Extensive subcutaneous emphysema secondary to endodontic treatment.

Subcutaneous emphysema is a relatively rare phenomenon, in the context of dentistry related to iatrogenic injury, with only 32 cases reported between 1993 and 2008. This article aims to discuss the relevance and importance of this issue to dentists, including how to identify the condition and its management.

Impact of obesity, lifestyle factors and health interventions on breast cancer survivors.

The incidences of both breast cancer and obesity are rising in the UK. Obesity increases the risk of developing breast cancer in the postmenopausal population and leads to worse outcomes in those of all ages treated for early-stage breast cancer. In this review we explore the multifactorial reasons behind this association and the clinical trial evidence for the benefits of physical activity and dietary interventions in the early and metastatic patient groups. As more people with breast cancer are cured, and those with metastatic disease are living longer, cancer survivorship is becoming increasingly important. Therefore, ensuring the long-term implications of cancer and cancer treatment are addressed is vital. Although there remains a lack of definitive evidence that deliberate weight loss after a diagnosis of breast cancer reduces disease recurrence, a number of studies have reported benefits of weight loss and of physical activity. However, the limited data currently available mean that clinicians remain unclear on the optimal lifestyle advice to give their patients. Further high-quality research is needed to provide this evidence base, which will be required to optimise clinical care and for the commissioning of lifestyle interventions in the UK in breast cancer survivors.

Immune responses against SARS-CoV-2 variants after two and three doses of vaccine in B-cell malignancies: UK PROSECO study.

Patients with hematological malignancies are at increased risk of severe COVID-19 outcomes due to compromised immune responses, but the insights of these studies have been compromised due to intrinsic limitations in study design. Here we present the PROSECO prospective observational study ( NCT04858568 ) on 457 patients with lymphoma that received two or three COVID-19 vaccine doses. We show undetectable humoral responses following two vaccine doses in 52% of patients undergoing active anticancer treatment. Moreover, 60% of patients on anti-CD20 therapy had undetectable antibodies following full vaccination within 12 months of receiving their anticancer therapy. However, 70% of individuals with indolent B-cell lymphoma displayed improved antibody responses following booster vaccination. Notably, 63% of all patients displayed antigen-specific T-cell responses, which increased after a third dose irrespective of their cancer treatment status. Our results emphasize the urgency of careful monitoring of COVID-19-specific immune responses to guide vaccination schemes in these vulnerable populations.

Carvedilol targets ß-arrestins to rewire innate immunity and improve oncolytic adenoviral therapy.

Oncolytic viruses are being tested in clinical trials, including in women with ovarian cancer. We use a drug-repurposing approach to identify existing drugs that enhance the activity of oncolytic adenoviruses. This reveals that carvedilol, a ß-arrestin-biased ß-blocker, synergises with both wild-type adenovirus and the E1A-CR2-deleted oncolytic adenovirus, dl922-947. Synergy is not due to ß-adrenergic blockade but is dependent on ß-arrestins and is reversed by ß-arrestin CRISPR gene editing. Co-treatment with dl922-947 and carvedilol causes increased viral DNA replication, greater viral protein expression and higher titres of infectious viral particles. Carvedilol also enhances viral efficacy in orthotopic, intraperitoneal murine models, achieving more rapid tumour clearance than virus alone. Increased anti-cancer activity is associated with an intratumoural inflammatory cell infiltrate and systemic cytokine release. In summary, carvedilol augments the activity of oncolytic adenoviruses via ß-arrestins to re-wire cytokine networks and innate immunity and could therefore improve oncolytic viruses for cancer patient treatment.

BCG Vaccine Protection Against Mycobacterium tuberculosis Infection by Level of Exposure in The Gambia.

In Indonesia, BCG vaccine protection against Mycobacterium tuberculosis infection decreased with increasing exposure to the pathogen. We aimed to validate these findings in Africa. Poisson regression was used to estimate BCG protection, stratified by pathogen exposure using an exposure score, against enzyme-linked immunospot assay conversion at 3 months in 220 Gambian case contacts. Although the interaction between BCG and exposure was not significant (P = .13), BCG protection was strongest in the lowest-exposure tertile (relative risk, 0.35 [95% confidence interval, .15-.82; P = .02] vs 0.50 [.30-.83; P = .008] and 0.71 (.45-1.13; P = .1] for the middle and highest-exposure tertiles, respectively. These results are consistent with those from Indonesia.

