bluuebunny/crossref_metadata_2025 huggingface dataset:
Maturation of hematopoietic stem cells from prehematopoietic stem cells is accompanied by up-regulation of PD-L1
Authors: Tober Joanna , Maijenburg Marijke M.W. , Li Yan , Gao Long , Hadland Brandon K. , Gao Peng , Minoura Kodai , Bernstein Irwin D. , Tan Kai , Speck Nancy A.
Published: December 2017

Hematopoietic stem cells (HSCs) mature from pre-HSCs that originate in the major arteries of the embryo. To identify HSCs from in vitro sources, it will be necessary to refine markers of HSCs matured ex vivo. We purified and compared the transcriptomes of pre-HSCs, HSCs matured ex vivo, and fetal liver HSCs. We found that HSC maturation in vivo or ex vivo is accompanied by the down-regulation of genes involved in embryonic development and vasculogenesis, and up-regulation of genes involved in hematopoietic organ development, lymphoid development, and immune responses. Ex vivo matured HSCs more closely resemble fetal liver HSCs than pre-HSCs, but are not their molecular equivalents. We show that ex vivo–matured and fetal liver HSCs express programmed death ligand 1 (PD-L1). PD-L1 does not mark all pre-HSCs, but cell surface PD-L1 was present on HSCs matured ex vivo. PD-L1 signaling is not required for engraftment of embryonic HSCs. Hence, up-regulation of PD-L1 is a correlate of, but not a requirement for, HSC maturation.
Iron modulation of erythropoiesis is associated with Scribble-mediated control of the erythropoietin receptor
Authors: Khalil Shadi , Delehanty Lorrie , Grado Stephen , Holy Maja , White Zollie , Freeman Katie , Kurita Ryo , Nakamura Yukio , Bullock Grant , Goldfarb Adam
Published: December 2017

Iron-restricted human anemias are associated with the acquisition of marrow resistance to the hematopoietic cytokine erythropoietin (Epo). Regulation of Epo responsiveness by iron availability serves as the basis for intravenous iron therapy in anemias of chronic disease. Epo engagement of its receptor normally promotes survival, proliferation, and differentiation of erythroid progenitors. However, Epo resistance caused by iron restriction selectively impairs proliferation and differentiation while preserving viability. Our results reveal that iron restriction limits surface display of Epo receptor in primary progenitors and that mice with enforced surface retention of the receptor fail to develop anemia with iron deprivation. A mechanistic pathway is identified in which erythroid iron restriction down-regulates a receptor control element, Scribble, through the mediation of the iron-sensing transferrin receptor 2. Scribble deficiency reduces surface expression of Epo receptor but selectively retains survival signaling via Akt. This mechanism integrates nutrient sensing with receptor function to permit modulation of progenitor expansion without compromising survival.
γδ T cells provide the early source of IFN-γ to aggravate lesions in spinal cord injury
Authors: Sun Guodong , Yang Shuxian , Cao Guangchao , Wang Qianghua , Hao Jianlei , Wen Qiong , Li Zhizhong , So Kwok-Fai , Liu Zonghua , Zhou Sufang , Zhao Yongxiang , Yang Hengwen , Zhou Libing , Yin Zhinan
Published: December 2017

Immune responses and neuroinflammation are critically involved in spinal cord injury (SCI). γδ T cells, a small subset of T cells, regulate the inflammation process in many diseases, yet their function in SCI is still poorly understood. In this paper, we demonstrate that mice deficient in γδ T cells (TCRδ−/−) showed improved functional recovery after SCI. γδ T cells are detected at the lesion sites within 24 hours after injury and are predominantly of the Vγ4 subtype and express the inflammatory cytokine IFN-γ. Inactivating IFN-γ signaling in macrophages results in a significantly reduced production of proinflammatory cytokines in the cerebrospinal fluid (CSF) of mice with SCIs and improves functional recovery. Furthermore, treatment of SCI with anti-Vγ4 antibodies has a beneficial effect, similar to that obtained with anti–TNF-α. In SCI patients, γδ T cells are detected in the CSF, and most of them are IFN-γ positive. In conclusion, manipulation of γδ T cell functions may be a potential approach for future SCI treatment.
Obesity alters the long-term fitness of the hematopoietic stem cell compartment through modulation of Gfi1 expression
Authors: Lee Jung-Mi , Govindarajah Vinothini , Goddard Bryan , Hinge Ashwini , Muench David E. , Filippi Marie-Dominique , Aronow Bruce , Cancelas Jose A. , Salomonis Nathan , Grimes H. Leighton , Reynaud Damien
Published: December 2017

Obesity is a chronic organismal stress that disrupts multiple systemic and tissue-specific functions. In this study, we describe the impact of obesity on the activity of the hematopoietic stem cell (HSC) compartment. We show that obesity alters the composition of the HSC compartment and its activity in response to hematopoietic stress. The impact of obesity on HSC function is progressively acquired but persists after weight loss or transplantation into a normal environment. Mechanistically, we establish that the oxidative stress induced by obesity dysregulates the expression of the transcription factor Gfi1 and that increased Gfi1 expression is required for the abnormal HSC function induced by obesity. These results demonstrate that obesity produces durable changes in HSC function and phenotype and that elevation of Gfi1 expression in response to the oxidative environment is a key driver of the altered HSC properties observed in obesity. Altogether, these data provide phenotypic and mechanistic insight into durable hematopoietic dysregulations resulting from obesity.
Continuous activity of Foxo1 is required to prevent anergy and maintain the memory state of CD8+ T cells
Authors: Delpoux Arnaud , Michelini Rodrigo Hess , Verma Shilpi , Lai Chen-Yen , Omilusik Kyla D. , Utzschneider Daniel T. , Redwood Alec J. , Goldrath Ananda W. , Benedict Chris A. , Hedrick Stephen M.
Published: December 2017

