SFRP1 decreases WNT-Mediated M2 macrophage marker expression in breast tissue.

The Wnt family of secreted proteins are involved in mammary gland development and tumorigenesis. It has recently been shown that Wnt ligands promote M2 macrophage polarization and so we sought to determine the effects of a Wnt signaling antagonist, Secreted Frizzled Related Protein 1 (SFRP1), on M2 marker expression. We measured a murine M2 marker (Arg1) in mice with a targeted deletion of Sfrp1 during different stages of mammary gland development including puberty, pregnancy, and lactation, as well as in response to obesity. Next, to determine whether Wnt signaling/antagonism affects human M2 markers (CD209 and CCL18), we treated a human patient derived explant (PDE) breast tissue sample with exogenous Wnt3a in the presence and absence of rSFRP1. Finally, we expanded our PDE study to 13 patients and performed bulk RNAseq analysis following the treatment described above. We found that in loss of Sfrp1 in the murine mammary gland increased Arg1 expression. Moreover, we showed that Wnt3a increases CD209 and CCL18 mRNA and protein expression in breast PDEs and that their expression is decreased in response to rSFRP1. Our RNAseq analysis unveiled novel genes that were affected by Wnt3a treatment and subsequently reversed when rSFRP1 was added. Validation of these data exhibited that chemokines involved in promoting macrophage polarization and cancer metastasis, including CCL11 and CCL26, were stimulated by Wnt3a signaling and their expression was abrogated by treatment with rSFRP1. Our data suggest that SFRP1 may be an important mediator that tempers Wnt signaling in the tumor microenvironment.

The effect of delay of excisional biopsy on upstage rate for atypical ductal hyperplasia, flat epithelial atypia, intraductal papilloma, and radial scar.

PURPOSE: When Core Needle Biopsy (CNB) demonstrates Atypical Ductal Hyperplasia (ADH), Flat Epithelial Atypia (FEA), Intraductal Papilloma (IDP), or Radial Scar/Complex Sclerosing Lesion (RS), excisional biopsy (EB) is often performed to rule out underlying malignancy with upstage rates (UR) ranging between 1 and 20%. The COVID-19 pandemic led to delayed EB for many patients. We sought to evaluate whether this delay was associated with higher UR. METHODS: We performed a retrospective analysis of women who underwent CNB and then EB for ADH, FEA, IDP, or RS between 2017 and 2021 using an IRB-approved repository. UR was evaluated by days between CNB and EB. RESULTS: 473 patients met inclusion. 55 were upstaged to cancer (11.6%). 178 patients had pure ADH on CNB and 37 were upstaged (20.8%). 50 patients had pure FEA and 3 were upstaged (6%). 132 had pure IDP and 7 were upstaged (5.3%). 98 had pure RS and 1 was upstaged (1%). 7/15 (46.7%) had a combination of diagnoses or diagnosis with palpable mass and were upstaged. Days between CNB and EB were < 60 for 275 patients (58.1%), 60-90 for 108 (22.8%), 91-120 for 43 (9.1%), and > 120 for 47 (9.9%). There was no significant difference in UR (10.9% for < 60, 14.8% for 60-90, 7% for 90-120, and 12.8% for > 120, p = 0.54). UR for ADH was clinically increased after 60 days (27.8 vs. 17.5%), but this did not reach statistical significance (p = 0.1). CONCLUSION: Surgical delay was not associated with an increased UR.

Interindividual variation contributes to differential PCB 126 induced gene expression in primary breast epithelial cells and tissues.

