics. This study tested how different types of semantics - general semantics and two forms of personal semantics - impact access to personal episodic memories. In two experiments, participants made a series of true/false judgments about a prime statement, which reflected a general semantic fact, a context-dependent (e.g., repeated event) or context-independent (e.g., trait), personal semantic fact and then retrieved a specific past episodic memory. There was a significantly stronger priming effect for accessing specific episodic memories after judging personal semantic facts versus general facts. We also found that context-dependent and -independent personal semantic facts had separable priming effects on episodic memory. These findings support a continuum model of memory and verifies that there are multiple forms of personal knowledge.

Is e-cigarette use in non-smoking young adults associated with later smoking? A systematic review and meta-analysis.

OBJECTIVE: The aim of this review was to investigate whether e-cigarette use compared with non-use in young non-smokers is associated with subsequent cigarette smoking. DATA SOURCES: PubMed, Embase, Web of Science, Wiley Cochrane Library databases, and the 2018 Society for Research on Nicotine and Tobacco and Society for Behavioural Medicine conference abstracts. STUDY SELECTION: All studies of young people (up to age 30 years) with a measure of e-cigarette use prior to smoking and an outcome measure of smoking where an OR could be calculated were included (excluding reviews and animal studies). DATA EXTRACTION: Independent extraction was completed by multiple authors using a preprepared extraction form. DATA SYNTHESIS: Of 9199 results, 17 studies were included in the meta-analysis. There was strong evidence for an association between e-cigarette use among non-smokers and later smoking (OR: 4.59, 95% CI: 3.60 to 5.85) when the results were meta-analysed in a random-effects model. However, there was high heterogeneity (I2 =88%). CONCLUSIONS: Although the association between e-cigarette use among non-smokers and subsequent smoking appears strong, the available evidence is limited by the reliance on self-report measures of smoking history without biochemical verification. None of the studies included negative controls which would provide stronger evidence for whether the association may be causal. Much of the evidence also failed to consider the nicotine content of e-liquids used by non-smokers meaning it is difficult to make conclusions about whether nicotine is the mechanism driving this association.

Evaluation of the recombinant proteins RlpB and VacJ as a vaccine for protection against Glaesserella parasuis in pigs.

BACKGROUND: Glaesserella parasuis, the causative agent of Glӓsser's disease, is widespread in swine globally resulting in significant economic losses to the swine industry. Prevention of Glӓsser's disease in pigs has been plagued with an inability to design broadly protective vaccines, as many bacterin based platforms generate serovar or strain specific immunity. Subunit vaccines are of interest to provide protective immunity to multiple strains of G. parasuis. Selected proteins for subunit vaccination should be widespread, highly conserved, and surface exposed. RESULTS: Two candidate proteins for subunit vaccination (RlpB and VacJ) against G. parasuis were identified using random mutagenesis and an in vitro organ culture system. Pigs were vaccinated with recombinant RlpB and VacJ, outer membrane proteins with important contributions to cellular function and viability. Though high antibody titers to the recombinant proteins and increased interferon-γ producing cells were found in subunit vaccinated animals, the pigs were not protected from developing systemic disease. CONCLUSIONS: It appears there may be insufficient RlpB and VacJ exposed on the bacterial surface for antibody to bind, preventing high RlpB and VacJ specific antibody titers from protecting animals from G. parasuis. Additionally, this work confirms the importance of utilizing the natural host species when assessing the efficacy of vaccine candidates.