Search

Purpose: MitraClip is the sole percutaneous device approved for functional mitral regurgitation (MR; FMR) but MR recurs in over one third of patients. As device-induced mechanical effects are a potential cause for MR recurrence, we tested the hypothesis that MitraClip increases leaflet stress and procedure-related strain in sub-valvular left ventricular (LV) myocardium in FMR associated with coronary disease (FMR-CAD). Methods: Simulations were performed using finite element models of the LV + mitral valve based on MRI of 5 sheep with FMR-CAD. Models were modified to have a 20% increase in LV volume (↑LV_VOLUME) and MitraClip was simulated with contracting beam elements (virtual sutures) placed between nodes in the center edge of the anterior (AL) and posterior (PL) mitral leaflets. Effects of MitraClip on leaflet stress in the peri-MitraClip region of AL and PL, septo-lateral annular diameter (SLAD), and procedure-related radial strain (Err) in the sub-valvular myocardium were calculated. Results: MitraClip increased peri-MitraClip leaflet stress at end-diastole (ED) by 22.3±7.1 kPa (p<0.0001) in AL and 14.8±1.2 kPa (p<0.0001) in PL. MitraClip decreased SLAD by 6.1±2.2 mm (p<0.0001) and increased Err in the sub-valvular lateral LV myocardium at ED by 0.09±0.04 (p<0.0001)). Furthermore, MitraClip in ↑LV_VOLUME was associated with persistent effects at ED but also at end-systole where peri-MitraClip leaflet stress was increased in AL by 31.9±14.4 kPa (p = 0.0268) and in PL by 22.5±23.7 kPa (p = 0.0101). Conclusions: MitraClip for FMR-CAD increases mitral leaflet stress and radial strain in LV sub-valvular myocardium. Mechanical effects of MitraClip are augmented by LV enlargement. [ABSTRACT FROM AUTHOR]

Fricative consonants are known to be pronounced by controlling turbulent flow inside a vocal tract. In this study, a simplified vocal tract model was proposed to investigate the characteristics of flow and sound during production of the fricative [s] in a word context. By controlling the inlet flow rate and tongue speed, the acoustic characteristics of [s] were reproduced by the model. The measurements with a microphone and a hot-wire anemometer showed that the flow velocity at the teeth gap and far-field sound pressure started oscillating before the tongue reached the /s/ position, and continued during tongue descent. This behaviour was not affected by the changes of the tongue speed. These results indicate that there is a time shift between source generation and tongue movement. This time shift can be a physical constraint in the articulation of words which include /s/. With the proposed model, we could investigate the effects of tongue speed on the flow and sound generation in a parametric way. The proposed methodology is applicable for other phonemes to further explore the aeroacoustics of phonation. [ABSTRACT FROM AUTHOR]

Background: Fetal monitoring based on electrocardiographic (ECG) morphology is obtained from a single unipolar fetal scalp electrode. Ideally, it should be obtained from multiple leads, as ECG waveform depends on alignment between electrode and electrical heart axis. This alignment is unknown in fetuses. Besides, fetuses are surrounded by conductive media, which may influence ECG waveform. We explored the influence of electrode position and head orientation on ECG waveforms of unipolar and bipolar scalp ECGs recorded in air and in conductive medium. Methods: We recorded ECGs in one adult subject at five different scalp positions in five different head orientations both in dry and immersed conditions. The ratio between T-amplitude and QRS-amplitude (T/QRS ratio) of unipolar and bipolar scalp ECGs was determined and compared between all conditions. Results: In the dry condition, we observed in the unipolar leads little to no difference between different electrode positions (maximal T/QRS difference 0.00–0.01) and minor differences between head orientations (0.02–0.03), whereas bipolar leads showed no recognizable ECG signal at all. During the immersed condition, we found variation in the unipolar leads, both between electrode positions (maximal T/QRS difference 0.02–0.05) and between head orientations (0.03–0.06). Bipolar leads showed different ECG signals in contrasting head orientations. Conclusions: Both unipolar and bipolar scalp lead-derived ECG waveforms are influenced by electrode position and head orientation when the subject is submerged in a conductive medium. Fetal monitoring based on single scalp lead ECG waveform might be suboptimal, as it lacks correction for fetal head orientation and electrode position. [ABSTRACT FROM AUTHOR]

Objectives: An extended-wavelength diffuse reflectance spectroscopy (EWDRS) technique was evaluated for its ability to differentiate between and classify different skin and tissue types in an in vivo pig model. Materials and methods: EWDRS recordings (450–1550 nm) were made on skin with different degrees of pigmentation as well as on the pig snout and tongue. The recordings were used to train a support vector machine to identify and classify the different skin and tissue types. Results: The resulting EWDRS curves for each skin and tissue type had a unique profile. The support vector machine was able to classify each skin and tissue type with an overall accuracy of 98.2%. The sensitivity and specificity were between 96.4 and 100.0% for all skin and tissue types. Conclusion: EWDRS can be used in vivo to differentiate between different skin and tissue types with good accuracy. Further development of the technique may potentially lead to a novel diagnostic tool for e.g. non-invasive tumor margin delineation. [ABSTRACT FROM AUTHOR]

Honey bees, Apis mellifera, are a globally significant pollinator species and are currently in decline, with losses attributed to an array of interacting environmental stressors. Extremely low frequency electromagnetic fields (ELF EMFs) are a lesser-known abiotic environmental factor that are emitted from a variety of anthropogenic sources, including power lines, and have recently been shown to have a significant impact on the cognitive abilities and behaviour of honey bees. Here we have investigated the effects of field-realistic levels of ELF EMFs on aversive learning and aggression levels, which are critical factors for bees to maintain colony strength. Bees were exposed for 17 h to 100 μT or 1000 μT ELF EMFs, or a sham control. A sting extension response (SER) assay was conducted to determine the effects of ELF EMFs on aversive learning, while an intruder assay was conducted to determine the effects of ELF EMFs on aggression levels. Exposure to both 100 μT and 1000 μT ELF EMF reduced aversive learning performance by over 20%. Exposure to 100 μT ELF EMFs also increased aggression scores by 60%, in response to intruder bees from foreign hives. These results indicate that short-term exposure to ELF EMFs, at levels that could be encountered in bee hives placed under power lines, reduced aversive learning and increased aggression levels. These behavioural changes could have wider ecological implications in terms of the ability of bees to interact with, and respond appropriately to, threats and negative environmental stimuli. [ABSTRACT FROM AUTHOR]

The origins of agriculture in Southwest Asia over 10,000 years ago and its subsequent spread into Europe during the Neolithic have been the focus of much archaeological research over the past several decades. Increasingly more sophisticated analytical techniques have allowed for better understanding of the complex interactions that occurred amongst humans, animals, and their environments during this transition. The Aegean Islands are critically situated where Anatolia and the mainland Greece meet, making the region pivotal for understanding the movement of the Neolithic into Europe. Located on the largest Turkish Aegean island of Gökçeada, the site of Uğurlu Höyük dates to the early Neolithic and has been the subject of ongoing excavations and research integrating a rigorous dating program with comprehensive zooarchaeological research. This paper focuses on the combination of bone collagen and tooth enamel stable isotope data with existing archaeological data to develop a fine-resolution picture of the spread of the Neolithic, particularly the importation and management of domestic fauna on Gökçeada, with broader relevance for understanding Aegean-Anatolian interactions. The stable isotope values from the fauna at Uğurlu have been used for both diachronic intrasite analyses and intersite comparisons between contemporaneous mainland sites. Integrating stable isotope and zooarchaeological datasets makes Uğurlu one of the first island sites to provide a comprehensive understanding of the geographic origin of Neolithic livestock populations and the timing of their spread from Anatolia into Europe during the process of Neolithization. [ABSTRACT FROM AUTHOR]

Plantar fasciitis is a frequently occurring overuse injury of the foot. Shoes with a stiff rocker profile are a commonly prescribed treatment modality used to alleviate complaints associated with plantar fasciitis. In rocker shoes the apex position was moved proximally as compared to normal shoes, limiting the progression of the ground reaction forces (GRF) and peak plantarflexion moments during gait. A stiff sole minimizes dorsiflexion of the toes. The aim of this study was to investigate whether the biomechanical effects of rocker shoes lead to minimization of plantar aponeurosis (PA) strain during gait in patients with plantar fasciitis and in healthy young adults. 8 patients with plantar fasciitis (1 male, 7 females; mean age 55.0 ± 8.4 years) and 8 healthy young adults (8 females; mean age 24.1 ± 1.6 years) participated in the study. Each participant walked for 1 minute on an instrumented treadmill while wearing consecutively in random order shoes with a normal apex position (61.2 ± 2.8% apex) with flexible insole (FN), normal apex position with stiff insole (SN), proximal apex position (56.1 ± 2.6% apex) with flexible insole (FR) and proximal apex position with stiff insole (SR). Marker position data of the foot and lower leg and GRF were recorded. An OpenSim foot model was used to compute the change in PA length based on changes in foot segment positions during gait. The changes in PA length due to increases in Achilles tendon forces were computed based on previous data of a cadaver study. PA strain computed from both methods was not statistically different between shoe conditions. Peak Achilles tendon force, peak first metatarsophalangeal (MTP1) joint angle and peak plantarflexion moment were significantly lower when walking with the rocker shoe with a proximal apex position and a stiff insole for all subjects (p<.05). Changes in Achilles tendon forces during gait accounted for 65 ± 2% of the total PA strain. Rocker shoes with a stiff insole reduce peak dorsiflexion angles of the toes and plantar flexion moments, but not PA strain because the effects of a proximal apex position and stiff insole do not occur at the same time, but independently affect PA strain at 80–90% and 90–100% of the stance phase. Rocker shoes with an apex position of ~56% are insufficient to significantly reduce peak PA strain values in patients with plantar fasciitis and healthy young adults. [ABSTRACT FROM AUTHOR]

