A pragmatic randomized trial of mailed fecal immunochemical testing to increase colorectal cancer screening among low-income and minoritized populations.

BACKGROUND: Colorectal cancer (CRC) screening is underused, particularly among low-income and minoritized populations, for whom the coronavirus disease 2019 (COVID-19) pandemic has challenged progress in achieving equity. METHODS: A hub-and-spoke model was used. The hub was a nonacademic organization and the spokes were three community health center (CHC) systems overseeing numerous clinic sites. Via a cluster-randomized trial design, nine clinic sites were randomized to intervention and 16 clinic sites were randomized to usual care. Patient-level interventions included invitation letters, mailed fecal immunochemical tests (FITs), and call/text-based reminders. Year 1 intervention impact, which took place during the COVID-19 pandemic, was assessed as the proportion completing screening among individuals not up to date at baseline, which compared intervention and nonintervention clinics accounting for intraclinic cluster variation; confidence intervals (CIs) around differences not including 0 were interpreted as statistically significant. RESULTS: Among 26,736 patients who met eligibility criteria, approximately 58% were female, 55% were Hispanic individuals, and 44% were Spanish speaking. The proportion completing screening was 11.5 percentage points (ppts) (95% CI, 6.1-16.9 ppts) higher in intervention versus usual care clinics. Variation in differences between intervention and usual care clinics was observed by sex (12.6 ppts [95% CI, 7.2-18.0 ppts] for females; 8.8 ppts [95% CI, 4.7-13.9 ppts] for males) and by racial and ethnic group (13.8 ppts [95% CI, 7.0-20.6 ppts] for Hispanic individuals; 13.0 ppts [95% CI, 3.6-22.4 ppts] for Asian individuals; 11.3 ppts [95% CI, 5.8-16.8 ppts] for non-Hispanic White individuals; 6.1 ppts [95% CI, 0.8-10.4 ppts] for Black individuals). CONCLUSIONS: A regional mailed FIT intervention was effective for increasing CRC screening rates across CHC systems serving diverse, low-income populations.

Examining the Effectiveness of Provider Incentives to Increase CRC Screening Uptake in Neighborhood Healthcare: A California Federally Qualified Health Center.

As an awardee of the Centers for Disease Control and Prevention's Colorectal Cancer Control Program, the California Department of Public Health partnered with Neighborhood Healthcare to implement evidence-based interventions and provider incentives (incentives offered to support staff, e.g., medical assistants, phlebotomists, front office staff, lab technicians) to improve colorectal cancer screening uptake. The objective of this study was to evaluate the effectiveness and cost of the provider incentive intervention implemented by Neighborhood Healthcare to increase colorectal cancer screening uptake. We collected and analyzed process and cost data to assess fecal immunochemical test (FIT) kit return rates to the health centers and the number of completed FIT kits. We estimated the costs of the preexisting interventions and the new interventions. Analyses were conducted for two time periods: preimplementation and implementation. Most Neighborhood Healthcare health centers experienced an increase in the percentage of FIT kit returns (average of 3.6 percentage points) and individuals screened (an average increase of 111 FIT kits per month) from the baseline period through the implementation period. The cost of the incentive intervention for each additional screen was $66.79. In conclusion, the results indicate that incentive programs can have an overall positive impact on both the percentage of FIT kits returned and the number of individuals screened.

Military and Nonmilitary TBI Associations with Hearing Loss and Self-Reported Hearing Difficulty among Active-Duty Service Members and Veterans.