Upon infection with an intracellular pathogen, cytotoxic CD8+ T cells develop diverse differentiation states characterized by function, localization, longevity, and the capacity for self-renewal. The program of differentiation is determined, in part, by FOXO1, a transcription factor known to integrate extrinsic input in order to specify survival, DNA repair, self-renewal, and proliferation. At issue is whether the state of T cell differentiation is specified by initial conditions of activation or is actively maintained. To study the spectrum of T cell differentiation, we have analyzed an infection with mouse cytomegalovirus, a persistent-latent virus that elicits different cytotoxic T cell responses characterized as acute resolving or inflationary. Our results show that FOXO1 is continuously required for all the phenotypic characteristics of memory-effector T cells such that with acute inactivation of the gene encoding FOXO1, T cells revert to a short-lived effector phenotype, exhibit reduced viability, and manifest characteristics of anergy.
Quasi-optimality of a pressure-robust nonconforming finite element method for the Stokes-problem
Authors: Linke A. , Merdon C. , Neilan M. , Neumann F.
Published: December 2017

Nearly all classical inf-sup stable mixed finite element methods for the incompressible Stokes equations are not pressure-robust, i.e., the velocity error is dependent on the pressure. However, recent results show that pressure-robustness can be recovered by a nonstandard discretization of the right-hand side alone. This variational crime introduces a consistency error in the method which can be estimated in a straightforward manner provided that the exact velocity solution is sufficiently smooth. The purpose of this paper is to analyze the pressure-robust scheme with low regularity. The numerical analysis applies divergence-free

H
1

H^1

-conforming Stokes finite element methods as a theoretical tool. As an example, pressure-robust velocity and pressure a priori error estimates will be presented for the (first-order) nonconforming Crouzeix–Raviart element. A key feature in the analysis is the dependence of the errors on the Helmholtz projector of the right-hand side data, and not on the entire data term. Numerical examples illustrate the theoretical results.
Einstein submanifolds with flat normal bundle in space forms are holonomic
Authors: Dajczer Marcos , Onti Christos-Raent , Vlachos Theodoros
Published: December 2017

A well-known result asserts that any isometric immersion with flat normal bundle of a Riemannian manifold with constant sectional curvature into a space form is (at least locally) holonomic. In this note, we show that this conclusion remains valid for the larger class of Einstein manifolds. As an application, when assuming that the index of relative nullity of the immersion is a positive constant we conclude that the submanifold has the structure of a generalized cylinder over a submanifold with flat normal bundle.
The 𝑡-structure induced by an 𝑛-tilting module
Authors: Bazzoni Silvana
Published: December 2017

We study the

t
t

-structure induced by an

n
n

-tilting module

T
T

in the derived category

D

(
R
)

\mathcal {D}(R)

of a ring

R
R

. Our main objective is to determine when the heart of the

t
t

-structure is a Grothendieck category. We obtain characterizations in terms of properties of the module category over the endomorphism ring of

T
T

and, as a main result, we prove that the heart is a Grothendieck category if and only if

T
T

is a pure projective

R
R

-module.
Complex Riemannian foliations of open Kähler manifolds
Authors: Murphy Thomas , Nagy Paul-Andi
Published: December 2017

Classification results for complex Riemannian foliations are obtained. For open subsets of irreducible Hermitian symmetric spaces of compact type, where one has explicit control over the curvature tensor, we completely classify such foliations by studying the infinitesimal model associated with the canonical connection. We also establish results for symmetric spaces of noncompact type and a general rigidity result for any irreducible Kähler manifold.
Mitotic defects lead to neuronal aneuploidy and apoptosis in frontotemporal lobar degeneration caused by MAPT mutations
Authors: Caneus Julbert , Granic Antoneta , Rademakers Rosa , Dickson Dennis W. , Coughlan Christina M. , Chial Heidi J. , Potter Huntington
Published: December 2017

Mutant Tau (MAPT) can lead to frontotemporal lobar degeneration (FTLD). Previous studies associated MAPT mutations and altered function with aneuploidy and chromosome instability in human lymphocytes and in Drosophila development. Here we examine whether FTLD-causing mutations in human MAPT induce aneuploidy and apoptosis in the mammalian brain. First, aneuploidy was found in brain cells from MAPT mutant transgenic mice expressing FTLD mutant human MAPT. Then brain neurons from mice homozygous or heterozygous for the Tau (Mapt) null allele were found to exhibit increasing levels of aneuploidy with decreasing Tau gene dosage. To determine whether aneuploidy leads to neurodegeneration in FTLD, we measured aneuploidy and apoptosis in brain cells from patients with MAPT mutations and identified both increased aneuploidy and apoptosis in the same brain neurons and glia. To determine whether there is a direct relationship between MAPT-induced aneuploidy and apoptosis, we expressed FTLD-causing mutant forms of MAPT in karyotypically normal human cells and found that they cause aneuploidy and mitotic spindle defects that then result in apoptosis. Collectively, our findings reveal a neurodegenerative pathway in FTLD-MAPT in which neurons and glia exhibit mitotic spindle abnormalities, chromosome mis-segregation, and aneuploidy, which then lead to apoptosis.
Relief from nitrogen starvation triggers transient destabilization of glycolytic mRNAs inSaccharomyces cerevisiaecells
Authors: Tesnière Catherine , Pradal Martine , Bessière Chloé , Sanchez Isabelle , Blondin Bruno , Bigey Frédéric
Published: December 2017

