Community-Based Upper Extremity Power Training for Youth with Cerebral Palsy: A Pilot Study.

Aim: To examine the effects of an upper-extremity, community-based, and power-training intervention.Methods: Twelve participants with cerebral palsy (CP) [8 males, 4 females; mean age 14 years 6 months (SD 5 years 4 months), range 7-24] were randomly assigned to a rest-training (RT; n = 6) or training-rest (n = 6) group in this randomized, cross-over design. Training took place in participants' home or school, three times per week for 6 weeks. We examined changes in upper extremity average power output (Pavg) in watts (W) and changes in function via the Pediatric Outcomes Data Collection Instrument (PODCI).Results: Each participant completed at least 15 of the 18 total training sessions (91.2% adherence). Pavg increased 92.2% on average among participants (p < .05). There was a significant three-way interaction among treatment, sequence, and period with the data stratified by (Bimanual Fine Motor Function [BFMF]) level on the pain subscale of the PODCI (p = 0.0118). All participants decreased pain after training with the exception of individuals with lower functioning (BFMF II-V) in the RT group.Conclusion: A community-based upper extremity power-training intervention was feasible and effective at improving power among young people with CP and has the potential to improve pain.

The Determinants of Physical Activity in Rural Women, Aged 20 to 44 Years, in Georgia.

Physical activity rates in rural women are very low. The purpose of this study was to explore the determinants of physical activity in rural women aged 20 to 44 years. A survey was used to collect data on a cluster sample of 184 participants. This study was guided by Self-Determination Theory. Survey data suggest that the highest type of motivation was identified regulation, and husband's support had the strongest effect on physical activity. Findings suggest that a history of sports participation can lead to the formation of intrinsic motivation. The results will assist in developing effective physical activity interventions.

Transcriptional responses to loss or gain of function of the leucine-rich repeat kinase 2 (LRRK2) gene uncover biological processes modulated by LRRK2 activity.

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are the most common genetic cause of Parkinson's disease (PD) and cause both autosomal dominant familial and sporadic PD. Currently, the physiological and pathogenic activities of LRRK2 are poorly understood. To decipher the biological functions of LRRK2, including the genes and pathways modulated by LRRK2 kinase activity in vivo, we assayed genome-wide mRNA expression in the brain and peripheral tissues from LRRK2 knockout (KO) and kinase hyperactive G2019S (G2019S) transgenic mice. Subtle but significant differences in mRNA expression were observed relative to wild-type (WT) controls in the cortex, striatum and kidney of KO animals, but only in the striatum in the G2019S model. In contrast, robust, consistent and highly significant differences were identified by the direct comparison of KO and G2019S profiles in the cortex, striatum, kidney and muscle, indicating opposite effects on mRNA expression by the two models relative to WT. Ribosomal and glycolytic biological functions were consistently and significantly up-regulated in LRRK2 G2019S compared with LRRK2 KO tissues. Genes involved in membrane-bound organelles, oxidative phosphorylation, mRNA processing and the endoplasmic reticulum were down-regulated in LRRK2 G2019S mice compared with KO. We confirmed the expression patterns of 35 LRRK2-regulated genes using quantitative reverse transcription polymerase chain reaction. These findings provide the first description of the transcriptional responses to genetically modified LRRK2 activity and provide preclinical target engagement and/or pharmacodynamic biomarker strategies for LRRK2 and may inform future therapeutic strategies for LRRK2-associated PD.

Recommendations and administration of the HPV vaccine to 11- to 12-year-old girls and boys: a statewide survey of Georgia vaccines for children provider practices.

OBJECTIVE: This study explores the prevalence and provider- and practice-related correlates of physician recommendation and administration of the quadrivalent human papillomavirus (HPV) vaccine, Gardasil, to 11- to 12-year-old girls and the intention to recommend the HPV vaccine to 11- to 12-year-old boys in Georgia. The study also describes physician knowledge about and barriers to HPV vaccination. MATERIALS AND METHODS: This cross-sectional study was conducted from December 2010 to February 2011. The study sample was drawn using the Georgia Vaccines for Children (VFC) provider list as a sampling frame and probability 1-stage cluster sampling with counties as clusters. The final analytic sample was restricted to 206 provider locations. Weighted percentages and corresponding statistics were calculated accounting for selection probabilities, nonresponse, and the cluster sample design. RESULTS: Among Georgia VFC providers attending to 11- to 12-year-old girls, 46% had always recommended that their patients get the HPV vaccination and 41% had vaccinated their female patients. Among Georgia VFC providers attending to 11- to 12-year-old boys, 20% would always recommend that their male patients get vaccinated.Physicians most frequently endorsed costs of stocking the vaccine (73%), upfront costs (69%), vaccination (68%), and insurance reimbursements (63%) as barriers to their HPV vaccination practices. CONCLUSIONS: Despite the Advisory Committee on Immunization Practices' recommendations on HPV vaccination, the prevalence of recommending and administering the HPV vaccine to female and male patients, aged 11 to 12 years, by VFC providers is an ongoing challenge in Georgia.