Activated platelets release adenosine trisphosphate (ATP) and bioluminescence analysis of ATP release is usually used to monitor activation of platelets induced by various stimulants. However, bioluminescence analysis of ATP possesses poor linearity, the signal is quickly attenuated, and the accuracy of ATP release from platelets is hard to determine accurately enough to be used in a high throughput screening of platelet inhibitors. The present study was designed to optimize bioluminescence analysis of ATP released by platelets and expand its application in high throughput screening of platelet inhibitors. The results showed that accuracy of ATP analysis was significantly improved by adding coenzyme A (CoA) and signal attenuation of ATP analysis was greatly postponed by adding bovine serum albumin (BSA) both in Hank's balanced salt solution (HBSS) and Tyrode's buffer. Furthermore, ATP release of activated platelets and inhibitory effects of Ly294002 and Staurosporine on platelet activation were accurately determined by our optimized bioluminescence analysis of ATP. Thus, we have successfully constructed an optimized bioluminescence analysis of ATP which can be used in high throughput screening of platelet inhibitors. [ABSTRACT FROM AUTHOR]

Malignant gliomas remain incurable with a poor prognosis despite of aggressive treatment. We have been studying the development of brain tumors in a glioma rat model, where rats develop brain tumors after prenatal exposure to ethylnitrosourea (ENU), and there is a sizable interval between when the first pathological changes are noted and tumors become detectable with MRI. Our aim to define a molecular timeline through proteomic profiling of the cerebrospinal fluid (CSF) such that brain tumor commitment can be revealed earlier than at the presymptomatic stage. A comparative proteomic approach was applied to profile CSF collected serially either before, at and after the time MRI becomes positive. Elastic net (EN) based models were developed to infer the timeline of normal or tumor development respectively, mirroring a chronology of precisely timed, "clocked", adaptations. These CSF changes were later quantified by longitudinal entropy analyses of the EN predictive metric. False discovery rates (FDR) were computed to control the expected proportion of the EN models that are due to multiple hypothesis testing. Our ENU rat brain tumor dating EN model indicated that protein content in CSF is programmed even before tumor MRI detection. The findings of the precisely timed CSF tumor microenvironment changes at presymptomatic stages, deviation from the normal development timeline, may provide the groundwork for the understanding of adaptation of the brain environment in tumorigenesis to devise effective brain tumor management strategies. [ABSTRACT FROM AUTHOR]

Although there is good evidence to indicate a major role of intrinsic impairment of the contractile apparatus in muscle weakness seen in several pathophysiological conditions, the factors responsible for control of myofibrillar function are not fully understood. To investigate the role of mechanical load in myofibrillar function, we compared the skinned fiber force between denervated (DEN) and dexamethasone-treated (DEX) rat skeletal muscles with or without neuromuscular electrical stimulation (ES) training. DEN and DEX were induced by cutting the sciatic nerve and daily injection of dexamethasone (5 mg/kg/day) for 7 days, respectively. For ES training, plantarflexor muscles were electrically stimulated to produce four sets of five isometric contractions each day. In situ maximum torque was markedly depressed in the DEN muscles compared to the DEX muscles (-74% vs. -10%), whereas there was not much difference in the degree of atrophy in gastrocnemius muscles between DEN and DEX groups (-24% vs. -17%). Similar results were obtained in the skinned fiber preparation, with a greater reduction in maximum Ca2+-activated force in the DEN than in the DEX group (-53% vs. -16%). Moreover, there was a parallel decline in myosin heavy chain (MyHC) and actin content per muscle volume in DEN muscles, but not in DEX muscles, which was associated with upregulation of NADPH oxidase (NOX) 2, neuronal nitric oxide synthase (nNOS), and endothelial NOS expression, translocation of nNOS from the membrane to the cytosol, and augmentation of mRNA levels of muscle RING finger protein 1 (MuRF-1) and atrogin-1. Importantly, mechanical load evoked by ES protects against DEN- and DEX-induced myofibrillar dysfunction and these molecular alterations. Our findings provide novel insights regarding the difference in intrinsic contractile properties between DEN and DEX and suggest an important role of mechanical load in preserving myofibrillar function in skeletal muscle. [ABSTRACT FROM AUTHOR]

To understand the effect of attention on neuronal dynamics, we propose a multi-module network, with each module consisting of fully interconnected groups of excitatory and inhibitory neurons. This network shows transitive dynamics among quasi-attractors as its typical dynamics. When the release of acetylcholine onto the network is simulated by attention, the transitive dynamics change into stable dynamics in which the system converges to an attractor. We found that this network can reproduce three experimentally observed properties of attention-dependent response modulation, namely an increase in the firing rate, a decrease in the Fano factor of the firing rate, and a decrease in the correlation coefficients between the firing rates of pairs of neurons. Moreover, we also showed theoretically that the release of acetylcholine increases the sensitivity to bottom-up inputs by changing the response function. [ABSTRACT FROM AUTHOR]

Extrusion of xenobiotics is essential for allowing animals to remove toxic substances present in their diet or generated as a biproduct of their metabolism. By transporting a wide range of potentially noxious substrates, active transporters of the ABC transporter family play an important role in xenobiotic extrusion. One such class of transporters are the multidrug resistance P-glycoprotein transporters. Here, we investigated P-glycoprotein transport in the Malpighian tubules of the desert locust (Schistocerca gregaria), a species whose diet includes plants that contain toxic secondary metabolites. To this end, we studied transporter physiology using a modified Ramsay assay in which ex vivo Malpighian tubules are incubated in different solutions containing the P-glycoprotein substrate dye rhodamine B in combination with different concentrations of the P-glycoprotein inhibitor verapamil. To determine the quantity of the P-glycoprotein substrate extruded we developed a simple and cheap method as an alternative to liquid chromatography–mass spectrometry, radiolabelled alkaloids or confocal microscopy. Our evidence shows that: (i) the Malpighian tubules contain a P-glycoprotein; (ii) tubule surface area is positively correlated with the tubule fluid secretion rate; and (iii) as the fluid secretion rate increases so too does the net extrusion of rhodamine B. We were able to quantify precisely the relationships between the fluid secretion, surface area, and net extrusion. We interpret these results in the context of the life history and foraging ecology of desert locusts. We argue that P-glycoproteins contribute to the removal of xenobiotic substances from the haemolymph, thereby enabling gregarious desert locusts to maintain toxicity through the ingestion of toxic plants without suffering the deleterious effects themselves. [ABSTRACT FROM AUTHOR]

Deficits in the ankle plantarflexor muscles, such as weakness and contracture, occur commonly in conditions such as cerebral palsy, stroke, muscular dystrophy, Charcot-Marie-Tooth disease, and sarcopenia. While these deficits likely contribute to observed gait pathologies, determining cause-effect relationships is difficult due to the often co-occurring biomechanical and neural deficits. To elucidate the effects of weakness and contracture, we systematically introduced isolated deficits into a musculoskeletal model and generated simulations of walking to predict gait adaptations due to these deficits. We trained a planar model containing 9 degrees of freedom and 18 musculotendon actuators to walk using a custom optimization framework through which we imposed simple objectives, such as minimizing cost of transport while avoiding falling and injury, and maintaining head stability. We first generated gaits at prescribed speeds between 0.50 m/s and 2.00 m/s that reproduced experimentally observed kinematic, kinetic, and metabolic trends for walking. We then generated a gait at self-selected walking speed; quantitative comparisons between our simulation and experimental data for joint angles, joint moments, and ground reaction forces showed root-mean-squared errors of less than 1.6 standard deviations and normalized cross-correlations above 0.8 except for knee joint moment trajectories. Finally, we applied mild, moderate, and severe levels of muscle weakness or contracture to either the soleus (SOL) or gastrocnemius (GAS) or both of these major plantarflexors (PF) and retrained the model to walk at a self-selected speed. The model was robust to all deficits, finding a stable gait in all cases. Severe PF weakness caused the model to adopt a slower, "heel-walking" gait. Severe contracture of only SOL or both PF yielded similar results: the model adopted a "toe-walking" gait with excessive hip and knee flexion during stance. These results highlight how plantarflexor weakness and contracture may contribute to observed gait patterns. [ABSTRACT FROM AUTHOR]

