Novel antibodies that selectively block mouse IL-12 enable the re-evaluation of the role of IL-12 in immune protection and pathology

The dimeric cytokine IL-12 is important in the control of various infections but also contributes to the pathology of certain diseases making it a potential target for therapy. However, its specific inhibition with antibodies is complicated by the fact that its two subunits are present in other cytokines: p40 in IL-23 and p35 in IL-35. This has led to erroneous conclusions like the alleged implication of IL-12 in experimental autoimmune encephalomyelitis (EAE). Here, we report the development of a mouse anti-mouse IL-12 vaccine and the production of monoclonal antibodies (mAbs) that do not react with p40 or p35 (in IL-35) but specifically recognize and functionally inhibit the IL-12 heterodimer. Using one of these mAbs, MM12A1.6, that strongly inhibited IFN-γ production and LPS-induced septic shock after viral infection, we demonstrate the critical role played by IL-12 in the rejection of male skin graft by female C57BL/6 syngeneic recipients and in the clearance of an immunogenic mastocytoma tumor variant by DBA/2 mice, but not in a parent to F1 immune aggression model nor in MOG-induced EAE, which was clearly prevented by anti-p40 mAb C17.8. Given this selective inhibition of IL-12, these mAbs provide new options for reassessing IL-12 function in vivo.     

Informing a home time measure reflective of quality of life: A data driven investigation of time frames and settings of health care utilization

Objective

To evaluate short- and long-term measures of health care utilization—days in the emergency department (ED), inpatient (IP) care, and rehabilitation in a post-acute care (PAC) facility—to understand how home time (i.e., days alive and not in an acute or PAC setting) corresponds to quality of life (QoL).

Data Sources

Survey data on community-residing veterans combined with multipayer administrative data on health care utilization.

Study Design

VA or Medicare health care utilization, quantified as days of care received in the ED, IP, and PAC in the 6 and 18 months preceding survey completion, were used to predict seven QoL-related measures collected during the survey. Elastic net machine learning was used to construct models, with resulting regression coefficients used to develop a weighted utilization variable. This was then compared with an unweighted count of days with any utilization.

Principal Findings

In the short term (6 months), PAC utilization emerged as the most salient predictor of decreased QoL, whereas no setting predominated in the long term (18 months). Results varied by outcome and time frame, with some protective effects observed. In the 6-month time frame, each weighted day of utilization was associated with a greater likelihood of activity of daily living deficits (0.5%, 95% CI: 0.1%–0.9%), as was the case with each unweighted day of utilization (0.6%, 95% CI: 0.3%–1.0%). The same was true in the 18-month time frame (for both weighted and unweighted, 0.1%, 95% CI: 0.0%–0.3%). Days of utilization were also significantly associated with greater rates of instrumental ADL deficits and fair/poor health, albeit not consistently across all models. Neither measure outperformed the other in direct comparisons.

Conclusions

These results can provide guidance on how to measure home time using multipayer administrative data. While no setting predominated in the long term, all settings were significant predictors of QoL measures.     

Antenatal care and pregnancy outcomes in a safe motherhood health voucher system in rural Kenya, 2007–2013

Setting: A rural private health facility, Ruby Medical Centre (RMC), participating in a safe motherhood health voucher system for poor women in Kiambu County, Kenya.Objectives: Between 2007 and 2013, to determine 1) the number of women who delivered at the RMC, their characteristics and pregnancy-related outcomes, and 2) the number of women who received an incomplete antenatal care (ANC) package and associated factors.Design: Retrospective cross-sectional study using routine programme data.Results: During the study period, 2635 women delivered at the RMC: 50% were aged 16–24 years, 60% transferred in from other facilities and 59% started ANC in the third trimester of pregnancy. Of the 2635 women, 1793 (68%) received an incomplete ANC package: 347 (13%) missed essential blood tests, 312 (12%) missed the tetanus toxoid immunisation and 1672 (65%) had fewer than four visits. Presenting late and starting ANC elsewhere were associated with an incomplete package. One pregnancy-related mortality occurred; the stillbirth rate was 10 per 1000 births.Conclusion: This first assessment of the health voucher system in rural Kenya showed problems in ANC quality. Despite favourable pregnancy-related outcomes, increased efforts should be made to ensure earlier presentation of pregnant women, comprehensive ANC, and more consistent and accurate monitoring of reproductive indicators and interventions.     

The anatomy of the clavicle

The clavicle has a complex osteologic structure that makes morphological analysis extremely difficult. A three‐dimensional study was conducted to examine the anatomical variations and characteristics of the bone. Sixty‐eight human cadaver clavicles were dissected, CAT‐scanned, and reconstructed. An automated parameterization and correspondence shape analysis system was developed. A new length, designated as centerline (CL) length, was defined and measured. This length represents the true length of the clavicle. The endpoint length was measured as the distance between two endpoints. The width and curvature were measured in the axial (AX) and frontal (FR) plane and defined along the CL. Next gender and side characteristics and variations were examined. The mean CL length was 159.0 ± 11.0 mm. The mean endpoint length was 149.4 ± 10.3 mm, which was statistically significantly shorter than the CL. The male clavicle was significantly longer (166.8 ± 7.3 mm vs. 151.0 ± 8.2 mm), wider (14.6 ± 1.5 mm vs. 12.7 ± 1.3 mm lateral FR plane, 25.9 ± 4.1 mm vs. 23.5 ± 3.0 mm lateral AX plane and 24.7 ± 2.8 mm vs. 22.8 ± 2.8 mm medial AX plane), and more curved (10.8 ± 2.8 mm vs. 8.6 ± 2.3 mm medial and 10.5 ± 3.3 mm vs. 9.1 ± 2.5 mm lateral) than the female one. Left clavicles were significant longer (159.8 ± 10.9 mm vs. 158.0 ± 11.2 mm) than right clavicles. A novel three‐dimensional system was developed, used and tested in order to explore the anatomical variations and characteristics of the human clavicle. This information, together with the automated system, can be applied to future clavicle populations and to the design of fixation plates for clavicle fractures. Clin. Anat. 27:712–723, 2014. © 2013 Wiley Periodicals, Inc.