Xerostomia Pilot Fudan: Acupuncture for Prevention of Radiation-Induced Xerostomia

Conditions:   Head and Neck Cancer;   Xerostomia
Intervention:   Other: Acupuncture
Sponsor:   M.D. Anderson Cancer Center
Recruiting - verified August 2017

http://ift.tt/2uWWlX7

Human Remains and Funerary Rites in the Phoenician Necropolis of Motya (Sicily)

Abstract

The aim of this paper is to examine the fresh evidence retrieved in the early cemetery or 'archaic necropolis' (8^th-6^th century BC) on the island of Motya, one of the main Phoenician colonies in the Mediterranean. Because of its integrity and the large number of finds, the cemetery has been considered one of the most relevant sites for the study of early burial customs in the West.

The absence of anthropological data, completely neglected in the past, was a major shortcoming of previous research. This failing is now being rectified by a new project of fieldwork and excavation undertaken on the island by a team from Palermo University.

This report provides a close examination of the human remains from a group of 32 graves discovered during three seasons (2013-2015) in a combined archaeological and taphonomic perspective, and contributes to shed light on the funerary practices of the Phoenicians in Sicily.

http://ift.tt/2uJuJFP

Xerostomia Pilot Fudan: Acupuncture for Prevention of Radiation-Induced Xerostomia

Conditions:   Head and Neck Cancer;   Xerostomia
Intervention:   Other: Acupuncture
Sponsor:   M.D. Anderson Cancer Center
Recruiting - verified August 2017

http://ift.tt/2uWWlX7

Pernambuco index: predictability of the complexity of surgery for impacted lower third molars

This study aimed to develop and validate an index of surgical difficulty for the removal of impacted lower third molars. The study was performed in two steps. The first was a cross-sectional analysis of clinical, demographic, and radiographic variables collected from patients undergoing the removal of an impacted lower third molar between 2008 and 2012. The second step was a prospective cohort study involving the same surgical procedures to validate the index; this was performed between 2013 and 2016.

http://ift.tt/2fH4LQy

The expression of endogenous hydrogen sulfide signal during distraction osteogenesis in a rabbit model

The hydrogen sulfide (H2S) signal system plays an important role in bone metabolism. However, the role of endogenous H2S during distraction osteogenesis (DO) remains unclear. Sixty-two male New Zealand White rabbits were subjected to right mandibular DO. Before distraction, the animals were divided randomly into two groups: group A, 0.5mm twice/day for 10 days; group B, 1.25mm twice/day for 4 days. Plasma and distraction gap tissue were harvested to determine the H2S signal. The osteogenesis effect was also evaluated.

http://ift.tt/2i0YIqF

Use of buccal cortex as interpositional graft in mandibular setbacks

The most commonly used options for mandibular fixation after sagittal split ramus osteotomy (SSRO) are monocortical plates and bicortical screws, which have comparable stability.1 We have recently changed our practice to the routine use of bicortical screws where possible, particularly for mandibular setbacks. They are faster to place and need to be removed less often than miniplates.2

http://ift.tt/2vyp0Fw

A matched-guise study on L2, heritage, and native Spanish speakers’ attitudes to Spanish in the State of Washington

By means of a matched-guise study, this paper examines the attitudes of L2, heritage, and native Spanish speakers in the state of Washington toward Mexican-accented and English-accented Spanish. We interpret our findings in the wake of previous research on language attitudes and ideologies related to Spanish in the United States which shows that Spanish and those who speak it as a first or heritage language are thought to have a lower socioeconomic status than English and Anglophones. 97 Spanish-speaking participants residing in Washington (N=95) and the Pacific Northwest (N=2) rated 4 voices along six-point semantic differential scales falling into the dimensions of superiority, solidarity, language competence, and physical characteristics. We submitted mean scores to a linear mixed-effects model. Contrary to our expectations, all groups rated the Mexican-accented guises higher than the English-accented guises in the dimension of superiority. Also unforeseen, the L2 speakers rated the Mexican-accented voices higher in the dimension of solidarity. We consider the high level of education of the respondents and, for the L2 subjects, their experience as advanced Spanish language speakers, as likely explanations for the observed attenuation of well-documented prevailing stereotypes directed at Latinos from the monolingual community at large.

http://ift.tt/2i19Tjk

Welsh English intonation and social identity

This paper is a sociophonetic study concerned with state-of-the-art description of Welsh English (WE) pitch patterns which may serve as WE regional and social markers. WE pitch patterns in authentic spontaneous conversations are correlated with social factors of regional and cultural background (North Wales, South Wales, Cardiff), generation of speakers (young, middle-aged, old), gender (men, women) and social class (middle, working). The data are compared to Received Pronunciation (RP) tone nomenclature (Crystal, 1969) in search of systemic (i.e. concerned with the total repertoire of tones in each variety), distributional and realisational differences. Within the identical tone systems a considerable difference in the distribution of certain WE pitch configurations is interpreted as the impact of the Welsh language. The data are further specified to the dominant pattern frequency in each region, age, gender and social class. Special reference is made to the acoustic structure of rise-falls in North Wales, which is a new subject of research.

http://ift.tt/2fGazcU

Langues de France et Charte européenne des langues régionales ou minoritaires: inventaire critique des arguments anti-ratification (2014-2015) [Languages of France and the European Charter for Regional or Minority Languages]

The deliberations in France surrounding the potential ratification of the European Charter for Regional or Minority Languages (from January 2014 to October 2015) resulted in a national debate unheard of since 1999, providing new insight into resistance towards promoting these languages in the public space. Despite a recent survey claiming that 'the ideological barriers on this issue have now almost disappeared', the virulent arguments opposing ratification eventually triumphed in the Senate. Basing ourselves on comments published in the media by a range of opponents to ratification of the Charter, we review here the various ideological strategies used to preserve the linguistic status quo in France and to maintain the supremacy of French.

http://ift.tt/2i1AzR2

Enoncés de type OV et positionnements sociaux dans l’espagnol parlé par les Quichuas équatoriens à Cali (Colombie) [OV constructions and stance in the Spanish spoken by Ecuadorian Quichuas in Cali (Columbia)]

Members of the indigenous Quichuan minority population living in Cali within an asymmetrical contact setting usually make use of linguistic marked elements from two varieties of Spanish which they speak: Andean Spanish and Spanish from Cali. One of these marked linguistic elements is OV syntactic constructions, highly frequent in Andean Spanish. A sequential conversation analysis shows that when Quichuas in Cali interact with someone outside the group, they may express differentiation through the use of OV constructions. Construed as a social positioning, this differentiation takes place in an act of stance (Du Bois 2002, 2007; Jaffe 2009; Johnstone 2009; Kiesling 2011) which arises with an evaluation of a referent in the discourse situation by a speaker, then triggers a social positioning that finally leads to a disalignment vis-à-vis another speaker. This article discusses the social effects of linguistic marked forms such as OV constructions in an understudied area (Cali, Colombia) within a field of research (Spanish-Quichua contact) that usually focuses on contact issues from a typological perspective.

http://ift.tt/2i08M3l

La pluralización de haber presentacional en el español peninsular: datos de Twitter [The pluralization of presentational haber in Peninsular Spanish: Data from Twitter]

In this paper we explore whether Twitter data can be used in dialectological studies of morphosyntactic alternations in Peninsular Spanish. Specifically, drawing on a corpus of tweets we evaluate the hypothesis that in Peninsular Spanish, as in Caribbean Spanish, the pluralization of presentational haber (e.g., había(n) fiestas 'there were parties') is constrained by two domain-general cognitive constraints on language production: markedness of coding and statistical preemption. Then, we analyze the geographic distribution of haber pluralization in Peninsular Spanish. The results show that haber is pluralized in 11% (N= 611/5,500) of the cases. The mixed-effects logistic regression analysis supports that nouns which can easily be imagined as starting points of a series of events, the absence of negation, and verb tenses other than the preterit favor pluralization. To explore the geographic distribution of haber pluralization in Peninsular Spanish, we use a generalized additive mixed model, which generates a line that runs approximately from Lérida in the north of Spain to Almería in the south, crossing Teruel and Albacete. East of that line, the pluralized variant has a higher probability of occurrence, but it is not absent from other areas of the Peninsula. We conclude that (i) haber pluralization in Peninsular Spanish is constrained by domain-general cognitive constraints on language production and that (ii) tweets constitute a viable alternative to spoken language data in dialectological studies of morphosyntactic variation.

http://ift.tt/2fHo9Nc

Common language in the workplace: An approach devoid of social perspective?

This paper puts under scrutiny a contemporary management tool called "common language". This concept derives both from the idea of "freedom" of speech in the workplace, as set up by the Auroux Act, and from the "participative" management approach that emerged in the early 1980s. "Common language" has been developed as part of corporate culture consisting in creating a common culture in which workers can identify themselves; the aim being to coordinate the workers' actions so they contribute to corporate success. We analyze "common language" as a theoretical construct within a corpus of corporate communication manuals. This study is multidisciplinary: it is mainly based on sociology, sociolinguistics and discourse analysis. We postulate that "common language" is a vision devoid of social perspective, based on an endemic culture where linguistic, cultural, historical and thus social questions are minimized. This interpretation leads us to question whether freedom of speech in the workplace is real or not. Indeed, in the corporate communication manuals studied, language at work is limited to a "theoretical reason". Ultimately, the rationalization of language in the workplace suggests a technological rationality close to classical management.

http://ift.tt/2i0wUTA

Prescriptivism, nation, and style: The role of nonclassical elements in the stylistic stratification of Modern Hebrew

Modern Hebrew (MH) presents an interesting case of a national language whose crystallisation involved not only intensive planning, but also unplanned processes of stratification, which has resulted in a continuous reevaluation and reallocation of existing features. The role of nonclassical inherited elements in this progression is revealing, as they emblematise popular 'authentic' usage on the one hand and diasporic (i.e. nonnative) premodern being on the other, thus exposing the tension between standard and nonstandard language. This study examines the stylistic status of two such elements, be'im 'if' and bixde 'for', 'in order', in two major phases in the short history of MH, in order to characterise the prescriptive discourse of MH and its national undertones.

http://ift.tt/2fHAcuh

Haitian Creole. Structure, Variation, Status, Origin. Albert Valdman (2015) Sheffield and Bristol, CT, Equinox ISBN 978-1845533885. Pp. 494

http://ift.tt/2i04NDU

Doing Sociolinguistics: A practical guide to data collection and analysis, Miriam Meyerhoff, Erik Schleef, and Laurel MacKenzie (2015) New York: Routledge ISBN: 9780415698207 (pbk). Pp. xxii + 190

http://ift.tt/2fHo7oy

Imprisoned in English: The Hazards of English as a Default Language, Anna Wierzbicka (2014) Oxford: Oxford University Press ISBN 978-0199321506 (pbk). Pp. xii + 287

http://ift.tt/2i0ZeF9

L2 Pragmatic Development in Study Abroad Contexts, Wei Ren (2015) Bern: Peter Lang; ISBN 1424-8689 (pbk). Pp. 256

http://ift.tt/2fHA9i5

Speak English or What? Codeswitching and Interpreter Use in New York City Courts. Philipp Sebastian Angermeyer (2015) [Oxford Studies in Language and Law] Oxford and New York: Oxford University Press ISBN 978-0-19-933756-9. Pp 248

http://ift.tt/2i0jwi4

The Handbook of Conversation Analysis, Jack Sidnell and Tanya Stivers (eds) (2013) Chichester, West Sussex, UK: Blackwell ISBN 978-1-4443-3208-7 (Hardback) Pp. 825

http://ift.tt/2w5vwFu

The Oxford Handbook of Sociolinguistics, Robert Bayley, Richard Cameron, and Ceil Lucas (eds) (2015), New York: Oxford University Press ISBN 9780190233747 Pp. 194

http://ift.tt/2vWBhoc

Cancer risks and survival in patients with multiple primary melanomas: Association with family history of melanoma and germline CDKN2A mutation status

Worse outcomes have been noted in patients with multiple primary melanomas (MPMs) than in patients with single primary melanomas.

http://ift.tt/2uIBZlc

Correction

Connolly KL, Nehal KS, Dusza SW, et al. Assessment of intraoperative pain during Mohs micrographic surgery (MMS): An opportunity for improved patient care. J Am Acad Dermatol. 2016;75(3):590-594.

http://ift.tt/2uJ18wg

Variations in risk of asthma and seasonal allergies between early- and late-onset pediatric atopic dermatitis: A cohort study

Atopic dermatitis is associated with other allergic conditions, but variations in this "atopic march" are poorly understood.

http://ift.tt/2w8zcFr

Use of the Hemangioma Severity Scale to facilitate treatment decisions for infantile hemangiomas

The Hemangioma Severity Scale (HSS) assesses the severity of an infantile hemangioma (IH).

http://ift.tt/2w8zLz4

Reflections of the Editor-in-Chief.

