Ετικέτες

Δευτέρα 14 Μαΐου 2018

Technological behaviour in the early Acheulean of EF-HR (Olduvai Gorge, Tanzania)

S00472484.gif

Publication date: Available online 27 April 2018
Source:Journal of Human Evolution
Author(s): Ignacio de la Torre, Rafael Mora
Technological strategies of early humans are discussed in the light of a recently excavated stone tool assemblage from EF-HR, an archaeological site older than 1.33 Ma at Olduvai Gorge, Tanzania. Renewed fieldwork at EF-HR has unearthed a lithic collection containing over 2300 artefacts (including a hundred handaxes in stratigraphic position), which represents one of the largest assemblages for the early Acheulean in East Africa. Our technological study shows co-occurrence of two distinctive reduction sequences in the same assemblage, one aimed at obtaining small flakes and the other focused on the production of large, thick, heavy flakes that were then used as blanks for handaxe shaping. Flaking of small cores is expedient and low intensity, and knapping methods are similar to those observed in earlier Oldowan assemblages. Large Cutting Tools (LCTs) show no evidence of planform and biconvex symmetry, and shaping sequences are brief and discontinuous, indicating short use-lives for handaxes. Bifaces are rare and atypical. Recurrent morphotypes are knives, which are poorly-shaped, scraper-like, large-sized handaxes. Despite the apparent expediency of EF-HR handaxe production, a closer inspection of the interplay between debitage and façonnage stages reveals remarkably standardized procedural patterns. Large Cutting Tool blanks were produced following fixed knapping rules resulting in flakes with a specific morphology and mass distribution. Adapted to the idiosyncrasies of each blank, shaping was almost invariably imposed over the same areas in all LCTs and sought to produce morphotypes that, technologically, are remarkably identical to each other. This strongly supports the existence of mental templates and technical rules that were systematically practiced in LCT production at EF-HR, and underscore the structured nature of technological behaviour at the onset of the Acheulean in East Africa.



https://ift.tt/2wKkUwQ

Editorial Board

elsevier-non-solus.png

Publication date: June 2018
Source:Journal of Human Evolution, Volume 119





https://ift.tt/2GfYLWs

Frank Brown (1943–2017)

elsevier-non-solus.png

Publication date: June 2018
Source:Journal of Human Evolution, Volume 119
Author(s): Craig S. Feibel, Bernard Wood




https://ift.tt/2rFfoXq

Patterns of lateral enamel growth in Homo naledi as assessed through perikymata distribution and number

S00472484.gif

Publication date: Available online 27 April 2018
Source:Journal of Human Evolution
Author(s): Debbie Guatelli-Steinberg, Mackie C. O'Hara, Adeline Le Cabec, Lucas K. Delezene, Donald J. Reid, Matthew M. Skinner, Lee R. Berger
Perikymata, incremental growth lines visible on tooth enamel surfaces, differ in their distribution and number among hominin species, although with overlapping patterns. This study asks: (1) How does the distribution of perikymata along the lateral enamel surface of Homo naledi anterior teeth compare to that of other hominins? (2) When both perikymata distribution and number are analyzed together, how distinct is H. naledi from other hominins? A total of 19 permanent anterior teeth (incisors and canines) of H. naledi were compared, by tooth type, to permanent anterior teeth of other hominins: Australopithecus afarensis, Australopithecus africanus, Paranthropus robustus, Paranthropus boisei, Homo ergaster/Homo erectus, other early Homo, Neandertals, and modern humans, with varying sample sizes. Repeated measures analyses of the percentage of perikymata per decile of reconstructed crown height yielded several statistically significant differences between H. naledi and other hominins. Canonical variates analysis of percentage of perikymata in the cervical half of the crown together with perikymata number revealed that, in 8 of 19 cases, H. naledi teeth were significantly unlikely to be classified as other hominins, while exhibiting least difference from modern humans (especially southern Africans). In a cross-validated analysis, 68% of the H. naledi teeth were classified as such, while 32% were classified as modern human (most often southern African). Of 313 comparative teeth use for this analysis, only 1.9% were classified as H. naledi. What tends to differentiate H. naledi anterior tooth crowns from those of most other hominins, including some modern humans, is strongly skewed perikymata distributions combined with perikymata numbers that fall in the middle to lower ranges of hominin values. H. naledi therefore tends toward a particular combination of these features that is less often seen in other hominins. Implications of these data for the growth and development of H. naledi anterior teeth are considered.



https://ift.tt/2GeWLht

Mesopithecus pentelicus from the Turolian locality of Kryopigi (Kassandra, Chalkidiki, Greece)

S00472484.gif

Publication date: Available online 10 May 2018
Source:Journal of Human Evolution
Author(s): Georgios Lazaridis, Evangelia Tsoukala, Todd C. Rae, Asier Gómez-Olivencia, Doris Nagel, Antonis Bartsiokas
New material of the Mio-Pliocene colobine Mesopithecus from the Turolian locality of Kryopigi (Greece) is described here. It includes a complete skull with the atlas attached and other dental and postcranial elements representing at least five individuals (four males and one female). The material is compared with Mesopithecus delsoni, Mesopithecus pentelicus, Mesopithecus monspessulanus and intermediate forms from more than a dozen Turolian localities of the Greco-Iranian province. These comparisons support the attribution of the Kryopigi material to M. pentelicus. The chronostratigraphic distribution of Mesopithecus species and intermediate forms suggests that the Kryopigi fauna could be dated as younger than the Perivolaki locality with M. delsoni/pentelicus (7.1–7.3 Ma, MN12) and older than the Dytiko localities with M. aff. pentelicus, M. cf. pentelicus and M. cf. monspessulanus (?middle MN13). The dimensions of the atlas are within the distribution of extant colobines. The skull shows bite-marks, probably caused by the hyaena Adcrocuta eximia.



https://ift.tt/2L16QlJ

Reevaluation of ‘endocostal ossifications’ on the Kebara 2 Neanderthal ribs

alertIcon.gif

Publication date: Available online 10 May 2018
Source:Journal of Human Evolution
Author(s): Daniel García-Martínez, Manuel Campo Martín, Armando González Martín, Óscar Cambra-Moo, Alon Barash, Markus Bastir




https://ift.tt/2GfUfre

The effect of ontogeny on estimates of KNM-WT 15000's adult body size

S00472484.gif

Publication date: Available online 10 May 2018
Source:Journal of Human Evolution
Author(s): Deborah L. Cunningham, Ronda R. Graves, Daniel J. Wescott, Robert C. McCarthy
The Homo erectus specimen KNM-WT 15000 has played a critical role in our understanding of body size evolution. New interpretations suggest that KNM-WT 15000 had a younger age-at-death and a more rapid ontogenetic trajectory than previously suggested. Recent fossil discoveries and new interpretations suggest a wide range of body size and shape variation in H. erectus. Based on these new insights, we argue that KNM-WT 15000's adult stature and body mass could have been much smaller than has been traditionally presented in the literature. Using chimpanzee and modern human growth trajectories, we bracketed the range of possibilities for KNM-WT 15000's adult body size between 160.0 and 177.7 cm (5′3″–5′10″) for stature and 60.0 and 82.7 kg (132–182 lbs.) for body mass. These estimates put KNM-WT 15000 near the mean rather than among the largest known H. erectus specimens.



https://ift.tt/2L15jMg

A new tephrochronology for early diverse stone tool technologies and long-distance raw material transport in the Middle to Late Pleistocene Kapthurin Formation, East Africa

S00472484.gif

Publication date: Available online 10 May 2018
Source:Journal of Human Evolution
Author(s): Nick Blegen, Brian R. Jicha, Sally McBrearty
The Middle to Late Pleistocene (780–10 ka) of East Africa records evidence of significant behavioral change, early fossils of Homo sapiens, and the dispersals of our species across and out of Africa. Studying human evolution in this time period thus requires an extensive and precise chronology relating behavioral evidence from archaeological sequences to aspects of hominin biology and evidence of past environments from fossils and geological sequences. Tephrochronology provides the chronostratigraphic resolution to achieve this through correlation and dating of volcanic ashes. The tephrochronology of the Kapthurin Formation presented here, based on tephra correlations and 40Ar/39Ar dates, provides new ages between 395.6 ± 3.5 ka and 465.3 ± 1.0 ka for nine sites showing diverse blade and Levallois methods of core reduction. These are >110 kyr older than previously known in East Africa. New 40Ar/39Ar dates provide a refined age of 222.5 ± 0.6 ka for early evidence of long-distance (166 km) obsidian transport at the Sibilo School Road Site. A tephra correlation between the Baringo and Victoria basins also provides a new date of ∼100 ka for the Middle Stone Age site of Keraswanin. By providing new and older dates for 11 sites containing several important aspects of hominin behavior and extending the chronology of the Kapthurin Formation forward by ∼130,000 years, the tephrochronology presented here contributes one of the longest and most refined chronostratigraphic frameworks of Middle through Late Pleistocene East Africa. This tephrochronology thus provides the foundation to understand the process of modern human behavioral evolution as it relates to biological and paleoenvironmental circumstances.



https://ift.tt/2Ggzzzd

From the Oldowan to the Acheulean at Olduvai Gorge, Tanzania – An introduction to the special issue

alertIcon.gif

Publication date: Available online 10 May 2018
Source:Journal of Human Evolution
Author(s): Ignacio de la Torre, Lindsay McHenry, Jackson Njau




https://ift.tt/2L3mjSe

Was the last common ancestor aping a chimp or just monkeying around?

alertIcon.gif

Publication date: Available online 9 May 2018
Source:Journal of Human Evolution
Author(s): Scott A. Williams




https://ift.tt/2GfYxP6

Human-like hip joint loading in Australopithecus africanus and Paranthropus robustus

S00472484.gif

Publication date: Available online 27 April 2018
Source:Journal of Human Evolution
Author(s): Timothy M. Ryan, Kristian J. Carlson, Adam D. Gordon, Nina Jablonski, Colin N. Shaw, Jay T. Stock
Adaptations indicative of habitual bipedalism are present in the earliest recognized hominins. However, debate persists about various aspects of bipedal locomotor behavior in fossil hominins, including the nature of gait kinematics, locomotor variability across different species, and the degree to which various australopith species engaged in arboreal behaviors. In this study, we analyze variation in trabecular bone structure of the femoral head using a sample of modern humans, extant non-human hominoids, baboons, and fossil hominins attributed to Australopithecus africanus, Paranthropus robustus, and the genus Homo. We use μCT data to characterize the fabric anisotropy, material orientation, and bone volume fraction of trabecular bone to reconstruct hip joint loading conditions in these fossil hominins. Femoral head trabecular bone fabric structure in australopiths is more similar to that of modern humans and Pleistocene Homo than extant apes, indicating that these australopith individuals walked with human-like hip kinematics, including a more limited range of habitual hip joint postures (e.g., a more extended hip) during bipedalism. Our results also indicate that australopiths have robust femoral head trabecular bone, suggesting overall increased loading of the musculoskeletal system comparable to that imposed by extant apes. These results provide new evidence of human-like bipedal locomotion in Pliocene hominins, even while other aspects of their musculoskeletal systems retain ape-like characteristics.



https://ift.tt/2rITFxy

A biplanar X-ray approach for studying the 3D dynamics of human track formation

S00472484.gif

Publication date: Available online 9 May 2018
Source:Journal of Human Evolution
Author(s): Kevin G. Hatala, David A. Perry, Stephen M. Gatesy
Recent discoveries have made hominin tracks an increasingly prevalent component of the human fossil record, and these data have the capacity to inform long-standing debates regarding the biomechanics of hominin locomotion. However, there is currently no consensus on how to decipher biomechanical variables from hominin tracks. These debates can be linked to our generally limited understanding of the complex interactions between anatomy, motion, and substrate that give rise to track morphology. These interactions are difficult to study because direct visualization of the track formation process is impeded by foot and substrate opacity. To address these obstacles, we developed biplanar X-ray and computer animation methods, derived from X-ray Reconstruction of Moving Morphology (XROMM), to analyze the 3D dynamics of three human subjects' feet as they walked across four substrates (three deformable muds and rigid composite panel). By imaging and reconstructing 3D positions of external markers, we quantified the 3D dynamics at the foot-substrate interface. Foot shape, specifically heel and medial longitudinal arch deformation, was significantly affected by substrate rigidity. In deformable muds, we found that depths measured across tracks did not directly reflect the motions of the corresponding regions of the foot, and that track outlines were not perfectly representative of foot size. These results highlight the complex, dynamic nature of track formation, and the experimental methods presented here offer a promising avenue for developing and refining methods for accurately inferring foot anatomy and gait biomechanics from fossil hominin tracks.