Nitrogen replenishment of nitrogen-starved yeast cells resulted in substantial transcriptome changes. There was an unexplained rapid, transient down-regulation of glycolytic genes. This unexpected result prompted us to search for the factors controlling these changes, among which is the possible involvement of different nutrient-sensing pathways such as the TORC1 and cAMP/PKA pathways. To that end, the effects of various gene deletions or chemical blocking agents were tested by investigating the expression of PGK1, one of the glycolytic genes most affected after nitrogen replenishment. We report here that several factors affected glycolytic mRNA stability, among which were glucose sensing, protein elongation, nitrogen metabolism, and TOR signaling. Ammonium sensing was not involved in the response, but ammonium metabolism was required. Thus, our results suggest that, in the presence of glucose, carbon/nitrogen cross-talk is likely involved in the response to nitrogen upshift. Our data suggest that posttranscriptional control of glycolytic gene expression may be an important response to nitrogen replenishment.
Force-dependent binding of vinculin to α-catenin regulates cell–cell contact stability and collective cell behavior
Authors: Seddiki Rima , Narayana Gautham Hari Narayana Sankara , Strale Pierre-Olivier , Balcioglu Hayri Emrah , Peyret Grégoire , Yao Mingxi , Le Anh Phuong , Teck Lim Chwee , Yan Jie , Ladoux Benoit , Mège René Marc
Published: December 2017

The shaping of a multicellular body and repair of adult tissues require fine-­tuning of cell adhesion, cell mechanics, and intercellular transmission of mechanical load. Adherens junctions (AJs) are the major intercellular junctions by which cells sense and exert mechanical force on each other. However, how AJs adapt to mechanical stress and how this adaptation contributes to cell–cell cohesion and eventually to tissue-scale dynamics and mechanics remains largely unknown. Here, by analyzing the tension-dependent recruitment of vinculin, α-catenin, and F-actin as a function of stiffness, as well as the dynamics of GFP-tagged wild-type and mutated α-catenins, altered for their binding capability to vinculin, we demonstrate that the force-dependent binding of vinculin stabilizes α-catenin and is responsible for AJ adaptation to force. Challenging cadherin complexes mechanical coupling with magnetic tweezers, and cell–cell cohesion during collective cell movements, further highlight that tension-dependent adaptation of AJs regulates cell–cell contact dynamics and coordinated collective cell migration. Altogether, these data demonstrate that the force-dependent α-catenin/vinculin interaction, manipulated here by mutagenesis and mechanical control, is a core regulator of AJ mechanics and long-range cell–cell interactions.
Moesin is involved in polarity maintenance and cortical remodeling during asymmetric cell division
Authors: Abeysundara Namal , Simmonds Andrew J. , Hughes Sarah C.
Published: December 2017

An intact actomyosin network is essential for anchoring polarity proteins to the cell cortex and maintaining cell size asymmetry during asymmetric cell division of Drosophila neuroblasts (NBs). However, the mechanisms that control changes in actomyosin dynamics during asymmetric cell division remain unclear. We find that the actin-binding protein, Moesin, is essential for NB proliferation and mitotic progression in the developing brain. During metaphase, phosphorylated Moesin (p-Moesin) is enriched at the apical cortex, and loss of Moesin leads to defects in apical polarity maintenance and cortical stability. This asymmetric distribution of p-Moesin is determined by components of the apical polarity complex and Slik kinase. During later stages of mitosis, p-Moesin localization shifts more basally, contributing to asymmetric cortical extension and myosin basal furrow positioning. Our findings reveal Moesin as a novel apical polarity protein that drives cortical remodeling of dividing NBs, which is essential for polarity maintenance and initial establishment of cell size asymmetry.
CHROMIXS: automatic and interactive analysis of chromatography-coupled small-angle X-ray scattering data
Authors: Panjkovich Alejandro , Svergun Dmitri I
Published: December 2017

Size-exclusion chromatography (SEC) coupled to small-angle X-ray scattering (SAXS), also known as inline SEC-SAXS, is being increasingly used for the structural analysis of biological macromolecules, complexes and mixtures in solution. A single SEC-SAXS run generates thousands of individual SAXS profiles from the eluting solute and their analysis requires a correct identification of buffer and sample regions, a rather laborous task. We present CHROMIXS (as in CHROMatography Inline X-ray Scattering), a program for rapid reduction and analysis, both automatically and interactively, of SEC-SAXS data.

