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Recent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis’s anti-inflammatory properties may underlie this relationship by reducing chronic neuroinflammation in PWH. This study examined relations between cannabis use and inflammatory biomarkers in cerebrospinal fluid (CSF) and plasma, and cognitive correlates of these biomarkers within a community-based sample of PWH.
263 individuals were categorized into four groups: HIV− non-cannabis users (n = 65), HIV+ non-cannabis users (n = 105), HIV+ moderate cannabis users (n = 62), and HIV+ daily cannabis users (n = 31). Differences in pro-inflammatory biomarkers (IL-6, MCP-1/CCL2, IP-10/CXCL10, sCD14, sTNFR-II, TNF-α) by study group were determined by Kruskal–Wallis tests. Multivariable linear regressions examined relationships between biomarkers and seven cognitive domains, adjusting for age, sex/gender, race, education, and current CD4 count.
HIV+ daily cannabis users showed lower MCP-1 and IP-10 levels in CSF compared to HIV+ non-cannabis users (p = .015; p = .039) and were similar to HIV− non-cannabis users. Plasma biomarkers showed no differences by cannabis use. Among PWH, lower CSF MCP-1 and lower CSF IP-10 were associated with better learning performance (all ps < .05).
Current daily cannabis use was associated with lower levels of pro-inflammatory chemokines implicated in HIV pathogenesis and these chemokines were linked to the cognitive domain of learning which is commonly impaired in PWH. Cannabinoid-related reductions of MCP-1 and IP-10, if confirmed, suggest a role for medicinal cannabis in the mitigation of persistent inflammation and cognitive impacts of HIV.
The objectives were to examine clinical characteristics, length of recovery, and the prevalence of delayed physician-documented recovery, compare clinical outcomes among those with sport-related concussion (SRC) and non-sport-related concussion (nSRC), and identify risk factors for delayed recovery.
Included patients (8–18 years) were assessed ≤14 days post-injury at a multidisciplinary concussion program and diagnosed with an acute SRC or nSRC. Physician-documented clinical recovery was defined as returning to pre-injury symptom status, attending full-time school without symptoms, completing Return-to-Sport strategy as needed, and normal physical examination. Delayed physician-documented recovery was defined as >28 days post-injury.
Four hundred and fifteen patients were included (77.8% SRC). There was no difference in loss of consciousness (SRC: 9.9% vs nSRC: 13.0%, p = 0.39) or post-traumatic amnesia (SRC: 24.1% vs SRC: 31.5%, p = 0.15) at the time of injury or any differences in median Post-Concussion Symptom Scale scores (SRC: 20 vs nSRC: 23, p = 0.15) at initial assessment. Among those with complete clinical follow-up, the median physician-documented clinical recovery was 20 days (SRC: 19 vs nSRC: 23; p = 0.37). There was no difference in the proportion of patients who developed delayed physician-documented recovery (SRC: 27.7% vs nSRC: 36.1%; p = 0.19). Higher initial symptom score increased the risk of delayed physician-documented recovery (IRR: 1.39; 95% CI: 1.29, 1.49). Greater material deprivation and social deprivation were associated with an increased risk of delayed physician-documented recovery.
Most pediatric concussion patients who undergo early medical assessment and complete follow-up appear to make a complete clinical recovery within 4 weeks, regardless of mechanism.
ABSTRACT IMPACT: The knowledge acquired from my research can inform the development of early diagnostic methods for HIV-associated neurocognitive disorders. OBJECTIVES/GOALS: In the era of combination antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HAND) remains high but the neural mechanisms are unclear. We examined whether older people with HIV (PWH) with minimal cognitive impairment have reduced functional connectivity in frontostriatal circuits compared to controls. METHODS/STUDY POPULATION: 99 PWH (mean age 56.6 years, 75% male, 62% Black, mean duration of HIV-infection 26.2 years ±9.3, 90% viral load <50 copies, 98% on stable cART) and 38 demographically-comparable controls (mean age 54.5 years, 71% male, 58% Black) participated in a cross-sectional study. A 7-domain neuropsychological battery and an Activities of Daily Living index were used to determine HAND diagnoses: 32 PWH met criteria for asymptomatic to mild HAND. Motor skill was assessed using the Grooved Pegboard Test by measuring performance speed. Structural MRI and resting-state functional MRI were collected. Seed-to-voxel analyses were conducted using 4 distinct regions in the striatum as seed regions. We used a voxel threshold of p<0.001 and cluster threshold of p<0.05 (FDR-corrected) after controlling for demographic variables. RESULTS/ANTICIPATED RESULTS: Compared to controls, PWH had lower resting state functional connectivity between the default mode region of the striatum (i.e., medial caudate) and bilateral superior frontal gyrus, supplementary motor cortex and paracingulate gyrus (p<0.05; cluster size: 567 voxels). Also, compared to controls, PWH had reduced resting state functional connectivity between the motor division of the striatum (i.e., posterior putamen) and anterior cingulate cortex and left supplementary motor cortex (p<0.05, cluster size: 405 voxels). Performance speed on the Grooved Pegboard motor test negatively correlated with functional connectivity between the motor region of the striatum and supplementary motor frontal regions in all participants (Spearman’s rho=-0.18, p=0.04). DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results support the hypothesis that frontostriatal abnormalities are widely present in PWH and might play a key role in HAND development. Our data suggest that dysfunction within the frontostriatal circuits may be involved in motor impairment in PWH, and ongoing inflammation may contribute to motor impairment and frontostriatal injury.
