Spaceflight-induced alterations in cerebral artery vasoconstrictor, mechanical, and structural properties: implications for elevated cerebral perfusion and intracranial pressure.

Evidence indicates that cerebral blood flow is both increased and diminished in astronauts on return to Earth. Data from ground-based animal models simulating the effects of microgravity have shown that decrements in cerebral perfusion are associated with enhanced vasoconstriction and structural remodeling of cerebral arteries. Based on these results, the purpose of this study was to test the hypothesis that 13 d of spaceflight [Space Transportation System (STS)-135 shuttle mission] enhances myogenic vasoconstriction, increases medial wall thickness, and elicits no change in the mechanical properties of mouse cerebral arteries. Basilar and posterior communicating arteries (PCAs) were isolated from 9-wk-old female C57BL/6 mice for in vitro vascular and mechanical testing. Contrary to that hypothesized, myogenic vasoconstrictor responses were lower and vascular distensibility greater in arteries from spaceflight group (SF) mice (n=7) relative to ground-based control group (GC) mice (n=12). Basilar artery maximal diameter was greater in SF mice (SF: 236±9 µm and GC: 215±5 µm) with no difference in medial wall thickness (SF: 12.4±1.6 µm; GC: 12.2±1.2 µm). Stiffness of the PCA, as characterized via nanoindentation, was lower in SF mice (SF: 3.4±0.3 N/m; GC: 5.4±0.8 N/m). Collectively, spaceflight-induced reductions in myogenic vasoconstriction and stiffness and increases in maximal diameter of cerebral arteries signify that elevations in brain blood flow may occur during spaceflight. Such changes in cerebral vascular control of perfusion could contribute to increases in intracranial pressure and an associated impairment of visual acuity in astronauts during spaceflight.

Effects of hindlimb unweighting on the mechanical and structure properties of the rat abdominal aorta.

Previous studies have shown that hindlimb unweighting of rats, a model of microgravity, reduces evoked contractile tension of peripheral conduit arteries. It has been hypothesized that this diminished contractile tension is the result of alterations in the mechanical properties of these arteries (e.g., active and passive mechanics). Therefore, the purpose of this study was to determine whether the reduced contractile force of the abdominal aorta from 2-wk hindlimb-unweighted (HU) rats results from a mechanical function deficit resulting from structural vascular alterations or material property changes. Aortas were isolated from control (C) and HU rats, and vasoconstrictor responses to norepinephrine (10(-9)-10(-4) M) and AVP (10(-9)-10(-5) M) were tested in vitro. In a second series of tests, the active and passive Cauchy stress-stretch relations were determined by incrementally increasing the uniaxial displacement of the aortic rings. Maximal Cauchy stress in response to norepinephrine and AVP were less in aortic rings from HU rats. The active Cauchy stress-stretch response indicated that, although maximum stress was lower in aortas from HU rats (C, 8.1 +/- 0.2 kPa; HU, 7.0 +/- 0.4 kPa), it was achieved at a similar hoop stretch. There were also no differences in the passive Cauchy stress-stretch response or the gross vascular morphology (e.g., medial cross-sectional area: C, 0.30 +/- 0.02 mm(2); HU, 0.32 +/- 0.01 mm(2)) between groups and no differences in resting or basal vascular tone at the displacement that elicits peak developed tension between groups (resting tension: C, 1.71 +/- 0.06 g; HU, 1.78 +/- 0.14 g). These results indicate that HU does not alter the functional mechanical properties of conduit arteries. However, the significantly lower active Cauchy stress of aortas from HU rats demonstrates a true contractile deficit in these arteries.

Stochastic ontogenetic allometry: the statistical dynamics of relative growth.

