bluuebunny/crossref_metadata_2025 huggingface dataset:
Helix–strand interaction regulates stability and aggregation of the human mitochondrial membrane protein channel VDAC3
Authors: Gupta Ankit , Mahalakshmi Radhakrishnan
Published: January 2019

Voltage-dependent anion channels (VDACs) are β-sheet–rich transmembrane β-barrels that are vital for metabolite transport across the mitochondrial membrane. Under cellular stress, human VDACs hetero-oligomerize and coaggregate with proteins that can form amyloidogenic and neurodegenerative deposits, implicating a role for VDACs in proteotoxicity. However, whether VDACs possess intrinsic interaction sites that can lead to protein aggregation is not known. Here, we couple a systematic thiol replacement strategy with far-UV circular dichroism spectropolarimetry and UV scattering spectroscopy to map aggregation-prone regions of human VDACs, using isoform 3 as our model VDAC. We show that the region comprising strands β7–β9 is highly aggregation prone. Further, we find that an α1–β7–β9 interaction (involving the hVDAC3 N-terminal α1 helix) can lower protein aggregation, whereas perturbations of this interaction promote VDAC aggregation. We also show that hVDAC3 aggregation proceeds via a partially unfolded structure. Our findings allow us to propose a plausible mechanism for the role of human VDACs in forming proteotoxic aggregates in the cell. The key target sites on VDACs—strands β7–β9—may be useful for developing VDAC aggregation inhibitors.
Automorphism groups of finite topological rank
Authors: Kaplan Itay , Simon Pierre
Published: January 2019

We offer a criterion for showing that the automorphism group of an ultrahomogeneous structure is topologically 2-generated and even has a cyclically dense conjugacy class. We then show how finite topological rank of the automorphism group of an

ω
\omega

-categorical structure can go down to reducts. Together, those results prove that a large number of

ω
\omega

-categorical structures that appear in the literature have an automorphism group of finite topological rank. In fact, we are not aware of any

ω
\omega

-categorical structure to which they do not apply (assuming the automorphism group has no compact quotients). We end with a few questions and conjectures.
Irreducible 3-manifolds that cannot be obtained by 0-surgery on a knot
Authors: Hedden Matthew , Kim Min Hoon , Mark Thomas , Park Kyungbae
Published: January 2019

We give two infinite families of examples of closed, orientable, irreducible 3-manifolds

M
M

such that

b
1

(
M
)
=
1

b_1(M)=1

and

π
1

(
M
)

\pi _1(M)

has weight 1, but

M
M

is not the result of Dehn surgery along a knot in the 3-sphere. This answers a question of Aschenbrenner, Friedl, and Wilton and provides the first examples of irreducible manifolds with

b
1

=
1

b_1=1

that are known not to be surgery on a knot in the 3-sphere. One family consists of Seifert fibered 3-manifolds, while each member of the other family is not even homology cobordant to any Seifert fibered 3-manifold. None of our examples are homology cobordant to any manifold obtained by Dehn surgery along a knot in the 3-sphere.
Universality results for zeros of random holomorphic sections
Authors: Bayraktar Turgay , Coman Dan , Marinescu George
Published: January 2019

In this work we prove a universality result regarding the equidistribution of zeros of random holomorphic sections associated to a sequence of singular Hermitian holomorphic line bundles on a compact Kähler complex space

X
X

. Namely, under mild moment assumptions, we show that the asymptotic distribution of zeros of random holomorphic sections is independent of the choice of the probability measure on the space of holomorphic sections. In the case when

X
X

is a compact Kähler manifold, we also prove an off-diagonal exponential decay estimate for the Bergman kernels of a sequence of positive line bundles on

X
X

.
C/EBPβ suppresses keratinocyte autonomous type 1 IFN response and p53 to increase cell survival and susceptibility to UVB-induced skin cancer
Authors: Tam Hann W , Hall Jonathan R , Messenger Zachary J , Jima Dereje D , House John S , Linder Keith , Smart Robert C
Published: January 2019

p53 is activated by DNA damage and oncogenic stimuli to regulate senescence, apoptosis and cell-cycle arrest, which are essential to prevent cancer. Here, we utilized UVB radiation, a potent inducer of DNA damage, p53, apoptosis and skin cancer to investigate the mechanism of CCAAT/enhancer binding protein-β (C/EBPβ) in regulating p53-mediated apoptosis in keratinocytes and to test whether the deletion of C/EBPβ in epidermis can protect mice from UVB-induced skin cancer. UVB-treatment of C/EBPβ skin conditional knockout (CKOβ) mice increased p53 protein levels in epidermis and enhanced p53-dependent apoptotic activity 3-fold compared with UVB-treated control mice. UVB increased C/EBPβ levels through a p53-dependent pathway and stimulated the formation of a C/EBPβ-p53 protein complex; knockdown of C/EBPβ increased p53 protein stability in keratinocytes. These results suggest a p53-C/EBPβ feedback loop, whereby C/EBPβ, a transcriptional target of a p53 pathway, functions as a survival factor by negatively regulating p53 apoptotic activity in response to DNA damage. RNAseq analysis of UVB-treated CKOβ epidermis unexpectedly revealed that type 1 interferon (IFN) pathway was the most highly enriched pathway. Numerous pro-apoptotic interferon stimulated genes were upregulated including some known to enhance p53 apoptosis. Our results indicate that p53 and IFN pathways function together in response to DNA damage to result in the activation of extrinsic apoptosis pathways and caspase 8 cleavage. Last, we observed CKOβ mice were resistant to UVB-induced skin cancer. Our results suggest that C/EBPβ represses apoptosis through keratinocyte autonomous suppression of the type 1 IFN response and p53 to increase cell survival and susceptibility to UVB-induced skin cancer.
Comparing the epidemiology, clinical characteristics and prognostic factors of acute myeloid leukemia with and without acute promyelocytic leukemia
Authors: Kamath Geetanjali R , Tremblay Douglas , Coltoff Alexander , Caro Jessica , Lancman Guido , Bhalla Sheena , Najfeld Vesna , Mascarenhas John , Taioli Emanuela
Published: January 2019