Availability and implementation

CHROMIXS is freely available to academic users as part of the ATSAS software suite (www.embl-hamburg.de/biosaxs/download.html).
Unforeseen pathologies caused by malaria
Authors: Lee Michelle Sue Jann , Coban Cevayir
Published: December 2017

Individuals from malaria-endemic regions often acquire partial immunity after multiple repeated infections throughout their lives. This partial immunity prevents them from developing severe complications and they often remain asymptomatic with a persistent, low parasite density in the blood, and therefore the necessity for treatment is neglected. These patients with chronic, asymptomatic malaria serve as a reservoir for Plasmodium parasite transmission, becoming a major obstacle for eradication efforts. The constant exposure to malaria infection may have benefits in the short term by conferring protection from acute, severe malaria; however, it may cause substantially more harm in the long term. Rather than the parasite burden itself, the complications induced by the dysregulated immune responses and the tissue damage done by the parasites and their products can cause chronic and irreversible suffering. Furthermore, the complete clearance of parasites in the body may not lead to complete recovery from the disease as complications can still persist. The fact that there are chronic pathologies caused by malaria that mostly remain obscure and have the potential to cause a serious burden has recently been gaining attention. Here, we present and discuss the evidence of unforeseen pathologies and the risks associated with malaria.
Is the East Asian flora ancient or not?
Authors: Chen Yong-Sheng , Deng Tao , Zhou Zhuo , Sun Hang
Published: December 2017

The East Asian flora (EAF) is a key biodiversity hotspot for understanding the origin and evolution of Northern Hemisphere floras, but there is an ongoing debate on whether it is a museum or a cradle for seed plants. Within the EAF, two main floras, the Sino-Himalayan Flora (mainly the Rhododendron Flora) and the Sino-Japanese Flora (mainly the Metasequoia Flora), have been recognized. Previous studies suggested that the EAF is ancient and the Metasequoia Flora is older than the Rhododendron Flora. To test this hypothesis, we synthesized molecular as well as fossil data on seed plants, focusing on the biogeographical origins and historical evolution of the EAF. We compared the ages of its two constituent floras, and examined the impact of the Asian monsoon and other environmental changes on the development of EAF through meta-analysis. Our results suggest that the EAF might be relatively young, with most of its clades originating since the Miocene. The Rhododendron Flora and the Metasequoia Flora are probably of a similar age. The formation and development of the Asian monsoon might have been the main factors that have driven the evolution of EAF. In the Rhododendron Flora, the north-south mountain chains increased the concentration of species and reduced extinction, and the barriers between the east and west have resulted in species differentiation, which triggered it to become a diversity center. The EAF appears to have multiple biogeographical origins, having closely affiliated not only with other floras in the Northern Hemisphere, but also with Gondwanan floras.
The nature of EU Pegasi: An Algol-type binary with a δ Scuti-type component
Authors: Yang Yuangui , Yuan Huiyu , Dai Haifeng , Zhang Xiliang
Published: December 2017

The comprehensive photometry and spectroscopy for the neglected eclipsing binary EU Pegasi are presented. We determine its spectral type to be A3V. With the W-D program, the photometric solution was deduced from the four-color light curves. The results imply that EU Peg is a detached binary with a mass ratio of q = 0.3105(± 0.0011), whose components nearly fill their Roche lobes. The low-amplitude pulsation occurs around the secondary eclipse, which may be attributed to the more massive component. Three frequencies are preliminarily explored by the Fourier analysis. The pulsating frequency at f1 = 34.1 c d−1 is a p-mode pulsation. The orbital period may be undergoing a secular decrease, superimposed by a cyclic variation. The period decreases at a rate of dP/dt = −7.34 ± 1.06 d yr−1, which may be attributed to mass loss from the system due to stellar wind. The cyclic oscillation, with Pmod = 31.0 ± 1.4 yr and A = 0.0054 ± 0.0010 d, may be caused by the light-time effect due to the assumed third body. With its evolution, the pulsating binary EU Peg will evolve from the detached configuration to the semi-detached case.
Quantitative Trait Loci Mapping of Multiple Independent Loci for Resistance to Fusarium oxysporum f. sp. vasinfectum Races 1 and 4 in an Interspecific Cotton Population
Authors: Wang Congli , Ulloa Mauricio , Duong Tra , Roberts Philip A.
Published: December 2017

Fusarium wilt, caused by the soilborne fungal pathogen Fusarium oxysporum f. sp. vasinfectum, is a vascular disease of cotton (Gossypium spp.). F. oxysporum f. sp. vasinfectum race 1 (FOV1) causes major plant injury and yield loss in G. hirsutum cultivars with coinfection with root-knot nematode (Meloidogyne incognita), while F. oxysporum f. sp. vasinfectum race 4 (FOV4) causes plant damage without nematode coinfection in G. hirsutum and in G. barbadense cultivars. Quantitative trait loci (QTL) analysis of the interspecific cross G. barbadense Pima S-7 × G. hirsutum Acala NemX revealed separate multiple loci determining resistance to FOV1 and FOV4, confirming that race specificity occurs in F. oxysporum f. sp. vasinfectum. Based on the area under the disease progress stairs, six major QTLs on chromosomes (Chrs) 1, 2, 12, 15 (2), and 21 contributing 7 to 15% to FOV1 resistance and two major QTLs on Chrs 14 and 17 contributing 12 to 33% to FOV4 resistance were identified. Minor-effect QTLs contributing to resistance to both FOV1 and FOV4 were also identified. These results define and establish a pathosystem of race-specific resistance under polygenic control. This research also validates the importance of previously reported markers and chromosome regions and adds new information for the location of F. oxysporum f. sp. vasinfectum resistance genes. Some F8 recombinant inbred lines have resistance to both FOV1 and FOV4 and also to root-knot nematode, providing multiple resistance sources for breeding.
Fake It ’Til You Make It: Pressures to Measure Up in Surgical Training
Authors: Patel Priyanka , Martimianakis Maria A. , Zilbert Nathan R. , Mui Carween , Hammond Mobilio Melanie , Kitto Simon , Moulton Carol-anne
Published: December 2017

Purpose

Expectations of certainty and confidence in surgical culture are a source of internal conflict for surgeons and learners, with surgeons describing a pressure to project an image that is, at times, inconsistent with how they feel internally. The authors explored surgical residents’ perceptions of “impression management” and its effects on surgical judgment and decision making.

