bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating a brief mental health intervention into primary care services for patients with HIV and diabetes in South Africa: study protocol for a trial-based economic evaluation
Authors: Mutyambizi-Mafunda Vimbayi , Myers Bronwyn , Sorsdahl Katherine , Lund Crick , Naledi Tracey , Cleary Susan
Published: May 2019

Introduction

Depression and alcohol use disorders are international public health priorities for which there is a substantial treatment gap. Brief mental health interventions delivered by lay health workers in primary care services may reduce this gap. There is limited economic evidence assessing the cost-effectiveness of such interventions in low-income and middle-income countries. This paper describes the proposed economic evaluation of a health systems intervention testing the effectiveness, cost-effectiveness and cost-utility of two task-sharing approaches to integrating services for common mental disorders with HIV and diabetes primary care services.

Methods and analysis

This evaluation will be conducted as part of a three-armed cluster randomised controlled trial of clinical effectiveness. Trial clinical outcome measures will include primary outcomes for risk of depression and alcohol use, and secondary outcomes for risk of chronic disease (HIV and diabetes) treatment failure. The cost-effectiveness analysis will evaluate cost per unit change in Alcohol Use Disorder Identification Test and Centre for Epidemiological Studies scale on Depression scores as well as cost per unit change in HIV RNA viral load and haemoglobin A1c, producing results of provider and patient cost per patient year for each study arm and chronic disease. The cost utility analyses will provide results of cost per quality-adjusted life year gained. Additional analyses relevant for implementation including budget impact analyses will be conducted to inform the development of a business case for scaling up the country’s investment in mental health services.

Ethics and dissemination

The Western Cape Department of Health (WCDoH) (WC2016_RP6_9), the South African Medical Research Council (EC 004-2/2015), the University of Cape Town (089/2015) and Oxford University (OxTREC 2–17) provided ethical approval for this study. Results dissemination will include policy briefs, social media, peer-reviewed papers, a policy dialogue workshop and press briefings.

Trial registration number

PACTR201610001825405.
Effectiveness and cost-effectiveness of Self-Help Plus (SH+) for preventing mental disorders in refugees and asylum seekers in Europe and Turkey: study protocols for two randomised controlled trials
Authors: Purgato Marianna , Carswell Kenneth , Acarturk Ceren , Au Teresa , Akbai Sena , Anttila Minna , Baumgartner Josef , Bailey Della , Biondi Massimo , Bird Martha , Churchill Rachel , Eskici Sevde , Hansen Louise Juul , Heron Paul , Ilkkursun Zeynep , Kilian Reinhold , Koesters Markus , Lantta Tella , Nosè Michela , Ostuzzi Giovanni , Papola Davide , Popa Mariana , Sijbrandij Marit , Tarsitani Lorenzo , Tedeschi Federico , Turrini Giulia , Uygun Ersin , Välimäki Maritta Anneli , Wancata Johannes , White Ross , Zanini Elisa , Cuijpers Pim , Barbui Corrado , Van Ommeren Mark
Published: May 2019

Introduction

This article describes two randomised controlled trials that will evaluate the effectiveness and cost-effectiveness of Self-Help Plus (SH+), a group self-help intervention developed by the WHO to reduce distress. In these trials SH+ is being tested as a preventative intervention to lower the incidence of mental disorders in asylum seekers and refugees with psychological distress resettled in Europe and Turkey.

Methods and analysis

Two prospective, multicentre, randomised, rater-blinded, parallel-group studies will follow participants over a period of 12 months. One trial will be conducted in Europe and one in Turkey. In each trial, 600 asylum seekers and refugees screening positive on the General Health Questionnaire (≥3), but without a formal diagnosis of any mental disorders according to the Mini International Neuropsychiatric Interview, will be randomly allocated to SH+or to enhanced treatment-as-usual. The primary outcome will be a lower incidence of mental disorders at 6 month follow-up. Secondary outcomes will include the evaluation of psychological symptoms, functioning, well-being, treatment acceptability and indicators of intervention cost-effectiveness.

Ethics and dissemination

The two trials received ethical clearance from the local Ethics Committees of the participating sites (seven sites), as well as from the WHO Ethics Committee. All participants will provide informed consent before screening and before study inclusion (a two-step procedure). The results of the trials will be disseminated in agreement with a dissemination plan that includes publication(s) in peer-reviewed journals and presentations at relevant national and international conferences and meetings.

Trials registration numbers

NCT03571347,NCT03587896.
International Cancer Microbiome Consortium consensus statement on the role of the human microbiome in carcinogenesis
Authors: Scott Alasdair J , Alexander James L , Merrifield Claire A , Cunningham David , Jobin Christian , Brown Robert , Alverdy John , O’Keefe Stephen J , Gaskins H Rex , Teare Julian , Yu Jun , Hughes David J , Verstraelen Hans , Burton Jeremy , O’Toole Paul W , Rosenberg Daniel W , Marchesi Julian R , Kinross James M
Published: May 2019

Objective

In this consensus statement, an international panel of experts deliver their opinions on key questions regarding the contribution of the human microbiome to carcinogenesis.

Design

International experts in oncology and/or microbiome research were approached by personal communication to form a panel. A structured, iterative, methodology based around a 1-day roundtable discussion was employed to derive expert consensus on key questions in microbiome-oncology research.