Mechanical loading is essential for the maintenance of musculoskeletal homeostasis. Cartilage has been demonstrated to be highly mechanoresponsive, but the mechanisms by which chondrocytes respond to mechanical stimuli are not clearly understood. The goal of the study was to determine how LRP4, LRP5, and LRP6 within canonical Wnt-signaling are regulated in simulated microgravity and cyclic hydrostatic pressure, and to investigate the potential role of LRP 4/5/6 in cartilage degeneration. Rat chondrosacroma cell (RCS) pellets were stimulated using either cyclic hydrostatic pressure (1Hz, 7.5 MPa, 4hr/day) or simulated microgravity in a rotating wall vessel (RWV) bioreactor (11RPM, 24hr/day). LRP4/5/6 mRNA expression was assessed by RT-qPCR and LRP5 protein expression was determined by fluorescent immunostaining. To further evaluate our in vitro findings in vivo, mice were subjected to hindlimb suspension for 14 days and the femoral heads stained for LRP5 expression. We found that, in vitro, LRP4/5/6 mRNA expression is modulated in a time-dependent manner by mechanical stimulation. Additionally, LRP5 protein expression is upregulated in response to both simulated microgravity and cyclic hydrostatic pressure. LRP5 is also upregulated in vivo in the articular cartilage of hindlimb suspended mice. This is the first study to examine how LRP4/5/6, critical receptors within musculoskeletal biology, respond to mechanical stimulation. Further elucidation of this mechanism could provide significant clinical benefit for the identification of pharmaceutical targets for the maintenance of cartilage health. [ABSTRACT FROM AUTHOR]

Purpose: The effects of gravity on bevacizumab or the recommended head position after intraocular bevacizumab injection have not been reported. To evaluate the effect of gravity on bevacizumab in vitro, we added bevacizumab to the upper part of a test tube filled with balanced salt solution (BSS) and examined its distribution over time. Materials and methods: Sixty-four test tubes were divided equally into two groups; group 1 (32, collected from upper part of the tube) and group 2 (32, collected from lower part of the tube). Each test tube was filled with 5 mL BSS before bevacizumab (1.25 mg/0.05 mL) was added, and then stored at 36°C. Bevacizumab concentration in 8 test tubes from each group was measured at 12, 24, 48, and 168 h using an enzyme-linked immunosorbent analysis (ELISA) kit. Mann–Whitney and Jonckheere–Terpstra tests were used for statistical analysis. Results: Bevacizumab concentration was significantly higher in Group 2 than in Group 1 at 12, 24, 48, and 168 h (12, 24, 48, and 168 h; P < 0.01 each; Mann–Whitney test). The mean change in bevacizumab concentration over time tended to increase in Group 1 (P < 0.01; Jonckheere–Terpstra test), but tended to decrease in Group 2 (P < 0.01; Jonckheere–Terpstra test). Conclusions: The significant differences in concentration between the upper and lower parts even after a considerable amount of storage time showed that bevacizumab did not dissolve immediately and diffused evenly throughout the solution. It appeared that more bevacizumab settled in the lower part of the tube than in the upper part because of gravitational force. However, the concentration difference between the upper and lower parts decreased as bevacizumab gradually diffused over time, indicating that the difference in concentration due to gravity was more significant at the beginning of bevacizumab injection. [ABSTRACT FROM AUTHOR]

When we perform a movement we generally have a clear distinction between which parts of the world constitute our body and which parts do not. However, how the sense of ownership over our body supports movement is not yet fully understood. We aimed to see whether a sense of ownership over the hand supports the performance of rapid hand movements. In three experiments (n = 48, n = 30, n = 24), we presented participants with congruent and incongruent visuotactile and visuoproprioceptive information regarding their own hand. In keeping with previous experiments, multisensory disintegration resulted in a reduction in the subjective sensation of ownership over the hand, as reflected in questionnaire responses. Following sensory stimulation, participants were required to rapidly abduct their index finger whilst the movement was tracked. We examined the hypothesis that, should a sense of ownership over the limb be necessary for generating rapid movements with that limb, reaction time would increase when hand ownership was reduced, whilst the acceleration and velocity of the movement would decrease. We observed that reductions in own hand ownership did not interfere with rapid index finger abduction, suggesting that the motor system may not be reliant on a subjective sense of ownership over the body in order to generate movement. [ABSTRACT FROM AUTHOR]

Previous studies reported a significant association between postural control and lower-limb strength of several muscle groups, however, they were focused especially on knee muscles and ankle plantar and dorsal flexors. The aim of the present study is to examine the correlation between the muscle strength of ankle invertors, evertors, plantar flexors, and dorsal flexors and the control of bipedal stance in young and older adults. Thirty one young (aged 22.8 ± 2.6 years) and thirty one older adults (aged 70.5 ± 7.2 years) voluntarily participated in this study. Ankle muscle strength was evaluated by an isokinetic dynamometer. Normalized peak torque and work were averaged for four repetitions and for both lower limbs. The control of bipedal stance was evaluated by the sample entropy derived from an accelerometer placed on the lumbar spine while the subject stood on a foam pad with eyes open. Results showed significant age-related differences in ankle muscle strength and sample entropy in medial-lateral direction. More interestingly, the correlation between ankle muscle strength and the sample entropy was significantly different between young and older adults. Indeed, no significant correlation was observed in the younger adults. Conversely, in the older adults, the work of the ankle evertors positively correlated with sample entropy in the medial-lateral direction during bipedal stance (r = 0.36), whereas the peak torque and work of the dorsal flexors were significantly correlated with sample entropy in the anterior-posterior direction during bipedal stance (r = 0.44 for both variables). In the young adults, results suggest that, standing on foam with eyes open is a relatively easy postural task that does not require the full ankle muscle strength capacity. Taken together, the present findings suggest that older adults have a different association between ankle muscle strength and the sample entropy during bipedal stance. [ABSTRACT FROM AUTHOR]

The transport and distribution of charged molecules in polyelectrolyte solutions are of both fundamental and practical importance. A practical example, which is the specific subject addressed in the present paper, is the transport and distribution of charged species into cartilage. The charged species could be a contrast agent or a drug molecule involved in diagnosis or treatment of the widespread degenerative disease osteoarthritis, which leads to degradation of articular cartilage. Associated scientific issues include the rate of transport and the equilibrium concentrations of the charged species in the cartilage and the synovial fluid. To address these questions, we present results from magnetic resonance micro-imaging experiments on a model system of articular cartilage. The experiments yield temporally and spatially resolved data on the transport of a negatively charged contrast agent (charge = -2), used in medical examinations of cartilage, into a polyelectrolyte solution, which is designed to capture the electrostatic interactions in cartilage. Also presented is a theoretical analysis of the transport where the relevant differential equations are solved using finite element techniques as well as treated with approximate analytical expressions. In the analysis, non-ideal effects are included in the treatment of the mobile species in the system. This is made possible by using results from previous Monte Carlo simulations. The results demonstrate the importance of taking non-idealities into account when data from measurements of transport of charged solutes in a system with fixed charges from biological polyelectrolytes are analyzed. [ABSTRACT FROM AUTHOR]

Plant trichomes originate from epidermal cell, forming protective structure from abiotic and biotic stresses. Different from the unicellular trichome in Arabidopsis, tomato trichomes are multicellular structure and can be classified into seven different types based on cell number, shape and the presence of glandular cells. Despite the importance of tomato trichomes in insect resistance, our understanding of the tomato trichome morphogenesis remains elusive. In this study, we quantitatively analyzed morphological traits of trichomes in tomato and further performed live imaging of cytoskeletons in stably transformed lines with actin and microtubule markers. At different developmental stages, two types of cytoskeletons exhibited distinct patterns in different trichome cells, ranging from transverse, spiral to longitudinal. This gradual transition of actin filament angle from basal to top cells could correlate with the spatial expansion mode in different cells. Further genetic screen for aberrant trichome morphology led to the discovery of a number of independent mutations in SCAR/WAVE and ARP2/3 complex, which resulted in actin bundling and distorted trichomes. Disruption of microtubules caused isotropic expansion while abolished actin filaments entirely inhibited axial extension of trichomes, indicating that microtubules and actin filaments may control distinct aspects of trichome cell expansion. Our results shed light on the roles of cytoskeletons in the formation of multicellular structure of tomato trichomes. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) were obtained from human bone marrow and amplified in cultures supplemented with human platelet lysate in order to generate myofibroblasts. When MSCs were seeded in solid collagen scaffolds, they differentiated into myofibroblasts that were observed to strongly bind to the substrate, forming a 3D cell scaffold network that developed tension and shortening after KCl stimulation. Moreover, MSC-laden scaffolds recapitulated the Frank-Starling mechanism so that active tension increased in response to increases in the initial length of the contractile system. This constituted a bioengineering tissue that exhibited the contractile properties observed in both striated and smooth muscles. By using the A. F. Huxley formalism, we determined the myosin crossbridge (CB) kinetics of attachment (f1) and detachment (g1 and g2), maximum myosin ATPase activity, molar myosin concentration, unitary CB force and maximum CB efficiency. CB kinetics were dramatically slow, characterizing the non-muscle myosin type IIA (NMMIIA) present in myofibroblasts. When MSCs were seeded in solid collagen scaffolds functionalized with Arg-Gly-Asp (RGD), contractility increased and CB kinetics were modified, whereas the unitary NMMIIA-CB force and maximum CB efficiency did not change. In conclusion, we provided a non-muscle bioengineering tissue whose molecular mechanical characteristics of NMMIIA were very close to those of a non-muscle contractile tissue such as the human placenta. [ABSTRACT FROM AUTHOR]

