bluuebunny/crossref_metadata_2025 huggingface dataset:
Are physical factors associated with poor prognosis following a whiplash trauma?: a protocol for a systematic review and data synthesis
Authors: Alalawi Ahmed , Gallina Alessio , Sterling Michele , Falla Deborah
Published: November 2019

Introduction

Mitigating the transition from acute to chronic whiplash-associated disorders (WAD) is fundamental, and this could be achieved through early identification of individuals at risk. Several physical factors such as angular velocity, smoothness of neck movement and coactivation of neck flexors and extensors, have been observed in patients with WAD, but their predictive ability after a whiplash injury have not been considered in previous reviews. Therefore, the aim of the current protocol is to outline the protocol for a systematic review that synthesises the current evidence of which physical factors can predict ongoing pain and disability following a whiplash trauma.

Methods and analysis

Two independent reviewers will search for studies in several electronic databases including MEDLINE, Embase, CINAHL, PsycINFO, Scopus and Web of Science as well as grey literature. Observational cohort studies will be considered if they involve participants with acute WAD followed for at least 3 months post-injury. Studies will be required to assess the prognostic ability of one or more physical factors that directly involve a body function and/or structure and can be measured objectively. Further, patient-reported outcomes of physical function will be considered. The primary outcome for this review is Neck Disability Index, while all other validated measures will be considered as secondary outcomes. Risk of bias across individual studies will be assessed using the Quality In Prognostic Studies tool along with the Grades of Recommendation, Assessment, Development and Evaluation method to assess the quality of evidence. A meta-analysis will be conducted depending on homogeneity and the number of available studies. If appropriate, data will be pooled and presented as odds ratios, otherwise, a qualitative synthesis will be conducted.

Ethics and dissemination

Ethical approval is not required for this systematic review. The result from this review will be published in peer-reviewed journals.

PROSPERO registration number

CRD42019122559
Early warning score adjusted for age to predict the composite outcome of mortality, cardiac arrest or unplanned intensive care unit admission using observational vital-sign data: a multicentre development and validation
Authors: Shamout Farah , Zhu Tingting , Clifton Lei , Briggs Jim , Prytherch David , Meredith Paul , Tarassenko Lionel , Watkinson Peter J , Clifton David A
Published: November 2019

Objectives

Early warning scores (EWS) alerting for in-hospital deterioration are commonly developed using routinely collected vital-sign data from the whole in-hospital population. As these in-hospital populations are dominated by those over the age of 45 years, resultant scores may perform less well in younger age groups. We developed and validated an age-specific early warning score (ASEWS) derived from statistical distributions of vital signs.

Design

Observational cohort study.

Setting

Oxford University Hospitals (OUH) July 2013 to March 2018 and Portsmouth Hospitals (PH) NHS Trust January 2010 to March 2017 within the Hospital Alerting Via Electronic Noticeboard database.

Participants

Hospitalised patients with electronically documented vital-sign observations

Outcome

Composite outcome of unplanned intensive care unit admission, mortality and cardiac arrest.

Methods and results

Statistical distributions of vital signs were used to develop an ASEWS to predict the composite outcome within 24 hours. The OUH development set consisted of 2 538 099 vital-sign observation sets from 142 806 admissions (mean age (SD): 59.8 (20.3)). We compared the performance of ASEWS to the National Early Warning Score (NEWS) and our previous EWS (MCEWS) on an OUH validation set consisting of 581 571 observation sets from 25 407 emergency admissions (mean age (SD): 63.0 (21.4)) and a PH validation set consisting of 5 865 997 observation sets from 233 632 emergency admissions (mean age (SD): 64.3 (21.1)). ASEWS performed better in the 16–45 years age group in the OUH validation set (AUROC 0.820 (95% CI 0.815 to 0.824)) and PH validation set (AUROC 0.840 (95% CI 0.839 to 0.841)) than NEWS (AUROC 0.763 (95% CI 0.758 to 0.768) and AUROC 0.836 (95% CI 0.835 to 0.838) respectively) and MCEWS (AUROC 0.808 (95% CI 0.803 to 0.812) and AUROC 0.833 (95% CI 0.831 to 0.834) respectively). Differences in performance were not consistent in the elder age group.

Conclusions

Accounting for age-related vital sign changes can more accurately detect deterioration in younger patients.
Home care for terminally ill patients: the experiences of family caregivers with and without paid work
Authors: Bijnsdorp Femmy M , van der Beek Allard J , Pasman H Roeline W , Boot Cécile R L , de Boer Alice H , Plaisier Inger , Onwuteaka-Philipsen Bregje D
Published: November 2019

Objectives

To facilitate care at the end of life at home, support from family caregivers is crucial. A substantial number of these family caregivers also work. Work in relation to care for terminally ill patients has received limited attention. To better understand the context in which these family caregivers provide care, we provide a detailed overview of the situation and experiences of family caregivers of terminally ill patients at home, with and without paid work.

Methods

We used a pooled cross-section of data from the Dutch Informal Care Study, collected in 2014 and 2016. All working and non-working family caregivers of terminally ill patients at home were included (n=292).