OBJECTIVE: Identify associations between self-reported history of military and nonmilitary traumatic brain injury (TBI) on hearing loss and hearing difficulty from the Noise Outcomes in Servicemembers Epidemiology (NOISE) study. STUDY DESIGN: Cross-sectional. SETTING: Multi-institutional tertiary referral centers. PATIENTS: Four hundred seventy-three Active-Duty Service members (ADSM) and 502 veterans. EXPOSURE: Self-reported history of no TBI, military TBI only, nonmilitary TBI only, both military and nonmilitary TBI. MAIN OUTCOME MEASURES: Pure-tone hearing thresholds, Speech Recognition In Noise Test (SPRINT), Hearing Handicap Inventory for Adults (HHIA), and Speech, Spatial and Qualities of Hearing Scale (SSQ)-12. RESULTS: 25% (120/473) of ADSM and 41% (204/502) of veterans self-reported a TBI. Military TBI was associated with poorer hearing thresholds in all frequency ranges in veterans (adjusted mean difference, 1.8 dB; 95% confidence interval [CI], 0.5-3.0; 3.3, 0.8-5.8; 5.1; 1.7-8.5, respectively), and in the high frequency range in ADSM (mean difference, 3.2 dB; 95% CI, 0.1-6.3). Veterans with military TBI only and nonmilitary TBI only had lower odds of correctly identifying speech in noise than veterans with no TBI (odds ratio [OR], 0.78; 95% CI, 0.72-0.83; 0.90; 0.84-0.98). ADSM with a military TBI (OR, 5.7; 95% CI, 2.6-12.5) and veterans with any TBI history (OR, 2.5; 95% CI, 1.5-4.3; OR, 2.2; 95% CI, 1.3-3.8; OR, 4.5; 95% CI, 2.1-9.8) were more likely to report hearing difficulty on HHIA. SSQ-12 results corroborated HHIA findings. CONCLUSIONS: Military TBI was associated with poorer hearing thresholds in veterans and ADSM, and poorer SPRINT scores in veterans. Military TBI was associated with poorer self-perceived hearing ability in ADSM. All types of TBI were associated with poorer self-perceived hearing ability in veterans, although the strength of this association was greatest for military TBI.

Medical Assistant Health Coaching for Type 2 Diabetes in Primary Care: Results From a Pragmatic Cluster Randomized Controlled Trial.

OBJECTIVE: This cluster (clinic-level) randomized controlled trial (RCT) compared medical assistant (MA) health coaching (MAC) with usual care (UC) among at-risk adults with type 2 diabetes in two diverse real-world primary care environments: a federally qualified health center (FQHC; Neighborhood Healthcare) and a large nonprofit private insurance-based health system (Scripps Health). RESEARCH DESIGN AND METHODS: A total of 600 adults with type 2 diabetes who met one or more of the following criteria in the last 90 days were enrolled: HbA1c ≥8% and/or LDL cholesterol ≥100 mg/dL and/or systolic blood pressure (SBP) ≥140 mmHg. Participants at MAC clinics received in-person and telephone self-management support from a specially trained MA health coach for 12 months. Electronic medical records were used to examine clinical outcomes in the overall sample. Behavioral and psychosocial outcomes were evaluated in a subsample (n = 300). RESULTS: All clinical outcomes improved significantly over 1 year in the overall sample (P < 0.001). The reduction in HbA1c was significantly greater in the MAC versus UC group (unstandardized Binteraction = -0.06; P = 0.002). A significant time by group by site interaction also showed that MAC resulted in greater improvements in LDL cholesterol than UC at Neighborhood Healthcare relative to Scripps Health (Binteraction = -1.78 vs. 1.49; P < 0.05). No other statistically significant effects were observed. CONCLUSIONS: This was the first large-scale pragmatic RCT supporting the real-world effectiveness of MAC for type 2 diabetes in U.S. primary care settings. Findings suggest that this team-based approach may be particularly effective in improving diabetes outcomes in FQHC settings.

Thyroid hormone receptor isoform-specific modification by small ubiquitin-like modifier (SUMO) modulates thyroid hormone-dependent gene regulation.

Thyroid hormone receptor (TR) α and ß mediate thyroid hormone action at target tissues. TR isoforms have specific roles in development and in adult tissues. The mechanisms underlying TR isoform-specific action, however, are not well understood. We demonstrate that posttranslational modification of TR by conjugation of small SUMO to TRα and TRß plays an important role in triiodothyronine (T3) action and TR isoform specificity. TRα was sumoylated at lysines 283 and 389, and TRß at lysines 50, 146, and 443. Sumoylation of TRß was ligand-dependent, and sumoylation of TRα was ligand-independent. TRα-SUMO conjugation utilized the E3 ligase PIASxß and TRß-SUMO conjugation utilized predominantly PIAS1. SUMO1 and SUMO3 conjugation to TR was important for T3-dependent gene regulation, as demonstrated in transient transfection assay and studies of endogenous gene regulation. The functional role of SUMO1 and SUMO3 in T3 induction in transient expression assays was closely matched to the pattern of TR and cofactor recruitment to thyroid hormone response elements (TREs) as determined by ChIP assays. SUMO1 was required for the T3-induced recruitment of the co-activator CREB-binding protein (CBP) and release of nuclear receptor co-repressor (NCoR) on a TRE but had no significant effect on TR DNA binding. SUMO1 was required for T3-mediated recruitment of NCoR and release of CBP from the TSHß-negative TRE. SUMO3 was required for T3-stimulated TR binding to the TSHß-negative TRE and recruitment of NCoR. These findings demonstrate that conjugation of SUMO to TR has a TR-isoform preference and is important for T3-dependent gene induction and repression.