Impact of school flu vaccine program on student absences.

Literature provides evidence that school attendance correlates with academic performance and student success. Influenza is a contributing factor to school absences. Primary prevention for influenza includes immunization. School-located influenza vaccine (SLIV) programs provide greater access for students to be immunized. A retrospective review of preexisting data from four academic years was conducted to examine the relationship between SLIV participation and absenteeism among students at eight public elementary schools in Effingham County, Georgia. Results identified differences in average frequency of absences between SLIV and non-SLIV years as well as between SLIV participants and nonparticipants for the 2 SLIV years. Implications for practice include the potential for increased herd immunity among students, which may also extend to other parties within the school community and at home, thus promoting overall wellness and future student success.

The effect of music-based listening interventions on the volume, fat content, and caloric content of breast milk-produced by mothers of premature and critically ill infants.

PURPOSE: Maternal breast milk is considered the nutritional "gold standard" for all infants, especially premature infants. However, preterm mothers are at risk of not producing adequate milk. Multiple factors affect the production of milk, including stress, fatigue, and the separation of the breastfeeding dyad-for example, when mother or infant is hospitalized. The purpose of this study was to examine the effects of listening and visual interventions on the quantity and quality of breast milk produced by mothers using a double electric breast pump. SUBJECTS: Mothers of 162 preterm infants were randomly assigned to 1 of 4 groups. METHODS: The control group received standard nursing care, whereas mothers in the 3 experimental groups additionally listened to a recording of 1 of 3 music-based listening interventions while using the pump. RESULTS: Mothers in the experimental groups produced significantly more milk (P < .0012). Mothers in these groups also produced milk with significantly higher fat content during the first 6 days of the study.

Discovery of the selective androgen receptor modulator MK-0773 using a rational development strategy based on differential transcriptional requirements for androgenic anabolism versus reproductive physiology.

Selective androgen receptor modulators (SARMs) are androgen receptor (AR) ligands that induce anabolism while having reduced effects in reproductive tissues. In various experimental contexts SARMs fully activate, partially activate, or even antagonize the AR, but how these complex activities translate into tissue selectivity is not known. Here, we probed receptor function using >1000 synthetic AR ligands. These compounds produced a spectrum of activities in each assay ranging from 0 to 100% of maximal response. By testing different classes of compounds in ovariectomized rats, we established that ligands that transactivated a model promoter 40-80% of an agonist, recruited the coactivator GRIP-1 <15%, and stabilized the N-/C-terminal interdomain interaction <7% induced bone formation with reduced effects in the uterus and in sebaceous glands. Using these criteria, multiple SARMs were synthesized including MK-0773, a 4-aza-steroid that exhibited tissue selectivity in humans. Thus, AR activated to moderate levels due to reduced cofactor recruitment, and N-/C-terminal interactions produce a fully anabolic response, whereas more complete receptor activation is required for reproductive effects. This bimodal activation provides a molecular basis for the development of SARMs.

Early cardiac pacemaker placement for life-threatening bradycardia in traumatic spinal cord injury.