Oncolytic virus immunotherapies in ovarian cancer: moving beyond adenoviruses.

Ovarian cancer is the 5th most common cancer in UK women with a high relapse rate. The overall survival for ovarian cancer has remained low for decades prompting a real need for new therapies. Recurrent ovarian cancer remains confined in the peritoneal cavity in >80% of the patients, providing an opportunity for locoregional administration of novel therapeutics, including gene and viral therapy approaches. Immunotherapy is an expanding field, and includes oncolytic viruses as well as monoclonal antibodies, immune checkpoint inhibitors, and therapeutic vaccines. Oncolytic viruses cause direct cancer cell cytolysis and immunogenic cell death and subsequent release of tumor antigens that will prime for a potent tumor-specific immunity. This effect may be further enhanced when the viruses are engineered to express, or coadministered with, immunostimulatory molecules. Currently, the most commonly used and well-characterized vectors utilized for virotherapy purposes are adenoviruses. They have been shown to work synergistically with traditional chemotherapy and radiotherapy and have met with success in clinical trials. However, pre-existing immunity and poor in vivo models limit our ability to fully investigate the potential of oncolytic adenovirus as effective immunotherapies which in turn fosters the need to develop alternative viral vectors. In this review we cover recent advances in adenovirus-based oncolytic therapies targeting ovarian cancer and recent advances in mapping immune responses to oncolytic virus therapies in ovarian cancer.

Tickled to death: analysing public perceptions of 'cute' videos of threatened species (slow lorises - Nycticebus spp.) on Web 2.0 sites.

BACKGROUND: The internet is gaining importance in global wildlife trade and changing perceptions of threatened species. There is little data available to examine the impact that popular Web 2.0 sites play on public perceptions of threatened species. YouTube videos portraying wildlife allow us to quantify these perceptions. METHODOLOGY/PRINCIPAL FINDINGS: Focussing on a group of threatened and globally protected primates, slow lorises, we quantify public attitudes towards wildlife conservation by analysing 12,411 comments and associated data posted on a viral YouTube video 'tickling slow loris' over a 33-months period. In the initial months a quarter of commentators indicated wanting a loris as a pet, but as facts about their conservation and ecology became more prevalent this dropped significantly. Endorsements, where people were directed to the site by celebrities, resulted mostly in numerous neutral responses with few links to conservation or awareness. Two conservation-related events, linked to Wikipedia and the airing of a television documentary, led to an increase in awareness, and ultimately to the removal of the analysed video. CONCLUSIONS/SIGNIFICANCE: Slow loris videos that have gone viral have introduced these primates to a large cross-section of society that would not normally come into contact with them. Analyses of webometric data posted on the internet allow us quickly to gauge societal sentiments. We showed a clear temporal change in some views expressed but without an apparent increase in knowledge about the conservation plight of the species, or the illegal nature of slow loris trade. Celebrity endorsement of videos showing protected wildlife increases visits to such sites, but does not educate about conservation issues. The strong desire of commentators to express their want for one as a pet demonstrates the need for Web 2.0 sites to provide a mechanism via which illegal animal material can be identified and policed.

The Ebbinghaus illusion deceives adults but not young children.

The sensitivity of size perception to context has been used to distinguish between 'vision for action' and 'vision for perception', and to study cultural, psychopathological, and developmental differences in perception. The status of that evidence is much debated, however. Here we use a rigorous double dissociation paradigm based on the Ebbinghaus illusion, and find that for children below 7 years of age size discrimination is much less affected by surround size. Young children are less accurate than adults when context is helpful, but more accurate when context is misleading. Even by the age of 10 years context-sensitivity is still not at adult levels. Therefore, size contrast as shown by the Ebbinghaus illusion is not a built-in property of the ventral pathway subserving vision for perception but a late development of it, and low sensitivity to the Ebbinghaus illusion in autism is not primary to the pathology. Our findings also show that, although adults in Western cultures have low context-sensitivity relative to East Asians, they have high context-sensitivity relative to children. Overall, these findings reveal a gradual developmental trend toward ever broader contextual syntheses. Such developments are advantageous, but the price paid for them is that, when context is misleading, adults literally see the world less accurately than they did as children.

