Physical activity regulates the immune response to breast cancer by a hematopoietic stem cell-autonomous mechanism.

Physical activity is a modifiable lifestyle factor that is associated with a decreased risk for the development of breast cancer. While the exact mechanisms for the reduction in cancer risk due to physical activity are largely unknown, it is postulated that the biological reduction in cancer risk is driven by improvements in inflammation and immune function with exercise. Hematopoietic stem cells (HSCs) are the progenitor for all of the cells of the immune system and are involved in cancer immunosurveillance through differentiation into cytotoxic cell population. In this study, we investigate the role of physical activity (PA) in a spontaneously occurring model of breast cancer over time, with a focus on tumor incidence, circulating and tumor-infiltrating immune cells as well gene expression profiles of tumors and hematopoietic stem cells. Furthermore, we show that, in addition to a direct effect of PA on the immune cells of tumor-bearing mice, PA reduces the oxidative stress in HSCs of wildtype and tumor-bearing mice, and by doing so, alters the differentiation of the HSCs towards T cells in order to enhance cancer immunosurveillance.

A distinct class of hematopoietic stem cells develop from the human yellow bone marrow.

Aging and metabolic diseases are accompanied by systemic inflammation, but the mechanisms that induce this state are not known. We developed a human bone-marrow organoid system to explore mechanisms underlying metabolic-disease associated systemic inflammation. We find that a distinct type of hematopoietic stem cell (HSC) develops in the adipose-rich, yellow bone marrow, which is known to gradually replace the hematopoietic red marrow as we age and during metabolic disease. Unlike HSCs derived from the red bone marrow, HSCs derived from the yellow bone marrow have higher proliferation rates, increase myeloid differentiation, skew towards pro-inflammatory M1 macrophage differentiation, and express a distinct transcriptomic profile associated with responsiveness to wounding. Yellow marrow-derived HSCs express higher levels of the leptin receptor, which we find to be further increased in patients with type 2 diabetes. Our work demonstrates that the human long bone yellow marrow is a niche for a distinct class of HSCs which could underlie hematopoietic dysfunction during aging and metabolic disease processes suggesting a shared inflammaging mechanism.

Characterization and management of type II and complex endoleaks after fenestrated/branched endovascular aneurysm repair.

INTRODUCTION: Endoleaks are more common after fenestrated/branched endovascular aneurysm repair (F/B-EVAR) than infrarenal EVAR secondary to the length of aortic coverage and number of component junctions. Although reports have focused on type I and III endoleaks, less is known regarding type II endoleaks after F/B-EVAR. We hypothesized that type II endoleaks would be common and often complex (associated with additional endoleak types), given the potential for multiple inflow and outflow sources. We sought to describe the incidence and complexity of type II endoleaks after F/B-EVAR. METHODS: F/B-EVAR data prospectively collected at a single institution in an investigational device exemption clinical trial (G130210) were retrospectively analyzed (2014-2021). Endoleaks were characterized by type, time to detection, and management. Primary endoleaks were defined as those present on completion imaging or at first postoperative imaging, and secondary were those on subsequent imaging. Recurrent endoleaks were those that developed after a successfully resolved endoleak. Reinterventions were considered for type I or III endoleaks or any endoleak associated with sac growth >5 mm. Technical success defined as the absence of flow in the aneurysm sac at procedure conclusion and methods of intervention were captured. RESULTS: Among 335 consecutive F/B-EVARs (mean ± standard deviation follow-up: 2.5 ± 1.5 years), 125 patients (37%) experienced 166 endoleaks (81 primary, 72 secondary, and 13 recurrent). Of these 125 patients, 50 (40% of patients) underwent 71 interventions for 60 endoleaks. Type II endoleaks were the most frequent (n = 100, 60%), with 20 identified during the index procedure, 12 (60%) of which resolved before 30-day follow-up. Of the 100 type II endoleaks, 20 (20%; 12 primary, 5 secondary, and 3 recurrent) were associated with sac growth; 15 (75%) of those with associated sac growth underwent intervention. At intervention, 6 (40%) were reclassified as complex, with a concomitant type I or type III endoleak. Initial technical success for endoleak treatment was 96% (68 of 71). There were 13 recurrences, all of which were associated with complex endoleaks. CONCLUSIONS: Nearly half of the patients who underwent F/B-EVAR experienced an endoleak. The majority were classified as type II, with nearly a fifth associated with sac expansion. Interventions for a type II endoleak frequently led to reclassification as complex, with a concomitant type I or III endoleak not appreciated on computed tomography angiography and/or duplex. Further study is needed to determine if the primary treatment goal for complex aneurysm repair is sac stability or sac regression, as this would inform both the importance of properly classifying endoleaks noninvasively and the intervention threshold for managing type II endoleaks.

