Food deserts, endometrial cancer survivors, and healthy food access: Is it equitable in rural America? - A geospatial analysis.

OBJECTIVE: To examine endometrial cancer survivors' access to healthy food resources recommended by the Society of Gynecologic Oncology (SGO) in relation to food deserts and social health determinants. METHODS: Participants included women seen for endometrial cancer treatment at an academic medical center in the Deep South from 2015 to 2020 who lived in South Carolina. Demographic and comorbidity data were abstracted from medical records. Food desert data were obtained from the United States Department of Agriculture (USDA). Each patient was assigned a socioeconomic (SES) score (SES-1 = low, SES-5 = high) using census data and a social vulnerability index (SVI) using Center for Disease Control and Prevention (CDC) data for neighborhood adverse health effects. Geospatial techniques assessed patients' driving distance from home to a healthy food resource. RESULTS: Of the 736 endometrial cancer survivors, 31% identified as African American, and 30% lived in low SES (SES-1, SES-2) census blocks. Most survivors had low grade disease (63%) and 76% with stage 1-2 disease. Seventy percent of patients were obese (BMI ≥30 kg/m2). Forty percent of survivors lived in a food desert. Survivors living in a food desert with low SES had significantly higher social vulnerability (p = 0.0001) and lower median income (p = 0.0001). Those with low SES and living in a food desert drove further (p = 0.05, range 0.017-12.0 miles). CONCLUSION: Obesity rates were high in endometrial cancer survivors living in the Deep South. Survivors with higher social vulnerability and lower SES were more likely to live in food deserts with decreased access to healthy food resources.

Polygenic Variation Underlying Educational Attainment and Attention-Deficit/Hyperactivity Disorder Indexes Behavior Ratings of Executive Functions in Child Psychiatry Outpatients.

OBJECTIVE: We leveraged common genetic variation underlying ADHD, educational attainment (EA) and cognition (COG) to understand the nature of the Behavior Rating Inventory for Executive Functions (BRIEF) and its relationship to academic functioning. METHOD: Participants were 991 youth, ages 7 to 17, consecutively referred for neuropsychiatric evaluation. Polygenic scores (PGS) for ADHD, EA, and COG were related to the BRIEF using regression analyses. Structural equation models were used to examine the associations between the PGS, BRIEF and academic outcomes (math, reading, and special education services [EDPLAN]). RESULTS: After modeling the PGS together, only the EA and ADHD PGS significantly associated with the BRIEF. The BRIEF partially mediated the relationships between EA PGS with math and EDPLAN and fully mediated the relationship between ADHD PGS and EDPLAN. CONCLUSION: Genetic data extend evidence that the BRIEF measures a construct relevant to educational success that differs from what is indexed by cognitive testing.

Point-of-care biomarker assay for rapid multiplexed detection of CRP and IP-10.

Rapid and accurate measurements of immune protein markers are essential for diagnosis and treatment in all clinical settings. The recent pandemic has revealed a stark need for developing new tools and assays that could be rapidly used in diverse settings and provide useful information to clinicians. Here, we describe the development and test application of a novel one-step CRP/IP-10 duplex assay for the LightDeck platform capable of delivering reproducible and accurate measurements in under eight minutes. We used the optimized assay to measure CRP and IP-10 levels in human blood and serum samples from healthy, SARS-CoV-2 (COVID-19) positive, and influenza-like illness (ILI) presenting patients. Our results agreed with previously published analyte levels and enabled us to make statistically significant comparisons relevant to multiple clinical parameters. Our duplex assay is a simple and powerful tool for aiding prognostic decision-making in diverse settings.

The Influence of Absorbent Products on Skin Integrity: A Scoping Review.

PURPOSE: Absorbent products are commonly used to absorb urine and fecal matter and to mitigate potential skin complications such as incontinence-associated dermatitis (IAD). Evidence concerning the effect these products have on skin integrity is limited. This scoping review aimed to explore the evidence/literature on the effect of absorbent containment products on skin integrity. METHOD: A scoping literature review. SEARCH STRATEGY: The electronic databases CINAHL, Embase, MEDLINE, and Scopus were searched for published articles between 2014 and 2019. Inclusion criteria were studies that focused on urinary and/or fecal incontinence, use of incontinent absorbent containment products, impact on skin integrity, and published in English. The search identified a total of 441 articles that were identified for the title and abstract review. FINDINGS: Twelve studies met inclusion criteria and were included in the review. Variability in the study designs did not allow firm conclusions regarding which absorbent products contributed to or prevented IAD. Specifically, we found variations in assessment of IAD, study settings, and types of products used. IMPLICATIONS: There is insufficient evidence to support the effectiveness of one product category over another for maintaining skin integrity in persons with urinary or fecal incontinence. This paucity of evidence illustrates the need for standardized terminology, a widely used instrument for assessment of IAD, and identification of a standard absorbent product. Additional research using both in vitro and in vivo models, along with real-world clinical studies, is needed to enhance current knowledge and evidence of the impact of absorbent products on skin integrity.

