bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological doses of melatonin impede cognitive decline in tau‐related Alzheimer models, once tauopathy is initiated, by restoring the autophagic flux
Authors: Luengo Enrique , Buendia Izaskun , Fernández‐Mendívil Cristina , Trigo‐Alonso Paula , Negredo Pilar , Michalska Patrycja , Hernández‐García Borja , Sánchez‐Ramos Cristina , Bernal Juan A. , Ikezu Tsuneya , León Rafael , López Manuela G. 
Published: April 2019

AbstractAlterations in autophagy are increasingly being recognized in the pathogenesis of proteinopathies like Alzheimer's disease (AD). This study was conducted to evaluate whether melatonin treatment could provide beneficial effects in an Alzheimer model related to tauopathy by improving the autophagic flux and, thereby, prevent cognitive decline. The injection of AAV‐hTauP301L viral vectors and treatment/injection with okadaic acid were used to achieve mouse and human ex vivo, and in vivo tau‐related models. Melatonin (10 μmol/L) impeded oxidative stress, tau hyperphosphorylation, and cell death by restoring autophagy flux in the ex vivo models. In the in vivo studies, intracerebroventricular injection of AAV‐hTauP301L increased oxidative stress, neuroinflammation, and tau hyperphosphorylation in the hippocampus 7 days after the injection, without inducing cognitive impairment; however, when animals were maintained for 28 days, cognitive decline was apparent. Interestingly, late melatonin treatment (10 mg/kg), starting once the alterations mentioned above were established (from day 7 to day 28), reduced oxidative stress, neuroinflammation, tau hyperphosphorylation, and caspase‐3 activation; these observations correlated with restoration of the autophagy flux and memory improvement. This study highlights the importance of autophagic dysregulation in tauopathy and how administration of pharmacological doses of melatonin, once tauopathy is initiated, can restore the autophagy flux, reduce proteinopathy, and prevent cognitive decline. We therefore propose exogenous melatonin supplementation or the development of melatonin derivatives to improve autophagy flux for the treatment of proteinopathies like AD.
Behavioural weight management interventions for postnatal women: A systematic review of systematic reviews of randomized controlled trials
Authors: Ferguson Janice A. , Daley Amanda J. , Parretti Helen M. 
Published: April 2019

SummaryThis systematic review of systematic reviews investigated the effectiveness of lifestyle weight management interventions for postnatal women. We systematically reviewed Medline (PubMed), Embase, CINAHL Plus, The Cochrane Library, and Scopus from 2000 until January 2018, to identify systematic reviews of randomized controlled trials that evaluated the effectiveness of behavioural lifestyle interventions for weight management in postnatal women. Results were summarized both descriptively and statistically using a mega meta‐analysis of data from randomized controlled trials included in previous systematic reviews. Nine systematic reviews met our inclusion criteria. Overall the reviews concluded that lifestyle interventions involving physical activity and/or dietary changes resulted in a reduction in postnatal weight. Results from the overall mega meta‐analysis confirmed this finding with a mean difference of −1.7 kg (95% CI, −2.3 to −1.1). Findings for subgroup analyses gave mean differences of −1.9 kg (95% CI, −2.9 to −1.0) for combined diet and physical activity interventions, −1.6 kg (95% CI, −2.1 to −1.2) for physical activity–only interventions, and −9.3 kg (95% CI, −16.5 to −2.1) for diet‐only interventions (one study). Heterogeneity varied from 0% to 68%. Interventions involving lifestyle interventions appeared to be effective in reducing weight in postnatal women, although these findings should be interpreted with some caution due to statistical heterogeneity.
Cognitive decline reduces household spending among older people
Authors: Oba Hikaru , Kadoya Yoshihiko , Matsuoka Teruyuki , Narumoto Jin 
Published: April 2019