Method

The authors used a constructivist grounded theory approach to conduct and analyze 15 semistructured interviews with general surgery trainees at an urban Canadian academic health center between 2012 and 2014. Interviews explored impression management in the context of resident learning and performance. Analysis was inductive, whereby emergent themes contributed to a developing conceptual framework, and deductive, using an existing theory of impression management.

Results

Residents described sensing an “expectation” to portray an image aligned with the ideal surgical stereotype of confidence and certainty, and shared strategies used to mirror this image. Impression management strategies were used to portray an image of competence, with the aim to improve access to teaching and evaluations. Unintended consequences of impression management on decision making, patient safety, and resident wellness were identified.

Conclusions

These findings contribute to a deeper understanding of the potential impact of the sociocultural context on residency training, and provide a language allowing for more explicit discussions about the impact of surgical culture on trainee behaviors. Translation includes formal instruction of these concepts in the curriculum so that trainees better recognize, reflect on, and cope with the pressures to perform in front of others.
Percutaneous Kyphoplasty
Authors: Yilmaz Atilla , Çakir Mürteza , Yücetaş Cem Şeyho , Urfali Boran , Üçler Necati , Altaş Murat , Aras Mustafa , Serarslan Yurdal , Koç Rahmi Kemal
Published: December 2017

Study Design.

A multicenter retrospective study of patients who underwent unilateral and bilateral balloon kyphoplasty.

Objective.

The aim of this study was to compare the radiographic and clinical results of unilateral and bilateral balloon kyphoplasty to treat osteoporotic vertebral compression fractures.

Summary of Background Data.

Percutaneous kyphoplasty has long been used as a successful method in the treatment of osteoporotic vertebral compression fractures. Although the bilateral approach is considered to be the mainstay application of percutaneous kyphoplasty, the unilateral approach has also been shown to be sufficient and even more effective in some cases.

Methods.

A total of 87 patients who underwent percutaneous kyphoplasty due to osteoporotic vertebral compression fractures between 2009 and 2016 were retrospectively evaluated and divided into two groups as patients who underwent unilateral or bilateral percutaneous kyphoplasty. Unilateral percutaneous kyphoplasty was performed in 36 and bilateral percutaneous kyphoplasty in 51 patients. The groups were compared in terms of clinical outcomes, radiological findings, and complications. Clinical outcomes were evaluated using Visual Analogue Scale and Oswestry Disability Index and the radiological findings were evaluated by comparing the preoperative and postoperative day 1 and year 1 values of anterior, middle, and posterior vertebral heights and kyphosis angle.

Results.

Clinical improvement occurred in both groups but no significant difference was observed. In radiological workup, no significant difference was found between the groups in terms of improvements in vertebral heights and kyphosis angle. Operative time and the amount of cement used for the surgery were significantly lower in the patients that underwent unilateral kyphoplasty.

Conclusion.

Unilateral percutaneous kyphoplasty is as effective as bilateral percutaneous kyphoplasty both radiologically and clinically. Operative time and the amount of cement used for the surgery are significantly lower in unilateral kyphoplasty, which may play a role in decreasing complication rates.

Level of Evidence: 3
Bladder cancer risk in users of selected drugs for cardiovascular disease prevention
Authors: Guercio Valentina , Turati Federica , Bosetti Cristina , Polesel Jerry , Serraino Diego , Montella Maurizio , Libra Massimo , Galfano Antonio , La Vecchia Carlo , Tavani Alessandra
Published: December 2017

The aim of this study was to investigate the relation between bladder cancer risk and the use of selected drugs for cardiovascular disease (CVD) prevention, such as aspirin, statins, and calcium channel blockers (CCBs). We analyzed data from a multicentric case–control study carried out in Italy between 2003 and 2014, including 690 bladder cancer cases and 665 hospital controls. Odds ratios (ORs) of bladder cancer and corresponding 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models. The ORs for bladder cancer were 1.21 (95% CI: 0.87–1.68) for regular use of aspirin, 0.72 (95% CI: 0.54–0.97) for use of any CCBs, and 1.32 (95% CI: 0.87–1.99) for use of any statins. A slight inverse association was found with duration of use of CCBs, whereas no consistent association was found with duration of use, age at first use, and frequency for aspirin and statin use, or with indication of use for aspirin (as an analgesic or, for CVD prevention). No significant association was found for various combinations of drugs or for all drugs combined (OR=1.23, 95% CI: 0.31–4.85). Our data indicate the lack of a relevant association between the use of selected drugs for CVD prevention and bladder cancer risk, although suggest a potential favorable role for CCBs.
Patient-centered Contraceptive Counseling and Prescribing
Authors: RIVLIN KATHERINE , ISLEY MICHELLE M.
Published: December 2017

Learning how to best meet a patient’s contraceptive needs improves her chances of using her birth control consistently and is crucial to providing patient-centered care. The best contraceptive method for an individual patient is the one that is safe and that she is most comfortable using. Women’s health care providers must be equipped to talk to each patient about her needs and options. The shared decision-making model in contraceptive counseling allows the patient and provider to work together in order to meet a patient’s needs while remaining medically safe.
CHANGES IN PLASMA VASCULAR ENDOTHELIAL GROWTH FACTOR LEVEL AFTER INTRAVITREAL INJECTION OF BEVACIZUMAB, AFLIBERCEPT, OR RANIBIZUMAB FOR DIABETIC MACULAR EDEMA
Authors: Hirano Takao , Toriyama Yuichi , Iesato Yasuhiro , Imai Akira , Murata Toshinori
Published: December 2017

Purpose:

The aim of this study was to investigate the changes in plasma vascular endothelial growth factor (VEGF) level depending on the severity of diabetic retinopathy (DR) or diabetic macular edema (DME) and after intravitreal injection of bevacizumab, aflibercept, or ranibizumab for treatment of DME.

