Differential growth and development of the upper and lower human thorax

The difficulties in quantifying the 3D form and spatial relationships of the skeletal components of the ribcage present a barrier to studies of the growth of the thoracic skeleton. Thus, most studies to date have relied on traditional measurements such as distances and indices from single or few ribs. It is currently known that adult-like thoracic shape is achieved early, by the end of the second postnatal year, with the circular cross-section of the newborn thorax transforming into the ovoid shape of adults; and that the ribs become inclined such that their anterior borders come to lie inferior to their posterior. Here we present a study that revisits growth changes using geometric morphometrics applied to extensive landmark data taken from the ribcage. We digitized 402 (semi) landmarks on 3D reconstructions to assess growth changes in 27 computed tomography-scanned modern humans representing newborns to adults of both sexes. Our analyses show a curved ontogenetic trajectory, resulting from different ontogenetic growth allometries of upper and lower thoracic units. Adult thoracic morphology is achieved later than predicted, by diverse modifications in different anatomical regions during different ontogenetic stages. Besides a marked increase in antero-posterior dimensions, there is an increase in medio-lateral dimensions of the upper thorax, relative to the lower thorax. This transforms the pyramidal infant thorax into the barrel-shaped one of adults. Rib descent is produced by complex changes in 3D curvature. Developmental differences between upper and lower thoracic regions relate to differential timings and rates of maturation of the respiratory and digestive systems, the spine and the locomotor system. Our findings are relevant to understanding how changes in the relative rates of growth of these systems and structures impacted on the development and evolution of modern human body shapeCGL2012-37279 (Spanish Ministry for Economy and Competition) Fyssen-foundation (http://www.fondationfyssen.fr

Plasma levels of mitochondrial and nuclear DNA in patients with massive pulmonary embolism in the emergency department: A prospective cohort study

Introduction: Cell-free plasma mitochondrial DNA (mt-DNA) and nuclear DNA (n-DNA) are biomarkers with prognostic utility in conditions associated with a high rate of cell death. This exploratory study aimed to determine the plasma levels of both nucleic acids in patients with massive and submassive pulmonary embolism (PE) and to compare them with other biomarkers, such as heart-type fatty acid-binding protein (H-FABP) and troponin I (Tn-I) Methods: This was a prospective observational study of 37 consecutive patients with massive PE, 37 patients with submassive PE, and 37 healthy subjects. Quantifications of plasma mt-DNA and n-DNA with real-time quantitative polymerase chain reaction (PCR), and plasma H-FABP and Tn-I by commercial assays, were done on blood samples drawn within 4 hours after presentation at the emergency department. Results: Plasma mt-DNA and n-DNA concentrations were much higher in patients with massive PE (median, 2,970 GE/ml; interquartile range (IQR), 1,050 to 5,485; and 3,325 GE/ml, IQR: 1,080 to 5,790, respectively) than in patients with submassive PE (870 GE/ml and 1,245 GE/ml, respectively; P < 0.01) or controls (185 GE/ml and 520 GE/ml, respectively). Eighteen patients with massive PE died of a PE-related cause by day 15 of observation. Plasma mt- DNA and n-DNA values were 2.3-fold and 1.9-fold higher in the subgroup of nonsurviving patients than in survivors. H-FABP and Tn-I values were also higher in patients with massive PE who died (7.3 ng/ml and 0.023 ng/ml, respectively) than in those who survived (6.4 ng/ml, and 0.016 ng/ml, respectively). By receiver operating curve (ROC) analysis, the best cutoff values for predicting 15-day mortality were 3,380 GE/ml for mt-DNA, 6.8 ng/ml for H-FABP, 3,625 GE/ml for n-DNA, and 0.020 ng/ml for Tn-I, based on the calculated areas under the curve (AUCs) of 0.89 (95% confidence interval (CI), 0.78 to 0.99), 0.76 (95% CI, 0.69 to 093), 0.73 (95% CI, 0.58 to 0.91), and 0.59 (95% CI, 0.41 to 0.79), respectively. By stepwise logistic regression, a plasma mt-DNA concentration greater than 3,380 GE/ml (adjusted odds ratio (OR), 8.22; 95% CI, 1.72 to 39.18; P 6.8 ng/ml (OR, 5.36; 95% CI, 1.06 to 27.08; P < 0.01) were the only independent predictors of mortality. Conclusions: mt-DNA and H-FBAP might be promising markers for predicting 15-day mortality in massive PE, with mt-DNA having better prognostic accuracy.This work was supported partially by grants from Plan Nacional I+D+I (SAF 2008-05347 and SAF2011-23575) and from Fundación Mutua Madrileña de Investigación Biomédica (2008 and 2011) to Francisco Arnalich and Carmen Montie