The objective was to evaluate vaginal temperature as a thermoregulatory response of Nellore heifers under different microclimatic conditions. The study was conducted during one year in an experimental area located at 54°37′W, 20°27′S, and 530 m of altitude in Brazil. Twenty-four Nellore females were reared in integrated crop-livestock-forestry systems with different shading patterns. The randomized complete block experimental design was utilized with a sub subdivided plots scheme, with plot corresponding to the production systems, the subplot to the season of the year, and the sub subplot, the hours of the day. To characterize the microclimate, data regarding air and black globe temperatures, and air relative humidity were collected and from them, temperature-humidity index was calculated. Vaginal temperature was obtained by using a bottom-type temperature logger (i-button) attached to an adapted intravaginal device. The black-globe temperature explained the variation on vaginal temperature. Increases on vaginal temperature were only observed, on average, two hours after the increase of black-globe temperature. The microclimatic conditions found in the systems, resulting from the various tree densities, modify the vaginal temperature in different degrees, demonstrating that the shading effect is not always accompanied by improvements in thermal comfort. The system with intermediate density showed a better microclimatic condition and, consequently, a lower increase in vaginal temperature. The interaction between air temperature, humidity and solar radiation resulted in adverse environmental conditions, however, Nellore heifers showed good adaptation to the environment. In conclusion, vaginal temperature is a good indicator to evaluate the thermoregulatory response in Nellore heifers. [ABSTRACT FROM AUTHOR]

Inertial measurement unit (IMU)-based gait analysis can be used to quantitatively analyze the bilateral coordination and gait asymmetry (GA). The purpose of this study was to investigate changes in bilateral coordination and GA due to gait speed using an IMU based gait analysis and identify spatiotemporal factors affecting bilateral coordination and GA. Eighty healthy adults (40 men and 40 women) participated in the study. The mean age was 26.2 years, and the mean body mass index was 22.8 kg/m2. Three different walking speeds (80%, 100%, and 120% of preferred walking speed) on a treadmill were applied for 1 min of continuous level walking using a shoe-type IMU-based gait analysis system. The phase coordination index (PCI) and GA were calculated on three different walking speeds. Several variables (gait speed, height, body mass index, cadence, and step length) were analyzed as possible factors affecting the PCI and GA. Bilateral coordination and GA improved during fast walking (p = 0.005 and p = 0.019, respectively) and deteriorated during slow walking (p<0.001 and p = 0.008, respectively), compared with the participants’ preferred walking speeds. The correlation analysis revealed that PCI was negatively correlated with step length at each walking condition and lower gait speed was negatively correlated with PCI and GA during slow walking. Both bilateral coordination and GA had a negative linear relationship with gait speed, showing an improvement in the fast walking condition and deterioration in the slow walking condition. Step length was the factor associated with the change in the bilateral coordination. [ABSTRACT FROM AUTHOR]

Electrical impedance myography (EIM) is a technique for the assessment of muscle health and composition and has been shown to be sensitive to a variety of muscle pathologies including neurogenic atrophy and connective tissue deposition. However, it has been minimally studied in pure inflammation. In this study, we sought to assess EIM sensitivity to experimental inflammation induced by the localized intramuscular injection of λ-carrageenan. A total of 91 mice underwent 1–1000 kHz EIM measurements of gastrocnemius using a needle array, followed by injection of either 0.3% λ-carrageenan in phosphate-buffered saline (PBS) or PBS alone. Animals were then remeasured with EIM at 4, 24, 48, or 72 hours and euthanized and quantitative assessment of muscle histology was performed. Parallel alterations in both 5 and 50 kHz EIM values were identified at 4 and 24 hours, including reductions in phase, reactance, and resistance. In PBS-treated animals these values normalized by 48 hours, whereas substantial reductions in phase and reactance in 5 kHz EIM values persisted at 48 and 72 hours (i.e., values of phase 72 hours post-injection were 6.51 ± 0.40 degrees for λ-carrageenan versus 8.44 ± 0.35 degrees for PBS p<0.001, n = 11 per group). The degree of basophilic area observed in muscle sections by histology correlated to the degree of phase change at these two time points (Rspearman = -0.51, p = 0.0029). Changes in low frequency EIM parameters are sensitive to the presence of inflammatory infiltrates, and have the potential of serving as a simple means of quantifying the presence and extent of muscle inflammation without the need for biopsy. [ABSTRACT FROM AUTHOR]

Humans and other animals effortlessly identify natural sounds and categorize them into behaviorally relevant categories. Yet, the acoustic features and neural transformations that enable sound recognition and the formation of perceptual categories are largely unknown. Here, using multichannel neural recordings in the auditory midbrain of unanesthetized female rabbits, we first demonstrate that neural ensemble activity in the auditory midbrain displays highly structured correlations that vary with distinct natural sound stimuli. These stimulus-driven correlations can be used to accurately identify individual sounds using single-response trials, even when the sounds do not differ in their spectral content. Combining neural recordings and an auditory model, we then show how correlations between frequency-organized auditory channels can contribute to discrimination of not just individual sounds but sound categories. For both the model and neural data, spectral and temporal correlations achieved similar categorization performance and appear to contribute equally. Moreover, both the neural and model classifiers achieve their best task performance when they accumulate evidence over a time frame of approximately 1–2 seconds, mirroring human perceptual trends. These results together suggest that time-frequency correlations in sounds may be reflected in the correlations between auditory midbrain ensembles and that these correlations may play an important role in the identification and categorization of natural sounds. [ABSTRACT FROM AUTHOR]

Collapse of the lateral cerebral ventricles after ventriculo-peritoneal drainage is a fatal complication in dogs with internal hydrocephalus. It occurs due to excessive outflow of cerebrospinal fluid into the peritoneal cavity (overshunting). In most shunt systems, one-way valves with different pressure settings regulate flow into the distal catheter to avoid overshunting. The rationale for the choice of an appropriate opening pressure is a setting at the upper limit of normal intracranial pressure in dogs. However, physiological intraventricular pressure in normal dogs vary between 5 and 12 mm Hg. Furthermore, we hypothesise that intraventricular pressure in hydrocephalic dogs might differ from pressure in normal dogs and we also consider that normotensive hydrocephalus exists in dogs, as in humans. In order to evaluate intraventricular pressure in hydrocephalic dogs, twenty-three client owned dogs with newly diagnosed communicating internal hydrocephalus were examined before implantation of a ventriculo-peritoneal shunt using a single use piezo-resistive strain-gauge sensor (MicroSensor ICP probe). Ventricular volume and brain volume were measured before surgery, based on magnetic resonance images. Total ventricular volume was calculated and expressed in relation to the total volume of the brain, including the cerebrum, cerebellum, and brainstem (ventricle-brain index). Multiple logistic regression analysis was performed to assess the influence of the covariates “age”, “gender”, “duration of clinical signs”, “body weight”, and “ventricle-brain index” on intraventricular pressure. The mean cerebrospinal fluid pressure in the hydrocephalic dogs was 8.8 mm Hg (standard deviation 4.22), ranging from 3–18 mm Hg. The covariates “age”, (P = 0.782), “gender” (P = 0.162), “body weight”, (P = 0.065), or ventricle-brain index (P = 0.27)” were not correlated with intraventricular pressure. The duration of clinical signs before surgery, however, was correlated with intraventricular pressure (P< 0.0001). Dogs with internal hydrocephalus do not necessarily have increased intraventricular pressure. Normotensive communicating hydrocephalus exists in dogs. [ABSTRACT FROM AUTHOR]

Introduction: Percutaneous pedicle screw (PPS) can provide internal fixation of the thoracolumbar spine through a minimally invasive surgical procedure. PPS fixation has been widely used to treat various spinal diseases. Rigid fixation of PPS is essential for managing osteoporotic spine in order to prevent the risks of screw loosening and implant failure. We recently developed a novel augmentation method using hydroxyapatite (HA) granules for PPS fixation. The aim of this study was to evaluate the strength and stiffness of PPS fixation augmented with HA granules using an osteoporotic bone model. Methods: Screws were inserted into uniform synthetic bone (sawbones) with and without augmentation. The uniaxial pullout strength and insertion torque of the screws were evaluated. In addition, each screw underwent cyclic toggling under incrementally increasing physiological loads until 2 mm of screwhead displacement occurred. The maximal pullout strength (N), maximal insertion torque (N·cm), number of toggle cycles and maximal load (N) required to achieve 2-mm screwhead displacement were compared between the screws with and without augmentation. Results: The maximal pullout strength was significantly stronger for screws with augmentation than for those without augmentation (302 ± 19 N vs. 254 ± 17 N, p < 0.05). In addition, the maximal insertion torque was significantly increased in screws with augmentation compared to those without augmentation (48 ± 4 N·cm vs. 26 ± 5 N·cm, p < 0.05). Furthermore, the number of toggle cycles and the maximal load required to reach 2 mm of displacement were significantly greater in screws with augmentation than in those without augmentation (106 ± 9 vs. 52 ± 10 cycles; 152 ± 4 N vs. 124 ± 5 N, p < 0.05). Conclusions: Augmentation using HA granules significantly enhanced the rigidity of PPS fixation in the osteoporotic bone model. The present study suggested that novel augmentation with HA granules may be a useful technique for PPS fixation in patients with osteoporotic spine. [ABSTRACT FROM AUTHOR]