https://ift.tt/2GfY1AE

New hominin postcranial remains from locality OMO 323, Shungura Formation, Lower Omo Valley, southwestern Ethiopia

alertIcon.gif

Publication date: Available online 27 April 2018
Source:Journal of Human Evolution
Author(s): Guillaume Daver, Gilles Berillon, Caroline Jacquier, Yann Ardagna, Meklit Yadeta, Tiphaine Maurin, Antoine Souron, Cécile Blondel, Yves Coppens, Jean-Renaud Boisserie




https://ift.tt/2rITouw

Large mammal diets and paleoecology across the Oldowan–Acheulean transition at Olduvai Gorge, Tanzania from stable isotope and tooth wear analyses

S00472484.gif

Publication date: Available online 8 May 2018
Source:Journal of Human Evolution
Author(s): Kevin T. Uno, Florent Rivals, Faysal Bibi, Michael Pante, Jackson Njau, Ignacio de la Torre
The well-dated Pleistocene sediments at Olduvai Gorge have yielded a rich record of hominin fossils, stone tools, and vertebrate faunal remains that, taken together, provide insight to hominin behavior and paleoecology. Since 2008, the Olduvai Geochronology and Archaeology Project (OGAP) has undertaken extensive excavations in Bed II that have yielded a large collection of early Pleistocene stone tools and fossils. The strata of Lower, Middle and Upper Bed II at Olduvai Gorge capture the critical transition from Oldowan to Acheulean technology and therefore provide an opportunity to explore the possible role of biotic and abiotic change during the transition. Here, we analyze newly discovered and existing fossil teeth from Bed II sites using stable isotope and tooth wear methods to investigate the diets of large mammals. We reconstruct the dietary ecology of Bed II mammals and evaluate whether vegetation or hydroclimate shifts are associated with the technological change. Combined isotope and tooth wear data suggest most mammals were C4 grazers or mixed feeders. Carbon isotope data from bulk enamel samples indicate that a large majority of Bed II large mammals analyzed had diets comprising mostly C4 vegetation (>75% of diet), whereas only a small number of individuals had either mixed C3–C4 or mostly C3 diets (<25% C4). Mesowear generally indicates an increase of the abrasiveness of the diet between intervals IIA and IIB (∼1.66 Ma), probably reflecting increased grazing. Microwear indicates more abrasive diets in interval IIA suggesting stronger seasonal differences at the time of death during this interval. This is also supported by the intratooth isotope profiles from Equus oldowayensis molars, which suggest a possible decrease in seasonality across the transition. Neither stable isotope nor tooth wear analyses indicate major vegetation or hydrological change across the Oldowan–Acheulean transition.



https://ift.tt/2Gh3iYS

Reconstruction, endocranial form and taxonomic affinity of the early Homo calvaria KNM-ER 42700

S00472484.gif

Publication date: Available online 26 April 2018
Source:Journal of Human Evolution
Author(s): Simon Neubauer, Philipp Gunz, Louise Leakey, Meave Leakey, Jean-Jacques Hublin, Fred Spoor
When first described, the small calvaria KNM-ER 42700 from Ileret, Kenya, was considered a late juvenile or young adult and assigned to Homo erectus. However, this species attribution has subsequently been challenged because the specimen's neurocranial shape differs substantially from that of H. erectus adults. Here, (1) we describe the postmortem damage and deformation that could have influenced previous shape analyses, (2) present digital reconstructions based on computed tomographic scans correcting for these taphonomic defects, and (3) analyze the reconstructed endocranial shape and form, considering both static allometry among adults and ontogenetic allometry. To this end, we use geometric morphometrics to analyze the shape of digital endocasts based on landmarks and semilandmarks. Corroborating previous studies of the external surface, we find that the endocranial shape of KNM-ER 42700 falls outside the known adult variation of H. erectus. With an endocranial volume estimate between 721 and 744 ml, size cannot explain its atypical endocranial shape when static allometry within H. erectus is considered. However, the analysis of ontogenetic allometry suggests that it may be a H. erectus individual that is younger than previously thought and had not yet reached adult endocranial shape. Future work should therefore comprehensively review all cranial indicators of its developmental age, including closure of the spheno-occipital synchondrosis. An alternative hypothesis is that KNM-ER 42700 represents an as yet unidentified species of early Homo. Importantly, KNM-ER 42700 should not be included in the adult hypodigm of H. erectus.



https://ift.tt/2KYpU3M

Is there a Developed Oldowan A at Olduvai Gorge? A diachronic analysis of the Oldowan in Bed I and Lower-Middle Bed II at Olduvai Gorge, Tanzania

S00472484.gif

Publication date: Available online 8 May 2018
Source:Journal of Human Evolution
Author(s): Tomos Proffitt
Debates regarding the validity of the Developed Oldowan as separate cultural facies within the Oldowan techno-complex have primarily concentrated on the Developed Oldowan B/Acheulean transition, with little attention paid to the validity of the Developed Oldowan A (DOA) as a valid technological differentiation. This study presents a diachronic technological analysis and comparison of Oldowan and DOA lithic assemblages from Olduvai Gorge, Tanzania, dated between 1.84 and 1.6 Ma, to test the validity of Leakey's original distinction between these two cultural facies. The results from this comparative analysis show very few technological differences between the lithic assemblages previously assigned to the DOA and Classic Oldowan. Significant diachronic variation in raw material availability and use is, however, identified between Bed I and Lower/Middle Bed II of Olduvai Gorge, which may go some way to explaining the originally perceived techno-cultural differences. The results suggest an increase in hominin knapping and percussive activities, as well as a clear ability to preferentially select high quality raw materials stratigraphically above Tuff IF. Technological innovation and complexity, however, does not seem to vary significantly between the Classic Oldowan and DOA assemblages. The results of this analysis along with similar studies from the wider eastern African region lead to the conclusion that the term Developed Oldowan A should no longer be used.



https://ift.tt/2GfXheQ

The costs of living at the edge: Seasonal stress in wild savanna-dwelling chimpanzees

Publication date: Available online 21 April 2018
Source:Journal of Human Evolution
Author(s): Erin G. Wessling, Hjalmar S. Kühl, Roger Mundry, Tobias Deschner, Jill D. Pruetz
Adaptations associated with shifting from a predominately forested habitat to a more open environment are considered a crucial step in hominin evolution. Understanding how chimpanzees, one of our closest-living relatives, are exposed to the selection pressures associated with living in a relatively sparse, hot, and dry environment can inform us about the relative importance of potential environmental stressors involved in adaptations to drier environments. We investigated the extent to which chimpanzees living in an extreme savanna habitat experience seasonal variability in either energy balance or thermoregulation (dehydration and heat exposure), as well as whether these potential environmental constraints are taxing to chimpanzee individuals. Specifically, we tested the hypothesis that savanna environments impose seasonally-relevant costs to chimpanzees. To this end, we collected 368 urine samples from one community of chimpanzees at Fongoli, Senegal, and measured c-peptide, creatinine, and cortisol as measures of physiological responses to environmental food, water, and heat constraints, respectively. We then evaluated the influence of climatic and phenological factors on these indicators. Results illustrated significant seasonal variation in all biomarkers, which corresponded to relevant ecological correlates. Furthermore, creatinine but not c-peptide correlated with cortisol levels, suggesting that chimpanzees in this environment endure periods of heat and dehydration stress, but are able to avoid stressful levels of negative energy balance. Using savanna chimpanzees as a referential model, our research lends support to the notion that thermoregulatory challenges were a significant factor in hominin evolution, and suggests these challenges may have overshadowed the challenges of maintaining adequate energetic balance during the expansion of the hominin range from wetter to drier environments.



https://ift.tt/2KZWRgl

Mandibular ramus shape variation and ontogeny in Homo sapiens and Homo neanderthalensis

S00472484.gif

Publication date: Available online 30 April 2018
Source:Journal of Human Evolution
Author(s): Claire E. Terhune, Terrence B. Ritzman, Chris A. Robinson
As the interface between the mandible and cranium, the mandibular ramus is functionally significant and its morphology has been suggested to be informative for taxonomic and phylogenetic analyses. In primates, and particularly in great apes and humans, ramus morphology is highly variable, especially in the shape of the coronoid process and the relationship of the ramus to the alveolar margin. Here we compare ramus shape variation through ontogeny in Homo neanderthalensis to that of modern and fossil Homo sapiens using geometric morphometric analyses of two-dimensional semilandmarks and univariate measurements of ramus angulation and relative coronoid and condyle height. Results suggest that ramus, especially coronoid, morphology varies within and among subadult and adult modern human populations, with the Alaskan Inuit being particularly distinct. We also identify significant differences in overall anterosuperior ramus and coronoid shapes between H. sapiens and H. neanderthalensis, both in adults and throughout ontogeny. These shape differences are subtle, however, and we therefore suggest caution when using ramus morphology to diagnose group membership for individual specimens of these taxa. Furthermore, we argue that these morphologies are unlikely to be representative of differences in masticatory biomechanics and/or paramasticatory behaviors between Neanderthals and modern humans, as has been suggested by previous authors. Assessments of ontogenetic patterns of shape change reveal that the typical Neanderthal ramus morphology is established early in ontogeny, and there is little evidence for divergent postnatal ontogenetic allometric trajectories between Neanderthals and modern humans as a whole. This analysis informs our understanding of intraspecific patterns of mandibular shape variation and ontogeny in H. sapiens and can shed further light on overall developmental and life history differences between H. sapiens and H. neanderthalensis.



https://ift.tt/2rIU8ji

An anti-NMDA receptor encephalitis mimicking an HIV encephalitis

S15216616.gif

Publication date: Available online 14 May 2018
Source:Clinical Immunology
Author(s): Fatiha Haneche, Sophie Demeret, Dimitri Psimaras, Christine Katlama, Valérie Pourcher
The incidence of HIV associated neurocognitive disorders (HAND) were reduced with the use of antiretroviral therapy. In case of neuropsychiatric symptoms, after elimination of all infections, auto-immune encephalitis could be evocated as a differential diagnosis. We describe a case of anti-N-Methyl-d-Aspartate receptor encephalitis in an HIV-1 infected woman.



https://ift.tt/2IiD2iI

Aortic Stenosis: Then and Now.

Author: Braunwald, Eugene MD
Page: 2099-2100


https://ift.tt/2wGc3MC

Natriuretic Peptide-Guided Heart Failure Therapy After the GUIDE-IT Study.

Author: Januzzi, James L. Jr.; Richards, A. Mark MD, PhD
Page: 2101-2103


https://ift.tt/2rFDPE0

Impact of Bystander Automated External Defibrillator Use on Survival and Functional Outcomes in Shockable Observed Public Cardiac Arrests.

Author: Pollack, Ross A. BS; Brown, Siobhan P. PhD; Rea, Thomas MD, MPH; Aufderheide, Tom MD; Barbic, David MD; Buick, Jason E. MSc; Christenson, Jim MD; Idris, Ahamed H. MD; Jasti, Jamie BS; Kampp, Michael BS; Kudenchuk, Peter MD; May, Susanne PhD; Muhr, Marc EMT-P; Nichol, Graham MD, MPH; Ornato, Joseph P. MD; Sopko, George MD, MPH; Vaillancourt, Christian MD, MSc; Morrison, Laurie MD, MSc; Weisfeldt, Myron MD; the ROC Investigators
Page: 2104-2113


https://ift.tt/2KpkPAm

Association Between Early Hyperoxia Exposure After Resuscitation From Cardiac Arrest and Neurological Disability: Prospective Multicenter Protocol-Directed Cohort Study.

