Portable Microfluidic Viscometer for Formulation Development and in Situ Quality Control of Protein and Antibody Solutions.

Viscosity of protein solutions is a critical product quality attribute for protein therapeutics such as monoclonal antibodies. Here we introduce a portable single-use analytical chip-based viscometer for determining the viscosity of protein solutions using low sample volumes of 10 µL. Through the combined use of a microfluidic viscometer, a smartphone camera for image capture, and an automated data processing algorithm for the calculation of the viscosity of fluids, we enable measurement of viscosity of multiple samples in parallel. We first validate the viscometer using glycerol-water mixtures and subsequently demonstrate the ability to perform rapid characterization of viscosity in four different monoclonal antibody formulations in a broad concentration (1 to 320 mg/mL) and viscosity (1 to 600 cP) range, showing excellent agreement with values obtained by a conventional cone-plate rheometer. Not only does the platform offer benefits of viscosity measurements using minimal sample volumes, but enables higher throughput compared to gold-standard methodologies owing to multiplexing of the measurement and single-use characteristics of the viscometer, thus showing great promise in developability studies. Additionally, as our platform has the capability of performing viscosity measurements at the point of sample collection, it offers the opportunity to employ viscosity measurement as an in situ quality control of therapeutic proteins and antibodies.

The rostral micro-tooth morphology of blue marlin, Makaira nigricans.

Billfish rostra potentially have several functions; however, their role in feeding is unequivocal in some species. Recent work linked morphological variation in rostral micro-teeth to differences in feeding behavior in two billfish species, the striped marlin (Kajikia audax) and the sailfish (Istiophorus platypterus). Here, we present the rostral micro-tooth morphology for a third billfish species, the blue marlin (Makaira nigricans), for which the use of the rostrum in feeding behavior is still undocumented from systematic observations in the wild. We measured the micro-teeth on rostrum tips of blue marlin, striped marlin, and sailfish using a micro-computed tomography approach and compared the tooth morphology among the three species. This was done after an analysis of video-recorded hunting behavior of striped marlin and sailfish revealed that both species strike prey predominantly with the first third of the rostrum, which provided the justification to focus our analysis on the rostrum tips. In blue marlin, intact micro-teeth were longer compared to striped marlin but not to sailfish. Blue marlin had a higher fraction of broken teeth than both striped marlin and sailfish, and broken teeth were distributed more evenly on the rostrum. Micro-tooth regrowth was equally low in both marlin species but higher in sailfish. Based on the differences and similarities in the micro-tooth morphology between the billfish species, we discuss potential feeding-related rostrum use in blue marlin. We put forward the hypothesis that blue marlin might use their rostra in high-speed dashes as observed in striped marlin, rather than in the high-precision rostral strikes described for sailfish, possibly focusing on larger prey organisms.

Effectiveness of the miWe Simulator Training on Powered Wheelchair-driving Skills: A Randomized Controlled Trial.

OBJECTIVES: To evaluate the effectiveness of a home-based simulator training, in comparison with a videogame-based training, in terms of powered wheelchair driving skills, skills use in a real-world setting, and driving confidence. DESIGN: Single-blinded randomized controlled trial. SETTING: Community. PARTICIPANTS: New powered wheelchair users (N=47) randomly allocated to simulator group (n=24, 2 drop-out) and control group (n=23, 3 drop-out). INTERVENTIONS: The miWe wheelchair simulator (simulator group) or a kart driving videogame (control group) was setted-up at participants' homes (computer + joystick). They were instructed to use it at least 20 minutes every 2 days, during a period of 2 weeks. PRIMARY OUTCOME MEASURE(S): Assessments were done at baseline (T1) and post-training (T2) using the Wheelchair Skills Test Questionnaire (WST-Q, version 4.1), Wheelchair Confidence Scale (WheelCon), Assistive Technology Outcomes Profile for Mobility, and Life-Space Assessment (LSA). The time necessary to complete 6 WST tasks was measured with a stopwatch. RESULTS: Participants of the simulator group significantly increased their WST-Q capacity score at T2 by 7.5% (P<.05), whereas the control group remained at the same score (P=.218). Participants of both groups rolled backward and went through a door significantly faster at T2 (P=.007; P=.016), but their speed did not change for the other skills. The WheelCon score significantly increased after training (+4% for the control group and +3.5% for the simulator group, P=.001). There was no T1-T2 difference between groups for the WST-Q performance scores (P=.119), the ATOP-Activity (P=.686), the ATOP-Participation scores (P=.814), and the LSA score (P=.335). No adverse events or side effects were reported during data collection or training. CONCLUSIONS: Participants of both groups improved some skills and their wheelchair driving confidence. The simulator training group also demonstrated a modest post-training gain in their WST-Q capacity, but more studies would be needed to explore the long-term effects of the McGill immersive wheelchair simulator (miWe) simulator on driving skills.

