Electrophoretic Microfluidic Characterization of mRNA- and pDNA-Loaded Lipid Nanoparticles.

Lipid nanoparticles (LNPs) are clinically advanced nonviral gene delivery vehicles with a demonstrated ability to address viral, oncological, and genetic diseases. However, the further development of LNP therapies requires rapid analytical techniques to support their development and manufacturing. The method developed and described in this paper presents an approach to rapidly and accurately analyze LNPs for optimized therapeutic loading by utilizing an electrophoresis microfluidic platform to analyze the composition of LNPs with different clinical lipid compositions (Onpattro, Comirnaty, and Spikevax) and nucleic acid (plasmid DNA (pDNA) and messenger RNA (mRNA)) formulations. This method enables the high-throughput screening of LNPs using a 96- or 384-well plate with approximate times of 2-4 min per sample using a total volume of 11 µL. The lipid analysis requires concentrations approximately between 109 and 1010 particles/mL and has an average precision error of 10.4% and a prediction error of 19.1% when compared to using a NanoSight, while the nucleic acid analysis requires low concentrations of 1.17 ng/µL for pDNA and 0.17 ng/µL for mRNA and has an average precision error of 4.8% and a prediction error of 9.4% when compared to using a PicoGreen and RiboGreen assay. In addition, our method quantifies the relative concentration of nucleic acid per LNP. Utilizing this approach, we observed an average of 263 ± 62.2 mRNA per LNP and 126.3 ± 21.2 pDNA per LNP for the LNP formulations used in this study, where the accuracy of these estimations is dependent on reference standards. We foresee the utility of this technique in the high-throughput characterization of LNPs during manufacturing and formulation research and development.

VasCog Screen test: sensitive in detecting cognitive impairment in patients who had a stroke or with heart failure.

INTRODUCTION: Vascular diseases, such as stroke and heart failure (HF), are associated with cognitive decline. Vascular cognitive impairment (CI) is commonly found in patients who had a stroke and with HF, ranging from mild CI to dementia. Early detection of CI is crucial for effective management and rehabilitation. This study aimed to develop the VasCog Screen test, a screening tool to detect CI in patients who had a stroke and with HF. METHOD: 427 patients who had a stroke and with HF were assessed using cognitive measures including Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and a formal neuropsychological battery. The short-MoCA was derived and combined with Symbol Digit Modalities Test (SDMT) to create the VasCog Screen. The discriminatory ability of different tests for CI was compared, establishing optimal cut-off points. Variants of short-MoCA including the SDMT were also evaluated. RESULTS: Similar prevalence rates of CI were found in stroke and HF cohorts. The most prevalent neuropsychological impairment was visuomotor speed, followed by visual memory and visuoconstruction. More than half of the patients were found to have CI. The VasCog Screen outperformed MMSE, MoCA and short-MoCA in detecting CI. The addition of SDMT to variants of the short-MoCA increased diagnostic accuracy. CONCLUSION: The VasCog Screen test offers a cognitive screening tool, which is sensitive to cognitive deficits characteristically found in patients who had a stroke and with HF. It was found to have good sensitivity, specificity and classification accuracy. It is easy to administer in busy clinics, enabling early detection of CI and facilitating appropriate interventions.

Cognitive control adjustments are dependent on the level of conflict.

The congruency sequence effect (CSE) is one of the most investigated effects in the cognitive control literature. The conflict monitoring theory suggests that the CSE is the result of adjustments in cognitive control based on perceived conflict. A recent paper by Zhang and colleagues, has investigated whether the manipulation of conflict level by changing distractor incompatibility in a flanker task affects the amount of adjustments in cognitive control. Their study produced mixed findings, somewhat supporting the original conflict monitoring theory, but also suggesting other explanations, such as the repetition expectancy account. We replicated the experimental design in a multisite online study (N = 347), with Hungarian, Italian, and Singaporean participants. Our results supported the prediction that changes in the level of conflict trigger conflict adaptation, revealing that increasing conflict levels induced stronger adaptive control. Bayesian hypothesis testing indicated a monotonic reduction in congruency effects as a function of previous conflict strength. This finding is in line with the extension of the traditional conflict monitoring theory, as well as other theories like affective signaling and expected value of control, implying that the relationship between conflict and interference effects is gradual, rather than a binary function.

Train-your-brain program to reduce depression, anxiety, and stress in stroke survivors: a pilot community-based cognitive intervention study.