BACKGROUND: High cervical spinal cord injury (CSCI) can cause life-threatening bradycardia from autonomic instability that may be resistant to pharmacologic interventions. Placement of a cardiac pacemaker, traditionally reserved for patients refractory to drug therapy, may be lifesaving. METHODS: Our Level I trauma center registry found all patients with CSCI from 2003 to 2009. A retrospective chart review identified major events involving the circulatory system: those exhibiting bradycardia (minor, heart rate 40-60/min; major, heart rate <40/min), hypotension (systolic blood pressure <80 mm Hg), asystole, and cardiac arrest. Records of pharmacological interventions (e.g., atropine) and details of pacemaker placement (e.g., timing and any complications) were reviewed. Statistical differences were determined by Wilcoxon signed-rank test, with p < 0.05 as significant. RESULTS: Of the 106 patients with CSCI, 15 (14%) had bradycardia and 7 of those (47%) underwent cardiac pacemaker placement. Six of seven patients had reviewable data. A total of 35 events occurred in these six patients before pacemaker placement. Subsequent to placement, there were zero events of cardiovascular instability (p = 0.0135). Major bradycardic episodes were reduced from 9 to 0 (p = 0.0206) and incidents requiring atropine administration from 9 to 0 (p = 0.0197). Four survived; two patients died from pulmonary complications. There were no complications related to pacemaker insertion. CONCLUSIONS: Patients with CSCI life-threatening complications of bradycardia benefit from early placement of a cardiac pacemaker. Early stabilization may facilitate transfer out of the intensive care unit, mobilization, physical therapy, rehabilitation, and outcome.

Identification of anabolic selective androgen receptor modulators with reduced activities in reproductive tissues and sebaceous glands.

Androgen replacement therapy is a promising strategy for the treatment of frailty; however, androgens pose risks for unwanted effects including virilization and hypertrophy of reproductive organs. Selective Androgen Receptor Modulators (SARMs) retain the anabolic properties of androgens in bone and muscle while having reduced effects in other tissues. We describe two structurally similar 4-aza-steroidal androgen receptor (AR) ligands, Cl-4AS-1, a full agonist, and TFM-4AS-1, which is a SARM. TFM-4AS-1 is a potent AR ligand (IC(50), 38 nm) that partially activates an AR-dependent MMTV promoter (55% of maximal response) while antagonizing the N-terminal/C-terminal interaction within AR that is required for full receptor activation. Microarray analyses of MDA-MB-453 cells show that whereas Cl-4AS-1 behaves like 5alpha-dihydrotestosterone (DHT), TFM-4AS-1 acts as a gene-selective agonist, inducing some genes as effectively as DHT and others to a lesser extent or not at all. This gene-selective agonism manifests as tissue-selectivity: in ovariectomized rats, Cl-4AS-1 mimics DHT while TFM-4AS-1 promotes the accrual of bone and muscle mass while having reduced effects on reproductive organs and sebaceous glands. Moreover, TFM-4AS-1 does not promote prostate growth and antagonizes DHT in seminal vesicles. To confirm that the biochemical properties of TFM-4AS-1 confer tissue selectivity, we identified a structurally unrelated compound, FTBU-1, with partial agonist activity coupled with antagonism of the N-terminal/C-terminal interaction and found that it also behaves as a SARM. TFM-4AS-1 and FTBU-1 represent two new classes of SARMs and will allow for comparative studies aimed at understanding the biophysical and physiological basis of tissue-selective effects of nuclear receptor ligands.

Characteristics of problem drinking in an urban South American indigenous population.

This 2002 Medcen Foundation-funded study explored characteristics of problem drinking among 211 urban Venezuelan Native Americans of Arawak origin. Prevalence of problem drinking using Alcohol Use Disorders Identification Tests was 88.5% among men and 17.3% among women. Periodic binge drinking was marked by loss of control, failure to meet obligations, and alcohol-related trauma. Focus group participants noted that previous occasional binge drinking by men has been replaced by frequent male and female heavy weekend drinking, violence, and death. Limitations and implications are discussed. Awareness of high levels of problem drinking and desire for assistance present compelling mandates for community intervention efforts.

The false claims act and its impact on medical practices.

A lawsuit under the federal False Claims Act can threaten the survival of a medical practice. The Act prohibits a range of misconduct involving the submission of false claims to the government, as well as the knowing and improper retention of overpayments of government funds. Violations of the Act result in liability for treble damages and civil penalties of as much as $11,000 per violation. Although the Act imposes liability only on persons who act "knowingly," the "knowing" requirement is met if the person acts with deliberate ignorance or reckless disregard of the circumstances. The Act contains a "qui tam provision under which a whistleblower, acting on behalf of the government, may file suit to enforce the Act's terms, and if the lawsuit is successful, can receive a substantial percentage of the government's recovery.

Using a Checklist to Improve Family Communication in Trauma Care.

