Correlative light-electron microscopy methods to characterize the ultrastructural features of the replicative and dormant liver stages of Plasmodium parasites.

BACKGROUND: The infection of the liver by Plasmodium parasites is an obligatory step leading to malaria disease. Following hepatocyte invasion, parasites differentiate into replicative liver stage schizonts and, in the case of Plasmodium species causing relapsing malaria, into hypnozoites that can lie dormant for extended periods of time before activating. The liver stages of Plasmodium remain elusive because of technical challenges, including low infection rate. This has been hindering experimentations with well-established technologies, such as electron microscopy. A deeper understanding of hypnozoite biology could prove essential in the development of radical cure therapeutics against malaria. RESULTS: The liver stages of the rodent parasite Plasmodium berghei, causing non-relapsing malaria, and the simian parasite Plasmodium cynomolgi, causing relapsing malaria, were characterized in human Huh7 cells or primary non-human primate hepatocytes using Correlative Light-Electron Microscopy (CLEM). Specifically, CLEM approaches that rely on GFP-expressing parasites (GFP-CLEM) or on an immunofluorescence assay (IFA-CLEM) were used for imaging liver stages. The results from P. berghei showed that host and parasite organelles can be identified and imaged at high resolution using both CLEM approaches. While IFA-CLEM was associated with more pronounced extraction of cellular content, samples' features were generally well preserved. Using IFA-CLEM, a collection of micrographs was acquired for P. cynomolgi liver stage schizonts and hypnozoites, demonstrating the potential of this approach for characterizing the liver stages of Plasmodium species causing relapsing malaria. CONCLUSIONS: A CLEM approach that does not rely on parasites expressing genetically encoded tags was developed, therefore suitable for imaging the liver stages of Plasmodium species that lack established protocols to perform genetic engineering. This study also provides a dataset that characterizes the ultrastructural features of liver stage schizonts and hypnozoites from the simian parasite species P. cynomolgi.

Spatial Response Discrimination May Elicit a Simon Effect on a Non-Complementary Task.

When paired participants are each assigned a complementary half of the Simon task, a joint Simon effect (JSE) has been observed. Co-representation, a cognitive representation of not only one's own task but also that of the co-actor, has been one of several proposed mechanisms in the JSE. Using the response-discrimination hypothesis as a framework, we tested whether it was sufficient to highlight alternative task keys in a two-person setting in which a non-complementary task was completed to elicit a Simon effect (SE). In our design, the participant's role was to perform the Go/No-Go Simon task and the co-actor's role was to initiate each trial for the participant. In one two-person setting participant group (SK group), the same task key was assigned to both the participant and the co-actor; another group (OK) was assigned spatially opposite task keys. In a third group (joint setting, TS group), the standard joint Simon task was also completed to verify that a JSE could be replicated. We hypothesized that an SE would be elicited in the OK group, since opposite task keys would uniquely promote spatial coding. We found a weak but marginally significant SE in the OK group but not in the SK group. These results suggest that, on a non-complementary task, response discrimination may contribute to the emergence of a SE in a two-person setting, while it does not have the same impact as a complementary task completed in a joint setting (TS group) that may afford more robust response representations that reveal the enhanced so-called JSE.

Magnetic resonance imaging demonstrates gyral abnormalities in Tourette syndrome.

Tourette syndrome (TS) is a neurological disorder characterized by involuntary and repetitive movements known as tics. A retrospective analysis of magnetic resonance imaging (MRI) scans from 39 children and adolescents with TS was performed and subsequently compared with MRI scans from 834 neurotypical controls. The purpose of this study was to identify any differences in the regions of motor circuitry in TS to further our understanding of their disturbances in motor control (i.e., motor tics). Measures of volume, cortical thickness, surface area, and surface curvature for specific motor regions were derived from each MRI scan. The results revealed increased surface curvature in the opercular part of the inferior frontal gyrus and the triangular part of the inferior frontal gyrus in the TS group compared with the neurotypical control group. These novel findings offer some of the first evidence for surface curvature differences in motor circuitry regions in TS, which may be associated with known motor and vocal tics.

