bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between stopping prescriptions for opioids, length of opioid treatment, and overdose or suicide deaths in US veterans: observational evaluation
Authors: Oliva Elizabeth M , Bowe Thomas , Manhapra Ajay , Kertesz Stefan , Hah Jennifer M , Henderson Patricia , Robinson Amy , Paik Meenah , Sandbrink Friedhelm , Gordon Adam J , Trafton Jodie A
Published: March 2020

Objective

To examine the associations between stopping treatment with opioids, length of treatment, and death from overdose or suicide in the Veterans Health Administration.

Design

Observational evaluation.

Setting

Veterans Health Administration.

Participants

1 394 102 patients in the Veterans Health Administration with an outpatient prescription for an opioid analgesic from fiscal year 2013 to the end of fiscal year 2014 (1 October 2012 to 30 September 2014).

Main outcome measures

A multivariable Cox non-proportional hazards regression model examined death from overdose or suicide, with the interaction of time varying opioid cessation by length of treatment (≤30, 31-90, 91-400, and >400 days) as the main covariates. Stopping treatment with opioids was measured as the time when a patient was estimated to have no prescription for opioids, up to the end of the next fiscal year (2014) or the patient’s death.

Results

2887 deaths from overdose or suicide were found. The incidence of stopping opioid treatment was 57.4% (n
=
799 668) overall, and based on length of opioid treatment was 32.0% (≤30 days), 8.7% (31-90 days), 22.7% (91-400 days), and 36.6% (>400 days). The interaction between stopping treatment with opioids and length of treatment was significant (P<0.001); stopping treatment was associated with an increased risk of death from overdose or suicide regardless of the length of treatment, with the risk increasing the longer patients were treated. Hazard ratios for patients who stopped opioid treatment (with reference values for all other covariates) were 1.67 (≤30 days), 2.80 (31-90 days), 3.95 (91-400 days), and 6.77 (>400 days). Descriptive life table data suggested that death rates for overdose or suicide increased immediately after starting or stopping treatment with opioids, with the incidence decreasing over about three to 12 months.

Conclusions

Patients were at greater risk of death from overdose or suicide after stopping opioid treatment, with an increase in the risk the longer patients had been treated before stopping. Descriptive data suggested that starting treatment with opioids was also a risk period. Strategies to mitigate the risk in these periods are not currently a focus of guidelines for long term use of opioids. The associations observed cannot be assumed to be causal; the context in which opioid prescriptions were started and stopped might contribute to risk and was not investigated. Safer prescribing of opioids should take a broader view on patient safety and mitigate the risk from the patient’s perspective. Factors to address are those that place patients at risk for overdose or suicide after beginning and stopping opioid treatment, especially in the first three months.
Do employer-sponsored health insurance schemes affect the utilisation of medically trained providers and out-of-pocket payments among ready-made garment workers? A case–control study in Bangladesh
Authors: Ahmed Sayem , Sarker Abdur Razzaque , Sultana Marufa , Roth Felix , Mahumud Rashidul Alam , Kamruzzaman Md , Hasan Md Zahid , Mirelman Andrew J. , Islam Ziaul , Niessen Louis W. , Rehnberg Clas , Khan AK Azad , Gyr Niklaus , Khan Jahangir A.M.
Published: March 2020

Objective

We estimated the effect of an employer-sponsored health insurance (ESHI) scheme on healthcare utilisation of medically trained providers and reduction of out-of-pocket (OOP) expenditure among ready-made garment (RMG) workers.

Design

We used a case–control study design with cross-sectional preintervention and postintervention surveys.

Settings

The study was conducted among workers of seven purposively selected RMG factories in Shafipur, Gazipur in Bangladesh.

Participants

In total, 1924 RMG workers (480 from the insured and 482 from the uninsured, in each period) were surveyed from insured and uninsured RMG factories, respectively, in the preintervention (October 2013) and postintervention (April 2015) period.

Interventions

We tested the effect of a pilot ESHI scheme which was implemented for 1 year.

Outcome measures

The outcome measures were utilisation of medically trained providers and reduction of OOP expenditure among RMG workers. We estimated difference-in-difference (DiD) and applied two-part regression model to measure the association between healthcare utilisation, OOP payments and ESHI scheme membership while controlling for the socioeconomic characteristics of workers.

Results

The ESHI scheme increased healthcare utilisation of medically trained providers by 26.1% (DiD=26.1; p<0.01) among insured workers compared with uninsured workers. While accounting for covariates, the effect on utilisation significantly reduced to 18.4% (p<0.05). The DiD estimate showed that OOP expenditure among insured workers decreased by −3700 Bangladeshi taka and -1100 Bangladeshi taka compared with uninsured workers when using healthcare services from medically trained providers or all provider respectively, although not significant. The multiple two-part models also reported similar results.

Conclusion

The ESHI scheme significantly increased utilisation of medically trained providers among RMG workers. However, it has no significant effect on OOP expenditure. It can be recommended that an educational intervention be provided to RMG workers to improve their healthcare-seeking behaviours and increase their utilisation of ESHI-designated healthcare providers while keeping OOP payments low.
Epidemiological study of a developmentally and culturally sensitive preschool intervention to improve school readiness of children in Addis Ababa, Ethiopia
Authors: Deyessa Negussie , Webb Simon , Duku Eric , Garland Ann , Fish Irving , Janus Magdalena , Desta Menelik
Published: March 2020

Background

Early childhood is a dynamic period of physical, psychosocial and cognitive development, where age appropriate intervention during the preschool years influences psychosocial, behavioural and academic achievement of children. This study evaluated the impact of a comprehensive preschool intervention on psychosocial, cognitive and behavioural school preparedness among children in Addis Ababa, Ethiopia.

