Healthy-Shopping Dynamics: the Relative Healthiness of Food Purchases Throughout Shopping Trips

The obesity epidemic is largely driven by the overconsumption of unhealthy foods. Whereas existing research predominantly studies the healthiness of single food purchases, we investigate how the relative healthiness of a series of sequential purchases evolves throughout a single shopping trip. Our research demonstrates healthy-shopping dynamics, especially among overweight shoppers

Volcanic impacts on peatland microbial communities: A tephropalaeoecological hypothesis-test

Volcanic eruptions affect peatlands around the world, depositing volcanic ash (tephra) and a variety of chemicals including compounds of sulphur. These volcanic impacts may be important for many reasons, in particular sulphur deposition has been shown to suppress peatland methane flux, potentially reinforcing climatic cooling. Experiments have shown that sulphur deposition also forces changes in testate amoeba communities, potentially relating to the reduced methane flux. Large volcanic eruptions in regions with extensive peatlands are relatively rare so it is difficult to assess the extent to which volcanic eruptions affect peatland microbial communities; palaeoecological analyses across tephra layers provide a means to resolve this uncertainty. In this study, testate amoebae were analysed across multiple monoliths from a peatland in southern Alaska containing two tephras, probably representing the 1883 eruption of Augustine Volcano and a 20th Century eruption of Redoubt Volcano. Results showed relatively distinct and often statistically significant changes in testate amoeba community coincident with tephra layers which largely matched the response found in experimental studies of sulphur deposition. The results suggest volcanic impacts on peatland microbial communities which might relate to changes in methane flux

Heat-induced BRCA2 degradation in human tumours provides rationale for hyperthermia-PARP-inhibitor combination therapies

Purpose: Hyperthermia (40–44 °C) effectively sensitises tumours to radiotherapy by locally altering tumour biology. One of the effects of heat at the cellular level is inhibition of DNA repair by homologous recombination via degradation of the BRCA2-protein. This suggests that hyperthermia can expand the group of patients that benefit from PARP-inhibitors, a drug exploiting homologous recombination deficiency. Here, we explore whether the molecular mechanisms that cause heat-mediated degradation of BRCA2 are conserved in cell lines from various origins and, most importantly, whether, BRCA2 protein levels can be attenuated by heat in freshly biopted human tumours. Experimental design: Cells from four established cell lines and from freshly biopsied material of cervical (15), head- and neck (9) or bladder tumours (27) were heated to 42 °C for 60 min ex vivo. In vivo hyperthermia was studied by taking two biopsies of the same breast or cervical tumour: one before and one after treatment. BRCA2 protein levels were measured by immunoblotting. Results: We found decreased BRCA2-levels after hyperthermia in all established cell lines and in 91% of all tumours treated ex vivo. For tumours treated with hyperthermia in vivo, technical issues and intra-tumour heterogeneity prevented obtaining interpretable results. Conclusions: This study demonstrates that heat-mediated degradation of BRCA2 occurs in tumour material directly derived from patients. Although BRCA2-degradation may not be a practical biomarker for heat deposition in situ, it does suggest that application of hyperthermia could be an effective method to expand the patient group that could benefit from PARP-inhibitors

Evaluation of T2-W MR imaging and diffusion-weighted imaging for the early post-treatment local response assessment of patients treated conservatively for cervical cancer: a multicentre study

