B cells promote tumor progression in a mouse model of HPV‐mediated cervical cancer

Enhancing anti‐tumor immunity and preventing tumor escape are efficient strategies to increase the efficacy of therapeutic cancer vaccines. However, the treatment of advanced tumors remains difficult, mainly due to the immunosuppressive tumor microenvironment. Regulatory T cells and myeloid‐derived suppressor cells have been extensively studied, and their role in suppressing tumor immunity is now well established. In contrast, the role of B lymphocytes in tumor immunity remains unclear because B cells can promote tumor immunity or display regulatory functions to control excessive inflammation, mainly through IL‐10 secretion. Here, in a mouse model of HPV‐related cancer, we demonstrate that B cells accumulated in the draining lymph node of tumor‐bearing mice, due to a prolonged survival, and showed a decreased expression of MHC class II and CD86 molecules and an increased expression of Ly6A/E, PD‐L1 and CD39, suggesting potential immunoregulatory properties. However, B cells from tumor‐bearing mice did not show an increased ability to secrete IL‐10 and a deficiency in IL‐10 production did not impair tumor growth. In contrast, in B cell‐deficient μMT mice, tumor rejection occurred due to a strong T cell‐dependent anti‐tumor response. Genetic analysis based on single nucleotide polymorphisms identified genetic variants associated with tumor rejection in μMT mice, which could potentially affect reactive oxygen species production and NK cell activity. Our results demonstrate that B cells play a detrimental role in anti‐tumor immunity and suggest that targeting B cells could enhance the anti‐tumor response and improve the efficacy of therapeutic cancer vaccines.     

The life course approach: explaining the association between height and dental caries in Brazilian adolescents

AIM: To investigate the relationship between height and dental caries in Brazilian adolescents. METHODS: A cross-sectional survey design was used to collect retrospective data. Of 764 eligible 13-year-old adolescents enrolled in urban private or public schools in a Brazilian town, 652 were clinically examined and interviewed. Data were collected on socioeconomic circumstances, family related variables, oral health behaviour and anthropometric measures (height and weight). Dental caries was measured by decayed, missing and filled teeth (DMFT) index. The DMFT was categorized according to two levels of severity (low DMFT 6) using the 75th percentile of the distribution as the cut-off point. Data analysis involved multiple logistic regression. RESULTS: Adolescents who were the second or later child were 1.90 times more likely to have a high DMFT, whilst being a taller adolescent had a protective effect on caries experience (OR = 0.04; 95% CI = 0.00-0.79). In addition, adolescents from rural areas (OR = 2.74; 95% CI = 1.56-4.82), those whose mothers had less than 8 years of education (OR = 2.10; 95% CI = 1.03-4.27) and those who reported high levels of paternal punishment (OR = 1.60; 95% CI = 1.02-2.52) had an increased risk of having a high DMFT. CONCLUSION: There is a relationship between height and dental caries experience in this sample of Brazilian adolescents.     

The relationship between traumatic dental injuries and adolescents' development along the life course

Few models have been proposed to explain the aetiology of traumatic dental injuries. Those that have, focus on risk factors at present stage of life. The contribution of risk factors for dental injuries at different stages of life needs to be investigated. OBJECTIVES: To test the relationship between life course experiences and the occurrence of traumatic dental injuries in adolescents. METHODS: A cross-sectional survey was used to collect data retrospectively. Out of a total number of 764 eligible 13-year-old-adolescents enrolled in private and public schools located in urban areas in the town of Cianorte, Brazil, 652 (85%) agreed to participate in the study. They were interviewed and examined for traumatic dental injuries by two trained dental epidemiologists using validated criteria. The interviews collected information on socioeconomic circumstances, family related variables, school grade and anthropometric measures (height and weight). RESULTS: Adolescent boys, those from non-nuclear families, those reporting high levels of paternal punishment and those who were at lower grades at school for their age were more likely to experience dental injuries than girls, adolescents from nuclear families, those reporting low levels of paternal punishment and those who were at higher grades at school. CONCLUSION: It was concluded that adolescents who experienced adverse psychosocial environments along the life course had more traumatic dental injuries than their counterparts who experienced more favourable environments.     

Play-based procedural preparation and support intervention for cranial radiation

Purpose

The primary objective of this study was to examine the relationship between play-based procedural preparation and support intervention and use of sedation in children with central nervous system (CNS) tumors during radiation therapy. The secondary objective was to analyze the cost-effectiveness of the intervention compared to costs associated with daily sedation.

Methods

A retrospective chart review was conducted, and 116 children aged 5–12 years met criteria for inclusion. Outcome measures included the total number of radiation treatments received, the number of treatments received with and without sedation, and the type and duration of interventions, which consisted of developmentally appropriate play, education, preparation, and distraction provided by a certified child life specialist.

