Does Risk of Brain Cancer Increase with Intracranial Volume? A Population-Based Case-Control Study

Abstract

Background

Glioma is the most common primary brain tumor and is believed to arise from glial stem cells. Despite large efforts there are limited established risk factors. It has been suggested that tissue with more stem cells may exhibit higher risk of cancer due to chance alone. Assuming a positive correlation between the number of stem cell divisions in an organ and size of the same organ, we hypothesized that variation in intracranial volume, as a proxy for brain size may be linked to risk of high-grade glioma.

Methods

Intracranial volume was calculated from pre-treatment 3D T1-weighted MRI brain scans from 124 patients with high-grade glioma and 995 general population based controls. Binomial logistic regression analyses were performed to ascertain the effect of intracranial volume and sex on the likelihood that participants have high-grade glioma.

Results

An increase in intracranial volume of 100 mL was associated with an odds ratio (OR) of high-grade glioma of 1.69 (95 % CI 1.44 to 1.98; P < 0.001). After adjusting for intracranial volume, female sex emerged as a risk factor for high-grade glioma (OR for male sex = 0.56, 95 % CI 0.33 to 0.93; P = 0.026).

Conclusions

Intracranial volume is strongly associated with risk of high-grade glioma. After correcting for intracranial volume, risk of high-grade glioma was higher in women. The development of glioma is correlated to brain size and may to a large extent be a stochastic event related to the number of cells at risk.

Antibody therapy targeting CD19 for B-cell non-Hodgkin lymphoma

Combined immunotherapy encompassing intratumoral poly-ICLC, dendritic-cell vaccination and radiotherapy in advanced cancer patients

Abstract

BACKGROUND

Combination immunotherapy has the potential to achieve additive or synergistic effects. Combined local injections of dsRNA analogues (mimicking viral RNA) and repeated vaccinations with tumor-lysate loaded dendritic cells shows efficacy against colon cancer mouse models. In the context of immunotherapy, radiotherapy can exert beneficial abscopal effects.

PATIENTS AND METHODS

In this two-cohort pilot phase I study, 15 advanced cancer patients received two 4-week cycles of four intradermal daily doses of monocyte-derived dendritic cells preloaded with autologous tumor lysate and matured for 24h with poly-ICLC (Hiltonol), TNF-α and IFN-α. On days +8 and +10 of each cycle, patients received intratumoral image-guided 0.25 mg injections of the dsRNA-analogue Hiltonol. Cyclophosphamide 600 mg/m² was administered one week before. Six patients received stereotactic ablative radiotherapy (SABR) on selected tumor lesions, including those injected with Hiltonol. Expression of 25 immune-relevant genes was sequentially monitored by RT-PCR on circulating PBMCs and serum concentrations of a cytokine panel were sequentially determined before and during treatment. Pre- and post-treatment PBMC from patients achieving durable stable disease were studied by IFNγ ELISPOT-assays responding to tumor-lysate loaded DC and by TCRβ sequencing.

RESULTS

Combined treatment was, safe and well tolerated. One heavily pretreated castration-resistant prostate cancer patient experienced a remarkable mixed abscopal response to SABR+immunotherapy. No objective responses were observed, while nine patients presented stable disease (five of them in the six-patient radiotherapy cohort). Intratumoral Hiltonol increased IFN-β and IFN-α mRNA in circulating PBMC. DC vaccination increased serum IL-12 and IL-1β concentrations, especially in patients presenting stable disease (SD). IFNγ-ELISPOT reactivity to tumor lysates was observed in two patients experiencing durable SD.

CONCLUSIONS

This radio-immunotherapy combination strategy, aimed at resembling viral infection in tumor tissue in combination with a dendritic-cell vaccine and SABR, is safe and shows immune-associated activity and signs of preliminary clinical efficacy.

Detection of somatic RAS mutations in circulating tumor DNA from metastatic colorectal cancer patients: are we ready for clinical use?