Creating synergies among education/research, practice, and policy environments to build capacity for the scholar role in occupational therapy and physiotherapy in the Canadian context.

Scholarly practice (SP) is considered a key competency of occupational therapy and physiotherapy. To date, the three sectors-education/research, practice, and policy/regulation-that support SP have been working relatively independently. The goals of this project were to (a) understand how representatives of the three sectors conceptualize SP; (b) define each sector's individual and collective roles in supporting SP; (c) identify factors influencing the enactment of SP and the specific needs of how best to support SP; and (d) co-develop goals and strategies to support SP across all sectors. We used interpretive description methodology. Consistent with an integrated knowledge translation approach, partners representing the three sectors across Canada recruited individuals from each sector, developed the content and questions for three focus groups, and collected and analyzed the data. Inspired by the Consolidated Framework for Implementation Research, we developed the questions for the second focus group. We analyzed the data using an inductive thematic analysis method. Thirty-nine participants from the three sectors participated. Themes related to participants' conceptualization of SP included (a) ongoing process, (b) reflective process, (c) broad concept, and (d) collective effort. Themes describing factors influencing and supporting SP were (a) recognition, (b) appropriate conceptualization, (c) social network, (d) accessibility to resources, and (e) forces outside of practitioners' effort. Goals to support SP included (a) further recognizing SP, (b) sustaining SP competency, and (c) ensuring access to information. SP requires collaborative and integrated intersectoral support and further recognition of its importance through the collaboration of multiple stakeholders.

Lacunae rostralis: A new structure on the rostrum of sailfish Istiophorus platypterus.

Recent comparative studies of billfishes (Istiophoridae and Xiphiidae) have provided evidence of differences in the form and function of the rostra (bill) among species. Here, we report the discovery of a new structure, lacuna rostralis, on the rostra of sailfish Istiophorus platypterus, which is absent on the rostra of swordfish Xiphias gladius, striped marlin Kajikia audax and blue marlin Makaira nigricans. The lacunae rostralis are small cavities that contain teeth. They were found on the ventral rostrum surface of all I. platypterus specimens examined and dorsally in half of them. Ventrally, the lacunae rostralis were most prominent in the mid-section of the rostrum. Dorsally, they occurred closer to the tip. The density of lacunae rostralis increased towards the rostrum tip but, because they are smaller in size, the percentage of rostrum coverage decreased. The teeth located within the lacunae rostralis were found to be different in size, location and orientation from the previously identified micro-teeth of billfish. We propose two potential functions of the lacunae rostralis that both relate to the use of the bill in feeding: mechanoreception of prey before tapping it with the bill and more efficient prey handling via the creation of suction, or physical grip.

Gaze behavior during pedestrian interactions in a community environment: a real-world perspective.

Locomotor adaptations, as required for community walking, rely heavily on the sense of vision. Little is known, however, about gaze behavior during pedestrian interactions while ambulating in the community. Our objective was to characterize gaze behavior while walking in a community environment and interacting with pedestrians of different locations and directions. Twelve healthy young individuals were assessed as they walked in a shopping mall from a pre-set location to a goal located 20 m ahead. Eye movements were recorded with a binocular eye-tracker and temporal distance factors were assessed using wearable sensors from a full-body motion capture system. Participants exhibited more numerous and longer gaze episodes on pedestrians (GEP) that were walking in the same direction as themselves vs. those that were in the opposite direction. The relative durations of GEPs, however, showed no significant differences between pedestrians walking in the same vs. opposite direction. Longer durations of GEPs were also observed for centrally located pedestrians compared to those located on either side, but this was the case only for pedestrians that were walking in the same direction as participants. In addition, pedestrians in the centre, and even more so those on the right, were fixated at farther distances compared to those on the left. Results indicate that healthy young individuals modulate their gaze behavior as a function of the location and direction of pedestrians when ambulating in a community environment. The observed modulation is interpreted as being caused by an interplay between collision risk, pedestrian visibility, presence of leaders and social conventions (right-sided circulation). Present results also establish baseline measures for the quantification of defective visuomotor strategies in individuals with mobility disorders.