Methods

Employing a cluster-sampling design, 150 preschool children who received the basic preschool curriculum (non-intervention) were compared with 100 randomly selected children who received a comprehensive preschool curriculum (intervention) using the Early Development Instrument (EDI) in five domains. Sample t-tests compared means of domain scores. Binary logistic regression analysed proportions of vulnerability in domains and overall.

Result

There were no group differences in gender, age, special need status or child’s first language. Intervention children had higher domain scores on social competence (mean difference 0.67 (SE=0.26)), emotional maturity (mean difference 0.77 (SE=0.29)), language and cognitive development (mean difference 0.67 (SE=0.40)), communication and general knowledge (mean difference 0.82 (SE=0.34)). Accounting for confounding variables, intervention children had a lower chance of overall vulnerability to domain problems (adjusted OR (AOR)=0.38; 95% CI 0.13 to 1.15), language and cognitive development (AOR=0.21; 95% CI 0.03 to 1.64), and social competence (AOR=0.20; 95% CI 0.08 to 0.45).

Conclusion

The comprehensive intervention was associated with better outcomes on early childhood development across four domains. It is recommended to extend this programme to other areas of Ethiopia, where children do not have appropriate school preparation, to reduce risk of school dropout, negative personal and societal outcomes.
Individual-level and area-level socioeconomic inequalities in hearing impairment among Chinese adults: a population-based study
Authors: Luo Yanan , Gao Jiamin , Zheng Xiaoying
Published: March 2020

Background

It is unclear whether individual-level and area-level socioeconomic status (SES) is associated with hearing impairment (HI). This study determines an association of individual SES, area SES and their interaction with HI among working-aged adults.

Methods

Data were obtained from the large, population-based sample of the Second China National Sample Survey on Disability, a cross-sectional study conducted in China. A total of 1 333 528 participants aged 25–59 years were included. HI was measured by pure-tone audiometry (PTA) and audiologists further ascertained for a final diagnosis. Individual SES was defined as a summed of z-scored of education level and household income per capita, and area SES was calculated as a summed of z-scored of county-level income per capita, high school rate, poverty rate and rate of upper-class occupation. Multilevel logistic regression was used.

Results

Individual and area SES were associated with HI among Chinese working-aged adults. A 1-SD increase in individual SES was associated with decreased risk of HI (OR=0.3, 95% CI: 0.3 to 0.3). Area SES was positively related to HI (OR=1.2, 95%CI: 1.2 to 1.3). The cross-level interaction on individual and area SES was significantly associated with HI, indicating that among those who lived in higher SES areas, participants with lower SES had a greater likelihood to develop HI.

Conclusions

Significant individual and area socioeconomic inequalities were observed in HI among Chinese working-aged adults. Lower SES adults who resided in prosperous areas may face more deprivation on hearing health than those with higher SES.
Anatomy and function of the fornix in the context of its potential as a therapeutic target
Authors: Senova Suhan , Fomenko Anton , Gondard Elise , Lozano Andres M
Published: March 2020

The fornix is a white matter bundle located in the mesial aspect of the cerebral hemispheres, which connects various nodes of a limbic circuitry and is believed to play a key role in cognition and episodic memory recall. As the most prevalent cause of dementia, Alzheimer’s disease (AD) dramatically impairs the quality of life of patients and imposes a significant societal burden on the healthcare system. As an established treatment for movement disorders, deep brain stimulation (DBS) is currently being investigated in preclinical and clinical studies for treatment of memory impairment in AD by modulating fornix activity. Optimal target and stimulation parameters to potentially rescue memory deficits have yet to be determined. The aim of this review is to consolidate the structural and functional aspects of the fornix in the context of neuromodulation for memory deficits. We first present an anatomical and functional overview of the fibres and structures interconnected by the fornix. Recent evidence from preclinical models suggests that the fornix is subdivided into two distinct functional axes: a septohippocampal pathway and a subiculothalamic pathway. Each pathway’s target and origin structures are presented, followed by a discussion of their oscillatory dynamics and functional connectivity. Overall, neuromodulation of each pathway of the fornix is discussed in the context of evidence-based forniceal DBS strategies. It is not yet known whether driving fornix activity can enhance cognition—optimal target and stimulation parameters to rescue memory deficits have yet to be determined.
Work-related adverse respiratory health outcomes at a machine manufacturing facility with a cluster of bronchiolitis, alveolar ductitis and emphysema (BADE)
Authors: Cummings Kristin J , Stanton Marcia L , Kreiss Kathleen , Boylstein Randy J , Park Ju-Hyeong , Cox-Ganser Jean M , Virji M Abbas , Edwards Nicole T , Segal Leopoldo N , Blaser Martin J , Weissman David N , Nett Randall J
Published: March 2020

Objectives

Four machine manufacturing facility workers had a novel occupational lung disease of uncertain aetiology characterised by lymphocytic bronchiolitis, alveolar ductitis and emphysema (BADE). We aimed to evaluate current workers’ respiratory health in relation to job category and relative exposure to endotoxin, which is aerosolised from in-use metalworking fluid.

Methods

We offered a questionnaire and spirometry at baseline and 3.5 year follow-up. Endotoxin exposures were quantified for 16 production and non-production job groups. Forced expiratory volume in one second (FEV1) decline ≥10% was considered excessive. We examined SMRs compared with US adults, adjusted prevalence ratios (aPRs) for health outcomes by endotoxin exposure tertiles and predictors of excessive FEV1decline.