Modern concepts of patient-centered care emphasize effective communication with patients and families, an essential requirement in acute trauma settings. We hypothesized that using a checklist to guide the initial family conversation would improve the family's perception of the interaction. Institutional Review Board-approved, prospective pre/post study involving families of trauma patients admitted to our Level I trauma center for >24 hours. In the control group, families received information according to existing practices. In the study group, residents gave patient information to a first-degree family member using a checklist that guided the interaction. The checklist included a physician introduction, patient condition, list of known injuries, admission unit or intensive care unit, any consultants involved, plans for additional studies or operations, and opportunity for family to ask questions. An 11-item survey was administered 24 to 48 hours after admission to each group that evaluated the trauma team's communication in the areas of physician introduction, patient condition, ongoing treatment, and family perception of the interaction. Responses were on a Likert scale and analyzed using the Wilcoxon-Mann-Whitney test. There were 130 patients in each group. The study group had significantly (P < 0.05) better responses in 8 of 11 items surveyed: physician spoke to family, physician introduction, understanding of their relative's injuries, admitting unit, consultants involved, urgent surgical procedures required, ongoing diagnostic studies, and understanding of the treatment plan. In conclusion, using a checklist improves the perception of the initial communication between the trauma team and family members of trauma patients, especially their understanding of the treatment plan.

The LATS2/KPM tumor suppressor is a negative regulator of the androgen receptor.

The androgen receptor (AR) is a member of the steroid receptor superfamily that plays critical roles in the development and maintenance of the male reproductive system and in prostate cancer. Actions of AR are controlled by interaction with several classes of coregulators. In this study, we have identified LATS2/KPM as a novel AR-interacting protein. Human LATS1 and LATS2 are tumor suppressors that are homologs of Drosophila warts/lats. The interaction surface of LATS2 is mapped to the central region of the protein, whereas the AR ligand binding domain is sufficient for this interaction. LATS2 functions as a modulator of AR by inhibiting androgen-regulated gene expression. The mechanism of LATS2-mediated repression of AR activity appears to involve the inhibition of AR NH2- and COOH-terminal interaction. Chromatin immunoprecipitation assays in human prostate carcinoma cells reveal that LATS2 and AR are present in the protein complex that binds at the promoter and enhancer regions of prostate-specific antigen, and overexpression of LATS2 results in a reduction in androgen-induced expression of endogenous prostate-specific antigen mRNA. Immunohistochemistry shows that LATS2 and AR are localized within the prostate epithelium and that LATS2 expression is lower in human prostate tumor samples than in normal prostate. The results suggest that LATS2 may play a role in AR-mediated transcription and contribute to the development of prostate cancer.

Hemoglobin A1c levels in diagnosed and undiagnosed black, Hispanic, and white persons with diabetes: results from NHANES 1999-2000.

PURPOSE: Although the prevalence of diabetes among various racial/ethnic groups has been well studied, little is known about the racial/ ethnic differences in Hemoglobin A1c (HbA1c) in diagnosed and undiagnosed diabetes. HbA1c correlates with morbidity and mortality in diabetes. Knowledge of the racial/ethnic differences in HbA1c would impact screening and intervention in primary care settings. This study describes racial/ethnic differences in HbA1c among US Black, Hispanic, and White diagnosed and undiagnosed persons with diabetes. METHODS: This study included participants in the 1999-2000 National Health and Nutrition Examination Survey who were > or =20 years old with a HbA1c measurement. The association between HbA1c and race in diagnosed and undiagnosed persons with diabetes (with body mass index [BMI] and age as covariates) was determined. The distribution of HbA1c and mean HbA1c in diagnosed and undiagnosed diabetes and the rates of diagnosed and undiagnosed diabetes with their corresponding HbA1c levels are described by race/ethnicity. RESULTS: Estimated diabetes prevalence in US persons > or =20 years is 8.2%, with 2.3% having undiagnosed diabetes. Whites with diabetes had lower mean HbA1c levels (7.6%, standard error [SEI 0.2) than Blacks (8.1%, SE 0.3) or Hispanics (8.2%, SE .3). Whites with diagnosed diabetes were less likely to have HbA1c> or =11% (1.7%) than Blacks (11.1%) or Hispanics (10.4%). Hispanics with undiagnosed diabetes were more likely to have HbA1c-7% (60.5%) than Blacks (39.3%) or Whites (37.8%). CONCLUSIONS: Significant numbers of persons with diabetes are undiagnosed. There are significant racial/ethnic differences in HbA1c levels, which are significantly higher in Blacks and Hispanics. Comprehensive risk-based screening and intervention for diabetes is needed in order to address racial and ethnic disparities, especially in minorities.