Author: Roberts, Brian W. MD; Kilgannon, J. Hope MD; Hunter, Benton R. MD; Puskarich, Michael A. MD; Pierce, Lisa BA; Donnino, Michael MD; Leary, Marion RN, MPH, MSN; Kline, Jeffrey A. MD; Jones, Alan E. MD; Shapiro, Nathan I. MD, MPH; Abella, Benjamin S. MD, MPhil; Trzeciak, Stephen MD, MPH
Page: 2114-2124


https://ift.tt/2IezEt0

Oxygen After Cardiac Arrest: Enough Is Enough?.

Author: McKenzie, Nicole F. MPH, PG Dip (Critical Care), B Nurs, RN; Dobb, Geoffrey J. BSc, MB BS, FRCP, FRCA, FANZCA, FCICM
Page: 2125-2127


https://ift.tt/2wGHrux

Hospital Variation in Adherence Rates to Secondary Prevention Medications and the Implications on Quality.

Author: Mathews, Robin MD; Wang, William BS; Kaltenbach, Lisa A. MS; Thomas, Laine PhD; Shah, Rashmee U. MD, MS; Ali, Murtuza MD; Peterson, Eric D. MD, MPH; Wang, Tracy Y. MD, MHS, MSc
Page: 2128-2138


https://ift.tt/2IhmA6r

Accounting for Nonadherence.

Author: Spatz, Erica S. MD; MHS; Curtis, Jeptha P. MD
Page: 2139-2141


https://ift.tt/2KoH8WW

Six-Year Changes in Physical Activity and the Risk of Incident Heart Failure: ARIC Study.

Author: Florido, Roberta MD; Kwak, Lucia MS; Lazo, Mariana MD, PhD, ScM; Nambi, Vijay MD, PhD; Ahmed, Haitham M. MD, MPH; Hegde, Sheila M. MD; Gerstenblith, Gary MD; Blumenthal, Roger S. MD; Ballantyne, Christie M. MD; Selvin, Elizabeth PhD, MPH; Folsom, Aaron R. MD, MPH; Coresh, Josef MD, PhD; Ndumele, Chiadi E. MD, PhD
Page: 2142-2151


https://ift.tt/2IlKDRK

Complement Receptor C5aR1 Plays an Evolutionarily Conserved Role in Successful Cardiac Regeneration.

Author: Natarajan, Niranjana PhD; Abbas, Yamen BS; Bryant, Donald M. PhD; Gonzalez-Rosa, Juan Manuel PhD; Sharpe, Michka BS; Uygur, Aysu PhD; Cocco-Delgado, Lucas H.; Ho, Nhi Ngoc BS; Gerard, Norma P. PhD; Gerard, Craig J. MD, PhD; MacRae, Calum A. MD; Burns, Caroline E. PhD; Burns, C. Geoffrey PhD; Whited, Jessica L. PhD; Lee, Richard T. MD
Page: 2152-2165


https://ift.tt/2wDxb6g

Socioeconomic Status and Cardiovascular Outcomes: Challenges and Interventions.

Author: Schultz, William M. MD; Kelli, Heval M. MD; Lisko, John C. MD; Varghese, Tina MD; Shen, Jia MD; Sandesara, Pratik MD; Quyyumi, Arshed A. MD; Taylor, Herman A. MD; Gulati, Martha MD; Harold, John G. MD; Mieres, Jennifer H. MD; Ferdinand, Keith C. MD; Mensah, George A MD; Sperling, Laurence S. MD
Page: 2166-2178


https://ift.tt/2rF7GfY

Effect of Liraglutide on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Polyvascular Disease: Results of the LEADER Trial.

Author: Verma, Subodh MD, PhD; Bhatt, Deepak L. MD, MPH; Bain, Stephen C. MD; Buse, John B. MD, PhD; Mann, Johannes F.E. MD; Marso, Steven P. MD; Nauck, Michael A. MD; Poulter, Neil R. FMedSci; Pratley, Richard E. MD; Zinman, Bernard MD; Michelsen, Marie M. MD; Monk Fries, Tea MD, PhD; Rasmussen, Soren MSc, PhD; Leiter, Lawrence A. MD; the LEADER Publication Committee on behalf of the LEADER Trial Investigators
Page: 2179-2183


https://ift.tt/2KpkA8q

Letter by Romeo et al Regarding Article, "Immediate and Midterm Cardiac Remodeling After Surgical Pulmonary Valve Replacement in Adults With Repaired Tetralogy of Fallot: A Prospective Cardiovascular Magnetic Resonance and Clinical Study".

Author: Romeo, Jamie L.R. MSc; Bogers, Ad J.J.C. MD, PhD; Mokhles, Mostafa M. MD, PhD
Page: 2184-2185


https://ift.tt/2Iio0xp

Response by Heng et al to Letter Regarding Article, "Immediate and Midterm Cardiac Remodeling After Surgical Pulmonary Valve Replacement in Adults With Repaired Tetralogy of Fallot: A Prospective Cardiovascular Magnetic Resonance and Clinical Study".

Author: Heng, Ee Ling MBBS, BSc, PhD; Diller, Gerhard-Paul MD, PhD; Gatzoulis, Michael A. MD, PhD; Babu-Narayan, Sonya V. MBBS, BSc, PhD
Page: 2186-2187


https://ift.tt/2wGHeaJ

Letter by Adabag et al Regarding Article, "Age and Outcomes of Primary Prevention Implantable Cardioverter-Defibrillators in Patients With Nonischemic Systolic Heart Failure".

Author: Adabag, Selcuk MD, MS; Wininger, Michael PhD; Singh, Steve N. MD
Page: 2188-2189


https://ift.tt/2IinPlJ

Response by Elming et al to Letter Regarding Article, "Age and Outcomes of Primary Prevention Implantable Cardioverter-Defibrillators in Patients With Nonischemic Systolic Heart Failure".

Author: Elming, Marie Bayer MD; Signorovitch, James PhD; Kober, Lars MD, DMSc; Thune, Jens Jakob MD, PhD
Page: 2190


https://ift.tt/2wGH5nH

Letter by Koshy et al Regarding Article, "Assessment of Remote Heart Rhythm Sampling Using the AliveCor Heart Monitor to Screen for Atrial Fibrillation: The REHEARSE-AF Study".

Author: Koshy, Anoop N. MBBS; Sajeev, Jithin K. MBChB; Teh, Andrew W. MBBS, PhD
Page: 2191-2192


https://ift.tt/2rIL91y

Response by Halcox and Wareham to Letter Regarding Article, "Assessment of Remote Heart Rhythm Sampling Using the AliveCor Heart Monitor to Screen for Atrial Fibrillation: The REHEARSE-AF Study".

Author: Halcox, Julian P.J. MD; Wareham, Kathie RN
Page: 2193-2194


https://ift.tt/2wDwQk0

Letter by Koh Regarding Article, "Day-to-Day Blood Pressure Variability and Risk of Dementia in a General Japanese Elderly Population: The Hisayama Study".

Author: Koh, Kwang Kon MD, PhD
Page: 2195-2196


https://ift.tt/2IiYdF8

Evaluation and Management of Right-Sided Heart Failure: A Scientific Statement From the American Heart Association.

Author: Konstam, Marvin A. MD, Chair; Kiernan, Michael S. MD, MS, FAHA, Co-Chair; Bernstein, Daniel MD; Bozkurt, Biykem MD, PhD, FAHA; Jacob, Miriam MD; Kapur, Navin K. MD; Kociol, Robb D. MD, MS; Lewis, Eldrin F. MD, MPH, FAHA; Mehra, Mandeep R. MD; Pagani, Francis D. MD, PhD, FAHA; Raval, Amish N. MD, FAHA; Ward, Carey MD; On behalf of the American Heart Association Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; and Council on Cardiovascular Surgery and Anesthesia
Page: e578-e622


https://ift.tt/2wDwHgs

Atrial Fibrillation Burden: Moving Beyond Atrial Fibrillation as a Binary Entity: A Scientific Statement From the American Heart Association.

Author: Chen, Lin Y. MD, MS, FAHA, Chair; Chung, Mina K. MD, FAHA, Vice Chair; Allen, Larry A. MD, MHS, FAHA; Ezekowitz, Michael MBChB, DPhil, FAHA; Furie, Karen L. MD, MPH, FAHA; McCabe, Pamela PhD, RN; Noseworthy, Peter A. MD; Perez, Marco V. MD; Turakhia, Mintu P. MD, MAS; On behalf of the American Heart Association Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Quality of Care and Outcomes Research; and Stroke Council
Page: e623-e644


https://ift.tt/2rGvdga

Effects of ceftriaxone-induced intestinal dysbacteriosis on regulatory T cells validated by anaphylactic mice

S15675769.gif

Publication date: July 2018
Source:International Immunopharmacology, Volume 60
Author(s): Xia Luo, Zengfeng Pan, Shuang Luo, Qi Liu, Shaowei Huang, Guanghua Yang, Feifei Nong, Yajun Fu, Xiangliang Deng, Lian Zhou
Both probiotics and pathogens in the human gut express pathogen-associated molecular patterns (PAMPs) and die with the release of endotoxin and bacterial DNA, which can stimulate our immune system and cause immune reaction. However, it's interesting and fascinating to address why the normal intestinal flora will not generate immunological rejection like the pathogen does. By investigating the changes in cells and molecules relevant to immune tolerance in mice with ceftriaxone-induced dysbacteriosis, our study discovered that both the Evenness indexes and Shannon Wiener index of intestinal flora showed a decrease in dysbacteriosis mice. Moreover, the proportion of αβ+TCR+CD3+CD4CD8 cells, CD3+γδTCR+ cells and CD4+CD25+FoxP3+ cells in the Peyer's patches (PPs), mesenteric lymph nodes (MLNs) and spleen (SP) and the level of TGF-β1, IL-2, IL-4 and IL-10 in the serum also changed. Intestinal dysbacteriosis in an asthma murine model resulted in enhancement of immunologic response to the allergen ovalbumin (OVA), which was an agent that aggravates asthma symptoms. In summary, it is integral to maintain a certain amount or variety of intestinal microflora for regulatory T cells to act in averting hypersensitivity.



https://ift.tt/2rFAjJO

A systematic review on the frequency of BRCA promoter methylation in breast and ovarian carcinomas of BRCA germline mutation carriers: Mutually exclusive, or not?