Hemiparetic walking after stroke is typically slow, asymmetric, and inefficient, significantly impacting activities of daily living. Extensive research shows that functional, intensive, and task-specific gait training is instrumental for effective gait rehabilitation, characteristics that our group aims to encourage with soft robotic exosuits. However, standard clinical assessments may lack the precision and frequency to detect subtle changes in intervention efficacy during both conventional and exosuit-assisted gait training, potentially impeding targeted therapy regimes. In this paper, we use exosuit-integrated inertial sensors to reconstruct three clinically meaningful gait metrics related to circumduction, foot clearance, and stride length. Our method corrects sensor drift using instantaneous information from both sides of the body. This approach makes our method robust to irregular walking conditions poststroke as well as usable in real-time applications, such as real-time movement monitoring, exosuit assistance control, and biofeedback. We validate our algorithm in eight people poststroke in comparison to lab-based optical motion capture. Mean errors were below 0.2 cm (9.9%) for circumduction, −0.6 cm (−3.5%) for foot clearance, and 3.8 cm (3.6%) for stride length. A single-participant case study shows our technique’s promise in daily-living environments by detecting exosuit-induced changes in gait while walking in a busy outdoor plaza.
There is growing evidence that species and communities are responding to, and will continue to be affected by, climate change. For species at risk, vulnerability can be reduced by ensuring that their habitat is extensive, connected and provides opportunities for dispersal and/or gene flow, facilitating a biological response through migration or adaptation. For woodland epiphytes, vulnerability might also be reduced by ensuring sufficient habitat heterogeneity, so that microhabitats provide suitable local microclimates, even as the larger scale climate continues to change (i.e. microrefugia). This study used fuzzy set ordination to compare bryophyte and lichen epiphyte community composition to a large-scale gradient from an oceanic to a relatively more continental macroclimate. The residuals from this relationship identified microhabitats in which species composition reflected a climate that was more oceanic or more continental than would be expected given the prevailing macroclimate. Comparing these residuals to features that operate at different scales to create the microclimate (landscape, stand and tree-scale), it was possible to identify how one might engineer microrefugia into existing or new woodland, in order to reduce epiphyte vulnerability to climate change. Multimodel inference was used to identify the most important features for consideration, which included local effects such as height on the bole, angle of bole lean and bark water holding capacity, as well as tree species and tree age, and within the landscape, topographic wetness and physical exposure.
Experiencing poverty increases vulnerability for dysregulated hypothalamic–pituitary–adrenal (HPA) axis functioning and compromises long-term health. Positive parenting buffers children from HPA axis reactivity, yet this has primarily been documented among families not experiencing poverty. We tested the theorized power of positive parenting in 124 parent–child dyads recruited from Early Head Start (Mage = 25.21 months) by examining child cortisol trajectories using five samples collected across a standardized stress paradigm. Piecewise latent growth models revealed that positive parenting buffered children's stress responses when controlling for time of day, last stress task completed, and demographics. Positive parenting also interacted with income such that positive parenting was especially protective for cortisol reactivity in families experiencing greater poverty. Findings suggest that positive parenting behaviors are important for protecting children in families experiencing low income from heightened or prolonged physiologic stress reactivity to an acute stressor.