The association of care transitions measure-15 score and outcomes after discharge from the NICU.

BACKGROUND: Our objectives were (1) to describe Care Transitions Measure (CTM) scores among caregivers of preterm infants after discharge from the neonatal intensive care unit (NICU) and (2) to describe the association of CTM scores with readmissions, enrollment in public assistance programs, and caregiver quality of life scores. METHODS: The study design was a cross-sectional study. We estimated adjusted associations between CTM scores (validated measure of transition) with outcomes using unconditional logistic and linear regression models and completed an E-value analysis on readmissions to quantify the minimum amount of unmeasured confounding. RESULTS: One hundred sixty-nine parents answered the questionnaire (85% response rate). The majority of our sample was Hispanic (72.5%), non-English speaking (67.1%) and reported an annual income of <$20,000 (58%). Nearly 28% of the infants discharged from the NICU were readmitted within a year from discharge. After adjusting for confounders, we identified that a positive 10-point change of CTM score was associated with an odds ratio (95% CI) of 0.74 (0.58, 0.98) for readmission (p = 0.01), 1.02 (1, 1.05) for enrollment in early intervention, 1.03 (1, 1.05) for enrollment in food assistance programs, and a unit change (95% CI) 0.41 (0.27, 0.56) in the Multicultural Quality of Life Index score (p < 0.0001). The associated E-value for readmissions was 1.6 (CI 1.1) suggesting moderate confounding. CONCLUSION: The CTM may be a useful screening tool to predict certain outcomes for infants and their families after NICU discharge. However, further work must be done to identify unobserved confounding factors such as parenting confidence, problem-solving and patient activation.

Augmented feedback for manual wheelchair propulsion technique training in a virtual reality simulator.

BACKGROUND: Motor learning of appropriate manual wheelchair propulsion is critical, as incorrect technique elevates risk for upper extremity pain. Virtual reality simulators allow users to practice this complex task in a safe and realistic environment. Additionally, augmented feedback (AF) may be provided in order to optimize learning. The purpose of this study was to investigate the effects of providing AF with various delivery schedules on motor learning and transfer of this skill to over-ground propulsion. METHODS: Thirty healthy young adults were randomly assigned to three groups. During a virtual reality propulsion training session, the high-frequency AF group received AF in the form of knowledge of performance throughout all propulsion training; the faded AF group received this AF in a faded schedule (high relative frequency of AF early in practice, with relative frequency of AF provision diminishing throughout practice); and the control group underwent training with no AF. Propulsion assessments were performed at baseline and 48 h after practice in both virtual and real environments to measure retention and transfer, respectively. RESULTS: Compared to the control group, both feedback groups exhibited significant improvements in contact angle and push frequency in both environments after training. Small, non-significant between-group differences were also found between the high-frequency and faded feedback groups. CONCLUSION: Virtual reality training is an effective learning intervention for acquisition, retention, and transfer of appropriate manual wheelchair propulsion technique when such training includes AF regarding propulsion biomechanics.

Walking with robot-generated haptic forces in a virtual environment: a new approach to analyze lower limb coordination.