AimThe purpose of the present study was to investigate the effect of cognitive decline on household spending.MethodsThe panel data covered the years 2007–2009 and were taken from the Japanese Study of Aging and Retirement, with data extracted for 253 participants aged 65 years and over. Sociodemographic characteristics, functional status, depressive symptoms, and monthly household spending excluding spending for shelter (e.g. mortgage) were used in the analysis. Cognitive function was evaluated by delayed recall and serial 7s and represented by the sum of both scores. Changes in spending and cognitive function scores were calculated by subtracting 2007 scores from 2009 scores. Participants were divided into two groups: cognitive decline and no cognitive decline. The effect of cognitive decline on changes in household spending was estimated.ResultsAlthough the cognitive decline group had more severe depressive symptoms than the no cognitive decline group in 2009, cognitive decline was the only factor related to change in household spending.ConclusionThe results imply that cognitive decline may cause a decline in household spending in older people. Focusing on changes in household spending behaviour might help detect cognitive impairment in older people.
The Mean, Variance and Correlation for Bivariate Recurrent Event Data with a Terminal Event
Authors: Scheike Thomas H. , Eriksson Frank , Tribler Siri 
Published: April 2019

SummaryRecurrent events in the presence of a terminal event are often encountered in a biomedical setting. The marginal mean of the number of recurrent events in a specified time period is a useful non-parametric summary of recurrent events data also in the presence of a terminal event. Other useful non-parametric summaries, that are simple to compute, are the distribution function of the number of recurrent events for each point in time and the variance of the number of recurrent events. For bivariate recurrent events, still in the presence of a terminal event, we suggest a simple non-parametric estimator of the covariance or correlation of the marginal number of events for both processes. When there is no terminal event the correlation is useful, but when there is an important terminal event we suggest an adjustment for correlation induced by the terminal event to obtain a measure that reflects the dependence in the recurrent event processes among survivors only. Our estimators can be used for deciding whether the two recurrent events are correlated and in what way. We provide large sample properties of our estimators and show their performance in small samples by simulations. The estimators are applied in a study of catheter complications among patients receiving home parenteral nutrition through a central venous catheter, and we show a positive correlation between the number of infections and the number of occlusion defects.
Protein kinase A‐mediated phosphorylation of naked cuticle homolog 2 stimulates cell‐surface delivery of transforming growth factor‐α for epidermal growth factor receptor transactivation
Authors: Cao Zheng , Singh Bhuminder , Li Cunxi , Markham Nicholas O. , Carrington Léolène J. , Franklin Jeffrey L. , Graves‐Deal Ramona , Kennedy Eileen J. , Goldenring James R. , Coffey Robert J. 
Published: April 2019

AbstractThe classic mode of G protein‐coupled receptor (GPCR)‐mediated transactivation of the receptor tyrosine kinase epidermal growth factor receptor (EGFR) transactivation occurs via matrix metalloprotease (MMP)‐mediated cleavage of plasma membrane‐anchored EGFR ligands. Herein, we show that the Gαs‐activating GPCR ligands vasoactive intestinal peptide (VIP) and prostaglandin E2 (PGE2) transactivate EGFR through increased cell‐surface delivery of the EGFR ligand transforming growth factor‐α (TGFα) in polarizing madin‐darby canine kidney (MDCK) and Caco‐2 cells. This is achieved by PKA‐mediated phosphorylation of naked cuticle homolog 2 (NKD2), previously shown to bind TGFα and direct delivery of TGFα‐containing vesicles to the basolateral surface of polarized epithelial cells. VIP and PGE2 rapidly activate protein kinase A (PKA) that then phosphorylates NKD2 at Ser‐223, a process that is facilitated by the molecular scaffold A‐kinase anchoring protein 12 (AKAP12). This phosphorylation stabilized NKD2, ensuring efficient cell‐surface delivery of TGFα and increased EGFR activation. Thus, GPCR‐triggered, PKA/AKAP12/NKD2‐regulated targeting of TGFα to the cell surface represents a new mode of EGFR transactivation that occurs proximal to ligand cleavage by MMPs.
Can a nurse-led community-based model of hypertension care improve hypertension control in Ghana? Results from the ComHIP cohort study
Authors: Adler Alma J , Laar Amos , Prieto-Merino David , Der Reina M M , Mangortey Debbie , Dirks Rebecca , Lamptey Peter , Perel Pablo 
Published: April 2019