PCB 126 is a pervasive, dioxin-like chemical pollutant which can activate the aryl hydrocarbon receptor (AhR). Despite being banned from the market, PCB 126 can be detected in breast milk to this day. The extent to which interindividual variation impacts the adverse responses to this chemical in the breast tissue remains unclear. This study aimed to investigate the impact of 3 nM PCB 126 on gene expression in a panel of genetically diverse benign human breast epithelial cell (HBEC) cultures and patient derived breast tissues. Six patient derived HBEC cultures were treated with 3 nM PCB 126. RNAseq was used to interrogate the impact of exposure on differential gene expression. Gene expression changes from the top critical pathways were confirmed via qRT-PCR in a larger panel of benign patient derived HBEC cultures, as well as in patient-derived breast tissue explant cultures. RNAseq analysis of HBEC cultures revealed a signature of 144 genes significantly altered by 3 nM PCB 126 treatment. Confirmation of 8 targets using a panel of 12 HBEC cultures and commercially available breast cell lines demonstrated that while the induction of canonical downstream target gene, CYP1A1, was consistent across our primary HBECs, other genes including AREG, S100A8, IL1A, IL1B, MMP7, and CCL28 exhibited significant variability across individuals. The dependence on the activity of the aryl hydrocarbon receptor was confirmed using inhibitors. PCB 126 can induce significant and consistent changes in gene expression associated with xenobiotic metabolism in benign breast epithelial cells. Although the induction of most genes was reliant on the AhR, significant variability was noted between genes and individuals. These data suggest that there is a bifurcation of the pathway following AhR activation that contributes to the variation in interindividual responses.

Syringomatous adenoma of the nipple with microcalcifications on mammography: A case report.

Syringomatous adenoma of the nipple (SAN) is a rare benign lesion which often presents as a subareolar mass with associated nipple shape changes including pruritus, crusting, and discharge It is thought that syringomatous tumors arise from eccrine glands of the nipple and areola. Due to its locally infiltrative growth pattern the main differential is with low-grade adenosquamous carcinoma which requires more aggressive surgical treatment. Syringomatous adenoma of the nipple can recur, and therefore complete local excision is recommended. We present a case of a syringomatous adenoma of the nipple diagnosed after nearly 5 years of observation with microcalcifications noted on mammography.

Gene expression signature of atypical breast hyperplasia and regulation by SFRP1.

BACKGROUND: Atypical breast hyperplasias (AH) have a 10-year risk of progression to invasive cancer estimated at 4-7%, with the overall risk of developing breast cancer increased by ~ 4-fold. AH lesions are estrogen receptor alpha positive (ERα+) and represent risk indicators and/or precursor lesions to low grade ERα+ tumors. Therefore, molecular profiles of AH lesions offer insights into the earliest changes in the breast epithelium, rendering it susceptible to oncogenic transformation. METHODS: In this study, women were selected who were diagnosed with ductal or lobular AH, but no breast cancer prior to or within the 2-year follow-up. Paired AH and histologically normal benign (HNB) tissues from patients were microdissected. RNA was isolated, amplified linearly, labeled, and hybridized to whole transcriptome microarrays to determine gene expression profiles. Genes that were differentially expressed between AH and HNB were identified using a paired analysis. Gene expression signatures distinguishing AH and HNB were defined using AGNES and PAM methods. Regulation of gene networks was investigated using breast epithelial cell lines, explant cultures of normal breast tissue and mouse tissues. RESULTS: A 99-gene signature discriminated the histologically normal and AH tissues in 81% of the cases. Network analysis identified coordinated alterations in signaling through ERα, epidermal growth factor receptors, and androgen receptor which were associated with the development of both lobular and ductal AH. Decreased expression of SFRP1 was also consistently lower in AH. Knockdown of SFRP1 in 76N-Tert cells resulted altered expression of 13 genes similarly to that observed in AH. An SFRP1-regulated network was also observed in tissues from mice lacking Sfrp1. Re-expression of SFRP1 in MCF7 cells provided further support for the SFRP1-regulated network. Treatment of breast explant cultures with rSFRP1 dampened estrogen-induced progesterone receptor levels. CONCLUSIONS: The alterations in gene expression were observed in both ductal and lobular AH suggesting shared underlying mechanisms predisposing to AH. Loss of SFRP1 expression is a significant regulator of AH transcriptional profiles driving previously unidentified changes affecting responses to estrogen and possibly other pathways. The gene signature and pathways provide insights into alterations contributing to AH breast lesions.

Bisphenol-A in breast adipose tissue of breast cancer cases and controls.

We evaluated whether bisphenol-A (BPA) could be quantified in breast adipose tissue samples provided by 36 breast cancer mastectomy patients and 14 reduction mammoplasty patients. Samples of breast adipose tissue were collected and BPA concentration was quantified using HPLC-ESI-MS/MS. BPA was detectable above the limit of quantitation of 0.38 ng/g in 30.6% of samples. BPA concentrations varied within- and between breasts and were similar between cases and controls (0.39 vs 0.41 ng/g, p = 0.74).