Associations Between Maternal Obesity and Pregnancy Hyperglycemia and Timing of Pubertal Onset in Adolescent Girls: A Population-Based Study

Abstract

Early puberty is associated with adverse health outcomes. We investigated whether in utero exposure to maternal obesity is associated with daughters' pubertal timing using 15,267 racially/ethnically diverse Kaiser Permanente Northern California members age 6-11 years with pediatrician-assessed Tanner staging (2003-2017). We extracted maternal body mass index (BMI) during pregnancy from the electronic health record. Using a proportional hazards model with interval censoring we examined the associations between maternal obesity and girl's pubertal timing, and effect modification by race/ethnicity and mediation by pre-pubertal BMI. Maternal obesity (BMI ≥30 kg/m²) or overweight (BMI 25-29.9 kg/m²) was associated with earlier breast onset in girls [hazard ratio (HR) = 1.39, 95% confidence interval (CI): 1.30, 1.49; HR = 1.21, 95% CI: 1.13, 1.29, respectively], adjusting for girls' race/ethnicity, maternal age, education, parity and smoking during pregnancy. There was interaction by race/ethnicity for associations between maternal obesity and girls' pubic hair onset: associations were strongest among Asian and white girls [HR = 1.53, 95% CI: 1.24, 1.90; HR = 1.34, 95% CI: 1.18, 1.52, respectively] and absent for African-American girls. Adjustment for girls' pre-pubertal BMI only slightly attenuated associations. Our results suggest the importance of maternal metabolic factors during pregnancy on girls' pubertal timing and potential differences in the associations by race/ethnicity.

The Association of Arsenic Exposure and Arsenic Metabolism with the Metabolic Syndrome and its Individual Components: Prospective Evidence from the Strong Heart Family Study

Abstract

Inorganic arsenic exposure is ubiquitous and both exposure and inter-individual differences in its metabolism have been associated with cardiometabolic risk. The association between arsenic exposure and arsenic metabolism with metabolic syndrome and its individual components, however, is relatively unknown. We used poisson regression with robust variance to evaluate the association between baseline arsenic exposure (urine arsenic levels) and metabolism (relative percentage of arsenic species over their sum) with incident metabolic syndrome and its individual components (elevated waist circumference, elevated triglycerides, reduced HDL, hypertension, elevated fasting plasma glucose) in 1,047 participants from the Strong Heart Family Study, a prospective family-based cohort in American Indian communities (baseline visits in 1998-1999 and 2001-2003, follow-up visits in 2001-2003 and 2006-2009). 32% of participants developed metabolic syndrome over follow-up. An IQR increase in arsenic exposure was associated with 1.19 (95% CI: 1.01, 1.41) greater risk for elevated fasting plasma glucose but not with other individual components or overall metabolic syndrome. Arsenic metabolism, specifically lower MMA% and higher DMA% was associated with higher risk of overall metabolic syndrome and elevated waist circumference, but not with any other component. These findings support there is a contrasting and independent association between arsenic exposure and arsenic metabolism with metabolic outcomes which may contribute to overall diabetes risk.

RE: “PROSPECTIVE COHORT STUDY OF UTERINE FIBROIDS AND MISCARRIAGE RISK”

THE AUTHORS REPLY

Impact of dynamical and microphysical schemes on black carbon prediction in a regional climate model over India

Abstract

Aerosol concentrations and their properties strongly depend on dynamics of atmosphere. Effects of physical and dynamical parameterizations on meteorology and black carbon (BC) mass in Weather Research and Forecasting model coupled with Chemistry (WRF-CHEM) are investigated over India. Simulations are performed in ten experiments considering two boundary layer, three cumulus parameterization, and five microphysics schemes during winter and monsoon of 2008. Morrison double-moment physical parameterization, Yonsei University boundary layer parameterization with Kain-Fritsch and Grell-Freitas cumulus parameterization schemes are found suitable to simulate meteorology and BC mass over India. BC mass is found to be underestimated in almost all experiments during winter; while, BC mass is overestimated in monsoon over Ahmedabad, Delhi, and Kanpur, which suggests inefficient wet scavenging of BC in monsoon, while lower emission rate may cause differences in winter. The results will be useful in understanding parameterizations and their impact on aerosols.

On valuing impairment

Abstract

In The Minority Body, Elizabeth Barnes rejects prevailing social constructionist accounts of disability for two reasons. First, because they understand disability in terms of oppressive social responses to bodily impairment, they cannot make sense of disability pride. Second, they maintain a problematic distinction between impairment and disability. In response to these challenges, this paper defends a version of the social model of disability, which we call the Social Exclusion Model. On our account, to be disabled is to be in a bodily or psychological state that is represented as an impairment in the prevailing ideology of one's society, and to be excluded from valuable activities on the basis of this representation. While this model refers to a distinction between disability and impairment, it makes no presuppositions about which bodies function 'normally' and which do not. It is the ideology of impairment rather than impairment itself that does any work to determine whether a person is disabled. We argue that this model answers some of the important objections that Barnes raises against prevailing social constructionist accounts of disability, and that it's focus on the oppressive social positioning of disabled people gives it explanatory power that Barnes's own account lacks.