Results

Working family caregivers reported more care tasks, and shared care tasks with others more often than non-working caregivers. No differences between working and non-working caregivers were found in negative and positive experiences. Non-working caregivers provided care more often because the care recipient wanted to be helped by them or because there was no one else available than working caregivers. About 70% of the working caregivers were able to combine work and family caregiving successfully.

Conclusions

Working and non-working family caregivers of terminally ill patients at home have similar burden and positive experiences. Working family caregivers vary in their ability to combine work and care. Although the majority of working family caregivers successfully combine work and care, a substantial number struggle and need more support with care tasks at home or responsibilities at work.
Palliative care training in undergraduate medical, nursing and allied health: a survey
Authors: White Nicola , Oostendorp Linda JM , Minton Ollie , Yardley Sarah , Stone Patrick
Published: November 2019

Objectives

Impending death is poorly recognised. Many undergraduate healthcare professionals will not have experience of meeting or caring for someone who is dying. As death can occur in any setting, at any time, it is vital that all healthcare students, regardless of the setting they go on to work in, have end-of-life care (EOLC) training. The aim was to determine current palliative care training at the undergraduate level, in multiple professions, in recognising and communicating dying.

Methods

Current UK undergraduate courses in medicine, adult nursing, occupational therapy, social work and physiotherapy were included. All courses received an email asking what training is currently offered in the recognition and communication of dying, and what time was dedicated to this.

Results

A total of 73/198 (37%) courses responded to the request for information. 18/20 medical courses provided training in recognising when patients were dying (median 2 hours), and 17/20 provided training in the communication of dying (median 3 hours). 80% (43/54) of nursing and allied health professional courses provided some training in EOLC. Many of the course organisers expressed frustration at the lack of resources, funding and time to include more training. Those courses with more palliative care provision often had a ‘champion’ to advocate for it.

Conclusions

Training in EOLC was inconsistent across courses and professions. Further research is needed to understand how to remove the barriers identified and to improve the consistency of current training.
Submaximal angioplasty in the treatment of patients with symptomatic ICAD: a systematic review and meta-analysis
Authors: Seyedsaadat Seyed Mohammad , Yolcu Yagiz Ugur , Neuhaus Ain , Rizvi Asim , Alzuabi Muayad , Murad Mohammad H , Brinjikji Waleed , Bydon Mohamad , Kallmes David F
Published: November 2019

Introduction

Management approaches for intracranial atherosclerosis include medical, surgical, or endovascular treatment. Among endovascular treatments, recent studies have stated that submaximal angioplasty (SA) may offer considerable benefits and be a promising alternative to aggressive medical therapyand/or stenting in the treatment of intracranial atherosclerotic disease (ICAD).

Objective

To investigate the rates of periprocedural and long-term cerebrovascular accidents, mortality, and restenosis in patients with symptomatic ICAD who were treated with SA.

Methods

An electronic database search was performed for relevant studies that reported clinical outcomes of patients with ICAD following SA. Outcomes of interest were incidence of transient ischemic attack, intracerebral hemorrhage, stroke, and mortality in the periprocedural period and at 1 year. The periprocedural period was defined as the time from SA until 30 days after the procedure. Technical success and restenosis rates after the procedure were also analyzed.

Results

A total of 19 studies with 777 patients were identified. The technical success rate was 93% (95% CI 85% to 98%). The incidence of 30-day and 1-year stroke (all types) was 3% (95% CI 1% to 5%) and 5% (95% CI 4% to 8%), respectively. Thirty-day and 1-year mortality was found to be 1% (95% CI 0% to 2%) and 2% (95% CI 0% to 4%), respectively. The combined incidence of stroke or death was 5% (95% CI 3% to 8%) at 30 days, and 9% (95% CI 7% to 12%) at 1 year.

Conclusion

The findings suggest that SA might be a promising alternative treatment in the treatment of symptomatic ICAD due to its favorable technical profile, periprocedural safety, and long-term efficacy. A randomized clinical trial is warranted to compare the safety and efficacy of SA with 'gold standard' medical treatment.
Diagnostic value of plasma biochemistry, haematology, radiography and endoscopic visualisation for hepatic disease in psittacine birds
Authors: Hung Cher Shi‐Yee , Sladakovic Izidora , Divers Stephen J
Published: November 2019

Background

Hepatic disease in psittacine birds is common but challenging to diagnose. This retrospective study evaluates the diagnostic value of plasma biochemistry, haematology, radiography and endoscopic visualisation in psittaciforms with suspected hepatic disease that underwent endoscopic liver biopsy.

Methods

Clinical records of 28 companion psittaciforms from a veterinary teaching hospital (2007–2016) were reviewed. Diagnostic results were categorised as abnormal or normal and compared with histopathology for agreement or disagreement. Statistical significance was determined by kappa test for agreement and McNemar's test for disagreement.

Results

11 of 28 psittaciforms (39.3 per cent) had clinical signs considered specific for liver disease. 25 of 28 (89.3 per cent) psittaciforms had histopathological liver lesions. Gross changes radiographically and endoscopically agreed with histopathology in 57.1 per cent and 53.6 per cent of cases, respectively. Aspartate aminotransferase (AST) (48.1 per cent), creatine phosphokinase (73.1 per cent) and albumin by protein electrophoresis (50 per cent) showed the highest agreement. Kappa was not significant for any parameters, while McNemar's test for disagreement was significant for radiography, endoscopy, AST, lactate dehydrogenase, bile acid, total protein (chemistry), cholesterol, triglycerides, uric acid and glucose.