ObjectivesTo evaluate the effectiveness of the Community-based Hypertension Improvement Project (ComHIP) in increasing hypertension control.SettingLower Manya Krobo, Eastern Region, Ghana.ParticipantsAll adult hypertensive community members, except pregnant women, were eligible for inclusion in the study. We enrolled 1339 participants, 69% of whom were female. A total of 552 had a 6-month visit, and 338 had a 12-month visit.InterventionsWe report on a package of interventions where community-based cardiovascular disease (CVD) nurses were trained by FHI 360. CVD nurses confirmed diagnoses of known hypertensives and newly screened individuals. Participants were treated according to the clinical guidelines established through the project’s Technical Steering Committee. Patients received three types of reminder and adherence messages. We used CommCare, a cloud-based system, as a case management and referral tool.Primary outcomeHypertension control defined as blood pressure (BP) under 140/90 mm Hg. Secondary outcomes: changes in BP and knowledge of risk factors for hypertension.ResultsAfter 1 year of intervention, 72% (95% CI: 67% to 77%) of participants had their hypertension under control. Systolic BP was reduced by 12.2 mm Hg (95% CI: 14.4 to 10.1) and diastolic BP by 7.5 mm Hg (95% CI: 9.9 to 6.1). Due to low retention, we were unable to look at knowledge of risk factors. Factors associated with remaining in the programme for 12 months included education, older age, hypertension under control at enrolment and enrolment date. The majority of patients who remained in the programme were on treatment, with two-thirds taking at least two medications.ConclusionsPatients retained in ComHIP had increased BP control. However, high loss to follow-up limits potential public health impact of these types of programmes. To minimise the impact of externalities, programmes should include standard procedures and backup systems to maximise the possibility that patients stay in the programme.
No effects of cerebellar transcranial direct current stimulation on force field and visuomotor reach adaptation in young and healthy subjects
Authors: Mamlins A. , Hulst T. , Donchin O. , Timmann D. , Claassen J. 
Published: April 2019

Previous studies have shown that cerebellar transcranial direct current stimulation (tDCS) leads to faster adaptation of arm reaching movements to visuomotor rotation and force field perturbations in healthy subjects. The first aim of the present study was to confirm a stimulation-dependent effect on motor adaptation. Second, we investigated whether tDCS effects differ depending on onset, that is, before or at the beginning of the adaptation phase. A total of 120 healthy and right-handed subjects (60 women, mean age 23.2 ± SD 2.7 yr, range 18–31 yr) were tested. Subjects moved a cursor with a manipulandum to one of eight targets presented on a vertically orientated screen. Three baseline blocks were followed by one adaptation block and three washout blocks. Sixty subjects did a force field adaptation task (FF), and 60 subjects did a visuomotor adaptation task (VM). Equal numbers of subjects received anodal, cathodal, or sham cerebellar tDCS beginning either in the third baseline block or at the start of the adaptation block. In FF and VM, tDCS and the onset of tDCS did not show a significant effect on motor adaptation (all P values >0.05). We were unable to support previous findings of modulatory cerebellar tDCS effects in reaching adaptation tasks in healthy subjects. Prior to possible application in patients with cerebellar disease, future experiments are needed to determine which tDCS and task parameters lead to robust tDCS effects. NEW & NOTEWORTHY Transcranial direct current stimulation (tDCS) is a promising tool to improve motor learning. We investigated whether cerebellar tDCS improves motor learning in force field and visuomotor tasks in healthy subjects and what influence the onset of stimulation has. We did not find stimulation effects of tDCS or an effect of onset of stimulation. A reevaluation of cerebellar tDCS in healthy subjects and at the end of the clinical potential in cerebellar patients is demanded.
Adaptation to Coriolis force perturbations of postural sway requires an asymmetric two-leg model
Authors: Bakshi Avijit , DiZio Paul , Lackner James R. 
Published: April 2019