Publication date: Available online 14 May 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Shoko Vos, Paul Joannes van Diest, Cathy Beatrice Moelans
BackgroundA considerable number of breast and ovarian carcinomas are due to underlying BRCA gene aberrations. Of these, BRCA germline mutations and BRCA promoter methylation are thought to be mutually exclusive, which could be exploited in clinical practice. However, this paradigm has not been studied extensively and systematically.ObjectiveTo systematically investigate to what extent BRCA promoter methylation has been reported in breast and ovarian carcinomas of BRCA germline mutation carriers.MethodsA comprehensive search on BRCA promoter methylation was performed in PubMed and Embase databases. Two authors independently selected studies, assessed study quality and extracted data according to PRISMA and QUADAS-2 guidelines.Results21 articles met the inclusion criteria. BRCA1 methylation was found in at least 10/276 (3,6%) breast and 2/174 (1,1%) ovarian carcinomas of BRCA germline mutation carriers, and BRCA2 methylation was found in at least 7/131 (5.3%) breast and 0/51 (0.0%) ovarian carcinomas of BRCA germline mutation carriers. Methylation frequencies varied between individual CpG sites. The selected studies showed important differences in methodology and performed in general a limited methylation and incomplete mutation analysis.ConclusionsBRCA methylation is rare in breast and ovarian carcinomas of BRCA germline mutation carriers, although the frequency of BRCA promoter methylation may be underestimated. This could have major implications for clinical practice, including referral for genetic testing and BRCAness analysis for treatment decision-making.



https://ift.tt/2wINKh2

Micropatterned biodegradable polyesters clicked with CQAASIKVAV promote cell alignment, directional migration, and neurite outgrowth

Publication date: Available online 13 May 2018
Source:Acta Biomaterialia
Author(s): Deteng Zhang, Sai Wu, Jianyong Feng, Yiyuan Duan, Dongming Xing, Changyou Gao
The interplay of microstructures and biological cues is critical to regulate the behaviors of Schwann cells (SCs) in terms of cellular spatial arrangement and directional migration as well as neurite orientation for bridging the proximal and distal stumps of the injured peripheral nervous system. In this study, stripe micropatterns having ridges/grooves of width 20/20 and 20/40 μm were fabricated on the surface of maleimide-functionalized biodegradable poly(ester carbonate) (P(LLA-MTMC)) films by the polydimethylsiloxane mold-pressing method, respectively. The laminin-derived CQAASIKVAV peptides end-capped with an –SH group were then grafted by the thiol-ene click reaction under mild conditions to obtain micropatterned and peptide-grafted films. SCs cultured on these films, especially on the 20/40-μm film, displayed faster and aligned adhesion as well as a larger number of elongated cells with a higher length-to-width (L/W) ratio along the stripe direction than those on the flat-pep film. The migration rate of SCs was significantly enhanced in parallel to the stripe direction with a large net displacement. The micropatterned and peptide-grafted films, especially the 20/40-μm film, could promote SC proliferation and nerve growth factor (NGF) secretion in a manner similar to that of the peptide-grafted planar film. Moreover, the neurites of rat pheochromocytoma 12 (PC12) cells sprouted along the ridges with a longer average length on the micropatterned and peptide-grafted films. The synergistic effect of physical patterns and biological cues was evaluated by considering the results of cell adhesion force; immunofluorescence staining of vinculin; fluorescence staining of F-actin and the nucleus; as well as gene expression of neural cadherin (NCAD), neurocan (NCAN), and myelin protein zero (P0).Statement of significanceThe interplay of microstructures and biological cues is critical to regulate the behaviors of Schwann cells (SCs) and nerve cells, and thereby the regeneration of peripheral nerve system. In this study, the combined micropatterning and CQAASIKVAV grafting endowed the modified P(LLA-MTMC) films with both contact guidance and bioactive chemical cues to enhance cell proliferation, directional alignment and migration, longer net displacement and larger NGF secretion, and stronger neurite outgrowth of SCs and PC12 cells. Hence, the integration of physical micropatterns and bioactive molecules is an effective way to obtain featured biomaterials for the regeneration of nerves and other types of tissues.

Graphical abstract

image


https://ift.tt/2GgJuoh

VideoEndocrinology™ High-Impact Videos

ve-cover.jpg

VideoEndocrinology™
The Official Journal of: American Thyroid Association

FREE ACCESS through May 28, 2018.
Watch now:

Postoperative Continuous Pressure Monitoring in Thyroid Surgery: Pathophysiology of Post-Thyroidectomy Hemorrhage
Ulrich Wirth, Thomas von Ahnen, Stefan Schopf, Hans Martin Schardey 

Transaxillary Robotic Parathyroidectomy: Huge Parathyroid Adenoma
Patrick Aidan, Maroun Bechara  

Thyroid Fine-Needle Aspiration and Smearing Techniques
Mitsuyoshi Hirokawa, Ayana Suzuki, Akira Miyauchi

 

The post VideoEndocrinology™ High-Impact Videos appeared first on American Thyroid Association.



https://ift.tt/2wF0C7L

Issue Information

logo-header-1518778866647.png

Molecular Oral Microbiology, Volume 33, Issue 3, Page i-iv, June 2018.


https://ift.tt/2wGqsbI

Single-Cell Transcriptomics Meets Lineage Tracing

Publication date: Available online 10 May 2018
Source:Cell Stem Cell
Author(s): Lennart Kester, Alexander van Oudenaarden
Reconstructing lineage relationships between cells within a tissue or organism is a long-standing aim in biology. Traditionally, lineage tracing has been achieved through the (genetic) labeling of a cell followed by the tracking of its offspring. Currently, lineage trajectories can also be predicted using single-cell transcriptomics. Although single-cell transcriptomics provides detailed phenotypic information, the predicted lineage trajectories do not necessarily reflect genetic relationships. Recently, techniques have been developed that unite these strategies. In this Review, we discuss transcriptome-based lineage trajectory prediction algorithms, single-cell genetic lineage tracing, and the promising combination of these techniques for stem cell and cancer research.

Teaser

In this Review, Kester and van Oudenaarden discuss transcriptome-based lineage trajectory prediction algorithms, single-cell genetic lineage tracing, and the promising combination of these techniques for stem cell and cancer research.


https://ift.tt/2IG2CBu

HippoCA3mpal Stem Cell Models Expose Dysfunctional Circuits in Schizophrenia

Publication date: 3 May 2018
Source:Cell Stem Cell, Volume 22, Issue 5
Author(s): Mandy Johnstone, Rana Fetit
In this issue of Cell Stem Cell, Sarkar et al. (2018) describe an efficient method for the generation of human hippocampal pyramidal neurons from stem cells. They developed a compelling in vitro model that recapitulates synaptic connectivity within the hippocampus and showed that cells derived from patients with schizophrenia exhibit abnormal electrical activity.

Teaser

In this issue of Cell Stem Cell, Sarkar et al. (2018) describe an efficient method for the generation of human hippocampal pyramidal neurons from stem cells. They developed a compelling in vitro model that recapitulates synaptic connectivity within the hippocampus and showed that cells derived from patients with schizophrenia exhibit abnormal electrical activity.


https://ift.tt/2IlhguH

Intestinal Stem Cells Live Off the Fat of the Land

Publication date: 3 May 2018
Source:Cell Stem Cell, Volume 22, Issue 5
Author(s): Derek A.G. Barisas, Thaddeus S. Stappenbeck
In this issue of Cell Stem Cell, Mihaylova et al. (2018) show that short-term fasting increases serum levels of long-chain fatty acids, presumably derived from the host. This effect in turn can rescue age-related phenotypes that occur in intestinal epithelial stem cells.

Teaser

In this issue of Cell Stem Cell, Mihaylova et al. (2018) show that short-term fasting increases serum levels of long-chain fatty acids, presumably derived from the host. This effect in turn can rescue age-related phenotypes that occur in intestinal epithelial stem cells.


https://ift.tt/2jVYWgV

Stem Cells Sheltered from Air-Raids Repair Airways

Publication date: 3 May 2018
Source:Cell Stem Cell, Volume 22, Issue 5
Author(s): Ying Yang, Wellington V. Cardoso
Submucosal glands contribute to the luminal secretions of conducting airways in the respiratory tract. In this issue of Cell Stem Cell, both Tata et al. (2018) and Lynch et al. (2018) report that myoepithelial cells of submucosal glands serve as reserve stem cells to regenerate the damaged surface epithelium following severe airway injury.

Teaser

Submucosal glands contribute to the luminal secretions of conducting airways in the respiratory tract. In this issue of Cell Stem Cell, both Tata et al. (2018) and Lynch et al. (2018) report that myoepithelial cells of submucosal glands serve as reserve stem cells to regenerate the damaged surface epithelium following severe airway injury.


https://ift.tt/2IlJtS2

Patient-Derived iPSC-Hypothamic Neurons: The Ultimate Protocol

Publication date: 3 May 2018
Source:Cell Stem Cell, Volume 22, Issue 5
Author(s): Maria Consolata Miletta, Tamas L. Horvath
Several methods for making hypothalamic-like neurons (iHTNs) from human or mouse induced pluripotent stem cells (iPSCs) with varying efficiencies exist. In this issue of Cell Stem Cell, Rajamani et al. (2018) devise a new, efficient method to differentiate iPSCs from super-obese and normal donors into iHTNS and investigate their different molecular profiles and hormone responses.

Teaser

Several methods for making hypothalamic-like neurons (iHTNs) from human or mouse induced pluripotent stem cells (iPSCs) with varying efficiencies exist. In this issue of Cell Stem Cell, Rajamani et al. (2018) devise a new, efficient method to differentiate iPSCs from super-obese and normal donors into iHTNS and investigate their different molecular profiles and hormone responses.


https://ift.tt/2ILz6dw

A Linc1405/Eomes Complex Promotes Cardiac Mesoderm Specification and Cardiogenesis

Publication date: Available online 10 May 2018
Source:Cell Stem Cell
Author(s): Xudong Guo, Yanxin Xu, Zikang Wang, Yukang Wu, Jiayu Chen, Guiying Wang, Chenqi Lu, Wenwen Jia, Jiajie Xi, Songcheng Zhu, Zeyidan Jiapaer, Xiaoping Wan, Zhongmin Liu, Shaorong Gao, Jiuhong Kang
Large intergenic non-coding RNAs (lincRNAs) play widespread roles in epigenetic regulation during multiple differentiation processes, but little is known about their mode of action in cardiac differentiation. Here, we identified the key roles of a lincRNA, termed linc1405, in modulating the core network of cardiac differentiation by functionally interacting with Eomes. Chromatin- and RNA-immunoprecipitation assays showed that exon 2 of linc1405 physically mediates a complex consisting of Eomes, trithorax group (TrxG) subunit WDR5, and histone acetyltransferase GCN5 binding at the enhancer region of Mesp1 gene and activates its expression during cardiac mesoderm specification of embryonic stem cells. Importantly, linc1405 co-localizes with Eomes, WDR5, and GCN5 at the primitive streak, and linc1405 depletion impairs heart development and function in vivo. In summary, linc1405 mediates a Eomes/WDR5/GCN5 complex that contributes to cardiogenesis, highlighting the critical roles of lincRNA-based complexes in the epigenetic regulation of cardiogenesis in vitro and in vivo.

Graphical abstract

image

Teaser

Kang and colleagues identify linc1405 as a crucial regulator of cardiac differentiation via its interaction with Eomes. Linc1405 mediates an Eomes/WDR5/GCN5 regulatory complex at the Mesp1 enhancer, which coordinates Mesp1 expression and cardiac specification. They also show that linc1405 depletion results in impaired heart development and function in vivo.


https://ift.tt/2IiePJm

Crinkle-Cut Brain Organoids

Publication date: 3 May 2018
Source:Cell Stem Cell, Volume 22, Issue 5
Author(s): Madeline A. Lancaster
In large mammalian brains, including those of humans, the surface of the cortex is highly folded. How these convolutions form is still unclear, but recent work in Nature Physics by Karzbrun et al. (2018) supports a mechanism involving differential surface swelling combined with internal constraint.

Teaser

In large mammalian brains, including those of humans, the surface of the cortex is highly folded. How these convolutions form is still unclear, but recent work in Nature Physics by Karzbrun et al. (2018) supports a mechanism involving differential surface swelling combined with internal constraint.


https://ift.tt/2IHP7kT

The Lysosome, Elixir of Neural Stem Cell Youth

Publication date: 3 May 2018
Source:Cell Stem Cell, Volume 22, Issue 5
Author(s): Milos S. Simic, Andrew Dillin
Recently in Science, Leeman et al. find that perturbing lysosomal activity of quiescent NSCs directly impedes their ability to become activated, similar to what happens during aging. Excitingly, they could rejuvenate old quiescent NSCs by enhancing the lysosome pathway, ameliorating their ability to clear protein aggregates and become activated.

Teaser

Recently in Science, Leeman et al. find that perturbing lysosomal activity of quiescent NSCs directly impedes their ability to become activated, similar to what happens during aging. Excitingly, they could rejuvenate old quiescent NSCs by enhancing the lysosome pathway, ameliorating their ability to clear protein aggregates and become activated.


https://ift.tt/2Ik7adm

Mentoring the Next Generation: Hongkui Deng

Publication date: 3 May 2018
Source:Cell Stem Cell, Volume 22, Issue 5

Mentor-mentee relationships are essential for professional development, but developing these interpersonal skills is not often highlighted as a priority in scientific endeavors. In a yearlong series, Cell Stem Cell interviews prominent scientists who have prioritized mentorship over the years. Here, we chat with Dr. Hongkui Deng about his views.



https://ift.tt/2jXwoE1

Causes and Consequences of Hematopoietic Stem Cell Heterogeneity

Publication date: 3 May 2018
Source:Cell Stem Cell, Volume 22, Issue 5
Author(s): Simon Haas, Andreas Trumpp, Michael D. Milsom
Blood and immune cells derive from multipotent hematopoietic stem cells (HSCs). Classically, stem and progenitor populations have been considered discrete homogeneous populations. However, recent technological advances have revealed significant HSC heterogeneity, with evidence for early HSC lineage segregation and the presence of lineage-biased HSCs and lineage-restricted progenitors within the HSC compartment. These and other findings challenge many aspects of the classical view of HSC biology. We review the most recent findings regarding the causes and consequences of HSC heterogeneity, discuss their far-reaching implications, and suggest that so-called continuum-based models may help consolidate apparently divergent experimental observations in this field.