Acute promyelocytic leukemia (APL) is a particularly aggressive subtype of acute myeloid leukemia (AML), with high rates of early death. It is important to examine how epidemiological characteristics, clinical and treatment factors, cytogenetic and genetic data affect survival and differ between APL and non-APL AML patients. We analyzed population data from the New York State Cancer Registry to characterize AML including APL incidence rates by demographics. APL incidence rates were higher among Hispanics than non-Hispanics [incidence rate ratio = 1.22; 95% confidence interval (CI) = 1.02–1.43]; and among foreign-born than USA-born persons. APL incidence rates increased more rapidly through 1995–2014 than non-APL AML; and its frequency increased faster among foreign-born persons. In a hospital cohort of 390 AML patients, the risk of death was significantly higher among APL patients with FLT3-internal tandem duplications than those without [hazard ratio (HR) = 11.74; 95% CI = 1.03–134.5]; and among APL patients with secondary versus de novo disease (HR = 17.32; 95% CI = 1.56–192.1). Among non-APL AML patients, risk of death was significantly associated with prior chemotherapy with antitubulin agents after adjusting for age, gender and ethnicity (adjusted HR = 3.30; 95% CI = 1.49–7.32); and separately with older age, unfavorable cytogenetics and complex karyotype. This study highlights FLT3-internal tandem duplications as a prognostic factor in APL and proposes consideration of prior antitubulin therapy as a prognostic factor in non-APL AML.
The effect of the extent of surgical insult on orthodontic tooth movement
Authors: Chang Joy , Chen Po-Jung , Dutra Eliane H , Nanda Ravindra , Yadav Sumit
Published: January 2019

Objective

The primary objective of this study was to investigate how the extent of surgical insult affects the orthodontic tooth movement (OTM) and the alveolar bone modelling and remodelling in a rodent model.

Material and methods

15-week-old male Wistar rats were used in the research and they were randomly divided into three treatment groups: (1) OTM only (N = 8); (2) OTM + 2 alveolar decortication (AD) (less surgical insult) (N = 8); and (3) OTM + 4 AD (more surgical insult) (N = 8). A nickel-titanium spring delivering 5–8 g of force was used to protract the molar mesially using maxillary incisors as an anchorage. AD was done using a hand piece and a round bur, adjacent to the left first maxillary molar on the palatal alveolar bone. After 14 days of OTM Wistar rats were killed and microfocus computed tomography and histological analysis were performed.

Results

The OTM + 4AD group presented with a significant increase (P < 0.05) in the rate of tooth movement when compared to OTM + 2AD group and OTM only group. In addition, the OTM + 4AD group had a significant decrease in bone volume and tissue density (P < 0.05) and a significant increase (P < 0.05) in the trabecular spacing and trabecular thickness when compared to OTM only. Histological quantification of tartrate-resistant acid phosphatase indicated a significant percent increase (P < 0.05) in OTM + 4AD group, when compared to OTM + 2AD and OTM only group.

Results

Increased surgical insult increases the rate of OTM. Additionally, increased surgical insult decreases the bone volume and the tissue density.
Prospective evaluation of intestinal decompression in treatment of acute bowel obstruction from Crohn’s disease
Authors: Liu Rui-Qing , Qiao Shuai-Hua , Wang Ke-Hao , Guo Zhen , Li Yi , Cao Lei , Gong Jian-Feng , Wang Zhi-Ming , Zhu Wei-Ming
Published: January 2019

Background

Conservative therapy for Crohn’s disease (CD)-related acute bowel obstruction is essential to avoid emergent surgery. The present study aimed to evaluate the efficacy of using a long intestinal decompression tube (LT) in treatment of CD with acute intestinal obstruction.

Methods

This is a prospective observational study. Comparative analysis was performed in CD patients treated with LT (the LT group) and nasogastric tube (the GT group). The primary outcome was the avoidance of emergent surgery. Additionally, predictive factors for failure of decompression and subsequent surgery were investigated.

Results

There were 27 and 42 CD patients treated with LT and GT, respectively, in emergent situations. Twelve (44.4%) patients using LT were managed conservatively without laparotomy, while only nine (21.4%) patients in the GT group were spared from emergent surgery (P < 0.05). Both in surgery-free and in surgery patients, the time to alleviation of symptoms was significantly shorter in the LT groups than in the GT groups (both P < 0.01). C-reactive protein decrease after intubation and 48-hour drainage volume >500 mL were predictors of unavoidable surgery (both P < 0.05). The rate of temporary stoma and incidence of incision infection in the LT surgery group were significantly lower than those in the GT group (both P < 0.05). No significant differences were observed in the frequency of medical and surgical recurrences between the LT and GT groups (all P > 0.05).