As the pathophysiology of Covid-19 emerges, this paper describes dysphagia as a sequela of the disease, including its diagnosis and management, hypothesised causes, symptomatology in relation to viral progression, and concurrent variables such as intubation, tracheostomy and delirium, at a tertiary UK hospital.
During the first wave of the Covid-19 pandemic, 208 out of 736 patients (28.9 per cent) admitted to our institution with SARS-CoV-2 were referred for swallow assessment. Of the 208 patients, 102 were admitted to the intensive treatment unit for mechanical ventilation support, of which 82 were tracheostomised. The majority of patients regained near normal swallow function prior to discharge, regardless of intubation duration or tracheostomy status.
Dysphagia is prevalent in patients admitted either to the intensive treatment unit or the ward with Covid-19 related respiratory issues. This paper describes the crucial role of intensive swallow rehabilitation to manage dysphagia associated with this disease, including therapeutic respiratory weaning for those with a tracheostomy.
Bibliometric methods were used to analyse the major research trends, themes and topics over the last 30 years in the parasitology discipline. The tools used were SciMAT, VOSviewer and SWIFT-Review in conjunction with the parasitology literature contained in the MEDLINE, Web of Science, Scopus and Dimensions databases. The analyses show that the major research themes are dynamic and continually changing with time, although some themes identified based on keywords such as malaria, nematode, epidemiology and phylogeny are consistently referenced over time. We note the major impact of countries like Brazil has had on the literature of parasitology research. The increase in recent times of research productivity on ‘antiparasitics’ is discussed, as well as the change in emphasis on different antiparasitic drugs and insecticides over time. In summary, innovation in parasitology is global, extensive, multidisciplinary, constantly evolving and closely aligned with the availability of technology.
Humans are intrinsically social beings. Over time we are shaped by our lived experiences, particularly through our connections and interactions with others. By examining the profound nature of these social relationships, we can begin to understand how the mind emerges across the lifespan and regulates such experiences. In this chapter, we will explore relationships with family, friends, and romantic partners to develop an understanding of our innate social nature and the direct link this has to well-being and health.
Science has made evident the positive effects of relationships on well-being, including longevity, happiness, and mental health. The World Health Organization defines health as “a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity” . Therefore, the absence of disease alone does not signify well-being. Rather, well-being is a quality of life in which there is the presence of positive affective processes, a sense of satisfaction, purpose, and fulfillment in life, and the absence of enduring negative emotions [2, 3].
Implantable neural interfaces are important tools to accelerate neuroscience research and translate clinical neurotechnologies. The promise of a bidirectional communication link between the nervous system of humans and computers is compelling, yet important materials challenges must be first addressed to improve the reliability of implantable neural interfaces. This perspective highlights recent progress and challenges related to arguably two of the most common failure modes for implantable neural interfaces: (1) compromised barrier layers and packaging leading to failure of electronic components; (2) encapsulation and rejection of the implant due to injurious tissue–biomaterials interactions, which erode the quality and bandwidth of signals across the biology–technology interface. Innovative materials and device design concepts could address these failure modes to improve device performance and broaden the translational prospects of neural interfaces. A brief overview of contemporary neural interfaces is presented and followed by recent progress in chemistry, materials, and fabrication techniques to improve in vivo reliability, including novel barrier materials and harmonizing the various incongruences of the tissue–device interface. Challenges and opportunities related to the clinical translation of neural interfaces are also discussed.
Although early-life adversity can undermine healthy development, children growing up in harsh environments may develop intact, or even enhanced, skills for solving problems in high-adversity contexts (i.e., “hidden talents”). Here we situate the hidden talents model within a larger interdisciplinary framework. Summarizing theory and research on hidden talents, we propose that stress-adapted skills represent a form of adaptive intelligence that enables individuals to function within the constraints of harsh, unpredictable environments. We discuss the alignment of the hidden talents model with current knowledge about human brain development following early adversity; examine potential applications of this perspective to multiple sectors concerned with youth from harsh environments, including education, social services, and juvenile justice; and compare the hidden talents model with contemporary developmental resilience models. We conclude that the hidden talents approach offers exciting new directions for research on developmental adaptations to childhood adversity, with translational implications for leveraging stress-adapted skills to more effectively tailor education, jobs, and interventions to fit the needs and potentials of individuals from a diverse range of life circumstances. This approach affords a well-rounded view of people who live with adversity that avoids stigma and communicates a novel, distinctive, and strength-based message.