Results

Some 18 experts convened for the roundtable discussion and five key questions were identified regarding: (1) the relevance of dysbiosis/an altered gut microbiome to carcinogenesis; (2) potential mechanisms of microbiota-induced carcinogenesis; (3) conceptual frameworks describing how the human microbiome may drive carcinogenesis; (4) causation versus association; and (5) future directions for research in the field.

The panel considered that, despite mechanistic and supporting evidence from animal and human studies, there is currently no direct evidence that the human commensal microbiome is a key determinant in the aetiopathogenesis of cancer. The panel cited the lack of large longitudinal, cohort studies as a principal deciding factor and agreed that this should be a future research priority. However, while acknowledging gaps in the evidence, expert opinion was that the microbiome, alongside environmental factors and an epigenetically/genetically vulnerable host, represents one apex of a tripartite, multidirectional interactome that drives carcinogenesis.

Conclusion

Data from longitudinal cohort studies are needed to confirm the role of the human microbiome as a key driver in the aetiopathogenesis of cancer.
Electrocardiographic landmarks of idiopathic ventricular arrhythmia origins
Authors: Tzeis Stylianos , Asvestas Dimitrios , Yen Ho Siew , Vardas Panos
Published: May 2019

Idiopathic ventricular arrhythmias occur in the absence of underlying structural heart disease and less commonly in the presence of coexistent, but mechanistically unrelated, myocardial scar. These arrhythmias originate from several anatomical sites in both ventricles, with a predilection in outflow tract structures. The 12-lead surface ECG is the initial mapping tool, which is widely used to identify their origin. Specific features can predict the site of idiopathic ventricular arrhythmias, thus differentiating right from left ventricular, as well as endocardial from epicardial origins. In this review, we aim to analyse electrocardiographic landmarks for determination of idiopathic ventricular arrhythmia sources, with specific emphasis on pertinent caveats and anatomical relationships.
Exact solutions for n-layer concentric flow of PTT fluids through a cylindrical pipe
Authors: Siddiqui A.M. , Azim Q.A. , Imran M.
Published: May 2019

Flows of multiple layers of fluids are encountered in many industrial and manufacturing processes. This paper investigates the concentric n-layer flow for Phan–Thien–Tanner (PTT) fluids through a cylindrical pipe. Finitely many immiscible non-Newtonian fluids are considered to be flowing concentrically in a tube. The flow is modelled using the exponential PTT fluid model and exact solutions for velocity fields and volume flow rates are computed. It has been shown that the corresponding results for linear PTT fluid model as well as Newtonian fluids can be deduced from the obtained expressions, and that they match with the present literature. It has also been observed that for such layered flow, the non-Newtonian parameters significantly affect the flow of fluids in adjacent layers. The effects of involved parameters on the velocity profiles are also shown graphically. We show that a unique velocity maximum exists along the axis of the pipe. Moreover, it is observed with the help of an example that layer thickness can be adjusted to obtain maximal flow rate with a given pressure gradient.
Tools to understand seasonality in health: quantification of microbe loads and analyses of compositional ecoimmunological data reveal complex patterns in Mojave Desert Tortoise (Gopherus agassizii) populations
Authors: Sandmeier F.C. , Leonard K.L. , Tracy C.R. , Drake K.K. , Esque T.E. , Nussear K. , Germano J.M.
Published: May 2019

Using data from six wild Mojave Desert Tortoise (Gopherus agassizii (Cooper, 1861)) populations, we quantified seasonal differences in immune system measurements and microbial load in the respiratory tract, pertinent to this species’ susceptibility to upper respiratory tract disease. We quantified bacteria-killing activity of blood plasma and differential leukocyte counts to detect trends in temporal variation in immune function. We used centered log-ratio (clr) transformations of leukocyte counts and stress that such transformations are necessary for compositional data. We tested animals for the potential pathogen Pasteurella testudinis Snipes and Biberstein, 1982 with a newly created quantitative polymerase chain reaction (qPCR) assay, as well as for the known respiratory pathogens Mycoplasma agassizii Brown et al., 2001 and Mycoplasma testudineum Brown et al., 2004. We found very little disease and suggest that P. testudinis is a prevalent, commensal microbe in these Mojave Desert Tortoise populations, and its quantification may be a tool to study natural fluctuations in microbe levels in Mojave Desert Tortoise respiratory tracts. Our analyses showed that both the potential for inflammatory responses and microbe levels are highest in the spring for healthy Mojave Desert Tortoises, when lymphocyte levels are lowest. The genetic and statistical tools that we used are easily applicable to other wildlife systems and provide the necessary data to quantify species-wide trends in health and test hypotheses pertinent to host–microbe dynamics.
Multiplicativity of Connes’ calculus
Authors: Chakraborty Partha Sarathi , Guin Satyajit
Published: May 2019

In his book on noncommutative geometry, Connes constructed a differential graded algebra out of a spectral triple. Lack of monoidality of this construction is investigated. We identify a suitable monoidal subcategory of the category of spectral triples and show that when restricted to this subcategory the construction of Connes is monoidal. Richness of this subcategory is exhibited by establishing a faithful endofunctor to this subcategory.
Asymptotics of the Wilson polynomials
Authors: Li Yu-Tian , Wang Xiang-Sheng , Wong Roderick
Published: May 2019