Initial single-center experience using Fiber Optic RealShape guidance in complex endovascular aortic repair.

OBJECTIVE: In the present study, we have described the technical success using Fiber Optic RealShape (FORS) endovascular guidance and its effects on the overall procedural time and radiation usage during complex endovascular aortic repair (EVAR). METHODS: Fenestrated and branched EVARs performed at a single center from 2017 to 2022 were prospectively studied. FORS-guided procedures were matched retrospectively 1:3 to non-FORS-guided procedures by the incorporated target arteries and body mass index. Technical success was defined as successful target vessel cannulation using FORS for the entirety of navigation (wire insertion to exchange for a stiff wire). The predictors of technical success were evaluated via logistic regression. The procedural times and radiation doses were compared between the matched cohorts using the Wilcoxon rank sum test. RESULTS: A total of 21 FORS-guided procedures were matched to 61 non-FORS-guided procedures. A total of 95 FORS cannulations were attempted (87 for the visceral target artery and 8 for the bifurcate gate). Technical success was achieved in 81 cannulations (85%); 15 (16%) were completed without the use of live fluoroscopy. The univariate predictors of FORS technical success included <50% target artery stenosis, <50% target artery calcification, and the target vessel attempted (P < .05 for each). FORS failures were attributed to device material properties in six cases, device failure in two cases, and the wire/catheter combination in six. The use of FORS guidance was associated with shorter median procedural and fluoroscopy times and a lower dose area product and air kerma (P ≤ .0001 for each). CONCLUSIONS: The results from our initial experience with FORS during complex EVAR, including our learning curve, has shown promise, with acceptable technical success and reductions in procedural times and radiation usage.

Successful implementation of a nurse-navigator-run program using natural language processing identifying patients with an abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysms (AAA) are often identified incidentally on imaging studies. Patients and/or providers are frequently unaware of these AAA and the need for long-term follow-up. We sought to evaluate the outcome of a nurse-navigator-run AAA program that uses a natural language processing (NLP) algorithm applied to the electronic medical record (EMR) to identify patients with imaging report-identified AAA not being followed actively. METHODS: A commercially available AAA-specific NLP system was run on EMR data at a large, academic, tertiary hospital with an 11-year historical look back (January 1, 2010, to June 2, 2021), to identify and characterize AAA. Beginning June 3, 2021, a direct link between the NLP system and the EMR enabled for real-time review of imaging reports for new AAA cases. A nurse-navigator (1.0 full-time equivalent) used software filters to categorize AAA according to predefined metrics, including repair status and adherence to Society for Vascular Surgery imaging surveillance protocol. The nurse-navigator then interfaced with patients and providers to reestablish care for patients not being followed actively. The nurse-navigator characterized patients as case closed (eg, deceased, appropriate follow-up elsewhere, refuses follow-up), cases awaiting review, and cases reviewed and placed in ongoing surveillance using AAA-specific software. The primary outcome measures were yield of surveillance imaging performed or scheduled, new clinic visits, and AAA operations for patients not being followed actively. RESULTS: During the prospective study period (January 1, 2021, to December 30, 2021), 6,340,505 imaging reports were processed by the NLP. After filtering for studies likely to include abdominal aorta, 243,889 imaging reports were evaluated, resulting in the identification of 6495 patients with AAA. Of these, 2937 cases were reviewed and closed, 1183 were reviewed and placed in ongoing surveillance, and 2375 are awaiting review. When stratifying those reviewed and placed in ongoing surveillance by maximum aortic diameter, 258 were 2.5 to 3.4 cm, 163 were 3.5 to 3.9 cm, 213 were 4 to 5 cm, and 49 were larger than 5 cm; 36 were saccular, 86 previously underwent open repair, 274 previously underwent endovascular repair, and 104 were other. This process yielded 29 new patient clinic visits, 40 finalized imaging studies, 29 scheduled imaging studies, and 4 AAA operations in 3 patients among patients not being followed actively. CONCLUSIONS: The application of an AAA program leveraging NLP successfully identifies patients with AAA not receiving appropriate surveillance or counseling and repair. This program offers an opportunity to improve best practice-based care across a large health system.