Vitamin D Status and Cardiovascular Risk in Obesity: Effect of Physical Activity in Nonvitamin D Supplemented Adolescents

Metabolic Syndrome and Related Disorders, Ahead of Print.

Untangling Waist Circumference and Hip Circumference from Body Mass Index with a Body Shape Index, Hip Index, and Anthropometric Risk Indicator

Metabolic Syndrome and Related Disorders, Ahead of Print.

Sexual Coercion and Women's Education: A Pilot Study

Violence and Gender, Ahead of Print.

Addressing Onset and Desistance of Bullying Behavior: Surveying Perpetrators

Violence and Gender, Ahead of Print.

Erratum to: Perioperative Corticosteroids Reduce Short-Term Edema and Ecchymosis in Rhinoplasty: A Meta-Analysis

Coroneos CJ, Voineskos SH, Cook DJ, Farrokhyar F, Thoma A. Perioperative Corticosteroids Reduce Short-Term Edema and Ecchymosis in Rhinoplasty: A Meta-Analysis. Aesthet Surg J. 2016; 36(2):136–146; DOI: https://doi.org/10.1093/asj/sjv138

Response to “The Importance of Clinically Relevant Research When Making Comparisons”

We thank you for the opportunity to respond to this Letter to the Editor entitled "The Importance of Clinically Relevant Research When Making Comparisons"¹ which attempts to critique our recent publication "Hypochlorous Acid vs Povidone-Iodine Containing Irrigants: Which Antiseptic is More Effective for Breast Implant Pocket Irrigation?"²

The Importance of Clinically Relevant Research When Making Comparisons

We wish to thank the authors for their efforts in Australia to acquire and evaluate this product "PhaseOne" which is a form of pure hypochlorous acid (HOCl) not available in their country and that has never been marketed there.¹ The authors of this study have previously published quite interesting and significant findings regarding dried biofilms on hard surfaces in the healthcare environment.^2-4 In this particular study, though, standard methods that might be considered directly applicable to disinfection of soiled hard surfaces and equipment⁵ – involving addition of 5% bovine calf serum (BCS) to simulate surface "soiling" – were inappropriately applied to the evaluation of the potential performance of antiseptics in the surgical breast pocket at time of implant placement. Based on actual protein measurements of pocket fluid taken at the time of breast implant surgery (as noted below), the use of the 5% bovine serum in the experiments in this study, and the excessively high relative resultant levels of protein in relation to the amount of antiseptic tested, has produced invalid findings that have no relevance to the actual clinical setting.

Decadal changes in surface ozone at the tropical station Thiruvananthapuram (8.542° N, 76.858° E), India: effects of anthropogenic activities and meteorological variability

Abstract

This paper presents the first observational results from an Indian station on the long-term changes in surface ozone (O₃)—a major environmental pollutant and green house gas—over a period of about 40 years. It is based on the in situ measurements carried out during 1973–1975, 1983–1985, 1997–1998 and 2004–2014 at the tropical coastal station, Thiruvananthapuram. From 1973 to 1997, surface O₃ shows a slow increase of ~ 0.1 ppb year⁻¹ and a faster increase of 0.4 ppb year⁻¹ afterwards till 2009 after which it showed a levelling off till 2012 followed by a minor decrease. The highest rate of increase is observed during 2005 to 2009 (2 ppb year⁻¹), and the overall increase from 1973 to 2012 is ~ 10 ppb. The increase in day time O₃ (peak O₃) is estimated as 0.42 ppb year⁻¹ during 1997–2012 and 2.93 ppb year⁻¹ during 2006–2012. Interestingly, the long-term trend in O₃ showed seasonal dependence which is more pronounced during O₃ peaking seasons (winter/summer). The observed trends were analysed in the light of the changes in NO₂, a major outcome of anthropogenic activities and methane which has both natural and anthropogenic sources and also meteorological parameters. Surface O₃ and NO_x exhibited positive association, but with varying rate of increase of O₃ for NO_x < 4 and > 4 ppb. Methane, a precursor of O₃ also showed increase in tune with O₃. Unlike many other high-latitude locations, meteorology plays a significant role in the long-term trends in O₃ at this tropical site with water vapour abundance and strong solar irradiance which favour photochemistry. A comparison with the corresponding changes in the satellite-retrieved tropospheric column O₃ (TCO) also showed an increase of 0.03 DU year⁻¹ during 1996–2005 which enhanced to 0.12 DU year⁻¹ after 2005. Both surface O₃ and satellite-retrieved TCO were positively correlated with daily maximum temperature, increasing at the rate of 1.54 ppb °C⁻¹ and 1.9 DU °C⁻¹, respectively, on yearly basis. Surface O₃ is found to be negatively correlated with water vapour content (ρ_v) at this tropical site, but at higher levels of ρ_v, O₃ shows a positive trend.