BACKGROUND: Walking with a haptic tensile force applied to the hand in a virtual environment (VE) can induce adaptation effects in both chronic stroke and non-stroke individuals. These effects are reflected in spatiotemporal outcomes such as gait speed. However, the concurrent kinematic changes occurring in bilateral lower limb coordination have yet to be explored. METHODS: Chronic stroke participants were stratified based on overground gait speed into lower functioning (LF < 0.8 m/s, N = 7) and higher functioning (HF ≥ 0.8 m/s, N = 7) subgroups. These subgroups and an age-matched control group (N = 14, CG) walked on a self-paced treadmill in a VE with either robot-generated haptic leash forces delivered to the hand and then released or with an instrumented cane. Walking in both leash (10 and 15 N) and cane conditions were compared to pre-force baseline values to evaluate changes in lower limb coordination outcomes. RESULTS: All groups showed some kinematic changes in thigh, leg and foot segments when gait speed increased during force and post-force leash as well as cane walking. These changes were also reflected in intersegmental coordination and 3D phase diagrams, which illustrated increased intersegmental trajectory areas (p < 0.05) and angular velocity. These increases could also be observed when the paretic leg transitions from stance to swing phases while walking with the haptic leash. The Sobolev norm values accounted for both angular position and angular velocity, providing a single value for potentially quantifying bilateral (i.e. non-paretic vs paretic) coordination during walking. These values tended to increase (p < 0.05) proportionally for both limbs during force and post-force epochs as gait speed tended to increase. CONCLUSIONS: Individuals with chronic stroke who increased their gait speed when walking with tensile haptic forces and immediately after force removal, also displayed moderate concurrent changes in lower limb intersegmental coordination patterns in terms of angular displacement and velocity. Similar results were also seen with cane walking. Although symmetry was less affected, these findings appear favourable to the functional recovery of gait. Both the use of 3D phase diagrams and assigning Sobolev norm values are potentially effective for detecting and quantifying these coordination changes.

Feasibility and preliminary efficacy of a combined virtual reality, robotics and electrical stimulation intervention in upper extremity stroke rehabilitation.

BACKGROUND: Approximately 80% of individuals with chronic stroke present with long lasting upper extremity (UE) impairments. We designed the perSonalized UPper Extremity Rehabilitation (SUPER) intervention, which combines robotics, virtual reality activities, and neuromuscular electrical stimulation (NMES). The objectives of our study were to determine the feasibility and the preliminary efficacy of the SUPER intervention in individuals with moderate/severe stroke. METHODS: Stroke participants (n = 28) received a 4-week intervention (3 × per week), tailored to their functional level. The functional integrity of the corticospinal tract was assessed using the Predict Recovery Potential algorithm, involving measurements of motor evoked potentials and manual muscle testing. Those with low potential for hand recovery (shoulder group; n = 18) received a robotic-rehabilitation intervention focusing on elbow and shoulder movements only. Those with a good potential for hand recovery (hand group; n = 10) received EMG-triggered NMES, in addition to robot therapy. The primary outcomes were the Fugl-Meyer UE assessment and the ABILHAND assessment. Secondary outcomes included the Motor Activity Log and the Stroke Impact Scale. RESULTS: Eighteen participants (64%), in either the hand or the shoulder group, showed changes in the Fugl-Meyer UE or in the ABILHAND assessment superior to the minimal clinically important difference. CONCLUSIONS: This indicates that our personalized approach is feasible and may be beneficial in improving UE function in individuals with moderate to severe impairments due to stroke. TRIAL REGISTRATION: ClinicalTrials.gov NCT03903770. Registered 4 April 2019. Registered retrospectively.

Impact of Confounding on Cost, Survival, and Length-of-Stay Outcomes for Neonates with Hypoplastic Left Heart Syndrome Undergoing Stage 1 Palliation Surgery.

The objective of this analysis was to update trends in LOS and costs by survivorship and ECMO use among neonates with hypoplastic left heart syndrome (HLHS) undergoing stage 1 palliation surgery using 2016 data from the Healthcare Cost and Utilization Project Kids' Inpatient Database. We identified neonates ≤ 28 days old with HLHS undergoing Stage 1 surgery, defined as a Norwood procedure with modified Blalock-Taussig (BT) shunt, Sano modification, or both. Multivariable regression with year random effects was used to compare LOS and costs by hospital region, case volume, survivorship, and ECMO vs. no ECMO. An E-value analysis, an approach for conducting sensitivity analysis for unmeasured confounding, was performed to determine if unmeasured confounding contributed to the observed effects. Significant differences in total costs, LOS, and mortality were noted by hospital region, ECMO use, and sub-analyses of case volume. However, other than ECMO use and mortality, the maximum E-value confidence interval bound was 1.71, suggesting that these differences would disappear with an unmeasured confounder 1.71 times more associated with both the outcome and exposure (e.g., socioeconomic factors, environment, etc.) Our findings confirm previous literature demonstrating significant resource utilization among Norwood patients, particularly those undergoing ECMO use. Based on our E-value analysis, differences by hospital region and case volume can be explained by moderate unobserved confounding, rather than a reflection of the quality of care provided. Future analyses on surgical quality must account for unobserved factors to provide meaningful information for quality improvement.