In this paper, we study the asymptotic behavior of the Wilson polynomials [Formula: see text] as their degree tends to infinity. These polynomials lie on the top level of the Askey scheme of hypergeometric orthogonal polynomials. Infinite asymptotic expansions are derived for these polynomials in various cases, for instance, (i) when the variable [Formula: see text] is fixed and (ii) when the variable is rescaled as [Formula: see text] with [Formula: see text]. Case (ii) has two subcases, namely, (a) zero-free zone ([Formula: see text]) and (b) oscillatory region [Formula: see text]. Corresponding results are also obtained in these cases (iii) when [Formula: see text] lies in a neighborhood of the transition point [Formula: see text], and (iv) when [Formula: see text] is in the neighborhood of the transition point [Formula: see text]. The expansions in the last two cases hold uniformly in [Formula: see text]. Case (iv) is also the only unsettled case in a sequence of works on the asymptotic analysis of linear difference equations.
Interacting dark energy model in the brane scenario: A dynamical system analysis
Authors: Biswas Sujay Kr. , Chakraborty Subenoy
Published: May 2019

The present work is a second in the series of investigations of the background dynamics in brane cosmology when dark energy is coupled to dark matter by a suitable interaction. Here, dark matter is chosen in the form of perfect fluid with barotropic equation of state, while a real scalar field with self-interacting potential is chosen as dark energy. The scalar field potential is chosen as exponential or hyperbolic in nature and three different choices for the interactions between the dark species are considered. In the background of spatially flat, homogeneous and isotropic Friedmann–Robertson–Walker (FRW) brane model, the evolution equations are reduced to an autonomous system by suitable transformation of variables and a series of critical points are obtained for different interactions. By analyzing the critical points, we have found a cosmologically viable model describing an early inflationary scenario to dark energy-dominated era connecting through a matter-dominated phase.
From Neurorobotic Localization to Autonomous Vehicles
Authors: Espada Yoan , Cuperlier Nicolas , Bresson Guillaume , Romain Olivier
Published: May 2019

The navigation of autonomous vehicles is confronted to the problem of an efficient place recognition system which is able to handle outdoor environments on the long run. The current Simultaneous Localization and Mapping (SLAM) and place recognition solutions have limitations that prevent them from achieving the performances needed for autonomous driving. This paper suggests handling the problem from another perspective by taking inspiration from biological models. We propose a neural architecture for the localization of an autonomous vehicle based on a neurorobotic model of the place cells (PC) found in the hippocampus of mammals. This model is based on an attentional mechanism and only takes into account visual information from a mono-camera and the orientation information to self-localize. It has the advantage to work with low resolution camera without the need of calibration. It also does not need a long learning phase as it uses a one-shot learning system. Such a localization model has already been integrated in a robot control architecture which allows for successful navigation both in indoor and small outdoor environments. The contribution of this paper is to study how it passes the scale change by evaluating the performance of this model over much larger outdoor environments. Eight experiments using real data (image and orientation) grabbed by a moving vehicle are studied (coming from the KITTI odometry datasets and datasets taken with VEDECOM vehicles). Results show the strong adaptability to different kinds of environments of this bio-inspired model primarily developed for indoor navigation.
Massively Parallel Assays and Quantitative Sequence–Function Relationships
Authors: Kinney Justin B. , McCandlish David M.
Published: May 2019

Over the last decade, a rich variety of massively parallel assays have revolutionized our understanding of how biological sequences encode quantitative molecular phenotypes. These assays include deep mutational scanning, high-throughput SELEX, and massively parallel reporter assays. Here, we review these experimental methods and how the data they produce can be used to quantitatively model sequence–function relationships. In doing so, we touch on a diverse range of topics, including the identification of clinically relevant genomic variants, the modeling of transcription factor binding to DNA, the functional and evolutionary landscapes of proteins, and cis-regulatory mechanisms in both transcription and mRNA splicing. We further describe a unified conceptual framework and a core set of mathematical modeling strategies that studies in these diverse areas can make use of. Finally, we highlight key aspects of experimental design and mathematical modeling that are important for the results of such studies to be interpretable and reproducible.
Rebel Use of Law and Courts
Authors: Ginsburg Tom
Published: May 2019

Militant organizations and rebel groups are an enduring feature of political life in much of the world. As scholars pay greater attention to rebel governance strategies, the role of law and courts is coming to the fore. We observe a good deal of variation across rebel groups in terms of their legal infrastructure and its organizational differentiation. This article surveys the recent literature and develops a framework for understanding why rebel groups vary in their use of law and also explores the consequences of legal governance for subject populations, for rebels themselves, and for external actors.
Cellular Functions and Mechanisms of Action of Small Heat Shock Proteins
Authors: Mogk Axel , Ruger-Herreros Carmen , Bukau Bernd
Published: May 2019

Small heat shock proteins (sHsps) constitute a diverse chaperone family that shares the α-crystallin domain, which is flanked by variable, disordered N- and C-terminal extensions. sHsps act as the first line of cellular defense against protein unfolding stress. They form dynamic, large oligomers that represent inactive storage forms. Stress conditions cause a rapid increase in cellular sHsp levels and trigger conformational rearrangements, resulting in exposure of substrate-binding sites and sHsp activation. sHsps bind to early-unfolding intermediates of misfolding proteins in an ATP-independent manner and sequester them in sHsp/substrate complexes. Sequestration protects substrates from further uncontrolled aggregation and facilitates their refolding by ATP-dependent Hsp70-Hsp100 disaggregases. Some sHsps with particularly strong sequestrase activity, such as yeast Hsp42, are critical factors for forming large, microscopically visible deposition sites of misfolded proteins in vivo. These sites are organizing centers for triaging substrates to distinct quality control pathways, preferentially Hsp70-dependent refolding and selective autophagy.
A fluorescent reporter assay of differential gene expression response to insulin in hepatocytes
Authors: McKimpson Wendy M. , Accili Domenico
Published: May 2019