Results

Among 388 (89%) baseline participants, SMRs were elevated for wheeze (2.5 (95% CI 2.1 to 3.0)), but not obstruction (0.5 (95% CI 0.3 to 1.1)). Mean endotoxin exposures (range: 0.09–28.4 EU/m3) were highest for machine shop jobs. Higher exposure was associated with exertional dyspnea (aPR=2.8 (95% CI 1.4 to 5.7)), but not lung function. Of 250 (64%) follow-up participants, 11 (4%) had excessive FEV1decline (range: 403–2074 mL); 10 worked in production. Wheeze (aPR=3.6 (95% CI 1.1 to 12.1)) and medium (1.3–7.5 EU/m3) endotoxin exposure (aPR=10.5 (95% CI 1.3 to 83.1)) at baseline were associated with excessive decline. One production worker with excessive decline had BADE on subsequent lung biopsy.

Conclusions

Lung function loss and BADE were associated with production work. Relationships with relative endotoxin exposure indicate work-related adverse respiratory health outcomes beyond the sentinel disease cluster, including an incident BADE case. Until causative factors and effective preventive strategies for BADE are determined, exposure minimisation and medical surveillance of affected workforces are recommended.
Implementation of targeted screening for lung cancer in a high-risk population within routine NHS practice using low-dose computed tomography
Authors: Grover Helen , Ross Thomas , Fuller Elizabeth
Published: March 2020

We report a primary care-based lung cancer targeted screening programme using low-dose CT (LDCT) in South Tyneside and Sunderland. Ever smokers with ≥10 pack-years aged 55–74 years were identified at annual COPD review. 925 individuals attended for LDCT. 2% (n=19/925) had lung cancer diagnosed. 66.7% (n=14/21) had early stage disease and 78.9% (n=15/19) were offered treatment with curative intent. 79.3% of individuals attending for LDCT were ranked in the lowest deprivation quintiles. This approach has been successfully established in routine NHS practice; it is effective with improvements in stage of disease and engages individuals in deprived areas.
Conformal invariance versus Weyl invariance
Authors: Alvarez Enrique , Anero Jesus , Santos-Garcia Raquel
Published: March 2020

The most general Lagrangian describing spin 2 particles in flat spacetime and containing operators up to (mass) dimension 6 is carefully analyzed, determining the precise conditions for it to be invariant under linearized (transverse) diffeomorphisms, linearized Weyl rescalings, and conformal transformations.
Prospect for constraining holographic dark energy with gravitational wave standard sirens from the Einstein Telescope
Authors: Zhang Jing-Fei , Dong Hong-Yan , Qi Jing-Zhao , Zhang Xin
Published: March 2020

We study the holographic dark energy (HDE) model by using the future gravitational wave (GW) standard siren data observed from the Einstein Telescope (ET) in this work. We simulate 1000 GW standard siren data based on a 10-year observation of the ET to make this analysis. We find that all the cosmological parameters in the HDE model can be tremendously improved by including the GW standard siren data in the cosmological fit. The GW data combined with the current cosmic microwave background anisotropies, baryon acoustic oscillations, and type Ia supernovae data will measure the cosmological parameters $$\Omega _{\mathrm{m}}$$Ωm, $$H_0$$H0, and c in the HDE model to be at the accuracies of 1.28%, 0.59%, and 3.69%, respectively. A comparison with the cosmological constant model and the constant-w dark energy model shows that, compared to the standard model, the parameter degeneracies will be broken more thoroughly in a dynamical dark energy model. We find that the GW data alone can provide a fairly good measurement for $$H_0$$H0, but for other cosmological parameters the GW data alone can only provide rather weak measurements. However, due to the fact that the parameter degeneracies can be broken by the GW data, the standard sirens can play an essential role in improving the parameter estimation.
Thermodynamic geometry of AdS black holes and black holes in a cavity
Authors: Wang Peng , Wu Houwen , Yang Haitang
Published: March 2020

The thermodynamic geometry has been proved to be quite useful in understanding the microscopic structure of black holes. We investigate the phase structure, thermodynamic geometry and critical behavior of a Reissner–Nordstrom-AdS black hole and a Reissner–Nordstrom black hole in a cavity, which can reach equilibrium in a canonical ensemble. Although the phase structure and critical behavior of both cases show striking resemblance, we find that there exist significant differences between the thermodynamic geometry of these two cases. Our results imply that there may be a connection between the black hole microstates and its boundary condition.
A comparative study of the linear and colour-flavour-locked equation of states for compact objects
Authors: Thirukkanesh S. , Kaisavelu Anand , Govender Megan
Published: March 2020

In this work we present a general framework for obtaining exact solutions to the Einstein field equations describing strange stars obeying a colour-flavour-locked (CFL) equation of state. Starting off with a spherically symmetric metric in isotropic coordinates describing the interior of the star, we impose a CFL equation of state to reduce the problem to a single-generating function of the gravitational potentials. Our approach leads to an infinite class of solutions of the field equations. In order to test the physical viability of our solutions, we subscribe a particular model to stringent stability tests. In particular, we show that a linear equation of state described by the MIT Bag model mimics the CFL equation of state describing strange stars with interacting quark matter. This is an interesting result which connects the more robust and mathematically tractable linear equation of state to the fundamental physics describing nuclear matter in the quark regime.
(-)-Epigallocatechin Gallate Promotes MicroRNA 145 Expression against Myocardial Hypoxic Injury through Dab2/Wnt3a/β-catenin
Authors: Lin Chiu-Mei , Fang Wei-Jen , Wang Bao-Wei , Pan Chun-Ming , Chua Su-Kiat , Hou Sheng-Wen , Shyu Kou-Gi
Published: March 2020