Conclusion

Overall, changes on plasma biochemistry, radiography or endoscopy are non‐specific and do not consistently agree with histopathology results. Endoscopic liver biopsy is highly recommended if there is clinical suspicion of hepatic disease.
Prevalence and clinical significance of the medullary rim sign identified on ultrasound of feline kidneys
Authors: Ferreira Amy , Marwood Rachel , Batchelor Daniel , Maddox Thomas , Mortier Jeremy R
Published: November 2019

Objectives

The medullary rim sign (MRS) is an ultrasonographic (US) feature identified in normal and diseased feline kidneys. The prevalence and potential clinical significance of the MRS in a referral hospital cat population was investigated.

Methods

Retrospective case–control study. US images from 661 cats were reviewed. Cats with an MRS were identified and compared with equal number of time‐matched control cats. Medical data and MRS features, including thickness, intensity and symmetry, were collected. Associations between independent variables and the MRS were examined with conditional and unconditional logistic regression, with initial univariable, and subsequent multivariable analysis.

Results

Of the 661 reviewed cats, 243 (36.8 per cent) showed a variation of the MRS. A thin MRS (133 cats) was not associated with azotaemic renal disease (P=0.87). A thick MRS (110 cats) was associated with azotaemic renal disease (P=0.001). There was an association between the presence of MRS and a final diagnosis of feline infectious peritonitis (FIP) (P=0.028).

Conclusions

The MRS is a common finding in cats. In this cat population, a thick MRS was associated with azotaemic renal disease, while a thin MRS was not. In cases with a clinical suspicion of FIP, the MRS may be related to the underlying disease process and not be an incidental finding.
Multi-objective and multi-period optimization of a regional timber supply network with uncertainty
Authors: Chen Cheng , Gan Jianbang , Zhang Zhengxiong , Qiu Rongzu
Published: November 2019

To assess the impacts of uncertainty and environmental objectives on the configuration of timber supply networks, we develop a generic multi-period, mixed-integer fuzzy linear programming model with demand uncertainty and two objectives of minimizing total transportation cost and greenhouse gas (GHG) emissions. We then use the triangular fuzzy number method to define the uncertain demands and convert the model into its equivalent auxiliary crisp counterpart. To derive Pareto solutions more efficiently, we propose the nondominated sorting genetic algorithm (NSGA-II) to solve the model. Finally, we apply the model framework and solution method to a real-world case of regional timber supply in Fujian, China, to demonstrate their applicability. The simulation results of the model show that trade-offs exist between total cost and GHG emissions and that the proper selection of the number and locations of distribution centers can help reduce both the cost and GHG emissions. Demand uncertainty and supply fluctuations across different time periods can increase the cost and GHG emissions. Our empirical results provide useful insights into the design and management of regional timber supply networks, and our generic model is applicable to the analysis of regional supply networks of other products or materials besides timber.
Antimatter gravity and the Universe
Authors: Hajdukovic Dragan Slavkov
Published: November 2019

The aim of this brief review is twofold. First, we give an overview of the unprecedented experimental efforts to measure the gravitational acceleration of antimatter; with antihydrogen, in three competing experiments at CERN (AEGIS, ALPHA and GBAR), and with muonium and positronium in other laboratories in the world. Second, we present the 21st Century’s attempts to develop a new model of the Universe with the assumed gravitational repulsion between matter and antimatter; so far, three radically different and incompatible theoretical paradigms have been proposed. Two of these three models, Dirac–Milne Cosmology (that incorporates CPT violation) and the Lattice Universe (based on CPT symmetry), assume a symmetric Universe composed of equal amounts of matter and antimatter, with antimatter somehow “hidden” in cosmic voids; this hypothesis produced encouraging preliminary results. The heart of the third model is the hypothesis that quantum vacuum fluctuations are virtual gravitational dipoles; for the first time, this hypothesis makes possible and inevitable to include the quantum vacuum as a source of gravity. Standard Model matter is considered as the only content of the Universe, while phenomena usually attributed to dark matter and dark energy are explained as the local and global effects of the gravitational polarization of the quantum vacuum by the immersed baryonic matter. An additional feature is that we might live in a cyclic Universe alternatively dominated by matter and antimatter. In about three years, we will know if there is gravitational repulsion between matter and antimatter; a discovery that can forever change our understanding of the Universe.
Modified gravity in the framework of holographic dark energy
Authors: Granda L. N. , Rojas G. D.
Published: November 2019

The modified gravity is considered in the framework of the holographic dark energy (DE). An analysis of the autonomous system, the critical points and their stability is presented. Unlike the DE models based on [Formula: see text], it is found that working in the holographic frame enriches the possibility of accelerated and matter-type points for different cosmological scenarios, making viable trajectories of successful [Formula: see text] models that are not allowed without the consideration of the holographic framework. The implications for the Hu–Sawicki model are analyzed.
A magnetic-monopole-based mechanism to the formation of the Hot Big Bang modeled Universe
Authors: Peng Qiu-He , Liu Jing-Jing , Chou Chi-Kang
Published: November 2019