Insulin regulates multiple hepatic metabolic pathways in a seemingly heterogeneous manner. To understand this heterogeneity, we hypothesized that different subpopulations of hepatocytes have different sensitivity to insulin. To test this hypothesis, we developed a fluorescent reporter in which the insulin-responsive fatty acid synthase (FAS) promoter drove expression of a time-dependent fluorescent protein (“timer”) and characterized timer expression in flow-sorted cell populations. In Hepa1c1c7 and AML12 hepatocytes, we found that different cell populations express distinct timer fluorescence following insulin treatment, consistent with cellular heterogeneity in the response to insulin. RNA measurements indicated an enrichment of forkhead box O transcription factors in cells with a greater response to insulin. Moreover, we found evidence of increased Akt activation. These data are consistent with a heterogeneous cellular response to insulin and raise the possibility that these different subpopulations underlie the peculiar pathophysiology of hepatic insulin resistance.
Separate and combined effects of KCa and KATP channel blockade with NOS inhibition on cutaneous vasodilation and sweating in older men during heat stress
Authors: McGarr Gregory W. , Fujii Naoto , Muia Caroline M. , Nishiyasu Takeshi , Kenny Glen P.
Published: May 2019

Our objective in this study was to examine the separate and combined effects of potassium (K+) channels and nitric oxide synthase (NOS) on cutaneous vasodilation and sweating in older men during rest and exercise in the heat. In 13 habitually active men (61 ± 4 yr), cutaneous vascular conductance and local sweat rate were assessed at six dorsal forearm skin sites continuously perfused with either 1) lactated Ringer (control), 2) 10 mM NG-nitro-l-arginine methyl ester (l-NAME, NOS inhibitor), 3) 50 mM tetraethylammonium (TEA; Ca2+-activated K+ channel blocker), 4) 5 mM glybenclamide (GLY; ATP-sensitive K+ channel blocker), 5) 50 mM TEA + 10 mM l-NAME, and 6) 5 mM GLY + 10 mM l-NAME via microdialysis. Participants rested in non-heat stress (25°C) and heat stress (35°C) conditions for ∼60 min each, followed by 50 min of moderate-intensity cycling (∼55% V̇o2peak) and 30 min of recovery in the heat. During rest and exercise in the heat, l-NAME, TEA + l-NAME, and GLY + l-NAME attenuated CVC relative to control (all P ≤ 0.05), although l-NAME was not different from TEA + l-NAME or GLY + l-NAME (all P > 0.05). TEA attenuated CVC during rest, whereas GLY attenuated CVC during exercise (both P ≤ 0.05). Additionally, whereas neither l-NAME nor TEA altered sweating throughout the protocol (all P > 0.05), combined TEA + l-NAME attenuated sweating during exercise in the heat ( P ≤ 0.05). We conclude that in habitually active older men blockade of KCa and KATP channels attenuates cutaneous vasodilation during rest and exercise in the heat, respectively, and these effects are NOS dependent. Furthermore, combined NOS inhibition and KCa channel blockade attenuates sweating during exercise in the heat.
Early hyperbaric oxygen therapy improves survival in a model of severe sepsis
Authors: Halbach Jonathan L. , Prieto James M. , Wang Andrew W. , Hawisher Dennis , Cauvi David M. , Reyes Tony , Okerblom Jonathan , Ramirez-Sanchez Israel , Villarreal Francisco , Patel Hemal H. , Bickler Stephen W. , Perdrizet George A. , De Maio Antonio
Published: May 2019

Sepsis is a major clinical challenge, with therapy limited to supportive interventions. Therefore, the search for novel remedial approaches is of great importance. We addressed whether hyperbaric oxygen therapy (HBOT) could improve the outcome of sepsis using an acute experimental mouse model. Sepsis was induced in male CD-1 mice by cecal ligation and puncture (CLP) tailored to result in 80–90% mortality within 72 h of the insult. After CLP, mice were randomized into two groups receiving HBOT or not at different times after the initial insult or subjected to multiple HBOT treatments. HBOT conditions were 98% oxygen pressurized to 2.4 atmospheres for 1 h. HBOT within 1 h after CLP resulted in 52% survival in comparison with mice that did not receive the treatment (13% survival). Multiple HBOT at 1 and 6 h or 1, 6, and 21 h displayed an increase in survival of >50%, but they were not significantly different from a single treatment after 1 h of CLP. Treatments at 6 or 21 h after CLP, excluding the 1 h of treatment, did not show any protective effect. Early HBO treatment did not modify bacterial counts after CLP, but it was associated with decreased expression of TNF-α, IL-6, and IL-10 expression in the liver within 3 h after CLP. The decrease of cytokine expression was reproduced in cultured macrophages after exposure to HBOT. Early HBOT could be of benefit in the treatment of sepsis, and the protective mechanism may be related to a reduction in the systemic inflammatory response.
Knockout of Na+-glucose cotransporter SGLT1 mitigates diabetes-induced upregulation of nitric oxide synthase NOS1 in the macula densa and glomerular hyperfiltration
Authors: Song Panai , Huang Winnie , Onishi Akira , Patel Rohit , Kim Young Chul , van Ginkel Charlotte , Fu Yiling , Freeman Brent , Koepsell Hermann , Thomson Scott , Liu Ruisheng , Vallon Volker
Published: May 2019