The Role of Awareness on Motor-Sensory Temporal Recalibration.

Temporal recalibration (TR) may arise to realign asynchronous stimuli after exposure to a short, constant delay between voluntary movement and sensory stimulus. The objective of this study was to determine if awareness of the temporal lag between a motor response (i.e., a keypress) and a sensory event (i.e., a visual flash) is necessary for TR to occur. We further investigated whether manipulating the required motor and perceptual judgment tasks modified the influence of awareness on TR. Participants (n = 48) were randomly divided between two groups (Group 1: Aware and Group 2: Unaware). The Aware group was told of the temporal lag between their keypress and visual flash at the beginning of the experiment, whereas the Unaware group was not. All participants completed eight blocks of trials, in which the motor task (single or repetitive tap), perceptual judgment task (judging the temporal order of the keypress in relation to the visual flash or judging whether the two stimuli were simultaneous or not), and fixed temporal lag between keypress and visual flash (0 or 100 ms) varied. TR was determined by comparing judgments between corresponding blocks of trials in which the temporal lag was 0 or 100 ms. Results revealed that both the Aware and Unaware groups demonstrated a similar magnitude of TR across all motor and perceptual judgment tasks, such that the magnitude of TR did not vary between Aware and Unaware participants. These results suggest that awareness of a temporal lag does not influence the magnitude of TR achieved and that motor and perceptual judgment task demands do not modulate the influence of awareness on TR.

Overcoming Cough and Angioedema: Advocating for the Use of ARBs Over ACE Inhibitors.

Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors have comparable efficacy, but ARBs have a preferential safety profile with particular regard to cough and angioedema. Although guidelines have historically advocated for ACE inhibitor use before ARBs simply because of earlier market entry, data accumulation, and generic availability, updated verbiage advises an "ACE inhibitor or ARB" recommendation, as opposed to the classic "ACE inhibitor then ARB" approach. Despite these updates, clinical inertia in favor of ACE inhibitor use before ARBs overwhelmingly remains. Prescribers and educators should consider an "ARBs only" mentality, especially in high angioedema-risk groups such as black patients.

Structural magnetic resonance imaging demonstrates volumetric brain abnormalities in down syndrome: Newborns to young adults.

Down syndrome (DS) is a genetic disorder caused by the presence of an extra full or partial copy of chromosome 21 and characterized by intellectual disability. We hypothesize that performing a retrospective analysis of 73 magnetic resonance imaging (MRI) examinations of participants with DS (aged 0 to 22 years) and comparing them to a large cohort of 993 brain MRI examinations of neurotypical participants (aged 0 to 32 years), will assist in better understanding what brain differences may explain phenotypic developmental features in DS, as well as to provide valuable confirmation of prospective literature findings clinically. Measurements for both absolute volumes and volumes corrected as a percentage of estimated total intracranial volume (%ETIV) were extracted from each examination. Our results presented novel findings such as volume increases (%ETIV) in the perirhinal cortex, entorhinal cortex, choroid plexus, and Brodmann's areas (BA) 3a, 3b, and 44, as well as volume decreases (%ETIV) in the white matter of the cuneus, the paracentral lobule, the postcentral gyrus, and the supramarginal gyrus. We also confirmed volumetric brain abnormalities previously discussed in the literature. Findings suggest the presence of volumetric brain abnormalities in DS that can be detected clinically with MRI.

Validity of Random Triglyceride Levels in Infants Receiving Parenteral Nutrition.