There are some particle physics theories that go beyond the so-called “standard cosmological model” to predict the existence of magnetic monopoles (MMs). The discovery of MMs would be an incredible breakthrough in high-energy physics. The existence of MMs in the early Universe has been speculated and anticipated from Grand Unified Theory. If MMs exist, the inverse powers of the unification mass will not suppress the baryon number violating effects of grand unified gauge theories. Therefore, MM catalyzing nucleon decay is a typical strong interaction. This phenomenon is due to the boundary conditions that must be imposed on the core of MM fermion fields. We present a possible mechanism to explain the formation of the Hot Big Bang Cosmology. The main ingredient in our model is nucleon decay catalyzed by MMs (i.e. the Rubakov–Callan effect). It is shown that Hot Big Bang developed naturally because the luminosity due to the Rubakov–Callan effect is much greater than the Eddington luminosity (i.e. [Formula: see text]).
CC-RTSV: Cross-Cellular Based Redundant TSV Design for 3D ICs
Authors: Ni Tianming , Shu Yue , Chang Hao , Lu Lin , Dai Guangzhen , Zhu Shidong , Qu Chengming , Huang Zhengfeng
Published: November 2019

Due to the winding level of the thinned wafers and the surface roughness of silicon dies, the quality of through-silicon vias (TSVs) varies during the fabrication and bonding process. If one TSV exhibits a defect during its manufacturing process, the probability of multiple defects occurring in the TSVs neighboring increases the faulty TSVs (FTSV), i.e., the TSV defects tend to be clustered which significantly reduces the yield of three-dimensional integrated circuits (3D-ICs). To resolve the clustered TSV faults, router-based and ring-based redundant TSV (RTSV) architecture were proposed. However, the repair rate is low and the hardware overhead is high. In this paper, we propose a novel cross-cellular based RTSV architecture to utilize the area more efficiently as well as to maintain high yield. The simulation results show that the proposed architecture has higher repair rate as well as more cost-effective overhead, compared with router-based and ring-based methods.
Wood–Saxon alpha potential for p-nuclei 106Cd and 113In
Authors: Basak Dipali , Basu Chinmay
Published: November 2019

Alpha elastic scattering of [Formula: see text]-nuclei was studied for calculating optical potentials. Choice of the [Formula: see text]-optical potentials is important to measure the reaction rates of [Formula: see text]-process. [Formula: see text] and [Formula: see text] elastic scattering cross-section data were used to determine the potential parameter sets at [Formula: see text][Formula: see text]MeV for [Formula: see text] and [Formula: see text], 18.8[Formula: see text]MeV for [Formula: see text] system. A Wood–Saxon potential form factor is used for both real and imaginary parts. The potential parameters extracted in the present study exhibit a satisfactory result with respect to existing global potential parameters.
Phase II Monitoring of Poisson Regression Profiles in Multi-Stage Processes
Authors: Derakhshani Reza , Esmaeeli Hamid , Amiri Amirhossein
Published: November 2019

Quality of final production multi-stage processes depends on several quality characteristics in the previous stages, which is referred to as cascade property. Sometimes, the quality of a process or product is characterized by a functional relationship known as profile. In some applications, this relationship is a Poisson regression profile. In this paper, Phase II monitoring of Poisson regression profile in multi-stage processes is investigated. Then, four methods are proposed and their performances are compared through simulation studies in terms of the average run length (ARL) criterion. In order to investigate the method performance, an illustrative example and a real example are also presented.
Porphyrin–diketopyrrolopyrrole conjugates and related structures: Synthesis, properties and applications
Authors: Almodôvar Vítor A. S. , Tomé Augusto C.
Published: November 2019

A large diversity of porphyrin–diketopyrrolopyrrole conjugates and related structures formed by diketopyrrolopyrrole units and pyrrole-based moieties such as phthalocyanine, porphycene, calix[4]pyrrole or BODIPY have been reported since 2010. The new compounds, whether small molecules or polymeric materials, exhibit very interesting photophysical properties and have been tested in a range of technical or biological applications. This review summarizes the advances in the synthesis of such compounds. Their photophysical properties and potential applications are also briefly discussed.
On semireversible rings
Authors: Roy Debraj , Subedi Tikaram
Published: November 2019

In this paper, we introduce and study a new class of rings which we call semireversible rings. A ring [Formula: see text] is called semireversible if for any [Formula: see text] implies there exists a positive integer [Formula: see text] such that [Formula: see text]. We observe that the class of semireversible rings strictly lies between the class of central reversible rings and weakly reversible rings. Some relations are provided between semireversible rings and many other known classes of rings. Some extensions of semireversible rings such as ring of fractions, Dorroh extension, subrings of matrix rings are investigated. Finally, we study semireversible rings via modules over them wherein among other results, we prove that a semireversible left (right) SF-ring is strongly regular.
On the sigma chromatic number of the join of a finite number of paths and cycles
Authors: Garciano Agnes D. , Lagura Maria Czarina T. , Marcelo Reginaldo M.
Published: November 2019