How does childhood economic disadvantage lead to crime?

BACKGROUND: This study sought to examine the associations between indices of socio-economic deprivation in childhood and later involvement in crime. METHOD: Data were gathered as part of the Christchurch Health and Development Study. In this project a cohort of 1,265 children born in Christchurch in 1977 have been studied from birth to age 21 years. The measures collected included: self-reported property and violent crime (15-16, 17-18, and 20-21 years); officially recorded convictions for property/violent crime; measures of childhood socio-economic status; and a series of intervening factors, including parenting (use of physical punishment, maternal care, family change, parental attachment, parental offending), individual (conduct and attention problems), school (truancy, suspensions, examination performance, scholastic ability), and peer factors (affiliations with deviant and substance using peers). RESULTS: The results suggest that childhood socio-economic disadvantage was associated with clear increases in rates of both self-reported crime and officially recorded convictions. However, using block recursive negative binomial regression models a range of parental, individual, school, and peer factors were found to intervene between socio-economic disadvantage and crime. Following introduction of these measures into the models, the association between socio-economic disadvantage and crime became both statistically and practically non-significant. CONCLUSIONS: This study suggests that the higher rates of crime found amongst young people from socio-economically disadvantaged families reflect a life course process in which adverse family, individual, school, and peer factors combine to increase individual susceptibility to crime.

Deviant peer affiliations and depression: confounding or causation?

Data gathered from 2 longitudinal studies (the Christchurch Health and Development study of a birth cohort of 1,265 New Zealand participants studied to 21 years and the Quebec Study of 240 Canadian participants studied to 13 years) was used to examine the linkages between deviant peer affiliations and depression in adolescence. Both studies produced similar conclusions: a) increasing peer affiliations were associated with significant (p < .0001) increases in depressive symptoms; b) the associations between peer affiliations and depression could not be fully explained by confounding factors; and c) peer affiliations and depressive symptoms were linked by a causal chain process in which deviant peer affiliations led to increased externalizing behaviors with the negative consequences of these behaviors leading to depression.

Risky driving behaviour in young people: prevalence, personal characteristics and traffic accidents.

OBJECTIVES: This research aimed to examine the prevalence of risky driving behaviour among young people, the characteristics of those who engage in risky driving behaviour, and the association between risky driving behaviours and accident risk. METHODS: Data were gathered during the course of the Christchurch Health and Development Study. As part of this longitudinal study, data were gathered on self-reported risky driving behaviours (18-21 years), traffic accidents (18-21 years) and a variety of individual characteristics for 907 participants who reported having driven a motor vehicle. RESULTS: More than 90% of drivers engaged in some form of risky driving behaviour. Those most likely to engage in frequent risky driving behaviours were: males (p < 0.0001), who exhibited alcohol (p < 0.0001) or cannabis abuse (p < 0.001) in adolescence, who were involved in violent/property crime (p < 0.01) and who affiliated with delinquent or substance-using peers (p < 0.05). There was a strong (p < 0.0001) association between the extent of risky driving behaviour and traffic accident risk. CONCLUSIONS: Risky driving behaviours are common among young people, particularly among young males prone to externalizing behaviours (substance abuse, crime and affiliations with deviant peers). Risky driving is strongly linked to traffic accident risk. IMPLICATIONS: There is a continued need to target risky driving behaviours among young people. Efforts to reduce risky driving should be targeted in particular at the high-risk group of young males prone to externalizing behaviours. More generally, the results suggest the need for a multistrategy approach to the reduction of traffic accidents that focuses on the full spectrum of risky driving behaviours.

Cannabis use and psychosocial adjustment in adolescence and young adulthood.