Individual-specific variation in the respiratory activities of HMECs and their bioenergetic response to IGF1 and TNFα.

Metabolic reprograming is a hallmark of cancer cells. However, the roles of pre-existing differences in normal cells metabolism toward cancer risk is not known. In order to assess pre-existing variations in normal cell metabolism, we have quantified the inter-individual variation in oxidative metabolism of normal primary human mammary epithelial cells (HMECs). We then assessed their response to selected cytokines such as insulin growth factor 1 (IGF1) and tumor necrosis factor alpha (TNFα), which are associated with breast cancer risk. Specifically, we compared the oxidative metabolism of HMECs obtained from women with breast cancer and without cancer. Our data show considerable inter-individual variation in respiratory activities of HMECs from different women. A bioenergetic parameter called pyruvate-stimulated respiration (PySR) was identified as a key distinguishing feature of HMECs from women with breast cancer and without cancer. Samples showing PySR over 20% of basal respiration rate were considered PySR+ve and the rest as PySR-ve . By this criterion, HMECs from tumor-affected breasts (AB) and non-tumor affected breasts (NAB) of cancer patients were mostly PySR-ve (88% and 89%, respectively), while HMECs from non-cancer patients were mostly PySR+ve (57%). This suggests that PySR-ve/+ve phenotypes are individual-specific and are not caused by field effects due to the presence of tumor. The effects of IGF1 and TNFα treatments on HMECs revealed that both suppressed respiration and extracellular acidification. In addition, IGF1 altered PySR-ve/+ve phenotypes. These results reveal individual-specific differences in pyruvate metabolism of normal breast epithelial cells and its association with breast cancer risk.

The association between family caregivers' involvement in managing older adults' medications and caregivers' information-seeking behavior.

OBJECTIVES: 1) To explore the association between family caregivers' involvement in managing care recipients' medications and their information-seeking behavior related to caregiving; and 2) to examine the sources used by caregivers when seeking information. METHODS: A retrospective analysis of cross-sectional data from 2 national studies, the 2011 National Health and Aging Trends Study (NHATS) and its supplement, the National Study of Caregiving (NSOC), was conducted. A nationally representative sample of community-dwelling adults (≥65 years of age) completed NHATS interviews, and a sample of their family caregivers participated in NSOC. Caregiver involvement in medication management was assessed with the use of 2 items asking caregivers if they helped keep track of care recipients' medications or helped with injecting medications. Information seeking was assessed with the use of an item asking caregivers if they ever looked for caregiving-related information. RESULTS: Out of 1367 caregivers interviewed, 54% reported helping to keep track of care recipients' medications and 8.7% assisting with injecting medications. Approximately 10.2% (n = 149) of caregivers reported seeking information to help them care for their care recipients. Caregivers sought information primarily on their own either through online resources or asking friends or relatives (73.3%). Sixty-four percent also sought information from medical providers or social workers. Adult children of caregivers were more likely to seek information for their older adult parents, based on bivariate analysis (P <0.01). In multivariable-adjusted models, caregivers who helped to keep track of medications had 2.30 (95% confidence interval [CI] 1.18 to 4.51) times higher odds of seeking information to help them to provide care for their care recipients. Caregivers helping with injecting medications were less likely to seek information (odds ratio 0.32, 95% CI 0.14 to 0.76). CONCLUSION: Specific caregiver responsibilities, such as assisting with medication management activities, are associated with caregivers' information-seeking behavior related to care recipients' health. Health care providers, including pharmacists, can play an important role in helping caregivers to identify proper resources for information and in educating them about medication management.

Increased risk of upstage when combinations of breast lesions of uncertain malignant potential are found on core needle biopsy: The need for surgical excision.