Methods:

Plasma VEGF level was evaluated in 72 patients with DR and changes were measured in 42 patients with DME receiving intravitreal injections of bevacizumab, aflibercept, or ranibizumab at the initial injection.

Results:

There were no correlations between plasma VEGF level and the severity of DME or DR. Baseline plasma VEGF level (51.9 pg/mL) was significantly reduced using bevacizumab to 11.9 pg/mL after 1 week and 24.1 pg/mL after 4 weeks (P = 0.0130 and 0.0201, respectively). In aflibercept-treated eyes, plasma VEGF decreased from 52.2 pg/mL to 7.8 pg/mL and 12.6 pg/mL, respectively, at the same time points (both P < 0.001). No such reductions were observed in patients receiving ranibizumab.

Conclusion:

Baseline plasma VEGF level showed no correlations with DR or DME severity, whereas intravitreal injection of bevacizumab or aflibercept significantly reduced plasma VEGF for up to 4 weeks and ranibizumab produced no such effects. Changes in plasma VEGF level seemed not to be critical in progression or treatment of DME and DR.
Isoniazid for the Prevention of Tuberculosis in HIV-Infected Children
Authors: Charan Jaykaran , Goyal Jagdish Prasad , Reljic Tea , Emmanuel Patricia , Patel Atul , Kumar Ambuj
Published: December 2017

Background:

Isoniazid is recommended for prevention of tuberculosis (TB) in HIV-infected adults, but its efficacy in children living with HIV (CLHIV) is not known. We performed a systematic review to assess the efficacy of isoniazid for the prevention of TB in CLHIV.

Methods:

We searched PubMed, Cochrane Clinical Trial Registry and Google Scholar from inception to December 2016. Any randomized controlled trial assessing the role of isoniazid for the prevention of TB in CLHIV was eligible for inclusion. The primary endpoint was TB incidence; secondary end points were mortality, overall survival and severe adverse events. Dual independent extraction of all data was performed. Data were pooled under a random effects model and summarized either as risk ratio (RR) or hazard ratio along with 95% confidence intervals (CIs).

Results:

Of 931 references, 3 randomized controlled trials enrolling 977 patients met the inclusion criteria. Pooled results showed a statistically nonsignificant reduction in TB incidence (RR: 0.70; 95% CI: 0.47–1.04; P = 0.07) and mortality (RR: 0.94; 95% CI: 0.39–2.23; P = 0.88) with the use of isoniazid compared with placebo. One study was stopped early because of excess deaths in the placebo arm. However, results from subgroup analysis restricted to only completed trials did not change the overall findings.

Conclusions:

Isoniazid did not reduce the incidence of TB in CLHIV. All included studies were performed in regions with high prevalence of TB making the overall generalizability limited.
Nephrotoxicity With Vancomycin in the Pediatric Population
Authors: Fiorito Theresa M. , Luther Megan K. , Dennehy Penelope H. , LaPlante Kerry L. , Matson Kelly L.
Published: December 2017

Background:

Vancomycin is frequently used to treat methicillin-resistant Staphylococcus aureus infections in pediatric patients. Vancomycin exposure may lead to an increase in frequency of nephrotoxicity. Our aim was to conduct a systematic review to describe predictors of nephrotoxicity associated with vancomycin, including documented trough concentrations ≥15 mg/L. We also aimed to use a meta-analysis to assess the impact of a vancomycin trough ≥15 mg/L on nephrotoxicity.

Methods:

A literature search was performed using PubMed, Cochrane Library, Embase and Web of Sciences database. We included randomized clinical trials and observational studies evaluating the relationship between vancomycin troughs and nephrotoxicity in pediatric-age patients. Studies not measuring troughs or defining a different cut-off point than 15 mg/L were excluded. Data on age, exclusion criteria, nephrotoxicity definition, risk factors for nephrotoxicity and vancomycin trough levels were extracted from selected papers.

Results:

Ten studies were identified for meta-analysis. All subjects had comparatively normal baseline serum creatinine values. Common risk factors identified included elevated (≥15 mg/L) trough levels, renal impairment, hypovolemia and concurrent use of nephrotoxic medications. Troughs ≥15 mg/L increased nephrotoxicity by 2.7-fold (odds ratio (OR), 2.71; 95% confidence interval: 1.82–4.05; I
2 = 40%; Q = 0.09). These odds were further increased among patients in the pediatric intensive care unit (OR, 3.61; 95% confidence interval: 1.21–10.74; I
2 = 45%; Q = 0.18).

Conclusions:

Though the rate of vancomycin-induced nephrotoxicity is increased in pediatric patients with higher vancomycin troughs, other factors such as intensive care unit admission, hypovolemia and concurrent nephrotoxic drug use appear to contribute to the development of nephrotoxicity.
Perceptions of Integration of the Clinical Pharmacist into the Patient Care Medical Home Model
Authors: McFarland M. Shawn , Lamb Kristen , Hughes Jonathan , Thomas Ashley , Gatwood Justin , Hathaway Jacob
Published: December 2017

Introduction:

The patient-centered medical home (PCMH) model is a multidisciplinary, team-based approach to healthcare that focuses on actively involving the patient in clinical decision making. The Veterans Health Administration (VA), while desiring to be a national leader in the delivery of primary care services, used the principles of the PCMH model to design the patient-aligned care team (PACT). The purpose of this study, was to explore the perception of the PACT members after integration of a clinical pharmacist to the PACT.