National vegetation classification (NVC) has been widely applied as a framework for mapping and conserving plant species and community types. However, a limited availability of expertise has prevented NVCs from being developed and used in cryptogam-dominated systems, such as for temperate and boreal epiphyte communities. This study simplified a recent systematically sampled NVC, trialled for epiphyte communities in Scotland, by reducing the original list of 82 community indicators to 34 easily recognisable species (lichens, mosses and liverworts). These were subsequently sampled from woodland sites positioned in Scotland’s temperate rain forest zone. Sites were positioned among localities in less intensively managed landscapes (northwest Scotland) through to peri-urban environments (southern Scotland), grouping sites for each locality based on a contrast in woodland temporal continuity (ancient or recent). The richness and diversity of epiphyte community indicators were compared with easily measured variables reflecting stand heterogeneity or ecological stability, and woodland temporal continuity, with air pollution as a covariable. Richness and diversity were significantly explained by the ecological stability of woodland stands, heterogeneity of the light environment, and nitrogen pollution. This demonstrates a tool that can be deployed by the non-specialist, with appropriate training, to quantify the condition of a woodland stand through consequences for its epiphytes in globally important temperate rain forest. The pattern of richness and diversity was consistent with the co-occurrence of particular indicator species, which represent the range of epiphyte community types supported by a woodland.
OBJECTIVES/GOALS: The history of immune suppression, especially CD4 nadir, has been shown to be a strong predictor of HIV-associated neurocognitive disorders (HAND). However, the potential mechanism of this association is not well understood. This study examined the relationship between CD4 nadir and brain atrophy. METHODS/STUDY POPULATION: Fifty-nine people with HIV participated in the cross-sectional study (mean age, 56.5 ± 5.8; age range, 41-69; 15 females; 46 African-Americans). High resolution structural MRI images were obtained using a 3T Siemens scanner. From a comprehensive 7-domain neuropsychological test battery, a global deficit score (GDS) and HAND diagnoses were determined for each participant. The correlation between CD4 nadir (the lowest ever lymphocyte CD4 count) and cortical thickness was investigated using a vertex-wise non-parametric approach with a conservative statistical threshold of p < 0.05 (FWE-corrected). RESULTS/ANTICIPATED RESULTS: Out of the 59 participants, 12 met standard Frascati criteria for asymptomatic neurocognitive impairment (ANI) and two met the criteria for mild neurocognitive disorder (MND). Across all participants, low CD4 nadir was associated with widespread cortical thinning, especially in the frontal and temporal regions. Higher GDS (indicating worse global neurocognitive function) was associated with bilateral frontal cortical thinning, and the association largely persisted in the subset of participants who did not meet HAND criteria. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that the low CD4 nadir may be associated with widespread neural injury in the brain, especially in the frontal and temporal regions. This spatial profile might contribute to the prevalence/phenotypes of HAND in the cART era, such as the frequently observed deficits in the executive domain.
Prenatal alcohol exposure (PAE) produces physiological and behavioural abnormalities that are consistent with altered serotonin (5-HT) function in male rats. Whether alterations in the 5-HT system persist into adulthood and are present in females remains unknown.
1) the effects of PAE on the number of 5-HT neurons in the brainstem in female adult rats;
2) the potential influence of ovarian sex steroids, estradiol (E2) and progesterone (P4) on this population of 5-HT neurons.
Female offspring from prenatal ethanol (PAE), pair-fed (PF) and ad lib-fed control (C) dams were studied in adulthood. Females were assigned to the following groups: 1) ovariectomized (OVX); 2) ovariectomized with estradiol replacement (OVX+E2; mean plasma concentration: 64 pg/ml); 3) ovariectomized and replaced with estradiol (as above) and progesterone (OVX+E2+P4; mean plasma concentration for P4:12 ng/ml); 4) Sham surgery (SHAM). Immunocytochemistry for 5-HT was performed.
PAE decreased the number of 5-HT-ir neurons in the dorsal raphe (DR) in OVX females. There was no effect of PAE the number of DR 5HT-ir neurons in OVX+E2 group, suggesting a possible neuroprotective role of estradiol in PAE animals. Treatment with both progesterone and estradiol compared to estradiol alone caused a further decrease in number of DR 5-HT-ir neurons in PAE but not C or PF animals.
These results provide evidence of the enduring effects of PAE on the serotonergic system, and suggest a role for the ovarian sex steroids in mediating these effects.
IMPART (CIHR) to JHS, NIH/NIAAA AA007789 and HELP to JW.