BACKGROUND: In the absence of stochasticity, allometric growth throughout ontogeny is axiomatically described by the logarithm-transformed power-law model, θt = log(a) b + kφ(t), where θt ≡ θ(t) and φt ≡ φ(t) are the logarithmic sizes of two traits at any given time t. Realistically, however, stochasticity is an inherent property of ontogenetic allometry. Due to the inherent stochasticity in both θt and φt, the ontogenetic allometry coefficients, log(a) b and k, can vary with t and have intricate temporal distributions that are governed by the central and mixed moments of the random ontogenetic growth functions, θt and φt. Unfortunately, there is no probabilistic model for analyzing these informative ontogenetic statistical moments. METHODOLOGY/PRINCIPAL FINDINGS: This study treats θt and φt as correlated stochastic processes to formulate the exact probabilistic version of each of the ontogenetic allometry coefficients. In particular, the statistical dynamics of relative growth is addressed by analyzing the allometric growth factors that affect the temporal distribution of the probabilistic version of the relative growth rate, k ≡ Dt(u<Ωt>)/Dt(v<Ωt>), where <Ωt> is the expected value of the ratio of stochastic θt to stochastic φt, and u<Ωt> and v<Ωt> are the numerator and the denominator of <Ωt>, respectively. These allometric growth factors, which provide important insight into ontogenetic allometry but appear only when stochasticity is introduced, describe the central and mixed moments of θt and φt as differentiable real-valued functions of t. CONCLUSIONS/SIGNIFICANCE: Failure to account for the inherent stochasticity in both θt and φt leads not only to the miscalculation of k, but also to the omission of all of the informative ontogenetic statistical moments that affect the size of traits and the timing and rate of development of traits. Furthermore, even though the stochastic process θt and the stochastic process φt are linearly related, k can vary with t.

Hydrodynamics-based functional forms of activity metabolism: a case for the power-law polynomial function in animal swimming energetics.

The first-degree power-law polynomial function is frequently used to describe activity metabolism for steady swimming animals. This function has been used in hydrodynamics-based metabolic studies to evaluate important parameters of energetic costs, such as the standard metabolic rate and the drag power indices. In theory, however, the power-law polynomial function of any degree greater than one can be used to describe activity metabolism for steady swimming animals. In fact, activity metabolism has been described by the conventional exponential function and the cubic polynomial function, although only the power-law polynomial function models drag power since it conforms to hydrodynamic laws. Consequently, the first-degree power-law polynomial function yields incorrect parameter values of energetic costs if activity metabolism is governed by the power-law polynomial function of any degree greater than one. This issue is important in bioenergetics because correct comparisons of energetic costs among different steady swimming animals cannot be made unless the degree of the power-law polynomial function derives from activity metabolism. In other words, a hydrodynamics-based functional form of activity metabolism is a power-law polynomial function of any degree greater than or equal to one. Therefore, the degree of the power-law polynomial function should be treated as a parameter, not as a constant. This new treatment not only conforms to hydrodynamic laws, but also ensures correct comparisons of energetic costs among different steady swimming animals. Furthermore, the exponential power-law function, which is a new hydrodynamics-based functional form of activity metabolism, is a special case of the power-law polynomial function. Hence, the link between the hydrodynamics of steady swimming and the exponential-based metabolic model is defined.

Evolution with stochastic fitness and stochastic migration.

BACKGROUND: Migration between local populations plays an important role in evolution - influencing local adaptation, speciation, extinction, and the maintenance of genetic variation. Like other evolutionary mechanisms, migration is a stochastic process, involving both random and deterministic elements. Many models of evolution have incorporated migration, but these have all been based on simplifying assumptions, such as low migration rate, weak selection, or large population size. We thus have no truly general and exact mathematical description of evolution that incorporates migration. METHODOLOGY/PRINCIPAL FINDINGS: We derive an exact equation for directional evolution, essentially a stochastic Price equation with migration, that encompasses all processes, both deterministic and stochastic, contributing to directional change in an open population. Using this result, we show that increasing the variance in migration rates reduces the impact of migration relative to selection. This means that models that treat migration as a single parameter tend to be biassed - overestimating the relative impact of immigration. We further show that selection and migration interact in complex ways, one result being that a strategy for which fitness is negatively correlated with migration rates (high fitness when migration is low) will tend to increase in frequency, even if it has lower mean fitness than do other strategies. Finally, we derive an equation for the effective migration rate, which allows some of the complex stochastic processes that we identify to be incorporated into models with a single migration parameter. CONCLUSIONS/SIGNIFICANCE: As has previously been shown with selection, the role of migration in evolution is determined by the entire distributions of immigration and emigration rates, not just by the mean values. The interactions of stochastic migration with stochastic selection produce evolutionary processes that are invisible to deterministic evolutionary theory.

99mTechnetium-ciprofloxacin scintigraphy for the evaluation of spinal infections: a preliminary report.