Introduction: Stroke is a major cause of death and disability worldwide, and it often results in depression, anxiety, stress, and cognitive impairment in survivors. There is a lack of community-based cognitive interventions for stroke survivors. This pilot single trial aimed to assess the feasibility, acceptability, and perceived effectiveness of a community-based cognitive intervention program called Train-Your-Brain (TYB) for stroke survivors and caregivers. The study focused on improvements in emotional and psychological well-being, as well as cognitive functioning. Methods: A quasi-experimental design was used in this study. A total of 48 participants were recruited and assessed using Depression, Anxiety, Stress Scale - 21 items (DASS-21), Montreal Cognitive Assessment (MoCA) and Symbol Digits Modality Test (SDMT) before and after the intervention. The TYB program consisted of nine sessions and was conducted via the Zoom software application. Participants provided feedback on the program, highlighting areas for improvement. Results: Twenty-seven stroke survivors and 21 caregivers completed the program. Participants expressed high satisfaction with the TYB program but recommended avoiding assessments in December and customizing the program for stroke survivors and caregivers. Stroke survivors showed significant improvements in depression and stress scores, while caregivers experienced no significant improvements after the program. While there was a slight improvement in stroke survivors' cognitive scores after the program, it was not statistically significant. Caregivers, however, experienced a significant decline in cognitive scores. Discussion: The TYB program provided group support and validation, resulting in improved mood and reduced stress among stroke survivors. Cultural collectivism played a significant role in fostering group cohesion. However, the program's limited focus on caregivers and timing of assessments during the December holidays may have affected the outcomes. The TYB program demonstrated feasibility and potential effectiveness in alleviating psychological distress and enhancing cognitive function among stroke survivors. Future research should explore long-term effects, larger sample sizes, and non-English-speaking populations to enhance generalizability. Tailored interventions for caregivers are necessary.

Addressing mood and fatigue in return-to-work programmes after stroke: a systematic review.

Introduction: Return-to-work is a key rehabilitation goal for many working aged stroke survivors, promoting an overall improvement of quality of life, social integration, and emotional wellbeing. Conversely, the failure to return-to-work contributes to a loss of identity, lowered self-esteem, social isolation, poorer quality of life and health outcomes. Return-to-work programmes have largely focused on physical and vocational rehabilitation, while neglecting to include mood and fatigue management. This is despite the knowledge that stroke results in changes in physical, cognitive, and emotional functioning, which all impact one's ability to return to work. The purpose of this systematic review is to conduct a comprehensive and up-to-date search of randomised controlled trials (RCTs) of return-to-work programmes after stroke. The focus is especially on examining components of mood and fatigue if they were included, and to also report on the screening tools used to measure mood and fatigue. Method: Searches were performed using 7 electronic databases for RCTs published in English from inception to 4 January 2023. A narrative synthesis of intervention design and outcomes was provided. Results: The search yielded 5 RCTs that satisfied the selection criteria (n = 626). Three studies included components of mood and fatigue management in the intervention, of which 2 studies found a higher percentage of subjects in the intervention group returning to work compared to those in the control group. The remaining 2 studies which did not include components of mood and fatigue management did not find any significant differences in return-to-work rates between the intervention and control groups. Screening tools to assess mood or fatigue were included in 3 studies. Conclusion: Overall, the findings demonstrated that mood and fatigue are poorly addressed in rehabilitation programmes aimed at improving return-to-work after stroke, despite being a significant predictor of return-to-work. There is limited and inconsistent use of mood and fatigue screening tools. The findings were generally able to provide guidance and recommendations in the development of a stroke rehabilitation programme for return-to-work, highlighting the need to include components addressing and measuring psychological support and fatigue management.

Does Watching Videos With Natural Scenery Restore Attentional Resources?

Existing studies have shown that direct exposure to a real nature environment has a restorative effect on attentional resources after a mentally fatiguing task. However, it remains unclear whether virtual nature simulations can serve as a substitute for real nature experienced in the outdoors to restore executive attention. Given the mixed findings in the literature, the present study sought to examine if viewing videos with natural scenery (vs. a control with urban scenery) restores participants' working memory capacity - measured by an operation span task - in a high-powered pre-registered within-subject experimental study. Overall, our within-subject experiment did not find any evidence to support the benefit of watching videos with natural scenery on restoration of executive attention. Moreover, the results from our Bayesian analyses further showed substantial support for the null hypothesis. Our study suggests that virtual nature simulations, even with the use of videos, may not be able to replicate the experiences of nature in the outdoors and restore attentional resources.

Protecting endangered megafauna through AI analysis of drone images in a low-connectivity setting: a case study from Namibia.

