Layer-specific and whole wall global longitudinal strain predict major adverse cardiovascular events in patients with stable angina pectoris

The International Journal of Cardiovascular Imaging - Global longitudinal strain (GLS) has proven to be a powerful prognostic marker in various patient populations, but the prognostic value of...     

The long‐term influence of repetitive cellular cardiac rejections on left ventricular longitudinal myocardial deformation in heart transplant recipients

The aim of the study was to evaluate the long‐term influence of repeated acute cellular rejections on left ventricular longitudinal deformation in heart transplantation (HTX) patients. One hundred and seventy‐eight HTX patients were included in the study. Rejections were classified according to the International Society of Heart and Lung Transplantation (ISHLT) classification (0R–3R). Patients were divided into three groups according to rejection scores (RSs). Group 1: <50% of biopsies with 1R rejection and no ≥2R rejections; Group 2: ≥50% of biopsies with 1R rejection or one biopsy with ≥2R rejection; Group 3: ≥Two biopsies with ≥2R rejections. All patients had a comprehensive echocardiographic examination and coronary angiography. We found significantly decreasing global longitudinal strain (GLS) comparing to rejection groups (GLS group 1: ?16.8 ± 2.4 (%); GLS group 2: ?15.9 ± 3.3 (%); GLS group 3: ?14.5 ± 2.9 (%), P = 0.0003). After excluding patients with LVEF < 50% or vasculopathy, GLS was still significantly reduced according to RS groups (P = 0.0096). Total number of 1R and 2R rejections correlated significant to GLS in a linear regression model. In contrast, we found fractional shortening and LVEF to be unaffected by repeated rejections. In conclusion, repeated cardiac rejections lead to impaired graft function as detected by decreasing magnitude of GLS. In contrast, traditional systolic graft function surveillance by LVEF did not correlate to rejection burden.     

Secular trends of dental status in five 70-year-old cohorts between 1971 and 2001

Abstract – Objective: The aims of this study, which are part of the gerontological and geriatric population studies in Göteborg, Sweden (H70), were to describe cohort differences and trends in dental status and utilization of dental care in 70‐year‐olds. The study is based on five cohorts examined in 1971/72, 1976/77, 1981/82, 1992/93 and 2000/01 (called cohort I, II, III, V and VI, respectively). The total number of participants was 2290 and varied between 386 and 583 in the different cohorts. The proportion of dentate 70‐year‐olds changed gradually from 49% in the first to 93% in the last cohort. The mean number of teeth in the dentate 70‐year‐olds was 14 in cohort I and 21 in cohort VI. The proportion of subjects with 20 or more teeth changed from 13% in cohort I, to 20% in cohort III, and to 65% in cohort VI. In cohort I, 76% of the 70‐year‐olds had some kind of removable denture; 37% in cohort III, but only 17% in cohort VI. About 20% of all 70‐year‐olds in cohort I reported regular yearly visits to a dentist. The corresponding figures in cohort III and cohort VI were 50% and 80%, respectively. Even though positive cohort trends were observed in all studied subgroups, factors such as low education, smoking, being un‐married, having high waist circumference and being physically inactive were negatively associated with dental status at the end of the study period as well as at the beginning.     

Distinct Subsets of Noncoding RNAs Are Strongly Associated With BMD and Fracture,Studied in Weight-Bearing and Non–Weight-Bearing Human Bone