Methods:

This was a single-center cross-sectional study conducted at an integrated Veterans Health Administration system. We electronically surveyed PACT staff practicing within VA-Tennessee Valley Health Care System as of October 1, 2016 using a modified version of the Medicine Medication Use Processes Matrix (MUPM) containing 19 items on five theoretical grouping of processes (evaluation and management, monitoring, medication review, documentation, and education) and two groupings(clinician satisfaction and access).

Results:

Ninety-one complete responses were received. Perceptions were positive, with 79% rated as either 4 (“moderate contribution”) or 5 (“major contribution”). Individual responses based on discipline, with the exception of the medical support assistant were rated positive, specifically job satisfaction.

Conclusions:

This study evaluated the perceptions of clinical pharmacist integration into the PACT model. Respondents perceived clinical pharmacist beneficial.
Role of Full-spectrum Endoscopy in Colorectal Cancer Screening
Authors: Núñez-Rodríguez Henar , Diez-Redondo Pilar , Pérez-Miranda Manuel , Gonzalez Sagrado Manuel , Conde Rosa , De la Serna Carlos
Published: December 2017

Goals:

The aim of this study was to compare a new, full-spectrum endoscope (Fuse; EndoChoice, Alpharetta, GA) to standard forward-viewing colonoscopy in the detection of colorectal neoplasms.

Background:

Colonoscopy, the gold standard for the detection of colorectal cancer, fails to detect 22% to 28% of polyps, increasing the risk of interval cancer. Endoscopic improvement of the adenoma detection rate decrease interval carcinomas. Full-spectrum endoscopy (FUSE) (330-degree field of view), in a tandem study, has been shown to reduce the adenoma miss rate.

Study:

Prospective, randomized study of 249 patients in patients referred from the colorectal screening program with a positive fecal occult blood test (FOBT). Patients were randomized to standard forward-viewing colonoscopy (170 degrees) or to full-spectrum colonoscopy with the Fuse system (330 degrees). Study variables were the adenoma detection rate, the polyp detection rate, the mean number of adenomas per procedure, the lesions detected according to the location, morphology and size, cecal intubation rate, total procedure time, insertion time to the cecum, therapeutic success, and adverse events.

Results:

The Fuse system did not produce a significantly higher adenoma detection rate than standard forward-viewing colonoscopy (FUSE 73.1% vs. standard colonoscopy 68.1%; P=0.47) but did have a significantly longer insertion time (FUSE 6.2 min vs. standard colonoscopy 4.2 min; P< 0.001). Further analysis failed to reveal any significant difference in polyp/adenoma detection rates by lesion size or colonic section.

Conclusions:

FUSE did not detect significantly more colorectal neoplasia than forward viewing colonoscopy in a medium-risk CRC screening population with positive FOBT.
Association between celiac disease and schizophrenia: a meta-analysis
Authors: Wijarnpreecha Karn , Jaruvongvanich Veeravich , Cheungpasitporn Wisit , Ungprasert Patompong
Published: December 2017

Background/objective

Recent epidemiologic studies have suggested that patients with celiac disease might be at an increased risk of schizophrenia. However, the data on this risk remain inconclusive. This meta-analysis was conducted with the aim to summarize all available evidence.

Methods

A literature search was carried out using MEDLINE and Embase database from inception to June 2017. Studies that compared the risk of schizophrenia among patients with celiac disease versus individuals without celiac disease were included. Pooled odds ratio and 95% confidence interval were calculated using a random-effect, generic inverse-variance method.

Results

Of the 284 retrieved studies, four met our eligibility criteria and were included in the analysis. We found a higher risk of schizophrenia among patients with celiac disease compared with individuals without celiac disease with the pooled odds ratio of 2.03 (95% confidence interval: 1.45–2.86). The statistical heterogeneity of this study was insignificant (I
2=0%).

Conclusion

This systematic review and meta-analysis found a significantly higher risk of schizophrenia among patients with celiac disease.
Short article: Presence, extent and location of pancreatic necrosis are independent of aetiology in acute pancreatitis
Authors: Verdonk Robert C. , Sternby Hanna , Dimova Alexandra , Ignatavicius Povilas , Koiva Peter , Penttila Anne K. , Ilzarbe Lucas , Regner Sara , Rosendahl Jonas , Bollen Thomas L.
Published: December 2017

Objective

The most common aetiologies of acute pancreatitis (AP) are gallstones, alcohol and idiopathic. The impact of the aetiology of AP on the extent and morphology of pancreatic and extrapancreatic necrosis (EXPN) has not been clearly established. The aim of the present study was to assess the influence of aetiology on the presence and location of pancreatic necrosis in patients with AP.

Patients and methods

We carried out a post-hoc analysis of a previously established multicentre cohort of patients with AP in whom a computed tomography was available for review. Clinical data were obtained from the medical records. All computed tomographies were revised by the same expert radiologist. The impact of aetiology on pancreatic and EXPN was calculated.

Results

In total, 159 patients with necrotizing pancreatitis were identified from a cohort of 285 patients. The most frequent aetiologies were biliary (105 patients, 37%), followed by alcohol (102 patients, 36%) and other aetiologies including idiopathic (78 patients, 27%). No relationship was found between the aetiology and the presence of pancreatic necrosis, EXPN, location of pancreatic necrosis or presence of collections.