Purpose: Diffusion magnetic resonance imaging and tractography has an important role in the visualization of brain white matter and assessment of tissue microstructure. There is a lack of correspondence between diffusion metrics of live tissue, ex vivo tissue, and histological findings. The objective of this study is to elucidate this connection by determining the specific diffusion alterations between live and ex vivo brain tissue. This may have an important role in the incorporation of diffusion imaging in ex vivo studies as a complement to histological sectioning as well as investigations of novel neurosurgical techniques. Methods: This study presents a method of high angular resolution diffusion imaging and tractography of intact and non-fixed ex vivo piglet brains. Most studies involving ex vivo brain specimens have been formalin-fixed or excised from their original biological environment, processes both of which are known to affect diffusion parameters. Thus, non-fixed ex vivo tissue is used. A region-of-interest based analysis of diffusion tensor metrics are compared to in vivo subjects in a selection of major white matter bundles in order to assess the translatability of ex vivo diffusion measurements. Results: Tractography was successfully achieved in both in vivo and ex vivo groups. No significant differences were found in tract connectivity, average streamline length, or apparent fiber density. Significantly decreased diffusivity (mean, axial, and radial; p<0.0005) in the non-fixed ex vivo group and unaltered fractional anisotropy (p>0.059) between groups were observed. Conclusion: This study validates the extrapolation of non-fixed fractional anisotropy measurements to live tissue and the potential use of ex vivo tissue for methodological development. [ABSTRACT FROM AUTHOR]

Direct lightning strikes to the human head can lead to various effects, ranging from burnings to death. The biological and physical mechanisms of a direct lightning strike in the human head are not well understood. The aim of this paper is to design an experimental setup to measure the spatial and temporal current distribution during a direct lightning strike to physical head phantoms to establish normative values for personal lightning protection equipment design and testing. We created head phantoms made of agarose, replicating the geometric and dielectric properties of scalp, skull, and intracranial volume. The bases of the three compartments were galvanically contacted via copper electrodes to measure the current per compartment. We used pulse generators to apply aperiodic voltage and current signals that modelled lightning components. Our experiments indicated that the scalp compartment was exposed to the current with a fraction of 80–90%. The brain and skull compartments were exposed between 6–13% and 3–6% of the total measured current respectively. In case of a flashover, most of the current (98–99%) flowed through the discharge channel. Unlike previous theoretical estimates and measurements in technical setups, we observed considerably longer times for the flashover to build up. In our experiments, the time to build up a fully formed flashover varied from approximately 30–700 μs. The observed current patterns in cases without and with flashover provided information on regions of possible damage in the human head. Consequently, we identified the phenomenon of a flashover as a potential mechanism for humans to survive a lightning strike. Our measured current distributions and amplitudes formed the base for normative values, which can be used in later experimental investigations regarding the possibilities of individual lightning protection equipment for humans. [ABSTRACT FROM AUTHOR]

Globally, gains in sweet corn [Zea mays L.var. rugosa (or saccharata)] are a fraction of the yield advances made in field corn (Zea mays L.) in the last half-century. Grain yield improvement of field corn is associated with increased tolerance to higher plant densities (i.e., crowding stress). Processing sweet corn hybrids that tolerate crowding stress have been identified; however, such hybrids appear to be under-planted in the processing sweet corn. Using crowding stress tolerant (CST) hybrids, the objectives of this study were to: (1) identify optimum plant densities for a range of growing conditions; (2) quantify gaps in production between current and optimum plant densities; and (3) enumerate changes in yield and ear traits when shifting from current to optimum plant densities. Using a CST shrunken-2 (sh2) processing sweet corn hybrid, on-farm plant density trials were conducted in thirty fields across the states of Illinois, Minnesota and Wisconsin, from 2013 to 2017 in order to capture a wide variety of growing conditions. Linear mixed-effects models were used to identify the optimum plant density corresponding to maximum ear mass (Mt ha-1), case production (cases ha-1), and profitability to the processor ($ ha-1). Kernel moisture, indicative of plant development, was unaffected by plant density. Ear traits, such as ear number and ear mass per plant, average ear length, and filled ear length declined linearly with increasing plant density. Nonetheless, there was a large economic benefit to the grower and processor by shifting to higher plant densities in most environments. This research shows that increasing plant densities of CST hybrids from current (58,475 plants ha-1) to optimum (73,075 plants ha-1) could improve processing sweet corn green ear yield and processor profitability on average of 1.13 Mt ha-1 and $525 ha-1, respectively. [ABSTRACT FROM AUTHOR]

The blood flow through the major vessels holds great diagnostic potential for the identification of cardiovascular complications and is therefore routinely assessed with current diagnostic modalities. Heart valves are subject to high hydrodynamic loads which render them prone to premature degradation. Failing native aortic valves are routinely replaced with bioprosthetic heart valves. This type of prosthesis is limited by a durability that is often less than the patient’s life expectancy. Frequent assessment of valvular function can therefore help to ensure good long-term outcomes and to plan reinterventions. In this article, we describe how unsupervised novelty detection algorithms can be used to automate the interpretation of blood flow data to improve outcomes through early detection of adverse cardiovascular events without requiring repeated check-ups in a clinical environment. The proposed method was tested in an in-vitro flow loop which allowed simulating a failing aortic valve in a laboratory setting. Aortic regurgitation of increasing severity was deliberately introduced with tube-shaped inserts, preventing complete valve closure during diastole. Blood flow recordings from a flow meter at the location of the ascending aorta were analyzed with the algorithms introduced in this article and a diagnostic index was defined that reflects the severity of valvular degradation. The results indicate that the proposed methodology offers a high sensitivity towards pathological changes of valvular function and that it is capable of automatically identifying valvular degradation. Such methods may be a step towards computer-assisted diagnostics and telemedicine that provide the clinician with novel tools to improve patient care. [ABSTRACT FROM AUTHOR]

Aim: To investigate the correlation between the dorsal tongue porphyrin autofluorescence, revealed using VELscope, and Candida saprophytism. Material and methods: Consecutive patients underwent an autofluorescence examination by the VELscope device to establish the presence or absence of porphyrin fluorescence. A tongue swab was collected for the Candida cultural test. Sensitivity, specificity, accuracy, negative predictive value and positive predictive value were calculated considering the oral swab as the gold standard. The degree of agreement between the two tests was calculated using Cohen's K coefficient. Results: One hundred twenty-six patients were enrolled. Porphyrin fluorescence method showed a sensitivity of 78%, specificity of 76% and an accuracy of 78%. Negative predictive value and positive predictive value were respectively 90% and 59%. The strength of agreement between the two methods resulted to be moderate (k = 0.551). Conclusions: Off-label use of tongue autofluorescence examination to detect the presence of Candida species is characterized by a loss of porphyrin fluorescence. The high negative predictive value of porphyrin fluorescence loss suggests its use in preliminary selection of Candida carriers, in order to plan preventive and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Sport fencing is an open-skilled combat sport practiced around the world. Although previous research addressed kinematics of the lunge and fleche, there are currently no studies on the flick. The flick is a high-level action that involves bending the blade toward the opponent, much like a whip or fly-fishing cast. The aim of our research was to identify the kinematic variables that significantly influence scoring success in two elite foil fencers. In particular, we asked what aspect of the movement each individual fencer can change to improve their likelihood of scoring. Two elite foil fencers of similar skill were instructed to execute flicks at a dummy target that mimicked the opponent’s shoulder. High speed video (650 fps) captured the motion of the tip of the foil, blade of the foil, and limb joints; the latter were used to calculate joint angular velocities, hand height and distance throughout the flick. Scoring success was determined with a conventional scoring box. Our results showed that the two fencers exhibited significantly different kinematics, coordination and scoring. Using three complementary regression approaches, we showed that each fencer could improve scoring by changing specific aspects of their kinematics. For fencer A, only improvement in consistency in distance from the target would improve scoring. For fencer B, the changes were more complex. In addition to improvement in consistency in distance, fencer B could also increase (finger, wrist) or decrease (shoulder) joint angular velocity or improve consistency of limb joint angular velocities. Unexpectedly, and in contrast to common coaching practice, hand height had only a weak effect, possibly because both fencers had learnt to keep their hand high at the end of the action. In summary, our results emphasize that coaching of elite fencers should be individualized. [ABSTRACT FROM AUTHOR]

