Aortic root motion for the assessment of left ventricular function in acute myocardial infarction.

In a group of patients with various cardiac disorders positive correlation between aortic root motion amplitude and stroke volume was observed: (y=3.41 + 0.061 chi, r=0.719n=27), where y is the aortic wall motion amplitude in mm and chi is the stroke volume in ml. During the serial investigation of 40 patients with acute myocardial infarction aortic root systolic motion amplitude was significantly different between patients groups, selected by the categories of Killip (1967). Biggest amplitudes were found in patients with complicated course, smallest amplitudes in cardiogenic shock. Aortic root systolic motion increased in a parallel direction with the clinical improvement of the patients. Aortic root echos are easily detectable, independent from segmental dysfunction, therefore useful in monitoring of left ventricular function of patients with acute myocardial infarction.     

In vivo Doppler optical coherence tomography of mucocutaneous telangiectases in hereditary hemorrhagic telangiectasia

BACKGROUND: Hereditary hemorrhagic telangiectasia is characterized by mucocutaneous telangiectases and visceral arteriovenous malformations. Knowledge is limited concerning the development hemodynamics of mucocutaneous telangiectases. Doppler optical coherence tomography can demonstrate microvascular blood flow at flow rates as low as 20 microm/second, which is up to approximately 100 times more sensitive than Doppler US. The aims of this study were to collect in vivo Doppler optical coherence tomography images of mucocutaneous telangiectases and normal surrounding mucosa and skin, and to gain experience for an in vivo GI endoscopic study. It was hypothesized that visibly normal areas may have occult telangiectases and that mucocutaneous telangiectases that have bled may have a higher rate of blood flow than mucocutaneous telangiectases with no history of bleeding. METHODS: Twelve patients with hereditary hemorrhagic telangiectasia and mucocutaneous telangiectases were studied. Two to 3 visible mucocutaneous telangiectases on the digits, lips, and tongue were imaged with Doppler optical coherence tomography, along with visually normal surrounding areas at each site. The Doppler optical coherence tomography images were obtained in 0.5 second by using 1310 nm light. RESULTS: A total of 67 mucocutaneous telangiectases from the 12 patients were imaged (38 digit, 16 lip, 13 tongue). Blood flow was demonstrated within every mucocutaneous telangiectasis imaged. Doppler optical coherence tomography did not identify any abnormal vasculature within visually normal areas. Mucocutaneous telangiectases with a history of bleeding (n = 18) were situated closer to the surface, compared with mucocutaneous telangiectases with no bleeding history (n = 49), but there was no difference in the Doppler flow appearance. CONCLUSIONS: Visually normal areas in patients with hereditary hemorrhagic telangiectasia did not appear to have abnormal vasculature. Mucocutaneous telangiectases with a history of bleeding were more superficial but were otherwise similar to mucocutaneous telangiectases with no bleeding history.     

Device Closure of a Secundum Atrial Septal Defect in a 4‐Month‐Old Infant with a Marginal Left Ventricle Following Coarctation Repair

A male infant presented at birth with severe coarctation of the aorta and marginal left ventricular and mitral valve dimensions associated with a large secundum atrial septal defect. Following successful arch repair, the left ventricle remained small with preferential left‐to‐right atrial shunting and a dilated right ventricle. Clinically, the infant continued with tachypnea, poor feeding, and failure to thrive. At 4 months of age, the defect was closed with an Amplatzer Atrial Septal Occluder which resulted in immediate left ventricular cavity enlargement and clinical improvement.     

Mode of action of iron (III) chelators as antimalarials: II. Evidence for differential effects on parasite iron-dependent nucleic acid synthesis