Background: Intravenous lipid emulsions (IL) are an important part of parenteral nutrition (PN) to meet essential fatty acid (EFA) requirements and metabolic demands of neonates and preterm infants. Some critically-ill neonates may not metabolize IL effectively which can lead to hypertriglyceridemia. Risks associated with this include increased pulmonary vascular resistance, displaced bilirubins, and platelet or macrophage dysfunction. Serum triglyceride (TG) concentration is used as a marker for lipid tolerance and predictor of potential complications involved with IL administration, but the clinical significance of this is still debated. Management of TG levels with regard to timing of laboratory tests, the ideal goal range, and duration of infusion of IL varies across institutions and is not standardized. Methods: Single-center, retrospective study of newborn infants receiving parenteral nutrition (PN). Fasting and non-fasting TG levels were drawn during the same lipid infusion of 2-3g/kg/day. The primary outcome was the difference between fasting and non-fasting TG levels. Statistical assessment of continuous data was done with student t-test and nominal data was evaluated using X2-test and logistic regression. Results: Forty infants were included with mean gestational age at birth of 29.5 ± 3.4 weeks and mean birth weight of 1.3 ± 0.5 kg. Mean time between lab draws while on same IL dose was 11.6 ± 0.2 h with resulting mean fasting and non-fasting (random) TG levels 82 ± 40 mg/dL (95% CI 68.4, 97.6) and 101 ± 40 mg/dL (95% CI 88.5, 115.8), respectively. Mean difference between TG levels during lipid-free interval and during infusion was -18.6 ± 51.2 mg/dL (95% CI -35.0, -2.3; p = 0.03). Conclusion: We concluded there is no difference in the management of IL, when TG level was drawn randomly or as fasting sample. Obtaining TG level during routine lab draws is appropriate. We extrapolated that the administration of IL over 24 h will not interfere with TG level.

The influence of social context and social connection on visual perceptual processes.

The aim of this study was twofold: (1) to re-test whether a minimal social context has an influence on gaze patterns, and (2) to determine if a social connection (i.e., friendship) has a modulatory effect on gaze patterns in a minimal social context. In Experiment 1, two unacquainted participants were paired and seated at separate testing stations in the same room. At the beginning of each trial, participants were informed whether they were looking at different image sets (solo trials), or the same image set (joint trials). Image sets consisted of a positive, a negative, and two neutral images. No explicit task instructions were provided and there was no interaction between participants during the task. Experiment 2 was identical to Experiment 1, except that participants were paired with a friend. The fixation-based metrics of interest were time to first fixation (TFF) and total fixation duration (TFD). The findings revealed that social context has a modulatory effect on attentional capture (i.e., TFF) irrespective of social connection. Unexpectedly, a negativity bias was found to hold attention (i.e., TFD) regardless of social context. However, having a social connection did increase the time spent looking at positive images on the joint trials. Having a social connection with another person seems to alter looking behaviour such that more time is spent looking at positive images on the joint trials compared to the solo trials. These findings highlight the importance of evaluating both TFD and TFF to develop a better understanding of the factors underlying joint perception.

Whose turn is it anyway? The moderating role of response-execution certainty on the joint Simon effect.

When a two-choice "Simon task" is distributed between two people, performance in the shared go/no-go task resembles performance in the whole task alone. This finding has been described as the joint Simon effect (JSE). Unlike the individual go/no-go task, not only is the typical joint Simon task shared with another person, but also the imperative stimuli dictate whose turn it is to respond. Therefore, in the current study, we asked whether removing the agent discrimination component of the joint Simon task influences co-representation. Participants performed the typical joint Simon task, which was compared to two turn-taking versions of the task. For these turn-taking tasks, pairs predictably alternated turns on consecutive trials, with their respective imperative stimulus presented either on 100% of their turns (fully predictable group) or on 83% of their turns (response-uncertainty group, 17% no-go catch trials). The JSE was absent in the fully predictable, turn-taking task, but emerged similarly under the response-uncertainty condition and the typical joint Simon task condition where there is both turn and response-execution-related uncertainty. These results demonstrate that conflict related to agent discrimination is likely not a critical factor driving the JSE, whereas conflict surrounding the need to execute a response (and hence the degree of preparation) appears fundamental to co-representation.

Bimanual joint action: correlated timing or "bimanual" movements accomplished by two people.

