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51.
David A. Drew Hocine Tighiouart Tammy Scott Amy Kantor Li Fan Carlo Artusi Mario Plebani Daniel E. Weiner Mark J. Sarnak 《Clinical journal of the American Society of Nephrology》2014,9(8):1426-1433
Background and objectives
Levels of asymmetric dimethylarginine, an inhibitor of nitric oxide synthase, are elevated in kidney disease and associated with mortality in white European hemodialysis populations. Nitric oxide production and degradation are partially genetically determined and differ by racial background. No studies have measured asymmetric dimethylarginine in African Americans on dialysis and assessed whether differences exist in its association with mortality by race.Design, setting, participants, & measurements
Asymmetric dimethylarginine was measured in 259 patients on maintenance hemodialysis assembled from 2004 to 2012 in Boston area outpatient centers. Cox proportional hazards models were used to determine the association between asymmetric dimethylarginine and all-cause mortality, and an interaction with race was tested.Results
Mean (SD) age was 63 (17) years, 46% were women, and 22% were African American. Mean asymmetric dimethylarginine in non–African Americans was 0.79 µmol/L (0.16) versus 0.70 µmol/L (0.11) in African Americans (P<0.001); 130 patients died over a median follow-up of 2.3 years. African Americans had lower mortality risk than non–African Americans (hazard ratio, 0.27; 95% confidence interval, 0.15 to 0.50) that was robust to adjustment for age, comorbidity, and asymmetric dimethylarginine (hazard ratio, 0.35; 95% confidence interval, 0.17 to 0.69). An interaction was noted between race and asymmetric dimethylarginine (P=0.03), such that asymmetric dimethylarginine was associated with higher mortality in non–African Americans (adjusted hazard ratio, 1.29; 95% confidence interval, 1.06 to 1.57 per 1 SD higher asymmetric dimethylarginine) but not in African Americans (adjusted hazard ratio, 0.57; 95% confidence interval, 0.28 to 1.18). Additional adjustment for fibroblast growth factor 23 partially attenuated the association for non–African Americans (adjusted hazard ratio, 1.22; 95% confidence interval, 0.98 to 1.50).Conclusions
African Americans have lower asymmetric dimethylarginine levels and lower hazard for mortality compared with non–African Americans. Levels of asymmetric dimethylarginine did not explain lower hazard for mortality in non–African American patients. High asymmetric dimethylarginine was a risk factor for mortality exclusively in non–African Americans. Mechanisms explaining these relationships need to be evaluated. 相似文献52.
53.
Tammy T. Nguyen Sang S. Oh David Weaver Agnieszka Lewandowska Dane Maxfield Max-Hinderk Schuler Nathan K. Smith Jane Macfarlane Gerald Saunders Cheryl A. Palmer Valentina Debattisti Takumi Koshiba Stefan Pulst Eva L. Feldman Gy?rgy Hajnóczky Janet M. Shaw 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(35):E3631-E3640
Defective mitochondrial distribution in neurons is proposed to cause ATP depletion and calcium-buffering deficiencies that compromise cell function. However, it is unclear whether aberrant mitochondrial motility and distribution alone are sufficient to cause neurological disease. Calcium-binding mitochondrial Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and retrograde transport in neurons. Using two new KO mouse models, we demonstrate that Miro1 is essential for development of cranial motor nuclei required for respiratory control and maintenance of upper motor neurons required for ambulation. Neuron-specific loss of Miro1 causes depletion of mitochondria from corticospinal tract axons and progressive neurological deficits mirroring human upper motor neuron disease. Although Miro1-deficient neurons exhibit defects in retrograde axonal mitochondrial transport, mitochondrial respiratory function continues. Moreover, Miro1 is not essential for calcium-mediated inhibition of mitochondrial movement or mitochondrial calcium buffering. Our findings indicate that defects in mitochondrial motility and distribution are sufficient to cause neurological disease.Motor neuron diseases (MNDs), including ALS and spastic paraplegia (SP), are characterized by the progressive, length-dependent degeneration of motor neurons, leading to muscle atrophy, paralysis, and, in some cases, premature death. There are both inherited and sporadic forms of MNDs, which can affect upper motor neurons, lower motor neurons, or both. Although the molecular and cellular causes of most MNDs are unknown, many are associated with defects in axonal transport of cellular components required for neuron function and maintenance (1–6).A subset of MNDs is associated with impaired mitochondrial respiration and mitochondrial distribution. This observation has led to the hypothesis that neurodegeneration results from defects in mitochondrial motility and distribution, which, in turn, cause subcellular ATP depletion and interfere with mitochondrial calcium ([Ca2+]m) buffering at sites of high synaptic activity (reviewed in ref. 7). It is not known, however, whether mitochondrial motility defects are a primary cause or a secondary consequence of MND progression. In