MicroRNA 145 (miR-145) is a critical modulator of cardiovascular diseases. The downregulation of myocardial miR-145 is followed by an increase in disabled-2 (Dab2) expression in cardiomyocytes. (-)-epigallocatechin gallate (EGCG) is a flavonoid that has been evaluated extensively due to its diverse pharmacological properties including anti-inflammatory effects. The aim of this study was to investigate the cardioprotective effects of EGCG under hypoxia-induced stress in vitro and in vivo. The hypoxic insult led to the suppression of miR-145 expression in cultured rat cardiomyocytes in a concentration-dependent manner. Western blotting and real-time PCR were performed. In rat myocardial infarction study, in situ hybridization, and immunofluorescent analyses were adopted. The western blot and real-time PCR data revealed that hypoxic stress with 2.5% O2 suppressed the expression of miR-145 and Wnt3a/[Formula: see text]-catenin in cultured rat cardiomyocytes but augmented Dab2. Treatment with EGCG attenuated Dab2 expression, but increased Wnt3a and [Formula: see text]-catenin in hypoxic cultured cardiomyocytes. Following in vivo myocardial infarction (MI) study, the data revealed the myocardial infarct area reduced by 48.5%, 44.6%, and 48.5% in EGCG (50[Formula: see text]mg/kg) or miR-145 dominant or Dab2 siRNA groups after myocardial infarction for 28 days, respectively. This study demonstrated that EGCG increased miR-145, Wnt3a, and [Formula: see text]-catenin expression but attenuated Dab2 expression. Moreover, EGCG ameliorated myocardial ischemia in vivo. The novel suppressive effect was mediated through the miR-145 and Dab2/Wnt3a/[Formula: see text]-catenin pathways.
Enhancement of Ionic Conductivity and Dielectric Permittivity for PMMA-Based Polymer Electrolyte with BaTiO3NanoFiller
Authors: Sathyanathan T. , Pugazhendhi Sugumaran C.
Published: March 2020

The design of the lithium polymer battery with excellent performance needs proper exploration of the materials. Poly(methyl methacrylate) (PMMA)-hosted solid nanocomposite polymer electrolyte systems are prepared by solvent-casting technique. A fixed amount of propylene carbonate (PC) is used as a plasticizer, barium titanate (BaTiO[Formula: see text] as a nanofiller and lithium hexafluorophosphate (LiPF[Formula: see text] as a dopant salt. The characterization of nanocomposite solid polymer electrolyte (SPE) was carried out using scanning electron microscope (SEM), and the outcome revealed the formation of a three-dimensional network with dispersed nanofillers. The dielectric constants and ionic conductivities for different wt.% of nanofiller with different temperature ranges are measured by impedance analyzer. It is observed that for 15[Formula: see text]wt.% of nanofiller-mixed electrolyte sample, a highest dielectric constant of 5166 and a maximum ionic conductivity of [Formula: see text] S[Formula: see text][Formula: see text][Formula: see text]cm[Formula: see text] are achieved.
Fault seal modelling – the influence of fluid properties on fault sealing capacity in hydrocarbon and CO
2
systems
Authors: Karolytė Rūta , Johnson Gareth , Yielding Graham , Gilfillan Stuart M.V.
Published: March 2020

Fault seal analysis is a key part of understanding the hydrocarbon trapping mechanisms in the petroleum industry. Fault seal research has also been expanded to CO
2
–brine systems for the application to carbon capture and storage (CCS). The wetting properties of rock-forming minerals in the presence of hydrocarbons or CO
2
are a source of uncertainty in the calculations of capillary threshold pressure, which defines the fault sealing capacity. Here, we explore this uncertainty in a comparison study between two fault-sealed fields located in the Otway Basin, SE Australia. The Katnook Field in the Penola Trough is a methane field, while Boggy Creek in Port Campbell contains a high-CO
2
–methane mixture. Two industry standard fault seal modelling methods, one based on laboratory measurements of fault samples and the other based on a calibration of a global dataset of known sealing faults, are used to discuss their relative strengths and applicability to the CO
2
storage context. We identify a range of interfacial tensions and contact angle values in the hydrocarbon–water system under the conditions assumed by the second method. Based on this, the uncertainty related to the spread in fluid properties was determined to be 24% of the calculated threshold capillary pressure value. We propose a methodology of threshold capillary pressure conversion from hydrocarbons–brine to the CO
2
–brine system, using an input of appropriate interfacial tension and contact angle under reservoir conditions. The method can be used for any fluid system where fluid properties are defined by these two parameters.