Adjunct Antihyperglycemic Agents in Overweight and Obese Adults With Type 1 Diabetes.

OBJECTIVE: People with type 1 diabetes often have suboptimal glycemic control. The gold standard of treatment is basal-bolus insulin or subcutaneous insulin infusion via insulin pump. Although insulin therapy improves glycemic control, weight gain and hypoglycemia often limit achievement of hemoglobin A1C (A1C) goals. The number of people with type 1 diabetes who are overweight or obese is increasing, and there are many similarities between what was historically called type 1 and type 2 diabetes. Therefore, there is rationale for using antihyperglycemic agents that target other pathophysiological abnormalities to facilitate weight loss and improve glycemic control. DATA SOURCES: We performed a MEDLINE search from 1975 through October 2018 to identify articles that studied noninsulin agents in adults with type 1 diabetes and body mass index (BMI) ≥25 kg/m2. STUDY SELECTION AND DATA EXTRACTION: Identified articles were included if the study duration was ≥4 weeks, included ≥20 patients, and set mean baseline BMI ⩾25kg/m2. DATA SYNTHESIS: This review summarizes 32 clinical trials. Amylin mimetics, sodium-glucose-like transporter-2 inhibitors, and glucagon-like-peptide-1 receptor agonists demonstrate the greatest improvements in body weight and A1C. The most common adverse effects are hypoglycemia and ketosis. Relevance to Patient Care and Clinical Practice: Patients with type 1 diabetes may have interest in starting noninsulin agents. Clinicians need to be knowledgeable in the efficacy and adverse effect profile of these agents, specifically in people with type 1 diabetes. CONCLUSIONS: Adding noninsulin antihyperglycemic agents may benefit select overweight or obese adults with type 1 diabetes. These agents are off-label, and if used, close monitoring is essential.

Predicting neuroblastoma using developmental signals and a logic-based model.

Genomic information from human patient samples of pediatric neuroblastoma cancers and known outcomes have led to specific gene lists put forward as high risk for disease progression. However, the reliance on gene expression correlations rather than mechanistic insight has shown limited potential and suggests a critical need for molecular network models that better predict neuroblastoma progression. In this study, we construct and simulate a molecular network of developmental genes and downstream signals in a 6-gene input logic model that predicts a favorable/unfavorable outcome based on the outcome of the four cell states including cell differentiation, proliferation, apoptosis, and angiogenesis. We simulate the mis-expression of the tyrosine receptor kinases, trkA and trkB, two prognostic indicators of neuroblastoma, and find differences in the number and probability distribution of steady state outcomes. We validate the mechanistic model assumptions using RNAseq of the SHSY5Y human neuroblastoma cell line to define the input states and confirm the predicted outcome with antibody staining. Lastly, we apply input gene signatures from 77 published human patient samples and show that our model makes more accurate disease outcome predictions for early stage disease than any current neuroblastoma gene list. These findings highlight the predictive strength of a logic-based model based on developmental genes and offer a better understanding of the molecular network interactions during neuroblastoma disease progression.

Single-cell transcriptome analysis of avian neural crest migration reveals signatures of invasion and molecular transitions.

Neural crest cells migrate throughout the embryo, but how cells move in a directed and collective manner has remained unclear. Here, we perform the first single-cell transcriptome analysis of cranial neural crest cell migration at three progressive stages in chick and identify and establish hierarchical relationships between cell position and time-specific transcriptional signatures. We determine a novel transcriptional signature of the most invasive neural crest Trailblazer cells that is consistent during migration and enriched for approximately 900 genes. Knockdown of several Trailblazer genes shows significant but modest changes to total distance migrated. However, in vivo expression analysis by RNAscope and immunohistochemistry reveals some salt and pepper patterns that include strong individual Trailblazer gene expression in cells within other subregions of the migratory stream. These data provide new insights into the molecular diversity and dynamics within a neural crest cell migratory stream that underlie complex directed and collective cell behaviors.

DAN (NBL1) promotes collective neural crest migration by restraining uncontrolled invasion.

Neural crest cells are both highly migratory and significant to vertebrate organogenesis. However, the signals that regulate neural crest cell migration remain unclear. In this study, we test the function of differential screening-selected gene aberrant in neuroblastoma (DAN), a bone morphogenetic protein (BMP) antagonist we detected by analysis of the chick cranial mesoderm. Our analysis shows that, before neural crest cell exit from the hindbrain, DAN is expressed in the mesoderm, and then it becomes absent along cell migratory pathways. Cranial neural crest and metastatic melanoma cells avoid DAN protein stripes in vitro. Addition of DAN reduces the speed of migrating cells in vivo and in vitro, respectively. In vivo loss of function of DAN results in enhanced neural crest cell migration by increasing speed and directionality. Computer model simulations support the hypothesis that DAN restrains cell migration by regulating cell speed. Collectively, our results identify DAN as a novel factor that inhibits uncontrolled neural crest and metastatic melanoma invasion and promotes collective migration in a manner consistent with the inhibition of BMP signaling.