Na+-glucose cotransporter (SGLT)1 mediates glucose reabsorption in late proximal tubules. SGLT1 also mediates macula densa (MD) sensing of an increase in luminal glucose, which increases nitric oxide (NO) synthase 1 (MD-NOS1)-mediated NO formation and potentially glomerular filtratrion rate (GFR). Here, the contribution of SGLT1 was tested by gene knockout (−/−) in type 1 diabetic Akita mice. A low-glucose diet was used to prevent intestinal malabsorption in Sglt1−/−mice and minimize the contribution of intestinal SGLT1. Hyperglycemia was modestly reduced in Sglt1−/−versus littermate wild-type Akita mice (480 vs. 550 mg/dl), associated with reduced diabetes-induced increases in GFR, kidney weight, glomerular size, and albuminuria. Blunted hyperfiltration was confirmed in streptozotocin-induced diabetic Sglt1−/−mice, associated with similar hyperglycemia versus wild-type mice (350 vs. 385 mg/dl). Absence of SGLT1 attenuated upregulation of MD-NOS1 protein expression in diabetic Akita mice and in response to SGLT2 inhibition in nondiabetic mice. During SGLT2 inhibition in Akita mice, Sglt1−/−mice had likewise reduced blood glucose (200 vs. 300 mg/dl), associated with lesser MD-NOS1 expression, GFR, kidney weight, glomerular size, and albuminuria. Absence of Sglt1 in Akita mice increased systolic blood pressure, associated with suppressed renal renin mRNA expression. This may reflect fluid retention due to blunted hyperfiltration. SGLT2 inhibition prevented the blood pressure increase in Sglt1−/−Akita mice, possibly due to additive glucosuric/diuretic effects. The data indicate that SGLT1 contributes to diabetic hyperfiltration and limits diabetic hypertension. Potential mechanisms include its role in glucose-driven upregulation of MD-NOS1 expression. This pathway may increase GFR to maintain volume balance when enhanced MD glucose delivery indicates upstream saturation of SGLTs and thus hyperreabsorption.
A versatile aquaporin-2 cell system for quantitative temporal expression and live cell imaging
Authors: Holst Mikkel R. , Nejsum Lene N.
Published: May 2019

Aquaporin-2 (AQP2) fine tunes urine concentration in response to the antidiuretic hormone vasopressin. In addition, AQP2 has been suggested to promote cell migration and epithelial morphogenesis. A cell system allowing temporal and quantitative control of expression levels of AQP2 and phospho-mimicking mutants has been missing, as has a system allowing expression of fluorescently tagged AQP2 for time-lapse imaging. In the present study, we generated and validated a Flp-In T-REx Madin-Darby canine kidney cell system for temporal and quantitative control of AQP2 and phospho-mimicking mutants. We verified that expression levels can be temporally and quantitatively controlled and that AQP2 translocated to the plasma membrane in response to elevated cAMP, which also induced S256 phosphorylation. The phospho-mimicking mutants AQP2-S256A and AQP2-S256D localized as previously described, primarily intracellular and to the plasma membrane, respectively. Induction of AQP2 expression in combination with transient, low expression of enhanced green fluorescent protein-tagged AQP2 enabled expression without aggregation and correct translocation in response to elevated cAMP. Interestingly, time-lapse imaging revealed AQP2-containing tubulating endosomes and that tubulation significantly decreased 30 min after cAMP elevation. This was mirrored by the phospho-mimicking mutants AQP2-S256A and AQP2-S256D, where AQP2-S256A-containing endosomes tubulated, whereas AQP2-S256D-containing endosomes did not. Thus, this cell system enables a multitude of cell-based assays warranted to provide deeper insights into the mechanisms of AQP2 regulation and effects on cell migration and epithelial morphogenesis.
Differential effects of aging and physical activity on corticospinal excitability of upper and lower limb muscles
Authors: Rozand Vianney , Senefeld Jonathon W. , Sundberg Christopher W. , Smith Ashleigh E. , Hunter Sandra K.
Published: May 2019

Corticospinal tract excitability can be altered by age, physical activity (PA), and possibly sex, but whether these effects differ between upper and lower limb muscles is unknown. We determined the influence of age, PA, and sex on corticospinal excitability of an upper limb and a lower limb muscle during submaximal contractions by comparing stimulus-response curves of motor evoked potentials (MEPs). Transcranial magnetic stimulation (TMS) was used to evoke stimulus-response curves in active muscles by incrementally increasing the stimulator intensity from below the active motor threshold (AMT) until a plateau in MEP amplitudes was achieved. Stimulus-response curves were analyzed from the first dorsal interosseous (FDI) of 30 young (23.9 ± 3.8 yr) and 33 older (72.6 ± 5.6 yr) men and women and the vastus lateralis (VL) of 13 young (23.2 ± 2.2 yr) and 25 older (72.7 ± 5.5 yr) men and women. Corticospinal excitability was determined by fitting the curves with a four-parameter sigmoidal curve and calculating the maximal slope (slopemax). PA was assessed with triaxial accelerometry, and participants were dichotomized into high-PA (>10,000 steps/day, n = 15) or low-PA (<10,000 steps/day, n = 43) groups. Young adults had larger FDI MEP amplitudes (% maximum amplitude of compound muscle action potential) at higher TMS intensities (120–150% AMT) and greater slopemax than older adults ( P < 0.05), with no differences between high- and low-PA groups ( P > 0.05). VL MEP amplitudes and slopemax, however, were lower in the high-PA than low-PA participants, with no age or sex differences. These data suggest that aging and PA, but not sex, differentially influence the excitability of the corticospinal tracts projecting to muscles of the upper compared with the lower limb.