Supplementary material:
(1) Fault seal modelling methods and calculations, and (2) hydrocarbon and CO
2
interfacial tensions and contact angle values collected in the literature are available at
https://doi.org/10.6084/m9.figshare.c.4877049

This article is part of the Energy Geoscience Series available at
https://www.lyellcollection.org/cc/energy-geoscience-series
Steps Towards the Use of TiS2 Electrodes in Ca Batteries
Authors: Verrelli R. , Black A. , Dugas R. , Tchitchekova D. , Ponrouch A. , Palacin M. R.
Published: March 2020

A comparative study of the reduction of TiS2 in diverse electrolyte formulations involving Ca(BF4)2 and Ca(TFSI)2 salts was carried out at different temperatures (from 25 °C to 100 °C). While for the former salt intercalation of calcium is only observed at high temperatures, calcium intercalated phases are also observed for the latter even at room temperature. The nature of the electrolyte does also have an impact on the relative amounts of the phases formed. Since Ca(TFSI)2 based electrolytes do not enable calcium plating, cycling was attempted using activated carbon as counterelectrode, and the reversibility of the process was ascertained. Even if corrosion of stainless steel current collectors and side reactions do still prevent proper cyclability, the results achieved should contribute to the establishment of reliable and viable cell set-up and methodology for the unambiguous study of the intercalation process in multivalent battery systems.
ADAM17 protects against elastase-induced emphysema by suppressing CD62L+ leukocyte infiltration in mice
Authors: Suzuki Shoji , Ishii Makoto , Asakura Takanori , Namkoong Ho , Okamori Satoshi , Yagi Kazuma , Kamata Hirofumi , Kusumoto Tatsuya , Kagawa Shizuko , Hegab Ahmed E. , Yoda Masaki , Horiuchi Keisuke , Hasegawa Naoki , Betsuyaku Tomoko
Published: March 2020

Pulmonary emphysema is a major manifestation of chronic obstructive pulmonary disease and is associated with chronic pulmonary inflammation caused by cigarette smoking, with contributions from immune cells such as neutrophils, macrophages, and lymphocytes. Although matrix metalloproteinases are well known to contribute to emphysema progression, the role of a disintegrin and metalloproteinase (ADAM) family proteins, other major metalloproteinases, in disease pathogenesis is largely unknown. ADAM17 is a major sheddase that cleaves various cell surface proteins, including CD62L, an adhesion molecule that plays a critical role in promoting the migration of immune cells to the site of inflammation. In the present study, we aimed to investigate the potential role of ADAM17 and CD62L in the development of elastase-induced emphysema. Control and Adam17flox/flox/Mx1-Cre ( Adam17ΔMx1) mice (8–10 wk old) were intratracheally injected with 5 units of porcine pancreas elastase and monitored for 35 days after injection. Lung alveolar destruction was evaluated by analyzing the mean linear intercepts of lung tissue specimens and by histopathological examination. Mean linear intercepts data indicated that the degree of elastase-induced emphysema was significantly more severe in Adam17ΔMx1 mice. Furthermore, flow cytometry showed that CD62L+ neutrophil, CD62L+ macrophage, and CD62L+ B lymphocyte numbers were significantly increased in Adam17ΔMx1 mice. Moreover, the pharmacological depletion of CD62L+ cells with a CD62L-neutralizing antibody ameliorated the extent of emphysema in Adam17ΔMx1 mice. Collectively, these results suggest that ADAM17 possibly suppresses the progression of emphysema by proteolytically processing CD62L in immune cells and that ADAM17 and CD62L could be novel therapeutic targets for treating pulmonary emphysema.
Phenotype transitions induced by mechanical stimuli in airway smooth muscle are regulated by differential interactions of parvin isoforms with paxillin and Akt
Authors: Huang Youliang , Gunst Susan J.
Published: March 2020

Mechanical tension and humoral stimuli can induce transitions in airway smooth muscle phenotype between a synthetic inflammatory state that promotes cytokine secretion and a differentiated state that promotes the expression of smooth muscle phenotype-specific proteins. When tissues are maintained under high tension, Akt activation and eotaxin secretion are suppressed, but expression of the differentiation marker protein, smooth muscle myosin heavy chain (SmMHC), is promoted. When tissues are maintained under low tension, Akt activation and eotaxin secretion are stimulated, and the differentiated phenotype is suppressed. We hypothesized that mechanical stimuli are differentially transduced to Akt-mediated signaling pathways that regulate phenotype expression by α-parvin and β-parvin integrin-linked kinase/PINCH/parvin (IPP) signaling complexes within integrin adhesomes. High tension or ACh triggered paxillin phosphorylation and the binding of phospho-paxillin to β-parvin IPP complexes. This inhibited Akt activation and promoted SmMHC expression. Low tension or IL-4 did not elicit paxillin phosphorylation and triggered the binding of unphosphorylated paxillin to α-parvin IPP complexes, which promoted Akt activation and eotaxin secretion and suppressed SmMHC expression. Expression of a nonphosphorylatable paxillin mutant or β-parvin depletion by siRNA promoted the inflammatory phenotype, whereas the depletion of α-parvin promoted the differentiated phenotype. Results demonstrate that phenotype expression is regulated by the differential interaction of phosphorylated and unphosphorylated paxillin with α-parvin and β-parvin IPP complexes and that these complexes have opposite effects on the activation of Akt. Our results describe a novel molecular mechanism for transduction of mechanical and humoral stimuli within integrin signaling complexes to regulate phenotype expression in airway smooth muscle.
Renal and segmental artery hemodynamic response to acute, mild hypercapnia
Authors: Chapman Christopher L. , Schlader Zachary J. , Reed Emma L. , Worley Morgan L. , Johnson Blair D.
Published: March 2020