Hemoglobin A1c monitoring practices before lower extremity bypass in patients with diabetes vary broadly and do not predict outcomes.

OBJECTIVE: Hemoglobin A1c (HbA1c) is used as a marker of glycemic control, but the role of HbA1c before lower extremity bypass (LEB) in patients with diabetes remains unclear. We sought to characterize patients with diabetes undergoing LEB with and without HbA1c monitoring and to determine if HbA1c monitoring practices correlate with better outcomes. METHODS: The Vascular Quality Initiative was queried for all LEB in patients with diabetes (2010-2020). Patients with diabetes were characterized based on therapy: diet-controlled, noninsulin medication use, or insulin use. Glycemic control was characterized by preoperative HbA1c within 6 months of surgery: unknown control (no HbA1c), well-controlled (HbA1c <7%), poorly-controlled (HbA1c 7%-10%), and uncontrolled (HbA1c >10%). Centers with >5 LEB/y were stratified into terciles according to rate of HbA1c monitoring. The unadjusted associations between glycemic control and in-hospital major adverse limb events, major adverse cardiac events, and mortality were assessed with univariate methods. The independent association of center-level HbA1c monitoring with 5-year survival and 3-year amputation-free survival (AFS) was determined with Kaplan-Meier analyses and Cox regression modeling, adjusted for differences in patient characteristics and center volume. RESULTS: Of 16,092 patients with diabetes undergoing LEB, 4055 (25%) did not have a documented HbA1c. Insulin use was less common in no A1c (48%) and well-controlled diabetes (39%) compared with poorly controlled (67%) and uncontrolled diabetes (78%) (P < .01). In univariate analyses, glycemic control was not associated with differences for in-hospital major adverse limb events, major adverse cardiac events, or mortality. Of 162 centers, HbA1c monitoring practices varied widely (range: 12.5%-100% of LEB). The 3-year AFS and 5-year survival were worse in the highest monitoring tercile vs the lowest (73.6% vs 77.3%, P < .01, 72.1% vs 77.5%, P < .01, respectively). On multivariable analyses, centers in the highest tercile of monitoring had the greatest hazard of AFS (hazard ratio: 1.21, 95% confidence interval: 1.1-1.3, P < .001) and overall mortality (hazard ratio: 1.19, 95% confidence interval: 1.1-1.3, P < 0.001), compared with the centers in the lowest tercile of monitoring. CONCLUSIONS: Patients with diabetes and no preoperative HbA1c monitoring do not have worse LEB outcomes compared with those with HbA1c monitoring. Preoperative HbA1c monitoring varies widely, suggesting broad differences in practice and documentation. Centers with the highest rates of monitoring demonstrated inferior outcomes, likely due to other confounding unmeasured variables. These findings indicate that HbA1c monitoring before LEB, unto itself, should not be used as a measure of surgical quality.

Detecting direct oral anticoagulants in trauma patients using liquid chromatography-mass spectrometry: A novel approach to medication reconciliation.