Teaser

Haas et al. review the most recent findings regarding the causes and consequences of HSC heterogeneity, discuss their far-reaching implications, and suggest that so-called continuum-based models may help consolidate apparently divergent experimental observations in this field.


https://ift.tt/2Ij7Qji

Blood Development: Hematopoietic Stem Cell Dependence and Independence

Publication date: 3 May 2018
Source:Cell Stem Cell, Volume 22, Issue 5
Author(s): Elaine Dzierzak, Anna Bigas
Evidence of the diversity and multi-layered organization of the hematopoietic system is leading to new insights that may inform ex vivo production of blood cells. Interestingly, not all long-lived hematopoietic cells derive from hematopoietic stem cells (HSCs). Here we review the current knowledge on HSC-dependent cell lineages and HSC-independent tissue-resident hematopoietic cells and how they arise during embryonic development. Classical embryological and genetic experiments, cell fate tracing data, single-cell imaging, and transcriptomics studies provide information on the molecular/cell trajectories that form the complete hematopoietic system. We also discuss the current developmentally informed efforts toward generating engraftable and multilineage blood cells.

Teaser

Dzierzak and Bigas review the current knowledge on molecular/cell trajectories that generate the complete hematopoietic system, informed by classical embryological and genetic experiments, cell fate tracing data, single-cell imaging, and transcriptomics studies. The authors also discuss the current developmentally informed efforts toward generating engraftable and multilineage blood cells.


https://ift.tt/2jXkdHm

Efficient Generation of CA3 Neurons from Human Pluripotent Stem Cells Enables Modeling of Hippocampal Connectivity In Vitro

Publication date: 3 May 2018
Source:Cell Stem Cell, Volume 22, Issue 5
Author(s): Anindita Sarkar, Arianna Mei, Apua C.M. Paquola, Shani Stern, Cedric Bardy, Jason R. Klug, Stacy Kim, Neda Neshat, Hyung Joon Kim, Manching Ku, Maxim N. Shokhirev, David H. Adamowicz, Maria C. Marchetto, Roberto Jappelli, Jennifer A. Erwin, Krishnan Padmanabhan, Matthew Shtrahman, Xin Jin, Fred H. Gage
Despite widespread interest in using human induced pluripotent stem cells (hiPSCs) in neurological disease modeling, a suitable model system to study human neuronal connectivity is lacking. Here, we report a comprehensive and efficient differentiation paradigm for hiPSCs that generate multiple CA3 pyramidal neuron subtypes as detected by single-cell RNA sequencing (RNA-seq). This differentiation paradigm exhibits characteristics of neuronal network maturation, and rabies virus tracing revealed synaptic connections between stem cell-derived dentate gyrus (DG) and CA3 neurons in vitro recapitulating the neuronal connectivity within the hippocampus. Because hippocampal dysfunction has been implicated in schizophrenia, we applied DG and CA3 differentiation paradigms to schizophrenia-patient-derived hiPSCs. We detected reduced activity in DG-CA3 co-culture and deficits in spontaneous and evoked activity in CA3 neurons from schizophrenia-patient-derived hiPSCs. Our approach offers critical insights into the network activity aspects of schizophrenia and may serve as a promising tool for modeling diseases with hippocampal vulnerability.Video Abstract

Graphical abstract

image

Teaser

Sarkar et al. established a differentiation paradigm that generates human CA3 pyramidal neurons from ESCs and iPSCs and recapitulates hippocampal connectivity in vitro. This work reveals reduced levels of activity of schizophrenia-patient-derived neurons, offering opportunities for modeling diseases with hippocampal vulnerability.


https://ift.tt/2IimC9U

Super-Obese Patient-Derived iPSC Hypothalamic Neurons Exhibit Obesogenic Signatures and Hormone Responses

Publication date: 3 May 2018
Source:Cell Stem Cell, Volume 22, Issue 5
Author(s): Uthra Rajamani, Andrew R. Gross, Brooke E. Hjelm, Adolfo Sequeira, Marquis P. Vawter, Jie Tang, Vineela Gangalapudi, Yizhou Wang, Allen M. Andres, Roberta A. Gottlieb, Dhruv Sareen
The hypothalamus contains neurons that integrate hunger and satiety endocrine signals from the periphery and are implicated in the pathophysiology of obesity. The limited availability of human hypothalamic neurons hampers our understanding of obesity disease mechanisms. To address this, we generated human induced pluripotent stem cells (hiPSCs) from multiple normal body mass index (BMI; BMI ≤ 25) subjects and super-obese (OBS) donors (BMI ≥ 50) with polygenic coding variants in obesity-associated genes. We developed a method to reliably differentiate hiPSCs into hypothalamic-like neurons (iHTNs) capable of secreting orexigenic and anorexigenic neuropeptides. Transcriptomic profiling revealed that, although iHTNs maintain a fetal identity, they respond appropriately to metabolic hormones ghrelin and leptin. Notably, OBS iHTNs retained disease signatures and phenotypes of high BMI, exhibiting dysregulated respiratory function, ghrelin-leptin signaling, axonal guidance, glutamate receptors, and endoplasmic reticulum (ER) stress pathways. Thus, human iHTNs provide a powerful platform to study obesity and gene-environment interactions.

Graphical abstract

image

Teaser

Human hypothalamic neurons (HTNs) implicated in obesity have a limited availability. This study describes a reliable method for generating functional hormone-responsive HTNs from multiple normal and obese patient reprogrammed hiPSCs. Obese-patient-induced HTNs retained transcriptome profiles and functional phenotypes of high BMI, exhibiting aberrant obesity-related metabolic and respiratory pathways.


https://ift.tt/2IHJDXc

Spred1 Safeguards Hematopoietic Homeostasis against Diet-Induced Systemic Stress

Publication date: 3 May 2018
Source:Cell Stem Cell, Volume 22, Issue 5
Author(s): Yuko Tadokoro, Takayuki Hoshii, Satoshi Yamazaki, Koji Eto, Hideo Ema, Masahiko Kobayashi, Masaya Ueno, Kumiko Ohta, Yuriko Arai, Eiji Hara, Kenichi Harada, Masanobu Oshima, Hiroko Oshima, Fumio Arai, Akihiko Yoshimura, Hiromitsu Nakauchi, Atsushi Hirao
Stem cell self-renewal is critical for tissue homeostasis, and its dysregulation can lead to organ failure or tumorigenesis. While obesity can induce varied abnormalities in bone marrow components, it is unclear how diet might affect hematopoietic stem cell (HSC) self-renewal. Here, we show that Spred1, a negative regulator of RAS-MAPK signaling, safeguards HSC homeostasis in animals fed a high-fat diet (HFD). Under steady-state conditions, Spred1 negatively regulates HSC self-renewal and fitness, in part through Rho kinase activity. Spred1 deficiency mitigates HSC failure induced by infection mimetics and prolongs HSC lifespan, but it does not initiate leukemogenesis due to compensatory upregulation of Spred2. In contrast, HFD induces ERK hyperactivation and aberrant self-renewal in Spred1-deficient HSCs, resulting in functional HSC failure, severe anemia, and myeloproliferative neoplasm-like disease. HFD-induced hematopoietic abnormalities are mediated partly through alterations to the gut microbiota. Together, these findings reveal that diet-induced stress disrupts fine-tuning of Spred1-mediated signals to govern HSC homeostasis.

Graphical abstract

image

Teaser

Tadokoro et al. show that Spred1 negatively regulates HSC self-renewal in a manner supported by ROCK activity and that Spred1 safeguards HSC homeostasis under high-fat diet (HFD) conditions by regulating HSC self-renewal. The gut microbiota dysbiosis induced by HFD disrupts the fine-tuning of Spred1-mediated signals that govern HSC homeostasis.


https://ift.tt/2IlgHkz

PRC1 Fine-tunes Gene Repression and Activation to Safeguard Skin Development and Stem Cell Specification

Publication date: 3 May 2018
Source:Cell Stem Cell, Volume 22, Issue 5
Author(s): Idan Cohen, Dejian Zhao, Carmit Bar, Victor J. Valdes, Katherine L. Dauber-Decker, Minh Binh Nguyen, Manabu Nakayama, Michael Rendl, Wendy A. Bickmore, Haruhiko Koseki, Deyou Zheng, Elena Ezhkova
Polycomb repressive complexes (PRCs) 1 and 2 are essential chromatin regulators of cell identity. PRC1, a dominant executer of Polycomb-mediated control, functions as multiple sub-complexes that possess catalytic-dependent H2AK119 mono-ubiquitination (H2AK119ub) and catalytic-independent activities. Here, we show that, despite its well-established repressor functions, PRC1 binds to both silent and active genes. Through in vivo loss-of-function studies, we show that global PRC1 function is essential for skin development and stem cell (SC) specification, whereas PRC1 catalytic activity is dispensable. Further dissection demonstrated that both canonical and non-canonical PRC1 complexes bind to repressed genes, marked by H2AK119ub and PRC2-mediated H3K27me3. Interestingly, loss of canonical PRC1, PRC1 catalytic activity, or PRC2 leads to expansion of mechanosensitive Merkel cells in neonatal skin. Non-canonical PRC1 complexes, however, also bind to and promote expression of genes critical for skin development and SC formation. Together, our findings highlight PRC1's diverse roles in executing a precise developmental program.

Graphical abstract

image

Teaser

Cohen et al. show that Polycomb repressive complex 1 (PRC1), a critical chromatin regulator, is essential for skin epithelium morphogenesis and stem cell specification. By coupling in vivo chromatin and transcriptional profiling with loss-of-function studies, the authors show that PRC1 controls skin development through regulation of silent and active genes.


https://ift.tt/2jUPRVC

Retinoid-Sensitive Epigenetic Regulation of the Hoxb Cluster Maintains Normal Hematopoiesis and Inhibits Leukemogenesis

Publication date: 3 May 2018
Source:Cell Stem Cell, Volume 22, Issue 5
Author(s): Pengxu Qian, Bony De Kumar, Xi C. He, Christof Nolte, Madelaine Gogol, Youngwook Ahn, Shiyuan Chen, Zhenrui Li, Hanzhang Xu, John M. Perry, Deqing Hu, Fang Tao, Meng Zhao, Yingli Han, Kate Hall, Allison Peak, Ariel Paulson, Chongbei Zhao, Aparna Venkatraman, Andrew Box, Anoja Perera, Jeffrey S. Haug, Tari Parmely, Hua Li, Robb Krumlauf, Linheng Li
Hox genes modulate the properties of hematopoietic stem cells (HSCs) and reacquired Hox expression in progenitors contributes to leukemogenesis. Here, our transcriptome and DNA methylome analyses revealed that Hoxb cluster and retinoid signaling genes are predominantly enriched in LT-HSCs, and this coordinate regulation of Hoxb expression is mediated by a retinoid-dependent cis-regulatory element, distal element RARE (DERARE). Deletion of the DERARE reduced Hoxb expression, resulting in changes to many downstream signaling pathways (e.g., non-canonical Wnt signaling) and loss of HSC self-renewal and reconstitution capacity. DNA methyltransferases mediate DNA methylation on the DERARE, leading to reduced Hoxb cluster expression. Acute myeloid leukemia patients with DNMT3A mutations exhibit DERARE hypomethylation, elevated HOXB expression, and adverse outcomes. CRISPR-Cas9-mediated specific DNA methylation at DERARE attenuated HOXB expression and alleviated leukemogenesis. Collectively, these findings demonstrate pivotal roles for retinoid signaling and the DERARE in maintaining HSCs and preventing leukemogenesis by coordinate regulation of Hoxb genes.

