Drifting Diaphyses: Asymmetry in Diametric Growth and Adaptation Along the Humeral and Femoral Length

This study quantifies regional histomorphological variation along the human humeral and femoral diaphysis in order to gain information on diaphyseal growth and modeling drift patterns. Three thin sections at 40, 50, and 60% bone length were prepared from a modern Mexican skeletal sample with known age and sex to give a longitudinal perspective on the drifting cortex (12 adults and juveniles total, 7 male and 5 female). Point‐count techniques were applied across eight cross‐sectional regions of interest using the starburst sampling pattern to quantify percent periosteal and endosteal primary lamellar bone at each diaphyseal level. The results of this study show a posterio‐medial drift pattern in the humerus with a posterior rotational trend along the diaphysis. In the femur, we observed a consistent lateral to anteriolateral drift and an increase in primary lamellar bone area of both, periosteal and endosteal origin, towards the distal part of the diaphysis. These observations characterize drifting diaphyses in greater detail, raising important questions about how to resolve microscopic and macroscopic cross‐sectional analysis towards a more complete understanding of bone growth and mechanical adaptation. Accounting for modeling drift has the potential to positively impact age and physical activity estimation, and explain some of the significant regional variation in bone histomorphology seen within (and between) bone cross‐sections due to differing ages of tissue formation. More study is necessary, however, to discern between possible drift scenarios and characterize populational variation. Anat Rec, 298:1689–1699, 2015. © 2015 Wiley Periodicals, Inc.     

What constitutes efficacy for a human immunodeficiency virus vaccine that ameliorates viremia: issues involving surrogate end points in phase 3 trials

Initial human immunodeficiency virus (HIV) vaccines are unlikely to prevent acquisition of HIV in all recipients. Moreover, several HIV vaccines are under evaluation that are designed to reduce viremia after acquisition of infection. Such vaccines could provide important benefits to delay HIV progression and to reduce transmission. The decision to license a vaccine on the basis of observed effects on virus load and other postinfection surrogate end points in an efficacy trial is complicated by uncertainty about whether the vaccine effects will persist and reliably predict clinical effects, and by the challenge in interpreting the data posed by treatment of some seroconverters with antiretroviral drugs. Here, we evaluate how analyses of certain surrogate end points can be used for inferring clinically significant vaccine effects and propose end points that could be evaluated in efficacy trials to support licensure. The assessment suggests that a vaccine demonstrating moderately durable effects to delay therapy and to ameliorate viremia merits consideration for licensure.     

Radioimmunoassay for leukotriene B4

A rabbit immunized with leukotriene B₄ [LTB₄; (5S,12R)-6, 14-cis-8, 10-trans-icosatetraenoic acid] coupled to bovine serum albumin via the 12-oxy function of the lipid produced antibodies having an average association constant (K_a) for [14,15-³H]LTB₄ of 3.2 × 10⁹ M^-1 at 37°C and in a concentration of 0.37 μg/ml of the immune plasma. When 10 μl of anti-LTB₄ and 3.9 nCi of [14,15-³H]LTB₄ (28 Ci/mmol; 1 Ci = 3.7 × 10¹⁰ becquerels) were incubated in a volume of 250 μl, 50% inhibition of radioligand binding was achieved with 0.31 ng of LTB₄ and with 1.95 ng of (5S,12S)-6-trans-8-cis-LTB₄. The sulfidopeptide leukotrienes, LTC₄ and LTD₄, displaced the radioligand from this antibody with less than 1/100th the activity of LTB₄, and the diastereoisomers of 6-trans-LTB₄, 5-L-hydroxy-6-trans-8,11,14-cis-icosatetraenoic acid (5-HETE), and three prostaglandins were minimally effective. The specificity of this radioimmunoassay was further shown by assessment of the immunoreactive products generated from calcium ionophore (A23187)-activated rat serosal mast cells and human neutrophils after reversed-phase HPLC. Resolution of the supernatants from each cell type yielded a single immunoreactive peak that coeluted with synthetic LTB₄ and quantitatively correlated with the physical measurement by integrated A₂₆₉ in that peak; UV-absorbing peaks eluting at other retention times were not immunoreactive. The immunoreactive LTB₄ generated averaged 4.6 ng per 10⁶ rat mast cells and resolution of the supernatants by reversed-phase HPLC without a prior extraction step gave a recovery of 54%, validating the direct applicability of this sensitive and specific assay for LTB₄, a highly potent chemotactic factor, to unfractionated biologic fluids.     

Are ovarian steroids required for ovum maturation and fertilization? Effects of cyanoketone on the in vitro perfused rabbit ovary

An isolated perfused rabbit ovary preparation was used to determine the effects of cyanoketone, a potent inhibitor of 3 beta-hydroxysteroid dehydrogenase, on ovulation, ovum maturation and fertilizability, and steroid production. In the first experiment, cyanoketone (10(-4) M) was added to the perfusate of one ovary. The contralateral control ovary was perfused with medium alone. Thirty minutes after the onset of perfusion, hCG (50 IU) was added to the perfusate of both ovaries. The ovulatory efficiency of ovaries treated with cyanoketone plus hCG (82.3 +/- 4.6%) was similar to that of ovaries treated with hCG alone (84.8 +/- 4.4%). No difference was observed in the degree of ovum maturity or degeneration between control and cyanoketone-treated ovaries. Progesterone and estradiol production were significantly reduced by cyanoketone treatment; concentrations in the perfusate of ovaries treated with cyanoketone were 9.7% and 8.0% of the control values, respectively, 2 h after exposure to hCG. The concentration of 17-hydroxypregnenolone was not affected by cyanoketone treatment. Exposure to cyanoketone resulted in a significant (P less than 0.005) reduction in the fertilizability of ova ovulated and fertilized in vitro. In the second experiment, the percentage of ova that showed evidence of normal fertilization was significantly (P less than 0.025) increased in ovaries perfused with cyanoketone plus estradiol (64.5%) compared to that in ovaries perfused with cyanoketone alone (32.4%). In the third experiment, the addition of progesterone to the perfusate did not affect fertilizability of ovulated ova in ovaries perfused with cyanoketone plus estradiol. These results suggest that the presence of estradiol in the ovarian steroid environment may be essential for fertilizability of ova, but not for the processes of ovulation or meiotic maturation.     

Relocation of blood gas laboratory to the emergency department helps decrease lactic acid values

Importance

Emergency Physicians often rely on Lactic Acid (LA) values to make important clinical decisions. Accuracy of LA values improve when blood gas analysis is performed in the emergency department (ED) as opposed to a satellite laboratory (SL).

Drivers of Emerging Infectious Disease Events as a Framework for Digital Detection

The growing field of digital disease detection, or epidemic intelligence, attempts to improve timely detection and awareness of infectious disease (ID) events. Early detection remains an important priority; thus, the next frontier for ID surveillance is to improve the recognition and monitoring of drivers (antecedent conditions) of ID emergence for signals that precede disease events. These data could help alert public health officials to indicators of elevated ID risk, thereby triggering targeted active surveillance and interventions. We believe that ID emergence risks can be anticipated through surveillance of their drivers, just as successful warning systems of climate-based, meteorologically sensitive diseases are supported by improved temperature and precipitation data. We present approaches to driver surveillance, gaps in the current literature, and a scientific framework for the creation of a digital warning system. Fulfilling the promise of driver surveillance will require concerted action to expand the collection of appropriate digital driver data.