Conclusion

We found no association between the aetiology of AP and the presence, extent and anatomical location of pancreatic necrosis.
Factors associated with the true location of ingested fishbones
Authors: Lu Yen-Ting , Chen Hung-Wen , Tseng Yao-Ying , Chen Chia-Hsi , Lu Ying-Chou
Published: December 2017

Objectives

Fishbone ingestion is a common problem worldwide, and the first step for managing this condition is to locate the fishbone precisely. However, until now, no study has analysed the true location of fishbone and its associated factors. Thus, this study identified the factors predicting the true location of fishbone and subsequently attempted to provide a management algorithm for fishbone ingestion.

Patients and methods

This retrospective study was carried out at St Martin De Porres Hospital, Taiwan, between January 2015 and January 2016. All patients were diagnosed as having fishbone ingestion within the pharynx and underwent fishbone removal.

Results

This study included 198 consecutive patients with a mean age of 43.1 years (range: 1–84 years). The sensitivity of lateral neck radiography in the diagnosis of fishbone in the pharynx was only 22%. The fishbone locations were as follows: the tonsil in 72 (36.4%) patients, the tongue base / vallecula in 112 (56.6%) and the hypopharynx in 14 (7.0%). Multiple logistic regression analysis showed that patient age and fishbone length were significant independent risk factors associated with the true location of fishbone ingestion. Among all patients, fishbone was removed transorally under direct vision in 73 (36.9%) patients and using flexible nasopharyngoscopy in 125 (63.1%) patients.

Conclusion

Patient age and fishbone length are important independent factors associated with the location of ingested fishbone. Lateral neck radiography is not beneficial for diagnosing fishbone ingestion within the pharynx. Flexible nasopharyngoscopy, by contrast, is an important method for the diagnosis and treatment of fishbone ingestion within this location.
Assessing the Organizational Characteristics Influencing Quality Improvement Implementation in Saudi Hospitals
Authors: Shamsuddin Alaraki Mohammad
Published: December 2017

Background:

The health care system in Saudi Arabia has serious problems with quality and safety that can be reduced through systematic quality improvement (QI) activities. Despite the use of different QI models to improve health care in Saudi hospitals during the last 2 decades, consistent improvements have not yet been achieved and the results are still far below expectations. This may reflect a problem in introducing and implementing the QI models in the local contexts. The objective of this study is to assess the extent of QI implementation in Saudi hospitals and to identify the organizational characteristics that make Saudi hospitals particularly challenging for QI. Understanding these characteristics can inform efforts to improve them and may lead to more successful implementation.

Methods:

A mixed-methods approach was conducted using 2 data collection tools: questionnaires and interviews. The quantitative phase (questionnaires) aimed to uncover the current level of QI implementation in Saudi hospital as measured by 7 critical dimensions adapted from the literature. The qualitative phase (interviews) aimed to understand the organizational characteristics that impede or underpin QI in Saudi hospitals.

Results and Discussion:

The QI implementation was found to be significantly poor across the 7 dimensions with average score ranging between 22.80 ± 0.57 and 2.11 ± 0.69 on a 5-point Likert scale and with P value of less than .05. We also found that the current level of QI implementation helped Saudi hospitals neither to improve “customer satisfaction” nor to achieve measurable improvements in “quality results” scoring significantly low at 2.11 ± 0.69 with P value of .000 and 2.47 ± 0.57 with P value of .000, respectively. Our study confirms the presence of a multitude of organizational barriers that impede QI in Saudi hospitals. These are related to organizational culture, human resources management, processes and systems, and structure. These 4 were found to have the strongest impact on QI in Saudi hospitals.

Conclusion:

It appears that the most important contributing factors to the successful implementation of QI in Saudi hospitals are proper human resources utilization and effective quality management. Through careful planning, change management, proper utilization of human resources, supportive quality information systems, focus on processes and systems, structural support, and an organizational culture that is compatible with QI philosophy, Saudi hospitals will be more capable in achieving sustained measureable improvements in the quality and safety of patient care.
Framework for Research on Implementation of Process Redesigns
Authors: Ashok Mahima , Hung Dorothy , Rojas-Smith Lucia , Halpern Michael T. , Harrison Michael
Published: December 2017

Background:

Complex system interventions benefit from close attention to factors affecting implementation and resultant outcomes. This article describes a framework for examining these factors in process redesign (PR) and for assessing PR outcomes.

Methods:

Using literature scans and expert comment on draft frameworks based on the Consolidated Framework for Implementation Research, a team of researchers developed the PR framework for the Agency for Healthcare Research and Quality. As a case study, an independent team of researchers in a large care system subsequently applied the PR framework to implementation of Lean-based primary care redesigns.

Results:

The PR framework adds 2 domains to the Consolidated Framework for Implementation Research, focused on relevant measures of implementation and outcomes, as well as some new constructs to the Consolidated Framework for Implementation Research. Using the PR framework to guide a study of primary care PR, researchers found that the health care reform environment encouraged staff recognition of need for redesign, but physicians worried about key redesign issues, including colocation with care team partners and the competencies of the individuals assigned to manage new workflows. Team member acceptance of the redesign was also influenced by other features of the implementation process and contextual features, including the decision style of the local clinic.

Conclusions:

The PR framework helped guide the qualitative study and aided researchers in informing their leadership about critical issues affecting PR implementation.