Recent Publications by CFE Educators

BACKGROUND

Human hip morphology is variable, and some variations (or hip morphotypes) such as coxa profunda and coxa recta (cam-type hip) are associated with femoroacetabular impingement and the development of osteoarthrosis. Currently, however, this variability is unexplained. A broader perspective with background information on the morphology of the proximal femur of nonhuman apes is lacking. Specifically, no studies exist of nonhuman ape femora that quantify concavity and its variability.

QUESTIONS/PURPOSES

We hypothesized that, when compared with modern humans, the nonhuman apes would show (1) greater proximal femoral concavity; (2) less variability in concavity; and (3) less sexual dimorphism in proximal femoral morphology.

METHODS

Using identical methods, we compared 10 morphological parameters in 375 human femora that are part of the Hamann-Todd collection at the Cleveland Museum of Natural History with 210 nonhuman ape femora that are part of the collection of the Royal Museum for Central Africa, Tervuren, Belgium, and the Muséum National d'Histoire Naturelle, Paris, France.

RESULTS

The nonhuman apes have larger proximal femoral concavity than modern humans. This morphology is almost uniform without large variability or large differences neither between species nor between sexes.

CONCLUSIONS

Variability is seen in human but not in nonhuman ape proximal femoral morphology. An evolutionary explanation can be that proximal femoral concavity is more important for the nonhuman apes, for example for climbing, than for modern humans, where a lack of concavity may be related to high loading of the hip, for example in running.

OPINION STATEMENT

While not all multiple sclerosis (MS) relapses require treatment, relapses that are bothersome or that impair function should prompt consideration of timely treatment to restore function and minimize disability. Patients with suspected MS relapses should be evaluated to confirm the diagnosis, exclude other causes of neurological dysfunction, and identify potential triggers for relapse or pseudo-relapse, such as urinary tract infections, fever, or metabolic derangements. The diagnosis of an MS relapse is clinical, but MRI may be useful for confirmation and to evaluate for multifocal disease activity. High-dose oral or intravenous glucocorticoids, with or without an oral taper, are first-line therapy for MS relapses. Adrenocorticotropic hormone (ACTH) provides an alternative to glucocorticoid treatment but is currently much more expensive and does not have proven superiority. If the acute neurological deficits remain severe after steroid treatment, and particularly if there is persistent abnormal contrast-enhancement of the symptomatic lesion on repeat MRI, plasma exchange (PLEX) should be considered as an acute rescue therapy for relapse. In exceptional cases, particularly fulminant or tumefactive disease that fails to improve following treatment with steroids and PLEX, cytoxic agents such as cyclophosphamide or B cell-depleting regimens such as rituximab may be considered, although risk must be carefully weighed and the kinetics of such regimens indicate that they probably serve more to accelerate remission of disease activity than as an immediate relapse remedy. A single dose of natalizumab given as acute therapy for MS relapse was shown not to improve clinical outcomes in a randomized controlled trial. Attention to symptom management and promotion of neurorehabilitation are important aspects of MS relapse care. Neuroprotective and neuroreparative therapies remain under investigation, but are likely to become important complementary elements of relapse therapy in the future. Relapses serve as important indicators of MS disease activity. In the context of the emerging treatment paradigm of targeting freedom from evidence of MS disease activity, relapses should prompt consideration of transitioning to a disease-modifying treatment that may offer better efficacy.

BACKGROUND

Prostate cancer incidence and mortality rates vary across populations, with African American men exhibiting the highest rates. To date, genome-wide association studies have identified 104 SNPs independently associated with prostate cancer in men of European ancestry.

METHODS

We investigated whether the ability to replicate findings for these 104 SNPs in African American, Asian, and Latino populations depends on variation in risk allele frequencies (RAF), strength of associations, and/or patterns of linkage disequilibrium (LD) at the associated loci. We extracted estimates of effect from the literature, and determined RAF and LD information across the populations from the 1000 Genomes Project.

RESULTS

Risk variants were largely replicated across populations. Relative to Europeans, 83% had smaller effect sizes among African Americans and 73% demonstrated smaller effect sizes among Latinos. Among Asians, however, 56% showed larger effect sizes than among Europeans. The largest difference in RAFs was observed between European and African ancestry populations, but this difference did not impact our ability to replicate. The extent of LD within 250 kb of risk loci in Asian ancestry populations was suggestively lower for variants that did not replicate (P = 0.013).

CONCLUSIONS

Despite substantial overlap in prostate cancer risk SNPs across populations, the variation in prostate cancer incidence among different populations may still in part reflect unique underlying genetic architectures.

IMPACT

Studying different ancestral populations is crucial for deciphering the genetic basis of prostate cancer.