We investigated mechanisms resulting in low bone mineral density (BMD) and susceptibility to fracture by comparing noncoding RNAs (ncRNAs) in biopsies of non–weight-bearing (NWB) iliac (n = 84) and weight bearing (WB) femoral (n = 18) postmenopausal bone across BMDs varying from normal (T-score > −1.0) to osteoporotic (T-score ≤ −2.5). Global bone ncRNA concentrations were determined by PCR and microchip analyses. Association with BMD or fracture, adjusted by age and body mass index, were calculated using linear and logistic regression and least absolute shrinkage and selection operator (Lasso) analysis. At 10% false discovery rate (FDR), 75 iliac bone ncRNAs and 94 femoral bone ncRNAs were associated with total hip BMD. Eight of the ncRNAs were common for the two sites, but five of them (miR-484, miR-328-3p, miR-27a-5p, miR-28-3p, and miR-409-3p) correlated positively to BMD in femoral bone, but negatively in iliac bone. Of predicted pathways recognized in bone metabolism, ECM-receptor interaction and proteoglycans in cancer emerged at both sites, whereas fatty acid metabolism and focal adhesion were only identified in iliac bone. Lasso analysis and cross-validations identified sets of nine bone ncRNAs correlating strongly with adjusted total hip BMD in both femoral and iliac bone. Twenty-eight iliac ncRNAs were associated with risk of fracture (FDR < 0.1). The small nucleolar RNAs, RNU44 and RNU48, have a function in stabilization of ribosomal RNAs (rRNAs), and their association with fracture and BMD suggest that aberrant processing of rRNAs may be involved in development of osteoporosis. Cis-eQTL (expressed quantitative trait loci) analysis of the iliac bone biopsies identified two loci associated with microRNAs (miRNAs), one previously identified in a heel-BMD genomewide association study (GWAS). In this comprehensive investigation of the skeletal genetic background in postmenopausal women, we identified functional bone ncRNAs associated to fracture and BMD, representing distinct subsets in WB and NWB skeletal sites. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Flow disturbances generated by feeding and swimming zooplankton

Interactions between planktonic organisms, such as detection of prey, predators, and mates, are often mediated by fluid signals. Consequently, many plankton predators perceive their prey from the fluid disturbances that it generates when it feeds and swims. Zooplankton should therefore seek to minimize the fluid disturbance that they produce. By means of particle image velocimetry, we describe the fluid disturbances produced by feeding and swimming in zooplankton with diverse propulsion mechanisms and ranging from 10-µm flagellates to greater than millimeter-sized copepods. We show that zooplankton, in which feeding and swimming are separate processes, produce flow disturbances during swimming with a much faster spatial attenuation (velocity u varies with distance r as u ∝ r⁻³ to r⁻⁴) than that produced by zooplankton for which feeding and propulsion are the same process (u ∝ r⁻¹ to r⁻²). As a result, the spatial extension of the fluid disturbance produced by swimmers is an order of magnitude smaller than that produced by feeders at similar Reynolds numbers. The “quiet” propulsion of swimmers is achieved either through swimming erratically by short-lasting power strokes, generating viscous vortex rings, or by “breast-stroke swimming.” Both produce rapidly attenuating flows. The more “noisy” swimming of those that are constrained by a need to simultaneously feed is due to constantly beating flagella or appendages that are positioned either anteriorly or posteriorly on the (cell) body. These patterns transcend differences in size and taxonomy and have thus evolved multiple times, suggesting a strong selective pressure to minimize predation risk.Zooplankters move to feed, find food, and find mates, so moving is critical to the efficient execution of essential functions. However, moving comes at a predation risk: Swimming increases the predator encounter velocity (encounter rate increases with prey velocity to a power ≤1), and feeding and swimming generate fluid disturbances that may be perceived by rheotactic predators, thus increasing the predator’s detection distance (encounter rate increases with detection distance squared) (1–5). So, the advantages of moving and feeding must be traded off against the associated risks, and organisms should aim at moving and foraging in ways that reduce the predation risk and optimize the trade-off (6, 7). They may do so by moving in patterns that minimize encounter rates (8) and/or they may feed and propel themselves in ways that generate only small fluid disturbances (9). For example, theoretical models suggest that zooplankton that swim by a sequence of jumps may create a smaller fluid disturbance than similar-sized ones that swim smoothly (9), that a hovering zooplankter generates a larger fluid signal than one that cruises through the water (10, 11), and that a zooplankter moving at low Reynolds numbers will generate a relatively larger fluid signal than one moving at higher Reynolds numbers (11). Thus, motility patterns and propulsion modes may strongly influence predation risk and must be subject to strong selection pressure during evolution.Zooplankton span a huge taxonomic diversity and a large size range (from microns to centimeters) and their propulsion mechanisms vary substantially (12). Unicellular plankton may use one or more flagella or cilia, and the flagella may be