A crew of two rowing together in perfect synchrony is an example of a task that requires each performer to maintain meticulous timing when coordinating their movements with the other. At the individual level, temporal coordination of the limbs has been observed in bimanual pointing movements even when made to targets of different distance. Timing of the arms is not independent; rather there is a natural temporal coupling. The aim of this experiment was to investigate whether the temporal characteristics of pointing movements can be observed under joint conditions. Sixteen pairs of participants made short and long, unimanual and bimanual pointing movements. In the unimanual and bimanual solo conditions, participants made the movements alone. In the joint condition, each participant contributed one arm to the joint "bimanual" movements. Absolute temporal coupling at movement initiation and termination was measured by the differences in reaction time and total response time. Relative temporal coupling at movement initiation and termination was measured by correlating reaction time and total response time of the left and right limbs. Pointing movements had synchronous movement termination in the bimanual solo conditions and asynchronous termination in the unimanual solo and bimanual joint conditions. The initiation and termination of the arms were not correlated in the unimanual solo condition (initiation r = 0.01, termination r = 0.03). Small-to-medium correlations (r = 0.19, r = 0.24) were observed in the bimanual joint condition, and they were larger than the unimanual solo condition (p = 0.022, p = 0.063). As expected, there were large correlations in the bimanual solo conditions (r = 0.91, r = 0.81). Our findings suggest that absolute temporal coupling does not occur between individuals, but there is evidence for relative temporal coupling in the bimanual joint condition.

A Characterization of Movement Skills in Obese Children With and Without Prader-Willi Syndrome.

PURPOSE: The aim of this study was twofold: (a) to measure and compare motor proficiency in obese children with Prader-Willi syndrome (OB-PWS) to that in obese children without PWS (OB), and (b) to compare motor proficiency in OB-PWS and OB to normative data. METHOD: Motor proficiency was measured using the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition-Complete Form, a norm-referenced assessment of motor function. Participants were 18 OB-PWS and 44 OB (8 to 11 years of age). The scores on the 8 subtests and the total motor composite were used to compare OB-PWS and OB. Furthermore, the scores on the 4 motor-area composites were used to compare OB-PWS and OB against normative data. RESULTS: OB-PWS scored significantly lower than OB across all 8 subtests. OB-PWS also had significantly lower motor proficiency scores on all motor-area composites when compared with the normative sample. OB-PWS most frequently (67%-83%) scored well below average on the gross motor subtests. Although not as high as on the gross motor subtests, this finding also held true for the fine motor subtests with 39% to 45% of OB-PWS scoring well below average. CONCLUSION: Motor proficiency is very poor in OB-PWS, in particular for gross motor skills. Physical, neurological, and developmental characteristics inherent to the syndrome may explain this low performance.

Breast Cancer and Mammography Screening: Knowledge, Beliefs and Predictors for Asian Immigrant Women Attending a Specialized Clinic in British Columbia, Canada.

Screening mammography (MMG) reduces breast cancer mortality; however, Asian immigrant women underutilize MMG. The Asian Women's Health Clinic (AWHC) was established to promote women's cancer screening amongst this population. This study evaluated the rate, and predictors, of MMG amongst women attending the AWHC. Women (N = 98) attending the AWHC completed a questionnaire. Descriptive statistics and multivariable logistic regression evaluated rate and predictors of MMG. Most participants (87 %, n = 85) reported having had a mammogram. Significant MMG predictors were: lower perceived MMG barriers [lifetime: OR (CI) 1.19 (1.01-1.49); past 2 years: OR (CI) 1.11 (1.01-1.25)], and knowing someone with breast cancer [past year: OR (CI) 3.42 (1.25-9.85); past 2 years: OR (CI) 4.91 (1.32-2.13)]. Even amongst women using preventive medicine, 13 % report never having had a mammogram. More research is needed into innovative interventions, e.g. the AWHC, and breast cancer-related outcomes amongst Asian immigrant women.

Therapists' perceptions of social media and video game technologies in upper limb rehabilitation.