Graphical abstract

image

Teaser

Hox genes are regulators of HSC maintenance and contributors in leukemogenesis. Li and colleagues elucidate a mechanism for how the retinoid-dependent cis-regulatory element DERARE maintains normal hematopoiesis but prevents leukemogenesis by coordinate regulation of Hoxb cluster genes in a methylation-dependent manner.


https://ift.tt/2IlgiP5

The Dystrophin Glycoprotein Complex Regulates the Epigenetic Activation of Muscle Stem Cell Commitment

Publication date: 3 May 2018
Source:Cell Stem Cell, Volume 22, Issue 5
Author(s): Natasha C. Chang, Marie-Claude Sincennes, Fabien P. Chevalier, Caroline E. Brun, Melanie Lacaria, Jessica Segalés, Pura Muñoz-Cánoves, Hong Ming, Michael A. Rudnicki
Asymmetrically dividing muscle stem cells in skeletal muscle give rise to committed cells, where the myogenic determination factor Myf5 is transcriptionally activated by Pax7. This activation is dependent on Carm1, which methylates Pax7 on multiple arginine residues, to recruit the ASH2L:MLL1/2:WDR5:RBBP5 histone methyltransferase complex to the proximal promoter of Myf5. Here, we found that Carm1 is a specific substrate of p38γ/MAPK12 and that phosphorylation of Carm1 prevents its nuclear translocation. Basal localization of the p38γ/p-Carm1 complex in muscle stem cells occurs via binding to the dystrophin-glycoprotein complex (DGC) through β1-syntrophin. In dystrophin-deficient muscle stem cells undergoing asymmetric division, p38γ/β1-syntrophin interactions are abrogated, resulting in enhanced Carm1 phosphorylation. The resulting progenitors exhibit reduced Carm1 binding to Pax7, reduced H3K4-methylation of chromatin, and reduced transcription of Myf5 and other Pax7 target genes. Therefore, our experiments suggest that dysregulation of p38γ/Carm1 results in altered epigenetic gene regulation in Duchenne muscular dystrophy.

Graphical abstract

image

Teaser

Establishment of cell polarity by the dystrophin complex is required for muscle stem cell asymmetric divisions. Chang et al. identify p38γ MAPK as a critical downstream regulator of satellite stem cell commitment, providing a link between dystrophin and epigenetic gene regulation to mediate asymmetric fates of daughter satellite cells.


https://ift.tt/2jWPZ71

Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging

Publication date: 3 May 2018
Source:Cell Stem Cell, Volume 22, Issue 5
Author(s): Maria M. Mihaylova, Chia-Wei Cheng, Amanda Q. Cao, Surya Tripathi, Miyeko D. Mana, Khristian E. Bauer-Rowe, Monther Abu-Remaileh, Laura Clavain, Aysegul Erdemir, Caroline A. Lewis, Elizaveta Freinkman, Audrey S. Dickey, Albert R. La Spada, Yanmei Huang, George W. Bell, Vikram Deshpande, Peter Carmeliet, Pekka Katajisto, David M. Sabatini, Ömer H. Yilmaz
Diet has a profound effect on tissue regeneration in diverse organisms, and low caloric states such as intermittent fasting have beneficial effects on organismal health and age-associated loss of tissue function. The role of adult stem and progenitor cells in responding to short-term fasting and whether such responses improve regeneration are not well studied. Here we show that a 24 hr fast augments intestinal stem cell (ISC) function in young and aged mice by inducing a fatty acid oxidation (FAO) program and that pharmacological activation of this program mimics many effects of fasting. Acute genetic disruption of Cpt1a, the rate-limiting enzyme in FAO, abrogates ISC-enhancing effects of fasting, but long-term Cpt1a deletion decreases ISC numbers and function, implicating a role for FAO in ISC maintenance. These findings highlight a role for FAO in mediating pro-regenerative effects of fasting in intestinal biology, and they may represent a viable strategy for enhancing intestinal regeneration.

Graphical abstract

image

Teaser

Mihaylova et al. show that short-term fasting promotes intestinal stem and progenitor cell function in young and aged mice by inducing a robust fatty acid oxidation (FAO) program. PPARδ agonists emulate these effects, showing that fatty acid metabolism has positive effects on young and old ISCs.


https://ift.tt/2Ik6WD2

Evolving Industry Partnerships and Investments in Cell and Gene Therapies

Publication date: 3 May 2018
Source:Cell Stem Cell, Volume 22, Issue 5
Author(s): Devyn M. Smith, Emily J. Culme-Seymour, Chris Mason




https://ift.tt/2IBU12V

Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate Mouse Tracheal Epithelium

Publication date: 3 May 2018
Source:Cell Stem Cell, Volume 22, Issue 5
Author(s): Thomas J. Lynch, Preston J. Anderson, Pavana G. Rotti, Scott R. Tyler, Adrianne K. Crooke, Soon H. Choi, Daniel T. Montoro, Carolyn L. Silverman, Weam Shahin, Rui Zhao, Chandler W. Jensen-Cody, Andrea Adamcakova-Dodd, T. Idil Apak Evans, Weiliang Xie, Yulong Zhang, Hongmei Mou, B. Paul Herring, Peter S. Thorne, Jayaraj Rajagopal, Charles Yeaman, Kalpaj R. Parekh, John F. Engelhardt




https://ift.tt/2rDW382

Editorial Board

elsevier-non-solus.png

Publication date: April 2018
Source:Best Practice & Research Clinical Endocrinology & Metabolism, Volume 32, Issue 2





https://ift.tt/2rGQJkl

Two cases of discrete adenoid pseudogland formation within benign intradermal melanocytic nevi

Journal of Cutaneous Pathology, EarlyView.


https://ift.tt/2wEZiSi

Disseminated Kaposi sarcoma with epithelioid morphology in an HIV/AIDS patient: A previously unreported variant

Journal of Cutaneous Pathology, EarlyView.


https://ift.tt/2IHT3lu

Oral juvenile xanthogranuloma in a child: Clinical, histological and immunohistochemical profile of a rare entity

Journal of Cutaneous Pathology, EarlyView.


https://ift.tt/2KmYDH7

Bone fragility in Turner syndrome: Fracture prevalence and risk factors determined by a national patient survey

Clinical Endocrinology, EarlyView.


https://ift.tt/2wEYwom

Building Blocks of Social Cognition: Mirror, Mentalize, Share?

S00109452.gif

Publication date: Available online 14 May 2018
Source:Cortex
Author(s): Daniel Alcalá-López, Kai Vogeley, Ferdinand Binkofski, Danilo Bzdok
During the past decade, novel approaches to study social interaction have expanded and questioned long-standing knowledge about how humans understand others. We aim to portray and reconcile the key psychological processes and neural mechanisms underlying navigation of the social environment. Theoretical accounts mostly revolved around either abstract inferences or embodied simulations, whereas experimental studies mostly focused on theory of mind or mentalizing, empathy, and action imitation. The tension between theories of and experiments on social cognition is systematically revisited to foster new theoretical and empirical studies in the fields. We finally retrace differential impairments in social capacities as a means to re-conceptualize psychopathological disturbance in psychiatry, including schizophrenia, borderline personality, and autism.



https://ift.tt/2Kq4taZ

The role of sentinel lymph node biopsy as a staging procedure in patients with melanoma – A critical appraisal

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2rIlpCs

Contact dermatitis to Dermabond Advance®

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2wM3OhQ

A ticking time bomb: A case of Lyme disease

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2rH3Qme

Pancreatic panniculitis: A case series from a tertiary university hospital in Spain

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2wFFTRo

A rare case of chronic expanding haematoma in the occipital region mimicking a malignant soft tissue tumour

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2IgqE6V

Chemotherapy‐induced alopecia: A novel observation

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2wIr3JS

Successful treatment of a skin tears with a single‐use negative pressure wound therapy device

Dermatologic Therapy, EarlyView.


https://ift.tt/2wHRIqh

Noninvasive size reduction of lipoma with an insulated monopolar radiofrequency microneedle device

Dermatologic Therapy, EarlyView.


https://ift.tt/2rIkbqQ

Promoting new concepts of skincare via skinomics and systems biology—From traditional skincare and efficacy‐based skincare to precision skincare

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2IIJ5QX

Antioxidant properties evaluation of topical astaxanthin formulations as anti‐aging products

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2IiDgGh

3D skin surface reconstruction from a single image by merging global curvature and local texture using the guided filtering for 3D haptic palpation

Skin Research and Technology, EarlyView.


https://ift.tt/2rI0nE5

Fundamental supply of skin blood flow in the Chinese Han population: Measurements by a full‐field laser perfusion imager

Skin Research and Technology, EarlyView.


https://ift.tt/2GetenK

Ultrasound of pancreatic panniculitis

Skin Research and Technology, EarlyView.


https://ift.tt/2KZbZe5

Does the gastrointestinal microbiome contribute to the ‘obesity paradox’ in melanoma survival?

British Journal of Dermatology, EarlyView.


https://ift.tt/2jZ8sQy

The prevalence of honorary authorship in the dermatological literature

British Journal of Dermatology, EarlyView.


https://ift.tt/2KqxAdZ

Automated scoring of vitiligo using superpixel‐generated computerized digital image analysis of clinical photographs: a novel and consistent way to score vitiligo

British Journal of Dermatology, EarlyView.


https://ift.tt/2IE9hwc

Profound consequences of hidradenitis suppurativa: a review

British Journal of Dermatology, EarlyView.


https://ift.tt/2KqxqTV

Baseline neutrophil‐to‐lymphocyte ratio in patients with advanced melanoma treated with immune checkpoint inhibitors

British Journal of Dermatology, EarlyView.


https://ift.tt/2jYaG2K

Drug survival of secukinumab for moderate‐to‐severe plaque psoriasis: reply from authors

British Journal of Dermatology, EarlyView.


https://ift.tt/2Kqxinp

Response to: Response to comments on: "Complementary and alternative therapies for restless legs syndrome: An evidence-based systematic review - by Mohammad Alwardat - SMRV_2018_33

Thank you for your concern and comment on our paper entitled " Complementary and alternative therapies for restless legs syndrome: An evidence-based systematic review".

https://ift.tt/2jXRwdi

A new approach to assess the effect of photodamage on corneocyte envelope maturity using combined hydrophobicity and mechanical fragility assays

International Journal of Cosmetic Science, EarlyView.


https://ift.tt/2jVeQbt

Adenosine‐loaded dissolving microneedle patches to improve skin wrinkles, dermal density, elasticity and hydration

International Journal of Cosmetic Science, Volume 40, Issue 2, Page 199-206, April 2018.


https://ift.tt/2KjOzPl

Issue Information

International Journal of Cosmetic Science, Volume 40, Issue 2, Page i-iv, April 2018.


https://ift.tt/2jWDKr5

Localized genital bullous pemphigoid

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2KZkLZn

Unilateral periorbital swelling: a diagnostic dilemma

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2GdLei9

Oral Fumaderm® to treat cutaneous sarcoidosis

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2L1VMEH

A case of neutrophilic dermatoses including pyoderma gangrenosum as a continuous disease spectrum to SAPHO syndrome

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2GdLbTv

Rapid growth rate is associated with poor prognosis in cutaneous squamous cell carcinoma

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2rJibyH

Cutaneous manifestations of JAK2+ myeloproliferative neoplasms

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2GeoEpy

Sustained response of graft‐versus‐host disease‐associated angiomatosis treated with propranolol

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2rH1Sm7

A polymorphous rash of an uncommon blistering disease

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2GdL6iF

Association between serum interleukin‐17A and clinical response to tofacitinib and etanercept in moderate to severe psoriasis

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2L0n3aH

A solitary and tender acral papule in a young patient

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2GdKZUh

CD8+ T cell‐mediated interface dermatitis during combination chemotherapy with mogamulizumab in a patient with adult T‐cell leukaemia/lymphoma

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2KZkGF3

Tattoo‐related squamous proliferations: a spectrum of reactive hyperplasia

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2GeoAWQ

Cartilage hair hypoplasia with cutaneous lymphomatoid granulomatosis

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2L0pSZe

Positive clinical outcome of an oral in situ melanoma: 6 years of follow‐up

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2GdKVUx

Depigmentation efficacy of galacturonic acid through tyrosinase regulation in B16 murine melanoma cells and a three‐dimensional human skin equivalent

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2rFVGun

Issue Information

Clinical and Experimental Dermatology, Volume 43, Issue 4, Page i-373-374, June 2018.


https://ift.tt/2IiSL1a

Zinc‐responsive exfoliative dermatitis in a 17‐year‐old girl with delayed puberty

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2jXbG7i

Arthur J. Moss, MD: In Memoriam



https://ift.tt/2KYRle5

Device Closure of Patent Foramen Ovale in Patients With Cryptogenic Stroke: The Tide Has Turned



https://ift.tt/2L0bgcz

Carvedilol for Prevention of Chemotherapy-Related Cardiotoxicity: The CECCY Trial

AbstractBackground

Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with β-blockers remains controversial.