Impaired Healing of a Donor Site Following Harvest of Bone: A Case Study.

BACKGROUND: A 77-year-old man with diabetes mellitus and hypertension experienced wound dehiscence and tissue necrosis following harvesting of bone from the mid-portion of his right fibula needed to create an osteofascial cutaneous graft, a free flap removing an artery and a vein to the bone-fibula and skin, via peroneal vessels. CASE: The patient experienced delayed wound healing due to multiple local and systemic factors, including possible venous insufficiency and effects related to radiation treatment to his jaw. He was referred to Home Health for wound care related to dehiscence of the surgical bone donor site. This case study describes assessment and management of this complex wound. CONCLUSION: Our experiences with this case reinforce the need for thorough assessment of both local and systemic factors when managing a complex wound. We recommend evaluation of lower extremity vascular status prior to surgery. We further recommend consideration of postoperative compression bandaging of the lower limb, after ruling out arterial insufficiency, to assist venous return. The course of wound healing in this case also suggests that the effects of radiation on wound healing are not limited to the area being radiated.

Biases in preferences for sequences of outcomes in monkeys.

Movies, vacations, and meals are all examples of events composed of a sequence of smaller events. How do we go from our evaluations of each scene in a movie to an evaluation of the sequence as a whole? In theory, we should simply average the values of the individual events. In practice, however, we are biased towards sequences where each element tends to be better than the previous, where the last value is large, and we overweight the best (or worst) part of the sequence. To study how general these biases are we examined monkeys' preferences for sequences of rewards in a novel reward repeat task. Monkeys were first given a sequence of rewards and then chose between repeating the sequence or receiving a standard comparator sequence. We found that, like humans, monkeys overweight events that happen later in a sequence, so much so that adding a small reward to the end of a sequence can paradoxically reduce its value. Monkeys were also biased towards sequences with large peak values (the highest value in the sequence), but only following a working memory challenge, suggesting that this preference may be driven by memory limitations. These results demonstrate the cross-species nature of biases in preferences for sequences of outcomes. In addition, monkeys' consistent preference for sequences in which large values occur later challenges the generality of discounting models of intertemporal choice in animals.

Canine perianal gland carcinoma-associated antigens defined by monoclonal antibodies.

This study was conducted to distinguish canine perianal gland carcinomas from adenomas using monoclonal antibodies (MAbs). The adenomas generally retain the lobular architecture, but some may contain focal areas of cellular pleomorphism. These changes may suggest malignant transformation and have led to discordant interpretations. To address this histopathological confusion, two perianal gland carcinoma-associated antigens were defined by mouse MAbs 4A9 and 1A10. These MAbs, generated against a canine mammary carcinoma cell line, reacted strongly with perianal gland carcinoma in preliminary screening and therefore were selected for further investigation. Cellular expression of antigens was examined by indirect immunoperoxidase (IP) assay using MAbs 4A9 and 1A10 against formalin-fixed, paraffin-embedded sections of normal and tumor tissue. Of 25 perianal gland carcinomas, 4A9 antigen was expressed in 100% and 1A10 antigen in 84%. In contrast, perianal gland adenomas were negative for both antigens, and little or no reactivity was detected with normal perianal glands. With eight perianal gland tumors, diagnosis of carcinoma versus adenoma was histologically equivocal, while IP assays consistently revealed focal expression of the 4A9 and 1A10 antigens in these tumors, and the staining coincided with foci of anaplastic cells having a high mitotic index. This group of tumors was designated adenoma/carcinoma in situ. Results suggest that 4A9 and 1A10 antigens are markers of carcinoma and malignant transformation in canine perianal gland tumors, and can be very useful as diagnostic reagents where the identification of carcinoma versus adenoma requires additional clarification beyond routine histopathological examination.

Canine mammary tumor cells transfected with B7-1 or B7-2 stimulate proliferation of peripheral blood mononuclear cells.

Neoplastic cells are believed to evade the immune system due, in part, to their inability to successfully provide a secondary, costimulatory signal for a T lymphocyte proliferative response. This report describes the generation and investigation of genetically engineered canine mammary tumor (CMT) cells that express canine B7-1, canine B7-2, or human B7-2. These transfected cells were used as stimulators in an allogeneic, costimulation assay. CMT cells transfected with canine B7-1 induced the greatest proliferation (7-fold increase), followed by CMT cells transfected with canine B7-2 (5-fold increase). The specificity of the canine B7-2 stimulatory response was demonstrated by a 38% reduction in proliferation caused by an anti-canine B7-2 blocking antibody. These results suggest that canine mammary tumor cells transfected with canine B7-1 or canine B7-2 may be useful for immunotherapeutic purposes.