Impedance cardiography: the next vital sign technology?

OBJECTIVE: To evaluate the following: (1) the intramethod variability of impedance cardiography (ICG) cardiac output (CO) measurements via the latest generation monitor and thermodilution CO measurements (CO-TDs); (2) the intermethod comparison of ICG CO and CO-TD; and (3) comparisons of the intergeneration ICG CO equation to CO-TD, using the latest ICG CO equation, the ZMARC (CO-ICG), and the predecessor equations for measuring the ICG CO of Kubicek (CO-K), Sramek (CO-S), and Sramek-Bernstein (CO-SB). DESIGN: Prospective study. SETTING: A cardiovascular-thoracic surgery ICU in a community university-affiliated hospital. PATIENTS: Post-coronary artery bypass graft patients (n = 53) in whom 210 pairs of CO measurements were made. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The CO-ICG was determined simultaneously while the nurse was performing the CO-TD. Variability within the monitoring method was better for CO-ICG compared to CO-TD (6.3% vs 24.7%, respectively). The correlation, bias, and precision of the CO-ICG was good compared to CO-TD (r(2) = 0.658; r = 0.811; bias, -0.17 L/min; precision, 1.09 L/min; CO-ICG = 1.00 x CO-TD - 0.17; p < 0.001). A steady improvement in agreement of the previous ICG methodologies compared to CO-TD was observed as follows: (1) CO-K: r(2) = 0.309; r = 0.556; bias, -1.71 L/min; precision, 1.81 L/min; CO-K = 0.78 x CO-TD - 0.45; p < 0.001; (2) CO-S: r(2) = 0.361; r = 0.601; bias, -1.46 L/min; precision, 1.63 L/min; CO-S = 0.80 x CO-TD - 0.36; p < 0.001; and (3) CO-SB: r(2) = 0.469; r = 0.685; bias, -0.77 L/min; precision, 1.69 L/min; CO-SB = 1.03 x CO-TD - 0.95; p < 0.001. The CO-ICG demonstrated the closest agreement to CO-TD. CONCLUSION: The latest ICG technology for determining CO (CO-ICG) is less variable and more reproducible in an intrapatient sense than is CO-TD, it is equivalent to the average accepted CO-TD in post-coronary artery bypass graft patients, and showed marked improvement in agreement with CO-TD compared to measurements made using previous generation ICG CO equations.

Impact of a surgical oncologist on general surgery residency training program.

BACKGROUND: To assess the impact of adding a surgical oncologist to our faculty we examined the operative experience in our program before and after the addition. METHODS: Operative case numbers reported to the American Board of Surgery over a 10-year period were analyzed. This time period encompassed 5 years before and after the addition of a surgical oncologist to our faculty. All defined category case numbers were examined using t test analysis. Significance was defined as a P value of less than 0.05. RESULTS: The overall caseload increased in the time period after the faculty addition. There was a statistically significant increase in skin/soft tissue, breast, esophagus, small intestine, large intestine, live, spleen, and endocrine cases. No statistical significance was seen in head/neck, stomach, pancreas, and biliary cases. CONCLUSIONS: The addition of a surgical oncologist to our faculty coincides with a statistically significant increase in areas of skin/soft tissue, breast, esophagus, small intestine, large intestine, liver, spleen, and endocrine. Other areas not statistically significant may reflect referral patterns or this particular oncologist's preferences of practice.

Rat tail skin temperature regulation by estrogen, phytoestrogens and tamoxifen.

OBJECTIVE: Develop a rat model for the evaluation of estrogenic agents on estrogen deficiency-induced changes in thermoregulation. METHODS: OVX rats are impaired in thermoregulation which manifests itself as an elevation in basal tail skin temperature (TST) and are less able to respond to temperature changes than intact rats. RESULTS: Administration of estrogen subcutaneously to estrogen-depleted rats either as depot formulation, biodegradable pellets, or daily injections, suppressed the increased TST. OVX rats maintained on a diet devoid of phytoestrogens had a higher TST by several degrees than OVX rats fed normal chow, offering greater ability to test estrogenic agents on thermoregulation. Depletion of estrogen in intact rats via chronic administration of leuprolide acetate, a GnRH agonist, also increased TST, which was in turn suppressed by estrogen. In intact rats, tamoxifen exhibited estrogen antagonistic activity elevating TST, while in OVX rats, tamoxifen acted as an agonist by suppressing TST. CONCLUSION: OVX rats kept on a diet devoid of phytoestrogens are a sensitive model for estrogen-dependent thermoregulation.