Author: Hill, Joseph A. MD, PhD

Page: 613-614

http://ift.tt/2vWDdNx

Charting Our Future Together: Turning Discovery Science Into Cardiovascular Health.

Author: Gibbons, Gary H. MD

Page: 615-617

http://ift.tt/2vDXW6o

Particulate Matter Exposure and Stress Hormone Levels: A Randomized, Double-Blind, Crossover Trial of Air Purification.

Author: Li, Huichu MS *; Cai, Jing PhD *; Chen, Renjie PhD; Zhao, Zhuohui PhD; Ying, Zhekang PhD; Wang, Lin PhD; Chen, Jianmin PhD; Hao, Ke ScD; Kinney, Patrick L. ScD; Chen, Honglei MD, PhD; Kan, Haidong MD, PhD

Page: 618-627

http://ift.tt/2vWqlqI

"Stressed" About Air Pollution: Time for Personal Action.

Author: Brook, Robert D. MD; Rajagopalan, Sanjay MD

Page: 628-631

http://ift.tt/2vDrwZC

Predictors and Association With Clinical Outcomes of the Changes in Exercise Capacity After Transcatheter Aortic Valve Replacement.

Author: Abdul-Jawad Altisent, Omar MD; Puri, Rishi MBBS, PhD; Regueiro, Ander MD; Chamandi, Chekrallah MD; Rodriguez-Gabella, Tania MD; del Trigo, Maria MD; Campelo-Parada, Francisco MD; Couture, Thomas MS; Marsal, Josep Ramon MSc; Cote, Melanie MSc; Paradis, Jean-Michel MD; DeLarochelliere, Robert MD; Doyle, Daniel MD; Mohammadi, Siamak MD; Dumont, Eric MD; Rodes-Cabau, Josep MD

Page: 632-643

http://ift.tt/2vWM2Ho

Walking as a Window to Risk and Resiliency.

Author: Alexander, Karen P. MD

Page: 644-645

http://ift.tt/2vDZjle

Potent Thrombolytic Effect of N-Acetylcysteine on Arterial Thrombi.

Author: Martinez de Lizarrondo, Sara PhD; Gakuba, Clement MD, PhD; Herbig, Bradley A. PhD; Repesse, Yohann PhD; Ali, Carine PhD; Denis, Cecile V. PhD; Lenting, Peter J. PhD; Touze, Emmanuel MD, PhD; Diamond, Scott L. PhD; Vivien, Denis PhD; Gauberti, Maxime PhD

Page: 646-660

http://ift.tt/2vWtkiR

Thrombolytic Potential of N-Acetylcysteine: Evidence for Significant Benefit in Mitigating Arterial Thrombosis.

Author: Lillicrap, David MD

Page: 661-663

http://ift.tt/2vDNCv0

Plasminogen Activator Inhibitor Type I Controls Cardiomyocyte Transforming Growth Factor-[beta] and Cardiac Fibrosis.

Author: Flevaris, Panagiotis MD, PhD; Khan, Sadiya S. MD, MS; Eren, Mesut PhD; Schuldt, Adam J. T. MD, PhD; Shah, Sanjiv J. MD; Lee, Daniel C. MD; Gupta, Sweta MD, MS; Shapiro, Amy D. MD; Burridge, Paul W. PhD; Ghosh, Asish K. PhD; Vaughan, Douglas E. MD

Page: 664-679

http://ift.tt/2vWKY6h

Cardiomyocyte Regeneration: A Consensus Statement.

Author: Eschenhagen, Thomas MD *; Bolli, Roberto MD; Braun, Thomas MD; Field, Loren J. PhD; Fleischmann, Bernd K. MD; Frisen, Jonas MD, PhD; Giacca, Mauro MD, PhD; Hare, Joshua M. MD; Houser, Steven PhD *; Lee, Richard T. MD; Marban, Eduardo MD; Martin, James F. MD, PhD; Molkentin, Jeffery D. PhD; Murry, Charles E. MD, PhD; Riley, Paul R. PhD; Ruiz-Lozano, Pilar PhD; Sadek, Hesham A. MD, PhD *; Sussman, Mark A. PhD; Hill, Joseph A. MD, PhD *

Page: 680-686

http://ift.tt/2vDruks

Eleventh Oriental Congress of Cardiology.

Author: Ge, Junbo MD

Page: 687-688

http://ift.tt/2vWIYec

From the Literature.

Author: Hampton, Tracy PhD

Page: 689-690

http://ift.tt/2vDXUeM

Acute Coronary Syndrome: What Is the Affected Artery? Where Is the Occlusion Located? And How Important Is the Myocardial Mass Involved?.

Author: Fiol-Sala, Miguel MD; Bayes de Luna, Antonio MD

Page: 691-693

http://ift.tt/2vWKXzf

Letter by Rowshani et al Regarding Article, "Gene Expression Profiling for the Identification and Classification of Antibody-Mediated Heart Rejection".

Author: Rowshani, Ajda T. MD, PhD; Caliskan, Kadir MD, PhD; von der Thusen, Jan H. MD, PhD

Page: 694-695

http://ift.tt/2vDNBXY

Letter by Moayedi et al Regarding Article, "Gene Expression Profiling for the Identification and Classification of Antibody-Mediated Heart Rejection".

Author: Moayedi, Yasbanoo MD; Duero Posada, Juan MD; Alhussein, Mosaad MD; Ross, Heather Joan MD, MHSc

Page: 696-697

http://ift.tt/2vWVpXw

Response by Loupy et al to Letters Regarding Article, "Gene Expression Profiling for the Identification and Classification of Antibody-Mediated Heart Rejection".

Author: Loupy, Alexandre MD, PhD; Hidalgo, Luis PhD; Duong, Jean Paul MD, PhD; Bruneval, Patrick MD, PhD; Jouven, Xavier MD, PhD; Halloran, Philip F. MD, PhD

Page: 698-699

http://ift.tt/2vDUF6X

American Heart Association's Call to Action for Payment and Delivery System Reform.

Author: Bufalino, Vincent J. MD, FAHA, Chair; Berkowitz, Scott A. MD, MBA; Gardner, Timothy J. MD, FAHA; Pina, Ileana L. MD, MPH, FAHA; Konig, Madeleine MPH; On behalf of the AHA Expert Panel on Payment and Delivery System Reform

Page: e162-e171

http://ift.tt/2vVVLxw

Lessons from CTLA-4 deficiency and checkpoint inhibition

Bernice Lo | Ussama M Abdel-Motal

http://ift.tt/2i0kkUb

Cancer vaccines in the era of checkpoint blockade: the magic is in the adjuvant

Willem W Overwijk

http://ift.tt/2fHrRXv

Transgelin expressing myofibroblasts orchestrate ventral midline closure through TGF-{beta} signalling [RESEARCH ARTICLE]

Bashar Aldeiri, Urmas Roostalu, Alessandra Albertini, Jason Wong, Antonino Morabito, and Giulio Cossu

Ventral body wall (VBW) defects are among the most common congenital malformations, yet their embryonic origin and underlying molecular mechanisms have remained poorly characterized. Although transforming growth factor beta (TGF-β) signalling is essential for VBW closure the responding cells are not known. Here we identify a population of migratory myofibroblasts at the leading edge of the closing VBW that express the actin-binding protein Transgelin (TAGLN) and TGF-β receptor (TGFβR). These cells respond to a temporally regulated TGF-β2 gradient originating from the epithelium of the primary body wall. Targeted elimination of TGFβR2 in TAGLN⁺ cells impairs midline closure and prevents the correct subsequent patterning of the musculature and skeletal components. Remarkably, deletion of TGFβR2 in myogenic or chondrogenic progenitor cells does not manifest in midline defects. Our results thus indicate a pivotal significance of VBW myofibroblast in orchestrating ventral midline closure by mediating the response to TGF-β gradient. Altogether, our data enables us to distinguish a highly regulated epithelial-mesenchymal signalling and successive cellular migration events in VBW closure that explain early morphological changes underlying the development of congenital VBW defects.

http://ift.tt/2w57nyJ

Differing contributions of the first and second pharyngeal arches to tympanic membrane formation in the mouse and chick [RESEARCH ARTICLE]

Toshiko Furutera, Masaki Takechi, Taro Kitazawa, Junko Takei, Takahiko Yamada, Tri Vu Hoang, Filippo M. Rijli, Hiroki Kurihara, Shigeru Kuratani, and Sachiko Iseki

We have proposed that independent origins of the tympanic membrane (TM), consisting of the external auditory meatus (EAM) and first pharyngeal pouch, are linked with distinctive middle ear structures in terms of dorsal-ventral patterning of the pharyngeal arches during amniote evolution. However, previous studies have suggested that the first pharyngeal arch (PA1) is crucial for TM formation in both the mouse and chick. In this study, we compare TM formation along the anterior-posterior axis in these animals using Hoxa2 expression as a marker of the second pharyngeal arch (PA2). In the chick, the EAM begins to invaginate at the surface ectoderm of PA2, not at the first pharyngeal cleft, and the entire TM forms in PA2. Chick-quail chimera that have lost PA2 and duplicated PA1 suggest that TM formation is achieved by developmental interaction between a portion of the EAM and the columella auris in PA2, and that PA1 also contributes to formation of the remaining part of the EAM. In contrast, in the mouse, TM formation highly associates with interdependent relationship between the EAM and tympanic ring in PA1.

http://ift.tt/2wZnAC2

H2Av facilitates H3S10 phosphorylation but is not required for heat shock-induced chromatin decondensation or transcriptional elongation [RESEARCH ARTICLE]

Yeran Li, Chao Wang, Weili Cai, Saheli Sengupta, Michael Zavortink, Huai Deng, Jack Girton, Jorgen Johansen, and Kristen M. Johansen

A model has been proposed where JIL-1 kinase-mediated H3S10 and H2Av phosphorylation is required for transcriptional elongation and heat shock-induced chromatin decondensation to occur. However, here we show that while H3S10 phosphorylation is indeed compromised in the H2Av null mutant we find that chromatin decondensation at heat shock loci is unaffected both in the absence of JIL-1 as well as of H2Av and that there is no discernable decrease in the elongating form of Pol II in either mutant. Furthermore, mRNA for the major heat shock protein Hsp70 is transcribed at robust levels in both H2Av and JIL-1 null mutants. Using a different chromatin remodeling paradigm that is JIL-1 dependent we provide evidence that ectopic tethering of JIL-1 and subsequent H3S10 phosphorylation recruits PARP-1 to the remodeling site independently of H2Av phosphorylation. Thus these data strongly suggest that H2Av or H3S10 phosphorylation by JIL-1 is not required for chromatin decondensation or transcriptional elongation in Drosophila.

http://ift.tt/2w5kmR4

Pitx1 directly modulates the core limb development program to implement hindlimb identity [RESEARCH ARTICLE]

Stephen Nemec, Maëva Luxey, Deepak Jain, Aurelie Huang Sung, Tomi Pastinen, and Jacques Drouin

