Drosophila Bruce Can Potently Suppress Rpr- and Grim-Dependent but Not Hid-Dependent Cell Death

Bruce is a large protein (530 kDa) that contains an N-terminal baculovirus IAP repeat (BIR) and a C-terminal ubiquitin conjugation domain (E2) 1, 2. BRUCE upregulation occurs in some cancers and contributes to the resistance of these cells to DNA-damaging chemotherapeutic drugs [2]. However, it is still unknown whether Bruce inhibits apoptosis directly or instead plays some other more indirect role in mediating chemoresistance, perhaps by promoting drug export, decreasing the efficacy of DNA damage-dependent cell death signaling, or by promoting DNA repair. Here, we demonstrate, using gain-of-function and deletion alleles, that Drosophila Bruce (dBruce) can potently inhibit cell death induced by the essential Drosophila cell death activators Reaper (Rpr) and Grim but not Head involution defective (Hid). The dBruce BIR domain is not sufficient for this activity, and the E2 domain is likely required. dBruce does not promote Rpr or Grim degradation directly, but its antiapoptotic actions do require that their N termini, required for interaction with DIAP1 BIR2, be intact. dBruce does not block the activity of the apical cell death caspase Dronc or the proapoptotic Bcl-2 family member Debcl/Drob-1/dBorg-1/Dbok. Together, these results argue that dBruce can regulate cell death at a novel point

Rates and Predictors of Colorectal Cancer Screening

Introduction: Despite widespread recommendations for colorectal cancer screening, the U.S. screening rate is low. The objectives of this study were to describe the rates and predictors of colorectal cancer screening use by examining groups in two categories — 1) those who have ever been screened and 2) those with up-to-date screening — and to assess whether trends and predictors change over time. Methods: We analyzed data from the 2000 and 2003 National Health Interview Surveys about the use of fecal occult blood tests, sigmoidoscopies, and colonoscopies for adults aged 50 years and older and without a history of colorectal cancer (N = 11,574 in 2000 and N = 11,779 in 2003). Results: Rates in the 2000 study population of those who have ever been screened for colorectal cancer (53%) had increased in the 2003 study population (55%) as had the rates in the 2003 study population of those with up-to-date colorectal screening (53%) compared with the rates in the 2000 study population (38%). Among those who were ever screened, 76% were up-to-date with screening in 2003, compared with 68% in 2000. There was increased use of colonoscopies but decreased use of fecal occult blood tests and sigmoidoscopies. Individuals were more likely to be up-to-date with screening if they had higher income, higher education, insurance coverage, a usual source of care, and a dental visit in the last year than if these predictors were not evident. Since 2000, these predictors of colorectal cancer screening use have remained stable. Conclusion: Although there has been relatively limited success in increasing overall screening, it is encouraging that most people in the group of those who have ever been screened are up-to-date with colorectal cancer screening. Predictors for colorectal screening were stable over time despite changes in screening policies and rates. Further research is needed to uncover barriers to colorectal cancer screening

Utilization of cardiac monitoring tests in women with nonmetastatic breast cancer treated with trastuzumab.

AimsTrastuzumab, one of the best known examples of personalized medicine, requires regular cardiac monitoring because it can cause heart failure. We aimed to assess the utilization of cardiac monitoring in women with nonmetastatic breast cancer receiving trastuzumab-based chemotherapy in routine clinical practice.Patients & methodsThe medical records of women continuously enrolled in a large national health insurance plan who were diagnosed with nonmetastatic breast cancer and treated with trastuzumab from 2006 to 2008 were reviewed (n = 109). The primary outcome variables were the use and type of cardiac monitoring testing before and during trastuzumab therapy. An exploratory multivariable logistic regression analysis was performed to identify predictors for receiving cardiac monitoring both at baseline and during trastuzumab treatment.ResultsMonitoring both before and during therapy was less common (62%), although 74% had cardiac monitoring before therapy and 80% had at least one test during therapy. Radionuclide ventriculogram was utilized more often than echocardiography (48 vs 42%). Only the use of anthracycline (odds ratio: 2.39; 95% CI: 1.01-5.71) was significantly associated with use of a cardiac monitoring both at baseline and during trastuzumab treatment.ConclusionThe use of cardiac monitoring testing was variable and opportunities to improve quality and reduce cost are evident. These results have clinical implications for other personalized medicine interventions requiring regular laboratory monitoring

Factors Associated with Arkansans’ First Use of Telehealth during the COVID-19 Pandemic

