Sequencing-based functional assays for classification of BRCA2 variants in mouse ESCs.

Sequencing of genes, such as BRCA1 and BRCA2, is recommended for individuals with a personal or family history of early onset and/or bilateral breast and/or ovarian cancer or a history of male breast cancer. Such sequencing efforts have resulted in the identification of more than 17,000 BRCA2 variants. The functional significance of most variants remains unknown; consequently, they are called variants of uncertain clinical significance (VUSs).

A computational model for classification of BRCA2 variants using mouse embryonic stem cell-based functional assays.

Sequencing-based genetic tests to identify individuals at increased risk of hereditary breast and ovarian cancers have resulted in the identification of more than 40,000 sequence variants of BRCA1 and BRCA2. A majority of these variants are considered to be variants of uncertain significance (VUS) because their impact on disease risk remains unknown, largely due to lack of sufficient familial linkage and epidemiological data. Several assays have been developed to examine the effect of VUS on protein function, which can be used to assess their impact on cancer susceptibility.

Calibration of Pathogenicity Due to Variant-Induced Leaky Splicing Defects by Using Exon 3 as a Model System.

is a clinically actionable gene implicated in breast and ovarian cancer predisposition that has become a high priority target for improving the classification of variants of unknown significance (VUS). Among all VUS, those causing partial/leaky splicing defects are the most challenging to classify because the minimal level of full-length (FL) transcripts required for normal function remains to be established. Here, we explored exon 3 (e3) as a model for calibrating variant-induced spliceogenicity and estimating thresholds for haploinsufficiency.

Functional evaluation of five BRCA2 unclassified variants identified in a Sri Lankan cohort with inherited cancer syndromes using a mouse embryonic stem cell-based assay.

Next-generation sequencing of Sri Lankan families with inherited cancer syndromes resulted in the identification of five BRCA2 variants of unknown clinical significance. Interpreting such variants poses significant challenges for both clinicians and patients. Using a mouse embryonic stem cell-based functional assay, we found I785V, N830D, and K2077N to be functionally indistinguishable from wild-type BRCA2.

Synthetic viability by BRCA2 and PARP1/ARTD1 deficiencies.

Poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) olaparib has been approved for treatment of advanced ovarian cancer associated with BRCA1 and BRCA2 mutations. BRCA1- and BRCA2-mutated cells, which are homologous recombination (HR) deficient, are hypersensitive to PARPi through the mechanism of synthetic lethality. Here we examine the effect of PARPi on HR-proficient cells.

Impact of typical rather than nutrient-dense food choices in the US Department of Agriculture Food Patterns.

Background: The US Department of Agriculture (USDA) Food Patterns, released as part of the 2010 Dietary Guidelines for Americans, are designed to meet nutrient needs without exceeding energy requirements. They identify amounts to consume from each food group and recommend that nutrient-dense forms-lean or low-fat, without added sugars or salt-be consumed. Americans fall short of most food group intake targets and do not consume foods in nutrient-dense forms.

Updated US Department of Agriculture Food Patterns meet goals of the 2010 dietary guidelines.

The US Department of Agriculture Food Patterns were updated for the 2010 Dietary Guidelines for Americans to meet new nutrition goals and incorporate results of food pattern modeling requested by the Dietary Guidelines Advisory Committee. The purpose of this article is to describe the process used and changes in the updated patterns. Changes include renaming the Meat and Beans and Milk Groups to the Protein Foods and Dairy Groups, respectively, to be more encompassing of foods in each.

The US Department of Agriculture Automated Multiple-Pass Method reduces bias in the collection of energy intakes.

Background: The US Department of Agriculture Automated Multiple-Pass Method (AMPM) is used for collecting 24-h dietary recalls in What We Eat In America, the dietary interview component of the National Health and Nutrition Examination Survey. Because the data have important program and policy applications, it is essential that the validity of the method be tested.

Objective: The accuracy of the AMPM was evaluated by comparing reported energy intake (EI) with total energy expenditure (TEE) by using the doubly labeled water (DLW) technique.

Effect of snacking frequency on adolescents' dietary intakes and meeting national recommendations.

Purpose: To determine how snacking level impacts intake of nutrients and food groups and assists in meeting recommendations outlined in the U.S. Department of Agriculture's MyPyramid Food Guidance System.

Older adults who use vitamin/mineral supplements differ from nonusers in nutrient intake adequacy and dietary attitudes.

Objective: To measure nutrient intake adequacy of vitamin/mineral supplement users and nonusers aged 51 years and older, determine the efficacy of supplement practices in compensating for dietary deficits, and identify predictors of supplement use.

Design: Analyses of two 24-hour recalls, demographic variables, and attitude questions collected during the Continuing Survey of Food Intakes by Individuals and Diet and Health Knowledge Survey in 1994 to 1996. Data were weighted to be representative of older Americans.

Tumor resection cavity administered iodine-131-labeled antitenascin 81C6 radioimmunotherapy in patients with malignant glioma: neuropathology aspects.

Introduction: The neurohistological findings in patients treated with targeted beta emitters such as (131)I are poorly described. We report a histopathologic analysis from patients treated with combined external beam therapy and a brachytherapy consisting of a (131)I-labeled monoclonal antibody (mAb) injected into surgically created resection cavities during brain tumor resections.

Methods: Directed tissue samples of the cavity walls were obtained because of suspected tumor recurrence from 28 patients.

A new portion size estimation aid for wedge-shaped foods.

Dietary surveys are important for understanding food consumption patterns in national studies, clinical research, and patient counseling. Portion size estimation aids usually increase accuracy of consumers' reports of the amount of food they ate in dietary surveys. However, wedge-shaped foods (eg, pie, cake, and pizza) pose special problems; this shape is not easily estimated by previously available portion size estimation aids.

Accuracy of reporting dietary intake using various portion-size aids in-person and via telephone.

Objective: This study compared the accuracy with which respondents reported food intake using different portion-size estimation aids (PSEAs) and determined whether the interview technique affected the accuracy of reporting.

Design: Participants chose preweighed foods from a buffet line, leftovers were weighed, and actual amounts eaten were calculated. The next day during dietary interviews, participants estimated amounts eaten using one of four procedures, including telephone or in-person interviews, two-dimensional or three-dimensional PSEAs, and guiding or not guiding participants to certain aids.

Dietary behaviors associated with total fat and saturated fat intake.

Objective: To estimate percentages of US adults who have adopted behaviors promoted by dietary guidance about how to reduce fat intake, and to assess relationships between these behaviors and intake of energy from total and saturated fat.

Design: Relationships were examined between intake of total and saturated fat from two 24-hour recalls in the US Department of Agriculture's 1994-1996 Continuing Survey of Food Intakes by Individuals and responses to 19 fat-related behavior questions on the follow-up Diet and Health Knowledge Survey (DHKS).

Subjects: Data are from a national sample of 5,649 individuals 20 years of age and older.