BACKGROUND: Management of breast lesions of uncertain malignant potential diagnosed at core needle biopsy (CNB) is controversial due to variable upstage rate (UR) with surgical excision (SE). METHODS: We performed an IRB-approved retrospective analysis of adult women who underwent CNB demonstrating atypical ductal hyperplasia (ADH), flat epithelial atypia, radial scar, or intraductal papilloma then SE between 2010 and 2022. We evaluated CNB pathology for combination diagnoses (CD), defined as multiple primary lesions or primary with lobular neoplasia (LN), and surgical pathology for upstage. RESULTS: 719 patients were included. UR was 12.2% (88/719). CD experienced higher UR than pure (17.7% (45/254) vs. 9.2% (43/465), p â€‹= â€‹0.001). ADH/LN had the highest UR of all CD (34.6% (9/26), p â€‹= â€‹0.001). Increased size (15.6 vs. 10.5 â€‹mm, p â€‹< â€‹0.001), distance from nipple (79 vs. 66 â€‹mm, p â€‹< â€‹0.001), and personal history of breast cancer (p â€‹= â€‹0.04) were associated with UR. CONCLUSIONS: CD was associated with increased UR. ADH/LN had the highest UR.

Student pharmacists' attitudes toward complementary and alternative medicine.

OBJECTIVES: To explore student pharmacists' attitudes toward complementary and alternative medicine (CAM) and examine factors shaping students' attitudes. DESIGN: Descriptive, exploratory, nonexperimental study. SETTING: Electronic survey of student pharmacists between March and October 2011. PARTICIPANTS: 887 student pharmacists in 10 U.S. colleges/schools of pharmacy. INTERVENTION: Cross-sectional survey. MAIN OUTCOME MEASURES: Student pharmacists' attitudes regarding CAM using the attitudes toward CAM scale (15 items), attitudes toward specific CAM therapies (13 items), influence of factors (e.g., coursework, personal experience) on attitudes (18 items), and demographic characteristics (15 items). RESULTS: Mean (±SD) score on the attitudes toward CAM scale was 52.57 ± 7.65 (of a possible 75; higher score indicated more favorable attitudes). Students agreed that a patient's health beliefs should be integrated in the patient care process (4.39 ± 0.70 [of 5]) and that knowledge about CAM would be required in future pharmacy practice (4.05 ± 0.83). Scores on the attitudes toward CAM scale varied by gender (women higher than men, P = 0.001), race/ethnicity (nonwhite higher than white, P < 0.001), type of institution (private higher than public, P < 0.001), previous CAM coursework (P < 0.001), and previous CAM use (P < 0.001). Personal experience, pharmacy education (e.g., coursework and faculty attitudes), and family background were important factors shaping students' attitudes. CONCLUSION: Student pharmacists hold generally favorable views of CAM, and both personal and educational factors shape their views. These results provide insight into factors shaping future pharmacists' perceptions of CAM. Additional research is needed to examine how attitudes influence future pharmacists' confidence and willingness to talk to patients about CAM.

Outcomes of a Multidisciplinary Team in the Management of Patients with Early-Stage Breast Cancer Undergoing Neoadjuvant Chemotherapy at a Community Cancer Center.

Background: The utilization of neoadjuvant chemotherapy (NAC) remains highly variable in clinical practice. The implementation of NAC requires coordination of handoffs between a multidisciplinary team (MDT). This study aims to assess the outcomes of an MDT in the management of early-stage breast cancer patients undergoing neoadjuvant chemotherapy at a community cancer center. Methods: We conducted a retrospective case series on patients receiving NAC for early-stage operable or locally advanced breast cancer coordinated by an MDT. Outcomes of interest included the rate of downstaging of cancer in the breast and axilla, time from biopsy to NAC, time from completion of NAC to surgery, and time from surgery to radiation therapy (RT). Results: Ninety-four patients underwent NAC; 84% were White and mean age was 56.5 yrs. Of them, 87 (92.5%) had clinical stage II or III cancer, and 43 (45.8%) had positive lymph nodes. Thirty-nine patients (42.9%) were triple negative, 28 (30.8%) were human epidermal growth factor receptor (HER-2)+, and 24 (26.2%) were estrogen receptor (ER) +HER-2-. Of 91 patients, 23 (25.3%) achieved pCR; 84 patients (91.4%) had downstaging of the breast tumor, and 30 (33%) had axillary downstaging. The median time from diagnosis to NAC was 37.5 days, the time from completion of NAC to surgery was 29 days, and the time from surgery to RT was 49.5 days. Conclusions: Our MDT provided timely, coordinated, and consistent care for patients with early-stage breast cancer undergoing NAC as evidenced by time to treatment outcomes consistent with recommended national trends.