UNLABELLED: Currently available laboratory and imaging tests have limitations diagnosing and following patients with spinal infections. We evaluated 17 Technetium-99m labeled ciprofloxacin scintigraphy studies in 11 patients who had the diagnosis of a spinal infection based on the Centers for Disease Control and Prevention criteria. Three of the 17 studies were performed in three patients within 2 months from the onset of the symptoms. All of these three studies showed increased uptake of the radiopharmaceutical in the area of the spinal infection. Fourteen studies were performed during the followup period (from 210 to 690 days after the onset of symptoms) in nine patients with spinal infections. Ten of the 14 studies performed in five patients with an active spine infection showed positive results while the patients had evidence for active spinal infection at the time of the testing. Four studies were performed during the followup period in four patients who at the time of the nuclear imaging testing had no symptoms, signs, or laboratory or other imaging evidence for active infection. All four studies showed negative results. The results of this preliminary study show that scintigraphy with 99mTc-ciprofloxacin may be useful in the diagnosis of active spinal infections. LEVEL OF EVIDENCE: Diagnostic study, level II-1 (Testing of previously developed diagnostic criteria on consecutive patients [with universally applied reference "gold" standard]). Please see Guidelines for Authors for a complete description of levels of evidence.

Extragenital bowenoid papulosis associated with atypical human papillomavirus genotypes.

BACKGROUND: Bowenoid papulosis typically appears as grouped violaceous or red-brown papules in the genital or perianal regions and clinically resembles condylomata acuminata. Isolated extragenital bowenoid papulosis is rare and has been reported in only a few case reports. OBJECTIVES: A 51-year-old immunocompetent, healthy woman had two solitary papules on the elbow; a 41-year-old HIV-positive man had a solitary cutaneous plaque on the abdomen. No genital, periungual, or other extragenital sites of involvement were noted in either patient. The diagnosis was confirmed histologically in both cases. Lesional skin from the female patient was tested with the Digenehybrid HPV DNA assay and was positive for a mixture of low-risk HPV subtypes (6, 11, 42, 43, 44). Lesional skin from the male patient was tested with polymerase chain reaction (PCR). Consensus primers targeted for the HPV L1 region, which is a highly conserved sequence common to more than 20 HPV subtypes encoding a viral capsid protein, were used. PCR using the consensus primers was positive, but type-specific probes for HPV types 6, 11, 16, 18, 45, 31, 33, 35, and 39 were negative. CONCLUSIONS: To our knowledge, our male patient represents the first case of isolated bowenoid papulosis of the abdominal skin. Isolated upper-extremity bowenoid papulosis in our female patient is also a unique case in both location and involvement of low-risk HPV types (6, 11, 42, 43, 44), which have not been previously associated with extragenital bowenoid papulosis.

Effects of aging on vasoconstrictor and mechanical properties of rat skeletal muscle arterioles.

Exercise capacity and skeletal muscle blood flow during exercise are reduced with advancing age. This reduction in blood flow capacity may be related to increased reactivity of skeletal muscle resistance vessels to vasoconstrictor stimuli. The purpose of this study was to test the hypothesis that aging results in increased vasoconstrictor responses of skeletal muscle resistance arterioles. First-order (1A) arterioles (90-220 microm) from the gastrocnemius and soleus muscles of young (4 mo) and aged (24 mo) Fischer-344 rats were isolated, cannulated, and pressurized via hydrostatic reservoirs. Vasoconstriction in response to increases in norepinephrine (NE; 1 x 10(-9)-1 x 10(-4) M) and KCl (20-100 mM) concentrations and increases in intraluminal pressure (10-130 cmH(2)O) were evaluated in the absence of flow. Responses to NE and KCl were similar in both soleus and gastrocnemius muscle arterioles from young and aged rats. In contrast, active myogenic responses to changes in intraluminal pressure were diminished in soleus and gastrocnemius arterioles from aged rats. To assess whether alterations in the mechanical properties of resistance arterioles underlie altered myogenic responsiveness, passive diameter responses to pressure and mechanical stiffness were evaluated. There was no effect of age on the structural behavior (passive pressure-diameter relationship) or stiffness of arterioles from either the soleus or gastrocnemius muscles. These results suggest that aging does not result in a nonspecific decrease in vasoconstrictor responsiveness of skeletal muscle arterioles. Rather, aging-induced adaptations of vasoreactivity of resistance arterioles appear to be limited to mechanisms that are uniquely involved in the signaling of the myogenic response.