Let [Formula: see text] be a simple connected graph and [Formula: see text] a coloring of the vertices in [Formula: see text] For any [Formula: see text], let [Formula: see text] be the sum of colors of the vertices adjacent to [Formula: see text]. Then [Formula: see text] is called a sigma coloring of [Formula: see text] if for any two adjacent vertices [Formula: see text]. The minimum number of colors needed in a sigma coloring of [Formula: see text] is the sigma chromatic number of [Formula: see text], denoted by [Formula: see text]

In this paper, we prescribe a sigma coloring of the join of paths and cycles. As a consequence, we determine the sigma chromatic number of the join of a finite number of paths and cycles. In particular, let [Formula: see text], where [Formula: see text] or [Formula: see text] with [Formula: see text] If [Formula: see text], where [Formula: see text] and [Formula: see text], then [Formula: see text] if [Formula: see text] is an odd cycle, for some [Formula: see text] and [Formula: see text] otherwise.
Symmetries of the quaternionic Ginibre ensemble
Authors: Dubach Guillaume
Published: November 2019

We establish a few properties of eigenvalues and eigenvectors of the quaternionic Ginibre ensemble (QGE), analogous to what is known in the complex Ginibre case (see [7, 11, 14]). We first recover a version of Kostlan’s theorem that was already at the heart of an argument by Rider [1], namely, that the set of the squared radii of the eigenvalues is distributed as a set of independent gamma variables. Our proof technique uses the De Bruijn identity and properties of Pfaffians; it also allows to prove that the high powers of these eigenvalues are independent. These results extend to any potential beyond the Gaussian case, as long as radial symmetry holds; this includes for instance truncations of quaternionic unitary matrices, products of quaternionic Ginibre matrices, and the quaternionic spherical ensemble.

We then study the eigenvectors of quaternionic Ginibre matrices. Angles between eigenvectors and the matrix of overlaps both exhibit some specific features that can be compared to the complex case. In particular, we compute the distribution and the limit of the diagonal overlap associated to an eigenvalue that is conditioned to be at the origin. This complements a recent study of overlaps in quaternionic ensembles by Akemann, Förster and Kieburg [1, 2].
Real-time visualization of titin dynamics reveals extensive reversible photobleaching in human induced pluripotent stem cell-derived cardiomyocytes
Authors: Cadar Adrian G. , Feaster Tromondae K. , Bersell Kevin R. , Wang Lili , Hong TingTing , Balsamo Joseph A. , Zhang Zhentao , Chun Young Wook , Nam Young-Jae , Gotthardt Michael , Knollmann Björn C. , Roden Dan M. , Lim Chee C. , Hong Charles C.
Published: November 2019

Fluorescence recovery after photobleaching (FRAP) has been useful in delineating cardiac myofilament biology, and innovations in fluorophore chemistry have expanded the array of microscopic assays used. However, one assumption in FRAP is the irreversible photobleaching of fluorescent proteins after laser excitation. Here we demonstrate reversible photobleaching regarding the photoconvertible fluorescent protein mEos3.2. We used CRISPR/Cas9 genome editing in human induced pluripotent stem cells (hiPSCs) to knock-in mEos3.2 into the COOH terminus of titin to visualize sarcomeric titin incorporation and turnover. Upon cardiac induction, the titin-mEos3.2 fusion protein is expressed and integrated in the sarcomeres of hiPSC-derived cardiomyocytes (CMs). STORM imaging shows M-band clustered regions of bound titin-mEos3.2 with few soluble titin-mEos3.2 molecules. FRAP revealed a baseline titin-mEos3.2 fluorescence recovery of 68% and half-life of ~1.2 h, suggesting a rapid exchange of sarcomeric titin with soluble titin. However, paraformaldehyde-fixed and permeabilized titin-mEos3.2 hiPSC-CMs surprisingly revealed a 55% fluorescence recovery. Whole cell FRAP analysis in paraformaldehyde-fixed, cycloheximide-treated, and untreated titin-mEos3.2 hiPSC-CMs displayed no significant differences in fluorescence recovery. FRAP in fixed HEK 293T expressing cytosolic mEos3.2 demonstrates a 58% fluorescence recovery. These data suggest that titin-mEos3.2 is subject to reversible photobleaching following FRAP. Using a mouse titin-eGFP model, we demonstrate that no reversible photobleaching occurs. Our results reveal that reversible photobleaching accounts for the majority of titin recovery in the titin-mEos3.2 hiPSC-CM model and should warrant as a caution in the extrapolation of reliable FRAP data from specific fluorescent proteins in long-term cell imaging.
Multiple poloxamers increase plasma membrane repair capacity in muscle and nonmuscle cells
Authors: Kwiatkowski Thomas A. , Rose Aubrey L. , Jung Rachel , Capati Ana , Hallak Diana , Yan Rosalie , Weisleder Noah
Published: November 2019