Objectives

This prospective, randomized, double-blind, placebo-controlled study sought to evaluate the role of carvedilol in preventing ANT cardiotoxicity.

Methods

The authors randomized 200 patients with HER2-negative breast cancer tumor status and normal left ventricular ejection fraction (LVEF) referred for ANT (240 mg/m2) to receive carvedilol or placebo until chemotherapy completion. The primary endpoint was prevention of a ≥10% reduction in LVEF at 6 months. Secondary outcomes were effects of carvedilol on troponin I, B-type natriuretic peptide, and diastolic dysfunction.

Results

Primary endpoint occurred in 14 patients (14.5%) in the carvedilol group and 13 patients (13.5%) in the placebo group (p = 1.0). No differences in changes of LVEF or B-type natriuretic peptide were noted between groups. A significant difference existed between groups in troponin I levels over time, with lower levels in the carvedilol group (p = 0.003). Additionally, a lower incidence of diastolic dysfunction was noted in the carvedilol group (p = 0.039). A nonsignificant trend toward a less-pronounced increase in LV end-diastolic diameter during the follow-up was noted in the carvedilol group (44.1 ± 3.64 mm to 45.2 ± 3.2 mm vs. 44.9 ± 3.6 mm to 46.4 ± 4.0 mm; p = 0.057).

Conclusions

In this largest clinical trial of β-blockers for prevention of cardiotoxicity under contemporary ANT dosage, the authors noted a 13.5% to 14.5% incidence of cardiotoxicity. In this scenario, carvedilol had no impact on the incidence of early onset of LVEF reduction. However, the use of carvedilol resulted in a significant reduction in troponin levels and diastolic dysfunction. (Carvedilol Effect in Preventing Chemotherapy-Induced Cardiotoxicity [CECCY]; NCT01724450)



https://ift.tt/2L1kxRJ

His Bundle Pacing: The Holy Grail of Pacing?



https://ift.tt/2KZ4eo8

Beta-Blockers for Primary Prevention of Anthracycline Cardiotoxicity: Not Quite Ready for Prime Time



https://ift.tt/2rJ4ZJe

Epicardial Adipose Tissue May Mediate Deleterious Effects of Obesity and Inflammation on the Myocardium

Abstract

Epicardial adipose tissue has unique properties that distinguish it from other depots of visceral fat. Rather than having distinct boundaries, the epicardium shares an unobstructed microcirculation with the underlying myocardium, and in healthy conditions, produces cytokines that nourish the heart. However, in chronic inflammatory disorders (especially those leading to heart failure with preserved ejection fraction), the epicardium becomes a site of deranged adipogenesis, leading to the secretion of proinflammatory adipokines that can cause atrial and ventricular fibrosis. Accordingly, in patients at risk of heart failure with preserved ejection fraction, drugs that promote the accumulation or inflammation of epicardial adipocytes may lead to heart failure, whereas treatments that ameliorate the proinflammatory characteristics of epicardial fat may reduce the risk of heart failure. These observations suggest that epicardial adipose tissue is a transducer of the adverse effects of systemic inflammation and metabolic disorders on the heart, and thus, represents an important target for therapeutic interventions.



https://ift.tt/2IjEjdd

Genetic Etiology for Alcohol-Induced Cardiac Toxicity

AbstractBackground

Alcoholic cardiomyopathy (ACM) is defined by a dilated and impaired left ventricle due to chronic excess alcohol consumption. It is largely unknown which factors determine cardiac toxicity on exposure to alcohol.

Objectives

This study sought to evaluate the role of variation in cardiomyopathy-associated genes in the pathophysiology of ACM, and to examine the effects of alcohol intake and genotype on dilated cardiomyopathy (DCM) severity.

Methods

The authors characterized 141 ACM cases, 716 DCM cases, and 445 healthy volunteers. The authors compared the prevalence of rare, protein-altering variants in 9 genes associated with inherited DCM. They evaluated the effect of genotype and alcohol consumption on phenotype in DCM.

Results

Variants in well-characterized DCM-causing genes were more prevalent in patients with ACM than control subjects (13.5% vs. 2.9%; p = 1.2 x10–5), but similar between patients with ACM and DCM (19.4%; p = 0.12) and with a predominant burden of titin truncating variants (TTNtv) (9.9%). Separately, we identified an interaction between TTN genotype and excess alcohol consumption in a cohort of DCM patients not meeting ACM criteria. On multivariate analysis, DCM patients with a TTNtv who consumed excess alcohol had an 8.7% absolute reduction in ejection fraction (95% confidence interval: –2.3% to –15.1%; p < 0.007) compared with those without TTNtv and excess alcohol consumption. The presence of TTNtv did not predict phenotype, outcome, or functional recovery on treatment in ACM patients.

Conclusions

TTNtv represent a prevalent genetic predisposition for ACM, and are also associated with a worse left ventricular ejection fraction in DCM patients who consume alcohol above recommended levels. Familial evaluation and genetic testing should be considered in patients presenting with ACM.



https://ift.tt/2KVl2N3

JACC Instructions for Authors



https://ift.tt/2rLYrKa

Alcoholic Cardiomyopathy: Is it Time for Genetic Testing?



https://ift.tt/2rJmTeX

Cryptogenic Stroke and High-Risk Patent Foramen Ovale: The DEFENSE-PFO Trial

AbstractBackground

Recent reports showing the favorable role of patent foramen ovale (PFO) closure in patients with cryptogenic stroke have raised the issue of selecting optimal candidates.

Objectives

This study, DEFENSE-PFO (Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale), evaluated whether the benefits of PFO closure can be determined on the basis of the morphologic characteristics of the PFO, as evaluated by transesophageal echocardiography.

Methods

Patients with cryptogenic stroke and high-risk PFO were divided between a transcatheter PFO closure and a medication-only group. High-risk PFO included PFO with atrial septal aneurysm, hypermobility (phasic septal excursion into either atrium ≥10 mm), or PFO size (maximum separation of the septum primum from the secundum) ≥2 mm. The primary endpoint was a composite of stroke, vascular death, or Thrombolysis In Myocardial Infarction–defined major bleeding during 2 years of follow-up.

Results

From September 2011 until October 2017, 120 patients (mean age: 51.8 years) underwent randomization. PFO size, frequency of septal aneurysm (13.3% vs. 8.3%; p = 0.56), and hypermobility (45.0% vs. 46.7%; p > 0.99) were similar between the groups. All PFO closures were successful. The primary endpoint occurred exclusively in the medication-only group (6 of 60 patients; 2-year event rate: 12.9% [log-rank p = 0.013]; 2-year rate of ischemic stroke: 10.5% [p = 0.023]). The events in the medication-only group included ischemic stroke (n = 5), cerebral hemorrhage (n = 1), Thrombolysis In Myocardial Infarction–defined major bleeding (n = 2), and transient ischemic attack (n = 1). Nonfatal procedural complications included development of atrial fibrillation (n = 2), pericardial effusion (n = 1), and pseudoaneurysm (n = 1).

Conclusions

PFO closure in patients with high-risk PFO characteristics resulted in a lower rate of the primary endpoint as well as stroke recurrence. (Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale [DEFENSE-PFO]; NCT01550588)



https://ift.tt/2rI8KPk

Major Adverse Limb Events and Mortality in Patients With Peripheral Artery Disease: The COMPASS Trial

AbstractBackground

Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). There is limited information on the prognosis of patients who experience MALE.

Objectives

Among participants with lower extremity PAD, this study investigated: 1) if hospitalizations, MACE, amputations, and deaths are higher after the first episode of MALE compared with patients with PAD who do not experience MALE; and 2) the impact of treatment with low-dose rivaroxaban and aspirin compared with aspirin alone on the incidence of MALE, peripheral vascular interventions, and all peripheral vascular outcomes over a median follow-up of 21 months.

Methods

We analyzed outcomes in 6,391 patients with lower extremity PAD who were enrolled in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial. COMPASS was a randomized, double-blind placebo-controlled study of low-dose rivaroxaban and aspirin combination or rivaroxaban alone compared with aspirin alone. MALE was defined as severe limb ischemia leading to an intervention or major vascular amputation.

Results

A total of 128 patients experienced an incident of MALE. After MALE, the 1-year cumulative risk of a subsequent hospitalization was 61.5%; for vascular amputations, it was 20.5%; for death, it was 8.3%; and for MACE, it was 3.7%. The MALE index event significantly increased the risk of experiencing subsequent hospitalizations (hazard ratio [HR]: 7.21; p < 0.0001), subsequent amputations (HR: 197.5; p < 0.0001), and death (HR: 3.23; p < 0.001). Compared with aspirin alone, the combination of rivaroxaban 2.5 mg twice daily and aspirin lowered the incidence of MALE by 43% (p = 0.01), total vascular amputations by 58% (p = 0.01), peripheral vascular interventions by 24% (p = 0.03), and all peripheral vascular outcomes by 24% (p = 0.02).

Conclusions

Among individuals with lower extremity PAD, the development of MALE is associated with a poor prognosis, making prevention of this condition of utmost importance. The combination of rivaroxaban 2.5 mg twice daily and aspirin significantly lowered the incidence of MALE and the related complications, and this combination should be considered as an important therapy for patients with PAD. (Cardiovascular Outcomes for People Using Anticoagulation Strategies [COMPASS]; NCT01776424)



https://ift.tt/2Ig1C7Z

Psychopharmacology and Cardiovascular Disease

Abstract

This review discusses common mental health disorders and their associations with cardiovascular disease risks. Commonly found mental health disorders include depression, anxiety, and personality types. The link between depression and cardiovascular disease mortality has been established. Depression is also common in patients with heart failure. In addition to discussing psychological disorders, a review of psychotropic drugs is also included. Drugs are described for therapy for depression and anxiety, as well as associations with cardiovascular drug-drug interactions. Drug-drug interactions are more common and potentially dangerous in elderly patients, in whom the conditions often coexist. The most common drug-drug interactions involve the P450 system of enzymes.



https://ift.tt/2rI308g

Antithrombotic Therapy and Major Adverse Limb Events in Peripheral Artery Disease: A Step Forward



https://ift.tt/2rI48Zy

Helping ACC Members Deliver Higher-Quality Care



https://ift.tt/2rIP9yr

Clinical Outcomes of His Bundle Pacing Compared to Right Ventricular Pacing

AbstractBackground

Right ventricular pacing (RVP) is associated with heart failure and increased mortality. His bundle pacing (HBP) is a physiological alternative to RVP.

Objectives

This study sought to evaluate clinical outcomes of HBP compared to RVP.

Methods

All patients requiring initial pacemaker implantation between October 1, 2013, and December 31, 2016, were included in the study. Permanent HBP was attempted in consecutive patients at 1 hospital and RVP at a sister hospital. Implant characteristics, all-cause mortality, heart failure hospitalization (HFH), and upgrades to biventricular pacing (BiVP) were tracked. Primary outcome was the combined endpoint of death, HFH, or upgrade to BiVP. Secondary endpoints were mortality and HFH.