Tinnitus Screener: Short-Term Test-Retest Reliability.

PURPOSE: The Tinnitus Screener was introduced in 2015 as a four-item algorithmic instrument to assess the temporal characteristics of a person's reported tinnitus. The Tinnitus Screener was then revised as a six-item version to include a new temporal category and to capture tinnitus duration (acute < 6 months vs. chronic ≥ 6 months). When contrasted with audiologist assessment, the four-item Tinnitus Screener was determined to be highly valid, but the short-term reliability of either version remained unknown. The present analysis focused on determining the test-retest reliability of the six-item Tinnitus Screener. Additionally, we sought to determine whether reliability differed by respondent age, sex, military status, and hearing loss. METHOD: The Tinnitus Screener was administered to 190 military Service members and 250 military Veterans at two time points separated by 7-31 days. Our analysis focused on test-retest reliability of responses as measured by the kappa coefficient, overall and within subsamples. Percent agreement of tinnitus categorization (temporal categories) and classification (positive/negative) between the two time points was also evaluated. RESULTS: Constant or intermittent tinnitus was found in 31% of Service members and 53% of Veterans. Overall, kappa reliability coefficients were high, near .80, indicating substantial reliability. The majority (96%) of reliability coefficients for the Tinnitus Screener within subsamples were similarly high, ranging from .68 to .88. CONCLUSIONS: The updated version of the Tinnitus Screener is shown to be a reliable instrument. The Tinnitus Screener is recommended to inform clinical decision making by determining the temporal characteristics of tinnitus.

Prevalence and Risk Factors of Self-reported Dizziness in Post-9/11 Service Members and Veterans.

INTRODUCTION: Dizziness is prevalent in the general population, but little is known about its prevalence in the U.S. military population. Dizziness is commonly associated with blast exposure and traumatic brain injury (TBI), but the potential independent contributions of blast and TBI have yet to be evaluated. This study's goal was to estimate the prevalence of dizziness among post-9/11 service members and Veterans and to examine independent and joint associations between military TBI history, blast exposure, and self-reported dizziness. MATERIALS AND METHODS: The study sample consisted of service members (n = 424) and recently separated (< ∼2.5 years) Veterans (n = 492) enrolled in the Noise Outcomes in Service members Epidemiology (NOISE) Study. We examined associations between self-reported history of probable TBI and blast exposure and recent dizziness using logistic regression. Models were stratified by service member versus Veteran status and adjusted to account for potentially confounding demographic and military characteristics. RESULTS: Overall, 22% of service members and 31% of Veterans self-reported dizziness. Compared to those with neither TBI nor blast exposure history, both service members and Veterans with TBI (with or without blast) were three to four times more likely to self-report dizziness. Those with blast exposure but no TBI history were not more likely to self-report dizziness. There was no evidence of an interaction effect between blast exposure and a history of TBI on the occurrence of dizziness. CONCLUSION: Self-reported dizziness was prevalent in this sample of service members and Veterans. Probable TBI history, with or without blast exposure, was associated with dizziness, but blast exposure without TBI history was not. This suggests that treatment guidelines for TBI-related dizziness may not need to be tailored to the injury mechanism. However, future efforts should be directed toward the understanding of the pathophysiology of TBI on self-reported dizziness, which is fundamental to the design of treatment strategies.

Dulce Digital-Me: protocol for a randomized controlled trial of an adaptive mHealth intervention for underserved Hispanics with diabetes.