Forelimbs (FL) and hindlimbs (HL) develop complex musculoskeletal structures that rely on the deployment of a conserved developmental program. Pitx1, a transcription factor gene with expression restricted to HL and absent from FL, plays an important role in generating HL features. The genomic mechanisms by which Pitx1 effects HL identity remain poorly understood, however. Here, we use expression profiling and analysis of direct Pitx1 targets to characterize the HL- and FL-restricted genetic programs and situate the Pitx1-dependent gene network within the context of limb-specific gene regulation. We show that Pitx1 is a critical component of a narrow network of HL-restricted regulators, acting on a developmental program that is shared between FL and HL. Pitx1 targets sites that are in a similar chromatin state in FL and HL and controls expression of patterning genes as well as the chondrogenic program, consistent with impaired chondrogenesis in Pitx1-/- HL. These findings support a model in which multifactorial actions of a limited number of HL regulators redirect the generic limb development program in order to generate the limb's unique structural features.

http://ift.tt/2wZ8Lz7

Hypothalamic sonic hedgehog is required for cell specification and proliferation of LHX3/LHX4 pituitary embryonic precursors [RESEARCH ARTICLE]

G. Carreno, J. Apps, E. J. Lodge, L. Panousopoulos, S. Haston, J. M. Gonzalez-Meljem, H. Hahn, C. L. Andoniadou, and J. P. Martinez-Barbera

Sonic hedgehog (SHH) is an essential morphogenetic signal dictating cell fate decisions in several developing organs in mammals. In vitro data suggest that SHH is required to specify LHX3+/LHX4+ Rathke's pouch (RP) progenitor identity. However, in vivo studies have failed to reveal such a function, supporting instead, a critical role for SHH in promoting proliferation of these RP progenitors and for differentiation of pituitary cell types. Here, we have used a genetic approach to demonstrate that activation of the SHH pathway is necessary to induce LHX3+/LHX4+ RP identity in mouse embryos. First, we show that conditional deletion of Shh in the anterior hypothalamus results in a fully penetrant phenotype characterised by a complete arrest of RP development, with lack of Lhx3/Lhx4 expression in RP epithelium at 9.0 dpc (days post coitum) and total loss of pituitary tissue by 12.5 dpc. Conversely, over-activation of the SHH pathway by conditional deletion of Ptch1 in RP progenitors leads to severe hyperplasia and enlargement of the Sox2+ve stem cell compartment by the end of gestation.

http://ift.tt/2w5pLHM

Heart morphogenesis gene regulatory networks revealed by temporal expression analysis [RESEARCH ARTICLE]

Jonathon T. Hill, Bradley Demarest, Megan Smith, Bushra Gorsi, and H. Joseph Yost

During embryogenesis, the heart forms as a linear tube that then undergoes multiple simultaneous morphogenetic events to obtain its mature shape. To understand the gene regulatory networks (GRNs) driving this phase of heart development, during which many congenital heart disease malformations likely arise, we conducted an RNA-seq time course in zebrafish from 30 hpf to 72 hpf and identified 5,861 genes with altered expression. We then clustered the genes by temporal expression pattern, identified transcription factor binding motifs enriched in each cluster, and generated a model GRN for the major gene batteries in heart morphogenesis. This approach predicted hundreds of regulatory interactions and found batteries enriched in specific cell and tissue types, indicating that the approach can be used to narrow the search for novel genetic markers and regulatory interactions. Subsequent analyses confirmed the GRN using two mutants, Tbx5 and Nkx2-5, and identified sets of duplicated zebrafish genes that do not show temporal subfunctionalization. This dataset provides an essential resource for future studies on the genetic/epigenetic pathways implicated in congenital heart defects and the mechanisms of cardiac transcriptional regulation.

http://ift.tt/2wZ2Fib

Fgf10+ progenitors give rise to the chick hypothalamus by rostral and caudal growth and differentiation [RESEARCH ARTICLE]

Travis Fu, Matthew Towers, and Marysia Placzek

Classical descriptions of the hypothalamus divide it into three rostro-caudal domains but little is known about their embryonic origins. To investigate this we performed targeted fate-mapping, molecular characterisation and cell cycle analyses in the embryonic chick. Presumptive hypothalamic cells derive from the rostral diencephalic ventral midline, lie above the prechordal mesendoderm and express Fgf10. Fgf10⁺ progenitors undergo anisotropic growth: those displaced rostrally differentiate into anterior cells, then those displaced caudally differentiate into mammillary cells. A stable population of Fgf10⁺ progenitors is retained within the tuberal domain, a subset of these give rise to the tuberal infundibulum, the precursor of the posterior pituitary. Pharmacological approaches reveal that Shh signalling promotes the growth and differentiation of anterior progenitors and also orchestrates the development of the infundibulum and Rathke's pouch, the precursor of the anterior pituitary. Together our studies identify a hypothalamic progenitor population defined by Fgf10 and highlight a role for Shh signalling in the integrated development of the hypothalamus and pituitary.

http://ift.tt/2w5octx

Cytoplasmic poly (A) binding protein (PABPC2) critically regulates epidermal maintenance and turnover in planarian Schmidtea mediterranea [RESEARCH ARTICLE]

Dhiru Bansal, Jahnavi Kulkarni, Kavana Nadahalli, Vairavan Lakshmanan, Srikar Krishna, Vidyanand Sasidharan, Jini Geo, Shilpa Dilipkumar, Renu Pasricha, Akash Gulyani, Srikala Raghavan, and Dasaradhi Palakodeti

Identifying key cellular events that facilitate stem cell function and tissue organization is critical for understanding the process of regeneration. Planarians are powerful model system to study regeneration and stem cell (neoblast) function. Here, using planaria, we show that the initial events of regeneration, such as epithelialization and epidermal organization are critically regulated by a novel cytoplasmic Poly A binding protein, SMED-PABPC2. Knockdown (KD) of Smed-pabpc2 leads to defects in epidermal lineage specification, disorganization of epidermis and ECM, and deregulated wound healing resulting in the selective failure of neoblast proliferation near the wound region. Polysome profiling suggested epidermal lineage transcripts, including zfp-1, to be translationally regulated by SMED-PABPC2. Together, our results uncover a novel role of SMED-PABPC2 in the maintenance of epidermal and ECM integrity, critical for wound healing, and subsequent processes for regeneration.

http://ift.tt/2wZbRTO

The miR-124 family of microRNAs is critical for regeneration of the brain and visual system in the planarian Schmidtea mediterranea [RESEARCH ARTICLE]

Sasidharan Vidyanand, Srujan Marepally, Sarah A. Elliott, Srishti Baid, Vairavan Lakshmanan, Nishtha Nayyar, Dhiru Bansal, Alejandro Sanchez Alvarado, Praveen Kumar Vemula, and Dasaradhi Palakodeti

Brain regeneration in planarians is mediated by precise spatiotemporal control of gene expression and is critical for multiple aspects of neurogenesis. However, the mechanisms underpinning the gene regulation essential for brain regeneration are largely unknown. Here, we investigated the role of the miR-124 family of microRNAs in planarian brain regeneration. The miR-124 family (miR-124) is highly conserved in animals and it regulates neurogenesis by facilitating neural differentiation. Yet, its role in neural wiring and brain organization is not known. In this study, we developed a novel method for delivering anti-miRs using liposomes for the functional knockdown (KD) of microRNAs. KD of Smed-miR-124 revealed a critical role for these miRNAs in neuronal organization during planarian brain regeneration. Our results also demonstrated an essential role for miR-124 in the generation of eye progenitors. Additionally, miR-124 regulates Smed-slit-1, an axon guidance protein, either by targeting slit-1 mRNA or by potentially modulating the canonical Notch pathway. Together, our results reveal a role for miR-124 in regulating the regeneration of a functional brain and visual system.

http://ift.tt/2w5rUD4

Are Disagreements in Caregiver and Patient Assessment of Patient Health Associated with Increased Caregiver Burden in Caregivers of Older Adults with Cancer?

AbstractBackground.As patients age, caregivers increasingly provide essential support and patient information. We sought to determine if patient‐caregiver assessments of patient health differ and if differences contribute to burden in caregivers of older adults with cancer.Materials and Methods.One hundred patients, aged ≥65, and their caregivers independently assessed patient function, comorbidity, nutrition, social activity, social support, and mental health. Caregivers completed the Caregiver Strain Index (CSI). Patient‐caregiver assessments were compared using the Wilcoxon signed rank test and paired t test. Association between caregiver burden and differences between patient‐caregiver assessments was examined using generalized linear regression.Results.Median patient age was 70 (range 65–91) and 70% had advanced disease. Sixty percent of patients reported requiring help with instrumental activities of daily living (IADLs); most had good social support (median Medical Outcomes Study [MOS]‐Social Support Survey score 92) and mental health (median Mental Health Inventory score 85).Caregivers were a median age of 66 (range 28–85), 73% female, 68% spousal caregivers, and 79% lived with the patient. Caregivers rated patients as having poorer physical function (more IADLs dependency [p = .008], lower Karnofsky Performance Status [p = .02], lower MOS‐Physical Function [p < .0001]), poorer mental health (p = .0002), and having more social support (p = .03) than patients themselves. Three‐quarters of caregivers experienced some caregiver burden (mean CSI score 3.1). Only differences in patient‐caregiver assessment of the patient's need for help with IADLs were associated with increased caregiver burden (p = .03).Conclusion.Patient‐caregiver assessments of patient function, mental health, and social support differ. However, only differences in assessment of IADLs dependency were associated with increased caregiver burden.Implications for Practice.As patients age, there is a higher incidence of frailty and cognitive impairments. As a result, caregivers play an increasingly vital role in providing information about patient health to healthcare providers, which is used to help healthcare providers tailor treatments and optimize patient health. These findings highlight that caregiver reporting in older adults with cancer may not replace patient reporting in those older adults who are otherwise able to self‐report. Furthermore, clinicians should check for caregiver burden in caregivers who report providing more help with instrumental activities of daily living than patients themselves report and provide appropriate support as needed.

http://ift.tt/2wZoNZU

Characterization of the human thyroid epigenome

The thyroid gland, necessary for normal human growth and development, functions as an essential regulator of metabolism by the production and secretion of appropriate levels of thyroid hormone. However, assessment of abnormal thyroid function may be challenging suggesting a more fundamental understanding of normal function is needed. One way to characterize normal gland function is to study the epigenome and resulting transcriptome within its constituent cells. This study generates the first published reference epigenomes for human thyroid from four individuals using ChIP-seq and RNA-seq. We profiled six histone modifications (H3K4me1, H3K4me3, H3K27ac, H3K36me3, H3K9me3, H3K27me3) identified chromatin states using a hidden Markov model, produced a novel quantitative metric for model selection, and established epigenomic maps of 19 chromatin states. We found that epigenetic features characterizing promoters and transcription elongation tend to be more consistent than regions characterizing enhancers or Polycomb repressed regions and that epigenetically active genes consistent across all epigenomes tend to have higher expression than those not marked as epigenetically active in all epigenomes. We also identified a set of 18 genes epigenetically active and consistently expressed in the thyroid that are likely highly relevant to thyroid function. Altogether, these epigenomes represent a powerful resource to develop a deeper understanding of the underlying molecular biology of thyroid function and provide contextual information of thyroid and human epigenomic data for comparison and integration into future studies.