Purpose: To investigate cerebral microstructural alterations in patients treated with calcineurin inhibitors (CNI) after orthotopic liver transplantation (OLT) using quantitative magnetic resonance imaging (qMRI) and a cross-sectional study design. Methods: Cerebral qMRI was performed in 85 patients in a median 10 years after OLT compared to 31 healthy controls. Patients were treated with different dosages of CNI or with a CNI-free immunosuppression (CNI-free: n = 19; CNI-low: n = 36; CNI-standard: n = 30). T2-, T2*- and T2’- relaxation times, as well as apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in brain gray and white matter by using the regions of interest method. Results: In comparison to controls, patients revealed significantly increased T2, T2*, T2’, ADC and reduced FA, predominantly in the frontal white matter, indicating microstructural brain alterations represented by increased free water (increased T2), reduced neuronal metabolism (increased T2’) and a lower degree of spatial organization of the nervous fibers (reduced FA). CNI-low and CNI-free patients showed more alterations than CNI-standard patients. Analysis of their history revealed impairment of kidney function while under standard CNI dose suggesting that these patients may be more vulnerable to toxic CNI side-effects. Conclusion: Our findings suggest that the individual sensitivity to toxic side effects should be considered when choosing an appropriate immunosuppressive regimen in patients after liver transplantation. [ABSTRACT FROM AUTHOR]

Inverse dynamics problems are usually solved in the analysis of human gait to obtain reaction forces and moments at the joints. However, these actions are not the actual forces and moments supported by the joint structure, because they do not consider the forces of the muscles acting across the joint. Therefore, to analyse bone-on bone forces it is necessary to estimate those muscle forces. Usually, this problem is addressed by means of optimization algorithms. One of the parameters required to solve this problem is the musculotendon geometry. These data are usually taken from cadavers or MRI data from several subjects, different from the analysed subject. Then, the model is scaled to the subject morphology. This procedure constitutes a source of error. The goals of this work were two. First, to perform a sensitivity analysis of the influence of muscle insertion locations on the muscle forces acting on the hip joint and on the hip joint bone-on-bone forces. Second, to compare the hip joint bone-on-bone forces during gait cycle obtained through muscle insertion locations taken from a musculoskeletal model template and a scaling procedure to those obtained from a subject-specific model using an MRI of the subject. The problem was solved using OpenSim. Results showed that anatomical variability should be analysed from two perspectives. One the one hand, throughout the gait cycle, in a global way. On the other hand, at a characteristic instant of the gait cycle. Variations of ±1 cm in the position of the attachment points of certain muscles caused variations of up to 14.21% in averaged deviation of the muscle forces and 58.96% in the peak force in the modified muscle and variations up to 57.23% in the averaged deviation of the muscle force and up to 117.23% in the peak force in the rest of muscles. Then, the influence of that variability on muscle activity patterns and hip bone-on-bone forces could be described more precisely. A biomechanical analysis of a subject-specific musculoskeletal model was carried out. Using MRI data, variations up to 5 cm in the location of the insertion points were introduced. These modifications showed significant differences between the baseline model and the customized model: within the range [-12%, 10%] for muscle forces and around 35% of body weight for hip bone-on-bone forces. [ABSTRACT FROM AUTHOR]

Mechanical stimulation appears to play a key role in cartilage homeostasis maintenance, but it can also contribute to osteoarthritis (OA) pathogenesis. Accumulating evidence suggests that cartilage loading in the physiological range contributes to tissue integrity maintenance, whereas excessive or reduced loading have catabolic effects. However, how mechanical stimuli can regulate joint homeostasis is still not completely elucidated and few data are available on human cartilage. We aimed at investigating human OA cartilage response to ex vivo loading at physiological intensity. Cartilage explants from ten OA patients were subjected to ex vivo controlled compression, then recovered and used for gene and protein expression analysis of cartilage homeostasis markers. Compressed samples were compared to uncompressed ones in presence or without interleukin 1β (IL-1β) or interleukin 4 (IL-4). Cartilage explants compressed in combination with IL-4 treatment showed the best histological scores. Mechanical stimulation was able to significantly modify the expression of collagen type II (collagen 2), aggrecan, SOX9 transcription factor, cartilage oligomeric matrix protein (COMP), collagen degradation marker C2C and vascular endothelial growth factor (VEGF). Conversely, ADAMTS4 metallopeptidase, interleukin 4 receptor alpha (IL4Rα), chondroitin sulfate 846 epitope (CS846), procollagen type 2 C-propeptide (CPII) and glycosaminoglycans (GAG) appeared not modulated. Our data suggest that physiological compression of OA human cartilage modulates the inflammatory milieu by differently affecting the expression of components and homeostasis regulators of the cartilage extracellular matrix. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the concurrent validity of two different inertial measurement units for measuring spatiotemporal parameters during running on a treadmill, by comparing data with a high-speed video analysis (VA) at 1,000 Hz. Forty-nine endurance runners performed a running protocol on a treadmill at comfortable velocity (i.e., 3.25 ± 0.36 m.s-1). Those wearable devices (i.e., Stryd™ and RunScribe™ systems) were compared to a high-speed VA, as a reference system for measuring spatiotemporal parameters (i.e. contact time [CT], flight time [FT], step frequency [SF] and step length [SL]) during running at comfortable velocity. The pairwise comparison revealed that the Stryd™ system underestimated CT (5.2%, p < 0.001) and overestimated FT (15.1%, p < 0.001) compared to the VA; whereas the RunScribe™ system underestimated CT (2.3%, p = 0.009). No significant differences were observed in SF and SL between the wearable devices and VA. The intra class correlation coefficient (ICC) revealed an almost perfect association between both systems and high-speed VA (ICC > 0.81). The Bland-Altman plots revealed heteroscedasticity of error (r2 = 0.166) for the CT from the Stryd™ system, whereas no heteroscedasticity of error (r2 < 0.1) was revealed in the rest of parameters. In conclusion, the results obtained suggest that both foot pods are valid tools for measuring spatiotemporal parameters during running on a treadmill at comfortable velocity. If the limits of agreement of both systems are considered in respect to high-speed VA, the RunScribe™ seems to be a more accurate system for measuring temporal parameters and SL than the Stryd™ system. [ABSTRACT FROM AUTHOR]

Little is known regarding how repetitive finger movement performance impacts other fine motor control tasks, such as circle drawing, in persons with Parkinson’s disease (PD). Previous research has shown that impairments in repetitive finger movements emerge at rates near to and above 2 Hz in most persons with PD. Thus, the purpose of this study was to compare circle drawing performance in persons with PD that demonstrate impairment in repetitive finger movement and those that do not. Twenty-two participants with PD and twelve healthy older adults completed the study. Only participants with PD completed the repetitive finger movement task. From the kinematic data for the repetitive finger movement task, participants were grouped into Hasteners and Non-Hasteners. Participants with PD and the healthy older adults completed a series of circle drawing tasks at two different target sizes (1 cm and 2 cm) and three pacing conditions (Self-paced, 1.25 Hz, and 2.5 Hz). Kinematic and electromyography data were recorded and compared between groups. Results revealed that, in general, persons with PD demonstrate impairments in circle drawing and associated electromyography activity compared to healthy older adults. Moreover, persons with PD that hasten during repetitive finger movements demonstrate significantly increased movement rate during circle drawing, while those persons with PD that do not hasten demonstrate a significant increase in width variability. This suggests that differing motor control mechanisms may play a role in the performance of fine motor tasks in persons with PD. Continued research is needed to better understand differences in circle drawing performance among persons with PD to inform future development of patient-centered treatments. [ABSTRACT FROM AUTHOR]

In this paper, we present a new multi-focus microscope (MFM) system based on a phase mask and HiLo algorithm, achieving high-speed (20 volumes per second), high-resolution, low-noise 3-D fluorescent imaging. During imaging, the emissions from the specimen at nine different depths are simultaneously modulated and focused to different regions on a single CCD chip, i.e., the CCD chip is subdivided into nine regions to record images from the different selected depths. Next, HiLo algorithm is applied to remove the background noises and to form clean 3-D images. To visualize larger volumes, the nine layers are scanned axially, realizing fast 3-D imaging. In the imaging experiments, a mouse kidney sample of ~ 60 × 60 × 16 μm3 is visualized with only 10 raw images, demonstrating substantially enhanced resolution and contrast as well as suppressed background noises. The new method will find important applications in 3-D fluorescent imaging, e.g., recording fast dynamic events at multiple depths in vivo. [ABSTRACT FROM AUTHOR]