In the companion paper (Bakshi A, DiZio P, Lackner JR. J Neurophysiol. In press, 2019), we reported how voluntary forward-backward sway in a rotating room generated medial-lateral Coriolis forces that initially deviated intended body sway paths. Pure fore-aft sway was gradually restored over per-rotation trials, and a negative aftereffect occurred during postrotation sway. Force plate recordings showed that subjects learned to compensate for the Coriolis forces by executing a bimodal torque, the distribution of which was asymmetric across the two legs and of opposite sign for forward vs. backward sway. To explain these results, we have developed an asymmetric, nonparallel-leg, inverted pendulum model to characterize upright balance control in two dimensions. Fore-aft and medial-lateral sway amplitudes can be biomechanically coupled or independent. Biomechanical coupling occurs when Coriolis forces orthogonal to the direction of movement perturb sway about the ankles. The model includes a mechanism for alternating engagement/disengagement of each leg and for asymmetric drive to the ankles to achieve adaptation to Coriolis force-induced two-dimensional sway. The model predicts the adaptive control underlying the adaptation of voluntary postural sway to Coriolis forces. A stability analysis of the model generates parameter values that match those measured experimentally, and the parameterized model simulations reproduce the experimentally observed sway trajectories.NEW & NOTEWORTHY This paper presents a novel nonparallel leg model of postural control that correctly predicts the perturbations of voluntary sway that occur in a rotating environment and the adaptive changes that occur to restore faithful movement trajectories. This engaged leg model (ELM) predicts the asymmetries in force distribution and their patterns between the two legs to restore accurate movement trajectories. ELM has clinical relevance for pathologies that generate postural asymmetries and for altered gravitoinertial force conditions.
Generalization via superposition: combined effects of mixed reference frame representations for explicit and implicit learning in a visuomotor adaptation task
Authors: Poh Eugene , Taylor Jordan A. 
Published: April 2019

Studies on generalization of learned visuomotor perturbations have generally focused on whether learning is coded in extrinsic or intrinsic reference frames. This dichotomy, however, is challenged by recent findings showing that learning is represented in a mixed reference frame. Overlooked in this framework is how learning appears to consist of multiple processes, such as explicit reaiming and implicit motor adaptation. Therefore, the proposed mixed representation may simply reflect the superposition of explicit and implicit generalization functions, each represented in different reference frames. Here we characterized the individual generalization functions of explicit and implicit learning in relative isolation to determine whether their combination could predict the overall generalization function when both processes are in operation. We modified the form of feedback in a visuomotor rotation task in an attempt to isolate explicit and implicit learning and tested generalization across new limb postures to dissociate the extrinsic/intrinsic representations. We found that the amplitude of explicit generalization was reduced with postural change and was only marginally shifted, resembling an extrinsic representation. In contrast, implicit generalization maintained its amplitude but was significantly shifted, resembling a mixed representation. A linear combination of individual explicit and implicit generalization functions accounted for nearly 85% of the variance associated with the generalization function in a typical visuomotor rotation task, where both processes are in operation. This suggests that each form of learning results from a mixed representation with distinct extrinsic and intrinsic contributions and the combination of these features shapes the generalization pattern observed at novel limb postures.NEW & NOTEWORTHY Generalization following learning in visuomotor adaptation tasks can reflect how the brain represents what it learns. In this study, we isolated explicit and implicit forms of learning and showed that they are derived from a mixed reference frame representation with distinct extrinsic and intrinsic contributions. Furthermore, we showed that the overall generalization pattern at novel workspaces is due to the superposition of independent generalization effects developed by explicit and implicit learning processes.
Saccadic suppression measured by steady-state visual evoked potentials
Authors: Chen Jing , Valsecchi Matteo , Gegenfurtner Karl R. 
Published: April 2019