NEW & NOTEWORTHY Excitability of the corticospinal tract projecting to the first dorsal interosseous assessed with transcranial magnetic stimulation was reduced with age but independent of regular physical activity (steps/day) and sex of the individual. In contrast, corticospinal excitability of the vastus lateralis was not affected by age but was reduced in individuals achieving more than the physical activity recommendations of 10,000 steps/day. Aging and activity differentially affect corticospinal excitability of upper and lower limb muscles.
Sensorimotor priors are effector dependent
Authors: Yin Cong , Wang Huijun , Wei Kunlin , Körding Konrad P.
Published: May 2019

During sensorimotor tasks, subjects use sensory feedback but also prior information. It is often assumed that the sensorimotor prior is just given by the experiment and that the details for acquiring this prior (e.g., the effector) are irrelevant. However, recent research has suggested that the construction of priors is nontrivial. To test if the sensorimotor details matter for the construction of a prior, we designed two tasks that differ only in the effectors that subjects use to indicate their estimate. For both a typical reaching setting and an atypical wrist rotation setting, prior and feedback uncertainty matter as quantitatively predicted by Bayesian statistics. However, in violation of simple Bayesian models, the importance of the prior differs across effectors. Subjects overly rely on their prior in the typical reaching case compared with the wrist case. The brain is not naively Bayesian with a single and veridical prior.

NEW & NOTEWORTHY Traditional Bayesian models often assume that we learn statistics of movements and use the information as a prior to guide subsequent movements. The effector is merely a reporting modality for information processing. We asked subjects to perform a visuomotor learning task with different effectors (finger or wrist). Surprisingly, we found that prior information is used differently between the effectors, suggesting that learning of the prior is related to the movement context such as the effector involved or that naive models of Bayesian behavior need to be extended.
The Effectiveness of the Whole Body Cryotherapy Strategies: A Comparison of Different Duration and Temperature on the Antioxidative Status in the Experimental Rat Model
Authors: Romuk Ewa , Skrzep-Poloczek Bronisława , Wiśniowska Bernadeta , Owczarek Aleksander J. , Choręza Piotr , Sieroń Aleksander , Birkner Ewa , Stygar Dominika
Published: May 2019

Background. We examined the effectiveness of the systemic cryotherapy in terms of the temperature and duration of the therapeutic series measured by oxidative stress markers in the rat animal model.Methods. Antioxidants in serum, plasma, liver, and erythrocytes were evaluated in two study groups following 1 min exposure to − 60°C and − 90°C, for 5 and 10 days.Results. Superoxide dismutase activity in the tissues was lower than in the serum. The glutathione peroxidase was significantly higher in − 60°C than in − 90°C, in both 5 and 10 days of exposition. The liver catalase CAT were significantly lower in − 60°C when compared to − 90°C for 5 and 10 sessions of exposure. In all analysed tissues, the sessions of cryotherapy, – 60/5 and – 60/10, were more effective in reduction malondialdehyde than sessions of − 90/5 and − 90/10. The highest total antioxidant capacity was observed in the − 60/5 group.Conclusions. Whole body cryotherapy based on temperature − 60°C may be considered as more beneficial than − 90°C for most of the oxidative stress (OS) markers measured in the selected tissues. The temp. − 60°C is more beneficial than − 90°C when measured by activity of Total SOD, CAT, and GPx. The therapeutic sessions − 60/10 and − 60/5 were the optimal schemes of WBC model in terms of TAC and MDA amount.
Comparison Study between Batch and Continuous Processes to Obtain Chitosan-Based High Porous Biomaterial for Biological Applications
Authors: Ursu Alina Violeta , Furtuna Diana , Requia Laura , Larafa Safa , de Baynast Hélène , Michaud Philippe , Djelveh Gholamreza , Delattre Cédric
Published: May 2019