BACKGROUND: Accurate medication reconciliation in trauma patients is essential but difficult. Currently, there is no established clinical method of detecting direct oral anticoagulants (DOACs) in trauma patients. We hypothesized that a liquid chromatography-mass spectrometry (LCMS)-based assay can be used to accurately detect DOACs in trauma patients upon hospital arrival. METHODS: Plasma samples were collected from 356 patients who provided informed consent including 10 healthy controls, 19 known positive or negative controls, and 327 trauma patients older than 65 years who were evaluated at our large, urban level 1 trauma center. The assay methodology was developed in healthy and known controls to detect apixaban, rivaroxaban, and dabigatran using LCMS and then applied to 327 samples from trauma patients. Standard medication reconciliation processes in the electronic medical record documenting DOAC usage were compared with LCMS results to determine overall accuracy, sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of the assay. RESULTS: Of 356 patients, 39 (10.96%) were on DOACs: 21 were on apixaban, 14 on rivaroxaban, and 4 on dabigatran. The overall accuracy of the assay for detecting any DOAC was 98.60%, with a sensitivity of 94.87% and specificity of 99.05% (PPV, 92.50%; NPV, 99.37%). The assay detected apixaban with a sensitivity of 90.48% and specificity of 99.10% (PPV, 86.36%; NPV 99.40%). There were three false-positive results and two false-negative LCMS results for apixaban. Dabigatran and rivaroxaban were detected with 100% sensitivity and specificity. CONCLUSION: This LCMS-based assay was highly accurate in detecting DOACs in trauma patients. Further studies need to confirm the clinical efficacy of this LCMS assay and its value for medication reconciliation in trauma patients. LEVEL OF EVIDENCE: Diagnostic Test, level III.

Imaging Obtained Up To 12 Months Preoperatively Is Adequate for Planning Fenestrated/Branched Endovascular Aortic Aneurysm Repair.

OBJECTIVES: Patients referred for fenestrated/branched endovascular aortic repair (F/BEVAR) often present with a previous computed tomography angiogram (CTA), but it is unknown how recent the CTA must be to ensure accurate F/BEVAR planning. We sought to determine whether anatomic planning parameters change significantly between a CTA used for F/BEVAR planning and a CTA obtained 6 to 12 months prior. METHODS: Two blinded observers reviewed preoperative CTAs from 21 patients who underwent F/BEVAR. Each patient had a "recent" scan obtained 0 to 6 months before F/BEVAR planning and a "prior" scan obtained 6 to 12 months before the "recent" CTA. Standard measurements included (1) target vessel separation distances, (2) target vessel origin clock position, and (3) proximal F/BEVAR device diameter. Clinically significant differences for target vessel separation distance, target vessel origin clock position, and proximal F/BEVAR device diameter were predefined as >5 mm, >30 minutes, and >4 mm, respectively. Differences between "recent"/"prior" CTA scans were examined by paired t test. RESULTS: Mean time interval between paired "recent"/"prior" CTAs was 8.0 months (standard deviation: ±1.7). Mean difference in paired "recent"/"prior" target vessel distance (relative to celiac artery [CA]) was 2.6 mm for the superior mesenteric artery (SMA), 2.5 mm for the right renal artery (RRA), and 3.3 mm for the left renal artery (LRA). Of the 21 paired "recent"/"prior" CTAs, clinically significant differences were observed in 2, 4, and 2 patients for SMA, RRA, and LRA target vessel distance, respectively. Target vessel clock position (SMA reference at 12:00) varied by 12 minutes for the CA, 13 minutes for the RRA, and 15 minutes for the LRA. One paired "recent"/"prior" CTA was found to have a clinically significant difference for the LRA. No clinically significant differences were observed for proximal device diameter. CONCLUSIONS: In patients who underwent successful F/BEVAR, measurement comparisons between CTAs obtained up to 1 year prior were minor and unlikely to yield clinically significant changes to F/BEVAR design.

Use of fenestrated-branched endovascular aneurysm repair to treat Carrel patch aneurysmal degeneration after open thoracoabdominal aortic aneurysm repair.

