Serum cholesterol levels in a multiracial sample of 7,439 preschool children from Arizona.

BACKGROUND. The distribution and correlates of serum levels of total cholesterol were studied in cross-sectional analyses of 7,439 1 to 4 year olds examined through the Arizona Department of Health Services. RESULTS. Mean cholesterol levels increased with age, and levels among 2 year olds approached those seen in adolescents. Racial and ethnic differences in cholesterol levels were observed: mean (age-adjusted) levels were 147 mg/dl among American Indians (n = 622), 153 mg/dl among Hispanics (n = 3165), 154 mg/dl among non-Hispanic whites (n = 3448), and 163 mg/dl among blacks (n = 204). Cholesterol levels were not associated either with obesity, as assessed by relative weight or the Quetelet index, or with breast-feeding during infancy. Very overweight (greater than or equal to 20 kg/m2) 3 and 4 year olds, however, tended to have higher mean levels of cholesterol than did other children. The proportion of children with borderline (170 to 199 mg/dl) or high (greater than or equal to 200 mg/dl) levels of cholesterol varied by race/ethnicity: borderline (high) levels were seen among 14% (3%) of American Indians and 29% (11%) of blacks. The proportions of white and Hispanic children having cholesterol levels between 170 and 199 mg/dl or greater than or equal to 200 mg/dl were midway between those seen among American Indians and blacks. CONCLUSION. Additional information on the interrelationships of lipids and lipoproteins may aid in the identification of children who will be at increased risk for cardiovascular disease in adulthood.     

IgE and IgG4 epitope mapping by microarray immunoassay reveals the diversity of immune response to the peanut allergen, Ara h 2

BACKGROUND: Detailed assessment of antibody responses to allergens reveals clinically relevant information about both host response and antigen structure. Microarray technology offers advantages of scale and parallel design over previous methods of epitope mapping. OBJECTIVE: We designed a redundant peptide microarray for IgE and IgG4 epitope mapping of the previously characterized peanut allergen, Ara h 2. METHODS: Six complete sets of overlapping peptides were commercially synthesized and site-specifically bound to epoxy-derivatized glass slides in triplicate. Peptides were 10, 15, or 20 amino acids in length with an offset of either 2 or 3 amino acids. A total of 10 control and 45 peanut-allergic sera were assayed. Specific IgE and IgG4 were detected by using fluorochrome-labeled monoclonal secondary antibodies. RESULTS: By using 15-mer and 20-mer peptides, we could define 11 antigenic regions, whereas only 5 were identifiable using 10-mers. Controls and patients produced IgG4 recognizing a comparable number of Ara h 2 peptides, although the dominant epitopes were distinct. As expected, patient IgE bound a larger number of Ara h 2 peptides (9.4% vs 0.9%). IgE and IgG4 epitopes recognized by patients were largely the same, and there was a positive association between IgE and IgG(4) signal, suggesting coordinate regulation. Cluster analysis of peptide binding patterns confirmed the specificity of antibody-peptide interactions and was used to define 9 core epitopes ranging from 6 to 16 residues in length-7 of which (78%) agreed with previous mapping. CONCLUSION: Epitope mapping by microarray peptide immunoassay and cluster analysis reveals interpatient heterogeneity and a more detailed map.     

The costs and effects of a nutritional education program following work-site cholesterol screening.

OBJECTIVES. The purpose of this study was to assess the costs and impact of a nutrition education program following a cholesterol screening. METHODS. Forty work-sites were randomly assigned to one of two educational interventions: a "usual" intervention of 5 minutes of counseling, or a "special" intervention of 2 hours of behaviorally based education on dietary changes to lower serum cholesterol. Costs were monitored, and cholesterol levels were retested 6 and 12 months later. RESULTS. The total per-person cost for screening and the educational intervention was about $50. Cholesterol levels differed little between the two intervention groups 6 months after screening, but after 12 months those in the special intervention worksites showed a 6.5% drop in cholesterol, whereas those at the usual intervention worksites showed a drop of only 3.0%. Hence a 3.5% cholesterol reduction was attributable to the special intervention. CONCLUSIONS. A behaviorally based nutrition education program following cholesterol screening can have a meaningful impact on long-term cholesterol levels at a low cost. Nutrition education in work-sites may therefore be a useful way to lower the risk of heart disease in communities.     

Impact of a Regional Pharmacy Call Center on Telephone Access Metrics Within the Veterans Health Administration

Purpose:

To establish a cost-effective centralized pharmacy call center to serve the patients of Veterans Integrated Service Network (VISN) 11 that would meet established performance metrics.

Methods:

A pilot project began in August 2011 with the Indianapolis VA Medical Center (VAMC) and the Health Resource Center (HRC) in Topeka, Kansas. The Indianapolis VAMC used a first-call resolution business model consisting of pharmacy technicians receiving tier 1 phone calls that could be escalated to a tier 2 line that consisted of lead technicians and pharmacists, while the HRC utilized general telephone agents that would transfer unresolved calls to the primary facility. Pre- and post-VISN 11 Pharmacy Call Center performance metrics were compared for each of the 7 facilities in the network with the goals being monthly average abandoned call rate less than 5% and average speed to answer less than 30 seconds. Cost per call was also compared.

