130 research outputs found

    Echocardiographic Identification of Elevated Filling Pressures in LVAD Patients∗

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    Sediment destabilization by animal tubes

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    Laboratory flume ex periments we re conducted in order to test the influence on sediment e rodibility of varying densities of the tube-building polychaete worm Owenia fusiformis. Experiments were performed on isolated individuals, in order to measure approximate spatial limits of isolated tube effects, and on arrays of individuals at densities reported previously to be associated with stable beds...

    The ecological significance of giant clams in coral reef ecosystems

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    AbstractGiant clams (Hippopus and Tridacna species) are thought to play various ecological roles in coral reef ecosystems, but most of these have not previously been quantified. Using data from the literature and our own studies we elucidate the ecological functions of giant clams. We show how their tissues are food for a wide array of predators and scavengers, while their discharges of live zooxanthellae, faeces, and gametes are eaten by opportunistic feeders. The shells of giant clams provide substrate for colonization by epibionts, while commensal and ectoparasitic organisms live within their mantle cavities. Giant clams increase the topographic heterogeneity of the reef, act as reservoirs of zooxanthellae (Symbiodinium spp.), and also potentially counteract eutrophication via water filtering. Finally, dense populations of giant clams produce large quantities of calcium carbonate shell material that are eventually incorporated into the reef framework. Unfortunately, giant clams are under great pressure from overfishing and extirpations are likely to be detrimental to coral reefs. A greater understanding of the numerous contributions giant clams provide will reinforce the case for their conservation

    Postcardiac transplant survival in the current era in patients receiving continuous-flow left ventricular assist devices

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    ObjectivesContinuous-flow left ventricular assist devices have become the standard of care for patients with heart failure requiring mechanical circulatory support as a bridge to transplant. However, data on long-term post-transplant survival for these patients are limited. We evaluated the effect of continuous-flow left ventricular assist devices on postcardiac transplant survival in the current era.MethodsAll patients who received a continuous-flow left ventricular assist device as a bridge to transplant at a single center from June 2005 to September 2011 were evaluated.ResultsOf the 167 patients who received a continuous-flow left ventricular assist device as a bridge to transplant, 77 (46%) underwent cardiac transplantation, 27 died before transplantation (16%), and 63 (38%) remain listed for transplantation and continued with left ventricular assist device support. The mean age of the transplanted patients was 54.5 ± 11.9 years, 57% had an ischemic etiology, and 20% were women. The overall mean duration of left ventricular assist device support before transplantation was 310 ± 227 days (range, 67-1230 days). The mean duration of left ventricular assist device support did not change in patients who had received a left ventricular assist device in the early period of the study (2005-2008, n = 62) compared with those who had received a left ventricular assist device later (2009-2011, n = 78, 373 vs 392 days, P = NS). In addition, no difference was seen in survival between those patients supported with a left ventricular assist device for fewer than 180 days or longer than 180 days before transplantation (P = NS). The actuarial survival after transplantation at 30 days and 1, 3, and 5 years by Kaplan-Meier analysis was 98.7%, 93.0%, 91.1%, and 88.0%, respectively.ConclusionsThe short- and long-term post-transplant survival for patients bridged with a continuous-flow left ventricular assist device in the current era has been excellent. Furthermore, the duration of left ventricular assist device support did not affect post-transplant survival. The hemodynamic benefits of ventricular unloading with continuous-flow left ventricular assist devices, in addition to their durability and reduced patient morbidity, have contributed to improved post-transplant survival

    Pharmacologic reductions of total tau levels; implications for the role of microtubule dynamics in regulating tau expression

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    The microtubule-associated protein tau (MAPT) is a pathological component of several neurodegenerative diseases and clinical dementias. Here, we have investigated the effects of a series of commercially available FDA-approved compounds and natural products on total tau protein levels using a cell-based approach that allows for the rapid and efficient measurement of changes in protein expression. RESULTS: The compounds that reduced tau largely fell within 3 functional categories with the largest percentage being microtubule regulators. Several of these candidates were validated in both a human neuroglioma and a human neuroblastoma cell line. While these drugs lead to a rapid reduction in tau protein levels, a selective decrease in MAPT mRNA expression was also observed. CONCLUSION: These findings suggest that the identified compounds that reduce tau levels may act either through direct effects on the MAPT promoter itself or by altering a feedback transcriptional mechanism regulating MAPT transcription. This is particularly interesting in light of recent evidence suggesting that MAPT 5' UTR mutations in late-onset PD and PSP cases alter the expression of tau mRNA. In fact, one of the compounds we identified, rotenone, has been used extensively to model PD in rodents. These observations may provide key insights into the mechanism of tau turnover within the neuron while also providing the first evidence that selectively reducing tau protein levels may be possible using compounds that are FDA-approved for other uses

    Historical development of accelerometry measures and methods for physical activity and sedentary behavior research worldwide: A scoping review of observational studies of adults