BACKGROUND: By 2034, the number of US individuals with diabetes is predicted to increase from 23.7 to 44.1 million, and annual diabetes-related spending is expected to grow from $113 to $336 billion. Up to 55% of US Hispanics born in the year 2000 are expected to develop diabetes during their lifetime. Poor healthcare access and cultural barriers prevent optimal care, adherence, and clinical benefit, placing Hispanics at disproportionate risk for costly diabetes complications. Mobile technology is increasingly prevalent in all populations and can circumvent such barriers. Our group developed Dulce Digital, an educational text messaging program that improved glycemic control relative to usual care. Dulce Digital-Me (DD-Me) has been tailored to a participant's individual needs with a greater focus on health behavior change. METHODS: This is a three-arm, parallel group, randomized trial with equal allocation ratio enrolling Hispanic adults with low income and poorly managed type 2 diabetes (N = 414) from a San Diego County Federally Qualified Health Center. Participants are randomized to receive Dulce Digital, Dulce Digital-Me-Automated, or Dulce Digital-Me-Telephonic. The DD-Me groups include Dulce Digital components plus personalized goal-setting and feedback delivered via algorithm-driven automated text messaging (DD-Me-Automated) or by the care team health coach (DD-Me-Telephonic) over a 12-month follow-up period. The study will examine the comparative effectiveness of the three groups in improving diabetes clinical control [HbA1c, primary outcome; low-density lipoprotein cholesterol (LDL-C), and systolic blood pressure (SBP)] and patient-provider communication and patient adherence (i.e., medication, self-management tasks) over 12 months and will examine cost-effectiveness of the three interventions. DISCUSSION: Our comparative evaluation of three mHealth approaches will elucidate how technology can be integrated most effectively and efficiently within primary care-based chronic care model approaches to reduce diabetes disparities in Hispanics and will assess two modes of personalized messaging delivery (i.e., automated messaging vs. telephonic by health coach) to inform cost and acceptability. TRIAL REGISTRATION: NCT03130699-All items from the WHO Trial Registration data set are available in https://clinicaltrials.gov/ct2/show/study/NCT03130699 .

C-terminal mechano-growth factor induces heme oxygenase-1-mediated neuroprotection of SH-SY5Y cells via the protein kinase Cϵ/Nrf2 pathway.

Recently, a variant of insulin-like growth factor-1, mechano-growth factor (MGF), has been discovered whose 24-amino-acid carboxy end is protective in models of stroke, nerve injury, and amyotrophic lateral sclerosis, suggesting broad-spectrum neuroprotective properties. Moreover, we recently demonstrated in vitro and in vivo that a modified protease-resistant 24-amino-acid MGF derivative (MGF24) protects dopaminergic neurons from oxidative stress-induced apoptosis via induction of the stress response protein heme oxygenase-1. However, the underlying mechanism by which MGF24 up-regulates heme oxygenase-1 expression is unknown. In this study, we demonstrate that MGF24-induced heme oxygenase-1 up-regulation is dependent on activation of protein kinase Cϵ and NF-E2-related factor-2 (Nrf2). MGF24 induces nuclear translocation of Nrf2, and siRNA knockdown of Nrf2 or of heme oxygenase-1 prevents MGF24-induced heme oxygenase-1 up-regulation and neuroprotection of SH-SY5Y cells against 6-hydroxydopamine-induced cell death. Pharmacological inhibition of ERK, p38 MAPK, PI3K/Akt, or PKC signaling revealed that only PKC inhibition by GF109203X prevents MGF24's ability to protect against 6-hydroxydopamine-induced cell death. GF109203X also prevented MGF24-induced Nrf2 nuclear translocation and heme oxygenase-1 up-regulation. siRNA knockdown of protein kinase Cϵ blocks MGF24-induced Nfr2 nuclear translocation, heme oxygenase-1 expression, and neuroprotection. Taken together, these results demonstrate that PKC activity is needed for MGF24's activation of Nrf2, which in turn increases heme oxygenase-1 expression, a critical event in mediating MGF24's neuroprotection against 6-hydroxydopamine-induced apoptosis.

The COVID-19 Pandemic: Identifying Adaptive Solutions for Colorectal Cancer Screening in Underserved Communities.