Objective. To examine the factors associated with the first use of telehealth during the COVID-19 pandemic using Andersen’s Model of Healthcare Utilization. Andersen’s Model of Healthcare Utilization allowed the categorization of the independent variables into the following: (1) predisposing factors, including sociodemographic variables and health beliefs; (2) enabling factors, including socioeconomic status and access to care; and (3) need for care, including preexisting or newly diagnosed conditions and reasons to seek out care or to utilize a new mode of care. Methods. Potential respondents (n = 4,077) were identified for recruitment from a volunteer registry in Arkansas. Recruitment emails provided a study description, the opportunity to verify meeting the study’s inclusion criteria and to consent for participation, and a link to follow to complete the survey online. The online survey responses were collected between July and August of 2020 (n = 1,137). Results. Telehealth utilization included two categories: (1) utilizers reported the first use of telehealth services during the pandemic, and (2) nonutilizers reported they had never used telehealth. Lower odds of reporting telehealth utilization during the pandemic were associated with race (Black; OR = 0:57, CI [0.33, 0.96]) and education (high School or less; OR = 0:45, CI [0.25, 0.83]). Higher odds of reporting telehealth utilization included having more than one provider (OR = 2:33, CI [1.30, 4.18]), more physical (OR = 1:12, CI [1.00, 1.25]) and mental (OR 1.53, CI [1.24, 1.88]) health conditions, and changes in healthcare delivery during the pandemic (OR = 3:49, CI [2.78, 4.38]). Conclusions. The results illustrate that disparities exist in Arkansans’ utilization of telehealth services during the pandemic. Future research should explore the disparities in telehealth utilization and how telehealth may be used to address disparities in care for Black Arkansans and those with low socioeconomic status

Differential Regulation of Primitive Myelopoiesis in the Zebrafish by Spi-1/Pu.1 and C/ebp1

The zebrafish has become a powerful tool for analysis of vertebrate hematopoiesis. Zebrafish, unlike mammals, have a robust primitive myeloid pathway that generates both granulocytes and macrophages. It is not clear how this unique primitive myeloid pathway relates to mammalian definitive hematopoiesis. In this study, we show that the two myeloid subsets can be distinguished using RNA in situ hybridization. Using a morpholino-antisense gene knockdown approach, we have characterized the hematopoietic defects resulting from knockdown of the myeloid transcription factor gene pu.1 and the unique zebrafish gene c/ebp1. Severe reduction of pu.1 resulted in complete loss of primitive macrophage development, with effects on granulocyte development only with maximal knockdown. Reduction of c/ebp1 did not ablate initial macrophage or granulocyte development, but resulted in loss of expression of the secondary granule gene lys C. These data reveal strong functional conservation of pu.1 between zebrafish primitive myelopoiesis and mammalian definitive myelopoiesis. Further, these results are consistent with a conserved role between c/ebp1 and mammalian C/EBPE, whose ortholog in zebrafish has not been identified. These studies validate the examination of zebrafish primitive myeloid development as a model for human myelopoiesis, and form a framework for identification and analysis of myeloid mutants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63190/1/zeb.2007.0505.pd

Maternal fucosyltransferase 2 status affects the gut bifidobacterial communities of breastfed infants.

BackgroundIndividuals with inactive alleles of the fucosyltransferase 2 gene (FUT2; termed the 'secretor' gene) are common in many populations. Some members of the genus Bifidobacterium, common infant gut commensals, are known to consume 2'-fucosylated glycans found in the breast milk of secretor mothers. We investigated the effects of maternal secretor status on the developing infant microbiota with a special emphasis on bifidobacterial species abundance.ResultsOn average, bifidobacteria were established earlier and more often in infants fed by secretor mothers than in infants fed by non-secretor mothers. In secretor-fed infants, the relative abundance of the Bifidobacterium longum group was most strongly correlated with high percentages of the order Bifidobacteriales. Conversely, in non-secretor-fed infants, Bifidobacterium breve was positively correlated with Bifidobacteriales, while the B. longum group was negatively correlated. A higher percentage of bifidobacteria isolated from secretor-fed infants consumed 2'-fucosyllactose. Infant feces with high levels of bifidobacteria had lower milk oligosaccharide levels in the feces and higher amounts of lactate. Furthermore, feces containing different bifidobacterial species possessed differing amounts of oligosaccharides, suggesting differential consumption in situ.ConclusionsInfants fed by non-secretor mothers are delayed in the establishment of a bifidobacteria-laden microbiota. This delay may be due to difficulties in the infant acquiring a species of bifidobacteria able to consume the specific milk oligosaccharides delivered by the mother. This work provides mechanistic insight into how milk glycans enrich specific beneficial bacterial populations in infants and reveals clues for enhancing enrichment of bifidobacterial populations in at risk populations - such as premature infants