Conclusions

Endoscopic placement of LT could improve the emergent status in CD patients with acute bowel obstruction. The drainage output and changes in C-reactive protein after intubation could serve as practical predictive indices for subsequent surgery. Compared to traditional GT decompression, LT decompression was associated with fewer short-term complications and did not appear to affect long-term recurrence.
A framework to assess cultural safety in Australian public policy
Authors: Mackean Tamara , Fisher Matthew , Friel Sharon , Baum Frances
Published: January 2019

The concept of cultural safety (CS) has been developed as a critical perspective on healthcare provided to Indigenous service users in neo-colonial countries such as New Zealand, Australia and Canada. Unlike other frameworks for culturally competent healthcare, a CS approach recognizes impacts of colonization and power inequalities on Indigenous peoples and asks how these may manifest in healthcare settings. It has been argued that CS thinking is suited to critical analysis of public policy, but there has been limited work in this direction. Drawing on literature on CS in Australian healthcare, we defined a CS framework consisting of five concepts: reflexivity, dialogue, reducing power differences, decolonization and regardful care. Our research examined whether and in what terms this framework could be adapted as a tool for critical analysis of Australian public policy as it affects Aboriginal and Torres Strait Islander peoples. We used a collaborative inquiry process combining perspectives of an Aboriginal researcher and a non-Indigenous researcher. We developed a thematic analysis framework to examine how the five concepts might be reflected in contemporary writings on policy by leading Aboriginal or Torres Strait Islander thinkers. We found the framework is applicable as a tool for policy analysis; bringing together key concerns raised by Aboriginal and Torres Strait Islander leaders and critical concepts such as sovereignty and interface thinking. We concluded the framework is likely to be a useful tool for critical, systemic thinking about public policy as it affects Indigenous peoples and for specifying areas where performance can be improved to achieve culturally safe policy.
Nonsense-mediated mRNA decay efficiency varies in choroideremia providing a target to boost small molecule therapeutics
Authors: Sarkar Hajrah , Mitsios Andreas , Smart Matthew , Skinner Jane , Welch Ailsa A , Kalatzis Vasiliki , Coffey Peter J , Dubis Adam M , Webster Andrew R , Moosajee Mariya
Published: January 2019

Choroideremia (CHM) is an x-linked recessive chorioretinal dystrophy, with 30% caused by nonsense mutations in the CHM gene resulting in an in-frame premature termination codon (PTC). Nonsense-mediated mRNA decay (NMD) is the cell’s natural surveillance mechanism that detects and destroys PTC-containing transcripts, with UPF1 being the central NMD modulator. NMD efficiency can be variable amongst individuals with some transcripts escaping destruction, leading to the production of a truncated non-functional or partially functional protein. Nonsense suppression drugs, such as ataluren, target these transcripts and read-through the PTC, leading to the production of a full length functional protein. Patients with higher transcript levels are considered to respond better to these drugs, as more substrate is available for read-through. Using Quantitative reverse transcription PCR (RT-qPCR), we show that CHM mRNA expression in blood from nonsense mutation CHM patients is 2.8-fold lower than controls, and varies widely amongst patients, with 40% variation between those carrying the same UGA mutation [c.715 C>T; p.(R239*)]. These results indicate that although NMD machinery is at work, efficiency is highly variable and not wholly dependent on mutation position. No significant difference in CHM mRNA levels was seen between two patients’ fibroblasts and their induced pluripotent stem cell-derived retinal pigment epithelium. There was no correlation between CHM mRNA expression and genotype, phenotype or UPF1 transcript levels. NMD inhibition with caffeine was shown to restore CHM mRNA transcripts to near wild-type levels. Baseline mRNA levels may provide a prognostic indicator for response to nonsense suppression therapy, and caffeine may be a useful adjunct to enhance treatment efficacy where indicated.
Spatio-temporal dynamics and behavioural ecology of a “demersal” fish population as detected using research survey pelagic trawl catches: the Eastern Baltic Sea cod (Gadus morhua)
Authors: Casini Michele , Tian Huidong , Hansson Martin , Grygiel Włodzimierz , Strods Guntars , Statkus Romas , Sepp Elor , Gröhsler Tomas , Orio Alessandro , Larson Niklas
Published: January 2019

Cod is usually monitored for scientific purposes using bottom trawl surveys, although its regular pelagic occurrence is well documented. Here we analysed, using Generalized Additive Models, the spatio-temporal changes in the Eastern Baltic cod adult population using pelagic catches from an acoustic survey covering 37 years and the whole central Baltic Sea. Our analysis shows that in the northern areas cod catch per unit effort (CPUE, kg h-1) was high in the early 1980s whereas it dropped and remained very low thereafter. Conversely, in the southernmost area CPUE largely oscillated after the early 1990s. Our model was able to capture key ecological features of the Baltic cod such as preferred depth of occurrence and response to hypoxic conditions. The model also revealed a clear daily cycle of CPUEs, indicating diel vertical migrations at the population level. The temporal trends of pelagic CPUEs generally followed those from the bottom trawl surveys, although differences were observed especially in the recent years with a relative decline in the cod occurring in the pelagic waters. Our results point to the great potential of acoustic survey trawl catches to complement bottom trawl surveys for investigating the spatio-temporal population dynamics and behaviour of the Baltic cod.
A virtual element method for a nonlocal FitzHugh–Nagumo model of cardiac electrophysiology
Authors: Anaya Verónica , Bendahmane Mostafa , Mora David , Sepúlveda Mauricio
Published: January 2019