Assessing the numbers and distribution of at-risk megafauna such as the black rhino (Diceros bicornis) is key to effective conservation, yet such data are difficult to obtain. Many current monitoring technologies are invasive to the target animals and expensive. Satellite monitoring is emerging as a potential tool for very large animals (e.g., elephant) but detecting smaller species requires higher resolution imaging. Drones can deliver the required resolution and speed of monitoring, but challenges remain in delivering automated monitoring systems where internet connectivity is unreliable or absent. This study describes a model built to run on a drone to identify in situ images of megafauna. Compared with previously reported studies, this automated detection framework has a lower hardware cost and can function with a reduced internet bandwidth requirement for local network communication. It proposes the use of a Jetson Xavier NX, onboard a Parrot Anafi drone, connected to the internet throughout the flight to deliver a lightweight web-based notification system upon detection of the target species. The GPS location with the detected target species images is sent using MQ Telemetry Transport (MQTT), a lightweight messaging protocol using a publisher/subscriber architecture for IoT devices. It provides reliable message delivery when internet connection is sporadic. We used a YOLOv5l6 object detection architecture trained to identify a bounding box for one of five objects of interest in a frame of video. At an intersection over union (IoU) threshold of 0.5, our model achieved an average precision (AP) of 0.81 for black rhino (our primary target) and 0.83 for giraffe (Giraffa giraffa). The model was less successful at identifying the other smaller objects which were not our primary targets: 0.34, 0.25, and 0.42 for ostrich (Struthio camelus australis), springbok (Antidorcas marsupialis) and human respectively. We used several techniques to optimize performance and overcome the inherent challenge of small objects (animals) in the data. Although our primary focus for the development of the model was rhino, we included other species classes to emulate field conditions where many animal species are encountered, and thus reduce the false positive occurrence rate for rhino detections. To constrain model overfitting, we trained the model on a dataset with varied terrain, angle and lighting conditions and used data augmentation techniques (i.e., GANs). We used image tiling and a relatively larger (i.e., higher resolution) image input size to compensate for the difficulty faced in detecting small objects when using YOLO. In this study, we demonstrated the potential of a drone-based AI pipeline model to automate the detection of free-ranging megafauna detection in a remote setting and create alerts to a wildlife manager in a relatively poorly connected field environment.

Dispositional gratitude, health-related factors, and lipid profiles in midlife: a biomarker study.

Dispositional gratitude has emerged in the literature to be associated with many health benefits in measures ranging from self-reported health to biomarkers of cardiovascular risk. However, little is known about the link between dispositional gratitude and lipid profiles. Drawing from the Gratitude and Self-improvement Model that grateful individuals are more likely to strive for actual self-improvement such as engaging in healthy lifestyles, we investigated the relation between dispositional gratitude and serum lipid levels. Participants consisted of 1800 adults from the National Survey of Midlife Development in the United States (MIDUS) 2: Biomarker Project (N = 1054) and MIDUS Refresher: Biomarker Project (N = 746). Serum lipid profiles were measured through fasting blood samples. After controlling for demographics, use of antihyperlipidemic mediation, and personality traits, we found that higher dispositional gratitude was associated with lower triglyceride levels. Results also revealed that healthy diets and lower BMI partially mediated the gratitude-triglyceride association. However, some variations in the analytic method may influence the associations between gratitude and triglycerides levels. Our findings provide preliminary evidence suggesting dispositional gratitude as a promising psychological factor that is associated with a healthier lipid profile.

Spatial Errors in Automated Geocoding of Incident Locations in Australian Suicide Mortality Data.

BACKGROUND: There is increasing interest in the spatial analysis of suicide data to identify high-risk (often public) locations likely to benefit from access restriction measures. The identification of such locations, however, relies on accurately geocoded data. This study aims to examine the extent to which common completeness and positional spatial errors are present in suicide data due to the underlying geocoding process. METHODS: Using Australian suicide mortality data from the National Coronial Information System for the period of 2008-2017, we compared the custodian automated geocoding process to an alternate multiphase process. Descriptive and kernel density cluster analyses were conducted to ascertain data completeness (address matching rates) and positional accuracy (distance revised) differences between the two datasets. RESULTS: The alternate geocoding process initially improved address matching from 67.8% in the custodian dataset to 78.4%. Additional manual identification of nonaddress features (such as cliffs or bridges) improved overall match rates to 94.6%. Nearly half (49.2%) of nonresidential suicide locations were revised more than 1,000 m from data custodian coordinates. Spatial misattribution rates were greatest at the smallest levels of geography. Kernel density maps showed clear misidentification of hotspots relying solely on autogeocoded data. CONCLUSION: Suicide incidents that occur at nonresidential addresses are being erroneously geocoded to centralized fall-back locations in autogeocoding processes, which can lead to misidentification of suicide clusters. Our findings provide insights toward defining the nature of the problem and refining geocoding processes, so that suicide data can be used reliably for the detection of suicide hotspots. See video abstract at, http://links.lww.com/EDE/B862.

Stories and perspective taking: Augmenting dental students' understanding of patient care.