Various previous studies established that the amphiphilic tri-block copolymer known as poloxamer 188 (P188) or Pluronic-F68 can stabilize the plasma membrane following a variety of injuries to multiple mammalian cell types. This characteristic led to proposals for the use of P188 as a therapeutic treatment for various disease states, including muscular dystrophy. Previous studies suggest that P188 increases plasma membrane integrity by resealing plasma membrane disruptions through its affinity for the hydrophobic lipid chains on the lipid bilayer. P188 is one of a large family of copolymers that share the same basic tri-block structure consisting of a middle hydrophobic propylene oxide segment flanked by two hydrophilic ethylene oxide moieties [poly(ethylene oxide)80-poly(propylene oxide)27-poly(ethylene oxide)80]. Despite the similarities of P188 to the other poloxamers in this chemical family, there has been little investigation into the membrane-resealing properties of these other poloxamers. In this study we assessed the resealing properties of poloxamers P181, P124, P182, P234, P108, P407, and P338 on human embryonic kidney 293 (HEK293) cells and isolated muscle from the mdx mouse model of Duchenne muscular dystrophy. Cell membrane injuries from glass bead wounding and multiphoton laser injury show that the majority of poloxamers in our panel improved the plasma membrane resealing of both HEK293 cells and dystrophic muscle fibers. These findings indicate that many tri-block copolymers share characteristics that can increase plasma membrane resealing and that identification of these shared characteristics could help guide design of future therapeutic approaches.
Budesonide enhances agonist-induced bronchodilation in human small airways by increasing cAMP production in airway smooth muscle
Authors: Koziol-White Cynthia , Johnstone Timothy B. , Corpuz Maia L. , Cao Gaoyuan , Orfanos Sarah , Parikh Vishal , Deeney Brian , Tliba Omar , Ostrom Rennolds S. , Dainty Ian , Panettieri Reynold A.
Published: November 2019

The nongenomic mechanisms by which glucocorticoids modulate β2 agonist-induced-bronchodilation remain elusive. Our studies aimed to elucidate mechanisms mediating the beneficial effects of glucocorticoids on agonist-induced bronchodilation. Utilizing human precision-cut lung slices (hPCLS), we measured bronchodilation to formoterol, prostaglandin E2 (PGE2), cholera toxin (CTX), or forskolin in the presence and absence of budesonide. Using cultured human airway smooth muscle (HASM), intracellular cAMP was measured in live cells following exposure to formoterol, PGE2, or forskolin in the presence or absence of budesonide. We showed that simultaneous budesonide administration amplified formoterol-induced bronchodilation and attenuated agonist-induced phosphorylation of myosin light chain, a necessary signaling event mediating force generation. In parallel studies, cAMP levels were augmented by simultaneous exposure of HASM cells to formoterol and budesonide. Budesonide, fluticasone, and prednisone alone rapidly increased cAMP levels, but steroids alone had little effect on bronchodilation in hPCLS. Bronchodilation induced by PGE2, CTX, or forskolin was also augmented by simultaneous exposure to budesonide in hPCLS. Furthermore, HASM cells expressed membrane-bound glucocorticoid receptors that failed to translocate with glucocorticoid stimulation and that potentially mediated the rapid effects of steroids on β2 agonist-induced bronchodilation. Knockdown of glucocorticoid receptor-α had little effect on budesonide-induced and steroid-dependent augmentation of formoterol-induced cAMP generation in HASM. Collectively, these studies suggest that glucocorticoids amplify cAMP-dependent bronchodilation by directly increasing cAMP levels. These studies identify a molecular mechanism by which the combination of glucocorticoids and β2 agonists may augment bronchodilation in diseases such as asthma or chronic obstructive pulmonary disease.
Blockade of angiotensin-converting enzyme or tumor necrosis factor-α reverses maternal high-fat diet-induced sensitization of angiotensin II hypertension in male rat offspring
Authors: Wang Xue-Fang , Li Jian-Dong , Huo Yan-Li , Zhang Yu-Ping , Fang Zhi-Qin , Wang Hai-Ping , Peng Wei , Johnson Alan Kim , Xue Baojian
Published: November 2019

Maternal high-fat diet (HFD) is associated with metabolic syndrome and cardiovascular diseases in adult offspring. Our previous study demonstrated that maternal HFD enhances pressor responses to ANG II or a proinflammatory cytokine (PIC), which is associated with increased expression of brain renin-angiotensin system (RAS) components and PICs in adult offspring. The present study further investigated whether inhibition of angiotensin-converting enzyme (ACE) or tumor necrosis factor-α (TNF-α) blocks sensitization of ANG II hypertension in offspring of HFD dams. All offspring were bred from dams with normal fat diet (NFD) or HFD starting two weeks before mating and maintained until weaning of the offspring. Then the weaned offspring were treated with an ACE inhibitor (captopril) or a TNF-α inhibitor (pentoxifylline) in the drinking water through the end of testing with a slow-pressor dose of ANG II. RT-PCR analyses of the lamina terminalis and paraventricular nucleus revealed upregulation of mRNA expression of several RAS components and PICs in male offspring of HFD dams when compared with age-matched offspring of NFD dams. The enhanced gene expression was attenuated by blockade of either RAS or PICs. Likewise, ANG II administration produced an augmented pressor response in offspring of HFD dams. This was abolished by either ACE or TNF-α inhibitor. Taken together, this study provides mechanistic evidence and a therapeutic strategy that systemic inhibition of the RAS and PICs can block maternal HFD-induced sensitization of ANG II hypertension, which is associated with attenuation of brain RAS and PIC expression in offspring.
Separation of hemodynamic signals from GCaMP fluorescence measured with wide-field imaging
Authors: Valley M. T. , Moore M. G. , Zhuang J. , Mesa N. , Castelli D. , Sullivan D. , Reimers M. , Waters J.
Published: November 2019