Profound increases (>15 mmHg) in arterial carbon dioxide (i.e., hypercapnia) reduce renal blood flow. However, a relatively brief and mild hypercapnia can occur in patients with sleep apnea or in those receiving supplemental oxygen therapy during an acute exacerbation of chronic obstructive pulmonary disease. We tested the hypothesis that a brief, mild hypercapnic exposure increases vascular resistance in the renal and segmental arteries. Blood velocity in 14 healthy adults (26 ± 4 yr; 7 women, 7 men) was measured in the renal and segmental arteries with Doppler ultrasound while subjects breathed room air (Air) and while they breathed a 3% CO2, 21% O2, 76% N2 gas mixture for 5 min (CO2). The end-tidal partial pressure of CO2 ([Formula: see text]) was measured via capnography. Mean arterial pressure (MAP) was measured beat to beat via the Penaz method. Vascular resistance in the renal and segmental arteries was calculated as MAP divided by blood velocity. [Formula: see text] increased with CO2 (Air: 45 ± 3, CO2: 48 ± 3 mmHg, P < 0.01), but there were no changes in MAP ( P = 0.77). CO2 decreased blood velocity in the renal (Air: 35.2 ± 8.1, CO2: 32.2 ± 7.3 cm/s, P < 0.01) and segmental (Air: 24.2 ± 5.1, CO2: 21.8 ± 4.2 cm/s, P < 0.01) arteries and increased vascular resistance in the renal (Air: 2.7 ± 0.9, CO2: 3.0 ± 0.9 mmHg·cm−1·s, P < 0.01) and segmental (Air: 3.9 ± 1.0, CO2: 4.4 ± 1.0 mmHg·cm−1·s, P < 0.01) arteries. These data provide evidence that the kidneys are hemodynamically responsive to a mild and acute hypercapnic stimulus in healthy humans.
Chemical sympathectomy reduces peripheral inflammatory responses to acute and chronic sleep fragmentation
Authors: Mishra Ila , Pullum Keelee B. , Thayer Domnique C. , Plummer Erica R. , Conkright Benjamin W. , Morris Andrew J. , O’Hara Bruce F. , Demas Gregory E. , Ashley Noah T.
Published: March 2020

Sleep loss contributes to the development of cardiovascular, metabolic, and neurological disorders by promoting a systemic proinflammatory phenotype. The neuroendocrine-immune mechanisms contributing to such pathologies are poorly understood. The sympathetic nervous system (SNS) regulates immunity and is often activated following sleep disturbances. The aims of this study were to determine 1) the effect of SNS inhibition on inflammatory responses to sleep fragmentation (SF) and 2) whether homeostasis can be restored after 1 wk of recovery sleep. We measured stress responses (norepinephrine and corticosterone), gene expression levels of pro- and anti-inflammatory cytokines in peripheral (heart, liver, and spleen) tissues, and protein levels of cytokines and chemokines in serum of female mice that were subjected to acute SF for 24 h, chronic SF for 8 wk, or 7 days of recovery after chronic SF. In each experiment, SF and control mice were chemically sympathectomized with 6-hydroxydopamine (6-OHDA) or injected with vehicle. Both acute and chronic SF elevated mRNA and protein levels of cytokines in peripheral tissues. Changes in inflammatory responses mirrored stress-axes activation, with increased corticosterone and norepinephrine in SF mice. 6-OHDA treatment significantly alleviated SF-induced inflammation, thus providing evidence of SNS regulation of peripheral inflammation from SF. Effects of chronic SF were more severe than acute SF, and 1 wk of recovery from SF sufficiently alleviated peripheral inflammatory responses but not NE responses.
Functional dedifferentiation of the brain during healthy aging
Authors: Rakesh Divyangana , Fernando Kavisha B. , Mansour L. Sina
Published: March 2020

Nonpathological aging is associated with significant cognitive deficits. Thus, the underlying neurobiology of aging-associated cognitive decline warrants investigation. In a recent study, Chong et al. (Chong JSX, Ng KK, Tandi J, Wang C, Poh J-H, Lo JC, Chee MWL, Zhou JH. J Neurosci 39: 5534–5550, 2019) provided insights into the association between cognitive decline and the loss of functional specialization in the brains of older adults. Here, we introduce the novel graph theoretical approach utilized and discuss the significance of their findings and broader implications on aging. We also provide alternate perspectives of their findings and suggest directions for future work.
A platform for semiautomated voluntary training of common marmosets for behavioral neuroscience
Authors: Walker Jeffrey D. , Pirschel Friederice , Gidmark Nicholas , MacLean Jason N. , Hatsopoulos Nicholas G.
Published: March 2020

Generally behavioral neuroscience studies of the common marmoset employ adaptations of well-established training methods used with macaque monkeys. However, in many cases these approaches do not readily generalize to marmosets indicating a need for alternatives. Here we present the development of one such alternate: a platform for semiautomated, voluntary in-home cage behavioral training that allows for the study of naturalistic behaviors. We describe the design and production of a modular behavioral training apparatus using CAD software and digital fabrication. We demonstrate that this apparatus permits voluntary behavioral training and data collection throughout the marmoset’s waking hours with little experimenter intervention. Furthermore, we demonstrate the use of this apparatus to reconstruct the kinematics of the marmoset’s upper limb movement during natural foraging behavior.