Iron chelation treatment of red blood cells infected with Plasmodium falciparum selectively intervenes with iron-dependent metabolism of malaria parasites and inhibits their development. Highly permeant hydroxamate iron chelator RSFileum2 affects all parasite stages when cultures are continuously exposed to drug, but affects primarily ring stages when assessed for irreversible effects, ie, sustained inhibition remaining after drug removal. On the other hand, the hydrophilic and poorly permeant desferrioxamine (DFO) affects primarily trophozoite/schizont stages when tested either in the continuous mode or irreversible mode. Unlike parasites, mammalian cells subjected to similar drug treatment show complete growth recovery once drugs are removed. Our studies indicate that parasites display a limited capacity to recover from intracellular iron depletion evoked by iron chelators. Based on these findings we provide a working model in which the irreversible effects of RSFs on rings are explained by the absence of pathways for iron acquisition/utilization by early forms of parasites. Trophozoite/schizonts can partially recover from RSFileum2 treatments, but show no DNA synthesis following DFO treatment even after drug removal and iron replenishment by permeant iron carriers. At trophozoite stage, the parasite uses a limited pathway for refurnishing its iron-containing enzymes, thus overcoming iron deprivation caused by permeant RSFileum2, but not by DFO because this latter drug is not easily removable from parasites. Their DNA synthesis is blocked by the hydroxamate iron chelators probably by affecting synthesis of ribonucleotide reductase (RNRase). Presumably in parasites, prolonged repression of the enzyme leads also to irreversible loss of activity. The action profiles of RSFileum2 and DFO presented in this study have implications for improved chemotherapeutic performance by combined drug treatment and future drug design based on specific intervention at parasite DNA synthesis.     

A novel temporal‐predominant neuro‐astroglial tauopathy associated with TMEM106B gene polymorphism in FTLD/ALS‐TDP

Polymorphisms in TMEM106B, a gene on chromosome 7p21.3 involved in lysosomal trafficking, correlates to worse neuropathological, and clinical outcomes in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) with TDP‐43 inclusions. In a small cohort of C9orf72 expansion carriers, we previously found an atypical, neuroglial tauopathy in cases harboring a TMEM106B rs1990622 A/A genotype. To test whether TMEM106B genotype affects the risk of developing atypical tauopathy under a recessive genotype model (presence versus absence of two major alleles: A/A vs. A/G and G/G). We characterized the atypical tauopathy neuropathologically and determined its frequency by TMEM106B rs1990622 genotypes in 90 postmortem cases with a primary diagnosis of FTLD/ALS‐TDP [mean age at death 65.5 years (±8.1), 40% female]. We investigated the effect of this new atypical tauopathy on demographics and clinical and neuropsychological metrics. We also genotyped TMEM106B in an independent series with phenotypically similar cases. Sixteen cases (16/90, 17.7 %) showed the temporal‐predominant neuro‐astroglial tauopathy, and 93.7% of them carried an A/A genotype (vs. ~35% in a population cohort). The odds ratio of FTLD/ALS‐TDP individuals with the A/A genotype showing neuro‐astroglial tauopathy was 13.9. Individuals with this tauopathy were older at onset (p = 0.01). The validation cohort had a similarly high proportion of rs1990622 A/A genotype. TDP‐43 and tau changes co‐occur in a subset of neurons. Our data add to the growing body of evidence that TMEM106B polymorphisms may modulate neurodegeneration. A distinctive medial temporal predominant, 4‐repeat, neuro‐astroglial tauopathy strongly correlates to TMEM106B A/A genotype in FTLD/ALS‐TDP cases.     

Serum leptin, soluble leptin receptor, free leptin index and bone mineral density in patients with primary biliary cirrhosis

BACKGROUND/AIM: The pathophysiology of osteoporosis in chronic liver diseases is unknown. Recent data suggest that serum leptin is associated with bone mineral density (BMD). In animal studies leptin was found to be a potent inhibitor of bone formation. We investigated the relationship between serum leptin levels, soluble leptin receptor (sOB-R), free leptin index (FLI) and BMD in patients with primary biliary cirrhosis (PBC). PATIENTS AND METHODS: Ninety-four female patients with PBC were included in this study; 122 healthy women served as controls. Serum leptin levels were measured by radioimmunoassay, sOB-R by enzyme-linked immunosorbent assay. BMD was measured by dual energy X-ray absorptiometry in the lumbar spine and femoral neck. RESULTS: Serum leptin was significantly lower in patients with PBC compared with healthy controls. No difference was found between the body mass index (BMI) of patients and controls. There was a strong positive correlation between leptin and BMI. In PBC no association was found between leptin, sOB-R and liver function tests, histological stages or the presence of osteoporosis. Osteoporosis was present in 38 patients. A positive correlation was found between serum leptin and femoral neck z-score even after adjustment for BMI, whereas serum sOB-R correlated inversely with the serum leptin level. There was no difference in FLI between the subgroups of PBC patients according to the stages of the disease. CONCLUSIONS: We found a lower serum leptin level and a higher sOB-R in patients with PBC, which could not be explained by the difference in BMI. As leptin was associated with BMD, it may be hypothesized that leptin is involved in the complex regulation of bone metabolism in PBC.     