The 2019 novel coronavirus disease (COVID-19) pandemic has dramatically impacted numerous health and economic fronts. Because of the stay-at-home mandate and practice of physical distancing, nearly all preventive care measures have been halted, including colorectal cancer (CRC) screening. The health consequences of this temporary suspension are of great concern, particularly for underserved populations, who experience substantial CRC-related disparities. In this commentary, we describe challenges and opportunities to deliver COVID-19-adapted CRC screening to medically underserved populations receiving care in community health centers (CHC). This perspective is based on key informant interviews with CHC medical directors, teleconference discussions, and strategic planning assessments. To address the unprecedented challenges created by the COVID-19 pandemic, we identify 2 broad calls to action: invest in CHCs now and support equitable and adaptable telehealth solutions now and in the future. We also recommend 4 CRC-specific calls to action: establish COVID-19-adapted best practices to implement mailed fecal immunochemical test programs, implement grassroots advocacy to identify community gastroenterologists who commit to performing colonoscopies for CHC patients, assess cancer prevention priorities among individuals in underserved communities, and assess regional CRC screening and follow-up barriers and solutions. The COVID-19 pandemic may further exacerbate existing CRC screening disparities in underserved individuals. This will likely lead to delayed diagnosis, a shift to later-stage disease, and increased CRC deaths. To prevent this from happening, we call for timely action and a commitment to address the current extraordinary CRC screening challenges for vulnerable populations.

Medical assistant health coaching ("MAC") for type 2 diabetes in diverse primary care settings: A pragmatic, cluster-randomized controlled trial protocol.

In the US, nearly 11% of adults were living with diagnosed diabetes in 2017, and significant type 2 diabetes (T2D) disparities are experienced by socioeconomically disadvantaged, racial/ethnic minority populations, including Hispanics. The standard 15-min primary care visit does not allow for the ongoing self-management support that is needed to meet the complex needs of individuals with diabetes. "Team-based" chronic care delivery is an alternative approach that supplements physician care with contact from allied health personnel in the primary care setting (e.g., medical assistants; MAs) who are specially trained to provide ongoing self-management support or "health coaching." While rigorous trials have shown MA health coaching to improve diabetes outcomes, less is known about if and how such a model can be integrated within real world, primary care clinic workflows. Medical Assistant Health Coaching for Type 2 Diabetes in Diverse Primary Care Settings - A Pragmatic, Cluster-Randomized Controlled Trial will address this gap. Specifically, this study compares MA health coaching versus usual care in improving diabetes clinical control among N = 600 at-risk adults with T2D, and is being conducted at four primary care clinics that are part of two health systems that serve large, ethnically/racially, and socioeconomically diverse populations in Southern California. Electronic medical records are used to identify eligible patients at both health systems, and to examine change in clinical control over one year in the overall sample. Changes in behavioral and psychosocial outcomes are being evaluated by telephone assessment in a subset (n = 300) of participants, and rigorous process and cost evaluations will assess potential for sustainability and scalability.

Modified Sequence Method to Assess Baroreflex Sensitivity in Rats.

Baroreceptors respond to fluctuations in blood pressure (BP) by modifying physiology in order to maintain a homeostatic set point. Baroreflex sensitivity (BRS) is used to quantify baroreceptor function and is a useful metric for tracking cardiovascular disease state and treatment effects. Pathological conditions such as hypertension (HTN) alter baroreflex function and reduce BRS. Traditionally, the sequence method is used to measure BRS, in which the linear slope of concomitant changes in BP and RR intervals are assessed. However, in rats, a high respiratory rate reduces the reliability of the sequence method. Here, we present a modified sequence method that captures BRS at lower frequencies and decreases the variability of the BRS estimate. This method was demonstrated using ECG and BP data from two groups of HTN rats: Sham rats and rats treated with vagus nerve stimulation. The modified sequence method resulted in lower BRS estimates than the traditional sequence technique when applied to the same data sets. Additionally, the modified sequence method resulted in lower BRS estimate variability.

A mutant thyroid hormone receptor alpha antagonizes peroxisome proliferator-activated receptor alpha signaling in vivo and impairs fatty acid oxidation.