http://ift.tt/2vDIJSV

The impact of IUGR on pancreatic islet development and {beta}-cell function

Placental insufficiency is a primary cause of intrauterine growth restriction (IUGR). IUGR increases the risk of developing type 2 diabetes mellitus (T2DM) throughout life, which indicates that insults from placental insufficiency impair β-cell development during the perinatal period because β-cells have a central role in the regulation of glucose tolerance. The severely IUGR fetal pancreas is characterized by smaller islets, less β-cells, and lower insulin secretion. Because of the important associations among impaired islet growth, β-cell dysfunction, impaired fetal growth, and the propensity for T2DM, significant progress has been made in understanding the pathophysiology of IUGR and programing events in the fetal endocrine pancreas. Animal models of IUGR replicate many of the observations in severe cases of human IUGR and allow us to refine our understanding of the pathophysiology of developmental and functional defects in islet from IUGR fetuses. Almost all models demonstrate a phenotype of progressive loss of β-cell mass and impaired β-cell function. This review will first provide evidence of impaired human islet development and β-cell function associated with IUGR and the impact on glucose homeostasis including the development of glucose intolerance and diabetes in adulthood. We then discuss evidence for the mechanisms regulating β-cell mass and insulin secretion in the IUGR fetus, including the role of hypoxia, catecholamines, nutrients, growth factors, and pancreatic vascularity. We focus on recent evidence from experimental interventions in established models of IUGR to understand better the pathophysiological mechanisms linking placental insufficiency with impaired islet development and β-cell function.

http://ift.tt/2vW7L1P

Barbed snore surgery for concentric at the velum collapse: the Alianza technique

Recently, new conservative and non-resective surgical techniques, including palatopharyngeal surgical lifting and suspension (the 'Roman blinds technique') and modular barbed snore surgery (MBSS), have been successfully introduced for the treatment of obstructive sleep apnea syndrome (OSAS). This pilot longitudinal study describes our preliminary experience with the 'Alianza technique' (the simultaneous use of Roman blinds and MBSS) in mild to moderate OSAS patients with concentric pharyngeal collapse at the velum, previously documented by means of drug-induced sleep endoscopy.

http://ift.tt/2uInkqp

Influence of ignited sediments on external phosphorus adsorption and sedimentary phosphorus forms

Abstract

Phosphorus (P) adsorpted by sediments, when covered by and mixed with ignited sediments from Meiliang Bay in Tai Lake, was analyzed in the laboratory. Potassium dihydrogen phosphate (KH₂PO₄) was added to the parallel experimental units to simulate periodic external P input. Based on the Langmuir model, the sediments after ignition had a greater S_max (maximum P adsorption), a lower equilibrium phosphorus concentration at zero adsorption (EPC₀), and a lower degree of phosphorus saturation in comparison with sediments without ignition. This was confirmed by the variation in the dissolved inorganic phosphorus in the overlying water. When sediments were mixed with or covered by the ignited sediments, 5.985 and 5.978 mg of input P disappeared from the overlying water, respectively. However, when the sediments were mixed with the ignited sediments, 84.18% of the input P was converted to HCl-P, whereas when they were covered by the ignited sediments, sedimentary P was released, mainly from Fe/Al-P (up to 87.50%). This was attributed to differences in the microenvironments where less-intense anaerobic conditions were formed in the mixed sediments than in the sediments covered by the ignited sediments. This suggests that the injection of ignited sediments into existing sediments enhances their P adsorption and retention. It is favor of the control of the eutrophication with a simple technology.

http://ift.tt/2w4Y4yI

Chest circumference and birth weight are good predictors of lung function in preschool children from an e-waste recycling area

Abstract

The purpose of this study was to investigate the associations between birth weight, chest circumference, and lung function in preschool children from e-waste exposure area. A total of 206 preschool children from Guiyu (an e-waste recycling area) and Haojiang and Xiashan (the reference areas) in China were recruited and required to undergo physical examination, blood tests, and lung function tests during the study period. Birth outcome such as birth weight and birth height were obtained by questionnaire. Children living in the e-waste-exposed area have a lower birth weight, chest circumference, height, and lung function when compare to their peers from the reference areas (all p value <0.05). Both Spearman and partial correlation analyses showed that birth weight and chest circumference were positively correlated with lung function levels including forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV₁). After adjustment for the potential confounders in further linear regression analyses, birth weight, and chest circumference were positively associated with lung function levels, respectively. Taken together, birth weight and chest circumference may be good predictors for lung function levels in preschool children.

http://ift.tt/2wZ2hAy

HIV status and hearing loss among children between 6 and 12 years of age at a large urban health facility in south western Uganda

Pediatric HIV infection and treatment may increase the risk for hearing loss (HL), both sensorineural (SNHL) and conductive hearing loss (CHL). There is limited data on this subject, especially from sub Saharan Africa. The aim of this study was therefore to compare the prevalence of hearing loss among HIV positive and negative children, to determine the types of hearing loss and whether Nevirapine (NVP) based antiretroviral therapy (ART) is associated with HL.

http://ift.tt/2vWjXjt

Indicators of Dysphagia in Aged Care Facilities

Purpose

The current cross-sectional study aimed to investigate risk factors for dysphagia in elderly individuals in aged care facilities.

Method

A total of 878 individuals from 42 aged care facilities were recruited for this study. The dependent outcome was speech therapist-determined swallowing function. Independent factors were Eating Assessment Tool score, oral motor assessment score, Mini-Mental State Examination, medical history, and various functional status ratings. Binomial logistic regression was used to identify independent variables associated with dysphagia in this cohort.

Results

Two statistical models were constructed. Model 1 used variables from case files without the need for hands-on assessment, and Model 2 used variables that could be obtained from hands-on assessment. Variables positively associated with dysphagia identified in Model 1 were male gender, total dependence for activities of daily living, need for feeding assistance, mobility, requiring assistance walking or using a wheelchair, and history of pneumonia. Variables positively associated with dysphagia identified in Model 2 were Mini-Mental State Examination score, edentulousness, and oral motor assessments score.

Conclusions

Cognitive function, dentition, and oral motor function are significant indicators associated with the presence of swallowing in the elderly. When assessing the frail elderly, case file information can help clinicians identify frail elderly individuals who may be suffering from dysphagia.

http://article/doi/10.1044/2017_JSLHR-S-17-0028/2649235/Indicators-of-Dysphagia-in-Aged-Care-Facilities

The Effect of Dynamic Pitch on Speech Recognition in Temporally Modulated Noise

Purpose

This study investigated the effect of dynamic pitch in target speech on older and younger listeners' speech recognition in temporally modulated noise. First, we examined whether the benefit from dynamic-pitch cues depends on the temporal modulation of noise. Second, we tested whether older listeners can benefit from dynamic-pitch cues for speech recognition in noise. Last, we explored the individual factors that predict the amount of dynamic-pitch benefit for speech recognition in noise.

Method

Younger listeners with normal hearing and older listeners with varying levels of hearing sensitivity participated in the study, in which speech reception thresholds were measured with sentences in nonspeech noise.

Results

The younger listeners benefited more from dynamic pitch for speech recognition in temporally modulated noise than unmodulated noise. Older listeners were able to benefit from the dynamic-pitch cues but received less benefit from noise modulation than the younger listeners. For those older listeners with hearing loss, the amount of hearing loss strongly predicted the dynamic-pitch benefit for speech recognition in noise.

Conclusions

Dynamic-pitch cues aid speech recognition in noise, particularly when noise has temporal modulation. Hearing loss negatively affects the dynamic-pitch benefit to older listeners with significant hearing loss.

http://article/doi/10.1044/2017_JSLHR-H-16-0389/2648979/The-Effect-of-Dynamic-Pitch-on-Speech-Recognition

Alveolar and Postalveolar Voiceless Fricative and Affricate Productions of Spanish–English Bilingual Children With Cochlear Implants

Purpose

This study investigates the production of voiceless alveolar and postalveolar fricatives and affricates by bilingual and monolingual children with hearing loss who use cochlear implants (CIs) and their peers with normal hearing (NH).

Method

Fifty-four children participated in our study, including 12 Spanish–English bilingual CI users (M = 6;0 [years;months]), 12 monolingual English-speaking children with CIs (M = 6;1), 20 bilingual children with NH (M = 6;5), and 10 monolingual English-speaking children with NH (M = 5;10). Picture elicitation targeting /s/, /tʃ/, and /ʃ/ was administered. Repeated-measures analyses of variance comparing group means for frication duration, rise time, and centroid frequency were conducted for the effects of CI use and bilingualism.

Results

All groups distinguished the target sounds in the 3 acoustic parameters examined. Regarding frication duration and rise time, the Spanish productions of bilingual children with CIs differed from their bilingual peers with NH. English frication duration patterns for bilingual versus monolingual CI users also differed. Centroid frequency was a stronger place cue for children with NH than for children with CIs.

Conclusion

Patterns of fricative and affricate production display effects of bilingualism and diminished signal, yielding unique patterns for bilingual and monolingual CI users.

http://article/doi/10.1044/2017_JSLHR-S-16-0125/2648980/Alveolar-and-Postalveolar-Voiceless-Fricative-and

Physicochemical and adsorptive characteristics of activated carbons from waste polyester textiles utilizing MgO template method

Abstract

Activated carbons with high specific surface areas were produced, utilizing waste polyester textiles as carbon precursor by magnesium oxide (MgO) template method. Magnesium chloride (MgCl₂), magnesium citrate (MgCi), and MgO were employed as MgO precursors to prepare activated carbons (AC-MgCl₂, AC-MgCi, and AC-MgO). Thermogravimetry-differential scanning calorimetry was conducted to investigate the pore-forming mechanism, and N₂ adsorption/desorption isotherms, XRD, SEM-EDS, TEM, FTIR and pH_pzc were achieved to analyze physicochemical characteristics of the samples. The specific surface areas of AC-MgCl₂ (1173 m²/g) and AC-MgCi (1336 m²/g) were much higher than that of AC-MgO (450 m²/g), and the pores sizes of which were micro-mesoporous, mesoporous, and macropores, respectively, due to the formation of MgO crystal with different sizes. All activated carbons had abundant acidic oxygen groups. In addition, batch adsorption experiments were carried out to investigate the adsorptive characteristics of the prepared activated carbons toward Cr(VI). The adsorption kinetics fitted well with the pseudo-second order, and the adsorptive capacity of AC-MgCl₂ (42.55 mg/g) was higher than those of AC-MgCi (40.93 mg/g) and AC-MgO (35.87 mg/g).

http://ift.tt/2uIOGMI

A pilot study comparing T-regulatory cell function among healthy children in different areas of Gansu, China

Abstract

Immune system is critical to protecting human health from toxic substances. Our previously published research had found an important link between polycyclic aromatic hydrocarbons (PAHs) in ambient air and changes at the DNA level in immune cells that led to impaired function of regulatory T (Treg) cells in children living in California, USA. But molecular and cellular pathways of these changes remain unclear. The present study aims to explore whether exposure to PAHs leads to changes in Treg cells functions of children living in Gansu, China, where ambient air pollution levels are much higher than those in California, and to explore potential mechanisms of PAH-induced immunological dysfunctions. Air pollutions in Lanzhou and Lintao, Gansu Province, were measured from December 2015 to June 2016. Healthy children were recruited from both cities and enrolled in this pilot study. Demographic information was collected by questionnaires. Blood samples were collected. Peripheral blood Treg cells were analyzed for Treg cells percentage by flow cytometry. Gene expression of forkhead box transcription factor 3 (Foxp3), transforming growth factor-β (TGF-β), and interleukin 35 (IL35) were examined by reverse transcription-polymerase chain reaction (RT-PCR). The results indicated PAH concentration (as sum of 16 PAHs) in Lintao was over two times higher than that was in Lanzhou (707 vs. 326 ng/m³), whereas PM_2.5 concentration was comparable in two cities (55.3 in Lintao vs. 65.7 μg/m³ in Lanzhou). Notably, we observed lower gene expressions for Foxp3 (P < 0.05), IL35 (P < 0.05), and TGF-β, in children living in Lintao, suggesting an impairment of Treg cells function potentially associated with higher PAH exposure in Lintao. However, no significant difference was observed in Treg cells % among CD4⁺ T cells between Lanzhou and Lintao groups.

http://ift.tt/2w7KwSo

Assessing landscape and contaminant point-sources as spatial determinants of water quality in the Vermilion River System, Ontario, Canada

