Citations

AbstractIncreased activation of the major pro‐inflammatory NF‐κB pathway leads to numerous age‐related diseases, including chronic liver disease (CLD). Rapamycin, an inhibitor of mTOR, extends lifespan and healthspan, potentially via suppression of inflammaging, a process which is partially dependent on NF‐κB signalling. However, it is unknown if rapamycin has beneficial effects in the context of compromised NF‐κB signalling, such as that which occurs in several age‐related chronic diseases. In this study, we investigated whether rapamycin could ameliorate age‐associated phenotypes in a mouse model of genetically enhanced NF‐κB activity (nfκb1−/−) characterized by low‐grade chronic inflammation, accelerated aging and CLD. We found that, despite showing no beneficial effects in lifespan and inflammaging, rapamycin reduced frailty and improved long‐term memory, neuromuscular coordination and tissue architecture. Importantly, markers of cellular senescence, a known driver of age‐related pathology, were alleviated in rapamycin‐fed animals. Our results indicate that, in conditions of genetically enhanced NF‐κB, rapamycin delays aging phenotypes and improves healthspan uncoupled from its role as a suppressor of inflammation.

Abstract The treatment of newly diagnosed oligodendroglioma has been revolutionized in the past decade by multiple studies demonstrating that the addition of chemotherapy to radiation therapy results in a significant survival benefit. While the most direct evidence comes from clinical trials that utilized PCV, a chemotherapy regimen consisting of procarbazine, CCNU (lomustine), and vincristine, there is circumstantial evidence suggesting that the oral agent temozolomide (TMZ), which is both better tolerated and logistically simpler than PCV, may also be effective. The lack of currently available direct comparative data for PCV vs TMZ results in a diversity of practice. In this article, Ruff and Buckner argue for PCV as part of the standard-of-care regimen for newly diagnosed anaplastic oligodendroglioma, while Geurts and van den Bent defend the use of TMZ.

Abstract Complicated craniofacial malformations interfacing with multiple intracellular regulatory mechanisms, lead to ambiguous growth patterns in Apert syndrome. This study aims to explore the chronology and pathogenesis of the development of craniofacial anatomic relationships and to verify the positional correlates between skull and facial structures in Apert syndrome. Fifty-four computed tomography scans (Apert, n = 18; control, n = 36) were included and divided into 3 age subgroups. Craniofacial 3-dimensional cephalometries were analyzed by Materialize software. The angle between sella-nasion plane and maxillary plane widens 7.74° (P = 0.003) prior to 6 months of age; thereafter, this widening increases by 10.36° (P < 0.001) in 6 months to 2 years of age, and remains increased by 8.9° (P = 0.046) throughout childhood. The angle between Frankfort horizontal plane and maxillary plane widens 5.17° (P = 0.022) before 6 months. Angles SNA, SNB, and ANB showed decreases, averaging 12.23° (P < 0.001), 5.19° (P = 0.004), and 6.72° (P = 0.001), respectively. The linear measurements showed synchronicity and continuing deformity into adulthood. Between 6 months to 2 years of age, the distance from sella to nasion (S-N), anterior nasal spine (S-ANS), and posterior nasal spine (S-PNS) decreased 8% (P = 0.006), 16% (P < 0.001), and 19% (P = 0.002), respectively, and remained shortened into adulthood. The angulation changes occur earlier in development than linear distance reduction in Apert syndrome patients compared with controls. Angular adjustments were not sufficient to maintain normal cranial base length. Facial deformity of Apert syndrome temporally begins with the midface, and affects orbit and mandible later in life.

Background:In Crouzon’s syndrome, cranial base deformities begin sequentially in the anterior cranial fossa initially, and later to the posterior cranial base. Facial characteristics are likely related to cranial base development. The temporal correlation between cranial base development and facial features is in need of clarification in Crouzon’s patients, to clarify initial sites of deformity, which may impact surgical decision making.Methods:Thirty-six computed tomography scans of unoperated Crouzon’s syndrome patients and 54 controls were included and divided into 5 age-subgroups. All the planes used for analysis were set as perpendicular to a defined “midplane” to offset the confounding factor caused by potential asymmetry.Results:The angle between Sella-Nasion plane and Frankfort horizontal plane was significantly increased before 6 months of age (P= 0.014), with an average 70% (P< 0.001) increase ultimately into adulthood. The angle between SN and maxillary plane and the angle between Sella-Nasion and occlusal planes increased consistently through infancy to adulthood (124% and 42%, respectively, bothP< 0.001). The relative angle of mandibular plane to Frankfort horizontal plane increased before 6 months (28%,P= 0.007) with a peak timeframe from 2 to 18 years. Facial lateral curvature related measurements indicate the whole face is inclined posteriorly and inferiorly direction in relation to the anterior cranial base.Conclusion:Crouzon’s facial malformation development is synchronous and positionally correlational with cranial base deformity. It transmitted from orbit to mandible, with the most evident morphologic changes are in the orbit and midface.

Background: The Pediatric Orthopaedic Society of North America (POSNA) funds grants to improve pediatric musculoskeletal care and maximize new knowledge through publications, presentations, and further funding. We assessed the productivity of POSNA grants by number and rate of grant-specific publications, citations, and extramural funding; determined whether project type or completion status was associated with extramural funding; and compared the success of POSNA-funded versus all other podium presentations by publication rate and POSNA awards. Methods: We reviewed final reports for all 85 POSNA grants from 2003 to 2014. To determine grant productivity, we assessed the publication, presentation, and extramural funding rates, and the percentage of grants that achieved at least 1 scholarly output (publication or presentation). Citation counts were determined within 3 years after publication. Results: Overall, each grant achieved ~1.53 publications and 15.4 citations. Thirty-three percent secured extramural funding. However, 25% of grants could not be tracked to a scholarly product. Projects that reached completion and were of the basic science type (compared with clinical) were more likely to receive extramural funding. Compared with all other podiums, a greater proportion of POSNA-funded presentations led to a publication (64% vs. 48%, respectively; P=0.02) and were more likely to receive a POSNA award. Approximately 52% of funded projects were not presented at POSNA meetings. Conclusions: Although most POSNA-funded projects led to scholarly output, 25% of them produced no publications or podium presentations. POSNA-funded projects were more likely to lead to a publication and to have a higher chance of winning a POSNA award compared with all other projects. The POSNA grant process is effective at identifying impactful research, but continued process improvement, such as a prospectively maintained database of grant recipient productivity and improved tracking of grant submission histories, are both in development as the first steps to improve accountability of grant recipients in translating their projects to scholarly products.