Foaming process can be monitored under batch or continuous flows conditions. In the batch process, foaming is time-dependent and the foaming efficiency is controlled by the operator. On the other hand, in the continuous process, the foaming efficiency is only monitored by gas and liquid flow rates. The aim of this work is to compare the two technologies to perform porous scaffold biomaterial based on chitosan (a biocompatible polysaccharide) as well as calcium (Ca2+) and silica (SiO2) (two osteogenesis compounds). Diverse recipes using chitosan (CS) solution (2% (w/v)) in acetic acid (1% (v/v in distilled water)) mixed with whey protein isolate (WPI) (2% (w/v)) as natural surfactant were studied. They were supplemented or not by hydroxyapatite powder (HAp) and tetraethyl orthosilicate (TEOS). A jacketed narrow annular gap unit (NAGU) was used to perform the continuous foaming process. For all experimentations, the mixture flow rate was maintained at 30 mL min-1. The influence of operating conditions such as gas and liquid flow rates was studied to obtain foams and final scaffold material with different densities and porosities. Some other recipes followed foaming under batch conditions. Generally, the recipes were placed in a vessel under mixing allowing the gas phase to come from the roof of the vessel. In this case, it becomes very difficult to control the density and the size distribution of bubbles in the final product. In both cases, liquid foams were analysed (density, bubble size distribution) and then freeze-dried for mechanical and porosity investigations using the dynamic mechanical analysis (DMA) system and scanning electron microscopy (SEM). It has been shown that the controlled injected gas affected the continuous phase, resulting in a lighter and higher porous structure, a more homogeneous appearance, and a more uniform distribution of osteogenesis components compared to one obtained using batch operation. The obtained porous materials exhibited good properties (porosity, interconnectivity, and good HAp and silica distribution) and potential for future bone regeneration applications.
Ion-Imprinted Electrochemical Sensor Based on Copper Nanoparticles-Polyaniline Matrix for Nitrate Detection
Authors: Essousi Houda , Barhoumi Houcine , Bibani Malek , Ktari Nadia , Wendler Frank , Al-Hamry Ammar , Kanoun Olfa
Published: May 2019

This study reports a new chemical sensor based on ion-imprinted polymer matrix using copper nanoparticles-polyaniline nanocomposite (IIP-Cu-NPs/PANI). This sensor was prepared by electropolymerization using aniline as a functional monomer and nitrate as template onto the copper nanoparticles-modified glassy carbon (GC) electrode surface. Both ion-imprinted (IIP) and nonimprinted (NIP) electrochemical sensor surfaces were evaluated using UV-Visible spectrometry and scanning electron microscopy (SEM). The electrochemical analysis was made via cyclic voltammetry (CV), linear sweep voltammetry (LSV), and impedance spectroscopy (IS). Throughout this study various analytical parameters, such as scan rate, pH value, concentration of monomer and template, and electropolymerization cycles, were optimized. Under the optimum conditions, the peaks current of nitrate was linear to its concentration in the range of 1μM-0.1M with a detection limit of 31μM and 5μM by EIS and LSV. The developed imprinted nitrate sensor was successfully applied for nitrate determination in different real water samples with acceptable recovery rates.
Characteristics and Management of Emergency Department Patients Presenting with C2 Cervical Spine Fractures
Authors: Tadros Allison , Sharon Melinda , Craig Kristen , Krantz William
Published: May 2019

Background. C2 cervical fractures account for approximately 18% of cervical spine injuries. Few studies have examined patients presenting to an emergency department (ED) with this injury relative to demographics, injury mechanism, and hospital course. Objectives. To compare multiple variables of ED patients presenting with these types of injuries. Methods. In this retrospective cohort study, data were obtained from the Trauma Registry of an academic trauma referral center from January 1, 2011, to December 31, 2015. Patients who presented with a C2 fracture were identified. Information regarding the patient’s gender, age, mechanism of injury, associated injuries, if a procedure was required, disposition, and mortality was extracted. Comparative analyses were conducted between cases over or under age 60. Results. Between January 1, 2011, to December 31, 2015, a total of 139 patients with C2 fractures were identified. Most patients were 60 years or older (79%). Of those, 62% were female, and falls were the most common mechanism (78%). Of those under 60, 50% were female and motor vehicle crashes (MVCs) were the most common mechanism (71%). Odontoid fractures comprised 84% of C2 fractures. Only 6% had an associated spinal cord injury. Less than one-third of patients required operative intervention for their spinal injuries, and intervention was more common in older patients. Following admission, 19% of patients required placement into a nursing home or skilled nursing facility. Conclusions. C2 fractures are more common in older adults and usually resulted from falls. Odontoid fractures are most common. Most C2 fractures do not result in neurologic injury, and only a third were treated surgically. However, several patients were unable to return to their homes following their injury.
Hepatic Fat Content and Liver Enzymes Are Associated with Circulating Free and Protein-Bound Advanced Glycation End Products, Which Are Associated with Low-Grade Inflammation: The CODAM Study
Authors: Bijnen Mitchell , van Greevenbroek Marleen M. J. , van der Kallen Carla J. H. , Scheijen Jean L. , van de Waarenburg Marjo P. H. , Stehouwer Coen D. A. , Wouters Kristiaan , Schalkwijk Casper G.
Published: May 2019