Abstract

The Vermilion River and major tributaries (VRMT) are located in the Vermilion watershed (4272 km²) in north-central Ontario, Canada. This watershed not only is dominated by natural land-cover but also has a legacy of mining and other development activities. The VRMT receive various point (e.g., sewage effluent) and non-point (e.g., mining activity runoff) inputs, in addition to flow regulation features. Further development in the Vermilion watershed has been proposed, raising concerns about cumulative impacts to ecosystem health in the VRMT. Due to the lack of historical assessments on riverine-health in the VRMT, a comprehensive suite of water quality parameters was collected monthly at 28 sites during the ice-free period of 2013 and 2014. Canadian water quality guidelines and objectives were not met by an assortment of water quality parameters, including nutrients and metals. This demonstrates that the VRMT is an impacted system with several pollution hotspots, particularly downstream of wastewater treatment facilities. Water quality throughout the river system appeared to be influenced by three distinct land-cover categories: forest, barren, and agriculture. Three spatial pathway models (geographical, topographical, and river network) were employed to assess the complex interactions between spatial pathways, stressors, and water quality condition. Topographical landscape analyses were performed at five different scales, where the strongest relationships between water quality and land-use occurred at the catchment scale. Sites on the main stem of Junction Creek, a tributary impacted by industrial and urban development, had above average concentrations for the majority of water quality parameters measured, including metals and nitrogen. The river network pathway (i.e., asymmetric eigenvector map (AEM)) and topographical feature (i.e., catchment land-use) models explained most of the variation in water quality (62.2%), indicating that they may be useful tools in assessing the spatial determinants of water quality decline.

http://ift.tt/2uIaOao

Comparison of Live Rat Femoral Artery Model with Intraoperative Microvascular Anastomosis

J reconstr Microsurg
DOI: 10.1055/s-0037-1605378

Background The live rat femoral artery model is the gold standard in high-fidelity simulation for microvascular anastomosis worldwide. Despite widespread use, there is a paucity of evidence for its validity. This study aims to determine the correlation between microvascular anastomosis in the live rat femoral artery model and clinical performance. Methods Twenty-nine microsurgical fellows were included in the study. At the beginning and end of the 1-year fellowship, fellows were assessed performing arterial microvascular anastomoses in the laboratory in a live rat femoral artery model. Each procedure was digitally video recorded and blinded. Fellows were also assessed in the operating room at the beginning and end of training performing microvascular anastomoses in multiple free flap cases. Validated tools were used for assessment, and duration of procedure was also recorded. The results from the evaluations were compared and interfellow comparisons were performed. Results At both the beginning and end of the fellowship, there was no significant correlation between clinical performance evaluations during operating room cases and laboratory evaluations. In the laboratory, higher performance scores were associated with faster times at both the beginning and end of the fellowship. Conclusion Contrary to conventional wisdom, microsurgical skill in the live rat femoral artery model in the laboratory does not correlate with clinical performance in the operating room. This calls into question the utility of this model for training purposes. Further research is necessary to corroborate these results and potentially establish experimental models with greater validity and reliability.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Effect of Monopolar Cutting Mode against Bipolar Diathermy on Surgical Dissection of Microvessels

J reconstr Microsurg
DOI: 10.1055/s-0037-1604438

Background An ideal vessel dissection will be to maximize bleeding control through coagulation while minimizing vessel damage. Among the diathermy methods, there has been no report comparing the effect on vessels. This study aims to verify the effect of bipolar diathermy against monopolar diathermy cutting mode for vessel dissection. Methods A total of 18 Sprague–Dawley rats were divided into three groups according to the method of pedicle dissection for 6 × 6 cm sized abdominal flap; (group 0) surgical scissors, (group 1) monopolar diathermy cutting mode and (group 2) bipolar diathermy. They were evaluated for the temperature of device tip and the radiating heat to the surrounding tissue, change in vessel diameter, flow velocity, and perfusion to the skin flap during dissection. Final flap survival rate and pathology of the vessels were also evaluated. Results Significantly higher radiating heat was observed using bipolar diathermy (average: 37.5°C) compared with group using monopolar diathermy (average: 34.4°C) (p value 0.045). However, there were no differences in vessel diameter, skin flap perfusion, flow velocity, and flap survival rate among the groups. Conclusions Both monopolar diathermy cutting mode and bipolar diathermy are safe to use to dissect the pedicle vessels when used adequately. Although it has no significant difference in relations to flap survival, vessel spasm, and perfusion/velocity to the flap, the extent of histologic damage may be less in monopolar diathermy cutting mode. Using monopolar diathermy cutting mode may provide efficiency to achieve ligation in small vessels during pedicle dissection but requires finesse technique and a learning curve.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2i1qumS

How novel structures inform understanding of complement function

Abstract

During the last decade, the complement field has experienced outstanding advancements in the mechanistic understanding of how complement activators are recognized, what C3 activation means, how protein complexes like the C3 convertases and the membrane attack complex are assembled, and how positive and negative complement regulators perform their function. All of this has been made possible mostly because of the contributions of structural biology to the study of the complement components. The wealth of novel structural data has frequently provided support to previously held knowledge, but often has added alternative and unexpected insights into complement function. Here, we will review some of these findings focusing in the alternative and terminal complement pathways.

http://ift.tt/2wYCt7w

Presidential Health: Secrets, Surprises, and Controversies

How much do you know about the history of presidential health?
Medscape Family Medicine

http://ift.tt/2fFjkE4

Omalizumab Benefits Patients With Chronic Inducible Urticaria

The recombinant anti-immunoglobulin E (IgE) monoclonal antibody omalizumab has 'substantial benefits' in treating various forms of chronic inducible urticaria (CIndU), according to a new systematic review.
Reuters Health Information

http://ift.tt/2uMMKly

Monoclonal Antibody 5F11G11

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy Aug 2017, Vol. 36, No. 4: 196-197.


http://ift.tt/2vCVJIa

Monoclonal Antibody 1C11 Mouse Monoclonal Antibody Against Mortalin

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy Aug 2017, Vol. 36, No. 4: 192-193.


http://ift.tt/2vWngHi

Expression, Purification, and Refolding of Human Lipocalin 6 and Production of a Monoclonal Antibody Against This Protein

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy Aug 2017, Vol. 36, No. 4: 185-191.


http://ift.tt/2vDp9pQ

Chicken HMGB1 Monoclonal Antibody

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy Aug 2017, Vol. 36, No. 4: 194-195.


http://ift.tt/2vVJSre

Establishment of a Monoclonal Antibody Against chGILZ

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy Aug 2017, Vol. 36, No. 4: 176-180.


http://ift.tt/2vCLhR5

Insomnia in Primary Care: Misreported, Mishandled, and Just Plain Missed

http://ift.tt/2uVFCUa

Change in End-Expiratory Lung Volume During Sleep in Patients at Risk for Obstructive Sleep Apnea

Study Objectives:

As lung volume decreases radial traction on the upper airway is reduced, making it more collapsible. The purpose of this study was to measure change in end-expiratory lung volume (EELV) following sleep onset and to evaluate the relationship between change in EELV and sleep-disordered breathing.

Methods:

Twenty subjects underwent overnight polysomnography, of whom 14 (70%) had obstructive sleep apnea (OSA). Change in EELV was measured throughout the night using magnetometry. Sleep was staged and respiratory events scored using American Academy of Sleep Medicine criteria. An additional 10 subjects had change in EELV measured simultaneously by magnetometer and spirometer while awake.

Results:

In the subjects studied while awake, change in EELV calculated from magnetometer data correlated very strongly (r = 0.89, P < .001) with that obtained by spirometry. In the 20 subjects who underwent polysomnography, there was a decline in EELV for sleep stages N1, N2, N3, and R (REM sleep); 17.9 ± 121.0 mL (mean ± standard deviation), 228.5 ± 151.8 mL, 198.1 ± 122.1 mL, and 316.7 ± 131.9 mL, respectively. Mean EELV reduction during stage R sleep doubled that noted during non-stage R sleep (316.7 ± 131.9 mL versus 150.9 ± 89.7 mL, respectively) (P < .001). The difference in EELV between non-stage R and stage R sleep inversely correlated with mean oxygen saturation (r = −0.56, P = .06). EELV reduction in individuals with moderate and severe OSA was greater than in those with mild SDB but did not reach statistical significance.

Conclusions:

Magnetometry provides a precise, unobtrusive, and continuous means to study lung volume changes during sleep. EELV declines from sleep onset, reaching its nadir during stage R sleep. The reduction in EELV in stage R sleep was associated with lower mean oxygen saturation but was not associated with greater sleep-disordered breathing.

Citation:

Koo P, Gartman EJ, Sethi JM, Kawar E, McCool FD. Change in end-expiratory lung volume during sleep in patients at risk for obstructive sleep apnea. J Clin Sleep Med. 2017;13(8):941–947.

http://ift.tt/2uD4nJL

Validated Measures of Insomnia, Function, Sleepiness, and Nasal Obstruction in a CPAP Alternatives Clinic Population

Study Objectives:

Although efficacious in the treatment of obstructive sleep apnea (OSA), continuous positive airway pressure (CPAP) can be difficult to tolerate, with long-term adherence rates approaching 50%. CPAP alternatives clinics specialize in the evaluation and treatment of CPAP-intolerant patients; yet this population has not been studied in the literature. To better understand these patients, we sought to assess insomnia, sleep-related functional status, sleepiness, and nasal obstruction, utilizing data from validated instruments.

Methods:

After approval from the Emory University Institutional Review Board, a retrospective chart review was performed from September 2015 to September 2016 of new patient visits at the Emory CPAP alternatives clinic. Patient demographics and responses were recorded from the Insomnia Severity Index, Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), Epworth Sleepiness Scale, and Nasal Obstruction Symptom Evaluation questionnaires.

Results:

A total of 172 patients were included, with 81% having moderate-severe OSA. Most of the patients demonstrated moderate-severe clinical insomnia and at least moderate nasal obstruction. FOSQ-10 scores indicated sleep-related functional impairment in 88%. However, most patients did not demonstrate excessive daytime sleepiness.

Conclusion:

This patient population demonstrates significant symptomatology and functional impairment. Because of the severity of their OSA, they are at increased risk of complications. In order to mitigate the detrimental effects of OSA, these significantly impacted patients should be identified and encouraged to seek CPAP alternatives clinics that specialize in the treatment of this population.

Citation:

Lam AS, Collop NA, Bliwise DL, Dedhia RC. Validated measures of insomnia, function, sleepiness, and nasal obstruction in a CPAP alternatives clinic population. J Clin Sleep Med. 2017;13(8):949–957.

http://ift.tt/2uW1yi3

Allergic and Non-Allergic Rhinitis Are Common in Obstructive Sleep Apnea but Not Associated With Disease Severity

Study Objectives:

Several studies have suggested that rhinitis contributes to the pathogenesis of obstructive sleep apnea (OSA). We aimed to investigate the prevalence and influence of allergic rhinitis (AR) and non-allergic rhinitis (NAR) on severity of OSA.

Methods:

Two hundred forty patients with OSA confirmed by standardized polysomnography were assessed for presence of AR and NAR, using validated questionnaires and skin prick tests. Data comparison was carried out by using chi-square test, analysis of variance, and least significant difference test. Associations between severity of OSA and rhinitis, age, sex, and body mass index were assessed with ordinal logistic regression analysis.

Results:

The prevalence of AR and NAR among patients with OSA was 27.1% and 28.7%, respectively, with no significant differences in the severity of rhinitis. Ordinal logistic regression analysis showed AR and NAR were not the risk factors for severity of OSA. There were significant differences of polysomnography parameters in sleep efficiency (79.7 ± 2.0 versus 85.2 ± 1.4 between AR and NAR; 79.7 ± 2.0 versus 87.2 ± 1.4 between AR and no-rhinitis) and arousal index (36.8 ± 4.1 versus 24.7 ± 3.5 between AR and no-rhinitis). Patients with NAR had lower average arterial oxygen saturation (91.9 ± 0.6 versus 94.0 ± 0.6) and minimal arterial oxygen saturation (70.6 ± 1.7 versus 77.3 ± 1.8), compared with subjects categorized as no-rhinitis.