We present a virtual element method (VEM) for a nonlocal reaction–diffusion system of the cardiac electric field. For this system, we analyze an $H^1$-conforming discretization by means of VEM that can make use of general polygonal meshes. Under standard assumptions on the computational domain, we establish the convergence of the discrete solution by considering a series of a priori estimates and by using a general $L^p$ compactness criterion. Moreover, we obtain optimal order space-time error estimates in the $L^2$ norm. Finally, we report some numerical tests supporting the theoretical results.
A posteriori error analysis for random scalar conservation laws using the stochastic Galerkin method
Authors: Meyer Fabian , Rohde Christian , Giesselmann Jan
Published: January 2019

In this article we present an a posteriori error estimator for the spatial–stochastic error of a Galerkin-type discretization of an initial value problem for a random hyperbolic conservation law. For the stochastic discretization we use the stochastic Galerkin method and for the spatial–temporal discretization of the stochastic Galerkin system a Runge–Kutta discontinuous Galerkin method. The estimator is obtained using smooth reconstructions of the discrete solution. Combined with the relative entropy stability framework of Dafermos (2016, Hyperbolic Conservation Laws in Continuum Physics, 4th edn., Grundlehren der Mathematischen Wissenschaften [Fundamental Principles of Mathematical Sciences], vol. 325, Berlin, Springer, pp. xxxviii+826), this leads to computable error bounds for the space–stochastic discretization error. Moreover, it turns out that the error estimator admits a splitting into one part representing the spatial error, and a remaining term, which can be interpreted as the stochastic error. This decomposition allows us to balance the errors arising from spatial and stochastic discretization. We conclude with some numerical examples confirming the theoretical findings.
Fox H-kernel and θ-deformation of the Cauchy Two-Matrix Model and Bures Ensemble
Authors: Forrester Peter J , Li Shi-Hao
Published: January 2019

A $\theta $-deformation of the Laguerre weighted Cauchy two-matrix model, and the Bures ensemble, is introduced. Such a deformation is familiar from the Muttalib–Borodin ensemble. The $\theta $-deformed Cauchy–Laguerre two-matrix model is a two-component determinantal point process. It is shown that the correlation kernel, and its hard edge scaled limit, can be written in terms of particular Fox H-functions, generalising the Meijer G-function class known from the study of the case $\theta = 1$. In the $\theta =1$ case, it is shown that the Laguerre–Bures ensemble is related to the Laguerre–Cauchy two-matrix model, notwithstanding the Bures ensemble corresponding to a Pfaffian point process. This carries over to the $\theta $-deformed case, allowing explicit expressions involving Fox H-functions for the correlation kernel, and its hard edge scaling limit, to also be obtained for the $\theta $-deformed Laguerre–Bures ensemble. The hard edge scaling limit is in the Raney class $(\theta /2+1,1/2)$.
Diverse Clinical Isolates of Mycobacterium tuberculosis Develop Macrophage-Induced Rifampin Tolerance
Authors: Adams Kristin N , Verma Amit Kumar , Gopalaswamy Radha , Adikesavalu Harresh , Singhal Dinesh Kumar , Tripathy Srikanth , Ranganathan Uma Devi , Sherman David R , Urdahl Kevin B , Ramakrishnan Lalita , Hernandez Rafael E
Published: January 2019

Mycobacterium tuberculosis develops tolerance to multiple antibiotics when residing in host macrophages. We demonstrate that macrophage-induced tolerance to rifampin is common across major lineages of M. tuberculosis, except for Beijing-family lineage 2 strains.
Cholera toxin B induces interleukin-1β production from resident peritoneal macrophages through the pyrin inflammasome as well as the NLRP3 inflammasome
Authors: Orimo Takashi , Sasaki Izumi , Hemmi Hiroaki , Ozasa Toshiya , Fukuda-Ohta Yuri , Ohta Tomokazu , Morinaka Mio , Kitauchi Mariko , Yamaguchi Takako , Sato Yayoi , Tanaka Takashi , Hoshino Katsuaki , Katayama Kei-ichi , Fukuda Shinji , Miyake Kensuke , Yamamoto Masahiro , Satoh Takashi , Furukawa Koichi , Kuroda Etsushi , Ishii Ken J , Takeda Kiyoshi , Kaisho Tsuneyasu
Published: January 2019

Cholera toxin B (CTB) is a subunit of cholera toxin, a bacterial enterotoxin secreted by Vibrio cholerae and also functions as an immune adjuvant. However, it remains unclear how CTB activates immune cells. We here evaluated whether or how CTB induces production of a pro-inflammatory cytokine, interleukin-1β (IL-1β). CTB induced IL-1β production not only from bone marrow-derived macrophages (BMMs) but also from resident peritoneal macrophages in synergy with O111:B4-derived lipopolysaccharide (LPS O111:B4) that can bind to CTB. Meanwhile, when prestimulated with O55:B5-derived LPS (LPS O55:B5) that fails to bind to CTB, resident peritoneal macrophages, but not BMMs, produced IL-1β in response to CTB. The CTB-induced IL-1β production in synergy with LPS in both peritoneal macrophages and BMMs was dependent on ganglioside GM1, which is required for internalization of CTB. Notably, not only the NLRP3 inflammasome but also the pyrin inflammasome were involved in CTB-induced IL-1β production from resident peritoneal macrophages, while only the NLRP3 inflammasome was involved in that from BMMs. In response to CTB, a Rho family small GTPase, RhoA, which activates pyrin inflammasome upon various kinds of biochemical modification, increased its phosphorylation at serine-188 in a GM1-dependent manner. This phosphorylation as well as CTB-induced IL-1β productions were dependent on protein kinase A (PKA), indicating critical involvement of PKA-dependent RhoA phosphorylation in CTB-induced IL-1β production. Taken together, these results suggest that CTB, incorporated through GM1, can activate resident peritoneal macrophages to produce IL-1β in synergy with LPS through novel mechanisms in which pyrin as well as NLRP3 inflammasomes are involved.
Rapid Genetic Code Evolution in Green Algal Mitochondrial Genomes
Authors: Noutahi Emmanuel , Calderon Virginie , Blanchette Mathieu , El-Mabrouk Nadia , Lang Bernd Franz
Published: January 2019