Two patients with a history of open type II thoracoabdominal aortic aneurysm repair presented with saccular aneurysmal degeneration of the Carrel patch. The degenerated segments measured 6.2 cm and 7.4 cm, respectively, and involved the celiac artery, superior mesenteric artery, and right renal artery. Both patients successfully underwent a custom fenestrated-branched endovascular aneurysm repair with downgoing branches to the celiac artery, superior mesenteric artery, and right renal artery and a stented fenestration to the left renal artery. Completion angiography demonstrated no endoleak and patent visceral-renal segments. Both patients were discharged home on postoperative day 2.

Medications and patient safety in the trauma setting: a systematic review.

Background: Medication errors account for the most common adverse events and a significant cause of mortality in the USA. The Joint Commission has required medication reconciliation since 2006. We aimed to survey the literature and determine the challenges and effectiveness of medication reconciliation in the trauma patient population. Materials and methods: We conducted a systematic review of the literature to determine the effectiveness of medication reconciliation in trauma patients. English language articles were retrieved from PubMed/Medline, CINAHL, and Cochrane Review databases with search terms "trauma OR injury, AND medication reconciliation OR med rec OR med rek, AND effectiveness OR errors OR intervention OR improvements." Results: The search resulted in 82 articles. After screening for relevance and duplicates, the 43 remaining were further reviewed, and only four articles, which presented results on medication reconciliation in 3041 trauma patients, were included. Two were retrospective and two were prospective. Two showed only 4% accuracy at time of admission with 48% of medication reconciliations having at least one medication discrepancy. There were major differences across the studies prohibiting comparative statistical analysis. Conclusions: Trauma medication reconciliation is important because of the potential for adverse outcomes given the emergent nature of the illness. The few articles published at this time on medication reconciliation in trauma suggest poor accuracy. Numerous strategies have been implemented in general medicine to improve its accuracy, but these have not yet been studied in trauma. This topic is an important but unrecognized area of research in this field.

Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease.

Defective mitochondrial distribution in neurons is proposed to cause ATP depletion and calcium-buffering deficiencies that compromise cell function. However, it is unclear whether aberrant mitochondrial motility and distribution alone are sufficient to cause neurological disease. Calcium-binding mitochondrial Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and retrograde transport in neurons. Using two new KO mouse models, we demonstrate that Miro1 is essential for development of cranial motor nuclei required for respiratory control and maintenance of upper motor neurons required for ambulation. Neuron-specific loss of Miro1 causes depletion of mitochondria from corticospinal tract axons and progressive neurological deficits mirroring human upper motor neuron disease. Although Miro1-deficient neurons exhibit defects in retrograde axonal mitochondrial transport, mitochondrial respiratory function continues. Moreover, Miro1 is not essential for calcium-mediated inhibition of mitochondrial movement or mitochondrial calcium buffering. Our findings indicate that defects in mitochondrial motility and distribution are sufficient to cause neurological disease.

Mitochondrial SKN-1/Nrf mediates a conserved starvation response.

SKN-1/Nrf plays multiple essential roles in development and cellular homeostasis. We demonstrate that SKN-1 executes a specific and appropriate transcriptional response to changes in available nutrients, leading to metabolic adaptation. We isolated gain-of-function (gf) alleles of skn-1, affecting a domain of SKN-1 that binds the transcription factor MXL-3 and the mitochondrial outer membrane protein PGAM-5. These skn-1(gf) mutants perceive a state of starvation even in the presence of plentiful food. The aberrant monitoring of cellular nutritional status leads to an altered survival response in which skn-1(gf) mutants transcriptionally activate genes associated with metabolism, adaptation to starvation, aging, and survival. The triggered starvation response is conserved in mice with constitutively activated Nrf and may contribute to the tumorgenicity associated with activating Nrf mutations in mammalian somatic cells. Our findings delineate an evolutionarily conserved metabolic axis of SKN-1/Nrf, further establishing the complexity of this pathway.