Conclusions:

This study suggests that despite a comparatively high prevalence in patients with OSA, the presence or severity of AR or NAR does not influence the severity of OSA; however, rhinitis may significantly disturb sleep in patients with OSA.

Citation:

Zheng M, Wang X, Ge S, Gu Y, Ding X, Zhang Y, Ye J, Zhang L. Allergic and non-allergic rhinitis are common in obstructive sleep apnea but not associated with disease severity. J Clin Sleep Med. 2017;13(8):959–966.

http://ift.tt/2uDddXV

Self-Reported Sleep Quality, Duration, and Health-Related Quality of Life in Older Chinese: Evidence From a Rural Town in Suzhou, China

Study Objectives:

To determine the associations of self-reported sleep quality and duration with health-related quality of life (HRQOL) in older Chinese.

Methods:

We analyzed community-based cross-sectional data of 5,539 individuals aged 60 years and older in the Weitang Geriatric Disease Study. Information of sleep quality and duration were self-reported through participants' responses to predefined questions; HRQOL data were collected by using the European Quality of Life-5 Dimensions (EQ-5D). We estimated the associations of sleep quality and duration with the EQ-5D index and visual analog scale (VAS) scores using linear regression models. The associations between sleep quality and duration and EQ-5D–detected health problems were modeled using logistic regression.

Results:

In multiple linear models adjusting sociodemographic factors, health conditions, and lifestyle habits, both EQ-5D index and VAS scores declined with deterioration of sleep quality. The coefficients for poor and intermediate sleep quality were −0.053 (95% confidence interval [CI]:−0.065, −0.042) and −0.022 (95% CI: −0.030, −0.013), respectively, in relation to EQ-5D index score. They were −5.2 (95% CI: −6.7, −2.4) and − 3.8 (95% CI: −4.9, −2.7) in modeling the EQ-5D VAS score. HRQOL declined as sleep duration decreased below 7.01 hours or exceeded 8.01 hours, though most of the associations did not reach statistical significance. In multiple logistic models, poor sleep quality was associated with problems of mobility, pain/discomfort, and anxiety/ depression; short sleep duration was associated with mobility problems.

Conclusions:

Poor sleep quality and extreme sleep durations appeared to be negatively associated with HRQOL in older Chinese adults.

Citation:

Pan CW, Cong X, Zhou HJ, Li J, Sun HP, Xu Y, Wang P. Self-reported sleep quality, duration, and health-related quality of life in older Chinese: evidence from a rural town in Suzhou, China. J Clin Sleep Med. 2017;13(8):967–974.

http://ift.tt/2uVKd8V

Success of Tonsillectomy for Obstructive Sleep Apnea in Children With Down Syndrome

Study Objectives:

Obstructive sleep apnea (OSA) is common in children with Down syndrome (DS) and associated with significant morbidity. In the current study we examined polysomnographic outcomes of children with DS who underwent tonsillectomy.

Methods:

A retrospective chart review of children with DS who underwent a tonsillectomy between 2009–2015 was performed. All children had either a concurrent adenoidectomy or had previously underwent an adenoidectomy. Children with preoperative and postoperative polysomnograms within 6 months of surgery were included in the analysis. Preoperative OSA severity was categorized by obstructive apnea-hypopnea index (OAHI) as follows: mild = 1.5–4.9 events/h; moderate = 5–9.9 events/h; severe ≥ 10 events/h.

Results:

Seventy-five children with DS met inclusion criteria. The cohort included 41 males and 34 females with mean age of 5.1 years (± 3.6 years), range of 0.51–16.60 years. Preoperative OSA severity was as follows, mild = 8/75; moderate = 16/75; severe = 51/75. Cure rates varied depending on definition: 12% for OAHI < 1 event/h and 21% for OAHI < 2 events/h. 48% had residual OAHI < 5 events/h. On postoperative PSG 16/75 saw resolution (OAHI < 2) in OSA; mild = 21/75; moderate = 20/75; severe = 18/75. 48% moderate/severe patients saw conversion to mild or cure. Overall, tonsillectomy resulted in significant improvements in multiple respiratory parameters, including OAHI (OAHI; 21.3 ± 19.7 to 8.0 ± 8.1, P < .001), percent sleep time with oxygen saturations < 90% (19.0 ± 25.0 to 6.1 ± 10.1, P < .001), and percent sleep time with end-tidal carbon dioxide above 50 mmHg (7.7 ± 18.0 to 1.8 ± 6.6, P = .001). Average asleep oxygen saturation was associated with postoperative OSA severity.

Conclusions:

Children with DS and OSA who undergo tonsillectomy experience improvements in both respiratory event frequency and gas exchange but approximately half still have moderate to severe residual OSA.

Citation:

Ingram DG, Ruiz AG, Gao D, Friedman NR. Success of tonsillectomy for obstructive sleep apnea in children with Down syndrome. J Clin Sleep Med. 2017;13(8):975–980.

http://ift.tt/2uDuKPs

High-Flow, Heated, Humidified Air Via Nasal Cannula Treats CPAP-Intolerant Children With Obstructive Sleep Apnea

Study Objectives:

Continuous positive airway pressure (CPAP) is effective but challenging for children with obstructive sleep apnea (OSA). High-flow air via open nasal cannula (HFNC) as treatment in children remains controversial. We report the efficacy of HFNC in children with OSA and CPAP intolerance, a titration protocol, and a discussion of potential mechanisms.

Methods:

Patients aged 1 to 18 years with OSA (defined by obstructive apnea-hypopnea index [OAHI] greater than 1 event/h) and CPAP intolerance were enrolled. Routine polysomnography data obtained during 1 night wearing HFNC was compared with diagnostic data by Wilcoxon rank-sum test.

Results:

Ten school-age subjects (representing all patients attempting HFNC at our institution to date) with varied medical conditions, moderate to severe OSA, and CPAP intolerance wore HFNC from 10 to 50 L/min of room air with oxygen supplementation if needed (room air alone for 6 of the 10). HFNC reduced median OAHI from 11.1 events/h (interquartile range 8.7–18.8 events/h) to 2.1 events/h (1.7–2.2 events/h; P = .002); increased oxyhemoglobin saturation (SpO₂) mean from 91.3% (89.6% to 93.5%) to 94.9% (92.4% to 96.0%; P < .002); increased SpO₂ nadir from 76.0% (67.3% to 82.3%) to 79.5% (77.2% to 86.0%; P = .032); decreased SpO₂ desaturation index from 19.2 events/h (12.7–25.8 events/h) to 6.4 events/h (4.7–10.7 events/h; P = .013); and reduced heart rate from 88 bpm (86–91 bpm) to 74 bpm (67–81 bpm; P = .004). Stratified analysis of the 6 subjects with only room air via HFNC, the OAHI, obstructive hypopnea index, and mean SpO₂ still demonstrated improvements (P = .031).

Conclusions:

High-flow nasal cannula reduces respiratory events, improves oxygenation, reduces heart rate, and may be effective for CPAP intolerant children with moderate to severe OSA. Our data suggest HFNC warrants further study and consideration by payers as OSA therapy.

Citation:

Hawkins S, Huston S, Campbell K, Halbower A. High-flow, heated, humidified air via nasal cannula treats CPAP-intolerant children with obstructive sleep apnea. J Clin Sleep Med. 2017;13(8):981–989.

http://ift.tt/2uVCLe7

Veterans Affairs Primary Care Provider Perceptions of Insomnia Treatment

Study Objectives:

Insomnia is a widespread issue among United States adults and rates of insomnia among veterans are even higher than the general population. Prior research examining primary care provider (PCP) perspectives on insomnia treatment found that: sleep hygiene and pharmacotherapy are the primary treatments offered; PCPs tend to focus on perceived causes of insomnia rather than the insomnia itself; and neither patients nor providers are satisfied with insomnia treatment options. Although insomnia complaints are typically first reported to primary care providers, little research has focused on perspectives regarding insomnia treatment among PCPs working in the largest integrated health care system in the United States—the Veterans Affairs (VA) health care system. This study was conducted to examine VA PCP perceptions of the availability of insomnia treatments, identify specific strategies offered by PCPs, and examine perceptions regarding the importance of treating insomnia and the role of comorbid conditions.

Methods:

A survey was conducted within the VA health care system. Primary care providers completed surveys electronically.

Results:

A high percentage of veterans (modal response = 20% to 39%) seen in VA primary care settings report an insomnia complaint to their provider. Almost half of respondents do not consistently document insomnia in the medical record (46% endorsed "sometimes," "rarely," or "never"). PCPs routinely advise sleep hygiene recommendations for insomnia (ie, avoid stimulants before bedtime [84.3%], and keep the bedroom environment quiet and dark and comfortable [68.6%]) and many are uncertain if cognitive behavioral therapy for insomnia is available at their facility (43.1%).

Conclusions:

Findings point to the need for systems-level changes within health care systems, including the adoption of evidence-based clinical practice standards for insomnia and PCP education about the processes that maintain insomnia.

Commentary:

A commentary on this article appears in this issue on page 937.

Citation:

Ulmer CS, Bosworth HB, Beckham JC, Germain A, Jeffreys AS, Edelman D, Macy S, Kirby A, Voils CI. Veterans affairs primary care provider perceptions of insomnia treatment. J Clin Sleep Med. 2017;13(8):991–999.

http://ift.tt/2uDzN2u

Binge Viewing, Sleep, and the Role of Pre-Sleep Arousal

Study Objectives:

To investigate the prevalence of binge viewing, its association with sleep and examine arousal as an underlying mechanism of this association.

Methods:

Four hundred twenty-three adults (aged 18–25 years old, 61.9% female) completed an online survey assessing regular television viewing, binge viewing, sleep quality (Pittsburgh Sleep Quality Index), fatigue (Fatigue Assessment Scale), insomnia (Bergen Insomnia Scale), and pre-sleep arousal (Pre-Sleep Arousal Scale). Regression analyses were conducted. Mediation analysis was performed using PROCESS Macro.

Results:

There were 80.6% who identified themselves as a binge viewer. Among those who binge viewed (n = 341), 20.2% had binge viewed at least a few times a week during the past month. Among poor sleepers (Pittsburgh Sleep Quality Index > 5), 32.6% had a poor sleep quality associated with being a binge viewer. Higher binge viewing frequency was associated with a poorer sleep quality, increased fatigue and more symptoms of insomnia, whereas regular television viewing was not. Cognitive pre-sleep arousal fully mediated these relationships.

Conclusions:

New viewing styles such as binge viewing are increasingly prevalent and may pose a threat to sleep. Increased cognitive arousal functions as the mechanism explaining these effects. Measures of media exposure should take into account the user's level of engagement with media. Interventions aimed at (1) alerting viewers about excessive viewing duration and (2) reducing arousal before sleep may be useful ways to tackle sleep problems in binge viewers.

Citation:

Exelmans L, Van den Bulck J. Binge viewing, sleep, and the role of pre-sleep arousal. J Clin Sleep Med. 2017;13(8):1001–1008.

http://ift.tt/2uW89cg

Evaluation of Continuous Negative External Pressure (cNEP) for the Treatment of Obstructive Sleep Apnea: A Pilot Study

Study Objectives:

To determine if the application of continuous negative external pressure (cNEP) is effective and safe in individuals with obstructive sleep apnea (OSA) during an overnight in-laboratory sleep study.

Methods:

A prospective, open-label pilot study in subjects with documented OSA recruited from the patient population at one sleep clinic. The intervention was application and titration of cNEP during overnight polysomnography.

Results:

Of the 15 subjects studied (mean apnea-hypopnea index [AHI] at baseline, 43.9 events/h), 13 (87%) were responders to cNEP: 9 had an excellent response (AHI < 5 events/h) and 4 had a partial response (AHI < 50% baseline and < 15 events/h). Three minor, self-limited adverse events occurred, which appeared related to contact pressure of the cNEP device on the skin.