BACKGROUND: The application of technologies, such as video gaming and social media for rehabilitation, is garnering interest in the medical field. However, little research has examined clinicians' perspectives regarding technology adoption by their clients. OBJECTIVE: The objective of our study was to explore therapists' perceptions of how young people and adults with hemiplegia use gaming and social media technologies in daily life and in rehabilitation, and to identify barriers to using these technologies in rehabilitation. METHODS: We conducted two focus groups comprised of ten occupational therapists/physiotherapists who provide neurorehabilitation to individuals with hemiplegia secondary to stroke or cerebral palsy. Data was analyzed using inductive thematic analysis. The diffusion of innovations theory provided a framework to interpret emerging themes. RESULTS: Therapists were using technology in a limited capacity. They identified barriers to using social media and gaming technology with their clients, including a lack of age appropriateness, privacy issues with social media, limited transfer of training, and a lack of accessibility of current systems. Therapists also questioned their role in the context of technology-based interventions. The opportunity for social interaction was perceived as a major benefit of integrated gaming and social media. CONCLUSIONS: This study reveals the complexities associated with adopting new technologies in clinical practice, including the need to consider both client and clinician factors. Despite reporting several challenges with applying gaming and social media technology with clinical populations, therapists identified opportunities for increased social interactions and were willing to help shape the development of an upper limb training system that could more readily meet the needs of clients with hemiplegia. By considering the needs of both therapists and clients, technology developers may increase the likelihood that clinicians will adopt innovative technologies.

Perceptions of Technology and Its Use for Therapeutic Application for Individuals With Hemiparesis: Findings From Adult and Pediatric Focus Groups.

BACKGROUND: Digital technology is becoming an increasingly popular means of delivering meaningful therapy to individuals with neurological impairments. An understanding of clients' technology use and their perspectives on incorporating technology into rehabilitation can provide researchers and designers with valuable information to inform development of technologies and technology-based rehabilitation programs. OBJECTIVE: This study was designed to establish the current use and perceptions of gaming, social media, and robotics technologies for rehabilitative purposes from the perspective of adults and children with upper limb impairments to identify barriers and enablers to their adoption and use. METHODS: We conducted three focus groups consisting of pediatric (n=7, mean age 11.0 years) and adult (n=8, mean age 60.8 years) participants with hemiparesis affecting their upper limb. We applied thematic analysis methods to the resulting data. RESULTS: We identified three key themes: (1) clients' use of technology in everyday life and rehabilitation, (2) barriers to use, and (3) enablers to therapy. Participants had limited exposure to technology for therapeutic purposes, but all acknowledged the potential benefits in providing motivation and interest for the performance of repetitive task practice. Adult participants requested efficacious, simple, and easy-to-use technology for rehabilitation with programs that could be individualized for them and expressed that they wanted these programs to provide a motivating means of repeated practice of therapeutic movements. In contrast, pediatric participants emphasized a desire for technology for rehabilitation that offered opportunities for social interaction and interactive games involving their whole body and not only their affected limb. Perceived safety and privacy were concerns for both groups. CONCLUSIONS: Our findings highlight that all participants were open to the integration of technology into rehabilitation. Adult participants were more pragmatically motivated by potential recovery gains, whereas pediatric participants were more intrinsically motivated by access to games.

Unconscious and out of control: subliminal priming is insensitive to observer expectations.

We asked whether the influence of an invisible prime on movement is dependent on conscious movement expectations. Participants reached to a central target, which triggered a directional prime-mask arrow sequence. Participants were instructed that the visible arrows (masks) would most often signal a movement modification in a specific (biased) direction. Kinematic analyses revealed that responses to the visible mask were influenced by participants' intentional bias, as movements were fastest when the more probable mask was displayed. In addition, responses were influenced by the invisible prime without regard to its relationship to the more probable mask. Analysis of the time of initial trajectory modifications revealed that both primes influenced responses in a similar manner after accounting for participants' bias. These results imply that invisible stimuli automatically activate their associated responses and that unconscious priming of the motor system is insensitive to the conscious expectations of the participant making the pointing movements.

Reaction time effects due to imperative stimulus modality are absent when a startle elicits a pre-programmed action.