The UK has longstanding problems with psychiatry recruitment. Various initiatives aim to improve psychiatry's image among medical students, but involve research and none are student-led. Providing opportunities to take part in psychiatry research and quality improvement could increase the number of students who choose to enter the speciality.
We have developed the student psychiatry audit and research collaborative (SPARC), a student-led initiative for nationwide collaboration in high-quality research and audits.
Our model is inspired by the success of the UK Student audit and research in surgery (STARSurg). Area teams, located in medical schools, take part in multi-centre projects. The area teams consist of medical students, who have the main responsibility for collecting data; a junior doctor, to supervise the process; and a consultant, with overall responsibility for patient care. The data collected centrally and analysed by a team of medical students and doctors. Student leads from each site are named authors on resulting papers. All other students are acknowledged and are able to present the work.
We have completed our first audits in Cardiff and London; other sites will return data in 2017. Student feedback indicated a high level of satisfaction with the project and interest in psychiatry as a future career.
This initiative aims to tackle the recruitment problems in psychiatry by giving students a chance to take part in high quality research and audits.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Venous thromboembolism (VTE) is a potentially fatal condition. Hospital-associated VTE leads to more than 25,000 deaths per year in the UK. Therefore identification of at-risk patients is crucial. Psychiatric in-patients have unique factors which may affect their risk of VTE (antipsychotic prescription, restraint) however there are currently no UK guidelines which specifically address VTE risk in this population.
We assessed VTE risk among psychiatric inpatients in Cardiff and Vale university health board, Wales, UK, and whether proformas currently provided for VTE risk assessment were being completed.
All acute adult in-patient and old age psychiatric wards were assessed by a team of medical students and a junior doctor over three days. We used the UK department of health VTE risk assessment tool which was adapted to include factors specific for psychiatric patients. We also assessed if there were concerns about prescribing VTE prophylaxis (compression stockings or anticoagulants), because of a history of self-harm or ligature use.
Of the 145 patients included, 0% had a completed VTE risk assessment form. We found 38.6% to be at an increased risk of VTE and there were concerns about prescribing VTE prophylaxis in 31% of patients.
Our findings suggest that VTE risk assessment is not being carried out on psychiatric wards. Staff education is needed to improve awareness of VTE. Specific guidance for this population is needed due to the presence of unique risk factors in psychiatric in-patients and concerns regarding VTE prophylaxis.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Mechanistic models (MMs) have served as causal pathway analysis and ‘decision-support’ tools within animal production systems for decades. Such models quantitatively define how a biological system works based on causal relationships and use that cumulative biological knowledge to generate predictions and recommendations (in practice) and generate/evaluate hypotheses (in research). Their limitations revolve around obtaining sufficiently accurate inputs, user training and accuracy/precision of predictions on-farm. The new wave in digitalization technologies may negate some of these challenges. New data-driven (DD) modelling methods such as machine learning (ML) and deep learning (DL) examine patterns in data to produce accurate predictions (forecasting, classification of animals, etc.). The deluge of sensor data and new self-learning modelling techniques may address some of the limitations of traditional MM approaches – access to input data (e.g. sensors) and on-farm calibration. However, most of these new methods lack transparency in the reasoning behind predictions, in contrast to MM that have historically been used to translate knowledge into wisdom. The objective of this paper is to propose means to hybridize these two seemingly divergent methodologies to advance the models we use in animal production systems and support movement towards truly knowledge-based precision agriculture. In order to identify potential niches for models in animal production of the future, a cross-species (dairy, swine and poultry) examination of the current state of the art in MM and new DD methodologies (ML, DL analytics) is undertaken. We hypothesize that there are several ways via which synergy may be achieved to advance both our predictive capabilities and system understanding, being: (1) building and utilizing data streams (e.g. intake, rumination behaviour, rumen sensors, activity sensors, environmental sensors, cameras and near IR) to apply MM in real-time and/or with new resolution and capabilities; (2) hybridization of MM and DD approaches where, for example, a ML framework is augmented by MM-generated parameters or predicted outcomes and (3) hybridization of the MM and DD approaches, where biological bounds are placed on parameters within a MM framework, and the DD system parameterizes the MM for individual animals, farms or other such clusters of data. As animal systems modellers, we should expand our toolbox to explore new DD approaches and big data to find opportunities to increase understanding of biological systems, find new patterns in data and move the field towards intelligent, knowledge-based precision agriculture systems.