Conclusions:

In this pilot study, cNEP appears to be safe and effective during short-term use in subjects with OSA. Further studies are warranted.

Citation:

Kram JA, Woidtke RV, Klein KB, Rose RM. Evaluation of continuous negative external pressure (cNEP) for the treatment of obstructive sleep apnea: a pilot study. J Clin Sleep Med. 2017;13(8):1009–1012.

http://ift.tt/2uDD9CD

A Case of “Abnormally Abnormal” Hypoxic Ventilatory Responses: A Novel NPARM PHOX 2B Gene Mutation

Congenital central hypoventilation syndrome (CCHS) is a rare disorder associated with dysregulation of the autonomic ventilatory response to hypoxia and hypercarbia usually caused by polyalanine repeat expansion mutations in the PHOX 2B gene. Non-polyalanine repeat mutations (NPARM) represent approximately 10% of cases, and usually require continuous ventilation during sleep, although our knowledge of disease progression is limited. Here we present a case with a novel NPARM CCHS mutation associated with a premature stop codon for the PHOX 2B protein. Despite the type of the mutation, patient management with supplementary oxygen has been sufficient. Experience from our case may help when counseling parents.

Citation:

Unger SA, Guillot M, Urquhart DS. A case of "abnormally abnormal" hypoxic ventilatory responses: a novel NPARM PHOX 2B gene mutation. J Clin Sleep Med. 2017;13(8):1013–1015.

http://ift.tt/2uVMscd

Parental Fitness Questioned on the Grounds of Narcolepsy: Presentation of Two Cases

We report two cases of fathers whose parental fitness was questioned during divorce and custody litigation because of narcolepsy type 2 and type 1, respectively. These cases highlighted both the existence of a narcolepsy-related stigma and the need to involve sleep experts in custody assessments when concerns about the parental fitness are related to a sleep disorder, expanding the field of interest of the growing "sleep forensics."

Citation:

Barbero L, Govi A, Pizza F, Plazzi G, Ingravallo F. Parental fitness questioned on the grounds of narcolepsy: presentation of two cases. J Clin Sleep Med. 2017;13(8):1017–1018.

http://ift.tt/2uDqVK3

JACC Instructions for Authors

http://ift.tt/2uVT0I9

Vascular Burden Impact on Echocardiographic Valvular Graft Degeneration Following a Ross Procedure in Young Adults

http://ift.tt/2uDAgBN

Relationship of Alcohol Consumption to All-Cause, Cardiovascular, and Cancer-Related Mortality in U.S. Adults

AbstractBackground

Previous studies have revealed inconsistent findings regarding the association of light to moderate alcohol consumption with cardiovascular disease (CVD) and cancer mortality.

Objectives

The aim of this study was to examine the association between alcohol consumption and risk of mortality from all causes, cancer, and CVD in U.S. adults.

Methods

Data were obtained by linking 13 waves of the National Health Interview Surveys (1997 to 2009) to the National Death Index records through December 31, 2011. A total of 333,247 participants ≥18 years of age were included. Self-reported alcohol consumption patterns were categorized into 6 groups: lifetime abstainers; lifetime infrequent drinkers; former drinkers; and current light, moderate, or heavy drinkers. Secondary exposure included participants' binge-drinking status. The main outcome was all-cause, cancer, or CVD mortality.

Results

After a median follow-up of 8.2 years (2.7 million person-years), 34,754 participants died of all causes (including 8,947 CVD deaths and 8,427 cancer deaths). Compared with lifetime abstainers, those who were light or moderate alcohol consumers were at a reduced risk of mortality for all causes (light—hazard ratio [HR]: 0.79; 95% confidence interval [CI]: 0.76 to 0.82; moderate—HR: 0.78; 95% CI: 0.74 to 0.82) and CVD (light—HR: 0.74; 95% CI: 0.69 to 0.80; moderate—HR: 0.71; 95% CI: 0.64 to 0.78), respectively. In contrast, there was a significantly increased risk of mortality for all causes (HR: 1.11; 95% CI: 1.04 to 1.19) and cancer (HR: 1.27; 95% CI: 1.13 to 1.42) in adults with heavy alcohol consumption. Binge drinking ≥1 d/week was also associated with an increased risk of mortality for all causes (HR: 1.13; 95% CI: 1.04 to 1.23) and cancer (HR: 1.22; 95% CI: 1.05 to 1.41).

Conclusions

Light and moderate alcohol intake might have a protective effect on all-cause and CVD-specific mortality in U.S. adults. Heavy or binge drinking was associated with increased risk of all-cause and cancer-specific mortality.

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Alcohol and Health: Praise of the J Curves

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Aspirin for the Prevention of Infective Endocarditis?

http://ift.tt/2uD0swo

Risk of Arterial Thromboembolism in Patients With Cancer

AbstractBackground

The risk of arterial thromboembolism in patients with cancer is incompletely understood.

Objectives

The authors aimed to better define this epidemiological relationship, including the effects of cancer stage.

Methods

Using the Surveillance Epidemiology and End Results–Medicare linked database, the authors identified patients with a new primary diagnosis of breast, lung, prostate, colorectal, bladder, pancreatic, or gastric cancer or non-Hodgkin lymphoma from 2002 to 2011. They were individually matched by demographics and comorbidities to a Medicare enrollee without cancer, and each pair was followed through 2012. Validated diagnosis codes were used to identify arterial thromboembolism, defined as myocardial infarction or ischemic stroke. Cumulative incidence rates were calculated using competing risk survival statistics. Cox hazards analysis was used to compare rates between groups at discrete time points.

Results

The authors identified 279,719 pairs of patients with cancer and matched control patients. The 6-month cumulative incidence of arterial thromboembolism was 4.7% (95% confidence interval [CI]: 4.6% to 4.8%) in patients with cancer compared with 2.2% (95% CI: 2.1% to 2.2%) in control patients (hazard ratio [HR]: 2.2; 95% CI: 2.1 to 2.3). The 6-month cumulative incidence of myocardial infarction was 2.0% (95% CI: 1.9% to 2.0%) in patients with cancer compared with 0.7% (95% CI: 0.6% to 0.7%) in control patients (HR: 2.9; 95% CI: 2.8 to 3.1). The 6-month cumulative incidence of ischemic stroke was 3.0% (95% CI: 2.9% to 3.1%) in patients with cancer compared with 1.6% (95% CI: 1.6% to 1.7%) in control patients (HR: 1.9; 95% CI: 1.8 to 2.0). Excess risk varied by cancer type (greatest for lung), correlated with cancer stage, and generally had resolved by 1 year.

Conclusions

Patients with incident cancer face a substantially increased short-term risk of arterial thromboembolism.

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2017 AHA/ACC Key Data Elements and Definitions for Ambulatory Electronic Health Records in Pediatric and Congenital Cardiology: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards

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Cancer and Clot: Between a Rock and a Hard Place

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Coronary Artery Disease Affects Symptomatology of Aortic Valve Stenosis

http://ift.tt/2uD0sMU

Geometry as a Confounder When Assessing Ventricular Systolic Function: Comparison Between Ejection Fraction and Strain

AbstractBackground

Preserved left ventricular (LV) ejection fraction (EF) and reduced myocardial strain are reported in patients with hypertrophic cardiomyopathy, ischemic heart disease, diabetes mellitus, and more.

Objectives

The authors performed a combined mathematical and echocardiographic study to understand the inconsistencies between EF and strains.

Methods

An analytical equation showing the relationship between EF and the 4 parameters, global longitudinal strain (GLS), global circumferential strain (GCS), wall thickness, and short-axis diameter, was derived from an elliptical LV model. The equation was validated by measuring the 4 parameters by echocardiography in 100 subjects with EF ranging from 16% to 72% and comparing model-predicted EF with measured EF. The effect of the different parameters on EF was explored in the model and compared with findings in the patients.

Results

Calculated EF had very good agreement with measured EF (r = 0.95). The model showed that GCS contributes more than twice as much to EF than GLS. A significant reduction of GLS could be compensated by a small increase of GCS or wall thickness or reduced diameter. The model further demonstrated how EF can be maintained in ventricles with increased wall thickness or reduced diameter, despite reductions in both longitudinal and circumferential shortening. This was consistent with similar EF in 20 control subjects and 20 hypertrophic cardiomyopathy patients with increased wall thickness and reductions in both circumferential and longitudinal shortening (all p < 0.01).

Conclusions

Reduced deformation despite preserved EF can be explained through geometric factors. Due to geometric confounders, strain better reflects systolic function in patients with preserved EF.

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Correction

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Strain Echocardiography: The New Gold Standard for Imaging Ventricular Function?

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Aortic Bioprosthetic Valve Durability: Incidence, Mechanisms, Predictors, and Management of Surgical and Transcatheter Valve Degeneration

Abstract

In recent times, there has been a considerable increase in the use of aortic bioprostheses (vs. mechanical prostheses) for treating aortic valve disease, and this tendency is likely to continue in the near future. However, the occurrence of structural valve degeneration, limiting valve durability, remains an important drawback of surgical and transcatheter bioprostheses. In this paper, we provide an overview of bioprosthetic valve durability, focusing on the definition, incidence, mechanisms, predictive factors, and management of structural degeneration of aortic bioprostheses.

http://ift.tt/2uVIobX

Pharmacological and Activated Fibroblast Targeting of G{beta}{gamma}-GRK2 After Myocardial Ischemia Attenuates Heart Failure Progression

AbstractBackground

Cardiac fibroblasts are a critical cell population responsible for myocardial extracellular matrix homeostasis. Upon injury or pathological stimulation, these cells transform to an activated myofibroblast state and play a fundamental role in myocardial fibrosis and remodeling. Chronic sympathetic overstimulation, a hallmark of heart failure (HF), induces pathological signaling through G protein β (Gβ) subunits and their interaction with G protein–coupled receptor kinase 2 (GRK2).

Objectives

This study investigated the hypothesis that Gβ-GRK2 inhibition and/or ablation after myocardial injury would attenuate pathological myofibroblast activation and cardiac remodeling.

Methods

The therapeutic potential of small molecule Gβ-GRK2 inhibition, alone or in combination with activated fibroblast- or myocyte-specific GRK2 ablation—each initiated after myocardial ischemia–reperfusion (I/R) injury—was investigated to evaluate the possible salutary effects on post-I/R fibroblast activation, pathological remodeling, and cardiac dysfunction.

Results

Small molecule Gβ-GRK2 inhibition initiated 1 week post-injury was cardioprotective in the I/R model of chronic HF, including preservation of cardiac contractility and a reduction in cardiac fibrotic remodeling. Systemic small molecule Gβ-GRK2 inhibition initiated 1 week post-I/R in cardiomyocyte-restricted GRK2 ablated mice (also post-I/R) still demonstrated significant cardioprotection, which suggested a potential protective role beyond the cardiomyocyte. Inducible ablation of GRK2 in activated fibroblasts (i.e., myofibroblasts) post-I/R injury demonstrated significant functional cardioprotection with reduced myofibroblast transformation and fibrosis. Systemic small molecule Gβ-GRK2 inhibition initiated 1 week post-I/R provided little to no further protection in mice with ablation of GRK2 in activated fibroblasts alone. Finally, Gβ-GRK2 inhibition significantly attenuated activation characteristics of failing human cardiac fibroblasts isolated from end-stage HF patients.

Conclusions

These findings suggested consideration of a paradigm shift in the understanding of the therapeutic role of Gβ-GRK2 inhibition in treating HF and the potential therapeutic role for Gβ-GRK2 inhibition in limiting pathological myofibroblast activation, interstitial fibrosis, and HF progression.

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MACRA Is a Law: Practice Transformation Is the Goal

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{beta}-Adrenergic Blockade in Ischemia-Reperfusion Injury: {beta}ARKing Up a New Tree

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The Time-Varying Risk of Cardiovascular and Noncardiovascular Readmissions Early After Acute Myocardial Infarction

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Catecholamine-Dependent {beta}-Adrenergic Signaling in a Pluripotent Stem Cell Model of Takotsubo Cardiomyopathy

AbstractBackground

Takotsubo syndrome (TTS) is characterized by an acute left ventricular dysfunction and is associated with life-threating complications in the acute phase. The underlying disease mechanism in TTS is still unknown. A genetic basis has been suggested to be involved in the pathogenesis.