Wide-field calcium imaging is often used to measure brain dynamics in behaving mice. With a large field of view and a high sampling rate, wide-field imaging can monitor activity from several distant cortical areas simultaneously, revealing cortical interactions. Interpretation of wide-field images is complicated, however, by the absorption of light by hemoglobin, which can substantially affect the measured fluorescence. One approach to separating hemodynamics and calcium signals is to use multiwavelength backscatter recordings to measure light absorption by hemoglobin. Following this approach, we develop a spatially detailed regression-based method to estimate hemodynamics. This Spatial Model is based on a linear form of the Beer–Lambert relationship but is fit at every pixel in the image and does not rely on the estimation of physical parameters. In awake mice of three transgenic lines, the Spatial Model offers improved separation of hemodynamics and changes in GCaMP fluorescence. The improvement is pronounced near blood vessels and, in contrast with the Beer–Lambert equations, can remove vascular artifacts along the sagittal midline and in general permits more accurate fluorescence-based determination of neuronal activity across the cortex.

NEW & NOTEWORTHY This paper addresses a well-known and strong source of contamination in wide-field calcium-imaging data: hemodynamics. To guide researchers toward the best method to separate calcium signals from hemodynamics, we compare the performance of several methods in three commonly used mouse lines and present a novel regression model that outperforms the other techniques we consider.
Binocular 3D otolith-ocular reflexes: responses of chinchillas to prosthetic electrical stimulation targeting the utricle and saccule
Authors: Hageman Kristin N. , Chow Margaret R. , Roberts Dale , Boutros Peter J. , Tooker Angela , Lee Kye , Felix Sarah , Pannu Satinderpall S. , Haque Razi , Della Santina Charles C.
Published: November 2019

From animal experiments by Cohen and Suzuki et al. in the 1960s to the first-in-human clinical trials now in progress, prosthetic electrical stimulation targeting semicircular canal branches of the vestibular nerve has proven effective at driving directionally appropriate vestibulo-ocular reflex eye movements, postural responses, and perception. That work was considerably facilitated by the fact that all hair cells and primary afferent neurons in each canal have the same directional sensitivity to head rotation, the three canals’ ampullary nerves are geometrically distinct from one another, and electrically evoked three-dimensional (3D) canal-ocular reflex responses approximate a simple vector sum of linearly independent components representing relative excitation of each of the three canals. In contrast, selective prosthetic stimulation of the utricle and saccule has been difficult to achieve, because hair cells and afferents with many different directional sensitivities are densely packed in those endorgans and the relationship between 3D otolith-ocular reflex responses and the natural and/or prosthetic stimuli that elicit them is more complex. As a result, controversy exists regarding whether selective, controllable stimulation of electrically evoked otolith-ocular reflexes (eeOOR) is possible. Using micromachined, planar arrays of electrodes implanted in the labyrinth, we quantified 3D, binocular eeOOR responses to prosthetic electrical stimulation targeting the utricle, saccule, and semicircular canals of alert chinchillas. Stimuli delivered via near-bipolar electrode pairs near the maculae elicited sustained ocular countertilt responses that grew reliably with pulse rate and pulse amplitude, varied in direction according to which stimulating electrode was employed, and exhibited temporal dynamics consistent with responses expected for isolated macular stimulation.

NEW & NOTEWORTHY As the second in a pair of papers on Binocular 3D Otolith-Ocular Reflexes, this paper describes new planar electrode arrays and vestibular prosthesis architecture designed to target the three semicircular canals and the utricle and saccule. With this technological advancement, electrically evoked otolith-ocular reflexes due to stimulation via utricle- and saccule-targeted electrodes were recorded in chinchillas. Results demonstrate advances toward achieving selective stimulation of the utricle and saccule.
Zebrafish Models of Human Skeletal Disorders: Embryo and Adult Swimming Together
Authors: Carnovali Marta , Banfi Giuseppe , Mariotti Massimo
Published: November 2019

Danio rerio(zebrafish) is an elective model organism for the study of vertebrate development because of its high degree of homology with human genes and organs, including bone. Zebrafish embryos, because of the optical clarity, small size, and fast development, can be easily used in large-scale mutagenesis experiments to isolate mutants with developmental skeletal defects and in high-throughput screenings to find new chemical compounds for the ability to revert the pathological phenotype. On the other hand, the adult zebrafish represents another powerful resource for pathogenic and therapeutic studies about adult human bone diseases. In fish, some characteristics such as bone turnover, reparation, and remodeling of the adult bone tissue cannot be found at the embryonic stage. Several pathological models have been established in adult zebrafish such as bone injury models, osteoporosis, and genetic diseases such as osteogenesis imperfecta. Given the growing interest for metabolic diseases and their complications, adult zebrafish models of type 2 diabetes and obesity have been recently generated and analyzed for bone complications using scales as model system. Interestingly, an osteoporosis-like phenotype has been found to be associated with metabolic alterations suggesting that bone complications share the same mechanisms in humans and fish. Embryo and adult represent powerful resources in rapid development to study bone physiology and pathology from different points of view.
Development and Validation of an HPLC Method for Simultaneous Assay of MCI and MI in Shampoos Containing Plant Extracts
Authors: Thi Huong Hoa Le , Tran Ngoc Hung Vo , Thu Trang Do , Nguyen Hung Thu Thai , Le Dinh Chi
Published: November 2019