Visual sensitivity is severely impaired during the execution of saccadic eye movements. This phenomenon has been extensively characterized in human psychophysics and nonhuman primate single-neuron studies, but a physiological characterization in humans is less established. Here, we used a method based on steady-state visually evoked potential (SSVEP), an oscillatory brain response to periodic visual stimulation, to examine how saccades affect visual sensitivity. Observers made horizontal saccades back and forth, while horizontal black-and-white gratings flickered at 5–30 Hz in the background. We analyzed EEG epochs with a length of 0.3 s either centered at saccade onset (saccade epochs) or centered at fixations half a second before the saccade (fixation epochs). Compared with fixation epochs, saccade epochs showed a broadband power increase, which most likely resulted from saccade-related EEG activity. The execution of saccades, however, led to an average reduction of 57% in the SSVEP amplitude at the stimulation frequency. This result provides additional evidence for an active saccadic suppression in the early visual cortex in humans. Compared with previous functional MRI and EEG studies, an advantage of this approach lies in its capability to trace the temporal dynamics of neural activity throughout the time course of a saccade. In contrast to previous electrophysiological studies in nonhuman primates, we did not find any evidence for postsaccadic enhancement, even though simulation results show that our method would have been able to detect it. We conclude that SSVEP is a useful technique to investigate the neural correlates of visual perception during saccadic eye movements in humans. NEW & NOTEWORTHY We make fast ballistic saccadic eye movements a few times every second. At the time of saccades, visual sensitivity is severely impaired. The present study uses steady-state visually evoked potentials to reveal a neural correlate of the fine temporal dynamics of these modulations at the time of saccades in humans. We observed a strong reduction (57%) of visually driven neural activity associated with saccades but did not find any evidence for postsaccadic enhancement.
Eye movements do not play an important role in the adaptation of hand tracking to a visuomotor rotation
Authors: Gouirand Niels , Mathew James , Brenner Eli , Danion Frederic R. 
Published: April 2019

Adapting hand movements to changes in our body or the environment is essential for skilled motor behavior. Although eye movements are known to assist hand movement control, how eye movements might contribute to the adaptation of hand movements remains largely unexplored. To determine to what extent eye movements contribute to visuomotor adaptation of hand tracking, participants were asked to track a visual target that followed an unpredictable trajectory with a cursor using a joystick. During blocks of trials, participants were either allowed to look wherever they liked or required to fixate a cross at the center of the screen. Eye movements were tracked to ensure gaze fixation as well as to examine free gaze behavior. The cursor initially responded normally to the joystick, but after several trials, the direction in which it responded was rotated by 90°. Although fixating the eyes had a detrimental influence on hand tracking performance, participants exhibited a rather similar time course of adaptation to rotated visual feedback in the gaze-fixed and gaze-free conditions. More importantly, there was extensive transfer of adaptation between the gaze-fixed and gaze-free conditions. We conclude that although eye movements are relevant for the online control of hand tracking, they do not play an important role in the visuomotor adaptation of such tracking. These results suggest that participants do not adapt by changing the mapping between eye and hand movements, but rather by changing the mapping between hand movements and the cursor’s motion independently of eye movements. NEW & NOTEWORTHY Eye movements assist hand movements in everyday activities, but their contribution to visuomotor adaptation remains largely unknown. We compared adaptation of hand tracking under free gaze and fixed gaze. Although our results confirm that following the target with the eyes increases the accuracy of hand movements, they unexpectedly demonstrate that gaze fixation does not hinder adaptation. These results suggest that eye movements have distinct contributions for online control and visuomotor adaptation of hand movements.