Eradication of eucalyptus sprouts after chemical weeding over time in State of Bahia, Brazil.

This study evaluated the eradication of eucalyptus sprouts after chemical weeding using a diagrammatic scale over time. The research was conducted in fields planted with eucalyptus in forest reform areas, in Itabela, Bahia, Brazil, during the pre-planting herbicide application. The application was carried out in five fields, which were considered as sample units of the different treatments. The effectiveness of chemical weeding for controlling sprout growth was evaluated in fifty plants per treatment, randomly selected in three periods after application. The plants were evaluated visually using a diagrammatic scale to assign scores between 1 and 5 to the sprout control percentage. After the visual evaluations, the frequency distribution of the sprouting percentage for each score was calculated. Subsequently, the scores were submitted to a clustering analysis by the Ward method, to evaluate the relationship between different fields and periods for each treatment in homogeneous clusters. The results showed that treatments only controlled the sprouts in the short term, without providing effective eradication. The diagrammatic scoring scale allowed evaluating the vegetative vigor of the eucalyptus sprouts, generating interpretable information on the different evaluated treatments, making it a useful tool for managing silvicultural treatments and evaluating the application efficacy of phytosanitary products.

Will virtual rehabilitation replace clinicians: a contemporary debate about technological versus human obsolescence.

This article is inspired by a pseudo Oxford-style debate, which was held in Tel Aviv University, Israel at the International Conference on Virtual Rehabilitation (ICVR) 2019, which is the official conference of the International Society for Virtual Rehabilitation. The debate, between two 2-person teams with a moderator, was organized by the ICVR Program committee to address the question "Will virtual rehabilitation replace clinicians?" It brought together five academics with technical, research, and/or clinical backgrounds-Gerry Fluet, Tal Krasovsky, Anat Lubetzky, Philippe Archambault, W. Geoffrey Wright-to debate the pros and cons of using virtual reality (VR) and related technologies to help assess, diagnose, treat, and track recovery, and more specifically investigate the likelihood that advanced technology will ultimately replace human clinicians. Both teams were assigned a side to defend, whether it represented their own viewpoint or not, and to take whatever positions necessary to make a persuasive argument and win the debate. In this paper we present a recapitulation of the arguments presented by both sides, and further include an in-depth consideration of the question. We attempt to judiciously lay out a number of arguments that fall along a spectrum from moderate to extreme; the most extreme and/or indefensible positions are presented for rhetorical and demonstrative purposes. Although there may not be a clear answer today, this paper raises questions which are related to the basic nature of the rehabilitation profession, and to the current and potential role of technology within it.

Visual perceptual deficits and their contribution to walking dysfunction in individuals with post-stroke visual neglect.

BACKGROUND: Unilateral spatial neglect (USN), a highly prevalent and disabling post-stroke deficit, severely affects functional mobility. Visual perceptual abilities (VPAs) are essential in activities involving mobility. However, whether and to what extent post-stroke USN affects VPAs and how they contribute to mobility impairments remains unclear. OBJECTIVES: To estimate the extent to which VPAs in left and right visual hemispaces are (1) affected in post-stroke USN; and (2) contribute to goal-directed locomotion. METHODS: Individuals with (USN+, n = 15) and without (USN-, n = 15) post-stroke USN and healthy controls (HC, n = 15) completed (1) psychophysical evaluation of contrast sensitivity, optic flow direction and coherence, and shape discrimination; and (2) goal-directed locomotion tasks. RESULTS: Higher discrimination thresholds were found for all VPAs in the USN+ group compared to USN- and HC groups (p < 0.05). Psychophysical tests showed high sensitivity in detecting deficits in individuals with a history of USN or with no USN on traditional assessments, and were found to be significantly correlated with goal-directed locomotor impairments. CONCLUSION: Deficits in VPAs may account for the functional difficulties experienced by individuals with post-stroke USN. Psychophysical tests used in the present study offer important advantages and can be implemented to enhance USN diagnostics and rehabilitation.