addition, it has been difficult to isolate the primary effect of mitochondrial motility defects in MNDs because most mutations that impair mitochondrial motility in neurons also affect transport of other organelles and vesicles (1, 8–11).In mammals, the movement of neuronal mitochondria between the cell body and the synapse is controlled by adaptors called trafficking kinesin proteins (Trak1 and Trak2) and molecular motors (kinesin heavy chain and dynein), which transport the organelle in the anterograde or retrograde direction along axonal microtubule tracks (7, 12–24). Mitochondrial Rho (Miro) GTPase proteins are critical for transport because they are the only known surface receptors that attach mitochondria to these adaptors and motors (12–15, 18, 25, 26). Miro proteins are tail-anchored in the outer mitochondrial membrane with two GTPase domains and two predicted calcium-binding embryonic fibroblast (EF) hand motifs facing the cytoplasm (12, 13, 25, 27, 28). A recent Miro structure revealed two additional EF hands that were not predicted from the primary sequence (29). Studies in cultured cells suggest that Miro proteins also function as calcium sensors (via their EF hands) to regulate kinesin-mediated mitochondrial “stopping” in axons (15, 16, 26). Miro-mediated movement appears to be inhibited when cytoplasmic calcium is elevated in active synapses, effectively recruiting mitochondria to regions where calcium buffering and energy are needed. Despite this progress, the physiological relevance of these findings has not yet been tested in a mammalian animal model. In addition, mammals ubiquitously express two Miro orthologs, Miro1 and Miro2, which are 60% identical (12, 13). However, the individual roles of Miro1 and Miro2 in neuronal development, maintenance, and survival have no been evaluated.We describe two new mouse models that establish the importance of Miro1-mediated mitochondrial motility and distribution in mammalian neuronal function and maintenance. We show that Miro1 is essential for development/maintenance of specific cranial neurons, function of postmitotic motor neurons, and retrograde mitochondrial motility in axons. Loss of Miro1-directed retrograde mitochondrial transport is sufficient to cause MND phenotypes in mice without abrogating mitochondrial respiratory function. Furthermore, Miro1 is not essential for calcium-mediated inhibition of mitochondrial movement or [Ca2+]m buffering. These findings have an impact on current models for Miro1 function and introduce a specific and rapidly progressing mouse model for MND. 相似文献
54.
Paolo Spirito Camillo Autore Francesco Formisano Gabriele Egidy Assenza Elena Biagini Tammy S. Haas Sergio Bongioanni Christopher Semsarian Emmanuela Devoto Beatrice Musumeci Francesco Lai Laura Yeates Maria Rosa Conte Claudio Rapezzi Luca Boni Barry J. Maron 《The American journal of cardiology》2014
55.
Elena Biagini Iacopo Olivotto Maria Iascone Maria I. Parodi Francesca Girolami Giulia Frisso Camillo Autore Giuseppe Limongelli Massimiliano Cecconi Barry J. Maron Martin S. Maron Stefania Rosmini Francesco Formisano Beatrice Musumeci Franco Cecchi Attilio Iacovoni Tammy S. Haas Maria L. Bacchi Reggiani Paolo Ferrazzi Francesco Salvatore Paolo Spirito Claudio Rapezzi 《The American journal of cardiology》2014
56.
Joel L. Pederson Melissa S. Chapot Steven R. Simms Reza Sohbati Tammy M. Rittenour Andrew S. Murray Gary Cox 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(36):12986-12991
Rock art compels interest from both researchers and a broader public, inspiring many
hypotheses about its cultural origin and meaning, but it is notoriously difficult to
date numerically. Barrier Canyon-style (BCS) pictographs of the Colorado Plateau are
among the most debated examples; hypotheses about its age span the entire Holocene
epoch and previous attempts at direct radiocarbon dating have failed. We provide
multiple age constraints through the use of cross-cutting relations and new and
broadly applicable approaches in optically stimulated luminescence dating at the
Great Gallery panel, the type section of BCS art in Canyonlands National Park,
southeastern Utah. Alluvial chronostratigraphy constrains the burial and exhumation
of the alcove containing the panel, and limits are also set by our related research
dating both a rockfall that removed some figures and the rock’s exposure
duration before that time. Results provide a maximum possible age, a minimum age, and
an exposure time window for the creation of the Great Gallery panel, respectively.
The only prior hypothesis not disproven is a late Archaic origin for BCS rock art,
although our age result of A.D. ∼1–1100 coincides better with the
transition to and rise of the subsequent Fremont culture. This chronology is for the
type locality only, and variability in the age of other sites is likely.
Nevertheless, results suggest that BCS rock art represents an artistic tradition that
spanned cultures and the transition from foraging to farming in the region.Archaeology is focused upon material records, contextualized in
time. Rock art is a record with the potential to provide unique insight into the dynamics
and evolution of culture, but it generally lacks stratigraphic or chronologic context.