Hyperspectral interference tomography of nacre

Structural characterization of biologically formed materials is essential for understanding biological phenomena and their enviro-nment, and for generating new bio-inspired engineering concepts. For example, nacre—the inner lining of some mollusk shells—encodes local environmental conditions throughout its formation and has exceptional strength due to its nanoscale brick-and-mortar structure. This layered structure, comprising alternating transparent aragonite (CaCO₃) tablets and thinner organic polymer layers, also results in stunning interference colors. Existing methods of structural characterization of nacre rely on some form of cross-sectional analysis, such as scanning or transmission electron microscopy or polarization-dependent imaging contrast (PIC) mapping. However, these techniques are destructive and too time- and resource-intensive to analyze large sample areas. Here, we present an all-optical, rapid, and nondestructive imaging technique—hyperspectral interference tomography (HIT)—to spatially map the structural parameters of nacre and other disordered layered materials. We combined hyperspectral imaging with optical-interference modeling to infer the mean tablet thickness and its disorder in nacre across entire mollusk shells from red and rainbow abalone (Haliotis rufescens and Haliotis iris) at various stages of development. We observed that in red abalone, unexpectedly, nacre tablet thickness decreases with age of the mollusk, despite roughly similar appearance of nacre at all ages and positions in the shell. Our rapid, inexpensive, and nondestructive method can be readily applied to in-field studies.

Complex optical phenomena can emerge from a variety of biological or bio-inspired processes, from arrays of colors in peacocks (1) and other birds (2), butterflies (3), and opals (4), to the metal-like sheen of herring (5) and unique polarization-dependent properties of jewel beetles (6) and Pollia fruit (7). Nacre, or mother-of-pearl, is a prominent biologically formed mineral structure found throughout our oceans. It lines the inside of the shells formed by many mollusks, including bivalves, cephalopods, and gastropods. It features brilliant iridescent colors (Fig. 1) and is studied and emulated in part because of its outstanding mechanical performance (8, 9). The striking, colorful appearance of nacre has been a source of scientific curiosity since the days of Brewster (10), Rayleigh (11), and Raman (12, 13), and is the product of optical interference resulting from multiple interface reflections as light propagates through its stratified structure comprising stacks of transparent polygonal aragonite tablets (CaCO₃) interspersed with organic polymer (chitin and proteins) layers (14–16) (Fig. 1A). Nacre is one of seven mollusk shell structures (17). In the nacre structure, the aragonite tablets are typically 5 to 10 μm in diameter and hundreds of nanometers thick [200 to 1,100 nm across all shells, and 250 to 500 nm in red abalone (18)], while the organic sheets are an order of magnitude thinner (14, 16, 19). In columnar nacre formed by gastropods like abalone and snails (Fig. 1), co-oriented tablets are stacked on top of one another, while in sheet nacre formed by bivalves like pearl oysters and pen shells, co-oriented tablets are staggered diagonally (18) (see Movie S1 for an animation showing how co-oriented tablets are stacked in columnar nacre). Despite the significant structural and formation–mechanism differences, the thicknesses of tablets and organic layers are similar in columnar and sheet nacre, and so are the optical and mechanical behavior (20). The resulting palette of colors is primarily dependent on the nacre tablet thickness and the viewing angle, and the optical response that yields these colors can be understood as that of a Bragg reflector (21) with disorder in the layer thicknesses, where the optical band gaps are determined by the thicknesses of the transparent layers (5, 22, 23). Thus, the spectrum of light reflected from a nacre surface encodes information about its physical structure (Fig. 1 B–D).Open in a separate windowFig. 1.(A) Nacre, the colorful iridescent inner lining of some mollusk shells. Here, the red abalone, or H. rufescens, shell features columnar nacre, which comprises thousands of layers of polygonal aragonite tablets interspersed with organic sheets. (B) A close-up photograph of the nacre surface shows a variety of colors and nonuniformities. (C and D) Given a broadband white light source illuminating nacre at a fixed angle of incidence, variations in color are observed due to the difference in average thickness of aragonite tablets comprising nacre. (E) Hyperspectral interference tomography (HIT) setup: A hyperspectral camera collects predominantly specular reflectance data across a sample illuminated by a collimated source at a fixed angle of incidence from the normal to the sample (θ). The reflected light is polarized using a wire-grid polarizer. (F) A color photograph of a region of nacre that was analyzed. (G) Map of the mean tablet thickness (MTT) obtained using HIT, overlaid on a grayscale rendering of the photograph in F. Highlighted in red is a 5 × 5-mm region used to analyze the ontogeny of nacre in Fig. 4. The region around this area was masked off using opaque tape, which is highlighted with the dashed white box.Understanding and characterizing the structure of nacre and other biomaterials have deep and surprising implications. For example, the average thickness of the tablets comprising ancient nacre can be used as a proxy for local ocean temperatures at the time of nacre formation, enabling paleoclimatology spanning hundreds of millions of years (18, 24, 25). The structure of nacre is also an inspiration for engineered materials thousands of times stronger than the constituent materials (15, 26, 27). To that end, new techniques have been developed to probe and understand the structure of nacre, such as polarization-dependent imaging contrast (PIC) mapping using X-ray absorption near-edge structure spectroscopy combined with photoemission electron spectromicroscopy (18, 28, 29), or X-ray nanotomography (30). However, these characterization techniques such as cross-sectional electron microscopy result in the destruction of the sample and are time-consuming and costly.Here, we present a method for rapid, nondestructive, and large-scale structural characterization of disordered and nonuniform stratified thin-film materials and apply it to the analysis of nacre. Our all-optical method employs hyperspectral imaging combined with thin-film modeling to extract nacre mean tablet thicknesses (MTTs) and tablet degree of disorder (σ)—defined as the standard deviation of the thicknesses—across large areas (Fig. 1 E–G). This characterization method is designated as hyperspectral interference tomography (HIT). We used HIT to map the structure of mollusk shell nacre across many stages of development and identified a previously unexplored relationship between the age of the organism and the structure of the nacre layer. We investigated two particular species of nacre-forming mollusks, Haliotis rufescens (red abalone) and Haliotis iris (paua, or rainbow abalone; data only in SI Appendix), for which the aragonite tablet thicknesses lie within a range of 250 to 500 nm (18, 31); however, the method is applicable to any other transparent layered structure of animal, plant, geologic, or synthetic origin.     