Protein-solvent interfaces in human Y145Stop prion protein amyloid fibrils probed by paramagnetic solid-state NMR spectroscopy.

The C-terminally truncated Y145Stop variant of prion protein (PrP23-144), which is associated with heritable PrP cerebral amyloid angiopathy in humans and also capable of triggering a transmissible prion disease in mice, serves as a useful in vitro model for investigating the molecular and structural basis of amyloid strains and cross-seeding specificities. Here, we determine the protein-solvent interfaces in human PrP23-144 amyloid fibrils generated from recombinant 13C,15N-enriched protein and incubated in aqueous solution containing paramagnetic Cu(II)-EDTA, by measuring residue-specific 15N longitudinal paramagnetic relaxation enhancements using two-dimensional magic-angle spinning solid-state NMR spectroscopy. To further probe the interactions of the amyloid core residues with solvent molecules we perform complementary measurements of amide hydrogen/deuterium exchange detected by solid-state NMR and solution NMR methods. The solvent accessibility data are evaluated in the context of the structural model for human PrP23-144 amyloid.

Viewpoints from families for improving transition from NICU-to-home for infants with medical complexity at a safety net hospital: a qualitative study.

BACKGROUND: We have limited information on families' experiences during transition and after discharge from the neonatal intensive care unit. METHODS: Open-ended semi-structured interviews were conducted with English or Spanish- speaking families enrolled in Medicaid in an urban high-risk infant follow up clinic at a safety-net center, which serves preterm and high-risk term infants. We generated salient themes using inductive-deductive thematic analysis. RESULTS: Twenty-one participants completed the study. The infant's median (IQR) birth weight was 1750 (1305, 2641) grams; 71% were Hispanic and 10% were Black non-Hispanic; 62% reported living in a neighborhood with 3-4th quartile economic hardship. All were classified as having chronic disease per the Pediatric Medical Complexity Algorithm and 67% had medical complexity. A conceptual model was constructed and the analysis revealed major themes describing families' challenges and ideas to support transition centered on the parent-child role and parent self-efficacy. The challenges were: (1) comparison to normal babies, (2) caregiver mental health, (3) need for information. Ideas to support transition included, (1) support systems, (2) interventions using mobile health technology (3) improved communication to the primary care provider and (4) information regarding financial assistance programs. Specific subthemes differed in frequency counts between infants with and without medical complexity. CONCLUSIONS: Families often compare their preterm or high-risk infant to their peers and mothers feel great anxiety and stress. However, families often found hope and resilience in peer support and cited that in addition to information needs, interventions using mobile health technology and transition and financial systems could better support families after discharge.

Augmented feedback for powered wheelchair training in a virtual environment.

BACKGROUND: Powered wheelchair (PW) driving is a complex activity and requires the acquisition of several skills. Given the risks involved with PW use, safe and effective training methods are needed. Virtual reality training allows users to practice difficult tasks in a safe environment. An additional benefit is that augmented feedback can be provided to optimize learning. The purpose of this study was to investigate whether providing augmented feedback during powered wheelchair simulator training results in superior performance, and whether skills learned in a virtual environment transfer to real PW driving. METHODS: Forty healthy young adults were randomly allocated to two groups: one received augmented feedback during simulator training while the control group received no augmented feedback. PW driving performance was assessed at baseline in both the real and virtual environment (RE and VE), after training in VE and two days later in VE and RE (retention and transfer tests). RESULTS: Both groups showed significantly better task completion time and number of collisions in the VE after training and these results were maintained two days later. The transfer test indicated better performance in the RE compared to baseline for both groups. Because time and collisions interact, a post-hoc 2D Kolmogonov-Smirnov test was used to investigate the differences in the speed-accuracy distributions for each group; a significant difference was found for the group receiving augmented feedback, before and after training, whereas the difference was not significant for the control group. There were no differences at the retention test, suggesting that augmented feedback was most effective during and immediately after training. CONCLUSIONS: PW simulator training is effective in improving task completion time and number of collisions. A small effect of augmented feedback was seen when looking at differences in the speed-accuracy distributions, highlighting the importance of accounting for the speed-accuracy tradeoff for PW driving.

Structural Studies of Amyloid Fibrils by Paramagnetic Solid-State Nuclear Magnetic Resonance Spectroscopy.