AIM: To examine the associations between frequency of cannabis use and psychosocial outcomes in adolescence/young adulthood. DESIGN: A 21-year longitudinal study of the health, development and adjustment of a birth cohort of 1265 New Zealand children. MEASUREMENTS: Annual assessments of the frequency of cannabis use were obtained for the period from age 14-21 years, together with measures of psychosocial outcomes including property/violent crime, depression, suicidal ideation, suicide attempt and other illicit drug use. FINDINGS: The frequency of cannabis use was associated significantly with all outcomes, and particularly other illicit drug use. Statistical control for confounding by both fixed and time-dynamic factors substantially reduced the strength of association between cannabis use and outcome measures. Nevertheless, cannabis use remained significantly (P < 0.05) associated with all outcomes and particularly other illicit drug use, after adjustment for confounding. For the measures of crime, suicidal behaviours and other illicit drug use there was evidence of age related variation in the strength of association with cannabis use, with younger (14-15 years old) users being more affected by regular cannabis use than older (20-21 years old) regular users. However, the association between cannabis use and depression did not vary with age. CONCLUSIONS: Cannabis use, and particularly regular or heavy use, was associated with increased rates of a range of adjustment problems in adolescence/ young adulthood-other illicit drug use, crime, depression and suicidal behaviours-with these adverse effects being most evident for school-aged regular users. The findings reinforce public health concerns about minimizing the use of cannabis among school-aged populations.

Deviant peer affiliations, crime and substance use: a fixed effects regression analysis.

The present study was designed to assess the influence of deviant peer affiliations on crime and substance use in adolescence/young adulthood. Data were used from a 21-year longitudinal study of health, development, and adjustment of a birth cohort of 1,265 New Zealand children. Annual assessments of deviant peer affiliations were obtained for the period from age 14-21 years, together with measures of psychosocial outcomes including, violent crime, property crime, alcohol abuse, cannabis abuse, and nicotine dependence. Affiliating with deviant peers was found to be significantly associated with each of these outcomes (p < .0001). Statistical control for confounding by both fixed and time dynamic factors reduced the strength of association between deviant peer affiliations and outcome measures. Nevertheless, deviant peer affiliations remained significantly associated (p < .0001) with all outcomes. For violent/property crime, cannabis and alcohol abuse there was significant evidence of age-related variation in the strength of association with deviant peer affiliations, with deviant peer affiliations having greater influence on younger participants (14-15 years) than older participants (20-21 years). These results suggest that deviant peer affiliations are associated with increased rates of a range of adjustment problems in adolescence/young adulthood with deviant peer affiliations being most influential at younger ages.

Epidural analgesia does not prolong the third stage of labour.

PURPOSE: To investigate whether there is an association between epidural analgesia and duration of third stage of labour, and between epidural analgesia and type of placental delivery (spontaneous vs expressed vs manual). METHODS: We examined, retrospectively, the computerized labour and delivery data of all 7,468 parturients who had vaginal deliveries from 1996 to 1999 at the Civic Campus of the Ottawa Hospital. RESULTS: There was no difference in duration of third stage of labour between women with and without epidural pain relief who had spontaneous or expressed (fundal pressure/gentle cord traction) placental delivery. Duration of third stage of labour was shorter in women with epidural analgesia requiring manual removal of placenta. (25.3 min vs 40.1 min, P < 0.0001). The incidence of expressed placental delivery or manual removal of placenta was not different between the groups. CONCLUSIONS: We conclude that there is no clinically important difference in duration of third stage of labour between women with or without epidural analgesia who have spontaneous placental delivery or placental expulsion with fundal pressure/gentle cord traction. However, duration of third stage of labour was shorter in women who received epidural analgesia and required manual removal of the placenta.

Anesthetic management of a parturient with Ehlers Danlos syndrome type IV.

PURPOSE: To describe the anesthetic management of a parturient with Ehlers Danlos syndrome (EDS) type IV. CLINICAL FEATURES: A 29-yr-old pregnant woman with EDS type IV was seen in the Obstetric Anesthesia Pre-assessment Clinic at 30 weeks gestation. She had a history of vertebral artery dissection, resulting in a transient neurological deficit at 22 yr of age. She had a normal vaginal delivery with continuous epidural analgesia for the delivery of her first child at 27 yr of age, before the diagnosis of EDS was made. Recent fibroblast culture demonstrated the production of abnormal procollagen type III, which is pathognomonic for EDS type IV. The patient and obstetrician preferred a repeat vaginal birth with instrumental delivery in the second stage. Analgesia for labour and delivery was provided with a continuous epidural infusion of ropivacaine and fentanyl. She delivered a healthy female infant with the use of outlet forceps, without complications. CONCLUSION: A pre-delivery, multidisciplinary, individualized management plan is required in patients with EDS, a rare disease with variable clinical features. In the case described, continuous epidural analgesia was effective and associated with excellent maternal and fetal outcomes.