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    This scoping review identified observational studies of adults that utilized accelerometry to assess physical activity and sedentary behavior. Key elements on accelerometry data collection were abstracted to describe current practices and completeness of reporting. We searched three databases (PubMed, Web of Science, and SPORTDiscus) on June 1, 2021 for articles published up to that date. We included studies of non-institutionalized adults with an analytic sample size of at least 500. The search returned 5686 unique records. After reviewing 1027 full-text publications, we identified and abstracted accelerometry characteristics on 155 unique observational studies (154 cross-sectional/cohort studies and 1 case control study). The countries with the highest number of studies included the United States, the United Kingdom, and Japan. Fewer studies were identified from the continent of Africa. Five of these studies were distributed donor studies, where participants connected their devices to an application and voluntarily shared data with researchers. Data collection occurred between 1999 to 2019. Most studies used one accelerometer (94.2%), but 8 studies (5.2%) used 2 accelerometers and 1 study (0.6%) used 4 accelerometers. Accelerometers were more commonly worn on the hip (48.4%) as compared to the wrist (22.3%), thigh (5.4%), other locations (14.9%), or not reported (9.0%). Overall, 12.7% of the accelerometers collected raw accelerations and 44.6% were worn for 24 hours/day throughout the collection period. The review identified 155 observational studies of adults that collected accelerometry, utilizing a wide range of accelerometer data processing methods. Researchers inconsistently reported key aspects of the process from collection to analysis, which needs addressing to support accurate comparisons across studies

    The incidence, risk factors, and outcomes associated with late right-sided heart failure in patients supported with an axial-flow left ventricular assist device

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    BACKGROUND: Early right-sided heart failure (RHF) after left ventricular assist device (LVAD) implantation is associated with increased mortality, but little is known about patients who develop late RHF (LRHF). We evaluated the incidence, risk factors, and clinical impact of LRHF in patients supported by axial-flow LVADs. METHODS: Data were analyzed from 537 patients enrolled in the HeartMate II (HM II; Thoratec/St. Jude) destination therapy clinical trial. LRHF was defined as the development of clinical RHF accompanied by the need for inotropic support occurring more than 30 days after discharge from the index LVAD implant hospitalization. Clinical variables, quality of life, rehospitalizations, and survival were compared between patients with and without LRHF. RESULTS: LRHF developed in 41 patients (8%), with a median time to LRHF of 480 days. A higher preoperative blood urea nitrogen and increased central venous pressure-to-pulmonary capillary wedge pressure ratio were independent predictors of LRHF. The Michigan and HMII RHF risk scores were both associated with an increased likelihood of LRHF (p < 0.05). Patients with LRHF had worse quality of life according to the Kansas City Cardiomyopathy Questionnaire (61 ± 26 vs 70 ± 21; p < 0.05), poorer functional capacity by 6-minute walk distance (275 ± 189 m vs 312 ± 216 m; p < 0.05), and more rehospitalizations (6 vs 3; p < 0.001). LRHF was associated with decreased survival (p < 0.001). CONCLUSIONS: LRHF is an important complication in patients with LVADs and is associated with worse quality of life, reduced functional capacity, more frequent hospitalizations, and worse survival compared with those without LRHF

    Early intervention for lactate dehydrogenase elevation improves clinical outcomes in patients with the HeartMate II left ventricular assist device: Insights from the PREVENT study

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    BACKGROUND: Hemolysis, assessed by elevated serum lactate dehydrogenase (LDH), is strongly associated with HeartMate II pump thrombosis (PT). However, it is unknown whether early intervention for elevated LDH circumvents the risk of serious PT requiring pump exchange. We sought to evaluate the relationship between elevated LDH and clinical outcomes, the effectiveness of early medical intervention, and risk factors for elevated LDH. METHODS: We studied 268 patients in the prospective, multicenter PREVENT study who had 2 or more LDH measurements at ≥30 days post-implant. Elevated LDH was defined as LDH ≥2.5× upper limit of normal (ULN) for 2 consecutive measurements. RESULTS: Fourteen percent of patients had elevated LDH. Stroke-free survival at 6 months was lower in patients with elevated LDH vs patients with normal LDH (83 ± 6% vs 93 ± 2%, p = 0.035). Elevated LDH resolved without intervention in 19% of patients, with intensified medical therapy in 43% and required surgical intervention in 38%. For patients receiving only medical therapy, survival was 94 ± 6% at 6 months post-treatment. In this subgroup, resolution of symptoms with intensified medical therapy was sustained in 15 of 16 patients, with PT occurring in 1 patient at 171 days after initial treatment for elevated LDH (202 days post-implant). Early medical intervention at moderately elevated LDH (2.5× to 3.2× ULN), as compared with higher levels (>3.2× ULN), led to more sustained resolution of symptoms without subsequent PT or need for surgical intervention (91% vs 26% at 6 months post-treatment, p = 0.002). CONCLUSIONS: Early medical intervention can successfully resolve moderate LDH elevations (2.5× to 3.2× ULN) with a low incidence of death or PT at 6 months post-treatment

    A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease

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    Deferasirox is a once-daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open-label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change in liver iron concentration (LIC) using biosusceptometry, was a secondary objective. A total of 195 adult and paediatric patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events most commonly associated with deferasirox were mild, including transient nausea, vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies with deferasirox were occasionally associated with mild non-progressive increases in serum creatinine and reversible elevations in liver function tests. Discontinuation rates from deferasirox (11·4%) and deferoxamine (11·1%) were similar. Over 1 year, similar dose-dependent LIC reductions were observed with deferasirox and deferoxamine. Once-daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease
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