When an acoustic stimulus that is sufficiently intense to elicit a startle response is delivered in conjunction with the "go" signal in a simple reaction time (RT) task, RT is greatly reduced. It has been suggested that this effect is due to the startle interacting with voluntary response channels to directly trigger the pre-programmed action. Alternatively, it may be that the startling stimulus simply increases activation along the sensory and motor pathways allowing for faster stimulus-response processing. In the present study a startling acoustic stimulus (SAS) was presented in addition to a visual or an auditory imperative stimulus (IS) in a simple RT task. Results showed that the pre-programmed response was initiated much faster when participants were startled. However, while differences in RT due to IS modality were observed in control trials, this difference was absent for startle trials. This result indicates that the SAS does not simply speed processing along the normal stimulus-response channels, but acts to release the pre-planned movement via a separate, faster neural pathway.

Social support in the post-abortion recovery room: evidence from patients, support persons and nurses in a Vancouver clinic.

BACKGROUND: The benefits of social support in post-surgical recovery are well documented; social support decreases preoperative stress and postoperative recovery time. However, a paucity of studies have examined the effect of social support in the context of pregnancy termination. This study is the first to examine the effect of postoperative accompaniment from the patient, support person and nurses' perspective. STUDY DESIGN: This study was carried out in two phases. In Phase I, no accompaniment was allowed in the post-anesthesia recovery room (PAR); in Phase II, accompaniment was permitted. All participants completed pre- and postoperative questionnaires. RESULTS: The perception of accompaniment was overwhelmingly positive in patients and support people. Patients in Phase II demonstrated a high (over 95%) acceptance of accompaniment in the recovery room. It was found that 96.8% reported they would choose to be accompanied in the recovery room again if they had to have another abortion. Support persons felt very strongly that their presence was helpful to the patient. The decrease in pre- to postoperative anxiety levels was significantly greater in those women who were accompanied. However, overall, nurses demonstrated a negative attitude towards accompaniment in the recovery room. CONCLUSION: In summary, the presence of a support person in the PAR was perceived in a positive manner by patients and support people. However, the reasoning behind the negative opinion of nurses requires further study before PAR accompaniment can be considered a possibility in the context of pregnancy termination.

Considerations for the use of a startling acoustic stimulus in studies of motor preparation in humans.

Recent studies have used a loud (> 120 dB) startle-eliciting acoustic stimulus as a probe to investigate early motor response preparation in humans. The use of a startle in these studies has provided insight into not only the neurophysiological substrates underlying motor preparation, but also into the behavioural response strategies associated with particular stimulus-response sets. However, as the use of startle as a probe for preparation is a relatively new technique, a standard protocol within the context of movement paradigms does not yet exist. Here we review the recent literature using startle as a probe during the preparation phase of movement tasks, with an emphasis on how the experimental parameters affect the results obtained. Additionally, an overview of the literature surrounding the startle stimulus parameters is provided, and factors affecting the startle response are considered. In particular, we provide a review of the factors that should be taken into consideration when using a startling stimulus in human research.

Movement duration does not affect automatic online control.

Pisella et al. (2000) have shown that fast aiming movements are automatically modified on-line in response to a change in target position. Specifically, when a movement is less than 300ms in duration the reach is completed to a target's new location even when one never intended to respond to the target jump. In contrast, when movements are slower, the reach is completed according to instructions. At present, it is unclear if it is possible for one's intentions to guide the initial stages of these slow movements. To determine if the intentional control mechanism can guide the initial stages of a slow aiming movement, participants aimed to targets that could jump at movement onset, with a slow and very slow movement time goal. In particular, participants were to point towards ("pro-point") or away from ("anti-point") the target jump, with a movement time goal of 500 or 1200ms. Results showed that in the anti-point condition, movement trajectories first deviated in the same direction as the target jump, followed by a response in the intended (opposite) direction. This suggests that while movement outcome is controlled by the intentional system, even in these slow aiming movements the automatic system is engaged at movement onset.