A general process for the development of peptide-based immunoassays for monoclonal antibodies.

PURPOSE: Monoclonal antibodies (mAb) are an important and growing class of cancer therapeutics, but pharmacokinetic analyses have in many cases been constrained by the lack of standard and robust pharmacologic assays. The goal of this project was to develop a general method for the production of immunoassays that can measure the levels of therapeutic monoclonal antibodies in biologic samples at relevant concentrations. METHODS: Alemtuzumab and rituximab are monoclonal approved for the treatment of B-cell malignancies and were used as a model system. Phage-displayed peptide libraries were screened for peptide sequences recognized by alemtuzumab (anti-CD52) or rituximab (anti-CD20). Synthetic biotinylated peptides were used in enzyme-linked immunosorbent assays (ELISA). Peptides directly synthesized on polymer resin beads were used in an immunofluorescent-based assay. RESULTS: Peptide mimetope sequences were recovered for both mAb and confirmed by competitive staining and kinetic measurements. A peptide-based ELISA method was developed for each. The assay for rituximab had a limit of detection of 4 microg/ml, and the assay for alemtuzumab had a limit of detection of 1 microg/ml. Antibody-specific staining of peptide conjugated beads could be seen in a dose-dependent manner. CONCLUSION: Phage-displayed peptide libraries can be a source of highly specific mimetopes for therapeutic mAb. The biotinylated forms of those peptides are compatible with conventional ELISA methods with sensitivities comparable to other assay methods and sufficient for pharmacological studies of those mAb given at high dose. The process outlined here can be applied to any mAb to enable improved pharmacokinetic analysis during the development and clinical use of this class of therapies.

Targeted disruption of p53 attenuates doxorubicin-induced cardiac toxicity in mice.

Use of the chemotherapeutic agent doxorubicin (Dox) is limited by dose-dependent cardiotoxic effects. The molecular mechanism underlying these toxicities are incompletely understood, but previous results have demonstrated that Dox induces p53 expression. Because p53 is an important regulator of the cell birth and death we hypothesized that targeted disruption of the p53 gene would attenuate Dox-induced cardiotoxicity. To test this, female 6-8 wk old C57BL wild-type (WT) or p53 knockout (p53 KO) mice were randomized to either saline or Dox 20 mg/kg via intraperitoneal injection. Animals were serially imaged with high-frequency (14 MHz) two-dimensional echocardiography. Measurements of left ventricle (LV) systolic function as assessed by fractional shortening (FS) demonstrated a decline in WT mice as early as 4 days after Dox injection and by 2 wk demonstrated a reduction of 31 +/- 16% (P < 0.05) from the baseline. In contrast, in p53 KO mice, LV FS was unchanged over the 2 wk period following Dox injection. Apoptosis of cardiac myocytes as measured by the TUNEL and ligase reactions were significantly increased at 24 h after Dox treatment in WT mice but not in p53 KO mice. After Dox injection, levels of myocardial glutathione and Cu/Zn superoxide dismutase were preserved in p53 KO mice, but not in WT animals. These observations suggest that p53 mediated signals are likely to play a significant role in Dox-induced cardiac toxicity and that they may modulate Dox-induced oxidative stress.

Evaluation of pulsed Doppler tissue velocity imaging for assessing systolic function of murine global heart failure.

The feasibility of Doppler tissue imaging (DTI) for assessing global systolic function has not been determined in small animals, particularly at near-conscious heart rates. Therefore, we compared DTI measurements with conventional M-mode-derived fractional shortening in murine global left ventricular systolic dysfunction induced by intraperitoneal doxorubicin (Dox) injection. In all, 13 female C57BL mice received 20 mg/kg of Dox and 12 mice received saline injection (controls). DTI signals were obtained from the inferior wall through parasternal short-axis views. The heart rate was kept at near-conscious level throughout DTI measurements (approximately 500/min). Left ventricular systolic dysfunction was detectable by measurements of fractional shortening from 4 to 14 days after Dox administration. Among DTI measurements, peak systolic velocity and time to peak systolic velocity decreased from 4 to 14 days after Dox injection. Our results indicate that these new DTI measurements appear feasible to assess global left ventricular systolic dysfunction in mice.