Results

HBP was successful in 304 of 332 consecutive patients (92%), whereas 433 patients underwent RVP. The primary endpoint of death, HFH, or upgrade to BiVP was significantly reduced in the HBP group (83 of 332 patients [25%]) compared to RVP (137 of 433 patients [32%]; hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.534 to 0.944; p = 0.02). This difference was observed primarily in patients with ventricular pacing >20% (25% in HBP vs. 36% in RVP; HR: 0.65; 95% CI: 0.456 to 0.927; p = 0.02). The incidence of HFH was significantly reduced in HBP (12.4% vs. 17.6%; HR: 0.63; 95% CI: 0.430 to 0.931; p = 0.02). There was a trend toward reduced mortality in HBP (17.2% vs. 21.4%, respectively; p = 0.06).

Conclusions

Permanent HBP was feasible and safe in a large real-world population requiring permanent pacemakers. His bundle pacing was associated with reduction in the combined endpoint of death, HFH, or upgrade to BiVP compared to RVP in patients requiring permanent pacemakers.



https://ift.tt/2rG9jZT

Ticagrelor and Central Sleep Apnea



https://ift.tt/2rHMx3I

The potential role of endocrine disrupting chemicals in cellulite

alertIcon.gif

Publication date: Available online 14 May 2018
Source:Medical Hypotheses
Author(s): Maria Mazioti
Cellulite constitutes a major aesthetic concern affecting the majority of post-adolescent women. Current epidemiological evidence supports that the prevalence of cellulite is significantly higher in industrialized societies indicating that environmental factors have crucial role in its pathogenesis and perpetuation. Endocrine disrupting chemicals, which exist ubiquitously in the environment, are able to alter hormonal and homeostatic systems. Several of them exert agonist effects by binding to estrogen receptors and mimicking the biological activity of estrogens. Since elevated estrogen concentration is prerequisite for cellulite, the present article suggests that endocrine disrupting chemicals may be key determinants in the initiation and deterioration of cellulite either by stimulating estrogen receptors or increasing their circulating levels due to interference with enzymes and binding proteins.



https://ift.tt/2KobpFg

Adverse effects of media reports on the treatment of osteoporosis

Abstract

Purpose

The review focused on the role that media reporting plays in the level of public awareness about osteoporosis and its influence on osteoporosis treatment decisions.

Methods

We reviewed the literature on the role of media on three main aspects influencing patient adherence to osteoporosis treatment: the awareness of osteoporosis as a major health problem, the perception of the effectiveness of osteoporosis medications, and the fear of adverse effects with osteoporosis medications.

Results

A review of the literature confirmed what is routinely observed in clinical practice—that media report can strongly influence the level of awareness of osteoporosis and fracture risk. Inadequate and/or incorrect information on osteoporosis in the media are associated with a low level of awareness of the disease. High-risk patients may have a poor understanding of the need for treatment. Alarming information in the media over the last 2 decades regarding effectiveness and safety of long-term osteoporosis treatment is associated with reduction in the use of osteoporosis medications.

Conclusions

There is a gap between the application of clinical recommendations and patient perceptions of osteoporosis and its treatment. There is a need for better education of patients and practitioners aimed at recognizing the serious consequences of fractures and understanding the expected benefits and potential risks of treatment. Media reports that disseminate evidence-based information on the balance of benefits and risks could help to reduce the osteoporosis treatment gap and mitigate the crisis in osteoporosis care.



https://ift.tt/2KZLzIU

Phenylmethimazole abrogates diet-induced inflammation, glucose intolerance and NAFLD

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of both metabolic and inflammatory diseases and has become the leading chronic liver disease worldwide. High-fat (HF) diets promote an increased uptake and storage of free fatty acids (FFAs) and triglycerides (TGs) in hepatocytes, which initiates steatosis and induces lipotoxicity, inflammation and insulin resistance. Activation and signaling of Toll-like receptor 4 (TLR4) by FFAs induces inflammation evident in NAFLD and insulin resistance. Currently, there are no effective treatments to specifically target inflammation associated with this disease. We have established the efficacy of phenylmethimazole (C10) to prevent lipopolysaccharide and palmitate-induced TLR4 signaling. Because TLR4 is a key mediator in pro-inflammatory responses, it is a potential therapeutic target for NAFLD. Here, we show that treatment with C10 inhibits HF diet-induced inflammation in both liver and mesenteric adipose tissue measured by a decrease in mRNA levels of pro-inflammatory cytokines. Additionally, C10 treatment improves glucose tolerance and hepatic steatosis despite the development of obesity due to HF diet feeding. Administration of C10 after 16 weeks of HF diet feeding reversed glucose intolerance, hepatic inflammation, and improved hepatic steatosis. Thus, our findings establish C10 as a potential therapeutic for the treatment of NAFLD.



https://ift.tt/2Ge6CnI

Estrogen receptor subtypes dictate the proliferative nature of the mammary gland

Estrogen induces proliferation of breast epithelial cells and is responsible for breast development at puberty. This tightly regulated control is lost in estrogen-receptor-positive (ER+) breast cancers, which comprise over 70% of all breast cancers. Currently, breast cancer diagnosis and treatment considers only the α isoform of ER; however, there is a second ER, ERβ. Whilst ERα mediates estrogen-driven proliferation of the normal breast in puberty and breast cancers, ERβ has been shown to exert an anti-proliferative effect on the normal breast. It is not known how the expression of each ER (alone or in combination) correlates with the ability of estrogen to induce proliferation in the breast. We assessed the levels of each ER in normal mouse mammary glands subdivided into proliferative and non-proliferative regions. ERα was most abundant in the proliferative regions of younger mice, with ERβ expressed most abundantly in old mice. We correlated this expression profile with function by showing that the ability of estrogen to induce proliferation was reduced in older mice. To show that the ER profile associated with breast cancer risk, we assessed ER expression in parous mice which are known to have a reduced risk of developing ERα breast cancer. ERα expression was significantly decreased yet co-localization analysis revealed ERβ expression increased with parity. Parous mice had less unopposed nuclear ERα expression and increased levels of ERβ. These changes suggest that the nuclear expression of ERs dictates the proliferative nature of the breast and may explain the decreased breast cancer risk with parity.



https://ift.tt/2jTsMCG

Characteristics and sources of ambient refractory black carbon aerosols: Insights from soot particle aerosol mass spectrometer

S13522310.gif

Publication date: July 2018
Source:Atmospheric Environment, Volume 185
Author(s): Junfeng Wang, Yangzhou Wu, Xinlei Ge, Yafei Shen, Shun Ge, Mindong Chen
This short communication investigated the characteristics and sources of refractory black carbon (rBC) aerosols using an Aerodyne soot-particle aerosol mass spectrometer (SP-AMS). The SP-AMS dataset acquired at suburban Nanjing observed carbon clusters (Cn+) up to n = 160, which was classified into three groups (low-C: C1+-C5+; mid-C: C6+-C31+; full-C (fullerenes): C32+-C160+). A simple method was first developed to reduce influences of organic molecules on the Cn+ signals. We found that the temporal variations of low-C and mid-C varied similarly, but were substantially different from full-C, indicating different source contributions. Furthermore, positive matrix factorization analyses showed that the C1+/C3+ ratios of traffic-, industry-, cooking-related rBC were 0.88, 1.29 and 0.01, respectively. We propose such C1+/C3+ ratios can be used as references to distinguish different sources for rBC in ambient conditions, yet further verifications with more field data are still required, and whether or not such ratios in rBC cores are stable upon atmospheric ageing remains to be elucidated.



https://ift.tt/2Ijc1eQ

N2O and CH4 emissions from N-fertilized rice paddy soil can be mitigated by wood vinegar application at an appropriate rate

alertIcon.gif

Publication date: July 2018
Source:Atmospheric Environment, Volume 185
Author(s): Haijun Sun, Yanfang Feng, Yang Ji, Weiming Shi, Linzhang Yang, Baoshan Xing
To understand the impacts of wood vinegar (WV), a by-product of biochar production, on N2O and CH4 emissions and their total global warming potential (GWPt) from N-fertilized rice paddy soil, a soil column experiment was conducted using three treatments: 240 kg urea-N ha−1 accompanied with 0, 5, and 10 t WV ha−1, respectively. Results showed that N2O and CH4 emission flux patterns were dominated by water regime of rice growth cycle, which was independent with WV application. The total N2O, CH4 emission loads and GWPt over rice season of three N received treatments were 6.41–8.85 kg ha−1, 127.7–405.0 kg ha−1, and 5.24–12.03 t CO2-e ha−1, respectively. Rice seasonal N2O and CH4 emissions were synchronously mitigated by 22.4% and 36.4%, respectively, when WV was applied at 5 t ha−1. Consequently, 5 t ha−1 WV treatment reduced 31.5% of GWPt compared with the urea treatment. In addition, 10 t ha−1 WV treatment exerted a more positive effect on suppressing N2O with 27.6% reduction. However, it increased GWPt by 57.2% because its CH4 emission load was increased by 101.8%. In conclusion, WV amendment applied at an appropriate rate (5 t ha−1) or combination with other CH4 control technologies were suggested to reduce both N2O and CH4 emissions and thereby the GWPt in N-fertilized rice paddy soil.



https://ift.tt/2IgDu51

Patterns of care analysis for head & neck cancer of unknown primary site: a survey inside the German society of radiation oncology (DEGRO)

Abstract

Background

Due to the absence of randomized trials, the optimal management for squamous cell cancer of unknown primary in the head and neck region (SCCHN CUP) remains controversial. Current strategies are based on retrospective studies, clinical experience, and institutional policies.

Methods

An anonymous questionnaire with a total of 24 questions was created and distributed by the use of an online version (Google Forms®, Google, Mountain View, CA, USA) as well as a printout version as equivalent option. An email with a link to the survey and the questionnaire as attachment was sent to 361 DEGRO(German Society of Radiation Oncology)-associated departments. Frequency distributions of responses for each question were calculated. The data were also analyzed by type of practice. Representativity of the sample size for the DEGRO was also evaluated.

Results

66 responses were received including answers from 20 (30%) university departments, 16 (24%) non-university institutions, and 30 (46%) radiation oncology practices. 95% of the participants routinely present these cases in an interdisciplinary tumor board and use intensity modulated radiotherapy (IMRT) techniques for SCCHN CUP treatment. Surgery includes neck dissection in 83% and tonsillectomy in 73% of the cases. Human papilloma virus (HPV) status is routinely determined in 82% of the departments. Statistically significant differences between universities and institutions and clinics and practices could be found with respect to positron emission tomography-computed tomography (PET-CT) utilization, indications for chemotherapy, radiotherapy volumes, and cumulative doses.

Conclusion

Diagnostics and treatment for SCCHN CUP within the DEGRO remain heterogeneous. A prospective register trial with standard operation procedures is warranted to homogenize and possibly improve management.



https://ift.tt/2IerdOp

Highly sensitive fluorescent detection of p53 protein based on DNA functionalized Fe3O4 nanoparticles

Publication date: 1 September 2018
Source:Talanta, Volume 187
Author(s): Qunfang Xu, Kaixin Liang, Ren-Yu Liu, Liu Deng, Min Zhang, Liangfang Shen, You-Nian Liu
The accurate quantification of p53 protein expression level is of great importance for cancer diagnosis. Here, a highly sensitive fluorescent sensor based on DNA functionalized magnetic nanoparticles was developed for the detection of p53 protein expression. Instead of a monoclonal antibody, a consensus DNA was employed to capture p53 protein. Meanwhile the fluorescent dye tethered DNA was used as the signal output instead of enzyme tagged nanoparticle or antibody. Consequently, our developed method is cost-effective for both the p53 capture and detection by compared with the conventional immunoassay. The biosensor developed by the above strategy was used to quantitatively detect p53, which yields a detection limit of 8 p.M. with the linear range of 50 p.M. to 2 nM. The sensitive for specific p53 detection was achieved due to the facile magnetic separation from the complex condition, and the reduced non-specific absorption effect by dextran. Moreover, the method is able to measure p53 from real cell lysate without extensive sample pretreatment/separation. The developed p53 biosensor has high sensitivity, good selectivity and reliable accuracy. It demonstrates great potential in clinical cancer diagnosis and early detection of cancer.

Graphical abstract

image


https://ift.tt/2GfdWiD

Αναζήτηση αυτού του ιστολογίου