Advanced glycation end products (AGEs) accumulate in fatty livers and may contribute to low-grade inflammation (LGI), potentially via their receptor, RAGE. It is unknown if the AGE accumulation in fatty livers results in elevated circulating AGEs. In a cohort study, we investigated the association of liver fat and hepatocellular damage with circulating AGEs and soluble RAGE (sRAGE) and subsequently the association of circulating AGEs and sRAGE with LGI. Cross-sectional associations of liver fat percentage (eLF%; ln-transformed) and liver enzymes (LE score; standardized) with circulating AGEs (free CML, CEL, and MG-H1 in nM and protein-bound CML, CEL, and pentosidine in nmol/mmol lysine; ln-transformed) and sRAGE (pg/ml, ln-transformed) and additionally of AGEs and sRAGE with LGI (standardized) were determined by multiple linear regression. eLF% was positively associated with circulating free CEL (β=0.090; 95% CI 0.041; 0.139) but inversely with protein-bound CML (β=−0.071; 95% CI -0.108; -0.034). Similarly, the LE score was positively associated with free CML (β=0.044; 95% CI 0.012; 0.076) and CEL (β=0.040; 95% CI 0.009; 0.072) but inversely with protein-bound CML (β=−0.037; 95% CI -0.060; -0.013). Free CML (β=0.297; 95% CI 0.049; 0.545) was positively associated with LGI, while protein-bound CML (β=−0.547; 95% CI -0.888; -0.207) was inversely associated, although this association was absent after adjustment for BMI. eLF% and LE score were not associated with sRAGE and sRAGE not with LGI after adjustment for BMI. Liver fat and enzymes were positively associated with circulating free AGEs, which were associated with LGI. In contrast, inverse relations were observed of liver fat and enzymes with circulating protein-bound AGEs and of protein-bound AGEs with LGI. These data suggest that hepatic steatosis and inflammation affect the formation and degradation of hepatic protein-bound AGEs resulting in elevated circulating free AGE levels. These alterations in AGE levels might influence LGI, but this is likely independent of RAGE.
Magnetic Resonance Imaging of Chiari Malformation Type I in Adult Patients with Dysphagia
Authors: Lu Feng , Chen Zan , Wu Hao , Jian Feng-Zeng
Published: May 2019

Objective. To explore the magnetic resonance imaging (MRI) characteristics of Chiari malformation type I (CMI) in patients with dysphagia.Methods. Adult patients diagnosed with CMI were retrospectively and consecutively reviewed from January 2013 to December 2016. Symptoms and medical characteristics were recorded. According to the clinical manifestations, we divided the patients into two groups. The first group had 21 patients with symptoms of dysphagia and the second group had 71 patients with nondysphagia symptoms. Various length or angle measurements of the posterior cranial fossa (PCF), syringomyelia, and degree of cerebellar tonsillar herniation were investigated using magnetic resonance imaging (MRI). Univariate, correlation, and multivariate logistic regression analyses were used to compare and analyze the data of the two groups.Results. The mean length of the clivus, height of PCF, and slope inclination angle of clivus significantly decreased in the dysphagia group compared to the nondysphagia group. The mean cranial spinal angle (CSA) and degree of cerebellar tonsillar herniation were significantly larger in the dysphagia group. There were no correlations between the age, sex, disease duration, and the length of cerebellar tonsillar herniation or CSA. There was a positive correlation between dysphagia level and CSA (r=-0.50; p=0.021). Among CSA, age, sex, the degree of tonsillar herniation, syringomyelia, and disease duration, CSA was the individual sign that correlated significantly with dysphagia (OR: 1.447; 95% CI: 1.182-1.698; P<0.001). Interactions between CSA and the degree of cerebellar tonsillar herniation, syringomyelia, and dysphagia existed (OR: 1.104; 95% CI: 1.042-1.170; P=0.001 and OR: 1.081; 95% CI: 1.023-1.142; P=0.006, respectively).Conclusions. The CMI patients with dysphagia were more likely to have a large CSA on MRI compared with CMI patients without dysphagia. An increased probability with syringomyelia or length of cerebellar tonsillar herniation can enhance the contribution of CSA to dysphagia in patients with CMI.
Tempol Attenuates Neuropathic Pain by Inhibiting Nitric Oxide Production
Authors: Jia Donglin , Wang Huan , Han Bin , Zhang Liping , Guo Jianrong
Published: May 2019

Background. Neuropathic pain not only affects individual life quality but also increases economic burden for the society. Treatment to alleviate neuropathic pain is required. Methodology. Fifty rats were randomly assigned into sham, spinal nerve ligation, and three treatment groups with different doses of Tempol (100, 200, and 300 mg/kg, respectively), with 10 rats in each group. A neuropathic pain model was created with spinal nerve L5 and L6 ligation. Mechanical allodynia and thermal hyperalgesia were tested preoperatively (day 0) and postoperatively (days 1, 3, 5, and 7). Spinal cord levels of nitric oxide, as well as activities of nitric oxide synthase and acetylcholinesterase, were tested in postoperative day 7. Results. Compared with rats in the spinal nerve ligation group, rats in Tempol treatment groups had decreased responses to mechanical pain and cold plate stimulations. A high dose of Tempol produced more attenuating effects. The level of nitric oxide and activity of nitric oxide synthase were also decreased with Tempol treatments, whereas no significant changes were observed in the activity of acetylcholinesterase. Conclusions. Tempol attenuated an experimental rat model with neuropathic pain by inhibiting nitric oxide production.
Geometrically Nonlinear Analysis for Elastic Beam Using Point Interpolation Meshless Method
Authors: He Cheng , Wu Xinhai , Wang Tao , He Huan
Published: May 2019

The intrinsic beam theory, as one of the exact beam formulas, is quite suitable to describe large deformation of the flexible curved beam and has been widely used in many engineering applications. Owing to the advantages of the intrinsic beam theory, the resulted equations are expressed in first‐order partial differential form with second‐order nonlinear terms. In order to solve the intrinsic beam equations in a relative simple way, in this paper, the point interpolation meshless method was employed to obtain the discretization equations of motion. Different from those equations by using the finite element method, only the differential of the shape functions are needed to form the final discrete equations. Thus, the present method does not need integration process for all elements during each time step. The proposed method has been demonstrated by a numerical example, and results show that this method is highly efficient in treating this type of problem with good accuracy.