Effects of silver nanoparticles on stress biomarkers of Channa striatus : immuno-protective or toxic?

Abstract

Nanotechnology is a novel arena with promising applications in the field of medicine, industry, and agriculture including fisheries. Cross-disciplinary interactions and the application of this technology in biological systems have led to the innovation of novel nanoparticle antioxidants, which are the subject of our study. In context with above background, we designed an experiment on nano-silver to elucidate its role for mitigation of abiotic and biotic stress. Three diets were formulated viz. silver nanoparticles (Ag-NPs) incorporated at 0.5 and 1 mg/kg diet and control diet (Ag-NPs at 0 mg/kg). Fish were exposed to sublethal level of 1/25th of LC₅₀ (4 ppm) of lead (Pb) and temperature at 34 °C. The effect of Ag-NPs on productive performance (weight gain %, feed conversion ratio, protein efficiency ratio, and specific growth rate), stress biomarkers (catalase, super oxide dismutase, glutathione-s-transferase, acetylcholine esterase, cortisol, heat shock protein), biochemical and immunological response (protein and carbohydrate metabolic enzymes, phagocytic activity, serum total protein and albumin: globulin ratio), histopathology alterations in the liver and gill as well as survival of Channa striatus, following challenge with pathogenic bacteria were evaluated. Dietary Ag-NPs at 0.5-mg supplementation improved growth performance, immunity, survival, and reduced stress biomarker such as HSP 70, cortisol, and blood glucose in various fish tissues. Exposure to Pb and high temperature and group fed with Ag-NPs (1 mg/kg diet) demonstrated remarkable changes in the histo-architect of liver such as pyknotic nuclei, pyknosis, leucocyte infiltration, hemorrhage and karyokinesis, blood vessels with nucleated, lipid vacuoles in the liver tissue. Histology of gill displayed hyperplasia, aneurism, blood congestion, severe telengiectiasis, epithelial lifting, curling of secondary lamella, hyperplasia of epithelial cell of secondary lamella in the group exposed to lead and high temperature and supplemented with Ag-NPs at 1 mg/kg diet. In addition to histopathology, feeding with Ag-NPs at 1 mg/kg diet deteriorated and altered all studied parameters including reduced growth performance. Results obtained in the present study suggest that supplementation of Ag-NPs at 0.5 mg/kg diet has a definitive role to play in the mitigation of abiotic and biotic stress in C. striatus.

Management of Pediatric Urticaria with Review of the Literature on Chronic Spontaneous Urticaria in Children

Publication date: Available online 14 March 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Moshe Ben-Shoshan, Clive E. Grattan
There are substantial knowledge gaps related to diagnosis and management of pediatric cases of chronic urticaria, and in particular chronic spontaneous urticaria (CSU). In this article we aimed to review the diagnosis and management of chronic urticaria in children and CSU in particular. We conducted a systematic review of articles published in English and French on pediatric CSU management in the last 10 years. We included experimental studies (eg, randomized controlled trials), other experimental designs (eg, nonrandomized methods of assignment, controlled before-after studies, and interrupted time series), and observational studies (eg, prospective or retrospective cohort studies, cross-sectional studies, case-control studies, and case reports). Our findings highlight the efficacy of second-generation antihistamines for the treatment of CSU in children and supports the use of omalizumab for more severe cases. However, our study also reveals severe knowledge gaps related to the best management strategy in children with more severe/refractory cases of CSU. Future studies are required to establish the beneficial effect of high doses of second-generation antihistamines as well as the effectiveness and safety of omalizumab and other biologics in young children.