A simple, easy-to-implement HPLC method was developed and validated for simultaneous determination of two isothiazolinone preservatives, methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI), in hair care shampoo containing plant extracts. In this method, shampoo samples were first dissolved in isopropyl myristate and then MCI and MI were extracted from isopropyl myristate layer by a mixture of methanol and 0.02 M phosphate buffer solution pH 3.0 (30: 70, v/v) and analyzed on an analytical biphenyl column maintained at 25°C with a mixture of methanol and water (10: 90, v/v) in isocratic elution mode as mobile phase. Total flow rate of mobile phase was maintained at 1.0 mL per minute. The UV detection was performed at 274 nm. Injection volume was 50 μl. The method was fully validated in terms of specificity, linearity, precision, accuracy, and robustness according to requirements of AOAC International and was proved as reliable and suitable for the intended application.
Effects of Physical Exercise Programs on Sarcopenia Management, Dynapenia, and Physical Performance in the Elderly: A Systematic Review of Randomized Clinical Trials
Authors: de Mello Renato Gorga Bandeira , Dalla Corte Roberta Rigo , Gioscia Joana , Moriguchi Emilio Hideyuki
Published: November 2019

Introduction. Sarcopenia is a prevalent condition in the elderly population, imposing a significant impact over their functional ability as well as their quality of life. Furthermore, it is associated with greater incidence of major geriatric outcomes, as reduced mobility, falls, loss of independence, cognitive impairment, and all-cause mortality. Physical Exercise Programs directed to improve muscle mass and its function may be key to reduce sarcopenia consequences. However, a significant heterogeneity is found in clinical trials, especially as a consequence of different exercise protocols applied to research subjects. Objectives. To access the effects of physical exercise programs compared to no exercise interventions to improve sarcopenia components and its determinants in sarcopenic elder individuals. Methods. A systematic review was conducted in the Pubmed database to identify randomized clinical trials (RCTs) which tested the effects of physical exercise programs to manage sarcopenia components in sarcopenic elder individuals. Two independent reviewers assessed the studies’ eligibility according to specified inclusion criteria in a four-step strategy. Data regarding population characteristics, muscle mass, muscle quality, muscle strength, and muscle function were extracted from each one of the included studies. Assessment of quality and individual studies risk of bias were assessed through Cochrane Risk of Bias Tool®. Assuming theoretical expected heterogeneity among studies, especially regarding different physical exercise programs and different outcome measurements, authors decided to be conservative and present study results in descriptive tables. Results. Search strategy retrieved 298 papers on PubMed database. Three more were identified through manual search, being 301 studies revised for inclusion. 278 were excluded during title/abstract review. After further evaluation of 23 full-texts, 5 RCTs were included. All 5 trials tested the efficacy of isolated exercise programs to improve sarcopenia components in the elderly compared to no physical intervention. Resistance training was the main intervention component in all included trials compared to inactive control groups (health education mainly). Physical training improved muscle strength, muscle quality, and muscle function compared to inactive control groups. Considering muscle mass, no differences were demonstrated. Data meta-analysis was not possible to be performed due to high heterogeneity among trials and small number of studies for each outcome comparison. Conclusion. Heterogeneity among trials and small number of RCTs limited robust conclusions and data meta-analysis. However, resistance training protocols can improve muscle strength and physical performance in elders previously diagnosed with sarcopenia, although its effect size and clinical impact are barely relevant.
Social Risk Assessment and Management for Major Construction Projects in China Based on Fuzzy Integrated Analysis
Authors: Miao Junxia , Huang Dechun , He Zhengqi
Published: November 2019

With the vigorous development of major engineering projects in China, the social risks associated with major construction projects not only challenge the success of projects but also threaten social harmony and stability. Therefore, it is of great practical significance to assess and manage social risks. This paper aims to identify and evaluate the social risk factors by conducting a survey and assess the overall risk level of major construction projects (MCPs) with fuzzy integrated approach. First, 35 social risk factors and related stakeholders were identified based on literature analysis and case study. Then, 18 critical social risk factors (CSRFs) were selected and classified into six groups (CSRGs) based on a questionnaire survey. Next, using fuzzy integrated method, the probability of occurrence (PO), magnitude of impact (MI), the integrated risk level (IRL) of each CSRF and CSRG, and the overall risk of MCPs were calculated. As a result, “unfair compensation for housing demolition and land requisition” was the most critical social risk factor, and “policy/legal risk” was the most critical social risk group. The overall risk of MCPs was between moderate and high. At last, a social risk synthetic management framework was established, which can provide reference for policymakers and project decision makers to effectively manage the social risks.