Results:

The average abandoned call rate for the network during the year prior to VISN 11 Pharmacy Call Center implementation (August 2010-July 2011) was 15.66% and decreased to 3% in July 2014. The average abandoned call rate decreased for each individual facility. In fiscal year 2014, the VISN 11 Pharmacy Call Center was operating at a cost of $4.35 per call while providing more services than the HRC, resulting in less workload being transferred back to the individual facilities.

Conclusion:

A centralized VISN pharmacy call center is a reasonable alternative to individual facility call centers or the HRC.     

Translational cell biology of highly malignant osteosarcoma

Highly malignant osteosarcoma (HMO) is the most frequent malignant bone tumor preferentially occurring in adolescents and children with a second more flat peak in patients over the age of 60. The younger patients benefit from combined neoadjuvant chemotherapy with 65–70% 5-year survival rate. In patients with metastatic HMO the 5-year survival rate is consistently poor with approximately 30%. In the last several years strategies for target therapies have been developed by using next generation sequencing (NGS) for defining targetable molecular factors. However, it has so far been challenging to establish an effective target therapy for so-called ‘orphan tumors’ without recognizable driver mutations, including HMO. The molecular genetic studies using NGS have shown that HMOs are genomically unstable tumors with highly complex chaotic karyotypes. Before the background of this genetic complexity more investigations should be performed in the future for defining targetable biological factors. As the prognosis could not be improved for 40 years one may expect improvements for patients only by gaining a deeper understanding of the cell and molecular biology of HMO. The cell of origin of HMO is being clarified now. The majority of studies indicate that an osteoblastic progenitor cell is probably the cell of origin of HMO and not an undifferentiated mesenchymal stem cell. This means that the established histopathological definition of HMO through verification of osteoid production by the osteoblastic cells is well justified and will probably be the cornerstone for a precise differential diagnosis of HMO also in the years to come.     

K-ras mutation detection in colorectal cancer using the Pyrosequencing technique

The identification of gene mutations is a critical goal for the assessment of diagnosis and prognosis in cancer disease, particularly by direct sequencing. Pyrosequencing is a straightforward, non-electrophoretic DNA sequencing method using the luciferase-luciferin light release as a signal for nucleotide incorporation into a PCR template DNA. In this study, we aimed to investigate mutations in the K-ras gene using Pyrosequencing technology, because its reliable chemistry and robust detection mechanism allow for rapid, real-time detection of sequencing events. For the simultaneous detection of the predominant K-ras codons 12 and 13 mutations, we established a sequencing protocol based on the design of a single PCR primer pair and a single sequencing primer. The assay has been validated with DNA from 65 colorectal carcinomas. Furthermore, analysis of the rare K-ras codon 61 mutation was included. In 29% (19/65) of the patients, the K-ras gene was found to be mutated, whereas codons 12 and 13 were most frequently affected (18/65, 27.7%). Mutations with the highest frequency were G-->A transitions (12/19, 63%), followed by G-->T transversions (5/19, 26%). Overall survival was significantly shorter in patients with a tumor containing K-ras codon 12 mutations than in those without K-ras codon 12 mutations (p=0.024). In conclusion, we found Pyrosequencing to be a suitable technology for fast detection of hot-spot mutations in the K-ras oncogene. We demonstrated an important relationship between K-ras codon 12 mutations and overall survival in colorectal cancer patients.     

Amygdala volume and depressive symptoms in patients with borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is characterized by a high prevalence of comorbid psychiatric disorders, including major depression (MD). The aim of this study was to examine whether a co-occurrence of MD is associated with structural changes in the amygdala of BPD patients. METHODS: Twenty-five right-handed, female patients with BPD and 25 matched healthy control subjects were examined. Diagnoses of BPD and MD were made according to DSM IV. Depressive symptomatology was determined with the Hamilton Depression Scale (HAMD). Magnetic resonance imaging scans were performed with 1.5 T Magnetom Vision (Siemens, Erlangen, Germany). The software program "BRAINS" was applied for brain volumetry and segmentation. The amygdala was delineated as "region of interest." RESULTS: Comparison of amygdala volumes between the whole group of BPD patients and control subjects revealed no significant difference. Amygdala volumes in both hemispheres were significantly larger in BPD patients with MD compared with those without MD. There was a significant correlation in BPD patients between left amygdala volume and depressive symptoms as measured by HAMD. CONCLUSIONS: Correlation of amygdala volume with depression in BPD patients might indicate a causal relationship. Future studies should clarify whether amygdala enlargement is a risk factor for MD in BPD patients or a consequence of the affective disorder.