Interpretation of the origin and meaning of rock art is indirect at best, or simply
speculative. In the case of some pictographs, pigments may include or have enough accessory
carbon for accelerator mass spectrometry (AMS) radiocarbon dating (1–4). In other special situations, such as
caves, minimum age constraints have been obtained by various techniques of dating material
that overlies or entombs rock art (5–7). However,
most rock art remains undatable and researchers rely upon stylistic comparison and indirect
associations with artifacts at nearby sites (8, 9). The case in point for this study is arguably the
most compelling and debated rock art in the United States—the Barrier Canyon style
(BCS) of the Colorado Plateau. Previous attempts to derive an absolute chronology have
failed and its age remains unknown, with widely ranging hypotheses that have remained
untested until now.The continued development of dating techniques offers new possibilities for hypothesis
testing. The optically stimulated luminescence (OSL) signals from mineral grains make it
possible to date the deposition of most sediment that is exposed to a few seconds of full
sunlight before burial, and its use in the earth and cultural sciences has greatly
increased (10, 11). Among the latest applications of OSL are techniques dating the outer
surfaces of rock clasts that have become shielded from light, including those with
archaeological context (12–15). Recent work has furthermore used the “bleaching” profile of
decreasing luminescence signal toward the surface of rock to estimate exposure time to
sunlight (16, 17). Using these dating tools, we can constrain the age of rock art and gain new
insight into past cultures and landscapes.Here, we synthesize results from three approaches to dating the type section of BCS art,
the Great Gallery in Canyonlands National Park of southeastern Utah. Through dating the
full alluvial stratigraphy and a rockfall event that both have incontrovertible
cross-cutting relations with the rock art, and then by determining the exposure duration of
a painted rock surface, we greatly narrow the window of time when the rock art was created.
These approaches do not require direct sampling of rock art and have strong potential for
application to other archaeological and surface processes research. Although our results
are only for the type section of BCS art, and chronological variability should be expected
for the style across the region, they suggest that BCS art coincides with the transition to
agriculture in the northern Colorado Plateau and may not have been limited to a specific
archaeological culture. 相似文献
57.
Systemic lupus erythematosus (SLE) is a chronic, relapsing autoimmune connective tissue disease, primarily affecting the skin, joints, kidneys, heart, lungs, nervous system, blood elements, and serosal membranes. SLE is characterized by cytokine dysregulation, polyclonal B-cell activation, autoantibody production, and increased immune complex formation due to aberrations involving hyperactive B cells, T cells, and cells of the monocytic lineage. The symptoms of SLE are often diverse and nonspecific, and timely identification of SLE and associated comorbidities in patients is critical as aggressive monitoring and therapy may be warranted, especially in patients with poor prognoses. Based on the up-to-date understanding of the pathophysiology of SLE, the first targeted biological agent belimumab has been approved by the US Food and Drug Administration (FDA) in more than 50 years, and many targeted agents are being evaluated in late-stage clinical trials. There is a clear need to discuss how and when to incorporate new and emerging biological agents in managing patients with SLE. Additionally, the potential for increased risk of infections is a factor that heavily influences the rheumatologist?s decision to use biological agents in managing patients with SLE. Hence, in this roundtable educational activity, expert faculty will review and discuss the strategies for timely diagnosis of SLE and associated comorbidities. They will also discuss the current understanding of the pathophysiology of SLE and how new and emerging biological agents help address the underlying pathophysiological aberrations in patients with SLE. The faculty will also review strategies to minimize the risk of infections and other toxicities in patients with SLE. 相似文献
58.
Dean S. Picone Raj Padwal Norm R. C. Campbell Pierre Boutouyrie Tammy M. Brady Michael Hecht Olsen Christian Delles Cintia Lombardi Azra Mahmud Yaxing Meng Gontse G. Mokwatsi Pedro Ordunez Hoang T. Phan Giacomo Pucci Aletta E. Schutte KiChul Sung XinHua Zhang James E. Sharman for the Accuracy in Measurement of Blood Pressure Collaborative 《Journal of clinical hypertension (Greenwich, Conn.)》2020,22(12):2167
Hypertension guidelines recommend that blood pressure (BP) should be measured using a monitor that has passed validation testing for accuracy. BP monitors that have not undergone rigorous validation testing can still be cleared by regulatory authorities for marketing and sale. This is the situation for most BP monitors worldwide. Thus, consumers (patients, health professionals, procurement officers, and general public) may unwittingly purchase BP monitors that are non‐validated and more likely to be inaccurate. Without prior knowledge of these issues, it is extremely difficult for consumers to distinguish validated from non‐validated BP monitors. For the above reasons, the aim of this paper is to provide consumers guidance on how to check whether a BP monitor has been properly validated for accuracy. The process involves making an online search of listings of BP monitors that have been assessed for validation status. Only those monitors that have been properly validated are recommended for BP measurement. There are numerous different online listings of BP monitors, several are country‐specific and two are general (international) listings. Because monitors can be marketed using alternative model names in different countries, if a monitor is not found on one listing, it may be worthwhile cross‐checking with a different listing. This information is widely relevant to anyone seeking to purchase a home, clinic, or ambulatory BP monitor, including individual consumers for use personally or policy makers and those procuring monitors for use in healthcare systems, and retailers looking to stock only validated BP monitors. 相似文献
59.
60.
Michelle Berresheim Jodi Wilkie Kara A. Nerenberg Quazi Ibrahim Tammy J. Bungard 《Thrombosis research》2014