smooth or plumose, which has implications for whether the cell is pulled or pushed by the beating flagellum (13). Ciliates may have the cilia rather evenly distributed on the cell surface or concentrated on certain parts of the cell, typically either anteriorly or as an equatorial band. Small animals may have an anterior “corona” of cilia (e.g., rotifers and many pelagic invertebrate larvae) to generate feeding currents and propulsion, or they may have beating or vibrating appendages that can be positioned anteriorly, ventrally, or laterally. The implications and potential adaptive value of this diversity of propulsion modes for feeding and survival are largely unexplored.Various idealized models, simplifying the swimming organisms to combinations of point forces acting on the water, have been used to describe the fluid disturbance generated by moving and feeding plankton. A self-propelled plankton is often described by a so-called stresslet (two oppositely directed point forces of equal magnitude), a hovering one by a stokeslet (a stationary point force), and a jumping animal by an impulsive stresslet (a stresslet working impulsively) (9, 11, 12). These highly idealized models yield very different predictions of the spatial attenuation of the fluid disturbance and, thus, of how far away the feeding and swimming animal can be detected. A few studies have compared observed flow patterns with those predicted from these simple models and in some cases found fair comparisons (4, 14–17). However, numerical simulations as well as observations of self-propelled microplankton have demonstrated that the distribution of propulsion forces, i.e., the position of flagella, cilia, or appendages on the (cell) body, may have a profound effect on the imposed fluid flow (18, 19). Also, most of the idealized models ignore the fact that swimming in most cases is unsteady, which leads to fluctuating flows at scales smaller than the Stokes length scale (ν/ω, where ν is the kinematic viscosity and ω is the beat frequency) (e.g., ref. 19). The simple, idealized models hitherto applied may be insufficient to represent the diverse propulsion modes observed in real organisms and to understand the associated trade-offs.Feeding and swimming are often part of the same process in zooplankton. Many zooplankton generate a feeding current that at the same time propels the animal through the water. In others, feeding and swimming are separate processes. For example, ambush feeding “sit-and-wait” zooplankters do not move as part of feeding but may swim to undertake vertical migration or to search for mates or patches of elevated food availability. Also, many of the plankton that generate a feeding current by vibrating appendages may in addition swim by using the same appendages in a different way (e.g., the nauplius larvae of most crustaceans) or by using other swimming appendages dedicated to propel themselves (most pelagic copepods and cladocerans).Whereas feeding and swimming may both compromise the survival of the organism, the trade-offs may be different. To get sufficient food, zooplankters need to daily clear a volume of water for prey that corresponds to about 10⁶ times their own body volume (20, 21) and hence, implicit in the feeding process is the need to examine or process large volumes of water. In contrast, dedicated swimming should translate the organism through the water as quietly as possible. Thus, we hypothesize that in microplankton, dedicated swimming produces flow fields that attenuate more readily and/or have a smaller spatial extension than the cases in which feeding and propulsion are intimately related.In this study we use particle image velocimetry (PIV) to describe the flow fields generated by micron- to millimeter-sized feeding and swimming zooplankton that use a variety of propulsion modes. We show that—across taxa and sizes—dedicated swimming produces flow fields with a much smaller spatial extension and a faster spatial attenuation than those produced by the plankton for which feeding and swimming are integrated, and we characterize the propulsion modes that minimize susceptibility to rheotactic predators.     

Epoetin alfa and darbepoetin alfa for the treatment of chemotherapy-related anemia in cancer patients in Sweden: Comparative analysis of drug utilization, costs, and hematologic response

A retrospective chart review was performed at 3 Swedish hospitals to evaluate the utilization, outcomes, and cost of using epoetin alfa or darbepoetin alfa to treat cancer patients with chemotherapy-related anemia. Data on dosage, duration of treatment, hematologic response, red blood cell transfusions, and healthcare resource consumption were collected and analyzed at various time points following the initiation of drug therapy. A significantly faster hematologic response and increase in hemoglobin were observed in patients treated with epoetin alfa. Dosages used in clinical practice appeared to be lower than those recommended by Swedish treatment guidelines. There were no significant differences in resource utilization or healthcare costs between the 2 treatment groups. By day 112, the mean treatment cost per patient, in Swedish kronors (SEK), was SEK74,701 (~US$9800 or E8300) with epoetin alfa and SEK85,285 (~US$11,000 or E9500) with darbepoetin alfa. Drug acquisition and administration accounted for 81 % and 67% of the total cost of epoetin alfa and darbepoetin alfa therapy, respectively; the remainder of the total cost was for hospitalization and transfusions.