Application of paramagnetic solid-state NMR to amyloids is demonstrated, using Y145Stop human prion protein modified with nitroxide spin-label or EDTA-Cu2+ tags as a model. By using sample preparation protocols based on seeding with preformed fibrils, we show that paramagnetic protein analogs can be induced into adopting the wild-type amyloid structure. Measurements of residue-specific intramolecular and intermolecular paramagnetic relaxation enhancements enable determination of protein fold within the fibril core and protofilament assembly. These methods are expected to be widely applicable to other amyloids and protein assemblies.

Emphysema induced by elastase alters the mRNA relative levels from DNA repair genes in acute lung injury in response to sepsis induced by lipopolysaccharide administration in Wistar rats.

Purpose/Aim of the study: Patients suffering from chronic obstructive pulmonary disease (COPD) in association with acute respiratory distress syndrome (ARDS) present oxidative stress in lung cells, with production of free radicals and DNA lesions in pulmonary and adjacent cells. Once the DNA molecule is damaged, a set of enzymatic mechanisms are trigged to preserve genetic code integrity and cellular homeostasis. These enzymatic mechanisms include the base and the nucleotide excision repair pathways, as well as telomere regulation. Thus, the aim of this work was to evaluate the mRNA levels from APEX1, ERCC2, TP53, and TRF2 genes in lung tissue from Wistar rats affected by acute lung injury in response to sepsis and emphysema. MATERIALS AND METHODS: Adult male Wistar rats were randomized into 4 groups (n = 6, for each group): control, emphysema, sepsis, and emphysema with sepsis. Pulmonary emphysema was induced by intratracheal instillation of elastase (12 IU/animal) and sepsis induced by intraperitoneal Escherichia coli lipopolysaccharide (LPS) injection (10 mg/kg). Lungs were removed, and samples were withdrawn for histological analysis and total RNA extraction, cDNA synthesis, and mRNA level evaluation by real time quantitative polymerase chain reaction. RESULTS: Data show acute lung injury by LPS and emphysema by elastase and that APEX1, ERCC2, TP53, and TRF2 mRNA levels are increased significantly (p < 0.01) in emphysema with sepsis group. CONCLUSION: Our results suggest that alteration in mRNA levels from DNA repair and genomic stability could be part of cell response to acute lung injury in response to emphysema and sepsis.

Post-stroke unilateral spatial neglect: virtual reality-based navigation and detection tasks reveal lateralized and non-lateralized deficits in tasks of varying perceptual and cognitive demands.

BACKGROUND: Unilateral spatial neglect (USN), a highly prevalent and disabling post-stroke impairment, has been shown to affect the recovery of locomotor and navigation skills needed for community mobility. We recently found that USN alters goal-directed locomotion in conditions of different cognitive/perceptual demands. However, sensorimotor post-stroke dysfunction (e.g. decreased walking speed) could have influenced the results. Analogous to a previously used goal-directed locomotor paradigm, a seated, joystick-driven navigation experiment, minimizing locomotor demands, was employed in individuals with and without post-stroke USN (USN+ and USN-, respectively) and healthy controls (HC). METHODS: Participants (n = 15 per group) performed a seated, joystick-driven navigation and detection time task to targets 7 m away at 0°, ±15°/30° in actual (visually-guided), remembered (memory-guided) and shifting (visually-guided with representational updating component) conditions while immersed in a 3D virtual reality environment. RESULTS: Greater end-point mediolateral errors to left-sided targets (remembered and shifting conditions) and overall lengthier onsets in reorientation strategy (shifting condition) were found for USN+ vs. USN- and vs. HC (p < 0.05). USN+ individuals mostly overshot left targets (- 15°/- 30°). Greater delays in detection time for target locations across the visual spectrum (left, middle and right) were found in USN+ vs. USN- and HC groups (p < 0.05). CONCLUSION: USN-related attentional-perceptual deficits alter navigation abilities in memory-guided and shifting conditions, independently of post-stroke locomotor deficits. Lateralized and non-lateralized deficits in object detection are found. The employed paradigm could be considered in the design and development of sensitive and functional assessment methods for neglect; thereby addressing the drawbacks of currently used traditional paper-and-pencil tools.