Thyroid hormone regulates the balance between lipolysis and lipogenesis. We previously reported that male mice with a dominant-negative P398H mutation introduced into the TRalpha gene have visceral obesity, hyperleptinemia, and reduced catecholamine-stimulated lipolysis in white adipose tissue. Based on our observation of hepatic steatosis in the TRalpha P398H male mice, we used in vitro and in vivo models to investigate the influence of the TRalpha P398H mutant on peroxisome proliferator-activated receptor-alpha (PPARalpha) signaling. Wild-type TRalpha and the P398H mutant significantly reduced PPARalpha-mediated transcription in transient transfection assays. T(3) reversed the inhibition of PPARalpha action by wild-type TRalpha but not the P398H mutant. Chromatin immunoprecipitation assays demonstrated that the P398H mutant reduces PPARalpha binding to peroxisome proliferator receptor elements. In gel shift assays, the P398H mutant directly bound the peroxisome proliferator-activated receptor response element and inhibited PPARalpha binding, which was not reversed by addition of retinoid X receptor. The TRalpha R384C and PV dominant-negative mutants are not associated in vivo with a metabolic phenotype and had reduced (PV) or absent (R384C) PPARalpha inhibition compared with P398H. The metabolic phenotype of the P398H mutant mice is due, in part, to unique properties of the P398H mutant receptor interfering with PPARalpha signaling. The P398H mutant is a potential probe to characterize the physiological role of thyroid hormone receptor/PPARalpha interactions.

Dulce Digital: An mHealth SMS-Based Intervention Improves Glycemic Control in Hispanics With Type 2 Diabetes.

OBJECTIVE: Type 2 diabetes is growing in epidemic proportions and disproportionately affects lower-income, diverse communities. Text messaging may provide one of the most rapid methods to overcome the "digital divide" to improve care. RESEARCH DESIGN AND METHODS: A randomized, nonblinded, parallel-groups clinical trial design allocated N = 126 low-income, Hispanic participants with poorly controlled type 2 diabetes to receive the Dulce Digital intervention or usual care (UC). Dulce Digital participants received up to three motivational, educational, and/or call-to-action text messages per day over 6 months. The primary outcome was HbA1c; lipids, blood pressure, and BMI were secondary outcomes. Satisfaction and acceptability were evaluated via focus groups and self-report survey items. RESULTS: The majority of patients were middle-aged (mean age 48.43 years, SD 9.80), female (75%), born in Mexico (91%), and uninsured (75%) and reported less than a ninth-grade education level (73%) and mean baseline HbA1c 9.5% (80 mmol/mol), SD 1.3, and fasting plasma glucose 187.17 mg/dL, SD 64.75. A statistically significant time-by-group interaction effect indicated that the Dulce Digital group achieved a significantly greater reduction in HbA1c over time compared with UC (P = 0.03). No statistically significant effects were observed for secondary clinical indicators. The number of blood glucose values texted in by participants was a statistically significant predictor of month 6 HbA1c (P < 0.05). Satisfaction and acceptability ratings for the Dulce Digital intervention were high. CONCLUSIONS: Use of a simple, low-cost text messaging program was found to be highly acceptable in this sample of high-risk, Hispanic individuals with type 2 diabetes and resulted in greater improvement in glycemic control compared with UC.

Thyroid hormone regulates endogenous amyloid-beta precursor protein gene expression and processing in both in vitro and in vivo models.

Thyroid hormone negatively regulates the amyloid-beta precursor protein (APP) gene in thyroid hormone receptor (TR)-transfected neuroblastoma cells. A negative thyroid hormone response element (nTRE) that mediates this regulation has been identified in the first exon of the APP gene. We demonstrate in an in vivo system that expression of APP mRNA, APP protein, and APP secretase cleavage products in mouse brain is influenced by thyroid status. Adult female mice were made hyperthyroid or hypothyroid for 3 weeks and compared to euthyroid mice. APP gene product expression was increased in hypothyroid mouse brain and reduced in hyperthyroid mouse brain, when compared to euthyroid controls. We observed similar effects of thyroid hormone on endogenous APP gene expression in human neuroblastoma cells. The incidence of hypothyroidism increases with age, and localized hypothyroidism of central nervous system has been reported in some patients with Alzheimer's disease (AD). Reduced action of thyroid hormone on the APP gene may contribute to AD pathology by increasing APP expression and the levels of processed APP products. These findings may be an underlying mechanism contributing to the association of hypothyroidism with AD in the elderly, as well as identifying a potential therapeutic target. Pharmacologic supplementation of thyroid hormone, or its analogs, may reduce APP gene expression and beta amyloid peptide accumulation.