NEW & NOTEWORTHY The study of marmosets in neuroscience has grown rapidly and presents unique challenges. We address those challenges with an innovative platform for semiautomated, voluntary training that allows marmosets to train throughout their waking hours with minimal experimenter intervention. We describe the use of this platform to capture upper limb kinematics during foraging and to expand the opportunities for behavioral training beyond the limits of traditional training sessions. This flexible platform can easily incorporate other tasks.
Ridge Alterations following Socket Preservation Using a Collagen Membrane in Dogs
Authors: Lyu Chengqi , Shao Zhengwei , Zou Derong , Lu Jiayu
Published: March 2020

Background. The healing process following tooth extraction results in alveolar ridge resorption. The dimensional changes may complicate the subsequent implant procedure. Socket preservation using absorbable collagen membranes or a combination of membranes with calcium phosphate cement (CPC) particles might ensure that the alveolar ridge retains a suitable morphology for implant placement. Objective. To evaluate the quality and quantity of new bone regenerated after application of either collagen membranes alone covering the sockets or a combination of membranes with CPC particles added into the sockets in dogs. Materials and Methods. Six dogs were included in this study. The mandibular premolars were extracted. For each hemimandible, three premolar extraction sites were randomly assigned to one of the following treatments: a covering collagen membrane, CPC with a covering collagen membrane, and a socket left empty. Cone‐beam computed tomography (CBCT) measurements, polyfluorochrome sequential labeling, and histological assessments were performed to investigate the healing ability and repair processes within a 6‐month observation period. Results. Buccal bone height in the membrane group was significantly higher than that in the membrane+CPC and blank groups at 4 and 6 months after extraction. The mineral apposition rate over 2‐4 months and the alizarin red‐stained area in the membrane group were significantly higher than those in the other two groups. Histological analysis after 6 months of healing showed significantly higher amounts of newly formed bone in the membrane group than in the other groups. Conclusion. Extraction sites treated with collagen barrier membranes showed better protection than sites not covered with membranes. And the buccal bone wall of the socket was well preserved by collagen membrane without extra CPC materials. Socket preservation using absorbable membranes alone yielded better quality and quantity of regenerated bone inside the socket site.
MiR‐92b‐3p is Induced by Advanced Glycation End Products and Involved in the Pathogenesis of Diabetic Nephropathy
Authors: Wang Li-ping , Geng Jia-nan , Sun Bo , Sun Cheng-bo , Shi Yan , Yu Xiao-yan
Published: March 2020

Purpose. The current study aims to examine the effects of advanced glycation end products (AGEs) on the microRNA (miRNA) expression profile in the kidney tissues of rats. Methods. Wistar rats were randomly divided into three equal experiment groups: the AGE group, the RSA group, and the control group. The rats in the AGE group and the RSA group were administered with advanced glycation end products (AGEs) and rat serum albumin (RSA) via the tail vein, respectively, whereas the control group received PBS. Total RNA was prepared from the rat kidney tissues, and the miRNA expression profiles in different experiment groups were compared by microarray analysis. The expression levels of selected differential miRNAs were verified by RT‐qPCR. Target gene prediction was conducted using algorithms such as TargetScan, miRanda, and PICTar. Functional analysis was performed to determine the putative biological roles of the validated miRNAs. Results. The microarray study revealed 451 upregulated and 320 downregulated miRNAs in the AGE group compared with the RSA group (p < 0.05). Seven miRNAs, including miR‐21‐5p, miR‐92b‐3p, miR‐140‐3p, miR‐196a‐5p, miR‐181b‐5p, miR‐186‐5p, and miR‐192‐5p, were screened and verified using RT‐qPCR, of which, the change of miR‐92b‐3p was the most obvious according to the miRNA expression different multiple and p value. Furthermore, the expression trend of miR‐92b‐3p measured by RT‐qPCR was shown to be consistent with the microarray results. Bioinformatics analysis and luciferase reporter assay identified Smad7 was a direct target of miR‐92b‐3p. Both immunohistochemical and western blotting showed that Smad7 expression was significantly suppressed in the kidney tissues from the AGE group compared with the control and RSA groups. Conclusion. The results of the current study suggested that miR‐92b‐3p could mediate AGE‐induced development of renal abnormalities through targeting Smad7 in rats with DN.
Preoperative Neutrophil‐to‐Lymphocyte Ratio Was a Predictor of Overall Survival in Small Renal Cell Carcinoma: An Analysis of 384 Consecutive Patients
Authors: Zhao Hao , Li Wang , Le Xiang , Li Zixiang , Ge Peng
Published: March 2020

Objective. The aim of this study was to investigate the prognostic significance of the preoperative neutrophil‐to‐lymphocyte ratio (NLR) in small renal cell carcinoma (sRCC, ≤4 cm). Methods. This study was approved by the review board (NO.XYFY2019‐KL032‐01). Between 2007 and 2016, a total of 384 consecutive patients who underwent curative surgery for sRCC at our institution were evaluated. Patients were divided into high NLR and low NLR groups by plotting the NLR receiver operating characteristic curve. The Kaplan–Meier method was utilized to graphically display survivor functions. Univariate and multivariate Cox proportional hazards regression analysis addressed time to overall survival (OS) and cancer‐specific survival (CSS). Results. Of the 384 patients, 264 (68.8%) were males and 120 (31.2%) were females. Median follow‐up time after surgical resection was 54 months. One hundred and eighty‐seven (48.7%) patients had a high NLR (≥1.97), and the remaining 197 (51.3%) had a low NLR (<1.97). Patients with high NLR were more likely to be aged compared with patients with low NLR (P = 0.028). High NLR was associated with decreased OS and CSS compared with low NLR (P = 0.002, P = 0.065, respectively, the log‐rank test). Multivariate Cox model analysis showed that the high NLR was an independent prognostic factor for OS (hazard ratio: 3.145, 95% confidence interval: 1.158–8.545, P = 0.025). Conclusions. Elevated preoperative NLR is an independent adverse prognostic factor for OS after surgery with curative intent for sRCC.
Unitarity of Singh-Hagen Model in D Dimensions
Authors: Mendonça Elias L. , Schimidt Bittencourt R.
Published: March 2020