Individual versus Standardized Running Protocols in the Determination of VO2max

The purpose of this study was to determine whether an individually designed incremental exercise protocol results in greater rates of oxygen uptake (VO_2max) than standardized testing. Fourteen well-trained, male runners performed five incremental protocols in randomized order to measure their VO_2max: i) an incremental test (INC_S+I) with pre-defined increases in speed (2 min at 8.64 km·h⁻¹, then a rise of 1.44 km·h⁻¹ every 30 s up to 14.4 km·h⁻¹) and thereafter inclination (0.5° every 30 s); ii) an incremental test (INC_I) at constant speed (14.4 km·h⁻¹) and increasing inclination (2° every 2 min from the initial 0°); iii) an incremental test (INC_S) at constant inclination (0°) and increasing speed (0.5 km·h⁻¹ every 30 s from the initial 12.0 km·h⁻¹); iv) a graded exercise protocol (GXP) at a 1° incline with increasing speed (initially 8.64 km·h⁻¹ + 1.44 km·h⁻¹ every 5 min); v) an individual exercise protocol (INDXP) in which the runner chose the inclination and speed. VO_2max was lowest (-4.2%) during the GXP (p = 0.01; d = 0.06-0.61) compared to all other tests. The highest rating of perceived exertion, heart rate, ventilation and end-exercise blood lactate concentration were similar between the different protocols (p < 0.05). The time to exhaustion ranged from 7 min 18 sec (INC_S) to 25 min 30 sec (GXP) (p = 0.01).The VO_2max attained by employing an individual treadmill protocol does not differ from the values derived from various standardized incremental protocols.

Key points

• The mean maximum oxygen uptake during the GXP was lower than for all other tests.
• Differences in the maximum rate of oxygen uptake between the various protocols exhibited considerable inter-individual variation.
• From the current findings, it can be concluded that well trained athletes are able to perform an individually designed treadmill running protocol.

Key words: Maximum oxygen uptake, aerobic power, treadmill running, ramp test, treadmill protocol