Objectives

The aims of the study were to establish an in vitro induced pluripotent stem cell (iPSC) model of TTS, to test the hypothesis of altered β-adrenergic signaling in TTS iPSC-cardiomyocytes (CMs), and to explore whether genetic susceptibility underlies the pathophysiology of TTS.

Methods

Somatic cells of patients with TTS and control subjects were reprogrammed to iPSCs and differentiated into CMs. Three-month-old CMs were subjected to catecholamine stimulation to simulate neurohumoral overstimulation. We investigated β-adrenergic signaling and TTS cardiomyocyte function.

Results

Enhanced β-adrenergic signaling in TTS-iPSC-CMs under catecholamine-induced stress increased expression of the cardiac stress marker NR4A1; cyclic adenosine monophosphate levels; and cyclic adenosine monophosphate–dependent protein kinase A–mediated hyperphosphorylation of RYR2-S2808, PLN-S16, TNI-S23/24, and Cav1.2-S1928, and leads to a reduced calcium time to transient 50% decay. These cellular catecholamine-dependent responses were mainly mediated by β₁-adrenoceptor signaling in TTS. Engineered heart muscles from TTS-iPSC-CMs showed an impaired force of contraction and a higher sensitivity to isoprenaline-stimulated inotropy compared with control subjects. In addition, altered electrical activity and increased lipid accumulation were detected in catecholamine-treated TTS-iPSC-CMs, and were confirmed by differentially expressed lipid transporters CD36 and CPT1C. Furthermore, we uncovered genetic variants in different key regulators of cardiac function.

Conclusions

Enhanced β-adrenergic signaling and higher sensitivity to catecholamine-induced toxicity were identified as mechanisms associated with the TTS phenotype. (International Takotsubo Registry [InterTAK Registry] [InterTAK]; NCT01947621)

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Reply: Coronary Artery Disease Affects Symptomatology of Aortic Valve Stenosis

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Stress in a Dish: Exploring the Mechanisms of Takotsubo Syndrome

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Anterior superior alveolar nerve injury after extended endoscopic medial maxillectomy: a preclinical study to predict neurological morbidity

Background

Endoscopic medial maxillectomies (EMMs) are used to optimize exposure of the maxillary sinus and retromaxillary areas. Although in type D EMM (Sturmann-Canfield procedure) the anterior superior alveolar nerve (ASAN) is always at risk of injury, only 29% of patients complained of alveolar process and dental anesthesia. The purpose of this anatomical study is to assess the neural anastomotic network of the ASAN (ASAN-NAN) and describe different extensions of type D EMMs in a preclinical setting.

Methods

The ASAN and its medial anastomotic branches (MABs) and lateral anastomotic branches (LABs) were evaluated by cone-beam computerized tomography (CBCT). Five different extensions of type D (D1 to D5) EMMs were identified and nerves at risk of injury in each type were assessed by CBCT. Moreover, quantification of surgical corridors was performed on cadaver heads with a neuronavigation system.

Results

Fifty-seven CBCT scans were analyzed. The ASAN would be spared in 16.3% of cases with a type D1 EMM, while it would be injured in the majority of type D2 to D5 resections. At least 1 nerve of the ASAN-NAN was spared in 96.6%, 93%, 74.6%, 0%, and 65.8% of type D1 to D5 EMMs, respectively. Two cadaver heads were dissected and the incremental volume and number of maxillary subsites exposed was assessed in type D1 to D5 EMMs.

Conclusion

ASAN function impairment is probably compensated by LABs and MABs. If this hypothesis will be validated in a prospective study on patients, preoperative CBCT evaluation could predict neurological morbidity after type D EMM, and allow tailoring the procedure to minimize impairment of the ASAN-NAN.

http://ift.tt/2fFug4B

The innate immune system and beyond

http://ift.tt/2i03ll5

Efficacy of endoscopic sinus surgery for chronic rhinosinusitis following primary radiotherapy and concurrent chemotherapy for nasopharyngeal carcinoma

Background

Chronic rhinosinusitis (CRS) is a downstream complication following radiotherapy or chemoradiation for nasopharyngeal carcinoma (NPC). Endoscopic sinus surgery (ESS) is an accepted therapy for medically refractory CRS, but its efficacy in addressing CRS symptoms in patients with previously irradiated NPC is unclear.

Methods

All patients at the Stanford Sinus Center with a history of radiation therapy or chemoradiation for NPC between 2006 and 2015 were reviewed. Patients without antecedent CRS prior to NPC treatment (n = 26) were retrospectively divided into 2 cohorts based on whether they developed postirradiation CRS and underwent ESS (surgical group, n = 13) or did not develop CRS (control, n = 13). Demographic and clinical characteristics were collected, and temporal changes in 22-item Sino-Nasal Outcome Test (SNOT-22) score were compared.

Results

The median time following primary irradiation to initial presentation was 6.8 and 6.5 years in the surgical and control groups, respectively. The surgical cohort had statistically greater baseline SNOT-22 scores than the control group (45 vs 14, p = 0.0198). At 6 to 12 months postoperatively, the surgical group demonstrated statistically significant and clinically meaningful improvements in SNOT-22 scores when compared to controls (15-point decrease vs 0, p = 0.0040), ultimately resulting in similar SNOT-22 scores for both groups (28 vs 18, p = 0.3687). The rhinologic, extranasal, and ear/face subdomain scores of the surgical group were significantly greater than those of the control group preoperatively (rhinologic: p = 0.0010; extranasal: p = 0.0179; ear/face: p = 0.0068), but these disparities resolved postoperatively (rhinologic: p = 0.1461; extranasal: p = 0.3131; ear/face: p = 0.3401).

Conclusion

ESS appears to effectively manage recalcitrant CRS symptoms in patients previously treated with radiation therapy and concurrent chemotherapy for NPC.

http://ift.tt/2fFp0xX

Anterior superior alveolar nerve injury after extended endoscopic medial maxillectomy: a preclinical study to predict neurological morbidity

Background

Endoscopic medial maxillectomies (EMMs) are used to optimize exposure of the maxillary sinus and retromaxillary areas. Although in type D EMM (Sturmann-Canfield procedure) the anterior superior alveolar nerve (ASAN) is always at risk of injury, only 29% of patients complained of alveolar process and dental anesthesia. The purpose of this anatomical study is to assess the neural anastomotic network of the ASAN (ASAN-NAN) and describe different extensions of type D EMMs in a preclinical setting.

Methods

The ASAN and its medial anastomotic branches (MABs) and lateral anastomotic branches (LABs) were evaluated by cone-beam computerized tomography (CBCT). Five different extensions of type D (D1 to D5) EMMs were identified and nerves at risk of injury in each type were assessed by CBCT. Moreover, quantification of surgical corridors was performed on cadaver heads with a neuronavigation system.

Results

Fifty-seven CBCT scans were analyzed. The ASAN would be spared in 16.3% of cases with a type D1 EMM, while it would be injured in the majority of type D2 to D5 resections. At least 1 nerve of the ASAN-NAN was spared in 96.6%, 93%, 74.6%, 0%, and 65.8% of type D1 to D5 EMMs, respectively. Two cadaver heads were dissected and the incremental volume and number of maxillary subsites exposed was assessed in type D1 to D5 EMMs.

Conclusion

ASAN function impairment is probably compensated by LABs and MABs. If this hypothesis will be validated in a prospective study on patients, preoperative CBCT evaluation could predict neurological morbidity after type D EMM, and allow tailoring the procedure to minimize impairment of the ASAN-NAN.

http://ift.tt/2fFug4B

The innate immune system and beyond

http://ift.tt/2i03ll5

Efficacy of endoscopic sinus surgery for chronic rhinosinusitis following primary radiotherapy and concurrent chemotherapy for nasopharyngeal carcinoma

Background

Chronic rhinosinusitis (CRS) is a downstream complication following radiotherapy or chemoradiation for nasopharyngeal carcinoma (NPC). Endoscopic sinus surgery (ESS) is an accepted therapy for medically refractory CRS, but its efficacy in addressing CRS symptoms in patients with previously irradiated NPC is unclear.

Methods

All patients at the Stanford Sinus Center with a history of radiation therapy or chemoradiation for NPC between 2006 and 2015 were reviewed. Patients without antecedent CRS prior to NPC treatment (n = 26) were retrospectively divided into 2 cohorts based on whether they developed postirradiation CRS and underwent ESS (surgical group, n = 13) or did not develop CRS (control, n = 13). Demographic and clinical characteristics were collected, and temporal changes in 22-item Sino-Nasal Outcome Test (SNOT-22) score were compared.

Results

The median time following primary irradiation to initial presentation was 6.8 and 6.5 years in the surgical and control groups, respectively. The surgical cohort had statistically greater baseline SNOT-22 scores than the control group (45 vs 14, p = 0.0198). At 6 to 12 months postoperatively, the surgical group demonstrated statistically significant and clinically meaningful improvements in SNOT-22 scores when compared to controls (15-point decrease vs 0, p = 0.0040), ultimately resulting in similar SNOT-22 scores for both groups (28 vs 18, p = 0.3687). The rhinologic, extranasal, and ear/face subdomain scores of the surgical group were significantly greater than those of the control group preoperatively (rhinologic: p = 0.0010; extranasal: p = 0.0179; ear/face: p = 0.0068), but these disparities resolved postoperatively (rhinologic: p = 0.1461; extranasal: p = 0.3131; ear/face: p = 0.3401).

Conclusion

ESS appears to effectively manage recalcitrant CRS symptoms in patients previously treated with radiation therapy and concurrent chemotherapy for NPC.

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Differential effect of TGFβ on the proteome of cancer associated fibroblasts and cancer epithelial cells in a co-culture approach - a short report

Abstract

Background

Solid tumors contain various components that together form the tumor microenvironment. Cancer associated fibroblasts (CAFs) are capable of secreting and responding to signaling molecules and growth factors. Due to their role in tumor development, CAFs are considered as potential therapeutic targets. A prominent tumor-associated signaling molecule is transforming growth factor β (TGFβ), an inducer of epithelial-to-mesenchymal transition (EMT). The differential action of TGFβ on CAFs and ETCs (epithelial tumor cells) has recently gained interest. Here, we aimed to investigate the effects of TGFβ on CAFs and ETCs at the proteomic level.

Methods

We established a 2D co-culture system of differentially fluorescently labeled CAFs and ETCs and stimulated this co-culture system with TGFβ. The respective cell types were separated using FACS and subjected to quantitative analyses of individual proteomes using mass spectrometry.

Results

We found that TGFβ treatment had a strong impact on the proteome composition of CAFs, whereas ETCs responded only marginally to TGFβ. Quantitative proteomic analyses of the different cell types revealed up-regulation of extracellular matrix (ECM) proteins in TGFβ treated CAFs. In addition, we found that the TGFβ treated CAFs exhibited increased N-cadherin levels.

Conclusions

From our data we conclude that CAFs respond to TGFβ treatment by changing their proteome composition, while ETCs appear to be rather resilient.

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Defining Radioiodine-Refractory Differentiated Thyroid Cancer: Efficacy and Safety of Lenvatinib by Radioiodine-Refractory Criteria in the SELECT Trial

Thyroid , Vol. 0, No. 0.


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An Exploratory Study of Fatigue and Physical Activity in Canadian Thyroid Cancer Patients

Thyroid , Vol. 0, No. 0.


http://ift.tt/2uV68wQ

Defining Radioiodine-Refractory Differentiated Thyroid Cancer: Efficacy and Safety of Lenvatinib by Radioiodine-Refractory Criteria in the SELECT Trial

Thyroid , Vol. 0, No. 0.


http://ift.tt/2uCYpbI