The particle content of the Singh-Hagen model (SH) in D dimensions is revisited. We suggest a complete set of spin-projection operators acting on totally symmetric rank-3 fields. We give a general expression for the propagator and determine the coefficients of the SH model confirming previous results of the literature. Adding source terms, we provide a unitarity analysis in D dimensions. In addition, we have also analyzed the positivity of the massless Hamiltonian.
Auto-antibodies to p53 and the Subsequent Development of Colorectal Cancer in a United States Prospective Cohort Consortium
Authors: Butt J , Blot WJ , Visvanathan K , Le Marchand L , Chen Y , Sesso HD , Wassertheil-Smoller S , Ho GYF , Tinker LE , Potter JD , Song M , Berndt S , Waterboer T , Pawlita M , Epplein M
Published: March 2020

Auto-antibodies to tumor suppressor p53 are found in a subset of colorectal cancer (CRC) patients. A prospective cohort study in the US (Cancer Prevention Study II) has recently reported a statistically significant 1.8-fold increased odds for the development of CRC based on pre-diagnostic sero-positivity for p53; the magnitude of this association decreased with longer time-span between blood sampling and diagnosis. In the present study, we sought to examine this association in a large US CRC cohort consortium to evaluate the potential utility of p53 auto-antibodies as an early CRC detection biomarker. Methods: Antibody responses to p53 were measured in pre-diagnostic blood samples of 3,702 incident CRC cases (median [range] follow-up: 7.3 years [0–40 years]) and an equal number of controls, matched by age, race, and sex, from 9 US prospective cohorts. The association of sero-positivity to p53 with CRC risk, overall and by time between blood draw and diagnosis, was determined by conditional logistic regression. Results: Overall, 5% of controls and 7% of cases were sero-positive to p53, resulting in a statistically significant 33% increased CRC risk (OR: 1.33; 95% CI: 1.09, 1.61). The association was strongest for CRC diagnoses within 2 years after blood draw (OR: 2.73; 95% CI: 1.67, 4.45), with 15% sero-positive cases compared to 6% sero-positive controls. The number of sero-positive cases decreased with longer follow-up time (2–<5 years: 9%; 5–<10 years: 6%; ≥10 years: 3%) down to a proportion similar to that in controls resulting in the absence of an association of p53 sero-positivity with CRC risk after more than 5 years between blood draw and CRC diagnosis. Conclusion: In this large consortium of prospective cohorts, we found that pre-diagnostic sero-positivity to the tumor suppressor p53 was statistically significantly associated with a 2.7-fold increased risk of a subsequent CRC diagnosis within 2 years after blood draw, replicating the findings of the one previous cohort study examining this association. The findings suggest that while p53 sero-positivity may not be a useful predictor of long-term CRC risk, p53 auto-antibodies might be considered as part of a marker panel for early detection of this cancer.
Accelerometer-measured Physical Activity and Breast Cancer Incidence in the WHI OPACH Study
Authors: Parada H , Bellettiere J , Evenson KR , LaMonte MJ , LaCroix AZ
Published: March 2020

To examine the associations between accelerometer-measured physical activity (PA) and breast cancer incidence among a cohort of postmenopausal women. Methods: This longitudinal study included 6,382 women (mean age 79 ± 6 years; 49.4% non-Hispanic white, 33.7% non-Hispanic Black, 16.9% Hispanic) without a history of breast cancer who participated in the Women's Health Initiative (WHI) Objective Physical Activity and Cardiovascular Health (OPACH) Study. During 2012–2013, participants wore an ActiGraph GT3X+ accelerometer at the hip for up to 7 days. Accelerometer intensity counts were specially calibrated to PA in older women. The resulting data were used to compute minutes per day spent in total PA, light intensity PA (e.g., usual walking), and moderate-to-vigorous PA (MVPA; e.g., brisk walking). Physician-adjudicated first diagnosis of in situ (n = 18) or invasive (n = 103) breast cancer was ascertained over a median follow-up of 5.6 years. We used multivariable Cox regression to estimate covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for tertiles and one-standard deviation (SD) unit increments of PA exposures in association with breast cancer incidence. We examined effect measure modification by age, race/ethnicity, body mass index (BMI), and smoking history. Results: The highest (vs. lowest) tertile of total PA was associated with a breast cancer incidence HR of 0.67 (95% CI = 0.43–1.05) and this association was more pronounced for MVPA (HR = 0.61, 95% CI = 0.38–1.00) than for light PA (HR = 0.81, 95% CI = 0.53–1.26). In BMI-stratified analyses, HRs for total (PInteraction = 0.04) and light PA (PInteraction = 0.01), but not MVPA (PInteraction = 0.79), were stronger among women with BMI ≥ 30 kg/m2 (n cancer events = 48; total PA HRper one-SD = 0.69, 95% CI = 0.50–0.96; light PA HR = 0.69, 95% CI = 0.50–0.95) than among women with BMI < 30 kg/m2 (n cancer events = 73; total PA HRper one-SD = 1.07, 95% CI = 0.84–1.38; light PA HR = 1.13, 95% CI = 0.89–1.44). Age, race/ethnicity, and cigarette smoking history did not strongly modify these associations (PInteraction's ≥ 0.16). Conclusions: Engaging in high levels of PA may play a beneficial role in the prevention of breast cancer in older women, and in particular among postmenopausal women with BMI ≥ 30 kg/m2.