Results

The results of univariate analyses showed that age, tumor location, and total number and duration of interventions were significantly associated with sedation use during radiation therapy. Multivariate analyses showed that, after adjustment for age, tumor location, and craniospinal radiation, a significant relationship was found between the total number and duration of the interventions and sedation use. The implementation of a play-based procedural preparation and support intervention provided by a certified child life specialist significantly reduced health-care costs by decreasing the necessity of daily sedation.

Conclusions

Support interventions provided by child life specialists significantly decreased both sedation use and the cost associated with daily sedation during cranial radiation therapy in children with CNS tumors. This study supports the value of the child life professional as a play-based developmental specialist and a crucial component of cost-effective healthcare.

     

Profiling postprandial thermogenesis in muscle and fat of sheep and the central effect of leptin administration

Brown adipose tissue thermogenesis is an important component of energy expenditure as exemplified in rodents. Other tissues such as white adipose tissue and muscle are also capable of thermogenesis, but regulation of heat production in these tissues is poorly understood. We used a relatively large animal model, the ovariectomized sheep, in which site-specific temperature measurements were made as an index of thermogenic output. Dataloggers were implanted into the retroperitoneal (visceral) fat, gluteal (sc) fat, and skeletal muscle of the hind limb, and were programmed to record temperature every 15 min. Animals (n = 4) were then placed on a feeding schedule (fed between 1100 and 1600 h) to entrain a postprandial response in thermogenesis. Baseline thermogenesis (0800-1100 h) was higher (P < 0.05) in visceral fat and muscle than in gluteal fat, whereas the amplitude of the postprandial increase was similar at all three sites. Intracerebroventricular infusion into the lateral ventricle of either vehicle (artificial cerebrospinal fluid) or leptin (10 microg/h at 100 microl/h) for 24 h (0900-0900) was performed in a cross-over design with a 1-wk recovery period between treatments. Central leptin infusion did not alter the basal thermogenic rate but markedly enhanced the postprandial response in both fat and muscle tissues. This was manifest by increased (P < 0.05) amplitude and duration of the postprandial thermogenic response, and the effect was greater in muscle and visceral fat than in gluteal fat. These data demonstrate that leptin is able to regulate thermogenesis in muscle, providing a novel target for the manipulation of energy balance.     

Laboratory investigation of immune responses to acellular pertussis vaccines when used for boosting adolescents after primary immunisation with whole cell pertussis vaccines: a comparison with data from clinical study

The lack of unequivocal immunological correlates of human protection and an absence of a validated animal model for acellular pertussis vaccines, compounded by limited opportunity to undertake efficacy studies in humans and laboratory evaluation side by side, has made it difficult to compare vaccines and formulations. In the present study, the effect on the booster response to pertussis in adolescents primed in infancy with whole cell pertussis vaccine, of three low dose acellular pertussis/diphtheria/tetanus toxoid (TdPa) formulations with or without inactivated poliomyelitis vaccine (IPV) components, was investigated. To assess the relationship between laboratory vaccine evaluation and clinical trial performance, parallel evaluation of the same TdPa vaccines were carried out in a mouse booster model with whole cell pertussis vaccine priming. Prior to boosting, the clinical subjects had low cell mediated immune responses (CMI) responses to pertussis vaccine components. After boosting, all TdPa formulations stimulated CMI responses to the pertussis vaccine components assessed. The booster responses to the pertussis antigens remained skewed towards Th1 type even though acellular pertussis vaccines were used. In general the antibody and CMI responses to pertussis antigens in the mouse model followed the trend seen in the human subjects. Protection against aerosol challenge with virulent Bordetella pertussis was related to the magnitude of the antibody and CMI responses in the mouse model. As in the human subjects, the responses remained skewed towards Th1 type.     

Normalization of gene expression measurements in tumor tissues: comparison of 13 endogenous control genes

For interpretation of quantitative gene expression measurements in clinical tumor samples, a normalizer is necessary to correct expression data for differences in cellular input, RNA quality, and RT efficiency between samples. In many studies, a single housekeeping gene is used for normalization. However, no unequivocal single reference gene (with proven invariable expression between cells) has been identified yet. As the best alternative, the mean expression of multiple housekeeping genes can be used for normalization. In this study, no attempt was made to determine the gold-standard gene for normalization, but to identify the best single housekeeping gene that could accurately replace the measurement of multiple genes. Expression patterns of 13 frequently used housekeeping genes were determined in 80 normal and tumor samples from colorectal, breast, prostate, skin, and bladder tissues with real-time quantitative RT-PCR. These genes included, large ribosomal protein, beta-actin, cyclophilin A, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerokinase 1, beta-2-microglobin, beta-glucuronidase, hypoxanthine ribosyltransferase (HPRT), TATA-box-binding protein, transferrin receptor, porphobilinogen deaminase, ATP synthase 6, and 18S ribosomal RNA. Principal component analysis was used to analyze these expression patterns, independent of the level of expression. Our approach identified HPRT as the single best reference gene that could be used as an accurate and economic alternative for the measurement of multiple housekeeping genes. We recommend this gene for future studies to standardize gene expression measurements in cancer research and tumor diagnostics until a definite gold standard has been determined.