The adverse effects of heat on plant yield strongly depend on its duration and the phenological stage of the crops when the heat occurs. To clarify the effects of these two aspects of heat stress, systematic research was conducted under controlled conditions on 101 wheat cultivars of various geographic origin. Different durations of heat stress (5, 10 and 15 days) were applied starting from three developmental stages (ZD49: booting stage, ZD59: heading, ZD72: 6th day after heading). Various morphological, yield-related traits and physiological parameters were measured to determine the stress response patterns of the wheat genotypes under combinations of the duration and the timing of heat stress. Phenological timing significantly influenced the thousand-kernel weight and reproductive tiller number. The duration of heat stress was the most significant component in determining both seed number and seed weight, as well as the grain yield consequently, explaining 51.6% of its phenotypic variance. Irrespective of the developmental phase, the yield-related traits gradually deteriorated over time, and even a 5-day heat stress was sufficient to cause significant reductions. ZD59 was significantly more sensitive to heat than either ZD49 or ZD72. The photosynthetic activity of the flag leaf was mostly determined by heat stress duration. No significant associations were noted between physiological parameters and heat stress response as measured by grain yield. Significant differences were observed between the wheat genotypes in heat stress responses, which varied greatly with developmental phase. Based on the grain yield across developmental phases and heat stress treatments, eight major response groups of wheat genotypes could be identified, and among them, three clusters were the most heat-tolerant. These cultivars are currently included in crossing schemes, partially for the identification of the genetic determinants of heat stress response and partially for the development of new wheat varieties with better heat tolerance. [ABSTRACT FROM AUTHOR]

The bovine dry period is a non-lactating period between consecutive lactations characterized by mammary gland involution and redevelopment phases to replace senescent mammary epithelial cells with active cells primed for the next lactation. Dairy cows exposed to heat stress during the dry period experience milk yield reductions between 3–7.5 kg/d in the next lactation, partially attributed to processes associated with mammary cell growth and turnover during the dry period. However, the carry-over impact of dry period heat stress on mammary morphology during lactation has yet to be determined. In the current study, we hypothesized that exposure to heat stress during the dry period would alter alveolar microstructure and cellular turnover (i.e. proliferation and apoptosis) during lactation. Cows were either subjected to heat stress (HT, access to shade; n = 12) or cooling (CL, access to shade, fans, and soakers; n = 12) for a 46 d dry period. Upon calving, all cows were treated similarly with access to cooling for their entire lactation. Six cows per treatment were randomly selected for mammary gland biopsies at 14, 42, and 84 days in milk. Tissues were sectioned and stained for histological analysis. During lactation, HT cows produced 4 kg less colostrum and 3.7 kg less milk compared with CL cows. Lactating mammary gland microstructure was impacted after exposure to dry period heat stress; HT cows had fewer alveoli and a higher proportion of connective tissue in the mammary gland relative to CL cows, however alveolar area was similar between treatments. Rates of mammary epithelial cell proliferation and apoptosis were similar between treatment groups. This suggests that heat stress exposure during the dry period leads to reductions in milk yield that could be caused, in part, by a reduction in alveoli number in the lactating mammary gland but not to dynamic alterations in cellular turnover once lactation is established. [ABSTRACT FROM AUTHOR]

The aim of this project was to investigate the effects of different types of graft material, and different remaining segments of the native TM on its motion. In twelve human temporal bones, controlled TM perforations were made to simulate three different conditions. (1) Central perforation leaving both annular and umbo rims of native TM. (2) Central perforation leaving only a malleal rim of native TM. (3) Central perforation leaving only an annular rim of native TM. Five different graft materials (1) perichondrium (2) silastic (3) thin cartilage (4) thick cartilage (5) Lotriderm® cream were used to reconstruct each perforation condition. Umbo and stapes vibrations to acoustic stimuli from 250 to 6349 Hz were measured using a scanning laser Doppler vibrometer. Results showed that at low frequencies: in the Two Rims condition, all grafting materials except thick cartilage and Lotriderm cream showed no significant difference in umbo velocity from the Normal TM, while only Lotriderm cream showed a significant decrease in stapes velocity; in the Malleal Rim condition, all materials showed a significant decrease in both umbo and stapes velocities; in the Annular Rim condition, all grafting materials except Lotriderm and perichondrium showed no significant difference from the Normal TM in stapes velocity. Umbo data might not be reliable in some conditions because of coverage by the graft. At middle and high frequencies: all materials showed a significant difference from the Normal TM in both umbo and stapes velocities for all perforation conditions except in the Annular Rim condition, in which silastic and perichondrium showed no significant difference from the Normal TM at umbo velocity in the middle frequencies. In the low frequencies, the choice of repair material does not seem to have a large effect on sound transfer. Our data also suggests that the annular rim could be important for low frequency sound transfer. [ABSTRACT FROM AUTHOR]

Purpose: To describe individual sleeping patterns and nocturnal cardiac autonomic activity of National team female soccer players during an international tournament. Materials and methods: Twenty elite female soccer players (aged 25.2±3.1 years) wore wrist actigraph units and heart rate (HR) monitors during night-sleep throughout 9 consecutive days (6 day-time training sessions [DT], 2 day-time matches [DM], and 1 evening-time match [EM]) of an international tournament. Training and match loads were monitored using the session-rating of perceived exertion (s-RPE) and wearable 18-Hz GPS (total distance covered [TD], training and match exposure time, and high-speed running [HSR]) to characterize training and match loads. Results: Individually, s-RPE, TD, exposure time, and HSR during training sessions ranged from 20 to 680 arbitrary units (AU), 892 to 5176 m, 20 to 76 min, and 80 to 1140 m, respectively. During matches, s-RPE, TD, exposure time, and HSR ranged from 149 to 876 AU, 2236 to 11210 m, 20 to 98 min, and 629 to 3213 m, respectively. Individually, players slept less than recommended (<7 hours) on several days of the tournament, especially after EM (n = 8; TST ranging between 6:00–6:54 h). Total sleep time coefficient of variation (CV) ranged between 3.1 and 18.7%. However, all players presented good sleep quality (i.e., sleep efficiency ≥75%; individual range between: 75–98%) on each day of the tournament. Most of the players presented small fluctuations in nocturnal cardiac autonomic activity (individual nocturnal heart rate variability [HRV] ranged from 3.91–5.37 ms and HRV CV ranged from 2.8–9.0%), while two players presented higher HRV CV (11.5 and 11.7%; respectively). Conclusion: Overall, this study highlights the substantial individual variability in sleep and HRV measures, suggesting the adoption of an individual approach to monitor sleep, training and match loads and recovery, to better understand how players cope with highly demanding competitions. [ABSTRACT FROM AUTHOR]

Transient receptor potential (TRP) proteins form Ca2+-permeable, nonselective cation channels, but their role in neuronal Ca2+ homeostasis is elusive. In the present paper, we show that TRPC channels potently regulate synaptic plasticity by changing the presynaptic Ca2+-homeostasis of hippocampal neurons. Specifically, loss of TRPC1/C4/C5 channels decreases basal-evoked secretion, decreases the pool size of readily releasable vesicles, and accelerates synaptic depression during high-frequency stimulation (HFS). In contrast, primary TRPC5 channel-expressing neurons, identified by a novel TRPC5–τ-green fluorescent protein (τGFP) knockin mouse line, show strong short-term enhancement (STE) of synaptic signaling during HFS, indicating a key role of TRPC5 in short-term plasticity. Lentiviral expression of either TRPC1 or TRPC5 turns classic synaptic depression of wild-type neurons into STE, demonstrating that TRPCs are instrumental in regulating synaptic plasticity. Presynaptic Ca2+ imaging shows that TRPC activity strongly boosts synaptic Ca2+ dynamics, showing that TRPC channels provide an additional presynaptic Ca2+ entry pathway, which efficiently regulates synaptic strength and plasticity. [ABSTRACT FROM AUTHOR]

The mammalian olfactory bulb (OB) plays an essential role in odor processing during the perception of smell. Optical imaging of the OB has proven to be a key tool in elucidating the spatial odor mapping and temporal dynamics that underlie higher-order odor processing. Much is known about the activation of olfactory sensory neuron (OSN) glomerular responses in the dorsal olfactory bulb (dOB) during odor presentation. However, the dorsal bulb provides access to only approximately 25% of all glomeruli, and little is known about how the lateral bulb functions during this critical process. Here, we report, for the first time, simultaneous measurements of OSN glomerular activity from both the dOB and the lateral olfactory bulb (lOB), thus describing odor-specific spatial mapping and the temporal dynamics of olfactory input to both the dorsal and lateral bulb. Odor responses in the lateral bulb tended to be most prominent in the dorso-lateral (D-L) region. Lateral glomeruli became active in a dorso-ventral (D-V) sequence upon odor inhalation, unlike the anterio-posterior (A-P) activity wave typical of the dorsal glomeruli. Across the entire D-L bulb, the spatial organization of these dynamics can be explained neither by the purely mechanosensitive dynamics (to breathing clean air) nor by the response amplitudes across glomeruli. Instead, these dynamics can be explained by a combination of zonal receptor distributions, associated OB projections, and air flow paths across the epithelium upon inhalation. Remarkably, we also found that a subset of OSN glomeruli in the lOB was highly sensitive to extranasal air pressure changes, a response type that has not been reported in dorsal glomeruli. [ABSTRACT FROM AUTHOR]