INTRODUCTION: Medical schools have reported on the integration of humanities, through literature, which offer diverse content and approaches that can be used to enhance patient care. The integration of humanities in dental education is a recent development. At the International Medical University (IMU) Malaysia, a literature module which focused on perspective taking activities was offered to the Bachelor of Dentistry program. We aimed to study if the module impacted dental students' understanding of patient care. METHODS: Third-year undergraduate dental students were facilitated to discuss stories, engage in perspective taking activities and keep a portfolio for assessment in the Stories and Perspectives selective. Thematic analysis was used to analyze the data in their portfolios. RESULTS: The dental students identified key learning points that would better prepare them for patient-centered care. Three themes emerged: (1) facilitate empathy in students, (2) stimulate self-awareness in students, and (3) motivate students to be perceptive communicators. Students were able to appreciate the complexities of care giving as it involved taking into account the thoughts and feelings of the other while recognizing their own mental state. They further valued the choice of appropriate words and actions in mediating this process. CONCLUSION: The potential for incorporating humanities based approaches to teach patient care to dental students is favorable. Reading stories and extending this to perspective taking activities to induce creative ways to shift between experiences of self and other is a positive approach in preparing health professionals for care giving encounters.

Length of post-traumatic amnesia and its prediction of neuropsychological outcome following severe to extremely severe traumatic brain injury in a litigating sample.

Primary Objective: The aim of the current study was to examine the relationship between duration of post-traumatic amnesia (PTA) and neuropsychological outcome at one or more years following severe to extremely severe traumatic brain injury (TBI) in a litigating sample. Research Design: Retrospective study design, using data collected from 2010 to 2017. Methods and Procedures: Data from 41 cases obtained from a private medicolegal neuropsychological database was examined. The database comprised information pertaining to TBI etiology, TBI severity parameters, demographic variables, neuropsychological test results and scores on psychological questionnaires. PTA duration was examined as a continuous variable. All cases that demonstrated non-credible effort were excluded. Main Outcomes and Results: Continuous PTA duration was not found to be a significant predictor of cognitive impairment across domains of verbal intellect, non-verbal intellect, working memory, information processing speed, immediate memory, delayed memory, and executive functioning. Conclusions: The predictive relationship between duration of PTA and cognitive impairment that has been reported in non-litigating populations did not exist in a litigating TBI sample. Findings illustrate the importance of investigating the relationships between injury variables and cognitive outcome in a population undergoing litigation, to provide better understanding of outcome in this subgroup of patients with TBI.

Assessors for communication skills: SPs or healthcare professionals?

INTRODUCTION: The complexity of modern medicine creates more challenges for teaching and assessment of communication skills in undergraduate medical programme. This research was conducted to study the level of communication skills among undergraduate medical students and to determine the difference between simulated patients and clinical instructors' assessment of communication skills. METHODS: This comparative study was conducted for three months at the Clinical Skills and Simulation Centre of the International Medical University in Malaysia. The modified Calgary-Cambridge checklist was used to assess the communication skills of 50 first year and 50 second year medical students (five-minutes pre-recorded interview videos on the scenario of sore throat). These videos were reviewed and scored by simulated patients (SPs), communication skills instructors (CSIs) and non-communication skills instructors (non-CSIs). RESULTS: Better performance was observed among the undergraduate medical students, who had formal training in communication skills with a significant difference in overall scores detected among the first and second year medical students (p = 0.0008). A non-significant difference existed between the scores of SPs and CSIs for Year 1 (p = 0.151). CONCLUSIONS: The SPs could be trained and involved in assessment of communication skills. Formal training in communication skills is necessary in the undergraduate medical programme.

Fast-track protocols in colorectal surgery.

Fast-track surgery (FTS) is a set of protocols aimed to reduce the physiological burden of surgery thus improving outcomes. FTS aims to use evidence-based practice to reduce complications, improve post-operative quality of life and decrease hospital length of stay. This review seeks to examine the evidence base for protocols employed in colorectal surgery in the areas of pre-operative preparation, anaesthetic management, intraoperative and surgical factors and post-operative care. Despite the evidence that recovery after colorectal surgery can be enhanced by using these approaches, implementation of FTS protocols has been slow. Acceptance of FTS protocols by all members of the multi-disciplinary team and a change in organisational structure to accommodate structured peri-operative care, are imperative to implementation.

A role for skin gammadelta T cells in wound repair.

Gammadelta T cell receptor-bearing dendritic epidermal T cells (DETCs) found in murine skin recognize antigen expressed by damaged or stressed keratinocytes. Activated DETCs produce keratinocyte growth factors (KGFs) and chemokines, raising the possibility that DETCs play a role in tissue repair. We performed wound healing studies and found defects in keratinocyte proliferation and tissue reepithelialization in the absence of wild-type DETCs. In vitro skin organ culture studies demonstrated that adding DETCs or recombinant KGF restored normal wound healing in gammadelta DETC-deficient skin. We propose that DETCs recognize antigen expressed by injured keratinocytes and produce factors that directly affect wound repair.