Genetic code deviations involving stop codons have been previously reported in mitochondrial genomes of several green plants (Viridiplantae), most notably chlorophyte algae (Chlorophyta). However, as changes in codon recognition from one amino acid to another are more difficult to infer, such changes might have gone unnoticed in particular lineages with high evolutionary rates that are otherwise prone to codon reassignments. To gain further insight into the evolution of the mitochondrial genetic code in green plants, we have conducted an in-depth study across mtDNAs from 51 green plants (32 chlorophytes and 19 streptophytes). Besides confirming known stop-to-sense reassignments, our study documents the first cases of sense-to-sense codon reassignments in Chlorophyta mtDNAs. In several Sphaeropleales, we report the decoding of AGG codons (normally arginine) as alanine, by tRNA(CCU) of various origins that carry the recognition signature for alanine tRNA synthetase. In Chromochloris, we identify tRNA variants decoding AGG as methionine and the synonymous codon CGG as leucine. Finally, we find strong evidence supporting the decoding of AUA codons (normally isoleucine) as methionine in Pycnococcus. Our results rely on a recently developed conceptual framework (CoreTracker) that predicts codon reassignments based on the disparity between DNA sequence (codons) and the derived protein sequence. These predictions are then validated by an evaluation of tRNA phylogeny, to identify the evolution of new tRNAs via gene duplication and loss, and structural modifications that lead to the assignment of new tRNA identities and a change in the genetic code.
The Impact of Alvimopan on Return of Bowel Function After Major Spine Surgery – A Prospective, Randomized, Double-Blind Study
Authors: Dunn Lauren K , Thiele Robert H , Lin Michelle C , Nemergut Edward C , Durieux Marcel E , Tsang Siny , Shaffrey Mark E , Smith Justin S , Shaffrey Christopher I , Naik Bhiken I
Published: January 2019

BACKGROUND

Pain management following major spine surgery requires high doses of opioids and is associated with a risk of opioid-induced constipation. Peripheral mu-receptor antagonists decrease the gastrointestinal complications of perioperative systemic opioid administration without antagonizing the analgesic benefits of these drugs.

OBJECTIVE

To investigate the impact of alvimopan in opioid-naive patients undergoing major spine surgery.

METHODS

Patients undergoing >3 levels of thoracic and/or lumbar spine surgery were enrolled in this prospective, randomized, double-blind study to receive either alvimopan or placebo prior to and following surgery. Opioid consumption; pain scores; and time of first oral intake, flatus, and bowel movement were recorded.

RESULTS

A total of 24 patients were assigned to the active group and 25 were assigned to the placebo group. There was no significant difference in demographics between the groups. Postoperatively, the alvimopan group reported earlier time to first solid intake [median (range): alvimopan: 15 h (3-25) vs placebo: 17 h (3-46), P < .001], passing of flatus [median (range): alvimopan: 22 h (7-63) vs placebo: 28 h (10-58), P < .001], and first bowel movement [median (range): alvimopan: 50 h (22-80) vs placebo: 64 h (40-114), P < .001]. The alvimopan group had higher pain scores (maximum, minimum, and median); however, there was no significant difference between the groups with postoperative opioid use.

CONCLUSION

This study shows that the perioperative use of alvimopan significantly reduced the time to return of bowel function with no increase in postoperative opioid use despite a slight increase in pain scores.
The Effect of Low-Carbohydrate and Low-Fat Diets on Pain in Individuals with Knee Osteoarthritis
Authors: Strath Larissa J , Jones Catherine D , Philip George Alan , Lukens Shannon L , Morrison Shannon A , Soleymani Taraneh , Locher Julie L , Gower Barbara A , Sorge Robert E
Published: January 2019

Objective

Osteoarthritis is the most prominent form of arthritis, affecting approximately 15% of the population in the United States. Knee osteoarthritis (KOA) has become one of the leading causes of disability in older adults. Besides knee replacement, there are no curative treatments for KOA, so persistent pain is commonly treated with opioids, acetaminophen, and nonsteroidal anti-inflammatory drugs. However, these drugs have many unpleasant side effects, so there is a need for alternative forms of pain management. We sought to test the efficacy of a dietary intervention to reduce KOA.

Design

A randomized controlled pilot study to test the efficacy of two dietary interventions.

Subjects

Adults 65–75 years of age with KOA.

Methods

Participants were asked to follow one of two dietary interventions (low-carbohydrate [LCD], low-fat [LFD]) or continue to eat as usual (control [CTRL]) over 12 weeks. Functional pain, self-reported pain, quality of life, and depression were assessed every three weeks. Serum from before and after the diet intervention was analyzed for oxidative stress.