Magnetic Resonance Imaging (MRI) has become a valuable imaging modality in ophthalmology, especially for the diagnosis and treatment planning of patients with uveal melanoma, the most common primary intra-ocular tumor. We aim to develop and evaluate the value of silent Zero Echo Time (ZTE) MRI to image patients with ocular tumors at 7Tesla. Therefore, ZTE and different types of magnetization-prepared ZTE (FLAIR, SPIR, T2 and Saturation recovery), have been developed. After an initial validation with 7 healthy subjects, nine patients with an eye tumor have been evaluated. The ZTE scans were compared to their Cartesian equivalent in terms of contrast, motion-sensitivity, diagnostic quality and patient comfort. All volunteers and especially the patients reported a more comfortable experience during the ZTE scans, which had at least a 10 dB lower sound pressure. The image contrast in the native ZTE was poor, but in the different magnetization-prepared ZTE, the eye lens, cornea and retina were clearly discriminated. Overall the T2-prepared scan yielded the best contrast, especially between tumor and healthy tissue, and proved to be robust against eye motion. Although the intrinsic 3D nature of the ZTE-technique provides an accurate analysis of the tumor morphology, the quality of the ZTE-images is lower than their Cartesian equivalent. In conclusion, the quality of magnetization-prepared ZTE images is sufficient to assess the 3D tumor morphology, but insufficient for more detailed evaluations. As such this technique can be an option for patients who cannot comply with the sound-levels of Cartesian scans, but for other patients the conventional Cartesian scans offer a better image quality. [ABSTRACT FROM AUTHOR]

Background: To analyze the goodness of fit of the load-velocity relationship in a machine-based, single-joint exercise performed both in a bilateral and unilateral manner, as well as to study its accuracy to estimate one repetition maximum (1-RM). Methods: Fifteen resistance trained males performed an incremental test in the bilateral and unilateral leg extension exercise up to the 1-RM in two separate occasions. Mean vertical velocity of the weight plates in the leg extension machine was measured for every repetition using a smartphone application (My Lift). Results: Linear regression analyses showed a high goodness of fit (R2 > 0.93) and small standard errors of estimate (SEE < 5%1-RM) both in the bilateral and unilateral leg extension when individual load-velocity regressions for each participant were computed. Unilateral load-velocity relationships showed significant differences in the intercept of the regression line with the Y-axis and the velocity at each percentage of the 1-RM (Cohen’s d > 1.0, p< 0.05). Finally, non-significant differences were observed between actual and estimated 1-RM from the load-velocity relationships (r = 0.88.0–96, Cohen’s d < 0.2, p> 0.05). Conclusions: This proof of concept highlights that computing load-velocity relationships in a machine-based, single-joint, angular exercise can be appropriately performed by measuring the mean vertical velocity of the weight plates. These results could help strength and conditioning researchers and coaches who wish to analyze load-velocity relationship in other common machine-based exercises. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between sympathetic activity, reactive hyperemia and brachial artery flow-mediated dilation (FMD). Background: It is claimed that major surgery has an impact on endothelial function, as observed by post-operative reduced brachial artery FMD response. However, another explanation for the observed reduced FMD response post-operatively may be sympathetic stress-induced reduction in blood flow. Methods: Seventeen healthy volunteers with a median age (25th-75th percentiles) of 23.5 (23–24.8) years were recruited. Participants’ brachial blood flow and FMD response were measured (i) during normal non-stress conditions (Normal1); (ii) during exposure to ice water; and (iii) afterwards, under normal non-stress conditions (Normal2). We continuously measured arterial blood pressure (Finometer), heart rate (ECG), skin blood flow of the index finger (laser Doppler), and brachial artery blood flow and diameter (Ultrasound Doppler). Measurements were taken at baseline; before a 5-min suprasystolic forearm occlusion; and following a 3-min post-occlusion, to measure reactive hyperemia and FMD. Results: Median (25th-75th percentiles) FMD response after exposure to ice water was reduced compared to non-stress conditions [4.9 (2.9–8.4) % during ice water vs. 9.7 (7.6–12.2) % Normal1 and 9.7 (6.4–10.3) % Normal2, P < 0.001]. Blood flow 60 s after cuff-deflation during ice water exposure was significantly reduced to 328 (289–421) mL compared to non-stress conditions (both P < 0.05). No differences were observed between Normal1 [446 (359–506) mL] and Normal2 [455 (365–515) mL] (both P > 0.05). Heart rate significantly increased during ice water exposure [67 (59–69) beats/min)] compared to 55 (49–60) beats/min during Normal1 and 54 (47–60) beats/min during Normal2 (both P < 0.05). MAP did not change during Normal1 [72 (64–84)] or during Normal2 [71 (65–81) mm Hg] (both P > 0.05), but increased to 86 (75–98) mm Hg during ice water exposure (P < 0.05). Conclusions: Increased sympathetic activity resulted in decreased blood flow and brachial artery FMD response in healthy volunteers, independent of endothelial dysfunction. Future studies should adjust for blood flow when interpreting the FMD response. [ABSTRACT FROM AUTHOR]

Objective: Systematic Review was used to evaluate the efficacy and safety of Dalfampridine (DAP) in the treatment of Mobility Disability (MS) in patients with Multiple Sclerosis. Methods: Clinical randomized controlled studies about DAP and placebo in the treatment of Mobility Disability in patients with Multiple Sclerosis until March 2019 were explored by searching Embase, PubMed, Cochrane, Web of Knowledge, and ClinicalTrials.gov. Literature screening, data extraction, quality assessment, and statistical analysis were performed by using Stata 14.0. Results: 10 papers were included in the meta-analysis, and the number of patients was 2100. In conclusion, the application of DAP in clinical can significantly improve the Mobility Disability of patients [OR = 2.73, 95%CI (1.66, 4.50), P<0.001, I2 = 74.1%] and boost the mobility speed of patients in Timing 24 Minute Walk Test (T24FW) [SMD = 3,08, 95%CI(1,58, 4.58), P<0.001, I2 = 98.7%]. There are no significant differences of the incidence of adverse events [RR = 1.06, 95%CI (0.99, 1.14), P = 0.928, I2 = 0.0%] and urinary tract infection [RR = 1.21, 95%CI(0.91, 1.60), P = 0.145, I2 = 37.2%] between the DAP test group (Doses≤10 mg) and the placebo control group, and the incidence of adverse events [RR = 1.14, 95%CI(1.02, 1.28), P = 0.793, I2 = 0.0%] and urinary tract infection[RR = 3.05, 95%CI(1.04, 8.99), P = 0.680, I2 = 0.0%] for the DAP test group (Doses>10 mg) is a litter higher than the placebo control group. Conclusion: DAP can effectively improve Mobility Disability in patients with Multiple Sclerosis, which is safe and reliable in specific DAP usage doses. [ABSTRACT FROM AUTHOR]

In the mouse spinal cord, V1 interneurons are a heterogeneous population of inhibitory spinal interneurons that have been implicated in regulating the frequency of the locomotor rhythm and in organizing flexor and extensor alternation. By introducing archaerhodopsin into engrailed-1-positive neurons, we demonstrate that the function of V1 neurons in locomotor-like activity is more complex than previously thought. In the whole cord, V1 hyperpolarization increased the rhythmic synaptic drive to flexor and extensor motoneurons, increased the spiking in each cycle, and slowed the locomotor-like rhythm. In the hemicord, V1 hyperpolarization accelerated the rhythm after an initial period of tonic activity, implying that a subset of V1 neurons are active in the hemicord, which was confirmed by calcium imaging. Hyperpolarizing V1 neurons resulted in an equalization of the duty cycle in flexor and extensors from an asymmetrical pattern in control recordings in which the extensor bursts were longer than the flexor bursts. Our results suggest that V1 interneurons are composed of several subsets with different functional roles. Furthermore, during V1 hyperpolarization, the default state of the locomotor central pattern generator (CPG) is symmetrical, with antagonist motoneurons each firing with an approximately 50% duty cycle. We hypothesize that one function of the V1 population is to set the burst durations of muscles to be appropriate to their biomechanical function and to adapt to the environmental demands, such as changes in locomotor speed. [ABSTRACT FROM AUTHOR]

Congenital nystagmus, involuntary oscillating small eye movements, is commonly thought to originate from aberrant interactions between brainstem nuclei and foveal cortical pathways. Here, we investigated whether nystagmus associated with congenital stationary night blindness (CSNB) results from primary deficits in the retina. We found that CSNB patients as well as an animal model (nob mice), both of which lacked functional nyctalopin protein (NYX, nyx) in ON bipolar cells (BCs) at their synapse with photoreceptors, showed oscillating eye movements at a frequency of 4–7 Hz. nob ON direction-selective ganglion cells (DSGCs), which detect global motion and project to the accessory optic system (AOS), oscillated with the same frequency as their eyes. In the dark, individual ganglion cells (GCs) oscillated asynchronously, but their oscillations became synchronized by light stimulation. Likewise, both patient and nob mice oscillating eye movements were only present in the light when contrast was present. Retinal pharmacological and genetic manipulations that blocked nob GC oscillations also eliminated their oscillating eye movements, and retinal pharmacological manipulations that reduced the oscillation frequency of nob GCs also reduced the oscillation frequency of their eye movements. We conclude that, in nob mice, synchronized oscillations of retinal GCs, most likely the ON-DCGCs, cause nystagmus with properties similar to those associated with CSNB in humans. These results show that the nob mouse is the first animal model for a form of congenital nystagmus, paving the way for development of therapeutic strategies. [ABSTRACT FROM AUTHOR]