The Influence of Screening Mammography Cessation and Resumption on Breast Cancer Presentation and Treatment: A Multi-Hospital Health System Experience During the Early COVID-19 Pandemic.

Objective: To assess the impact of the coronavirus disease-2019 (COVID-19) pandemic screening restrictions on the diagnosis and treatment of breast cancer in a single health system. Materials and Methods: We performed a retrospective, cohort investigation of breast cancer patients at a multi-institution health system from March 1, 2019 to December 31, 2020 with two time periods related to the pandemic: "Early phase" (March 18 - June 7) reflecting the time of the screening mammography moratorium and "Late phase" (June 8 - December 31) to reflect the time once screening mammography resumed. 2020 was compared to 2019 to exclude potential differences from temporal or seasonal changes. Variables included demographics, COVID related-deferral, cancer specific data, method of detection, type of treatment recommended and received. Results: Fewer patients presented with a breast cancer diagnosis during Early phase 2020 when compared to any other time period. Numbers increased significantly in Late phase 2020; total numbers of patients seen in 2020 approached but did not completely reach that of 2019. When compared to other time periods, patients who presented during the moratorium on screening were younger, more likely to be black, had a higher Body Mass Index, and were more likely to have a human epidermal growth factor receptor 2 positive tumor. There was a slight increase in size of presenting tumor and node positivity, although no differences in breast or axillary surgical management were identified. Conclusion: Despite an increase in tumor size and positive nodal status seen during the screening moratorium, surgical treatment was not negatively impacted.

Health literacy and self-care of patients with heart failure.

BACKGROUND AND RESEARCH OBJECTIVE: Today's complex healthcare system relies heavily on sophisticated self-care regimens. To navigate the system and follow self-care protocols, patients must be able to understand and use health information, which requires health literacy. However, nearly 90 million Americans lack the necessary health literacy skills to adequately care for themselves in the face of a complex healthcare system and self-care regimens. Understanding how to effectively care for one's self is thought to improve heart failure symptoms and patient outcomes, but little is actually known about how health literacy influences self-care in patients with heart failure. The purpose of this pilot study was to examine the relationship between health literacy and self-care of patients with heart failure. SUBJECTS AND METHODS: Patients with a diagnosis of heart failure were recruited from a variety of community settings. Participants completed the Short-Form Test of Functional Health Literacy (measured health literacy), the Self-care Index of Heart Failure (measured self-care maintenance, management, and confidence), and a demographic questionnaire. Spearman ρ correlations were used to assess the strength of the relationship between health literacy level and self-care scores. RESULTS AND CONCLUSIONS: Among the 49 participants recruited, health literacy was positively related to self-care maintenance (Rs = 0.357, P = .006). Health literacy had a negative relationship with self-care management (Rs = -0.573, P = .001). There was no association between health literacy and self-care confidence (Rs = 0.201, P = .083). This project provides preliminary data regarding the association between health literacy and self-care in heart failure, showing support for higher health-literate patients performing more self-care maintenance, which has been shown to improve patient outcomes in heart failure. Patients with higher health literacy trended toward having greater self-care confidence, which can increase the likelihood of performing self-care, but this finding was not statistically significant. It was unexpected to find that lower health-literate patients performed more self-care management.

Preliminary study of the contraceptive effect of a self-assembling intrauterine device (iUPODs) in mares maintained in a paddock with a fertile stallion.

There is an urgent need for practical methods of population control (i.e., contraception and/or sterilization) for free-roaming (i.e., "wild" or "feral") horses and burros on Western Public Lands in the United States. The objective of this study was to evaluate the contraceptive efficacy of a novel self-assembling three-part polymer-coated magnetic intrauterine device termed as an intrauterine POD (self-assembling; iUPOD) when there are natural breeding conditions when iUPOD use was managed by veterinary professionals with no prior experience with the device. Six mares were administered an iUPOD and were then housed continuously with a fertile stallion for 91 days. The intrauterine POD retention and contraceptive efficacy were 100%. Two mares had prolonged corpus luteum function (for 37 and 91 days) immediately after iUPOD placement. For the estrous cycles of the other mares, the duration of diestrus was 7.8 ± 2.7 days (mean ± S.D.). Four of the mares (67%) became pregnant when in a paddock with the same stallion the year after iUPOD removal. These results are encouraging for use of the iUPOD as a practical and reversible method of fertility control in free-roaming horses and burros.