Results

Over a period of 12 weeks, the LCD reduced pain intensity and unpleasantness in some functional pain tasks, as well as self-reported pain, compared with the LFD and CTRL. The LCD also significantly reduced oxidative stress and the adipokine leptin compared with the LFD and CTRL. Reduction in oxidative stress was related to reduced functional pain.

Conclusions

We present evidence suggesting that oxidative stress may be related to functional pain, and lowering it through our LCD intervention could provide relief from pain and be an opioid alternative.
Added value of biomarkers compared with clinical parameters for the prediction of radiographic spinal progression in axial spondyloarthritis
Authors: Rademacher Judith , Tietz Lorraine Madeline , Le Lien , Hartl Agnes , Hermann Kay-Geert A. , Sieper Joachim , Mansmann Ulrich , Rudwaleit Martin , Poddubnyy Denis
Published: January 2019

Objectives

The objective of this study was to examine whether adding biomarkers to routine clinical parameters improves prediction of radiographic spinal progression in axial spondyloarthritis.

Methods

One hundred and seventeen patients with ankylosing spondylitis who completed the Effects of NSAIDs on RAdiographic Damage in Ankylosing Spondylitis (ENRADAS) trial were included. Radiographic spinal progression was defined as worsening of the modified Stoke Ankylosing Spondylitis Spine Score by ⩾2 points after 2 years. A clinical prediction model was constructed out of baseline syndesmophytes, elevated CRP, cigarette smoking and male sex. The following serum biomarkers were measured at baseline by ELISA: MMP3, VEGF, calprotectin, leptin, high molecular weight adiponectin, osteoprotegerin, sclerostin, N-terminal telopeptide, procollagen type II N-terminal propeptide and serum amyloid A.

Results

Repeated cross-validation analyses revealed one biomarker combination with potential added predictive value in addition to the clinical model: leptin + high molecular weight adiponectin + VEGF. This biomarker combination showed an area under the curve (AUC)Biomarkers = 0.731 (95% CI: 0.614, 0.848), which was numerically superior to the clinical model [AUCClinical = 0.665 (95% CI: 0.553, 0.776)]. A combination of clinical parameters + biomarkers showed an improved predictive value compared with the clinical model reflected by AUCClinical+Biomarkers = 0.768 (95% CI: 0.666, 0.871), though not statistically significant (P = 0.051). However, by considering the part of the receiver operating characteristic curve with a specificity ⩾75% resulting in partial AUC (pAUC), the improvement becomes significant (pAUCClinical+Biomarkers = 0.119; pAUCClinical = 0.053; P = 0.01).

Conclusion

Biomarkers show potential to improve the prediction of radiographic spinal progression in axial spondyloarthritis when used in addition to the clinical parameters, though the added value seems to be rather small.
Measuring spinal mobility in early axial spondyloarthritis: does it matter?
Authors: Marques Mary Lucy , Ramiro Sofia , Goupille Philippe , Dougados Maxime , van Gaalen Floris , van der Heijde Désirée
Published: January 2019

Objectives

To investigate the frequency and order of impairment of spinal mobility measures (SMMs) and their cross-sectional and longitudinal usefulness in early axial spondyloarthritis.

Methods

SMMs measurements of patients from the DESIR (5-year data) and SPACE (2.6 (1.9) years of follow-up) cohorts were analysed. Cross-sectional (group level) and longitudinal (individual level) analyses were performed comparing SMMs to pre-defined cut-offs derived from healthy individuals. Subgroup analyses were used to study patient and disease characteristics potentially influencing spinal mobility. Reliability was analysed using intraclass correlation coefficients and the smallest detectable change.

Results

In 328 DESIR and 148 SPACE patients, lateral spinal flexion (LSF) and mSchober were the most impaired SMMs. If both (LSF and mSchober) were measured, 84% (DESIR) and 74% (SPACE) of the patients with impairment in ≥1 SMM would be captured. LSF and Bath AS Metrology Index best discriminated between subgroups of patients (higher impairment in patients ever treated with biologics, with higher disease activity and presence of baseline syndesmophytes): e.g. 31% of LSF impairment in patients with Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1 in ≥2/3 visits vs 49% in those with ASDS ≥ 2.1. A high variability in SMMs within the same patient over time was observed, even when restricting the analysis to patients with low disease activity. Reliability of SMMs was ‘fair’ to ‘good’ (inter-reader intraclass correlation coefficients (2, 1): 0.55–0.84; intrareader intraclass correlation coefficients (2, 1): 0.49–0.72). Smallest detectable changes were in general high, e.g. 5.1 cm for LSF.