Objectives: To compare MR imaging with or without DWI and clinical response evaluation (CRE) in the local control evaluation of cervical carcinoma after radiotherapy. Methods: In a multicentre university setting, we prospectively included 107 patients with primary cervical cancer treated with radiotherapy. Sensitivity and specificity for CRE and MR imaging (with pre-therapy MR imaging as reference) (2 readers) were evaluated using cautious and strict criteria for identifying residual tumour. Nested logistic regression models were constructed for CRE, subsequently adding MR imaging with and without DWI as independent variables, as well as the pre- to post-treatment change in apparent diffusion coefficient (delta ADC). Results: Using cautious criteria, CRE and MR imaging with DWI (reader 1/reader 2) have comparable high specificity (83% and 89%/95%, respectively), whereas MR imaging without DWI showed significantly lower specificity (63%/53%) than CRE. Using strict criteria, CRE and MR imaging with DWI both showed very high specificity (99% and 92%/95%, respectively), whereas MR imaging without DWI showed significantly lower specificity (89%/77%) than CRE. All sensitivities were not significantly different. Addition of MR imaging with DWI to CRE has statistically significant incremental value in identifying residual tumour (reader 1: estimate, 1.06; p = 0.001) (reader 2: estimate, 0.62; p = 0.02). Adding the delta ADC did not have significant incremental value in detecting residual tumour. Conclusions: DWI significantly increases the specificity of MR imaging in the detection of local residual tumour. Furthermore, MR imaging with DWI has significant incremental diagnostic value over CRE, whereas adding the delta ADC has no incremental diagnostic value. Key Points: • If MR imaging is used for response evaluation, DWI should be incorporated• MR imaging with DWI has diagnostic value comparable/complementary to clinical response evaluation• Inter-reader agreement is moderate to fair for two experienced radiologist readers• Quantitative measurements of ADC early post-therapy have limited diagnostic valu

Families with BAP1-tumor predisposition syndrome in The Netherlands: Path to identification and a proposal for genetic screening guidelines

Germline pathogenic variants in the BRCA1-associated protein-1 (BAP1) gene cause the BAP1-tumor predisposition syndrome (BAP1-TPDS, OMIM 614327). BAP1-TPDS is associated with an increased risk of developing uveal melanoma (UM), cutaneous melanoma (CM), malignant mesothelioma (MMe), renal cell carcinoma (RCC), meningioma, cholangiocarcinoma, multiple non-melanoma skin cancers, and BAP1-inactivated nevi. Because of this increased risk, it is important to identify patients with BAP1-TPDS. The associated tumors are treated by different medical disciplines, emphasizing the need for generally applicable guidelines for initiating genetic analysis. In this study, we describe the path to identification of BAP1-TPDS in 21 probands found in the Netherlands and the family history at the time of presentation. We report two cases of de novo BAP1 germline mutations (2/21, 9.5%). Findings of this study combined with previously published literature, led to a proposal of guidelines for genetic referral. We recommend genetic analysis in patients with ≥2 BAP1-TPDS-associated tumors in their medical history and/or family history. We also propose to test germline BAP1 in patients diagnosed with UM <40 years, CM <18 years, MMe <50 years, or RCC <46 years. Furthermore, other candidate susceptibility genes for tumor types associated with BAP1-TPDS are discussed, which can be included in gene panels when testing patients

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P = 9.2 x 10(-20)), ER-negative BC (P = 1.1 x 10(-13)), BRCA1-associated BC (P = 7.7 x 10(-16)) and triple negative BC (P-diff = 2 x 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P = 2 x 10(-3)) and ABHD8 (PPeer reviewe

Childhood osteomyelitis: imaging characteristics

The purpose of this review is to illustrate the imaging findings of childhood osteomyelitis. The diagnosis of childhood osteomyelitis can be challenging. Clinical presentation and laboratory results can differ and are relatively unreliable. To date, its role in the assessment of treatment efficacy is not yet clear. This review article provides an overview of the different imaging modalities and imaging characteristics of childhood osteomyelitis. Levels of evidence for different modalities are presented. Paediatric radiology plays a pivotal role in the diagnosis of childhood osteomyelitis and can also be used to guide therapy and intervention. Although imaging is essential in the diagnostic process, cooperation between the physician and radiologist remains the cornerstone in accurately diagnosing childhood osteomyelitis. MAIN MESSAGES: • Imaging plays a pivotal role in the diagnosis of childhood osteomyelitis. • Cooperation between the clinician and radiologist is a very important aspect of making the diagnosis. • The initial imaging modality in childhood osteomyelitis is conventional imaging. • Normal conventional imaging does not exclude osteomyeliti