Evaluation of a Proprietary Slow-Release Oxytocin Formulation on Corpus Luteum Function in Mares.

Prolonging function of the corpus luteum (CL) is a method of suppressing estrus that relies on continued secretion of endogenous progesterone to keep mares out of heat naturally. The use of oxytocin treatment to prolong CL function is gaining increasing use, and the most common treatment protocol involves administration of 60 units of oxytocin intramuscularly (IM) once daily on days 7-14 after ovulation (eight daily treatments). Although that protocol induces prolonged CL function in ≥70% of treated mares, the need for daily administration is a drawback to its use. Therefore, the objective of this study was to evaluate the efficacy of a proprietary slow-release oxytocin formulation (SR-OT) for prolonging CL function that requires only two treatments. Mares were examined via transrectal palpation and ultrasonography to determine the day of ovulation (day 0) and then randomly assigned to a nontreated control group and an SR-OT treatment group (n = 8 mares/group). Mares in the treated group received 1.0 mL of SR-OT containing 2,400 IU oxytocin IM once on day 7 and again on day 10 after ovulation. Jugular blood samples were collected on day 0 and then every Monday, Wednesday, and Friday for 50 days for determination of the serum progesterone concentration. Mares were classified as having prolonged CL function if their progesterone concentration remained >1.0 ng/mL continuously for at least 30 days. Corpus luteum function was prolonged in 0/8 (0%) control mares and 6/8 (75%) of the SR-OT-treated mares (P < .01). The demonstrated efficacy of this two-injection, SR-OT protocol represents a 75% reduction in the number of oxytocin treatments compared with daily administration of oxytocin from day 7-14, making it a more practical treatment protocol.

Report of the 2018-2019 Student Affairs Standing Committee.

The 2018-2019 Student Affairs Standing Committee addressed charges related to examining the institutional leadership models and professional development needs of faculty and staff to optimize achievement of Strategic Priority #1 on the applicant pipeline. The report provides five recommendations to AACP and twelve suggestions for colleges and schools of pharmacy. The committee focused on the need to develop tailored leadership training and mentoring programs for admissions personnel on relevant topics, including change management, holistic thinking, leadership, problem solving, technical knowledge, professional development, paths for promotion, conflict resolution, networking, persuasive communication, and strategic planning. Rather than develop new resources, the committee identified existing professional competencies and assessment resources developed by other organizations for student affairs and admissions personnel that could spur enhanced strategic marketing and professional development opportunities in pharmacy education. It also reaffirmed the need for student diversity and the use of data to drive strategic decisions in recruitment. To identify gaps in knowledge among AACP member institutions, the committee analyzed the results of its fall 2018 survey on the current depth and breadth of student recruitment activities and their perceived effectiveness. The committee also recommended ways institutions can encourage faculty and others outside of the admissions office to participate in student recruitment activities. Finally, the committee concluded that it will be necessary for colleges and schools to collaborate across the academy to promote the benefits of pharmacy profession to prospective students, rather than individual colleges and schools of pharmacy, and be more responsive to the expectations of Gen Z students before the tide in applications will shift in a positive direction.

Iatrogenic Hyperinsulinemia, Not Hyperglycemia, Drives Insulin Resistance in Type 1 Diabetes as Revealed by Comparison With GCK-MODY (MODY2).

Although insulin resistance consistently occurs with type 1 diabetes, its predominant driver is uncertain. We therefore determined the relative contributions of hyperglycemia and iatrogenic hyperinsulinemia to insulin resistance using hyperinsulinemic-euglycemic clamps in three participant groups (n = 10/group) with differing insulinemia and glycemia: healthy control subjects (euinsulinemia and euglycemia), glucokinase-maturity-onset diabetes of the young (GCK-MODY; euinsulinemia and hyperglycemia), and type 1 diabetes (hyperinsulinemia and hyperglycemia matching GCK-MODY). We assessed the contribution of hyperglycemia by comparing insulin sensitivity in control and GCK-MODY and the contribution of hyperinsulinemia by comparing GCK-MODY and type 1 diabetes. Hemoglobin A1c was normal in control subjects and similarly elevated for type 1 diabetes and GCK-MODY. Basal insulin levels in control subjects and GCK-MODY were nearly equal but were 2.5-fold higher in type 1 diabetes. Low-dose insulin infusion suppressed endogenous glucose production similarly in all groups and suppressed nonesterified fatty acids similarly between control subjects and GCK-MODY, but to a lesser extent for type 1 diabetes. High-dose insulin infusion stimulated glucose disposal similarly in control subjects and GCK-MODY but was 29% and 22% less effective in type 1 diabetes, respectively. Multivariable linear regression showed that insulinemia-but not glycemia-was significantly associated with muscle insulin sensitivity. These data suggest that iatrogenic hyperinsulinemia predominates in driving insulin resistance in type 1 diabetes.