Conclusion

Cross-sectional use of SMMs, at the group level, is informative in patients with early axial spondyloarthritis. However, the high variation of SMMs over time impairs their use, at the individual patient level.
‘Losing My Raise’: minimum wage increases, status loss and job satisfaction among low-wage employees
Authors: Storer Adam , Reich Adam
Published: January 2019

Policymakers concerned with economic inequality regularly advocate for laws to increase the minimum wage. The impact of such laws on low-wage employment levels has been studied extensively within the field of labor economics. Yet, the vast majority of this literature has failed to explore how changes in the minimum wage impact the actual experience of low-wage work. We first discuss qualitative evidence that Walmart, the largest low-wage employer in the country, adjusts to minimum wage increases by compressing wages at the lower end of its wage distribution. We then make use of an innovative source of data to explore quantitatively the impact of such compression on workers’ experiences of their jobs at Walmart. Using a difference-in-difference approach, we find that a higher minimum wage raises job satisfaction for workers who have worked at the company for under a year, but decreases job satisfaction for longer-term and marginally higher status employees.
Changing employment relations under a fractured corporate elite
Authors: Benton Richard , Hafeez Aibak , Mun Eunmi
Published: January 2019

Shareholder power is often cited as contributing to the deterioration of employment relations. However, managerial power also shapes how shareholder pressures affect workers. In this article, we examine how managerial power contributed to the initial durability and eventual decline of white-collar benefits in the era of shareholder primacy. One traditional source of elite power is the network of overlapping board appointments which helped corporate leaders resist shareholder pressures that weaken employment relations and benefits. More recently, this network has begun to fracture and leaders are no longer able to draw on collective resources in resisting shareholders. We investigate how shifting bases of elite power affect white-collar benefits, focusing on employee stock ownership plans, work–life balance policies and profit-sharing plans. Using a panel of S&P 1500 firms from 1998 to 2011, we show that firms densely connected in the board interlock network were more likely to adopt white-collar benefits; but these benefits began to erode as the network fractured. We discuss the consequences of a disempowered corporate elite for employment stability.
Molecular Detection of QoI Resistance in Colletotrichum gloeosporioides Causing Strawberry Anthracnose Based on Loop-Mediated Isothermal Amplification Assay
Authors: Wu J. Y. , Hu X. R. , Zhang C. Q.
Published: January 2019

Anthracnose is one of the most common diseases in strawberry plants. Colletotrichum gloeosporioides is the major cause of anthracnose in China, including Zhejiang Province. Early, specific, reliable, and time-saving detection is urgently needed to prevent the further spread of C. gloeosporioides, guiding farmers to utilize chemicals to control anthracnose. In this study, we showed that the high resistance to pyraclostrobin, caused by a point mutation at codon 143 (GGT→GCT) in the cytochrome b gene of C. gloeosporioides was prevalent in the strawberry growing regions, and we developed a loop-mediated isothermal amplification (LAMP) assay as a detection method. Primer sets S0 and S4 could be used to specifically detect C. gloeosporioides isolates and the G143A mutations, respectively. A detection limit of 10−2 ng (10 pg), which is at least 10-fold more sensitive than conventional polymerase chain reaction, was achieved by the LAMP assay. Here, we utilized lateral-flow devices (LFDs), nitrocellulose membranes that can absorb nucleic acids, to acquire the total genomic DNA of strawberry plants within 2 min. The LFD membranes were used as DNA templates for the LAMP assays to accurately detect strawberry plants infected with C. gloeosporioides. This diagnostic method for strawberry anthracnose was accomplished within 1 h, including the sample preparation and LAMP assays. Collectively, we developed a sensitive and practical method for monitoring C. gloeosporioides and its quinone outside inhibitor–resistant mutants. The LAMP assay for detection of C. gloeosporioides in strawberry plants has great potential for rapid strawberry anthracnose surveillance and will provide farmers with advice on preventing C gloeosporioides at the early stages of strawberry development.
Concept Mapping During Simulation Debriefing to Encourage Active Learning, Critical Thinking, and Connections to Clinical Concepts
Authors: Odreman Holldrid A. , Clyens Dawn
Published: January 2019

This pilot study showed how concept mapping during debriefing made a difference in the learning experience of participants. After a 20-minute video showing the clinical interaction between nurses and a patient, 34 nursing students debriefed their observations in either a traditional team debriefing session or in a debriefing session using concept mapping. Results showed an increase in analysis of thoughts, feelings, and critical thinking and connections to clinical concepts for students who used concept mapping during the debriefing session. Results suggest the application of concept mapping during debriefing as a useful teaching modality to help make connections to clinical concepts.
Recommended screenings for chlamydia and gonorrhea
Authors: O'Byrne Patrick
Published: January 2019

Chlamydia and gonorrhea are the most commonly diagnosed bacterial sexually transmitted infections (STIs), and both are increasing in incidence. Because these STIs are often asymptomatic and found at extragenital sites, such as the pharynx and rectum, it is important that clinicians know when and how to screen for them. This article reviews recent updates to Canadian screening guidelines, including the evidence that led to updates on this topic.
Finger Trap Traction and Distal Radius Fractures
Authors: Rohman Lebur , Love Alisdair , Michla Yusuf
Published: January 2019

Distal radius fractures are among the most common fractures worldwide. Initial first aid treatment for any fracture is reduction, then to hold the reduction and then rehabilitate. It is common practice to attempt manual manipulation and if satisfactory reduction is not achieved the reduction is abandoned in favor of a manipulation in theater with or without K-wire fixation or open reduction and internal fixation. The finger trap method of applying traction to distal radius fractures is a technique many of us are aware of but have not actually attempted in clinical practice. Furthermore, there are no easily accessible articles describing its use. Therefore this article describes a case in which additional techniques of reduction of a distal radius fracture were used successfully and will help to inform on how to carry out this technique.
Personality traits and diabetes incidence among postmenopausal women
Authors: Luo Juhua , Manson JoAnn E. , Weitlauf Julie C. , Shadyab Aladdin H. , Rapp Stephen R. , Garcia Lorena , Jonasson Junmei M. , Tindle Hilary A. , Nassir Rami , Wactawski-Wende Jean , Hendryx Michael
Published: January 2019

Objective:

We examined whether personality traits, including optimism, ambivalence over emotional expressiveness, negative emotional expressiveness, and hostility, were associated with risk of developing type 2 diabetes (hereafter diabetes) among postmenopausal women.