Effect of antihypertensive samples on physician prescribing patterns.

OBJECTIVE: This study evaluated the effect of pharmaceutical samples on the prescribing habits of family practice residents and faculty in the treatment of hypertension. METHODS: Charts from two time periods were reviewed for a diagnosis of hypertension--January and February 1997 when drug samples were available and January and February 1998 when sample distribution was prohibited. Progress notes were assessed for medication prescribed, patient age, and doctor seen. Prescribed antihypertensive medications were defined as first- or second-line drugs based on the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Comparisons were made between the two time periods and between faculty and residents. RESULTS: Overall, faculty were much less likely than residents to prescribe first-line medications: 43% versus 57%. Following prohibition of sample distribution, there was an increase in first-line antihypertensive use from 38% to 61%. CONCLUSIONS: The prescription of first-line drugs for the treatment of hypertension increased after drug sample distribution was prohibited. Studies are needed to determine the extent to which drug sample availability affects prescription practices.

Aspirin prophylaxis in patients at low risk for cardiovascular disease: a systematic review of all-cause mortality.

OBJECTIVE: We investigated whether aspirin reduces all-cause mortality in low-risk patients. STUDY DESIGN: We systematically reviewed studies of aspirin for primary prevention to measure total mortality. We included all clinical trials, cohort studies, and case control studies that assessed primary prevention, included low-risk subjects, and measured total mortality. The quality of studies was evaluated with a standard scale. DATA SOURCES: MEDLINE, the Cochrane Library, and the Internet were systematically searched for studies with the key terms primary, prevention, aspirin, myocardial infarction, stroke, and mortality. Reference lists of identified trials and reviews also were examined. POPULATION: Active members in the Indiana Academy of Family Physicians 2000-2001 membership database (N = 1328). OUTCOMES MEASURED: Primary outcomes were myocardial infarction, stroke, and mortality. RESULTS: Three primary prevention studies met our criteria. Two clinical trials, the United States Physicians Health Study and British Doctors Study, demonstrated no significant decrease in mortality in the aspirin group alone or when results from the 2 studies were combined. The United States Physicians Health Study showed a lower rate of myocardial infarction (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.47-0.71). In the Nurses Health Study, a cohort study, taking aspirin at any dose was associated with higher rates of myocardial infarction (OR, 2.34; CI, 1.92-2.86), stroke (OR, 1.84; CI, 1.39-2.44), and all-cause mortality (OR, 1.83; CI, 1.57-2.14). CONCLUSIONS: There is currently no evidence to recommend for or against the use of aspirin to decrease mortality in low-risk individuals.

The preclinical efficacy, selectivity and pharmacologic profile of MK-5932, an insulin-sparing selective glucocorticoid receptor modulator.

Glucocorticoids are used widely in the treatment of inflammatory diseases, but use is accompanied by a significant burden of adverse effects. It has been hypothesized that gene- and cell-specific regulation of the glucocorticoid receptor by small molecule ligands could be translated into a therapeutic with an improved risk-benefit profile. MK-5932 is a highly selective glucocorticoid receptor modulator that is anti-inflammatory in vivo with an improved profile on glucose metabolism: Bungard et al. (2011). Bioorg. Med. Chem. 19, 7374-7386. Here we describe the full biological profile of MK-5932. Cytokine production following lipopolysaccharide (LPS) challenge was blocked by MK-5932 in both rat and human whole blood. Oral administration reduced inflammatory cytokine levels in the serum of rats challenged with LPS. MK-5932 was anti-inflammatory in a rat contact dermatitis model, but was differentiated from 6-methylprednisolone by a lack of elevation of fasting insulin or glucose levels after 7 days of dosing, even at high exposure levels. In fact, animals in the vehicle group were consistently hyperglycemic at the end of the study, and MK-5932 normalized glucose levels in a dose-dependent manner. MK-5932 was also anti-inflammatory in the rat collagen-induced arthritis and adjuvant-induced arthritis models. In healthy dogs, oral administration of MK-5932 exerted acute pharmacodynamic effects with potency comparable to prednisone, but with important differences on neutrophil counts, again suggestive of a dissociated profile. Important gaps in our understanding of mechanism of action remain, but MK-5932 will be a useful tool in dissecting the mechanisms of glucose dysregulation by therapeutic glucocortiocids.