Interstitial granulomatous dermatitis associated with darifenacin.

Interstitial granulomatous dermatitis is most commonly associated with rheumatoid arthritis (RA) but may be induced by medications as well. Darifenacin is a muscarinic antagonist which was FDA approved for the treatment of overactive bladder in December 2004. The authors describe a case of interstitial granulomatous dermatitis associated with darifenacin.

The Influence of Oblique Angle Forced Exercise in Surgically Destabilized Stifle Joints Is Synergistic with Bone, but Antagonistic with Cartilage in an Ovine Model of Osteoarthritis.

Large animal models of osteoarthritis are a necessary testing ground for FDA approval of human medicine applications. Sheep models have advantages over other available large animals, but development and progression of osteoarthritis in sheep is exceedingly slow, which handicaps progress in development of potential treatments. We combined oblique angle forced exercise to increase stress on the stifle, with surgical destabilization to hasten the development of osteoarthritis in ewes. Methods for early detection of clinical signs included radiography, urine, and serum biomarker assays and gait analysis and ex vivo we used microcomputed tomography and macroscopic joint analysis. Our model was able to produce clinically detectable signs of osteoarthritis in a relatively short period (14 weeks). Changes in bone were highly correlated between microcomputed tomography and radiographic analysis and changes in cartilage correlated well between urinary glycosaminoglycan levels and serum aggrecanase analyses. Exercise improved the negative effects of destabilization in bone but exacerbated the negative effects of destabilization in cartilage. These observations suggest that we may need to consider treatments for bone and cartilage separately. These results represent an improved large animal model of osteoarthritis with rapid onset of disease and superior detection of bone and soft tissue changes.

Development and validation of a scale to assess attitudes of health care administrators toward the use of e-mail communication between patients and physicians.

BACKGROUND: The medical profession has been slow in embracing the e-mail as a means of improving patient communications. Today, most physicians work in group practices where administrators seek to develop standard procedures for care delivery. To understand the slow adoption of e-mail technology among physicians when communicating with their patients, it is important to understand these administrators' attitudes. OBJECTIVE: The purpose of this study was to develop and purify a scale to measure health care administrators' attitudes toward the use of e-mail communication and identify associations between e-mail communication attitudes and administrators' demographic and practice-related characteristics. METHODS: A preliminary list of features for e-mail communication was generated by reviewing the literature and Rogers' diffusion theory. The features were grouped initially into 5 hypothesized dimensions: relative advantage, norms (established rules of the social system), complexity, compatibility, and infrastructure. Following pilot testing, the main survey instrument was mailed to a total of 1500 health care administrators. Attitudes toward features of e-mail communication scale were analyzed using exploratory factor analysis with promax rotation. Internal consistency of the scale and its subscales was determined using Cronbach's alpha and item-total correlations. RESULTS: The overall response rate was 8.7%. Scale purification procedures reduced the preliminary scale of 22 items to a final scale of 20 items. The reliability of the scale measured by Cronbach's alpha was 0.81. Norms was considered the major barrier to e-mail communication, whereas infrastructure was considered a facilitator, and other features like relative advantage, complexity, and compatibility issues were perceived more as a barrier than a facilitator. The item related to and usage of e-mail by staff was statistically significant with the overall scale score (P=0.0095), complexity subscale score (P=0.0168), and infrastructure subscale score (P=0.0480). The relationship between number of years of experience of the administrator and infrastructure subscale score was statistically significant (P=0.0480). CONCLUSION: A scale developed to determine the attitudes of health care administrators regarding e-mail communication between patients and physicians demonstrated adequate content validity and reliability.