Methods:

A total of 139,924 postmenopausal women without diabetes at baseline (between 1993 and 1998) aged 50 to 79 years from the Women's Health Initiative were prospectively followed for a mean of 14 (range 0.1-23) years. Multivariable Cox proportional hazards regression models were used to assess associations between personality traits and diabetes incidence adjusting for common demographic factors, health behaviors, and depressive symptoms. Personality traits were gathered at baseline using questionnaires. Diabetes during follow-up was assessed via self-report of physician-diagnosed treated diabetes.

Results:

There were 19,240 cases of diabetes during follow-up. Compared with women in the lowest quartile of optimism (least optimistic), women in the highest quartile (most optimistic) had 12% (hazard ratio [HR], 0.88; 95% confidence interval [CI]: 0.84-0.92) lower risk of incident diabetes. Compared with women in the lowest quartile for negative emotional expressiveness or hostility, women in the highest quartile had 9% (HR, 1.09; 95% CI: 1.05-1.14) and 17% (HR, 1.17; 95% CI: 1.12-1.23) higher risk of diabetes, respectively. The association of hostility with risk of diabetes was stronger among nonobese than obese women.

Conclusions:

Low optimism and high NEE and hostility were associated with increased risk of incident diabetes among postmenopausal women independent of major health behaviors and depressive symptoms. In addition to efforts to promote healthy behaviors, women's personality traits should be considered to guide clinical or programmatic intervention strategies in diabetes prevention.
Human-Centered Design of a Low Molecular Weight Heparin Order Set to Reduce Medication Errors
Authors: D'Souza Anishka , Wu Phillis , Jung Laura , Nungaray Karla , Richman Mark
Published: January 2019

Inpatient anticoagulation medication errors for venous thromboembolism (VTE) therapy are common. Our VTE Team identified frequent dosing and duplicate order errors for therapeutic-dose low molecular weight heparin, which (lacking computerized physician order entry) was ordered using blank forms. To decrease such errors, a nonmandatory order form with weight-based dosing and prechecked orders discontinuing existing injectable anticoagulation was developed using human-centered design innovation principles/processes emphasizing end-user engagement in all phases: observation, exploring solutions, and rapid prototyping/feedback. Three physicians independently reviewed ordering errors the year before versus after implementation. Before implementation, 11% of orders contained any error versus 10.5% after implementation (p = .82); 6.2% had a dosing or duplicate therapy error versus 4.2% after implementation (all made when the form was not used; p = .19). No dosing or duplicate therapy errors were made when the form was used. Were the form mandatory, all such ordering errors would likely have been eliminated, leaving 11% before versus 6.3% after implementation orders with any error (p = .015), and 6.2% before versus 0% after implementation orders with duplicate or dosing therapy errors (p < .001). Human-centered design of an anticoagulation order form can reduce anticoagulation order errors; such principles can be applied to other health care innovations, including electronic order sets.
Decreasing Adverse Events in Pediatric Patients With End-Stage Renal Disease
Authors: Childs Gwendolyn D. , Sims Rebekah
Published: January 2019

Children with end-stage renal disease (ESRD) are at a higher risk of adverse events when they live at a distance from a pediatric facility with specialty services specific to the disease process. At a children's hospital in the southeast, a dialysis unit provides care for 27 patients with chronic ESRD. Nineteen of the 27 patients live more than 1 hour away from the children's hospital. Over the past 3 years, adverse events have occurred in patients being treated at another hospital. These adverse events included sepsis, bacterial and fungal infections, and compromised residual glomerular filtration rate because of the administration of nephrotoxic medications. The purpose of this article is to describe the findings from an improvement effort aimed at decreasing adverse events in the pediatric patient population with ESRD who require urgent or emergent care using an emergency room dialysis card as a communication tool for patients, families, and providers.
Artificial liver support in acute and acute-on-chronic liver failure
Authors: Larsen Fin Stolze
Published: January 2019

Purpose of review

Liver failure is a life-threatening condition, and an artificial liver is highly desirable to replace the failing liver-functions in the waiting time for liver regeneration to happen or until liver transplantation can be undertaken. This review focuses on the efficacy of using artificial extracorporeal liver support devices.

Recent findings

Artificial liver support devices such as the molecular adsorbent recirculating system (MARS), fractionated plasma separation and adsorption, and therapeutic plasma exchange (TPE) are well tolerated. MARS and TPE improve systemic haemodynamics and the grade of hepatic encephalopathy. However, randomized, controlled trials of MARS and fractionated plasma separation and adsorption have failed to show improvement in survival in patients with acute liver failure (ALF) and patients with acute-on-chronic liver failure (ACLF). Only TPE improves survival in patients with ALF by ameliorate the release of ammonia, damage-associated molecular patterns and sB7 (CD80/86) from the necrotic liver. No randomized, controlled trials on survival in patients with ACLF using TPE have been done.

Liver support systems such as MARS and TPE may temporarily improve systemic haemodynamics and the degree of encephalopathy. However, TPE is the only procedure that improves survival in patients with ALF. The role of TPE in ACLF remains unknown.