Heterogeneity within the Asian American community.

BACKGROUND: Educational interventions are grounded on scientific data and assumptions about the community to be served. While the Pan Asian community is composed of multiple, ethnic subgroups, it is often treated as a single group for which one health promotion program will be applicable for all of its cultural subgroups. Compounding this stereotypical view of the Pan Asian community, there is sparse data about the cultural subgroups' similarities and dissimilarities. The Asian Grocery Store based cancer education program evaluation data provided an opportunity to compare data collected under identical circumstances from members of six Asian American cultural groups. METHODS: A convenience sample of 1,202 Asian American women evaluated the cultural alignment of a cancer education program, completing baseline and follow-up surveys that included questions about their breast cancer knowledge, attitudes, and screening behaviors. Participants took part in a brief education program that facilitated adherence to recommended screening guidelines. RESULTS: Unique recruitment methods were needed to attract participants from each ethnic group. Impressions gained from the aggregate data revealed different insights than the disaggregate data. Statistically significant variations existed among the subgroups' breast cancer knowledge, attitudes, and screening behaviors that could contribute to health disparities among the subgroups and within the aggregate Pan Asian community. CONCLUSION: Health promotion efforts of providers, educators, and policy makers can be enhanced if cultural differences are identified and taken into account when developing strategies to reduce health disparities and promote health equity.

Japanese American women: behaviors and attitudes toward breast cancer education and screening.

Moores University of California, San Diego, Cancer Center's Asian Grocery Store-Based Cancer Education Program trained bilingual, bicultural student health educators to provide breast cancer information to Japanese American women. A subset consented to help evaluate the program by completing baseline and follow-up surveys. Study participants reported high adherence to mammography screening guidelines, but lower than optimal adherence to clinical breast examination (CBE) and monthly breast self-examination (BSE) guidelines. While less than half of the women felt they had enough knowledge about breast cancer, nearly all indicated that they would be willing to share any knowledge they gained with loved ones and that their loved ones would be receptive to their information. A limitation of the study is its small sample.

Assessing the contribution of the herpes simplex virus DNA polymerase to spontaneous mutations.

BACKGROUND: The thymidine kinase (tk) mutagenesis assay is often utilized to determine the frequency of herpes simplex virus (HSV) replication-mediated mutations. Using this assay, clinical and laboratory HSV-2 isolates were shown to have a 10- to 80-fold higher frequency of spontaneous mutations compared to HSV-1. METHODS: A panel of HSV-1 and HSV-2, along with polymerase-recombinant viruses expressing type 2 polymerase (Pol) within a type 1 genome, were evaluated using the tk and non-HSV DNA mutagenesis assays to measure HSV replication-dependent errors and determine whether the higher mutation frequency of HSV-2 is a distinct property of type 2 polymerases. RESULTS: Although HSV-2 have mutation frequencies higher than HSV-1 in the tk assay, these errors are assay-specific. In fact, wild type HSV-1 and the antimutator HSV-1 PAAr5 exhibited a 2-4 fold higher frequency than HSV-2 in the non-HSV DNA mutatagenesis assay. Furthermore, regardless of assay, HSV-1 recombinants expressing HSV-2 Pol had error rates similar to HSV-1, whereas the high mutator virus, HSV-2 6757, consistently showed significant errors. Additionally, plasmid DNA containing the HSV-2 tk gene, but not type 1 tk or LacZ DNA, was shown to form an anisomorphic DNA structure. CONCLUSIONS: This study suggests that the Pol is not solely responsible for the virus-type specific differences in mutation frequency. Accordingly, it is possible that (a) mutations may be modulated by other viral polypeptides cooperating with Pol, and (b) the localized secondary structure of the viral genome may partially account for the apparently enhanced error frequency of HSV-2.