Systemic retinoic acid treatment induces sodium/iodide symporter expression and radioiodide uptake in mouse breast cancer models.

Lactating breast tissue and some breast cancers express the sodium/iodide symporter (NIS) and concentrate iodide. We recently demonstrated that all-trans retinoic acid (tRA) induces both NIS gene expression and iodide accumulation in vitro in well-differentiated human breast cancer cells (MCF-7). In the present study, we investigated the in vivo efficacy and specificity of tRA-stimulated iodide accumulation in mouse breast cancer models. Immunodeficient mice with MCF-7 xenograft tumors were treated with systemic tRA for 5 days. Iodide accumulation in the xenograft tumors was markedly increased, approximately 15-fold greater than levels without treatment, and the effects were tRA dose dependent. Iodide accumulation in other organs was not significantly influenced by tRA treatment. Significant induction of NIS mRNA and protein in the xenograft tumors was observed after tRA treatment. Iodide accumulation and NIS mRNA expression were also selectively induced in breast cancer tissues in transgenic mice expressing the oncogene, polyoma virus middle T antigen. These data demonstrate selective induction of functional NIS in breast cancer by tRA. Treatment with short-term systemic retinoic acid, followed by radioiodide administration, is a potential tool in the diagnosis and treatment of some differentiated breast cancer.

Thyroid hormone gene targets in ROS 17/2.8 osteoblast-like cells identified by differential display analysis.

Thyroid hormone plays an important role in bone development and metabolism. We used a polymerase chain reaction (PCR)-based mRNA differential display (DD) analysis to obtain a profile of thyroid hormone-responsive genes in osteoblast-like cells (ROS 17/2.8). ROS 17/2.8 cells were treated with 10(-8) M triiodothyronine (T(3)) for 2 and 24 hours. Total RNA was isolated, reverse-transcribed, and amplified using a total of 72 combinations (2 hours) and 240 combinations (24 hours) of 5' and 3' primers. At the 2-hour time point, 1 true-positive novel clone was identified and shown to be the mitochondrial gene, subunit 6 of ATP synthase (ATPase-6). At the 24-hour time point, 3 differentially expressed (DE) mRNAs were confirmed as true-positives including; nonmuscle alkali myosin light chain (NM aMLC), ATPase-6, and one novel clone. T(3)-induction of ATPase-6 mRNA in ROS 17/2.8 cells was seen at 2 and 4 hours, but was maximal at 24 hours (2.1-fold). T(3) induction of ATPase-6 mRNA was increased to fourfold in ROS 17/2.8 cells cultured at a low density. NM aMLC mRNA was modestly upregulated by T(3) in ROS 17/2.8 cells by 1.4-fold, and induction was augmented at low cell density to 1.7-fold. T(3) action on NM aMLC and on the mitochondrial gene ATPase 6, represent novel targets and potential mediators of thyroid hormone action on bone. Cell type, and the extent of cell differentiation, influences T(3) regulation of genes in osteoblast-derived cells.

Dulce Mothers: an intervention to reduce diabetes and cardiovascular risk in Latinas after gestational diabetes.

Latina women with prior gestational diabetes mellitus (GDM) are at elevated risk for type 2 diabetes mellitus and cardiovascular disease. Few primary prevention programs are designed for low socioeconomic status, Spanish-speaking populations. We examined the effectiveness of a Diabetes Prevention Program (DPP) translation in low-income Latinas with a history of GDM. Eighty-four Latinas, 18-45 years old with GDM in the past 3 years, underwent an 8-week peer-educator-led group intervention, with tailoring for Latino culture and recent motherhood. Lifestyle changes and diabetes and cardiovascular risk factors were assessed at study baseline, month 3 and month 6. Participants showed significant improvements in lipids, blood pressure, physical activity, dietary fat intake, and fatalistic and cultural diabetes beliefs (p < 0.05). Formative evaluation provides preliminary evidence of program acceptability. A peer-led, culturally appropriate DPP translation was effective in improving lifestyle changes and some indicators of cardiovascular and diabetes risk in Latinas with GDM.